Lack of additive effect between mechanisms of resistance to carbapenems and other beta-lactam agents in Pseudomonas aeruginosa

Abstract

Eighty-nine clinical isolates resistant (n = 61) or susceptible (n = 28) to imipenem and exhibiting the main patterns of susceptibility to other beta-lactam agents (wild type pattern, penicillinase pattern, constitutive cephalosporinase pattern) were studied in order to investigate (i) the mechanism of resistance involved and (ii) whether resistance to carbapenems affects the level of resistance to other beta-lactam agents and, conversely, if resistance to other beta-lactam agents affects the level of resistance to carbapenems. For this purpose, the presence of OprD protein in the cell wall was detected by Western blot and beta-lactamase activity by spectrophotometric assay and isoelectric focusing. OprD expression was not detectable in the imipenem-resistant (MIC > or = 16 micrograms/ml) strains. It was decreased in half the strains for which MICs of imipenem were 2 to 8 micrograms/ml and was close to a normal level in the most susceptible strains (MIC < or = 1 microgram/ml), thus demonstrating a direct correlation between the level of susceptibility to imipenem and the level of OprD expression. No imipenemase activity was detected in imipenem-resistant strains. Synergy between imipenem or meropenem and BRL 42715 was observed for all of the strains, demonstrating the role of cephalosporinase in carbapenem resistance. Within each pattern of susceptibility, the mean MICs of beta-lactam agents other than carbapenems were similar, whether the strains were susceptible or resistant to imipenem. Conversely, the mean MICs of imipenem or meropenem for either the imipenem-resistant or the imipenem-susceptible strains were similar, regardless of the susceptibility of these strains to the other beta-lactam agents. Thus, when several mechanisms of resistance to beta-lactam agents are present in the same strain of Pseudomonas aeruginosa, there is no additive effect between these mechanisms.