Abstract: Background: Acute respiratory tract infections (ARTI) are the main cause of inappropriate antibiotic prescribing. To date, there is limited evidence concerning whether low levels of antibiotic prescribing may impact patient safety. We investigate whether antibiotic prescribing for patients seeking primary care for ARTI correlates with the odds for hospitalization. Methods: Analysis of patient baseline data (n = 3669) within a cluster-randomized controlled trial. Adult patients suffering from ARTI in German primary care are included. The main outcome measure is acute hospitalization for respiratory infection and for any acute disease from 0 to 42 days after initial consultation. Results: Neither the antibiotic status of individual patients (OR 0.91; 95% CI: 0.49 to 1.69; p-value = 0.769) nor the physician-specific antibiotic prescription rates for ARTI (OR 1.22; 95% CI: 1.00 to 1.49; p-value = 0.054) had a significant effect on hospitalization. The following factors increased the odds for hospitalization: patient’s age, the ARTI being defined as lower respiratory tract infections (such as bronchitis) by the physician, the physician’s perception of disease severity, and being cared for within group practices (versus treated in single-handed practices). Conclusions: In a low-antibiotic-prescribing primary care setting such as Germany, lack of treatment with antibiotics for ARTI did not result in higher odds for hospitalization in an adult population.

Abstract: Introduction FCR is the current standard first line treatment regimen in advanced CLL (Hallek et al., Lancet, 2010), but is associated with significant side effects. The GCCLSG initiated an international phase III study in order to test the non-inferiority regarding efficacy and potentially better tolerability of BR compared to FCR in first-line therapy of physically fit pts without del(17p). Methods and Patients 688 CLL pts from 158 sites in five countries (Germany, Austria, Switzerland, Denmark and Czech Republic) were screened centrally for immunophenotype, genomic aberrations by FISH, IGHV sequenzing, comorbidity burden and renal function. 564 CLL pts with CIRS score ≤ 6, creatinine clearance 〉 70 ml/min and without del(17p) were enrolled between October 2008 and June 2011. Pts were randomly assigned to receive 6 courses of either FCR (N= 284; F 25mg/m2 i.v. d1–3, C 250 mg/m2 i.v. d1–3, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent courses; q 28 days) or BR (N=280; B 90mg/m2 i.v. d1+2, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent courses; q 28 days). The intent-to-treat population consisted of 561 pts, because three patients were excluded due to deferred treatment (1 pt decision, 1 treatment before randomization, 1 misdiagnosis). 22 % were Binet A, 38 % Binet B and 40 % Binet C. The median age was 62 years (yrs) (range 33 to 82), median CIRS score 2 (range 0-6). There were significantly more pts with unmutated IGVH in the BR arm (68%) in comparison to the FCR arm (55%; p=0.003). All other characteristics including median age were well balanced. A mean number of 5.27 courses was given in the FCR arm versus 5.41 courses in the BR arm (p=0.022). 70.6% (FCR) and 80.3% (BR) of pts received 6 courses (p=0.008). Dose was reduced by more than 10% in 27.3% (FCR) and 31.6% (BR) of all courses given (p = 0.012). Results The median observation time was 27.9 months (mo) in all pts alive. While response evaluation was missing in 14 pts, 547 pts (274 FCR; BR 273) were evaluable for response and all 561 pts (282 FCR; 279 BR) for progression-free survival (PFS), event-free survival (EFS) and OS. The overall response rate was identical in both arms with 97.8% (p=1.0). The complete response rate (CRR) (confirmed by central immunhistology) with FCR was 47.4% as compared to 38.1% with BR (p=0.031). MRD data were available at interim analysis from 192 pts (99 FCR; 93 BR) of the first 300pts. 71.7% of pts in the FCR and 66.7% in the BR arms achieved MRD-levels below 10-4 in peripheral blood at final staging (p=0.448). The complete MRD data set will be available by November. PFS was 85.0% at 2 yrs in the FCR arm and 78.2% in the BR arm (p=0.041). EFS was 82.6% at 2 yrs in the FCR arm and 75.7% in the BR arm (p=0.037).There was no difference in OS rate for the FCR vs BR arm (94.2% vs 95.8% at 2 years p=0.593). Hazard