Scientists stumble across new method of making antibiotics

Cancer researchers may have stumbled across a solution to reverse antibiotic drug resistance and stop infections like MRSA. | Via ScienceDaily

Experts warn we are decades behind in the race against superbugs having already exploited naturally occurring antibiotics, with the creation of new ones requiring time, money and ingenuity.

But a team of scientists at the University of Salford say they may have found a very simple way forward — even though they weren’t even looking for antibiotics.

And they have created and validated several new antibiotics already — many of which are as potent, or more so, than standard antibiotics, such as amoxicillin.

“A little like Alexander Fleming, we weren’t even looking for antibiotics rather researching into new compounds that might be effective against cancer stem cells,” explains Michael P. Lisanti, Chair of Translational Medicine at the University’s Biomedical Research Centre.

“I think we’ve accidentally invented a systemic way of creating new antibiotics which is simple, cheap and could be very significant in the fight against superbugs,” added Dr Federica Sotgia, a co-author on the study.

Full story at ScienceDaily

Full reference:  Bela Ozsvari et al.  Mitoriboscins: Mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast | Oncotarget, Advance Publications | published online July 7th 2017

Reducing antibiotic prescribing for children presenting to primary care with acute respiratory tract infection

Blair, P.S. et al. (2017) BMJ Open. 7:e014506

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Objective: To investigate recruitment and retention, data collection methods and the acceptability of a ‘within-consultation’ complex intervention designed to reduce antibiotic prescribing.

Conclusion: Differential recruitment may explain the paradoxical antibiotic prescribing rates. Future cluster level studies should consider designs which remove the need for individual consent postrandomisation and embed the intervention within electronic primary care records.

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Giving immediate antibiotics reduces deaths from sepsis

Giving immediate antibiotics (defined as within one hour) when people present to emergency departments with suspected sepsis reduces their risk of dying by a third compared with later administration. 

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This meta-analysis of observational data from 23,596 people in emergency department settings confirmed that giving antibiotics within one hour was linked to a lower risk of in-hospital mortality compared with giving antibiotics later.

This adds weight to recommendations from NICE and other organisations that antibiotics should be administered straight away in people with suspected sepsis. However, in practice up to a third of people in the UK do not receive antibiotics within the hour.

NHS England and the UK Sepsis Trust have recently launched a campaign to encourage all healthcare professionals to act quickly when they recognise sepsis.

Full reference: Johnston AN, Park J, Doi SA, et al. Effect of immediate administration of antibiotics in patients with sepsis in tertiary care: a systematic review and meta-analysis. Clinical Therapeutics.  2017;39(1):190-202.e6.

Interventions to improve antibiotic prescribing practices for hospital inpatients

Davey, P. et al. Cochrane Database of Systematic Reviews 2017, Issue 2. Art. No.: CD003543.

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Image source: Cochrane

Background: Antibiotic resistance is a major public health problem. Infections caused by multidrug-resistant bacteria are associated with prolonged hospital stay and death compared with infections caused by susceptible bacteria. Appropriate antibiotic use in hospitals should ensure effective treatment of patients with infection and reduce unnecessary prescriptions. We updated this systematic review to evaluate the impact of interventions to improve antibiotic prescribing to hospital inpatients.

Objectives: To estimate the effectiveness and safety of interventions to improve antibiotic prescribing to hospital inpatients and to investigate the effect of two intervention functions: restriction and enablement.

Authors’ conclusions:  We found high-certainty evidence that interventions are effective in increasing compliance with antibiotic policy and reducing duration of antibiotic treatment. Lower use of antibiotics probably does not increase mortality and likely reduces length of stay. Additional trials comparing antibiotic stewardship with no intervention are unlikely to change our conclusions. Enablement consistently increased the effect of interventions, including those with a restrictive component. Although feedback further increased intervention effect, it was used in only a minority of enabling interventions. Interventions were successful in safely reducing unnecessary antibiotic use in hospitals, despite the fact that the majority did not use the most effective behaviour change techniques. Consequently, effective dissemination of our findings could have considerable health service and policy impact. Future research should instead focus on targeting treatment and assessing other measures of patient safety, assess different stewardship interventions, and explore the barriers and facilitators to implementation. More research is required on unintended consequences of restrictive interventions.

Read the full review here

Effects of control interventions on Clostridium difficile infection in England

Dingle, K.E. et al. The Lancet Infectious Diseases. Published online: 24 January 2017

A colour-enhanced scanning electron micrograph image showing a cluster of Clostridium difficile on a surface.
Image source: Annie Cavanagh – Wellcome Images // CC BY-NC-ND 4.0

A colour-enhanced scanning electron micrograph image showing a cluster of Clostridium difficile on a surface.

Background: The control of Clostridium difficile infections is an international clinical challenge. The incidence of C difficile in England declined by roughly 80% after 2006, following the implementation of national control policies; we tested two hypotheses to investigate their role in this decline. First, if C difficile infection declines in England were driven by reductions in use of particular antibiotics, then incidence of C difficile infections caused by resistant isolates should decline faster than that caused by susceptible isolates across multiple genotypes. Second, if C difficile infection declines were driven by improvements in hospital infection control, then transmitted (secondary) cases should decline regardless of susceptibility.

Interpretation: Restricting fluoroquinolone prescribing appears to explain the decline in incidence of C difficile infections, above other measures, in Oxfordshire and Leeds, England. Antimicrobial stewardship should be a central component of C difficile infection control programmes.

