Abstract
BackgroundSporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. However, the influence of antibiotics on sporulation is unclear. The objective of our study was to evaluate the impact of ciprofloxacin, metronidazole, piperacillin/tazobactam, tigecycline, and vancomycin on C. difficile sporulation in vitro.MethodsThe reference strains ATCC 9689, 630, VPI 10463, and seven other clinical isolates of C. difficile were used, including three epidemic NAP1/027 isolates. Minimum inhibitory concentrations (MIC) were determined and sporulation was assessed after growth in the absence or presence of ≤0.5x MIC concentrations of each antibiotic.ResultsAll strains were sensitive to the antibiotics tested, except ribotype 027 isolates that were resistant to ciprofloxacin (MIC = 128 mg/L). Metronidazole and vancomycin generally did not significantly affect spore production in C. difficile, although vancomycin slightly affected sporulation of a few isolates. Ciprofloxacin inhibited sporulation of ribotype 027 isolates mainly. Interestingly, sub-MIC concentrations of piperacillin/tazobactam reduced spore formation in several isolates. However, the most striking observation was made with tigecycline, with an important reduction of spore formation in most isolates.ConclusionsThe capacity of C. difficile to sporulate can be significantly affected by certain antibiotics. The reduced sporulation observed with tigecycline and piperacillin/tazobactam might explain why these antibiotics are generally associated with lower risk of C. difficile infections. In addition, the inhibition of sporulation might partly explain the apparent efficacy of tigecycline for treatment of patients with recurrent infection.
Highlights
Sporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence
Some studies suggested that epidemic strains of C. difficile sporulate more efficiently and to higher levels than non epidemic strains, which might explain why epidemic strains disseminate in hospitals [12,13], but this hypothesis is a matter of debate [15,16]
Bacterial strains and growth conditions C. difficile reference strains ATCC 9689, ATCC 43255 (VPI 10463) and 630 were used along with 7 other clinical isolates that were purified from feces after alcohol shock and growth on CDMN selective agar (Clostridium difficile agar base supplemented with moxalactam and norfloxacin) (Oxoid, Canada)
Summary
Sporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. The emergence of an epidemic strain of C. difficile, NAP1/ 027, was associated with more severe disease, and a higher recurrence rate [1,2]. Prolonged disruption of the Spores of C. difficile are highly resistant to harsh environments and household disinfectants and are likely responsible for efficient dissemination of C. difficile in hospital settings [12,13]. They are resistant to all known antibiotics including metronidazole (MTZ) and vancomycin (VAN) [14]. Some studies suggested that epidemic strains of C. difficile sporulate more efficiently and to higher levels than non epidemic strains, which might explain why epidemic strains disseminate in hospitals [12,13], but this hypothesis is a matter of debate [15,16]
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