NIHR Signal Carefully managed antibiotic use could halve antibiotic-resistant infections

Published on 17 October 2017

Antibiotic stewardship programmes could halve the number of infections due to antibiotic-resistant bacteria compared with unguided prescribing. Combining these programmes with hand hygiene, such as washing hands with soap and water and using alcohol-based hand-rubs, could reduce antibiotic resistance further.

Bacterial resistance to existing antibiotics is increasing, and for some conditions, there aren’t enough new antibiotics available to treat infections caused by resistant bacteria.

Antibiotic stewardship involves promoting the appropriate use of antibiotics according to local resistance patterns and aims to give patients the right antibiotics for the right length of time and at the correct dose, reducing the unnecessary use of antibiotics.

Limitations of this review were that only 32 studies, half of all the studies found, could be combined in the analysis and some of the studies were over 20 years old.

Nevertheless, it highlights that antibiotic stewardship is effective and needs to be implemented across all care settings.

Carefully managed antibiotic use could halve antibiotic-resistant infections

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Why was this study needed?

Bacterial resistance to antibiotics is increasing in England. MRSA (methicillin-resistant Staphylococcus aureus) bloodstream infections increased by 15% in primary care between 2014 and 2015. Gram-negative bacteria such as Pseudomonas aeruginosa are also becoming more resistant.

Use of antibiotics can also lead to diarrhoea due to the selection of resistant bacteria in the gut, such as Clostridium difficile, and this can progress to very serious illness.

Antibiotic stewardship programmes have been shown to reduce antibiotic use and hospital costs. This is the first systematic review of the available evidence on the reduction of infections due to resistant bacteria and reducing the presence of those bacteria.

What did this study do?

This systematic review and meta-analysis included 76 studies of antibiotic stewardship programmes conducted in 20 countries. The programmes were assessed for between one and 12 years. Most (53%) were before and after studies.

Stewardship programmes included restricting antibiotic use, implementing guidelines, providing feedback, education, and systems to support decision-making. Other strategies included protocols for regular changes of first-line antibiotics for certain infections.

Some schemes were combined with procedures for controlling the spread of infections, such as hand hygiene.

The review only included two studies from the UK. There was significant variation between studies so the pooled results need to be interpreted with some caution.

What did it find?

  • Stewardship programmes appear to halve the incidence of multi-drug resistant gram-negative bacteria (51% reduction, incidence ratio [IR] 0.49, 95% CI 0.35 to 0.68). The researchers identified 598 infections during 3,551,589 bed days before stewardship programmes were in place compared to 374 infections during 3,579,045 bed days after implementation.
  • Stewardship programmes also appear to reduce the incidence of extended spectrum beta-lactamase producing gram-negative bacteria such as Escherichia coli by 48% (IR 0.52, 95% CI 0.27 to 0.98), MRSA by 37% (IR 0.63, 95% CI 0.45 to 0.88) and Clostridium difficile by 32% (IR 0.68, 95% CI 0.53 to 0.88).
  • Stewardship programmes alone may reduce overall antibiotic resistance by 19% (IR 0.81, 0.67-0.97). Combining stewardship programmes with procedures for controlling infection appears to reduce antibiotic resistance by 31% (IR 0.69, 95% CI 0.54 to 0.88).
  • Combining stewardship programmes with hand-hygiene appears to be the most effective combination, reducing antibiotic resistance by 66% (IR 0.34, 95% CI 0.21 to 0.54).
  • Interventions seemed to be more effective in haematology/oncology, although there were only three studies in this setting.

What does current guidance say on this issue?

NICE guidelines from 2015 recommend that commissioners and healthcare providers should establish an antibiotic stewardship programme across all care settings. This should include monitoring antimicrobial prescribing, local resistance patterns and incidence of concerning infections such as Clostridium difficile. They are in the process of producing 30 guidelines on when to prescribe antibiotics for conditions such as sinusitis, sore throat and urinary tract infections.

NICE 2017 guidance recommends that Clinical Commissioning Groups ensure resources and advice are also available for people who are prescribed or supplied with antimicrobials, to ensure they take them as instructed by their healthcare professional.

What are the implications?

This review supports current NICE guidance that commissioners should establish antibiotic stewardship programmes in hospitals and primary care.

Combining stewardship programmes with hand-hygiene measures appear to be more effective than stewardship programmes alone.

The barriers to implementing stewardship include a lack of resources (for example, the need for staff and funding), patients’ expectations about receiving antibiotics, and the influence of colleagues on the choice of antibiotics.

Healthcare providers should continue to prescribe antibiotics only when there is a clear clinical need and not for mild, self-limiting conditions such as coughs and sore throats.

Citation and Funding

Baur D, Gladstone BP, Burkert F, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17(9):990-1001.

