Relationship between outer membrane alterations and susceptibility to antimicrobial agents in isogenic strains of Klebsiella pneumoniae

The activities of beta-lactams, chloramphenicol, tetracycline, fluoroquinol ones and aminoglycosides against Klebsiella pneumoniae C3 (O1:K66, producin g porins OmpK35 and OmpK36) and a set of isogenic mutants derived from it l acking the O antigen of lipopolysaccharide (LPS), capsular K antigen, or on e or both porins were determined. MICs remained within one dilution step in mutants deficient in antigen O, in capsule or in one of the two porins. No increases in the MICs of aminoglycosides, fluoroquinolones, tetracycline a nd chloramphenicol were observed for strains deficient in the two porins, b ut the MICs of ampicillin, cephalothin, cefoxitin, cefotaxime and ceftazidi me for this type of mutant increased four- to >256-fold. The highest MICs o f beta-lactams were obtained in a porin-deficient mutant expressing increas ed beta-lactamase activity. It is concluded that isolated outer membrane al terations in K. pneumoniae are not decisive factors in increasing resistanc e to antimicrobial agents, but porin loss cooperates with beta-lactamase pr oduction to increase resistance to beta-lactams.