Australian guideline on management of diabetes-related foot infection: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease

Rationale: The panel decided to adopt the recommendation unchanged following screening, as judgements were consistent with the IWGDF and the recommendation was acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that despite a low quality of evidence for the recommendation, there was a strong (strength of) recommendation for it based on the clinical signs and symptoms of infection being widely accepted and the substantial benefits of rapid clinical identification of soft tissue diabetes-related foot infections. The recommendation was considered compatible and applicable to the Australian context, and the clinical expertise was considered to be available for its implementation across primary, secondary and tertiary healthcare providers.

The panel identified that future studies could investigate differences in the time to identify an infected foot in individuals with darker and lighter skin and could define differences in clinical symptoms of infection between these two groups in order to adapt tools that use these clinical symptoms of infection to individuals with different skin colours.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a strong (strength of) recommendation for the recommendation given that the classification system has been validated in full or part by three prospective and four retrospective cohort studies. The recommendation was considered compatible and applicable to the Australian context, and the panel considered that the clinical expertise for its implementation was available across primary, secondary and tertiary healthcare providers.

The panel noted that there are a number of versions of the IWGDF/IDSA classification scheme with the IWGDF classification scheme being the most recently updated in 2019 as part of the IWGDF guideline recommendation process. As such, this classification scheme is recommended for use in Australia. In addition, the panel noted that a number of clinicians working with patients with diabetes-related foot infections use the Society for Vascular Surgery Wound, Ischaemia and Foot Infection (WIfI) classification scheme [32] to assess diabetes-related foot disease. This includes an infection component which is very similar to the IWGDF classification scheme although it ranges from 0 (no infection) to 3 (severe infection) compared with 1 (no infection) to 4 (severe infection in the IWGDF classification scheme. In addition, it does not include the changes suggested by the 2019 IWGDF Guidelines to incorporate an ‘O’ when patients with moderate or severe infection have associated osteomyelitis.

The panel suggests that services use the IWGDF classification scheme to categorise patients in their service to assist with subsequent planning and management decisions.

The panel noted that given the ongoing changes to the IWGDF guidelines and no studies having validated these in the Australian context it would be beneficial to conduct further validation studies of this classification scheme in the Australian setting.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence but a strong (strength of) recommendation for the recommendation given that the desirable effects of hospitalisation on infection resolution, wound healing and mortality prevention in this setting likely outweigh the undesirable effects. The recommendation was considered compatible with most patients’ values, applicable to the Australian context and feasible in most Australian locations, although they noted that some patient subgroups may disagree and in some remote locations the application of this recommendation would be more difficult.

The panel noted that there is a need to compare outcomes from alternative models of practice that may be of particular relevance to remote locations and Aboriginal and Torres Strait Islander communities around Australia.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence and a weak (strength of) recommendation for the recommendation given the minimal evidence supporting this recommendation. The recommendation was considered compatible and applicable to the Australian context, with the appropriate expertise and resources available to undertake these tests in many locations, although it was noted that procalcitonin had the most barriers to use.

Consistent with the evidence that CRP correlates most consistently and strongly with infection severity and changes rapidly, enabling dynamic interpretation, CRP was considered likely to be the most useful biomarker in this setting for many Australian settings. Procalcitonin is not widely available in the Australian healthcare setting and many clinicians likely have a decreased understanding of when it is best utilised, and its interpretation compared with CRP and ESR. In addition, it may incur additional costs in some settings and there may be a delayed time to results. The panel noted that despite the correlation between ESR and infection, it is generally used less commonly than CRP by Australian Infectious Diseases physicians.

The IWGDF identified a need for additional research to correlate biomarkers with severity of infection, with careful identification of individuals who had been pre-treated with antibiotics. This was supported by the panel.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence for the use of foot temperature and quantitative microbial analysis to diagnose diabetes-related foot infection. They agreed that a weak (strength of) recommendation against their use was appropriate and consistent with minimal to no benefits, their low availability and in the case of quantitative microbial analysis, the associated potential delays and expense. The lack of resources and expertise recognised in the IWGDF guidelines also exist in the Australian setting. Thus, the recommendation against their use was considered applicable to the values of Australian patients.

