COVID-19 in the hotspot of Metropolitan Detroit: A multi-faceted health system experience.

Health systems were abruptly plunged into a crisis as SARS-CoV-2 exploded into a pandemic in spring 2020. In March-April 2020, Metropolitan Detroit was a US "hotspot." As a large health system with five hospitals and two behavioural health inpatient facilities, a health insurance company, a medical group and physician network, and 41 ambulatory clinics normally hosting over 10,000 daily patient encounters, the Henry Ford Health System deployed numerous strategies in the management of this upheaval. As hospitals and Emergency Departments were inundated with COVID-19 patients, other services and activities needed to shut down as state-mandated policies were promulgated, new internal and external communication networks established, and management of employees and resources such as ventilators, ICU beds, personal protective equipment, and laboratory supplies became critical challenges. We describe herein the system-wide strategies implemented and lessons learned in the operation of a health system in the initial throes of a global pandemic.

Daptomycin versus vancomycin for bloodstream infections due to methicillin-resistant Staphylococcus aureus with a high vancomycin minimum inhibitory concentration: a case-control study.

BACKGROUND: Reports have found a link between vancomycin treatment failure in methicillin-resistant Staphyloccocus aureus (MRSA) bloodstream infections (BSIs) and higher vancomycin minimum inhibitory concentrations (MICs), despite MICs being below the susceptibility breakpoint of 2 µg/mL. Consensus guidelines recommend considering use of alternative agents for infections involving a higher vancomycin MIC, despite few data to support this approach. METHODS: This retrospective case-control study evaluated the effectiveness and safety of vancomycin, compared with that of daptomycin, in the treatment of MRSA BSIs with a high vancomycin MIC (ie, >1 µg/mL). RESULTS: A total of 118 vancomycin-treated subjects were compared with 59 daptomycin-treated subjects. Clinical failure, defined compositely as mortality, microbiologic failure, and/or recurrence of infection, was numerically lower in daptomycin-treated subjects (31% vs 17%; P = .084) and was mainly driven by a lower incidence of mortality in the daptomycin group (20% vs 9%; P = .046). Factors independently associated with clinical failure included acute renal failure (odds ratio [OR], 3.91 [95% confidence interval {CI}, 1.05-14.56]) and vancomycin treatment group (OR, 3.13 [95%, CI, 1.00-9.76]). Right-sided endocarditis was independently associated with clinical success (OR, 0.07 [95% CI, .01-.83]). A comparison of 60-day mortality between vancomycin- and daptomycin-treated subjects found a higher probability of survival in the daptomycin-treated group (P = .022). CONCLUSIONS: The results demonstrated that daptomycin was associated with a better outcome compared with vancomycin for the treatment of BSIs due to MRSA with higher vancomycin MICs. These findings support the recommendations of recent guidelines, which suggest consideration of the switch to alternative agents when the isolate has a high vancomycin MIC or when patients are not improving during receipt of therapy.

Epidemiology and outcomes of complicated skin and soft tissue infections in hospitalized patients.

Complicated skin and soft tissue infections (cSSTIs) are among the most rapidly increasing reasons for hospitalization. To describe inpatients with regard to patient characteristics, cSSTI origin, appropriateness of initial antibiotics, and outcomes, we performed a retrospective cohort study in patients hospitalized for cSSTI. To identify independent predictors of outcomes, we performed multivariate analyses. Of 1,096 eligible patients, 48.7% had health care-associated (HCA) cSSTI and 51.3% had community-acquired (CA) cSSTI. After adjustment for baseline variables, hospital length of stay (LOS) was longer for HCA than for CA cSSTI (difference, 2.1 days; 95% confidence interval [CI], 0.8 to 3.5; P < 0.05). Other covariates associated with a longer LOS were need for dialysis (regression coefficient ± standard error, 4.5 ± 1.1) and diabetic wound diagnosis (2.6 ± 1.0) (all P < 0.05). In the subset with culture-positive cSSTI within 24 h of admission, the most common pathogen was Staphylococcus aureus (298/449 [66.4%]), of which 74.8% (223/298) were methicillin-resistant S. aureus (MRSA). Eighty-three patients (18.5%) received inappropriate initial antibiotics. After adjustment for other variables, the following were associated with inappropriate initial therapy: direct admission to hospital (not via emergency department), cSSTI caused by MRSA or mixed pathogens, and cSSTI caused by pathogens other than S. aureus or streptococci (all P < 0.05). We did not find an association between inappropriate therapy and outcomes, except in the subset with ulcers (adjusted odds ratio, 11.8; 95% CI, 1.3 to 111.1; P = 0.03). More studies are needed to examine the impact of HCA cSSTI and inappropriate initial therapy on outcomes.

