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.

No Difference in Risk of Amputation or Frequency of Surgical Interventions Between Patients With Diabetic and Nondiabetic Charcot Arthropathy.

BACKGROUND: The cause of Charcot neuro-osteoarthropathy (CN) is diabetes in approximately 75% of patients. Most reports on the clinical course and complications of CN focus on diabetic CN, and reports on nondiabetic CN are scarce. No study, to our knowledge, has compared the clinical course of patients initially treated nonoperatively for diabetic and nondiabetic CN. QUESTIONS/PURPOSES: Among patients with CN, are there differences between patients with diabetes and those without in terms of (1) the frequency of major amputation as ascertained by a competing risks survivorship estimator; (2) the frequency of surgery as ascertained by a competing risks survivorship estimator; (3) frequency of reactivation, as above; or (4) other complications (contralateral CN development or ulcers)? METHODS: Between January 1, 2006, and December 31, 2018, we treated 199 patients for diabetic CN. Eleven percent (22 of 199) were lost before the minimum study follow-up of 2 years or had incomplete datasets and could not be analyzed, and another 9% (18 of 199) were excluded for other prespecified reasons, leaving 80% (159 of 199) for analysis in this retrospective study at a mean follow-up duration since diagnosis of 6 ± 4 years. During that period, we also treated 78 patients for nondiabetic Charcot arthropathy. Eighteen percent (14 of 78) were lost before the minimum study follow-up and another 5% (four of 78 patients) were excluded for other prespecified reasons, leaving 77% (60 of 78) of patients for analysis here at a mean of 5 ± 3 years. Patients with diabetic CN were younger (59 ± 11 years versus 68 ± 11 years; p < 0.01), more likely to smoke cigarettes (37% [59 of 159] versus 20% [12 of 60]; p = 0.02), and had longer follow-up (6 ± 4 years versus 5 ± 3 years; p = 0.02) than those with nondiabetic CN. Gender, BMI, overall renal failure, dialysis, and presence of peripheral arterial disease did not differ between the groups. Age difference and length of follow-up were not considered disqualifying problems because of the later onset of idiopathic neuropathy and longer available patient follow-up in patients with diabetes, because our program adheres to the follow-up recommendations suggested by the International Working Group on the Diabetic Foot. Treatment was the same in both groups and included serial total-contact casting and restricted weightbearing until CN had resolved. Then, patients subsequently transitioned to orthopaedic footwear. CN reactivation was defined as clinical signs of the recurrence of CN activity and confirmation on MRI. Group-specific risks of the frequencies of major amputation, surgery, and CN reactivation were calculated, accounting for competing events. Group comparisons and confounder analyses were conducted on these data with a Cox regression analysis. Other complications (contralateral CN development and ulcers) are described descriptively to avoid pooling of complications with varying severity, which could be misleading. RESULTS: The risk of major amputation (defined as an above-ankle amputation), estimated using a competing risks survivorship estimator, was not different between the diabetic CN group and nondiabetic CN group at 10 years (8.8% [95% confidence interval 4.2% to 15%] versus 6.9% [95% CI 0.9% to 22%]; p = 0.4) after controlling for potentially confounding variables such as smoking and peripheral artery disease. The risk of any surgery was no different between the groups as estimated by the survivorship function at 10 years (53% [95% CI 42% to 63%] versus 58% [95% CI 23% to 82%]; p = 0.3), with smoking (hazard ratio 2.4 [95% CI 1.6 to 3.6]) and peripheral artery disease (HR 2.2 [95% CI 1.4 to 3.4]) being associated with diabetic CN. Likewise, there was no between-group difference in CN reactivation at 10 years (16% [95% CI 9% to 23%] versus 11% [95% CI 4.5% to 22%]; p = 0.7) after controlling for potentially confounding variables such as smoking and peripheral artery disease. Contralateral CN occurred in 17% (27 of 159) of patients in the diabetic group and in 10% (six of 60) of those in the nondiabetic group. Ulcers occurred in 74% (117 of 159) of patients in the diabetic group and in 65% (39 of 60) of those in the nondiabetic group. CONCLUSION: Irrespective of whether the etiology of CN is diabetic or nondiabetic, our results suggest that orthopaedic surgeons should use similar nonsurgical treatments, with total-contact casting until CN activity has resolved, and then proceed with orthopaedic footwear. A high frequency of foot ulcers must be anticipated and addressed as part of the treatment approach. LEVEL OF EVIDENCE: Level III, prognostic study.

Muscle atrophy in diabetic patients with Charcot foot: a case-control study.

