Levofloxacin resistant Escherichia coli sepsis following an ultrasound-guided transrectal prostate biopsy: Report of four cases and review of the literature

Authors


Tetsuya Miura md, Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki Cho, Chuo Ku, Kobe City 650-0017, Japan. Email: zet1212@yahoo.co.jp

Abstract

Abstract:  Fluoroquinolones are the most commonly used prophylactic antimicrobials for ultrasound-guided transrectal prostate biopsy due to their broad pathogen spectrum, pharmacokinetics, bioavailability and ease of oral administration. However, although Escherichia. coli (E. coli) is the most common pathogen associated with infections after transrectal prostate biopsy, the prevalence of fluoroquinolone resistant strains of E. coli is increasing. Levofloxacin resistant E. coli sepsis occurred in four (0.6%) of 665 patients who received oral levofloxacin prophylaxis and underwent transrectal prostate biopsy from July 2002 to December 2006 in this institute. All patients had obstructions of the lower urinary tract and three of the four had a history of previous use of quinolones. Although two of the four patients developed septic shock, all of the patients were treated with carbapenems immediately and made a complete recovery. Since a case of multiresistant E. coli sepsis and fatal anaerobic sepsis after transrectal prostate biopsy had been reported, intravenous carbapenem is recommended as antimicrobial therapy for sepsis after transrectal prostate biopsy.

Introduction

With the widespread popularity of prostate specific antigen (PSA) testing, an ultrasound-guided transrectal prostate biopsy (TPB) has become one of the most common urological procedures. Infectious complications of TPB are not unexpected. It has been reported that the incidence of febrile genitourinary infection ranges from 0.1% to 7%,1 with Escherichia coli (E. coli) being the most common organism.1 It is commonly accepted that the use of a prophylactic antimicrobial agent will lower the incidence of post biopsy infection, but little consensus exists as to the most appropriate antimicrobial regimens. Many drugs and drug regimens have been proposed. Fluoroquinolones are the most commonly used because of their broad spectrum of action and excellent bioavailability in the prostate.2 However, the prevalence of fluoroquinolone resistant E. coli is increasing. This report documents four cases of sepsis caused by levofloxacin (LVFX) resistant E. coli complicating TPB and reviews the relevant published reports.

Case reports

None of the patients had either bacteriuria or pyuria before TPB. All patients received oral levofloxacin prophylaxis, either at 300 mg/day for three days (case 1) or 600 mg/day for one day (cases 2–4). LVFX was taken orally 1 h before TPB and at 2 h and 8 h following the TPB. In case 1, oral administration continued for two days after TPB. LVFX resistant E. coli was isolated from both blood and urine in all cases.

Case 1

A 60-year-old man underwent a repeat TPB. He developed a high fever (39.6°C) the next evening following the biopsy. He immediately went to the hospital and was administered intravenous imipenem/cilastatin sodium (IPM/CS). After the administration of 1 g of IPM/CS daily for five days, he made a full recovery.

Case 2

A 58-year-old man underwent a repeat TPB. He developed chills and fever (40.0°C) the next evening after the biopsy, but he did not come to the hospital. Three days after the procedure he was found unconscious and was admitted to the hospital. He had hypoxemia and his blood pressure was low (80/55 mmHg). Laboratory data showed leukopenia and disseminated intravascular coagulation (DIC). He was immediately started on intravenous meropenem (MEPM). After the administration of MEPM, 1.5 g daily for four days and 1.0 g daily for four days, he made a complete recovery.

Case 3

A 79-year-old man in the course of steroid therapy for pemphigus foliaceus underwent a TPB. He developed a high fever (38.0°C) the next evening after the biopsy. Two days post biopsy he came to our hospital with fevers and rigors. His blood pressure was decreased (80/53 mmHg). Hypoxemia and DIC were not observed. He was immediately treated with intravenous IPM/CS. After the administration of 1.5 g IPM/CS daily for seven days, he made a full recovery.

Case 4

A 77-year-old man underwent a repeat TPB. Three days after the procedure he developed a high fever (38.0°C) and was admitted to the hospital. He was immediately started on intravenous MEPM. His blood and urine culture were negative for organisms. After the administration of 1.0 g MEPM daily for five days, the fever stabilized and he was discharged. Thirteen days after the TPB he was rehospitalized with fevers and rigors. He was immediately administered intravenous biapenem (BIPM). Both his blood and urine culture were positive for LVFX resistant E. coli. After administration of 0.9 g BIPM daily for two days and 0.6 g daily for three days, he made a complete recovery.

