Aim: To assess amoxicillin-clavulanate (AMC) for the oral therapy of diabetic foot infections (DFIs), especially for diabetic foot osteomyelitis (DFO). Methods:We performed a retrospective cohort analysis among 794 DFI episodes, including 339 DFO cases. Results:The median duration of antibiotic therapy after surgical debridement (including partial amputation) was 30 days (DFO, 30 days). Oral AMC was prescribed for a median of 20 days (interquartile range, 12-30 days). The median ratio of oral AMC among the entire antibiotic treatment was 0.9 (interquartile range, 0.7-1.0). After a median follow-up of 3.3 years, 178 DFIs (22%) overall recurred (DFO, 75; 22%). Overall, oral AMC led to 74% remission compared with 79% with other regimens (χ 2 -test; P = 0.15). In multivariate analyses and stratified subgroup analyses, oral AMC resulted in similar clinical outcomes to other antimicrobial regimens, when used orally from the start, after an initial parenteral therapy, or when prescribed for DFO.Conclusions: Oral AMC is a reasonable option when treating patients with DFIs and DFOs. K E Y W O R D Samoxillin-clavunalate, diabetic foot infections, failures, oral β-lactams, osteomyelitis

Background: Few studies have addressed the appropriate duration of antibiotic therapy for diabetic foot infections (DFI) with or without amputation. We will perform two randomized clinical trials (RCTs) to reduce the antibiotic use and associated adverse events in DFI. Methods: We hypothesize that shorter durations of postdebridement systemic antibiotic therapy are noninferior (10% margin, 80% power, alpha 5%) to existing (long) durations and we will perform two unblinded RCTs with a total of 400 DFI episodes (randomization 1:1) from 2019 to 2022. The primary outcome for both RCTs is remission of infection after a minimal follow-up of 2 months. The secondary outcomes for both RCTs are the incidence of adverse events and the overall treatment costs. The first RCT will allocate the total therapeutic amputations in two arms of 50 patients each: 1 versus 3 weeks of antibiotic therapy for residual osteomyelitis (positive microbiological samples of the residual bone stump); or 1 versus 4 days for remaining soft tissue infection. The second RCT will randomize the conservative approach (only surgical debridement without in toto amputation) in two arms with 50 patients each: 10 versus 20 days of antibiotic therapy for soft tissue infections; and 3 versus 6 weeks for osteomyelitis. All participants will have professional wound debridement, adequate off-loading, angiology evaluation, and a concomitant surgical, re-educational, podiatric, internist and infectiology care. During the surgeries, we will collect tissues for BioBanking and future laboratory studies. Discussion: Both parallel RCTs will respond to frequent questions regarding the duration of antibiotic use in the both major subsets of DFIs, to ensure the quality of care, and to avoid unnecessary excesses in terms of surgery and antibiotic use. Trial registration: ClinicalTrials.gov, NCT04081792. Registered on 4 September 2019.

Background: Few studies address the appropriate duration of antibiotic therapy for diabetic foot infections (DFI); with or without amputation. We will perform two randomized clinical trials (RCT) to reduce the antibiotic use and associated adverse events in DFI. Methods: We hypothesize that shorter durations of post-debridement systemic antibiotic therapy are non-inferior (10% margin, 80% power, ɑ 5%) to existing (long) durations and we will perform two unblinded RCTs with a total of 400 DFI episodes (randomization 1:1) from 2019 to 2022. The primary outcome for both RCT is “remission of infection” after a minimal follow-up of two months. The secondary outcomes for both RCT are the incidence of adverse events and the overall treatment costs. The First RCT will allocate the total therapeutic amputations in two arms of 50 patients each: 1 vs. 3 weeks of antibiotic therapy for residual osteomyelitis (positive microbiological samples of the residual bone stump); or 1 vs. 4 days for remaining soft tissue infection. The Second RCT will randomize the conservative approach (only surgical debridement without in toto amputation) in two arms with 50 patients each: 10 vs. 20 days of antibiotic therapy for soft tissue infections; and 3 vs. 6 weeks for osteomyelitis. All participants will have professional wound debridement, adequate off-loading, angiology evaluation, and a concomitant surgical, re-educational, podiatric, internist and infectiology care. During the surgeries, we will collect tissues for BioBanking and future laboratory studies. Discussion: Both parellel RCTs will repond to frequent questions regarding the duration of antibiotic use in the both major subsets of DFIs, to assure the quality of care, and to avoid unnecessary excesses in terms of surgery and antibiotic use. Trial registration: ClinicalTrial.gov NCT04081792. Registered on 4th September 2019. Protocol version: 2 (15th July 2019)

