Prolonged infusion antibiotics for suspected gram-negative infections in the ICU: a before-after study.

BACKGROUND: ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. OBJECTIVE: To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. METHODS: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). RESULTS: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). CONCLUSIONS: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

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

OBJECTIVES: To describe the impact of initially inappropriate antibiotic therapy on hospital length of stay in Gram-negative severe sepsis and septic shock. DESIGN: Retrospective cohort. SETTING: Academic urban hospital. PATIENTS: Patients with Gram-negative bacteremia (primary or secondary, nosocomial or non-nosocomial) and severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined initially inappropriate antibiotic therapy as occurring when the patient either was not administered an antibiotic within 24 hrs of sepsis onset or was treated with an antibiotic to which the culprit pathogen was resistant in vitro. The cohort included 760 subjects (mean age 59.3 ± 16.3 yrs, mean Acute Physiology and Chronic Health Evaluation II score 23.7 ± 6.7). More than half of infections were nosocomial (55.1%), and Escherichia coli represented the most common pathogen (n = 225). Pseudomonas species were isolated in 17.4% of patients. Nearly one-third of patients (31.3%) received initially inappropriate antibiotic therapy. Patients administered initially inappropriate antibiotic therapy were more likely to have a nosocomial infection, to have underlying cancer or diabetes or both, to require chronic hemodialysis, and to undergo mechanical ventilation. Those administered initially inappropriate antibiotic therapy also faced higher inhospital mortality. The unadjusted median length of stay after sepsis onset in those administered initially inappropriate antibiotic therapy was 11 days compared to 9 days in those treated appropriately (p = .028 by log-rank test). In a Cox model controlling for the multiple confounders noted, initially inappropriate antibiotic therapy independently correlated with continued hospitalization (adjusted hazard ratio 1.19, 95% confidence interval 1.01-1.40, p = .044). Adjusting for these covariates indicated that initially inappropriate antibiotic therapy independently increased the median attributable length of stay by 2 days. CONCLUSIONS: Initially inappropriate antibiotic therapy occurs in one-third of persons with severe sepsis and septic shock attributable to Gram-negative organisms. Beyond its impact on mortality, initially inappropriate antibiotic therapy is significantly associated with length of stay in this population. Efforts to decrease rates of initially inappropriate antibiotic therapy may serve to improve hospital resource use by leading to shorter overall hospital stays.

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

OBJECTIVE: Early therapy of sepsis involving fluid resuscitation and antibiotic administration has been shown to improve patient outcomes. A proactive tool to identify patients at risk for developing sepsis may decrease time to interventions and improve patient outcomes. The objective of this study was to evaluate whether the implementation of an automated sepsis screening and alert system facilitated early appropriate interventions. DESIGN: Prospective, observational, pilot study. SETTING: Six medicine wards in Barnes-Jewish Hospital, a 1250-bed academic medical center. PATIENTS: Patients identified by the sepsis screen while admitted to a medicine ward were included in the study. A total of 300 consecutive patients were identified comprising the nonintervention group (n=200) and the intervention group (n=100). INTERVENTIONS: A real-time sepsis alert was implemented for the intervention group, which notified the charge nurse on the patient's hospital ward by text page. MEASUREMENTS AND MAIN RESULTS: Within 12 hrs of the sepsis alert, interventions by the treating physicians were assessed, including new or escalated antibiotics, intravenous fluid administration, oxygen therapy, vasopressors, and diagnostic tests. After exclusion of patients without commitment to aggressive management, 181 patients in the nonintervention group and 89 patients in the intervention group were analyzed. Within 12 hrs of the sepsis alert, 70.8% of patients in the intervention group had received≥1 intervention vs. 55.8% in the nonintervention group (p=.018). Antibiotic escalation, intravenous fluid administration, oxygen therapy, and diagnostic tests were all increased in the intervention group. This was a single-center, institution- and patient-specific algorithm. CONCLUSIONS: The sepsis alert developed at Barnes-Jewish Hospital was shown to increase early therapeutic and diagnostic interventions among nonintensive care unit patients at risk for sepsis.