As identified by the IWGDF there is low availability of these techniques in the global context and quantitative microbial analysis is time-consuming and expensive. These considerations are also pertinent in Australia.

As identified by the IWGDF there is a need for further evaluation of infrared imaging when coupled to photographic assessment through telemedicine. Similarly, the role of quantitative and semi-quantitative microbial analysis in clinical management of diabetes-related foot infections needs further exploration. This will require consistent methodology such as consensus definitions for the presence of infection as well as procedures for collection and processing of samples.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a strong (strength of) recommendation for the recommendation. There is considerable evidence to support the use of the probe to bone test, ESR and plain X-rays to diagnose osteomyelitis in particular. The recommendation was considered compatible and applicable to the Australian context, with the appropriate expertise and resources available to undertake these tests in many locations, although it was noted that procalcitonin had the most barriers to use.

As described in the implementation section in Recommendation 3 procalcitonin is not widely available in the Australian healthcare setting, has less clinician expertise and in some settings may be associated with increased costs and delayed time to results. There is the potential to increase teaching of the probe to bone test, which is inexpensive and easy to learn and perform, to a broader clinical group.

The panel identified that larger studies are needed to identify the sensitivity and specificity of the described tests to identify osteomyelitis. Additional studies assessing teaching and implementation of the probe to bone test to improve interobserver reliability were also recommended.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence but a strong (strength of) recommendation for the recommendation given the lack of need for more expensive and less available imaging if a diagnosis is evident. The recommendation was considered compatible with most patients’ values, applicable to the Australian context and feasible in most Australian locations, although it was noted that in some patients additional imaging may be needed to determine the extent or complications, and thus the management of the osteomyelitis.

The panel noted that additional research could be undertaken to determine the sensitivity and specificity of a panel of low cost clinical, laboratory and radiological methods to diagnose osteomyelitis.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a strong (strength of) recommendation for the recommendation. There is considerable evidence to support the use of these investigations to diagnose osteomyelitis which all demonstrate good sensitivity and specificity. The recommendation was considered compatible and applicable to the Australian context, with the appropriate expertise and resources available to undertake these tests in most tertiary healthcare settings in Australia.

The panel noted that the imaging techniques are generally available in tertiary healthcare settings in Australia, however, they are regularly not available in rural and remote settings. Furthermore, PET-CT is not reimbursed through the Pharmaceutical Benefits Scheme for this indication, restricting accessibility to those unable or unwilling to pay the associated costs.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence but a strong (strength of) recommendation for the recommendation given that biopsy is considered the gold-standard for diagnosis of osteomyelitis and there is substantial benefit of using directed antibiotic therapy in individuals with recalcitrant infection or in those that are at higher risk of antibiotic resistance. The recommendation was considered compatible with most patients’ values given the increased chance of cure of infection, however, it was noted that there is the theoretical risk of introducing infection and a potential risk of fracture. The recommendation was considered applicable to the Australian context and feasible in most Australian locations, although expertise for percutaneous biopsy was noted to be low in many Australian locations.

The panel noted that the availability of percutaneous bone biopsy is variable across the Australian healthcare system. In many locations, experience and skill with this technique are not available, which potentially reduces the ability to implement this recommendation.

The panel identified that research on the availability and usage of percutaneous bone biopsy in patients with diabetes-related foot osteomyelitis across Australia would enable an assessment of current expertise and usage and inform future education and implementation of this procedure.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence but a strong (strength of) recommendation for the recommendation given the benefit of identifying the microbiological cause of infection in directing antibiotic therapy. Culture was noted to not only be important for pathogen identification but also to determine the susceptibility profile of these pathogens. The recommendation was considered compatible with most patients’ values, applicable to the Australian context and feasible in most Australian locations.

It is suggested that services consider recording whether microbiological specimens are taken for each patient with a diabetes-related foot infection, to enable evaluation of the proportion of patients receiving microbiological diagnoses.

The panel noted that studies to assess infection outcomes in patients from remote locations where access to microbiology diagnosis is difficult could be undertaken to compare treatment with directed antibiotic therapy versus treatment with empiric antibiotic therapy.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a strong (strength of) recommendation for the recommendation. In general tissue biopsy is the most appropriate specimen for soft tissue diabetes-related foot infections, given that biopsy is considered the gold-standard for diagnosis of infection and there is substantial benefit of using directed antibiotic therapy in individuals with recalcitrant infection or in those that are at higher risk of antibiotic resistance. The recommendation was considered compatible with most patients’ values, applicable to the Australian context and feasible in most Australian locations.

