Case Report

Cefazolin-Related Fever in Postoperative Spine Surgery:

A Case Report
Sirichai Wilartratsami MD*,
Pinpilai Jutasompakorn MD**, Panya Luksanapruksa MD*
* Department of Orthopedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
** Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Background: There have been few reports describing antibiotic related fever, especially in the beta-lactam class of antibiotics.
The present report is a case of postoperative immediate-onset cefazolin-related fever in a lumbar spine surgery patient.
Case Report: A 58-year-old woman presented with progressive low back pain and neurogenic claudication of both extremities
for six months. Magnetic resonance imagese (MRI) of the lumbar spine indicated central canal stenosis with nerve root
compression from L4 to S1. After decompressive laminectomy, pedicular screw fixation, and posterolateral fusion were
performed, the patient experienced postoperative fever without obvious evidence of infection. The blood and tip of drain
bacterial culture grew no organisms. After propholactic cefazolin was discontinued in postoperative day 5, the fever began to
declined and returned to normal on postoperative day 9.
Conclusion: Postoperative drug fever that is caused by prophylactic cefazolin may be delayed in diagnosis because drug
fever is usually diagnosed by exclusion after the elimination of other potential causes. The research authors would like to
encourage physicians to be aware of this entity. Prompt cause identification can obviate unnecessary diagnostic procedures
and inappropriate treatments.
Keywords: Drug fever, Cefazolin, Cephazolin, Cephalosporin, Adverse event, Spine surgery

J Med Assoc Thai 2014; 97 (Suppl. 9): S144-S148

Full text. e-Journal: http://www.jmatonline.com
Postoperative fever that is common in the first
few days after surgery, especially after a major
operation(1,2) is generally caused by inflammatory
stimulus from the stress of surgery and frequently
resolves itself spontaneously(3). Differential diagnosis
of postoperative fever includes infectious and noninfectious conditions such as wound sepsis,
atelectasis, urosepsis, drug fever, thrombophlebitis, and
deep vein thrombosis. Drug-related fever is most
common after administration of antibiotics, especially
in the beta-lactam class, and usually is resolved within
1 to 2 days after the termination of the drug. Cefazolin
is the most common prophylactic antibiotic used in
orthopedic surgery, including spine surgery. To our
knowledge, there has been only one previously reported
case in English research literature(4). While most
occurrences of postoperative cefazolin-related fever
have delayed onset after first administration, this report
Correspondence to:
Luksanapruksa P, Department of Orthopaedic Surgery, Faculty
of Medicine Siriraj Hospital, 2 Prannok Road, Bangkoknoi,
Bangkok 10700, Thailand.
Phone: 0-2419-7969
E-mail: panya.luk@mahidol.ac.th

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describes the first case of cefazolin-related fever in

postoperative lumbar spine surgery in Thailand, in
which the fever developed immediately after first
administration of the drug.
Case Report
A 58-year-old woman presented with
progressive low back pain and neurogenic claudication
of both extremities for 8 months. Past medical history
revealed no underlying disease or drug allergy. At the
time of admission, physical examination showed
pinprick sensation impairment at both sides of L5 and
S1 dermatome. According to Medical Research Council
scale, motor strength was graded 4/5 in the extensor
hullucis longus and flexor hullucis longus on both sides
of the body. The patients muscle tone, anal sphincter
tone, and deep tendon reflex were normal. Pre-operative
laboratory tests showed white blood cell count to be
4,970/mm 3 with 44.3% neutrophils and 0.8%
eosinophils. The lateral view of the lumbar spine
radiograph showed decreased disc space and
spondylolisthesis at the L4-5 and L5-S1 levels. Sagittal
lumbar magnetic resonance images (MRI) showed
spinal stenosis from hypertrophy of the ligamentum

J Med Assoc Thai Vol. 97 Suppl. 9 2014

flavum, with compressed nerve roots at the levels of L4

to S1 in T2 weighted MRI. Cefazolin was administered
as prophylactic antibiotic. Intra-operative findings
revealed venous congestion at the Para vertebral
muscles. Lateral recess and foraminal stenosis from
hypertrophy of the ligamentum flavum was found.
Decompressive laminectomy and posterolateral fusion
with local bone graft secured by pedicular screw system
was performed at the levels of L4 to S1.
After surgery the patient had a fever of 39
degrees Celsius on postoperative day 1 (Fig. 1). The
routine postoperative program was initiated, including
early ambulation and breathing exercises using triflow
spirometer. On postoperative day 2, the patient still
had a fever, which ranged from 38-38.5 degrees Celsius.
The surgical wound was normal and no discharge was
found. No skin rash was developed. Laboratory tests
showed the white blood cell count was 15,300/cumm
with 84.2% neutrophils and 0.4% eosinophils. Urinalysis
result had WBC 0-1 cell/HP and RBC 0-1 cell/HP. Serum
C-reactive protein (CRP) concentration was 13.81 mg/
L. Erythrocyte sedimentation rate (ESR) was 80 mm/
hour. No bacterial growth was reported from blood,
urine, and tip of drain cultures. Chest radiographic study
showed no evidence of pneumonia. Duplex scan
showed no deep vein thrombosis. The infectious
disease consultation team recommended discontinuing
the cefazolin. On that recommendation the cefazolin
was terminated on the morning of postoperative day 5.

