Change in parental knowledge, attitudes and practice of antibiotic use after a national intervention programme.

Background: Nation-wide multifaceted interventions to improve antibiotic use were undertaken in the former Yugoslav Republic of Macedonia in September 2014. This study aimed to assess the parental knowledge and attitudes about antibiotics, and self-medication practices in children, and evaluate the impact of interventions on these parameters. Methods: Pre-post-intervention surveys were conducted in May 2014-16 in three administrative regions in the country. Data were collected by interviewing parents of children younger than 15 years of age through a questionnaire. The analysis of knowledge, attitudes and antibiotic use involved descriptive quantitative statistics. The effects of interventions were assessed by a logistic and linear regression analysis. Results: Data from 1203 interviewees showed that 80% of parents knew that antibiotics could kill bacteria, while 40% believed antibiotics could kill viruses. One third of parents expressed potential dissatisfaction with doctors who would not agree with them on antibiotic use. More parents received information about not taking antibiotics unnecessarily after the interventions, but the rates decreased one year later. At baseline, 20% of the parents and 10% of the children who received antibiotics in previous year, took them without prescriptions. Parental self-medication rates did not change over time, while children rates decreased only in 2015. Conclusion: The insignificant and short-term changes in knowledge, attitudes and self-medication demonstrate that interventions need to be implemented for a longer period of time, at a large scale, with active health providers' engagement, and accompanied by inspections to promote appropriate use of antibiotics and discourage self-medication.

Antibiotic prescribing for children in primary care and adherence to treatment guidelines.

OBJECTIVES: Antibiotic use is unnecessarily high for paediatric respiratory tract infections (RTIs) in primary care, and implementation of treatment guidelines is difficult in practice. This study aims to assess guideline adherence to antibiotic prescribing for RTIs in children and examine potential variations across Dutch general practices. METHODS: We conducted a retrospective observational study, deriving data on diagnoses and prescriptions from the electronic health records-based NIVEL Primary Care Database. Patients <18 years of age with a diagnosis of fever, ear and respiratory infections (International Classification of Primary Care codes A03, H71, R72, R75, R76, R78 and R81) during 2010-12 were included. Antibiotics were linked to episodes of illness. Two types of disease-specific outcomes were used to assess adherence to national guidelines regarding antibiotic prescribing choices. Inter-practice variability in adherence was assessed with multilevel analysis. RESULTS: Half of the episodes with RTIs with restrictive prescribing policy and 65% of episodes with pneumonia were treated with antibiotics. General practitioners prescribed antibiotics for 40% of episodes with bronchitis, even though guidelines discourage antibiotic prescribing. First-choice antibiotics were prescribed in 50%-85% of episodes with selected diseases, with lowest values for narrow-spectrum penicillins. Levels of adherence to guidelines varied widely between diagnoses and between practices. CONCLUSIONS: Most paediatric RTIs in the Netherlands continue to be treated with antibiotics conservatively. Potential aspects of concern are the inappropriate antibiotic prescribing for acute bronchitis and the underuse of some first-choice antibiotics. Continuing progress may be achieved by targeting practices with lower adherence rates to guidelines.

WHO global research priorities for antimicrobial resistance in human health.

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR.

Antimicrobial Consumption in Latin American Countries: First Steps of a Long Road Ahead.

BACKGROUND: Irrational antimicrobial consumption (AMC) became one of the main global health problems in recent decades. OBJECTIVE: In order to understand AMC in Latin-American Region, we performed the present research in 6 countries. METHODS: Antimicrobial consumption (J01, A07A, P01AB groups) was registered in Argentina, Chile, Colombia, Costa Rica, Paraguay, and Peru. Source of information, AMC type, DDD (Defined Daily Doses), DID (DDD/1000 inhabitants/day), population were variables explored. Data was analyzed using the Global Antimicrobial Resistance and Use Surveillance System (GLASS) tool. RESULTS: Source of information included data from global, public, and private sectors. Total AMC was highly variable (range 1.91-36.26 DID). Penicillin was the most consumed group in all countries except in Paraguay, while macrolides and lincosamides were ranked second. In terms of type of AMC according to the WHO-AWaRe classification, it was found that for certain groups like "Reserve," there are similarities among all countries. CONCLUSION AND RELEVANCE: This paper shows the progress that 6 Latin-American countries made toward AMC surveillance. The study provides a standardized approach for building a national surveillance system for AMC data analysis. These steps will contribute to the inclusion of Latin-America among the regions of the world that have periodic, regular, and quality data of AMC.