Ratio for PFS, EFS and OS was 1.385, 1.375 and 0.842 respectively. PFS was assessed in pts 〈 65 yrs and ≥ 65 yrs. While there was a significant difference in pts 〈 65 yrs between both treatment arm (median PFS for BR 36.5 mo vs not reached for FCR; p=0.016), the difference disappeared in elderly pts (not reached vs. 45.6 mo; p=0.757). A multivariate analysis including treatment arm, Binet stage, age, sex, comorbidity, serum TK, serum beta2-microglobulin (Beta2M), del(11q) and IGHV status identified treatment arm, Beta2M, del(11q) and IGHV as independent prognostic factors for PFS and EFS. FCR treated pts had significantly more frequent severe, CTC grade 3 to 5, adverse events during the whole observation period (90.8% vs 78.5%; p 〈 0.001). Especially severe hematotoxicity was more frequent in the FCR arm (90.0% vs 66.9%, p 〈 0.001). The higher rate of severe neutropenia (81.7% vs 56.8%, p 〈 0.001) resulted in a significantly higher rate of severe infections (39.0% vs 25.4%, p=0.001) in the FCR arm, especially in the elderly (FCR: 47.4% vs BR: 26.5%; p=0.002). Treatment related mortality occurred in 3.9% (n=11) in the FCR and 2.1% (n=6) in the BR arm. Conclusion The results of this planned interim analysis show that FCR seems more efficient than BR in the first-line treatment of fit CLL pts with regard to higher CRR, as well as longer PFS and EFS. These advantages might be balanced by a higher rate of severe adverse events, in particular neutropenia and infections, associated with FCR. In light of these results, no firm recommendation of one regimen over the other can be given at the present time regarding the first-line use in CLL pts with good physical fitness. Disclosures: Eichhorst: Roche: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding. Gregor:Roche: Consultancy, Honoraria, Travel Support Other; Mundipharma: Travel Support, Travel Support Other. Plesner:Mundipharma: Research Funding. Trneny:Roche: Honoraria, Research Funding. Fischer:Roche: Travel grants Other; Mundipharma: Travel grants, Travel grants Other. Kneba:Roche: Consultancy, Research Funding. Wendtner:Roche: Consultancy, Research Funding; Mundipharma: Consultancy, Research Funding. Kreuzer:Roche: Honoraria; Mundipharma: Honoraria. Stilgenbauer:Roche: Consultancy, Research Funding, Travel grants Other; Mundipharma: Consultancy, Research Funding. Böttcher:Roche: Honoraria, Research Funding. Hallek:Janssen: Research Funding; Gilead: Research Funding; Roche: Research Funding.

Abstract: The aim of the present study was to explore the impact of strategies to reduce polypharmacy on mortality, hospitalization and change in number of drugs. Methods Systematic review and meta‐analysis: a systematic literature search targeting patients ≥65 years with polypharmacy (≥4 drugs), focusing on patient‐relevant outcome measures, was conducted. We included controlled studies aiming to reduce polypharmacy. Two reviewers independently assessed studies for eligibility, extracted data and evaluated study quality. Results Twenty‐five studies, including 10 980 participants, were included, comprising 21 randomized controlled trials and four nonrandomized controlled trials. The majority of the included studies aimed at improving quality or the appropriateness of prescribing by eliminating inappropriate and non‐evidence‐based drugs. These strategies to reduce polypharmacy had no effect on all‐cause mortality (odds ratio 1.02; 95% confidence interval 0.84, 1.23). Only single studies found improvements, in terms of reducing the number of hospital admissions, in favour of the intervention group. At baseline, patients were taking, on average, 7.4 drugs in both the intervention and the control groups. At follow‐up, the weighted mean number of drugs was reduced (−0.2) in the intervention group but increased (+0.2) in controls. Conclusions There is no convincing evidence that the strategies assessed in the present review are effective in reducing polypharmacy or have an impact on clinically relevant endpoints. Interventions are complex; it is still unclear how best to organize and implement them to achieve a reduction in inappropriate polypharmacy. There is therefore a need to develop more effective strategies to reduce inappropriate polypharmacy and to test them in large, pragmatic randomized controlled trials on effectiveness and feasibility.

