Influence of Skin Commensals on Therapeutic Outcomes of Surgically Debrided Diabetic Foot Infections-A Large Retrospective Comparative Study

In diabetic foot infections (DFI), the clinical virulence of skin commensals are generally presumed to be low. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria) and pathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pathogenic pathogens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxygen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs. 24 %, p = 0.23) or microbiological recurrence (11% vs. 17 %, p = 0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, the isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confidence interval 0.1-3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may also be based on oral non-beta-lactam antibiotic agents effective against the corresponding skin pathogens

Pseudomonal Diabetic Foot Infections: Vive la Différence?

Objective To assess the outcomes of diabetic foot infections (DFIs) due to Pseudomonas aeruginosa. Patients and Methods From April 24, 2013 to July 31, 2016, we analyzed data from patients prospectively enrolled in our clinical pathway of DFIs, comparing those with infection due to Pseudomonas with those without infection due to Pseudomonas. Results Overall, we assessed 1018 cases of DFIs: 392 with osteomyelitis and 626 with only soft tissue infections. The prevalence of P aeruginosa in deep wound cultures was 10% (104/1018); of the 1018 cultures, 22 were monomicrobial, 82 were polymicrobial, and 46 were with osteomyelitis. Overall, the patients were treated with a median of 1 surgical debridement and a total of 20 days of antibiotic therapy. In a comparison of crude groups, the proportion of clinical failures was significantly higher with Pseudomonas than with other pathogens (36/104 [35%] vs 218/914 [24%], respectively; P=.02). A multivariate analysis showed that pseudomonal DFIs did not recur more often than nonpseudomonal DFIs (hazard ratio, 1.0; 95% confidence interval, 0.6-1.7). Among the 104 cases of pseudomonal DFIs, there was no association between failure of treatment and the total duration of antibiotic therapy, duration of intravenous therapy, duration of combined antibiotic therapy with more than 1 agent, or duration of oral (fluoroquinolone) therapy. Among 15 cases of pseudomonal recurrence, 2 (13%) developed resistance to the antibiotic agent used for the index episode. Conclusion For DFIs caused by P aeruginosa, other than choosing an antibiotic agent that is active against the organism, it does not appear necessary to treat with a different therapeutic regimen compared with the treatment of nonpseudomonal DFIs. There is no difference

Moderate to Severe Soft Tissue Diabetic Foot Infections: A Randomized, Controlled, Pilot Trial of Post-Debridement Antibiotic Treatment for 10 versus 20 days

Background: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot (ST-DFI) remains unknown. Objective: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for ST-DFI results in similar rates of clinical remission and adverse events (AE). Summary Background Data: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. Methods: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of “clinical remission at two-months follow-up”. Results: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat (ITT) population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm (p = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; p = 0.71), and remission in the per-protocol (PP) population (25/32 vs. 18/27; p = 0.32). Overall, eight soft tissue DFIs in the 10-day arm and five cases in the 20-day arm recurred as a new osteomyelitis (8/35 [23%] versus 5/31 [16%]; p = 0.53). Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (ITT population, hazard ratio 0.6, 95%CI 0.3-1.1; PP population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. Conclusions: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way

Characterization of Proangiogenic Monocytes from Blood in Patients with Chronic Ischemic Diabetic Foot Ulcers and Controls

Many persons with diabetes mellitus have limb ischemia, which is a major clinical problem. A subset of human monocytes that expresses TIE-2 may enhance neovascularization. We performed 179 phlebotomies on 142 patients (or donors), including 61 patients/donors without diabetes or ischemia (controls), 39 diabetic nonischemic patients (controls), and 42 diabetic patients with severe limb ischemia requiring amputation. We compared these groups for the presence of TIE-2-positive proangiogenic monocytes. The proportion of proangiogenic monocytes in the venous blood (on hospital admission) was significantly increased in diabetic patients without ischemia (9.22% ± 1.19%), compared to controls (6.53% ± 0.58%) or ischemic diabetic patients (5.44% ± 0.56%) (P < 0.05). In this pilot evaluation, we succeeded in extracting potential proangiogenic TIE-2 monocytes from the blood of diabetic patients without ischemia, but less in patients with ischemia. The implications for therapeutic neoangiogenesis require further studies

X-Ray Versus Magnetic Resonance Imaging in Diabetic Foot Osteomyelitis: A Clinical Comparison

OBJECTIVE Radiographic imaging is an important diagnostic tool in diabetic foot osteomyelitis (DFO). It is unknown whether DFO cases diagnosed with conventional X-ray versus positive Magnetic Resonance Imaging (MRI) differ regarding epidemiology and treatment outcome. Theoretically, signs of inflammation on MRI without bone lesions might be easier to treat and predominate among selected clinical variables. METHODS Our clinical pathway for diabetic foot infections discourages the use of MRI for the diagnosis of DFO. We compared the epidemiology and therapy of non-amputated DFO with positive features on conventional X-ray, MRI, or both. Radiology specialists interpreted the images. The intraoperative aspect of bone during amputation and the results of bone cultures were considered gold standard for DFO diagnosis. RESULTS We prospectively followed 390 DFO episodes in 186 adult patients for a median of 2.9 years and performed 318 conventional X-rays (median costs 100 Swiss Francs; 100 US$) and 47 (47/390; 12$). Among them, 18 episodes were associated with positive MRI findings but lacked bone lesions on X-ray. After debridement, the median duration of systemic antibiotics was 28 days for MRI-only episodes and 30 days for X-ray-positive cases (Wilcoxon-ranksum-test; p=0.26). The corresponding median numbers of surgical debridements were 1 and 1; and remission was achieved in 25% and 27%, respectively. In multivariate logistic regression analysis, MRI-only episodes did not alter remission rate (odds ratio 0.5, 95%CI 0.1-5.2). CONCLUSIONS According to our clinical pathway, DFO episodes with positive MRI findings only did not differ epidemiologically and did not influence the choice of therapy nor remission rate

Is routine measurement of the serum C-reactive protein level helpful during antibiotic therapy for diabetic foot infection?

