11 minute read
The post-antibiotic apocalypse is coming, warns WHO
The post-antibiotic apocalypse is coming, warns WHO
By isolating, naming, and concentrating the antibacterial substance secreted by a penicillium mould, Dr Alexander Fleming discovered the first modern antibiotic in 1928. Subsequently, numerous antibiotics have been developed that are used to cure infections caused by bacteria.
Advertisement
Some 17 years after his discovery, he warned that “microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out…. In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted”.
Unfortunately, Dr Fleming’s words proved to be prophetic. The World Health Organization (WHO) warns that antibiotic resistance (ABR) is rising to dangerously high levels in all parts of the world.
New resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases, states the WHO. A growing list of infections – such as pneumonia, tuberculosis, blood poisoning, gonorrhoea, and foodborne diseases – are becoming harder, and sometimes impossible, to treat as antibiotics become less effective.
Without urgent action, we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill, warns the WHO.
Key drivers of antibiotic resistance
It is estimated that 700 000 people die annually as a result of ABR, and this figure is set to rise to 10 million by 2050 if no action is taken, according to Farley et al.
An analysis of global antibiotic consumption from 2000–2015 showed a 65% increase in antibiotic use, largely in low- and middleincome countries including South Africa. More than 80% of antibiotics are used in the primary care setting.
Suboptimal use of antibiotics is a key driver of ABR. ARB is evident in a patient for one month following an antibiotic course and can last for up to 12 months. It is therefore crucial to prescribe the fewest number of antibiotic courses for the shortest possible period of time.
A South African retrospective medical record review by Gasson et al (2018) showed that only 45% of antibiotic prescriptions (654) adhered to guideline recommendations. Studies show poor guideline compliance for respiratory problems, urinary tract infections, tonsillitis, and acute diarrhoea.
Variables associated with poor compliance to prescribing included seniority of the clinician, prescriber workload, patient age, and area-level socioeconomic status.
Studies show that prescribing empiric therapy via guidelines was associated with a 35% relative risk reduction in mortality, and de-escalation in therapy was associated with a 56% relative risk reduction in mortality.
Using antibiotics incorrectly and inappropriately by not following guidelines can contribute to the development of resistance, as well as poor clinical outcomes including patient morbidity, warn Gasson et al.
Farley et al (2017) conducted a survey among South African clinicians (n=264) to determine their knowledge of, attudes to, and perceptions of ABR.
They found that 97.1% of primary care prescribers believe that antibiotics are overused in South Africa, while 95.8% believe that ABR is a significant problem and 66.5% feel pressurised by patients to prescribe antibiotics.
Knowledge scores among prescribers were suboptimal (median 5/7). Knowledge scores were highest in younger respondents compared to older prescribers. A possible reason for this, postulate Farley et al, is that older prescribers having lower knowledge scores could be lack of teaching on ABR at the time of their undergraduate medical training compared with more recent graduates.
A novel finding is that knowledge scores are associated with prescribing behaviours. Higher knowledge scores were associated with using narrow-spectrum antibiotics, understanding the potential harm antibiotics can cause, trying alternative strategies such as explaining to patients the disease features that should prompt follow-up, and explaining duration of symptoms.
Antimicrobial prescribing in South Africa
In 2012, the South African Antibiotic Stewardship Programme, a multidisciplinary group of experts across human and animal health, public and private health sectors, was formed to implement antimicrobial stewardship (AMS) programmes in hospitals and primary care.
Data published by Schellack et al (2017) showed a compound annual growth rate of -2% over three years within the private sector antibiotic market.
The majority of the classes showed a decrease, with a 20% reduction in the medium/ narrow-spectrum penicillin class. The dominant class with a market share of 35% remained the broad-spectrum penicillin oral class, however, this too declined by 2%.
According to the authors, it is concerning that the class of all other antibacterials comprising daptomycin, fusidic acid, linezolid, and tigecycline, grew at a rate of 16%.
This increase may be due to inappropriate use as first-line therapies, lack of awareness of appropriate prescribing, or simply a desire to use newer more expensive therapies driven by availability or marketing by the pharmaceutical industry, as well as possible increases in resistance.
In the public sector, a compound annual growth rate of 11% was reported overall. Substantial increases were observed in four classes: All other antibacterials (6876%), injectable fluoroquinolones (287%), injectable cephalosporins (169%), and broad spectrum penicillins oral (167%).
