Risk factors for positive follow-up blood cultures in Gram-negative bacteremia among immunocompromised patients with neutropenia.

INTRODUCTION: Gram-negative bacillary bloodstream infection (GN-BSI) is a frequent clinical challenge among immunocompromised hosts and is associated with a high mortality. The utility of follow-up blood cultures (FUBCs) for GN-BSI in this population, particularly in the setting of neutropenia, is poorly defined. METHODS: We conducted a single-center, retrospective cohort study between the period of July 2018 and April 2022 to investigate the utility of FUBCs and delineate risk factors for positive cultures among neutropenic patients with monomicrobial GN-BSI. Univariate logistic regression was performed to assess risk factors associated with positive FUBCs. RESULTS: Of 206 patients, 98% had FUBCs performed, and 9% were positive. Risk factors for positive FUBCs included multidrug-resistant GN infection (OR 3.26; 95% confidence interval [CI] 1.22-8.72) and vascular catheter source (OR 4.82; CI 1.76-13.17). Among patients lacking these risk factors, the prevalence of positive FUBCs was low (2.8%) and the negative predictive value was 92%. Those with positive and negative FUBCs had similar rates of all-cause mortality (16.7% vs. 16.6%; p = .942) and microbiologic relapse (11.1% vs. 6.0%; p = .401) within 90-days of treatment completion. However, positive FUBCs were associated with prolonged hospitalization and longer duration of antimicrobial therapy. CONCLUSION: Positive FUBCs were infrequent in neutropenic patients with GN-BSI, and their occurrence did not significantly impact mortality or microbiologic relapse. Risk factors for positive FUBCs included multidrug resistant Gram-negative infection and vascular catheter source. Prospective studies will be necessary to elucidate the benefits and risks of FUBCs when managing GN-BSI in patients with underlying immune compromise.

Updates in Culture-Negative Endocarditis.

Blood culture-negative infective endocarditis (BCNE) is a challenging condition associated with significant morbidity and mortality. This review discusses the epidemiology, microbiology, diagnosis, and treatment of BCNE considering advancements in molecular diagnostics and increased access to cardiac surgery. BCNE can be categorized into bacterial endocarditis with sterilized blood cultures due to previous antibiotic treatment, endocarditis caused by fastidious microorganisms, and true BCNE caused by intracellular organisms that cannot be cultured using traditional techniques. Non-infectious causes such as nonbacterial thrombotic endocarditis should also be considered. Diagnostic approaches involve thorough patient history; blood and serum testing, including appropriate handling of blood cultures; serological testing; and molecular techniques such as targeted and shotgun metagenomic sequencing. Where available, evaluation of explanted cardiac tissue through histopathology and molecular techniques is crucial. The therapy for BCNE depends on the likely causative agent and the presence of prosthetic material, with surgical intervention often required.

Unexpected Adverse Events of Immune Checkpoint Inhibitors.

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter's syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis.

Association of adverse effects with high serum posaconazole concentrations.

Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000 ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000 ng/mL and 3000-4999 ng/mL (80% vs. 58.8%; P = 0.31). Posaconazole TDM should be performed for both treatment and prophylaxis indications and dose decrease for serum concentrations >3000 ng/mL should be considered.

Drug level monitoring is commonly used to evaluate appropriate dosing and effectiveness of posaconazole, a medication used to treat fungal infections. Patients with high levels commonly had side effects. Posaconazole monitoring should be completed, and doses reduced when levels are high.

Facial Majocchi's granuloma.

Majocchi's granuloma (MG) is an uncommon form of deep fungal folliculitis that is most frequently caused by dermatophytes. Here, we present a case of facial MG.

Dermatomyositis Associated with Lung Cancer: A Brief Review of the Current Literature and Retrospective Single Institution Experience.

Dermatomyositis is a rare inflammatory myopathy that is often related to lung cancer. In this retrospective observational study, we analyzed data from patients diagnosed with lung cancer at Soroka University Medical Center between January 2017 and July 2021. A total of 689 patients with lung cancer were included in this study, 97 of whom had small cell lung cancer and 592 had non-small cell lung cancer. We identified a single patient (60-year-old female) who presented with signs and symptoms of dermatomyositis, which was later confirmed to be associated with lung cancer as a paraneoplastic syndrome. Both our study and a recent review of the literature illustrate the temporal link between dermatomyositis and lung cancer, as well as reinforce the need for heightened cancer screenings in DM patients.

Bloodstream infections with rapidly growing nontuberculous mycobacteria.

