{'fraction_non_alphanumeric': 0.04095817301725208, 'fraction_numerical': 0.02829837408464689, 'mean_word_length': 5.329929300864101, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Stopping antibiotics after surgical amputation in diabetic foot and ankle infections—A daily practice cohort

Summary Objective The appropriate duration of antibiotic therapy for diabetic foot infections (DFI) after surgical amputations in toto is debated. There are discrepancies worldwide. Methods Using a clinical pathway for adult DFI patients (retrospective cohort analysis), we conducted a cluster‐controlled Cox regression analysis. Minimum follow‐up was 2 months. Results We followed 482 amputated DFI episodes for a median of 2.1 years after the index episode. The DFIs predominately affected the forefoot (n = 433; 90%). We diagnosed osteomyelitis in 239 cases (239/482; 50%). In total, 47 cases (10%) were complicated by bacteremia, 86 (18%) by abscesses and 139 (29%) presented with cellulitis. Surgical amputation involved the toes (n = 155), midfoot (280) and hindfoot (47). Overall, 178 cases (37%) required revascularization. After amputation, the median duration of antibiotic administration was 7 days (interquartile range, 1‐16 days). In 109 cases (25%), antibiotics were discontinued immediately after surgery. Overall, clinical failure occurred in 90 DFIs (17%), due to the same pathogens in only 38 cases. In multivariate analysis, neither duration of total postsurgical antibiotic administration (HR 1.0, 95% CI 0.99‐1.01) nor immediate postoperative discontinuation altered failure rate (HR 0.9, 0.5‐1.5). Conclusion According to our clinical pathway, we found no benefit in continuing postsurgical antibiotic administration in routine amputation for DFI. In the absence of residual infection (ie, resection at clear margins), antibiotics should be discontinued.


| Definitions and criteria
We used DFI definitions based on the IDSA guidelines criteria, which require clinical signs and symptoms of inflammation. 2 We included all DFI patients that were amputated or disarticulated in toto. Distal tibia and ankle amputations were included. We excluded amputations with no clinical signs of infection, regardless of microbiology results, 13 mid-tibia amputations, implant-related DFI and patients with <2 months of active follow-up. Osteomyelitis was diagnosed using clinical features (eg, visible bone), imaging (bone lesions without prior surgery or trauma 14 ) or microbiology (bacterial growth from surgically obtained bone specimens). We defined clinical failure as subsequent episodes of DFI occurring at the same location within 12 months. DFIs occurring later (ie, onset >12 months) were arbitrarily considered as new episodes. Microbiological failure was defined as recurrent DFI involving at least two of three pathogens from the index DFI recovered in deep tissue specimens. Remission was the absence of any clinical, laboratory or radiological evidence of failure at the end of follow-up. We considered antibiotics as broad-spectrum if piperacillin/tazobactam, glycopeptides, daptomycin, carbapenems or cefepime was used.

| Statistical analyses
We performed group comparisons using the Pearson chi-square test or the Wilcoxon rank-sum test. Cox regression analyses with cluster-control (random effect at patients' level) determined associations with failure. DFI episodes were censored at the last follow-up or occurrence of failure. We introduced independent variables having a P value ≤0.05 in the univariate analysis in a stepwise fashion in the multivariate model and checked for interaction (effect modification); antibiotic administration was automatically included into the final model. Age, total duration of antibiotic administration and duration of parenteral therapy were analysed both as continuous and categorical variables. The cut-off values of the strata were chosen according to the middle stratum positioned around the median value of that variable. We used Stata software (9.0, Stata™, College Station, TX, USA).

| Infections
The

| Antibiotic administrations
Prior to admission or initial surgical procedure, 96 episodes (20%) already received systemic antibiotic therapy, 20 but exact data on duration or dosage are lacking. Following amputation, median duration of systemic antibiotic administration was 7 days (IQR, 1-16 days) and median duration of parenteral use was 5 days (IQR, 0-12 days).
The entire antibiotic course was intravenous in 97 (20%) cases and oral in 69 cases (including perioperatively). In 109 cases (109/428; 25%), surgeons or physicians discontinued antibiotic administration immediately after amputation. The pathogens of these cases were not special or different from DFIs with antibiotic continuation.

| Outcomes
Among 482 amputation stumps, clinical failure at the same anatomical site occurred in 90 cases (17%) within one year. However, only 38 were microbiological failures (ie, due to the same microorganisms; 38/482; 8%). There was at least partial concordance of the three dominant pathogens isolated from wound cultures between the initial and subsequent DFI episodes in only 42% of cases. Hence, the majority of subsequent DFI episodes (58%) were "clinical recurrences", rather than "microbiological recurrences" according to our definitions. Additionally, progressive ischaemia without clinical DFI

| Multivariate adjustment
In view of the considerable case-mix inherent in DFI, we performed a Cox regression analysis. Specifically, stump failures were not associated with antibiotic therapy-related variations, limb revascularization, insulin therapy, surgical interventions, use of vacuum-assisted devices, or presence of abscesses or former hindfoot osteomyelitis. Table 2 shows these results for the entire study population and separately for cases with osteomyelitis. Hyperbaric oxygen use was protective in the univariate (HR 2.0; 95% CI 1.3-2.6), but not in the multivariate analysis and the osteomyelitis episodes-only analysis (Table 2). Finally, we repeated theses multivariate analyses for cases undergoing angioplasty. In this latter substratum, total duration of post-amputation antibiotics or their immediate interruption equally did not alter outcomes (HR 1.0, 95% CI 1.0-1.0) and HR 0.4, 95% CI 0.2-1.2), respectively.

This study of adult DFI patients from a defined clinical pathway
shows that the duration of antibiotic administration following radical amputation did not affect microbiological or clinical failure. This was equally true when interrupting antibiotic therapy immediately after wound closure and when analysing osteomyelitis cases alone.
Our study, with a total of 482 amputations in the infected diabetic foot, is to the best of our knowledge the largest existing single-centre database of its kind. It is unlikely that our findings are related to insufficient sample size. Also, since we included all hospitalized patients, this study reflects real-life conditions at our centre's clinical practice, thus reducing selection bias. Our rate of clinical recurrence (17%) is similar to that reported in the literature (15%, 20 18% 21 and 19% 6 depending on the studies). This is equally true regarding our microbiology-confirmed recurrence rate of 8%, which is shared by other groups (6%-8%, 22 9%, 6 and 8% 23 ) as well.
The literature on duration of antibiotic therapy in amputated DFI is sparse and consists mostly of expert opinions. 2,7,24,25 Available original data mainly concern two questions. Firstly, prevention against surgical site infection 26 following major amputation, not specifically in DFI. Studies unanimously advocate the use of prophylactic antibiotics generally for 0-48 hours 5,27 and up to 5 days. 25,28 Secondly, residual infection, with authors supporting culture of intraoperative bone samples from residual stumps, 21,29 rather than from the removed bone. 30 Kowalski et al 21  tations, compared to a 23% incidence following disarticulation. 29 Positive margins were associated with worse outcome despite a TA B L E 1 Comparison of demographic, clinical and treatment characteristics of amputated patients with a single episode, versus those with subsequent episodes, of diabetic foot infection(s)