Dalbavancin is a lipoglycopeptide with a long elimination half-life, currently licensed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults. Dalbavancin's potential in treating off-label complex gram-positive infections is promising and real-world experience in treating such infections is growing. However, clear guidance on extended dosing regimens is lacking. We aim to provide clear expert opinion based on recent pharmacokinetic literature and expert and real-world experience in infection areas that require >2 weeks of treatment. A single face-to-face meeting was held in September 2022 to collate expert opinion and present safety data of dalbavancin use in these clinical indications. A survey was completed by all authors on their individual experience with dalbavancin which highlighted the heterogeneity in the regimens used. After review of the survey data and recent literature, we present expert panel proposals which accommodate different healthcare settings and resource availability, and centre around the length of treatment duration including up to, or exceeding, 6 weeks. To achieve adequate dalbavancin concentrations for up to 6 weeks, 3,000mg of dalbavancin should be given over 4 weeks for the agreed complex infections requiring >2 weeks treatment. Therapeutic drug monitoring (TDM) is advised for longer treatment durations and in case of renal failure. Specific dosing recommendations for other special populations require further investigation. These proposals based on expert opinion have been defined to encourage best practice with dalbavancin to optimise its administration beyond the current approved licenced dose across different healthcare settings.
19 May 2005 in Journal of Antimicrobial Chemotherapy
Objectives: Linezolid is a new antibacterial agent with a broad spectrum of activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., and penicillin-resistant Streptococcus pneumoniae. The aim of this prospective, single-centre, open-label, two-arm study was to investigate the pharmacokinetics of linezolid during continuous venovenous haemofiltration (CVVH) in critically ill patients and to derive a dosage recommendation. Patients and methods: Twenty anuric ICU patients undergoing CVVH (mean age and body weight 60.7 ± 10.9 years and 86.0 ± 18.0 kg) were included. All patients received linezolid 600 mg intravenously every 12 h. CVVH was performed using highly permeable polysulphone membranes (PSHF 1200, Baxter, Germany and AV 400, Fresenius, Germany). Mean blood flow rate and ultrafiltration rate were 186 ± 15 and 40 ± 8 mL/min, respectively. Post-dilution was performed. Results: The pharmacokinetics of linezolid in critically ill patients with acute renal failure undergoing CVVH were comparable to healthy subjects and patients without renal impairment. The elimination half-life, total clearance and haemofiltration clearance were 4.3 ± 1.7 h, 9.3 ± 3.5 L/h and 1.9 ± 0.8 L/h, respectively. Conclusions: Our results showed that linezolid was highly removable by CVVH. These data suggest that a schedule of 600 mg linezolid at least twice daily may also be an appropriate dosing for patients with severe Gram-positive infections undergoing CVVH with both types of membranes.
Human monkeypox (MPX) cases are escalating worldwide. Smallpox vaccination, which was compulsory in Austria until 1981, was reported to confer 85% cross-protection against MPX. To assess the impact of smallpox vaccine-induced protection, the age-dependent vaccine-induced immunity against human MPX and the probability of infection according to age in the general population of Vienna, Austria, were determined using a modified susceptible-infected-removed model. Within the population born before 1981, the average vaccine-induced protective effect was calculated at 50.4%, whereas in the population born thereafter, protection was lacking. The overall probability of infection after exposure to an infected patient was calculated at 73.8%, which exceeds the threshold value of 46.9% for an index patient to infect at least one other person (R ≥1.0). Our model shows that if no additional interventions are taken, the collective immunization status of the population alone will not suffice to contain human MPX. Although the majority of cases have occurred in a subpopulation, given the steadily increasing incidence, dissemination into the general population remains possible, as observed before with HIV. Our model emphasizes the need for adequate containment measures and may aid in specific risk assessment because it can easily be adapted to other populations and cohorts worldwide.
1 October 2009 in The American Journal of Tropical Medicine and Hygiene
Albendazole therapy—alone or in combination with surgery—remains the standard of care for human echinococcosis depending on the stage of disease. However, only limited data are available on target site concentrations in liver cysts and data for non-liver cysts are lacking. We report on intra-cystic concentrations of the biologically active metabolite albendazole sulphoxide in non-liver cysts indicating a relative intra-cystic drug concentration of 48–156% compared with plasma levels. These data are evidence for a satisfactory penetration of albendazole sulphoxide into Echinococcus cysts localized in other organs than the liver and underline the usefulness of albendazole therapy for this indication.