Evaluation of therapeutic anticoagulation with enoxaparin and associated anti-Xa monitoring in patients with morbid obesity: a case series.

Our purpose was to describe anti-Xa levels, dosage requirements, and complications associated with enoxaparin treatment doses in patients with morbid obesity. Inpatients with a BMI >40 kg/m(2) at an academic medical center prescribed therapeutic enoxaparin from 2004 to 2010 who also had an associated anti-Xa level were included in this retrospective evaluation. Twenty-six patients were identified having median weight of 162 kg (range 106-243), median BMI of 49.5 kg/m(2) (range 40.1-98.1), and median enoxaparin duration of 4 days (range 1-32). Venous thromboembolism was the most common reason for anticoagulation (n = 19, 73%). The median starting dose was 0.8 mg/kg actual body weight (range 0.51-1; absolute dose 80-150 mg) every 12 h. Twelve patients (46%) achieved a goal anti-Xa level, 10 (38%) were above goal and 4 (15%) were uninterpretable. Among the 10 patients with anti-Xa levels above goal, the median initial dose was 0.85 mg/kg (range 0.75-1) versus 0.74 mg/kg (range 0.51-1) for patients at goal with similar median peak serum creatinine (PSCr) values between these two groups (P > 0.05). No bleeding events occurred in patients achieving goal anticoagulation versus 4/10 (40%) with high anti-Xa levels (P = 0.033) with similar median PSCr between these groups. No thrombotic events occurred while on therapy. The majority in this cohort with morbid obesity achieved anti-Xa levels at or above goal at doses less than the recommended 1 mg/kg every 12 h. Bleeding events were more frequent among patients with anti-Xa levels above goal, despite similar PSCr values.

Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to Gram-negative bacteria: a retrospective analysis.

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., beta-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.

Methicillin-resistant Staphylococcus aureus nasal colonization is a poor predictor of intensive care unit-acquired methicillin-resistant Staphylococcus aureus infections requiring antibiotic treatment.

OBJECTIVE: To test whether intensive care unit (ICU) nasal screening for methicillin-resistant Staphylococcus aureus (MRSA) predicts the presence or absence of MRSA infections requiring antimicrobial treatment. DESIGN: A prospective cohort study. SETTING: Medical ICU at Barnes-Jewish Hospital, a 1252-bed urban teaching hospital. PATIENTS: Seven hundred forty-nine consecutive patients admitted to the medical ICU over a 7-mo period (November 2007 through June 2008). INTERVENTIONS: Nasal swabs were obtained at ICU admission and weekly thereafter for MRSA detection by using polymerase chain reaction. All subjects were followed for the development of MRSA infection during their ICU stay. MEASUREMENTS AND MAIN RESULTS: One hundred sixty-four (21.9%) patients had positive nasal colonization with MRSA at the time of ICU admission. The predictive accuracy of MRSA nasal colonization for ICU-acquired MRSA infections, either lower respiratory tract infection or bloodstream infection, was poor (lower respiratory tract infection: sensitivity, 24.2%; specificity, 78.5%; positive predictive value, 17.7%; and negative predictive value, 84.4%; and bloodstream infection: sensitivity, 23.1%; specificity, 78.2%; positive predictive value, 11.0%; and negative predictive value, 89.7%). Addition of nasal-colonization results obtained during the ICU stay did not appreciably change the predictive accuracy of this test for identification of subsequent lower respiratory tract infections and bloodstream infections attributed to MRSA requiring antimicrobial treatment. CONCLUSIONS: In this analysis, nasal colonization with MRSA was found to be a poor predictor for the subsequent occurrence of MRSA lower respiratory tract infections and MRSA bloodstream infections requiring antimicrobial treatment. Clinicians should be cautious in using the results of nasal-colonization testing to determine the need for MRSA treatment among patients with ICU-acquired infections.

