Foot Osteomyelitis Location and Rates of Primary or Secondary Major Amputations in Patients With Diabetes

BACKGROUND Diabetic foot osteomyelitis (DFO) often leads to amputations in the lower extremity. Data on the influence of the initial anatomical DFO localization on ultimate major amputation are limited. METHODS In this retrospective analysis, 583 amputation episodes in 344 patients (78 females, 266 males) were analyzed. All received a form of amputation in combination with antibiotic therapy. A multivariate logistic regression analysis with the primary outcome "major amputation" defined as an amputation above the ankle joint was performed. The association of risk factors including location of DFO, coronary artery disease, peripheral artery disease, neuropathy, nephropathy, and Charcot neuro-osteoarthropathy was analyzed. RESULTS Among 583 episodes, DFO was located in the forefoot in 512 (87.8%), in the midfoot in 43 (7.4%), and in the hindfoot in 28 episodes (4.8%). Overall, 53 of 63 (84.1%) major amputations were performed because of DFO in the setting of peripheral artery disease as primary indication. Overall, limb loss occurred in 6.1% (31/512) of forefoot, 20.9% (9/43) of midfoot, and 46.4% (13/28) of hindfoot DFO. Among these, 22 (41.5%) were performed as the primary treatment, whereas 31 (58.5%) followed previously failed minor amputations. Among this latter group of secondary major amputations, the DFO was localized to the forefoot in 23 of 583 (3.9%), the midfoot in 4 of 583 (0.7%) and the hindfoot in 4 of 583 (0.7%). In multivariate logistic regression analysis, initial hindfoot localization was a significant factor (P < .05), whereas peripheral artery disease, smoking, and a midfoot DFO were not found to be risk factors. CONCLUSION In our retrospective series, the frequency of limb loss in DFO increased with more proximal initial foot DFO lesions, with almost half of patients losing their limbs with a hindfoot DFO. LEVEL OF EVIDENCE Level IV, retrospective cohort study

The impact of the length of total and intravenous systemic antibiotic therapy for the remission of diabetic foot infections

OBJECTIVE We investigated the impact of the total length of systemic antibiotic therapy (ABT) and its initial intravenous (IV) part on clinical failure (CF) and microbiological failure (MF) in diabetic foot infections (DFIs). METHODS In this single-center, retrospective, unmatched case-control study, we included DFI episodes treated with a combined surgical-antibiotic approach. RESULTS We included 721 DFI episodes, 537 with osteomyelitis (DFO). CF occurred in 191 (26.5%) and MF in 42 (5.8%) episodes. Multivariate Cox regression analysis showed that a short ABT of 8-21 days (hazard ratio [HR] 0.4; 95% CI 0.2-0.7) was inversely associated with CF. This was also applicable for IV ABT with relatively short durations of 2-7 days (HR 0.5; 95% CI 0.3-0.8) or 8-14 days (HR 0.6; 95% CI 0.4-0.9). We failed to detect a minimal threshold of total or IV ABT predictive for CF or MF. CONCLUSIONS Compared with total ABT of more than 84 days and IV therapy of more than 14 days, shorter total and IV ABT yielded no enhanced risk of CF or MF. Considering the "bias by indication" that is inherent to retrospective DFI studies, the best study design concerning the duration of ABT would be a stratified, prospective randomized trial, which is currently under way in our medical center

Comparative Efficacy of Conservative Surgery vs Minor Amputation for Diabetic Foot Osteomyelitis

BACKGROUND: There is uncertainty regarding the optimal surgical intervention for diabetic foot osteomyelitis (DFO). Conservative surgery-amputation-free resection of infected bone and soft tissues-is gaining traction as an alternative to minor amputation. Our primary objective was to explore the comparative effectiveness of conservative surgery and minor amputations in clinical failure risk 1 year after index intervention. We also aimed to explore microbiological recurrence at 1 year, and revision surgery risk over a 10-year study period. METHODS: Retrospective, single-center chart review of DFO patients undergoing either conservative surgery or minor amputation. We used multivariable Cox regression and Kaplan-Meier estimates to explore the effect of surgical intervention on clinical failure (recurrent diabetic foot infection at surgical site within 1 year after index operation), microbiological recurrence at 1 year, and revision surgery risk over a 10-year follow-up period. RESULTS: 651 patients were included (conservative surgery, n = 121; minor amputation, n = 530). Clinical failure occurred in 34 (28%) patients in the conservative surgery group, and in 111 (21%) of the minor amputation group at 1 year (P = .09). After controlling for potential confounders, we found no association between conservative surgery and clinical failure at 1 year (adjusted hazard ratio [HR] 1.3, 95% CI 0.8-2.1). We found no between-group differences in microbiological recurrence at 1 year (conservative surgery: 8 [6.6%]; minor amputation: 33 [6.2%]; P = .25; adjusted HR 1.1, 95% CI 0.5-2.6). Over the 10-year period, the conservative group underwent significantly more revision surgeries (conservative surgery: 85 [70.2%]; minor amputation: 252 [47.5%]; P < .01; adjusted HR 1.3, 95% CI 0.9-1.8). CONCLUSION: We found that with comorbidity-based patient selection, conservative surgery in the treatment of DFO was associated with the same rates of clinical failure and microbiological recurrence at 1 year, but with significantly more revision surgeries during follow-up, compared with minor amputations. LEVEL OF EVIDENCE: Level III, retrospective comparative effectiveness study

The Epidemiology of Antibiotic-Related Adverse Events in the Treatment of Diabetic Foot Infections: A Narrative Review of the Literature

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

Timing of Revascularization and Parenteral Antibiotic Treatment Associated with Therapeutic Failures in Ischemic Diabetic Foot Infections

