Impact of Antibiotic-Resistant Gram-Negative Bacilli Infections
Impact of Antibiotic-Resistant Gram-Negative Bacilli Infections
Objective: The impact of resistant (vs. nonresistant) Gram-negative infections on mortality remains unclear. We sought to define risk factors for and excess mortality from these infections.
Design: Prospective cohort study.
Setting: Inpatient surgical wards at a university hospital.
Patients: All patients in the general, transplant, and trauma surgery services diagnosed with Gram-negative rod (GNR) infection.
Measurements and Main Results: All culture-proven GNR infections (n = 924) from December 1996 to September 2000 were studied. Characteristics and outcomes were compared between GNR infections with and without antibiotic resistance. Univariate and logistic regression analysis identified factors associated with antibiotic-resistant GNR (rGNR) infection and mortality. rGNR infection (n = 203) was associated with increased Acute Physiology and Chronic Health Evaluation (APACHE) II scores (17.8 ± 0.5), multiple comorbidities, pneumonia and catheter infection, coexistent infection with antibiotic-resistant Gram-positive cocci and fungi, and high mortality (27.1%). Only seven isolates were resistant in vitro to all available antibiotics. Logistic regression demonstrated that rGNR infection was an independent predictor of mortality (odds ratio, 2.23; 95% confidence interval, 1.35-3.67; p = .002). Analysis of rGNR infection with controls matched by organism, age, APACHE II score, and site of infection, however, revealed that antibiotic resistance was not associated with increased mortality (23.6% vs. 29.2%, p = .35). Furthermore, analysis of all Pseudomonas aeruginosa infections demonstrated no significant difference in mortality between resistant and sensitive strains (18.9% vs. 20.0%, p = .85).
Conclusion: rGNRs are associated with prolonged hospital stay and increased mortality. Infection with rGNRs independently predicts mortality; however, this may be more closely related to selection of certain bacterial species with a high frequency of resistance rather than actual resistance to antibiotic therapy. Therefore, altering infection-control practices to limit the dissemination of certain bacterial species may be more effective than attempts to control only antibiotic-resistant isolates.
Multiple reports have revealed the increasing prevalence of antibiotic resistance among Gram-negative isolates. Frequently, these reports characterize the distribution of resistance to specific antibiotics among various pathogens but do not discuss outcomes beyond associations found by univariate methods without accounting for multiple potential confounding variables, including severity of illness, associated comorbidities, infection source, and organism. It remains unclear, therefore, whether antibiotic-resistant Gram-negative bacillary infections are a determinant of outcome or simply a reflection of underlying severity of illness, associated comorbidities, or host physiologic/immunologic compromise.
One further difficulty is the lack of uniform definitions for antibiotic resistance among Gram-negative isolates. Antibiotic resistance may be classified according to mechanism, single antibiotic resistance, resistance to a class of antibiotics, or multidrug resistance. In addition, the wide array of potential therapeutic agents and the greater variety of Gram-negative pathogens cannot conveniently be classified, as is the case for Gram-positive organisms. The result is a collection of reports with heterogeneous definitions and conclusions that may not necessarily be extrapolated between patient populations.
We therefore decided to examine the contribution of antibiotic resistance to outcomes among infected hospitalized patients and test the hypothesis that antibiotic-resistant Gram-negative rod (rGNR) infection is associated with worse outcomes using a prospectively collected database from a single university hospital. In addition, we sought to address the question of whether any negative outcomes were attributable to resistance to empirical antibiotic therapy or to the selection of certain pathogenic bacteria (e.g., Pseudomonas aeruginosa) with a high rate of intrinsic antimicrobial resistance.
Objective: The impact of resistant (vs. nonresistant) Gram-negative infections on mortality remains unclear. We sought to define risk factors for and excess mortality from these infections.
Design: Prospective cohort study.
Setting: Inpatient surgical wards at a university hospital.
Patients: All patients in the general, transplant, and trauma surgery services diagnosed with Gram-negative rod (GNR) infection.
Measurements and Main Results: All culture-proven GNR infections (n = 924) from December 1996 to September 2000 were studied. Characteristics and outcomes were compared between GNR infections with and without antibiotic resistance. Univariate and logistic regression analysis identified factors associated with antibiotic-resistant GNR (rGNR) infection and mortality. rGNR infection (n = 203) was associated with increased Acute Physiology and Chronic Health Evaluation (APACHE) II scores (17.8 ± 0.5), multiple comorbidities, pneumonia and catheter infection, coexistent infection with antibiotic-resistant Gram-positive cocci and fungi, and high mortality (27.1%). Only seven isolates were resistant in vitro to all available antibiotics. Logistic regression demonstrated that rGNR infection was an independent predictor of mortality (odds ratio, 2.23; 95% confidence interval, 1.35-3.67; p = .002). Analysis of rGNR infection with controls matched by organism, age, APACHE II score, and site of infection, however, revealed that antibiotic resistance was not associated with increased mortality (23.6% vs. 29.2%, p = .35). Furthermore, analysis of all Pseudomonas aeruginosa infections demonstrated no significant difference in mortality between resistant and sensitive strains (18.9% vs. 20.0%, p = .85).
Conclusion: rGNRs are associated with prolonged hospital stay and increased mortality. Infection with rGNRs independently predicts mortality; however, this may be more closely related to selection of certain bacterial species with a high frequency of resistance rather than actual resistance to antibiotic therapy. Therefore, altering infection-control practices to limit the dissemination of certain bacterial species may be more effective than attempts to control only antibiotic-resistant isolates.
Multiple reports have revealed the increasing prevalence of antibiotic resistance among Gram-negative isolates. Frequently, these reports characterize the distribution of resistance to specific antibiotics among various pathogens but do not discuss outcomes beyond associations found by univariate methods without accounting for multiple potential confounding variables, including severity of illness, associated comorbidities, infection source, and organism. It remains unclear, therefore, whether antibiotic-resistant Gram-negative bacillary infections are a determinant of outcome or simply a reflection of underlying severity of illness, associated comorbidities, or host physiologic/immunologic compromise.
One further difficulty is the lack of uniform definitions for antibiotic resistance among Gram-negative isolates. Antibiotic resistance may be classified according to mechanism, single antibiotic resistance, resistance to a class of antibiotics, or multidrug resistance. In addition, the wide array of potential therapeutic agents and the greater variety of Gram-negative pathogens cannot conveniently be classified, as is the case for Gram-positive organisms. The result is a collection of reports with heterogeneous definitions and conclusions that may not necessarily be extrapolated between patient populations.
We therefore decided to examine the contribution of antibiotic resistance to outcomes among infected hospitalized patients and test the hypothesis that antibiotic-resistant Gram-negative rod (rGNR) infection is associated with worse outcomes using a prospectively collected database from a single university hospital. In addition, we sought to address the question of whether any negative outcomes were attributable to resistance to empirical antibiotic therapy or to the selection of certain pathogenic bacteria (e.g., Pseudomonas aeruginosa) with a high rate of intrinsic antimicrobial resistance.
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