Ertapenem for Infections Caused by ESBL-producing Bacteria
Background: Infections caused by extended-spectrum β-lactamase (ESBL)–producing gram-negative organisms are a growing concern in hospitalized patients. Traditionally, these infections can be effectively treated by the carbapenem class of drugs. In 2005, our institution initiated a protocol for use of ertapenem, a carbapenem, as the first-line treatment option for these infections. It is unknown whether ertapenem is associated with similar clinical response and microbiologic cure rates as those achieved with group 2 carbapenems (imipenem, meropenem, doripenem).
Objective: To describe clinical response and microbiologic cure rates associated with ertapenem as first-line treatment of infections caused by ESBL-producing organisms.
Methods: This case series included patients who received ertapenem for more than 48 hours to treat a documented infection with a positive culture for an ESBL-producing organism. Efficacy was determined by the clinical response and microbiologic cure rates achieved with ertapenem.
Results: Seventy-three patients received ertapenem for a mean (SD) of 10.7 (5.9) days. The most common (59%) infection site was urine. The most common causative organisms were ESBL-producing Klebsiella pneumoniae (47%) and Escherichia coli (48%). Clinical response was observed in 78% of patients. Microbiologic cure was achieved in 92% of the evaluable population (n = 50). There were no significant differences in clinical or microbiologic cure rates across important subgroups.
Conclusions: Patients treated with ertapenem achieved favorable clinical response and microbiologic cure rates. Our data suggest that ertapenem can be used as an alternative to group 2 carbapenems for the treatment of infections caused by ESBL-producing gram-negative organisms.
Infections caused by extended-spectrum β-lactamase (ESBL)–producing gram-negative bacteria are occurring more frequently in hospitalized patients. These organisms can cause a variety of infections including, but not limited to, pneumonia, urinary tract infections, intraabdominal infections, and bacteremia. Carbapenems are considered the drugs of choice for ESBL-producing bacteria. Existing data demonstrate high (80-100%) clinical response rates and microbiologic cure with group 2 carbapenems such as imipenem and meropenem. With their continued use as first-line agents, concerns have arisen over maintaining their coverage against Pseudomonas aeruginosa and the potential for selecting multidrug-resistant strains. Ertapenem, a group 1 carbapenem with a narrower spectrum of activity, has a low minimum inhibitory concentration (MIC) against these organisms, making it very promising as a first-line agent.
Existing data have suggested high clinical success rates associated with ertapenem but these studies are limited by small sample sizes as well as both selection bias and significant pretreatment effect with a group 2 carbapenem. To date, there are insufficient data describing clinical and microbiologic outcomes with the use of ertapenem as a first-line agent for the management of ESBL-producing gram-negative organisms. Several in vitro studies have evaluated ertapenem and have shown excellent in vitro susceptibility to ESBL-producing Escherichia coli and Klebsiella pneumoniae with comparable MIC90 to that of group 2 carbapenems.
In 2005, our institution initiated a protocol for the use of ertapenem as a first-line agent for management of infections caused by ESBL-producing gram-negative organisms and concomitantly restricted use of imipenem. The ertapenem protocol was instituted in response to an increasing number of ESBL infections and the observed need for a narrower spectrum carbapenem as a first-line agent for the treatment of ESBL-producing organisms, and it allowed for the faster consolidation of empiric antibiotics. This protocol also restricted ertapenem use to approval by an infectious diseases physician for documented ESBL infections. It was not permitted for empiric use in other indications such as intraabdominal infections, except in the case of a history of ESBL infections. In conjunction, use of imipenem required prior approval by the infectious diseases service or antibiotic stewardship team.
We describe our institutional experience with clinical response and microbiologic cure rates of infections caused by ESBL-producing gram-negative bacteria when treated with ertapenem as a first-line agent.
Abstract and Introduction
Abstract
Background: Infections caused by extended-spectrum β-lactamase (ESBL)–producing gram-negative organisms are a growing concern in hospitalized patients. Traditionally, these infections can be effectively treated by the carbapenem class of drugs. In 2005, our institution initiated a protocol for use of ertapenem, a carbapenem, as the first-line treatment option for these infections. It is unknown whether ertapenem is associated with similar clinical response and microbiologic cure rates as those achieved with group 2 carbapenems (imipenem, meropenem, doripenem).
Objective: To describe clinical response and microbiologic cure rates associated with ertapenem as first-line treatment of infections caused by ESBL-producing organisms.
Methods: This case series included patients who received ertapenem for more than 48 hours to treat a documented infection with a positive culture for an ESBL-producing organism. Efficacy was determined by the clinical response and microbiologic cure rates achieved with ertapenem.
Results: Seventy-three patients received ertapenem for a mean (SD) of 10.7 (5.9) days. The most common (59%) infection site was urine. The most common causative organisms were ESBL-producing Klebsiella pneumoniae (47%) and Escherichia coli (48%). Clinical response was observed in 78% of patients. Microbiologic cure was achieved in 92% of the evaluable population (n = 50). There were no significant differences in clinical or microbiologic cure rates across important subgroups.
Conclusions: Patients treated with ertapenem achieved favorable clinical response and microbiologic cure rates. Our data suggest that ertapenem can be used as an alternative to group 2 carbapenems for the treatment of infections caused by ESBL-producing gram-negative organisms.
Introduction
Infections caused by extended-spectrum β-lactamase (ESBL)–producing gram-negative bacteria are occurring more frequently in hospitalized patients. These organisms can cause a variety of infections including, but not limited to, pneumonia, urinary tract infections, intraabdominal infections, and bacteremia. Carbapenems are considered the drugs of choice for ESBL-producing bacteria. Existing data demonstrate high (80-100%) clinical response rates and microbiologic cure with group 2 carbapenems such as imipenem and meropenem. With their continued use as first-line agents, concerns have arisen over maintaining their coverage against Pseudomonas aeruginosa and the potential for selecting multidrug-resistant strains. Ertapenem, a group 1 carbapenem with a narrower spectrum of activity, has a low minimum inhibitory concentration (MIC) against these organisms, making it very promising as a first-line agent.
Existing data have suggested high clinical success rates associated with ertapenem but these studies are limited by small sample sizes as well as both selection bias and significant pretreatment effect with a group 2 carbapenem. To date, there are insufficient data describing clinical and microbiologic outcomes with the use of ertapenem as a first-line agent for the management of ESBL-producing gram-negative organisms. Several in vitro studies have evaluated ertapenem and have shown excellent in vitro susceptibility to ESBL-producing Escherichia coli and Klebsiella pneumoniae with comparable MIC90 to that of group 2 carbapenems.
In 2005, our institution initiated a protocol for the use of ertapenem as a first-line agent for management of infections caused by ESBL-producing gram-negative organisms and concomitantly restricted use of imipenem. The ertapenem protocol was instituted in response to an increasing number of ESBL infections and the observed need for a narrower spectrum carbapenem as a first-line agent for the treatment of ESBL-producing organisms, and it allowed for the faster consolidation of empiric antibiotics. This protocol also restricted ertapenem use to approval by an infectious diseases physician for documented ESBL infections. It was not permitted for empiric use in other indications such as intraabdominal infections, except in the case of a history of ESBL infections. In conjunction, use of imipenem required prior approval by the infectious diseases service or antibiotic stewardship team.
We describe our institutional experience with clinical response and microbiologic cure rates of infections caused by ESBL-producing gram-negative bacteria when treated with ertapenem as a first-line agent.
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