The panel noted that although expertise for soft tissue biopsy is available in most Australian healthcare settings, this may be reduced in some rural and remote settings. Furthermore, in some locations, tissue specimens may potentially be processed more slowly than tissue swabs.

The panel noted that additional studies are needed to identify the likelihood of deep infection caused by a specific organism identified on a superficial swab. Furthermore, the panel suggests that the relative benefit of tissue samples versus swabs be assessed in clinical trials looking at patient outcomes.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence and a strong (strength of) recommendation against the recommendation given the lack of evidence for benefit of molecular microbiology techniques. The recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in most Australian locations given molecular microbiology techniques are rarely available.

There is low availability of molecular microbiology in the Australian context and the techniques are still relatively new and expensive.

The panel noted that there is a need for further development and investigation of molecular microbiology techniques including studies that compare results with standard cultures according to IWGDF grade of infection and assess patient-related outcomes.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a high quality of evidence and a strong (strength of) recommendation for the recommendation. Although evidence is based on good quality randomised controlled trials (RCTs), it was noted that the majority of these demonstrated that agents were non-inferior to each other, raising the possibility that other agents that have not been tested in RCTs may be similarly effective (i.e. agents such as cotrimoxazole and doxycycline which are commonly used for diabetes-related foot infections in Australia). The recommendation was considered compatible and applicable to the Australian context, where there is appropriate expertise and resources available to use these antibiotics in most primary, secondary and tertiary healthcare settings. The recommendation was consistent with existing Australian antibiotic guidelines [33].

The panel noted that multiple additional factors are important in determining the appropriate antibiotic to use for a patient, similar to those described in Recommendation 11, including severity of infection, route of administration, adverse drug reactions, current and prior microbiological results, local antibiotic resistance patterns, appropriate antimicrobial stewardship, antibiotic restrictions, cost and access. Specifically, some antibiotics will only be available in tertiary settings, and even then, more restricted antibiotics such as daptomycin may not be widely accessible.

The panel recommends that individual services should collaborate with their local antimicrobial stewardship team to evaluate their local antibiotic usage and compare it to similar services and centres where possible.

The panel noted there is a need for studies comparing regularly used empiric antibiotic regimens (rather than new antibiotics) in order to identify the best empiric regimen for different severity infections.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a strong (strength of) recommendation for the recommendation. The recommendation was considered compatible with most patients’ values, applicable to the Australian context and feasible in most Australian locations. It was noted that the list of considerations in the recommendation is not exhaustive and there are many additional patient-related considerations including patient acceptance of antibiotic frequency or administration type, patient adherence to a regimen, and patient preference to be treated in the outpatient setting or on country where possible. In addition, there should be a preference for narrower spectrum antibiotics where possible from an antimicrobial stewardship perspective. Conversely, at times it may be appropriate to use broader spectrum antibiotics if there is a history of recent infection or colonisation with multidrug resistant organisms or if local antimicrobial susceptibility profiles demonstrate an increased risk of such organisms.

As described in the Summary justification, the panel identified a number of additional implementation considerations, many of which are patient-related. These are described in additional detail in the Subgroup considerations below.

The panel noted that qualitative studies to explore and rank the factors most important for patients would assist clinicians in understanding patients’ preferences and providing the most balanced options when discussing treatment with patients. In addition, preferences could be assessed for specific patient subgroups such as those in geographically remote locations or Aboriginal and Torres Strait Islander Peoples.

Rationale: The panel decided to adapt this recommendation after full assessment based on having differences in judgements to IWGDF for quality of evidence (Table 2) and due to a lack of clarity around the population it referred to. The changes made to the original IWGDF recommendation included downgrading the quality of evidence from low to “very low” and including the phrase “skin and soft tissue” to define the relevant population of patients with diabetes-related foot infection (Table 3).