For ischemic diabetic foot infections (DFIs), revascularization ideally occurs before surgery, while a parenteral antibiotic treatment could be more efficacious than oral agents. In our tertiary center, we investigated the effects of the sequence between revascularization and surgery (emphasizing the perioperative period of 2 weeks before and after surgery), and the influence of administering parenteral antibiotic therapy on the outcomes of DFIs. Among 838 ischemic DFIs with moderate-to-severe symptomatic peripheral arterial disease, we revascularized 608 (72%; 562 angioplasties, 62 vascular surgeries) and surgically debrided all. The median length of postsurgical antibiotic therapy was 21 days (given parenterally for the initial 7 days). The median time delay between revascularization and debridement surgery was 7 days. During the long-term follow-up, treatment failed and required reoperation in 182 DFI episodes (30%). By multivariate Cox regression analyses, neither a delay between surgery and angioplasty (hazard ratio 1.0, 95% confidence interval 1.0-1.0), nor the postsurgical sequence of angioplasty (HR 0.9, 95% CI 0.5-1.8), nor long-duration parenteral antibiotic therapy (HR 1.0, 95% CI 0.9-1.1) prevented failures. Our results might indicate the feasibility of a more practical approach to ischemic DFIs in terms of timing of vascularization and more oral antibiotic use

Initial antibiotic therapy for postoperative moderate or severe diabetic foot infections: Broad versus narrow spectrum, empirical versus targeted

AIM To retrospectively evaluate clinical and microbiological outcomes after combined surgical and medical therapy for diabetic foot infections (DFIs), stratifying between the empirical versus the targeted nature, and between an empirical broad versus a narrow-spectrum, antibiotic therapy. METHODS We retrospectively assessed the rate of ultimate therapeutic failures for each of three types of initial postoperative antibiotic therapy: adequate empirical therapy; culture-guided therapy; and empirical inadequate therapy with a switch to targeted treatment based on available microbiological results. RESULTS We included data from 332 patients who underwent 716 DFI episodes of surgical debridement, including partial amputations. Clinical failure occurred in 40 of 194 (20.6%) episodes where adequate empirical therapy was given, in 77 of 291 (26.5%) episodes using culture-guided (and correct) therapy from the start, and in 73 of 231 (31.6%) episodes with switching from empirical inadequate therapy to culture-targeted therapy. Equally, a broad-spectrum antibiotic choice could not alter this failure risk. Group comparisons, Kaplan-Meier curves and Cox regression analyses failed to show either statistical superiority or inferiority of any of the initial antibiotic strategies. CONCLUSIONS In this study, the microbiological adequacy of the initial antibiotic regimen after (surgical) debridement for DFI did not alter therapeutic outcomes. We recommend that clinicians follow the stewardship approach of avoiding antibiotic de-escalation and start with a narrow-spectrum regimen based on the local epidemiology

Nutritional Interventions May Improve Outcomes of Patients Operated on for Diabetic Foot Infections: A Single-Center Case-Control Study

Aim While a patient's nutritional status is known to generally have a role in postoperative wound healing, there is little information on its role as therapy in the multifaceted problem of diabetic foot infections (DFIs). Methods We assessed this issue by conducting a retrospective case-control cohort study using a multivariate Cox regression model. The nutrition status of the DFI patients was assessed by professional nutritionists, who also orchestrated the nutritional intervention (counselling, composition of the intrahospital food) during hospitalization. Results Among 1,013 DFI episodes in 586 patients (median age 67 years; 882 with osteomyelitis), 191 (19%) received a professional assessment of their nutrition accompanied by between 1 and 6 nutritional interventions. DFI cases who had professional nutritionists' interventions had a significantly shorter hospital stay, had shorter antibiotic therapies, and tended to fewer surgical debridements. By multivariate analysis, episodes with low Nutritional Risk Status- (NRS-) Scores 1-3 were associated with significantly lower failure rates after therapy for DFI (Cox regression analysis; hazard ratio 0.2, 95% confidence interval 0.1-0.7). Conclusions In this retrospective cohort study, DFI episodes with low NRS-Score were associated with lower rates of clinical failure after DFI treatment, while nutritional interventions improved the outcome of DFI. We need prospective interventional trials for this treatment, and these are underway

Correction of hyperglycemia after surgery for diabetic foot infection and its association with clinical outcomes

Objective: Constantly high glycemia levels might influence outcomes in the management of patients undergoing surgery for diabetic foot infections (DFI). In our center for DFI, we performed a case-control study using a multivariate Cox regression model. Patients developing a new DFI could participate in the study several times. Results: Among 1013 different DFI episodes in 586 individual adult patients (type I diabetes 148 episodes [15%], 882 [87%] with osteomyelitis; median antibiotic therapy of 21 days), professional diabetes counselling was provided by a specialized diabetes nurse in 195 episodes (19%). At admission, blood glucose levels were elevated in 110 episodes (11%). Treatments normalized glycemia on postoperative day 3 in 353 episodes (35%) and on day 7 for 321 (32%) episodes. Glycemia levels entirely normalized for 367 episodes (36%) until the end of hospitalization. Overall, treatment of DFI episodes failed in 255 of 1013 cases (25%), requiring surgical revision. By multivariate analysis, neither the provision of diabetes counseling, nor attaining normalizations of daily glycemic levels at day 3, day 7, or overall, influenced the ultimate incidence of clinical failures. Thus, the rapidity or success of achieving normoglycemia do not appear to influence the risk of treatment failure for operated DFI episodes. Keywords: Diabetic foot infections; Glycemia; Insulin therapy; Outcomes; Surger