Chapter 2 Cardiology

Infectious Diseases

Infective Endocarditis

▪ Endocarditis is an infection of the valve of the heart leading to a fever and a murmur.

▪ About 75% of patients with IE have previously damaged heart valves, with mitral valvular disease being
the most common. Patients with mitral valve prolapse and associated regurgitation have a 5-8 times
higher risk of IE than those with a normal valve.

▪ It is very rare to have endocarditis develop on normal heart valves with the exception of injection drug
users.

▪ The risk of endocarditis is directly proportional to the degree of damage of the valves. Regurgitant and
stenotic lesions confer increased risk. Prosthetic valves are associated with the highest risk. Infection
can develop on normal valves if there is severe bacteremia with highly pathogenic organisms such as
occurs with injection drug use and Staphylococcus aureus.

▪ Dental procedures confer an increased, but very small risk of endocarditis. Even surgery of the mouth
or respiratory tract confers no risk unless there is a severe valvular disorder such as from an artificial
valve or cyanotic heart disease. Less invasive procedures such as endoscopy confer no increased risk
even with a biopsy.

▪ Viridans group streptococci (Streptococcus sanguinis) typically colonize the oral mucosa and are the
most common cause of IE following dental procedures.

▪ Clinical manifestations:
- Fever.

- New murmur or change in a murmur.

- Complications of endocarditis:
o Splinter hemorrhages.
o Janeway lesions (flat and painless).
o Osler nodes (raised and painful).
o Roth spots in the eyes.
o Brain (mycotic aneurysm).
o Kidney (hematuria, glomerulonephritis).
o Conjunctival petechiae.
o Splenomegaly.
o Septic emboli to the lungs.

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▪ Diagnosis:
- It is diagnosed with vegetations seen on echocardiogram and positive blood cultures.

- The best initial test:

o Blood culture (95%-99% sensitive).
o Transthoracic echocardiogram (60% sensitive but 95%-100% specific).
o Transesophageal echocardiogram (95% sensitive and specific).

❖ Establishing a Diagnosis of Culture Negative Endocarditis:

▪ The diagnosis is based on:
A. Oscillating vegetation on echocardiography.

B. Three minor criteria:

1. Fever >100.3°F (38°C).

2. Risk such as injection drug use or prosthetic valve.

3. Signs of embolic phenomena.

▪ HACEK is an acronym for organisms that are difficult to culture that cause endocarditis:
- Haemophilus aphrophilus.
- Haemophilus parainfluenzae.
- Actinobacillus.
- Cardiobacterium.
- Eikenella.
- Kingella.

▪ The most common causes of culture-negative endocarditis are Coxiella and Bartonella. Neither Coxiella
nor Bartonella will grow in regular culture media.

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▪ Treatment:
- The best initial empiric therapy is vancomycin and gentamicin. Add rifampin for prosthetic valve
endocarditis with Staphylococcus.

- When culture results are available, treat as indicated in the table “Treatment of Endocarditis”.

Organism Treatment

Viridans streptococci Ceftriaxone for 4 weeks

Staphylococcus aureus (sensitive) Oxacillin, nafcillin, or cefazolin

Fungal Amphotericin and valve replacement

Staphylococcus epidermidis or resistant Vancomycin

Staphylococcus

Enterococci Ampicillin and gentamicin

▪ Treatment of Resistant Organisms:

- Add an aminoglycoside and extend the duration of treatment.

▪ Treatment of Culture Negative Endocarditis:

- Use ceftriaxone for the HACEK group of organisms.

▪ Prophylaxis for Endocarditis:

- Two features are needed to establish the need for prophylaxis:
A. Significant cardiac defect:
o Prosthetic valve.
o Previous endocarditis.
o Cardiac transplant recipient with valvulopathy.
o Unrepaired cyanotic heart disease.

B. Risk of bacteremia:
o Dental work with blood.
o Respiratory tract surgery that produces bacteremia.

- The best initial management is amoxicillin prior to the procedure. If the patient is penicillin allergic,
then azithromycin, or clarithromycin, clindamycin is the answer.

- Endoscopic and genitourinary procedures do not need prophylaxis.

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▪ The criteria for surgery (valve replacement) in infective endocarditis:

- CHF from ruptured valve or chordae tendineae.
- Prosthetic valves.
- Fungal endocarditis.
- Abscess.
- AV block. Development of atrioventricular block in a patient with infective endocarditis should raise
suspicion for perivalvular abscess extending into the adjacent cardiac conduction tissues (perivalvular
abscess).
- Recurrent emboli while on antibiotics.

▪ The single strongest indication for surgery is acute valve rupture and CHF.

❖ N.B:
1. The diagnosis of infective endocarditis (IE) is based on the combination of clinical presentation,
laboratory studies (blood cultures), and results of cardiac imaging studies with the use of modified
Duke criteria.
▪ The most appropriate next step is to obtain serial blood cultures. It is recommended that a minimum of
3 blood cultures be obtained from separate venipuncture sites (not from a vascular catheter) over
several hours prior to initiating antibiotic therapy.
▪ In patients with acute illness, all 3 blood cultures should be obtained over a 1-hour period before
beginning empiric antibiotic therapy.

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2. The combination of fever, generalized weakness, tricuspid regurgitation, and Intravenous drug user
(IVDU) indicates likely right-sided infective endocarditis (IE). Staphylococcus aureus is the responsible
pathogen for more than half of IE cases in IVDU.
▪ Septic pulmonary emboli occur in up to 75% of patients with tricuspid endocarditis.
▪ Imaging may show pulmonary septic emboli as pulmonary infiltrates, abscesses, infarction, pulmonary
gangrene, or cavities.
▪ Empiric antibiotic treatment should be based on the conditions of the valves (prosthetic versus native)
and prior history of IVDU. Empiric therapy in a native valve should cover methicillin-susceptible and -
resistant staphylococci, streptococci, and enterococci. Vancomycin therefore is the most appropriate
antibiotic for empiric therapy in these patients due to its broad spectrum of activity. Once the organism
is identified in blood cultures, antibiotics can be changed to cover the appropriate organism.

3. Splenic abscess usually presents with the classic triad of fever, leukocytosis, and left upper-quadrant
abdominal pain.
▪ Infective endocarditis is most commonly associated with splenic abscess.
▪ Some studies have documented a 10%-20% incidence of associated splenic abscess or infarction with
left-sided endocarditis.
▪ Likely mechanisms include hematogenous seeding or septic emboli to the spleen. Splenic abscess is
most commonly due to Staphylococcus, Streptococcus, and Salmonella.
▪ Antibiotics alone for treating splenic abscess have a high mortality (up to 50% in some studies). As a
result, splenectomy is recommended for all patients. Percutaneous drainage may be an option in poor
surgical candidates.

4. Eikenella corrodens is a Gram-negative anaerobe and a common constituent of normal human oral
flora.
▪ Infective endocarditis due to E. corrodens is usually seen in the setting of poor dentition and/or
periodontal infection, along with dental procedures that involve manipulation of the gingival or oral
mucosa.

5. Meta-analysis showed a significantly increased risk of colorectal cancer and endocarditis in patients
with infection due to S. gallolyticus (S bovis biotype 1) compared to patients with S bovis biotype II
infection. Because of this association, all such patients should have further evaluation with colonoscopy
to look for underlying occult malignancy (colon cancer).

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Pneumonia

▪ Etiology:
- Pneumonia is an infection of the lung parenchyma.

- It is the 6th leading cause of death in the United States.

- Predisposing factors: cigarette smoking, diabetes, alcoholism, malnutrition, obstruction of the

bronchi from tumors, and immunosuppression in general.

- The most common cause of community-acquired pneumonia in all groups is S. pneumoniae (however,
viruses are the most common cause in children age <5).

- M. pneumoniae is the most common cause of atypical pneumonia.

- Hospital- acquired or ventilator-associated pneumonia shows a predominance of Gram-negative bacilli

such as E. coli, the other Enterobacteriaceae, or Pseudomonas, as well as MRSA.

