title: Forecasting carbapenem resistance from antimicrobial consumption surveillance: Lessons learnt from an OXA-48-producing Klebsiella pneumoniae outbreak in a West London renal unit.
abstract: This study aimed to forecast the incidence rate of carbapenem resistance and to assess the impact of an antimicrobial stewardship intervention using routine antimicrobial consumption surveillance data. Following an outbreak of OXA-48-producing Klebsiella pneumoniae (January 2008-April 2010) in a renal cohort in London, a forecasting ARIMA model was derived using meropenem consumption data [defined daily dose per 100 occupied bed-days (DDD/100OBD)] from 2005-2014 as a predictor of the incidence rate of OXA-48-producing organisms (number of new cases/year/100,000OBD). Interrupted times series assessed the impact of meropenem consumption restriction as part of the outbreak control. Meropenem consumption at lag -1 year (the preceding year), highly correlated with the incidence of OXA-48-producing organisms (r=0.71; P=0.005), was included as a predictor within the forecasting model. The number of cases/100,000OBD for 2014-2015 was estimated to be 4.96 (95% CI 2.53-7.39). Analysis of meropenem consumption pre- and post-intervention demonstrated an increase of 7.12 DDD/100OBD/year (95% CI 2.97-11.27; P<0.001) in the 4 years preceding the intervention, but a decrease thereafter. The change in slope was -9.11 DDD/100OBD/year (95% CI -13.82 to -4.39). Analysis of alternative antimicrobials showed a significant increase in amikacin consumption post-intervention from 0.54 to 3.41 DDD/100OBD/year (slope +0.72, 95% CI 0.29-1.15; P=0.01). Total antimicrobials significantly decreased from 176.21 to 126.24 DDD/100OBD/year (P=0.05). Surveillance of routinely collected antimicrobial consumption data may provide a key warning indicator to anticipate increased incidence of carbapenem-resistant organisms. Further validation using real-time data is needed.
authors.affiliation: The National Centre for Infection Prevention and Management, Imperial College London, Du Cane Road, London W12 ONN, UK. Electronic address: m.gharbi@imperial.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Gharbi
authors.affiliation: The National Centre for Infection Prevention and Management, Imperial College London, Du Cane Road, London W12 ONN, UK; Imperial College Healthcare NHS Trust, Du Cane Road, London W12 OHS, UK.
authors.forename: L S P
authors.initials: LS
authors.lastname: Moore
authors.affiliation: The National Centre for Infection Prevention and Management, Imperial College London, Du Cane Road, London W12 ONN, UK; Imperial College Healthcare NHS Trust, Du Cane Road, London W12 OHS, UK.
authors.forename: M
authors.initials: M
authors.lastname: Gilchrist
authors.affiliation: Imperial College Healthcare NHS Trust, Du Cane Road, London W12 OHS, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Thomas
authors.affiliation: The National Centre for Infection Prevention and Management, Imperial College London, Du Cane Road, London W12 ONN, UK; Imperial College Healthcare NHS Trust, Du Cane Road, London W12 OHS, UK.
authors.forename: K
authors.initials: K
authors.lastname: Bamford
authors.affiliation: The National Centre for Infection Prevention and Management, Imperial College London, Du Cane Road, London W12 ONN, UK; Imperial College Healthcare NHS Trust, Du Cane Road, London W12 OHS, UK.
authors.forename: E T
authors.initials: ET
authors.lastname: Brannigan
authors.affiliation: The National Centre for Infection Prevention and Management, Imperial College London, Du Cane Road, London W12 ONN, UK; Imperial College Healthcare NHS Trust, Du Cane Road, London W12 OHS, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Holmes
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004196:Disease Outbreaks; D004363:Drug Utilization; D062665:Epidemiological Monitoring; D005544:Forecasting; D006761:Hospitals; D006801:Humans; D015994:Incidence; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D008131:London / Q000453:epidemiology; D000077731:Meropenem; D015233:Models, Statistical; D012189:Retrospective Studies; D013845:Thienamycins / Q000627:therapeutic use*; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D001618:beta-Lactamases; C108449:oxacillinase; D000077731:Meropenem
keywords: Antimicrobial resistance; Antimicrobial stewardship; Carbapenemase; Healthcare-associated infection; Time series analyses