Effects of sub-MIC concentrations of antibiotics on growth of and toxin production by Clostridium difficile.

Abstract:

:Effects on growth and toxin A production of sub-MIC concentrations of six different antibiotics were investigated in three strains of Clostridium difficile: reference strain NCTC 11223, a fully sequenced strain (630) and a locally endemic isolate (strain 338a). The antibiotics chosen for investigation were the agents used to treat C. difficile-associated disease (CDAD), i.e. vancomycin and metronidazole, and four antibiotics that are commonly involved in precipitating CDAD (amoxycillin, clindamycin, cefoxitin and ceftriaxone). Strains were cultured in sublethal concentrations of antibiotics (1/2, 1/4 and 1/8 MIC) over 104 h and growth and toxin A production were measured three times a day. Effects varied between strain and antibiotic. The most common effect on growth of the strains was to increase the initial lag period by approximately 4 h, compared with antibiotic-free controls; however, strain NCTC 11223, which has high-level clindamycin resistance (> or = 512 microg ml(-1)), showed no lag whatsoever in comparison with the controls when grown in this antibiotic. The most common effect on production of toxin A was in the onset of toxin elaboration. Normally, toxins began to appear at low levels in the early stationary phase, before accumulating to high levels by the start of decline. In the presence of sub-MIC antibiotics, this onset appeared before that of the antibiotic-free controls. This effect was seen with metronidazole, amoxycillin and clindamycin, rarely with vancomycin and never with cefoxitin. These results suggest a very complex, strain-dependent relationship between the effects of growth and toxin production.

journal_name

J Med Microbiol

authors

Drummond LJ,Smith DGE,Poxton IR

doi

10.1099/jmm.0.05387-0

keywords:

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

1033-1038

issue

Pt 12

eissn

0022-2615

issn

1473-5644

journal_volume

52

pub_type

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