▪ Presentation:
- Patients with pneumonia present with cough, fever, and often sputum production. Severe pneumonia
of any cause may present with dyspnea.

- Bacterial infections such as S. pneumoniae, Haemophilus, and Klebsiella have significant purulent
sputum production because they are infections of the alveolar air space.

- The sputum with S. pneumoniae is described as rusty. The “rust” is simply hemoptysis. As the blood
oxidizes, it becomes brownish-red color.

- The sputum with Klebsiella pneumoniae is described as currant jelly. This is simply hemoptysis with
mucoid characteristics from a combination of the necrotizing nature of Klebsiella with the organism’s
thick mucopolysaccharide coating.

- Interstitial infections such as those caused by Pneumocystis pneumonia (PCP), viruses, Mycoplasma,
and sometimes Legionella often give a nonproductive or “dry” cough.

- Any cause of pneumonia may be associated with pleuritic chest pain. This is pain worsened by
inspiration. Commonly, pleuritic pain is associated with lobar pneumonia, such as that caused by
Pneumococcus. This is because of localized inflammation of the pleura by the infection.

- On physical examination pneumonia presents with rales, rhonchi, or signs of lung consolidation,
including dullness to percussion, bronchial breath sounds, increased vocal fremitus, and egophony.
- The respiratory rate is essential in determining the severity of a pneumonia. The respiratory rate is
often a close correlate of the level of oxygenation. Severe pneumonia leads to hypoxia, which leads to
hyperventilation.

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▪ Diagnosis:
- The most important initial test for any type of pneumonia is the chest x-ray.

- Besides being able to simply show the presence of disease, the chest x-ray gives the initial clue to
determining the diagnosis. The most important initial clue to the diagnosis is whether the infiltrates are
localized to a single lobe of the lung or whether they are bilateral and interstitial.

- S. pneumoniae (and other causes of “typical” pneumonia) usually appear as a lobar pneumonia with
parapneumonic pleural effusion.

- Interstitial infiltrates are associated with PCP, viral, Mycoplasma, Chlamydia, Coxiella, and sometimes
Legionella pneumoniae.

- Sputum should be obtained for both Gram stain as well as culture. Sputum culture is the most specific
diagnostic test for lobar pneumonia, such as with S. pneumoniae, Staphylococcus, Klebsiella, and
Haemophilus.

- The other organisms (viral, Mycoplasma, Chlamydia, Coxiella, etc.), the so-called “atypical” organisms,
will not show up on a Gram stain or regular bacterial culture for various reasons.

- Organism-specific diagnostic methods are as follows:

o Mycoplasma: Specific serologic antibody titers.
o Chlamydia pneumoniae, Coxiella, Coccidioidomycoses, and Chlamydia psittaci: All of these are
diagnosed with specific serologic antibody titers.
o Legionella: Specialized culture media with charcoal yeast extract and urine antigen tests.
o PCP: Bronchoalveolar lavage, increased LDH.

- Occasionally, more invasive tests are necessary to confirm the diagnosis such as bronchoscopy,
thoracentesis, pleural biopsy, or culture of pleural fluid. Ultimately, the most specific diagnostic test for
pneumonia is with an open lung biopsy.

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- Symptoms that help distinguish an atypical pneumonia due to Legionella from other causes of
community-acquired pneumonia (CAP) include high-grade fever (>39), gastrointestinal symptoms
(diarrhea), and neurologic symptoms (confusion). Hyponatremia (related to the inappropriate secretion
of ADH) and hepatic dysfunction are common.

- Legionella pneumophila is a gram-negative rod that stains poorly because it is primarily intracellular;
therefore, sputum Gram stain showing many neutrophils but no organisms is also characteristic in
buffered charcoal yeast extract agar.

- Urine antigen testing is rapidly available, highly specific, and the most common method to confirm the
diagnosis.

▪ Treatment:
- Treatment depends on whether the patient has a mild disease that can be treated as an outpatient or a
more severe illness that must be treated with IV antibiotics as a hospitalized inpatient.

- Patients with CAP are often risk stratified using the pneumonia severity index or CURB-65 criteria to
help guide treatment and treatment location (home, medical floor, intensive care unit) decisions.

- The specific organism causing pneumonia is rarely, if ever, known at the time that the initial
therapeutic decision must be made.

- Empiric therapy for pneumonia managed as an outpatient is with a macrolide, such as azithromycin or
clarithromycin. This is because of the high frequency of Mycoplasma and Chlamydia pneumoniae as the
cause of less severe community-acquired pneumonia (CAP). New fluoroquinolones (levofloxacin,
moxifloxacin, or gemifloxacin) are alternatives.

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- Hospitalized patients with CAP should receive either levofloxacin, moxifloxacin, or gatifloxacin or a
second- or third-generation cephalosporin such as cefotaxime or ceftriaxone combined with a
macrolide antibiotic such as azithromycin or clarithromycin.

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- Treatment of Hospital-Acquired Pneumonia:

o Those patients who develop pneumonia after 5-7 days in the hospital are at increased risk of infection
from drug-resistant, Gram-negative bacilli (Pseudomonas, Klebsiella, E. coli, etc.) or gram-positive cocci
such as methicillin-resistant Staphylococcus aureus (MRSA).

o Empiric therapy of hospital-acquired pneumonia is with third generation cephalosporins with

antipseudomonal activity (such as ceftazidime) or carbapenems (such as imipenem) or with beta-
lactam/beta-lactamase inhibitor combinations (such as piperacillin/tazobactam) and coverage for
MRSA with vancomycin or linezolid.

o Aminoglycosides (gentamicin, tobramycin, amikacin) are often added to empiric gram-negative

coverage for synergy and to ensure that the patient might be getting at least one drug if the bacteria is
multidrug resistant.

o Antibiotic therapy can then be adjusted when results of cultures (sputum, blood, bronchoalveolar
lavage, and/or pleural) become available.

❖ Ventilator-associated pneumonia (VAP):

▪ Ventilator-associated pneumonia (VAP) is a type of nosocomial pneumonia that usually develops > 48
hours after endotracheal intubation.

▪ It is most commonly caused by aerobic gram-negative bacilli (Pseudomonas aeruginosa, Escherichia

coli, Klebsiella pneumoniae) and gram-positive cocci (methicillin-resistant Staphylococcus aureus,
Streptococcus).

▪ Patients usually have fever, purulent secretions, difficulty with ventilation (increased respiratory rate,
decreased tidal volume), and leukocytosis.

▪ The first step is to obtain a chest x-ray. Patients with a normal chest x-ray are unlikely to have VAP and
should be evaluated for other causes.

▪ Those with an abnormal chest x- ray (alveolar infiltrates, air bronchograms, silhouetting of adjacent
solid organs) require lower respiratory tract sampling (tracheobronchial aspiration) for microscopic
analysis (Gram stain) and culture.

▪ Patients should receive empiric antibiotics (usually gram-positive, anti-pseudomonal, and gram-
negative coverage) until culture susceptibility results return as treatment delay can increase mortality.
However, respiratory tract sampling should be done prior to starting antibiotics as treatment can
decrease the sensitivity of both the Gram stain and culture.

❖ Pneumococcal vaccine:
▪ Those patients at increased risk for pneumonia should receive pneumococcal vaccine.

▪ Those who should receive the vaccine include:

- All patients age > 65.
- Those with any serious underlying lung, cardiac, liver, or renal disease.

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- Immunocompromised patients, such as those on steroids, HIV-positive persons, splenectomized

patients, diabetics, and those with leukemia or lymphoma, should be vaccinated at the earliest possible
opportunity.

▪ The vaccine is 60-70% effective. Re-dosing in 5 years is only necessary for those with severe
immunocompromise or in those who were originally vaccinated before the age of 65. In generally
healthy persons vaccinated age > 65, a single dose of vaccine is enough to confer lifelong immunity.

