Impact of previous antibiotic therapy on outcome of Gram-negative severe sepsis*

Objective:To determine whether exposure to antimicrobial agents in the previous 90 days resulted in decreased bacterial susceptibility and increased hospital mortality in patients with severe sepsis or septic shock attributed to Gram-negative bacteremia. Design:A retrospective cohort study of hospitalized patients (January 2002 to December 2007). Setting:Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. Patients:Seven hundred fifty-four consecutive patients with Gram-negative bacteremia complicated by severe sepsis or septic shock. Interventions:Data abstraction from computerized medical records. Measurements and Main Results:Escherichia coli (30.8%), Klebsiella pneumoniae (23.2%), and Pseudomonas aeruginosa (17.6%) were the most common isolates from blood cultures. Three hundred ten patients (41.1%) had recent antibiotic exposure. Cefepime was the most common agent with previous exposure (50.0%) followed by ciprofloxacin (32.6%) and imipenem or meropenem (28.7%). Patients with prior antibiotic exposure had significantly higher rates of resistance to cefepime (29.0% vs. 7.0%), piperacillin/tazobactam (31.9% vs. 11.5%), carbapenems (20.0% vs. 2.5%), ciprofloxacin (39.7% vs. 17.6%), and gentamicin (26.1% vs. 7.9%) (p < .001 for all comparisons). Patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% vs. 21.2%; p < .001) and hospital mortality (51.3% vs. 34.0%; p < .001) compared with patients without recent antibiotic exposure. Multivariate logistic regression analysis demonstrated that recent antibiotic exposure was independently associated with hospital mortality (adjusted odds ratio, 1.70; 95% confidence interval, 1.41–2.06; p = .005). Other variables independently associated with hospital mortality included use of vasopressors, infection resulting from P. aeruginosa, inappropriate initial antimicrobial therapy, increasing Acute Physiology and Chronic Health Evaluation II scores, and the number of acquired organ failures. Conclusions:Recent antibiotic exposure is associated with increased hospital mortality in Gram-negative bacteremia complicated by severe sepsis or septic shock. Clinicians caring for patients with severe sepsis or septic shock should consider recent antibiotic exposure when formulating empiric antimicrobial regimens for suspected Gram-negative bacterial infection.

[1]  S. Lapinsky,et al.  Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: A propensity-matched analysis* , 2010, Critical care medicine.

[2]  Alastair D Hay,et al.  Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis , 2010, BMJ : British Medical Journal.

[3]  Joshua A. Doherty,et al.  Empiric Combination Antibiotic Therapy Is Associated with Improved Outcome against Sepsis Due to Gram-Negative Bacteria: a Retrospective Analysis , 2010, Antimicrobial Agents and Chemotherapy.

[4]  C. Natanson,et al.  Bundled care for septic shock: An analysis of clinical trials* , 2010, Critical care medicine.

[5]  N. Nesseler,et al.  Risk factors for multidrug-resistant bacteria in patients with post-operative peritonitis requiring intensive care. , 2010, The Journal of antimicrobial chemotherapy.

[6]  B. Murray,et al.  Antibiotic-resistant bugs in the 21st century--a clinical super-challenge. , 2009, The New England journal of medicine.

[7]  Ricard Ferrer,et al.  Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. , 2009, American journal of respiratory and critical care medicine.

[8]  François Gouin,et al.  Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: A multicenter, prospective, observational study in France (2005–2006) , 2009, Critical care medicine.

[9]  J. Low,et al.  Clinical features and treatment outcomes of vancomycin-intermediate Staphylococcus aureus (VISA) and heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) in a tertiary care institution in Singapore , 2009, European Journal of Clinical Microbiology & Infectious Diseases.

[10]  Joshua A. Doherty,et al.  Hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis* , 2009, Critical care medicine.

[11]  K. Stellrecht,et al.  Predictors of high vancomycin MIC values among patients with methicillin-resistant Staphylococcus aureus bacteraemia. , 2008, The Journal of antimicrobial chemotherapy.

[12]  M. Kollef,et al.  Treatment-related risk factors for hospital mortality in Candida bloodstream infections* , 2008, Critical care medicine.

[13]  M. Kollef Broad-spectrum antimicrobials and the treatment of serious bacterial infections: getting it right up front. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  M. Levy,et al.  Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 , 2007, Intensive Care Medicine.

[15]  Á. Soriano,et al.  Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  M. Kollef,et al.  Health Care-Associated Pneumonia and Community-Acquired Pneumonia: a Single-Center Experience , 2007, Antimicrobial Agents and Chemotherapy.

[17]  L. McNutt,et al.  Identification of Patients With Pseudomonas aeruginosa Respiratory Tract Infections at Greatest Risk of Infection With Carbapenem-Resistant Isolates , 2007, Infection Control &#x0026; Hospital Epidemiology.

[18]  Jessina C. McGregor,et al.  Clinical Prediction Tool To Identify Patients with Pseudomonas aeruginosa Respiratory Tract Infections at Greatest Risk for Multidrug Resistance , 2006, Antimicrobial Agents and Chemotherapy.

[19]  Scott T. Micek,et al.  Before–after study of a standardized hospital order set for the management of septic shock* , 2006, Critical care medicine.

[20]  M. Falagas,et al.  Risk factors for the isolation of multi-drug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa: a systematic review of the literature. , 2006, The Journal of hospital infection.

[21]  E. D’Agata,et al.  The Importance of Addressing Multidrug Resistance and Not Assuming Single-Drug Resistance in Case-Control Studies , 2006, Infection Control &#x0026; Hospital Epidemiology.

[22]  W. Bilker,et al.  Fluoroquinolone-resistant Pseudomonas aeruginosa: assessment of risk factors and clinical impact. , 2006, The American journal of medicine.

[23]  J. Garnacho-Montero,et al.  Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis* , 2003, Critical care medicine.

[24]  Stephan Harbarth,et al.  Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. , 2003, The American journal of medicine.

[25]  R. Schein,et al.  The clinical evaluation committee in a large multicenter phase 3 trial of drotrecogin alfa (activated) in patients with severe sepsis (PROWESS): Role, methodology, and results* , 2003, Critical care medicine.

[26]  A. Combes,et al.  Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  R. Auckenthaler,et al.  Influence of previous exposure to antibiotic therapy on the susceptibility pattern of Pseudomonas aeruginosa bacteremic isolates. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[28]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[29]  G Sherman,et al.  Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. , 1999, Chest.

[30]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[31]  Aseem Kumar,et al.  Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: A multicenter, prospective, observational study in France (2005–2006) , 2010 .

[32]  J. Bartlett,et al.  Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[33]  Mary Jane Ferraro,et al.  Performance standards for antimicrobial susceptibility testing : twelfth informational supplement , 2002 .