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

OBJECTIVE: To evaluate the hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis on processes of medical care and patient outcomes. DESIGN: Retrospective, before and after study design. SETTING: Barnes-Jewish Hospital, a 1200-bed academic medical center. PATIENTS: Bacteremic patients with severe sepsis (200 from the 18-month before period and 200 from the 18-month after period). INTERVENTIONS: Hospital-wide implementation of a standardized order set for the management of bacteremic severe sepsis. MEASUREMENTS AND MAIN RESULTS: A total of 400 patients with bacteremia and severe sepsis were selected at random within the specified time periods. Patients in the after group received more intravenous fluids in the first 12 hours after onset of hypotension (1627 +/- 1862 mL vs. 2054 +/- 2237 mL; p = 0.04) and were more likely to receive appropriate initial antibiotic therapy (53.0% vs. 65.5%, p = 0.01). In-hospital mortality was statistically decreased in the after group (55.0% vs. 39.5%, p < 0.01), as was the hospital length of stay (28.7 +/- 30.1 days vs. 22.4 +/- 20.9 days; p = 0.02). Compared with the before group, the after group had reduced occurrence of renal failure (49.0% vs. 36.0%, p < 0.01), cardiovascular failure (70.5% vs. 57.0%, p < 0.01), and were less likely to require vasopressors after initial fluid resuscitation (68.5% vs. 52.5%, p < 0.01). CONCLUSIONS: The implementation of a hospital-wide standardized order set for the management of bacteremic severe sepsis was associated with greater fluid administration, improved antibiotic therapy, decreased incidence of organ failure, and improved survival.

Effects of an alternative cefepime dosing strategy in pulmonary and bloodstream infections caused by Enterobacter spp, Citrobacter freundii, and Pseudomonas aeruginosa: a single-center, open-label, prospective, observational study.

BACKGROUND: Various dosing strategies for cefepime have been developed in an effort to maximize pharmacodynamic exposure of this agent against gram-negative infections. An assessment of cefepime dosing strategies is warranted given recent reports of poorer treatment outcomes associated with cefepime compared with other antibiotics, particularly in patients infected with gram-negative organisms with elevated MICs. OBJECTIVES: The aims of this study were to compare the efficacy of cefepime IV at a dose of 1 g q8h (adjusted based on renal function) with those of other appropriate antimicrobials in the treatment of gramnegative pulmonary and bloodstream infections and to identify risk factors for treatment failure. METHODS: This single-center, open-label, prospective, observational study was conducted at a tertiary care center (Barnes-Jewish Hospital, St. Louis, Missouri). Isolates from infections in adult patients with bacteremia or pulmonary infection caused by Pseudomonas aeruginosa, Enterobacter aerogenes, Enterobacter cloacae, or Citrobacter freundii were assessed in a noninterventional manner. Infections were identified using an electronic notification system. Patients receiving appropriate monotherapy against the studied isolate within 24 hours of culture attainment were stratified into 1 of 3 cohorts according to treatment outcome, as follows: treatment success (resolution of initial fever or elevated white blood cell count to normal values plus the presence of repeat negative cultures from the initial site or below the quantitative definition for infection), improvement (treatment success without repeat negative cultures), or treatment failure (persistent or repeat positive cultures for the original organism at the infected site despite appropriate and adequate antimicrobial therapy, lack of resolution in fever or leukocytosis, switch to an alternative antibiotic, or the addition of another antibiotic with gram-negative coverage after > or =3 days of the initial regimen, relapse of infection within 14 days, or mortality attributable to the index infection). Multivariate regression analysis was used to examine risk factors associated with treatment failure. RESULTS: Data from 120 patients (56.7% male; mean age, 62.2 years) were analyzed. Treatment failure occurred in 48.6% (36/74) of patients who received cefepime versus 32.6% (15/46) of those who received other antibiotics; this difference was not statistically significant. The proportion of patients with markers of increased severity of illness (intensive care unit [P = 0.005] and mechanical ventilation [P = 0.002]) was significantly greater in the cefepime group compared with the group that received other antibiotics. Multivariate logistic regression identified infection with Pseudomonas aeruginosa (adjusted odds ratio [AOR], 1.40 [95% CI, 1.01-2.00]) and mechanical ventilation (AOR, 7.08 [95% CI, 1.80-31.3]) as being associated with treatment failure in patients who received cefepime. Mechanical ventilation (AOR, 3.97 [95% CI, 1.47-11.1]) and neutropenia (AOR, 5.26 [95% CI, 1.28-20.0]) were independent predictors of treatment failure among all patients studied. CONCLUSIONS: Based on these results in this small cohort, the efficacy of this cefepime dosing strategy (1 g q8h) appeared to be similar to that of other antimicrobials.

Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF.

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m(2) on Day 8) (FLAG-I) in relapsed/refractory AML. Three-quarters of patients also received concurrent G-CSF. Seventy-one patients were treated, 23 with FLAG-I and 48 with FLAG-IM. The median duration of follow-up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18-70) and 47 years (range 20-68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG-I and FLAG-IM. The complete remission (CR) rate in the FLAG-I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG-IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event-free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG-I over FLAG-IM. The patients who received G-CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G-CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG-I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G-CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.

Clinical validation of the AHRQ postoperative venous thromboembolism patient safety indicator.

BACKGROUND: The Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs) screen for potentially preventable complications in hospitalized patients using hospital administrative data. The PSI for postoperative venous thromboembolism (VTE) relies on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for deep vein thrombosis (DVT) or pulmonary embolism (PE) in secondary diagnoses fields. In a clinical validation study of the PSI for postoperative VTE, natural language processing (NLP), supplemented by pharmacy and billing data, was used to identify VTE events missed by medical records coders. METHODS: In a retrospective review of postsurgical discharges, charts were processed using the AHRQ PSI software. Cases were identified as possible false negatives by flagging charts for possible VTEs using pharmacy and billing data to identify all patients who were therapeutically anticoagulated or had placement of an inferior vena caval filter. All charts were reviewed by a physician blinded to screening results. Physician interpretation was considered the gold standard for VTE classification. RESULTS: The AHRQ PSI had a positive predictive value (PPV) of .545 (95% confidence interval [CI], .453-.634) and a negative predictive value (NPV) of .997 (95% CI, .995-.999). Sensitivity was .87 and specificity was .98. Secondary coding review suggested that all 9 false-negative results were miscoded; if they had been properly coded, the sensitivity would increase to 1.00. Most false-positive cases resulted from superficial venous clots identified by the PSI due to coding ambiguity. DISCUSSION: The VTE PSI performed well as a screening tool but generated a significant number of false-positive cases, a problem that could be substantially reduced with improved coding methods.

The modified APACHE II score outperforms Curb65 pneumonia severity score as a predictor of 30-day mortality in patients with methicillin-resistant Staphylococcus aureus pneumonia.

OBJECTIVE: To compare the predictive accuracy for 30-day mortality of the CURB65 score adopted by the British Thoracic Society and the simpler CRB65 score to APACHE (acute physiology and chronic health evaluation) II in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. PATIENTS: Adult patients requiring hospitalization identified to have MRSA pneumonia. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: Two hundred eighteen patients with MRSA pneumonia were identified over a 3-year period. Forty-four patients (20.2%) died during hospitalization. All three prediction rules had high negative predictive values but relatively low positive predictive values at most cut-off points examined. APACHE II had the greatest area under the receiver operating characteristic curve (0.805; 95% confidence interval [CI], 0.743 to 0.866) compared to CURB65 (0.634; 95% CI, 0.541 to 0.727) and CRB65 (0.643; 95% CI, 0.546 to 0.739) [p < 0.05 for both comparisons]. Similar results were obtained when the subgroups of community-acquired MRSA pneumonia and health-care-associated MRSA pneumonia were examined separately. CONCLUSIONS: APACHE II outperformed CURB65 and CRB65 for initial prognostic assessment in MRSA pneumonia.

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 ($68,597 +/- $55,466 vs $86,644 +/- $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.