PURPOSE: To evaluate the distribution and severity of muscle atrophy in diabetic patients with active Charcot foot (CF) compared to diabetic patients without CF. Furthermore, to correlate the muscle atrophy with severity of CF disease. MATERIAL/METHODS: In this retrospective study, MR images of 35 diabetic patients (21 male, median:62.1 years ± 9.9SD) with active CF were compared with an age- and gender-matched control group of diabetic patients without CF. Two readers evaluated fatty muscle infiltration (Goutallier-classification) in the mid- and hindfoot. Furthermore, muscle trophic (cross-sectional muscle area (CSA)), intramuscular edema (none/mild versus moderate/severe), and the severity of CF disease (Balgrist Score) were assessed. RESULTS: Interreader correlation for fatty infiltration was substantial to almost perfect (kappa-values:0.73-1.0). Frequency of fatty muscle infiltration was high in both groups (CF:97.1-100%; control:77.1-91.4%), but severe infiltration was significantly more frequent in CF patients (p-values: < 0.001-0.043). Muscle edema was also frequently seen in both groups, but significantly more often in the CF group (p-values: < 0.001-0.003). CSAs of hindfoot muscles were significantly smaller in the CF group. For the flexor digitorum brevis muscle, a cutoff value of 139 mm2 (sensitivity:62.9%; specificity:82.9%) in the hindfoot was found to differentiate between CF disease and the control group. No correlation was seen between fatty muscle infiltration and the Balgrist Score. CONCLUSION: Muscle atrophy and muscle edema are significantly more severe in diabetic patients with CF disease. Muscle atrophy does not correlate with the severity of active CF disease. A CSA < 139 mm2 of the flexor digitorum brevis muscle in the hindfoot may indicate CF disease.

Salami-Tactics: when is it time for a major cut after multiple minor amputations?

INTRODUCTION: Repetitive minor amputations carry the concomitant risks of multiple surgical procedures, major amputations have physical and economical major drawbacks. The aim of this study was to evaluate whether there is a distinct number of minor amputations predicting a major amputation in the same leg and to determine risk factors for major amputation in multiple minor amputations. MATERIALS AND METHODS: A retrospective chart review including 429 patients with 534 index minor amputations between 07/1984 and 06/2019 was conducted. Patient demographics and clinical data including number and level of re-amputations were extracted from medical records and statistically analyzed. RESULTS: 290 legs (54.3%) had one or multiple re-amputations after index minor amputation. 89 (16.7%) legs needed major amputation during follow up. Major amputation was performed at a mean of 32.5 (range 0 - 275.2) months after index minor amputation. No particular re-amputation demonstrated statistically significant elevated odds ratio (a.) to be a major amputation compared to the preceding amputation and (b.) to lead to a major amputation at any point during follow up. Stepwise multivariate Cox regression analysis revealed minor re-amputation within 90 days (HR 3.8, 95% CI 2.0-7.3, p <0.001) as the only risk factor for major amputation if at least one re-amputation had to be performed. CONCLUSIONS: There is no distinct number of prior minor amputations in one leg that would justify a major amputation on its own. If a re-amputation has to be done, the timepoint needs to be considered as re-amputations within 90 days carry a fourfold risk for major amputation. LEVEL OF EVIDENCE: Retrospective comparative study (Level III).

Long-term follow-up of conservative treatment of Charcot feet.

BACKGROUND: Charcot arthropathy (CN) can ultimately lead to limb loss despite appropriate treatment. Initial conservative treatment is the accepted treatment in case of a plantigrade foot. The aim of this retrospective study was to investigate the mid- to long-term clinical course of CN initially being treated conservatively, and to identify risk factors for reactivation and contralateral development of CN as well as common complications in CN. METHODS: A total of 184 Charcot feet in 159 patients (median age 60.0 (interquartile range (IQR) 15.5) years, 49 (30.1%) women) were retrospectively analyzed by patient chart review. Rates of limb salvage, reactivation, contralateral development and common complications were recorded. Statistical analysis was performed to identify possible risk factors for limb loss, CN reactivation, contralateral CN development, and ulcer development. RESULTS: Major amputation-free survival could be achieved in 92.9% feet after a median follow-up of 5.2 (IQR 4.25, range 2.2-11.25) years. CN recurrence occurred in 13.6%. 32.1% had bilateral CN involvement. Ulcers were present in 72.3%. 88.1% patients were ambulating in orthopaedic footwear without any further aids. Presence of Diabetes mellitus was associated with reactivation of CN, major amputation and ulcer recurrence. Smoking was associated with ulcer development and necessity of amputations. CONCLUSIONS: With consistent conservative treatment of CN with orthopaedic footwear or orthoses, limb preservation can be achieved in 92.9% after a median follow-up of 5.2 years. Patients with diabetic CN are at an increased risk of developing complications and CN reactivation. To prevent ulcers and amputations, every effort should be made to make patients stop smoking. LEVEL OF EVIDENCE: III, long-term retrospective cohort study.

