Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19.

The management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (n = 4), nirmatrelvir/ritonavir plus remdesivir (n = 4) or remdesivir plus molnupiravir (n = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.

Combination regimen of nirmatrelvir/ritonavir and molnupiravir for the treatment of persistent SARS-CoV-2 infection: A case report and a scoping review of the literature.

Immunocompromised patients still experience unpredictable courses of COVID-19, despite that effective vaccines and drugs against SARS-CoV-2 are now available. Antiviral combination regimens may have a role in SARS-CoV-2 infection in immunocompromised hosts, but current knowledge is still limited. We describe the case of a 73-year-old Italian man affected by follicular lymphoma with persistent SARS-CoV-2 infection who was successfully treated with co-administration of oral antivirals (10-day molnupiravir and nirmatrelvir/ritonavir). The therapy was well tolerated both from a clinical and biochemical standpoint, with no signs of toxicity. We also performed a scoping review, to sum up available knowledge on combined antiviral regimens including remdesivir, molnupiravir, or nirmatrelvir/ritonavir. Pending further studies on larger cohorts of patients, our report is consistent with available pre-clinical and clinical data, supporting the possible use of combination therapy in selected difficult-to-treat COVID-19 cases.

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Mycobacterium marinum: A brief update for clinical purposes.

Mycobacterium marinum (M. marinum) is a free-living, slow grower nontuberculous mycobacteria (NTM), strictly related to Mycobacterium tuberculosis, that causes disease in fresh and saltwater fish and it is one of the causes of extra-pulmonary mycobacterial infections, ranging in human from simple cutaneous lesions to disseminated forms in immunocompromised hosts. The first human cases of M. marinum infection were reported from skin lesions of swimmers in a contaminated pool, in 1951, in Sweden by Norden and Linell. Two conditions are required to develop M. marinum infection: (1) skin solution of continuity and (2) exposure to the contaminated water or direct contact with fish or shellfish. The so-called "fish-tank granuloma", the most frequent cutaneous manifestation of M. marinum infection, is characterized by a single papulonodular, verrucose and/or ulcerated granulomatous lesion in the inoculum site. Careful patient's history collection, high clinical suspicion and appropriate sample (e.g. cutaneous biopsy) for microbiological culture are crucial for a timely diagnosis. The treatment is not standardized yet and relies on administration of two active antimycobacterial agents, always guided by antimicrobial susceptibility test on culture, with macrolides and rifampin as pivotal drugs, as well as prompt surgery when feasible. In this narrative review, we provide to Clinicians an updated report of epidemiology, microbiological characteristics, clinical presentation, diagnosis, and management of M. marinum infection.

Anaerobic bloodstream infections in Italy (ITANAEROBY): A 5-year retrospective nationwide survey.

INTRODUCTION: A lack of updated data on the burden and profile of anaerobic bloodstream infections (ABIs) exists. We assessed the incidence of ABIs and trends in antimicrobial resistance in anaerobes isolated from blood in Italy. MATERIAL AND METHODS: We conducted a retrospective study on 17 Italian hospitals (2016-2020). Anaerobes isolated from blood culture and their in vitro susceptibility profiles (EUCAST-interpreted) were registered and analyzed. RESULTS: A total of 1960 ABIs were identified. The mean age of ABIs patients was 68.6 ± 18.5 years, 57.6% were males. The overall incidence rate of ABIs was 1.01 per 10.000 patient-days. Forty-seven% of ABIs occurred in medical wards, 17% in ICUs, 14% in surgical wards, 7% in hemato-oncology, 14% in outpatients. The three most common anti-anaerobic tested drugs were metronidazole (92%), clindamycin (89%) and amoxicillin/clavulanate (83%). The three most common isolated anaerobes were Bacteroides fragilis (n = 529), Cutibacterium acnes (n = 262) and Clostridium perfringens (n = 134). The lowest resistance rate (1.5%) was to carbapenems, whereas the highest rate (51%) was to penicillin. Clindamycin resistance was >20% for Bacteroides spp., Prevotella spp. and Clostridium spp. Metronidazole resistance was 9.2% after excluding C. acnes and Actinomyces spp. Bacteroides spp. showed an increased prevalence of clindamycin resistance through the study period: 19% in 2016, 33% in 2020 (p ≤ 0.001). CONCLUSIONS: Our data provide a comprehensive overview of the epidemiology of ABIs in Italy, filling a gap that has existed since 1995. Caution is needed when clindamycin is used as empirical anti-anaerobic drug.

BCG infection (BCGitis) following intravesical instillation for bladder cancer and time interval between treatment and presentation: A systematic review.

