Bactericidal activity of ertapenem against major intra-abdominal pathogens

Abstract

Treatment of intra-abdominal infections remains a challenge owing to their polymicrobial nature and associated mortality risk. Treatment regimens must provide broad-spectrum coverage, including Gram-positive and Gram-negative aerobic and anaerobic bacteria of gastrointestinal origin. Ertapenem is a long-acting 1-β-methyl parenteral group 1 carbapenem antibiotic that has a broad antibacterial spectrum and once-daily dosing supported by clinical studies. It is active against Gram-positive and Gram-negative bacteria, including Enterobacteriaceae, Streptococcus pneumoniae and most species of anaerobic bacteria. The aim of this study was to measure the killing effects of ertapenem against a selected group of strains responsible for intra-abdominal infections. Gram-negative isolates comprised the following species: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella ozaenae, Enterobacter cloacae and Proteus mirabilis (extended-spectrum β-lactamase (ESBL) producers and non-producers). Gram-positive isolates comprised methicillin-susceptible Staphylococcus aureus (MSSA), Enterococcus faecalis and anaerobic Bacteroides fragilis. Ertapenem activity was tested by determination of minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs). Killing curves were performed in monocultures and co-cultures at selected antibiotic concentrations. Ertapenem showed a rapid and potent bactericidal activity in the first few hours of the kinetic curves against E. coli (6 log 10 colony-forming unit (CFU) reduction in the first 2 h), B. fragilis (4 log 10 CFU reduction in 4 h), MSSA (3 log 10 CFU reduction in 4–6 h), K. ozaenae (ESBL+), K. pneumoniae (ESBL+ and −), E. cloacae (ESBL−) in 1 h and P. mirabilis (ESBL+) in the first 2 h. The potent bactericidal activity of ertapenem compared with ceftriaxone and piperacillin/tazobactam was well demonstrated in the co-cultures of E. coli–B. fragilis and E. coli–B. fragilis–E. faecalis, whilst ertapenem was shown to be bactericidal at 24 h in the mixed culture of S. aureus–P. mirabilis. These results support the potent in vitro bactericidal activity of ertapenem against all multiresistant strains selected in this study and the use of this drug in the treatment of intra-abdominal infections.