Abstract: Temperature above the physiological optimum is a stress condition frequently faced by bacteria in their natural environments. Here, we were interested in the correlation between levels of RNA and protein under heat stress. Changes in RNA and protein levels were documented in cultures of Rhodobacter sphaeroides using RNA sequencing, quantitative mass spectrometry, western blot analysis, in vivo [ 35 S] methionine‐labelling and plasmid‐borne reporter fusions. Changes in the transcriptome were extensive. Strikingly, the proteome remained unchanged except for very few proteins. Examples include a heat shock protein, a DUF1127 protein of unknown function and sigma factor proteins from leaderless transcripts. Insight from this study indicates that R. sphaeroides responds to heat stress by producing a broad range of transcripts while simultaneously preventing translation from nearly all of them, and that this selective production of protein depends on the untranslated region of the transcript. We conclude that measurements of transcript abundance are insufficient to understand gene regulation. Rather, translation can be an important checkpoint for protein expression under certain environmental conditions. Furthermore, during heat shock, regulation at the level of transcription might represent preparation for survival in an unpredictable environment while regulation at translation ensures production of only a few proteins.

Abstract: Introduction: For physically fit CLL pts with low comorbidity burden FCR is the standard frontline regimen in advanced CLL. The CLL10 study, an international phase III study evaluated the efficacy and tolerance of BR in comparison to FCR in frontline therapy of fit pts without del(17p). Methods and Patients: 158 sites in five countries (Germany, Austria, Switzerland, Denmark and Czech Republic) registered 688 CLL pts for central screening including immunophenotyping, FISH, comorbidity burden and renal function. 564 CLL pts with CIRS score ≤ 6, creatinine clearance 〉 70 ml/min and without del(17p) were enrolled between 10/2008 and 6/2011. Pts were randomly assigned 1:1 to receive 6 courses of FCR (N= 284; F 25mg/m2 i.v. d1–3, C 250 mg/m2 i.v. d1–3, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent cycles; q 28 days) or BR (N=280; B 90mg/m² i.v. d1+2, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent cycles; q 28 days). A general prophylactic use of antibiotics or growth factors was not recommended. Three patients (2 FCR, 1 BR) were excluded because of deferred treatment. The median CIRS score was 2. There was no difference in median age (61.6 years (yrs) for all pts), but a significantly higher proportion of pts ≥ 70 yrs was included in the BR arm (22% vs 14%, p=0.020). Binet A was present in 22%, Binet B in 38 % and Binet C in 40 %. Unmutated IGHV status was not balanced between both groups (68% in BR versus 55% in FCR arm; p=0.003). All other characteristics showed no differences. The mean number of administered FCR courses was 5.27 courses vs 5.41 BR course (p=0.017). Results: The median observation time for all patients was 35.9 months (mo). 