Along with the increasing global burden of diabetes, diabetic foot infections (DFI) and diabetic foot osteomyelitis (DFO) remain major challenges for patients and society. Despite progress in the development of prominent international guidelines, the optimal medical treatment for DFI and DFO remains unclear as to whether local antibiotics, that is, topical agents and local delivery systems, should be used alone or concomitant to conventional systemic antibiotics. To better inform clinicians in this evolving field, we performed a narrative review and summarized key relevant observational studies and clinical trials of non-prophylactic local antibiotics for the treatment of DFI and DFO, both alone and in combination with systemic antibiotics. We searched PubMed for studies published between January 2000 and October 2022, identified 388 potentially eligible records, and included 19 studies. Our findings highlight that evidence for adding local antibiotic delivery systems to standard DFO treatment remains limited. Furthermore, we found that so far, local antibiotic interventions have mainly targeted forefoot DFO, although there is marked variation in the design of the included studies. Suggestive evidence emerging from observational studies underscores that the addition of local agents to conventional systemic antibiotics might help to shorten the clinical healing time and overall recovery rates in infected diabetic foot ulcers, although the effectiveness of local antibiotics as a standalone approach remains overlooked. In conclusion, despite the heterogeneous body of evidence, the possibility that the addition of local antibiotics to conventional systemic treatment may improve outcomes in DFI and DFO cannot be ruled out. Antibiotic stewardship principles call for further research to elucidate the potential benefits of local antibiotics alone and in combination with conventional systemic antibiotics for the treatment of DFI and DFO.

Background: Daptomycin-induced eosinophilic pneumonia (DEP) is a rare but severe adverse effect and the risk factors are unknown. The aim of this study was to determine risk factors for DEP. Methods: A retrospective cohort study was performed at the Bone and Joint Infection Unit of the Hospital Universitari Bellvitge (January 2014–December 2018). To identify risk factors for DEP, cases were divided into two groups: those who developed DEP and those without DEP. Results: Among the whole cohort (n = 229) we identified 11 DEP cases (4.8%) and this percentage almost doubled in the subgroup of patients ≥70 years (8.1%). The risk factors for DEP were age ≥70 years (HR 10.19, 95%CI 1.28–80.93), therapy >14 days (7.71, 1.98–30.09) and total cumulative dose of daptomycin ≥10 g (5.30, 1.14–24.66). Conclusions: Clinicians should monitor cumulative daptomycin dosage to minimize DEP risk, and be cautious particularly in older patients when the total dose of daptomycin exceeds 10 g.

Background: To evaluate the efficacy and safety of long-term use of tedizolid in osteoarticular infections. Methods: Multicentric retrospective study (January 2017–March 2019) of osteoarticular infection cases treated with tedizolid. Failure: clinical worsening despite antibiotic treatment or the need of suppressive treatment. Results: Cases (n = 51; 59% women, mean age of 65 years) included osteoarthritis (n = 27, 53%), prosthetic joint infection (n = 17, 33.3%), and diabetic foot infections (n = 9, 18%); where, 59% were orthopedic device-related. Most frequent isolates were Staphylococcus spp. (65%, n = 47; S. aureus, 48%). Reasons for choosing tedizolid were potential drug-drug interaction (63%) and cytopenia (55%); median treatment duration was 29 days (interquartile range -IQR- 15–44), 24% received rifampicin (600 mg once daily) concomitantly, and adverse events were scarce (n = 3). Hemoglobin and platelet count stayed stable throughout treatment (from 108.6 g/L to 116.3 g/L, p = 0.079; and 240 × 10⁹/L to 239 × 10⁹/L, p = 0.942, respectively), also in the subgroup of cases with cytopenia. Among device-related infections, 33% were managed with implant retention. Median follow-up was 630 days and overall cure rate 83%; among failures (n = 8), 63% were device-related infections. Conclusions: Long-term use of tedizolid was effective, showing a better safety profile with less myelotoxicity and lower drug-drug interaction than linezolid. Confirmation of these advantages could make tedizolid the oxazolidinone of choice for most of osteoarticular infections.

Surgical site infection (SSI) after elective orthopedic foot and ankle surgery is uncommon and may be higher in selected patient groups. Our main aim was to investigate the risk factors for SSI in elective orthopedic foot surgery and the microbiological results of SSI in diabetic and non-diabetic patients, in a tertiary foot center between 2014 and 2022. Overall, 6138 elective surgeries were performed with an SSI risk of 1.88%. The main independent associations with SSI in a multivariate logistic regression analysis were an ASA score of 3–4 points, odds ratio (OR) 1.87 (95% confidence interval (CI) 1.20–2.90), internal, OR 2.33 (95% CI 1.56–3.49), and external material, OR 3.08 (95% CI 1.56–6.07), and more than two previous surgeries, OR 2.86 (95% CI 1.93–4.22). Diabetes mellitus showed an increased risk in the univariate analysis, OR 3.94 (95% CI 2.59–5.99), and in the group comparisons (three-fold risk). In the subgroup of diabetic foot patients, a pre-existing diabetic foot ulcer increased the risk for SSI, OR 2.99 (95% CI 1.21–7.41), compared to non-ulcered diabetic patients. In general, gram-positive cocci were the predominant pathogens in SSI. In contrast, polymicrobial infections with gram-negative bacilli were more common in contaminated foot surgeries. In the latter group, the perioperative antibiotic prophylaxis by second-generation cephalosporins did not cover 31% of future SSI pathogens. Additionally, selected groups of patients revealed differences in the microbiology of the SSI. Prospective studies are required to determine the importance of these findings for optimal perioperative antibiotic prophylactic measures.

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/Objectives: We evaluated the diabetic foot ulcer (DFU) microbiome in clinical situations identified as risk factors for a worse outcome and explored the roles of the most abundant microorganisms. Methods: A prospective multicenter cohort of diabetic patients with DFU were followed up for 6 months. We obtained a DFU tissue biopsy for microbiome analysis at the baseline visit. Genomic DNA was extracted (QIAamp DNA Mini Kit, Qiagen, Hilden, Germany) and quantified (QuantiFluor dsDNA System, Promega, Madison, WI, USA), with analysis of bacterial communities focusing on relative abundances (RA) and on alpha and beta diversity. Results: Overall, 59 DFUs were analyzed. DFUs of long duration (≥4 weeks) presented a higher RA of Gammaproteobacteria compared with ulcers of short duration (p = 0.02). Non-infected DFUs had a higher proportion of Actinobacteriota phyla than infected DFUs and, particularly, a higher RA of Corynebacterium genera (means ± SD: 0.063 ± 0.14 vs. 0.028 ± 0.13, respectively; p = 0.03). Regarding the pathogenic role of Staphylococcus aureus, DFUs with low S. aureus bacterial loads (<10⁶ CFU/mL) compared with those with high loads (≥10⁶ CFU/mL) showed a higher Corynebacterium RA (0.045 ± 0.08 vs. 0.003 ± 0.01, respectively; p = 0.01). Conclusions: In clinical situations associated with poor DFU outcomes, we observed a predominance of Gammaproteobacteria in the microbiome of long-duration ulcers and a higher RA of Corynebacterium in non-infected DFUs. An inverse relationship between the predominance of Corynebacterium and the S. aureus bacterial load in DFUs was also noted, which may suggest these commensals have a modulatory role. Further studies should explore the clinical utility of microbiome analysis for DFUs.