Facility-level Interventions

Use of South African guidelines for antimicrobial prescribing
Pre-prescription authorisation and/or prospective audit and feedback
The key components of an antimicrobial prescription chart

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These are interventions that occur across the units within a facility and will form part of the AMS policy of the hospital, determined by the HAMSC under consultation with their prescribers and staff.

Use of South African guidelines for antimicrobial prescribing

The use of guideline-adherent empirical antimicrobial therapy is associated with reduced mortality in hospitals²⁸, as well as other benefits including shorter duration of hospitalisation and fewer adverse events. Each HAMSC should adopt locally relevant antimicrobial prescribing guidelines for use at their facility. These guidelines could relate to specific infections (for example, the published South African guidelines on community-acquired pneumonia or meningitis) or could be adapted from existing guidelines such as the Standard Treatment Guidelines (STGs) and Essential medicines List (EML)²⁹ or from the South African Antimicrobial Stewardship Programme (SAASP) antibiotic guidelines³⁰ to include the most relevant infection syndromes encountered at the facility, and to incorporate local cumulative antibiograms, which describes the antimicrobial sensitivity rates for the organisms cultured, if available (see Annexure F for examples).

The diagnostic laboratory that processes microbiology specimens for the hospital, should generate these local cumulative antibiograms. This can be done either for the facility as a whole or focused on specific units or broad hospital subdivisions level (e.g. intensive care, medical, surgery, paediatrics, obstetrics and gynaecology) based on the size and complexity of the facility. These reports should include as a minimum:

• The frequency and relative frequency (percentage) of pathogens isolated from  blood culture, urine and respiratory tract specimens;
• Antibacterial susceptibility results stratified by pathogen (e.g. Enterobacteriaceae, non-fermenting Gram-negative bacilli) or pathogens from the ESKAPE group (i.e. Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.);
• Antifungal susceptibility results for Candida species.

The development and use of local guidelines should be coupled with a dissemination and communication plan and an implementation strategy for all health care providers and prescribers, so that prescribing practices are standardised at each facility. This could include induction and training for all current and new prescribers, making the guidelines available as a summary or in the form of clinical pathways, and the use of guidelines during ward rounds and in the pharmacy.

Pre-prescription authorisation and/or prospective audit and feedback

These strategies improve antimicrobial utilisation and reduce AMR, without negative impacts on patient outcomes, and are recommended as core components of AMS programmes, either as a single strategy or in combination.^31,32

AWaRe Antibiotics List

In June 2017, the WHO categorized antibiotics in the Essential Medicine List into three sections - Access, Watch and Reserve - with recommendations on when each category should be used.   WHO recommends that antibiotics in the Access group to be available always, as  this includes 1st and 2nd line treatments for a wide range of common infections, like amoxicillin, a widely used antibiotic to treat infections such as pneumonia.   The Watch group includes antibiotics that should be dramatically reduced to avoid further development of resistance. For example, the use of ciprofloxacin, used to treat cystitis and upper respiratory tract infections (such as bacterial sinusitis and bacterial bronchitis), The third group, Reserve, includes antibiotics such as colistin and some cephalosporins that should be considered last-resort options, and used only in the most severe circumstances when all other alternatives have failed, such as life-threatening infections due to multidrug-resistant bacteria

Pre-Prescription Authorisation (PPA)  requires justification from clinicians to obtain approval for certain antibiotics prior to prescribing (so called ‘restrictive’ policy). Whilst this strategy can be very effective in reducing overuse, it is also considered the most difficult for prescribers to comply with due the additional administrative burden required to get authorisation, the potential delay in initiating critical therapy and the overuse of unrestricted antibiotics. This strategy can only be effective if built together with the clinicians who will be prescribing and tested using repeated PDSA cycles to find the most appropriate way to perform PPA.³³

Specific areas such as Intensive Care Units and specific conditions can be exempt from pre-authorization.

Determination of the antibiotics to be pre-authorised may be based upon the AMR concerns of the facility, the antibiotics with high consumption or antibiotics considered “watch” or “reserve” by WHO³⁴ (see AWaRe antibiotics list) or last resort antibiotics such as carbapenems and colistin.

Prospective Audit and Feedback (PAF) is a method that allows the AMS programme to interact directly with prescribers in order to tailor specific antibiotic therapy for each patient. These strategies are employed after the initial prescribing and dispensing of the antibiotic (so-called ‘persuasive’ policy). This strategy has seen reduction in antimicrobial use and resistance with no negative impact on patient outcomes and has been used effectively in the public³⁵ and private sectors^36,37 in South Africa. The pharmacist or the AMS team in consultation with the prescriber can drive this audit and feedback process. To be successful, the PAF strategy needs to be built on top of an effective communication plan and good relationship between prescribers and pharmacists. It can occur at the bedside during the AMS team ward rounds or at the point of dispensing at the pharmacy during the script reviews.

Each strategy offers advantages and disadvantages, and their implementation is dependent on the resources and needs of each facility and should be determined in consultation with the prescribers, pharmacists and nurses. The table below gives practical examples for using PPA and PAF.

