A Retrospective Cohort Study Comparing Dual Therapy With Ceftaroline With Vancomycin or Daptomycin Monotherapy for High-Grade or Persistent MRSA Bacteremia.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious clinical infection associated with a high risk of mortality. Dual therapy is often used in patients with persistent bacteremia. Objective: This study aimed to compare the outcomes of vancomycin or daptomycin monotherapy with those of dual therapy with ceftaroline in high-grade or persistent MRSA bacteremia. Methods: We conducted a retrospective cohort study at a university teaching hospital between January 2014 and June 2021, involving adults initially treated with vancomycin or daptomycin. Patients were categorized into monotherapy and dual therapy groups. The primary outcome was 30-day mortality. Secondary outcomes included microbiological relapse and antibiotic-related adverse events. Results: In a group of 155 patients, 30-day mortality rates were similar between the monotherapy (23.4%) and dual therapy (22.6%) groups, with comparable microbiological relapse rates (6.5%). In inverse probability of treatment weighting analysis, we found no significant association between dual therapy and mortality (adjusted risk ratio [ARR] 1.38, 95% CI 0.64-2.41, P = 0.38) or microbiological relapse (ARR 0.95, 95% CI 0.31-2.73, P = 0.93). Dual therapy was associated with a lower risk of antibiotic-related adverse events (ARR 0.45, 95% CI 0.21-0.89, P = 0.02). Infectious diseases (ID) consultation was associated with a reduced mortality risk (ARR 0.27, 95% CI 0.07-0.95, P = 0.04). Conclusions: Dual therapy with ceftaroline did not reduce mortality risk compared with monotherapy in patients with MRSA bacteremia. However, patients with ID consultations showed a 73% reduction in mortality rates. Large-scale, prospective, and randomized controlled trials are needed to provide conclusive evidence regarding the potential benefits of dual therapy with ceftaroline for MRSA bacteremia.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

The influence of continuous renal replacement therapy on 1,3-ß-d-glucan levels in critically ill patients: a single-center retrospective propensity score study.

1,3-ß-d-Glucan (BDG) is commonly used for diagnosing invasive fungal infections (IFIs). While exposure to cellulose-based hemodialyzers is known to cause false-positive BDG results, the impact of modern hemofilters used in continuous renal replacement therapy (CRRT) remains unclear. This retrospective, single-center cohort study aimed to evaluate the effect of CRRT on BDG levels in critically ill patients. We included adult intensive care unit (ICU) patients with ≥1 BDG measurement between December 2019 and December 2020. The primary outcome was the rate of false-positive BDG results in patients exposed to CRRT compared to unexposed patients. Propensity score analysis was performed to control for confounding factors. A total of 103 ICU patients with ≥1 BDG level were identified. Most (72.8%) were medical ICU patients. Forty patients underwent CRRT using hemofilter membranes composed of sodium methallyl sulfonate copolymer (AN 69 HF) (82.5%) and of polyarylethersulfone (PAES) (17.5%). Among the 91 patients without proven IFI, 31 (34.1%) had false-positive BDG results. Univariable analysis showed an association between CRRT exposure and false-positive BDG results. However, the association between CRRT exposure and false-positive BDG results was no longer significant across three propensity score models employed: 1:1 match (n = 32) (odds ratio (OR) 1.65, p = .48), model-adjusted (n = 91) (OR 1.75, p = .38), quintile-adjusted (n = 91) (OR 1.78, p = .36). In this single-center retrospective analysis, exposure to synthetic CRRT membranes did not independently increase the risk of false-positive BDG results. Larger prospective studies are needed to further evaluate the association between CRRT exposure and false-positive BDG results in critically ill patients with suspected IFI.

A successful daptomycin and micafungin dosing strategy in veno-venous ECMO and continuous renal replacement.

WHAT IS KNOWN AND OBJECTIVE: Studies have demonstrated that ECMO leads to pharmacokinetic changes, with alterations in volume of distribution, clearance and drug sequestration by the circuit. We describe a successful dosing approach for daptomycin and micafungin for the treatment of VRE faecium bacteremia and C. glabrata fungemia in a patient receiving veno-venous ECMO and CRRT. CASE SUMMARY: We report a case of a patient with ARDS on veno-venous ECMO complicated by VRE faecium bacteremia and C. glabrata fungemia. The patient was treated with daptomycin 10 mg/kg every 24 h and micafungin 150 mg every 24 h for 14 days. Key observations included the documented bacteremia and fungemia clearance without the need for ECMO circuit exchange. WHAT IS NEW AND CONCLUSION: This case report demonstrates successful bacteremia and fungemia clearance in an adult without the need for ECMO circuit exchange. It also highlights the need for more research to identify optimal antimicrobial dosing strategies in similar scenarios.

A role for nebulized tranexamic acid in veno-venous ECMO patients.

WHAT IS KNOWN AND OBJECTIVE: Although pulmonary haemorrhage as a complication of ECMO has been well documented, optimal management is not fully elucidated. We describe the role of nebulized tranexamic acid as a therapeutic alternative. CASE SUMMARY: We report a case series of three patients with ARDS on ECMO complicated by pulmonary haemorrhage. These patients were treated with 500 mg of nebulized tranexamic acid via the endotracheal tube. Key observations included significant stabilization of haemodynamics, reduced circuit changes and less time off of anticoagulation. WHAT IS NEW AND CONCLUSION: This series demonstrates successful bleeding management with nebulized tranexamic acid, reducing the frequency of ECMO circuit changes, time off of anticoagulation and blood loss.

Breaking the mold: Insights into the clinical management and outcomes of rhinocerebral mucormycosis in adults.

