Clinical Studies
Carbapenems and piperacillin/tazobactam for the treatment of bacteremia caused by extended-spectrum β-lactamase–producing Proteus mirabilis

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Abstract

This study was intended to delineate the role of carbapenems and piperacillin/tazobactam in treating bacteremia caused by extended-spectrum β-lactamase (ESBL)–producing Proteus mirabilis. We performed a multicenter and retrospective study of the patients with ESBL-producing P. mirabilis bacteremia. The outcomes of the patients treated by piperacillin/tazobactam or a carbapenem for at least 48 hours and the MICs of the prescribed drugs for these isolates were analyzed. Forty-seven patients with available clinical data were included. The overall 30-day mortality rate was 29.8%. All available isolates (n = 44) were susceptible to ertapenem, meropenem, and doripenem, and 95.6% were susceptible to piperacillin/tazobactam; however, only 11.4% of the isolates were susceptible to imipenem. Among the 3 patients infected with isolates exhibiting non-susceptibility to imipenem (MIC ≥2 mg/L) who were treated with imipenem, none died within 28 days. The 30-day (14.3% versus 23.1%, P = 0.65) or in-hospital (19.1% versus 30.8%, P = 0.68) mortality rate of 21 patients treated by a carbapenem was lower than that of 13 treated by piperacillin/tazobactam. However, among those treated by piperacillin/tazobactam, the mortality rate of those infected by the isolates with lower piperacillin/tazobactam MICs (≤0.5/4 mg/L) was lower than that of the isolates with MICs of ≥1/4 mg/L (0%, 0/7 versus 60%, 3/5; P = 0.045). ESBL-producing P. mirabilis bacteremia is associated with significant mortality, and carbapenem therapy could be regarded as the drugs of choice. The role of piperacillin/tazobactam, especially for the infections due to the isolates with an MIC ≤0.5/4 mg/L, warrants more clinical studies.

Introduction

Proteus mirabilis, a member of the Enterobacteriaceae family, is a common cause of community- and healthcare-associated infections, including urinary tract infection and bacteremia (Chen et al., 2012). The prevalence of extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae isolates, although varied across in different geographic regions, increased worldwide in recent years (Lee et al., 2012, Liu et al., 2012, Sheng et al., 2013, Wang et al., 2011). Patients with infections caused by such pathogens were associated with delay in appropriate antimicrobial therapy due to multiple drug resistance and subsequently increased risks of clinical failure and mortality (Endimiani et al., 2005, Lee et al., 2012, Tumbarello et al., 2007, Wang et al., 2011). Cephalosporin therapy for infections due to ESBL-producing Escherichia coli, Klebsiella pneumoniae, or Klebsiella oxytoca has been associated with clinical failure and increased mortality. Therefore, the Clinical and Laboratory Standards Institute (CLSI) had recommended reporting ESBL-producing E. coli or Klebsiella isolates as being resistant to all penicillins, cephalosporins, and aztreonam (Gavin et al., 2006, Peterson, 2008). The rationale behind the recommendation of carbapenem therapy for all ESBL-producer infections, however, has been based solely on limited clinical experiences (Peterson, 2008, Rupp and Fey, 2003). Despite the CLSI recommendation that ESBL-producing isolates could be reported as being susceptible to β-lactam/β-lactamase inhibitors, many experts preferred carbapenems, but not β-lactam/β-lactamase inhibitors, to treat ESBL-producer infections (Gavin et al., 2006, Peterson, 2008). However, the increased carbapenem prescriptions have been associated with the emergence of carbapenem-resistant Enterobacteriaceae (CDC, 2013). Other antimicrobial agents, such as ampicillin/sulbactam, cefoperazone/sulbactam, or piperacillin/tazobactam, may be the alternative agents for ESBL-producing Enterobacteriaceae infections. Several studies had addressed the clinical role of piperacillin/tazobactam therapy for ESBL-producing Enterobacteriaceae infections (Gavin et al., 2006, Peterson, 2008), but no consensus was made. The aim of this study was to evaluate clinical outcome of adults with ESBL-producing P. mirabilis bacteremia treated by piperacillin/tazobactam or a carbapenem, in correlation with the MIC of treatment drug for the corresponding isolate.

Section snippets

Study design and settings

This retrospective study was conducted at 5 hospitals in Taiwan, including National Taiwan University Hospital and Far Eastern Memorial Hospital in northern Taiwan, National Cheng Kung University Hospital, Kaohsiung Medical University Hospital, and Chi-Mei Medical Center in southern Taiwan. During January 2005 to December 2012, adults (aged ≥18 years) with bacteremia due to ESBL-producing P. mirabilis were enrolled. Demographics, clinical characteristics, underlying disease, primary sources,

Results

During the study period, a total of 52 patients with ESBL-producing P. mirabilis bacteremia were identified. Five patients with incomplete clinical information were excluded. Eight P. mirabilis isolates from 8 patients were not preserved for further study. All patients received guideline concordant doses with appropriate renal function adjustment. For piperacillin-tazobactam, patients with creatinine clearance (Ccr) of >50 mL/min received 3.375–4.5 g every 6–8 hours, those with Ccr of 20–50

Discussion

Some studies had tried to identify the predictors of mortality in patients with ESBL-producing Enterobacteriaceae bacteremia (De Rosa et al., 2011, Tumbarello et al., 2007). However, ESBL-producing P. mirabilis was responsible for only 15.6%, 12.9% in the study population, respectively (De Rosa et al., 2011, Tumbarello et al., 2007). Other studies focused on the differences between ESBL-producing P. mirabilis bacteremia and non–ESBL-producer bacteremia (Endimiani et al., 2005, Kurihara et al.,

Competing interests

The authors declare that they have no competing interests.

Ethics statement

This study was approved by the Institutional Review Board of the National Taiwan University Hospital (NTUH IRB 201005033R).

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