Welcome to the Podiatry Arena forums, for communication between foot health professionals about podiatry and related topics.
You are currently viewing our podiatry forum as a guest which gives you limited access to view all podiatry discussions and access our other features. By joining our free global community of Podiatrists and other interested foot health care professionals you will have access to post podiatry topics (answer and ask questions), communicate privately with other members (PM), upload content, view attachments, receive a weekly email update of new discussions, earn CPD points and access many other special features. Registered users do not get displayed the advertisments in posted messages. Registration is fast, simple and absolutely free so please, join our global Podiatry community today!
If you have any problems with the registration process or your account login, please contact contact us.
A series of systematic reviews to inform a decision analysis for sampling and treating infected diabetic foot ulcers.
Health Technol Assess. 2006 Apr;10(12):1-238
OBJECTIVES: To review systematically the evidence on the performance of diagnostic tests used to identify infection in diabetic foot ulcers (DFUs) and of interventions to treat infected DFUs. To use estimates derived from the systematic reviews to create a decision analytic model in order to identify the most effective method of diagnosing and treating infection and to identify areas of research that would lead to large reductions in clinical uncertainty.
DATA SOURCES: Electronic databases covering period from inception of the database to November 2002.
REVIEW METHODS: Selected studies were assessed against validated criteria and described in a narrative review. The structure of a decision analytic model was derived for two groups of patients in whom diagnostic tests were likely to be used.
RESULTS: Three studies that investigated the performance of diagnostic tests for infection on populations including people with DFUs found that there was no evidence that single items on a clinical examination checklist were reliable in identifying infection in DFUs, that wound swabs perform poorly against wound biopsies, and that semi-quantitative analysis of wound swabs may be a useful alternative to quantitative analysis. However, few people with DFUs were included, so it was not possible to tell whether diagnostic performance differs for DFUs relative to wounds of other aetiologies. Twenty-three studies investigated the effectiveness (n = 23) or cost-effectiveness (n = 2) of antimicrobial agents for DFUs. Eight studied intravenous antibiotics, five oral antibiotics, four different topical agents such as dressings, four subcutaneous granulocyte colony stimulating factor (G-CSF), one evaluated oral and topical Ayurvedic preparations and one compared topical sugar versus antibiotics versus standard care. The majority of trials were underpowered and were too dissimilar to be pooled. There was no strong evidence for recommending any particular antimicrobial agent for the prevention of amputation, resolution of infection or ulcer healing. Topical pexiganan cream may be as effective as oral antibiotic treatment with ofloxacin for the resolution of local infection. Ampicillin and sulbactam were less costly than imipenem and cilastatin, a growth factor (G-CSF) was less costly than standard care and cadexomer iodine dressings may be less costly than daily dressings. A decision analytic model was derived for two groups of people, those for whom diagnostic testing would inform treatment -- people with ulcers which do not appear infected but whose ulcer is not progressing despite optimal concurrent treatment -- and those in whom a first course of antibiotics (prescribed empirically) have failed. There was insufficient information from the systematic reviews or interviews with experts to populate the model with transition probabilities for the sensitivity and specificity of diagnosis of infection in DFUs. Similarly, there was insufficient information on the probabilities of healing, amputation or death in the intervention studies for the two populations of interest. Therefore, we were unable to run the model to inform the most effective diagnostic and treatment strategy.
CONCLUSIONS: The available evidence is too weak to be able to draw reliable implications for practice. This means that, in terms of diagnosis, infection in DFUs cannot be reliably identified using clinical assessment. This has implications for determining which patients need formal diagnostic testing for infection, on whether empirical treatment with antibiotics (before the results of diagnostic tests are available) leads to better outcomes, and on identifying the optimal methods of diagnostic testing. With respect to treatment, it is not known whether treatment with systemic or local antibiotics leads to better outcomes or whether any particular agent is more effective. Limited evidence suggests that both G-CSF and cadexomer iodine dressings may be less expensive than 'standard' care, that ampicillin/sulbactam may be less costly than imipenem/cilastatin, and that an unlicensed cream (pexiganan) may be as effective as oral ofloxacin. Further research is needed to ascertain the characteristics of infection in people with DFUs that influence healing and amputation outcomes, to determine whether detecting infection prior to treatment offers any benefit over empirical therapy, and to establish the most effective and cost-effective methods for detecting infection, as well as the relative effectiveness and cost-effectiveness of antimicrobial interventions for DFU infection.