Long-term results after internal partial forefoot amputation (resection): a retrospective analysis.

INTRODUCTION: Internal partial forefoot amputation (IPFA) is a treatment option for osteomyelitis and refractory and recurrent chronic ulcers of the forefoot. The aim of our study was to assess the healing rate of chronic ulcers, risk of ulcer recurrence at the same area or re-ulceration at a different area and revision rate in patients treated with IPFA. MATERIALS AND METHODS: All patients who underwent IPFA of a phalanx and/or metatarsal head and/or sesamoids at our institution because of chronic ulceration of the forefoot and/or osteomyelitis from 2004 to 2014 were included. Information about patient characteristics, ulcer healing, new ulcer occurrence, and revision surgery were collected. Kaplan-Meier survival curves were plotted for new ulcer occurrence and revision surgery. RESULTS: A total of 102 patients were included (108 operated feet). 55.6% of our patients had diabetes. In 44 cases, an IPFA of a phalanx was performed, in 60 cases a metatarsal head resection and in 4 cases an isolated resection of sesamoids. The mean follow-up was 40.9 months. 91.2% of ulcers healed after a mean period of 1.3 months. In 56 feet (51.9%), a new ulcer occurred: 11 feet (10.2%) had an ulcer in the same area as initially (= ulcer recurrence), in 45 feet (41.7%) the ulcer was localized elsewhere (= re-ulceration). Revision surgery was necessary in 39 feet (36.1%). Only one major amputation and five complete transmetatarsal forefoot amputations were necessary during the follow-up period. Thus, the major amputation rate was 0.9%, and the minor amputation rate on the same ray was 13.9%. CONCLUSIONS: IPFA is a valuable treatment of chronic ulcers of the forefoot. However, new ulceration is a frequent event following this type of surgery. Our results are consistent with the reported re-ulceration rate after conservative treatment of diabetic foot ulcers. The number of major amputations is low after IPFA. LEVEL OF EVIDENCE: Retrospective Case Series Study (Level IV).

Mid-term walking ability after Charcot foot reconstruction using the Ilizarov ring fixator.

BACKGROUND: Failed conservative treatment and complications are indications for foot reconstruction in Charcot arthropathy. External fixation using the Ilizarov principles offers a one-stage procedure for deformity correction and resection of osteomyelitic bone. The aim of this study was to determine whether external fixation with an Ilizarov ring fixator leads reliably to walking ability. MATERIALS AND METHODS: 29 patients treated with an Ilizarov ring fixator for Charcot arthropathy were retrospectively analyzed. Radiologic fusion at final follow up was assessed separately on conventional X-rays by two authors. The association between walking ability and the presence of osteomyelitis at the time of reconstruction, and the presence of fusion at final follow up was investigated using Fisher's exact test. RESULTS: Mean follow up was 35 months (range 5.3-107) months; mean time of external fixation was 113 days. Ten patients (34.5%) reached fusion, but 19 did not (65.5%). Two patients needed below knee amputation. 26 of the remaining 27 patients maintained walking ability, 23 of those without assistive devices. Walking ability was independent from the presence of osteomyelitis at the time of reconstruction and from the presence of fusion. CONCLUSION: Foot reconstruction with an Ilizarov ring fixator led to limb salvage in 93%. The vast majority (96.3%) of patients with successful limb salvage was ambulatory, independent from radiologic fusion, and presence of osteomyelitis at the time of reconstruction. These findings encourage limb salvage and deformity correction in this difficult-to-treat disease, even with underlying osteomyelitis.

Outcome of Ray Resection as Definitive Treatment in Forefoot Infection or Ischemia: A Cohort Study.

