Epidemiology, Disposition, and Treatment of Ambulatory Veterans With Skin and Soft Tissue Infections.

BACKGROUND: Most skin and soft tissue infections (SSTIs) are managed in the outpatient setting, but data are lacking on treatment patterns outside the emergency department (ED). Available data suggest that there is poor adherence to SSTI treatment guidelines. METHODS: We conducted a retrospective cohort study of Veterans diagnosed with SSTIs in the ED or outpatient clinics from 1 January 2005 through 30 June 2018. The incidence of SSTIs over time was modeled using Poisson regression using robust standard errors. Antibiotic selection and incision and drainage (I&D) were described and compared between ambulatory settings. Anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotic use was compared to SSTI treatment guidelines. RESULTS: There were 1 740 992 incident SSTIs in 1 156 725 patients during the study period. The incidence of SSTIs significantly decreased from 4.58 per 1000 patient-years in 2005 to 3.27 per 1000 patient-years in 2018 (P < .001). There were lower rates of ß-lactam prescribing (32.5% vs 51.7%) in the ED compared to primary care (PC), and higher rates of anti-MRSA therapy (51.4% vs 35.1%) in the ED compared to PC. The I&D rate in the ED was 8.1% compared to 2.6% in PC. Antibiotic regimens without MRSA activity were prescribed in 24.9% of purulent SSTIs. Anti-MRSA antibiotics were prescribed in 40.1% of nonpurulent SSTIs. CONCLUSIONS: We found a decrease in the incidence of SSTIs in the outpatient setting over time. Treatment of SSTIs varied depending on the presenting ambulatory location. There is poor adherence to guidelines in regard to use of anti-MRSA therapies. Further study is needed to understand the impact of guideline nonadherence on patient outcomes.

Disproportionality Analysis of Safety with Nafcillin and Oxacillin with the FDA Adverse Event Reporting System (FAERS).

Antistaphylococcal penicillins such as nafcillin and oxacillin are among the first choices of treatment for severe invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections, although there has been limited safety evaluations between individual agents. Using the FDA Adverse Event Reports System (FAERS), oxacillin was observed to have a lower proportion of reports of acute renal failure (reporting odds ratio [ROR], 5.3 [95% confidence interval {CI}, 3.1 to 9.3] versus 21.3 [95% CI, 15.8 to 28.6], respectively) and hypokalemia (ROR, 0.7 [95% CI, 0.1 to 4.8] versus 11.4 [95% CI, 7.1 to 18.3], respectively) than nafcillin.

Nephrotoxicity comparison of two commercially available generic vancomycin products.

To date, no comparative clinical studies have investigated the effects of different vancomycin products on nephrotoxicity. The objective of this single-center, retrospective, matched-cohort study was to investigate the impact of two different vancomycin products on the development of nephrotoxicity. The study population included adults receiving a single vancomycin product, from either Pfizer or Hospira, for their entire course of therapy. Patients were matched based on underlying nephrotoxicity risk factors. Secondary outcomes included the need for renal replacement therapy, length of hospital stay, and in-hospital mortality. One-hundred forty-six matched pairs (n = 292) were included, and they had no significant differences in demographics, comorbid conditions, severity of illness, or vancomycin-associated nephrotoxicity risk factors. The frequency of nephrotoxicity was 8.9% in the Pfizer group and 11.0% in the Hospira group as defined by the 2009 consensus vancomycin guidelines (P = 0.56), 17.1% in the Pfizer group and 13.0% in the Hospira group as defined by the Acute Kidney Injury Network (AKIN) (P = 0.33), and 10.3% in the Pfizer group and 11.6% in the Hospira group as defined by RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria (P = 0.71). There were no differences between groups in regard to nephrotoxicity by any definition or in secondary outcomes. In multivariate analysis of overall nephrotoxicity risk factors, the type of vancomycin product was not independently associated with increased odds of developing nephrotoxicity according to the RIFLE criteria. Based on our results, there are no discernible differences between Pfizer and Hospira vancomycin products in the frequency of nephrotoxicity. Confirmation of these results with other types of vancomycin and different patient populations is warranted.

Automating detection of diagnostic error of infectious diseases using machine learning.

