In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile.

OBJECTIVES: SMT19969 is a novel antimicrobial under clinical development for the treatment of Clostridium difficile infection (CDI). The objective was to determine the comparative susceptibility of 82 C. difficile clinical isolates (which included ribotype 027 isolates and isolates with reduced metronidazole susceptibility) to SMT19969, fidaxomicin, vancomycin and metronidazole and to determine the killing kinetics and post-antibiotic effects of SMT19969, fidaxomicin and vancomycin against C. difficile. METHODS: MICs were determined by agar incorporation. Killing kinetics and post-antibiotic effects were determined against C. difficile BI1, 630 and 5325 (ribotypes 027, 012 and 078, respectively). RESULTS: SMT19969 showed potent inhibition of C. difficile (MIC90=0.125 mg/L) and was markedly more active than either metronidazole (MIC90 = 8 mg/L) or vancomycin (MIC90 = 2 mg/L). There were no differences in susceptibility to SMT19969 between different ribotypes. Fidaxomicin was typically one doubling dilution more active than SMT19969 and both agents maintained activity against isolates with reduced susceptibility to metronidazole. In addition, SMT19969 was bactericidal against the C. difficile strains tested, with reductions in viable counts to below the limit of detection by 24 h post-inoculation. Vancomycin was bacteriostatic against all three strains. Fidaxomicin was bactericidal although reduced killing was observed at concentrations <20 × MIC against C. difficile BI1 (ribotype 027) compared with other strains tested. CONCLUSIONS: These data demonstrate that SMT19969 is associated with potent and bactericidal activity against the strains tested and support further investigation of SMT19969 as potential therapy for CDI.

Comparison of fermentation of selected fructooligosaccharides and other fiber substrates by canine colonic microflora.

OBJECTIVE: To compare fermentation characteristics of fructooligosaccharides (FOS) and other fiber substrates that are commonly found in canine diets. SAMPLE POPULATION: Fecal samples from 3 adult dogs. PROCEDURE: The ability of fiber substrates to be used in microbial fermentation reactions was assessed by use of an in vitro fermentation system. Dogs were fed a commercially available food, and feces were collected for use as the microbial inoculum. Substrates used were beet pulp, cellulose, soy fiber, mannanoligosaccharides (MOS), FOS, and 4 inulin products (inulin 1, 2, 3, and 4). Each substrate was incubated anaerobically with fecal inoculum and growth media for 6, 12, and 24 hours, and production of short-chain fatty acids (SCFA) was measured. RESULTS: Total production of SCFA was higher for fermentation of the 4 inulin products and FOS, whereas fermentation of beet pulp, MOS, and soy fiber resulted in moderate concentrations of SCFA. Fermentation of cellulose produced the lowest concentrations of total SCFA without detection of butyrate or lactate. Butyrate production was greatest for fermentation of the 4 inulin products and FOS. Total lactate production was greatest for FOS and inulin 4. As expected, production of SCFA increased for all substrates as fermentation time increased. CONCLUSIONS AND CLINICAL RELEVANCE: Canine fecal microflora ferment FOS-containing substrates in a similar manner, with little fermentation of cellulose-based carbohydrates. Furthermore, results of an in vitro fermentation system indicate that fiber type affects the metabolic activity of microorganisms, thus influencing the amount and nature of the end products of fermentation.

Long-term backache after extradural or general anaesthesia for manual removal of placenta: preliminary report.

A questionnaire designed to investigate the incidence of newly acquired, long-term backache was sent to women who had previously undergone manual removal of the placenta during a 12-month period in one maternity hospital. There was a significantly greater incidence of long-term backache in patients who had extradural anaesthesia specifically for manual removal of the placenta compared with patients receiving a general anaesthetic for the same procedure. The results of this retrospective study in a small population warrant examination in a large, prospective, controlled investigation.