Antibacterial effect of meropenem and imipenem on Proteus mirabilis

Abstract

Phase-contrast microscopy, killing-curves and turbidimetric growth-curves were used in a comparative study of the antibacterial effects of a new carbapenem, meropenem (SM 7338) and imipenem on five strains of Proteus mirabilis. Despite the low MIC (0.2 mg/l) of imipenem for the five strains included in our study, the MBC remained relatively high (4.4 mg/l). During the first few hours of incubation, imipenem induced large lemon-shaped cells while the turbidity increased without substantial changes in culture viability. Later, most of the cell-wall deficient bacteria generated small spheroplasts until the antibiotic concentration exceeded 32 times the MIC. The MIC of meropenem was lower (0.03 mg/l) with an MBC (0.08 mg/l) very close to the MIC. Meropenem also induced large bodies but these cell-wall deficient bacteria did not generate small round bodies as observed with imipenem. In conclusion, imipenem produced in strains of Pr. mirabilis an amdinocillin-like change in cell morphology, responsible for the discrepancies observed between MIC and MBC. This effect was not observed with meropenem.

Morphological changes induced by imipenem and meropenem at sub-inhibitory concentrations in Acinetobacter baumannii

“…In the present study, both carbapenems induced substantial changes on the surface of all A. baumannii strains tested, resulting in the formation of spheroplasts > 3 lm in size. These results agree with those reported with other Gram-negative bacilli, and can therefore be considered to represent a specific characteristic of carbapenems [8][9][10][11].…”

“…Imipenem showed higher activity than meropenem against SS at 0.25· (89 ± 8 vs. 54 ± 15; p 0.016), 0.5· (92 ± 9 vs. 72 ± 7; p 0.003) and 1· the MIC (93 ± 8 vs. 75 ± 7; p 0.003), while meropenem was more active against RS at 0.25· (85.6 ± 3.5 vs. 13.5 ± 4; p < 0.0001), 0.5· (95 ± 2 vs. 9 ± 3; p < 0.0001) and 1· the MIC (97 ± 2.5 vs. 80 ± 5; p 0.01). This differential activity has also been observed with Proteus mirabilis [8], and it was hypothesised that it could result from the different PBP affinities of imipenem (which binds exclusively to PBP2) and meropenem (which binds primarily to PBP2, but also to PBP3). In the present study, both carbapenems induced substantial changes on the surface of all A. baumannii strains tested, resulting in the formation of spheroplasts > 3 lm in size.…”

Imipenem and Meropenem: Comparison of In Vitro Activity, Pharmacokinetics, Clinical Trials and Adverse Effects

“…Meropenem and imipenem are bactericidal against susceptible organisms as demonstrated by time-kill curve studies with Enterobacteriaceae (8)(9)(10). Both agents cause bacterial lysis in susceptible organisms by binding with high affinity to high molecular weight penicillin-binding proteins (PBPs).…”

“…Against Gram-positive aerobes, imipenem is in general two-to fourfold more active than meropenem (Table 1) (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)16,17,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Neither agent is active against MRSA or methicillin-resistant Staphlyococcus epidermidis.…”

Patrones de susceptibilidad antimicrobiana de bacterias gramnegativas aisladas de infecciones del tracto urinario en Venezuela: Resultados del estudio SMART 2009-2012

“…Esta resistencia inusual de P. mirabilis, no descrita anteriormente en Venezuela, podría estar relacionado con la degradación del antimicrobiano a través del tiempo o la concentración de Zinc en el medio, reportando falsa resistencia a imipenem, lo cual ya ha sido reportada para otras especies 43,44 . Sin embargo, hay que considerar lo referido anteriormente a imipenem como menos bactericida para Proteeae que para otras enterobacterias 45 . Además, se ha reportado la producción de metalo-β-lactamasas (MβLM) por P. mirabilis capaz de hidrolizar a los carbapenems, exhibiendo resistencia a nuevos β-lactámicos en ambientes hospitalarios 46 y en infecciones adquiridas en la comunidad 47 .…”