Pseudomonas pseudomallei Resistance to r-Lactam Antibiotics Due to Alterations in the Chromosomally Encoded 1-Lactamase

Pseudomonas pseudomallei, the causative agent of melioidosis, is generally susceptible to some of the newer extended-spectrum cephalosporins or to combinations of a,-lactam and clavulanic acid, a,-lactamase inhibitor. Resistance to these agents may, however, emerge during treatment. We report on alterations in the chromosomal D-lactamase associated with the development of resistance. Three resistance patterns resulted from three different mechanisms in the strains investigated. Derepression of the chromosomal enzyme resulted in a general increase in the MICs of all of the f8-lactams tested. The second mechanism observed was an insensitivity to inhibition of the D-lactamase by clavulanic acid. In this case, the level of susceptibility to,I-lactams as independent entities remained unchanged. The final "resistance " pattern occurred in a patient treated with ceftazidime and resulted in a I8-lactamase that was capable of hydrolyzing this antibiotic at detectable levels, but with reduced efficacy against other I-lactams. The net result was a strain that was generally susceptible to all of the I8-lactams tested except ceftazidime. In all cases, the level of susceptibility to antibiotics other than P-lactams remained unchanged. Such variability found within one genus over a relatively short time course suggests that treatment of infections caused by this organism should be carefully monitored to detect susceptibility alterations to the chosen therapy. Melioidosis is the name given to infections of humans or other animals caused by Pseudomonas pseudomallei (7, 18)