❖ N.B:
1. Alveolar consolidation in pneumonia causes hypoxemia due to right-to-left intrapulmonary shunting.
▪ Positional changes that make the consolidation more gravity dependent worsen ventilation/perfusion
mismatch, increase intrapulmonary shunting, and lead to worsened hypoxemia.
▪ In the normal lung of an upright patient, V and Q are highest in the bases of the lung as gravity creates
hydrostatic pressure acting on both air and blood. When this patient is lying on his left side, gravity
induces an increase in blood flow to the left lung, where there is markedly reduced V due to alveolar
consolidation. The result is a more profound V/Q mismatch (V remains approximately zero, but Q
increases), increased right-to-left intrapulmonary shunting, and worsening hypoxemia. The opposite
occurs when this patient is lying on his right side (decrease in Q to the area of alveolar consolidation),
leading to a more favorable V/Q mismatch and improvement in hypoxemia.

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2. Aspiration pneumonia is due to inhalation of oropharyngeal secretions colonized by pathogenic

bacteria. Aspiration risk factors include the following:
- Altered consciousness due to seizures, alcoholism, drug overdose, or sedation.
- Neurologic dysphagia (dementia, parkinsonism, cerebrovascular accident, myasthenia).
- Disruption of the gastroesophageal junction (esophageal disease, gastric reflux).
- Mechanical disruption of glottic closure (endotracheal intubation, bronchoscopy, endoscopy).
▪ Heavy alcohol users are at risk of aspiration if they have impaired consciousness.
▪ Patients usually present with indolent symptoms (days to weeks), foul-smelling sputum, and concurrent
periodontal disease.
▪ Imaging reveals infiltrate in the lower lobes or right middle lobe (aspiration while upright) or the
posterior segment of the upper lobes (aspiration while recumbent).
▪ The infectious organisms are frequently oral flora (mixed aerobic and anaerobic).
▪ Broad-spectrum antibiotics with good anaerobic coverage (clindamycin, amoxicillin-clavulanate) are the
mainstay of treatment.

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Urinary tract infection

▪ All UTIs can present with dysuria (frequency, urgency, burning) and a fever. The urinalysis shows
increased WBCs in all of them. E. coli is the most common cause. Quinolones are the best initial therapy
for pyelonephritis.

▪ The high incidence of UTIs in women is primarily due to the shorter length of the female urethra. After
the periurethral area becomes colonized by rectal flora, the bacteria ascend to the bladder to cause
infection. This is facilitated in females by a short urethra.

▪ Any form of obstruction or foreign body in the urinary system increase the risk of UTI. Foley catheter is
a foreign body. Neurogenic bladder is an obstruction.

▪ Frequency means multiple episodes of micturition. Polyuria is an increase in the volume of urine.

Cystitis

▪ Cystitis is infection of the urinary bladder. It is very common, mostly in women.

▪ Etiology:
- Any cause of urinary stasis or any foreign body predisposes (Tumors/stones/strictures/prostatic
hypertrophy/neurogenic bladder)

- Sexual intercourse in women (“honeymoon cystitis”).

- Catheters are a major cause.

▪ Microbiology:
- coli in >80%; second are Gram-negative bacilli such as Proteus, Klebsiella, Enterobacter, etc.;
enterococci occasionally, and Staph. saprophyticus in young women.

▪ Clinical presentation:
- Common presenting symptoms include dysuria, frequency, urgency, and suprapubic pain.

- On exam, there is suprapubic tenderness but no flank tenderness.

▪ Diagnosis:
- Best initial test is the urinalysis looking for WBCs, RBCs, protein, and bacteria; WBCs is the most
important with more than 10 WBCs.

- Positive leukocyte esterase signifies significant pyuria and positive nitrites indicate the presence of
Enterobacteriaceae which converts urinary nitrates to nitrites.

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- Urine culture with >100,000 colonies of bacteria per mL of urine confirmatory but not always necessary
with characteristic symptoms and a positive urinalysis.

▪ Treatment:
- Uncomplicated cystitis commonly occurs in otherwise healthy patients and has a low risk of treatment
failure. For uncomplicated cystitis, 3 days of trimethoprim/sulfamethoxazole, nitrofurantoin, or any
quinolone.

- Complicated cystitis refers to infections associated with factors that increase the risk of antibiotic
resistance or treatment failure.

- Such factors include diabetes, chronic kidney disease, pregnancy, immunocompromised state, or
urinary tract obstruction; hospital-acquired infection; or infection associated with a procedure
(cystoscopy) or indwelling foreign body (catheter, stent). These patients should have urine culture prior
to therapy.

- Complicated cystitis in otherwise stable patients may be managed with oral fluoroquinolones, but more
severe cases may require intravenous broad-spectrum antibiotics (ceftriaxone) while awaiting culture
results.

Chronic bacterial prostatitis

▪ Most cases arise in young or middle-aged men who smoke or have diabetes mellitus.

▪ Coliform bacteria (Escherichia coli) cause the majority of cases and generally gain access to the prostate
from the urethra via the intraprostatic reflux of urine.

▪ Manifestations are often subtle, but many patients have >1 of the following:
- Symptoms of recurrent urinary tract infections (dysuria, frequency, suprapubic tenderness, pyuria,
bacteriuria) that transiently improve with short courses of antibiotic therapy.

- Pain with ejaculation (discharge of prostatic fluid is irritative).

- Prostatic swelling and tenderness: however, notably, the prostate examination is often normal.

▪ Management:
- The diagnosis is generally made clinically, but confirmation requires prostatic massage followed by
examination of prostatic fluid (prostatic fluid bacteria > urine bacteria prior to prostatic massage).
- Eradication of the pathogen usually requires at least 6 weeks of antibiotic therapy (fluoroquinolone).

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Acute Bacterial Pyelonephritis

▪ Acute bacterial pyelonephritis is an acute patchy, most often unilateral, pyogenic infection of the
kidney. Infection usually occurs by ascension after entering the urethral meatus.

▪ Predisposing factors include obstruction due to strictures, tumors, calculi, prostatic hypertrophy, or
neurogenic bladder, vesicoureteral reflux.

▪ Women > men.

▪ E. coli is the most common pathogen; others include Klebsiella, Proteus, and Enterococcus.

▪ Patients who are immunosuppressed and subjected to indwelling catheters are more prone to Candida.

▪ Pathology shows polymorphonuclear neutrophils and leukocytes (in interstitial tissue and lumina of
tubules).

▪ Clinical findings include chills, fever, flank pain, nausea, vomiting, costovertebral angle tenderness,
increased frequency in urination, and dysuria.

▪ Diagnose with dysuria and flank pain. Confirm with clean-catch urine for urinalysis, culture, and
sensitivity.
▪ Urine (and blood) cultures should be obtained routinely before administration of empiric antibiotics.

▪ Urological imaging is typically reserved for patients with persistent clinical symptoms despite 48-72
hours of therapy, history of nephrolithiasis, complicated pyelonephritis, or unusual urinary findings
(gross hematuria, suspicion for urinary obstruction).

▪ Complicated pyelonephritis involves progression of the initial pyelonephritis to renal corticomedullary

abscess, perinephric abscess, emphysematous pyelonephritis, or papillary necrosis. Patients can
develop sepsis with multiorgan failure, shock, and renal failure.

▪ Treatment:
- Stable patients with uncomplicated pyelonephritis can be treated with oral antibiotics (usually a
fluoroquinolone), but unstable patients and those with complicated infection require intravenous
antibiotics (ceftriaxone).

- Because of increasing resistance to TMP/SMZ, which has approached almost 20% in some parts of the
United States, this agent is no longer recommended for empiric therapy until culture results and
antibiotic sensitivity results are available.