Although the panel downgraded the quality of evidence to very low, they agreed with the IWGDF that diabetes-related foot infections were an important health problem in Australia, and that the balance of effects favoured the use of initial intravenous antibiotics for severe (grade 4) skin and soft tissue diabetes-related foot infections. It was noted that a switch to oral therapy when the patient was clinically improving was appropriate for severe (grade 4) skin and soft tissue infections. Furthermore, it was noted that in the IWGDF guidelines this recommendation was intended to relate to people with skin and soft tissue infections, sitting under a sub-heading stating this, however, this was not clear when the recommendation was read outside the context of the overall IWGDF guideline document. The panel were unsure whether the critical outcome of clinical cure of infection would be consistently valued above all other outcomes by all patients (for example some patients may prefer avoidance of amputation and long term antibiotic suppression). They noted that the recommendation was likely acceptable and feasible in the Australian setting. Detailed justifications from the panel’s full assessment are provided in Supplementary Table S1.

One of the key research priorities identified by IWGDF was whether oral antibiotic therapy alone is as effective as parenteral treatment for diabetes-related foot infections, including diabetes-related foot osteomyelitis. The panel noted a need for studies to evaluate whether all patients with severe (grade 4) infections require initial parenteral antibiotic therapy. Furthermore, they identified a need for studies to explore the duration of initial parenteral antibiotics that is needed prior to oral switch for patients with severe (grade 4) diabetes-related foot infections and the factors that influence this decision.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence and a weak (strength of) recommendation for the recommendation. The recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in most Australian locations.

IWGDF highlighted a need to further understand whether complete oral therapy is as effective as parenteral treatment for diabetes-related foot infections. The panel agreed that studies are needed to compare the use of complete oral therapy with initial intravenous therapy in infections of moderate (grade 3) severity and that they should assess patient outcomes.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that when specifically considering the use of topical antibiotic agents for mild bacterial infection there was a moderate quality of evidence and a weak (strength of) recommendation against using currently available topical antimicrobial agents given a lack of evidence demonstrating efficacy of these agents, and their potential to increase the risk of antimicrobial resistance. The panel also noted that the use of anti-septic agents is considered separately in recommendation 27b. The recommendation was considered compatible with most patients’ values, and applicable and feasible in the Australian setting.

The panel noted that topical antimicrobial agents remain an important area of future research which have the potential to alter the treatment pathways of diabetes-related foot infections if efficacious and safe agents are identified.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a high quality of evidence and a strong (strength of) recommendation for the recommendation. The recommendation was consistent with existing Australian antibiotic guidelines [33], and considered compatible with patients’ values, applicable to the Australian context and feasible in primary, secondary and tertiary healthcare settings in Australia.

The panel recommends that services record the duration of antibiotic treatment provided to patients to enable an audit of treatment duration by infection severity compared with the guidelines.

The IWGDF identified a need for further studies to determine the optimal duration of treatment for skin and soft tissue infections. The panel noted that such studies should be categorised by infection severity and infecting microorganisms and should consider additional confounders such as severe peripheral artery disease.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence and a weak (strength of) recommendation for the recommendation. The recommendation was noted to be pragmatic and generally consistent with existing Australian antibiotic guidelines [33]. It was considered compatible with patients’ values, applicable to the Australian context and feasible in primary, secondary and tertiary healthcare settings in Australia.

See Recommendation 15a.

See Recommendation 15a.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence but a strong (strength of) recommendation for the recommendation. The recommendation was noted to be pragmatic and generally consistent with existing Australian practice. It was considered compatible with patients’ values, applicable to the Australian context and feasible in primary, secondary and tertiary healthcare settings in Australia.

See Recommendation 15a.

See Recommendation 15a.

Rationale: The panel decided to adapt this recommendation after full assessment based on having differences in judgements to IWGDF for balance of effects and the population impacted (Table 2). The changes made to the original IWGDF recommendation included downgrading the balance of effects from strong to “weak”, extending the recommendation to all locations in Australia by excluding the need for patients to reside in a temperate climate area and narrowing the population by adding the phrase “and have an acute infection” (Table 3).

