Antifungal Therapy in Fungal Necrotizing Soft Tissue Infections.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are life-threatening surgical emergencies associated with high morbidity and mortality. Fungal NSTIs are considered rare and have been largely understudied. The purpose of this study was to study the impact of fungal NSTIs and antifungal therapy on mortality after NSTIs. METHODS: A retrospective chart review was performed on patients with NSTIs from 2012 to 2018. Patient baseline characteristics, microbiologic data, antimicrobial therapy, and clinical outcomes were collected. Patients were excluded if they had comfort care before excision. The primary outcome measured was in-hospital mortality. RESULTS: A total of 215 patients met study criteria with a fungal species identified in 29 patients (13.5%). The most prevalent fungal organism was Candida tropicalis (n = 11). Fungal NSTIs were more prevalent in patients taking immunosuppressive medications (17.2% versus 3.2%, P = 0.01). A fungal NSTI was significantly associated with in-hospital mortality (odds ratio, 3.13; 95% confidence interval, 1.16-8.40; P = 0.02). Furthermore, fungal NSTI patients had longer lengths of stay (32 d [interquartile range, 16-53] versus 19 d [interquartile range, 11-31], P < 0.01), more likely to require initiation of renal replacement therapy (24.1% versus 8.6%, P = 0.02), and more likely to require mechanical ventilation (64.5% versus 42.0%, P = 0.02). Initiation of antifungals was associated with a significantly lower rate of in-hospital mortality (6.7% versus 57.1%, P = 0.01). CONCLUSIONS: Fungal NSTIs are more common in patients taking immunosuppressive medications and are significantly associated with in-hospital mortality. Antifungal therapy is associated with decreased in-hospital mortality in those with fungal NSTIs. Consideration should be given to adding antifungals in empiric treatment regimens, especially in those taking immunosuppressive medications.

Early Oral Step-Down Versus Continued Intravenous Antibiotic Treatment of Complicated Intra-Abdominal Infection.

Background: Complicated intra-abdominal infections (cIAIs) require a combined tactic, of source control and antimicrobial therapy. This study aimed to evaluate the safety and efficacy of oral step-down antimicrobial therapy in cIAIs after initial intravenous (IV) antimicrobial therapy. Methods: This retrospective cohort study included hospitalized adult patients diagnosed with a cIAI who received more than seven days of IV therapy from March 2017 to October 2021. Exclusion criteria included primary/peritoneal dialysis-related peritonitis, necrotizing pancreatitis, fistulizing inflammatory bowel disease, or upper gastrointestinal tract infection. Patients were assigned into two groups: IV-only or oral step-down therapy. The primary outcome was infection recurrence, defined as re-initiation of antimicrobial agents after a treatment-free period of more than or equal to three days. Secondary outcomes included treatment escalation, repeat source control procedure, treatment-related complications, and all-cause mortality. Results: The cohort consisted of 248 patients (199 IV-only and 49 oral step-down). Patients receiving IV-only therapy had a shorter median antimicrobial duration than the oral step-down group (13 vs. 23 d; p <0.0001). Infection recurrence occurred in 26 (13.1%) and 6 (12.2%) patients in the IV-only and oral step-down groups, respectively (p = 0.88). Treatment escalation, repeat source control, and 28-day mortality were similar between groups. Oral step-down therapy resulted in more adverse drug events (10.2% vs. 3.0%; p = 0.04). Discussion: Transition to oral step-down after initial IV therapy had a similar rate of infection recurrence as IV-only therapy but was associated with a longer duration of antimicrobial therapy and an increased rate of adverse drug reactions. Larger randomized non-inferiority studies are needed to confirm this approach.

Probable Encephalopathy and Spasticity in a Multiple Sclerosis Patient Following Carbapenem Administration: A Case Report and Brief Literature Review.

Purpose: The purpose of this case report is to describe spasticity and encephalopathy that developed in a multiple sclerosis patient following carbapenem administration. Summary: A 55-year-old female with multiple sclerosis developed spasticity and encephalopathy within 24 hours of meropenem and ertapenem administration. This was the second time that she had developed encephalopathy following carbapenem administration. The patient gradually recovered over four days following discontinuation of carbapenem therapy. Conclusion: Carbapenem neurotoxicity, a well-documented adverse effect, has been linked to several risk factors, including central nervous system lesions. Despite this, there is little evidence describing the risk of neurotoxicity in patients with multiple sclerosis. It is important to understand the potential adverse effects of carbapenems in specific patient populations to help guide appropriate treatment of infections.

Identification of Risk Factors for Intra-Abdominal Candidiasis.