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❖ N.B:
1. Asymptomatic bacteriuria (ASB) refers to the growth of >100,000 (105) colony-forming units/mL of a
single type of bacteria from a clean catch urine specimen in the absence of urinary tract infection
symptoms.
▪ The increased progesterone levels in pregnancy cause smooth muscle relaxation and ureteral dilation,
thereby increasing the risk for pyelonephritis and other obstetrical complications (preterm delivery, low
birth weight) from ASB.
▪ Therefore, all patients at the initial prenatal visit are screened for ASB. Patients whose screening urine
cultures are positive are treated with antibiotics. The most common pathogen is Escherichia coli.
▪ First-line antibiotics include cephalexin, amoxicillin-clavulanate, and nitrofurantoin. A repeat urine
culture is performed after antibiotic completion to determine clearance of infection.

2. Although urine culture is required for definitive identification, the presence of urinary alkalization (pH
>8) raises suspicion for a urease-producing bacterium such as Proteus mirabilis (most commonly) or
Klebsiella pneumoniae.
▪ Urease splits urea into ammonia and carbon dioxide; ammonia then converts to ammonium and
alkalinizes the urine. High urine pH reduces the solubility of phosphate, raising risk for development of
struvite stones (magnesium ammonia phosphate).

3. Catheter-associated urinary tract infection (CA-UTl) is a common complication of urinary catheter use.
▪ CA-UTl is most effectively prevented by avoiding unnecessary catheter use and minimizing the duration
of catheterization.
▪ However, in patients with neurogenic bladder, long-term catheter use is required. In these patients,
clean intermittent catheterization (CIC), which involves periodic insertion and removal (every 4-6
hours) of a clean urinary catheter and can often be performed by the patient, is usually the initial
treatment.
▪ CIC is associated with a significantly lower risk of CA-UTl compared with the use of indwelling catheters.

Perinephric Abscess

▪ Perinephric abscess is a collection of infected material surrounding the kidney and generally contained
within the surrounding Gerota fascia.

▪ It is very uncommon. Although any factor predisposing to pyelonephritis is contributory, stones are the
most important and are present in 20-60%.

▪ Pathophysiology:
- Arises from contiguous pyelonephritis that has formed a renal abscess.
- Rupture occurs through the cortex into the perinephric space.

▪ Microbiology:
- The same as in cystitis and pyelonephritis.

- E. coli most common, then Klebsiella, Proteus.

- Staph. aureus sometimes accounts for hematogenous cases.

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▪ Signs and Symptoms:

- Fever is the most common symptom.

- Look for pyelonephritis that does not resolve with appropriate therapy. When the choice of drug is
correct and the dose is correct, failure of an infection to resolve is often from an anatomic problem.

▪ Diagnosis:
- The best initial tests are urinalysis (normal 30%) and urine culture (normal 40%). Fever and pyuria with
negative urine culture or polymicrobial urine culture are suggestive.

- Imaging is essential; U/S is the best initial scan but CT or MRI scan offers better imaging.

- Aspiration of the abscess is needed for definitive bacteriologic diagnosis.

▪ Treatment:
- Antibiotics for Gram-negative rods.

- Third generation cephalosporins, antipseudomonal penicillin, or ticarcillin/clavulanate, often in

combination with an aminoglycoside, for example.

- Antibiotics alone are unlikely to be successful, Drainage (usually percutaneous) is necessary.

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Diarrhea

▪ Diarrhea is increased frequency or volume of stool per day (alternatively, it can be defined as few stools
per day but with watery consistency).

▪ The most common causes include an infectious, antibiotic-associated, or lactose-intolerance etiology,

irritable bowel syndrome, and carcinoid syndrome.

▪ Diagnosis:
- The first step in the evaluation of diarrhea is to see if there is hypovolemia as defined as hypotension or
orthostasis.

- This is more important than determining specific etiology because the patient could die while waiting
for the results to come back.

▪ Treatment:
- No matter the etiology, if the patient is hypotensive, febrile, and having abdominal pain, admit as
inpatient and give IV fluids and antibiotics.

Infectious Diarrhea/Food Poisoning

▪ Most infectious diarrhea is caused by contaminated food and water, so the overlap between infectious
diarrhea and food poisoning is considerable.

▪ A wide variety of agents can cause food poisoning:

- Campylobacter jejuni (the most common cause of acute gastroenteritis in children and adults in
industrialized countries).

- Salmonella (most commonly associated agent with contaminated poultry and eggs).

- E. coli (most common cause of travelers’ diarrhea; produces a wide spectrum of disease depending on
whether it makes toxin or is invasive).

- E. coli O157:H7 is associated with undercooked hamburger meat (beef products).

- The most frequently tested food item associated S. aureus food poisoning is a mayonnaise-containing
food like potato or macaroni salad.

- Bacillus cereus is associated with fried rice; the rice becomes contaminated with bacillus spores, and as
it is prepared for serving it is warmed only at a moderate temperature not hot enough to kill the spore.

- Giardia lamblia and cryptosporidiosis are acquired from contaminated water sources that have not
been appropriately filtered, such as fresh water on a camping trip.

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- Cryptosporidiosis is also associated with HIV, particularly when there is profound immunosuppression
and CD4 <50 cells.

▪ There are several types of Vibrio causing human disease:

- V. cholera (very rare in the United States).

- V. parahaemolyticus (associated with ingestion of contaminated shellfish).

- V. vulnificus (associated with ingestion of raw shellfish); causes severe disease in those with underlying
liver disease; also associated with iron overload and the development of bullous skin lesions.

▪ Viral infections such as rotavirus or Norwalk agents are most commonly associated with outbreaks in
children.

▪ Clostridia associations are as follows:

- C. Difficile with previous antibiotic use.

- C. Botulinum with ingestion of infected canned foods.

- C. Perfringens with ingestion of meat contaminated with spores due to unrefrigeration.

▪ Clinical Presentation:
- The most important feature of any person presenting with possible food poisoning is the presence or
absence of blood in the stool.

- Blood is most commonly associated with invasive enteric pathogens, such as Salmonella, Shigella,
Yersinia, invasive E. coli, and Campylobacter.

- Ingestion of ciguatera toxin causes symptoms within 2-6 hours, which includes paresthesias, numbness,
nausea, vomiting, and abdominal cramps. In severe cases, symptoms can be neurologic (weakness,
reversal of hot-cold sensations), and cardiovascular (hypotension). Neurologic symptoms can be severe,
progressive, and debilitating. There is no specific therapy to reverse ciguatera poisoning. The most
commonly implicated fish are barracuda, red snapper, and grouper.

- E. Coli O157:H7 and Shigella are associated with hemolytic uremic syndrome (HUS).

- Bacillus cereus and Staphylococcus predominantly present with vomiting within 1-6 hours of their
ingestion because they contain a preformed toxin. They can cause diarrhea later.

- Giardia, Cryptosporidium, Cyclospora, and most other protozoans do not cause bloody diarrhea. The
major protozoan associated with blood in the stool is Entamoeba histolytica.

- Viruses can give voluminous watery diarrhea but do not cause bloody diarrhea.

- Scombroid is a type of poisoning that occurs after ingestion of scombroid fish (tuna, mackerel, mahi
mahi), which may contain a lot of histamine. When ingested, scombroid can give symptoms within a

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few minutes: rash, diarrhea, vomiting, and wheezing, along with a burning sensation in the mouth,
dizziness, and paresthesias.

▪ Diagnosis:
- When there is no blood present in the stool, determine the etiology of the diarrhea via a stool test for
the presence of WBCs with methylene blue testing. WBCs will indicate that there is an invasive
pathogen, but only a culture will identify the specific type.

- Cryptosporidiosis diagnosis requires a unique test (a modified acid-fast test; it cannot be detected
reliably by the routine ova and parasite exam).

- Giardia diagnosis is best made with an ELISA stool antigen test.

▪ Treatment:
- Therapy is determined by the severity of disease:
o Mild infections with the invasive pathogens and viruses usually require only oral fluid and electrolyte
replacement.
o More severe infections, such as those producing high fever, abdominal pain, tachycardia, and
hypotension, require IV fluids and oral antibiotics.

- You rarely, if ever, have the luxury of knowing the specific etiology when the initial therapeutic decision
must be made. The best initial empiric antibiotic therapy of an invasive pathogen is a fluoroquinolone
(ciprofloxacin).