Identifying the most effective essential medicines policies for quality use of medicines: A replicability study using three World Health Organisation data-sets.

BACKGROUND: Poor quality use of medicines (QUM) has adverse outcomes. Governments' implementation of essential medicines (EM) policies is often suboptimal and there is limited information on which policies are most effective. METHODS: We analysed data on policy implementation from World Health Organisation (WHO) surveys in 2007 and 2011, and QUM data from surveys during 2006-2012 in developing and transitional countries. We compared QUM scores in countries that did or did not implement specific policies and regressed QUM composite scores on the numbers of policies implemented. We compared the ranking of policies in this and two previous studies, one from the same WHO databases (2003-2007) the other from data obtained during country visits in South-East Asia (2010-2015). The rankings of a common set of 17 policies were correlated and we identified those that were consistently highly ranked. FINDINGS: Fifty-three countries had data on both QUM and policy implementation. Forty policies were associated with effect sizes ranging from +13% to -5%. There was positive correlation between the composite QUM indicator and the number of policies reported implemented: (r) = 0.437 (95% CI 0.188 to 0.632). Comparison of policy rankings between the present and previous studies showed positive correlation with the WHO 2003-7 study: Spearman's rank correlation coefficient 0.498 (95% CI 0.022 to 0.789). Across the three studies, five policies were in the top five ranked positions 11 out of a possible 15 times: drugs available free at the point of care; a government QUM unit; undergraduate training of prescribers in standard treatment guidelines, antibiotics not available without prescription and generic substitution in the public sector. INTERPRETATION: Certain EM policies are associated with better QUM and impact increases with co-implementation. Analysis across three datasets provides a policy short-list as a minimum investment by countries trying to improve QUM and reduce antimicrobial drug misuse.

Age-Specific Antibiotic Prescribing and Adherence to Guidelines in Pediatric Patients in Primary Care.

BACKGROUND: Most antibiotics in children are used to treat viral and self-limiting conditions. This study aims to compare physicians' adherence to guidelines on antibiotic prescribing in fever and in ear and respiratory infections to children in different age groups in the Netherlands. METHODS: Data were used from the NIVEL Primary Care Database. For all pediatric episodes of fever, acute otitis media (AOM), streptococcal pharyngitis (strep throat), sinusitis, acute tonsillitis, acute bronchitis/bronchiolitis and pneumonia in 2012, we determined whether national guidelines were followed with regard to whether an antibiotic was prescribed, and the type of antibiotic. RESULTS: For diagnoses that generally do not require antibiotics, more prescriptions were found in adolescents' episodes compared with children 0-4 and 5-11 years of age, respectively, (bronchitis: 52.0% versus 42.4% and 42.7%, and fever: 16.8% versus 9.0% and 14.2%). The same was true for diagnoses that require antibiotics (strep throat: 76.5% versus 55.0% and 49.5%, pneumonia: 71.6% versus 60.2% and 69.8% and tonsillitis: 57.8% versus 54.8% and 49.7%), except for AOM (43.9% versus 52.4% and 39.6%). First-choice amoxicillin was prescribed more frequently in children 0-4 years of age than in age groups 5-11 and 11-17 years (AOM: 88.0% versus 83.2% and 81.8%, and pneumonia:74.7% versus 57.2% and 53.8%). First-choice narrow-spectrum penicillins were prescribed more often in adolescents than in age groups 0-4 and 5-11 years (strep throat: 72.0% versus 63.6%, and 60.9% and tonsillitis: 67.9% versus 33.1 and 45.9%). CONCLUSIONS: Concerning adherence patterns include high antibiotic rates for bronchitis, particularly in adolescents, and underuse of narrow-spectrum penicillins in the 0-4 years group.

Are age-appropriate antibiotic formulations missing from the WHO list of essential medicines for children? A comparison study.