Clinicians frequently monitor serum C-reactive protein (CRP) levels during therapy for diabetic foot infections (DFIs), but evidence supporting this is unclear. Using a database from prospective controlled DFI trials, with fixed duration of antibiotic therapy, we correlated the CRP levels at study enrolment and at end of therapy (EOT). Among 159 DFI episodes, 93 involved the bone and 66 the soft tissues. Overall, treatment cured 122 infections (77%), while 37 episodes (23%) recurred after a median of 53 days. The median CRP in the groups with cure versus failure differed minimally at enrolment (median 67 vs. 81 mg/L) or EOT (7 vs. 10 mg/L). Similarly, there was negligible difference in the percentage of CRP levels that normalized at EOT (39% vs. 35%). In our prospective cohorts, a blunt iterative monitoring of CRP during DFI treatment, without correlation with clinical findings, failed to predict treatment failures

The role of anaerobes in diabetic foot infections

Diabetic foot infections (DFI) are a common cause of morbidity and, on occasion, even mortality. Infection can be either mono- or polymicrobial, with a wide variety of potential pathogens. Anaerobes may be involved, particularly in wounds that are deeper or more chronic, and are more frequently identified when using modern molecular techniques, such as 16s PCR and pyrosequencing. It remains unclear whether the presence of anaerobes in DFI leads to more severe manifestations, or if these organisms are largely colonizers associated with the presence of greater degrees of tissue ischemia and necrosis. Commonly used empiric antibiotic therapy for diabetic foot infections is generally broad-spectrum and usually has activity against the most frequently identified anaerobes, such as Peptostreptococcus and Bacteroides species. Adequate surgical debridement and, when needed, foot revascularization may be at least as important as the choice of antibiotic to achieve a successful treatment outcome

Influence of Skin Commensals on Therapeutic Outcomes of Surgically Debrided Diabetic Foot Infections—A Large Retrospective Comparative Study

In diabetic foot infections (DFI), the clinical virulence of skin commensals are generally presumed to be low. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria) and pathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pathogenic pathogens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxygen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs. 24 %, p = 0.23) or microbiological recurrence (11% vs. 17 %, p = 0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, the isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confidence interval 0.1–3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may also be based on oral non-beta-lactam antibiotic agents effective against the corresponding skin pathogens

Remission in diabetic foot infections: Duration of antibiotic therapy and other possible associated factors

AIM To determine the most appropriate duration of antibiotic therapy for diabetic foot infections (DFIs). METHODS Using a clinical pathway for adult patients with DFIs (retrospective cohort analysis), we created a cluster-controlled Cox regression model to assess factors related to remission of infection, emphasizing antibiotic-related variables. We excluded total amputations as a result of DFI and DFI episodes with a follow-up time of <2 months. RESULTS Among 1018 DFI episodes in 482 patients, we identified 392 episodes of osteomyelitis, 626 soft tissue infections, 246 large abscesses, 322 episodes of cellulitis and 335 episodes of necrosis; 313 cases involved revascularization. Patients underwent surgical debridement for 824 episodes (81%), of which 596 (59%) required amputation. The median total duration of antibiotic therapy was 20 days. After a median follow-up of 3 years, 251 of the episodes (24.7%) were followed by ≥1 additional episode(s). Comparing patients with and without additional episodes, risk of recurrence was lower in those who underwent amputation, had type 1 diabetes, or underwent revascularization. On multivariate analysis including the entire study population, risk of remission was inversely associated with type 1 diabetes (hazard ratio [HR] 0.3, 95% confidence interval [CI] 0.2-0.6). Neither duration of antibiotic therapy nor parenteral treatment affected risk of recurrence (HR 1.0, 95% CI 0.99-1.01 for both). Similarly, neither >3 weeks versus 1 week versus 3 weeks overall and 0.6 (95% CI 0.2-1.3) for osteomyelitis cases only. Plotting of duration of antibiotic therapy failed to identify any optimal threshold for preventing recurrences. CONCLUSIONS Our analysis found no threshold for the optimal duration or route of administration of antibiotic therapy to prevent recurrences of DFI. These limited data might support possibly shorter treatment duration for patients with DFI

A randomized, controlled study to investigate the efficacy and safety of a topical gentamicin-collagen sponge in combination with systemic antibiotic therapy in diabetic patients with a moderate or severe foot ulcer infection

Abstract Background An adjunctive topical therapy with gentamicin-sponges to systemic antibiotic therapy might improve the healing of infected diabetic foot ulcers (DFUI). Methods Single-center, investigator-blinded pilot study, randomizing (1:1) the gentamicin-sponge with systemic antibiotic versus systemic antibiotics alone for patients with DFUI. Results We included 88 DFUI episodes with 43 patients in the gentamicin-sponge arm and 45 in the control arm. Overall, 64 (64/88; 73%) witnessed total clinical cure, 13 (15%) significant improvement, and 46 (52%) showed total eradication of all pathogens at the final visit. Regarding final clinical cure, there was no difference in favour of the gentamicin-sponges (26/45 vs. 31/43; p = 0.16). However, the gentamicin-sponge arm tended to a more rapid healing. In multivariate analysis adjusting for the case-mix, the variable “gentamicin-sponge” was not significantly associated with “cure and improvement”. Gentamicin-sponges were very well tolerated, without any attributed adverse events. Conclusions The gentamicin-sponge was very well tolerated, but did not significantly influence overall cure. Trial registration ClinicalTrials.gov (NCT01951768). Date 2 April 2013