Acute Pyelonephritis
Acute Pyelonephritis
emedicine.medscape.com
Acute Pyelonephritis
Updated: Jul 01, 2021
Author: Tibor Fulop, MD, PhD, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN
Overview
Practice Essentials
Acute pyelonephritis is a bacterial infection of the kidney parenchyma that can be organ- and/or life-threatening
and that often leads to scarring of the kidney. The bacteria in these cases have usually ascended from the lower
urinary tract, but may also reach the kidney via the bloodstream. Timely diagnosis and management of acute
pyelonephritis has a significant impact on patient outcomes.[1, 2] See the image below.
Fever - This is not always present, but when it is, the temperature often exceeds 103°F (39.4°C)
Costovertebral angle pain - Pain may be mild, moderate, or severe; flank or costovertebral angle tenderness is
most commonly unilateral over the involved kidney, although bilateral discomfort may be present
Nausea and/or vomiting - These vary in frequency and intensity, from absent to severe; anorexia is common in
patients with acute pyelonephritis
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Gross hematuria (hemorrhagic cystitis), unusual in males with pyelonephritis, occurs in 30-40% of females, most often
young women, with the disorder.
Symptoms usually develop over hours or over the course of a day but may not occur at the same time. If the patient is
male, elderly, or a child or has had symptoms for more than 7 days, the infection should be considered complicated
until proven otherwise.
The classic manifestations of acute pyelonephritis observed in adults are often absent in children, particularly neonates
and infants. In children aged 2 years or younger, the most common signs and symptoms of urinary tract infection (UTI)
are as follows:
Failure to thrive
Feeding difficulty
Fever
Vomiting
Elderly patients may present with typical manifestations of pyelonephritis, or they may experience the following:
Fever
Mental status change
Decompensation in another organ system
Generalized deterioration
Diagnosis
In the outpatient setting, pyelonephritis is usually suggested by a patient’s history and physical examination and
supported by urinalysis results. Urine specimens can be collected through the following methods:
Clean catch
Urethral catheterization
Suprapubic needle aspiration
Urine culture is indicated in any patient with pyelonephritis, whether treated in an inpatient or outpatient setting,
because of the possibility of antibiotic resistance.
Imaging studies that may be used in assessing acute pyelonephritis include the following:
Computed tomography (CT) scanning - To identify alterations in renal parenchymal perfusion; alterations in
contrast excretion, perinephric fluid, and nonrenal disease; gas-forming infections; hemorrhage; inflammatory
masses; and obstruction
Magnetic resonance imaging (MRI) – To detect kidney infection or masses and urinary obstruction, as well as to
evaluate renal vasculature
Ultrasonography - To screen for urinary obstruction in children admitted for febrile illnesses and to examine
patients for kidney abscesses, acute focal bacterial nephritis, and stones (in xanthogranulomatous
pyelonephritis)
Scintigraphy - To detect focal renal abnormalities
CT and MR urography - Used in the evaluation of hematuria
Management
Antibiotic therapy is essential in the treatment of acute pyelonephritis and prevents progression of the infection. Urine
culture and sensitivity testing should always be performed, and empirical therapy should be tailored to the infecting
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uropathogen.[3]
Patients presenting with complicated pyelonephritis should be managed as inpatients and treated empirically with
broad-spectrum parenteral antibiotics.
Outpatient care
Outpatient treatment is appropriate for patients who have an uncomplicated infection that does not warrant
hospitalization. Treatment can be with a single dose of a parenteral antibiotic followed by oral therapy, provided that
the patient is monitored within the first 48 hours.
Inpatient care
Supportive care
Monitoring of urine and blood culture results
Monitoring of comorbid conditions for deterioration
Maintenance of hydration status with IV fluids until hydration can be maintained with oral intake
IV antibiotics until defervescence and significant symptomatic improvement occur; convert to an oral regimen
tailored to urine or blood culture results
Surgery
In addition to antibiotics, surgery may be necessary to treat the following manifestations of acute pyelonephritis:
Renal cortical abscess (renal carbuncle): Surgical drainage (if patients do not respond to antibiotic therapy);
other surgical options are enucleation of the carbuncle and nephrectomy
Renal corticomedullary abscess: Incision and drainage, nephrectomy
Perinephric abscess: Drainage, nephrectomy
Calculi-related urinary tract infection (UTI): Extracorporeal shockwave lithotripsy (ESWL) or endoscopic,
percutaneous, or open surgery
Renal papillary necrosis: CT scan̶ guided drainage or surgical drainage with debridement
Xanthogranulomatous pyelonephritis: Nephrectomy
Background
Acute pyelonephritis is a potentially organ- and/or life-threatening infection that characteristically causes scarring of the
kidney.[4] An episode of acute pyelonephritis may lead to significant renal damage; acute kidney injury; abscess
formation (eg, nephric, perinephric); sepsis; or sepsis syndrome, septic shock, and multiorgan system failure.
A population-based study of acute pyelonephritis in the United States found overall annual rates of 15–17 cases per
10,000 females and 3–4 cases per 10,000 males.[5]
Diagnosing and managing acute pyelonephritis is not always straightforward. Wide variation exists in the clinical
presentation, severity, options, and disposition of the disease.
Patients in the age range of 5-65 years typically present with lower urinary tract infection (UTI) symptoms (eg, dysuria,
frequency, urgency, gross hematuria, suprapubic pain) and classic upper UTI symptoms (eg, flank pain, back pain),
with or without systemic signs and symptoms (eg, fever, chills, abdominal pain, nausea, vomiting, costovertebral angle
tenderness) and with or without leukocytosis. However, acute pyelonephritis can present as nonspecific symptoms.
A number of studies using immunochemical markers have shown that many women who initially present with lower
urinary tract symptoms actually have pyelonephritis. Their pyelonephritis is often identified when short-course therapy
for uncomplicated cystitis fails.
With patients at the extremes of age, the presentation may be so atypical that pyelonephritis is not in the differential
diagnosis. Infants may present with feeding difficulty or fever, and the elderly may have mental status change or fever.
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Acute pyelonephritis is complex, and there is no consistent set of signs and symptoms that is both sensitive and
specific for the diagnosis. Therefore, clinicians must maintain a high index of suspicion.
In contrast to the plethora of data available for the treatment of cystitis, less substantial data are available regarding
the appropriate antibiotic choice or duration of therapy for acute pyelonephritis. An additional cause for concern is the
growing resistance of uropathogens to standard agents. Nevertheless, useful recommendations can be made.
The current emphasis on cost-effectiveness and the advent of newer antibiotics have led clinicians to reevaluate the
benefit of hospitalization in patients with acute pyelonephritis. Most cases of uncomplicated pyelonephritis in young
women can be managed successfully on an outpatient basis. However, outpatient management of acute pyelonephritis
requires close follow-up care. The first follow-up visit should occur in 1-2 days, depending on the clinician's estimation
of the severity of the infection. Any deterioration or unsatisfactory improvement warrants admission for intravenous
antibiotics and evaluation for any complications. (See Treatment.)
Complicated pyelonephritis results from structural and functional abnormalities, urologic manipulations, or underlying
disease; it includes pyelonephritis in men and in the elderly. Any patient with complicated pyelonephritis should be
referred, if possible, to a physician trained in the management of these cases (eg, a nephrologist, urologist, or
infectious disease specialist). The patient will require ongoing management, including repeat cultures, metabolic
studies, and appropriate imaging studies.
Pathophysiology
Acute pyelonephritis results from bacterial invasion of the renal parenchyma. Bacteria usually reach the kidney by
ascending from the lower urinary tract.[6] In all age groups, episodes of bacteriuria occur commonly, but most are
asymptomatic and do not lead to infection. The development of infection is influenced by bacterial factors and host
factors.[7]
Bacteria may also reach the kidney via the bloodstream. Hematogenous sources of gram-positive organisms, such as
Staphylococcus, are intravenous drug abuse and endocarditis. Experimental evidence suggests that hematogenous
spread of gram-negative organisms to the kidney is less likely unless an underlying problem exists, such as an
obstruction. Little or no evidence supports lymphatic spread of uropathogens to the kidney.
Most bacterial data are derived from research with Escherichia coli, which accounts for 70-90% of uncomplicated UTIs
and 21-54% of complicated UTIs (ie, UTIs that are secondary to anatomic or functional abnormalities that impair
urinary tract drainage; are associated with metabolic disorders; or involve unusual pathogens). A subset of E coli, the
uropathogenic E coli (UPEC), also termed extraintestinal pathogenic E coli (ExPEC), accounts for most clinical isolates
from UTIs.
UPEC derives commonly from the phylogenetic groups B2 and D, which express distinctive O, K, and H antigens.
UPEC genes encode several postulated virulence factors (VFs), including adhesins, siderophores, protectins, and
toxins, as well as having the metabolic advantage of synthesizing essential substances.
Virulence factors
Adhesins have specific regions that attach to cell receptor epitopes in a lock-and-key fashion. Mannose-sensitive
adhesins (usually type 1 fimbriae) are present on essentially all E coli. They contribute to colonization (eg, bladder, gut,
mouth, vagina) and possibly pathogenesis of infection; however, they also attach to polymorphonuclear neutrophils
(PMNs), leading to bacterial clearance.
Mannose-resistant adhesins permit the bacteria to attach to epithelial cells, thereby resisting the cleansing action of
urine flow and bladder emptying. They also allow the bacteria to remain in close proximity to the epithelial cell,
enhancing the activity of other VFs.
The P fimbriae family of adhesins is epidemiologically associated with prostatitis, pyelonephritis (70-90% of strains),
and sepsis. This family of adhesins is associated with less than 20% of asymptomatic bacteriuria (ABU) strains. The
AFA/Dr family is associated with diarrhea, UTI, and particularly pyelonephritis in pregnancy. The S/F1C family is
associated with neonatal meningitis and UTI.
Siderophores are involved in iron uptake, an essential element for bacteria, and possibly adhesion. Protectins and their
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Toxins, which affect various host cell functions, include the following:
Alpha-hemolysin
Cytotoxic necrotizing factor–1
Cytolethal distending toxin
Secreted autotransporter toxin
No single VF is sufficient or necessary to promote pathogenesis. Apparently, multiple VFs are necessary to ensure
pathogenesis, although adhesins play an important role.
Bacterial strains that produce ABU may in some instances provide a measure of protection against symptomatic
infections from UPEC and other organisms. On the other hand, ABU may also cause increased morbidity and
mortality. Once bacteriuria is established, these strains appear to stop producing adhesins, allowing them to survive
and persist without producing an inflammatory reaction.
Pathogens
As noted above, UPEC account for most uncomplicated pyelonephritis cases and a significant portion of complicated
pyelonephritis cases. The following microorganisms are also commonly isolated:
Staphylococcus saprophyticus
Klebsiella pneumoniae
Proteus mirabilis
Enterococci
S aureus
Pseudomonas aeruginosa
Enterobacter species
This is the same spectrum of organisms cultured in cystitis. In 10-15% of symptomatic cystitis cases, cultures using
routine methods remain negative, although the symptoms typically respond to antibiotic therapy. In some cases,
cultures using selective media have grown Gardnerella vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum.
These data cannot be extended to acute pyelonephritis, but they do illustrate the difficulties in isolating the causative
organism.
Evidence suggests that the pathogenesis of pyelonephritis takes a 2-step path. First, UPEC attaches to the epithelium
and triggers an inflammatory response involving at least 2 receptors, glycosphingolipid (GSL) and Toll-like receptor 4
(TLR4). In the mouse model, GSL is the primary receptor and TLR4 is recruited and is an important receptor for the
release of chemokines. When TLR4 is genetically absent, an asymptomatic carrier state develops in the infected mice.
Second, as a result of the inflammatory response, chemokines (eg, interleukin-8 [IL-8], which is chemotactic for PMNs)
are released and attach to the neutrophil-activating chemokine receptor 1 (CXCR1), allowing PMNs to cross the
epithelial barrier into the urine. In children prone to pyelonephritis, for example, CXCR1 expression has been shown to
be significantly lower than in control subjects.
Several other host factors militate against symptomatic UTI. Phagocytosis of bacteria in urine is maximized at pH 6.5-
7.5 and osmolality of 485 mOsm; values deviating from these ranges lead to significantly reduced or absent
phagocytosis. Other important factors are the flushing action of urine flow in the ureter and bladder, the inhibition of
attachment of type 1 fimbriae E coli to uroepithelial cells by tubular cell–secreted Tamm-Horsfall protein, and the
inhibition of attachment by some surface mucopolysaccharides on the uroepithelial cells.
