Bactericidal activity of three beta-lactams alone or in combination with a beta-lactamase inhibitor and two aminoglycosides against Klebsiella pneumoniae harboring extended-spectrum beta-lactamases.

OBJECTIVE: To study the bactericidal activity of beta-lactam antibiotics (imipenem, cefepime, cefpirome) alone or in combination with a beta-lactamase inhibitor (sulbactam) in the presence or absence of aminoglycoside (amikacin or isepamicin) against Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases (ESBLs).
METHODS: We characterized 10 strains by means of analytic isoelectric focusing and pulsed-field gel electrophoresis. The ESBLs produced by these strains were derived from either TEM (TEM-1, TEM-2) or SHV-1. The killing-curve method was used for this bacterial investigation. Bacteria (final inoculum 5x105 CFU/mL) were incubated with antibiotics at clinical concentrations obtained in vivo.
RESULTS: All the combinations with cefepime or cefpirome + sulbactam were bactericidal, with a 4 log10 decrease being obtained within 6 h without regrowth at 24 h, whereas imipenem alone, and combinations, gave a bactericidal effect within 6 h. The two cephalosporins alone decreased the inoculum of 4 log10 at 6 h but regrowth was observed at 24 h. When the aminoglycoside was added, this bactericidal effect was obtained within 3 h with amikacin and within 1 h with isepamicin.
CONCLUSIONS: Cefepime + sulbactam or cefpirome + sulbactam may be an alternative to imipenem for the treatment of patients with ESBL-producing K. pneumoniae. Aminoglycosides are often associated in nosocomial infections due to ESBL-producing K. pneumoniae: isepamicin acted faster than amikacin, but both worked well. To conclude, it may be prudent to avoid extended-spectrum cephalosporins as single agent when treating serious infections due to ESBL-producing K. pneumoniae. Addition of a beta-lactamase inhibitor such as sulbactam +/- aminoglycoside is advisable to avoid failure of treatment.