Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis.

Isavuconazole is the newest triazole antifungal, and it displays a favorable pharmacokinetic and safety profile. Less is known about its long-term use in immunocompetent hosts. We performed a retrospective service evaluation of isavuconazole therapeutic drug monitoring in patients with chronic pulmonary aspergillosis. Adverse events (AEs) and dose adjustments made during routine clinical practice were recorded, and AEs were classified based on Common Terminology Criteria for Adverse Events v5.0. Forty-five patients (mean age, 64 years) had 285 isavuconazole blood drug levels measured (mean level, 4.1 mg/liter). A total of 117 measurements (41%) were performed on patients on a 100-mg daily dose instead of 200 mg, and all had blood levels of >1 mg/liter. Age (P = 0.012) and a daily dose of 200 mg versus 100 mg (P = 0.02) were independent predictors of levels of >6 mg/liter. AEs were recorded for 25 patients (56%). The mean drug level at the first measurement was 5.5 ± 2 mg/liter for patients reporting AEs, compared with 4.2 ± 1.7 mg/liter for those not reporting AEs (P = 0.032). The cutoff threshold best predictive of an AE was 4.6 mg/liter (area under the concentration-time curve, 0.710). Sixteen patients (36%) discontinued isavuconazole therapy due to AEs. Twenty-six patients (58%) continued on isavuconazole beyond 6 months. Asthma (P = 0.022) and a daily dose of 200 mg versus 100 mg (P = 0.048) were associated with AEs of grade 2 or higher. A reduced daily dose (100 mg versus 200 mg) of isavuconazole resulted in satisfactory drug levels in a substantial number of patients; it was better tolerated and enabled continuation of therapy for prolonged periods.

Predictors of antibiotic prescriptions: a knowledge, attitude and practice survey among physicians in tertiary hospitals in Nigeria.

BACKGROUND: As part of the Global Action Plan against antimicrobial resistance (AMR), countries are required to generate local evidence to inform context-specific implementation of national action plans against AMR (NAPAR). We aimed to evaluate the knowledge, attitude, and practice (KAP) regarding antibiotic prescriptions (APR) and AMR among physicians in tertiary hospitals in Nigeria, and to determine predictors of KAP of APR and AMR. METHODS: In this cross-sectional study, we enrolled physicians practicing in tertiary hospitals from all six geopolitical zones of Nigeria. Implementation of an antimicrobial stewardship programmes (ASP) by each selected hospital were assessed using a 12 item ASP checklist. We used a structured self-administered questionnaire to assess the KAP of APR and AMR. Frequency of prescriptions of 18 different antibiotics in the prior 6 months was assessed using a Likert's scale. KAP and prescription (Pr) scores were classified as good (score ≥ 80%) or average/poor (score < 80%). Independent predictors of good knowledge, attitude, and practice (KAPPr) were ascertained using an unconditional logistic regression model. RESULTS: A total of 1324 physicians out of 1778 (74% response rate) practicing in 12 tertiary hospitals in 11 states across all six geopolitical zones participated in the study. None of the participating hospitals had a formal ASP programme and majority did not implement antimicrobial stewardship strategies. The median KAPPr scores were 71.1%, 77%, 75% and 53.3%, for the knowledge, attitude, practice, and prescription components, respectively. Only 22.3%, 40.3%, 31.6% and 31.7% of study respondents had good KAPPr, respectively. All respondents had prescribed one or more antibiotics in the prior 6 months, mostly Amoxicillin-clavulanate (98%), fluoroquinolones (97%), and ceftriaxone (96.8%). About 68% of respondents had prescribed antibiotics from the World Health Organization reserve group. Prior AMR training, professional rank, department, and hospital of practice were independently associated with good KAPPr. CONCLUSIONS: Our study suggests gaps in knowledge and attitude of APR and AMR with inappropriate prescriptions of antibiotics among physicians practicing in tertiary hospitals in Nigeria. Nigeria's NAPAR should also target establishment and improvement of ASP in hospitals and address institutional, educational, and professional factors that may influence emergence of AMR in Nigeria.

A Multi-Site Knowledge Attitude and Practice Survey of Ebola Virus Disease in Nigeria.

BACKGROUND: The 2014 Ebola Virus Disease (EVD) outbreak was characterised by fear, misconceptions and irrational behaviours. We conducted a knowledge attitude and practice survey of EVD in Nigeria to inform implementation of effective control measures. METHODS: Between July 30th and September 30th 2014, we undertook a cross sectional study on knowledge, attitude and practice (KAP) of Ebola Virus Disease (EVD) among adults of the general population and healthcare workers (HCW) in three states of Nigeria, namely Bayelsa, Cross River and Kano states. Demographic information and data on KAP were obtained using a self-administered standardized questionnaire. The percentage KAP scores were categorised as good and poor. Independent predictors of good knowledge of EVD were ascertained using a binary logistic regression model. RESULTS: Out of 1035 study participants with median age of 32 years, 648 (62.6%) were males, 846 (81.7%) had tertiary education and 441 (42.6%) were HCW. There were 218, 239 and 578 respondents from Bayelsa, Cross River and Kano states respectively. The overall median percentage KAP scores and interquartile ranges (IQR) were 79.46% (15.07%), 95.0% (33.33%) and 49.95% (37.50%) respectively. Out of the 1035 respondents, 470 (45.4%), 544(52.56%) and 252 (24.35%) had good KAP of EVD defined using 80%, 90% and 70% score cut-offs respectively. Independent predictors of good knowledge of EVD were being a HCW (Odds Ratio-OR-2.89, 95% Confidence interval-CI of 1.41-5.90), reporting 'moderate to high fear of EVD' (OR-2.15, 95% CI-(1.47-3.13) and 'willingness to modify habit' (OR-1.68, 95% CI-1.23-2.30). CONCLUSION: Our results reveal suboptimal EVD-related knowledge, attitude and practice among adults in Nigeria. To effectively control future outbreaks of EVD in Nigeria, there is a need to implement public sensitization programmes that improve understanding of EVD and address EVD-related myths and misconceptions, especially among the general population.