Investigation of the Mei-yu Front Using a New Deformation

Infections in Oncology
Urosepsis Due to Fluoroquinolone-Resistant
Escherichia coli After Ultrasonographic-Guided
Transrectal Implantation of Fiducial Markers
David D. Buethe, MD, Wade J. Sexton, MD, John N. Greene, MD,
Bhisit Changcharoen, MD, and Pongsathorn Kue-A-Pai, MD
Escherichia coli (E coli) is the most common pathogen
of infectious complications surrounding transrectal
procedures of the prostate.1,2 The widespread practice of administering fluoroquinolone antimicrobial
prophylaxis prior to such procedures has reduced the
rate of periprocedural infections, yet the incidence of
fluoroquinolone-resistant E coli remains, which has
spurred investigations into preventive measures.2-7
The administration of preprocedural enemas to mechanically reduce bacterial count within the rectal
vault has failed to improve outcomes.2 However,
studies have identified recent antibiotic use and international travel as pertinent risk factors for the
development of fluoroquinolone-resistant infection.8
Further, these resistant strains of E coli have often
been found to exhibit resistance to other commonly
prescribed medications for urinary tract infections
(UTIs) and necessitate the administration of broadspectrum cephalosporins, broad-spectrum penicillins,
or carbapenems when a serious infection, such as
urosepsis, is suspected.4
Case Report
A man aged 57 years was diagnosed with Gleason
grade 3+4 adenocarcinoma of the prostate involving
10% to 25% of the tissue within 2 of 12 total biopsy
cores. Initial digital rectal examination (DRE) identified a benign gland without nodularity. Thus, the
tumor was clinically staged as T1cNxMx according
to the 2010 American Joint Commission on Cancer
From the Department of Genitourinary Oncology (DDB, WJS) and
the Division of Infectious Diseases and Tropical Medicine (JNG)
at the H. Lee Moffitt Cancer Center & Research Institute, Tampa,
Florida, and the Department of Medicine at Mahidol University
(BC, PK-A-P), Bangkok, Thailand.
Submitted February 8, 2012; accepted June 30, 2012.
Address correspondence to John N. Greene, MD, Division of Infectious Diseases and Tropical Medicine, Moffitt Cancer Center,
12902 Magnolia Drive, FOB-3 BMT PROG, Tampa, FL 33612.
E-mail: [email protected]
No significant relationship exists between the authors and the
companies/organizations whose products or services may be referenced in this article.
July 2013, Vol. 20, No. 3
guidelines9 and deemed to be an intermediate risk
with regard to recurrence as defined by the National
Comprehensive Cancer Network and the American
Urologic Association (AUA).10,11 Treatment options,
including radical prostatectomy, external beam radiation therapy, and interstitial brachytherapy, were
discussed with the patient in detail.
After he opted for external beam radiation therapy, the patient agreed to a treatment protocol inclusive
of intensity-modulated radiation therapy (IMRT) and
the prerequisite placement of gold fiducial markers.
Thus, 3 months following prostatic biopsy, he was
given an oral dose of 500 mg of levofloxacin prior to
the transrectal ultrasound (TRUS)-guided placement of
four gold fiducial markers within the prostate gland.
He also received levofloxacin 500 mg daily by mouth
for two days after the procedure. Two days following the placement of fiducial markers, he returned to
our facility complaining of fever, nausea, and vomiting. He was also experiencing perineal discomfort,
awakening chills, and malaise. He denied difficulty
with voiding.
On physical examination, the patient was febrile
(101.8° F), exhibited regular tachycardia (125 beats
per minute), was normotensive (140/78 mmHg), and
was without tachypnea (20 breaths per minute). His
abdomen was benign and the bladder was not palpable. No costovertebral angle tenderness was present. A gentle DRE demonstrated a firm, nontender
prostate without masses. There was no gross blood
in the rectal vault.
Serological evaluation noted a slight leukocytosis (12,500 k/μL) with the differential noting a left
shift. The patient was not anemic (16.6 g/dL), and he
was slightly thrombocytopenic (86 k/μL). Urinalysis
displayed yellow urine with a high specific gravity
(1.080) consistent with dehydration, a normal pH
(6.0), trace protein (30 mg/dL), negative nitrites, large
leukocyte esterase, pyuria (51-100 white blood cells/
high-powered field), and trace bacteria consistent with
an infectious process, and microscopic hematuria.
