Laura Shallcross

The role of the Panton-Valentine leucocidin toxin in staphylococcal disease: a systematic review and meta-analysis

Summary Background Invasive community-onset staphylococcal disease has emerged worldwide associated with Panton-Valentine leucocidin (PVL) toxin. Whether PVL is pathogenic or an epidemiological marker is unclear. We investigate the role of PVL in disease, colonisation, and clinical outcome. Methods We searched Medline and Embase for original research reporting the prevalence of PVL genes among Staphylococcus aureus pneumonia, bacteraemia, musculoskeletal infection, skin and soft-tissue infection, or colonisation published before Oct 1, 2011. We calculated odds ratios (ORs) to compare patients with PVL-positive colonisation and each infection relative to the odds of PVL-positive skin and soft-tissue infection. We did meta-analyses to estimate odds of infection or colonisation with a PVL-positive strain with fixed-effects or random-effects models, depending on the results of tests for heterogeneity. Results Of 509 articles identified by our search strategy, 76 studies from 31 countries met our inclusion criteria. PVL strains are strongly associated with skin and soft-tissue infections, but are comparatively rare in pneumonia (OR 0·37, 95% CI 0·22–0·63), musculoskeletal infections (0·44, 0·19–0·99), bacteraemias (0·10, 0·06–0·18), and colonising strains (0·07, 0·01–0·31). PVL-positive skin and soft-tissue infections are more likely to be treated surgically than are PVL-negative infections, and children with PVL-positive musculoskeletal disease might have increased morbidity. For other forms of disease we identified no evidence that PVL affects outcome. Interpretation PVL genes are consistently associated with skin and soft-tissue infections and are comparatively rare in invasive disease. This finding challenges the view that PVL mainly causes invasive disease with poor prognosis. Population-based studies are needed to define the role of PVL in mild, moderate, and severe disease and to inform control strategies. Funding None.

Trends in antibiotic prescribing in primary care for clinical syndromes subject to national recommendations to reduce antibiotic resistance, UK 1995–2011: analysis of a large database of primary care consultations

OBJECTIVES To measure trends in antibiotic prescribing in UK primary care in relation to nationally recommended best practice. PATIENTS AND METHODS A descriptive study linking individual patient data on diagnosis and prescription in a large primary care database, covering 537 UK general practices during 1995-2011. RESULTS The proportion of cough/cold episodes for which antibiotics were prescribed decreased from 47% in 1995 to 36% in 1999, before increasing to 51% in 2011. There was marked variation by primary care practice in 2011 [10th-90th percentile range (TNPR) 32%-65%]. Antibiotic prescribing for sore throats fell from 77% in 1995 to 62% in 1999 and then stayed broadly stable (TNPR 45%-78%). Where antibiotics were prescribed for sore throat, recommended antibiotics were used in 69% of cases in 2011 (64% in 1995). The use of recommended short-course trimethoprim for urinary tract infection (UTI) in women aged 16-74 years increased from 8% in 1995 to 50% in 2011; however, a quarter of practices prescribed short courses in ≤16% of episodes in 2011. For otitis media, 85% of prescriptions were for recommended antibiotics in 2011, increasing from 77% in 1995. All these changes in annual prescribing were highly statistically significant (P < 0.001). CONCLUSIONS The implementation of national guidelines in UK primary care has had mixed success, with prescribing for coughs/colds, both in total and as a proportion of consultations, now being greater than before recommendations were made to reduce it. Extensive variation by practice suggests that there is significant scope to improve prescribing, particularly for coughs/colds and for UTIs.

Panton-Valentine leukocidin associated staphylococcal disease: a cross-sectional study at a London hospital, England.