Abstract. Flucloxacillin (FLU) administered by the oral route is widely used for treating various infections, but there are no published retrospective or prospective trials of its efficacy, or its advantages or disadvantages compared to parenteral treatment or other antibiotics for treating osteomyelitis. Based on published in vitro data and expert opinions, other non-β-lactam oral antibiotics that have better bone penetration are generally preferred over oral FLU. We reviewed the literature for studies of oral FLU as therapy of osteomyelitis (OM), stratified by acute versus chronic and pediatric versus adult cases. In striking contrast to the prevailing opinions and the few descriptive data available, we found that treatment of OM with oral FLU does not appear to be associated with more clinical failures compared to other oral antibiotic agents. Because of its narrow antibiotic spectrum, infrequent severe adverse effects, and low cost, oral FLU is widely used in clinical practice. We therefore call for investigators to conduct prospective trials investigating the effectiveness and potential advantages of oral FLU for treating OM.

No abstract

The use of antibiotics for the treatment of diabetic foot infections (DFIs) over an extended period of time has been shown to be associated with adverse events (AEs), whereas interactions with concomitant patient medications must also be considered. The objective of this narrative review was to summarize the most frequent and most severe AEs reported in prospective trials and observational studies at the global level in DFI. Gastrointestinal intolerances were the most frequent AEs, from 5% to 22% among all therapies; this was more common when prolonged antibiotic administration was combined with oral beta-lactam or clindamycin or a higher dose of tetracyclines. The proportion of symptomatic colitis due to Clostridium difficile was variable depending on the antibiotic used (0.5% to 8%). Noteworthy serious AEs included hepatotoxicity due to beta-lactams (5% to 17%) or quinolones (3%); cytopenia’s related to linezolid (5%) and beta-lactams (6%); nausea under rifampicin, and renal failure under cotrimoxazole. Skin rash was found to rarely occur and was commonly associated with the use of penicillins or cotrimoxazole. AEs from prolonged antibiotic use in patients with DFI are costly in terms of longer hospitalization or additional monitoring care and can trigger additional investigations. The best way to prevent AEs is to keep the duration of antibiotic treatment short and with the lowest dose clinically necessary.

Background: Few studies address the appropriate duration of antibiotic therapy for diabetic foot infections (DFI); with or without amputation. We perform two randomized clinical trials (RCT) to reduce the antibiotic use and associated adverse events in DFI.Methods: We hypothesize that shorter durations of post-debridement systemic antibiotic therapy are non-inferior (10% margin, 80% power, ɑ 5%) to existing (long) durations and perform two unblinded RCTs with a total of 400 DFI episodes (randomization 1:1) from 2019 to 2022. The primary outcome for both RCT is "remission of infection" after a minimal follow-up of two months. The 1 st RCT allocates the amputations in two arms of 50 patients each: 1 vs. 3 weeks of antibiotic therapy for residual osteomyelitis (positive microbiological samples of the residual bone stump); or 1 vs. 4 days for remaining soft tissue infection. The 2 nd RCT randomizes the conservative approach in two arms with 50 patients each: 10 vs. 20 days of antibiotic therapy for soft tissue infections; and 3 vs. 6 weeks for osteomyelitis. All participants have professional wound debridement, adequate off-loading, angiology evaluation, and a concomitant surgical, re-educational, internist and infectiology care.During the surgeries, we collect tissues for BioBanking and future laboratory studies.Discussion: Both parellel RCT will enable to prescribe less antibiotics for DFI; for a conservative therapy and after amputation. Trial registration: ClinicalTrial.gov NCT04081792. Registered on 4 th September 2019. Protocol version : 2 (15 th July 2019) Study settingThe Balgrist University Hospital in Zurich is a tertiary referral center for DFI and amputations (emergency and elective consultations with a 24-hour service) and affiliated to the University of Zurich. Regarding DFIs, it resumes a multidisciplinary team composed of four diabetic foot surgeons, three internist physicians, a hospital pharmacist, five specialized wound nurses, musculoskeletal expert radiologists, a diabetes nurse, three nutritionists, a shoemaker, a prosthesis specialist, and up to four infectious diseases physicians who are specialized in orthopedic infections. Moreover, this team is supported by an in-house company for orthopedic footwear (Balgrist Tec) and individual adaptations of off-loading devices, a re-education unit, physical therapy, a research campus (Balgrist

Chronic diabetic foot osteomyelitis (DFO) is a frequent complication in adult polyneuropathy patients with long-standing diabetes mellitus. Regarding the conservative therapy, there are several crucial steps in adequate diagnosing and approaches. The management should be performed in a multidisciplinary approach following the findings of recent research, general principles of antibiotic therapy for bone; and according to (inter-)national guidance. In this chapter we emphasize the overview on the state-of-the-art management regarding the diagnosis and antibiotic therapy in DFO. In contrast, in this general narrative review and clinical recommendation, we skip the surgical, vascular and psychological aspects.