Analysis of pathogen and host factors related to clinical outcomes in patients with hospital-acquired pneumonia due to methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial pneumonia. To characterize pathogen-derived and host-related factors in intensive care unit (ICU) patients with MRSA pneumonia, we evaluated the Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) database. We performed multivariate regression analyses of 28-day mortality and clinical response using univariate analysis variables at a P level of <0.25. In isolates from 251 patients, the most common molecular characteristics were USA100 (55.0%) and USA300 (23.9%), SCCmec types II (64.1%) and IV (33.1%), and agr I (36.7%) and II (61.8%). Panton-Valentine leukocidin (PVL) was present in 21.9%, and vancomycin heteroresistance was present in 15.9%. Mortality occurred in 37.1% of patients; factors in the univariate analysis were age, APACHE II score, AIDS, cardiac disease, vascular disease, diabetes, SCCmec type II, PVL negativity, and higher vancomycin MIC (all P values were <0.05). In multivariate analysis, independent predictors were APACHE II score (odds ratio [OR], 1.090; 95% confidence interval [CI], 1.041 to 1.141; P < 0.001) and age (OR, 1.024; 95% CI, 1.003 to 1.046; P = 0.02). Clinical failure occurred in 36.8% of 201 evaluable patients; the only independent predictor was APACHE II score (OR, 1.082; 95% CI, 1.031 to 1.136; P = 0.002). In summary, APACHE II score (mortality, clinical failure) and age (mortality) were the only independent predictors, which is consistent with severity of illness in ICU patients with MRSA pneumonia. Interestingly, our univariate findings suggest that both pathogen and host factors influence outcomes. As the epidemiology of MRSA pneumonia continues to evolve, both pathogen- and host-related factors should be considered when describing epidemiological trends and outcomes of therapeutic interventions.

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.

Prediction of failure in vancomycin-treated methicillin-resistant Staphylococcus aureus bloodstream infection: a clinically useful risk stratification tool.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of bloodstream infection (BSI) and is often associated with invasive infections and high rates of mortality. Vancomycin has remained the mainstay of therapy for serious Gram-positive infections, particularly MRSA BSI; however, therapeutic failures with vancomycin have been increasingly reported. We conducted a comprehensive evaluation of the factors (patient, strain, infection, and treatment) involved in the etiology and management of MRSA BSI to create a risk stratification tool for clinicians. This study included consecutive patients with MRSA BSI treated with vancomycin over 2 years in an inner-city hospital in Detroit, MI. Classification and regression tree analysis (CART) was used to develop a risk prediction model that characterized vancomycin-treated patients at high risk of clinical failure. Of all factors, the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, with a cutoff point of 14, was found to be the strongest predictor of failure and was used to split the population into two groups. Forty-seven percent of the population had an APACHE-II score < 14, a value that was associated with low rates of clinical failure (11%) and mortality (4%). Fifty-four percent of the population had an APACHE-II score ≥ 14, which was associated with high rates of clinical failure (35%) and mortality (23%). The risk stratification model identified the interplay of three other predictors of failure, including the vancomycin MIC as determined by Vitek 2 analysis, the risk level of the source of BSI, and the USA300 strain type. This model can be a useful tool for clinicians to predict the likelihood of success or failure in vancomycin-treated patients with MRSA bloodstream infection.

Clinical and economic outcomes for patients with health care-associated Staphylococcus aureus pneumonia.

