Does ertapenem (Invanz) cover Pseudomonas aeruginosa?

From the Guidelines

Ertapenem does not provide reliable coverage against Pseudomonas aeruginosa. Unlike other carbapenems such as meropenem, imipenem, and doripenem, ertapenem has limited activity against Pseudomonas species due to its molecular structure and pharmacokinetic properties 1. If Pseudomonas coverage is needed, alternative carbapenems like meropenem (1g IV every 8 hours) or imipenem-cilastatin (500mg IV every 6 hours) should be used instead. This distinction is important in clinical practice, particularly when treating infections in settings where Pseudomonas is a concern, such as healthcare-associated pneumonia, febrile neutropenia, or complicated intra-abdominal infections in high-risk patients.

Key Points to Consider

• Ertapenem's lack of activity against Pseudomonas is related to its reduced ability to penetrate the outer membrane of this gram-negative organism and its susceptibility to efflux pumps that remove the antibiotic from bacterial cells.
• While ertapenem remains effective against many other gram-negative and gram-positive pathogens, including ESBL-producing Enterobacteriaceae, its Pseudomonas gap is a critical limitation to consider when selecting antimicrobial therapy.
• The choice of empiric antibiotic regimens in patients with intra-abdominal infections should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1.
• Carbapenems, such as meropenem and imipenem-cilastatin, offer a wide spectrum of antimicrobial activity against gram-positive and gram-negative aerobic and anaerobic pathogens, including Pseudomonas aeruginosa, and are considered the agents of choice for multidrug-resistant infections caused by Enterobacteriaceae 1.

From the FDA Drug Label

Ertapenem has in vitro activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. The following in vitro data are available, but their clinical significance is unknown At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ertapenem Gram-negative bacteria: Escherichia coli Haemophilus influenzae (beta-lactamase negative isolates only) Klebsiella pneumoniae Moraxella catarrhalis Proteus mirabilis The following in vitro data are available, but their clinical significance is unknown At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ertapenem Gram-negative bacteria: Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Enterobacter cloacae Haemophilus influenzae (beta-lactamase positive isolates only) Haemophilus parainfluenzae Klebsiella oxytoca (excluding ESBL producing isolates) Morganella morganii Proteus vulgaris Providencia rettgeri Providencia stuartii Serratia marcescens

Ertapenem does not cover Pseudomonas. The bacteria listed as susceptible to ertapenem do not include Pseudomonas aeruginosa. 2

From the Research

Ertapenem Coverage for Pseudomonas

• Ertapenem is a carbapenem antibiotic, but it does not cover Pseudomonas aeruginosa as effectively as other carbapenems like imipenem or meropenem 3.
• Studies have shown that ertapenem can select for Pseudomonas mutants with cross-resistance to other carbapenems, but this selectivity is minimized under clinical conditions due to the drug's strong protein binding 4.
• The optimal treatment for Pseudomonas aeruginosa infections involves the use of antipseudomonal antibiotics such as ceftazidime, piperacillin-tazobactam, or carbapenems like imipenem or meropenem 5, 6.
• In cases where Pseudomonas aeruginosa is resistant to imipenem, alternative treatments like piperacillin-tazobactam may be effective, especially when the minimum inhibitory concentration (MIC) is low 7.

Carbapenem Resistance and Pseudomonas

• The use of carbapenems like ertapenem can lead to the selection of resistant Pseudomonas strains, highlighting the need for antimicrobial stewardship to preserve the effectiveness of these antibiotics 3, 4.
• The emergence of carbapenem-resistant Pseudomonas aeruginosa strains necessitates the development of new antibiotics and treatment strategies, such as combination therapy or bacteriophage therapy 6.