We first informally examined sources of information, regulations, and experiences likely influencing prescribers. Skin infections including impetigo are very common among Aboriginal people supplied by government with housing inadequate for cultural demands and social use. From 10 population prevalence studies reporting data for children living in remote Aboriginal communities of northern Australia, the median prevalence of impetigo reported from these studies was 44.5% (9). Furthermore, the organism predominantly driving impetigo is Group A Streptococcus pyogenes (GAS) rather than Staphylococcus aureus (10). As a result of this epidemiological picture, the aims of prescribing to treat impetigo in the Kimberley are twofold: first, to accelerate skin healing and, also, to prevent serious GAS sequelae such as acute rheumatic fever and acute post-streptococcal glomerulonephritis (APSGN).

All authorized prescribers in Australia can access national Therapeutic Guidelines online.³ Because of the plurality of service organizations in our region as previously described, a suite of about 20 Kimberley-specific clinical protocols also is promoted upon arrival in the region at staff orientation and during in-service.⁴ These protocols are designed to support inexperienced health professionals unused to working in a setting as remote as the Kimberley and also to minimize prescribing deviations outside the agreed Kimberley standard drug list (KSDL) common to all services. We looked closely at the prescribing sections of one of these protocols, namely the Kimberley Skin Infections Protocol.⁵

We sought relevant pharmacological literature, also searching widely for community-based prescribing research conducted in remote settings with Aboriginal people rather than mainstream urban settings. We investigated the feasibility of a prescribing audit in the Kimberley but found both logistics and costs prohibitive as no standard audit tools were available. In addition, we resolved to obtain expert clinical input.

The AMS Committee agreed we could approach independent experts and reviewed the names of proposed experts for disciplinary background and relevant experience working in remote Aboriginal healthcare. Each of these then was first approached by email by SO requesting assistance in this AMS project. Our invitation outlined the purpose of our request and provided six article abstracts found in our literature review (available upon request from SO). We also attached the Kimberley antibiograms for the period July 2014–June 2015 (Figure 1) with the link to the current Kimberley Skin Infections Protocol. A structured response sheet presenting a list of 12 questions with a deadline for completion was used to guide expert review (Box 1). Development of these specific questions came out of our initial examination, earlier informal consultations, and literature review. About 4 weeks after initial invitation, one of us (JC) made a prompting telephone call or collegial reminder to any non-respondent to encourage response.

Throughout the process, we prepared project updates either verbally at meetings or in writing to the AMS Committee. Suggestions we submitted regarding process, selection of experts, and findings.

Prescribers in the Kimberley are either medical practitioners or, in circumscribed clinics in accordance with the WA Medicines and Poisons Act (2014) and regularly updated legislation, credentialed Remote Area Nurses (RANs). A pre-existing version of the Kimberley Skin Infections Protocol produced originally in 2010 had flucloxacillin orally for 6 days or, if adherence to an oral schedule would be difficult, intramuscular injection of long-acting benzathine benzylpenicillin (LA Bicillin^®) (LAB) for both adults and children.

This 2010 Protocol had been revised in some haste during 2014 in the context of an outbreak of APSGN in the Kimberley on the basis that GAS impetigo was the causative trigger. Changes introduced during this revision had included a prescribing recommendation to use SXT as an equivalent first-line oral alternative to intramuscular LAB. The AMS Committee itself had no formal record of these changes or AMS scrutiny. Released in December 2014, this version of the Protocol had been in place for about 1 year at the time that the AMS Committee first received data showing increasing MRSA resistance to SXT across the region. Anecdotally through emails between prescribers and queries to pharmacists, the use of SXT as first-line oral antibiotic for impetigo had increased over that year. A system of Standing Orders authorized by the Director-General of WA Health listed SXT as well as intramuscular LAB for use by RANs to treat “skin infections.”

None of the clinical record systems used in primary healthcare in the Kimberley could generate prescribing data linked to impetigo treatment in order to quantify actual prescribing behavior as part of this investigation. Examining turnover of stock and trends in SXT ordering by interrogating pharmacy imprests of each remote clinic setting also was precluded on the basis of available resources and, in any case, would have been far less precise.

From 15 experts and clinicians asked to provide input, we received 9 completed response sheets (60%) providing an appropriate diversity of disciplines including general practice, pediatric infectious diseases, clinical microbiology, clinical pharmacy, and experienced remote area pediatrics. Although every article provided with our structured response survey had been utilized by at least one respondent completing this section, crucially one had been used by all (11). As one additional article was cited by one respondent only (12), we were reassured that the resources we had provided were comprehensive and sufficient for respondents.

