Therapeutic Challenges Associated with Extended‐Spectrum, β‐Lactamase‐Producing Escherichia coli and Klebsiella pneumoniae

Abstract

The emergence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae, presents significant diagnostic and therapeutic challenges to the management of infections due to these organisms. Detection of resistant isolates is difficult based on routine susceptibility testing performed by a clinical microbiology laboratory. In addition, the utility of penicillins, cephalosporins, and aztreonam in treating serious infections due to these organisms is uncertain due to reports of treatment failure despite apparent in vitro susceptibility. A critical evaluation of the English literature was performed on treatment outcomes associated with ESBL-producing Enterobacteriaceae. Imipenem and extended-spectrum cephalosporins were commonly administered. Discordant outcomes in relation to in vitro susceptibility of the agent did not occur exclusively with cephalosporins but with all drugs including imipenem. Until more outcome data are available, drug selection must take into consideration whether or not an outbreak is occurring and whether therapy is empirical or definitive.

The continuing challenge of ESBLs

“…Based on retrospective and prospective analyses, carbapenems should be considered as the preferred treatment for infections due to ESBLproducing enterobacteria [87,92]. In an international study conducted by Paterson et al that includes ESBL-producing K. pneumoniae bloodstream isolates, patients who were treated with imipenem/cilistatin during the 5-day period after onset of infections had a 14-day mortality of 4.8%, compared with 27.6% when another in vitro active beta-lactam was used [80].…”

Extended-Spectrum β-Lactamases and Clinical Outcomes: Current Data

“…On the basis of a survey of the relevant clinical literature by Wong-Beringer [4], the carbapenems, especially imipenem, have demonstrated a relatively high rate of clinical success among patients infected with ESBL-producing E. coli or K. pneumoniae. Of 80 patients who received treatment with an imipenem-containing regimen, all but 3 had a favorable response or were cured.…”

“…Nevertheless, the clinical significance of infections caused by ESBL-producing bacteria remains unclear, primarily because few prospective studies have been designed specifically to evaluate clin- ical outcomes among a statistically meaningful number of patients [2,3]. Studies of this kind are essential for developing consensus guidelines (which are not currently available) for the treatment of infection due to ESBL-producing bacilli.A critical examination of the literature provides divergent views of the role of ESBL carriage in death and suggests that ESBL production may have its most marked effect on ceftazidime, but this could be a geographic or enzyme-specific variation [3,4]. The present review summarizes recent reports in the medical literature related to the clinical significance of ESBL expression and describes strategies for the treatment of infections caused by ESBL-producing pathogens.…”

Extended spectrum β-lactamase–producing Klebsiella pneumoniae chronic ambulatory peritoneal dialysis peritonitis treated successfully with polymyxin B

“…The reason for the increased adverse results are, in part, because of the delay in the initiation of appropriate antibiotic therapy secondary to delays in detecting the ESBL-producing strains. 12,13 Risk factors for acquiring infections with ESBLproducing organisms include length of stay in hospital, chronic care facilities, and use of ventilators, catheters, or cannulae. Previous exposure to some antibiotics can result in selective pressure that leads to ESBL-producing organisms.…”