Complicated infection
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Complicated UTI is an infection of the urinary tract in which the efficacy of antibiotics is reduced because of the
presence of one or more of the following:
For more information on this topic, see Pathophysiology of Complicated Urinary Tract Infections.
Obstruction
Obstruction is the most important factor. It negates the flushing effect of urine flow; allows urine to pool (urinary stasis),
providing bacteria a medium in which to multiply; and changes intrarenal blood flow, affecting neutrophil delivery.
Obstruction may be extrinsic or intrinsic. Extrinsic obstruction occurs with chronic constipation (particularly in children),
prostatic swelling/mass (eg, hypertrophy, infection, cancer), and retroperitoneal mass.
Intrinsic obstruction occurs with bladder outlet obstruction, cystocele, fungus ball, papillary necrosis, stricture, and
urinary stones. With increasing size of stone, the probability of stone passage decreases while the probability of
obstruction increases. Nonetheless, stones as small as 2 mm have resulted in obstruction, while 8-mm stones have
occasionally passed spontaneously.
Infectious stones, urease stones, or triple-phosphate stones composed of magnesium ammonium phosphate or
struvite and apatite account for 10-15% of all urinary stones. They develop secondary to the action of urea-splitting
organisms and can grow rapidly and branch out (ie, staghorn calculi).
If left untreated, staghorn calculi will destroy the kidney and may cause the death of the patient. Complications include
azotemia, hydropyonephrosis, perinephric abscess, pyelonephritis (severe or end-stage), sepsis, and
xanthogranulomatous pyelonephritis.
Incomplete bladder emptying may be related to medication (eg, anticholinergics). The spermicide nonoxynol-9 inhibits
the growth of lactobacilli. Lactobacilli produce hydrogen peroxide, which protects the vaginal ecosystem against
pathogens. Frequent sexual intercourse causes local mechanical trauma to the urethra in both partners.
Atrophic vaginal mucosa in postmenopausal women predisposes to the colonization of urinary tract pathogens and
UTIs because of the higher pH (5.5 vs 3.8) and the absence of lactobacilli. Bacterial prostatitis (acute or chronic)
produces bacteriuria, whereas nonbacterial prostatitis and pelviperineal pain syndrome (prostadynia) do not.
Unusual organisms include Mycoplasma, Pseudomonas, and urea-splitting organisms. Pseudomonas aeruginosa has
several mechanisms that promote adherence, including alginate, other membrane proteins, pili, and surface-
associated exoenzyme S.
Urea-splitting organisms produce urease, which hydrolyzes urea, yielding ammonia, bicarbonate, and carbonate; this
leads to a more alkaline urine and allows crystal formation (staghorn calculus) from the supersaturation of carbonate
apatite and struvite. Staghorn calculi continue to grow in size, leading to infection, obstruction, or both.
Complications of obstruction with superimposed infection include hydronephrosis, pyonephrosis, urosepsis, and
xanthogranulomatous pyelonephritis. Additionally, the pathogens can sequester in the struvite stones, protected from
the host’s immune system. Proteus species are the most common urea-splitting organisms. E coli, Klebsiella,
Pseudomonas, and Staphylococcus can also produce urease, however, and are sometimes involved in staghorn
calculus formation.
Pregnancy
Pregnancy produces hormonal and mechanical changes that predispose the woman to upper urinary traction
infections. Hydroureter of pregnancy, secondary to both hormonal and mechanical factors, manifests as dilatation of
the renal pelvis and ureters (greater on the left than on the right), with the ureters containing up to 200 mL of urine.
Progesterone decreases ureteral peristalsis and increases bladder capacity. The enlarging uterus displaces the
bladder, contributing to urinary stasis.
Diabetes
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Diabetes mellitus produces autonomic bladder neuropathy, glucosuria, leukocyte dysfunction, microangiopathy, and
nephrosclerosis; additionally, it leads to recurrent bladder instrumentation secondary to the neuropathy. Complicated
UTIs in patients who have diabetes mellitus include the following:
Etiology
Uropathogens that cause the majority of acute pyelonephritis cases and the frequency with which they are cultured in
uncomplicated versus complicated cases, are listed in Table 1. Unusual pathogens include mycobacteria, yeasts and
fungi, and opportunistic pathogens such as Corynebacterium urealyticum.
Table 1. Bacterial Etiology of Urinary Tract Infections (Open Table in a new window)
Gram negative
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Gram positive
Other <1 2
Adapted from Hooton TM. The current management strategies for community-acquired urinary tract infection.
Infect Dis Clin North Am. Jun 2003;17(2):303-32. [QxMD MEDLINE Link].
* S saprophyticus
Epidemiology
Epidemiologic data on the incidence of pyelonephritis are limited. A population-based study of acute pyelonephritis in
the United States found overall annual rates of 15-17 cases per 10,000 females and 3-4 cases per 10,000 males.[5] In
women aged 18−49 years, the estimated incidence is 28 cases per 10,000.[8] At least 250,000 cases of pyelonephritis
are diagnosed annually in the United States. The cost of treating acute pyelonephritis has been estimated to be $2.14
billion per year.[5]
Acute pyelonephritis develops in 20-30% of pregnant women with untreated asymptomatic bacteriuria (ABU) (2-9.5%),
most often during the late second and early third trimesters. The incidence of pyelonephritis in infants and children is
difficult to ascertain because of the infrequency of typical symptoms. Up to 25% of children with UTI and no signs or
symptoms of pyelonephritis do have bacteria demonstrable in the upper urinary tract.
No racial predilection of pyelonephritis has been demonstrated. Pyelonephritis is significantly more common in females
than in males, although this difference narrows considerably with increasing age, especially in patients aged 65 years
and older. In females, pyelonephritis shows a trimodal distribution, with an elevated incidence in girls aged 0-4 years, a
peak in women 15-35 years of age, and a gradual increase after age 50 years to another peak at 80 years of age.[5]
In males, the age distribution of pyelonephritis is bimodal. Males also demonstrate a peak incidence of pyelonephritis
at 0-4 years of age. Rates gradually increase after 35 years of age and peak at 85 years of age.[5]
Acute pyelonephritis shows a seasonal variation. In Washington state, cases occurred most frequently during the
months of July and August among females and during August and September in the male population.[5]
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Prognosis
Timely diagnosis and management of acute pyelonephritis has a significant impact on the outcome. Any patient with
acute pyelonephritis who deteriorates suddenly or does not respond to conventional therapy may have a complication,
resistant organism, or unrecognized comorbidity.
Pyelonephritis causes considerable morbidity. Data can be extrapolated from the morbidity data for acute lower urinary
tract infections: specifically, acute cystitis in women produces approximately 6.1 days with symptoms, 2.4 days of
restricted activity, 1.2 days that the patient is unable to work or attend class, and 0.4 days bedridden. In women aged
18−49 years, 7% of pyelonephritis cases require hospital admission.[8]
For patients with pyelonephritis who have an organ-threatening infection, the follow-up examination is important to be
sure that the patient is progressing satisfactorily and that recovery is complete. Failure to diagnose these
complications in a timely fashion could predispose the patient to a poor outcome. Pregnant patients with pyelonephritis
are at significant risk for premature labor.
Kofteridis et al found that acute pyelonephritis is linked to bacteremia, longer hospital stays, and higher mortality in
patients with diabetes mellitus.[9] In a retrospective study of 206 elderly patients, 88 of whom had diabetes,
bacteremia occurred in 30.7% of patients with diabetes but in only 11% of the control patients. Moreover, compared
with the control patients, patients with diabetes had longer-lasting fevers (median, 4.5 vs 2.5 days), longer hospital
stays (median, 10 vs 7 days), and higher mortality (12.5% vs 2.5%).
Mortality is higher in patients older than 65 years; it is also higher with septic shock, bedridden status, and
immunosuppression. In men, mortality is also increased with use of antibiotics during the previous month. Morbidity
(prolonged hospital stay) in both men and women is increased with a change in initial treatment, diabetes mellitus, and
long-term indwelling catheter.
Uncomplicated pyelonephritis
In healthy, nonpregnant women with uncomplicated disease, the prognosis is excellent for full recovery and minimal
damage to the kidney. In healthy men without any known complicating conditions, the prognosis is good for full
recovery; however, urologic evaluation is recommended to rule out an underlying complicating condition. In infants and
children, the prognosis is good. Importantly, children should undergo a urologic evaluation after the first episode to rule
out structural abnormalities.
Uncomplicated pyelonephritis is not a fatal disease in the antibiotic era. Pyelonephritis becomes a potentially fatal
disease when secondary conditions develop, such as emphysematous pyelonephritis (20-80% mortality rate),
perinephric abscess (20-50% mortality rate), or one of the sepsis syndromes (>25% overall mortality rate).
Emphysematous pyelonephritis
In emphysematous pyelonephritis, the mortality rate is 60% in cases in which the gas is localized to the renal
parenchyma, regardless of treatment. The mortality is 80% if the gas has spread in the perinephric space and the
patient is treated with antibiotics alone. In emphysematous pyelitis, the mortality rate is 20%.
Sepsis
The genitourinary system is the source of severe sepsis in 9.1% of all cases annually. The mortality for these GU-
related cases is 16.1%. Overall mortality from severe sepsis significantly increases with chronic kidney disease
(36.7%), acute renal dysfunction (38.2%), and age older than 64 years (25-42% with progressively increasing age to
older than 85 years). In the age range of 0-4 years, the mortality is 5%; for ages 5-50 years, it is less than 3%.
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over 65, complicated or bilateral pyelonephritis, and initial shock were independent risk factors for the occurrence of
AKI.[10]
A Danish population-based cohort study of 8760 patients found that preadmission impaired kidney function is a strong
risk factor for development of AKI in patients with pyelonephritis. The 30-day risk of AKI rose steadily from 16% in
patients with a preadmission estimated glomerular filtration ration (eGFR) ≥90 mL/min/1.73 m2 to 47% for patients with
preadmission eGFR of < 30.[11]
Kidney scarring
In children, kidney scarring can be detected in 6-15% after a febrile UTI. Of these patients, almost all males and some
females have demonstrable kidney scarring and a globally small kidney with smooth renal outlines in infancy, usually
associated with vesicoureteral reflux (VUR) and thought to be congenital. Most female infants do not have
demonstrable scarring on initial imaging, but they subsequently develop it. Delay in treatment of cystitis or
pyelonephritis, recurrent UTIs, urinary obstruction, and VUR increase the risk of scarring. In children, normal
ultrasonogram findings alone cannot reliably rule out the presence of either reflux or kidney scarring.[12]
Acute pyelonephritis (single episode; first UTI ever in one half of cases) in an adult woman leads to kidney scarring in
46%, as demonstrated by scintigraphic scanning 10 years later. Subsequent UTIs do not appear to affect the risk of
future scarring.
Kidney scarring has been demonstrated to be 4 times more likely after pyelonephritis in pregnant women than in
nonpregnant women. In addition, acute pyelonephritis during pregnancy is associated with the following complications:
Acute kidney transplant pyelonephritis occurring in the first 3 months after transplant has a significant association with
graft loss (>40%) by 96 months, as compared with all kidney transplant cases with or without the occurrence of
pyelonephritis at any time after the transplant up to 96 months (25-30%).
Patient Education
Patients must take antibiotics as directed and complete the course as prescribed. This minimizes the risk of recurrence
and the development of resistant organisms.
Patients should be advised to drink plenty of fluids, as avoidance of dehydration is important for both patient well-being
and kidney function. When under stress, men typically drink only enough liquid to replace two thirds of the loss. When
ill, individuals drink less and predispose themselves to dehydration. Unavoidable daily water loss is 1.5 L, of which
approximately 500 mL is replaced by the oxidation of carbohydrates. Because patients cannot measure urine specific
gravity at home, they should drink enough water or other liquid to produce light-colored urine, almost like water.
Presentation
History
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The classic presentation in acute pyelonephritis is the triad of fever, costovertebral angle pain, and nausea and/or
vomiting. These may not all be present, however, or they may not occur together temporally. Symptoms may be
minimal to severe and usually develop over hours or over the course of a day. Infrequently, symptoms develop over
several days and may even be present for a few weeks before the patient seeks medical care. Symptoms of cystitis
may or may not be present to varying degrees. These may include urinary frequency, hesitancy, lower abdominal pain,
and urgency.
Gross hematuria (hemorrhagic cystitis) is present in 30-40% of pyelonephritis cases in females, most often young
women. Gross hematuria is unusual in males and should prompt consideration of a more serious cause.