Fig. 1

At this point in time, the patients temperature was 38.2

degrees Celsius. On postoperative day 7, the patients
temperature continued to decline. The patient remained
afebrile for the next 24 hours and was discharged on
the morning of postoperative day 9.
Discussion
Drug fever is the febrile response that
temporally coincides with the administration of a drug,
which then disappears after discontinuation. The true
incidence of drug fever is unknown, but it has been
estimated to occur in approximately 10% of inpatients(5).
Drug fever should be considered in the differential
diagnosis of any patient with unexplained fever,
especially when no other cause for the fever can be
elucidated, sometimes after antimicrobial therapy has
already been started(6-8). The recognition of drug fever
is clinically important because, if drug fever is not
recognized diagnostically, patients may require
prolonged hospitalization, unnecessary medications,
and potentially harmful diagnostic or therapeutic
interventions (5,9). Drug fever has resulted in lifethreatening events (0.6%), hospitalization or prolonged
hospital stay (24.5%), and persistent disability (0.6%).
A favorable final outcome occurred in 96.9% of cases
after drug discontinuation(10).
Drug administration can upset the bodys
normal balance and cause a fever. The drug may interfere
with thermoregulation, increase the rate of metabolism,

Changes in patient temperature during the postoperative period.

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evoke a cellular or humoral immune response, mimic

endogenous pyrogen, or damage tissues. The most
common mechanism is probably an immunologic
hypersensitivity reaction mediated by drug-induced
antibodies(9) and its characteristics resemble those of
an allergic reaction(11).
Many factors may indicate the likelihood of a
drug-related fever. Males and the elderly appear
more prone to this condition. However, no apparent
associations of drug fever with systemic lupus erythematosus, atopy, female sex, or advanced age were
found(12). Vodovar et al reported that antibacterials
represented the most frequently reported drugs
(including amikacin, oxacillin, cefotaxime, ceftriaxone,
rifampicin, vancomycin, ciprofloxacin, isoniazid, and
cotrimoxazole) and that median time from drug
administration to fever onset was 2 days (1.0-10.5 days).
The median time for the diagnosis of drug fever
following cessation of the suspected drugs was 3 days
(1.0-11.5 days) after fever onset(10) Oizumi et al reported
that beta-lactams most frequently induced drug fever,
including piperacillin (17%), cefotaxime (15%),
ceftizoxime (14%), and cefoperazone (8%). In contrast,
the incidence of drug fever caused by ampicillin and
cefazolin were 3% and 0%, respectively(13).
Drug fever has no characteristic fever pattern
with a highly variable lag time between the initiation of
the offending agent and the onset of fever and an
infrequent association with either rash or eosinophilia(12). In non-sensitized individuals receiving a drug
for the first time, the onset of fever is highly variable
and differs among drug classes. However, fever
typically occurs seven to ten days after treatment and
usually resolves within 48 hours of discontinuing the
administration. Moreover, fever will rapidly reappear if
the drug is restarted(7,9,11).
The common clinical manifestations of druginduced fever, espeicially antibiotic, are low-grade fever
with early onset followed by remittent high-grade fever.
The highest diurnal body temperature rises gradually,
and then subsides abruptly after discontinuance of
the causative drug. This pattern of fever was found in
about 70% of the cases resulting in drug fever ransient
serum lactic dehydrogenase elevation was associated
with drug fever in about 51% of cases. Additionally,
the transient decrease of platelets and neutrophil
counts was found in 8% and 23% retrospectively of
drug fever cases(14). Re-challenge will frequently cause
recurrence of fever within a few hours and that may be
used to confirm the diagnosis. However, re-challenge
is controversial and should be undertaken with a high

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degree of caution, because there is thea potential of a

more severe drug reaction(7-9) .
In the present case, the diagnosis of drug fever
was delayed because the onset of fever appeared
immediately after the operation, which was highly
unusual, and the presence of allergic cutaneous
manifestations were not observed. The routine
investigations that were performed for purposes of
determininge the causes of the postoperative fever
included urinalysis, chest radiography, blood and urine
cultures, duplex scan for deep vein thrombosis, and tip
of drain culture. The results of these investigations
were negative, so drug fever was suspected. Seventytwo hours after discontinuation of cefazolin, the
patients temperature returned to normal. Drug rechallenge was not performed after discussing the risks
and beneifits with the patient. Prompt identification of
drug-related fever can obviate unnecessary diagnostic
procedures and inappropriate treatments(15,16).
Conclusion
The present a case study profiling a 58 yearold woman presenting with progressive back pain and
neurogenic claudication. The patient developed a
postoperative drug fever that was caused by
prophylactic cefazolin. Cefazolin was not initially
suspected and this caused a delayed diagnosis because
the fever appeared immediately after surgery. Drug fever
is usually diagnosed by exclusion after the elimination
of other potential causes. The authors would like to
encourage physicians to be aware of this entity.
What is already known on this topic?
Previous studies have revealed that drug fever
from cefazolin is a rare condition. Most of the known
antibiotic-related fever causes are penicillin and
cephalosporins, excluding cefazolin. Most of the cases
had median onset from drug administration to fever
and the median time that it took for patient temperature
to return to normal after cessation of the suspected
drugs ranged from 1-10 days.
What this study add?
The profiled case shows that drug fever from
cefazolin may be a possible cause of immediate
postoperative fever. Cefazolin as a possible cause may
delay fever management due to the necessity having
to rule out other possible causes of fever. The research
authors would like to encourage physicians to be aware
of this entity, especially in postoperative fever that has
unknown causes.

J Med Assoc Thai Vol. 97 Suppl. 9 2014

Potential conflicts of interest

None.
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