The DRE was inconsistent with acute bacterial
prostatitis. However, UTI, potentially complicated by
Cancer Control 233
bacteremia, was suspected, so initial doses of levofloxacin, vancomycin, and fluconazole were administered to the patient as empirical antibiotic coverage in the emergency department. On admission,
intravenous levofloxacin 500 mg daily, piperacillin/
tazobactam 4.6 g every 6 hours, and vancomycin 1
g 3 times daily were administered. By hospital day
2, the urine and blood cultures demonstrated Gramnegative rods, so the vancomycin was discontinued.
The final culture and sensitivities identified the pathogen as E coli sensitive to piperacillin/tazobactam and
trimethoprim/sulfamethoxazole but resistant to both
levofloxacin and ciprofloxacin. Therefore, only the
piperacillin/tazobactam was continued. The patient’s
fever defervesced, repeated blood and urine cultures
were negative, and he was discharged home on oral
trimethoprim/sulfamethoxazole: 2 double-strength
tablets twice daily for 10 days to complete a 14-day
course of culture-specific antibiotics appropriate for
a Gram-negative bacteremia and complex UTI. The
final diagnosis was UTI associated with urosepsis due
to fluoroquinolone-resistant E coli.
Recently, the delivery of radiation therapy has been
refined to tailor radiation fields to each patient and
to allow for the administration of escalated radiation
doses to targeted sites (eg, the prostate) while reducing
unnecessary exposure of adjacent organs. Dose escalation improves the efficacy and accuracy of radiation
therapy, thereby limiting adverse events to adjacent
organs such as the bladder and rectum.12-14 Of those
techniques, concomitant utilization of fiducial marker
placement and IMRT has allowed the radiation oncologist to adjust for real-time prostate motion during
therapy, which typically involves 1 to 5 minutes of
daily treatment 5 days per week over the course of 4 to
8 weeks. Increasingly, studies support this technique
as a simple, safe, and appropriate therapy.12-16 However, complications have been reported and include
urosepsis. Despite the risk of such severe infectious
complications, common minor infectious complications include fever (1.9%), UTI (3.2%), and prostatitis
(1.6%).16,17 A report of infectious complications following TRUS-guided prostatic biopsies, performed in
a similar setting and manner as TRUS-guided placement of fiducial markers, identified the rate of postprocedural sepsis due to fluoroquinolone-resistant E
coli as ranging from 0.1% to 0.9%.18 It has also been
noted that antibiotic prophylaxis significantly lessens
the rate of periprocedural infections affiliated with
TRUS-guided prostatic biopsies.3,18 Currently, the AUA
endorses the use of fluoroquinolone prophylaxis for
up to 24 hours surrounding transrectal procedures
involving the prostate, and 90.1% of urologists within
the United States are following this practice.19,20
234 Cancer Control
Sepsis is a rare complication after intraprostate
fiducial marker implantation. In a study of 1,021 patients who underwent intraprostatic fiducial marker
implantation, only 1 developed UTI and sepsis despite broad antibiotic prophylaxis with levofloxacin
and nitrofurantoin.17 Our patient exhibited urosepsis
secondary to a fluoroquinolone-resistant E coli strain
2 days after the TRUS-guided placement of intraprostatic fiducial markers, at which time a fluoroquinolone
(levofloxacin) had been administered. In accordance
with the AUA best practice guideline for prophylactic
antibiotic administration, a fluoroquinolone would be
the antimicrobial of choice prior to a TRUS-guided
prostate biopsy.19 As fiducial markers are inserted in
a similar fashion in which TRUS-guided biopsy of the
prostate is performed,13-15 and since there is a paucity
of data regarding infectious complications specifically
related to fiducial marker placement, it could be assumed that urologists employ similar antimicrobial
prophylaxis strategies prior to the execution of the
TRUS-guided placement of fiducial markers.
