Extensively drug resistant Pseudomonas aeruginosa: a study on carbapenem resistance mechanisms

Annalisa De Rosa

Pseudomonas aeruginosa (PA) is ubiquitous and is a common cause of healthcare-associated infections. It is hard to treat due to intrinsic or acquired antibiotic resistance. Carbapenems represent first line drugs in severe infections but resistance rate is growing. Ceftolozane/Tazobactam and Ceftazidim/Avibactam are new drugs approved to treat MDR PA; their efficacy strictly depends on underlining bacterial resistance mechanism, for example they are not active on Metallobetalactamases (MBL). In our study we focused on main represented carbapenem resistance mechanisms, we studied epidemiology and phenotypic effects and tried to understand which impact molecular microbiology could have in the clinical practice. We realized on 200 XDR PA PCR for carbapenemases, oprD sequencing and phenotypic tests for Efflux pump hyperexpression. Permeability alteration was the most represented resistance mechanism. On 19 strains tested all carried oprD mutations. 12/19 were also CPM positive. Overall 43/200 (21%) carried a carbapenemase-gene and all were MBL (Metallo Betalactamases). Meropenem resistance arised mainly from CPM or from specific oprD mutations in strategic sites.19 Carbapenemases negative strains were phenotipically tested for EP and 7/19 showed EP hyper expression and we assume all of them also had oprD mutation. CPM producing strains have higher MIC to Meropenem Fosfomicin and Gentamicin compared to CPM negatives. CPM producing strains are harder to treat. Resistance mechanisms should be routinely studied to better identify these bacteria and to set up an adequate antibiotic therapy. CPM-PCR could be soon introduced in the clinical practice to select cases in which the new drugs combinations are indicated.

Simone Agnello
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