The Epidemiology of Invasive, Multipleantibiotic–resistantKlebsiella pneumoniaeInfection in a Breeding Colony of Immunocompromised NSG Mice

Abstract

Klebsiella pneumoniae(Kp) is a gram-negative opportunistic pathogen that causes severe pneumonia, pyelonephritis, and sepsis in immunocompromised hosts. During a 4-mo interval, several NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) breeders and pups in our facilities were diagnosed withKpinfections. An initial 6 adult and 1 juvenile NSG mice were submitted for necropsy and histologic examination because of acute onset of diarrhea and death. The evaluation revealed typhlocolitis in 2 of the mice and tritrichomoniasis in all 7.Escherichia colipositive for polyketide synthase (pks+) andKpwere isolated from the intestines. Given a history of sepsis due topks+E. coliin NSG mice in our facilities and determination of its antimicrobial susceptibility, trimethoprim–sulfamethoxazole (TMP–SMX) was administered to the colony in the drinking water for 4 wk. After this intervention, an additional 21 mice became ill or died; 11 of these mice had suppurative pneumonia, meningoencephalitis, hepatitis, metritis, pyelonephritis, or sepsis.Kpwas cultured from pulmonary abscesses or blood of 10 of the mice. Whole-genome sequencing (WGS) indicated that theKpisolates contained genes associated with phenotypes found in pore-formingKpisolates cultured from humans with ulcerative colitis and primary sclerosing cholangitis. None of theKpisolates exhibited a hyperviscous phenotype, but 13 of 14 were resistant to TMP–SMX. Antimicrobial susceptibility testing indicated sensitivity of theKpto enrofloxacin, which was administered in the drinking water. Antibiotic sensitivity profiles were confirmed by WGS of theKpstrains; key virulence and resistance genes to quaternary ammonia compounds were also identified. Enrofloxacin treatment resulted in a marked reduction in mortality, and the study using the NSG mice was completed successfully. Our findings implicate intestinal translocation ofKpas the cause of pneumonia and systemic infections in NSG mice and highlight the importance of identification of enteric microbial pathogens and targeted antibiotic selection when treating bacterial infections in immunocompromised mice.