Hasse Melbye

Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries

Objective To describe variation in antibiotic prescribing for acute cough in contrasting European settings and the impact on recovery. Design Cross sectional observational study with clinicians from 14 primary care research networks in 13 European countries who recorded symptoms on presentation and management. Patients followed up for 28 days with patient diaries. Setting Primary care. Participants Adults with a new or worsening cough or clinical presentation suggestive of lower respiratory tract infection. Main outcome measures Prescribing of antibiotics by clinicians and total symptom severity scores over time. Results 3402 patients were recruited (clinicians completed a case report form for 99% (3368) of participants and 80% (2714) returned a symptom diary). Mean symptom severity scores at presentation ranged from 19 (scale range 0 to 100) in networks based in Spain and Italy to 38 in the network based in Sweden. Antibiotic prescribing by networks ranged from 20% to nearly 90% (53% overall), with wide variation in classes of antibiotics prescribed. Amoxicillin was overall the most common antibiotic prescribed, but this ranged from 3% of antibiotics prescribed in the Norwegian network to 83% in the English network. While fluoroquinolones were not prescribed at all in three networks, they were prescribed for 18% in the Milan network. After adjustment for clinical presentation and demographics, considerable differences remained in antibiotic prescribing, ranging from Norway (odds ratio 0.18, 95% confidence interval 0.11 to 0.30) to Slovakia (11.2, 6.20 to 20.27) compared with the overall mean (proportion prescribed: 0.53). The rate of recovery was similar for patients who were and were not prescribed antibiotics (coefficient −0.01, P<0.01) once clinical presentation was taken into account. Conclusions Variation in clinical presentation does not explain the considerable variation in antibiotic prescribing for acute cough in Europe. Variation in antibiotic prescribing is not associated with clinically important differences in recovery. Trial registration Clinicaltrials.gov NCT00353951.

Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled trial

Summary Background High-volume prescribing of antibiotics in primary care is a major driver of antibiotic resistance. Education of physicians and patients can lower prescribing levels, but it frequently relies on highly trained staff. We assessed whether internet-based training methods could alter prescribing practices in multiple health-care systems. Methods After a baseline audit in October to December, 2010, primary-care practices in six European countries were cluster randomised to usual care, training in the use of a C-reactive protein (CRP) test at point of care, in enhanced communication skills, or in both CRP and enhanced communication. Patients were recruited from February to May, 2011. This trial is registered, number ISRCTN99871214. Results The baseline audit, done in 259 practices, provided data for 6771 patients with lower-respiratory-tract infections (3742 [55·3%]) and upper-respiratory-tract infections (1416 [20·9%]), of whom 5355 (79·1%) were prescribed antibiotics. After randomisation, 246 practices were included and 4264 patients were recruited. The antibiotic prescribing rate was lower with CRP training than without (33% vs 48%, adjusted risk ratio 0·54, 95% CI 0·42–0·69) and with enhanced-communication training than without (36% vs 45%, 0·69, 0·54–0·87). The combined intervention was associated with the greatest reduction in prescribing rate (CRP risk ratio 0·53, 95% CI 0·36–0·74, p<0·0001; enhanced communication 0·68, 0·50–0·89, p=0·003; combined 0·38, 0·25–0·55, p<0·0001). Interpretation Internet training achieved important reductions in antibiotic prescribing for respiratory-tract infections across language and cultural boundaries. Funding European Commission Framework Programme 6, National Institute for Health Research, Research Foundation Flanders.

Pneumonia - a Clinical or Radiographic Diagnosis? Etiology and Clinical Features of Lower Respiratory Tract Infection in Adults in General Practice

Etiology and clinical manifestations have been studied in 153 adult patients with lower respiratory tract infection, and the results are presented according to clinical and radiographic diagnosis. Laboratory investigations revealed that bacterial infection, mycoplasma and chlamydia included, occurred as often in 22 patients whose clinical diagnoses of pneumonia were not evident radiographically, as in 20 patients with radiographic pneumonia. In the latter group significantly higher values of erythrocyte sedimentation rate and C-reactive protein were demonstrated. The most common pathogen was influenzavirus A, followed by respiratory syncytial virus, Streptococcus pneumoniae, and Mycoplasma pneumoniae. Chlamydia pneumoniae infection was found in 3 patients with radiographic pneumonia. The study supports the traditional view that patients with a positive chest radiograph as a rule present more serious manifestations of lower respiratory tract pathology than patients with a normal radiograph. However, as only 1/9 patients with pneumococcal infection and 2/7 with mycoplasmal infection had radiographic evidence of pneumonia, radiography alone did not seem to offer sufficient information for selecting patients for antibacterial therapy.

