title: Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study.
abstract: OBJECTIVE
  Early broad-spectrum antimicrobial treatment reduces mortality in patients with septic shock. In a multicenter, prospective observational study, we explored whether delayed appropriate antimicrobial therapy (AAT) influences outcome in Staphylococcus aureus bloodstream infection (SAB).
  
  
  METHODS
  Two hundred and fifty-six patients with SAB from ten German study centers were enrolled and followed for 3 months. Predisposing factors, clinical features, diagnostic procedures, antimicrobial therapy, and outcome were recorded. The appropriateness of antimicrobial therapy was judged by a trained physician based on in vitro activity, dosage, and duration of therapy. Therapy was considered to be delayed when more than 24 h elapsed between the first positive blood culture and the start of appropriate therapy. The association of delayed therapy with overall mortality and SAB-related events (i.e., attributable mortality or late SAB-related complications) was assessed by crosstabulation and propensity score-based logistic regression.
  
  
  RESULTS
  One hundred and sixty-eight patients received AAT during their hospital stay, of whom 42 (25%) received delayed AAT. The overall mortality and the occurrence of severe sepsis or septic shock were lower in patients with delayed AAT, pointing towards confounding by indication. Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval [CI] [0.39-2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95% CI [0.47-4.51], p 0.52) also failed to show a significant impact of delayed AAT on outcome.
  
  
  CONCLUSIONS
  In patients with SAB, early AAT may not improve survival. However, confounding by indication is a major challenge when analyzing and interpreting observational studies on the impact of delayed AAT.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, 50935, Cologne, Germany, achim.kaasch@uk-koeln.de.
authors.forename: A J
authors.initials: AJ
authors.lastname: Kaasch
authors.forename: S
authors.initials: S
authors.lastname: Rieg
authors.forename: J
authors.initials: J
authors.lastname: Kuetscher
authors.forename: H-R
authors.initials: HR
authors.lastname: Brodt
authors.forename: T
authors.initials: T
authors.lastname: Widmann
authors.forename: M
authors.initials: M
authors.lastname: Herrmann
authors.forename: C
authors.initials: C
authors.lastname: Meyer
authors.forename: T
authors.initials: T
authors.lastname: Welte
authors.forename: P
authors.initials: P
authors.lastname: Kern
authors.forename: U
authors.initials: U
authors.lastname: Haars
authors.forename: S
authors.initials: S
authors.lastname: Reuter
authors.forename: I
authors.initials: I
authors.lastname: Hübner
authors.forename: R
authors.initials: R
authors.lastname: Strauss
authors.forename: B
authors.initials: B
authors.lastname: Sinha
authors.forename: F M
authors.initials: FM
authors.lastname: Brunkhorst
authors.forename: M
authors.initials: M
authors.lastname: Hellmich
authors.forename: G
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: W V
authors.initials: WV
authors.lastname: Kern
authors.forename: H
authors.initials: H
authors.lastname: Seifert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D015331:Cohort Studies; D005260:Female; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents
references.citation: Clin Microbiol Infect. 2010 Jun;16(6):747-52
references.pmid: 19723135
references.citation: Clin Infect Dis. 2003 Jun 1;36(11):1418-23
references.pmid: 12766837
references.citation: J Infect. 2011 May;62(5):339-46
references.pmid: 21402101
references.citation: Antimicrob Agents Chemother. 2007 Oct;51(10):3510-5
references.pmid: 17646415
references.citation: J Clin Pathol. 2008 Jun;61(6):750-3
references.pmid: 18326019
references.citation: Infection. 2011 Jun;39(3):281-2
references.pmid: 21431340
references.citation: J Antimicrob Chemother. 2010 Dec;65(12):2658-65
references.pmid: 20947620
references.citation: Clin Infect Dis. 2008 Jan 15;46(2):193-200
references.pmid: 18171250
references.citation: Crit Care Med. 2003 Dec;31(12):2742-51
references.pmid: 14668610
references.citation: J Infect. 2009 Feb;58(2):131-7
references.pmid: 19211147
references.citation: Eur J Clin Microbiol Infect Dis. 2006 Mar;25(3):181-5
references.pmid: 16505987
references.citation: Crit Care Resusc. 2009 Dec;11(4):276-81
references.pmid: 20001878
references.citation: Am J Med. 2006 Nov;119(11):970-6
references.pmid: 17071166
references.citation: Pharmacoeconomics. 2009;27(5):421-30
references.pmid: 19586079
references.citation: Ann Intern Med. 2002 Nov 19;137(10):791-7
references.pmid: 12435215
references.citation: Arch Intern Med. 2000 Apr 10;160(7):1001-4
references.pmid: 10761966
references.citation: PLoS One. 2010 Jul 02;5(7):e11432
references.pmid: 20625395
references.citation: J Infect Dis. 1996 Apr;173(4):914-9
references.pmid: 8603971
references.citation: Clin Microbiol Infect. 2006 Jan;12(1):13-21
references.pmid: 16460541
references.citation: J Antimicrob Chemother. 2006 Mar;57(3):511-9
references.pmid: 16443700
references.citation: Crit Care Med. 2006 Jun;34(6):1589-96
references.pmid: 16625125
references.citation: J Antimicrob Chemother. 2004 Aug;54(2):489-97
references.pmid: 15254028
references.citation: Eur J Clin Microbiol Infect Dis. 2007 Apr;26(4):239-45
references.pmid: 17318479
references.citation: Chest. 2003 May;123(5):1615-24
references.pmid: 12740282
references.citation: Diagn Microbiol Infect Dis. 2006 Jul;55(3):179-84
references.pmid: 16631340
references.citation: Clin Infect Dis. 2010 Nov 1;51(9):1074-80
references.pmid: 20879856
references.citation: Crit Care Med. 2008 Jan;36(1):296-327
references.pmid: 18158437
references.citation: Crit Care Med. 1992 Jun;20(6):864-74
references.pmid: 1597042
references.citation: Infection. 2011 Apr;39(2):141-7
references.pmid: 21424856
references.citation: Clin Infect Dis. 2009 Oct 1;49(7):997-1005
references.pmid: 19719417