Using Belgian pharmacy dispensing data to assess antibiotic use for children in ambulatory care

Background The desired effect of antibiotics is compromised by the rapid escalation of antimicrobial resistance. Children are particularly at high-risk for unnecessary antibiotic prescribing, which is owing to clinicians’ diagnostic uncertainty combined with parents’ concerns and expectations. Recent Belgian data on ambulatory antibiotic prescribing practices for children are currently lacking. Therefore, we aim to analyse different aspects of antibiotic prescriptions for children in ambulatory care. Methods Pharmacy dispensing data on antibiotics for systematic use referring from 2010 to 2019 were retrieved from Farmanet, a database of pharmaceutical dispensations in community pharmacies. Population data were obtained from the Belgian statistical office (Statbel). Descriptive statistics were performed in Microsoft Excel. The Mann-Kendall test for trend analysis and the seasplot function for seasonality testing were conducted in R. Results The past decade, paediatric antibiotic use and expenditures have relatively decreased in Belgian ambulatory care with 35.5% and 44.3%, respectively. The highest volumes of antibiotics for children are prescribed by GPs working in Walloon region and rural areas, to younger children, and during winter. The most prescribed class of antibiotics for children are the penicillins and the biggest relative reduction in number of packages is seen for the sulfonamides and trimethoprim and quinolone antibacterials. Conclusions Paediatric antibiotic use has decreased in Belgian ambulatory care. Further initiatives are needed to promote prudent antibiotic prescribing in ambulatory care.

Delta T, a Useful Indicator for Pharmacy Dispensing Data to Monitor Medication Adherence

Introduction: Calculating patients’ medication availability from dispensing or refill data is a common method to estimate adherence. The most often used measures, such as the medication possession ratio (MPR), average medication supplies over an arbitrary period. Averaging masks the variability of refill behavior over time. Goal: To derive a new absolute adherence estimate from dispensing data. Method: Dispensing histories of patients with 19 refills of direct oral anticoagulants (DOAC) between 1 January 2008 and 31 December 2017 were extracted from 39 community pharmacies in Switzerland. The difference between the calculated and effective refill day (ΔT) was determined for each refill event. We graphed ΔT and its dichotomized version (dΔT) against the MPR, calculated mean ΔT and mean dΔT per refill, and applied cluster analysis. Results: We characterized 2204 refill events from 116 DOAC patients. MPR was high (0.975 ± 0.129) and showed a positive correlation with mean ΔT. Refills occurred on average 17.8 ± 27.9 days “too early”, with a mean of 75.8 ± 20.2 refills being “on time”. Four refill behavior patterns were identified including constant gaps within or at the end of the observation period, which were critical. Conclusion: We introduce a new absolute adherence estimate ΔT that characterizes every refill event and shows that the refill behavior of DOAC patients is dynamic.

Preceding group A streptococcus skin and throat infections are individually associated with acute rheumatic fever: evidence from New Zealand

IntroductionAcute rheumatic fever (ARF) is usually considered a consequence of group A streptococcus (GAS) pharyngitis, with GAS skin infections not considered a major trigger. The aim was to quantify the risk of ARF following a GAS-positive skin or throat swab.MethodsThis retrospective analysis used pre-existing administrative data. Throat and skin swab data (1 866 981 swabs) from the Auckland region, New Zealand and antibiotic dispensing data were used (2010–2017). Incident ARF cases were identified using hospitalisation data (2010–2018). The risk ratio (RR) of ARF following swab collection was estimated across selected features and timeframes. Antibiotic dispensing data were linked to investigate whether this altered ARF risk following GAS detection.ResultsARF risk increased following GAS detection in a throat or skin swab. Māori and Pacific Peoples had the highest ARF risk 8–90 days following a GAS-positive throat or skin swab, compared with a GAS-negative swab. During this period, the RR for Māori and Pacific Peoples following a GAS-positive throat swab was 4.8 (95% CI 3.6 to 6.4) and following a GAS-positive skin swab, the RR was 5.1 (95% CI 1.8 to 15.0). Antibiotic dispensing was not associated with a reduction in ARF risk following GAS detection in a throat swab (antibiotics not dispensed (RR: 4.1, 95% CI 2.7 to 6.2), antibiotics dispensed (RR: 4.3, 95% CI 2.5 to 7.4) or in a skin swab (antibiotics not dispensed (RR: 3.5, 95% CI 0.9 to 13.9), antibiotics dispensed (RR: 2.0, 95% CI 0.3 to 12.1).ConclusionsA GAS-positive throat or skin swab is strongly associated with subsequent ARF, particularly for Māori and Pacific Peoples. This study provides the first population-level evidence that GAS skin infection can trigger ARF.