The panel agreed with the IWGDF that diabetes-related foot infections were an important health problem in Australia, that the use of empiric narrower spectrum antibiotics had more desirable benefits than undesirable benefits, and that the quality of the evidence supporting this was low. However, the panel felt the balance of effects was weak, consistent with a conditional recommendation for narrower spectrum antibiotics in the described circumstances and consistent with the use of the word consider in the recommendation. The panel also noted that although the recommendation was likely acceptable and feasible in the Australian setting, Australian practice and guidelines [33] do not distinguish use of narrow spectrum antibiotics by climate and there is no local evidence to support such a distinction. However, both local guidelines [33] and studies [35] support use of narrower spectrum agents in acute infections. The panel noted that the definition of acute infection in the published literature has varied from less than 2 to 6 weeks and suggest that, in concordance with local guidelines [33], duration of infective symptoms of less than 4 weeks could be considered acute while noting broader therapy may be required for those with a duration of ulceration of greater than 6 weeks [35] and in those with recent antibiotic exposure [36]. Detailed justifications are described in Supplementary Table S2.

The panel noted that there is no evidence from the Australian context to suggest individuals living in tropical regions with acute infections cannot be treated with narrow spectrum antibiotics and current practice in Australia is to treat such individuals with narrow spectrum antibiotics. They also noted that in patients known to be colonised with MRSA or in areas with a high prevalence, prescribers should consider empiric coverage of MRSA. Many tropical regions of Australia are also remote and increased rates of MRSA may exist in some of these remote populations. Similarly, many Aboriginal and Torres Strait Islanders live in tropical regions of Australia and there is an increased rate of MRSA in some Aboriginal and Torres Strait Islander populations [5].

The panel identified a need for further studies to investigate whether a difference in patient outcomes exists between patients treated with narrow compared with broad spectrum antibiotics in patients with acute infections. They also highlighted the need for further studies comparing pathogens in acute infections between temperate and tropical regions of Australia.

Rationale: The panel decided to adapt this recommendation after full assessment based on having differences in judgements to IWGDF for the population impacted in the Australian setting (Table 2). This was achieved by extending the recommendation to all locations in Australia by excluding the need for patients to reside in a tropical/subtropical climate and including patients with chronic infections by adding the phrase “who have a chronic infection” (Table 3).

The panel agreed with the IWGDF that diabetes-related foot infections were an important health problem in Australia, that the use of empiric narrower spectrum antibiotics had more desirable benefits than undesirable benefits, that the quality of the evidence supporting this was low and the balance of effects was weak. The panel also noted that although the recommendation was likely acceptable and feasible in the Australian setting, similar to Recommendation 16, Australian practice and guidelines [33] do not distinguish use of antibiotic spectrum by climate and there is no local evidence to support such a distinction. However, both local guidelines [33] and studies [35] support use of broader spectrum agents in chronic infections and in the presence of chronic ulceration. As described in Recommendation 16, the panel noted that the definition of acute infection and thus chronic infection varies in the published literature and suggest that, in concordance with local guidelines [33], duration of infective symptoms of four or more weeks could be considered chronic while noting broader therapy may also be required for those with a duration of ulceration of greater than 6 weeks [35]. Detailed justifications are described in Supplementary Table S3.

See Recommendation 16.

See Recommendation 16.

Rationale: The panel decided to adapt this recommendation after full assessment based on minor differences in judgements to IWGDF for the population impacted in the Australian setting (Table 2). This was achieved by extending the recommendation to all locations in Australia by excluding the phrase “in temperate climates” (Table 3).

The panel agreed with the IWGDF that diabetes-related foot infections were an important health problem in Australia, that the use of empiric antibiotic treatment to cover P. aeruginosa in certain circumstances had more desirable benefits than undesirable benefits, that the quality of the evidence supporting this was low and the balance of effects was weak. The panel also noted that although the recommendation was likely acceptable and feasible in the Australian setting, P. aeruginosa can be a pathogen in temperate as well as tropical regions [35]. Detailed justifications are described in Supplementary Table S4.

The panel identified a number of potential areas for future research that related to this recommendation including:

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence but a strong (strength of) recommendation for the recommendation. The recommendation was considered to be consistent with antimicrobial stewardship principles. It was considered compatible with patients’ values, applicable to the Australian context and feasible in primary, secondary and tertiary healthcare settings in Australia.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence but a strong (strength of) recommendation for the recommendation. The recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in most secondary and tertiary healthcare settings in Australia.

