Use of vaccines as a key antimicrobial stewardship strategy

Vaccination may prevent bacterial infections and decrease the potential for transmission. Some effective vaccines may reduce bacterial colonisation and exposure to antimicrobials by minimising the spread of  resistant strains; in this regard, a substantial indirect immunity has been demonstrated that protects unvaccinated members of society. One of the best documented examples of the crucial role of vaccination has been an adjunct to an antimicrobial stewardship programme. Pneumococcal conjugate vaccines (PCVs), for example, target the most virulent pneumococcal serotypes, which are linked to invasive disease and associated with antibiotic resistance. In this regard, recent local data highlight the remarkable impact of the sequential introduction of 7- and 13-valent PCV (PCV7/PCV13) on the incidence of penicillin-, ceftriaxone- and multidrug-resistant pneumococcal infections in South Africa in only 4 years. Equally impressive have been vaccines  directed towards viruses such as influenza, which also have direct and indirect effects on antibiotic consumption

Optimising the administration of antibiotics in critically ill patients

Optimal outcome and a reduction in the potential for resistance require that appropriate pharmacokinetic (PK) targets are achieved. Consequently, we need to target drug concentrations that are significantly  higher than those conventionally presumed to be adequate. Drug exposure varies according to the  molecular weight, degree of ionisation, protein binding and lipid solubility of each agent. In critically ill patients,  hypoalbuminaemia increases the free fraction of hydrophilic drugs, which in turn increases the volume of distribution and clearance (CL), both of which result in reduced drug levels. Similarly, augmented renal clearance (ARC), defined as a creatinine clearance (CLcr) of >130 mL/min/1.73 m2, which occurs frequently in critically ill patients, particularly younger patients with normal or near-normal creatinine levels, may also significantly reduce drug exposure. Studies have demonstrated a greater mortality and lower cure with ARC, particularly with the additive effects of obesity, hypoalbuminaemia and increasing resistance, if conventional dosages are used. These concepts apply to antibiotics targeting Gram-negative and -positive organisms. Knowledge of PK and the resistance profiles of organisms in each environment is necessary to prescribe appropriately. This article discusses these issues and the doses that should be used

Viral haemorrhagic fevers in South Africa

Viral haemorrhagic fevers (VHFs) include a diverse array of diseases caused by a broad range of viruses  transmitted from various animal hosts and originating from almost all the continents in the world. These are potentially fatal and highly transmissible diseases without specific treatments or prophylactic vaccines. As  has been demonstrated during the Ebola virus disease outbreak in West Africa, the consequences of VHFs are  not limited to specific countries – they may become epidemic, and may have considerable economic impact   and disrupt local public health and social service structures. Intensive public health intervention is necessary  to contain these diseases. Here we provide a concise overview of the VHFs that are of current public health  importance to South Africa

Lung fibrosis in deceased HIV-infected patients with Pneumocystis pneumonia

Background. Pneumocystis pneumonia (PcP) is one of the most common opportunistic infections found in patients with HIV. The prognosis if ventilation is required is poor, with mortality of 36 - 80%. Although more recent studies have shown improved survival, our experience has been that close to 100% of such patients die, and we therefore decidedto investigate further.Methods. All patients with confirmed or suspected PcP who died owing to respiratory failure were eligible for the study. Where consent was obtained, trucut lung biopsies were performed post mortem, stored in formalin and sent for histopathological assessment.Results. Twelve adequate lung biopsies were obtained from 1 July 2008 to 28 February 2011 – 3 from men and 9 from women. The mean age was 34.7 years (range 24 - 46), and the mean admission CD4 count was 20.8(range 1 - 68) cells/ìl and median 18.5 cells/ìl. All specimens demonstrated typical PcP histopathology; in addition, 9 showed significant interstitial fibrosis. Three had co-infection with cytomegalovirus (CMV), two of which had fibrosis present. There was no evidence of TB or otherfungal infections.Conclusion. The high mortality seen in this cohort of PcP patients was due to intractable respiratory failure from interstitial lung fibrosis. Whereas the differential includes ventilator induced lung injury, drug resistanceor co-infections, we suggest that this is part of the disease progression in certain individuals. Further studies are required to identify interventions that could modify this process and improve outcomes in patients with PcP who require mechanical ventilation

The microbiome in chronic inflammatory airway disease: A threatened species

The human body is exposed to a multitude of microbes and infectious organisms  throughout life. Many of these organisms colonise the skin, gastrointestinal tract (GIT) and airway. We now recognise that this colonisation includes the lower airway,   previously thought to be sterile. These colonising organisms play an important role in disease prevention, including an array of chronic inflammatory conditions that are unrelated to infectious diseases. However, new evidence of immune dysregulation suggests that early colonisation, especially of the GIT and airway, by pathogenic micro-organisms, has deleterious effects that may contribute to the potential to induce  chronic inflammation in young children, which may only express itself in adult life

Quitting patient care and career break intentions among general practitioners in South West England: findings of a census survey of general practitioners

