Hostname: page-component-5c6d5d7d68-wp2c8 Total loading time: 0 Render date: 2024-08-17T23:08:34.232Z Has data issue: false hasContentIssue false

Optimizing Empirical Antimicrobial Therapy for Infection due to Gram-Negative Pathogens in the Intensive Care Unit: Utility of a Combination Antibiogram

Published online by Cambridge University Press:  02 January 2015

Jennifer Christoff*
Affiliation:
Section of Infectious Diseases, University of Chicago Medical Center, Chicago, Illinois
Jocelyn Tolentino
Affiliation:
Section of Infectious Diseases, University of Chicago Medical Center, Chicago, Illinois Infection Control Program, University of Chicago Medical Center, Chicago, Illinois
Emily Mawdsley
Affiliation:
Section of Infectious Diseases, University of Chicago Medical Center, Chicago, Illinois
Scott Matushek
Affiliation:
Clinical Microbiology Laboratory, University of Chicago Medical Center, Chicago, Illinois
David Pitrak
Affiliation:
Section of Infectious Diseases, University of Chicago Medical Center, Chicago, Illinois
Stephen G. Weber
Affiliation:
Section of Infectious Diseases, University of Chicago Medical Center, Chicago, Illinois Infection Control Program, University of Chicago Medical Center, Chicago, Illinois
*
University of Chicago Medical Center, 5841 S Maryland Ave (MC 5065), Chicago, IL 60637 (Jennifer.Christoff@uchospitals.edu)

Extract

Objective.

To determine whether the use of dual antimicrobial therapy based on the results of a combination antibiotic susceptibility report (antibiogram) increases the likelihood of selecting adequate empirical coverage in critically ill patients with infection due to potentially resistant gram-negative pathogens.

Design.

Retrospective data analysis.

Setting.

Urban academic medical center.

Methods.

An analysis of culture results and susceptibility data from intensive care unit patients determined by the clinical microbiology laboratory was performed. The proportion of 5 common gram-negative pathogens susceptible to monotherapy with 1 of 3 antipseudomonal antibiotics (piperacillin-tazobactam, ceftazidime, or imipenem) was compared with the proportion susceptible to each of these 3 “backbone” agents plus 1 of 4 additional antimicrobial agents used in combination.

Results.

More than 5,000 clinical isolates were examined. When all isolates recovered during the entire study period were included, the addition of any of the second antibiotics studied to each of the 3 backbone agents significantly increased the likelihood of covering the causative pathogen (P<.01 for each). The benefit of combination therapy was variable when results for each of the 5 organisms were examined individually. When temporal trends in susceptibility were examined, the decrease in the proportion of organisms susceptible to monotherapy was statistically significant for both imipenem and ceftazidime (P<.01).

Conclusions.

Reporting antibiotic susceptibility data in the form of a combination antibiogram may be useful to clinicians who are considering empirical antimicrobial therapy in the intensive care unit.