Susceptibility testing

Antimicrobial susceptibility testing was performed by the reference broth liquid microdilution method as described by the National Committee for Clinical Laboratory Standards (NCCLS).3 Isolated E. coli was deemed resistant only when the zones of inhibition were less than or equal to the resistance breakpoint recommended by the NCCLS guidelines.3

Discussion

Fluoroquinolones, which are effective against most of the expected Gram-negative and Gram-positive strains causing urinary tract infection, have excellent bioavailability in the prostate.4 In addition, since they are rapidly and completely absorbed from tablet formulations, oral and intravenous administration of fluoroquinolones have been considered interchangeable.4 Therefore, fluoroquinolones are the most common prophylactic antimicrobials used for a TPB because of their broad spectrum, pharmacokinetics, bioavailability and ease of oral administration. Shandera et al. surveyed 568 randomly selected American urologists and noted that 90.1% administered fluoroquinolones.2

However, although E. coli is the most common pathogen associated with infections after TPB, the prevalence of fluoroquinolone resistant strains of E. coli is increasing. In our institute, the rate of LVFX resistant strains among E. coli isolated from urine was 26.3% in 2006 (data not shown). Fluoroquinolone resistant E. coli have been shown to be highly prevalent in food animals given feed containing fluoroquinolone.5 Given the widespread use of fluoroquinolones in both humans and animals, it is probable that fluoroquinolone resistant E. coli are increasingly likely to be present in the colonic flora.5 In this setting, fluoroquinolone resistant E. coli infection after a TPB might be increasing, however, only two case reports of quinolone resistant E. coli sepsis complicating a TPB have been reported.6,7

Six hundred and sixty-five patients underwent a TPB from July 2002 to December 2006 in this institute. All patients received oral levofloxacin prophylaxis, either at 600 mg/day for one day or 300 mg/day for three days. Sepsis occurred in four (0.6%) patients and all of them were caused by LVFX resistant E. coli. The patients' characteristics are shown in Table 1. The risk factors for acquisition of urinary tract infection caused by quinolone resistant E. coli were identified by Ena et al. They reported that previous use of quinolones and the presence of a urinary tract disorder (prostatic obstruction, lithiasis, neoplasm, and recurrent urinary tract infection) were the strongest risk factors.8 In the four cases described in this report, all of the patients had an obstruction of the lower urinary tract and three of the four patients had a history of previous use of quinolones. It is important to evaluate those prebiopsy patient-related risk factors by obtaining a thorough history. In patients at high risk for quinolone resistant E. coli infection, combination prophylaxis of quinolones and intravenous broad spectrum agents such as piperacillin-tazobactam or carbapenem should be considered.

Table 1.  Patients characteristics
  1. LVFX, levofloxacin; MINO, minocycline; PIN, prostatic intraepithelial neoplasia; PSA, prostate specific antigen; SPFX, sparfloxacin.

Patient No.1234
Age60587977
History of biopsySecondSecondFirstSecond
PSA5.3 ng/ml7.8 ng/ml33.0 ng/ml9.6 ng/ml
Prostate volume46.7 ml31.2 ml63.7 ml39.3 ml
Max flow rate8.5 ml/s13.9 ml/s7.4 ml/s10.9 ml/s
PathologyNo malignancyNo malignancyPINNo malignancy
Past historyPemphigus foliaceus
Antimicrobial history (time)LVFX (1 year ago)SPFX (2 months ago)MINO (2 months ago)LVFX (2 years ago)

Though patients no. 2 and 3 delayed seeking medical attention and developed septic shock, all of the patients were administered carbapenems immediately and made a complete recovery. The antimicrobial susceptibility of LVFX resistant E. coli isolated from these four patients is shown in Table 2. Two cases of sepsis following a TPB caused by multiresistant E. coli with resistance to penicillins, cephalosporins, aminoglycosides and fluoroquinolones have been reported. The strains were sensitive to carbapenems.6 In addition, three cases of fatal anaerobic sepsis after a TPB have been reported.9 It was also reported that carbapenems are highly active against anaerobic bacteria (resistance rate, <0.5%), whereas low susceptibility rates were noted for ciprofloxacin (resistance rate, 75%).10 Therefore, the recommended antimicrobial therapy for sepsis following a TPB is intravenous carbapenems.

Table 2.  Antimicrobial susceptibility of levofloxacin resistant Escherichia coli isolated from four cases
  1. R, resistant; S, sensitive.

Pt No.1234
levofloxacinRRRR
ampicillinRRRR
piperacillinRRRR
cefazolinRSSS
cefmetazoleSSSS
ceftazidimeSSSS
amikacinSSSS
minocyclineRRRS
imipenemSSSS

The incidence of sepsis following a TPB is low, but it is potentially fatal. If treatment is delayed or inadequate therapy is administered, patients will develop septic shock which could be fatal. However, early appropriate antimicrobial therapy is usually successful. In order to perform early treatment, it is important to inform them the risk of infectious complications after a TPB and to caution them to consult a hospital immediately if fever occurs within at least two weeks following a TPB. Quinolone resistant organisms will continue to be a problem after a TPB, and urologists must exert more effort to prevent and treat such infections by obtaining a careful history, cautious informed consent, and appropriate antimicrobial treatment such as intravenous carbapenems.

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