title: Surveillance of carbapenem-resistant Klebsiella pneumoniae: tracking molecular epidemiology and outcomes through a regional network.
abstract: Carbapenem resistance in Gram-negative bacteria is on the rise in the United States. A regional network was established to study microbiological and genetic determinants of clinical outcomes in hospitalized patients with carbapenem-resistant (CR) Klebsiella pneumoniae in a prospective, multicenter, observational study. To this end, predefined clinical characteristics and outcomes were recorded and K. pneumoniae isolates were analyzed for strain typing and resistance mechanism determination. In a 14-month period, 251 patients were included. While most of the patients were admitted from long-term care settings, 28% of them were admitted from home. Hospitalizations were prolonged and complicated. Nonsusceptibility to colistin and tigecycline occurred in isolates from 7 and 45% of the patients, respectively. Most of the CR K. pneumoniae isolates belonged to repetitive extragenic palindromic PCR (rep-PCR) types A and B (both sequence type 258) and carried either blaKPC-2 (48%) or blaKPC-3 (51%). One isolate tested positive for blaNDM-1, a sentinel discovery in this region. Important differences between strain types were noted; rep-PCR type B strains were associated with blaKPC-3 (odds ratio [OR], 294; 95% confidence interval [CI], 58 to 2,552; P < 0.001), gentamicin nonsusceptibility (OR, 24; 95% CI, 8.39 to 79.38; P < 0.001), amikacin susceptibility (OR, 11.0; 95% CI, 3.21 to 42.42; P < 0.001), tigecycline nonsusceptibility (OR, 5.34; 95% CI, 1.30 to 36.41; P = 0.018), a shorter length of stay (OR, 0.98; 95% CI, 0.95 to 1.00; P = 0.043), and admission from a skilled-nursing facility (OR, 3.09; 95% CI, 1.26 to 8.08; P = 0.013). Our analysis shows that (i) CR K. pneumoniae is seen primarily in the elderly long-term care population and that (ii) regional monitoring of CR K. pneumoniae reveals insights into molecular characteristics. This work highlights the crucial role of ongoing surveillance of carbapenem resistance determinants.
authors.affiliation: Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA david_vanduin@med.unc.edu robert.bonomo@va.gov.
authors.forename: David
authors.initials: D
authors.lastname: van Duin
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Perez
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Rudin
authors.affiliation: Department of Infectious Diseases, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Cober
authors.affiliation: Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hanrahan
authors.affiliation: Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Ziegler
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Webber
authors.affiliation: Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fox
authors.affiliation: Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mason
authors.affiliation: Department of Microbiology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Richter
authors.affiliation: Department of Microbiology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Marianne
authors.initials: M
authors.lastname: Cline
authors.affiliation: Department of Microbiology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Hall
authors.affiliation: Division of Infectious Diseases, Detroit Medical Center, Wayne State University, Detroit, Michigan, USA.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jacobs
authors.affiliation: Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kalayjian
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Salata
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Segre
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Conlan
authors.affiliation: Department of Biostatistics and Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Evans
authors.affiliation: Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA david_vanduin@med.unc.edu robert.bonomo@va.gov.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017720:Molecular Epidemiology; D016133:Polymerase Chain Reaction; D062486:Public Health Surveillance; D016019:Survival Analysis; D013845:Thienamycins / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D015378:Imipenem; D000077731:Meropenem