▪ Organism-specific therapy is as follows:

- Giardia: metronidazole.

- Cryptosporidium: control of underlying HIV disease with antiretrovirals, nitazoxanide. Nitazoxanide is

the first truly useful therapy for cryptosporidiosis.

- Scombroid: antihistamines such as diphenhydramine.

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Antibiotic-Associated Diarrhea

▪ Antibiotic-associated diarrhea (AAD) is a benign, self-limited diarrhea following the use of

antimicrobials.

▪ Although clindamycin may be associated with the highest incidence of antibiotic-associated diarrhea
and Clostridium difficile (C. diff), any antibiotic can potentially cause diarrhea.

▪ C. difficile transmission is most common in the hospitalized setting, particularly when patients are
severely ill.

▪ C. difficile spores are acid-resistant, but proton pump inhibitors (PPIs) are thought to alter the colonic
microbiome, which increases the risk of C difficile proliferation.

▪ These intestinal bacteria (intestinal biomass) effectively suppress overgrowth of Clostridium difficile
and many other potentially pathogenic bacteria by competing for nutrients and adhesion sites within
the gut. Treatment with antibiotics can alter the intestinal balance of bacteria leading to a potential
overgrowth of pathogenic strains and clinical disease.

▪ Clinical Presentation and Diagnosis:

- The clinical manifestations of C. diff may vary from mild diarrhea (watery diarrhea) to fulminant colitis
with or without the presence of pseudomembranes.
- If a patient develops diarrhea several days to weeks (even up to 8 weeks) after using antibiotics,
evaluate for C. diff.

- Marked leukocytosis and systemic symptoms are evident in severe cases.

- The best initial test is a stool C. diff toxin test or PCR (Stool is never cultured for C. diff because it simply
will not grow in culture).

▪ Treatment:
- Oral metronidazole was previously used as first-line therapy but is no longer recommended due to
greater risk of recurrence.

- Treatment involves the cessation of the inciting antibiotic (if possible), infection control (contact
precautions), and antimicrobial therapy with oral vancomycin or fidaxomicin.

- IV vancomycin will have no effect in the bowel because it does not pass bowel wall. Similarly, oral
vancomycin will have no systemic effect.

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- Patients with fulminant disease (hypotension, ileus, megacolon) should be treated with high-dose oral
vancomycin and intravenous metronidazole; if ileus is present, vancomycin may be given rectally.

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Chronic Hepatitis B and C

▪ Viral hepatitis is an infection of the liver caused by hepatitis A, B, C, D, or E.

Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E

Transmission Feco-oral Parenteral, Primarily blood Parenteral, sexual Feco-oral
sexual (IVDU,
posttransfusion)
Disease - Asymptomatic - Acute; - Acute is - Co-infection - Normal patients:
Presentation (usually) occasionally usually with HBV: mild
severe subclinical. occasionally
- Mild acute severe - Pregnant patients:
- Chronic: 5- - 80% become Fulminant
- No chronic 10% adults, chronic - Superinfection hepatitis.
90% infants. with HBV:
- No sequalae - Primary often severe - No chronic
- Primary hepatocellular
hepatocellula carcinoma, - Cirrhosis,
r carcinoma, cirrhosis fulminant
cirrhosis hepatitis
Mortality < 0,5% 1-2% 0,5-1% High to very high - Normal patients:
1-2%

- Third trimester
pregnant patients:
25%

▪ Hepatitis A and E are transmitted by contaminated food and water. They are orally ingested and have
an asymptomatic incubation period of several weeks, with an average of 2-6 weeks. They cause
symptomatic disease for several days to weeks, have no chronic form, and do not lead to either
cirrhosis or hepatocellular carcinoma.

▪ Hepatitis B, C, and D are transmitted by the parenteral route. They can be acquired perinatally or
through sexual contact, blood transfusion, needlestick, and needle sharing.

▪ Hepatitis B and C can lead to a chronic form, which can cause cirrhosis and hepato-cellular carcinoma.

▪ Hepatitis C is the most common disease leading to the need for liver transplantation in the United
States.

▪ All forms can occasionally present with fulminant hepatic necrosis and acute liver failure.

▪ The most common presentation of acute hepatitis of any cause is jaundice, dark urine, light- colored
stool, fatigue, malaise, weight loss, and a tender liver. On physical examination the liver may be
enlarged.

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▪ You cannot distinguish the precise viral etiology of the hepatitis by initial presentation alone. In fact,
drug-induced hepatitis (that from isoniazid or massive alcohol use) may present with the same
symptoms.

▪ Hepatitis B and C can also produce symptoms similar to serum sickness, such as joint pain, rash,
vasculitis, and glomerulonephritis. They also lead to cryoglobulinemia. Hepatitis B has been associated
with the development of polyarteritis nodosa (PAN). Hepatitis E has been associated with a more
severe presentation in pregnant women.

▪ Diagnosis:
- All forms of viral and drug-induced hepatitis will produce elevated total and direct bilirubin levels.

- Viral hepatitis will produce both elevated ALT and AST, but ALT is usually greater than the AST.

- With drug- and alcohol-induced hepatitis, AST is usually more elevated than the ALT.

- Alkaline phosphatase and GGTP are less often elevated because these enzymes usually indicate damage
to the bile canalicular system or obstruction of the biliary system.

- If there is very severe damage to the liver, prothrombin time and albumin levels will be abnormal.

- Hepatitis A, C, D, and E are diagnosed as acute by the presence of the IgM antibody to each of these
specific viruses. IgG antibody to hepatitis A, C, D, and E indicates old, resolved disease.

- Hepatitis C activity can be followed with PCR-RNA viral load level.

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- Serological markers for the hepatitis B virus include the following:

A. HBsAg:
o The first virological marker detected in the serum after inoculation, it precedes both the elevation of
serum aminotransferases and the onset of clinical symptoms.

o It remains detectable during the entire symptomatic phase of acute hepatitis B and suggests infectivity.

B. Anti-HBs:
o Appearing in the serum after either successful HBV vaccination or the clearance of HBsAg, this marker
remains detectable for life.

o It serves as an indicator of noninfectivity and immunity.

o However, there is a time lag between the disappearance of HBsAg and the appearance of anti-HBs in
the serum, which is termed the "window period".

C. HBcAg: This marker is not detectable in serum as it is normally sequestrated within the HBsAg coat.

D. Anti-HBc:
o Appearing in the serum shortly after the emergence of HBsAg, this marker remains detectable long
after the patient recovers.

o The lgM fraction signals the acute/Recent phase infection, whereas the lgG fraction signal prior
exposure or chronic infection.

o Because lgM anti-HBc is present in the "window period," it is an important tool for diagnosis when
HBsAg has been cleared and anti-HBs is not yet detectable.

o Thus, lgM anti-HBc is the most specific marker for diagnosis of acute hepatitis B.

E. HBeAg:
o This antigen is detectable shortly after the appearance of HBsAg and indicates active viral replication
and high infectivity.

F. Anti-HBe: This marker suggests the cessation of active viral replication and low infectivity.

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❖ Interpretation of hepatitis B serology:

Tests Results Typical interpretation
HBsAg Negative
Anti-HBc Negative Susceptible individual
Anti-HBs Negative
HBsAg Positive
HBeAg Positive Viremia stage
DNA Polymerase Positive
HBV DNA Positive
HBsAg Positive
IgM anti-HBc Positive Acute HBV infection
Anti-HBs Negative
HBsAg Negative
IgM anti-HBc Positive Window phase
Anti-HBs Negative
HBsAg Positive
IgM anti-HBc Negative
IgG anti-HBc Positive Chronic HBV infection (High
HBeAg Positive infectivity)
Anti-HBe Negative
Anti-HBs Negative
HBsAg Positive
IgM anti-HBc Negative
IgG anti-HBc Positive Chronic HBV infection (Low
HBeAg Negative infectivity)
Anti-HBe Positive
Anti-HBs Negative
HBsAg Negative Immune individual following
IgG anti-HBc Positive natural infection
Anti-HBs Positive
HBsAg Negative Immune individual following
Anti-HBc Negative HBV Vaccination
Anti-HBs Positive

▪ Treatment:
- Treatment of HAV infection is largely supportive, and most patients completely recover in 3-6 weeks.