Pain may be mild, moderate, or severe. Flank pain may be unilateral or sometimes bilateral. Discomfort or pain may be
present in the back (lower or middle) and/or the suprapubic area. Patients may describe suprapubic symptoms as
discomfort, heaviness, pain, or pressure. Upper abdominal pain is unusual, and radiation of pain to the groin is
suggestive of a ureteral stone.
Fever is not always present. When present, it is not unusual for the temperature to exceed 103°F (39.4°C). The patient
may demonstrate rigor, and chills may be present in the absence of demonstrated fever. Malaise and weakness may
also be present.
Gastrointestinal symptoms vary. Anorexia is common. Nausea and vomiting vary in frequency and intensity from
absent to severe. Diarrhea occurs infrequently.
The classic signs and symptoms observed in adults are often absent in children, particularly neonates and infants. In
children 2 years of age and younger, the most common symptoms of urinary tract infection (UTI) are failure to thrive,
feeding difficulty, fever, and vomiting. When fever is present, pyelonephritis should be in the differential diagnosis.
Elderly patients may present with typical manifestations of pyelonephritis, or they may experience fever, mental status
change, decompensation in another organ system, or generalized deterioration.
Complicated pyelonephritis
The presence of any one of the above complicating factors should raise the clinician’s index of suspicion. In many
instances, more than one complicating factor is involved. In addition, if the patient is male, elderly, or a child or has had
symptoms for more than 7 days, the infection should be considered complicated until proven otherwise.
Physical Examination
The patient may or may not have a fever. If fever is present, the temperature may be greater than 103°F (39.4°C). In
contrast, the temperature may be subnormal in patients with associated sepsis. Tachycardia may or may not be
present, depending on associated fever, dehydration, and sepsis.
Blood pressure is usually within the reference range, unless the patient has underlying hypertension, in which case the
pressure may be elevated above the patient's baseline. A systolic blood pressure below 90 mm Hg suggests shock
secondary to sepsis or perinephric abscess.
The patient's appearance is variable. Most commonly, the patient is uncomfortable or appears ill. Patients usually do
not have a toxic appearance, unless there is an underlying problem, such as sepsis, perinephric abscess, or significant
dehydration.
On abdominal examination, suprapubic tenderness usually ranges from mild to moderate without rebound. Abdominal
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tenderness other than in the suprapubic area suggests another diagnosis. Patients usually do not have rigidity or
guarding, and bowel sounds are often normally active.
Flank or costovertebral angle (CVA) tenderness is most commonly unilateral over the involved kidney, although
bilateral discomfort may be present. Discomfort varies from absent to severe. This finding is usually not subtle and
may be elicited with mild or moderately firm palpation.
In women, a pelvic examination should be performed. Tenderness of the cervix, uterus, and adnexa should be absent.
Any positive finding suggests an additional or alternative diagnosis. A gynecologic cause of the symptoms should be
pursued if any of the following are present:
Complications
Complications occur more often in patients with diabetes mellitus, chronic kidney disease, sickle cell disease, kidney
transplant (particularly during the first 3 months), AIDS, and other immunocompromised states. It can sometimes be
difficult to determine whether the entities listed below are occurring as a complication of pyelonephritis or are occurring
in the absence of pyelonephritis but with signs and symptoms suggestive of pyelonephritis. The important point is to
have a high index of suspicion for these complications.
Abscesses
Abscesses may include renal cortical abscess, renal corticomedullary abscess, or perinephric abscess. Older adults
have a higher incidence of renal corticomedullary abscesses, which affect men and women equally.
Corticomedullary abscess
Patients with renal corticomedullary abscesses often present with chills, fever, and flank or abdominal pain, and
patients may have dysuria and/or nausea and vomiting. Leukocytosis may be present. Bacteriuria, pyuria, hematuria,
or proteinuria may be present, as the intrarenal abscesses drain in the collecting system, but the urinalysis results may
be normal in as many as 30% of patients. Bacteremia may be observed in acute focal or multifocal bacterial nephritis.
Corticomedullary abscess is usually associated with a urinary tract abnormality, such as vesicoureteral reflux or
obstruction. It is commonly caused by Enterobacteriaceae.
Acute focal bacterial nephritis (eg, acute lobar nephroma, focal pyelonephritis) that affects a single renal lobe,
with interstitial inflammation represented by marked polymorphonuclear leukocytes
Acute multifocal bacterial nephritis, with a similar process throughout the kidney that produces liquefaction and
abscess formation
Xanthogranulomatous pyelonephritis, with chronic parenchymal infection, granulomatous tissue, and perirenal
fibrosis
Emphysematous pyelonephritis, with severe, necrotizing infection
Perinephric abscess
The suppurative material of the abscess is located between the renal capsule and the surrounding renal fascia. The
material is secondary to chronic or recurrent pyelonephritis; rupture or extension of a suppurative process from within
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the kidney; or dissemination (blood, lymph) or direct extension from other sites of infection. Although it is usually
confined to the perinephric space, it may extend to the colon, flank, groin, lung (empyema, nephrobronchial fistula),
paracervical area, peritoneal cavity, psoas muscle, skin surface, or subphrenic space.
Fever
Chills
Unilateral flank pain (70%)
Dysuria (40%)
Nausea
Vomiting
Weight loss (25%)
Flank tenderness
Costovertebral angle tenderness
Abdominal tenderness (60%)
Referred pain (ie, hip, thigh, or knee)
Flank or abdominal mass (< 50%)
Pyuria (70%)
Sterile urine (40%)
Bacteremia (40%)
Curvature of the spine away from the involved kidney
One third of patients are diagnosed upon admission; another third are diagnosed at autopsy. Perinephric abscess is
not usually readily apparent; a high index of clinical awareness is necessary.
Renal cortical abscess (renal carbuncle) is an uncommon condition that is usually caused by the hematogenous
spread of S aureus. It occurs 3 times more commonly in men than in women. Microabscesses develop in the cortex
and coalesce to form a circumscribed abscess that may or may not communicate with the collecting system. This
process takes days to months.
Patients with renal cortical abscess may present with chills, fever, and flank or abdominal pain. A flank mass or a bulge
in the lumbar region may be evident. Some patients have abnormal results on lung examination of the affected side
(dullness to percussion, rales). Blood and urine culture results usually are negative, but the white blood cell (WBC)
count is often elevated.
Emphysematous pyelonephritis occurs in the left kidney in approximately two thirds of cases. The etiology is usually
Enterobacteriaceae (E coli, 60%), with some reported cases of Streptococcus species and Candida species. A triad of
diabetes, obstruction, and remote or recent pyelonephritis should raise clinical suspicion. Patient presentation includes
fever, chills, abdominal pain, nausea, vomiting, flank pain, flank mass (50%), crepitation (over thigh or flank), urinary
symptoms, and pyuria.
Emphysematous pyelitis (pneumopyonephrosis) involves gas that is localized to the collecting system. Diabetes
mellitus is present in 85-100% of patients. The left kidney is more frequently affected than the right. Presentation is
similar to that of pyelonephritis. On plain radiographs, the gas pattern is noted in the renal pelvis and may be seen in
the ureter. The patient should be admitted and treated with intravenous antibiotics. The mortality rate is 20%.
Emphysematous cystitis (cystitis emphysematosa) involves gas that is localized to the bladder secondary to a bladder
infection. Gas in the bladder is more frequently related to a fistula between the bladder and the colon or vagina than to
a gas-producing infection. As many as 80% of patients are diabetic.
Patient presentation is similar to that for pyelonephritis. Plain radiographs may demonstrate gas in the bladder wall or
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lumen, an air-fluid level in the bladder, or a cobblestone appearance to the bladder wall. CT scan is the study of choice
to help localize the gas to the proper organ. Treatment involves intravenous antibiotics and relief of any outlet
obstruction. This condition is not as serious as the other two previously described emphysematous conditions.
Xanthogranulomatous pyelonephritis
Xanthogranulomatous pyelonephritis is a rare form of pyelonephritis that is almost always associated with chronic
obstruction (eg, from staghorn calculus [75% of cases], other calculus, stricture, or tumor). In adults, the female-to-
male ratio is 3:1; in children, it is 1.1:1. It is a chronic infection that finally manifests acutely with fever and flank pain or
tenderness, and it may be complicated by a flank mass, cutaneous fistula, septic arthritis, or hematochezia if extension
has occurred beyond the renal capsule. Kidney function is absent (71%) or poor (25%) in almost all cases. Diagnosis
is difficult preoperatively.
Tuberculosis
Tuberculosis (TB) of the kidney results from hematogenous spread but is relatively rare in developing countries. Unlike
most other extrapulmonary manifestations of the disease, TB of the kidney does not become manifest until 5-15 years
after the primary infection. Constitutional symptoms are uncommon, and most patients present with symptoms of
bladder irritation.
Initially, pyuria is observed, and with progression of the disease, proteinuria and blood may be observed as well.
Repeated urine samples should be sent for mycobacterial culture. A loss of calyceal architecture and ureteric
obstruction may be observed on imaging studies.
Concurrent pulmonary disease is present in 5% of patients, and the tuberculin test rarely is helpful. Antituberculous
medicines should be administered for 6 months. If the ureter is obstructed, corticosteroids have been advocated; if
obstruction persists, surgical intervention is necessary.
DDx
Differential Diagnoses
Acute Abdomen and Pregnancy
Appendicitis
Cervicitis
Chronic Pyelonephritis
Endometritis
Urethritis
Workup
Workup
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Approach Considerations
In the outpatient setting, pyelonephritis is usually suggested by the history and physical examination and supported by
urinalysis results, which should include microscopic analysis. Other laboratory studies are used to identify complicating
conditions and to assist in determining whether the patient should be admitted.
Easily diagnosed cases typically occur in women, both pregnant and nonpregnant.[13] Insidious onset may occur in
the following:
Men
Patients at the extremes of age
Patients harboring subclinical pyelonephritis
Hospitalized patients
Imaging studies may be required to make the diagnosis in infants and children in whom pyelonephritis presents
insidiously. Imaging studies are rarely indicated for the diagnosis of acute pyelonephritis in an adult who presents with
typical signs and symptoms, but they may be warranted if the presentation is atypical or confusing. Imaging is also
warranted if the patient deteriorates or does not respond to therapy, in which case the important considerations are
nephrolithiasis, obstructive uropathy, and perinephric abscess.
Clean catch
Urethral catheterization
Suprapubic needle aspiration
Clean catch
When properly collected, a clean-catch specimen adequately reflects the microbiology of the urine in the bladder. This
technique can be performed by ambulatory females aged 6 years and older who do not have any limiting physical
handicap.
Importantly, female patients should wash only the area where urine is passed, wash front to back, hold the cup by the
outside, and keep the labia spread while collecting the urine. This is to ensure that the urine goes into the cup without
touching the labia. The presence of a large number of epithelial cells on microscopic examination suggests that the
specimen is not a true clean catch and is unreliable for culture because of contamination with vaginal contents.
Clean-catch technique can also be performed by ambulatory males aged 6 years and older who do not have any
limiting physical handicap. Specimens are usually reliable. Importantly, the patient should clean the head of the penis,
retract the foreskin (if uncircumcised), maintain a good stream, and hold the cup by the outside. In the presence of
epispadias or hypospadias, care must be taken to maintain a good stream while collecting the specimen.
Urethral catheterization
Catheterization poses a small risk of introducing bacteria into the normally sterile bladder environment. Circumstances
that justify this risk when a urine culture is necessary include the following:
For details on performing this procedure, see Urethral Catheterization in Women and Urethral Catheterization in Men.
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An alternative is lacking
To exclude contamination from other methods of collection
To verify the presence of an infecting organism that is otherwise considered a contaminant
To verify infection in an infant who has a positive culture result from a specimen obtained from a strap-on device
Urinalysis
Pyuria is defined as more than 5-10 white blood cells (WBCs) per high-power field (hpf) on a specimen spun at 2000
rpm for 5 minutes. Almost all patients with pyelonephritis have significant pyuria (> 20 WBCs/hpf), although the
numbers may be smaller, particularly in those with subacute pyelonephritis.
The dipstick leukocyte esterase test (LET) helps screen for pyuria. LET results have a sensitivity of 75-96% and a
specificity of 94-98% for detecting more than 10 WBC/hpf.
The nitrite production test (NPT) for bacteriuria has 92-100% sensitivity and 35-85% specificity. It may be falsely
negative in the presence of diuretic use, low dietary nitrate, or organisms that do not produce nitrate reductase (eg,
Enterococcus, Pseudomonas, Staphylococcus). Combined, the LET-NPT has a sensitivity of 79.2% and a specificity of
81%, which is too low for it to be used as the only screening study for bacteriuria.