Recently, there has been international concern at the rapid emergence of highly pathogenic strains of Staphylococcus aureus associated with a toxin called Panton-Valentine leukocidin (PVL). In the UK, these strains are considered to be rare and mainly severe. We estimate the proportion of staphylococcal infections that are caused by strains containing the PVL genes, and describe risk factors for these infections. Three hundred and ninety consecutive S. aureus clinical isolates, submitted for routine diagnostic purposes were screened for PVL genes. Risk factors for infection were identified from the patient medical record. 9.7% (95% CI 7.0-13.1%) of clinical isolates and 20.8% of skin and soft tissue specimens contained the genes for PVL. Methicillin-resistant S. aureus with PVL was rare (0.8% of all isolates) but PVL with methicillin-sensitive S. aureus was common (9.0% of all specimens). PVL infection was more frequent in males (OR 3.0, 95% CI 1.3-7.0), and in young adults aged 20-39 years (OR 3.7, 95% CI 1.3-10.4). Over half of PVL positive S. aureus infections originated in patients based in the community. Community-onset PVL-associated disease is common in the UK and mainly causes skin and soft tissue infections that do not require admission to hospital. Consideration should be given to current infection control strategy, which advocates household contact screening and decolonization on the assumption that PVL-associated disease is rare.

Tackling the threat of antimicrobial resistance: from policy to sustainable action.

Antibiotics underpin all of modern medicine, from routine major surgery through to caesarean sections and modern cancer therapies. These drugs have revolutionized how we practice medicine, but we are in a constant evolutionary battle to evade microbial resistance and this has become a major global public health problem. We have overused and misused these essential medicines both in the human and animal health sectors and this threatens the effectiveness of antimicrobials for future generations. We can only address the threat of antimicrobial resistance (AMR) through international collaboration across human and animal health sectors integrating social, economic and behavioural factors. Our global organizations are rising to the challenge with the recent World Health Assembly resolution on AMR and development of the Global Action plan but we must act now to avoid a return to a pre-antibiotic era.

Antibiotic overuse: a key driver of antimicrobial resistance

The widespread use of antibiotics is estimated to have extended average life expectancy by two decades, shifting the paradigm from communicable to non-communicable diseases. Antimicrobials and antibiotics in particular have paved the way for major advances in cancer treatment, organ transplantation, and surgery, irrevocably changing the scope of modern medicine. Every time a new antimicrobial is introduced, drug resistance to that antimicrobial follows, sometimes swiftly, and this occurs for antibiotics, antivirals, and antifungal therapies. Antimicrobial treatment places selective pressure on the organism, favouring the emergence of drug-resistant strains. This is not a new problem: antibiotic resistance emerged within a decade of the first clinical trials of penicillin, with more than 50% resistance among Staphylococcus aureus by the end of the 1940s. Until recently we have escaped the dire consequences of antimicrobial resistance because there has been a stream of new antibiotics. However, over the past 20 years the number of pharmaceutical companies investing in this area has dwindled from 18 to 4, inevitably leading to stalled drug development. Antimicrobial resistance affects every country because infections do not respect international boundaries or borders. Each time a person travels they take their active infections and colonising bacteria with them, spreading drug-resistant organisms across the globe. Many countries overuse antibiotics, particularly in hospitals. Although hospital prescribing accounts for only 20% of human usage, it is important because it is concentrated, and because hospitals are fertile breeding grounds for drug-resistant bacteria. In animals and …

Oseltamivir: the real world data

To coincide with the publication of an updated systematic review by the Cochrane group the BMJ invited Nick Freemantle and colleagues to consider the current status of observational studies of oseltamivir and their influence on policy and practice

Antibiotic prescribing frequency amongst patients in primary care: a cohort study using electronic health records

Background: Reducing inappropriate antibiotic prescribing in primary care is a public health priority. Objectives: We hypothesized that a subset of patients account for the majority of antibiotic prescriptions in primary care. We investigated the relationship between the total amount of antibiotics prescribed, individual-level antibiotic use and comorbidity. Methods: This was a cohort study using electronic health records from 1 948 390 adults registered with 385 primary care practices in the UK in 2011–13. We estimated the average number of antibiotic prescriptions per patient and the association between prescribing and comorbidity. We modelled the impact on total prescribing of reducing antibiotic use in those prescribed antibiotics most frequently. Results: On average 30.1% (586 194/1 948 390) of patients were prescribed at least one antibiotic per year. Nine percent (174 602/1 948 390) of patients were prescribed 53% (2 091 496/3 922 732) of the total amount of antibiotics, each of whom received at least five antibiotic prescriptions over 3 years. The presence of any comorbidity increased the prescribing rate by 44% [adjusted incidence rate ratio (IRR) 1.44, 95% CI 1.43–1.45]; rates of prescribing to women exceeded those in men by 62% (adjusted IRR 1.62, 95% CI 1.62–1.63). Conclusions: Half of antibiotics prescribed to adults in primary care were for <10% of patients. Efforts to tackle antimicrobial resistance should consider the impact of this on total prescribing.