Fluoroquinolones are potent, penetrate prostatic tissue well, are orally administered, and have
long-lasting urinary bactericidal activity against both
Gram-positive and Gram-negative bacteria. Urologists
frequently use these antibiotics in prostate-related
procedures, including the intraprostatic placement
of fiducial markers.1,13,16 This practice is consistent
with the 2011 guidelines of the European Association
of Urology, which recommend fluoroquinolones —
with ciprofloxacin superior to ofloxacin — for the
prophylactic antibiotic used for prostate biopsy21 and
is supported by the AUA, which offers the alternate
regimen using a second- or third-generation cephalosporin. If the patient has been allergic to penicillin, a
combination of an aminoglycoside and metronidazole
or clindamycin is appropriate.19
With the widespread adoption of periprocedural
fluoroquinolone administration, it is important to
note that there are many studies describing the rising incidence of fluoroquinolone-resistant E coli sepsis.1,3-7,18,22-24 A retrospective review of 1,273 patients
undergoing TRUS-guided prostate biopsy with levofloxacin or gatifloxacin prophylaxis demonstrated a
2.4% rate of infectious symptoms after biopsy, 50%
of which were secondary to fluoroquinolone-resistant
microbes.4 In that same cohort, of those Gram-negative bacilli that were resistant to fluoroquinolones, 44%
were also resistant to trimethoprim/sulfamethoxazole.
However, 100% of these resistant bacterial strains were
susceptible to ceftriaxone, ceftazidime, cefotaxime,
and cefotetan.4 These findings are substantiated by
another recent retrospective trial that implicated E
coli as the most common pathogen of prostatitis after
TRUS-guided prostate biopsy, followed by Klebsiella
pneumonia and Staphylococcus epidermidis.2 Of the
July 2013, Vol. 20, No. 3
isolated Gram-negative organisms that were implicated, 85.7% were resistant to fluoroquinolone but were
highly sensitive to third-generation cephalosporins
such as ceftriaxone (85.7%) and were 100% susceptible to the carbapenems imipenem and meropenem.
This supports the assertion by Zaytoun et al5 that
posttransrectal prostate procedure infections should
be managed with broad-spectrum cephalosporins.
To prevent infectious complications, the utilization of enemas to mechanically reduce the bacterial content of the rectal vault has been investigated.
However, the work of Mosharafa et al2 did not demonstrate a significant difference in postprocedural
complications between those who received a preprocedural enema and those who did not (P = .061).
Prior use of a fluoroquinolone within 6 months before
the procedure was a significant finding in this study,
resulting in a 3.8 times higher risk of the development
of acute prostatitis after TRUS-guided prostate biopsy
(P = .042). This finding was not isolated.8,22 Further,
Patel et al8 also identified recent travel — specifically
overseas — as a risk factor for the development of
infections due to fluoroquinolone-resistant E coli.
Another proposal to reduce infectious complications is the utilization of targeted antibiotic prophylaxis. Although it is standard practice to defer
transrectal instrumentation of the prostate until an
individual demonstrates sterile urine, some researchers are now investigating the use of a preprocedural
rectal swab, particularly in patients at risk for harboring fluoroquinolone-resistant microbes, which has
demonstrated the presence of these microbes in 22%
of all patients infected.22 If the culture is positive,
then an alternative nonquinolone antibiotic can be
prescribed for antimicrobial prophylaxis; a practice
now applied at the Moffitt Cancer Center.
We reported on a rare case of sepsis after transrectal
ultrasound (TRUS)-guided placement of gold fiducial
markers within the prostate when preparing a patient
for intensity-modulated radiation therapy. Despite a
lack of specific guidelines with respect to antibiotic
prophylaxis prior to TRUS-guided placement of fiducial markers within the prostate, guidelines specific to
transrectal prostate biopsy are applicable due to the
inherent similarities between both procedures. Antibiotic prophylaxis using a fluoroquinolone or second- or
third-generation cephalosporin remains a mainstay
of transrectal prostate manipulation, allowing for
an acceptably low rate of infectious complications.
However, there should be an increased suspicion of
fluoroquinolone-resistant microbes in the setting of
fiducial marker placement, which is often performed
in subsequent close chronological proximity to TRUSguided prostate biopsies. At this time, antimicrobial
July 2013, Vol. 20, No. 3
prophylaxis is generally administered using a fluoroquinolone. If fevers, chills, tachycardia, and/or hypotension are present following the TRUS-guided placement of fiducial markers within the prostate, empirical
treatment should cover fluoroquinolone-resistant microbes and include a broad-spectrum cephalosporin,
carbapenem, or broad-spectrum penicillin, with or
without an aminoglycoside. Future preprocedure selection of antibiotic prophylaxis may be guided by a
culture or rapid-detection systems that can be used to
rule out the presence of a fluoroquinolone-resistant
organism within the rectum and should take into account a patient’s recent receipt of antimicrobials.
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Cancer Control 235
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