Gross hematuria occurs infrequently with pyelonephritis and is more common with cystitis (hemorrhagic cystitis). When
gross hematuria is present, the differential should include calculi, cancer, glomerulonephritis, tuberculosis, trauma, and
vasculitis.
Microscopic hematuria may be present in patients with uncomplicated acute pyelonephritis, but other causes should be
considered, particularly calculi. This is especially true if the patient does not respond to therapy. White cell casts are
suggestive of pyelonephritis; however, centrifuge speeds (> 2000 rpm) used for urinalysis sediment preparation often
fracture them and lead to their absence in the sediment.
Proteinuria is expected (up to 2 g/day). When it exceeds 3 g/day, glomerulonephritis should be considered.
The presence of a single bacterium in an unspun urine specimen by oil-immersion microscopic examination is
equivalent to at least 105 colony-forming units (cfu)/mL. Bacteria are identified much more easily on a stained versus
an unstained specimen.
Urinary concentrations of NGAL may also help identify children with acute pyelonephritis who are at increased risk of
developing kidney scarring. In a study of 54 children, urinary NGAL levels were significantly higher in patients with
acute pyelonephritis with scarring than in those without scarring. At a cut-off value of 7.32 ng/ml, the sensitivity and
specificity of this marker for diagnosing scar formation were 81.3% and 66%, respectively.[15]
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Urine culture is indicated in any patient with pyelonephritis, whether treated in an inpatient or an outpatient setting,
because of the possibility of antibiotic resistance. Reliable results require proper specimen collection.
Blood cultures are indicated in any patient who is being admitted or who has already been admitted. Approximately 12-
20% of patients have cultures that are positive for infection. Bacteremia has not been associated with a poor outcome
unless sepsis or another significant comorbidity is present.
AIDS
Poorly controlled diabetes
Organ transplant (particularly kidney)
Other immunocompromised state
Sepsis syndrome
Septic shock
Imaging early in the presentation of acute pyelonephritis may be more useful than previously thought. In one study,
16% of patients admitted for acute pyelonephritis were found to have new and clinically significant abnormalities on
kidney imaging at the time of admission. Later in the hospital course, imaging studies are used for the prompt
evaluation of a potentially organ- or life-threatening complication.
Fever or positive blood culture results that persist for longer than 48 hours
Sudden worsening of the patient’s condition
Toxicity persisting for longer than 72 hours
Complicated urinary tract infection
After acute pyelonephritis has resolved, imaging studies may be used during a follow-up examination to identify urinary
tract abnormalities that can predispose the patient to infection. In addition, studies may be used in conjunction with
urologic procedures, including cystoscopy.
Computed Tomography
Contrast-enhanced helical/spiral computed tomography (CECT) is the imaging study of choice, both in adults and in
children with acute pyelonephritis. CECT is more sensitive than ultrasonography and intravenous pyelography (which
has only 25% sensitivity), and it can more readily identify alterations in kidney parenchymal perfusion, alterations in
contrast excretion, perinephric fluid, and nonrenal disease.
Noncontrast helical/spiral CT findings may be normal in acute pyelonephritis with mild parenchymal involvement, but
the findings are usually positive when the involvement is moderate or severe. It is the standard study for demonstrating
gas-forming infections, hemorrhage, inflammatory masses, and obstruction.
If findings are suggestive of nephrolithiasis complicating the presentation, a noncontrast CT scan of the kidneys,
ureters, and bladder (KUB) or a CT urogram should be obtained to exclude the possibility of obstruction or
hydronephrosis.[16] CT has 97% accuracy in identifying kidney stones. (See the images below.)
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Bilateral hydronephrosis.
Abscesses typically appear on CT scans as low-density masses with contrast enhancement of the wall from
inflamed/dilated blood vessels (see the image below). Acute focal bacterial nephritis has a lobar distribution of
inflammation, wedge-shaped hypodense lesions (postcontrast), and masslike hypodense lesions in severe infections.
Xanthogranulomatous pyelonephritis (see the images below, as well as Xanthogranulomatous Pyelonephritis Imaging)
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A study of diffusion-weighted MRI found that MRI had higher sensitivity than CT (with or without contrast) for the
diagnosis of acute pyelonephritis, and could differentiate areas of nephritis and kidney abscesses. However, MRI was
less useful than CT for the diagnosis of kidney calculi and emphysematous pyelonephritis.[18]
As there is no radiation exposure, MRI can be used in pregnancy.[19] The cost and availability of MRI remain
concerns, however.[19]
Ultrasonography
Ultrasonography (US) can sometimes detect acute pyelonephritis, but a negative study does not exclude the
possibility. Power Doppler US is superior to color Doppler US in the detection of pyelonephritis but remains inferior to
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Kidney US is nevertheless a useful imaging modality in patients with complicated UTIs, and it may be performed at the
bedside in a patient who is hemodynamically unstable. It is relatively inexpensive and does not involve radiation or
iodinated contrast. It is an alternative to CT to identify hydronephrosis if there is concern regarding nephrolithiasis.[16]
US is useful in screening for urinary obstruction in children admitted for febrile illnesses.
In a study of 207 patients with acute pyelonephritis, Enikeev et al reported that the main findings on US were the
following[20] :
On US, a kidney abscess may appear as a fluid-filled mass with a thick wall. Acute focal bacterial nephritis appears as
a poorly defined mass with low-amplitude echoes and disruption of the corticomedullary junction. In
xanthogranulomatous pyelonephritis, imaging reveals stones in approximately 70% of patients.
US findings may be falsely negative in 36% of cases of perinephric abscesses. Other drawbacks to US are the
difficulty in differentiating kidney abscess from tumor and the difficulty in interpreting results in obese patients.
Angiography may help differentiate kidney abscess from kidney tumor because an abscess often has increased
peripheral vascularization, while the remainder of the mass is avascular.
Scintigraphy
Scintigraphy with technetium-99m dimercaptosuccinic acid (99mTc-DMSA) is almost as sensitive clinically as contrast-
enhanced helical/spiral computed tomography (CECT) in detecting focal kidney abnormalities during acute
pyelonephritis in adults. DMSA is a radiotracer that localizes to the kidney cortex. This modality is not used much in
adults, however, because the findings are not specific; focal abnormalities may indicate abscess, cyst, infarct,
pyelonephritis, or tumor. Additionally,99mTc-DMSA scintigraphy is much less available in the acute setting than CECT.
In children, however,99mTc-DMSA scintigraphy is the preferred study, because it involves less radiation exposure than
CT scans. It is excellent for helping detect inflammation, scarring, and the distribution of function between kidneys.
In pediatric studies, diffusion-weighted magnetic resonance imaging (DW-MRI) compares favorably with 99mTc-DMSA
scintigraphy. A study in seven children with acute pyelonephritis diagnosed on scintigraphy within 7 days of fever onset
found that whole-body non-enhanced DW-MRI had 80% sensitivity and 100% specificity for detecting acute
pyelonepritis lesions.[21]
Bosakova et al reported that non-contrast DW-MRI has higher sensitivity than 99mTc-DMSA scintigraphy for
detecting acute inflammatory kidney lesions and multifocal lesions in pediatric patients with acute pyelonephritis. Their
prospective study included 31 children aged 3-18 years with a first episode of febrile urinary tract infection and without
a previously detected congenital urinary tract malformation, who were evaluated within 5 days of diagnosis. DW-
MRI confirmed acute inflammatory changes of the kidney parenchyma, mostly unilateral, in all 31 patients, whereas
scintigraphy detected inflammatory lesions in 22 (100% versus 71%; P = 0.002). [22]
CT and MR Urography
CT urography and MR urography are evolving modalities that surpass intravenous urography, which was the prior
mainstay of urinary tract imaging.[23] CT urography provides a detailed anatomic depiction of the urinary tract. MR
urography has the advantage of not using ionizing radiation and has the potential to provide more functional
information than CT. However, MR urography is less established than CT urography and is less reliable in providing
diagnostic image quality.[23]
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CT urography and MR urography are currently used in the evaluation of hematuria and will become more applicable to
the study of other urologic problems.
Findings of early renal papillary necrosis include a dilated calyceal fornix, retracted or irregular papillary tip, and
extension of contrast into the parenchyma. A club-shaped cavity in the medulla or papilla may be formed in later
disease. When a separated papilla is surrounded by contrast, a ring may be visualized, which is characteristic of
papillary necrosis.
Histologic Findings
Features of acute pyelonephritis include suppurative necrosis or abscess formation within the kidney substance. In
contrast, features of chronic pyelonephritis (chronic interstitial nephritis) include the following:
Treatment
Approach Considerations
Ambulatory younger women who present with signs and symptoms of uncomplicated acute pyelonephritis may be
candidates for outpatient therapy. They must be otherwise healthy and must not be pregnant. In addition, they must be
treated initially in the emergency department (ED) with vigorous oral or intravenous (IV) fluids, antipyretic pain
medication, and a dose of parenteral antibiotics. Studies have shown that outpatient therapy for selected patients is as
safe as inpatient therapy for a comparable group of patients and is much less expensive.
Use analgesics as needed. Early in the course of the illness, parenteral analgesics are often necessary to reduce
morbidity from symptoms. Nonsteroidal anti-inflammatory drugs and narcotics are complementary; do not assume that
one class is better than the other.
Admission is usually appropriate for patients who are severely ill, pregnant, or elderly or who have comorbid disorders
that increase the complexity of management or the complication rate (eg, diabetes mellitus, chronic lung disease,
congenital or acquired immunodeficiency). Admission may also be advisable for patients whose social situation is
unstable, because of the possibility of poor compliance or poor follow-up.
Emergency surgery may be indicated in a patient with fever or positive blood culture results persisting longer than 48
hours; in a patient whose condition deteriorates; or in a patient who appears toxic for longer than 72 hours. These
patients may have an abscess, emphysematous pyelonephritis, or an obstructing calculus. The etiology may not be
immediately evident, but an unexpected change in the clinical picture warrants immediate evaluation for potential
surgical intervention.
After recovery from the acute infection, patients may be candidates for elective surgery to reverse conditions that
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Congenital anomalies
Fistulae involving the urogenital tract
Prostatic hyperplasia
Kidney calculi
Vesicoureteral reflux
Antibiotic Selection
Antibiotic selection is typically empirical, because the results of blood or urine cultures are rarely available by the time
a decision must be made. Initial selection should be guided by local antibiotic resistance patterns. Culture results from
specimens collected before the initiation of therapy should be checked in 48 hours to determine antibiotic efficacy.
The pathogen in community-acquired infections is usually Escherichia coli or other Enterobacteriaceae. Acceptable
regimens may include fluoroquinolones, cephalosporins, penicillins, extended-spectrum penicillins, carbapenems, and
aminoglycosides.[24, 3] If enterococci are suggested on the basis of Gram stain results, ampicillin or vancomycin can
replace the fluoroquinolone. If any doubt exists as to the diagnosis, coverage of both Enterobacteriaceae and
enterococci is acceptable.
There is a higher incidence of enterococcal infections in hospitalized and other institutionalized patients. Ampicillin or
amoxicillin should be included in the regimen. If the patient is allergic to penicillin, vancomycin should be substituted.
In choosing an empirical antibiotic regimen, consideration should include the local antibiogram and drug-resistance
rates. For example, in a community with growing fluoroquinolone resistance, agents in that class may not be an ideal
first-line choice. In light of increasing resistance, short courses of treatment are preferred. In one clinical trial, a 7-day
course of oral ciprofloxacin was shown to be a safe and successful treatment for acute pyelonephritis in women,
including older women and those with more severe infection.[25]
For uncomplicated pyelonephritis, the American College of Physicians (ACP) recommends administering a short
course of fluoroquinolones (5 to 7 days) or trimethoprim-sulfamethoxazole (TMP-SMX; 14 days), based on antibiotic
susceptibility.[26]
Patient characteristics should also be considered. For example, patients who have been frequently exposed to
antibiotics (eg, solid-organ transplant and hematopoietic transplant patients) or are from institutional facilities are at a
greater risk for infection with drug-resistant pathogens, such as extended-spectrum beta-lactamase–producing or
carbapenemase-producing organisms.
