Mechanisms of beta-lactam resistance amongst Pseudomonas aeruginosa isolated in an Italian survey

Abstract

The mechanisms of resistance to beta-lactam antibiotics in 325 isolates of Pseudomonas aeruginosa were examined. These isolates were selected because of their resistance to meropenem and imipenem (breakpoint, >4 mg/L), carbenicillin (>128 mg/L), ceftazidime (>8 mg/L), piperacillin and ticarcillin/clavulanate (>64 mg/L). The most frequent mechanism of resistance was beta-lactamase-independent, so called 'intrinsic resistance', which was found in 183 isolates and was probably due to impermeability and/or efflux mechanisms. beta-Lactamase-mediated resistance was demonstrated in 111 strains (11.1%). Derepression of Ambler Class C chromosomal beta-lactamase was detected in 64 isolates, most of which were resistant to ceftazidime and piperacillin but susceptible to meropenem, whereas secondary plasmid-encoded beta-lactamases were found in 34 isolates, all of them resistant to carboxypenicillins and ureidopenicillins and susceptible to carbapenems. Twelve strains showed more than one plasmid-encoded beta-lactamase plus derepression of chromosomal Class C enzyme. Resistance to carbapenems was independent of resistance to other beta-lactam antibiotics, indicating a different mechanism of resistance, probably due to the loss of the D2 porin. In total, 32 strains were resistant to carbapenems: 24 only to imipenem and eight to both imipenem and meropenem.

Incidence of carbapenem-resistant <i> Pseudomonas aeruginosa</i> in diabetes and cancer patients

“…The causes of death were chronic renal failure (5), terminal respiratory arrest due to septicaemia (3), and septicaemia with progressive metastatic carcinoma (1). Among the 51 patients who survived, 8 (15.6%) needed readmission to the hospital.…”

“…[1] The introduction of carbapenems into clinical practice was of great help in the treatment of serious bacterial infections caused by β-lactam-resistant bacteria. Carbapenems, due to their stability to hydrolysis by most ß-lactamases, have been the drugs of choice for treatment of infections caused by penicillin-resistant or cephalosporin-resistant gram-negative infections.…”

Carbapenem Resistance Mechanisms in Pseudomonas aeruginosa Clinical Isolates

“…In addition to the OprD loss or drug efflux pumps, chromosomal AmpC ␤-lactamase plays an important role in carbapenem resistance in P. aeruginosa (16,21). Although the contributions of the OprD loss, the efflux systems, and ␤-lactamase in the carbapenem resistance have been well characterized in the laboratory strains, little data is available for how such factors play together in the clinical isolates of P. aeruginosa (2,4,31).Based on the carbapenem susceptibility patterns, the clinical isolates of carbapenem-resistant P. aeruginosa could be divided into three groups as the imipenem-resistant and meropenemsensitive group, the imipenem-sensitive and meropenem-resistant group, and the imipenem-resistant and meropenem-resistant group (2,4,17). This suggests that carbapenem resistance occurs by several mechanisms in concert for the clinical isolates.…”

“…In addition to the OprD loss or drug efflux pumps, chromosomal AmpC ␤-lactamase plays an important role in carbapenem resistance in P. aeruginosa (16,21). Although the contributions of the OprD loss, the efflux systems, and ␤-lactamase in the carbapenem resistance have been well characterized in the laboratory strains, little data is available for how such factors play together in the clinical isolates of P. aeruginosa (2,4,31).…”

Pseudomonas Aeruginosa AmpR Transcriptional Regulatory Network

“…Antibiotic resistant isolates of P. aeruginosa are selectively favored in vivo in CF patients (85,86). A major mechanism of ß-lactam resistance in P. aeruginosa is the overproduction of the chromosomal ß-lactamase, AmpC.…”