Effects of Imipenem, Cefotaxime and Cotrimoxazole on Aerobic Microbial Colonization of the Digestive Tract

Abstract

Superinfections originating from a digestive tract colonized by abnormally high concentrations of aerobic microorganisms as a result of impaired resistance to colonization (CR) may complicate antibiotic therapy. In this study, patients with a moderate to severe systemic infection were randomized to receive either cefotaxime (CTX, n = 10) or cotrimoxazole (CTR, n = 10), 2 antibiotic regimens presumed to spare CR; or imipenem/cilastine (I/C, n = 19). The effect on CR was measured indirectly by comparing the aerobic faecal flora before antibiotic treatment with that on day 8 of treatment. An increase in aerobic faecal flora denotes a disturbed CR, whereas a decrease means that the organism is sensitive to the effective faecal concentration of the antibiotic. Imipenem/cilastine-treated patients showed a significant increase in enterococci and Candida spp., while the number of aerobic Gram-negative rods remained constant. Cefotaxime-treated patients had evidence of an increase in enterococci, but not of Candida spp., and Escherichia coli numbers decreased significantly. In these patients the concentration of other Gram-negative aerobic rods showed a slight increase in 6 patients with a resistant Pseudomonas strain. Cotrimoxazole-treated patients showed a significant decrease in aerobic Gram-negative rods, a significant increase in Candida spp. and no change in enterococci. It is concluded that all 3 antimicrobial agents impair colonization resistance. Whether or not this is followed by overgrowth with resistant micro-organisms depends on the active faecal concentration of the antimicrobial agent and the MIC of the aerobic micro-organisms. The risk of overgrowth of the bowel with resistant Gram-negative bacilli appears to be smaller following cotrimoxazole than following cefotaxime or imipenem/cilastine.

Enlisting commensal microbes to resist antibiotic-resistant pathogens

“…Classical microbiologic studies led to the conclusion that obligate anaerobic commensal bacterial species were the most consequential contributors to resistance against S. enteritidis infection (Bohnhoff et al, 1964a). Autochthonous or exogenous Enterobacteriaceae were subsequently shown to markedly expand in the gastrointestinal tract of rodents and humans treated with antibiotics, and the term “colonization resistance” was coined to denote the microbiota’s capacity to inhibit expansion of Enterococci and Enterobacteriaceae in the gut lumen (Clasener et al, 1987; Van der Leur et al, 1993).…”

Comparative review of imipenem/cilastatin versus meropenem

“…However, other studies reported the stability of the Enterobacteriaceae population but an increased concentration of enterococci and Candida spp. [60][61][62]. The impact on anaerobic bacteria is even more uncertain as several studies reported the stability of such flora [60][61][62], while another study reported its disappearance [59].…”

“…[60][61][62]. The impact on anaerobic bacteria is even more uncertain as several studies reported the stability of such flora [60][61][62], while another study reported its disappearance [59].…”

Host Impairments in Patients with Neoplastic Diseases

“…Some drugs such as aztreonam and imipenem only appear ''friendly'' because they are inactivated by feces [30,40], whereas under the circumstance of diarrhea, parenteral feeding, and gut toxicity, normal stool is no longer produced so these agents may remain sufficiently active to destroy what remains of the colonization resistance. Initially, co-trimoxazole was thought to be neutral [27,34,[41][42][43][44][45], but other evidence suggests otherwise [46]. Individual antibiotics that appear to spare colonization resistance, such as ceftazidime and piperacillin, might have a marked impact when given in combination, leading to an increase in both Clostridium difficile as well as yeasts [47].…”