Omadacycline therapy for Mycobacterium abscessus species infections.

BACKGROUND: Antimicrobial resistance and therapy-related adverse effects make Mycobacterium abscessus treatment challenging. Omadacycline is a novel, bioavailable aminomethylcycline with favourable in vitro activity against M. abscessus. AIMS: To describe a case report and review the published literature describing outcomes for M. abscessus infections treated with omadacycline. METHODS: Systematic literature review. RESULTS: We identified three articles that, in addition to our case report, describe 18 patients. Pulmonary infections were most frequent. Minimum inhibitory concentrations were reported for two isolates (0.25 and 0.5 mg/L). Despite half the patients starting omadacycline because of failure of prior therapy, 15 (83%) had a favourable outcome, defined as 'cure', 'improvement' or 'clinical success' as determined by the primary study authors. One patient (6%) discontinued omadacycline because of gastrointestinal intolerance. CONCLUSIONS: Although the limited observational data and in vitro susceptibility results are encouraging, randomised control trials are required to determine the role of omadacycline as part of combination therapy for this most difficult-to-treat pathogen.

Subcutaneous ertapenem delivered by an Australian outpatient parenteral antimicrobial therapy service: a retrospective comparative efficacy study.

Subcutaneous (SC) administration of ertapenem in outpatient parenteral antimicrobial therapy (OPAT) services may be a practical alternative to intravenous delivery for complicated infections. The clinical features and outcomes according to route of administration were compared from a large Australian OPAT service. Chronic renal impairment was more common in the SC group, reflecting an opportunity for route of administration as a vein preservation strategy. Adverse events were uncommon and successful outcomes were not different between the groups.

A novel highly bio-available itraconazole formulation (SUBA®-Itraconazole) for anti-fungal prophylaxis in lung transplant recipients.

BACKGROUND: Antifungal prophylaxis remains a mainstay of lung transplantation, given invasive fungal infection is a common and serious complication after lung transplantation. Choice of systemic agent to prevent invasive fungal infection varies between centers and funding of agents remains challenging. Our center has recently changed from posaconazole to a highly bioavailable formulation of itraconazole (SUBA®-itraconazole) at substantially reduced cost, but safety and toxicity require further assessment. A retrospective study of lung transplant patients receiving systemic antifungal prophylaxis from December 2016 through December 2019 following change from posaconazole to itraconazole as standard practice. 150 patients with lung transplants were managed in this time period, with 88 (59%) receiving at least 1 mold-active triazole during the study period. 48 (58%) of these patients received SUBA®-itraconazole; 68 (82%) received posaconazole and 10 (12%) received voriconazole. The average cost per patient during the study period was significantly lower on SUBA®-itraconazole (mean $1548/patient/6 month course) than posaconazole (mean $16 921.35/patient/6 month course). Target trough concentrations for prophylaxis of itraconazole > 0.5 mg/L and posaconazole > 0.7 mg/L were achieved on empiric dosing in 49% and 68% respectively. Overall trough itraconazole (0.50 vs 1.12 mg/L, P < .001) and posaconazole (1.37 vs 2.10 mg/L P < .001) concentrations were significantly lower in patients with cystic fibrosis. Calcineurin inhibitor dose changes on introduction or cessation were similar for SUBA®-itraconazole and posaconazole. Breakthrough invasive fungal infection and toxicity were rare. SUBA®-itraconazole is well-tolerated, associated with rare breakthrough invasive fungal infection, and lower cost. Prospective studies following general introduction are required to determine long-term safety, tolerability, and efficacy.

Successful outpatient parenteral antibiotic therapy delivery via telemedicine.

