title: Trends in antibiotic susceptibility and incidence of late-onset Klebsiella pneumoniae neonatal sepsis over a six-year period in a neonatal intensive care unit in Karachi, Pakistan.
abstract: BACKGROUND
  The incidence, change in antibiotic susceptibility, and risk factors associated with mortality of late-onset Klebsiella pneumoniae sepsis during 2006-2011, in a neonatal intensive care unit (NICU) of a developing country, were analyzed.
  
  
  METHODS
  The medical records of neonates with a discharge diagnosis of sepsis due to late-onset K. pneumoniae were retrieved. Demographic features, gestational age, date and year of admission, antibiotic susceptibility of isolates, and discharge status were recorded. The late-onset K. pneumoniae incidence per 1000 NICU admissions and risk factors for mortality due to late-onset K. pneumoniae sepsis are reported.
  
  
  RESULTS
  During the period 2006-2011, 104 of 2768 neonates developed late-onset K. pneumoniae sepsis. The overall incidence of late-onset K. pneumoniae sepsis was 3.7% (37/1000 NICU admissions), with the highest annual incidence being 53/1000 in 2010. Most cases were males (n = 64; 62%) and most were premature and very low birth weight (n = 68; 65%). More than 80% of isolates were resistant to ampicillin + clavulanic acid, gentamicin, aztreonam, and cephalosporins. An increasing trend of resistance to amikacin, fluoroquinolones, piperacillin/tazobactam, and imipenem was observed. In 2011, three-quarters (72%; n=13) of late-onset K. pneumoniae were CR K. pneumoniae. Seventeen (16%) neonates died. Being male (p = 0.06, adjusted odds ratio (AOR) 9.2, 95% confidence interval (CI) 1.3-66.9), having an extremely low birth weight (p = 0.01, AOR 6.1, 95% CI 0.8-44.4), having severe thrombocytopenia (p = 0.07, AOR 3.9, 95% CI 1.2-13.0), and failure to achieve microbiological clearance (p < 0.001, AOR 19.6, 95% CI 4.0-98.0) were significantly associated with mortality due to late-onset K. pneumoniae sepsis.
  
  
  CONCLUSIONS
  There has been a rise in carbapenem-resistant strains of late-onset K. pneumoniae, associated with an increased mortality and limited antibacterial choices. Antimicrobial stewardship and rigorous infection control measures seem to be the only way to limit the spread of these strains.
authors.affiliation: Department of Paediatrics and Child Health, Aga Khan University Hospital, Stadium Road, PO Box 3500, Karachi 74800, Pakistan. Electronic address: ali.saleem@aku.edu.
authors.forename: Ali Faisal
authors.initials: AF
authors.lastname: Saleem
authors.forename: Farah Naz
authors.initials: FN
authors.lastname: Qamar
authors.forename: Hira
authors.initials: H
authors.lastname: Shahzad
authors.forename: Maqbool
authors.initials: M
authors.lastname: Qadir
authors.forename: Anita K M
authors.initials: AK
authors.lastname: Zaidi
mesh_terms: D017668:Age of Onset; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D003428:Cross Infection / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D005260:Female; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D008297:Male; D008826:Microbial Sensitivity Tests; D010154:Pakistan / Q000453:epidemiology; D012307:Risk Factors; D018805:Sepsis / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents
keywords: Carbapenem resistance; Incidence; Late-onset Klebsiella pneumoniae; NICU; Pakistan