For more information, see Pyelonephritis Empiric Therapy and Pyelonephritis Organism-Specific Therapy
Growing data suggest that oral antibiotic therapy, parenteral antibiotic therapy, and initial parenteral antibiotic therapy
followed by oral antibiotic therapy are equally effective regimens, although most of the studies have been small.[27,
28] Some clinicians believe that initiating therapy with an intravenous or intramuscular dose of medication reduces the
risk of therapeutic failure; other clinicians believe that a completely oral course is sufficient. Data exist to support both
assertions.
One conventional regimen comprises levofloxacin, 500 mg/day, given intravenously and then orally for 7-14 days. A
short-course regimen of intravenous levofloxacin at 750 mg/day for 5 days proved non-inferior to that conventional
regimen in a prospective, open-label, randomized, controlled clinical trial in 317 Chinese patients with complicated
urinary tract infections and acute pyelonephritis.[29]
To be considered for oral therapy, patients must meet several prerequisites. They must, of course, be able to tolerate
oral medication. In addition, they must have no indication for admission, and close monitoring to ensure good
compliance must be possible.
One prospective study supports using oral therapy alone in patients who can tolerate oral intake, lack signs of sepsis,
and do not show signs of obstruction or kidney suppuration on urinary tract ultrasonography. Another study
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(prospective, randomized, unblinded) in a controlled hospital setting found no difference in efficacy between oral and
intravenous ciprofloxacin for the initial management of severe pyelonephritis.
The 2010 guidelines from the Infectious Disease Society of America (IDSA) recommend that women with
pyelonephritis who require hospitalization be treated initially with an intravenous antimicrobial regimen. The choice of
antimicrobial agents should be based on local resistance data, with the regimen tailored on the basis of susceptibility
results.[3]
Although the guidelines recommend either 14 days of TMP-SMX or 7 days of ciprofloxacin for the treatment of
pyelonephritis, a study in 272 women with susceptible E coli pyelonephritis reported similar clinical outcomes with 7
days of TMP-SMX therapy compared with 7 days of ciprofloxacin.[30]
Because of the high rate of resistance of E coli, the empirical use of TMP-SMX should be avoided in patients who
require hospitalization. If beta-lactam drugs and fluoroquinolones are contraindicated, administer aztreonam
parenterally. As such, the patient will need to be admitted.
With complicated acute pyelonephritis, treat patients parenterally until defervescence and improvement in the clinical
condition warrants changing to oral antibiotics. Complete the course of therapy with an oral agent selected on the
basis of culture results.[28] Acceptable regimens include the following:
If the patient is allergic to penicillin, vancomycin should be substituted. Vancomycin or linezolid are options if
enterococci are a consideration.
Meropenem-vaborbactam (Vabomere) is a combination of the carbapenem antibiotic meropenem with the beta-
lactamase inhibitor vaborbactam. Specifically, vaborbactam inhibits bacterial production of the Klebsiella pneumoniae
carbapenemase (KPC) enzyme, which confers resistance to carbapenems. The US Food and Drug Administration
(FDA) has approved meropenem-vaborbactam for adults aged 18 years and older with pyelonephritis and other
complicated urinary tract infections (UTIs) caused by designated susceptible Enterobacteriaceae: Escherichia coli, K
pneumoniae, and Enterobacter cloacae species complex.[33]
The safety and efficacy of meropenem-vaborbactam were demonstrated in a study of more than 500 adults with
complicated UTI, including pyelonephritis, in which cure or improvement in symptoms and a negative urine culture
were seen in about 98% of patients treated with meropenem-vaborbactam, versus about 94% of patients treated with
piperacillin–tazobactam. Approximately 7 days after completing treatment, about 77% of patients treated with
meropenem-vaborbactam demonstrated resolution of symptoms and a negative urine culture, compared with about
73% of patients treated with piperacillin–tazobactam.[33]
Outpatient Treatment
Antibiotic therapy
Patients presenting with acute pyelonephritis can be treated with a single dose of a parenteral antibiotic followed by
oral therapy, provided they are monitored within the first 48 hours. In a study of febrile, nonpregnant women presenting
with symptoms of acute pyelonephritis, 25% were hospitalized; of nonhospitalized patients, 80% were treated with a
single parenteral dose of ceftriaxone or gentamicin, followed by oral therapy (usually TMP-SMX). Twelve percent
returned with persistent symptoms, most in the first day; most of those patients were admitted.[5]
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Acute pyelonephritis has customarily been treated with 14 days of antibiotics, and the IDSA guidelines maintain this
recommendation for TMP-SMX and beta-lactam agents. However, evidence suggests that in young, healthy women
who are receiving a fluoroquinolone, including ciprofloxacin, the course of treatment can be shortened to 7 days.
Levofloxacin, 750 mg/day, can be given for 5 days.[34, 35] Young, healthy males should complete a 14-day course.[3]
Outpatient treatment is appropriate for patients who have an uncomplicated infection that does not warrant
hospitalization. Oral antibiotics are used to treat patients with mild to moderate illness. (See Table 2, below, for a
description of outpatient treatments for pyelonephritis.)
First-line therapy
Second-line therapy
Trimethoprim/sulfamethoxazole* 160 mg/800 mg (Bactrim DS, Septra DS) 1 tablet PO BID for 14d
If trimethoprim/sulfamethoxazole is used when the susceptibility is not known, an initial single IV dose of
the following may also be given: ceftriaxone 1 g IV or a consolidated 24-h dose of an aminoglycoside
(gentamicin 7 mg/kg IV or tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)
Alternative therapy
Oral beta-lactams are not as effective for treating pyelonephritis; however, if they are used, administer with
a single dose of ceftriaxone 1 g IV or a consolidated 24-h dose of an aminoglycoside (gentamicin 7 mg/kg
IV or tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)
*Should generally be avoided in elderly patients because of the risk of affecting kidney function.
For female patients suspected of having acute pyelonephritis, the IDSA guidelines recommend sending urine for
culture and susceptibility testing and then starting empirical antibiotic therapy.[3]
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The fluoroquinolones are well tolerated and quite effective. They are probably the outpatient antibiotic treatment of
choice for pyelonephritis. They (along with TMP-SMX) do not eradicate the protective lactobacilli from the vagina. An
important caveat for the use of fluoroquinolones in the elderly is their potential to cause aortic aneurysm or dissection;
hypoglycemia; and a variety of neuropsychiatric symptoms, ranging from seizures to worsening of dementia.[36]
In communities where the prevalence of resistance in uropathogens to fluoroquinolones is not known to be greater
than 10%, the IDSA guidelines advise that patients who do not require hospitalization be treated with oral ciprofloxacin,
500 mg twice daily for 7 days, with or without an initial 400-mg dose of intravenous ciprofloxacin. If the uropathogen’s
fluoroquinolone resistance is greater than 10%, an initial intravenous dose of a long-acting parenteral antimicrobial (eg,
ceftriaxone, 1 g) is recommended.[3]
On an individual basis, for persons with community-onset UTI and fever, a case-control study found that the risk of
fluoroquinolone-resistant E coli infection increased if the patient had undergone recent hospitalization or urinary
catheterization or if the patient had used a fluoroquinolone within the past 6 months.[27]
Intravenous fluids
If oral intake is not tolerated, intravenous hydration is warranted. Intravenous fluids should include 1 L of 5% dextrose
in saline to reverse any existing ketosis, regardless of whether ketones are detected in the urine. Additional
intravenous hydration is accomplished with normal saline. Exercise caution regarding conditions that might be
adversely affected by improper amounts of fluid, saline, or glucose.
Follow-up
If the patient is not admitted at the time of diagnosis, follow-up reevaluation is important in 1-2 days to be sure the
patient is progressing properly. A good rule based on common sense is that if the managing clinician is concerned that
the patient may not respond well to outpatient management but still thinks the patient deserves a trial at home, the
initial follow-up visit should take place in 24 hours. If the clinician thinks that the patient will do quite well with outpatient
management, the initial follow-up visit can take place in 48 hours.
If the patient thinks that he or she is not progressing well or is getting worse, the patient should be evaluated
emergently for consideration for admission and intravenous antibiotics.
Continue supportive care by prescribing antiemetics, antipyretics, analgesics, and urinary tract analgesics as needed.
Have the patient complete a 14-day course of oral antibiotics. Evidence suggests that when treating a young, healthy
female, the course of treatment can be shortened to 7 days from 14 days, if the antibiotic being used is a
fluoroquinolone. Healthy young males should complete a 14-day course.
Obtain follow-up urine culture results in any patient with a complicated UTI, a complicated course, or increased risk of
infection. Urine cultures are generally not indicated in healthy, nonpregnant women with resolved symptoms.[13] All
patients with a complicated UTI should be considered for outpatient follow-up imaging of the urinary tract to identify
abnormalities that predispose to further infections.
Rest is essential for recovery. Activity should be minimal. The patient should not return to work for 2 weeks, so as to
allow time for the infection to be eliminated and for the patient to recover physical strength. Temper this
recommendation depending on the physical condition of the patient and the presence of comorbid conditions.
Inpatient Treatment
The decision regarding admission of a patient with acute pyelonephritis depends on age; host factors, such as
immunocompromising chemotherapy or chronic diseases, known urinary tract structural abnormalities, renal calculi,
recent hospitalization, or urinary tract instrumentation; and the patient's response to ED therapy.
Admit all patients with complicated UTI. Complicating factors include the following:
Structural urinary tract abnormalities (eg, calculi, tract anomalies, indwelling catheter, obstruction)
Metabolic disease (eg, diabetes, kidney insufficiency)
Impaired host defenses (eg, HIV, current chemotherapy, underlying active cancer)
Pregnancy
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Admission is also indicated for patients with apparent clinically uncomplicated pyelonephritis who have any of the
following:
In patients with acute pyelonephritis who require hospitalization, treatment begins with IV antibiotics. IV therapy should
be given for 24-48 hours or until severe symptoms improve. A systematic review of 8 randomized, controlled trials in
hospitalized patients with acute pyelonephritis found that early switching to oral antibiotic treatment appears to be as
effective and safe as exclusively IV regimens.[37]
Selection of a regimen should be based on local resistance data, and the regimen should be tailored on the basis of
susceptibility results. Recommended regimens are listed in Table 3, below. However, a multinational study in 184
patients found that cefazolin is non-inferior to ceftriaxone for the empirical treatment of acute pyelonephritis in
hospitalized patients. At 72 hours, defervescence or normalization of white blood cell count had occurred in 87.0% of
the cefazolin group versus 85.9% of the ceftriaxone group; in addition, no difference was observed between the two
groups for length of stay or 30-day readmission for cystitis or pyelonephritis.[38]
Table 3. Inpatient Treatment for Acute Pyelonephritis (Open Table in a new window)
First-line therapy
Second-line therapy
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All of the above can be administered with or without an aminoglycoside (except in pregnant patients); see
Aminoglycosides, below
Carbapenems:
Alternative therapy
Aminoglycosides (because of their potential nephrotoxicity, aminoglycoside antibiotics should be reserved for
patients with serious and potentially life-threatening infections, and their dosage and blood levels should be
carefully monitored to minimize the risk of nephrotoxicity):
However, an Israeli medical center that instituted a program of initial empirical treatment of pyelonephritis with
aminoglycosides reported higher rates of in vitro activity and lower overall mortality than with non-aminoglycoside
antibiotic therapy, without excess nephrotoxicity. In the study, which included 2026 patients, 715 treated with
aminoglycosides and 1311 treated with non-aminoglycoside drugs, aminoglycosides were more likely to have in vitro
activity against clinical isolates (odds ratio 2.0; P < 0.001); death at 30 days occurred in 55 (7.6%) versus 145 (11%)
patients treated with aminoglycosides and non-aminoglycoside drugs, respectively (adjusted hazard ratio 0.78; P =
0.013). The incidence of acute kidney injury was 2.5% versus 2.9%, respectively; P = 0.6).[39]
Duration of therapy
Duration of therapy should be at least 10-14 days, inclusive of initial IV therapy. Patient circumstances may warrant
more prolonged therapy.