547 pts (FCR 274 ; BR 273) were evaluable for response and all pts (282 FCR ; 279 BR) included for progression-free survival (PFS) and overall survival (OS) analysis. The overall response rate in both arms was 97.8% (p=1.0). The complete response (CR) rate according to IWCLL and confirmed by central bone marrow immunohistology was 40.7% with FCR compared to 31.5% with BR (p=0.026). Four-colour-flow MRD data from peripheral blood (sensitivity 10-4) were available from 355 pts (185 FCR; 170 BR) at final staging. In the FCR arm 74.1% and 62.9% in the BR arm respectively of all evaluated pts were MRD negative (p=0.024). Bone marrow samples, available in 129 FCR and 98 BR pts, were MRD negative in 58.1% and 31.6% of pts, respectively (p 〈 0.001). At 12 mo follow-up 58.2% of the pts in the FCR arm (46/79) were still MRD negative in comparison to 26.3% (20/76) after BR (p 〈 0.001). At 18 mo there were 53.8% (35/65) MRD negative cases versus 24.6% (16/65; p=0.006). Median PFS was 53.7 mo in the FCR arm and 43.2 mo in the BR arm (HR=1.589, 95% CI 1.25-2.079; p=0.001). While PFS was statistically not significant different between both arm in pts with mutated IGHV, pts with unmutated IGHV status had a median time to progression of 43.9 mo after FCR compared to 34.0 mo after BR (p=0.015). Physically fit subgroups (CIRS max 3, only one CIRS item, age 〈 65 yrs) benefited most from FCR therapy. The difference in PFS was statistically not significant between both arms in pts ≥ 65 years, CIRS 4-6 or 〉 1 CIRS item. Multivariate analysis identified treatment arm, age ≥ 65 yrs, male sex, high serum TK, del(11q), absence of del(13q) and IGHV status as independent prognostic factors for PFS. No difference in OS was observed (at 36 mo 90.6% for FCR vs 92.2% for BR; HR=1.030, 95% CI 0.618-1.717; p=0.910). For OS male gender, age ≥ 60 yrs, high serum TK and IGHV status were assessed as independent prognostic factors. Severe neutropenia was more often observed in the FCR arm (87.7% vs 67.8%, p 〈 0.001), but no significant difference in the incidence of anemia (14.2% vs. 12.0%; p=0.46) or thrombocytopenia (22.4% vs 16.5%; p=0.096) was documented. Severe infections occurred significantly more frequent (39.8% vs 25.4%, p=0.001) in the FCR arm during treatment phase until 6 months follow-up, especially in older pts (48.4% vs 26.8%; p=0.001). Treatment related mortality was 3.9% (FCR) and 2.1% (BR), respectively. Conclusion: The final analysis of the CLL10 study shows that FCR remains the standard therapy in very fit CLL patients, because it yields higher CR rates, more MRD negativity and longer PFS in comparison to BR. However, in elderly fit pts high toxicity rates and infection rates result into dose reductions leading to similar efficacy between both arms. Elderly fit pts or pts with previous infections might benefit from BR as alternative regimen. Disclosures Eichhorst: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grant Other; Mundipharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grant, Travel grant Other; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy. Off Label Use: The Combination of Bendamustine and Rituximab is not approved for frontline chemoimmunotherapy of CLL. Fink:Celgene: Other. Maurer:Mundipharma: Travel grant Other. Kiehl:Roche: Membership on an entity's Board of Directors or advisory committees. Gregor:Roche: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria. Trneny:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fischer:Roche: Other. Döhner:Roche: Research Funding. Kneba:Roche: Consultancy, Research Funding; Mundipharma: Consultancy, Research Funding. Wendtner:Mundipharma: Consultancy, Honoraria, Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Research Funding. Klapper:Hoffmann-La Roche: Research Funding; Takeda/Millenium: Research Funding. Kreuzer:Roche: Consultancy, Research Funding; Mundipharma: Consultancy, Research Funding. Stilgenbauer:Roche: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding. Böttcher:Roche: Honoraria, Research Funding, Travel grant Other. Hallek:Roche: Consultancy, Research Funding; Mundipharma: Consultancy, Research Funding.

