Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia.

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of body weight per day of DAP and 600 mg intravenous (i.v.) CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post hoc for measurement of interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an IL-10 concentration of >5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 26% (5/19) in the monotherapy group (P = 0.057). Here, we share the full results of this preliminary (but aborted) assessment of early DAP+CPT therapy versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection-associated mortality. (The clinical study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT02660346.).

Development of a bedside scoring system for predicting a first recurrence of Clostridium difficile-associated diarrhea.

PURPOSE: A scoring system for identifying patients at high or low risk for recurrent Clostridium difficile-associated diarrhea (CDAD) is described. METHODS: A retrospective cohort study was performed using data on adults with CDAD admitted to a 3-hospital system from 2009 to 2014. The primary endpoint was the rate of recurrent CDAD within 60 days of clinical cure of CDAD. Risk factors for CDAD recurrence were identified, and a risk prediction tool was developed using multivariate logistic regression. RESULTS: The CDAD cure rate in the study cohort (n = 340) was 92.3%; the 60-day recurrence rate was 16.9%. Five factors were significantly associated with high recurrence risk: presence of CDAD at admission, body temperature of >37.8 °C at admission, leukocytosis, nosocomial CDAD, and abdominal distention on CDAD presentation. From that information a risk prediction tool, the CDAD "recurrence score," was developed (1 point is assigned for each factor present, for a maximum score of 5). Validation testing of the recurrence score indicated an area under the receiver operating characteristic curve of 0.72 (95% confidence interval, 0.65-0.80). A score of ≥2 had a negative predictive value of 91%, while a score of ≥4 had a positive predictive value of 70%. CONCLUSION: If externally validated in future studies, a tool for predicting the risk of recurrent CDAD using data readily available at the time of presentation could allow clinicians to identify patients at high risk for recurrence, address modifiable risk factors, and select tailored treatments to improve patient outcomes.

Valganciclovir: therapeutic role in pediatric solid organ transplant recipients.

INTRODUCTION: Cytomegalovirus (CMV) infection is a common infectious complication after solid organ transplantation (SOT) and is associated with the increased risk of opportunistic infections and allograft rejection, as well as decreased patient survival. Ganciclovir has been the mainstay antiviral agent for prevention and treatment of CMV; however, its clinical use is hampered by the poor oral bioavailability and the need for intravenous access. Valganciclovir, an oral prodrug of ganciclovir, is up to 10 times more bioavailable than oral ganciclovir and has replaced ganciclovir as a first-line agent in the management of CMV in adult SOT patients. AREAS COVERED: This article examines the safety and efficacy of valganciclovir in pediatric SOT patients, with a particular focus on prophylaxis of CMV infections. An in-depth review of the literature, including pertinent data from the adult SOT population, and a discussion of unmet needs are provided. The pharmacokinetics and pharmacodynamics of valganciclovir in the pediatric population are also discussed. EXPERT OPINION: Existing evidence supports the use of valganciclovir in pediatric SOT patients for CMV prophylaxis. Although comprehensive data are lacking, valganciclovir is a treatment option for CMV infection in pediatric SOT patients. The role of valganciclovir in pediatrics is expected to grow given its demonstrated efficacy in a variety of clinical settings and its advantages over ganciclovir.

Procalcitonin levels associate with severity of Clostridium difficile infection.

OBJECTIVE: Clostridium difficile infection (CDI) is a major cause of morbidity and biomarkers that predict severity of illness are needed. Procalcitonin (PCT), a serum biomarker with specificity for bacterial infections, has been little studied in CDI. We hypothesized that PCT associated with CDI severity. DESIGN: Serum PCT levels were measured for 69 cases of CDI. Chart review was performed to evaluate the presence of severity markers and concurrent acute bacterial infection (CABI). We defined the binary variables clinical score as having fever (T >38°C), acute organ dysfunction (AOD), and/or WBC >15,000 cells/mm(3) and expanded score, which included the clinical score plus the following: ICU admission, no response to therapy, colectomy, and/or death. RESULTS: In univariate analysis log10 PCT associated with clinical score (OR 3.13, 95% CI 1.69-5.81, P<.001) and expanded score (OR 3.33, 95% CI 1.77-6.23, P<.001). In a multivariable model including the covariates log10 PCT, enzyme immunoassay for toxin A/B, ribotype 027, age, weighted Charlson-Deyo comorbidity index, CABI, and extended care facility residence, log10 PCT associated with clinical score (OR 3.09, 95% CI 1.5-6.35, P = .002) and expanded score (OR 3.06, 95% CI 1.49-6.26, P = .002). PCT >0.2 ng/mL was 81% sensitive/73% specific for a positive clinical score and had a negative predictive value of 90%. CONCLUSION: An elevated PCT level associated with the presence of CDI severity markers and CDI was unlikely to be severe with a serum PCT level below 0.2 ng/mL. The extent to which PCT changes during CDI therapy or predicts recurrent CDI remains to be quantified.

Improved serial analysis of V1 ribosomal sequence tags (SARST-V1) provides a rapid, comprehensive, sequence-based characterization of bacterial diversity and community composition.

Serial analysis of ribosomal sequence tags (SARST) is a recently developed technology that can generate large 16S rRNA gene (rrs) sequence data sets from microbiomes, but there are numerous enzymatic and purification steps required to construct the ribosomal sequence tag (RST) clone libraries. We report here an improved SARST method, which still targets the V1 hypervariable region of rrs genes, but reduces the number of enzymes, oligonucleotides, reagents, and technical steps needed to produce the RST clone libraries. The new method, hereafter referred to as SARST-V1, was used to examine the eubacterial diversity present in community DNA recovered from the microbiome resident in the ovine rumen. The 190 sequenced clones contained 1055 RSTs and no less than 236 unique phylotypes (based on > or = 95% sequence identity) that were assigned to eight different eubacterial phyla. Rarefaction and monomolecular curve analyses predicted that the complete RST clone library contains 99% of the 353 unique phylotypes predicted to exist in this microbiome. When compared with ribosomal intergenic spacer analysis (RISA) of the same community DNA sample, as well as a compilation of nine previously published conventional rrs clone libraries prepared from the same type of samples, the RST clone library provided a more comprehensive characterization of the eubacterial diversity present in rumen microbiomes. As such, SARST-V1 should be a useful tool applicable to comprehensive examination of diversity and composition in microbiomes and offers an affordable, sequence-based method for diversity analysis.