Faculty Bibliography

Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Out of 1381 non-duplicate studies, 10 met our inclusion criteria. We performed a random effects meta-analysis, based on crude odds ratios, and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds to have been exposed to vancomycin plus TZP, in comparison with vancomycin monotherapy (OR 8.15; 95% CI: 3.49-18.99), or vancomycin plus any other beta-lactam antibiotic (OR 3.48; 95% CI: 2.71-4.46). Based on the results of the Newcastle Ottawa Scale quality assessment, a secondary analysis including only higher quality studies (6 out of 10 studies) yielded again higher odds of exposure to vancomycin plus TZP, compared to vancomycin plus another beta-lactam antibiotic (OR 3.76; 95% CI: 2.56-5.51). Notably, even after controlling for possible publication bias our results remained statistically significant (OR 3.09; 95% CI: 2.30-4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.

Molecular diagnostic assays that test directly whole blood provide the ability to decrease inappropriate antimicrobial therapy and improve survival in patients with septic shock. We developed a decision analysis model to evaluate the cost-effectiveness of the addition of molecular assays to blood cultures in adults admitted to medical ICUs with septic shock. Under baseline assumptions, the use of molecular diagnostic methods was cost-saving in all cases that the length of hospital stay differed by 2 and 4 days between patients receiving appropriate and inappropriate antimicrobial therapy. In the case that the length of stay was the same, the use of molecular methods was cost-effective with an estimated incremental cost-effectiveness ratio (ICER) < $3000 per death averted. In the extreme that the length of stay between the 2 groups was the same, the highest cost reached was when the cost of the assay was $1000, with the estimated ICER being < $20,000 per death averted.

Background/UNASSIGNED:Influenza is a major cause of morbidity and mortality in patients diagnosed with heart failure. The aim of this study was to evaluate the effectiveness of influenza vaccination in this population in terms of reduction in all-cause mortality and rate of hospitalization. Methods/UNASSIGNED: Results/UNASSIGNED:We identified 8 studies that included a total of 82 354 patients with heart failure. In patients with heart failure who were vaccinated against influenza, we found a reduced risk of all-cause mortality (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51-0.87). No evidence of publication bias was found, and the effect was more pronounced during influenza season (HR, 0.49; 95% CI, 0.30-0.69), compared with noninfluenza season (HR, 0.79; 95% CI, 0.68-0.89). In terms of heart failure hospitalizations, we did not identify a statistically significant difference between the cohorts (HR, 0.62; 95% CI, 0.00-1.23). Conclusions/UNASSIGNED:Influenza vaccination was associated with a decreased risk of all-cause mortality in patients with heart failure, and this effect was more prominent during the influenza season.

Background/UNASSIGNED:ranks first among the pathogens of hospital-acquired infections with hospital-based preventive strategies being only partially successful in containing its spread. Methods/UNASSIGNED:infection (HO-CDI), using data from the Medicare Hospital Compare, Medicare Provider Utilization Part D, and other databases. Among the areas with the highest HO-CDI rates ("hot spots"), we conducted a geographically weighted regression (GWR) to quantify the effect of the decrease in the modifiable risk factors on the HO-CDI rate. Findings/UNASSIGNED: = 0.71, SD 0.19), with a 10% decrease in the rate of antimicrobial claims having the potential to lead to up to 23.1% decrease in the HO-CDI incidence in this area. Interpretation/UNASSIGNED:These results outline the association of HO-CDI with community practice and characteristics of the healthcare delivery system and support the need to further study the effect of community and nursing home-based antimicrobial and acid suppressant stewardship programs in the rate of HO-CDI in geographic areas that may cross state lines.

OBJECTIVES:Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED. METHODS:We developed a decision analysis model with primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients' length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described. Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed. RESULTS:Under baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER -$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity≥52%, panel efficiency≥39%, and assay cost≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained≤$20,000/death averted for every studied sensitivity (i.e. 0.5-0.95), panel efficiency≥34%, and assay cost≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was≤$135 and the panel efficiency was≥77%. CONCLUSIONS:The incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios.