The PROGRESS (Procalcitonin-guided Antimicrobial Therapy to Reduce Long-Term Sequelae of Infections) study
found that in septic patients, procalcitonin levels can be used to guide discontinuation of antibiotics. This multicenter
randomized trial in 266 patients, 95 of whom had acute pyelonephritis, used an ≥80% reduction in procalcitonin level or
any procalcitonin level of ≤0.5 µg/L at Day 5 or later as a criterion for discontinuing antibiotics.[40]
In PROGRESS, procalcitonin-guided discontinuation, compared with standard of care, resulted in a shorter median
length of antibiotic therapy (5 versus 10 days), a lower rate of infection-associated adverse events such as infections
by multidrug-resistant organisms and Clostridioides difficile (7.2% versus 15.3%), and lower 28-day mortality (15.2%
versus 28.2%). The cost of hospitalization was also reduced in the procalcitonin arm.[40]
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Abscesses
For renal cortical abscesses (renal carbuncles), surgical drainage was once the only treatment. However, modern
antibiotics alone often are curative. A semisynthetic penicillin, cephalosporin, fluoroquinolone, or vancomycin is
recommended. Generally, parenteral antibiotics should be administered for 10-14 days, followed by oral therapy for 2-4
weeks. Fever should resolve within 5-6 days, and pain should resolve within 24 hours. If parenteral antibiotic therapy is
successful, oral therapy is instituted for an additional 2-4 weeks.
If patients do not respond within 48 hours, percutaneous (or open) drainage should be performed. Other surgical
options are enucleation of the carbuncle or nephrectomy.
Treatment of renal corticomedullary abscess includes parenteral antibiotics for 48 hours (usually successful), incision
and drainage, and nephrectomy. If antibiotic therapy is successful, oral therapy is instituted for an additional 2 weeks.
Mortality associated with perinephric abscesses is 20-50%, but this rate can be decreased with early recognition,
surgical drainage, and antimicrobial therapy (not adequate alone). Antibiotics should include an aminoglycoside and an
antistaphylococcal agent. If Pseudomonas species are considered or demonstrated, an antipseudomonal beta-lactam
antibiotic should be added. For enterococci, an aminoglycoside and ampicillin are recommended. Other organisms that
have been reported include tuberculosis and fungi. Nephrectomy may be necessary.
Calculi-Related Infections
A major challenge with calculi-related UTI is that the organisms can survive within the calculus. In the presence of
acute infection, calculi must be removed immediately using cystoscopy or open surgical procedure. In a review of adult
patients with obstructive pyelonephritis due to a ureteral stone or kidney stone with hydronephrosis (n=311,100),
delayed decompression (2 or more days after admission) increased the odds of in-hospital death by 29% (odds ratio
1.29, 95% confidence interval 1.03-1.63, P=0.032).[41]
The preferred method of treatment is surgical. Options include extracorporeal shockwave lithotripsy (ESWL),
endoscopic methods, percutaneous methods, and open surgery. For staghorn calculus, the treatment of choice is to
remove the whole stone. Fragments left behind remain infected and will grow again. Antibiotic therapy should be used
in conjunction.
Although food and vitamin supplements that are rich in phosphorus and magnesium are advisable, remember that
magnesium (and other divalent cations) can chelate fluoroquinolones, preventing their absorption from the gut.
Acidifying agents have been used. Ascorbic acid does not significantly decrease urinary pH, and ammonium chloride
provides only temporary acidification. This approach is of little clinical usefulness. Urease inhibitors are effective in
reducing stone formation, but long-term use is fraught with neurosensory, hematologic, and dermatologic adverse
effects.
Parenteral agents that may be used empirically pending the result of a urine culture include the following:
Gentamicin
Cefotaxime
Ceftriaxone
Ceftazidime
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Cefepime
Piperacillin-tazobactam
Imipenem-cilastatin
Meropenem
Ciprofloxacin
Parenteral therapy should be continued until the fever and other symptoms resolve. Duration of therapy generally is 14
days. If the response is not good, CT-guided drainage or surgical drainage with debridement is indicated.
The treatment of choice for xanthogranulomatous pyelonephritis is nephrectomy after the patient is stabilized. See
Xanthogranulomatous Pyelonephritis for more information.
Pregnant Patients
Physiologic changes in the urinary tract predispose pregnant women to an increased risk of cystitis and pyelonephritis,
which may lead to preterm labor and kidney damage. Hydroureter of pregnancy develops around the seventh week
and progresses throughout the remainder of pregnancy; it resolves by 8 weeks post partum. The ureters may dilate
sufficiently to contain 200 mL or more of urine. In addition, the kidneys enlarge and bladder capacity may double. The
left kidney is more affected than the right.
The prevalence of bacteriuria in pregnancy is 2-25%, depending on the study criteria. Symptomatic UTI occurs in 1-3%
of all pregnancies and leads to premature labor in 20-50% of cases.
The recommendation is that all pregnant women have a screening urine culture at 16 weeks' gestation. If the results
are negative for a UTI, no additional cultures are indicated. If the patient has a history of recurrent UTIs, further
cultures and other screening techniques (eg, nitrite dipstick or urine Gram stain) may be needed to detect the
development of asymptomatic bacteriuria.
Successful treatment of bacteriuria prevents pyelonephritis. Fluoroquinolones and aminoglycosides should be avoided
in pregnancy. Accepted regimens for treating asymptomatic bacteriuria include the following:
Inpatient admission is warranted for any pregnant patient with pyelonephritis. The treatment of choice during
pregnancy includes the use of beta-lactam antibiotics. Intravenous antibiotics should be administered until the patient
is afebrile for 24 hours and symptomatically improved. It is recommended to avoid fluoroquinolones in pregnant
patients. Aminoglycosides should also be avoided due to potential risk of ototoxicity following prolonged fetal
exposure. See Table 4, below, for regimens for pyelonephritis in pregnant patients.
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Severe pyelonephritis
Once patients are afebrile for at least 48 hours, they can be switched to oral antibiotics, with the regimen choice
guided by results from susceptibility studies, and discharged to complete 10-14 days of treatment. Obtain an additional
urine culture 1-2 weeks after the completion of therapy to verify eradication of the infection. Obtain monthly urine
cultures until delivery to monitor the urine for recurrent infection.
Postcoital therapy with cephalexin or nitrofurantoin is recommended for prophylaxis against recurrent infection. If the
initial infection requires a second agent for clearing the infection or a recurrent infection occurs, suppressive therapy
until delivery is indicated with nitrofurantoin (50 mg or 100 mg at bedtime). Recurrent infection or persistent bacteriuria
is an indication for urological evaluation 3-6 months after delivery.
Caution should be used when prescribing nitrofurantoin for prophylaxis, as adverse effects of this medication
include peripheral neuropathy, pulmonary toxicity, and hepatotoxicity. Nitrofurantoin-induced liver injury and death have
been reported. Hepatotoxicity is reversible if recognized early and nitrofurantoin is stopped, so hepatic enzymes
should be monitored in women at higher doses or with prolonged use.[42]
Pediatric Patients
In pediatric patients with acute pyelonephritis, indications for immediate urologic referral include the following:
Aside from the effects of acute infection, the overriding concern is progressive deterioration in function of an already
compromised kidney (hypoplastic or dysplastic) secondary to scarring from recurrent pyelonephritis with or without
associated obstruction. Infants and preschool-aged children are at greatest risk. Initial management varies with patient
age and presentation.
Close follow-up examination, regardless of whether the patient is initially admitted, is essential to ensure recovery.
Immediate reevaluation is encouraged for any recurrence of symptoms. Neither treatment of asymptomatic bacteriuria
nor long-term suppressive therapy has been found to be effective.
Urologic evaluation is necessary to establish the presence of any urologic abnormality. The preferred imaging study for
the diagnosis of acute pyelonephritis is technetium-99m dimercaptosuccinic acid (99m Tc-DMSA) scintigraphy.
Ultrasonography is the imaging study of choice for the diagnosis of urinary tract structural abnormalities. (See
Workup/Scintigraphy).
Age-related data adapted from Harwood-Nuss and colleagues and Hansson and colleagues are presented below in
Table 5.[43, 44]
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Infants 6
Neonates weeks to 3 Children 3-6 years of age Children 6-11 years of age
years of age
UTI
frequency 1 1.5-3 1.5-3 1.2
(%)
Female-to-
1:1.5 10:1 10:1 30:1
male ratio
Route of
Blood Ascending Ascending Ascending
infection
Failure to Diarrhea,
thrive, fever, failure to Abdominal pain, dysuria,
hypothermia, thrive, fever, enuresis, fever, gross Dysuria, enuresis, fever,
Signs and irritability, irritability, poor hematuria, meningismus, flank pain or tenderness,
symptoms jaundice, poor feeding, strong-smelling urine, urinary urgency, urinary
feeding, strong- urinary urgency, urinary frequency
sepsis, smelling urine, frequency, vomiting
vomiting vomiting
Admit for Admit for Follow adult guidelines, Follow adult guidelines,
intravenous intravenous but avoid fluoroquinolones, but avoid fluoroquinolones,
ampicillin and ampicillin and which are theoretically which are theoretically
Management
gentamicin gentamicin contraindicated due to contraindicated due to
and further and further potential effects on the potential effects on the
evaluation evaluation musculoskeletal system musculoskeletal system
A regular diet is permitted as tolerated. Special diets, such as those for patients with diabetes mellitus, should be
honored. Maintaining hydration is very important. If admission is not indicated and the patient will be monitored in an
outpatient setting, hydration status should be normalized with intravenous fluids; the physician should not assume that
the patient can or will accomplish this with oral hydration alone.
Rest is essential for recovery. Activity should be minimized. Patients who are treated in an outpatient setting should not
return to work for 2 weeks in order to allow time for the infection to be eliminated. This time also allows the patient to
recover physical strength. This recommendation can be tempered in special circumstances as warranted by the
clinician.
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If these strategies do not eliminate infection, recurrence of infection, or relapse (reinfection less than 14 days after
completing an appropriate regimen), the patient needs to undergo systematic evaluation for predispositional anatomic,
functional, or structural abnormalities.
For more information, see the Medscape topic Prevention of Urinary Tract Infection (UTI).
Consultations
Consultation is indicated if the infection is complicated. Most cases of acute pyelonephritis occur in adult women and
are readily managed without consultation. The following are reasons for consulting various subspecialists:
A urologist may be consulted regarding patients with ureteral or urethral obstruction, urinary stones, urogenital
abnormality, or recurrent pyelonephritis, or for the first episode of pyelonephritis in an infant or child.
A nephrologist may be consulted regarding patients with acute kidney injury or advanced chronic kidney failure
or for neonates or infants.
An infectious disease specialist may be consulted regarding patients with an unusual or resistant pathogen,
those who are immunocompromised, patients with persisting fever (>48 hours) or toxicity (> 72 hours), or
patients whose blood culture results are positive for more than 48 hours.
An obstetrician may be consulted for patients who are pregnant.
Guidelines
Guidelines Summary
The United Kingdom's National Institute for Health and Care Excellence (NICE) has issued guidelines on acute
pyelonephritis in children, young people, and adults who do not have a urinary catheter in place. The
recommendations cover management, self care, and choice of first-line antibiotic; for second-line therapy, NICE
advises consulting with a local microbiologist.[45]
For non-pregnant women and males aged 16 years and over, first-choice oral antibiotics are as follows:
Cephalexin
Amoxicillin/clavulanate (if culture confirms susceptibility)
Trimethoprim (if culture confirms susceptibility)
Ciprofloxacin (but consider safety issues; discontinue at the first signs of a serious adverse reaction, including
tendon pain or inflammation)
First-choice intravenous (IV) antibiotics (eg, for patients who are vomiting, unable to take oral antibiotics, or severely
unwell) are as follows (antibiotics may be combined if susceptibility or sepsis is a concern):
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First-choice antibiotics for pregnant women aged 12 years and over are as follows:
Oral: Cephalexin
IV: Cefuroxime
For children < 3 months, the NICE guidelines recommend referral to a pediatric specialist for treatment with IV
antibiotics. For children > 3 months and adolescents under 16 years of age, first-choice oral antibiotics are as follows:
Cephalexin
Amoxicillin/clavulanate (if culture confirms susceptibility)
First-choice IV antibiotics for children > 3 months and adolescents under 16 years of age are as follows:
Medication
Medication Summary
Antibiotic therapy is essential in the treatment of acute pyelonephritis and prevents progression of the infection. Urine
culture and sensitivity testing should always be performed, and when results become available, empirical therapy
should be tailored to the infecting uropathogen.[3]
Patients presenting with complicated pyelonephritis should be managed as inpatients and treated empirically with
broad-spectrum parenteral antibiotics. Depending on patient presentation, antibiotic therapy can be completed with
oral therapy. Antibiotics are administered for at least 10-14 days. On the basis of patient presentation, longer duration
of therapy may be needed.
Sulfonamides
Class Summary
Sulfonamides such as trimethoprim-sulfamethoxazole(TMP-SMX) have bacteriocidal activity and are used in the
treatment of pyelonephritis.
