Antibiotic prescribing in Australian general practice could be substantially reduced

Background Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated. Because adverse events are treatment‐specific, rather than disease‐specific, it is possible to increase the number of adverse events available for analysis by combining randomised controlled trials (RCTs) of the same treatment across different diseases. Objectives To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Acute Respiratory Infections Group Specialised Register (2018, Issue 4); MEDLINE (Ovid, from 1946 to 8 May 2018); Embase (from 2010 to 8 May 2018); CINAHL (from 1981 to 8 May 2018); LILACS (from 1982 to 8 May 2018); and Web of Science (from 1955 to 8 May 2018). We searched clinical trial registries for current and completed trials (9 May 2018) and checked the reference lists of included studies and of previous Cochrane Reviews on macrolides. Selection criteria We included RCTs that compared a macrolide antibiotic to placebo for any indication. We included trials using any of the four most commonly used macrolide antibiotics: azithromycin, clarithromycin, erythromycin, or roxithromycin. Macrolides could be administered by any route. Concomitant medications were permitted provided they were equally available to both treatment and comparison groups. Data collection and analysis Two review authors independently extracted and collected data. We assessed the risk of bias of all included studies and the quality of evidence for each outcome of interest. We analysed specific adverse events, deaths, and subsequent carriage of macrolide‐resistant bacteria separately. The study participant was the unit of analysis for each adverse event. Any specific adverse events that occurred in 5% or more of any group were reported. We undertook a meta‐analysis when three or more included studies reported a specific adverse event. Main results We included 183 studies with a total of 252,886 participants (range 40 to 190,238). The indications for macrolide antibiotics varied greatly, with most studies using macrolides for the treatment or prevention of either acute respiratory tract infections, cardiovascular diseases, chronic respiratory diseases, gastrointestinal conditions, or urogynaecological problems. Most trials were conducted in secondary care settings. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin. Most studies (89%) reported some adverse events or at least stated that no adverse events were observed. Gastrointestinal adverse events were the most commonly reported type of adverse event. Compared to placebo, macrolides caused more diarrhoea (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.34 to 2.16; low‐quality evidence); more abdominal pain (OR 1.66, 95% CI 1.22 to 2.26; low‐quality evidence); and more nausea (OR 1.61, 95% CI 1.37 to 1.90; moderate‐quality evidence). Vomiting (OR 1.27, 95% CI 1.04 to 1.56; moderate‐quality evidence) and gastrointestinal disorders not otherwise specified (NOS) (OR 2.16, 95% CI 1.56 to 3.00; moderate‐quality evidence) were also reported more often in participants taking macrolides compared to placebo. The number of additional people (absolute difference in risk) who experienced adverse events from macrolides was: gastrointestinal disorders NOS 85/1000; diarrhoea 72/1000; abdominal pain 62/1000; nausea 47/1000; and vomiting 23/1000. The number needed to treat for an additional harmful outcome (NNTH) ranged from 12 (95% CI 8 to 23) for gastrointestinal disorders NOS to 17 (9 to 47) for abdominal pain; 19 (12 to 33) for diarrhoea; 19 (13 to 30) for nausea; and 45 (22 to 295) for vomiting. There was no clear consistent difference in gastrointestinal adverse events between different types of macrolides or route of administration. Taste disturbances were reported more often by participants taking macrolide antibiotics, although there were wide confidence intervals and moderate heterogeneity (OR 4.95, 95% CI 1.64 to 14.93; I² = 46%; low‐quality evidence). Compared with participants taking placebo, those taking macrolides experienced hearing loss more often, however only four studies reported this outcome (OR 1.30, 95% CI 1.00 to 1.70; I² = 0%; low‐quality evidence). We did not find any evidence that macrolides caused more cardiac disorders (OR 0.87, 95% CI 0.54 to 1.40; very low‐quality evidence); hepatobiliary disorders (OR 1.04, 95% CI 0.27 to 4.09; very low‐quality evidence); or changes in liver enzymes (OR 1.56, 95% CI 0.73 to 3.37; very low‐quality evidence) compared to placebo. We did not find any evidence that appetite loss, dizziness, headache, respiratory symptoms, blood infections, skin and soft tissue infections, itching, or rashes were reported more often by participants treated with macrolides compared to placebo. Macrolides caused less cough (OR 0.57, 95% CI 0.40 to 0.80; moderate‐quality evidence) and fewer respiratory tract infections (OR 0.70, 95% CI 0.62 to 0.80; moderate‐quality evidence) compared to placebo, probably because these are not adverse events, but rather characteristics of the indications for the antibiotics. Less fever (OR 0.73, 95% 0.54 to 1.00; moderate‐quality evidence) was also reported by participants taking macrolides compared to placebo, although these findings were non‐significant. There was no increase in mortality in...

