Scott T. Micek

Septic Shock Attributed to Candida Infection: Importance of Empiric Therapy and Source Control

BACKGROUND Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. METHODS A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). RESULTS Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. CONCLUSIONS The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical 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 (

Alternatives to Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

68,597 +/-

Antimicrobial Therapy Escalation and Hospital Mortality Among Patients With Health-Care-Associated Pneumonia: A Single-Center Experience

55,466 vs

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

86,644 +/-

Health Care—Associated Pneumonia (HCAP): A Critical Appraisal to Improve Identification, Management, and Outcomes—Proceedings of the HCAP Summit

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.

Inappropriate empiric antifungal therapy for candidemia in the ICU and hospital resource utilization: a retrospective cohort study

Vancomycin remains the reference standard for the treatment of systemic infection caused by methicillin-resistant Staphylococcus aureus (MRSA). However, as a result of limited tissue distribution, as well as the emergence of isolates with reduced susceptibility and in vitro resistance to vancomycin, the need for alternative therapies that target MRSA has become apparent. New treatment options for invasive MRSA infections include linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. Additionally, a number of new anti-MRSA compounds are in development, including novel glycopeptides (dalbavancin, telavancin, and oritavancin), ceftobiprole, and iclaprim. The present article will review clinical issues surrounding the newly marketed and investigational agents with activity against MRSA.

Hospital resource utilization and costs of inappropriate treatment of candidemia.

BACKGROUND Patients with health-care-associated pneumonia (HCAP) are frequently infected with a resistant pathogen and receive inappropriate empiric antibiotics (ie, pathogens resistant to administered treatment). Initial inappropriate treatment has been shown to increase hospital mortality. It is not known whether escalation in response to culture results mitigates this risk. METHODS We identified patients admitted with a culture-positive pneumonia between January 2003 and December 2005. HCAP patients met one or more of the following criteria indicating ongoing contact with the health-care system: recent hospitalization (< or = 12 months), admission from a nursing home, immunosuppression, or long-term dialysis. We compared survivors to nonsurvivors among those patients with HCAP still hospitalized beyond 48 h. RESULTS Of 431 HCAP patients, 396 patients (92%) were alive and still hospitalized beyond 48 h. The crude mortality rate was 21.5%. Compared to survivors, nonsurvivors were significantly more likely to be treated with inappropriate empiric antibiotics (37.6% vs 24.1%, p = 0.013). Although mortality was higher among patients receiving inappropriate than appropriate therapy (30.0% vs 18.3%, p = 0.013), this difference was more pronounced among nonbacteremic patients (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.26 to 4.75) than bacteremic patients (OR, 1.25; 95% CI, 0.41 to 3.57). In a logistic regression, inappropriate empiric antibiotic treatment among nonbacteremic patients was independently associated with mortality (OR, 2.88; 95% CI, 1.46 to 5.67); treatment escalation did not attenuate the risk of death. CONCLUSION Among HCAP patients alive and hospitalized beyond 48 h, hospital mortality was high and, in the absence of bacteremia, greater with initial inappropriate antibiotic treatment. Despite subsequent escalation, initial inappropriate antibiotic choice nearly tripled the risk of hospital death.

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.

A Comparison of Culture-Positive and Culture-Negative Health-Care-Associated Pneumonia

Increasingly, patients are receiving treatment at facilities other than hospitals, including long-term-health care facilities, assisted-living environments, rehabilitation facilities, and dialysis centers. As with hospital environments, nonhospital settings present their own unique risks of pneumonia. Traditionally, pneumonia in these facilities has been categorized as community-acquired pneumonia (CAP). However, the new designation for pneumonias acquired in these settings is health care-associated pneumonia (HCAP), which covers pneumonias acquired in health care environments outside of the traditional hospital setting and excludes hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and CAP. Although HCAP is currently treated with the same protocols as CAP, recent evidence indicates that HCAP differs from CAP with respect to pathogens and prognosis and, in fact, more closely resembles HAP and VAP. The HCAP Summit convened national infectious disease opinion leaders for the purpose of analyzing current literature, clinical trial data, diagnostic considerations, therapeutic options, and treatment guidelines related to HCAP. After an in-depth analysis of these areas, the infectious disease investigators participating in the summit were surveyed with regard to 10 clinical practice statements. The results were then compared with results of the same survey as completed by 744 Infectious Diseases Society of America members. The similarities and differences between those survey results are the basis of this publication.