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Effects of reducing beta-lactam antibiotic pressure on intestinal colonization of antibiotic-resistant gram-negative bacteriaOpen access

Saskia Nijssen| Ad Fluit| David van de Vijver| Janetta Top| Rob Willems| Marc J. M. Bonten
Original
Volume 36, Issue 3 / March , 2010

Pages 512 - 519

Abstract

Background

We determined the effects of two antibiotic policies (predominance of either β-lactam antibiotics or fluroquinolones) on acquisition with third-generation cephalosporin-resistant Enterobacteriaceae (CRE) and fluoroquinolone-resistant CRE (FCRE) in two ICUs, with monitoring of other variables that may influence acquisition.

Methods

After an 8-month baseline period, units were randomized to a predominant β-lactam antibiotic regimen (weekly cycling of ceftriaxone, amoxicillin–clavulanic acid and fluroquinolones) or a fluoroquinolone regimen for 3 months, with cross-over for another 3 months. Acquisition of CRE and FCRE was determined by microbiological surveillance.

Results

During baseline, acquisition rates for CRE and FCRE were 14/1,000 and 2/1,000 patient days at risk, respectively. Cross-transmission of CRE accounted for ≤25% of acquisitions, and CRE acquisition was associated with the use of β-lactam antibiotics (amoxicillin–clavulanic acid in particular). As compared to baseline, β-lactam antibiotic use [in defined daily dose (DDD)/1,000 patient days] was reduced from 854 to 526 (−39%) and 555 (−35%) during both intervention periods. Fluoroquinolone use was increased from 150 and 129 DDD/1,000 patient days in baseline and the β-lactam period to 514 DDD/1,000 patient days (+243%) in the fluoroquinolone period. Reductions in β-lactam use were not associated with reduced CRE acquisition [adjusted HRs were 1.0 (95% CR: 0.5–2.2) and 1.1 (95% CI: 0.5–2.5) during both periods, respectively]. Increased use of fluoroquinolones was associated with increased acquisition of FCRE [adjusted HR 4.1 (95% CI: 1.4–11.9; p < 0.01]. Infection control variables remained comparable during all periods.

Conclusion

A 35–39% reduction of β-lactam exposure was not associated with reduced acquisition of CRE, whereas a 243% increase of fluoroquinolone use increased acquisition of FCRE.

