Timothy Wiemken

Relationship of Vancomycin Minimum Inhibitory Concentration to Mortality in Patients With Methicillin-Resistant Staphylococcus aureus Hospital-Acquired, Ventilator-Associated, or Health-care-Associated Pneumonia

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-care-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality for patients with MRSA pneumonia has not been determined. METHODS Adult patients in ICUs with a diagnosis of MRSA HAP, VAP, or HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables. RESULTS The study sample consisted of 158 patients. All-cause mortality at day 28 was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL (P ≤ .001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality. CONCLUSIONS Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC, even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution, and alternative therapies should be considered.

Decrease in Long-term Survival for Hospitalized Patients With Community-Acquired Pneumonia

BACKGROUND The association of hospitalization because of community-acquired pneumonia (CAP) and long-term survival has not been fully examined. We measured the long-term survival of hospitalized patients with CAP adjusted for the effects of comorbidities. METHODS A cohort of adult patients admitted to the medical services of the Veterans Affairs Medical Center, Louisville, Kentucky, was retrospectively examined. A Kaplan-Meier survival curve was constructed to assess the effect of CAP admission status on patient survival. A Cox proportional hazards regression model included comorbidities as predictors and time to death as the outcome in the construction of a modified Charlson Comorbidity Index (mCCI). The mCCI was internally validated to evaluate the predictability of patient survival. The mCCI and age > 65 years were included as potential confounders in a final Cox proportional hazards regression model with CAP admission status as the main predictor and time to death as the outcome. RESULTS CAP was identified in 624 (9%) out of 6,971 patients. The Kaplan-Meier survival curve showed a significantly shorter survival among patients with CAP than those without CAP (P < .0001). The internal validation of the mCCI showed that patients were more likely to die as the mCCI increased (P < .0001). The Cox proportional hazards regression modeling the association between time to death and CAP admission after adjusting for elderly age and the mCCI showed that hospitalization due to CAP was a statistically significant predictor of decreased survival (hazard ratio, 1.4; 95% CI, 1.2-1.5; P < .0001). CONCLUSION There is a decreased long-term survival among hospitalized patients with CAP after adjusting for comorbidities and aging. Future research to understand the pathophysiology of the long-term CAP outcomes is necessary to develop treatment strategies.

Severity of Disease and Clinical Outcomes in Patients With Hospital-Acquired Pneumonia Due to Methicillin-Resistant Staphylococcus aureus Strains Not Influenced by the Presence of the Panton-Valentine Leukocidin Gene

BACKGROUND Patients with community-acquired pneumonia (CAP) infected with methicillin-resistant Staphylococcus aureus (MRSA) strains carrying the Panton-Valentine leukocidin (PVL) gene have severe clinical presentation and poor clinical outcomes. Antibiotics that suppress toxin production have been suggested for the management of these patients. The objective of this study was to compare the severity of disease and clinical outcomes of patients with hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) infected with MRSA carrying the PVL gene with those patients infected with MRSA strains that do not carry the PVL gene. METHODS This was a multicenter observational study of patients with HAP and VAP. MRSA isolates were subjected to genetic analysis to define the presence of the PVL gene, the USA type and the staphylococcal cassette chromosome mec type. Severity of disease was evaluated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary clinical outcome was mortality at hospital discharge. RESULTS A total of 109 cases of MRSA HAP/VAP were evaluated. The incidence of PVL(+) MRSA was 27%. APACHE II score at diagnosis of HAP/VAP was 21 ± 8 for PVL(+) MRSA and 20 ± 6 for PVL(-) MRSA (P = .67). Mortality was 10% (3/29) for patients with PVL(+) MRSA versus 10% (8/80) for patients with PVL(-) MRSA (P > .99). CONCLUSIONS In patients with HAP or VAP due to MRSA, severity of disease and clinical outcomes are not influenced by the presence of the PVL gene. Therapeutic strategies directed to block PVL exotoxin may not impact outcomes in these patients.

The effectiveness of the polysaccharide pneumococcal vaccine for the prevention of hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia in the elderly differs between the sexes: Results from the Community-Acquired Pneumonia Organization (CAPO) international cohort study

BACKGROUND The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) to prevent hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia (SpCAP) is controversial. Recent literature suggests that vaccine effectiveness may be influenced by sex. In this study, we define the effectiveness of prior PPV23 vaccination for the prevention of hospitalizations due to SpCAP, and evaluate the impact of sex on this effectiveness. METHODS This was a nested case-control study from the CAPO international cohort study database. SpCAP was defined as CAP plus S. pneumoniae identified in blood, bronchoalveolar lavage, sputum, or urinary antigen. Vaccination with PPV23 prior to hospitalization was defined as documented in the medical record. A propensity score-weighted logistic regression model was used to calculate odds ratios. The adjusted vaccine effectiveness (aVE) was calculated as 1-adjusted odds ratio. RESULTS From a total of 2688 elderly adult hospitalized patients with CAP, SpCAP was identified in 279 (10%). The overall aVE was 37% (95% CI: 10.1-55.4%, P=0.01). For males, the aVE was 34% (95% CI:-1.0% to 57.3%, P=0.06). For females the aVE was 68% (95% CI: 40.3-83.0%, P=0.001). CONCLUSIONS PPV23 protects elderly patients from hospitalization due to SpCAP, but female sex drives the effectiveness. Future analysis of vaccine trials should consider the importance of sex as a stratification factor.

Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: Results from the IMPACT-HAP study

IntroductionControversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP.MethodsThis was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success.ResultsA total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018).ConclusionsThis study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.