Background: Rhinocerebral mucormycosis is a rare, life-threatening fungal infection that affects the sinuses, nasal passages, and brain. Its management remains challenging owing to high mortality rates. Combination antifungal therapy is an area of ongoing research aimed at improving outcomes. We aimed to describe the clinical management and outcomes of patients with rhinocerebral mucormycosis who were treated with antifungal combination therapy. Methods: This retrospective case series included 10 patients diagnosed with rhinocerebral mucormycosis at two academic medical centers between January 2008 and July 2023 who received initial antifungal therapy with liposomal amphotericin B (L-AmB), alone or in combination, within 24 h of diagnosis. Clinical data were extracted from the medical records. Results: Most patients were males (70 %) with uncontrolled diabetes (71.4 %). L-AmB was used as the initial therapy in all patients, either as monotherapy (n = 4) or combination therapy (n = 6), followed by posaconazole maintenance. The combinations included L-AmB with posaconazole (n = 4), L-AmB with micafungin (n = 3), or both (n = 3). The overall mortality rate was 50 %. Survivors had high morbidity, with median 31-day hospitalizations and 50 % readmission rate. Conclusions: Despite aggressive management, rhinocerebral mucormycosis has high mortality and morbidity rates. While combination antifungal therapy aims to improve cure rates, our case series showed higher mortality rates than monotherapy. Additional research is warranted to optimize management approaches for this devastating infection.

Short versus long duration of ceftaroline combination therapy and outcomes in persistent or high-grade MRSA bacteremia: A retrospective single-center study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is associated with high mortality rates. Despite antibiotic therapy, persistent bacteremia is challenging to treat. Combination therapy with ceftaroline has emerged as a potential treatment option; however, the optimal duration and clinical implications after bacteremia clearance are unknown. METHODS: This retrospective cohort study examined patients with high-grade or persistent MRSA bacteremia who were treated with ceftaroline combination therapy at the University of New Mexico Hospital between January 2014 and June 2021. Patients were categorized into short- (<7 days) or long-duration (≥7 days) groups based on the duration of combination therapy after bacteremia clearance. Outcomes included 30-day all-cause mortality, bacteremia recurrence, post-bacteremia clearance length of stay, and adverse events. RESULTS: A total of 32 patients were included in this study. The most common sources of bacteremia were bone/joint and endovascular (28.1%, 9/32 each). The median duration of combination therapy after clearance was seven days (IQR 2.8, 11). Patients in the long-duration group had a lower Charlson comorbidity index (1.0 vs 5.5, p = 0.017) than those in the short-duration group. After adjusting for confounders, there was no significant difference in the 30-day all-cause mortality between the groups (AOR 0.17, 95% CI 0.007-1.85, p = 0.18). No association was found between combination therapy duration and recurrence (OR 2.53, 95% CI 0.19-inf, p = 0.24) or adverse drug events (OR 3.46, 95% CI 0.39-74.86, p = 0.31). After controlling for total hospital length of stay, there was no significant difference in the post-bacteremia clearance length of stay between the two groups (p = 0.37). CONCLUSIONS: Prolonging ceftaroline combination therapy after bacteremia clearance did not significantly improve outcomes in patients with persistent or high-grade MRSA bacteremia. The limitations of this study warrant cautious interpretation of its results. Larger studies are needed to determine the optimal duration and role of combination therapy for this difficult-to-treat infection.

Under the Skin: A Case Series of Clostridium sordellii Necrotizing Soft Tissue Infections in Patients Who Inject Drugs.

Clostridium sordellii has been well-associated as a cause of obstetric infections but is a less commonly recognized organism of necrotizing skin and soft tissue infections (NSTI). C. sordelli infections are rare with only 14 cases reported in the literature to date. These infections are often associated with profound septic shock and the mortality rate remains high. We report four patients who presented with C. sordellii NSTI over a period of two years at an academic medical center. Notably, injection drug use was the main risk factor for infection in these patients. Appropriate management of C. sordellii NSTI necessitates a combination of antibiotics and emergent surgical intervention. However, despite these efforts, the mortality rate remains high, with three of the four patients dying. Clinicians should consider NSTI in the differential diagnosis when evaluating skin and soft tissue infections in people who inject drugs. Furthermore, it is imperative to educate patients who engage in injection drug use on the potential risks associated with NSTI and inform them of warning signs that warrant immediate medical attention. The devastating consequences of C. sordellii-associated NSTI in this vulnerable population can be mitigated by enhancing awareness and facilitating early intervention.

A case series of Corynebacterium striatum native valve infective endocarditis.

Corynebacterium species isolated in blood cultures are commonly dismissed as a contaminant. They are also recognized as an uncommon pathogen in infective endocarditis. We report two cases of native valve endocarditis due to Corynebacterium striatum. The first patient, a 36-year-old female with hemolytic anemia, whose risk factor for endocarditis was a Port-a-Cath (Smiths Medical, Los Angeles, California) used for routine blood transfusions. She was diagnosed with triple valve endocarditis via transthoracic echocardiogram. Her multiple comorbidities made her a poor surgical candidate for valve replacement and she elected to go on hospice care after antibiotic treatment completion. The second patient, a 46-year-old, was found to have coronavirus disease 2019 (COVID-19) pneumonia in addition to persistent Corynebacterium striatum bacteremia. A transthoracic echocardiogram was highly suggestive of aortic valve endocarditis. A confirmatory transesophageal echocardiogram was unable to be obtained given his clinical instability and COVID-19 status. Unfortunately, this patient expired due to complications of severe COVID-19 pneumonia. We highlight the need for prompt recognition of risk factors of infective endocarditis due to uncommon pathogens that may aid in the diagnosis and treatment, while utilizing a multidisciplinary approach. Learning objective: The aim of this case series is to emphasize the importance of Corynebacterium species as a cause of native valve infectious endocarditis and to illustrate the challenges it poses in diagnosis and management.