While the increasing importance of methicillin-resistant Staphylococcus aureus (MRSA) as a pathogen in health care-associated S. aureus pneumonia has been documented widely, information on the clinical and economic consequences of such infections is limited. We retrospectively identified all patients admitted to a large U.S. urban teaching hospital between January 2005 and May 2008 with pneumonia and positive blood or respiratory cultures for S. aureus within 48 h of admission. Among these patients, those with suspected health care-associated pneumonia (HCAP) were identified using established criteria (e.g., recent hospitalization, admission from nursing home, or hemodialysis). Subjects were designated as having methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) HCAP, based on initial S. aureus isolates. Initial therapy was designated "appropriate" versus "inappropriate" based on the expected susceptibility of the organism to the regimen received. We identified 142 patients with evidence of S. aureus HCAP. Their mean (standard deviation [SD]) age was 64.5 (17) years. Eighty-seven patients (61%) had initial cultures that were positive for MRSA. Most ( approximately 90%) patients received appropriate initial antibiotic therapy (86% for MRSA versus 91% for MSSA; P = 0.783). There were no significant differences between MRSA and MSSA HCAP patients in mortality (29% versus 20%, respectively), surgery for pneumonia (22% versus 20%), receipt of mechanical ventilation (60% versus 58%), or admission to the intensive care unit (79% versus 76%). Mean (SD) total charges per admission were universally high ($98,170 [$94,707] for MRSA versus $104,121 [$91,314]) for MSSA [P = 0.712]). Almost two-thirds of patients admitted to hospital with S. aureus HCAP have evidence of MRSA infection. S. aureus HCAP, irrespective of MRSA versus MSSA status, is associated with significant mortality and high health care costs, despite appropriate initial antibiotic therapy.

Trends in US hospital admissions for skin and soft tissue infections.

Using data from the 2000-2004 US Healthcare Cost and Utilization Project National Inpatient Sample, we found that total hospital admissions for skin and soft tissue infections increased by 29% during 2000-2004; admissions for pneumonia were largely unchanged. These results are consistent with recent reported increases in community-associated methicillin-resistant Staphylococcus aureus infections.

Regulation of gene expression of hepatic drug metabolizing enzymes and transporters by the Toll-like receptor 2 ligand, lipoteichoic acid.

Expression of hepatic drug metabolizing enzymes (DMEs) is altered in infection and inflammation. However, the role of Gram+ve bacterial components and their receptor, Toll-like receptor (TLR) 2 in regulation of hepatic DMEs is unknown. Gene expression of DMEs is regulated by members of the nuclear receptor superfamily (PXR, CAR and RXRalpha). The TLR2 ligand, lipoteichoic acid (LTA) reduced RNA levels of CAR and its target genes, Cyp2b10, Cyp2a4 and Sultn in mouse liver ( approximately 60-80% reduction). Hepatic genes regulated by PXR and CAR, Cyp3a11 and Mrp2 were moderately reduced by LTA, along with approximately 50% reduction of PXR RNA and nuclear protein levels of RXRalpha. The effects of LTA were significantly attenuated by pre-treatment with the Kupffer cell inhibitor, gadolinium chloride, indicating that Kupffer cells contribute to LTA-mediated down-regulation of hepatic genes. These results indicate that treatment with Gram+ve bacterial components preferentially down-regulate CAR and its target genes in the liver.

Variations in pharmacy-based transition-of-care activities in the United States: a national survey.

PURPOSE: A national survey was conducted to assess pharmacist roles in transition-of-care (TOC) activities in the United States. METHODS: An online survey was sent to 1246 pharmacy directors who were members of the American Society of Health-System Pharmacists to assess their involvement in TOC activities including medication reconciliation, admission histories, medication counseling, and postdischarge follow-up; pharmacy student and pharmacy technician involvement in TOC activities; the use of technology to facilitate TOC activities; and barriers to performing such activities. RESULTS: A total of 393 respondents completed the survey (31.5% response rate). Twenty-seven percent of respondents indicated that pharmacists complete medication histories on admission, and 5% indicated that pharmacy technicians complete medication histories. Most respondents indicated that pharmacists do not routinely or consistently provide patients with tools to facilitate medication adherence before hospital discharge and that pharmacists do not routinely or consistently follow up with patients after discharge. Fifty-six percent of respondents indicated that pharmacists provide patient education for specific medications or for medications for specific diseases. Few respondents indicated that student pharmacists are involved with TOC activities. Most respondents either agreed or strongly agreed that it is important for pharmacists to be involved in TOC activities for hospitalized patients. CONCLUSION: Approximately one third of survey respondents indicated that pharmacists complete medication histories. Most respondents indicated that pharmacists do not routinely or consistently provide patients with tools to facilitate medication adherence before hospital discharge or follow up with patients after discharge. Lack of pharmacy staff resources and insufficient recognition of the value of pharmacists' provision of TOC by health care executives, medical staff, nursing staff, and other health care professionals were the most frequently cited barriers to pharmacists assuming more significant roles in the TOC at the respondent's institution.