Background: Intra-abdominal candidiasis (IAC) is associated with substantial morbidity and mortality in hospitalized patients. Identifying high-risk populations may facilitate early and selective directed therapy in appropriate patients and avoid unwarranted treatment and any associated adverse effects in those who are low risk. Patients and Methods: This retrospective, case-control study included patients >18 years of age admitted from July 1, 2010 to July 1, 2021 who had a microbiologically confirmed intra-abdominal infection (gastrointestinal culture positive for either a Candida spp. [cases] or bacterial isolate [controls] collected intra-operatively or from a drain placed within 24 hours). Patients receiving peritoneal dialysis treatment or with a peritoneal dialysis catheter in place or treated at an outside hospital were excluded. Multivariable regression was utilized to identify independent risk factors for the development of IAC. Results: Five hundred twenty-three patients were screened, and 250 met inclusion criteria (125 per cohort). Multivariable analysis identified exposure to corticosteroids (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.52-13.32; p < 0.0001), upper gastrointestinal tract surgery (OR, 3.51; 95% CI, 1.25-9.87; p = 0.017), and mechanical ventilation (OR, 3.09; 95% CI 1.5-6.37; p = 0.002) were independently associated with IAC. The area under the receiver operating characteristic (AUROC) and goodness of fit were 0.7813 and p = 0.5024, respectively. Conclusions: Exposure to corticosteroids, upper gastrointestinal tract surgery, and mechanical ventilation are independent risk factors for the development of microbiologically confirmed IAC suggesting these factors may help identify high-risk individuals requiring antifungal therapy.

A Review of the Evidence for Corticosteroids in COVID-19.

OBJECTIVE: To review available evidence on corticosteroids in acute respiratory distress syndrome (ARDS), Coronavirus Disease 2019 (COVID-19), and other viral pneumonias. DATA SOURCES: A literature search of MEDLINE, PubMed and clinicaltrials.gov was performed to identify studies between 1980 to 2020 using the following search terms: corticosteroids, COVID19, severe respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and influenza. Pre-printed articles were also reviewed at medRxiv.org. DATA ANALYSIS: Corticosteroids were not recommended early in the COVID-19 pandemic outside of the use for concomitant indications (i.e. ARDS, septic shock) as they have been associated with delayed time to viral clearance in other viral pneumonias. A randomized trial showed a mortality benefit with dexamethasone in COVID-19. Guidelines have been updated to include a strong recommendation for their use in COVID-19 in those hospitalized requiring supplemental oxygen or mechanical ventilation. CONCLUSION: Based on data from available randomized trials, patients that require respiratory support or mechanical ventilation benefit from corticosteroid therapy. Corticosteroids are an inexpensive and readily available therapy that should be standard of care in hospitalized COVID-19 patients requiring respiratory support.

Derivation and Validation of a Clinical Prediction Score to Identify the Isolation of Pseudomonas in Pneumonia.

Given the focus of existing clinical prediction scores on identifying drug-resistant pathogens as a whole, the application to individual pathogens and other institutions may yield weaker performance. This study aimed to develop a locally derived clinical prediction model for Pseudomonas-mediated pneumonia. This retrospective study included patients ≥18 years of age who were admitted to an academic medical center between 1 July 2010 and 31 July 2020 with a CDC National Healthcare Safety Network confirmed pneumonia diagnosis and were receiving antimicrobials during the index encounter, with a positive respiratory culture. Cystic fibrosis patients were excluded. Logistic regression analysis identified risk factors associated with the isolation of Pseudomonas aeruginosa from respiratory cultures within the derivation cohort (n = 186), which were weighted to generate a prediction score that was applied to the derivation and internal validation (n = 95) cohorts. A total of 281 patients met the inclusion criteria. Five predictor variables were identified, namely, tracheostomy status (4 points), chronic obstructive pulmonary disease (5 points), enteral nutrition (9 points), chronic steroid use (11 points), and Pseudomonas aeruginosa isolation from any culture in the prior 6 months (14 points). At a score of >11, the prediction score demonstrated a sensitivity of 52.4% (95% confidence interval [CI], 36.4 to 68.0%) and a specificity of 84.9% (95% CI, 72.4 to 93.35%) in the validation cohort. Score accuracy was 70.5% (95% CI, 60.3 to 79.4%), and the area under the receiver operating characteristic curve (AUROC) was 0.77 (95% CI, 0.68 to 0.87) in the validation cohort. A prediction score for identifying Pseudomonas aeruginosa in pneumonia was derived, which may have the potential to decrease the use of broad-spectrum antibiotics. Validation with larger and external cohorts is necessary. IMPORTANCE In this study, we aimed to develop a locally derived clinical prediction model for Pseudomonas-mediated pneumonia. Utilizing a locally validated prediction score may help direct therapeutic management and be generalizable to other clinical settings and similar populations for the selection of appropriate antimicrobial coverage when data are lacking. Our study highlights a unique patient population, including immunocompromised, structural lung disease, and transplant patients. Five predictor variables were identified, namely, tracheostomy status, chronic obstructive pulmonary disease, enteral nutrition, chronic steroid use, and Pseudomonas aeruginosa isolation from any culture in the prior 6 months. A prediction score for identifying Pseudomonas aeruginosa in pneumonia was derived, which may have the potential to decrease the use of broad-spectrum antibiotics, although validation with larger and external cohorts is necessary.