Predictors of in-hospital mortality for bloodstream infections caused by Enterobacter species or Citrobacter freundii.

STUDY OBJECTIVE: To identify predictors of in-hospital mortality among patients with bacteremia caused by Enterobacter cloacae, Enterobacter aerogenes, or Citrobacter freundii. DESIGN: Retrospective cohort study. SETTING: 1300-bed tertiary academic medical center. PATIENTS: One hundred twenty-four patients who had bloodstream infections caused by E. cloacae (3), E. aerogenes (71), or C. freundii (50) between 1998 and 2004. MEASUREMENTS AND MAIN RESULTS: Data from patients with bloodstream infections caused by Enterobacter sp or C. freundii were retrospectively segregated according to hospital survival (98 survivors, 26 nonsurvivors). Multiple patient characteristics and processes of care were evaluated to identify factors contributing to in-hospital mortality. Multiple logistic regression was performed based on univariate comparisons to determine independent risk factors for in-hospital mortality. Among the 124 cases of bacteremia, the crude in-hospital mortality rate was 21% (26 cases). Univariate analysis revealed that survivors were more likely to receive an aminoglycoside as part of their empiric antimicrobial regimen (40% [39/98]) compared with nonsurvivors (19% [5/26], p=0.05). Other factors related to antimicrobial therapy including choice and number of agents used did not differ between survivors and nonsurvivors (p>0.05). Vasopressor use (31% [30/98] vs 62% [16/26]), care in an intensive care unit (19% [19/98] vs 54% [14/26]), and acute renal failure (13% [13/98] vs 31% [8/26]) occurred more frequently in nonsurvivors (p<0.05). Multiple logistic regression identified resistance to second- or third-generation cephalosporins (adjusted odds ratio [OR] 5.16, 95% confidence interval [CI] 2.66-10.0, p=0.013), trimethoprim-sulfamethoxazole resistance (adjusted OR 5.44, 95% CI 2.53-11.7, p=0.027), and mechanical ventilation (adjusted OR 12.2, 95% CI 5.99-24.5, p<0.001) as independent determinants of mortality. CONCLUSION: Among patients with Enterobacter sp or C. freundii bloodstream infections, those with trimethoprim-sulfamethoxazole-resistant or second or third-generation cephalosporin-resistant strains or those who required mechanical ventilation had an increased risk of mortality.

Implementing a commercial rule base as a medication order safety net.

A commercial rule base (Cerner Multum) was used to identify medication orders exceeding recommended dosage limits at five hospitals within BJC HealthCare, an integrated health care system. During initial testing, clinical pharmacists determined that there was an excessive number of nuisance and clinically insignificant alerts, with an overall alert rate of 9.2%. A method for customizing the commercial rule base was implemented to increase rule specificity for problematic rules. The system was subsequently deployed at two facilities and achieved alert rates of less than 1%. Pharmacists screened these alerts and contacted ordering physicians in 21% of cases. Physicians made therapeutic changes in response to 38% of alerts presented to them. By applying simple techniques to customize rules, commercial rule bases can be used to rapidly deploy a safety net to screen drug orders for excessive dosages, while preserving the rule architecture for later implementations of more finely tuned clinical decision support.

Macrolides are associated with a better survival rate in patients hospitalized with community-acquired but not healthcare-associated pneumonia.

