Adjunctive Daptomycin in the Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Randomized, Controlled Trial.

BACKGROUND: Bloodstream infections (BSIs) with methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. Our objective in this study was to determine the efficacy of synergistic treatment with daptomycin when given with either cefazolin or cloxacillin for the treatment of MSSA BSI. METHODS: A randomized, double-blind, placebo-controlled trial was performed at 2 academic hospitals in Montreal, Canada. Patients aged ≥18 years with MSSA BSI receiving either cefazolin or cloxacillin monotherapy were considered for inclusion. In addition to the standard-of-care treatment, participants received a 5-day course of adjunctive daptomycin or placebo. The primary outcome was the duration of MSSA BSI in days. RESULTS: Of 318 participants screened, 115 were enrolled and 104 were included in the intention-to-treat analysis (median age, 67 years; 34.5% female). The median duration of bacteremia was 2.04 days among patients who received daptomycin vs 1.65 days in those who received placebo (absolute difference, 0.39 days; P = .40). In a modified intention-to-treat analysis that involved participants who remained bacteremic at the time of enrollment, we found a median duration of bacteremia of 3.06 days among patients who received daptomycin vs 3.0 days in those who received placebo (absolute difference, 0.06 days; P = .77). Ninety-day mortality in the daptomycin arm was 18.9% vs 17.7% in the placebo arm (P = 1.0). CONCLUSIONS: Among patients with MSSA BSIs, the administration of adjunctive daptomycin therapy to standard-of-care treatment did not shorten the duration of bacteremia and should not be routinely considered. CLINICAL TRIALS REGISTRATION: NCT02972983.

Evaluation of Strongyloides Awareness and Knowledge among Canadian Physicians Caring for Patients At Risk for Severe Strongyloidiasis: A National Cross-sectional Survey.

In Canada, a substantial proportion of migrants come from strongyloidiasis-endemic regions. Systematic screening for Strongyloides is not performed in immunocompromised patients in whom this infection could be potentially fatal. We aim to assess the level of Strongyloides awareness and knowledge among Canadian physicians caring for immunocompromised patients and identify factors currently associated with screening. Using an online survey distributed through Canadian medical associations, we collected information on physicians' demographics, practice setting, overall awareness and knowledge of Strongyloides, and current practices. Descriptive analysis and logistic regression models were performed to identify the factors associated with Strongyloides screening. Nineteen national and provincial medical associations agreed to participate. Between November 2020 and August 2021, 368 of 5,194 (7%) physicians that were contacted responded to our survey. Quebec (46%) and Ontario (24%) were the most responsive. Sixty-nine percent of respondents practiced medicine in academic settings. Infectious disease (ID) specialists/medical microbiologists (38%) followed by nephrologists (33%) were the most represented. Most respondents (95%) had heard about Strongyloides. However, 36% of non-ID specialists considered themselves unfamiliar. Forty percent of respondents did not or rarely performed screening for strongyloidiasis in high-risk populations. Screening was associated with younger-aged physicians (odds ratio [OR] 2.35; 95% confidence interval [CI] 1.07-5.18), physicians who frequently served migrants (OR 3.33; 95% CI 1.44-7.66), or those who had training in global health and ID/medical microbiology (OR 3.71; 95% CI 1.21-11.34 and OR 46.42; 95% CI 15.89-135.59, respectively). Our survey suggests a general lack of knowledge of Strongyloides among Canadian physicians that is associated with low rates of screening in high-risk populations.

Handheld infrared thermometer to evaluate cellulitis: the HI-TEC study.

OBJECTIVES: Differentiating cellulitis from pseudocellulitis is challenging, and misdiagnosis leads to unnecessary antimicrobial use and increased healthcare expenditure. Clinical diagnosis remains the criterion standard and may involve expert consultation. Our objective was to evaluate the usefulness of a handheld infrared thermometer to improve diagnostic certainty in cases of suspected cellulitis. METHODS: We conducted a cross-sectional study from August 2018 to January 2020 at a tertiary-care hospital in Montreal, Canada. We enrolled adult patients with suspected limb cellulitis. Using the infrared thermometer, we compared the average temperature of the affected area with that of the contralateral limb, and we used Youden's method to determine the optimal temperature difference which best differentiated cellulitis from pseudocellulitis as determined by an independent and blinded infectious diseases specialist. We used bootstrapping to estimate 95% confidence intervals for the sensitivity, specificity, and area under the receiver operating curve. RESULTS: Of 65 patients screened for enrolment, 52 patients were recruited (median age: 64 years, IQR 52-76); 39 of these were diagnosed with cellulitis and 13 were not. The mean temperature difference between affected and unaffected limbs was 2.6°C (95%CI 2.1-3.1°C) for patients with cellulitis and 0.4°C (95%CI -1.2°C to 2.1°C) for patients without (p < 0.001). An average temperature difference between limbs of 0.8°C or more was 95% sensitive (95%CI 74-100%) and 69% specific (95%CI 44-95%) for the diagnosis of cellulitis (c-statistic 0.82). CONCLUSIONS: In this proof-of-concept single-centre study, a handheld infrared thermometer was a useful aid to differentiate cellulitis from pseudocellulitis.