Laboratory Tests for Pneumonia in General Practice: The Diagnostic Values Depend on the Duration of Illness

The usefulness in the diagnosis of pneumonia of temperature and the laboratory tests: erythrocyte sedimentation rate (ESR), leucocyte count, and C-reactive protein (CRP) was evaluated against a radiographic reference standard in 402 adult patients with respiratory tract infection in general practice. Radiographic pneumonia was diagnosed in 20 patients. CRP and ESR were the most useful tests. CRP greater than 50 mg/l had lower sensitivity and likelihood ratio (LR), 0.50 and 4.8, respectively, compared with previous studies of selected patient populations. Among patients whose duration of illness exceeded six days the corresponding LR was 11.3, due to a higher specificity in this subgroup of patients. ESR and oral temperature were also more useful in this subgroup than in patients with a shorter duration of illness. A highly significant diagnostic contribution of adding ESR and CRP to history and physical examination, particularly when the illness had lasted one week or more, was demonstrated by logistic regression.

Influence of CRP testing and clinical findings on antibiotic prescribing in adults presenting with acute cough in primary care

Abstract Objective. Respiratory tract infections are the most common indication for antibiotic prescribing in primary care. The value of clinical findings in lower respiratory tract infection (LRTI) is known to be overrated. This study aimed to determine the independent influence of a point of care test (POCT) for C-reactive protein (CRP) on the prescription of antibiotics in patients with acute cough or symptoms suggestive of LRTI, and how symptoms and chest findings influence the decision to prescribe when the test is and is not used. Design. Prospective observational study of presentation and management of acute cough/LRTI in adults. Setting. Primary care research networks in Norway, Sweden, and Wales. Subjects. Adult patients contacting their GP with symptoms of acute cough/LRTI. Main outcome measures. Predictors of antibiotic prescribing were evaluated in those tested and those not tested with a POCT for CRP using logistic regression and receiver operating characteristic (ROC) curve analysis. Results. A total of 803 patients were recruited in the three networks. Among the 372 patients tested with a POCT for CRP, the CRP value was the strongest independent predictor of antibiotic prescribing, with an odds ratio (OR) of CRP ≥ 50 mg/L of 98.1. Crackles on auscultation and a patient preference for antibiotics perceived by the GP were the strongest predictors of antibiotic prescribing when the CRP test was not used. Conclusions. The CRP result is a major influence in the decision whether or not to prescribe antibiotics for acute cough. Clinicians attach less weight to discoloured sputum and abnormal lung sounds when a CRP value is available. CRP testing could prevent undue reliance on clinical features that poorly predict benefit from antibiotic treatment.

Are Patient Views about Antibiotics Related to Clinician Perceptions, Management and Outcome? A Multi-Country Study in Outpatients with Acute Cough

Background Outpatients with acute cough who expect, hope for or ask for antibiotics may be more unwell, benefit more from antibiotic treatment, and be more satisfied with care when they are prescribed antibiotics. Clinicians may not accurately identify those patients. Objective To explore whether patient views (expecting, hoping for or asking for antibiotics) are associated with illness presentation and resolution, whether patient views are accurately perceived by clinicians, and the association of all these factors with antibiotic prescribing and patient satisfaction with care. Methods Prospective observational study of 3402 adult patients with acute cough presenting in 14 primary care networks. Correlations and associations tested with multilevel logistic regression and McNemar ‘s tests, and Cohen’s Kappa, positive agreement (PA) and negative agreement (NA) calculated as appropriate. Results 1,213 (45.1%) patients expected, 1,093 (40.6%) hoped for, and 275 (10.2%) asked for antibiotics. Clinicians perceived 840 (31.3%) as wanting to be prescribed antibiotics (McNemar’s test, p<0.05). Their perception agreed modestly with the three patient views (Kappa’s = 0.29, 0.32 and 0.21, PA’s = 0.56, 0.56 and 0.33, NA’s = 0.72, 0.75 and 0.82, respectively). 1,464 (54.4%) patients were prescribed antibiotics. Illness presentation and resolution were similar for patients regardless their views. These associations were not modified by antibiotic treatment. Patient expectation and hope (OR:2.08, 95% CI:[1.48,2.93] and 2.48 [1.73,3.55], respectively), and clinician perception (12.18 [8.31,17.84]) were associated with antibiotic prescribing. 2,354 (92.6%) patients were satisfied. Only those hoping for antibiotics were less satisfied when antibiotics were not prescribed (0.39 [0.17,0.90]). Conclusion Patient views about antibiotic treatment were not useful for identifying those who will benefit from antibiotics. Clinician perceptions did not match with patient views, but particularly influenced antibiotic prescribing. Patients were generally satisfied with care, but those hoping for but not prescribed antibiotics were less satisfied. Clinicians need to more effectively elicit and address patient views about antibiotics.

Antibiotic prescribing for discoloured sputum in acute cough/lower respiratory tract infection

We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1–5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61–1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p = 0.68) or green (coefficient -0.01; p = 0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p = 0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.