Objective: To assess the availability and applicability of clinical indications from electronic prescriptions on antibiotic use in Danish general practice. Design: Retrospective cohort register-based study including the Danish National Prescription Register. Setting: Population-based study of routine electronic antibiotic prescriptions from Danish general practice. Subjects: All 975,626 patients who redeemed an antibiotic prescription at outpatient pharmacies during the 1-year study period (July 2012 to June 2013). Main outcome measures: Number of prescriptions per clinical indication. Number of antibiotic prescriptions per 1000 inhabitants by age and gender. Logistic regression analysis estimated the association between patient and provider factors and missing clinical indications on antibiotic prescriptions. Results: A total of 2.381.083 systemic antibiotic prescriptions were issued by Danish general practitioners in the study period. We identified three main clinical entities: urinary tract infections (n = 506.634), respiratory tract infections (n = 456.354) and unspecified infections (n = 416.354). Women were more exposed to antibiotics than men. Antibiotic use was high in children under 5 years and even higher in elderly people. In 32% of the issued prescriptions, the clinical indication was missing. This was mainly associated with antibiotic types. We found that a prescription for a urinary tract agent without a specific clinical indication was uncommon. Conclusion: Clinical indications from electronic prescriptions are accessible and available to provide an overview of drug use, in casu antibiotic prescriptions, in Danish general practice. These clinical indications may be further explored in detail to assess rational drug use and congruence with guidelines, but validation and optimisation of the system is preferable.

Excessive use of antibiotics is worldwide the most important reason for development of antimicrobial resistance. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. Initiatives have been taken to improve the quality of antibiotic prescribing in primary care, but only few studies have been designed to determine the effectiveness of multifaceted strategies across countries with different practice setting. The aim of this study was to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different health organization and different prevalence of antibiotic resistance.

• Preventing patients from developing an acute respiratory infection will obviate any need for antibiotic use downstream. Hygiene measures (such as physical barriers and hand hygiene), and possibly vaccination and exercise, may be effective for preventing some acute respiratory infections. • Patients overestimate the effectiveness of antibiotics: therefore public campaigns might contribute to minimise misconceptions. • Complementary and alternative medicines (e.g. zinc, caffeine, vitamin C, probiotics and Echinacea) are often proposed for preventing and treating acute respiratory infections, but evidence for efficacy is scarce. • General practitioners’ attitudes towards antibiotic prescribing are a major factor in the prescribing for acute respiratory infections. Professional interventions with educational components are effective, although they have modest effects, and are expensive. • General practitioners’ perceptions – that mistakenly assume as a default that patients want antibiotics for their acute respiratory infections – are often wrong. Shared decision making might be a solution, as it enables clinician and patient to participate jointly in making a health decision, having discussed the options together with the evidence for their harms as well as benefits. • General practitioners’ diagnostic uncertainty – often leading to an antibiotic prescription ‘just in case’ – might be addressed by exploiting strategies such as safety-netting, e.g. establishing with the patient a priori clearly defined actions to take if the course of the illness deviates from the expected. However, there is scant research undertaken in this area and evaluation of this strategy and its effects on patient care is needed. • The best strategies for the future are likely to focus on the best combination of the most effective interventions rather than any single one.