Richard M. Reichley

Pseudomonas aeruginosa Bloodstream Infection: Importance of Appropriate Initial Antimicrobial Treatment

ABSTRACT Pseudomonas aeruginosa bloodstream infection is a serious infection with significant patient mortality and health-care costs. Nevertheless, the relationship between initial appropriate antimicrobial treatment and clinical outcomes is not well established. This study was a retrospective cohort analysis employing automated patient medical records and the pharmacy database at Barnes-Jewish Hospital. Three hundred five patients with P. aeruginosa bloodstream infection were identified over a 6-year period (January 1997 through December 2002). Sixty-four (21.0%) patients died during hospitalization. Hospital mortality was statistically greater for patients receiving inappropriate initial antimicrobial treatment (n = 75) compared to appropriate initial treatment (n = 230) (30.7% versus 17.8%; P = 0.018). Multiple logistic regression analysis identified inappropriate initial antimicrobial treatment (adjusted odds ratio [AOR], 2.04; 95% confidence interval [CI], 1.42 to 2.92; P = 0.048), respiratory failure (AOR, 5.18; 95% CI, 3.30 to 8.13; P < 0.001), and circulatory shock (AOR, 4.00; 95% CI, 2.71 to 5.91; P < 0.001) as independent determinants of hospital mortality. Appropriate initial antimicrobial treatment was administered statistically more often among patients receiving empirical combination antimicrobial treatment for gram-negative bacteria compared to empirical monotherapy (79.4% versus 65.5%; P = 0.011). Inappropriate initial empirical antimicrobial treatment is associated with greater hospital mortality among patients with P. aeruginosa bloodstream infection. Inappropriate antimicrobial treatment of P. aeruginosa bloodstream infections may be minimized by increased use of combination antimicrobial treatment until susceptibility results become known.

Health Care-Associated Pneumonia and Community-Acquired Pneumonia: a Single-Center Experience

ABSTRACT Pneumonia occurring outside of the hospital setting has traditionally been categorized as community-acquired pneumonia (CAP). However, when pneumonia is associated with health care risk factors (prior hospitalization, dialysis, residing in a nursing home, immunocompromised state), it is now more appropriately classified as a health care-associated pneumonia (HCAP). The relative incidences of CAP and HCAP among patients requiring hospital admission is not well described. The objective of this retrospective cohort study, involving 639 patients with culture-positive CAP and HCAP admitted between 1 January 2003 and 31 December 2005, was to characterize the incidences, microbiology, and treatment patterns for CAP and HCAP among patients requiring hospital admission. HCAP was more common than CAP (67.4% versus 32.6%). The most common pathogens identified overall included methicillin-resistant Staphylococcus aureus (24.6%), Streptococcus pneumoniae (20.3%), Pseudomonas aeruginosa (18.8%), methicillin-sensitive Staphylococcus aureus (13.8%), and Haemophilus influenzae (8.5%). The hospital mortality rate was statistically greater among patients with HCAP than among those with CAP (24.6% versus 9.1%; P < 0.001). Administration of inappropriate initial antimicrobial treatment was statistically more common among HCAP patients (28.3% versus 13.0%; P < 0.001) and was identified as an independent risk factor for hospital mortality. Our study found that the incidence of HCAP was greater than that of CAP among patients with culture-positive pneumonia requiring hospitalization at Barnes-Jewish Hospital. Patients with HCAP were more likely to initially receive inappropriate antimicrobial treatment and had a greater risk of hospital mortality. Health care providers should differentiate patients with HCAP from those with CAP in order to provide more appropriate initial antimicrobial therapy.

The Importance of Fluid Management in Acute Lung Injury Secondary to Septic Shock

BACKGROUND Recent studies have suggested that early goal-directed resuscitation of patients with septic shock and conservative fluid management of patients with acute lung injury (ALI) can improve outcomes. Because these may be seen as potentially conflicting practices, we set out to determine the influence of fluid management on the outcomes of patients with septic shock complicated by ALI. METHODS A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, MO) and in the medical ICU of Mayo Medical Center (Rochester, MN). Patients hospitalized with septic shock were enrolled into the study if they met the American-European Consensus definition of ALI within 72 h of septic shock onset. Adequate initial fluid resuscitation (AIFR) was defined as the administration of an initial fluid bolus of >or= 20 mL/kg prior to and achievement of a central venous pressure of >or= 8 mm Hg within 6 h after the onset of therapy with vasopressors. Conservative late fluid management (CLFM) was defined as even-to-negative fluid balance measured on at least 2 consecutive days during the first 7 days after septic shock onset. RESULTS The study cohort was made up of 212 patients with ALI complicating septic shock. Hospital mortality was statistically lowest for those achieving both AIFR and CLFM and higher for those achieving only CLFM, those achieving only AIFR, and those achieving neither (17 of 93 patients [18.3%] vs 13 of 31 patients [41.9%] vs 30 of 53 patients [56.6%] vs 27 of 35 [77.1%], respectively; p < 0.001). CONCLUSIONS Both early and late fluid management of septic shock complicated by ALI can influence patient outcomes.

