Two Pragmatic Approaches to Skin and Soft Tissue Infections

The practice of infectious disease requires excellent communication between the ID consultant and primary care physicians (PCPs), internal medicine physicians, and hospitalists who are usually the first point of contact for patients. Important pieces of information for these front-line physicians are what to do (and not to do) as first steps in treating an infectious disease and when is the right time to call in the infectious disease consultant when things are not going well. In perusing the recent online table on contents for Open Forum Infectious Diseases I came across two papers in skin and soft tissue infections that are particularly practical to guiding these interactions between internal medicine and Infectious Disease physicians. These papers deal with the very common clinical issues of non-purulent lower extremity cellulitis and diabetic foot ulcer (DFU) infections.

In the first paper by Williams and colleagues from the UK, the frequently encountered clinical entity of non-purulent unilateral lower limb cellulitis is examined.¹ The authors point out the troubling data that ~ 20% of patients with this condition are considered antibiotic “failures” prompting rescue regimens of antibiotics and repeated health care visits.² Antibiotic failure in cellulitis is also a quite common reason for inpatient and outpatient infectious disease consultation. To better understand the natural history of lower limb cellulitis the authors took advantage of database from a multi-center interventional clinical trial in cellulitis. Data was examined in patients with unilateral lower limb cellulitis without abscess who had at least one follow-up appointment. The methods of assessment included 3 face to face visits at baseline, day 5 and day 10. The data collected included percentage of body surface area affected, limb circumference compared to unaffected limb and highest temperature of affected limb compared to unaffected limb. Pain scores were collected as were blood for a complete blood count (CBC), renal and liver function panels, and C reactive protein (CRP).

The data on the tempo of symptomatology over time compared with biochemical markers is quite compelling. On Day 10, the limb circumference of the affected limb and the highest temperature of the affected extremity was still statistically significantly greater than the non-affected extremity. The overall reduction in affected body surface area was approximately half at day 10 and slightly more than 50% still had pain at day 10. In contrast, there was relative stabilization of inflammatory markers including neutrophil count, neutrophil to lymphocyte ratio (NLR) and CRP over the first 3-5 days of antibiotic treatment. In total this data suggests that recovery from cellulitis is prolonged and that the need for urgent ID consultation and change in antibiotics should only be considered if there is worsening of objective physical exam findings. Additionally, the paper suggests that anti-inflammatories including non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may be considered as adjuvant agents in the treatment of lower extremity cellulitis.

The second paper by Schmidt and colleagues from University of Michigan examines the outpatient management practice of patients presenting with acute diabetic foot ulcer (DFU) infection.³ The authors nicely outline what is at stake in this setting as there is a 155-fold increased risk of amputation once an infected DFU develops and 85% of lower extremity amputations are preceded by the development of an infected DFU.^4,5 Many, but not all societies recommend that debridement and obtaining a deep wound culture (not a superficial swab) should be performed to guide antibiotic therapy.⁶ The authors performed a retrospective cohort study of patients presenting with acute diabetic foot ulcer in the outpatient setting at the University of Michigan to compare those treated with empiric antibiotics vs those treated with deep culture-based antibiotics. The primary outcome was hospitalization within 30 days from a diabetes-related foot complication with the secondary objectives being lower extremity amputation and death in the year since diagnosis.

The investigators were able to enroll 116 patients that had adequate follow-up with the vast majority (68%) having mild infections confined to the skin and subcutaneous tissue. Interestingly 39 or one-third of these patients were treated with empiric antibiotics despite existing guidelines. In the group with mild infection the 30-day hospitalization from diabetic-foot related complications was statistically significantly greater in the empiric antibiotic group compared with the culture-driven group 52% vs 37.7%; p=0.04. Translated into practical terms the relative risk of hospitalization was 1.87 times higher in the empiric antibiotic group and the number needed to treat (NNT) with culture-based antibiotic therapy to prevent one hospitalization was low at 4. This data significantly favors the practice of early culture-based antibiotic therapy over empiric antibiotic therapy.

The editors of Open Forum Infectious Diseases should be commended for publishing two practical manuscripts to help guide interactions between internal medicine physicians and infectious disease consultants. In the setting of lower limb cellulitis, the treating physician can be comfortable with “watchful waiting” reserving consultation and antibiotic changes to patients with worsening objective findings while in mild diabetic foot ulcers they should have a “quick trigger” to getting that patient to a wound clinic or infectious disease clinic comfortable in obtaining deep cultures to guide antimicrobial therapy.

References

1. Williams OM, Hamilton F, Brindle R. The Natural History of Antibiotic-Treated Lower Limb Cellulitis: Analysis of Data Extracted From a Multicenter Clinical Trial. Open Forum Infect Dis. 2023 Sep 29;10(10): ofad488. doi: 10.1093/ofid/ofad488. PMID: 37849504; PMCID: PMC10578506.
2. Obaitan I, Dwyer R, Lipworth AD, et al. Failure of antibiotics in cellulitis trials: a systematic review and meta-analysis. Am J Emerg Med. 2016 Aug;34(8):1645-52. doi: 10.1016/j.ajem.2016.05.064. Epub 2016 May 26. PMID: 27344098.
3. Schmidt BM, Kaye KS, Armstrong DG, Pop-Busui R. Empirical Antibiotic Therapy in Diabetic Foot Ulcer Infection Increases Hospitalization. Open Forum Infect Dis. 2023 Oct 5;10(10): ofad495. doi: 10.1093/ofid/ofad495. PMID: 37849506; PMCID: PMC10578503.
4. Lavery LA, Armstrong DG, Wunderlich RP, Mohler MJ, Wendel CS, Lipsky BA. Risk factors for foot infections in individuals with diabetes. Diabetes Care. 2006 Jun;29(6):1288-93. doi: 10.2337/dc05-2425. PMID: 16732010.
5. Edmonds M, Manu C, Vas P. The current burden of diabetic foot disease. J Clin Orthop Trauma. 2021 Feb 8; 17:88-93. doi: 10.1016/j.jcot.2021.01.017. PMID: 33680841; PMCID: PMC7919962.
6. Lipsky BA, Berendt AR, Cornia PB, et al. Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun;54(12): e132-73. doi: 10.1093/cid/cis346. PMID: 22619242.