Nearly 80% of the public market share was derived from trimethoprim combinations (37%), medium/narrow-spectrum penicillin (22%), and broad-spectrum penicillin oral (20%).
AMS programmes cornerstone of improved antibiotic use
AMS is defined as ‘a coherent set of actions which promote using antimicrobials in ways that ensure sustainable access to effective therapy for all who need them’.
Robust AMS programmes are widely considered the cornerstone of improved antibiotic use to combat resistance. Surveillance and infection prevention and control are also critical.
Global efforts aimed at actively addressing the problem of the growing number of resistant organisms, are underway. These efforts are spearheaded by the WHO, the American Centres for Disease Control and Prevention, the European Centre for Disease Prevention and Control and multiple professional organisations.
As mentioned already, the South African AMS Programme was launched in 2014. The objective of the programme is to:
» Strengthen, coordinate, and institutionalise interdisciplinary efforts through national and health establishment level governance structures
» Improve the appropriate use of diagnostics to identify pathogens and guide treatment
» Optimise surveillance and early detection of antimicrobial resistances to enable reporting
» Enhance infection prevention and control of the spread of resistant microbes to patients in healthcare settings, wide-reaching vaccination programmes and improvements in water and sanitation
» Promote appropriate use of antimicrobials in human and animal health through antimicrobial stewardship.
How effective are AMS programmes?
Davey et al reported on a Cochrane Review of 221 studies of antibiotic prescribing practices for hospital inpatients, bundling interventions into restriction and enablement. The duration of antibiotic treatment decreased significantly by 1.95 days.
The risk of death was the same in both the intervention and control groups (11%). With AMS interventions, the length of stay was reduced by 1.12 days. Both enablement and restriction were independently associated with increased antibiotic policy compliance.
Campion and Scully specifically reviewed the literature evaluating optimisation and deescalation of antibiotics in the intensive care unit (ICU). Beneficial strategies identified for the ICU include employing empiric guidelines for antibiotic use, collecting appropriate specimens and using molecular diagnostics, optimizing antibiotic dosing, and reducing the total therapy duration.
Empiric antibiotic therapy in sepsis should be directed at the suspected location of infection and known risk factors, such as immunosuppression and prior antibiotic exposure, not solely on providing grampositive, gram-negative, Pseudomonas, and methicillin-resistant Staphylococcus aureus (MRSA) coverage.
Prior IV antibiotic use, poor functional status, and comorbid conditions may increase the risks of multidrug-resistant organisms. Dual gram-negative coverage (the use of two agents with different mechanisms of action) for empiric coverage of infection, particularly in patients at risk for resistant organisms or reduced susceptibility, may be a useful strategy in critically ill patients, particularly when the susceptibility pattern for antipseudomonal beta-lactam antibiotics is <90%. A betalactam plus aminoglycoside may provide better empiric coverage over beta-lactam alone or beta-lactam plus fluoroquinolone.
Locally, Brink et al reported that a pharmacist-driven intervention resulted in a significant reduction in antibiotic use from 101.38 DDD/100 patient–days to 83.04 DDD/100 patient–days.
Boyles et al reported a decrease in antibiotic consumption from 592.0DDD/1000 patient days to 475.8DDD/1000 patient days, and cost savings of R373 620 – a reduction of 35%. A follow up study by the same authors reported sustained reduction in antibiotic consumption (1046 DDD/1000 patient days to 868 DDD/1000 patient days over a two-year period), amounting to a cost savings of R3.2m over four years.
How can antimicrobial stewardship be improved in South Africa?
A recently published study, which included South African doctors, found that there was a lack of consensus among prescribers about what constitutes inappropriate use. Inappropriate use is generally considered as prescribing antibiotics in the absence of bacterial infection.
But according to the authors, doctors frame antibiotic use not just in clinical, but also in moral and contextual terms. They recommend drawing up more specific definitions because judgements about appropriateness are morally and contextually framed.
They also strongly recommend that stewardship interventions should directly target behaviour change. According to Farley et al, their finding that knowledge scores are associated with positive prescribing behaviours suggests that improved education and training is likely to be an important intervention to address ABR in primary care prescribers.