Ray resection is frequently performed in cases of infection or ischemia, but the literature is scarce concerning its outcome as a definitive treatment. In this retrospective cohort study, we reviewed our cohort with transmetatarsal ray resection with a mean follow-up of 36.3 months. Reulcerations, transfer ulcers, and reamputations were determined. Risk factor analysis for revision surgery was conducted. Among 185 patients, 71 (38.4%) had revision surgery within a mean of 1.4 ± 2.6 years (range 2 days to 12.9 years), 22 (11.9%) had major amputations, 49 (26.5%) had minor amputations, 11 (5.9%) had same-ray reulceration, 40 (21.6%) had transfer ulceration, and 2 (1.1%) had both reulceration and transfer ulceration. Occurrence of a postoperative ulcer was statistically significantly associated with revision surgery (p < .01). In conclusion, metatarsal ray resection is a reasonable treatment option in cases of forefoot ischemia or infection to prevent major amputation but fails in 11.9%, and reulceration is associated with further revisions, making ulcer prevention paramount.

Predictors for reoperation after lower limb amputation in patients with peripheral arterial disease.

Background: Major amputations in patients with peripheral arterial disease (PAD) carry a high risk for complications, including revision of the amputation, sometimes to a higher level. Determining a safe level for amputation with good wound healing potential depends largely on vascular measurements. This study evaluated potential predictive factors for revision of major lower extremity amputations in patients with PAD. Patients and methods: A retrospective chart review of all major lower extremity amputations at our institution was conducted. Amputations due to trauma or tumor and below-ankle amputations were excluded. Patient demographics, level/type of amputation, level/time of revision, comorbidities and risk factors were extracted. Results: 180 patients with PAD, mean age 66.48 (range: 31-93) years, 125 (69.4%) male were included. Most (154/180, 86.6%) underwent below-knee amputation. 71 (39.4%) patients had coronary arterial disease, 104 (57.8%) had diabetes. More than half of patients, (93/138; 51.7%) had undergone previous balloon angioplasty. 44 (30%) patients required revision surgery: 42/180 (23.3%) were revised at the same level, and in 12/180 (6.7%) a more proximal amputation was necessary. PAD stage was not associated with the level of reamputation (p = 0.4369). Significantly more patients who had previous balloon angioplasty required revision surgery (66.7% versus 45.2%, p = 0.009). 67 (37.2%) patients underwent preoperative TcPO2 measurement: 40/67 (59.7%) had TcPO2 ≥ 40 mmHg; 4/67 (6%) had TcPO2 < 10 mmHG. Three patients with TcPO2 ≥ 40 mmHg, one with 30 mmHg ≤ TcPO2 ≤ 40 mmHg and one with 10 mmHg ≤ TcPO2 ≤ 20 mmHg required re-amputation to a more proximal level. Conclusions: TcPO2 measurements are useful for determining level of lower limb amputation and predicting wound healing problems when an amputation level with TcPO2 < 40 mmHg is chosen. In transtibial amputations, TcPO2 ≥ 40 mmHg does not safely predict wound healing.

Second Metatarsal Length and Transfer Ulcers After First Metatarsal Amputation in Diabetic Foot Infections.

BACKGROUND: Plantar transfer ulcers (TUs) underneath the second metatarsal head are frequent after first metatarsal ray amputations due to diabetic foot infections. Whether the second metatarsal length (2ML) is associated with TU occurrence in these patients is unclear. This study evaluated whether 2ML is associated with TU occurrence after first-ray amputations and whether ulcer-free survival is shorter in patients with "excess" 2ML. METHODS: Forty-two patients with a mean age of 67 (range 33-93) years, diabetes, and first metatarsal ray amputation (first amputation at the affected foot) were included. Two independent readers measured the 2ML using the Coughlin method. A protrusion of more than 4.0 mm of the second metatarsal was defined as "excess" 2ML. The effect of 2ML on ulcer occurrence was analyzed using a multivariate Cox regression model. A Kaplan-Meier curve for TU-free survival was constructed comparing the 2 groups of "normal" (n = 21) and "excess" 2ML (n = 21). RESULTS: Interrater reliability was excellent. TUs underneath the second metatarsal occurred in 15 (36%) patients. In agreement with our hypothesis, 2ML was nonsignificantly different in patients with TUs, recording a mean of 5.3 (SD 2.5) mm, compared to patients without 4.0 (SD 2.3) mm (hazard ratio [HR] 1.12, 95% CI 0.89-1.41), whereas insulin dependence was associated with ulcer occurrence (HR 0.33, 95% CI 0.11-0.99). CONCLUSION: In our relatively small study population with a cutoff level of 4 mm for excess 2ML, ulcer-free survival was similar in patients with "normal" and "excess" 2ML. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

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.

Current knowledge of morbidities and direct costs related to diabetic foot disorders: a literature review.

