title: Optimizing empiric antibiotic therapy in patients with severe β-lactam allergy.
abstract: Antibiotic selection is challenging in patients with severe β-lactam allergy due to declining reliability of alternate antibiotics. Organisms isolated from these patients may exhibit unique resistance phenotypes. The objective of this study was to determine which alternate antibiotics or combinations provide adequate empirical therapy for patients with β-lactam allergy who develop Gram-negative infections at our institution. We further sought to determine the effects of risk factors for drug resistance on empirical adequacy. A retrospective analysis was conducted for adult patients hospitalized from September 2009 to May 2010 who had a severe β-lactam allergy and a urine, blood, or respiratory culture positive for a Gram-negative organism and who met predefined criteria for infection. Patient characteristics, culture and susceptibility data, and predefined risk factors for antibiotic resistance were collected. Adequacies of β-lactam and alternate antibiotics were compared for all infections and selected subsets. The primary outcome was adequacy of each alternate antibiotic or combination for all infections. One hundred sixteen infections (40 pneumonias, 67 urinary tract infections, and 9 bacteremias) were identified. Single alternate agents were adequate less frequently than β-lactams and combination regimens. Only in cases without risk factors for resistance did single-agent regimens demonstrate acceptable adequacy rates; each factor conferred a doubling of risk for resistance. Resistance risk factors should be considered in selecting empirical antibiotics for Gram-negative pathogens in patients unable to take β-lactams due to severe allergy.
authors.affiliation: Wake Forest Baptist Health, Department of Pharmacy, Winston-Salem, North Carolina, USA.
authors.forename: Lindsey P
authors.initials: LP
authors.lastname: Koliscak
authors.forename: James W
authors.initials: JW
authors.lastname: Johnson
authors.forename: James R
authors.initials: JR
authors.lastname: Beardsley
authors.forename: David P
authors.initials: DP
authors.lastname: Miller
authors.forename: John C
authors.initials: JC
authors.lastname: Williamson
authors.forename: Vera P
authors.initials: VP
authors.lastname: Luther
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ohl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D004342:Drug Hypersensitivity / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D036262:Empirical Research; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D006801:Humans; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D012189:Retrospective Studies; D012306:Risk; D013752:Tetracycline / Q000627:therapeutic use; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D047090:beta-Lactams / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D047090:beta-Lactams; D013752:Tetracycline
references.citation: J Antimicrob Chemother. 2010 Feb;65(2):342-6
references.pmid: 20008043
references.citation: Crit Care Med. 2011 Aug;39(8):1859-65
references.pmid: 21499086
references.citation: Chest. 1997 Mar;111(3):676-85
references.pmid: 9118708
references.citation: Infect Control Hosp Epidemiol. 2009 Apr;30(4):325-31
references.pmid: 19220162
references.citation: Chest. 2008 Aug;134(2):281-287
references.pmid: 18682456
references.citation: N Engl J Med. 2006 Feb 9;354(6):601-9
references.pmid: 16467547
references.citation: Chest. 2006 Sep;130(3):787-93
references.pmid: 16963676
references.citation: Clin Infect Dis. 2008 Nov 1;47(9):1150-8
references.pmid: 18808361
references.citation: Chest. 1999 Feb;115(2):462-74
references.pmid: 10027448
references.citation: Infect Control Hosp Epidemiol. 2010 Mar;31(3):256-61
references.pmid: 20055664
references.citation: Ann Pharmacother. 2009 Feb;43(2):304-15
references.pmid: 19193579
references.citation: Ann Intern Med. 1987 Aug;107(2):204-15
references.pmid: 3300459
references.citation: Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416
references.pmid: 15699079
references.citation: Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
references.pmid: 20934625
references.citation: Infect Control Hosp Epidemiol. 2007 Oct;28(10):1175-80
references.pmid: 17828695
references.citation: Curr Opin Crit Care. 2011 Oct;17(5):472-9
references.pmid: 21900766
references.citation: Eur J Clin Microbiol Infect Dis. 2009 May;28(5):519-22
references.pmid: 18949495
references.citation: Antimicrob Agents Chemother. 2013 Dec;57(12):5918-23
references.pmid: 24041892