This study was funded by the German Centre for Infection Research (grant agreement number D.20.07860).

Bibliography

Department of Health. Annual Report of the Chief Medical Officer. Volume Two. 2011. Infections and the rise of antimicrobial resistance. London: Department of Health; 2013.

Department of Health. Department of Environment Food and Rural Affairs. UK Five Year Antimicrobial Resistance Strategy. 2013 to 2018. London: Department of Health; 2013.

NHS Choices. Antibiotics. London: Department of Health; 2016.

NHS Choices. MRSA. London: Department of Health; 2015.

NICE Antimicrobial stewardship: changing risk-related behaviours in the general population. NG 63. London: National Institute for Health and Care Excellence; 2017.

NICE Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use. NG 15. London: National Institute for Health and Care Excellence; 2015.

NICE. Key Therapeutic Topic 9. Antimicrobial stewardship: prescribing antibiotics. London: National Institute for Health and Care Excellence; 2017.

Public Health England. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR). Report 2016. London: Public Health England; 2016.

Public Health England. Managing common infections: guidance for consultation and adaptation. London: Public Health England; 2017.

Public Health England.  Quarterly Epidemiological  Commentary: Mandatory MRSA, MSSA and E. coli bacteraemia, and  C. difficile infection data (up to April-June 2016 ) London: Public Health England; 2016.

Why was this study needed?

Bacterial resistance to antibiotics is increasing in England. MRSA (methicillin-resistant Staphylococcus aureus) bloodstream infections increased by 15% in primary care between 2014 and 2015. Gram-negative bacteria such as Pseudomonas aeruginosa are also becoming more resistant.

Use of antibiotics can also lead to diarrhoea due to the selection of resistant bacteria in the gut, such as Clostridium difficile, and this can progress to very serious illness.

Antibiotic stewardship programmes have been shown to reduce antibiotic use and hospital costs. This is the first systematic review of the available evidence on the reduction of infections due to resistant bacteria and reducing the presence of those bacteria.

What did this study do?

This systematic review and meta-analysis included 76 studies of antibiotic stewardship programmes conducted in 20 countries. The programmes were assessed for between one and 12 years. Most (53%) were before and after studies.

Stewardship programmes included restricting antibiotic use, implementing guidelines, providing feedback, education, and systems to support decision-making. Other strategies included protocols for regular changes of first-line antibiotics for certain infections.

Some schemes were combined with procedures for controlling the spread of infections, such as hand hygiene.

The review only included two studies from the UK. There was significant variation between studies so the pooled results need to be interpreted with some caution.

What did it find?

  • Stewardship programmes appear to halve the incidence of multi-drug resistant gram-negative bacteria (51% reduction, incidence ratio [IR] 0.49, 95% CI 0.35 to 0.68). The researchers identified 598 infections during 3,551,589 bed days before stewardship programmes were in place compared to 374 infections during 3,579,045 bed days after implementation.
  • Stewardship programmes also appear to reduce the incidence of extended spectrum beta-lactamase producing gram-negative bacteria such as Escherichia coli by 48% (IR 0.52, 95% CI 0.27 to 0.98), MRSA by 37% (IR 0.63, 95% CI 0.45 to 0.88) and Clostridium difficile by 32% (IR 0.68, 95% CI 0.53 to 0.88).
  • Stewardship programmes alone may reduce overall antibiotic resistance by 19% (IR 0.81, 0.67-0.97). Combining stewardship programmes with procedures for controlling infection appears to reduce antibiotic resistance by 31% (IR 0.69, 95% CI 0.54 to 0.88).
  • Combining stewardship programmes with hand-hygiene appears to be the most effective combination, reducing antibiotic resistance by 66% (IR 0.34, 95% CI 0.21 to 0.54).
  • Interventions seemed to be more effective in haematology/oncology, although there were only three studies in this setting.

What does current guidance say on this issue?

NICE guidelines from 2015 recommend that commissioners and healthcare providers should establish an antibiotic stewardship programme across all care settings. This should include monitoring antimicrobial prescribing, local resistance patterns and incidence of concerning infections such as Clostridium difficile. They are in the process of producing 30 guidelines on when to prescribe antibiotics for conditions such as sinusitis, sore throat and urinary tract infections.

NICE 2017 guidance recommends that Clinical Commissioning Groups ensure resources and advice are also available for people who are prescribed or supplied with antimicrobials, to ensure they take them as instructed by their healthcare professional.

What are the implications?

This review supports current NICE guidance that commissioners should establish antibiotic stewardship programmes in hospitals and primary care.

Combining stewardship programmes with hand-hygiene measures appear to be more effective than stewardship programmes alone.

The barriers to implementing stewardship include a lack of resources (for example, the need for staff and funding), patients’ expectations about receiving antibiotics, and the influence of colleagues on the choice of antibiotics.

