Clinical Effectiveness and Pharmacokinetics of Dalbavancin in Treatment-Experienced Patients with Skin, Osteoarticular, or Vascular Infections

Dalbavancin (DBV) is a lipoglycopeptide approved for the treatment of Gram-positive infections of the skin and skin-associated structures (ABSSSIs). Currently, its off-label use at different dosages for other infections deserves attention. This work aimed to study the clinical effectiveness and tolerability of DBV in outpatients with ABSSSIs, osteoarticular (OA), or other infections, treated with either one or two 1500 mg doses of dalbavancin, for different scheduled periods. A liquid chromatography–tandem mass spectrometry method was used to measure total DBV concentrations. PK/PD parameters and the clinical and microbiological features of this cohort were evaluated in order to investigate the best predictors of treatment success in real-life settings. Of the 76 screened patients, 41 completed the PK study. Long-term PK was comparable to previous studies and showed significant differences between genders and dosing schedules. Few adverse events were observed, and treatment success was achieved in the vast majority of patients. Failure was associated with lower PK parameters, particularly C(max). Concluding, we were able to describe DBV PK and predictors of treatment success in selected infections in this cohort, finding DBV C(max) as a possible candidate for therapeutic drug-monitoring purposes, as well as highlighting the dual-dose one-week-apart treatment as the optimal choice for OA infections

Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort

Background: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. Methods: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. Results: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). Conclusions: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes

Disseminated Cryptococcosis Complicating Severe SARS-CoV-2 Infection

Opportunistic invasive fungal infections (IFI) have been described in severe SARS-CoV-2 infection. COVID-19-related cytokine storm, immune dysregulation and lymphopenia may increase IFI susceptibility in comorbid patients. We described the case of a 64-year-old man with respiratory failure due to SARS-CoV-2 infection complicated with disseminated cryptococosis. We analyzed the role played by the SARS-CoV-2-associated lymphopenia and the cumulative risk factors that lead to secondary infection by Cryptococcus neoformans, and its part in the dysregulation of the immunity response

Sequential or Combination Treatments as Rescue Therapies in Immunocompromised Patients with Persistent SARS-CoV-2 Infection in the Omicron Era: A Case Series

Prolonged SARS-CoV-2 infections are widely described in immunosuppressed patients, but safe and effective treatment strategies are lacking. We aimed to outline our approach to treating persistent COVID-19 in patients with immunosuppression from different causes. In this case series, we retrospectively enrolled all immunosuppressed patients with persistent SARS-CoV-2 infections treated at our centers between March 2022 and February 2023. Patients received different sequential or combination regimens, including antivirals (remdesivir, nirmatrelvir/ritonavir, or molnupiravir) and/or monoclonal antibodies (mAbs) (tixagevimab/cilgavimab or sotrovimab). The main outcome was a complete virological response (negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs) at the end of treatment. Fifteen patients were included as follows: eleven (11/15; 73%) with hematological disease and four (4/15; 27%) with recently diagnosed HIV/AIDS infection. Six patients (6/15; 40%) received a single antiviral course, four patients (4/15; 27%) received an antiviral and mAbs sequentially, and two patients (13%) received three lines of treatment (a sequence of three antivirals or two antivirals and mAbs). A combination of two antivirals or one antiviral plus mAbs was administered in three cases (3/15, 20%). One patient died while still positive for SARS-CoV-2, while fourteen (14/15; 93%) tested negative within 16 days after the end of treatment. The median time to negativization since the last treatment was 2.5 days. Both sequential and combination regimens used in this study demonstrated high efficacy and safety in the high-risk group of immunosuppressed patients

A Regional Observational Study on COVID-19-Associated Pulmonary Aspergillosis (CAPA) within Intensive Care Unit: Trying to Break the Mold

The reported incidence of COVID-19-associated pulmonary aspergillosis (CAPA) ranges between 2.4% and 35% in intensive care unit (ICU) patients, and awareness in the medical community is rising. We performed a regional retrospective observational study including patients diagnosed with CAPA defined according to the Modified AspICU Dutch/Belgian Mycosis Study Group and CAPA–EECMM, from five different ICUs, admitted between March, 2020 and September, 2021. Forty-five patients were included. The median age was 64 (IQR 60–72), mostly (73%) males. At ICU admission, the median Charlson comorbidity index was 3 (2–5), and the simplified acute physiology score (SAPS)-II score was 42 (31–56). The main underlying diseases were hypertension (46%), diabetes (36%) and pulmonary diseases (15%). CAPA was diagnosed within a median of 17 days (IQR 10–21.75) after symptoms onset and 9 days (IQR 3–11) after ICU admission. The overall 28-day mortality rate was 58%, and at univariate analysis, it was significantly associated with older age (p = 0.009) and SAPS-II score at admission (p = 0.032). The use of immunomodulatory agents, p = 0.061; broad-spectrum antibiotics, p = 0.091; positive culture for Aspergillus on BAL, p = 0.065; and hypertension, p = 0.083, were near reaching statistical significance. None of them were confirmed in multivariate analysis. In critically ill COVID-19 patients, CAPA acquired clinical relevance in terms of incidence and reported mortality. However, the risk between underdiagnosis—in the absence of specific invasive investigations, and with a consequent possible increase in mortality—and over-diagnosis (case identification with galactomannan on broncho-alveolar fluid alone) might be considered. Realistic incidence rates, based on local, real-life epidemiological data, might be helpful in guiding clinicians