The time is now for stewardship in diabetic foot infections
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Diabetes, first described in ancient Egypt, remains at the forefront of health care in modern times. Roughly 537 million adults aged 20 to 79 years are living with diabetes worldwide, a number expected to rise over the next decades.
Diabetic complications are vast. Diabetic foot infection (DFI) is a chronic, more severe complication that affects roughly 15% of people with diabetes. DFIs have been associated with decreased quality of life, frequent and prolonged hospitalizations and greater risk for lower extremity amputation. Almost all DFIs occur in open wounds, beginning with a break in the skin layer at an ulceration or trauma site in the setting of peripheral neuropathy and/or peripheral arterial disease, most commonly.
The spectrum of DFIs, ranging from superficial to contiguous spread into subcutaneous tissues and eventually bone, poses treatment challenges. In efforts to lessen the risk for poor clinical outcomes, treatment often encompasses broader than necessary antimicrobial therapy for gratuitous durations. In an era of increasing antimicrobial resistance, building a cohesive relationship between antimicrobial stewardship programs and DFI treatment strategies is warranted.
Diagnostic and microbiological testing considerations
The microbiology of DFIs is diverse and dependent on several factors, including geographic location, chronicity and specific exposures, such as water. Determination of which organisms are pathogenic and which are commensal is a persistent DFI treatment challenge. Obtaining optimal tissue cultures during an antibiotic-free period, if clinical stability allows, and avoiding tissue swabs to reduce contamination risks aid in culture yield and utility. Deeper soft tissue or sinus tract cultures may not correlate with bone pathogens, necessitating the need for bone cultures if osteomyelitis is suspected. A recent meta-analysis composed of 112 studies — 84 published between 2011 and 2019 — investigated microbiological prevalence of DFIs for 16,159 patients, of which 89.4% were positive for microbial growth. The most common organism isolated was Staphylococcus aureus, with 18% being MRSA. These data also supported a previous correlation that gram-positive organisms (eg, S. aureus, Streptococcus species, Enterococcus species) predominate in DFIs from more developed countries, reflecting possible differences in sanitation, hygiene or footwear use.
With S. aureus being the leading pathogen implicated in DFIs, MRSA coverage is a foundation of many empirical antibiotic regimens. Guidelines recommend empiric MRSA coverage in patients with a history of MRSA, if the local incidence of MRSA is high or if the infection is severe. Screening for MRSA nasal carriage may be a tool for antimicrobial stewardship programs to avoid anti-MRSA agent use or de-escalate antibiotic regimens more quickly in DFIs. A Veteran Affairs study investigated if the absence of MRSA nasal carriage predicts the absence of MRSA in cultures from inpatients with DFIs. Investigators found a negative predictive value (NPV) of MRSA nares screening for MRSA DFI was 89.6% for the large cohort (n = 8,163). The NPV was 89.2% for those with deep cultures compared with 90.3% for those with superficial cultures. The value and cost effectiveness of MRSA nasal decolonization is not yet known, lending to further exploration.
IV to oral switch
Another opportunity for antimicrobial stewardship collaboration in the setting of DFI treatment is transitioning from parenteral to enteral antibiotic regimens. There has long been a notion that parenteral antimicrobial therapy is needed in more severe DFIs, including diabetic foot osteomyelitis, to ensure high bone concentrations. Historical perceptions of limited antibiotic delivery to the foot due to blood flow impairment and decreased oral bioavailability may hamper efficacy.
The Oral vs. Intravenous Antibiotics for Bone and Joint Infection (OVIVA) study, an open-label randomized, controlled, multicenter trial from the United Kingdom, investigated 1,054 patients with complex bone and joint infections, including diabetic foot osteomyelitis. Patients received either IV or oral antibiotics to complete the first 6 weeks of treatment after about 1 week of IV therapy. The oral treatment was noninferior to entirely IV regimens and associated with fewer vascular access device complications and lower costs at year-1 follow-up. Oral penicillins, fluoroquinolones and macrolides made up a sizable portion of the oral antibiotic treatments; antibiotic regimens were at the discretion of the provider. Although many of the oral regimens used are highly bioavailable classics, OVIVA reinforces previous data showing success with oral regimens with bone involvement.
A bundled approach
Along the continuum of care, outpatient antimicrobial stewardship is ripe for exploration. Complex outpatient antimicrobial therapy (COpAT) is a novel term to describe outpatient oral antimicrobial courses for extended durations or ones that require outpatient monitoring, whereas outpatient parenteral antimicrobial therapy (OPAT) involves the intricacies of outpatient parenteral antimicrobial regimens, knowing not all DFIs will be suitable for oral antimicrobial therapy. Bundles have been developed to improve the reliability and delivery of essential health care processes to ensure quality care. Optimal DFI treatment is not often limited to antimicrobial therapy alone, also involving surgical procedures and adjunctive wound care. A bundled approach may help prompt routine reassessment of antimicrobial therapy (eg, culture follow-up, transitioning from IV to oral, therapy duration) and adherence to nonpharmacologic DFI therapies, especially with ongoing evolution in care delivery during pandemic times.
The time is now
The backbone principles of antimicrobial stewardship are applicable more than ever, even though the direct evidence for antimicrobial stewardship in DFIs is sparse. Ensuring a correct diagnosis, proper identification of relevant organisms and prescribing an optimal antibiotic regimen for the right duration can curb antibiotic misuse. Of equal importance are sustained preventive efforts with long-term foot care. As the number of persons living with diabetes grows, DFIs will persist. New molecular techniques, an evolving understanding of antimicrobial therapy and surgical approaches and healing and preventive measures will be most effective through a connected, multidisciplinary bundle comprising inpatient and outpatient settings. The time is now for antimicrobial stewardship in DFIs.
- References:
- International Diabetes Federation. Diabetes facts & figures. https://idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html. Updated Sept. 12, 2021. Accessed Jan. 6, 2022.
- Karamanou M, et al. World J Diabetes. 2016;doi:10.4239/wjd.v7.i1.1.
- Li HK, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1710926.
- Lipsky BA, et al. Diabetes Metab Res Rev. 2020;doi:10.1002/dmrr.3280.
- Lipsky BA, Uçkay . Medicina (Kaunas). 2021;doi:10.3390/medicina57040339.
- Macdonald KE, et al. BMC Infect Dis. 2021;doi:10.1186/s12879-021-06516-7.
- Mahoney MV, et al. Curr Infect Dis Rep. 2021;doi:10.1007/s11908-021-00766-x.
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- For more information:
- Jennifer Ross, PharmD, BCIDP, is an infectious diseases clinical pharmacist at M Health Fairview – University of Minnesota Medical Center. Ross can be reached at jross13@fairview.org.
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