OBJECTIVE: There is a global call for formulations, which are better suited for children of different age categories and in a variety of settings. One key public health area of interest is age-appropriate paediatric antibiotics. We aimed to identify clinically relevant paediatric formulations of antibiotics listed on pertinent formularies that were not on the WHO Essential Medicines List for Children (EMLc). METHODS: We compared four medicines lists versus the EMLc and contrasted paediatric antibiotic formulations in relation to administration routes, dosage forms and/or drug strengths. The additional formulations on comparator lists that differed from the EMLc formulations were evaluated for their added clinical values and costs. RESULTS: The analysis was based on 26 EMLc antibiotics. Seven oral and two parenteral formulations were considered clinically relevant for paediatric use. Frequently quoted benefits of oral formulations included: filling the gap of unmet therapeutic needs in certain age/weight groups (phenoxymethylpenicillin and metronidazole oral liquids, and nitrofurantoin capsules), and simplified administration and supply advantages (amoxicillin dispersible tablets, clyndamycin capsules, cloxacillin tablets, and sulfamethoxazole+trimethoprim tablets). Lower doses of ampicillin and cefazolin powder for injection could simplify the dosing in newborns and infants, reduce the risk of medical errors, and decrease the waste of medicines, but may target only narrow age/weight groups. CONCLUSIONS: The identified additional formulations of paediatric antibiotics on comparator lists may offer clinical benefits for low-resource settings, including simplified administration and increased dosing accuracy. The complexity of both procuring and managing multiple strengths and formulations also needs to be considered.

Prescribing for acute childhood infections in developing and transitional countries, 1990-2009.

BACKGROUND: Evidence of global progress in treating acute paediatric infections is lacking. OBJECTIVES: To assess progress over two decades in prescribing for childhood infections and interventions to improve treatment by reviewing empirical evidence in developing and transitional countries. METHODS: Data were systematically extracted on the use of medicines for diarrhoea, respiratory infections and malaria from published and unpublished studies (1990-2009) in children under 5 years of age. Medians of each indicator were calculated across studies by study year, geographic region, sector, country income level and prescriber type. To estimate intervention effects from studies meeting methodologically accepted design criteria [randomised controlled trials (RCTs), pre-post with control, and time series studies], the medians of the median effect sizes (median MES) were calculated across outcome measures. RESULTS: Data were extracted from 344 studies conducted in 78 countries with 394 distinct study groups in public (64%), private (22%) and other facilities to estimate trends over time. Of 226 intervention studies, only the 44 (19%) with an adequate study design were used to estimate intervention effects. Over time, use of anti-diarrhoeals for acute diarrhoea decreased significantly (P<0.01). However, treatment of malaria and acute respiratory infection remained largely sub-optimal. Multi-component interventions resulted in larger improvements than single-component ones. The median MES indicated a 28% improvement with community case-management, an 18% improvement with provider education combined with consumer education, but only 9% improvement with provider education alone. CONCLUSIONS: While diarrhoea treatment has improved over the last 20 years, treatment of other childhood illnesses remains sub-optimal. Multi-component interventions demonstrated some success in improving management of acute childhood illness.

Pediatric drug formulations: a review of challenges and progress.

Children differ from adults in many aspects of pharmacotherapy, including capabilities for drug administration, medicine-related toxicity, and taste preferences. It is essential that pediatric medicines are formulated to best suit a child's age, size, physiologic condition, and treatment requirements. To ensure adequate treatment of all children, different routes of administration, dosage forms, and strengths may be required. Many existing formulations are not suitable for children, which often leads to off-label and unlicensed use of adult medicines. New regulations, additional funding opportunities, and innovative collaborative research initiatives have resulted in some recent progress in the development of pediatric formulations. These advances include a paradigm shift toward oral solid formulations and a focus on novel preparations, including flexible, dispersible, and multiparticulate oral solid dosage forms. Such developments have enabled greater dose flexibility, easier administration, and better acceptance of drug formulations in children. However, new pediatric formulations address only a small part of all therapeutic needs in children; moreover, they are not always available. Five key issues need to be addressed to stimulate the further development of better medicines for children: (1) the continued prioritization of unmet formulation needs, particularly drug delivery in neonates and treatment gaps in pediatric cancers and childhood diseases in developing countries; (2) a better use of existing data to facilitate pediatric formulation development; (3) innovative technologies in adults that can be used to develop new pediatric formulations; (4) clinical feedback and practice-based evidence on the impact of novel formulations; and (5) improved access to new pediatric formulations.

Antibiotics for upper respiratory infections: public knowledge, beliefs and self-medication in the Republic of Macedonia.