Use of Primary Care Data for Detecting Impetigo Trends, United Kingdom, 1995-2010

Using a primary care database, we identified a major increase in impetigo in the United Kingdom during 1995–2010. Despite a doubled rate of primary care consultations, this increase was not identified by routine surveillance. Primary care databases are a valuable and underused source of surveillance data on infectious diseases.

Evidence for increasing severity of community-onset boils and abscesses in UK General Practice

In England, hospital admissions for severe staphylococcal boils and abscesses trebled between 1989 and 2004. We investigated this trend using routine data from primary and secondary care. We used The Health Improvement Network (THIN), a large primary-care database and national data on hospital admissions from Hospital Episode Statistics (HES). Time trends in the incidence of primary-care consultations for boils and abscesses were estimated for 1995-2010. HES data were used to calculate age-standardized hospital admission rates for boils, abscesses and cellulitis. The incidence of boil or abscess was 450 [95% confidence interval (CI) 447-452] per 100 000 person-years and increased slightly over the study period (incidence rate ratio 1·005, 95% CI 1·004-1·007). The rate of repeat consultation for a boil or abscess increased from 66 (95% CI 59-73) per 100 000 person-years in 1995 to peak at 97 (95% CI 94-101) per 100 000 person-years in 2006, remaining stable thereafter. Hospital admissions for abscesses, carbuncles, furuncles and cellulitis almost doubled, from 123 admissions per 100 000 in 1998/1999 to 236 admissions per 100 000 in 2010/2011. Rising hospitalization and recurrence rates set against a background of stable community incidence suggests increased disease severity. Patients may be experiencing more severe and recurrent staphylococcal skin disease with limited treatment options.

Incidence and recurrence of boils and abscesses within the first year: a cohort study in UK primary care

BACKGROUND Boils and abscesses are common in primary care but the burden of recurrent infection is unknown. AIM To investigate the incidence of and risk factors for recurrence of boil or abscess for individuals consulting primary care. DESIGN AND SETTING Cohort study using electronic health records from primary care in the UK. METHOD The Health Improvement Network (THIN) database was used to identify patients who had consulted their GP for a boil or abscess. Poisson regression was used to examine the relationship between age, sex, social deprivation, and consultation and to calculate the incidence of, and risk factors for, repeat consultation for a boil or abscess. RESULTS Overall, 164 461 individuals were identified who consulted their GP for a boil or abscess between 1995 and 2010. The incidence of first consultation for a boil or abscess was 512 (95% CI = 509 to 515) per 100 000 person-years in females and 387 (95% CI = 385 to 390) per 100 000 person-years in males. First consultations were most frequent in younger age groups (16-34 years) and those with the greatest levels of social deprivation. The rate of repeat consultation for a new infection during follow up was 107.5 (95% confidence interval [CI] = 105.6 to 109.4) per 1000 person-years. Obesity (relative risk [RR] 1.3, 95% CI = 1.2 to 1.3), diabetes (RR 1.3, 95% CI = 1.2 to 1.3), smoking (RR 1.3, 95% CI = 1.2 to 1.4), age <30 years (RR 1.2, 95% CI = 1.2 to 1.3), and prior antibiotic use (RR 1.4, 95% CI = 1.3-1.4) were all associated with repeat consultation for a boil or abscess. CONCLUSION Ten percent of patients with a boil or abscess develop a repeat boil or abscess within 12 months. Obesity, diabetes, young age, smoking, and prescription of an antibiotic in the 6 months before initial presentation were independently associated with recurrent infection, and may represent options for prevention.