Global Changes in the Epidemiology of Community-Acquired Pneumonia

Lower respiratory tract infections are the most common infectious cause of death in the world and the third most common cause of death globally (all causes). This article reviews the epidemiology of community-acquired pneumonia from a global perspective. Major areas of epidemiological work include (1) disease surveillance to define the burden of disease and to document outbreaks, (2) identification of risk factors for a disease to optimize prevention strategies, and (3) comparisons of treatment effects to improve clinical outcomes for patients with the disease.

Early administration of the first antimicrobials should be considered a marker of optimal care of patients with community-acquired pneumonia rather than a predictor of outcomes

BACKGROUND The effect of time of the first antimicrobial dose (TFAD) on the outcomes of community-acquired pneumonia (CAP) remains a controversy. METHODS This was an observational, retrospective study of consecutive adult patients hospitalized with CAP. TFAD was defined as the time in hours from arrival at the emergency department to the intravenous infusion of antimicrobial. All patients received appropriate antibiotic therapy according to available Infectious Diseases Society of America/American Thoracic Society guidelines during the time of our study. Multivariable analysis and a propensity score adjusted methodology were used to measure the association of TFAD with mortality, time to clinical stability (TCS), and length of stay in the hospital (LOS). RESULTS Data of 372 patients with CAP were studied. A total 29 (8.4%) patients died within 30 days of hospitalization. Our propensity-adjusted logistic regression model did not show a significant association between TFAD and mortality (p=0.148). Patients who died received antimicrobials significantly earlier than survivors: 5.7h vs. 7.5h, respectively (p=0.04). The LOS and TCS were not significantly affected by the TFAD; the LOS hazard ratio was 0.996 (95% confidence interval 0.97-1.02; p=0.774) and the TCS hazard ratio was 1.01 (95% confidence interval 0.98-1.03; p=0.604). CONCLUSIONS TFAD does not seem to be associated with the clinical outcome of patients with CAP. Early TFAD should be considered as an important marker of optimal care of patients with CAP rather than as a factor predicting outcomes.

Animals in Healthcare Facilities: Recommendations to Minimize Potential Risks

Animals may be present in healthcare facilities for multiple reasons. Although specific laws regarding the use of service animals in public facilities were established in the United States in 1990, the widespread presence of animals in hospitals, including service animals to assist in patient therapy and research, has resulted in the increased presence of animals in acute care hospitals and ambulatory medical settings. The role of animals in the transmission of zoonotic pathogens and cross-transmission of human pathogens in these settings remains poorly studied. Until more definitive information is available, priority should be placed on patient and healthcare provider safety, and the use of standard infection prevention and control measures to prevent animal-to-human transmission in healthcare settings. This paper aims to provide general guidance to the medical community regarding the management of animals in healthcare (AHC). The manuscript has four major goals:

Ruling Out Legionella in Community-acquired Pneumonia

BACKGROUND Assessing the likelihood for Legionella sp. in community-acquired pneumonia is important because of differences in treatment regimens. Currently used antigen tests and culture have limited sensitivity with important time delays, making empirical broad-spectrum coverage necessary. Therefore, a score with 6 variables recently has been proposed. We sought to validate these parameters in an independent cohort. METHODS We analyzed adult patients with community-acquired pneumonia from a large multinational database (Community Acquired Pneumonia Organization) who were treated between 2001 and 2012 with more than 4 of the 6 prespecified clinical variables available. Association and discrimination were assessed using logistic regression analysis and area under the curve (AUC). RESULTS Of 1939 included patients, the infectious cause was known in 594 (28.9%), including Streptococcus pneumoniae in 264 (13.6%) and Legionella sp. in 37 (1.9%). The proposed clinical predictors fever, cough, hyponatremia, lactate dehydrogenase, C-reactive protein, and platelet count were all associated or tended to be associated with Legionella cause. A logistic regression analysis including all these predictors showed excellent discrimination with an AUC of 0.91 (95% confidence interval, 0.87-0.94). The original dichotomized score showed good discrimination (AUC, 0.73; 95% confidence interval, 0.65-0.81) and a high negative predictive value of 99% for patients with less than 2 parameters present. CONCLUSIONS With the use of a large independent patient sample from an international database, this analysis validates previously proposed clinical variables to accurately rule out Legionella sp., which may help to optimize initial empiric therapy.

Emergence of methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of late-onset nosocomial pneumonia in intensive care patients in the USA ☆

OBJECTIVE To compare demographic and clinical characteristics, and methicillin-resistant Staphylococcus aureus (MRSA) strain characteristics, in patients with early-onset (EO) and late-onset (LO) MRSA nosocomial pneumonia. METHODS This was a retrospective analysis of data from a multicenter observational study of nosocomial pneumonia patients admitted between November 2008 and July 2010. Laboratory analyses performed on MRSA isolates included confirmation of antimicrobial susceptibility and heteroresistance to vancomycin, USA typing, staphylococcal cassette chromosome (SCC) mec typing, and detection of Panton-Valentine leukocidin (PVL) genes. RESULTS We identified 134 patients; 42 (31%) had EO MRSA pneumonia and 92 (69%) had LO MRSA pneumonia. The patients in the LO group were more likely to have risk factors for multidrug-resistant pathogens (98% vs. 76%, p<0.001). The MRSA USA300 strain was found with equal frequency in the EO and LO groups. Likewise, both groups had similar frequencies of isolates exhibiting PVL and SCCmec type IV. CONCLUSIONS Our findings provide further evidence of the continued migration of community-associated MRSA into the healthcare setting in the USA. MRSA USA300 genotype has emerged as a significant cause of LO nosocomial pneumonia in intensive care units. Appropriate anti-MRSA antimicrobial therapy should be considered for both EO and LO hospital-acquired pneumonia and ventilator-associated pneumonia.