Title: Assessment of doripenem, meropenem, and imipenem against respiratory isolates of <i>Pseudomonas aeroginosa</i> in a tertiary care hospital of north India
Abstract: Communication IntroductIonPseudomonas aeruginosa is one of the leading pathogens causing healthcare-associated infections particularly in immunocompromised and the critically ill patients.It is one of the most prevalent pathogens in nosocomial pneumonia, especially in patients with high-risk factors such as mechanical ventilation or catheter intubation.It has been acquiring multidrug resistance (MDR) at an alarming rate, raising much clinical concern as effective antimicrobial agents are limited and dwindling. [1] The development of carbapenem resistance, against P. aeruginosa infections is worrisome. [2]rbapenem resistance can be due to the production of enzymes, such as AmpC or a metallo-β-lactamase; overexpression of efflux pumps; porin deficiencies; or target site alterations.One of the major risk factors for carbapenem resistance is carbapenem use itself resulting in selective pressure on bacterial populations. [3]terature suggests, doripenem is an antipseudomonal carbapenem that has greater in vitro activity against P. aeruginosa isolates than other carbapenems and is less likely to select for carbapenem-resistant strains under experimental conditions. [4,5]Its 1-β-methyl side chain provides resistance to dehydropeptidase so that this molecule does not require the addition of cilastatin for protection from this enzyme.It is also remarkably stable after reconstitution, increasing the opportunity for prolonged infusion.The recommended dosing for doripenem is 0.5 g every 8 h (administered through 1 or 4 h infusions). [5]ripenem has been described as having the favorable attributes of both imipenem and meropenem against both Gram-positive and Gram-negative bacteria. [6]Data Objective: Pseudomonas aeruginosa is one of the leading pathogen causing healthcare-associated infections, particularly in immunocompromised and critically ill patients.The development of carbapenem resistance in P. aeruginosa infections is worrisome.Data specifically comparing the susceptibility of the three available carbapenems are lacking in the Indian subcontinent.Materials and Methods: We evaluated the minimum inhibitory concentrations (MICs) of the three commonly used carbapenems-imipenem, meropenem, and doripenem against, 435 P. aeruginosa isolates obtained from respiratory samples and compared their susceptibility patterns to determine the best possible carbapenem among those available that may be used in combination regimes.Results: Overall, 222 (51.0%) of isolates were susceptible to doripenem followed by imipenem 206 (47.3%) and meropenem 195 (44.8%), respectively.Two hundred and sixty-two (60.23%) strains were intermediate or resistant to at least one carbapenem.The MIC 90 of all three carbapenems was >32 µg/ml while the MIC 50 of meropenem was 16 µg/ml which was higher than MIC 50 of both imipenem (4 µg/ml) and doripenem (2 µg/ml).Conclusion: Our study revealed that doripenem exerted better in vitro activity against the tested bacteria compared to imipenem and meropenem, but the difference was not statistically significant.