Antianaerobic Antibiotic Therapy Promotes Overgrowth of Antibiotic-Resistant, Gram-Negative Bacilli and Vancomycin-Resistant Enterococci in the Stool of Colonized Patients

bInfections caused by multidrug-resistant pathogens are frequent and life threatening in critically ill patients. To investigate whether severe sepsis affects gut colonization by resistant pathogens and genetic exchange between opportunistic pathogens, we tested the intestinal-colonization ability of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain carrying the SHV-18 resistance gene and the transfer ability of the resistance gene to endogenous Escherichia coli under ceftriaxone treatment in rats with burn injury only or severe sepsis induced by burns plus endotoxin exposure. Without ceftriaxone treatment, the K. pneumoniae strain colonized the intestine in both septic and burned rats for a short time, with clearance occurring earlier in burn-only rats but never in sham burn rats. In both burned and septic rats, the colonization level of the challenge strain dropped at the beginning and then later increased during ceftriaxone treatment, after which it declined gradually. This pattern coincided with the change in resistance of K. pneumoniae to ceftriaxone during and after ceftriaxone treatment. Compared with burn-only injury, severe sepsis had a more significant effect on the change in antimicrobial resistance to ceftriaxone. Only in septic rats was the resistance gene successfully transferred from the challenge strain to endogenous E. coli during ceftriaxone treatment; the gene persisted for at least 4 weeks after ceftriaxone treatment. We concluded that severe sepsis can facilitate intestinal colonization by an exogenous resistant pathogen and the transfer of the resistance gene to a potential endogenous pathogen during antimicrobial treatment.

Section: Discussionmentioning

confidence: 83%

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confidence: 99%

Severe Sepsis Facilitates Intestinal Colonization by Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae and Transfer of the SHV-18 Resistance Gene to Escherichia coli during Antimicrobial Treatment

Guan

Liu

Zhou

et al. 2014

“…Intestinal colonization is often a precursor to the development of clinical infection (7,8), and patients who are at risk are often cocolonized with multiple pathogens concomitantly (9)(10)(11). Significant hospital-acquired pathogens expressing a clinically relevant antibiotic resistance phenotype in the modern antibiotic era include methicillin-resistant Staphylococcus aureus, multiresistant Gram-negative bacilli, vancomycin-resistant Enterococci (VRE), and Clostridium difficile, among others.…”

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confidence: 99%

Gastrointestinal Colonization with a Cephalosporinase-Producing Bacteroides Species Preserves Colonization Resistance against Vancomycin-Resistant Enterococcus and Clostridium difficile in Cephalosporin-Treated Mice

Stiefel

Nerandzic

Pultz

et al. 2014

Self Cite

Antibiotics that are excreted into the intestinal tract may disrupt the indigenous intestinal microbiota and promote colonization by health care-associated pathogens. ␤-Lactam, or penicillin-type, antibiotics are among the most widely utilized antibiotics worldwide and may also adversely affect the microbiota. Many bacteria are capable, however, of producing ␤-lactamase enzymes that inactivate ␤-lactam antibiotics. We hypothesized that prior establishment of intestinal colonization with a ␤-lactamaseproducing anaerobe might prevent these adverse effects of ␤-lactam antibiotics, by inactivating the portion of antibiotic that is excreted into the intestinal tract. Here, mice with a previously abolished microbiota received either oral normal saline or an oral cephalosporinase-producing strain of Bacteroides thetaiotaomicron for 3 days. Mice then received 3 days of subcutaneous ceftriaxone, followed by either oral administration of vancomycin-resistant Enterococcus (VRE) or sacrifice and assessment of in vitro growth of epidemic and nonepidemic strains of Clostridium difficile in murine cecal contents. Stool concentrations of VRE and ceftriaxone were measured, cecal levels of C. difficile 24 h after incubation were quantified, and denaturing gradient gel electrophoresis (DGGE) of microbial 16S rRNA genes was performed to evaluate the antibiotic effect on the microbiota. The results demonstrated that establishment of prior colonization with a ␤-lactamase-producing intestinal anaerobe inactivated intraintestinal ceftriaxone during treatment with this antibiotic, allowed recovery of the normal microbiota despite systemic ceftriaxone, and prevented overgrowth with VRE and epidemic and nonepidemic strains of C. difficile in mice. These findings describe a novel probiotic strategy to potentially prevent pathogen colonization in hospitalized patients.

“…Treatment of patients with broad-spectrum antimicrobial agents predisposes to the emergence of resistant bowel flora during therapy (1,4,12,22,23,26,27). Resistant organisms can emerge through genetic mutation or induction, can be acquired exogenously, or, if already present in undetectably low concentrations, may overgrow under selective pressure.…”

Section: Discussionmentioning

confidence: 99%

Acquisition of Resistant Bowel Flora during a Double-Blind Randomized Clinical Trial of Ertapenem versus Piperacillin-Tazobactam Therapy for Intraabdominal Infections

DiNubile

Chow

Satishchandran

et al. 2005

Bowel colonization with resistant bacteria can develop in patients receiving broad-spectrum antimicrobial therapy. We compared the impact of two antimicrobial regimens often used to treat intraabdominal infections on susceptibility patterns of bowel flora at the end of therapy. In a double-blind clinical trial, adults with complicated intraabdominal infection requiring surgery were randomized to receive piperacillin-tazobactam (3.375 g every 6 h) or ertapenem (1 g once a day) for 4 to 14 days. Rectal swabs were obtained at baseline and at the end of study therapy to determine the acquisition rates of Enterobacteriaceae resistant to the study drug, extended-spectrum ␤-lactamase (ESBL)-producing Escherichia coli or Klebsiella species, Pseudomonas aeruginosa resistant to imipenem or piperacillin-tazobactam, and vancomycin-resistant Enterococcus faecalis or Enterococcus faecium. Treated patients were assessable for the acquisition of resistant bacteria if appropriate specimens were obtained at both time points. Enterobacteriaceae resistant to the treatment received were acquired during study therapy by 8/122 assessable piperacillin-tazobactam recipients (6.6%) compared to 0/122 assessable ertapenem recipients (P ‫؍‬ 0.007). Neither ESBL-producing E. coli or Klebsiella species nor P. aeruginosa resistant to piperacillin-tazobactam was isolated from patients in either treatment group. Imipenem-resistant P. aeruginosa was acquired by two of the ertapenem recipients (1.6%) versus zero of the piperacillin-tazobactam recipients (P ‫؍‬ 0.50). Vancomycin-resistant enterococci were acquired during therapy by 8/125 assessable ertapenem recipients (6.4%) versus 2/123 assessable piperacillin-tazobactam recipients (1.6%; P ‫؍‬ 0.10). In this study, the acquisition of resistant Enterobacteriaceae occurred significantly more often in patients treated with piperacillin-tazobactam than in those treated with ertapenem.