Efficacy and Safety of Nirmatrelvir/Ritonavir, Molnupiravir, and Remdesivir in a Real-World Cohort of Outpatients with COVID-19 at High Risk of Progression: The PISA Outpatient Clinic Experience.

INTRODUCTION: Different antivirals are available for the treatment of outpatients with COVID-19. Our aim was to describe a real-world experience of outpatient management of COVID-19 subjects at high risk of progression. METHODS: This prospective observational study conducted in the University Hospital of Pisa (January 2022-July 2022) included consecutive COVID-19 outpatients with at least one risk factor for disease progression. Patients received nirmatrelvir/ritonavir, molnupiravir, or 3-day remdesivir, according to the Italian Medicines Agency (AIFA) indications. All patients were followed up until 30 days from the first positive nasopharyngeal swab. The primary endpoint was a composite of death or hospitalization. Secondary endpoints were occurrence of adverse events and a negative test within 10 days from the first positive test. Multivariable analysis was performed to identify factors associated with death or hospitalization. RESULTS: Overall, 562 outpatients were included: 114 (20.3%) received molnupiravir, 252 (44.8%) nirmatrelvir/ritonavir, and 196 (34.9%) 3-day remdesivir. The composite endpoint occurred in 2.5% of patients and was more frequent in patients treated with remdesivir (5.1%) compared with molnupiravir (1.8%) or nirmatrelvir/ritonavir (0.8%, ANOVA among groups p = 0.012). On multivariable Cox regression analysis, presence of ≥ 3 comorbidities, hematological disease, gastrointestinal symptoms, and each-day increment from symptoms onset were factors associated with death or hospitalization, while antiviral treatment was not a predictor. Adverse events occurred more frequently in the nirmatrelvir/ritonavir group (49.2%). Nirmatrelvir/ritonavir compared with remdesivir was associated with a higher probability of having a negative test within 10 days from the first positive one. CONCLUSION: Death or hospitalization did not differ among high-risk COVID-19 outpatients treated with currently available antivirals. Safety and time to a negative test differed among the three drugs.

An octopus gift: Mycobacterium marinum multiple skin lesions.

Mycobacterium marinum is a nontuberculous mycobacterium responsible of infections in humans, ranging from skin infection to disseminated infection in immunocompromised hosts. Clinical suspicion and prompt diagnosis are crucial to prescribe appropriate antimycobacterial treatment and avoid sequelae.

Cardiovascular implantable electronic device endocarditis treated with daptomycin with or without transvenous removal.

BACKGROUND AND METHODS: Nine patients with cardiovascular implantable electronic device (CIED) endocarditis were treated with daptomycin after the failure of previous treatment. The blood and CIED lead cultures of 1 patient were negative. In the other 8 patients, we observed 6 monomicrobic infections and 2 polymicrobic infections. Overall, 10 strains were isolated in these patients: 4 methicillin-sensitive Staphylococcus aureus, 2 methicillin-sensitive Staphylococcus epidermidis, 1 methicillin-resistant Staphylococcus aureus, 1 methicillin-resistant Staphylococcus epidermidis, 1 methicillin-sensitive Staphylococcus hominis, and 1 Propionibacterium acnes. The CIED was removed transvenously in 7 patients. Two patients were too sick for the removal of their CIED, and were cured with 6 mg/kg of daptomycin for 60 and 110 days, respectively, without adverse events. RESULTS: One patient died 4 days after the removal of his CIED because of a complicated abdominal aortic aneurysm. The other 8 patients were cured, with a mean follow-up of 17 ± 8 months. The removed leads were negative, after daptomycin therapy, in 4 cases out of 7. The mean ratio between peak daptomycin concentration and minimal inhibitory concentration (MIC) of the causative strains was 38.3 ± 18.5. For patients whose data were available, the ratio between peak daptomycin concentration and minimal bactericidal concentration (MBC) was 13.2 ± 3.2. CONCLUSION: Daptomycin monotherapy may be a useful therapeutic tool in difficult-to-treat CIED endocarditis, resulting in a high rate of cures and sterilized leads removed. The ratio between peak daptomycin concentration and MIC or MBC may be useful as predictive tool for treatment success.

Acute varicella-zoster virus necrotizing meningoencephalomyelitis with sudden visual loss and paraparesis in an HIV-infected patient.

We describe a case of acute varicella-zoster virus (VZV) hemorrhagic meningoencephalomyelitis in an HIV-infected patient. On admission the patient's CSF was mild haemorrhagic and xanthochromic after centrifugation and he had thoracic skin blisters. VZV DNA was isolated from both the thoracic blisters and CSF. Treatment consisted of aggressive antiviral, steroid and immunoglobulin therapy, which was able to stop disease progression. The patient survived but was left blind and paretic. In conclusion, a diagnosis of CNS infection caused by VZV, based upon CSF analysis and examination of the skin for typical blisters, requires aggressive empiric antiviral therapy in order to maximise patient survival.

Hepatitis C virus genotypes in the liver and serum of patients with chronic hepatitis C.

OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) genotypes in a central area of Italy (Umbria); to analyze the correspondence of the genotypes detected in serum and liver samples; to study the relationship between HCV genotypes and severity of liver disease; to test whether co-infection with more than one HCV subtype could be influenced by the source of infection. METHODS: Genotyping by polymerase chain reaction with core-specific primers (Okamoto method) was performed in the serum and liver from 48 consecutive patients with histologically confirmed chronic C hepatitis. RESULTS: HCV genotype 1b was the prevalent strain and was not associated with more severe histologic damage. Data show a very good correspondence between genotypes identified in serum and liver specimens (91%). Mixed infections (with subtypes 1b and 2a) correlated significantly with intravenous drug abuse (p=0.001). CONCLUSION: We confirmed that subtype 1b is prevalent in central Italy. Co-infection with more than one subtype is not rare in intravenous drug abusers.