BACKGROUND: Macrolide-based treatment has been associated with survival benefit in patients hospitalized with community-acquired pneumonia (CAP). However, the influence of macrolide therapy in all patients hospitalized with pneumonia, including healthcare-associated pneumonia (HCAP), is unclear. METHODS: Analysis of a retrospective single-center cohort. RESULTS: Community-acquired pneumonia was present in 220 (22.5%) of all patients with pneumonia admitted through the emergency department of Barnes-Jewish Hospital, and HCAP was present in 757. Macrolide-based treatment was administered to 411 patients (42.1%). These patients were more likely to have CAP than were patients not receiving macrolide-based therapy (35.3% vs. 13.3%; p<0.001) and had lower scores on the CURB-65 tool, a measure of the severity of illness (2.4±1.5 vs. 3.1±1.3; p<0.001). Patients receiving macrolides also had a lower hospital mortality rate in univariable analysis (12.7% vs. 27.2%; p<0.001). A propensity score analysis showed that macrolide-based treatment was associated with a lower in-hospital mortality rate (adjusted odds ratio [AOR] 0.67; 95% confidence interval [CI] 0.54-0.81; p=0.043). Separate propensity score analyses of patients with CAP (AOR 0.20; 95% CI 0.11-0.34; p=0.003) and HCAP (AOR 0.81; 95% CI 0.65-1.01; p=0.337) produced discordant findings. CONCLUSIONS: Macrolide-based treatment was associated with better survival in patients hospitalized with pneumonia. The survival advantage appeared predominantly among patients with CAP.

Health care-associated pneumonia (HCAP): empiric antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa predict optimal outcome.

Inappropriate initial antimicrobial therapy (IIAT) has been associated with decreased survival in patients with health care-associated pneumonia (HCAP). We performed a study to determine whether empiric HCAP antibiotic regimens targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are associated with greater appropriate therapy. A retrospective cohort study of culture-positive HCAP over 6 years (January 2003-December 2008) was performed at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. We identified 757 consecutive patients with HCAP. IIAT was administered to 213 (28%) patients. The pathogens most frequently associated with IIAT included P. aeruginosa (n=60, 28%), MRSA (n=58, 27%), and Acinetobacter species (n=32, 15%).Multivariate logistic regression analysis demonstrated that empiric anti-pseudomonal antibiotics (adjusted odds ratio [AOR], 1.75; 95% confidence interval [CI], 1.34-2.29; p=0.036), empiric anti-MRSA antibiotics (AOR, 1.71; 95% CI, 1.36-2.14; p=0.018), infection with Streptococcus pneumoniae (AOR, 2.82; 95% CI, 2.03-3.91; p=0.002), absence of Acinetobacter species infection (AOR, 10.57; 95% CI, 7.29-15.33; p<0.001), absence of P. aeruginosa infection (AOR, 1.69; 95% CI, 1.36-2.05; p=0.014), and absence of Stenotrophomonas maltophilia infection (AOR, 20.43; 95% CI, 9.35-44.66; p<0.001) are independent predictors of appropriate therapy for HCAP. Our study suggests that initial therapy for HCAP should include antibiotics targeting MRSA and P. aeruginosa in order to provide appropriate initial therapy. However, the selection of individual antibiotic agents should be based on local patterns of infection and adjusted when microbiology results become available.

Resistance to empiric antimicrobial treatment predicts outcome in severe sepsis associated with Gram-negative bacteremia.

BACKGROUND: Gram-negative bacteria are an important cause of severe sepsis. Recent studies have demonstrated reduced susceptibility of Gram-negative bacteria to currently available antimicrobial agents. METHODS: We performed a retrospective cohort study of patients with severe sepsis who were bacteremic with Pseudomonas aeruginosa, Acinetobacter species, or Enterobacteriaceae from 2002 to 2007. Patients were identified by the hospital informatics database and pertinent clinical data (demographics, baseline severity of illness, source of bacteremia, and therapy) were retrieved from electronic medical records. All patients were treated with antimicrobial agents within 12 hours of having blood cultures drawn that were subsequently positive for bacterial pathogens. The primary outcome was hospital mortality. RESULTS: A total of 535 patients with severe sepsis and Gram-negative bacteremia were identified. Hospital mortality was 43.6%, and 82 (15.3%) patients were treated with an antimicrobial regimen to which the causative pathogen was resistant. Patients infected with a resistant pathogen had significantly greater risk of hospital mortality (63.4% vs 40.0%; P < 0.001). In a multivariate analysis, infection with a pathogen that was resistant to the empiric antibiotic regimen, increasing APACHE II scores, infection with Pseudomonas aeruginosa, healthcare-associated hospital-onset infection, mechanical ventilation, and use of vasopressors were independently associated with hospital mortality. CONCLUSIONS: In severe sepsis attributed to Gram-negative bacteremia, initial treatment with an antibiotic regimen to which the causative pathogen is resistant was associated with increased hospital mortality. This finding suggests that rapid determination of bacterial susceptibility could influence treatment choices in patients with severe sepsis potentially improving their clinical outcomes.