Clinical Trials Increase Off-Study Drug Use: A Segmented Time-Series Analysis.

BACKGROUND: The effect of participation in a clinical trial on concomitant off-study investigational drug use has not been described. We sought to determine if participation in the Daptomycin as Adjunctive Therapy for Staphylococcus aureus bacteremia (DASH) trial increased overall daptomycin prescribing at study sites. METHODS: We retrospectively analyzed daptomycin use for 8 years preceding the trial, off-study daptomycin use during the trial itself (31 months), and daptomycin use for 6 fiscal months after trial completion. We used a segmented linear regression analysis of an interrupted time series to analyze changes in each drug's defined daily doses (DDD) per 1000 patient-days. As a control, we analyzed use of linezolid over these periods and also accounted for rates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections. RESULTS: For 1.5 years before the DASH trial, daptomycin use was decreasing by -0.30 DDD per 1000 patient-days per fiscal period (95% CI, -0.52 to -0.07). Following the initiation of the study, there was a statistically significant increase in daptomycin use of 0.28 DDD per 1000 patient-days per fiscal period (95% CI, 0.03 to 0.52), despite low, stable rates of MRSA and VRE infections. Following trial completion, daptomycin use decreased back toward prestudy rates. Use of linezolid remained stable throughout. CONCLUSIONS: Despite the DASH trial being a negative study, it impacted the prescribing habits of local clinicians during recruitment. Trialists should be aware of potential off-target study effects, and prescribers should be wary of early uptake of interventions before definitive study results.

Beta-Lactam/Beta-Lactamase Inhibitor Therapy for Potential AmpC-Producing Organisms: A Systematic Review and Meta-Analysis.

The optimal treatment for potential AmpC-producing Enterobacteriaceae, including Serratia, Providencia, Citrobacter, Enterobacter, and Morganella species, remains unknown. An updated systematic review and meta-analysis of studies comparing beta-lactam/beta-lactamase inhibitors with carbapenems in the treatment of bloodstream infections with these pathogens found no significant difference in 30-day mortality (OR, 1.13; 95% CI, 0.58 - 2.20).

MRSA colonization status as a predictor of clinical infection: A systematic review and meta-analysis.

BACKGROUND: Vancomycin is often used as empiric therapy for methicillin-resistant Staphylococcus aureus (MRSA), but can be associated with clinically important adverse events including renal failure. MRSA colonization swabs are primarily used for infection control; their use as a diagnostic test to inform the decision to add empiric vancomycin therapy has not been well elucidated. METHODS: We performed a Medline and Embase systematic review for peer-reviewed studies reporting the diagnostic accuracy of using MRSA colonization status to predict MRSA infections. Meta-analysis was performed using Cochrane guidelines. Grey literature was excluded. FINDINGS: 29 studies were included involving 24225 patients. In cases where the pathogen is not known to be S. aureus, specificities were greater than 85% for bacteremia, lower respiratory tract infections, skin and soft tissue infections (SSTI), and all infections pooled together. Sensitivities ranged between 54.0% and 77.5%. In cases where the pathogen is known to be S. aureus, we found studies on bacteremia and SSTI and arrived at pooled estimates of sensitivities ranging between 56.6% and 56.9%, and of specificities greater than 91%. Most importantly, for most infections in settings where the prevalence of MRSA as a causative organism is below 15%, the negative predictive value of a negative MRSA colonization swab exceeds 90%. INTERPRETATIONS: In settings of low-moderate MRSA prevalence, negative MRSA screening swabs may prevent unnecessary vancomycin use. More research is needed to assess if this strategy can mitigate the cost of screening in areas with a low MRSA colonization rate.