Therapeutic Options for Coronavirus Disease 2019 (COVID-19): Where Are We Now?

PURPOSE OF REVIEW: Rapidly evolving treatment paradigms of coronavirus disease 2019 (COVID-19) introduce challenges for clinicians to keep up with the pace of published literature and to critically appraise the voluminous data produced. This review summarizes the clinical evidence from key studies examining the place of therapy of recommended drugs and management strategies for COVID-19. RECENT FINDINGS: The global magnitude and duration of the pandemic have resulted in a flurry of interventional treatment trials evaluating both novel and repurposed drugs targeting various aspects of the viral life cycle. Additionally, clinical observations have documented various stages or phases of COVID-19 and underscored the importance of timing for the efficacy of studied therapies. Since the start of the COVID-19 pandemic, many observational, retrospective, and randomized controlled studies have been conducted to guide management of COVID-19 using drug therapies and other management strategies. Large, randomized, or adaptive platform trials have proven the most informative to guide recommended treatments to-date. Antimicrobial stewardship programs can play a pivotal role in ensuring appropriate use of COVID-19 therapies based on evolving clinical data and limiting unnecessary antibiotics given low rates of co-infection. SUMMARY: Given the rapidly evolving medical literature and treatment paradigms, it is recommended to reference continuously updated, curated guidelines from national and international sources. While the drugs and management strategies mentioned in this review represent the current state of recommendations, many therapies are still under investigation to further define optimal COVID-19 treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11908-021-00769-8.

Bronchoalveolar Lavage Gram Stains for Early Bacterial Identification in Pneumonia: Should They Stay or Should They Go?

OBJECTIVES: The primary endpoint was to determine the sensitivity and specificity of the bronchoalveolar lavage Gram stain in predicting culture results. Secondary endpoints included determining the proportion of Gram stains from bronchoalveolar lavages that accurately identify culture isolates and the duration of antibiotic treatment before bronchoalveolar lavage collection. DESIGN: Retrospective, observational study. SETTING: Four ICUs at a single academic medical center. SUBJECTS: Patients at least 18 years old admitted to an ICU with a diagnosis of pneumonia, collection of a bronchoalveolar lavage sample, and receipt of antibiotics. MEASUREMENTS AND MAIN RESULTS: Two-hundred five isolates were included. Gram stains for Gram-positive and Gram-negative isolates showed high specificity, 97.3% and 100%, respectively, but lower sensitivity at 61.9% and 54.2%, respectively. The positive predictive value and negative predictive value were 77.2% and 95.7% for Gram-positive isolates and 100% and 84.4% for Gram-negative isolates, respectively. Gram stains correctly identified isolates on the bronchoalveolar lavage culture in 61.9% of Gram-positive organisms and in 54.2% of Gram-negative organisms. CONCLUSIONS: Gram stains accurately identified causative organisms in a limited number of patients making the utility of the Gram stain an uncertain modality for predicting causative respiratory pathogens from bronchoalveolar lavage samples.

Review of nonopioid multimodal analgesia for surgical and trauma patients.

PURPOSE: Pain is a frequent finding in surgical and trauma patients, and effective pain control remains a common challenge in the hospital setting. Opioids have traditionally been the foundation of pain management; however, these agents are associated with various adverse effects and risks of dependence and diversion. SUMMARY: In response to the rising national opioid epidemic and the various risks associated with opioid use, multimodal pain management through use of nonopioid analgesics such as acetaminophen, nonsteroidal anti-inflammatory drugs, α 2 agonists, N-methyl-d-aspartate (NMDA) receptor antagonists, skeletal muscle relaxants, sodium channel blockers, and local anesthetics has gained popularity recently. Multimodal analgesia has synergistic therapeutic effects and can decrease adverse effects by enabling use of lower doses of each agent in the multimodal regimen. This review discusses properties of the various nonopioid analgesics and encourages pharmacists to play an active role in the selection, initiation, and dose-titration of multimodal analgesia. The choice of nonopioid agents should be based on patient comorbidities, hemodynamic stability, and the agents' respective adverse effect profiles. A multidisciplinary plan for management of pain should be formulated during transitions of care and is an area of opportunity for pharmacists to improve patient care. CONCLUSION: Multimodal analgesia effectively treats pain while decreasing adverse effects. There is mounting evidence to support use of this strategy to decrease opioid use. As medication experts, pharmacists can play a key role in the selection, initiation, and dose-titration of analgesic agents based on patient-specific factors.