- There is no effective therapy for acute hepatitis B. Treatment options of chronic hepatitis B include
interferon alpha (pegylated or standard), lamivudine, entecavir, ortenofovir.

- Interferon is a short-term treatment and cannot be given to patients with decompensated cirrhosis. It is
usually reserved for younger patients with compensated liver disease.

- Lamivudine has a diminished role due to increasing drug resistance.

- Entecavir and tenofovir (in countries where approved) have become preferred therapies due to lower
drug resistance and their ability to be used in decompensated cirrhosis.

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- With the approval of the newest hepatitis C drugs, the goal of HCV treatment is to cure the
virus, which can be done with a combination of drugs.

- There are a number of approved therapies to treat HCV, such as sofosbuvir/ledipasvir or

simeprevir/sofosbuvir.

- Simeprevir and sofosbuvir can be prescribed together with or without ribavirin, or each may be
separately combined with ribavirin and in some cases peginterferon as well.

- Sofosbuvir/ledipasvir, the current preferred HCV treatment, is 2 drugs formulated in to one daily pill.
For genotype 1, success rates of sofosbuvir/ledipasvir are around 94-99%, while treatment duration is
8-12 weeks. Both are direct-acting antivirals (DAAs) which means they directly interfere with hepatitis C
virus replication.

- Patients are considered cured when they have achieved what is known as a sustained virologic
response (SVR), or continuation of this undetectable status, 12-24 weeks after completing therapy.

- Reassurance is the most appropriate course of action for a patient with known immunity to hepatitis B
who is exposed to the disease. The HBIG and the hepatitis B vaccination series should be given to
patients with unknown immunity after exposure.

- There is no effective postexposure prophylaxis to hepatitis C, and there is no vaccine.

- All healthcare workers, IV drug users, and others at risk should be vaccinated for hepatitis B.

- All newborn children are vaccinated against hepatitis B and A. Hepatitis A vaccine should be given to
those traveling to countries that may have contaminated food and water, those with chronic liver
disease, and those with high risk sexual behavior.

❖ N.B:
1. Vertical transmission of hepatitis B from pregnant females to the unborn child can occur with active
hepatitis B infection.
▪ Typically, such transmission takes place during the passage of the fetus through the birth canal, but
transplacental infection can also occur.
▪ This is especially common in those women who developed acute hepatitis B infection in the third
trimester.
▪ The presence of HBeAg (a soluble protein that is a marker of viral replication and increased infectivity)
in the mother significantly increases the risk of vertical transmission of the virus.
▪ Were this woman HBeAg negative, her neonate's risk of infection would be 20%.
▪ If she were HBeAg positive, however, her neonate's risk of infection would be 95%.
▪ Moreover, should the infant become infected, his chance of progression to chronic hepatitis is 90%.
▪ Viral replication occurs rapidly in infected infants due to immune system immaturity in newborns. The
chance of progression to chronic hepatitis is 90% without treatment, which is higher than the chance of
progression in adults (<5%) and children (20%-30%).
▪ Over time, chronically infected newborns are at significant risk of disease progression to cirrhosis
and/or hepatocellular carcinoma.

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▪ Therefore, the newborns of all mothers with active hepatitis B should be passively immunized at birth
with hepatitis B immune globulin (HBIG), followed by active immunization with recombinant HBV
vaccine.

2. Up to 80% of patients infected with the hepatitis C virus (HCV) develop chronic hepatitis, making
hepatitis C the most common cause of chronic hepatitis. Patients with chronic HCV infection are also at
risk for cirrhosis.
▪ Acute viral hepatitis can be life threatening, especially in a patient with pre-existing chronic viral
hepatitis.
▪ Therefore, all patients with chronic HCV should be immunized against hepatitis A and B if they are not
already immune.
▪ The inactivated (killed) hepatitis A and B vaccines are both safe to administer during pregnancy.

3. Individuals with a history of high-risk sexual intercourse (unprotected or men who have sex with men)
should be screened for HIV and hepatitis B infection.
▪ Individuals who use injection drugs, have a high-risk needlestick exposure, or received blood
transfusions before 1992 )Donated blood and organs were not routinely tested in the United States
until 1992) should be screened for hepatitis C.

4. In this serologic marker graph, it appears that this patient has a persistence of HBsAg and HBeAg over a
long period with low to moderate levels of anti-HBcAg lgG and no detectable Anti-HBsAg.
▪ These findings are suggestive of an acute hepatitis B infection that has not resolved, but rather has
progressed to a highly infectious chronic hepatitis B (note the persistence of HBeAg and lack of anti-
HBeAg).

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Gas Gangrene (Clostridial Myonecrosis)

▪ Gas gangrene is the necrotizing destruction of muscle by gas-producing organisms, associated with
signs of sepsis.

▪ It is largely caused by the spread of infection from wounds contaminated by Clostridium perfringens
(the toxins produced by clostridia play a significant role in tissue damage).

▪ Symptoms:
- Usually begin <1-4 days of incubation after the wound; they include pain, swelling, and edema at the
site of the wound.

- Crepitation over the site and renal failure are late developments, usually prior to death.

▪ Diagnosis:
- A Gram stain of the wound shows Gram-positive rods, but no white cells.

- A culture may be positive for C. perfringens as early as 1 day; however, this is not necessarily diagnostic
because up to 30% of wounds can be colonized by Clostridia.

- Gas bubbles on x-ray are suggestive but may be caused by streptococci as well.

▪ Treatment:
- High-dose penicillin or clindamycin (if penicillin allergic) is necessary, but surgical debridement or
amputation is the absolute center of treatment.

- Hyperbaric oxygen may be of benefit, but this is still controversial.

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Central Nervous System Infections

Meningitis

▪ Meningitis is an infection or inflammation of the meninges, which is the connective tissue covering the
central nervous system (CNS).

▪ Etiology:
- Overall, most meningitis cases are caused by viruses. Viral meningitis is a usually self-limited
inflammation of the leptomeninges caused by a viral infection. Almost 90% of cases are caused by non-
polio enteroviruses, such as echovirus and coxsackievirus.

- Streptococcus pneumoniae is the most common cause of community-acquired bacterial meningitis in

adults.

- Neisseria meningitidis is a gram-negative diplococcus that causes life-threatening meningitis,

particularly in young children and adolescents (military, college students).

- Hemophilus influenzae (Rare since introduction of group B vaccine).

- Listeria monocytogenes is more common in those with immune system defects, particularly of the
cellular (T-cell) immune system and sometimes neutrophil defects. These defects include HIV, steroid
use, leukemia, lymphoma, and various chemotherapeutic agents. Since neonates and the elderly have
decreased T-cell immune function, Listeria is more common in them.

- Staphylococcus aureus is more common in those who have had any form of neurosurgery because
instrumentation and damage to the skin introduce the organism into the CNS.

- Cryptococcus is more common in those who are HIV positive and who have profound decreases in T-
cell counts to levels <100 cells.

- Rocky mountain spotted fever (RMSF) is common in those who have been exposed to ticks in the
appropriate geographic area.

- Lyme disease can also cause meningitis.

- Tuberculosis and syphilis are also associated with meningitis.

▪ Clinical Presentation:
- Regardless of microbiologic etiology, all forms of meningitis present with fever, photophobia,
headache, nuchal rigidity (neck stiffness, positive Kernig and Brudzinski signs), as well as nausea and
vomiting.

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- There is considerable overlap in the additional findings:

o Neck stifness or nuchal rigidity.
o Confusion and altered mental status.
o Focal neurological abnormalities. The most common being visual field and cranial nerve deficits. The
most common long-term neurologic deficit from bacterial meningitis is damage to the 8th cranial
nerve.