The mortality associated with invasive candidiasis remains unacceptably high. The T2 magnetic resonance (T2MR) assay is a novel US FDA-approved molecular diagnostic assay for the diagnosis of candidemia that can rapidly detect the five most commonly isolated Candida spp. In clinical trials, T2MR has exhibited good clinical sensitivity and specificity. Potential benefits from the adoption of T2MR technology in the diagnostic and therapeutic algorithms for invasive candidiasis can arise from timely diagnosis of disease, increased case detection, tailored therapy and decrease in empiric antifungal treatment. As everyday clinical experience with the assay is evolving, we discuss the utility of T2MR in invasive candidiasis with and without candidemia based on the currently available evidence regarding its performance.

Invasive candidiasis is a common healthcare-associated infection with a high mortality rate that can exceed 60% in cases of septic shock. Blood culture performance is far from ideal, due to the long time to positivity and suppression by antifungal agents. The T2 Magnetic Resonance (T2MR) assay is an FDA-approved qualitative molecular diagnostic method that can detect and speciate the 5 most common Candida spp.; namely, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei, in approximately 5 h. In a multicenter clinical trial that included both a prospective and a contrived arm to represent the full range of clinically relevant concentrations of Candida spp., T2MR demonstrated a sensitivity and specificity of 91.1% and 98.1%, respectively. The utility of T2MR in candidemia depends on the prevalence of disease in each clinical setting. In intensive care units and other high-prevalence settings, the incorporation of T2MR in diagnostic algorithms is very appealing. T2MR is expected to allow timely initiation of antifungal therapy and help with anti-fungal stewardship. In low-prevalence settings, the positive predictive value of T2MR might not be enough to justify initiation of antifungal treatment in itself. The performance of T2MR has not been studied in cases of deep-seated candidiasis. Despite some promising evidence in published clinical trials, further studies are needed to determine the performance of T2MR in invasive candidiasis without candidemia. Overall, experience with T2MR in everyday clinical practice is evolving but, in the right setting, this technology is expected to provide "actionable information" for the management of patients evaluated for candidemia.

The performance of blood culture for monitoring candidemia clearance is hampered by its low sensitivity, especially during antifungal therapy. The T2 magnetic resonance (T2MR) assay combines magnetic resonance with nanotechnology to identify whole Candida species cells. A multicenter clinical trial studied the performance of T2MR in monitoring candidemia clearance compared to blood culture. Adults with a blood culture positive for yeast were enrolled and had blood cultures and T2MR testing performed on prespecified days. Thirty-one patients completed the trial. Thirteen of the 31 patients (41.9%) had at least one positive surveillance T2MR and/or blood culture result. All positive blood cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance in the identified Candida sp., while only 7/23 (30.4%) T2MR results had an accompanying positive blood culture. There was one case of discordance in species identification between T2MR and the preenrollment blood culture with evidence to support deep-seated infection by the Candida spp. detected by the T2MR assay. Based on the log rank test, there was a statistically significant improvement in posttreatment surveillance using the T2MR assay compared to blood culture (P = 0.004). Limitations of the study include the small sample size and lack of outcome data. In conclusion, the T2MR assay significantly outperformed blood cultures for monitoring the clearance of candidemia in patients receiving antifungal therapy and may be useful in determining adequate source control, timing for deescalation, and optimal duration of treatment. However, further studies are needed to determine the viability of Candida species cells detected by the T2MR assay and correlate the results with patient outcomes. (This study is registered at ClinicalTrials.gov under registration number NCT02163889.).

The Powassan Virus is the arthropod-borne vector responsible for Powassan neuroinvasive disease. The virus was first isolated in 1958 and has been responsible for approximately 100 cases of neuroinvasive disease. Rates of infection have been on the rise over the past decade with numerous states reporting their first confirmed case; New Jersey, New Hampshire and Connecticut all reported their first case within the last five years. We present here the first confirmed case of Powassan neuroinvasive disease in the nearby state of Rhode Island. A previously healthy 81-year-old female with known tick exposure presented with fever, altered sensorium, seizures and focal neurological deficits. After an extensive work-up that was largely unrevealing Powassan encephalitis was suspected. The diagnosis was confirmed with serological testing consisting of Powassan IgM enzyme-linked immunosorbent assay and Powassan plaque reduction neutralization testing. The case study provides evidence for the increasing spread of Powassan neuroinvasive disease and reinforces the importance of requesting focused testing for Powassan Virus in patients from an endemic area with a clinically compatible syndrome.