Self-medication as part of the irrational use of antibiotics contributes to the spread of antimicrobial resistance. The aim of this community-based survey in Macedonia was to determine public knowledge, beliefs and self-medication with antibiotics for upper respiratory infections. A cross-sectional study was conducted in three administrative regions in Macedonia in April 2012. 402 eligible participants answered an anonymous questionnaire. The analysis of answers involved descriptive quantitative statistics (frequencies and percentages). We also tested for significant associations between demographic characteristics and non-prescription use of antibiotics. Our respondents demonstrated a relatively low level of public knowledge about antibiotics and upper respiratory infection treatments in comparison to the EU countries. The study found that 71.4% of participants stored antibiotics at home, and 43.3% purchased antibiotics over-the-counter in the last year, despite national regulation that restricts antibiotics as prescription-only medicines. Actual self-medication with antibiotics for a recent upper respiratory infection episode was reported in 17.8% of adults and 1.8% of children aged 0-4 years. We did not find any significant association between participants demography and non-prescription use of antibiotics. Our results put in the group of eastern and southern EU countries with the highest rates for non-prescription use of antibiotics in Europe. Multifaceted interventions are needed to prevent self-medication with antibiotics, including: enforcement of regulations that restrict over-the-counter sales of antibiotics, monitoring of antibiotic use and antimicrobial resistance rates and combined public education strategies.

Does shortening the training on Integrated Management of Childhood Illness guidelines reduce its effectiveness? A systematic review.

OBJECTIVE: Implementation of the Integrated Management of Childhood Illness (IMCI) strategy with an 11-day training course for health workers improves care for ill children in outpatient settings in developing countries. The 11-day course duration is recommended by the World Health Organization, which developed IMCI. Our aim was to determine if shortening the training (to reduce cost) reduces its effectiveness. METHODS: We conducted a systematic review to compare IMCI's effectiveness with standard training (duration ≥ 11 days) versus shortened training (5-10 days). Studies were identified from a search of MEDLINE, two existing systematic reviews, and by contacting investigators. We included published or unpublished studies that evaluated IMCI's effectiveness in developing countries and reported quantitative measures of health worker practices related to managing ill children under 5 years old in public or private health facilities. Summary measures were the median of effect sizes for all outcomes from a given study, and the percentage of patients needing oral antimicrobials or rehydration who were treated according to IMCI guidelines. FINDINGS: Twenty-nine studies were included. Direct comparisons from three studies showed little difference between standard and shortened training. Indirect comparisons from 26 studies revealed that effect sizes for standard training versus no IMCI were greater than shortened training versus no IMCI. Across all comparisons, differences ranged from -3 to +23 percentage-points, and our best estimate was a 2 to 16 percentage-point advantage for standard training. No result was statistically significant. After IMCI training (of any duration), 34% of ill children needing oral antimicrobials or rehydration were not receiving these treatments according to IMCI guidelines. CONCLUSIONS: Based on limited evidence, standard IMCI training seemed more effective than shortened training, although the difference might be small. As sizable performance gaps often existed after IMCI training, countries should consider implementing other interventions to support health workers after training, regardless of training duration.

Pharmacy practice in the Republic of Macedonia.

As part of wider reforms within the pharmaceutical sector, the pharmaceutical care concept has been introduced in the Republic of Macedonia. This article provides discussion on current opportunities and challenges which pharmacy practice face in Macedonia. The emphasis is on three prerequisites for the implementation of pharmaceutical care including: organization of pharmaceutical services, legislation, and professional training. The author argues that Macedonia possesses a favorable pharmacy workforce, solid legal basis and supportive structures of healthcare services in order to implement pharmaceutical care. Implementing pharmaceutical care has not been without its challenges, such as: lack of clinical skills, inadequate continuing education and the current remuneration structure for pharmacy services. While Good Pharmacy Practice (GPP) Guidelines have been developed, wider professional debate and practical steps have not been undertaken to promote the concept of pharmaceutical care nationally. Therefore, an integrated national approach to develop strategy, standards and tools for patient-oriented pharmaceutical practice has to be formulated. In addition, there is a need to undertake more comprehensive analysis of current pharmacy practice, to explore the awareness and willingness of the pharmacists to embrace pharmaceutical care practices, and to identify the opportunities and barriers for implementation of pharmacy practice.