- If the question describes more than one of these findings (stiff neck, focal abnormalities, confusion) you
cannot answer the “most likely diagnosis” question without additional information.

- If the question describes only one of them, you can answer the question:

Presentation Most likely diagnosis

Stiff neck (nuchal rigidity) Meningitis

Confusion Encephalitis

Focal neurological abnormalities Abscess

- Patients with viral meningitis can present with a viral prodrome of constitutional and upper respiratory
symptoms with low-grade fever. Focal neurologic signs are not usually seen. The cerebrospinal fluid
(CSF) will show pleocytosis with lymphocytic predominance. CSF gram stain will not show any
organisms. Treatment is supportive; in most patients, symptoms resolve within 7-10 days.

- Rash is associated with several types of meningitis:

o Petechial rash is suggestive of Neisseria.

o Rash on the wrists and ankles with centripetal spread toward the body including palms and soles is
suggestive of RMSF.

o Facial nerve palsy is suggestive of Lyme disease; the target-like erythema migrans rash of Lyme disease
is seldom present by the time the meningitis develops.

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▪ Diagnosis:
- Lumbar puncture is essential for establishing the diagnosis.

Bacterial Cryptococcus, Tuberculosis Viral

meningitis Lyme, Rickettsia

Cell count 1000s, 10s-100s 10s-100s 10s-100s

neutrophils lymphocytes lymphocytes lymphocytes

Protein level Elevated Possibly Markedly Usually normal

elevated elevated

Glucose level Decreased Possibly May be low Usually normal

decreased

Stain and Stain: 50-70%; Negative Negative Negative

culture culture: 90%

- The CSF cell count is the most important initial step in determining if there is meningitis (Normal CSF
cell count is <5 cells/mm3, which should be predominantly lymphocytes).

- The differential on the cell count is the best you can do to distinguish acute bacterial meningitis from
the many causes of an elevated lymphocyte count. You cannot distinguish the specifc bacterial
pathogen without a CSF culture.

- Only bacterial meningitis gives thousands of cells that are all neutrophils. A mild-to-moderate elevation
in lymphocytes, with several dozen to several hundred cells, can occur with viral infection, Rickettsia,
Lyme disease, tuberculosis, syphilis, or fungal (cryptococcal) etiology.

Thousands of neutrophils = acute bacterial meningitis

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- Without culture, the CSF characteristics (cell count, protein, glucose, color) cannot distinguish
between:
o Pneumococcus.
o Neisseria.
o Listeria.
o Staphylococcus.
o Haemophilus.

- CT scan of the head is the best initial diagnostic test if the patient has papilledema, focal motor deficits,
new onset seizures, severe abnormalities in mental status, or immunocompromised status (HIV,
immunosuppressive medications, post-transplantation).

- If lumbar puncture is delayed >20-30 minutes for any reason, the best initial step is to give an empiric
dose of antibiotics.

- If none of the above is present, a lumbar puncture can be safely done without doing a CT scan of the
head first, which can significantly delay the diagnosis.

- There are numerous causes of an elevated CSF lymphocyte count (CSF Lymphocytosis). In the
past this was referred to as “aseptic meningitis”. Aseptic simply means nonbacterial:
o All can elevate the protein.
o None is visible on Gram stain.
o None grows on bacterial culture media.
o They are indistinguishable without other features in the history or lab testing.

- Meningitis characterized by an increased CSF lymphocyte count is caused by:

o Cryptococcus.
o Tuberculosis.
o Rocky mountain spotted Fever (Rickettsia).
o Lyme disease.
o Viruses.

- HIV/AIDS is the most common risk or cryptococcal meningitis. Without AIDS in the history, there is no
specific CSF finding that would compel you to answer “India ink” or “cryptococcal antigen” as the
diagnostic tests.

- RMSF is detected with serologic testing in 95% of cases.

- The most accurate test of lyme disease is the ELISA or Western blot of the CSF.

▪ Treatment:
- Initial treatment is started without knowing the results of culture. When the CSF cell count shows
thousands of neutrophils, the “next best step in management” is to start:

Ceftriaxone + vancomycin + glucocorticoids (usually dexamethasone)

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- Empiric therapy of bacterial meningitis in adults is best achieved with vancomycin (because of the
increasing prevalence worldwide of pneumococci with decreasing sensitivity to penicillins) plus a third-
generation cephalosporin such as ceftriaxone.

- In neonates (age <28 days), cefotaxime should be used as ceftriaxone displaces bilirubin from albumin
and increases the risk of kernicterus.

- In immunocompromised patients (transplant recipients on immunosuppressants), the treatment of

choice is cefepime or ceftazidime plus vancomycin plus ampicillin.

- Cefepime is a fourth-generation cephalosporin that covers most of the major organisms of bacterial
meningitis (Streptococcus pneumoniae, Neisseria meningitidis, group B streptococci, Haemophilus
influenzae) as well as Pseudomonas aeruginosa. Vancomycin is used if you know you have definite or
suspected pneumococcal resistance to penicillin or if there is a chance of staphylococcal infection after
neurosurgery, and ampicillin covers Listeria monocytogenes.

- Dexamethasone (corticosteroid) therapy for patients with bacterial meningitis decreases mortality and
rates of deafness. The rationale for this is the inflammatory response elicited in the subarachnoid space
due to bacterial cell wall lysis after antibiotics are administered; this inflammatory reaction can worsen
morbidity and mortality due to bacterial meningitis. The benefit is greatest for patients with
pneumococcal meningitis. Dexamethasone should be continued for 4 days if bacterial meningitis is
confirmed and discontinued if the etiology is nonbacterial (viral, fungal, etc.).

- The close contacts of patients with Neisseria meningitidis should receive either rifampin or
ciprofloxacin to prevent nasopharyngeal colonization and a “carrier” state. Ceftriaxone and
azithromycin are considered alternatives.

- Prophylaxis should be given within 24 hours of identification o the source case. The hardest
issue is who is considered a “close contact”. These are:
o Household contacts.
o Anyone with possible salivary contact (kissing, eating utensils).
o Healthcare workers only if in direct contact with oral or respiratory secretions with mouth to-mouth
resuscitation.

- Who is not considered a “close contact”?

o Routine school and work contacts.
o Routine contact with healthcare workers.

- Lyme disease is best treated with ceftriaxone.

- Neurosyphilis is treated with high-dose IV penicillin.

- The best initial therapy for cryptococcal meningitis is amphotericin B and flucytosine. After several
weeks, this is followed by fluconazole.

- There is no treatment currently proven useful for viral meningitis.

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❖ N.B:
▪ In an infant with meningococcemia, watch out for Waterhouse-Friderichsen syndrome, which is
characterized by a sudden vasomotor collapse and skin rash (large purpuric lesions on the flanks) due
to adrenal hemorrhage.
▪ Fulminant meningococcemia can occur after a meningococcus infection, and approximately 10-20% of
infants present with vasomotor collapse, large petechiae and purpuric lesions. The condition carries an
almost 100% mortality.

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Encephalitis

▪ Encephalitis is an infection of the brain, whether in the meninges or the brain parenchyma.

▪ Although any bacterial, protozoal, or rickettsial infection can cause encephalitis, most cases are caused
by viruses, with herpes simplex (usually type I [HSV-1]) the most common.

▪ Varicella-zoster virus, CMV, enteroviruses, Eastern and Western equine encephalitis, St. Louis
encephalitis, and West Nile encephalitis are significantly less common causes.

▪ Patients present with fever and headache but these findings are nonspecific. Altered mental status with
fever and headache is the primary clue to the diagnosis.

▪ Patients may also have nuchal rigidity and focal neurological abnormalities, but there is no way to
confirm a diagnosis of encephalitis if all of these findings are present simultaneously.

▪ Diagnosis:
- Best initial test:
o CT scan of the head may show abnormalities of the temporal lobe in 20% to 50% of patients (HSV has a
predilection for involvement of the temporal lobes).
o MRI is abnormal in 90%.