Objective: Given recent concerns regarding general practitioner (GP) workforce capacity, we aimed to describe GPs’ career intentions, especially those which might impact on GP workforce availability over the next 5 years. Design: Census survey, conducted between April and June 2016 using postal and online responses , of all GPs on the National Health Service performers list and eligible to practise in primary care. Two reminders were used as necessary. Setting: South West England (population 3.5  million), a region with low overall socioeconomic deprivation. Participants: Eligible GPs were 2248 out of 3370 (67 % response rate). Main outcome measures: Reported likelihood of permanently leaving or reducing hours spent in direct patient care or of taking a career break within the next 5 years and present morale weighted for non-response. Results: Responders included 217 7 GPs engaged in patient care. Of these, 863 (37% weighted, 95%  CI 35 % to 39 %) reported a high likelihood of quitting direct patient care within the next 5 years. Overall, 1535 (70% weighted, 95%  CI 68 % to 72 %) respondents reported a career intention that would negatively impact GP workforce capacity over the next 5 years, through permanently leaving or reducing hours spent in direct patient care, or through taking a career break. GP age was an important predictor of career intentions; sharp increases in the proportion of GPs intending to quit patient care were evident from 52 years. Only 305 (14% weighted, 95%  CI 13 % to 16 %) reported high morale, while 1195 ( 54 % weighted, 95%  CI 52 % to 56 %) reported low morale. Low morale was particularly common among GP partners. Current morale strongly predicted GPs’ career intentions; those with very low morale were particularly likely to report intentions to quit patient care or to take a career break. Conclusions: A substantial majority of GPs in South West England report low morale. Many are considering career intentions which, if implemented, would adversely impact GP workforce capacity within a short time period. Study registration: NIHR HS&DR - 14/196/02, UKCRN ID 20700

Posterior Vitreous Detachment and the Posterior Hyaloid Membrane

PURPOSE: Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise anatomic definition. We investigated the morphologic appearance and molecular composition of the posterior hyaloid membrane to determine whether the structure clinically observed enveloping the posterior vitreous surface after posterior vitreous detachment is a true basement membrane and to postulate its origin. Understanding the relationship between the vitreous (in both its attached and detached state) and the internal limiting membrane of the retina is essential to understanding the cause of rhegmatogenous retinal detachment and vitreoretinal interface disorders, as well as potential future prophylactic and treatment strategies. DESIGN: Clinicohistologic correlation study. PARTICIPANTS: Thirty-six human donor globes. METHODS: Vitreous bodies identified to have posterior vitreous detachment were examined with phase-contrast microscopy and confocal microscopy after immunohistochemically staining for collagen IV basement membrane markers, in addition to extracellular proteins that characterize the vitreoretinal junction (fibronectin, laminin) and vitreous gel (opticin) markers. The posterior retina similarly was stained to evaluate the internal limiting membrane. Findings were correlated to the clinical appearance of the posterior hyaloid membrane observed during slit-lamp biomicroscopy after posterior vitreous detachment and compared with previously published studies. MAIN OUTCOME MEASURES: Morphologic appearance and molecular composition of the posterior hyaloid membrane. RESULTS: Phase-contrast microscopy consistently identified a creased and distinct glassy membranous sheet enveloping the posterior vitreous surface, correlating closely with the posterior hyaloid membrane observed during slit-lamp biomicroscopy in patients with posterior vitreous detachment. Immunofluorescent confocal micrographs demonstrated the enveloping membranous structure identified on phase-contrast microscopy to show positive stain results for type IV collagen. Immunofluorescence of the residual intact internal limiting membrane on the retinal surface also showed positive stain results for type IV collagen. CONCLUSIONS: The results of this study provide immunohistochemical evidence that the posterior hyaloid membrane is a true basement membrane enveloping the posterior hyaloid surface. Because this membranous structure is observed only after posterior vitreous detachment, the results of this study indicate that it forms part of the internal limiting membrane when the vitreous is in its attached state

Workforce predictive risk modelling: development of a model to identify general practices at risk of a supply−demand imbalance

Objective: This study aimed to develop a risk prediction model identifying general practices at risk of workforce supply–demand imbalance. Design: This is a secondary analysis of routine data on general practice workforce, patient experience and registered populations (2012 to 2016), combined with a census of general practitioners’ (GPs’) career intentions (2016). Setting/Participants: A hybrid approach was used to develop a model to predict workforce supply–demand imbalance based on practice factors using historical data (2012–2016) on all general practices in England (with over 1000 registered patients n=6398). The model was applied to current data (2016) to explore future risk for practices in South West England (n=368). Primary outcome measure: The primary outcome was a practice being in a state of workforce supply–demand imbalance operationally defined as being in the lowest third nationally of access scores according to the General Practice Patient Survey and the highest third nationally according to list size per full-time equivalent GP (weighted to the demographic distribution of registered patients and adjusted for deprivation). Results: Based on historical data, the predictive model had fair to good discriminatory ability to predict which practices faced supply–demand imbalance (area under receiver operating characteristic curve=0.755). Predictions using current data suggested that, on average, practices at highest risk of future supply–demand imbalance are currently characterised by having larger patient lists, employing more nurses, serving more deprived and younger populations, and having considerably worse patient experience ratings when compared with other practices. Incorporating findings from a survey of GP’s career intentions made little difference to predictions of future supply–demand risk status when compared with expected future workforce projections based only on routinely available data on GPs’ gender and age. Conclusions: It is possible to make reasonable predictions of an individual general practice’s future risk of undersupply of GP workforce with respect to its patient population. However, the predictions are inherently limited by the data available