Meropenem Use in Pediatric Oncology – Audit on Indication, Appropriateness and Consumption Comparing Patient Derived and Pharmacy Dispensing Data

ABSTRACT Background Meropenem is an important second- or third-line antibiotic in pediatric cancer patients with febrile neutropenia (FN). Concise utilization data of meropenem in this setting is limited. It remains unclear how drug dispensing data from the hospital pharmacy correlate with data derived from patients’ files. Methods Retrospective audit of meropenem-consumption in a University-affiliated pediatric oncology center in days of therapy (DOT)/100 inpatient days. The individual indication for meropenem was critically reviewed. The real consumption (in g/100 inpatient days) was compared with the drug amounts dispensed by the hospital pharmacy (in gram and in defined daily doses (DDD)/100 inpatient days). All patients receiving at least one dose of meropenem from 1st of April 2016 until the 30th of June 2018 were included. Result Of 235 consecutive patients, 45 (19%) received meropenem, comprising 57 FN events. The probability of receiving at least one dose of meropenem was significantly higher in patients with ALL, AML, NHL and certain CNS tumors. Preceding the use of meropenem, only 5% of patients were known to be colonized with multidrug-resistant Gram-negative pathogens. Meropenem was administered as first-line treatment in 26% of all meropenem cycles, in 74% of all FN events with meropenem, Piperacillin-Tazobactam was used for initial treatment. In 5 of 57 FN events (8.8%), initial blood cultures yielded a Gram-negative pathogen. Concerning definite treatment, appropriate alternatives to meropenem with a smaller spectrum of activity would have been available in 4 cases, but a de-escalation was not performed. The median length of therapy in the meropenem group was 6 days, the corresponding median for days of therapy (DOT) was 12 days. This corresponds with combination therapy in 56% of all meropenem treatments, mostly with teicoplanin. On average, drug dispensing data from the hospital pharmacy were 1.53 times higher than real use (relying on patients’ data) without a significant correlation. A higher Case-mix Index positively correlated with meropenem-consumption. Conclusion The use of meropenem should become a target of antibiotic stewardship programs in order to restrict its use to certain indications and preserve its outstanding role as second- or third-line antibiotic in this vulnerable population. Irrespective of the metrics used (g or DDD/100 inpatient days), pharmacy dispensing data do not accurately depict real patient-derived data concerning meropenem use in pediatric cancer patients.

Quality Appraisal of Ambulatory Oral Cephalosporin and Fluoroquinolone Use in the 16 German Federal States from 2014–2019

Background: Despite concerns about causing bacterial resistance and serious side effects, oral cephalosporins and fluoroquinolones are still frequently prescribed in Germany. We aimed to test a method for the detection of regional quality differences in the use of oral cephalosporins and fluoroquinolones and to apply this to the German federal states. Methods: Use of antibiotics from 2014–2019 was analyzed using dispensing data from community pharmacies claimed to the statutory health insurance (SHI) funds. Quality of regional antibiotic use in 2019 was assessed by calculating indicators based on defined daily doses per 1000 SHI-insured persons per day (DID). Oral cephalosporin and fluoroquinolone use was followed by linear regression analyses. Results: The method used was suitable to find meaningful quality differences in ambulatory oral cephalosporin and fluoroquinolone use between the German federal states. In 2019, DID varied from 1.62 in Brandenburg to 3.17 in Rhineland-Palatinate for cephalosporins and from 0.47 in Brandenburg to 0.89 in Saarland for fluoroquinolones. The city-states Hamburg, Bremen, and Berlin showed highest quality with the applied indicator set. From 2014–2019, a significant decrease in utilization of oral cephalosporins was found in all federal states. During 2017–2019, all states showed a significant decline of fluoroquinolone use.

