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.

Bioactive Glass in a Rare Case of Osteomyelitis of the Heel in a Guillain-Barré Syndrome: A Case Report.

Guillain-Barré syndrome (GBS) represents an acute inflammatory immune-mediated demyelinating polyradiculoneuropathy with an incidence of 0.6 per 100 000 people. In this article, we report the case of a 19-year-old girl affected by GBS since the age of 2 who presented at our clinic complaining for a chronic plantar hindfoot-infected ulceration. Serology showed increase of inflammatory markers and leukocytosis, and magnetic resonance imaging revealed osteomyelitis of calcaneum and soft tissue alterations with air bubbles. The patient was treated in our clinic by an integrated multidisciplinary approach consisting of immediate admission, soft tissue and bone debridement, and administration of antibiotics under the close control of infectious disease specialist. After the control of acute condition, the patient underwent negative pressure therapy associated with instillation of antiseptic solution until the restoration of bone and soft tissue loss of substance and, eventually, to the application of bioactive glass substitute until the achievement of complete wound healing.

Severe respiratory failure in an immunocompetent host with invasive pulmonary aspergillosis and H1N1 influenza.

Invasive pulmonary aspergillosis (IPA) is a life-threatening condition that usually occurs in immunocompromised hosts. However, according to recent reports it can affect immunocompetent hosts with severe influenza infection due to viral-dependent disruption of respiratory immune defenses. We present the case of a 61-year-old Caucasian man admitted to the Emergency Department with respiratory failure and fever, who was diagnosed with H1N1 influenza and IPA. Because of his poor general conditions, he was treated with a double antifungal scheme, although this lies outside the suggested treatment guidelines. This choice turned out to be extremely effective. He was discharged after one month and his clinical conditions showed rapid improvement, with nearly complete normalization of the radiological pattern in three months. IPA remains a life-threatening condition, even in immunocompetent hosts, and should therefore always be suspected; if necessary, a combined treatment should rapidly be started. We report this case as the interest in influenza-associated IPA is high, both due to the clinical severity of this condition, which is treatable if identified early, and the emerging importance of respiratory infections caused by viruses belonging to the SARS family, such as SARS-CoV-2.

Extensive Skull Base Osteomyelitis Secondary to Malignant Otitis Externa.

Skull base osteomyelitis is a severe complication of malignant otitis externa that affects the marrow of the temporal, sphenoid, and occipital bones. Skull base osteomyelitis is usually diagnosed based on clinical, microbiological, and radiological findings. Here, we present the imaging findings of a 76-year-old man who initially presented with right-sided malignant otitis externa, with the involvement of the otomastoid structures and ipsilateral temporal bone. Over the following 3 years, despite specific extended antibiotic therapy, the skull base osteomyelitis entirely involved the skull base, up to the contralateral petrous portion of the temporal bone, and it affected the cervical vertebral processes. This report describes an exceptional extent of unilateral malignant otitis externa with a severe involvement of the skull base on the contralateral side and the cervical spine.

Long-term, low-dose tigecycline to treat relapsing bloodstream infection due to KPC-producing Klebsiella pneumoniae after major hepatic surgery.

A 68-year-old male underwent a right hepatectomy, resection of the biliary convergence, and a left hepatic jejunostomy for a Klatskin tumour. The postoperative course was complicated by biliary abscesses with relapsing bloodstream infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp). A 2-week course of combination antibiotic therapy failed to provide source control and the bacteraemia relapsed. Success was obtained with a regimen of tigecycline 100mg daily for 2 months, followed by tigecycline 50mg daily for 6 months, then 50mg every 48h for 3 months. No side effects were reported.

Synergistic activity of colistin plus rifampin against colistin-resistant KPC-producing Klebsiella pneumoniae.

Infections caused by carbapenem-resistant KPC-producing Klebsiella pneumoniae are responsible for high rates of mortality and represent a major therapeutic challenge, especially when the isolates are also resistant to colistin. We used the checkerboard method to evaluate the synergistic activity of 10 antibiotic combinations against 13 colistin-resistant KPC-producing K. pneumoniae isolates (colistin MIC range of 8 to 128 mg/liter). Colistin plus rifampin was the only combination that demonstrated consistent synergistic bacteriostatic activity against 13/13 strains tested, reducing the colistin MIC below the susceptibility breakpoint (MIC ≤ 2 mg/liter) in 7/13 strains at rifampin concentrations ranging from 4 to 16 mg/liter. Bactericidal synergistic activity was also documented for 8/13 tested strains. Other antimicrobial combinations with carbapenems, gentamicin, and tigecycline showed variously synergistic results. Colistin plus rifampin also exhibited bacteriostatic synergistic activity against 4/4 colistin-susceptible KPC-producing K. pneumoniae isolates (colistin MIC range of 0.5 to 2 mg/liter) and 4/4 ertapenem-resistant extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolates (ertapenem MIC range of 16 to 32 mg/liter). Collectively, our data suggest that colistin plus rifampin is the most consistently synergistic combination against KPC-producing K. pneumoniae isolates, including colistin-resistant strains. Colistin-rifampin combinations may have a role in the treatment of multidrug-resistant K. pneumoniae and may possibly slow the selection of heteroresistant subpopulations during colistin therapy.