Pharmacokinetics of caspofungin increased dosage in a patient on rifampin-containing anti-tubercular treatment.

We describe a patient treated with caspofungin and rifampin; after increasing the dosage of the former (70 mg/day) we observed an unexpectedly lower plasma exposure (AUC0-24 79.5 µg/ml*h vs. 108.8 µg/ml*h). Although rifampin-mediated complete enzyme induction may take longer than 2 weeks, the clinical advantage of an increased caspofungin dose deserves clinical investigation.

Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients.

To date, there is no severe acute respiratory syndrome coronavirus 2-(SARS-CoV-2)-specific prognostic biomarker available. We assessed whether SARS-CoV-2 cycle threshold (Ct) value at diagnosis could predict novel CoronaVirus Disease 2019 (COVID-19) severity, clinical manifestations, and six-month sequelae. Hospitalized and outpatient cases were randomly sampled from the diagnoses of March 2020 and data collected at 6 months by interview and from the regional database for COVID-19 emergency. Patients were stratified according to their RNA-dependent-RNA-polymerase Ct in the nasopharyngeal swab at diagnosis as follows: Group A ≤ 20.0, 20.0 < group B ≤ 28.0, and Group C > 28.0. Disease severity was classified according to a composite scale evaluating hospital admission, worst oxygen support required, and survival. Two hundred patients were included, 27.5% in Groups A and B both, 45.0% in Group C; 90% of patients were symptomatic and 63.7% were hospitalized. The median time from COVID-19 onset to swab collection was five days. Lethality, disease severity, type, and number of signs and symptoms, as well as six-month sequelae distributed inversely among the groups with respect to SARS-CoV-2 Ct. After controlling for confounding, SARS-CoV-2 Ct at diagnosis was still associated with COVID-19-related death (p = 0.023), disease severity (p = 0.023), number of signs and symptoms (p < 0.01), and presence of six-month sequelae (p < 0.01). Early quantification of SARS-CoV-2 may be a useful predictive marker to inform differential strategies of clinical management and resource allocation.

Antiviral activity of maraviroc plus mirtazapine in a low-risk HIV-negative patient with progressive multifocal leukoencephalopathy.

A case of progressive multifocal leukoencephalopathy (PML) is described in an HIV-negative patient with mixed connective-tissue disease (MCTD) on a minimally immunosuppressive treatment with hydroxychloroquine. The patient presented with right-sided weakness, episodes of disorientation and loss of short-term memory and of vision in her right eye. PML was diagnosed by JCV DNA on cerebrospinal fluid and radiological criteria. She was treated with off-label maraviroc and mirtazapine but died two months after hospital admission, despite a surprising decrease in the viral load of cerebrospinal fluid three weeks after starting therapy. Prompt diagnosis and antiviral treatment of PML even in low-risk patients are warranted. Future studies are required to define the therapeutic role of maraviroc (MVC) and mirtazapine in this setting.

Ultrasound-guided intravenous catheter insertion in a prone patient using a T probe in emergency setting.

INTRODUCTION: Central venous catheterizations are common intraoperative procedures.Central venous catheter (CVC) placements are usually performed with patients lying in the supine position using real-time ultrasound (US) guidance. CASE DESCRIPTION: A 43-year-old man underwent open right popliteal artery reconstruction in the prone position for a limb-threatening injury. Excessive continuous intraoperative bleeding, increased by a coexisting pelvic fracture, was temporarily stabilized by a T POD device, but with the need of external fixation, required the placement of CVC, which was not feasible whilst in the prone position without US help.A view of the left internal jugular vein (IJV) was obtained with pediatric T probe and a CVC was placed using real-time US guidance, without complications. CONCLUSIONS: We demonstrated the feasibility and safety of US-guided CVC placements in an emergency setting.

Determinants of darunavir cerebrospinal fluid concentrations: impact of once-daily dosing and pharmacogenetics.

OBJECTIVES: To compare cerebrospinal fluid (CSF) darunavir and ritonavir concentrations in patients receiving darunavir/ritonavir 800/100 mg once daily or 600/100 mg twice daily. To determine the influence of single-nucleotide polymorphisms in the genes encoding for blood-brain barrier transporters (ABCB1 3435 C>T, ABCB1 1236 C>T, ABCB1 2677 G>T, SLCO1A2 38 A>G, SLCO1A2 516 A>C, ABCC2 -24 G>A) on darunavir and ritonavir penetration into CSF. DESIGN: Comparative pharmacokinetics study in patients. METHODS: Plasma and CSF darunavir and ritonavir concentrations (2-26 h after drug intake) were determined by a validated HPLC coupled with mass spectrometry method in adults on darunavir-based combination antiretroviral therapy undergoing a lumbar puncture. RESULTS: HIV-infected patients on once-daily darunavir/ritonavir had significantly lower CSF darunavir trough concentrations and CSF-to-plasma ratios than patients on darunavir/ritonavir twice-daily (10.7 versus 38.2 ng/ml and 0.32 versus 0.90%; P < 0.05). No significant effect of single-nucleotide polymorphisms in the genes encoding for blood-brain barrier transporters was noted apart from slightly higher CSF darunavir penetration in patients carrying OATP1A2 uncommon variants. CONCLUSIONS: This is the first study to compare darunavir CSF concentrations in patients taking the once-daily or the twice-daily dosage: our data show that darunavir and ritonavir dosing significantly affects not only CSF concentrations but also the extent of drug penetration into the CSF. Furthermore a minority of patients in the once-daily arm presented very low CSF concentration of potential concern for HIV control in the central nervous system. The relative importance of pharmacogenetics in influencing CSF darunavir pharmacokinetics deserves further clinical investigation.