Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study.

MedStar author(s):
Citation: Critical Care (London, England). 18(6):596, 2014.PMID: 25412897Institution: MedStar Washington Hospital CenterDepartment: Medicine/Pulmonary-Critical CareForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, Non-U.S. Gov'tSubject headings: *Anti-Bacterial Agents/tu [Therapeutic Use] | *Drug Resistance, Multiple, Bacterial/de [Drug Effects] | *Gram-Negative Bacterial Infections/dt [Drug Therapy] | *Gram-Negative Bacterial Infections/mo [Mortality] | *Hospital Mortality/td [Trends] | *Shock, Septic/dt [Drug Therapy] | *Shock, Septic/mo [Mortality] | Aged | Anti-Bacterial Agents/pd [Pharmacology] | Cohort Studies | Drug Resistance, Multiple, Bacterial/ph [Physiology] | Female | Gram-Negative Bacterial Infections/di [Diagnosis] | Humans | Male | Middle Aged | Retrospective Studies | Sepsis/di [Diagnosis] | Sepsis/dt [Drug Therapy] | Sepsis/mo [Mortality] | Shock, Septic/di [Diagnosis]Year: 2014Local holdings: Available online from MWHC library: 1997 - present (after 1 year)ISSN:
  • 1364-8535
Name of journal: Critical care (London, England)Abstract: CONCLUSIONS: MDR, an important determinant of non-IAAT, is associated with a three-fold increase in the risk of hospital mortality. Given the paucity of therapies to cover GN MDRs, prevention and development of new agents are critical.INTRODUCTION: The impact of in vitro resistance on initially appropriate antibiotic therapy (IAAT) remains unclear. We elucidated the relationship between non-IAAT and mortality, and between IAAT and multi-drug resistance (MDR) in sepsis due to Gram-negative bacteremia (GNS).METHODS: We conducted a single-center retrospective cohort study of adult intensive care unit patients with bacteremia and severe sepsis/septic shock caused by a gram-negative (GN) organism. We identified the following MDR pathogens: MDR P. aeruginosa, extended spectrum beta-lactamase and carbapenemase-producing organisms. IAAT was defined as exposure within 24 hours of infection onset to antibiotics active against identified pathogens based on in vitro susceptibility testing. We derived logistic regression models to examine a) predictors of hospital mortality and b) impact of MDR on non-IAAT. Proportions are presented for categorical variables, and median values with interquartile ranges (IQR) for continuous.RESULTS: Out of 1,064 patients with GNS, 351 (29.2%) did not survive hospitalization. Non-survivors were older (66.5 (55, 73.5) versus 63 (53, 72) years, P = 0.036), sicker (Acute Physiology and Chronic Health Evaluation II (19 (15, 25) versus 16 (12, 19), P < 0.001), and more likely to be on pressors (odds ratio (OR) 2.79, 95% confidence interval (CI) 2.12 to 3.68), mechanically ventilated (OR 3.06, 95% CI 2.29 to 4.10) have MDR (10.0% versus 4.0%, P < 0.001) and receive non-IAAT (43.4% versus 14.6%, P < 0.001). In a logistic regression model, non-IAAT was an independent predictor of hospital mortality (adjusted OR 3.87, 95% CI 2.77 to 5.41). In a separate model, MDR was strongly associated with the receipt of non-IAAT (adjusted OR 13.05, 95% CI 7.00 to 24.31).All authors: Kollef MH, Micek ST, Shorr AF, Vazquez-Guillamet C, Zilberberg MDFiscal year: FY2015Digital Object Identifier: Date added to catalog: 2016-01-13
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 25412897 Available 25412897

Available online from MWHC library: 1997 - present (after 1 year)

CONCLUSIONS: MDR, an important determinant of non-IAAT, is associated with a three-fold increase in the risk of hospital mortality. Given the paucity of therapies to cover GN MDRs, prevention and development of new agents are critical.

INTRODUCTION: The impact of in vitro resistance on initially appropriate antibiotic therapy (IAAT) remains unclear. We elucidated the relationship between non-IAAT and mortality, and between IAAT and multi-drug resistance (MDR) in sepsis due to Gram-negative bacteremia (GNS).

METHODS: We conducted a single-center retrospective cohort study of adult intensive care unit patients with bacteremia and severe sepsis/septic shock caused by a gram-negative (GN) organism. We identified the following MDR pathogens: MDR P. aeruginosa, extended spectrum beta-lactamase and carbapenemase-producing organisms. IAAT was defined as exposure within 24 hours of infection onset to antibiotics active against identified pathogens based on in vitro susceptibility testing. We derived logistic regression models to examine a) predictors of hospital mortality and b) impact of MDR on non-IAAT. Proportions are presented for categorical variables, and median values with interquartile ranges (IQR) for continuous.

RESULTS: Out of 1,064 patients with GNS, 351 (29.2%) did not survive hospitalization. Non-survivors were older (66.5 (55, 73.5) versus 63 (53, 72) years, P = 0.036), sicker (Acute Physiology and Chronic Health Evaluation II (19 (15, 25) versus 16 (12, 19), P < 0.001), and more likely to be on pressors (odds ratio (OR) 2.79, 95% confidence interval (CI) 2.12 to 3.68), mechanically ventilated (OR 3.06, 95% CI 2.29 to 4.10) have MDR (10.0% versus 4.0%, P < 0.001) and receive non-IAAT (43.4% versus 14.6%, P < 0.001). In a logistic regression model, non-IAAT was an independent predictor of hospital mortality (adjusted OR 3.87, 95% CI 2.77 to 5.41). In a separate model, MDR was strongly associated with the receipt of non-IAAT (adjusted OR 13.05, 95% CI 7.00 to 24.31).

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