Summary Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with ...pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.
Summary The increasing numbers of patients who are elderly and severely disabled has led to the introduction of a new category of pneumonia management: health-care-associated pneumonia (HCAP). An ...analysis of the available evidence in support of this category, however, reveals heterogeneous and misleading definitions of HCAP, reliance on microbiological data of questionable validity, failure to recognise the contribution of aspiration pneumonia, failure to control microbial patterns for functional status, and failure to recognise frequently applied restrictions of treatment escalation as bias in assessing outcomes. As a result, the concept of HCAP contributes to confusion more than it provides a guide to pneumonia management, and it potentially leads to overtreatment. We suggest a reassignment of the criteria for HCAP to reconstruct the triad of community-acquired pneumonia (with a recognised core group of elderly and disabled patients and a subgroup of younger patients), hospital-acquired pneumonia, and pneumonia in immunosuppressed patients.
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.
Summary Background Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall ...effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older. Methods Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated “moderately bad” or worse. Secondary outcomes were symptom severity in days 2–4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N). Findings 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated “moderately bad” or worse (hazard ratio 1·06, 95% CI 0·96–1·18; p=0·229) nor mean symptom severity (1·69 with placebo vs 1·62 with amoxicillin; difference −0·07 95% CI −0·15 to 0·007; p=0·074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 15·9% of 1021 patients vs 194 19·3% of 1006; p=0·043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11–174; p=0·025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595). Interpretation When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms. Funding European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.
Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual ...participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection.
We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling.
We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio OR 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio HR 1·23 95% CI 1·18-1·28; p<0·0001 for the increasing HR with each day's delay).
We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection.
F Hoffmann-La Roche.