The panel noted that mixed methods research to identify differences between rural and metropolitan services in time between first presentation and surgery and to identify barriers to timely surgery would likely assist in improving the referral pathways and processes for diabetes-related foot infections requiring surgery.

Rationale: The panel decided to adopt this recommendation after full assessment based on having no substantial differences in judgements to IWGDF.

The panel agreed with the IWGDF that there was a moderate quality of evidence and a strong (strength of) recommendation for the recommendation. The recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in primary, secondary and tertiary healthcare settings in Australia. The panel noted that according to the exclusion criteria in the sole RCT assessing this issue [37], uncomplicated forefoot osteomyelitis should be defined as osteomyelitis without severe (grade 4) infection, and without any of the following: necrotising tissue infection, bone exposed in the base of the ulcer, kidney injury, or peripheral artery disease. Detailed justifications are described in Supplementary Table S5.

The panel noted that the need to be able to identify an indication for surgical intervention requires a level of specialist surgical knowledge that may not be available in all locations.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a strong (strength of) recommendation for the recommendation. The recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in most secondary and tertiary healthcare settings in Australia.

The panel noted that further studies assessing outcomes such as amputation, wound healing, resolution of infection and mortality are needed for comparison of surgery versus no surgery for different subgroups of patients with diabetes-related foot infections.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence but a strong (strength of) recommendation for the recommendation. The recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in primary, secondary and tertiary healthcare settings in Australia. However, it was noted by the panel that there have been few clinical trials that have compared different antibiotic regimens for diabetes-related foot osteomyelitis and it would be reasonable to use antibiotics that are used for osteomyelitis that is not associated with diabetes-related foot infections.

As described in the Summary justification, few antibiotic regimens have been tested in clinical trials for diabetes-related foot osteomyelitis and it would be reasonable to use antibiotics that are used for osteomyelitis that is not associated with diabetes-related foot infections. Such antibiotics include beta-lactams, beta-lactam/beta-lactamase inhibitors, (fluoro) quinolones, glycopeptides and lipoglycopeptides, oxazolidinones, sulfonamides, lincosamides, rifamycins and fusidic acid [38‐41]. Trials into the benefit of adjunctive rifampicin are ongoing [42]. The panel noted that a single substudy in an RCT of tigecycline versus ertapenem +/− vancomycin found tigecycline had a statistically non-significant chance of cure but a higher adverse event rate [43]. The factors identified as important in choosing an antibiotic for skin and soft tissue infections in Recommendations 10 and 11 should also be considered when choosing an antibiotic for osteomyelitis.

As identified in Recommendation 10, the panel recommends that individual services should collaborate with their local antimicrobial stewardship team to evaluate their local antibiotic usage and compare it to similar services and centres where possible.

The panel noted there is a need for studies comparing regularly used empiric antibiotic regimens (rather than new antibiotics) when culture results are unknown in order to identify the best empiric regimen for different types and severity of osteomyelitis. This should include comparison of oral-only antibiotic regimens compared with regimens with initial intravenous antibiotics. In addition, there is a need to compare different regularly used antibiotics in patients with known pathogens to determine which are the most effective.

The panel disagreed with the IWGDF on a number of aspects relating to this recommendation. The population of patients with diabetes-related foot osteomyelitis was considered too heterogeneous, impacting on a number of aspects of the assessment. Given the poor representation of the breadth of clinical presentations of diabetes-related foot osteomyelitis in the literature the panel downgraded the certainty of evidence to low. Similarly, the heterogeneity of diabetes-related foot osteomyelitis meant that the balance of effects was considered to vary. The panel were unsure whether the critical outcome of clinical cure of infection would be consistently valued above others by all patients (for example some patients may prefer avoidance of amputation and long term antibiotic suppression). The acceptability of the recommendation by patients and providers in the Australian setting was considered likely to vary substantially based on the subgroup of osteomyelitis being treated. The recommendation was considered likely to be feasible in the Australian setting. Detailed justifications are described in Supplementary Table S6.

