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. This is due to ertapenem's molecular structure, which differs slightly from other carbapenems, resulting in reduced binding affinity to penicillin-binding proteins in Pseudomonas. 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. Alternatively, antipseudomonal agents such as piperacillin-tazobactam, cefepime, ceftazidime, ciprofloxacin, or combination therapy might be appropriate depending on the infection site, severity, and local resistance patterns. When treating suspected or confirmed Pseudomonas infections, it's essential to choose an agent with reliable antipseudomonal activity to ensure effective treatment, as recommended by guidelines such as those from the Infectious Diseases Society of America and the American Thoracic Society 1.

Some key points to consider when choosing an antibiotic for Pseudomonas infections include:

• The severity of the infection and the patient's underlying health status
• Local resistance patterns and antimicrobial susceptibility testing results 1
• The potential for adverse effects and interactions with other medications
• The need for combination therapy in certain cases, such as in patients with risk factors for Pseudomonas infection 1

In general, the choice of antibiotic should be guided by the most recent and highest-quality evidence available, taking into account the specific clinical context and patient needs. In this case, the most recent guideline from 2019 recommends using two antipseudomonal antibiotics to treat CAP due to P. aeruginosa because of the risk of non-susceptibility to a single antipseudomonal agent 1. However, the specific choice of antibiotic will depend on various factors, including the patient's medical history, the severity of the infection, and local resistance patterns.

From the FDA Drug Label

Ertapenem has in vitro activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. 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 However, the efficacy of ertapenem in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials: 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

• Pseudomonas aeruginosa is not listed as a susceptible organism in the provided text.
• The FDA drug label does not provide information that directly supports the use of ertapenem against Pseudomonas aeruginosa. The FDA drug label does not answer the question.

From the Research

Ertapenem Coverage for Pseudomonas aeruginosa

• Ertapenem, also known as Invanz, has limited coverage against Pseudomonas aeruginosa compared to other carbapenems such as imipenem and meropenem 2.
• A study published in 2004 found that ertapenem was less effective against multiple-resistant P. aeruginosa isolates compared to imipenem and meropenem, with resistance rates of 59.2% and 57.4% by disk diffusion and MicroScan methods, respectively 3.
• Another study published in 2007 noted that ertapenem lacks activity against Pseudomonas aeruginosa and Enterococcus spp., making it less suitable for treating nosocomial infections caused by these pathogens 2.
• In vitro experiments have shown that ertapenem can select for P. aeruginosa mutants with cross-resistance to imipenem and meropenem, but this selectivity is minimized under clinical conditions due to the drug's strong protein binding and rapid decline in serum concentration 4.
• A multicenter study published in 2010 found no association between ertapenem use and changes in antipseudomonal carbapenem susceptibility rates in 25 hospitals, suggesting that ertapenem use does not significantly impact the development of resistance to other carbapenems in P. aeruginosa 5.
• A review of the evidence published in 2012 concluded that ertapenem use does not result in decreased Pseudomonas susceptibility to other carbapenems, based on results from ten clinical studies evaluating the effect of ertapenem use on P. aeruginosa susceptibility 6.