Type
Original Article
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Sligl, W, Taylor, G, Brindley, PG. Five years of nosocomial gram-negative bacteremia in a general intensive care unit: epidemiology, antimicrobial susceptibility patterns, and outcomes. Int J Infect Dis 2006;10:320325.Google Scholar
2.Gardiner, DF, Scholand, SJ, Babinchak, T. Mortality and gram-negative rod bacteraemia in the intensive care unit. J Hosp Infect 2006;62:453457.Google Scholar
3.Fridkin, SK. Increasing prevalence of antimicrobial resistance in intensive care units. Crit Care Med 2001;29:N64N68.Google Scholar
4.Flournoy, DJ, Reinert, RL, Bell-Dixon, C, Gentry, CA. Increasing anti-microbial resistance in gram-negative bacilli isolated from patients in intensive care units. Am J Infect Control 2000;28:244250.CrossRefGoogle Scholar
5.Kollef, MH, Sherman, G, Ward, S, Fraser, VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999;115:462474.CrossRefGoogle ScholarPubMed
6.Ibrahim, EH, Sherman, G, Ward, S, Fraser, VJ, Kollef, MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000;118:146155.Google Scholar
7.Micek, ST, Lloyd, AE, Ritchie, DJ, Reichley, RM, Fraser, VJ, Kollef, MH. Pseudomonas aeruginosa bloodstream infection: importance of appropriate initial antimicrobial treatment. Antimicrob Agents Chemother 2005;49:13061311.Google Scholar
8.Lodise, TP JrPatel, N, Kwa, A, et al.Predictors of 30-day mortality among patients with Pseudomonas aeruginosa bloodstream infections: impact of delayed appropriate antibiotic selection. Antimicrob Agents Chemother 2007;51:35103515.CrossRefGoogle ScholarPubMed
9.Fraser, A, Paul, M, Almanasreh, N, et al; TREAT Study Group. Benefit of appropriate empirical antibiotic treatment: thirty-day mortality and duration of hospital stay. Am J Med 2006;119:970976.CrossRefGoogle Scholar
10.Kang, C, Kim, A, Kim, H, et al.Pseudomonas aeruginosa bacteremia: risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome. Clin Infect Dis 2003;37:745751.Google Scholar
11.National nosocomial infections surveillance (NNIS) systems report, data summary from January 1992–June 2001. Am J Infect Control 2001;29:404421.CrossRefGoogle Scholar
12.Jones, RN. Global epidemiology of antimicrobial resistance among community-acquired and nosocomial pathogens: a five-year summary from the SENTRY antimicrobial surveillance program (1997–2001). Semin Respir Crit Care Med 2003;24:121134.Google Scholar
13.Wroblewska, MM, Rudnicka, J, Marchel, H, Luczak, M. Multidrug-resistant bacteria isolated from patients hospitalised in intensive care units. Int J Antimicrob Agents 2006;27:285289.CrossRefGoogle ScholarPubMed
14.Kollef, MH. Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin Infect Dis 2000;31:S131S138.CrossRefGoogle ScholarPubMed
15.Clark, NM, Patterson, J, Lynch, JP 3rd. Antimicrobial resistance among gram-negative organisms in the intensive care unit. Curr Opin Crit Care 2003;9:413423.Google Scholar
16.Harbarth, S, Nobre, V, Pittet, D. Does antibiotic selection impact patient outcome? Clin Infect Dis 2007;44:8793.Google Scholar
17.Allan, JD, Moellering, RC JrAntimicrobial combinations in the therapy of infections due to gram-negative bacilli. Am J Med 1985;78:6576.CrossRefGoogle ScholarPubMed
18.Mouton, JW. Combination therapy as a tool to prevent emergence of bacterial resistance. Infection 1999;27:S24S28.Google Scholar
19.Scott, RE, Robson, HG. Synergistic activity of carbenicillin and gentamicin in experimental Pseudomonas bacteremia in neutropenic rats. Antitnicrob Agents Chemother 1976;10:646651.Google Scholar
20.Khakoo, RA, Kluge, RM. Effectiveness of gentamicin and carbenicillin in a rat model against infections with Pseudomonas aeruginosa resistant to gentamicin or gentamicin and carbenicillin. J Antimicrob Chemother 1979;5:5359.Google Scholar
21.Wade, JC, Standiford, HC, Drusano, GL, et al.Potential of imipenem as single-agent empiric antibiotic therapy of febrile neutropenic patients with cancer. Am J Med 1985;78:6272.Google Scholar
22.Eron, LJ, Harvey, L, Hixon, DL, Poretz, DM. Ciprofloxacin therapy of infections caused by Pseudomonas aeruginosa and other resistant bacteria. Antimicrob Agents Chemother 1985;28:308310.CrossRefGoogle ScholarPubMed
23.Verhagen, C, de Pauw, BE, Donnelly, JP, Williams, KJ, de Witte, T, Janssen, TH. Ceftazidime alone for treating Pseudomonas aeruginosa septicaemia in neutropenic patients. J Infect 1986;13:125131.Google Scholar
24.Liang, R, Yung, R, Chiu, E, et al.Ceftazidime versus imipenem-cislatin as initial monotherapy for febrile neutropenic patients. Antimicrob Agents Chemother 1990;34:13361341.Google Scholar
25.Chow, JW, Yu, VL. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents 1999;11:712.CrossRefGoogle ScholarPubMed
26.Safdar, N, Handelsman, J, Maki, DG. Does combination antimicrobial therapy reduce mortality in gram-negative bacteraemia? A meta-analysis. Lancet Infect Dis 2004;4:519527.CrossRefGoogle ScholarPubMed
27.Paul, M, Soares-Weiser, K, Leibovici, L. β-lactam monotherapy versus β-lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis. BMJ 2003;326:1111.Google Scholar
28.Paul, M, Benuri-Silbiger, I, Soares-Weiser, K, Leibovici, L. β-lactam mono-therapy versus β-lactam–aminoglycoside combination therapy for sepsis in immunocompetent patients: systemic review and meta-analysis of randomized trials. BMJ 2004;328:668.CrossRefGoogle Scholar
29.Leibovici, L, Paul, M, Poznanski, O, et al.Monotherapy versus β-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective, observational study. Antimicrob Agents Chemother 1997;41:11271133.Google Scholar
30.Mizuta, M, Linkin, DR, Nachamkin, I, et al.Identification of optimal combinations for empirical dual antimicrobial therapy of Pseudomonas aeruginosa infection: potential role of a combination antibiogram. Infect Control Hosp Epidemiol 2006;27:413415.Google Scholar
31.Apisarnthanarak, A, Mundy, LM. Role of combination antibiogram in empirical treatment of infection due to multidrug-resistant Acinetobacter baumannii. Infect Control Hosp Epidemiol 2008;29:678679.Google Scholar
32.Paterson, DL. Impact of antibiotic resistance in gram-negative bacilli on empirical and definitive antibiotic therapy. Clin Infect Dis 2008;47:S14S20.Google Scholar