Adherence to Prescribed Acamprosate in Alcohol Dependence and 1-Year Morbidities and Mortality: Utilizing a Data Linkage Methodology

Objectives: We tested the hypothesis that poor adherence is associated with a greater risk of alcohol-caused mortality and morbidities within the first year of discontinuing this medication. Materials and Methods: A retrospective cohort study of 3319 individuals who received acamprosate in the East of Scotland in a 10-year period was conducted using a health informatics approach with record linkage of dispensing data, hospital utilization (SMR) and General Register Office of Scotland (GROS) data. The primary outcome was adherence between one to six months after initiating acamprosate medication. The secondary outcome was all-cause morbidities and mortality. Results: Of the total 3319 individuals identified, a good adherence index of >80% was found in 59% of those prescribed acamprosate after three months and 6% after six months. There were significant linear trends of poorer adherence with increased risk of alcohol-caused mortality (Hazard Ratio, HR 1.2), medical morbidities especially neoplasm (HR 4.1) and poisoning (HR 1.4), and psychiatric morbidities especially stress (HR 35.1), psychotic (HR 5.6) and neurotic disorders, and directly alcohol induced conditions (7.4 HR) after adjustment for other factors within a one-year period of initiation of acamprosate treatment. Discussion and Conclusions: Further exploratory studies using this digitalized approach should be encouraged in order to capture role of compliance to acamprosate and other types of medication that are known to reduce relapse into alcohol dependence and its direct relationship to mortality and morbidities in this population.

Primary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides

Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection, and thus resistance to this antibiotic is a major cause of treatment failure. Here, we present the results of a retrospective observational study of clarithromycin resistance (Cla-res) in 4744 H. pylori-infected patients from Central Hungary. We use immunohistochemistry and fluorescence in situ hybridization on fixed gastric tissue samples to determine H. pylori infection and to infer Cla-res status, respectively. We correlate this information with macrolide dispensing data for the same patients (available through a prescription database) and develop a mathematical model of the population dynamics of Cla-res H. pylori infections. Cla-res is found in 5.5% of macrolide-naive patients (primary Cla-res), with no significant sex difference. The model predicts that this primary Cla-res originates from transmission of resistant bacteria in 98.7% of cases, and derives from spontaneous mutations in the other 1.3%. We find an age-dependent preponderance of female patients among secondary (macrolide-exposed) clarithromycin-resistant infections, predominantly associated with prior use of macrolides for non-eradication purposes. Our results shed light into the sources of primary resistant cases, and indicate that the growth rate of Cla-res prevalence would likely decrease if macrolides were no longer used for purposes other than H. pylori eradication.

Adherence to Prescribed Acamprosate® in Alcohol Dependence and 1-Year Morbidities and Mortality: Utilizing a Data Linkage Methodology

Objectives We tested the hypothesis that poor adherence is associated with a greater risk of alcohol-caused mortality and morbidities within the first year of discontinuing this medication. Materials and Methods Retrospective cohort study of 3319 individuals who received Acamprosate® in the East of Scotland in a 10-year period using a health informatics approach with record linkage of dispensing data, hospital utilization (SMR) and General Register Office of Scotland (GROS) data. Primary outcome was adherence between one to six months of initiating Acamprosate® medication. Secondary outcome was all cause morbidities and mortality. Results Of the total 3319 individuals identified, good adherence index of >80% was found in 59% of those prescribed Acamprosate® after three months and 6% after six months. There were significant linear trends of poorer adherence with increased risk of alcohol-caused mortality (HR1.2), medical morbidities especially neoplasm (HR 4.1|) and poisoning (HR 1.4) and psychiatric morbidities especially stress (HR 35.1), psychotic (HR 5.6) and neurotic disorders and directly alcohol induced conditions (7.4 HR) after adjustment for other factors within a one-year period of initiation of Acamprosate® treatment. Discussion and Conclusions Further exploratory studies using this digitalized approach should be encouraged in order to capture role of compliance to Acamprosate® and other types of medication that are known to reduce relapse into alcohol dependence and its direct relationship to mortality and morbidities in this population.