Predictors of 30-Day Mortality and Hospital Costs in Patients With Ventilator-Associated Pneumonia Attributed to Potentially Antibiotic- Resistant Gram-Negative Bacteria*

OBJECTIVE To identify predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia (VAP) attributed to potentially antibiotic-resistant Gram-negative bacteria (PARGNB) [Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia]. DESIGN A retrospective, single-center, observational cohort study. SETTING Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. PATIENTS Adult patients requiring hospitalization with microbiologically confirmed VAP attributed to PARGNB. INTERVENTIONS Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS Seventy-six patients with VAP attributed to PARGNB were identified over a 5-year period. Nineteen patients (25.0%) died during hospitalization. Patients receiving their first dose of appropriate antibiotic therapy within 24 h of BAL sampling had a statistically lower 30-day mortality rate compared to patients receiving the first dose of appropriate therapy >24 h after BAL (17.2% vs 50.0%; p = 0.005). VAP due to Acinetobacter species was most often initially treated with an inappropriate antibiotic regimen, followed by S maltophilia and P aeruginosa (66.7% vs 33.3% vs 17.2%; p = 0.017). Overall, total hospitalization costs were statistically similar in patients initially treated with an inappropriate antibiotic regimen compared to an appropriate regimen (

Empiric Combination Antibiotic Therapy Is Associated with Improved Outcome against Sepsis Due to Gram-Negative Bacteria: a Retrospective Analysis

68,597 +/-

Validation of a clinical score for assessing the risk of resistant pathogens in patients with pneumonia presenting to the emergency department.

55,466 vs

Inappropriate antibiotic therapy in Gram-negative sepsis increases hospital length of stay.

86,644 +/-

Hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis

64,433; p = 0.390). CONCLUSIONS These data suggest that inappropriate initial antibiotic therapy of microbiologically confirmed VAP attributed to PARGNB is associated with greater 30-day mortality. High rates of VAP attributed to antibiotic-resistant bacteria (eg, Acinetobacter species) may require changes in the local empiric antibiotic treatment of VAP in order to optimize the prescription of appropriate initial therapy.

Implementation of a real-time computerized sepsis alert in nonintensive care unit patients*

ABSTRACT The optimal approach for empirical antibiotic therapy in patients with severe sepsis and septic shock remains controversial. A retrospective cohort study was conducted in the intensive care units of a university hospital. The data from 760 patients with severe sepsis or septic shock associated with Gram-negative bacteremia was analyzed. Among this cohort, 238 (31.3%) patients received inappropriate initial antimicrobial therapy (IIAT). The hospital mortality rate was statistically greater among patients receiving IIAT compared to those initially treated with an appropriate antibiotic regimen (51.7% versus 36.4%; P < 0.001). Patients treated with an empirical combination antibiotic regimen directed against Gram-negative bacteria (i.e., β-lactam plus aminoglycoside or fluoroquinolone) were less likely to receive IIAT compared to monotherapy (22.2% versus 36.0%; P < 0.001). The addition of an aminoglycoside to a carbapenem would have increased appropriate initial therapy from 89.7 to 94.2%. Similarly, the addition of an aminoglycoside would have increased the appropriate initial therapy for cefepime (83.4 to 89.9%) and piperacillin-tazobactam (79.6 to 91.4%). Logistic regression analysis identified IIAT (adjusted odds ratio [AOR], 2.30; 95% confidence interval [CI] = 1.89 to 2.80) and increasing Apache II scores (1-point increments) (AOR, 1.11; 95% CI = 1.09 to 1.13) as independent predictors for hospital mortality. In conclusion, combination empirical antimicrobial therapy directed against Gram-negative bacteria was associated with greater initial appropriate therapy compared to monotherapy in patients with severe sepsis and septic shock. Our experience suggests that aminoglycosides offer broader coverage than fluoroquinolones as combination agents for patients with this serious infection.

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

BACKGROUND Resistant organisms (ROs) are increasingly implicated in pneumonia in patients presenting to the emergency department (ED). The concept of healthcare-associated pneumonia (HCAP) exists to help identify patients infected with ROs but may be overly broad. We sought to validate a previously developed score for determining the risk for an RO and to compare it with the HCAP definition. METHODS We evaluated adult patients admitted via the ED with bacterial pneumonia (January-December 2010). We defined methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and extended-spectrum β-lactamases as ROs. The risk score was as follows: 4, recent hospitalization; 3, nursing home; 2, chronic hemodialysis; 1, critically ill. We evaluated the screening value of the score and of HCAP by determining their areas under the receiver-operating characteristic (AUROC) curves for predicting ROs. RESULTS The cohort included 977 patients, and ROs were isolated in 46.7%. The most common organisms included MRSA (22.7%), P. aeruginosa (19.1%), and Streptococcus pneumoniae (19.1%). The risk score was higher in those with an RO (median score, 4 vs 1; P < .001). The AUROC for HCAP equaled 0.62 (95% confidence interval [CI], .58-.65) versus 0.71 (95% CI, .66-.73) for the risk score. As a screening test for ROs, a score > 0 had a high negative predictive value (84.5%) and could lead to fewer patients unnecessarily receiving broad-spectrum antibiotics. CONCLUSIONS ROs are common in patients presenting to the ED with pneumonia. A simple clinical risk score performs moderately well at classifying patients regarding their risk for an RO.