Diagnostic error, a cause of substantial morbidity and mortality, is largely discovered and evaluated through self-report and manual review, which is costly and not suitable to real-time intervention. Opportunities exist to leverage electronic health record data for automated detection of potential misdiagnosis, executed at scale and generalized across diseases. We propose a novel automated approach to identifying diagnostic divergence considering both diagnosis and risk of mortality. Our objective was to identify cases of emergency department infectious disease misdiagnoses by measuring the deviation between predicted diagnosis and documented diagnosis, weighted by mortality. Two machine learning models were trained for prediction of infectious disease and mortality using the first 24h of data. Charts were manually reviewed by clinicians to determine whether there could have been a more correct or timely diagnosis. The proposed approach was validated against manual reviews and compared using the Spearman rank correlation. We analyzed 6.5 million ED visits and over 700 million associated clinical features from over one hundred emergency departments. The testing set performances of the infectious disease (Macro F1 = 86.7, AUROC 90.6 to 94.7) and mortality model (Macro F1 = 97.6, AUROC 89.1 to 89.1) were in expected ranges. Human reviews and the proposed automated metric demonstrated positive correlations ranging from 0.231 to 0.358. The proposed approach for diagnostic deviation shows promise as a potential tool for clinicians to find diagnostic errors. Given the vast number of clinical features used in this analysis, further improvements likely need to either take greater account of data structure (what occurs before when) or involve natural language processing. Further work is needed to explain the potential reasons for divergence and to refine and validate the approach for implementation in real-world settings.

Weighted Blankets and Sleep Quality in Children with Autism Spectrum Disorders: A Single-Subject Design.

The purpose of the study was to explore the efficacy of weighted blanket applications and sleep quality in children with autism spectrum disorder and behavioral manifestations of sensory processing deficits. Two 4-year-old participants diagnosed with autism spectrum disorder who also experienced sleep disturbances took part in a single-subject design study. Objective sleep measures and caregiver surveys were tracked for a baseline period of eight days, followed by a 14-day weighted blanket intervention and a seven-day withdrawal phase. Caregiver reports and objective data were evaluated using visual analysis and the percentage of non-overlapping data methods. The results suggest minimal changes in sleep patterns as a result of the weighted blanket intervention. The findings based on using a weighted blanket intervention were enhanced morning mood after night use and a significantly decreased time to fall asleep for participants, though they were not strong enough to recommend for clinical use. Future directions include single-subject and cohort-designed studies exploring the efficacy of weighted blankets with increasing sleep quality among children with autism.

Oral ß-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source.

Importance: Oral ß-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there is a lack of outcomes data, specifically after initial treatment with parenteral antibiotics. Given the limited data and increasing limitations of fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), oral ß-lactam antibiotics may be a valuable additional treatment option. Objective: To compare definitive therapy with oral ß-lactam antibiotics vs fluoroquinolones or TMP-SMX for Enterobacterales bacteremia from a suspected urine source. Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 2007, to September 30, 2015, at 114 Veterans Affairs hospitals among 4089 adults with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia and matching urine culture results. Additional inclusion criteria were receipt of active parenteral antibiotic(s) followed by conversion to an oral antibiotic. Exclusion criteria were previous Enterobacterales bacteremia, urologic abscess, or chronic prostatitis. Data were analyzed from April 15, 2019, to July 26, 2020. Exposures: Conversion of therapy to an oral ß-lactam antibiotic vs fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics. Main Outcomes and Measures: The main outcome was a composite of either 30-day all-cause mortality or 30-day recurrent bacteremia. Propensity-based overlap weights were used to adjust for differences between groups. Log binomial regression models were used to estimate adjusted relative risks (aRRs) and adjusted risk differences (aRDs). Results: Of the 4089 eligible patients (3731 men [91.2%]; median age, 71 years [interquartile range, 63-81 years]), 955 received an oral ß-lactam antibiotic, and 3134 received fluoroquinolones or TMP-SMX. The primary outcome occurred for 42 patients (4.4%) who received ß-lactam antibiotics and 94 patients (3.0%) who received fluoroquinolones or TMP-SMX (aRD, 0.99% [95% CI, -0.42% to 2.40%]; aRR, 1.31 [95% CI, 0.87-1.95]). Mortality rates were 3.0% (n = 29) for patients receiving ß-lactam antibiotics vs 2.6% (n = 82) for those receiving fluoroquinolones or TMP-SMX (aRD, 0.06% [95% CI, -1.13% to 1.26%]; aRR, 1.02 [95% CI, 0.67-1.56]). Recurrent bacteremia rates were 1.5% (n = 14) among those receiving ß-lactam antibiotics vs 0.4% (n = 12) among those receiving fluoroquinolones or TMP-SMX (aRD, 1.03% [95% CI, 0.24%-1.82%]; aRR, 3.43 [95% CI, 0.42-27.90]). Conclusions and Relevance: In this cohort study of adults with E coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, the relative risk of recurrent bacteremia was not significantly higher with ß-lactam antibiotics compared with fluoroquinolones or TMP-SMX, and the absolute risk and risk difference were small (ie, <3%). No significant difference in mortality was observed. Oral ß-lactam antibiotics may be a reasonable step-down treatment option, primarily when alternative options are limited by resistance or adverse effects. Further study is needed because statistical power was limited owing to a low number of recurrent bacteremia events.

Inpatient Management of Uncomplicated Skin and Soft Tissue Infections in 34 Veterans Affairs Medical Centers: A Medication Use Evaluation.

