Impact of inadequate initial antimicrobial therapy on mortality in infections due to extended-spectrum beta-lactamase-producing enterobacteriaceae: variability by site of infection.
BACKGROUND
Infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) have increased markedly in recent years. Risk factors for mortality among ESBL-EK infections have not been studied.


METHODS
This retrospective cohort study was conducted in a 625-bed tertiary care medical center and a 344-bed urban community hospital to determine whether inadequate initial antimicrobial therapy (IIAT) (>48 hours between the time a culture was obtained and initiation of an agent to which the infecting organism was susceptible) is associated with mortality in ESBL-EK infections. All hospitalized patients with an ESBL-EK infection between June 1, 1997, and December 31, 2002, were eligible for inclusion. Subsequently, we conducted a nested case-control study to identify risk factors for IIAT.


RESULTS
Of 187 subjects, 32 (17.1%) died while in the hospital. Clinical site of infection was a significant effect modifier in the association between IIAT and mortality. The presence of IIAT was an independent risk factor for mortality, but only for nonurinary ESBL-EK infections (adjusted odds ratio [95% confidence interval], 10.04 [1.90-52.96]). Independent risk factors for IIAT were (1) infection with a multidrug-resistant ESBL-EK (ie, resistant to sulfamethoxazole-trimethoprim, aminoglycosides, and quinolones) (14.58 [1.91-111.36]) and (2) health care-acquired ESBL-EK infection (4.32 [1.49-12.54]).


CONCLUSIONS
Inadequate initial antimicrobial therapy is an independent risk factor for mortality in ESBL-EK infections, but only among nonurinary infections. Multidrug resistance was a strong risk factor for IIAT.
Hyle
Emily P
EP
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA. .
Lipworth
Adam D
AD
Zaoutis
Theoklis E
TE
Nachamkin
Irving
I
Bilker
Warren B
WB
Lautenbach
Ebbing
E
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000401:mortality*; D005260:Female; D006801:Humans; D007239:Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D007710:Klebsiella Infections / Q000188:drug therapy / Q000401:mortality*; D041121:Klebsiella oxytoca / Q000201:enzymology*; D007711:Klebsiella pneumoniae / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D017211:Treatment Failure; D001618:beta-Lactamases / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D001618:beta-Lactamases