Proactive therapeutic monitoring of dalbavancin concentrations in the long-term management of chronic osteoarticular/periprosthetic joint infections.

Here, we describe the use of proactive therapeutic drug monitoring (TDM) to individualize the optimal timing of drug injections in 16 adult patients with chronic osteoarticular infections receiving a median of 7 injections of dalbavancin (up to 12 injections in 15 months). Dalbavancin injections were repeated at medians of 39-47 days, with infusion intervals ranging from 26 to 69 days. TDM can facilitates a precise, targeted use of dalbavancin for infections requiring prolonged treatments.

Isolation of viable monkeypox virus from anal and urethral swabs, Italy, May to July 2022.

Anal and urethral samples from confirmed cases of monkeypox were screened for monkeypox virus (MPXV) by real-time PCR. Isolation of the virus was subsequently attempted in cell culture. Actively-replicating virus was demonstrated in 13 of 18 and 11 of 15 PCR-positive anal and urethral swabs, respectively, collected within 7 days from symptoms onset. Two asymptomatic secondary cases had detectable MPXV genetic material in urethral secretion and for one, MPXV was successfully isolated, supporting a potential MPXV sexual transmission hypothesis.

Exploring early COVID-19 therapies, variants, and viral clearance dynamics: Insights from a high-risk outpatients study.

This retrospective observational study investigates the impact of early COVID-19 therapies, including antivirals and monoclonal antibodies (mAbs), on time to achieve negative swab results in high-risk outpatients infected with specific Omicron sublineages. The study enrolled 104 patients from Luigi Sacco Hospital in Milan between December 2021 and March 2023, categorizing them based on the Omicron sublineage they were infected with (BA.1, BA.2, BA.4/BA.5) and the early treatment they received (antivirals or mAbs). Key data collected included demographic and clinical characteristics, initial and follow-up cycle threshold (Ct) values from qPCR tests, and the interval between swabs. The median age of the participants was 63 years (Interquartile Range [IQR] 54.0-76.5), and 55.8% were male. Among the patients, 15 received mAbs (14.4%), and 99 received antiviral treatments (95.2%) - specifically, Paxlovid (51.9%), Molnupiravir (21.1%), and Remdesivir (12.5%). No patients required hospitalization or experienced mortality during the one-month follow-up period. Regarding Omicron sublineages, 23 patients (22.1%) were infected with BA.1, 53 (51%) with BA.2, and 28 (26.9%) with BA.4/BA.5. The median interval between the initial and follow-up swabs was 6 days (IQR 6.0-7.0). Initial Ct values had a median of 18.5 (IQR 16.5-22.1), which increased to a median of 30.5 (IQR 27.1-33.0) at follow-up, indicating a reduction in viral load. A non-significant trend suggested that patients infected with BA.2 and BA.4/BA.5 sublineages might experience a faster increase in Ct values-indicating quicker viral load reduction - compared to those infected with BA.1, regardless of treatment type. However, this trend did not achieve statistical significance (p=0.609), likely due to the limited sample size and the absence of a clear trend curve. In summary, the study did not find a significant association between specific early therapies and the time to achieve swab negativization. These findings underscore the complex dynamics of viral clearance and highlight the need for further research with larger patient cohorts to refine treatment protocols for high-risk COVID-19 patients.

Therapeutic Drug Monitoring of Dalbavancin in Real Life: A Two-Year Experience.

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42-48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment.

Continuous Positive Airway Pressure in Elderly Patients with Severe COVID-19 Related Respiratory Failure.

The elderly population represents a high percentage of patients hospitalized for COVID-19 pneumonia and severe respiratory failure, for whom CPAP may be a treatment option. The aim of this study was to describe the CPAP support modalities and to explore factors associated with CPAP failure. In this retrospective study, 110 consecutive patients aged ≥ 75 years were enrolled. Median frailty score, baseline partial arterial pressure of oxygen to fraction of inspired oxygen ratio (P/F), and respiratory rate (RR) were 5, 108, and 30 cycles/min, respectively. Of the 110 patients that began CPAP treatment, 17 patients died within 72 h from baseline, while in 2 patients, CPAP was withdrawn for clinical improvement. Thus, of the 91 patients still on CPAP at day 3, 67% of them needed continuous CPAP delivery. Patients with RR ≥ 30 and with frailty score ≥ 5 had an odds ratio of continuous CPAP needing of 3 and 4, respectively. Patients unable to tolerate CPAP-free periods demonstrated higher mortality risk as compared to those able to tolerate intermittent CPAP (OR: 6.04, 95% CI 2.38−16.46, p < 0.001). The overall in-hospital mortality was 63.6%. Delirium occurred in 59.1%, with a mortality rate in this subgroup of 83.1%. In a time-varying Cox model, the hazard ratio of death was 2.9 in patients with baseline RR ≥ 30 cycle/min, 2.4 in those with baseline P/F < 100. In the same model, the hazard ratio of death was 20 in patients with delirium and a frailty score < 5 and 8.8 in those without delirium and with frailty ≥ 5, indicating a competitive effect between these two variables on the death risk. Conclusions: Respiratory impairment, frailty, and delirium predict treatment failure, with the latter two factors demonstrating a competitive effect on mortality risk. CPAP support may represent a feasible therapeutic option in elderly patients, although chances of a therapeutic benefit are markedly reduced in case of severe respiratory impairment, very frail baseline condition or delirium occurrence.