The panel noted that exclusion of this recommendation highlights the need for further well-designed studies to better characterise and define subsets of diabetes-related foot osteomyelitis and then investigate different durations of antibiotic therapy for these subgroups.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence and a weak (strength of) recommendation for the recommendation. The recommendation was noted to be consistent with existing Australian infection guidelines [33] where it is recommended that antibiotics are continued for 2 to 5 days after definitive surgery for osteomyelitis. It was considered compatible with patients’ values, applicable to the Australian context and feasible in primary, secondary and tertiary healthcare settings in Australia.

As described in the Summary justification, the panel believe that the duration that antibiotic therapy should be continued, described as ‘just a few days’ in the recommendation should be defined as 2 to 5 days. This is consistent with Australian infection guidelines and allows clinicians to await histopathology and culture results from tissue samples taken from the presumed uninfected residual bone margin to verify adequate surgical removal of infection.

The panel recommends that services record the duration of antibiotic treatment provided to patients post definitive surgery and whether tissue samples were sent from the presumed clean wound post-surgical debridement.

The panel noted that further studies on the duration of antibiotics post definitive surgery for osteomyelitis would be beneficial including identifying factors associated with poorer outcomes that may indicate a need for more prolonged antibiotic therapy. Standardisation of terminology, sampling technique and processing methods would aid research goals.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a weak (strength of) recommendation for considering transition to oral antibiotics after 5 to 7 days. The panel noted that uncertainty remains regarding the best timing of switch to oral agents and that clinician practice may differ. This recommendation reflects a change from previous practice and Australian guidelines but is consistent with emerging evidence suggesting early switch to bioavailable oral agents is equally efficacious to longer antibiotic therapy [44]. It is likely that some of the current uncertainty around best practice will be resolved in the short to medium term as further evidence and experience of early oral switch for bone and joint infections becomes available. It was considered applicable to the Australian context and feasible in most secondary and tertiary healthcare settings in Australia. The panel also noted that an earlier switch to oral agents would be considered preferable for most patients if clinically appropriate and as such the recommendation was considered compatible with patients’ values.

The panel noted that earlier transition to oral agents would potentially allow patients to return home more quickly and reduce the challenges that are associated with treatment.

The panel recommends that individual services record the duration of intravenous and oral antibiotic therapy to allow comparison of patient outcomes and between services.

The panel notes that this remains an area of active research and there is a need for further randomised trials to compare antibiotic regimens with early oral transition with longer intravenous regimens for diabetes-related foot osteomyelitis in different patient subgroups. Selection of effective oral agents requires a particular focus to understand the relative importance of bioavailability, bone penetration, biofilm activity and therapeutic drug monitoring.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a weak (strength of) recommendation for the recommendation. It was considered compatible with patients’ values, applicable to the Australian context and feasible in most tertiary healthcare settings in Australia.

The panel recommends that services record whether tissue samples were sent from the presumed clean wound post-surgical debridement.

The panel noted that additional studies comparing outcomes in patients with positive and negative stump cultures would be beneficial.

Rationale: The panel decided to adopt this recommendation after full assessment based on having no substantial differences in judgements to IWGDF.

The panel agreed with the IWGDF that there was a moderate quality of evidence and a strong (strength of) recommendation to continue antibiotics if proximal surgical samples suggested residual infection. The recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in secondary and tertiary healthcare settings in Australia. Detailed justifications are described in Supplementary Table S7.

See Recommendation 25a.

The IWGDF highlighted that there is a lack of an agreed definition of osteomyelitis in the diabetes-related foot, highlighting the need for consensus definitions of [1] stages of diabetes-related foot osteomyelitis and [2] outcome assessment, in addition to standardised collection and reporting methods for bone samples. The panel noted that additional studies comparing outcomes in patients with positive and negative stump cultures would be beneficial. In addition, there is a need for studies to investigate the optimal duration of antibiotics in patients with diabetes-related foot osteomyelitis treated with bone resection surgery.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence and a weak (strength of) recommendation against the use of hyperbaric oxygen or topical oxygen therapy for treating infection. The recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in tertiary healthcare settings in Australia.

The panel noted that hyperbaric oxygen therapy is not widely available throughout Australia and is generally only available in selected metropolitan and regional centres.