Many prescribers (87.5%) wished to have more education on the appropriate use of antibiotics and would value clearer guidelines to improve their antibiotic prescribing in hard copy (80.2%), on smart phone apps (79.7%) or on interactive internet platforms (74.7%).
Intervention strategies should focus on prescribers in the over-55 age group, and efforts should focus on patient education and patient-prescriber relationships to try to minimise the pressure placed on prescribers to prescribe when not necessary.
Interventions can include developing communication aids for prescriber/patient interactions, as 90.4% of prescribers requested education resource aids for discussions on ABR with patients.
This would assist with issues of confusion when explaining the difference between viral and bacterial infections that have arisen in similar studies. The majority (96.2%) of prescribers requested data on local resistance patterns, which opens up an opportunity to improve prescribing by introducing systems to supply up-to-date data on these.
Who is responsible for antimicrobial stewardship?
Roleplayers in the AMS programme: . Example actions:
Roleplayers in the AMS programme: Prescriber . Example actions: • Making accurate diagnoses • Following local antimicrobial guidelines • Regularly reviewing the need for therapy
Roleplayers in the AMS programme: Nurse. Example actions: • Taking cultures at appropriate times • Ensuring patients understand how to take antimicrobials on discharge
Roleplayers in the AMS programme: Microbiologist. Example actions: • Has a diagnostic, consultative, and advisory role, which extends into AMS activities • Following microbiological confirmation of infection, the clinical microbiologist is able to advise on appropriate antimicrobial therapy based on antimicrobial susceptibility results • Able to make informed decisions about empirical antimicrobial therapy based on pathogen surveillance and AMR trends/patterns at a given institution over a period of time
Roleplayers in the AMS programme: Pharmacist. Example actions: • Monitoring the choice of antibiotic, duration, indication for use • Reconciliation with biomarkers and patient clinical picture and diagnosis • Analysis of the consumption and total costs of the antibiotics used
Roleplayers in the AMS programme: Patient. Example actions: • Taking antimicrobial courses as recommended by the prescriber • Not storing or using leftover antimicrobials
Roleplayers in the AMS programme: Antimicrobial stewardship team. Example actions: • Developing guidelines for antimicrobial use • Supporting audit and feedback for prescribers • Educating prescribers
Roleplayers in the AMS programme: Hospital governance. Example actions: • Ensuring sufficient sustainable and dedicated funding for antimicrobial stewardship teams • Monitoring antimicrobial use and resistance • Investing in a Clinical Decision Support System • Enabling formulary restrictions
Roleplayers in the AMS programme: Pharmaceutical company. Example actions: • Limiting advertising of antimicrobials, especially broad spectrum • Helping ensure there is a continuous supply of antimicrobials
Roleplayers in the AMS programme: National policy maker. Example actions: • Prioritising and funding antimicrobial stewardship activities • Supporting the use of quality metrics and pay for performance
References
Boyles TH, Whitelaw A, Bamford C et al. Antibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or re-admission rates. PloS One, 2013.
Boyles TH, Naicker V, Rawoot N et al. Sustained reduction in antibiotic consumption in a South African public sector hospital: four-year outcomes from the Groote Schuur hospital antibiotic stewardship programme. S Afr Med J, 2017.
Chetty S, Reddy M, Ramsamy Y et al. Antimicrobial stewardship in South Africa: a scoping review of the published literature. JAC-Antimicrobial Resistance, 2019.
Farley E, Steward A, Davies MA et al. Antibiotic use and resistance: Knowledge, attitudes and perceptions among primary care prescribers in South Africa. SAMJ, 2017.
Dyar OJ, Hutter B, Schouten J et al. What is antimicrobial stewardship? CMI, 2017.
Gasson J, Blockman M and Willems B. Antibiotic prescribing practice and adherence to guidelines in primary care in the Cape Town Metro district, South Africa. S Afr Med J, 2018.
Manderson L. Prescribing, care and resistance: antibiotic use in urban South Africa. Humanities and Social Sciences Communications, 2020.
Schellack N, Benjamin D and Brink A. A situational analysis of current antimicrobial governance, regulation, and utilization in South Africa. Journal of Infectious Diseases, 2017.
Tarrant C, Krockow EM, Nakkawita WMID et al. Moral and Contextual Dimensions of Inappropriate” Antibiotic Prescribing in Secondary Care: A Three- Country Interview Study. Front Sociol, 2020. SF