Example	Pre-Prescription Authorisation (PPA)	Prospective Audit & Feedback (PAF)
1	Restrict use of all carbapenem antibiotics until authorisation by pharmacist according to guidelines.	Regular bedside ward rounds by AMS team to review prescription charts for carbapenems and other reserve antibiotics.
2	Require clear diagnosis before release of ceftriaxone by pharmacist.	Regular chart reviews and feedback by pharmacist.
3	Restriction of cefazolin to pre-operative prophylaxis (unless motivated for).	All antibiotics stopped by pharmacist on day 5 or 7 unless specifically motivated to extend.
4	Restriction of echinocandins for specialist use in invasive candidiasis resistant to fluconazole or Amphotericin B.	Echinocandin prescribed for an additional duration of 14 days after the first negative blood culture.

The specific strategy should be discussed at the level of the HAMSC and implemented by the AMS team.

Enabling tools for PPA and PAF

An important enabling tool for PAF and PPA is the use of a dedicated antimicrobial prescription chart (see Annexure G), and AMS programmes are strongly encouraged to implement this. These can be either a standalone dedicated chart purely for antibiotic prescriptions, or can be integrated into the general prescription chart, or may consist of an antimicrobial plan which is documented in the patient’s file including all the key components described below.³⁸ Their use has been demonstrated to be an effective tool for AMS. ^{34, 39, 40}

Prompting the prescriber to stop and consider what they’re treating, whether it is community- or hospital-acquired, duration of therapy etc., has both a useful pre-prescribing function, as well as assisting in post-prescribing feedback by the pharmacist or AMS team.

The key components of an antimicrobial prescription chart are as follows:

• Infection/site being treated;
• Whether it is community- or hospital acquired;
• Empiric, definitive (culture-directed) or prophylaxis indication for treatment;
• Dose, duration, route, patient’s weight;
• Whether cultures have been sent (and if result is positive).

Examples of standalone and integrated charts can be found at the following websites:

• South African Antibiotic Stewardship Programme, available at https://www.fidssa.co.za/SAASP/Prescription_Chart
• Best care... Always!, available at http://www.bestcare.org.za/file/view/Prescribing%20Tool%2003-2009. pdf/184539537/Prescribing%20Tool%20 03-2009.pdf
• See Annexure G for further details

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²⁸ Schuts, Emelie C Et al. Current evidence on hospital antimicrobial stewardship objectives: a systematic review and meta-analysis. The Lancet Infectious Diseases 2016;16(7):847 – 856.

²⁹ National Department of Health, Standard Treatment Guidelines and Essential Medicines List for South Africa: Hospital level, adults, 2015 edition; Hospital level, paediatrics, 2017 edition. Available from http://www.health.gov.za/index.php/standard-treatmentguidelines-and-essential-medicines-list

³⁰ South African Antibiotics Stewardship Programme (SAASP). A pocket guide to antibiotics prescribing for adults in South Africa, 2015, https://www.fidssa.co.za/Content/Documents/SAASP_Antibiotic_Guidelines_2015.pdf

³¹ Tamar F. Barlam, Sara E. Cosgrove, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America, Clinical Infectious Diseases 2016;62(10):e51–e77. https://doi.org/10.1093/cid/ciw118

³² Centers for Disease Control and Prevention (CDC). Get Smart for Healthcare: Overview and Evidence to Support Stewardship. Impact of ASP Interventions on Use. 2015. http://www.cdc.gov/getsmart/healthcare/evidence/asp-int-use.html

³³ SASOCP Position Statement on the Pharmacists Role in Antibiotics Stewardship, 2017.

³⁴ World Health Organization. Model List of Essential Medicines. Geneva; 2017. http://www.who.int/medicines/publications/essentialmedicines/en/ Boyles TH, Whitelaw A, Bamford C, Moodley M, Bonorchis K, et al. Antibiotic Stewardship Ward Rounds and a Dedicated Prescription Chart Reduce Antibiotic Consumption and Pharmacy Costs without Affecting Inpatient Mortality or Re

³⁵ Admission Rates. PLoS ONE 2013;8(12): e79747. doi:10.1371/journal.pone.0079747

³⁶ Brink AJ, Messina AP, Feldman C, Richards GA, van den Bergh D. From guidelines to practice: a pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals, Journal of Antimicrobial Chemotherapy 2017;72(4): 1227–1234.

³⁷ Brink, Adrian J et al. Antimicrobial stewardship across 47 South African hospitals: an implementation study. The Lancet Infectious Diseases 2016; 16(9): 1017-102.

³⁸ Pulcini C, Binda F et al. Developing core elements and checklist items for global hospital antimicrobial stewardship programme: A Consensus approach. ESCMID, 2018.

³⁹  Centers for Disease Control and Prevention (CDC). Get Smart for Healthcare: Overview and Evidence to Support Stewardship. Impact of ASP Interventions on Use. 2015. Available from http://www.cdc.gov/getsmart/healthcare/evidence/asp-int-use.html

⁴⁰  Ashiru-Oredope, D et al. Does an antimicrobial section on a drug chart influence prescribing? 2011. Available at https://www.pharmaceutical-journal.com/files/rps-pjonline/pdf/2011_jul_prescribing_antimicrobial_chart.pdf