OBJECTIVE: Intravesical Bacillus Calmette-Guèrin (BCG) is an effective treatment in non--muscle-invasive bladder cancer, however, extravesical BCG infection may occur in remote organs as a potentially serious complication. Researchers aimed to assess whether a different timing of BCG infection after intravesical administration of BCG could be identified and estimated for each single involved organ. METHODS: We performed a systematic literature review over systemic and genitourinary BCG infection case reports, including 271 published case reports for a total of 307 patients. Demographic data, clinical features, and timing of BCG infection development were collected and analyzed for each patient. RESULTS: BCG infection developed with a different timing from last instillation, depending on the involved organ. Among the genitourinary complications, penile lesions occurred as early as 1 (1;3) weeks, while orchiepididymitis occurred as late as 56 (6.25;156) weeks. At the same time, granulomatous hepatitis and lungs involvement such as miliary pulmonary BCG infection occurred earlier, with a median time of 1 (1;4) and 1 (1;6) weeks respectively, whereas vascular, osteoarticular, and muscular complications developed with a median timing from last instillation of 52 (20;104), 68 (14;156), and 93 (29;156) weeks, respectively. The analysis detected a cluster between lungs, liver, and bone marrow complications on one side and muscular and osteoarticular or vascular complications on the other side was also observed. CONCLUSIONS: BCG infection after intravesical BCG for bladder cancer may develop even several months or years after the last instillation, depending on the involved organs. When BCG infection interests one or more organ, 2 main associative patterns are common: one involving lungs, liver, and bone marrow, with earlier occurrence but lower rates of microbiological diagnosis achievement, and one involving muscular and osteoarticular or vascular districts, with later occurrence but higher rates of microbiological evidence.

The seXY side of COVID-19: what is behind female protection?

Not availble.

Mycobacterium chimaera infections: An update.

Mycobacterium chimaera is a non-tuberculous mycobacterium belonging to the Mycobacterium avium complex, described for the first time in 2004. It acts as an opportunistic pathogen, with infections, usually respiratory illnesses, occurring more frequently in immunocompromised patients or in patients with underlying respiratory diseases. During the last decade Mycobacterium chimaera disseminated infections following cardiothoracic surgery, especially open-heart surgery, have been increasingly reported worldwide. From a pathogenic standpoint, Mycobacterium chimaera is acquired during cardiopulmonary bypass via bioaerosols emitted from contaminated heater-cooler units water systems. Due to non-specific symptoms and long latency, postoperative Mycobacterium chimaera infections may not be promptly diagnosed and treated, and may become life-threatening. The indication for revision surgery needs to be carefully evaluated on a case-by-case basis, and antibiotic therapy should be based on drug susceptibility testing results. Our review aims to provide an updated account of microbiological characteristics, clinical presentation, diagnosis, and management of Mycobacterium chimaera infections, with a special focus on those developing after cardiothoracic surgery.

Isoniazid-induced Takayasu arteritis remission.

A 75-year-old man was admitted because of fever, unproductive cough, neck pain and upper limb claudication. The patient was febrile and hypotensive, and a cardiac systolic ejection murmur was heard. Blood tests showed normochromic anemia, elevated erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and alpha-2 and beta-2 globulins. In order to investigate neck pain, an ultrasound examination of the carotid arteries was performed which showed a carotid intima-media thickness reaching the maximum value of 2.3 mm in both carotid arteries. Ultrasound examination of the temporal artery and its rami demonstrated wall thickening, both in the common superficial temporal artery and its frontal and parietal rami. A temporal artery biopsy was performed and was consistent with Takayasu arteritis. A positive interferon-γ release assay revealed latent tuberculosis infection and isoniazid 300 mg every 24 hours was commenced. Neither corticosteroids nor other drugs were prescribed at that time. Two weeks later, ultrasound examination showed a significant reduction in the thickening of all investigated arteries. To our knowledge, this is the first case of isoniazid-induced Takayasu arteritis remission. We believe that isoniazid deserves further investigation regarding its potential immunomodulatory properties.

Management of abdominal aortic prosthetic graft and endograft infections. A multidisciplinary update.

Abdominal aortic graft infections (AGIs) occur in 1-5% of aortic prosthetic placements. It can result in limb amputation, pseudo-aneurysm formation, septic emboli, aorto-enteric fistulae, septic shock and death. The most frequently involved pathogens are methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci, followed by Enterobacteriaceae and uncommon bacteria. In case of gut involvement the presence of fungi has to be considered. Computed tomography angiography is actually the gold standard diagnostic imaging but magnetic resonance is a valid alternative. Nuclear medicine imaging is commonly used to improve sensitivity and specificity. Signs and symptoms are often aspecific and blood cultures can be negative, requiring alternative ways to detect the microorganism responsible for infection, such as 16S rRNA gene sequencing and molecular rapid diagnostic tests. Curative surgical intervention is the first choice approach, with in-situ reconstruction providing by far the best outcome and xenopericardial bovine patch as a promising option. For patients unable to undergo major surgery, the outcome of conservative approach remains uncertain but usually provides for life-long suppressive therapy. However, in selected cases an attempt of stopping antibiotic treatment after 3-6 months can be done. Given the difficulty in their management, we performed a review of AGIs, in order to raise awareness on clinical presentation, current available diagnostic tools, prophylaxis, surgical and anti-infective treatment of AGIs.