Emergence and Acquisition of Fluoroquinolone-Resistant Gram-Negative Bacilli in the Intestinal Tracts of Mice Treated with Fluoroquinolone Antimicrobial Agents

Self Cite

An understanding of the impact of antibiotics on the intestinal reservoir of KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is important to prevent its emergence. We used a mouse model to examine the effect of antibiotic treatment on the establishment and elimination of intestinal colonization with KPC-Kp. Mice (10 per group) received subcutaneous antibiotics daily for 8 days. On day 3 of treatment, 10 3 CFU of KPC-Kp was given orogastrically, and concentrations of KPC-Kp in stool were monitored. Additional experiments assessed the effects of antibiotic treatment on concentrations of total anaerobes and Bacteroides spp. in stool and the efficacy of orogastric gentamicin and polymyxin E in suppressing KPC-Kp colonization. Of four antibiotics with minimal activity against the KPC-Kp test strain (MIC > 16 g/ml), those that suppressed total anaerobes and bacteroides (i.e., clindamycin and piperacillin-tazobactam) promoted colonization by KPC-Kp (P < 0.001), whereas agents that did not suppress total anaerobes or bacteroides (i.e., ciprofloxacin and cefepime) did not (P ‫؍‬ 0.35). Of two agents with moderate activity against the KPC-Kp test strain, ertapenem (MIC, 4 g/ml) did not promote colonization by KPC-Kp, whereas tigecycline (MIC, 3 g/ml) did (P < 0.001), despite not reducing levels of total anaerobes or bacteroides. Orogastric treatment with gentamicin and polymyxin E suppressed KPC-Kp to undetectable levels in the majority of mice. These data suggest that antibiotics that disturb the intestinal anaerobic microflora and lack significant activity against KPC-Kp promote colonization by this organism. The administration of nonabsorbed oral antibiotics may be an effective strategy to suppress colonization with KPC-Kp.

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Effect of Antibiotic Treatment on Establishment and Elimination of Intestinal Colonization by KPC-Producing Klebsiella pneumoniae in Mice

Pérez

Pultz

Endimiani

et al. 2011

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“…To our knowledge, this study is the first using a model of natural gut colonization by pathogenic bacteria from a nonintestinal infection site and showing the emergence of resistant strains in this new intestinal population during fluoroquinolone treatment of a lung infection. Indeed, usually studies on intestinal colonization use orogastric gavage of bacteria already resistant to the antibiotic (6,14).…”

Section: Discussionmentioning

confidence: 99%

Emergence of Resistant Klebsiella pneumoniae in the Intestinal Tract during Successful Treatment of Klebsiella pneumoniae Lung Infection in Rats

Kesteman

Perrin-Guyomard

Laurentie

et al. 2010

Antibiotic treatment of lung infections may lead to the emergence of resistance in the gut flora. Appropriate dosing regimens could mitigate this adverse effect. In gnotobiotic rats harboring intestinal Escherichia coli and Enterococcus faecium populations, a lung infection by Klebsiella pneumoniae was instigated with two different sizes of inoculum to represent an early or a late initiation of antibiotic treatment. The rats were treated with marbofloxacin, an expanded-spectrum fluoroquinolone, by a single-shot administration or a fractionated regimen over 4 days. Intestinal bacterial populations were monitored during and after treatment. At the infection site, bacterial cure without any selection of resistance was observed. Whatever the dosage regimen, fluoroquinolone treatment had a transient negative impact on the E. coli gut population but not on that of E. faecium. The intestinal flora was colonized by the pathogenic lung bacteria, and there was the emergence of intestine-resistant K. pneumoniae, occurring more often in animals treated with a single marbofloxacin dose than with the fractionated dose. Bacterial cure without resistance selection at the infection site with fluoroquinolone treatment can be linked to colonization of the digestive tract by targeted pulmonary bacteria, followed by the emergence of resistance.

“…We used a well-established murine model (23)(24)(25)(27)(28)(29)(30)(31)(32)(33) to test intestinal colonization resistance to VRE. Mouse groups 1 and 3 received oral gavage with 0.5 ml of normal saline (NS) alone once/day for 3 days, delivered via a stainless steel feeding tube (Perfektum; Popper and Sons), as their microbiota was recovering from the piperacillin-tazobactam.…”

Section: Bacterial Strainsmentioning

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.