title: Evaluation of Ertapenem use with impact assessment on extended-spectrum beta-lactamases (ESBL) production and gram-negative resistance in Singapore General Hospital (SGH).
abstract: BACKGROUND
  Ertapenem (preferred choice for ESBL-producing organisms) use exhibited an increasing trend from 2006 to 2008. As extensive use of ertapenem might induce the mutation of resistant bacteria strains to ertapenem, we aimed to assess the appropriateness and impact of ertapenem-use, on ESBL production, the trends of gram-negative bacterial resistance and on the utilization of other antibiotics in our institution.
  
  
  METHODS
  Inpatients who received a dose of ertapenem during 1 January 2006 to 31 December 2008, were reviewed. Pertinent patient clinical data was extracted from the pharmacy databases and assessed for appropriateness based on dose and indication. Relevant data from Network for Antimicrobial Resistance Surveillance (Singapore) (NARSS) was extracted, to cross-correlate with ertapenem via time series to assess its impact on hospital epidemiology, trends of gram-negative resistance and consumption of other antibiotics from 2006 to mid-2010.
  
  
  RESULTS
  906 cases were reviewed. Ertapenem therapy was appropriate in 72.4% (93.7% success rate). CNS adverse events were noted in 3.2%. Readmission rate (30-day) due to re-infection (same pathogen) was 5.5%. Fifty cases had cultures growing Pseudomonas aeruginosa within 30 days of ertapenem initiation, with 25 cases growing carbapenem-resistant Pseudomonas aeruginosa.Ertapenem use increased from 0.45 DDD/100 patient days in 2006 to 1.2 DDD/100 patient days in mid-2010. Overall, the increasing trend of ertapenem consumption correlated with 1) increasing incidence-densities of ciprofloxacin-resistant/cephalosporin-resistant E. coli at zero time lag; 2) increasing incidence-densities of ertapenem-resistant Escherichia. coli and Klebsiella spp. at zero time lag; 3) increasing incidence-density of carbapenem-resistant Pseudomonas aeruginosa, at zero time lag.Increasing ertapenem consumption was significantly correlated with decreasing consumption of cefepime (R2 = 0.37344) 3 months later. It was significantly correlated with a decrease in imipenem consumption (R2 = 0.31081), with no time lag but was correlated with subsequent increasing consumption of meropenem (R2 = 0.4092) 6 months later.
  
  
  CONCLUSIONS
  Ertapenem use was appropriate. Increasing Ertapenem consumption did not result in a decreasing trend of ESBL producing enterobacteriaceae and could result in the selection for multi-drug resistant bacteria.
authors.forename: Cheryl Li-Ling
authors.initials: CL
authors.lastname: Lim
authors.forename: Winnie
authors.initials: W
authors.lastname: Lee
authors.forename: Amanda Ling-Chiu
authors.initials: AL
authors.lastname: Lee
authors.forename: Lisa Ting-Ting
authors.initials: LT
authors.lastname: Liew
authors.forename: Szu Chin
authors.initials: SC
authors.lastname: Nah
authors.forename: Choon Nam
authors.initials: CN
authors.lastname: Wan
authors.forename: Maciej Piotr
authors.initials: MP
authors.lastname: Chlebicki
authors.affiliation: Department of Pharmacy, Singapore General Hospital, Block 8 Level 2, Outram Road, Singapore 169608, Singapore. andrea.kwa.l.h@sgh.com.sg.
authors.forename: Andrea Lay-Hoon
authors.initials: AL
authors.lastname: Kwa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D000077727:Ertapenem; D005260:Female; D006090:Gram-Negative Bacteria / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006769:Hospitals, General / Q000706:statistics & numerical data; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D012846:Singapore; D013845:Thienamycins / Q000494:pharmacology; D055815:Young Adult; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D002511:Cephalosporins; D013845:Thienamycins; D047090:beta-Lactams; D015378:Imipenem; D001618:beta-Lactamases; D000077731:Meropenem; D000077727:Ertapenem