A comparison of culture-positive and culture-negative health-care-associated pneumonia.

OBJECTIVE: The aim of this study is to describe the initial antibiotic treatment regimens, severity of illness, and in-hospital mortality among culture-negative (CN) and culture-positive (CP) patients with health-care-associated pneumonia (HCAP). METHODS: We used a retrospective cohort study, examining adult patients with HCAP from Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. RESULTS: Eight hundred seventy patients with HCAP were identified over a 3-year period (January 2003 through December 2005) of whom 431 (49.5%) were CP. Among the non-CP patients, 290 (66.1%) had no respiratory cultures obtained, and 149 (33.9%) had no growth or nonpathogenic oral flora identified and were classified as CN. CN patients were more likely to have received an initial antibiotic regimen (ceftriaxone +/- azithromycin or moxifloxacin) targeting community-acquired pneumonia pathogens compared with CP patients (71.8% vs 25.5%, P < .001). Severity of illness as assessed by ICU admission and mechanical ventilation (MV) was statistically lower in CN compared with CP patients (ICU admittance 12.1% vs 48.7%, P < .001; MV: 6.7% vs 44.5%, P < .001). In-hospital mortality and hospital length of stay were also statistically lower for CN patients (mortality: 7.4% vs 24.6%, P < .001; hospital length of stay: 6.7 +/- 7.4 days vs 12.1 +/- 11.7 days, P < .001). CONCLUSIONS: In this analysis, patients with CN HCAP had lower severity of illness, hospital mortality, and hospital length of stay compared with CP patients. These data suggest that patients with CN HCAP differ substantially from patients with HCAP with positive microbiologic cultures.

Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients.

STUDY OBJECTIVE: To describe the characteristics and clinical outcomes of hematopoietic stem cell transplant (HSCT) recipients who received adjunctive cytomegalovirus intravenous immune globulin (CMV-IVIG) for probable or proven CMV disease. DESIGN: Retrospective cohort study. SETTING: Large, university-affiliated, tertiary-care medical center. PATIENTS: Thirty-five adult HSCT recipients who received at least one dose of CMV-IVIG for adjunctive treatment of probable or proven CMV disease between January 1, 1999, and December 31, 2007. MEASUREMENTS AND MAIN RESULTS: All-cause mortality at hospital discharge was the primary outcome. All patients received an allogeneic HSCT. Twenty-six patients (74%) had pneumonitis, nine (26%) had enteritis, and 29 (83%) had CMV viremia. All patients received concomitant antiviral therapy; 31 (89%) received ganciclovir, and 14 (40%) received foscarnet. All-cause mortality at hospital discharge was 49% (17 patients). Patient characteristics associated with mortality included requiring intubation for CMV pneumonia (11 [79%] of 14 nonsurvivors vs 3 (25%) of 12 survivors, p=0.016) and earlier disease onset after HSCT (median 48 days for nonsurvivors vs 106 days for survivors, p<0.001). In the multivariate analysis, only requiring intubation for CMV pneumonia remained a significant risk factor for increased mortality. A low rate of adverse events was attributed to CMV-IVIG, with mild hypertension (two patients [6%]) and erythema and chills (one patient [3%]) being the most common. CONCLUSION: The mortality rate in our study population was similar to previous reports in the literature and may be somewhat lower than rates reported with antiviral monotherapy. Our analysis suggests that factors associated with mortality include the need for intubation and, possibly, earlier onset of CMV disease after HSCT. Treatment with CMV-IVIG appears to be well tolerated in HSCT recipients. These findings support further trials of CMV-IVIG efficacy in this setting.