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Supporting better decision making for acute infection management in secondary care

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Background

The inappropriate use of antimicrobials drives antimicrobial resistance. We conducted a study to map physician decision-making processes for acute infection management in secondary care to identify potential targets for quality improvement interventions.

Methods

Physicians newly qualified to consultant level participated in semi-structured interviews. Interviews were audio recorded and transcribed verbatim for analysis using NVIVO11.0 software. Grounded theory methodology was applied. Analytical categories were created using constant comparison approach to the data and participants were recruited to the study until thematic saturation was reached.

Results

Twenty physicians were interviewed. The decision pathway for the management of acute infections follows a Bayesian-like step-wise approach, with information processed and systematically added to prior assumptions to guide management. The main emerging themes identified as determinants of the decision-making of individual physicians were (1) perceptions of providing ‘optimal’ care for the patient with infection by providing rapid and often intravenous therapy; (2) perceptions that stopping/de-escalating therapy was a senior doctor decision with junior trainees not expected to contribute; and (3) expectation of interactions with local guidelines and microbiology service advice. Feedback on review of junior doctor prescribing decisions was often lacking, causing frustration and confusion on appropriate practice within this cohort.

Conclusion

Interventions to improve infection management must incorporate mechanisms to promote distribution of responsibility for decisions made. The disparity between expectations of prescribers to start but not review/stop therapy must be urgently addressed with mechanisms to improve communication and feedback to junior prescribers to facilitate their continued development as prudent antimicrobial prescribers.

Full reference: Timothy Miles Rawson, T. M. et al: Mapping the decision pathways of acute infection management in secondary care among UK medical physicians: a qualitative study BMC Medicine 2016 14:208

Antibiotic prescribing and resistance

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Public Health England has published English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) report 2016.

The ESPAUR report includes national data on antibiotic prescribing and resistance, and hospital antimicrobial stewardship implementation. It forms a standard against which antimicrobial use and antimicrobial resistance can be compared in successive years and a resource for commissioning and implementing antimicrobial stewardship policies in England.

Additional link: PHE press release

Using a simple point-prevalence survey to define appropriate antibiotic prescribing in hospitalised children across the UK

Gharbi, M. et al. BMJ Open. 6:e012675

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Background: The National Health Service England, Commissioning for Quality and Innovation for Antimicrobial Resistance (CQUIN AMR) aims to reduce the total antibiotic consumption and the use of certain broad-spectrum antibiotics in secondary care. However, robust baseline antibiotic use data are lacking for hospitalised children. In this study, we aim to describe, compare and explain the prescription patterns of antibiotics within and between paediatric units in the UK and to provide a baseline for antibiotic prescribing for future improvement using CQUIN AMR guidance.

Methods: We conducted a cross-sectional study using a point prevalence survey (PPS) in 61 paediatric units across the UK. The standardised study protocol from the Antibiotic Resistance and Prescribing in European Children (ARPEC) project was used. All inpatients under 18 years of age present in the participating hospital on the day of the study were included except neonates.

Results: A total of 1247 (40.9%) of 3047 children hospitalised on the day of the PPS were on antibiotics. The proportion of children receiving antibiotics showed a wide variation between both district general and tertiary hospitals, with 36.4% ( 95% CI 33.4% to 39.4%) and 43.0% (95% CI 40.9% to 45.1%) of children prescribed antibiotics, respectively. About a quarter of children on antibiotic therapy received either a medical or surgical prophylaxis with parenteral administration being the main prescribed route for antibiotics (>60% of the prescriptions for both types of hospitals). General paediatrics units were surprisingly high prescribers of critical broad-spectrum antibiotics, that is, carbapenems and piperacillin-tazobactam.

Conclusions: We provide a robust baseline for antibiotic prescribing in hospitalised children in relation to current national stewardship efforts in the UK. Repeated PPS with further linkage to resistance data needs to be part of the antibiotic stewardship strategy to tackle the issue of suboptimal antibiotic use in hospitalised children.

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Patient engagement with infection management in secondary care

Rawson, T.M. et al. BMJ Open. 6:e011040

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Objective: To understand patient engagement with decision-making for infection management in secondary care and the consequences associated with current practices.

Design: A qualitative investigation using in-depth focus groups.

Participants: Fourteen members of the public who had received antimicrobials from secondary care in the preceding 12 months in the UK were identified for recruitment. Ten agreed to participate. All participants had experience of infection management in secondary care pathways across a variety of South-East England healthcare institutes. Study findings were subsequently tested through follow-up focus groups with 20 newly recruited citizens.

Results: Participants reported feelings of disempowerment during episodes of infection in secondary care. Information is communicated in a unilateral manner with individuals ‘told’ that they have an infection and will receive an antimicrobial (often unnamed), leading to loss of ownership, frustration, anxiety and ultimately distancing them from engaging with decision-making. This poor communication drives individuals to seek information from alternative sources, including online, which is associated with concerns over reliability and individualisation. Failures in communication and information provision by clinicians in secondary care influence individuals’ future ideas about infections and their management. This alters their future actions towards antimicrobials and can drive prescription non-adherence and loss to follow-up.

Conclusions: Current infection management and antimicrobial prescribing practices in secondary care fail to engage patients with the decision-making process. Secondary care physicians must not view infection management episodes as discrete events, but as cumulative experiences which have the potential to shape future patient behaviour and understanding of antimicrobial use.

Read the full article here