- Most accurate test:

o PCR of the CSF for herpes simplex (detecting viral DNA) is 95% to 99% sensitive and specific.
o The PCR is more accurate than a brain biopsy.

- Lumbar puncture usually shows cerebrospinal fluid (CSF) findings of elevated white blood cell count
with lymphocytic predominance, normal glucose, and elevated protein concentration.

▪ Treatment:
- Empiric treatment with intravenous acyclovir should be started while awaiting PCR results as
encephalitis is often associated with significant morbidity and mortality.

- Although famciclovir and valacyclovir have activity against HSV, they are not available intravenously.

- Acyclovir-resistant herpes is treated with foscarnet.

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Brain Abscess

▪ Brain abscess is a collection of infected material within the brain parenchyma.

▪ Brain abscess can arise from any cause of bacteremia in which seeding of the brain occurs. In addition,
local infection in the sinuses or otitis media can spread contiguously into the brain. The microbiology is
incredibly diverse:
- Anaerobes: 65%.
- Streptococci: 35%.
- Staphylococci: 35%.
- Gram-negative bacilli: 35%.

▪ How can the causative organisms add up to 170%? Because brain abscess is polymicrobial in one-third
to two-thirds of patients.

▪ Toxoplasmosis can reactivate in those with severe HIV disease when CD4 counts are very low (<50-
100/pL).

▪ Brain abscess presents with:

- Fever (50%).
- Headache (more than 80%).
- Focal neurological deficits (50%).
- Papilledema (25%).

▪ Diagnosis:
- The best initial test is either a CT or an MRI.

- The most accurate test is a brain biopsy.

- Neuroimaging cannot distinguish cancer rom infection. Both can give contrast-enhancing mass lesions
of the brain.

- Examination of the abscess fluid (obtained by stereotactic aspiration or surgical excision of the abscess)
for Gram stain and culture is essential.

- The CT-guided stereotactic aspiration of brain abscesses helps achieve all treatment goals. It drains the
contents of the abscess, reduces mass effect, and confirms diagnosis. It is minimally invasive, carries
minimal morbidity and mortality, and can be performed on compromised patients under local
anesthesia.

- In HIV-positive patients, 90% of brain lesions will be either toxoplasmosis or lymphoma. This is the only
circumstance where empiric therapy is sufficient to establish a specific diagnosis. If the lesion responds
to 10-14 days of therapy with pyrimethamine and sulfadiazine, continue to administer this therapy, as
it accurately predicts cerebral toxoplasmosis.

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▪ Treatment:
- Almost always, successful treatment requires a combination of surgical and medical management.

- Stereotactic aspiration (preferred) and surgical excision of the abscess are the methods used; the latter
is rarely used nowadays because of significant complications.

- With the exception of HIV-positive patients who are best treated with pyrimethamine and sulfadiazine,
therapy should be based on the specific etiology found.

- One example of a combination of therapy is penicillin, metronidazole, and a third-generation

cephalosporin, such as ceftazidime. Penicillin would cover the streptococci, metronidazole the
anaerobes, and ceftazidime the Gram-negative bacilli.

Neurocysticercosis

▪ Humans can be both intermediate and definitive host:

- Ingestion of larvae encysted in undercooked pork (humans are the definitive host) → Intestinal
infection.
- Ingestion of eggs excreted in feces of infected human carriers (humans are the intermediate host) →
larva penetrate intestinal wall and migrate via the blood to brain, heart and lungs → Cysticercosis,
neurocysticercosis.

▪ T. solium is endemic in central and south America and neurocysticercosis should be

considered in patients from these areas who develop seizures or neurologic symptoms.

▪ Tapeworms typically remain localized in the gastrointestinal tract, but shed eggs may pass to other
individuals via the fecal-oral route. Ingested eggs hatch in the small intestine, invade the bowel wall,
and spread hematogenously (brain, muscle, liver), causing cysticercosis.

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▪ Neurocysticercosis typically manifests as an adult-onset seizure. Less commonly, patients develop signs
of increased intracranial pressure (vomiting, headache, papilledema) due to obstruction of cerebral
spinal fluid outflow.

▪ Brain imaging (CT, MRI) usually reveals ≥1 cystic lesion with surrounding contrast enhancement and
edema without displacement of adjacent tissue. Diagnosis is typically made based on clinical and
radiologic findings; brain biopsy is rarely needed.

▪ Patients are treated with antiepileptics (phenytoin), antiparasitics (albendazole), and corticosteroids
(for brain inflammation).

Rabies Encephalitis

▪ Rabies is transmitted following a bite from an infected mammal.

▪ In developing countries, dogs account for >90% of transmission due to inadequate rabies control
programs. In contrast, rabies in domesticated animals is very rare in the United States due to effective
rabies vaccination. Most cases of rabies in the United States are due to bites from wild animals (bats,
raccoons, foxes, skunks).

▪ Once deposited in a wound, the virus stays local for a period of days or weeks before binding to
nicotinic acetylcholine receptors on peripheral nerve axons and traveling retrograde to the central
nervous system (dorsal root ganglia and spinal cord), where replication occurs.

▪ Common manifestations of rabies include a nonspecific, flu-like prodrome (malaise, anorexia, mild
fever, headache, nausea, vomiting) and a subsequent acute neurologic syndrome that includes
agitation, persistent fever, variable consciousness, and painful spasms with swallowing or inspiration.

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▪ Pharyngeal muscle spasms cause dysphagia, which can lead to the avoidance of food and water
(hydrophobia)

▪ Dysphagia along with hypersalivation due to autonomic dysfunction results in the "mouth foaming"
seen in rabies encephalitis.

▪ Generalized flaccid paralysis and coma follow the acute neurologic phase, with most patients dying
within two weeks of becoming comatose.

▪ The clinical presentation of restlessness, agitation, and dysphagia progressing to coma 30 to 50 days
following an exposure to cave bats is strongly suggestive of rabies encephalitis.

▪ Massive replication occurs within the central nervous system and the rabies virus spreads to other
organs through neural pathways; it is thought that at this point, postexposure prophylaxis is no longer
effective.

▪ Postexposure prophylaxis (PEP) consists of a series of rabies immunizations as well as rabies

immune globulin. However, not all patients require PEP:
a) Patients exposed to high-risk wild animals (bats, raccoons, foxes, skunks) should receive PEP for rabies
if the animal is unavailable for testing. In particular, bat bites can go unrecognized, so PEP is
recommended following direct exposure to bats (unless the patient is constantly aware of the bats and
is certain a bite was not inflicted).

b) Patients bitten by domestic animals (pets) in the United States do not require PEP if the pet is available
for testing. The incubation period for rabies is usually 1-3 months, but animals that are contagious
(have rabies virus in their saliva) will be symptomatic 5-10 days after becoming contagious. Therefore,
pets available for quarantine can be observed for 10 days for signs of rabies. However, if the pet is
unavailable for quarantine (or is symptomatic), PEP should be administered.

c) Patients bitten by low-risk animals (squirrels, chipmunks) do not need PEP.

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Cellulitis

▪ Cellulitis is a bacterial infection of the dermis and subcutaneous tissues with Staphylococcus and
Streptococcus.

▪ Cellulitis is characterized by redness, swelling, warmth and tenderness of the skin.

▪ Because it is below the dermal-epidermal junction, there is no oozing, crusting, weeping, or draining.

▪ Cellulitis involves the legs more often than the arms.

▪ Treatment:
- Topical antibiotics will not cover cellulitis. The infection is below the dermal/epidermal junction and
topical antibiotics will not reach it.

- Cellulitis is treated with the antibiotics prescribed for erysipelas on the basis of the severity of the
disease.

- If there is fever, hypotension, or signs of sepsis or if oral therapy has not been effective, then the
patient should receive IV therapy. Oxacillin, nafcillin, or cefazolin is the best therapy.

- Treatment is generally empiric because injecting and aspirating sterile saline for a specific microbiologic
diagnosis has only a 20% sensitivity.

- Oral therapy for MRSA is with clindamycin, TMP/SMX, or doxycycline.

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