BACKGROUND: Bloodstream infections (BSI) with rapidly growing mycobacteria (RGM) resulted in recent nosocomial outbreaks predominantly in immunocompromised patients. A little is known about the clinical implications of RGM BSI with different species. METHODS: We conducted a multicenter retrospective cohort study of patients with RGM BSI from November 2011 to December 2020. Demographic data, clinical presentation, laboratory and radiographic findings and microbiological characteristics were used to tabulate descriptive statistics. We performed a comparative analysis of patients with BSI due to Mycobacterium abscessus complex (MABC) vs. other RGM. RESULTS: We identified 32 patients with positive blood cultures for RGM, 4/32 (12.5%) were considered to have unclear significance. The most common source for RGM BSI was intravascular catheters (14/28, 50%). Compared to other sources, patients with catheter-related bloodstream infection (CRBSI) received a shorter course of antimicrobial therapy (median [IQR]: one month [0.37-2.25] vs. six months [2-12]), (P = 0.01). The most common species isolated were MABC (12/28, 42.9%), followed by Mycobacterium fortuitum group (6/28, 21.4%) and Mycobacterium chelonae (6/28, 21.4%). Compared to other RGM, MABC BSI was more likely to be secondary to skin and soft tissue infection, associated with longer hospital stay (P = 0.04) and higher death rates despite a higher number of antimicrobial agents used for empirical and directed therapy per patient. CONCLUSION: MABC BSI is associated with an overall more resistant profile, longer hospital stay, and higher death rate despite a more aggressive therapy approach.

Unexpected Vancomycin Pharmacokinetic Profile Secondary to Macromolecular Complexing: A Case Series.

BACKGROUND: The optimal dosing and monitoring of vancomycin has been largely debated for decades, with key guideline changes for recommended monitoring in 2009 and 2020. Current and past practices for pharmacokinetic dose optimization use serum drug assays to guide dose adjustment to effectively balance efficacy and the risks of toxicity. These assays detect both bound and unbound serum concentrations. Vancomycin is believed to be 50%-55% protein bound in most cases; however, some variability in this parameter has been previously published. The authors report 2 cases of abnormal vancomycin pharmacokinetics discovered based on unexpected serum levels during routine clinical care. METHODS: Unexpected vancomycin levels, observed during clinical care for 2 separate patients, were further evaluated to determine the source of the abnormal pharmacokinetics. In case 1, serial dilution was performed to assure that assay interference was not associated with the significant elevation (>100 mg/L). In both cases, samples were filtered using a Millipore Centrifree 30 KDa centrifugal filter to separate bound vancomycin, with a Protein G spin kit used to bind IgG and remove IgG complexes from the patient sample. In case 2, a polyethylene glycol precipitation was also performed to precipitate large-molecular-weight complexes. RESULTS: In both cases, laboratory analysis revealed abnormal vancomycin protein-binding profiles with macromolecular complex formation. Immunoglobulin G played a role in the macrocomplex in both patients. CONCLUSIONS: In cases of unusual or unexpected vancomycin pharmacokinetics in the absence of renal dysfunction, an abnormal protein-binding profile should be considered. Bound vancomycin may yield elevated serum levels, leading to poorly informed dose adjustments and risk for treatment failure. Given implications for therapeutic drug monitoring and unknown impacts on efficacy and toxicity, further investigations into population incidence and risk factors for abnormal protein binding of vancomycin are warranted.

Management and treatment of Aerococcus bacteremia and endocarditis.

OBJECTIVES: We describe our multicenter experience on diagnosis and management of Aerococcus bacteremia including the susceptibility profile of Aerococcus species and a suggested algorithm for clinicians. METHODS: Retrospective study of all patients with positive blood cultures for Aerococcus species from January 2005 to July 2020 in our institution with clinical data and susceptibility profile. Data were collected from both electronic health record and clinical microbiology laboratory database. RESULTS: There were 219 unique isolates with only the susceptibility profiles available, while 81 patients had clinical information available. Forty-nine of those cases were deemed as true bloodstream infection and the rest were of unclear clinical significance. Cases of endocarditis (n = 7) were high-grade, monomicrobial bacteremia caused by Aerococcus urinae. Patients with endocarditis were younger (66 vs 80 p < 0.05). The risk for endocarditis was higher if duration of symptoms was longer than 7 days (OR 105, 95% CI: 5-2271), or if there were septic emboli (OR 71, 95% CI: 3-1612). A DENOVA score cutoff of ≥ 3 was 100% sensitive and 89% specific in detecting endocarditis. The 30-day and 3-month all-cause mortality for bacteremia was 17% and 24%, respectively. Six out of seven patients with endocarditis survived. CONCLUSIONS: Antibiotic regimen for aerococcal bloodstream infections and endocarditis should be guided by species identification and antimicrobial susceptibility testing. DENOVA scoring system's performance in this study is more congruent to other studies. Hence, it can be used as an adjunctive tool in assessing the need for echocardiogram to rule out endocarditis. In our experience, two and four weeks of treatment for bloodstream infections and endocarditis, respectively, had good outcomes.

Time to Treat: Applying Lessons Learned from Other Viral Syndromes to SARS-CoV-2.

In many different infectious syndromes, most notably several viral conditions, time to therapy initiation from symptom onset has been identified as a critical component contributing to the success of therapy. Regarding COVID-19, several therapeutic antivirals, both repurposed and novel, have been evaluated for overall safety and efficacy. As the literature related to these therapies has expanded recently, a wide array of trial designs, time to therapy initiation thresholds, and clinical outcomes in regard to time to initiation have been reported. We describe the potential effects of time to therapy initiation on outcomes in patients with COVID-19 and detail the existing data surrounding this topic in relation to remdesivir, convalescent plasma, lopinavir/ritonavir, and hydroxychloroquine.