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Fluoroquinolones
Class Summary
Fluoroquinolones are acceptable agents for the treatment of pyelonephritis because they are highly effective against
gram-negative and gram-positive bacteria. A major concern with fluoroquinolones is the development of resistance
among uropathogens and other organisms. Oral fluoroquinolones are a treatment option for patients not requiring
hospitalization where the prevalence of resistance of community uropathogens does not exceed 10%.[3] According to
the IDSA 2010 guidelines, if the prevalence of fluoroquinolone resistance exceeds 10%, an initial 1-time intravenous
dose of a long-acting parenteral antimicrobial or a consolidated 24-hour dose of an aminoglycoside, is recommended.
[3] Fluoroquinolones should be avoided during pregnancy.
Levofloxacin (Levaquin)
Levofloxacin is also recommended as an oral antibiotic for patients with pyelonephritis not requiring hospitalization.
Recommended dose includes the administration of levofloxacin 750 mg for 5 days.
Class Summary
Oral beta-lactams are not as effective for treating pyelonephritis. Based on the IDSA 2010 guidelines, however, if they
are used, they should be administered with a single dose of ceftriaxone (Rocephin) 1 g IV ora consolidated 24-hour
dose of an aminoglycoside.[3]
Cefaclor
Cefaclor is indicated for the treatment of pyelonephritis, caused by Escherichia coli, Proteus mirabilis, Klebsiella
species, and coagulase-negative staphylococci. Cefaclor, 500 mg 3 times a day for 7 days, is recommended for
outpatient treatment of pyelonephritis.
Class Summary
Third-generation cephalosporins are broad-spectrum and have bactericidal activity. These drugs are the most active
against serious gram-negative pathogens and have some activity against gram-positive pathogens.
Ceftriaxone
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Ceftriaxone is a parenteral regimen that can be administered once daily in patients with pyelonephritis requiring
hospitalization. For patients with mild to moderate pyelonephritis, a dosage of 1 g every 24 hours is recommended.
Cefotaxime (Claforan)
Cefotaxime has bactericidal activity. It is indicated for the treatment of genitourinary infections caused by Escherichia
coli, Enterococcus species, and Klebsiella species, among others. For moderate to severe infections, the usual dose is
1-2 g IV or IM every 8 hours.
Cephalosporins, Other
Class Summary
Cefepime is a fourth-generation drug, which possesses the gram-negative activity of the third-generation agents and
the gram-positive activity of the first-generation drugs.
Cefepime (Maxipime)
Cefepime is a fourth-generation cephalosporin. It is indicated for the treatment of uncomplicated and complicated
cystitis, including (1) pyelonephritis caused by E coli or Klebsiella pneumoniae when the infection is severe or (2)
pyelonephritis caused by E coli, Klebsiella pneumoniae, or Proteus mirabilis when the infection is mild to moderate,
including cases associated with concurrent bacteremia with these microorganisms.
Penicillins, Amino
Class Summary
Aminopenicillins have a broad spectrum of are bactericidal activity against gram-positive and gram-negative
organisms.
Ampicillin
Penicillins such as ampicillin can be administered in combination with aminoglycosides for patients with pyelonephritis
who require hospitalization. Ampicillin has bactericidal activity against susceptible organisms.
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Penicillins, Extended-Spectrum
Class Summary
Extended-spectrum penicillins have a broad spectrum of bactericidal activity. They are used mainly in the treatment of
patients with pyelonephritis requiring hospitalization.[3] The extended-spectrum penicillins are also an option for
pregnant patients with pyelonephritis.
Piperacillin-tazobactam (Zosyn)
Piperacillin-tazobactam is useful as empirical therapy before the identification of causative organisms, because of its
broad spectrum of bactericidal activity against gram-positive and gram-negative organisms. The dosing
recommendation for severe pyelonephritis is 3.375 g IV every 6 hours.
Ampicillin-sulbactam (Unasyn)
Ampicillin has a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and
anaerobic bacteria. The presence of sulbactam in the ampicillin-sulbactam formulation effectively extends the
spectrum of ampicillin to include many bacteria normally resistant to it and to other beta-lactam antibiotics. Ampicillin-
sulbactam, 1.5 g IV every 6 hours, can be used for the treatment of pyelonephritis.
Carbapenems
Class Summary
Carbapenem antibiotics are broad-spectrum antibiotics that are structurally related to beta-lactam antibiotics.
Carbapenems can be used in the treatment of patients with pyelonephritis requiring hospitalization.[3] The extended-
spectrum penicillins are also an option for pregnant patients with pyelonephritis.
Doripenem (Doribax)
Doripenem is approved for the treatment of complicated cystitis, including pyelonephritis that is caused by E coli,
Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Acinetobacter baumannii. The usual dosage
is 500 mg IV every 8 hours. The duration of therapy can range from 10-14 days. Duration includes a possible switch to
an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been
demonstrated. Duration can be extended up to 14 days in patients with concurrent bacteremia.
Ertapenem (Invanz)
Ertapenem is approved for the treatment of complicated cystitis, including pyelonephritis caused by Escherichia coli
including cases with concurrent bacteremia or Klebsiella pneumoniae. Usual dosage is 1 g IV every 24 hours for 10-14
days. Duration includes a possible switch to an appropriate oral therapy after at least 3 days of parenteral therapy,
once clinical improvement has been demonstrated.
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Meropenem (Merrem)
Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that is effective against most gram-positive and
gram-negative bacteria. It can be administered at a dose of 500 mg IV every 8 hours.
Imipenem-cilastatin (Primaxin)
Imipenem/cilastatin has bactericidal activity against a wide range of gram-negative and gram-positive organisms. It is
an alternative treatment for pyelonephritis because infections resistant to other antibiotics (eg, cephalosporins,
penicillin, aminoglycosides) have been shown to respond to treatment with imipenem-cilastatin. The general dosing
recommendation is 500 mg IV every 6 hours.
Meropenem/vaborbactam (Vabomere)
Indicated for complicated urinary tract infections (cUTI) caused by carbapenem-resistant Enterobacteriaceae (CRE).
Vaborbactam is a non-suicidal beta-lactamase inhibitor that protects meropenem from degradation by certain serine
beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC). Vaborbactam does not have any antibacterial
activity and does not decrease the activity of meropenem against meropenem-susceptible organisms.
Aminoglycosides
Class Summary
Aminoglycosides are bactericidal antibiotics used primarily in the treatment of gram-negative infections. They are
commonly used in combination with drugs such as ampicillin. For example, gentamicin, an aminoglycoside antibiotic
that has gram-negative coverage, is used in combination with both an agent against gram-positive organisms and one
that covers anaerobes. Because of their potential nephrotoxicity, aminoglycosides should be reserved as a last resort,
for use in resistant or life-threatening infections. In addition, aminoglycosides should be avoided during pregnancy.
Gentamicin
Gentamicin is not the drug of choice for acute pyelonephritis. Consider using it when penicillins or other less toxic
drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and
gram-negative organisms. Dosing regimens are numerous; adjust the dose based on the creatinine clearance and
changes in volume of distribution. Gentamicin may be given intravenously or intramuscularly.
Tobramycin
Tobramycin has bactericidal activity against, and is used to treat infections caused by, E coli, Proteus species,
Klebsiella species, Serratia species, Enterobacter species, and Citrobacter species. Tobramycin can be administered
intravenously or intramuscularly. Dosage is based on weight and kidney function.
Amikacin
Amikacin has bactericidal activity against gram-negative organisms. Clinical studies have shown that amikacin is
clinically effective for serious complicated and recurrent cystitis. Amikacin can be administered intravenously or
intramuscularly. Dosage is based on weight and kidney function.
Plazomicin (Zemdri)
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Indicated for complicated urinary tract infections, including pyelonephritis caused by the following susceptible
microorganism(s): Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae. Plazomicin is
administered intravenously. Dose is based on weight and kidney function.
Glycopeptides
Class Summary
Glycopeptide antibiotics such as vancomycin have bactericidal activity and can be used as alternative therapy for
patients with pyelonephritis.
Vancomycin (Vancocin)
Vancomycin is a potent antibiotic directed against gram-positive organisms and is active against Enterococcus
species. Vancomycin is indicated for patients who cannot receive or did not respond to penicillins and cephalosporins
or patients who have infections with resistant staphylococci.
Monobactams
Class Summary
Unlike the penicillins and cephalosporins, aztreonam is a monobactam. Monobactams such as aztreonam are
bactericidal; however, they lack activity against gram-positive activity.
Aztreonam (Azactam)
Aztreonam is approved for the treatment of complicated and uncomplicated cystitis. It is approved for the treatment of
pyelonephritis caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa,
Enterobacter cloacae, Klebsiella oxytoca, Citrobacter species, and Serratia marcescens. Aztreonam lacks cross-
sensitivity with beta-lactam antibiotics and may be used in patients allergic to penicillins or cephalosporins. General
dosing recommendations include administering 1 g IV every 8-12 hours.
Urinary Analgesics
Class Summary
Use of a urinary analgesic is indicated when a patient has dysuria to such an extent that it disrupts activities of daily
living. These agents relieve pain, discomfort, and spasms of the bladder.
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use is compatible with antibacterial therapy and can help relieve pain and discomfort before antibacterial therapy
controls infection.
It is used for symptomatic relief of pain, burning, urgency, frequency, and other discomfort arising from irritation of
lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or passage of sounds or
catheters. Its analgesic action may reduce or eliminate the need for systemic analgesics or narcotics.
What are the signs and symptoms of acute pyelonephritis (kidney infection)?
What is the occurrence of gross hematuria (hemorrhagic cystitis) in acute pyelonephritis (kidney infection)?
What are the signs and symptoms of acute pyelonephritis (kidney infection) in children?
What are the signs and symptoms of acute pyelonephritis (kidney infection) in elderly patients?
What is the role of urinalysis in the diagnosis of acute pyelonephritis (kidney infection)?
When is urine culture indicated in patients with acute pyelonephritis (kidney infection)?
What is the role of imaging studies in the assessment of acute pyelonephritis (kidney infection)?
When is outpatient care indicated for the treatment of acute pyelonephritis (kidney infection)?
What is included in the inpatient care for acute pyelonephritis (kidney infection)?
Which factors make diagnosis and management of acute pyelonephritis (kidney infection) challenging?
What are the signs and symptoms of acute pyelonephritis (kidney infection)?
What is the presentation of acute pyelonephritis (kidney infection) in elderly patients and infants?
Which signs and symptoms are both sensitive and specific for the diagnosis of acute pyelonephritis (kidney infection)?
What are the effective antibiotic options and therapy duration for acute pyelonephritis (kidney infection)?
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What is the role of uropathogenic E coli (UPEC) in the pathogenesis of acute pyelonephritis (kidney infection)?
What is the role of mannose-resistant adhesins in the pathogenesis of acute pyelonephritis (kidney infection)?
What is the role of P fimbriae adhesins in the pathogenesis of acute pyelonephritis (kidney infection)?
What is the role of siderophores and protectins in the pathogenesis of acute pyelonephritis (kidney infection)?
Which toxins have a role in the pathogenesis of acute pyelonephritis (kidney infection)?
Which virulence factors promote the pathogenesis of acute pyelonephritis (kidney infection)?
What is the role of asymptomatic bacteriuria (ABU) strains in acute pyelonephritis (kidney infection)?
What is the 2-step path in the pathogenesis of acute pyelonephritis (kidney infection)?
Which factors reduce the efficacy of antibiotics for complicated urinary tract infection (UTI)?
What is the role of obstruction in the pathogenesis of acute pyelonephritis (kidney infection)?
What are the less common organisms in complicated urinary tract infection (UTI)?
What is the role of urea-splitting organisms in complicated urinary tract infection (UTI)?
How does pregnancy affect the pathophysiology of acute pyelonephritis (kidney infection)?
How does diabetes mellitus affect the pathophysiology of acute pyelonephritis (kidney infection)?
What is the prevalence of acute pyelonephritis in pregnant women and infants and children?
What are the race-, sex-, and age-related predilections of acute pyelonephritis (kidney infection)?
Does acute pyelonephritis (kidney infection) increase the risk of premature labor?
What are the mortality and morbidity rates in patients with acute pyelonephritis (kidney infection)?
What are the mortality rates in emphysematous pyelonephritis and emphysematous pyelitis?
What is the mortality rate for patients with sepsis and acute pyelonephritis (kidney infection)?
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Can acute pyelonephritis (kidney infection) cause acute renal failure (ARF)?
What is the prevalence of renal scarring in children with acute pyelonephritis (kidney infection)?
What is the prevalence of renal scarring in women with acute pyelonephritis (kidney infection)?
