title: Effect of antibiotic treatment on establishment and elimination of intestinal colonization by KPC-producing Klebsiella pneumoniae in mice.
abstract: 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 μg/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 μg/ml) did not promote colonization by KPC-Kp, whereas tigecycline (MIC, 3 μg/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.
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Perez
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pultz
authors.forename: Andrea
authors.initials: A
authors.lastname: Endimiani
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Donskey
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D005260:Female; D007422:Intestines / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase