Klebsiella pneumoniae strain 11978 was isolated in Turkey in 2001 and was found to be resistant to all ␤-lactams, including carbapenems. Cloning and expression in Escherichia coli identified five ␤-lactamases, including two novel oxacillinases. The ␤-lactamase OXA-48 hydrolyzed imipenem at a high level and was remotely related (less than 46% amino acid identity) to the other oxacillinases. It hydrolyzed penicillins and imipenem but not expanded-spectrum cephalosporins. The bla OXA-48 gene was plasmid encoded and not associated with an integron, in contrast to most of the oxacillinase genes. An insertion sequence, IS1999, was found immediately upstream of bla OXA-48 . Another plasmid that encoded a second oxacillinase gene, bla OXA-47 , located inside a class 1 integron was identified in K. pneumoniae 11978. OXA-47 had a narrow spectrum of hydrolysis activity and did not hydrolyze ceftazidime or imipenem, as is found for the ␤-lactamase (OXA-1) to which it is related. In addition, ␤-lactamases TEM-1 and SHV-2a were expressed from the same K. pneumoniae isolate. Analysis of the outer membrane proteins of this isolate revealed that it lacked a porin of ca. 36 kDa. Thus, the high-level resistance to ␤-lactams of this clinical isolate resulted from peculiar ␤-lactamases and modification of outer membrane proteins.

Resistance to fluoroquinolones has increased markedly since their introduction. Mechanisms of resistance to any antibiotic class might play a role in resistance to an unrelated antibiotic class. This study evaluated the relationship between extended-spectrum beta-lactamase (ESBL) production and ciprofloxacin resistance in Escherichia coli and Klebsiella pneumoniae strains isolated as causative agents of urinary tract infection. ESBL-producing strains were significantly more frequent among ciprofloxacin-resistant E. coli strains than among ciprofloxacin-susceptible E. coli strains (p = 0.015), but the difference was not significant among K. pneumoniae strains (p = 0.276).

The results suggest that the majority of S. typhimurium strains were closely related.

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