BACKGROUND: Skin and soft tissue infections (SSTIs) are a key antimicrobial stewardship target because they are a common infection in hospitalized patients, and non-guideline-concordant antibiotic use is frequent. To inform antimicrobial stewardship interventions, we evaluated the proportion of veterans hospitalized with SSTIs who received guideline-concordant empiric antibiotics or an appropriate total duration of antibiotics. METHODS: A retrospective medication use evaluation was performed in 34 Veterans Affairs Medical Centers between 2016 and 2017. Hospitalized patients who received antibiotics for uncomplicated SSTI were included. Exclusion criteria were complicated SSTI, severe immunosuppression, and antibiotics for any non-SSTI indication. Data were collected by manual chart review. The primary outcome was the proportion of patients receiving both guideline-concordant empiric antibiotics and appropriate treatment duration, defined as 5-10 days of antibiotics. Data were analyzed and reported using descriptive statistics. RESULTS: Of the 3890 patients manually evaluated for inclusion, 1828 patients met inclusion criteria. There were 1299 nonpurulent (71%) and 529 purulent SSTIs (29%). Overall, 250 patients (14%) received guideline-concordant empiric therapy and an appropriate duration. The most common reason for non-guideline-concordance was receipt of antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) in 906 patients (70%) with a nonpurulent SSTI. Additionally, 819 patients (45%) received broad-spectrum Gram-negative coverage, and 860 patients (48%) received an antibiotic duration >10 days. CONCLUSIONS: We identified 3 common opportunities to improve antibiotic use for patients hospitalized with uncomplicated SSTIs: use of anti-MRSA antibiotics in patients with nonpurulent SSTIs, use of broad-spectrum Gram-negative antibiotics, and prolonged durations of therapy.

Treatment Duration and Associated Outcomes for Skin and Soft Tissue Infections in Patients With Obesity or Heart Failure.

BACKGROUND: Although existing literature supports durations of 5-7 days for skin and soft tissue infections (SSTIs), longer durations are commonly used. Obesity and heart failure (HF) have been associated with increased risk for treatment failure of SSTIs; however, whether prolonged antibiotic durations reduce the risk of treatment failure is unknown. We evaluated practice patterns for SSTIs in patients with obesity and/or HF and whether short antibiotic durations (≤8 days) were associated with treatment failure. METHODS: We performed a single-center, retrospective cohort study of inpatients between January 1, 2006, and December 30, 2016, with SSTIs based on International Classification of Diseases (ICD) coding, and obesity and/or HF. Charts were manually reviewed to collect demographic, clinical, treatment, and outcome data. Propensity score matching was used to estimate the risk of treatment failure between the 2 groups. Secondary outcomes included length of stay, 30-day readmission, and Clostridium difficile infection rates. RESULTS: A total of 207 patients were included. Forty-nine (23.7%) received a short antibiotic duration and 158 (76.3%) a long duration. The median duration of therapy (interquartile range [IQR]) was 7 (7-8) days in the short group and 14 (10-15) days in the long group. In the propensity score-matched cohort, 28 (28.6%) treatment failures occurred in the long group, as compared with 5 (10.2%) in the short group (P = .02), as well as a shorter length of stay (IQR) in the short- vs long-duration group (2 [2-3] vs 3 [2-5] days, respectively; P = .002). There was no difference in other secondary outcomes. CONCLUSIONS: The majority of patients with obesity or HF received a longer antibiotic course for SSTIs; however, a longer antibiotic course was not associated with lower treatment failure rates. Higher failure rates in the long-duration group may be reflective of clinical decisions made in the face of diagnostic uncertainty and warrant further evaluation.

Top Questions in Uncomplicated, Non-Staphylococcus aureus Bacteremia.

The Infectious Diseases Society of America infection-specific guidelines provide limited guidance on the management of focal infections complicated by secondary bacteremias. We address the following 3 commonly encountered questions and management considerations regarding uncomplicated bacteremia not due to Staphylococcus aureus: the role and choice of oral antibiotics focusing on oral beta-lactams, the shortest effective duration of therapy, and the role of repeat blood cultures.

Multidrug-Resistant Organisms: Considerations in Antibiotic Selection and Administration.

Managing infections caused by multidrug-resistant organisms is a significant clinical challenge. Multidrug-resistant organisms' treatment is complicated in the pediatric population because of the lack of primary data, treatment guidelines, rapidly changing pharmacokinetic/pharmacodynamic parameters, and fewer approved antibiotic indications and dosing guidance. Treatment decisions must incorporate available pediatric data, clinical experience, and careful extrapolation from adult data while considering the unique challenges faced by children with complicated infections.

Strategies for the safe use of colistin.

Colistin has re-emerged as an essential antibiotic for the treatment of carbapenem-resistant Gram-negative infections. Unfortunately, its utility is limited by high rates of nephrotoxicity, even at potentially therapeutic concentrations, and an overall lack of understanding on how to optimally administer the agent. In this review, recent advancements in the understanding of the safety and efficacy of colistin are discussed and strategies and suggestions on how to balance the two are described.