Understanding variation in primary medical care : a nine-country qualitative study of clinicians accounts of the non-clinical factors that shape antibiotic prescribing decisions for lower respiratory tract infection

Objectives There is a wide variation between European countries in antibiotic prescribing for patients in primary care with lower respiratory tract infection (LRTI) that is not explained by case mix and clinical factors alone. Variation in antibiotic prescribing that is not warranted by differences in illness and clinical presentation may increase selection of resistant organisms, contributing to the problem of antibiotic resistance. This study aimed to investigate clinicians’ accounts of non-clinical factors that influence their antibiotic prescribing decision for patients with LRTI, to understand variation and identify opportunities for addressing possible unhelpful variation. Design Multicountry qualitative semistructured interview study, with data subjected to a five-stage analytic framework approach (familiarisation, developing a thematic framework from interview questions and emerging themes, indexing, charting and interpretation), and with interviewers commenting on preliminary analytic themes. Setting Primary care. Participants Eighty primary care clinicians randomly selected from primary care research networks based in nine European cities. Results Clinicians’ accounts identified non-clinical factors imposed by the healthcare system operating within specific regional primary care research networks, including patient access to antibiotics before consulting a doctor (Barcelona and Milan), systems to reduce patient expectations for antibiotics (Southampton and Antwerp) and lack of consistent treatment guidelines (Balatonfüred and Łódź). Secondly, accounts revealed factors related to specific characteristics of clinicians regardless of network (professional ethos, self-belief in decision-making and commitment to shared decision-making). Conclusions Addressing healthcare system factors (eg, limiting patients’ self-management with antibiotics before consulting in primary care, increased public awareness and provision of more consistent guidelines) may assist in reducing unhelpful variation in antibiotic prescribing. Promoting clinicians’ receptivity to change, confidence in decision-making and readiness to invest in explaining prescribing decisions may also be beneficial. As factors were emphasised differently between networks, local flexibility in interventions is likely to maximise effectiveness.

Usefulness of C-reactive protein testing in acute cough/respiratory tract infection: an open cluster-randomized clinical trial with C-reactive protein testing in the intervention group

BackgroundPoint of care testing for C-reactive protein (CRP) has shown promise as a measure to reduce unnecessary antibiotic prescribing in respiratory tract infections (RTI), but its use in primary care is still controversial. We aimed to evaluate the effect of CRP testing on the prescription of antibiotics, referral for radiography, and the outcome of patients in general practice with acute cough/RTI.MethodsAn open-cluster randomized clinical trial was conducted, with CRP testing performed in the intervention group. Antibiotic prescribing and referral for radiography were the main outcome measures.ResultsA total of 179 patients were included: 101 in the intervention group and 78 in the control group. The two groups were similar in clinical characteristics. In the intervention group, the antibiotic prescribing rate was 37.6%, which was significantly lower than that in the control group (58.9%) (P = 0.006). Referral for chest X-ray was also significantly lower in the intervention group (55.4%) than in the control group (75.6%) (P = 0.004). The recovery rate, as recorded by the GPs, was 92.9% and 93.6% in the intervention and control groups, respectively.ConclusionThe study showed that CRP testing in patients with acute cough/RTI may reduce antibiotic prescribing and referral for radiography, probably without compromising recovery.Trial registrationThe trial was registered in the ClinicalTrials.gov Protocol Registration System (identification number: NCT01794819).

Cost-effectiveness of point-of-care C-reactive protein testing to inform antibiotic prescribing decisions

BACKGROUND Point-of-care C-reactive protein (POCCRP) is a biomarker of inflammation that offers clinicians a rapid POC test to guide antibiotic prescribing decisions for acute cough and lower respiratory tract infections (LRTI). However, evidence that POCCRP is cost-effective is limited, particularly outside experimental settings. AIM To assess the cost-effectiveness of POCCRP as a diagnostic tool for acute cough and LRTI from the perspective of the health service. DESIGN AND SETTING Observational study of the presentation, management, and outcomes of patients with acute cough and LRTI in primary care settings in Norway and Sweden. METHOD Using hierarchical regression, data were analysed in terms of the effect on antibiotic use, cost, and patient outcomes (symptom severity after 7 and 14 days, time to recovery, and EQ-5D), while controlling for patient characteristics (self-reported symptom severity, comorbidities, and health-related quality of life) at first attendance. RESULTS POCCRP testing is associated with non-significant positive reductions in antibiotic prescribing (P = 0.078) and increased cost (P = 0.092). Despite the uncertainty, POCCRP testing is also associated with a cost per quality-adjusted life year (QALY) gain of €9391. At a willingness-to-pay threshold of €30,000 per QALY gained, there is a 70% probability of CRP being cost-effective. CONCLUSION POCCRP testing is likely to provide a cost-effective diagnostic intervention both in terms of reducing antibiotic prescribing and in terms of QALYs gained.