One of us, JW, was charged with the task of de-identifying and collating written responses. Extensive comments were considered over dedicated meetings of the working group. This process affirmed that antibiotic exposure raises risk for antibiotic resistance at individual as well as community and regional levels. All expert survey respondents confirmed the AMS risks and trade-offs inherent in first-line antibiotic choices in treating Aboriginal children with impetigo. These also included the options of oral versus intramuscular routes. A direct correlation between increasing antibiotic resistance, as observed by the locally produced antibiograms, and increasing SXT antibiotic exposure could not be excluded. Survey responses focused attention on a single study conducted in the Northern Territory comparing an oral antibiotic alternative to intramuscular LAB for the first-line treatment of impetigo in Aboriginal children (11). As explained by the researchers, their selection of SXT as this oral antibiotic alternative would cover MRSA as a causative organism and their previous in vitro study demonstrating susceptibility of GAS to SXT. They also explained that, if S. aureus was causative of impetigo in any given individual, then intramuscular LAB would be insufficient (11). Survey respondents’ comments generally agreed that impetigo within Australian Aboriginal populations is driven by S. pyogenes (GAS). Regardless of concomitant S. aureus carriage in skin infection, treatment of S. pyogenes alone results in clinical resolution. In the Kimberley, clinicians must manage high rates of GAS infections but also a wide range of clinical manifestations of S. aureus infections, ranging from simple boils and cellulitis to complex deep tissue and joint infections and life threatening sepsis. Our rates of community-acquired methicillin-resistant Staphylococcus aureus (ca-MRSA) are high. SXT should remain one of the region’s most precious oral antibiotic agents for ca-MRSA infections demonstrated to be sensitive to SXT.

Responses from our review also suggested the importance of separately addressing community-based treatment of S. aureus infections in any revision of the Kimberley Skin Infections Protocol. Treatment of non-impetigo cases known or suspected to be caused by S. aureus needed greater detail. As decided by the AMS Committee, a separate guideline for inpatient management will also be produced with clear links from the community-based Protocol to a hospital-based prescribing protocol. This hospital protocol for more severe infections requiring admission is under-way and will be informed by a concurrent study of diagnosis, treatment, and prescribing of impetigo in Aboriginal children once hospitalized (13).

Expert responses also helped us as a working group to highlight specific methodological aspects of previous research. One study showing a reduction by day seven of S. aureus carriage in Aboriginal children with impetigo had compared one of two previously un-trialed SXT regimes against intramuscular LAB based on non-adherence concerns (11). Specifically, the trial compared a 3-day course of SXT at a standard dose twice daily versus a 5-day course at a novel double-dose once-daily but, importantly, all doses were “directly observed” (11). Also known as directly observed therapy (DOT), such a standard for clinical treatment of patients with impetigo in the Kimberley was discussed at length by the working group. In addition, this trial had not assessed SXT resistance. Methods including pharmacokinetic/pharmacodynamic (PK/PD) analyses to determine PK/PD indices to optimize efficacy and avoid emerging resistance are needed for SXT (14, 15). Furthermore, it is known that SXT has a shorter half-life in children (16). As a working group so advised, we concluded that all antibiotic dosing regimes should be conventional and, in keeping with AMS principles and the evidence before us, conservative in a remote setting. Indeed, we were advised that the eTG specifies cephalexin for impetigo in non-Aboriginal children.

Survey responses also reinforced the role of environmental determinants of skin infections in Aboriginal children. As one respondent suggested: “… we have to make a start in addressing the environmental factors that are contributing to high rates of skin infection. It does need to be part of a wider strategy addressing the social determinants of health such as overcrowding though I accept that this is likely to be beyond the scope of the review.” Our working group agreed.

Readers can request from SO a full copy of the responses with AMS Committee permission.

Having discussed every written response and common themes, we prepared written recommendations for the AMS Committee in two sections: one, longer and comprising eight recommendations, addressed the first-line oral antibiotic alternative to intramuscular LAB for impetigo in Aboriginal children and, the second, comprising two recommendations about non-impetigo skin infections (Box 2). In response to local contextual factors influencing prescribing, we recommended retaining the option for an empiric oral antibiotic alternative alongside intramuscular LAB for the initial treatment of GAS impetigo in Aboriginal children in remote Australia. Consistent with AMS principles, SXT should be removed as this first-line oral alternative due to a disturbing increase in MRSA resistance to SXT in the region. In a setting of high (and rising) MRSA resistance to SXT, we were confident that we could recommend that SXT should be used selectively especially when other options were readily reaffirmed by experts participating in our survey. Until more evidence is available, we recommended compliance with the Australian Therapeutic Guidelines (eTG) prescribing recommendation for impetigo of cephalexin. Recommendations were also made about audit, community engagement, and environmental determinants (Box 2).

On the basis of this process and its own deliberations based on the diverse sources of input obtained, the AMS Committee endorsed these recommendations in October 2016 and requested a comprehensive review of the Kimberley Skin Infections Protocol. It provided a comprehensive report to the KAHPF Maternal and Child Health SubCommittee responsible for this review (due mid-2017) including an explanation of AMS principles. Additional consultation will take place. As the most recent antibiogram received by the AMS Committee from January 2015 to December 2015 showed continuing MRSA resistance to SXT in the Kimberley (19%), this initiative to apply sound AMS principles to community-based prescribing was timely. Unpublished data also made available shows that the WA121 strain of S. aureus now accounts for half of all strains of S. aureus found in the Kimberley. WA121 is routinely resistant to SXT (17, 18).