What are the possible complications of acute pyelonephritis (kidney infection) during pregnancy?
Does acute pyelonephritis (kidney infection) after renal transplantation increase the risk of graft failure?
How are antibiotics administered in patients with acute pyelonephritis (kidney infection)?
Presentation
What is the prevalence of gross hematuria (hemorrhagic cystitis) in patients with acute pyelonephritis (kidney
infection)?
What is the presentation of pain in patients with acute pyelonephritis (kidney infection)?
What is the presentation of GI symptoms in patients with acute pyelonephritis (kidney infection)?
What are the signs and symptoms of acute pyelonephritis (kidney infection) in children?
What are the physical findings in patients with acute pyelonephritis (kidney infection)?
What are the physical findings of fever in patients with acute pyelonephritis (kidney infection)?
What are blood pressure findings in patients with acute pyelonephritis (kidney infection)?
How is flank or costovertebral angle (CVA) tenderness characterized in patients with acute pyelonephritis (kidney
infection)?
In which patient groups is the risk for complication increased from acute pyelonephritis (kidney infection)?
Which abscesses may be present in patients with acute pyelonephritis (kidney infection)?
What is the pathogenesis of corticomedullary abscess in patients with acute pyelonephritis represent?
What is the pathogenesis of renal cortical abscess (renal carbuncle) in acute pyelonephritis (kidney infection)?
What is the presentation of renal cortical abscess (renal carbuncle) in acute pyelonephritis (kidney infection)?
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DDX
Workup
When is acute pyelonephritis (kidney infection) easily diagnosed and when might it present with an insidious onset?
What is the role of imaging studies in the diagnosis of acute pyelonephritis (kidney infection)?
Which collection methods are used for urine specimens for acute pyelonephritis (kidney infection)?
When is a suprapubic needle aspiration for collecting a urine specimen indicated in the diagnosis of acute
pyelonephritis (kidney infection)?
Who can perform a clean-catch technique for urine sample collection in acute pyelonephritis (kidney infection)?
How is the clean-catch technique for collecting urine specimen performed in female patients with acute pyelonephritis?
How is the clean-catch technique for collecting urine specimen performed in male patients with acute pyelonephritis
(kidney infection)?
When is urethral catheterization for collecting a urine specimen indicated for diagnosis of acute pyelonephritis (kidney
infection)?
Which tests are used for pyuria screening in the diagnosis of acute pyelonephritis (kidney infection)?
Which disorders should the included in the differential diagnosis acute pyelonephritis when gross hematuria
(hemorrhagic cystitis) is present?
What is the presentation of microscopic hematuria in patients with acute pyelonephritis (kidney infection)?
What is the significance of a proteinuria finding in the urinalysis of patients with acute pyelonephritis (kidney infection)?
What does the presence of a single bacterium in an unspun urine specimen indicate in the evaluation of acute
pyelonephritis (kidney infection)?
What is the role of urinary neutrophil gelatinase-associated lipocalin (NGAL) in the diagnosis of acute pyelonephritis
(kidney infection)?
When is a urine culture indicated in the evaluation of acute pyelonephritis (kidney infection)?
When is a blood culture indicated in the evaluation of acute pyelonephritis (kidney infection)?
What is the role of imaging studies in the diagnosis of acute pyelonephritis (kidney infection)?
What are the benefits of early imaging in acute pyelonephritis (kidney infection)?
When are imaging studies indicated in the evaluation of acute pyelonephritis (kidney infection)?
How are imaging studies used in the management of acute pyelonephritis (kidney infection)?
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What is the role of noncontrast helical/spiral CT scanning in the evaluation of acute pyelonephritis (kidney infection)?
When is a noncontrast CT scan of the kidneys, ureters, and bladder (KUB) or a CT urogram indicated in the evaluation
of acute pyelonephritis (kidney infection)?
What is the role of MRI in the evaluation of acute pyelonephritis (kidney infection)?
What is the role of ultrasonography (US) in the evaluation of acute pyelonephritis (kidney infection)?
What are the disadvantages of diagnostic ultrasonography (US) for acute pyelonephritis and when is renal
angiography indicated?
What is the role of scintigraphy in the evaluation of acute pyelonephritis (kidney infection)?
What is the role of CT urography or MR urography in the evaluation of acute pyelonephritis (kidney infection)?
Which studies are helpful in the diagnosis of papillary necrosis in acute pyelonephritis (kidney infection)?
Which findings suggest early renal papillary necrosis in acute pyelonephritis (kidney infection)?
Treatment
What is the role of analgesics in the treatment of acute pyelonephritis (kidney infection)?
When is hospitalization indicated for the treatment of acute pyelonephritis (kidney infection)?
Which antibiotics should be used to treat community-acquired acute pyelonephritis (kidney infection)?
Which antibiotics should be used to treat enterococcal infections in hospitalized and other institutionalized patients with
acute pyelonephritis (kidney infection)?
Which factors should be considered when choosing an empirical antibiotic regimen for acute pyelonephritis (kidney
infection)?
Is oral administration of antibiotics more effective than other regimens for the treatment of acute pyelonephritis (kidney
infection)?
When is oral therapy indicated for the treatment of acute pyelonephritis (kidney infection)?
What are the IDSA recommendations for inpatient treatment of women with pyelonephritis (kidney infection)?
When should the empirical use of TMP-SMZ be avoided for treatment of acute pyelonephritis (kidney infection)?
Which antibiotics are used for the treatment of complicated acute pyelonephritis (kidney infection)?
What is the IDSA recommendation for duration of antibiotic therapy for acute pyelonephritis?
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What are the IDSA recommendations for management of a female patient suspected of having acute pyelonephritis
(kidney infection)?
What are the IDSA recommendations for treatment of fluoroquinolone-resistant acute pyelonephritis (kidney infection)?
Which factors increase the risk of fluoroquinolone-resistant E coli infection in patients with acute pyelonephritis (kidney
infection)?
What are the supportive care options for acute pyelonephritis (kidney infection)?
Should activity be restricted during recovery from acute pyelonephritis (kidney infection)?
Which factors should be considered in the admission decision for patients with acute pyelonephritis (kidney infection)?
Which complicating factors are indications for admission of patients with acute pyelonephritis (kidney infection)?
Which patients with uncomplicated pyelonephritis (kidney infection) should be admitted for inpatient treatment?
What is the duration of inpatient antibiotic therapy for acute pyelonephritis (kidney infection)?
Which factors should be considered in the selection of an antibiotic regimen for acute pyelonephritis (kidney infection)
inpatient treatment?
What are the treatment options for abscesses in patients with acute pyelonephritis (kidney infection)?
When is surgical treatment of abscesses indicated in patients with acute pyelonephritis (kidney infection)?
What is included in the treatment of renal corticomedullary abscess in patients with acute pyelonephritis (kidney
infection)?
What is the mortality rate for perinephric abscesses in patients with acute pyelonephritis (kidney infection)?
What is the treatment for calculi-related infections in patients with acute pyelonephritis (kidney infection)?
What are the advantages and disadvantages of phosphorus and magnesium supplements in the treatment of calculi-
related infections in patients with acute pyelonephritis (kidney infection)?
What are the treatment options for renal papillary necrosis in patients with acute pyelonephritis (kidney infection)?
Which agents are used empirically to treat renal papillary necrosis in patients with acute pyelonephritis?
What is the duration of treatment for renal papillary necrosis in patients with acute pyelonephritis (kidney infection)?
Which factors increase the risk of pyelonephritis (kidney infection) during pregnancy?
What is the prevalence of bacteriuria and symptomatic urinary tract infection (UTI) during pregnancy?
What is the recommendation for urinary tract infection (UTI) screening in pregnant women?
Which regimens are used for the treatment of asymptomatic bacteriuria during pregnancy?
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What is the treatment for pregnant women with acute pyelonephritis (kidney infection)?
What therapy is recommended for prophylaxis against recurrent infection in pregnant women with acute pyelonephritis
(kidney infection)?
When is immediate urologic referral indicated for pediatric acute pyelonephritis (kidney infection)?
Which children are at increased risk for complications of acute pyelonephritis (kidney infection)?
Why is follow-up exam essential in pediatric patients with acute pyelonephritis (kidney infection)?
Which imaging studies are preferred for the urologic evaluation of pediatric patients with acute pyelonephritis?
What are age-related data for pediatric patients with acute pyelonephritis (kidney infection)?
Are dietary restrictions needed for pediatric patients with acute pyelonephritis (kidney infection)?
Are activity restrictions needed for pediatric patients with acute pyelonephritis (kidney infection)?
What are the deterrence and prevention strategies for pyelonephritis (kidney infection)?
Which specialist consultations are indicated for acute pyelonephritis (kidney infection)?
Guidelines
What are the NICE guidelines for treating acute pyelonephritis (kidney infection)?
Medications
What is the role of urine culture in the treatment of acute pyelonephritis (kidney infection)?
How should patients presenting with complicated pyelonephritis (kidney infection) be managed?
Which medications in the drug class Sulfonamides are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Fluoroquinolones are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Cephalosporins, Second Generation are used in the treatment of Acute
Pyelonephritis?
Which medications in the drug class Cephalosporins, Third Generation are used in the treatment of Acute
Pyelonephritis?
Which medications in the drug class Cephalosporins, Other are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Penicillins, Amino are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Penicillins, Extended-Spectrum are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Carbapenems are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Aminoglycosides are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Glycopeptides are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Monobactams are used in the treatment of Acute Pyelonephritis?
Which medications in the drug class Urinary Analgesics are used in the treatment of Acute Pyelonephritis?
Author
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Tibor Fulop, MD, PhD, FACP, FASN Professor of Medicine, Department of Medicine, Division of Nephrology, Medical
University of South Carolina College of Medicine; Attending Physician, Medical Services, Ralph H Johnson VA Medical
Center
Tibor Fulop, MD, PhD, FACP, FASN is a member of the following medical societies: American Academy of Urgent Care
Medicine, American College of Physicians, American Society of Hypertension, American Society of Nephrology,
International Society for Apheresis, International Society for Hemodialysis, Magyar Orvosi Kamara (Hungarian
Chamber of Medicine)
Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training
Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine;
Consulting Staff, Louisville Veterans Affairs Hospital
Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the
Advancement of Science, American Society for Bone and Mineral Research, American Society of Nephrology,
American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National
Kidney Foundation
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of
Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc.
Chief Editor
Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Interim Chair,
Deming Department of Medicine, Tulane University School of Medicine
Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American
Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for
Clinical Investigation
Acknowledgements
Amy J Behrman, MD Associate Professor, Department of Emergency Medicine, Director, Division of Occupational
Medicine, University of Pennsylvania School of Medicine
Amy J Behrman, MD is a member of the following medical societies: American College of Occupational and
Environmental Medicine
Christopher Edwards, MD Resident Physician, Department of Emergency Medicine, University of Pennsylvania School
of Medicine
Christopher Edwards, MD is a member of the following medical societies: American College of Emergency Physicians
and Society for Academic Emergency Medicine
Judith Green-McKenzie, MD, MPH Associate Professor, Director of Clinical Practice, Occupational Medicine
Residency Director, University of Pennsylvania School of Medicine
Judith Green-McKenzie, MD, MPH is a member of the following medical societies: American College of Occupational
and Environmental Medicine, American College of Physicians, American College of Preventive Medicine, National
Medical Association, and Society of General Internal Medicine
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20/02/22, 17:38
Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program,
Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting
Staff, Louisville Veterans Affairs Hospital
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of
Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology,
American Society for Bone and Mineral Research, American Society of Nephrology, American Society of
Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and
Phi Beta Kappa
Chike Magnus Nzerue, MD Associate Dean for Clinical Affairs, Vice-Chairman of Internal Medicine, Meharry Medical
College
Chike Magnus Nzerue, MD is a member of the following medical societies: American Association for the Advancement
of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine,
American Society of Nephrology, and National Kidney Foundation
Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM Associate Professor, Education Officer, Department of
Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel
Medicine
Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM is a member of the following medical societies: Alpha
Omega Alpha, American Academy of Emergency Medicine, American Society of Tropical Medicine and Hygiene,
International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society
William H Shoff, MD, DTM&H Director, PENN Travel Medicine; Associate Professor, Department of Emergency
Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine
William H Shoff, MD, DTM&H is a member of the following medical societies: American College of Physicians,
American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic
Emergency Medicine, and Wilderness Medical Society
Disclosure: Glaxo Smith Kline None None; Glaxo Smith Kline Honoraria Speaking and teaching
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference
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