Abstract: Introduction: FCR is still the standard frontline regimen for physically fit CLL pts without TP53 alteration. The international phase III CLL10 study demonstrated the inferiority of BR in comparison to FCR in this population. In order to evaluate long-term outcome and toxicity we performed an updated analysis after extended observation time. Methods and Patients: 561 pts were randomized as previously published (Eichhorst B et al., Lancet Oncol 2016). 282 and 279 pts were randomized to receive either 6 courses of FCR or BR respectively. After the end of treatment pts were followed 3-monthly for 2 years (yrs) and 6-monthly for 3 yrs, and afterwards annually until progressive disease (PD). After PD annual visits were documented either within the study or within the registry of the GCLLSG. Health related quality of life (HRQOL) was evaluated by using the EORTC C30 questionnaire, which was completed at baseline, after 3, 6 and 12 months and then annually until year 5. Results: After a median observation time of 58.2 months (mo) (range, 0 - 88 mo), the median progression-free survival (PFS) for FCR was 57.6 mo versus (vs) 42.3 mo for the BR arm [Hazard ratio (HR)=1.593 (95% confidence interval (CI), 1.271-1.996); p 〈 0.0001]. While PFS was statistically significant different in younger pts [≤ 65 years (yrs)] (median PFS 57.6 vs 38.2 mo.; p 〈 0.0001), the difference was statistically not significant in elderly pts [ 〉 65 yrs] (57.6 vs 42.3; p=0.134). Richter transformation (RT) was assessed as PD and occurred in 5 pts (1.8%) after FCR and 8 pts (2.9%) after BR. 77 (27.3%) pts following FCR and 108 (38.7%) following BR treatment received at least one subsequent therapy. BR was the most common second line therapy after prior FCR (42 pts), while BR re-exposure after frontline BR was performed in 31 pts. 33pts switched to FCR after BR first line therapy. So far, only 3 pts after FCR and 2 pts after BR received kinase inhibitors. 51 pts (18.1%) of the FCR arm and 54 (19.4%) pts of the BR arm deceased so far. Main cause of death in the FCR arm were secondary malignancies (14 pts; 5.0%), followed by CLL including RT (11 pts incl. 2 RT; 3.9%), infections (7 pts; 2.5%) and concomitant diseases (6 pts; 2.1%). In the BR arm CLL was the most common cause of death (15 pts incl. 6 pts with RT; 5.4%) followed by infections (12 pts; 4.3%) and concomitant disease and secondary malignancies (10 pts each; 4.3% each). Other causes of deaths were distributed similarly (incl. adverse events to frontline or relapse treatment or unknown). No differences in overall survival (OS) were observed (OS at 5 yrs, 80.9% for FCR vs 80.1% for BR; HR=1.108, 95% CI 0.755-1.627; p=0.599). The difference in OS for younger pts was statistically not significant (OS at 5-yrs 85.6% for FCR vs 81.1% for BR; p=0.119). Otherwise, 5-yrs OS was 78.8% for pts 〉 65 yrs receiving BR and 70.9% for those receiving FCR (p=0.238). Multivariate analysis identified treatment arm, male sex, high serum thymidine kinase (TK), del(11q) and unmuated IGHV status, but not age as independent prognostic factors for PFS. For OS only high serum TK and unmutated IGHV status were assessed as independent prognostic factors. Secondary neoplasia was documented in 49 (17.6%) of 279 FCR treated pts and 35 (12.5%) of 278 BR treated pts. No difference in the incidence rate of secondary solid tumors was observed between both arms (for FCR 28 (10.0%) and for BR 25 (9.1%)). Secondary MDS and/or AML occurred more frequently after FCR therapy (12 [4.3%] vs 2 [0.7%] ), particularly in pts 〉 65 yrs (6 [7.0%] vs 1 [0.9%] ). 540 of 561 pts (96.3%) were evaluable for HRQOL analysis, 272 pts of the FCR and 268 pts of the BR arm. No differences between both arms were detected with respect to global health status or any functional or symptom scale. As compared to an age- and sex-matched normal population functional scale values were impaired mostly during treatment phase and symptom scales also during follow-up. However, after the end of therapy and during follow-up global health status was improved. Conclusion: Long-term follow-up data of the CLL10 study confirm the superiority of FCR regimen in young (≤ 65 yrs) and fit CLL patients. However, importantly these data support the recommendation of using BR in fit elderly pts. This particular group of pts had