Healthcare providers should continue to prescribe antibiotics only when there is a clear clinical need and not for mild, self-limiting conditions such as coughs and sore throats.

Citation and Funding

Baur D, Gladstone BP, Burkert F, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17(9):990-1001.

This study was funded by the German Centre for Infection Research (grant agreement number D.20.07860).

Bibliography

Department of Health. Annual Report of the Chief Medical Officer. Volume Two. 2011. Infections and the rise of antimicrobial resistance. London: Department of Health; 2013.

Department of Health. Department of Environment Food and Rural Affairs. UK Five Year Antimicrobial Resistance Strategy. 2013 to 2018. London: Department of Health; 2013.

NHS Choices. Antibiotics. London: Department of Health; 2016.

NHS Choices. MRSA. London: Department of Health; 2015.

NICE Antimicrobial stewardship: changing risk-related behaviours in the general population. NG 63. London: National Institute for Health and Care Excellence; 2017.

NICE Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use. NG 15. London: National Institute for Health and Care Excellence; 2015.

NICE. Key Therapeutic Topic 9. Antimicrobial stewardship: prescribing antibiotics. London: National Institute for Health and Care Excellence; 2017.

Public Health England. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR). Report 2016. London: Public Health England; 2016.

Public Health England. Managing common infections: guidance for consultation and adaptation. London: Public Health England; 2017.

Public Health England.  Quarterly Epidemiological  Commentary: Mandatory MRSA, MSSA and E. coli bacteraemia, and  C. difficile infection data (up to April-June 2016 ) London: Public Health England; 2016.

Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis

Published on 21 June 2017

Baur, D.,Gladstone, B. P.,Burkert, F.,Carrara, E.,Foschi, F.,Dobele, S.,Tacconelli, E.

Lancet Infect Dis , 2017

BACKGROUND: Antibiotic stewardship programmes have been shown to reduce antibiotic use and hospital costs. We aimed to evaluate evidence of the effect of antibiotic stewardship on the incidence of infections and colonisation with antibiotic-resistant bacteria. METHODS: For this systematic review and meta-analysis, we searched PubMed, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Web of Science for studies published from Jan 1, 1960, to May 31, 2016, that analysed the effect of antibiotic stewardship programmes on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infections in hospital inpatients. Two authors independently assessed the eligibility of trials and extracted data. Studies involving long-term care facilities were excluded. The main outcomes were incidence ratios (IRs) of target infections and colonisation per 1000 patient-days before and after implementation of antibiotic stewardship. Meta-analyses were done with random-effect models and heterogeneity was calculated with the I2 method. FINDINGS: We included 32 studies in the meta-analysis, comprising 9 056 241 patient-days and 159 estimates of IRs. Antibiotic stewardship programmes reduced the incidence of infections and colonisation with multidrug-resistant Gram-negative bacteria (51% reduction; IR 0.49, 95% CI 0.35-0.68; p<0.0001), extended-spectrum beta-lactamase-producing Gram-negative bacteria (48%; 0.52, 0.27-0.98; p=0.0428), and meticillin-resistant Staphylococcus aureus (37%; 0.63, 0.45-0.88; p=0.0065), as well as the incidence of C difficile infections (32%; 0.68, 0.53-0.88; p=0.0029). Antibiotic stewardship programmes were more effective when implemented with infection control measures (IR 0.69, 0.54-0.88; p=0.0030), especially hand-hygiene interventions (0.34, 0.21-0.54; p<0.0001), than when implemented alone. Antibiotic stewardship did not affect the IRs of vancomycin-resistant enterococci and quinolone-resistant and aminoglycoside-resistant Gram-negative bacteria. Significant heterogeneity between studies was detected, which was partly explained by the type of interventions and co-resistance patterns of the target bacteria. INTERPRETATION: Antibiotic stewardship programmes significantly reduce the incidence of infections and colonisation with antibiotic-resistant bacteria and C difficile infections in hospital inpatients. These results provide stakeholders and policy makers with evidence for implementation of antibiotic stewardship interventions to reduce the burden of infections from antibiotic-resistant bacteria. FUNDING: German Center for Infection Research.

Expert commentary

The daily practice of antibiotic stewardship and infection control can be a daunting and uphill task. Advocates of antibiotic stewardship constantly need to appeal to senior management to sanction funding and to convince prescribers that patients are not being put at risk.

Systematic reviews and meta-analyses such as this provide valuable scientific evidence that the daily grind of antibiotic stewardship is worth the effort. The review demonstrates that the practice is still the preserve of high-income countries in the majority.

Perhaps studies like this will galvanise efforts in low and middle-income countries where antibiotic stewardship can have far-reaching effects.

Dr Nandini Shetty, Consultant Microbiologist, Public Health England and University College London Hospitals