Ceftaroline in CNS and ocular infections: a case series.

Background: There are limited data describing outcomes of patients treated with ceftaroline for infections with CNS or ocular involvement. Objectives: To describe outcomes of patients treated with ceftaroline for methicillin-resistant staphylococcal infections involving the CNS or eye. Patients and methods: This was a retrospective review of 10 patients at an academic medical centre who received ceftaroline for CNS or ocular infections. Results: All patients were treated with ceftaroline as part of a combination for salvage therapy. Four patients died, whereas six patients experienced clinical cure. Only one experienced microbiological recurrence. Conclusions: These preliminary data suggest that ceftaroline may be an option for salvage therapy of severe staphylococcal infections when used in combination.

CNS Aspergillosis and Cryptococcosis with Cytomegalovirus Pneumonia in a Patient with Chronic Lymphocytic Leukemia Treated with Acalabrutinib.

Bruton's tyrosine kinase inhibitors (BTKis) are the preferred treatment for chronic lymphocytic leukemia (CLL). Despite their therapeutic benefits, these targeted agents have been associated with an increased risk of invasive infections. We describe a 68-year-old male who developed multiple bacterial, fungal and viral infections while on treatment with acalabrutinib. To our knowledge, this is the first reported case of concomitant CNS infections with Cryptococcus neoformans and Aspergillus fumigatus, along with cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) pneumonia while on acalabrutinib. This case adds to the scarce literature of fungal and bacterial infections associated with acalabrutinib, raising the suspicion that infection risk is a medication class effect for BTKis.

Comparison of dosing strategies in obese patients prescribed intravenous acyclovir and evaluation of rate of acute kidney injury.

INTRODUCTION: There is limited guidance on the most appropriate dosing strategy for intravenous (IV) acyclovir in obese patients. The manufacturer's labelling suggests using ideal body weight (IBW); however, previous pharmacokinetic studies of obese patients have shown more rapid systemic clearance and lower area under the curve and peak concentrations compared with patients with a body mass index (BMI) < 30 kg/m2. Although pharmacokinetic data suggest that plasma concentrations of acyclovir are best predicted when using adjusted body weight (AdjBW) doses, there is concern about higher rates of acute kidney injury (AKI). METHODS: This was a retrospective cohort review of adult patients with a BMI ≥ 30 kg/m2 prescribed IV acyclovir ≥ 48 hours between 1 January 2014 and 31 August 2021 at a 511-bed academic medical centre. The primary objective was to compare AdjBW with IBW dosing in obese patients who had been prescribed IV acyclovir and to determine whether AdjBW dosing results in higher rates of AKI. RESULTS: Ninety-four patients were included: 61 were in the IBW cohort and 33 were in the AdjBW cohort. The median BMI [IQR] for all patients was 34.7 kg/m2 [31.8-40.6]. Patients in the AdjBW cohort received a significantly higher median acyclovir dose of 800 mg/dose [IQR 700-850] compared with 600 mg/dose [IQR 500-700] for the IBW cohort (P ≤ 0.0001). No patients dosed using AdjBW developed AKI compared with eight (13.1%) in the IBW group. CONCLUSION: In this study, 8.5% of all obese patients receiving acyclovir developed AKI. Further studies are needed to confirm dosing recommendations.

Antivirals With Activity Against Mpox: A Clinically Oriented Review.

Mpox virus is an emergent human pathogen. While it is less lethal than smallpox, it can still cause significant morbidity and mortality. In this review, we explore 3 antiviral agents with activity against mpox and other orthopoxviruses: cidofovir, brincidofovir, and tecovirimat. Cidofovir, and its prodrug brincidofovir, are inhibitors of DNA replication with a broad spectrum of activity against multiple families of double-stranded DNA viruses. Tecovirimat has more specific activity against orthopoxviruses and inhibits the formation of the extracellular enveloped virus necessary for cell-to-cell transmission. For each agent, we review basic pharmacology, data from animal models, and reported experience in human patients.

Limited Clinical Utility of Follow-up Blood Cultures in Patients With Streptococcal Bacteremia: An Opportunity for Blood Culture Stewardship.

BACKGROUND: The value of positive follow-up blood cultures (FUBCs) in streptococcal bacteremia has not been well defined. Therefore, we explored the frequency of and risk factors for positive FUBC in a retrospective cohort of patients with streptococcal bacteremia. METHODS: Adults ≥18 years of age, admitted with at least 1 positive blood culture for Streptococcus spp between 2013 and 2018 followed by at least 1 FUBC, were potentially eligible. Positive FUBCs were defined as cultures positive for the same streptococcal species drawn >24 hours after the index culture. We excluded patients with polymicrobial bacteremia. We compared the characteristics of patients with and without a positive FUBC. RESULTS: In our single-center cohort, we identified 590 patients with streptococcal bacteremia, and 314 patients met inclusion criteria. Ten patients had FUBC with Streptococcus spp (3.2%), 4 (1.3%) had a contaminant identified, and 3 (1.0%) had a new pathogen isolated. Endocarditis (5 of 10 [50.0%] vs 35 of 304 [11.5%]), epidural abscess (2 of 10 [20%] vs 4 of 304 [1.3%]), and discitis or vertebral osteomyelitis (3 of 10 [30.0%] vs 14 of 304 [4.6%]) were associated with positive FUBC. Patients with positive FUBC had a longer median length of stay (12.9 vs 7.1 days, P = .004) and longer duration of antibiotic treatment (14.9 vs 43.2 days, P = .03). CONCLUSIONS: Follow-up blood cultures among patients with streptococcal BSI are rarely positive. Clinicians could consider limiting follow-up blood cultures in patients at low risk for deep-seated streptococcal infections, persistent bacteremia, or endovascular infection.

Turtle Flexion Reflex Motor Patterns Show Windup, Mediated Partly by L-type Calcium Channels.

Windup is a form of multisecond temporal summation in which identical stimuli, delivered seconds apart, trigger increasingly strong neuronal responses. L-type Ca2+ channels have been shown to play an important role in the production of windup of spinal cord neuronal responses, initially in studies of turtle spinal cord and later in studies of mammalian spinal cord. L-type Ca2+ channels have also been shown to contribute to windup of limb withdrawal reflex (flexion reflex) in rats, but flexion reflex windup has not previously been described in turtles and its cellular mechanisms have not been studied. We studied windup of flexion reflex motor patterns, evoked with weak mechanical and electrical stimulation of the dorsal hindlimb foot skin and assessed via a hip flexor (HF) nerve recording, in spinal cord-transected and immobilized turtles in vivo. We found that an L-type Ca2+ channel antagonist, nifedipine, applied at concentrations of 50 µM or 100 µM to the hindlimb enlargement spinal cord, significantly reduced windup of flexion reflex motor patterns, while lower concentrations of nifedipine had no such effect. Nifedipine similarly reduced the amplitude of an individual flexion reflex motor pattern evoked by a stronger mechanical stimulus, in a dose-dependent manner, suggesting that L-type Ca2+ channels contribute to each flexion reflex as well as to multisecond summation of flexion reflex responses in turtles. We also found that we could elicit flexion reflex windup consistently using a 4-g von Frey filament, which is not usually considered a nociceptive stimulus. Thus, it may be that windup can be evoked by a wide range of tactile stimuli and that L-type calcium channels contribute to multisecond temporal summation of diverse tactile stimuli across vertebrates.