both a very good outcome after BR and compared to FCR a decreased risk of secondary MDS and/or AML. Disclosures Eichhorst: Novartis: Consultancy; Gilead: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Research Funding, Speakers Bureau. Bahlo:F. Hoffman-La Roche: Honoraria, Other: Travel grant. Maurer:Mundipharma: Other: Travel grants. Kiehl:Roche: Consultancy, Other: Travel grants, Speakers Bureau. Fischer:Roche: Other: travel grants. Kneba:Amgen: Research Funding; Roche: Consultancy, Honoraria, Other: Travel grants, Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants, Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants; Glaxo-SmithKline: Other: Travel grants; Janssen-Cilag: Consultancy, Honoraria, Other: Travel grants. Wendtner:Hoffmann-La Roche, Mundipharma, Janssen, Gilead, Abbvie, Servier, Morphosys: Consultancy, Other: Travle grants, Research Funding. Klapper:Roche, Novartis, Amgen, Takeda: Research Funding. Kreuzer:Roche Pharma GmbH and Mundipharma GmbH: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Research Funding, Speakers Bureau. Böttcher:Celgene: Research Funding; Hoffmann-LaRoche: Honoraria, Other: Travel grants, Research Funding; AbbVie: Honoraria, Research Funding. Stilgenbauer:GSK: Consultancy, Honoraria, Other: Travel grants , Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel grants, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel grants , Research Funding; Genzyme: Consultancy, Honoraria, Other: Travel grants , Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants , Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding; Celgene: Consultancy, Honoraria, Other: Travel grants , Research Funding; Genentech: Consultancy, Honoraria, Other: Travel grants , Research Funding; Mundipharma: Consultancy, Honoraria, Other: Travel grants , Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel grants , Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grants , Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel grants , Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Other: Travel grants , Research Funding. Fink:Celgene: Research Funding; Roche: Honoraria, Other: Travel grants; Mundipharma: Other: Travel grants; AbbVie: Other: Travel grants. Hallek:Celgene: Research Funding; Roche: Consultancy, Honoraria, Research Funding; Gilead: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria; GSK: Research Funding; Mundipharma: Research Funding; Janssen: Research Funding.

Abstract: With an average prescription rate of 50%, in German primary care antibiotics are still too frequently prescribed for respiratory tract infections. The over-prescription of antibiotics is often explained by perceived patient pressure and fears of a complicated disease progression. The CHANGE-2 trial will test the effectiveness of two interventions to reduce the rate of inappropriate antibiotic prescriptions for adults and children suffering from respiratory tract infections in German primary care. Methods/Design The study is a three-arm cluster-randomized controlled trial that measures antibiotic prescription rates over three successive winter periods and reverts to administrative data of the German statutory health insurance company AOK. More than 30,000 patients in two regions of Germany, who visit their general practitioner or pediatrician for respiratory tract infections will be included. Interventions are: A) communication training for general practitioners and pediatricians and B) intervention A plus point-of-care testing. Both interventions are tested against usual care. Outcome measure is the physicians’ antibiotic prescription rate for respiratory tract infections derived from data of the health insurance company AOK. Secondary outcomes include reconsultation rate, complications, and hospital admissions. Discussion Major aim of the study is to improve the process of decision-making and to ensure that patients who are likely to benefit from antibiotics are treated accordingly. Our approach is simple to implement and might be used rapidly among general practitioners and pediatricians. We expect the results of this trial to have major impact on antibiotic prescription strategies and practices in Germany, both among general practitioners and pediatricians. Trial registration The study is registered at the Current Controlled Trials Ltd (ISRCTN01559032)