Objectives: Most outpatient parenteral antimicrobial therapy (OPAT) services use a hospital-based model of care in which patients remain in proximity to large hospitals facilitating clinical review. We aimed to evaluate clinical outcomes and complication rates for patients living in geographically isolated locations managed by telemedicine-supported OPAT. Methods: This was a retrospective cohort study. Results: Between 2011 and 2015, we delivered 88 episodes of care involving 83 adult patients resulting in 2261 days of OPAT. The median age was 56 years, 8 of 83 (10%) were indigenous Australian and the median Charlson comorbidity index score was 2 (IQR 1-4). The median distance of patients' residence from our hospital was 288 km (IQR 201-715) and the median duration on the programme was 26 days (IQR 14-34). Bone and joint infections accounted for 75% of infections treated. Favourable clinical outcomes (improvement or cure) were achieved in 87% of patients and the unplanned, OPAT-related readmission rate was 8%. Nineteen percent and 10% of patients had drug-related and line-related adverse effects, respectively. Conclusions: Despite a complex case mix, our adverse event and readmission rates are similar to the published literature describing a non-telemedicine model to deliver OPAT. High rates of favourable clinical outcomes and likely cost benefits suggest that telemedicine-supported OPAT is an efficacious and safe substitute for inpatient care in our setting.

Predictors of Outcome in Pediatric Osteomyelitis: Five Years Experience in a Single Tertiary Center.

BACKGROUND: Acute haematogenous osteomyelitis is a bacterial infection of bone, which occurs most frequently in children. Outcomes are excellent for the majority of children, but a minority develop complicated osteomyelitis. Predicting which children will develop complicated osteomyelitis remains a challenge, particularly in developed countries where most patients are discharged home after a relatively short period in hospital. METHODS: We conducted a 5-year retrospective case note review of all children aged 3 months to 16 years admitted with a diagnosis of acute haematogenous osteomyelitis. We compared standardized clinical and laboratory parameters in those who developed simple and complicated osteomyelitis. RESULTS: Of the 299 children who met inclusion, 241 (80.6%) had simple and 58 (19.4%) had complicated osteomyelitis. The major predictors of complicated disease were older age, a temperature greater than 38.5°C and a higher C-reactive protein at admission. CONCLUSIONS: A risk prediction model, utilizing information available shortly after hospitalization, allows early identification of children at greatest risk of developing complicated osteomyelitis.

Continuous infusions of meropenem in ambulatory care: clinical efficacy, safety and stability.

OBJECTIVES: Concerns regarding the clinical impact of meropenem instability in continuous infusion (CI) devices may contribute to inconsistent uptake of this method of administration across outpatient parenteral antimicrobial therapy (OPAT) services. METHODS: We retrospectively reviewed the clinical efficacy and safety of CIs of meropenem in two Australian tertiary hospitals and assessed its stability under simulated OPAT conditions including in elastomeric infusion devices containing 1% (2.4 g) or 2% (4.8 g) concentrations at either 'room temperature' or 'cooled' conditions. Infusate aliquots were assayed at different time-points over 24 hours. RESULTS: Forty-one (82%) of 50 patients had clinical improvement or were cured. Adverse patient outcomes including hemato-, hepato- and nephrotoxicity were infrequent. Cooled infusers with 1% meropenem had a mean 24-hour recovery of 90.3%. Recoveries of 1% and 2% meropenem at room temperature and 2% under cooled conditions were 88%, 83% and 87%, respectively. Patients receiving 1% meropenem are likely to receive >95% of the maximum deliverable dose (MDD) over a 24-hour period whilst patients receiving 2% meropenem should receive 93% and 87% of the MDD under cooled and room temperature conditions, respectively. CONCLUSIONS: Meropenem infusers are likely to deliver ∼95% MDD and maintain effective plasma concentrations throughout the dosing period. These data reflect our local favourable clinical experience with meropenem CIs.

A case of pulmonary hemorrhage due to drug-induced pneumonitis secondary to ticagrelor therapy.

We report a case of significant pulmonary hemorrhage developing shortly after commencing ticagrelor and aspirin therapy and requiring coronary artery bypass grafting to safely cease the antiplatelet therapy. Lung biopsy findings were consistent with drug-induced lung injury. Clinicians should be aware of this significant adverse event with this drug class.