Diabetes is a chronic disease associated with numerous complications including diabetic foot disorders, which are associated with significant morbidity and mortality as well as high costs. The costs associated with diabetic foot disorders comprise those linked to care (direct) and loss of productivity and poor quality of life (indirect). Due to the constant increase in diabetes prevalence, it is expected that diabetic foot disorder will require more resources, both in terms of caregivers and economically. We reviewed findings on management, morbidity, mortality, and costs related to diabetic foot disorder.

Ulcer occurrence on adjacent toes and hallux valgus deformity after amputation of the second toe in diabetic patients.

BACKGROUND: Amputation of the second toe is associated with destabilization of the first toe. Possible consequences are hallux valgus deformity and subsequent pressure ulcers on the lateral side of the first or on the medial side of the third toe. The aim of this study was to investigate the incidence and possible influencing factors of interdigital ulcer development and hallux valgus deformity after second toe amputation. METHODS: Twenty-four cases of amputation of the second toe between 2004 and 2020 (mean age 68 ± 12 years; 79% males) were included with a mean follow-up of 36 ± 15 months. Ulcer development on the first, third, or fourth toe after amputation, the body mass index (BMI) and the amputation level (toe exarticulation versus transmetatarsal amputation) were recorded. Pre- and postoperative foot radiographs were evaluated for the shape of the first metatarsal head (round, flat, chevron-type), the hallux valgus angle, the first-second intermetatarsal angle, the distal metatarsal articular angle and the hallux valgus interphalangeal angle by two orthopedic surgeons for interobserver reliability. RESULTS: After amputation of the second toe, the interdigital ulcer rate on the adjacent toes was 50% and the postoperative hallux valgus rate was 71%. Neither the presence of hallux valgus deformity itself (r = .19, p = .37), nor the BMI (r = .09, p = .68), the shape of the first metatarsal head (r = - .09, p = .67), or the amputation level (r = .09, p = .69) was significantly correlated with ulcer development. The interobserver reliability of radiographic measurements was high, oscillating between 0.978 (p = .01) and 0.999 (p = .01). CONCLUSIONS: The interdigital ulcer rate on the first or third toe after second toe amputation was 50% and hallux valgus development was high. To date, evidence on influencing factors is lacking and this study could not identify parameters such as the BMI, the shape of the first metatarsal head or the amputation level as risk factors for the development of either hallux valgus deformity or ulcer occurrence after second toe amputation. TRIAL REGISTRATION: BASEC-Nr. 2019-01791.

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.

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.

Nonoperative Treatment of Charcot Neuro-osteoarthropathy.

Conservative treatment of Charcot neuro-osteoarthropathy (CN) aims to retain a stable, plantigrade, and ulcer-free foot, or to prevent progression of an already existing deformity. CN is treated with offloading in a total contact cast as long as CN activity is present. Transition to inactive CN is monitored by the resolution of clinical activity signs and by resolution of bony edema in MRI. Fitting of orthopedic depth insoles, orthopedic shoes, or ankle-foot orthosis should follow immediately after offloading has ended to prevent CN reactivation or ulcer development.

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.

Endoscopic Treatment of Stump Infection of the Residual Synovial Cavity After Through-the-Knee Amputation: A Case Report.

CASE: We report the case of a 35-year-old patient who presented with a septic residual synovial cavity infection 8 weeks after a through-the-knee amputation because of a parosteal sarcoma. An endoscopic evacuation of the turbid fluid and synovial debridement through parapatellar portals as in a standard knee arthroscopy was performed, in conjunction with appropriate antibiotic therapy. One year postoperatively, there were no signs of residual infection. CONCLUSION: Endoscopic treatment of a septic stump infection of the residual synovial cavity after through-the-knee amputation is feasible. In our case, this approach resulted in rapid wound healing and early prosthesis mobility.

Short and oral antimicrobial therapy for diabetic foot infection: a narrative review of current knowledge.

Diabetic foot infection is a frequent complication in long-standing diabetes mellitus. For antimicrobial therapy of this infection, both the optimal duration and the route of administration are often based more on expert opinion than on published evidence. We reviewed the scientific literature, specifically seeking prospective trials, and aimed at addressing two clinical issues: (1) shortening the currently recommended antibiotic duration and (2) using oral (rather than parenteral) therapy, especially after the patient has undergone debridement and revascularization. We also reviewed some older key articles that are critical to our understanding of the treatment of these infections, particularly with respect to diabetic foot osteomyelitis. Our conclusion is that the maximum duration of antibiotic therapy for osteomyelitis should be no more than to 4-6 weeks and might even be shorter in selected cases. In the future, in addition to conducting randomized trials and propagating national and international guidance, we should also explore innovative strategies, such as intraosseous antibiotic agents and bacteriophages.