The panel noted that there is a need for further randomised studies with infection outcomes to assess the role of hyperbaric oxygen therapy in diabetes-related foot infections.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a moderate quality of evidence and a weak (strength of) recommendation against the use of adjunctive granulocyte colony stimulating factor treatment for diabetes-related foot infection. It was considered compatible with patients’ values, applicable to the Australian context and feasible in primary, secondary and tertiary healthcare settings in Australia.

Rationale: The panel decided to adopt the recommendation unchanged following screening as judgements were consistent with the IWGDF and the recommendation was considered acceptable and applicable in the Australian setting (Table 1).

The panel agreed with the IWGDF that there was a low quality of evidence and a weak (strength of) recommendation to not use these topical therapies routinely as sole therapy or instead of antibiotics for established clinical infection. However, the panel noted that these may be used as an adjunct in combination with good wound care principles and that there may be a potential benefit to using adjunctive non-harmful traditional or complementary therapies, if only to maintain a therapeutic relationship in some patients. With these caveats, the recommendation was considered compatible with patients’ values, applicable to the Australian context and feasible in most primary, secondary and tertiary healthcare settings in Australia.

The panel noted that while these therapies should not be used as the primary treatment for treating infection, many clinicians use these therapies as an adjunct to wound care and as they generally have minimal evidence for efficacy or harm they may be considered following discussion between the patients and clinician. Further implementation considerations are detailed in the Subgroup considerations section below.

The panel suggests that the use of such therapies should be recorded by each service and a regular evaluation performed to review patient outcomes and adverse events in those using such therapies.

The panel noted that there is a need for additional high quality studies of adjunctive topical treatments in diabetes-related foot infections to determine whether there is added benefit from these therapies.

People living in geographically remote areas face a number of barriers to effective implementation of this guideline. Barriers include reduced access to diagnostic services including basic services such as X-ray and advanced services such as MRI or PET scan, delays in time to results for biomarkers or pathological sampling and reduced access to surgical and specialist foot expertise. In addition, options for treatment may be impacted with hospitalisation unavailable locally and reduced local access to intravenous antibiotics or surgery.

An inability to undergo local treatment may impact the choice of treatment for some patients who wish to be treated in their local community, with an increased preference given to non-surgical interventions, outpatient parenteral therapy, oral antibiotics or use of telehealth by some individuals. In many circumstances, treatment will still be required, and it is important that remote centres have clear referral pathways (including criteria for referral and who to contact) to ensure access to timely advice and transfer mechanisms. In addition, the use of technology such as telehealth appointments and patient-centred co-management arrangements such as joint appointments with general practitioners and specialists should be considered where feasible.

Given the increased risk of complications from diabetes-related foot infections, including amputations, in Aboriginal and Torres Strait Islander Peoples, it is vital that guidelines be adjusted to ensure inclusivity of this population. Cultural and language barriers need to be carefully assessed and mitigated through the support of Aboriginal health workers, Aboriginal liaison officers and interpreters as much as possible. Clinicians should aim to explore each patient’s understanding of their diabetes-related foot infection including predisposing factors, prognosis and potential treatment options.

As described in the section above, many of the potential barriers to implementation of the guideline that relate to geographically remote people also relate to a substantial proportion of Aboriginal and Torres Strait Islander Peoples due to 20% of Aboriginal and Torres Strait Islander Peoples living rurally [45] and a substantial proportion living in remote locations. An inability to undergo treatment locally may impact the choice of treatment for some patients who wish to be treated on country and/or near their local community, and clinicians should discuss alternative treatment options with patients including associated benefits and risks.

The panel highlighted that some Aboriginal and Torres Strait Islanders may wish to use a combination of traditional and western medicine and that clinicians should approach this with an open mind that positively fosters the therapeutic relationship and encourages engagement with medical services. In certain circumstances traditional medicine may be a potential harm, however, this should be addressed in a sensitive and culturally appropriate manner.

Prescribers should consider empiric MRSA coverage in patients known to be colonised with MRSA or those living in areas with a high prevalence of MRSA. An increased rate of MRSA has been identified in some Aboriginal and Torres Strait Islanders populations. For example, a study from Darwin found over 40% of Aboriginal and Torres Strait Islander patients with a diabetes-related foot infection had associated MRSA [5].

Prescribers should consider empiric MRSA coverage in patients known to be colonised with MRSA or those living in areas with a high prevalence of MRSA.