Keywords

References

  1. Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, Quinn JP (2003) Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA 289:885–888
    • View reference on publisher's website
    • View reference on PubMed
  2. Malhotra-Kumar S, Lammens C, Coenen S, Van HK, Goossens H (2007) Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet 369:482–490
    • View reference on publisher's website
    • View reference on PubMed
  3. Bonten MJ, Austin DJ, Lipsitch M (2001) Understanding the spread of antibiotic resistant pathogens in hospitals: mathematical models as tools for control. Clin Infect Dis 33:1739–1746
    • View reference on publisher's website
    • View reference on PubMed
  4. Bonten MJ, Slaughter S, Ambergen AW, Hayden MK, van Voorhis J, Nathan C, Weinstein RA (2006) The role of “colonization pressure” in the spread of vancomycin- resistant enterococci: an important infection control variable. Arch Intern Med 158:1127–1132
    • View reference on publisher's website
  5. Nijssen S, Bootsma M, Bonten M (2000) Potential confounding in evaluating infection-control interventions in hospital settings: changing antibiotic prescription. Clin Infect Dis 43:616–623
    • View reference on publisher's website
  6. Gruson D, Hilbert G, Vargas F, Valentino R, Bebear C, Allery A, Bebear C, Gbikpi-Benissan G, Cardinaud JP (2000) Rotation and restricted use of antibiotics in a medical intensive care unit. Am J Respir Crit Care Med 162:837–843
    • View reference on PubMed
  7. Martinez JA, Nicolas JM, Marco F, Horcajada JP, Garcia-Segarra G, Trilla A, Codina C, Torres A, Mensa (2006) Comparison of antimicrobial cycling and mixing strategies in two medical intensive care units. Crit Care Medicine 34:329–336
    • View reference on publisher's website
  8. Raymond DP, Pelletier SJ, Crabtree TD, Gleason TG, Hamm LL, Pruett TL, Sawyer RG (2001) Impact of a rotating empiric antibiotic schedule on infectious mortality in an intensive care unit. Crit Care Med 29:1101–1108
    • View reference on publisher's website
    • View reference on PubMed
  9. Warren DK, Hill HA, Merz LR, Kollef MH, Hayden MK, Fraser VJ, Fridkin SK (2004) Cycling empirical antimicrobial agents to prevent emergence of antimicrobial-resistant Gram-negative bacteria among intensive care unit patients. Crit Care Med 32:2450–2456
    • View reference on publisher's website
    • View reference on PubMed
  10. van Loon HJ, Vriens MR, Fluit AC, Troelstra A, van der Werken C, Verhoef J, Bonten MJ (2005) Antibiotic rotation and development of Gram-negative antibiotic resistance. Am J Respir Crit Care Med 171:480–487
    • View reference on publisher's website
    • View reference on PubMed
  11. National Committee for Clinical Laboratory Standards (1999) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7–A4. National Committee for Clinical Laboratory Standards, Wayne
  12. Grundmann H, Barwolff S, Tami A, Behnke M, Schwab F, Geffers C, Halle E, Göbel UB, Schiller R, Jonas D, Klare I, Weist K, Witte W, Beck-Beilecke K, Schumacher M, Rüden H, Gastmeier P (2005) How many infections are caused by patient-to-patient transmission in intensive care units? Crit Care Med 33:946–951
    • View reference on publisher's website
    • View reference on PubMed
  13. Willems RJ, Top J, van den Braak N, van Belkum A, Endtz H, Mevius D, Stobberingh E, van Den Bogaard A, van Embden JD (2000) Host specificity of vancomycin-resistant Enterococcus faecium. J Infect Dis 182:816–823
    • View reference on publisher's website
    • View reference on PubMed
  14. Austin DJ, Bonten MJM, Slaughter S, Weinstein RA, Anderson RM (1999) Vancomycin-resistant enterococci in Intensive Care hospital settings: transmission dynamics, persistence and the impact of infection control programs. Proc Natl Acad Sci USA 96:6908–6913
    • View reference on publisher's website
    • View reference on PubMed
  15. Sandoval C, Walter SD, McGeer A, Simor AE, Bradley SF, Moss LM, Loeb MB (2004) Nursing home residents and Enterobacteriaceae resistant to third-generation cephalosporins. Emerg Infect Dis 10:1050–1055
    • View reference on PubMed
  16. Kim PW, Harris AD, Roghmann MC, Morris JG Jr, Strinivasan A, Perencevich EN (2003) Epidemiological risk factors for isolation of ceftriaxone-resistant versus -susceptible citrobacter freundii in hospitalized patients. Antimicrob Agents Chemother 47:2882–2887
    • View reference on publisher's website
    • View reference on PubMed
  17. Torpdahl M, Skov MN, Sandvang D, Baggesen DL (2005) Genotypic characterization of Salmonella by multilocus sequence typing, pulsed-field gel electrophoresis and amplified fragment length polymorphism. J Microbiol Methods 63:173–184
    • View reference on publisher's website
    • View reference on PubMed
  18. Melles DC, van Leeuwen WB, Snijders SV, Horst-Kreft D, Peeters JK, Verbrugh HA, van Belkum A (2007) Comparison of multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and amplified fragment length polymorphism (AFLP) for genetic typing of Staphylococcus aureus. J Microbiol Methods 69:371–375
    • View reference on publisher's website
    • View reference on PubMed
  19. Meyer E, Schwab F, Gastmeier P, Rueden H, Daschner FD (2006) Surveillance of antimicrobial use and antimicrobial resistance in German intensive care units (SARI): a summary of the data from 2001 through 2004. Infection 34:303–309
    • View reference on publisher's website
    • View reference on PubMed
  20. Kern WV, de WK, Steib-Bauert M, Fellhauer M, Plangger A, Probst W (2005) Antibiotic use in non-university regional acute care general hospitals in southwestern Germany, 2001–2002. Infection 33:333–339
    • View reference on publisher's website
    • View reference on PubMed
  21. Grundmann H, Hori S, Winter B, Tami A, Austin DJ (2002) Risk factors for the transmission of methicillin-resistant Staphylococcus aureus in an adult intensive care unit: fitting a model to the data. J Infect Dis 185:481–488
    • View reference on publisher's website
    • View reference on PubMed
  22. Pittet D, Mourouga P, Perneger TV (1999) Compliance with handwashing in a teaching hospital. Ann Intern Med 130:126–130
    • View reference on PubMed
  23. Kim PW, Roghmann MC, Perencevich EN, Harris AD (2003) Rates of hand disinfection associated with glove use, patient isolation, and changes between exposure to various body sites. Am J Infect Control 31:97–103
    • View reference on publisher's website
    • View reference on PubMed
  24. McArdle FI, Lee RJ, Gibb AP, Walsh TS (2006) How much time is needed for hand hygiene in intensive care? A prospective trained observer study of rates of contact between healthcare workers and intensive care patients. J Hosp Infect 62:304–310
    • View reference on publisher's website
    • View reference on PubMed
  25. Nijssen S, Bonten MJ, Franklin C, Verhoef J, Hoepelman AI, Weinstein RA (2003) Relative risk of physicians and nurses to transmit pathogens in a medical intensive care unit. Arch Intern Med 163:2785–2786
    • View reference on publisher's website
    • View reference on PubMed
  26. Pittet D, Allegranzi B, Sax H, Dharan S, Pessoa-Silva CL, Donaldson L, Boyce JM, WHO Global Patient Safety Challenge, World Alliance for Patient Safety (2006) Evidence-based model for hand transmission during patient care and the role of improved practices. Lancet Infect Dis 6:641–652
    • View reference on publisher's website
    • View reference on PubMed
  27. Pittet D, Boyce JM (2003) Revolutionising hand hygiene in health-care settings: guidelines revisited. Lancet Infect Dis 3:269–270
    • View reference on publisher's website
    • View reference on PubMed

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