Bactericidal activity of ertapenem against major intra-abdominal pathogens

Treatment of intra-abdominal infections remains a challenge owing to their polymicrobial nature and associated mortality risk. Treatmentregimens must provide broad-spectrum coverage, including Gram-positive and Gram-negative aerobic and anaerobic bacteria of gastrointestinalorigin. Ertapenem is a long-acting 1--methyl parenteral group 1 carbapenem antibiotic that has a broad antibacterial spectrum and oncedailydosing 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 studywas to measure the killing effects of ertapenem againsta selected group of strains responsible for intra-abdominal infections. Gram-negative isolates comprised the following species: Escherichiacoli, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella ozaenae, Enterobacter cloacae and Proteus mirabilis (extended-spectrum -lactamase (ESBL) producers and non-producers). Gram-positive isolates comprised methicillin-susceptible Staphylococcus aureus (MSSA),Enterococcus faecalis and anaerobic Bacteroides fragilis. Ertapenem activitywas tested by determination of minimal inhibitory concentrations(MICs) and minimal bactericidal concentrations (MBCs). Killing curves were performed in monocultures and co-cultures at selected antibioticconcentrations. Ertapenem showed a rapid and potent bactericidal activity in the first few hours of the kinetic curves against E. coli (6 log10colony-forming unit (CFU) reduction in the first 2 h), B. fragilis (4 log10 CFU reduction in 4 h), MSSA (3 log10 CFU reduction in 4–6 h), K.ozaenae (ESBL+), K. pneumoniae (ESBL+ and−), E. cloacae (ESBL−) in 1h and P. mirabilis (ESBL+) in the first 2 h. The potent bactericidalactivity of ertapenem compared with ceftriaxone and piperacillin/tazobactam was well demonstrated in the co-cultures of E. coli–B. fragilisand 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. Theseresults support the potent in vitro bactericidal activity of ertapenem against all multiresistant strains selected in this study and the use of thisdrug in the treatment of intra-abdominal infections.