Nursing home-acquired pneumonia: course and management in the emergency department.

BACKGROUND: Pneumonia is among the foremost causes of hospitalization and mortality in patients residing in extended care facilities. Despite its prevalence, there is currently little literature focusing on the course and management of nursing home-acquired pneumonia (NHAP) in the emergency department (ED). Our objective was to investigate the ED presentation, course, management and outcomes in patients admitted through the ED with NHAP. METHODS: A retrospective chart review of nursing home patients with a presumptive or final diagnosis of pneumonia admitted through the ED was performed at two large hospitals in Detroit, Michigan. RESULTS: A total of 296 patients were included in the study from 2002 to 2007 with a mean age of 81.1 years (SD ± 10.95) and 55.4% females. Blood cultures were performed on 90.8% of patients in the ED; 17.8% of these revealed growths, but half of these were considered contaminants. Initial chest x-ray in the ED was read as possible pneumonia in 18.2% of patients; 73.9% were started on antibiotics (ABX) in the ED. Mean hospital length of stay (LOS) was 10.75 days (SD ± 9.35) and in-hospital mortality was 16.2%. Time until first ABX in univariate analysis was nearly significant (p = 0.053) for mortality prediction, and the appropriate versus inappropriate ABX (per the Infectious Diseases Society of America and American Thoracic Society guidelines) did not affect mortality. Patients treated with a single ABX had significantly increased LOS (p = 0.0089). There was poor correlation between LOS and time until first ABX as well as LOS and time until appropriate ABX with a correlation coefficient of -0.048 (p = 0.42) and -0.08 (p = 0.43), respectively. CONCLUSIONS: In this data set of NHAP patients admitted through the ED, we found a surprisingly low prevalence of true-positive blood cultures, high incidence of antibiotic pre-treatment at nursing homes prior to admission, high hospital mortality and low immunization rates. There was a wide spectrum of pathogens grown in blood culture. Only two thirds of the patients had dyspnea at presentation, and less than half had either cough or fever. On physical examination, about one fourth had no clinical findings consistent with pneumonia. Further, less than one fifth of chest x-rays were interpreted as possible pneumonia.

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.

Prevalence and risk factors associated with vancomycin-resistant Staphylococcus aureus precursor organism colonization among patients with chronic lower-extremity wounds in Southeastern Michigan.

BACKGROUND: Of the 13 US vancomycin-resistant Staphylococcus aureus (VRSA) cases, 8 were identified in southeastern Michigan, primarily in patients with chronic lower-extremity wounds. VRSA infections develop when the vanA gene from vancomycin-resistant enterococcus (VRE) transfers to S. aureus. Inc18-like plasmids in VRE and pSK41-like plasmids in S. aureus appear to be important precursors to this transfer. OBJECTIVE: Identify the prevalence of VRSA precursor organisms. DESIGN: Prospective cohort with embedded case-control study. PARTICIPANTS: Southeastern Michigan adults with chronic lower-extremity wounds. METHODS: Adults presenting to 3 southeastern Michigan medical centers during the period February 15 through March 4, 2011, with chronic lower-extremity wounds had wound, nares, and perirectal swab specimens cultured for S. aureus and VRE, which were tested for pSK41-like and Inc18-like plasmids by polymerase chain reaction. We interviewed participants and reviewed clinical records. Risk factors for pSK41-positive S. aureus were assessed among all study participants (cohort analysis) and among only S. aureus-colonized participants (case-control analysis). RESULTS: Of 179 participants with wound cultures, 26% were colonized with methicillin-susceptible S. aureus, 27% were colonized with methicillin-resistant S. aureus, and 4% were colonized with VRE, although only 17% consented to perirectal culture. Six participants (3%) had pSK41-positive S. aureus, and none had Inc18-positive VRE. Having chronic wounds for over 2 years was associated with pSK41-positive S. aureus colonization in both analyses. CONCLUSIONS: Colonization with VRSA precursor organisms was rare. Having long-standing chronic wounds was a risk factor for pSK41-positive S. aureus colonization. Additional investigation into the prevalence of VRSA precursors among a larger cohort of patients is warranted.

Incidence of nephrotoxicity and association with vancomycin use in intensive care unit patients with pneumonia: retrospective analysis of the IMPACT-HAP Database.

BACKGROUND: The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. OBJECTIVE: The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. METHODS: This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. RESULTS: Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, P = 0.0003). CONCLUSIONS: Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

Clinical and economic outcomes in patients with community-acquired Staphylococcus aureus pneumonia.

BACKGROUND: While the clinical and economic consequences of S. aureus pneumonia in healthcare settings have been well documented, much less is known about community-acquired S. aureus pneumonia (CAP). METHODS: We retrospectively identified all patients admitted to a large US urban teaching hospital between January 2005 and May 2008 with pneumonia and positive blood or respiratory cultures for S. aureus within 48 hours of admission. Patients with suspected healthcare-associated pneumonia (HCAP) were excluded from the study sample, using established criteria (eg, recent hospitalization, admission from nursing home, hemodialysis). Patients were designated as having methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) CAP based on initial S. aureus isolates. Initial therapy was designated "appropriate" vs. "inappropriate" based on expected susceptibility of the organism to the regimen received. RESULTS: We identified a total of 128 CAP patients with S. aureus isolates; mean (standard deviation [SD]) age was 60 (17) years. A total of 55 patients (43%) had initial cultures positive for MRSA. Patients with MRSA CAP were more likely to receive inappropriate initial therapy (24 [44%] vs. 13 [18%] for MSSA; P = 0.002). Approximately 25% of all patients underwent surgery for pneumonia, 69% received mechanical ventilation, 79% were admitted to intensive care unit (ICU), and 24% died in hospital. Mean (SD) length of stay was 17.0 (15.7) days, and total hospital charges averaged $127,922 ($154,605) per patient; there were no significant differences between patients with MRSA vs. MSSA CAP. CONCLUSION: Outcomes are poor, hospital stays are long, and costs of care are high in patients with S. aureus CAP, and do not differ between those with MRSA vs. MSSA.

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.

Comparative evaluation of epidemiology and outcomes of methicillin-resistant Staphylococcus aureus (MRSA) USA300 infections causing community- and healthcare-associated infections.

Methicillin-resistant Staphylococcus aureus (MRSA) USA300 clone is commonly found in the community and is being increasingly reported in the healthcare setting. A retrospective analysis was conducted to compare the epidemiology and outcomes between community-associated (CA) and healthcare-associated (HA) USA300 MRSA infections. The study enrolled 160 subjects with USA300 MRSA infections (47.5% CA-MRSA and 52.5% HA-MRSA). Failure in the HA group was higher (38.1%) compared with the CA group (23.7%) (P=0.05). Predictors of failure included male gender, age, presence of any co-morbidity, coronary artery disease, chronic kidney disease, history of MRSA, previous admission, fluoroquinolone exposure, HA infection and osteomyelitis (P

Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation.

Human embryonic stem cells (hESCs) demonstrate remarkable proliferative and developmental capacity. Clinical interest arises from their ability to provide an apparently unlimited cell supply for transplantation, and from the hope that they can be directed to desirable phenotypes in high purity. Here we present for the first time a method for obtaining oligodendrocytes and their progenitors in high yield from hESCs. We expanded hESCs, promoted their differentiation into oligodendroglial progenitors, amplified those progenitors, and then promoted oligodendroglial differentiation using positive selection and mechanical enrichment. Transplantation into the shiverer model of dysmyelination resulted in integration, differentiation into oligodendrocytes, and compact myelin formation, demonstrating that these cells display a functional phenotype. This differentiation protocol provides a means of generating human oligodendroglial lineage cells in high purity, for use in studies of lineage development, screening assays of oligodendroglial-specific compounds, and treating neurodegenerative diseases and traumatic injuries to the adult CNS.