OBJECTIVE: To investigate the change of bacterial load applied with iodophors and rivanol of diabetic foot ulcers (DFUs), furthermore to evaluate the effect of both in removing superficial microbes of DFUs.
METHODS: From March 2006 to March 2007, 30 patients were randomly divided into control group (group A, n = 10), iodophor group (group B, n = 10) and rivanol group (group C, n = 10). There were 18 males and 12 females with an average age of 59.8 years (range 46-78 years). The wound size ranged from 3 cm x 2 cm to 15 cm x 10 cm. The disease course was 6 weeks to 6 months (mean 2.1 months). Each wound was debrided and irrigated before process, then drug was compressed on the wound for 5 minutes, and irrigated again. The samples gained for three times, before, immediately and 24 hours after the process. Each sample was diluted before cultivation, the bacteria of wound were counted and compared among 3 groups.
RESULTS: The cultures of specimens showed that the load decreased in every group, each cultured colony of specimen grew well, and there were no significant differences between 3 groups immediately after procedure (P > 0.05). There were significant differences between group B and groups A, C (P < 0.05), but there were no significant difference between group A and group C 24 hours after treatment (P > 0.05).
CONCLUSION: Both iodophors and rivanol could remove the bacteria on the surface of wound. Topical germicide could reduced bacterial load in the wound of diabetic foot, the role of sterilizing and bacteriostasis of iodophors were better than that of rivanol.
Foot infections in diabetes (DFIs) in the out-patient setting: an Italian multicentre observational survey
S. Esposito, S. Leone, S. Noviello, M. Fiore, F. Ianniello, F. M. Felaco, F. Romagnoli and E. Sarli Diabet. Med. 25, 979–984 (2008)
Aims To conduct a multicentre observational study to describe management of foot infections in diabetes in the out-patient setting in Italy.
Patients and methods Ten centres equally distributed nationwide were asked to collect, by means of a spreadsheet (Access/Excel Microsoft program), data concerning 30 consecutive diabetic patients with foot infections deemed suitable for antibiotic treatment in the out-patient setting. Centres with ≥ 5 years' experience of out-patient management were selected. Data from 271 consecutive patients treated as out-patients were collected and analysed by the central coordinator. Statistical analysis was performed using the SPSS statistical software package.
Results Lesions were mainly located at the toes and midfoot (33.6 and 30.2%, respectively); 63 (23.2%) patients had multiple ulcers. Seventy (25.8%) patients also had concomitant osteomyelitis. Three hundred and four pathogens, including Gram-positive and Gram-negative aerobes and anaerobes, were isolated in 219/271 patients (80.8%) by culturing debrided tissue (71.2%) or purulent material (28.8%). Infections were polymicrobial in 33.8% of patients. The most common pathogens were Staphylococcus aureus (27.3%) and Pseudomonas spp. (20.4%); enterobacteriaceae, enterococci, streptococci and anaerobes accounted for 11.5, 7.6, 6.9 and 1.9%, respectively. Antibiotics were frequently administered by parenteral route and frequently in combination. Piperacillin/tazobactam was the parenteral antibiotic most frequently utilized (21.1%). Cure/improvement was observed in 93.4% of patients.
Conclusions Foot ulcers in diabetes are common and serious; the aetiology is often polymicrobial, often including S. aureus and Pseudomonas spp. Treatment in the out-patient setting is safe and effective, and penicillins together with β-lactamase inhibitors and fluoroquinolones are the most frequent choice.
Foot infections in diabetes (DFIs) in the out-patient setting: an Italian multicentre observational survey.
Esposito S, Leone S, Noviello S, Fiore M, Ianniello F, Felaco FM, Romagnoli F, Sarli E. Diabet Med. 2008 Aug;25(8):979-84.
AIMS: To conduct a multicentre observational study to describe management of foot infections in diabetes in the out-patient setting in Italy.
PATIENTS AND METHODS: Ten centres equally distributed nationwide were asked to collect, by means of a spreadsheet (Access/Excel Microsoft program), data concerning 30 consecutive diabetic patients with foot infections deemed suitable for antibiotic treatment in the out-patient setting. Centres with > or = 5 years' experience of out-patient management were selected. Data from 271 consecutive patients treated as out-patients were collected and analysed by the central coordinator. Statistical analysis was performed using the SPSS statistical software package.
RESULTS: Lesions were mainly located at the toes and midfoot (33.6 and 30.2%, respectively); 63 (23.2%) patients had multiple ulcers. Seventy (25.8%) patients also had concomitant osteomyelitis. Three hundred and four pathogens, including Gram-positive and Gram-negative aerobes and anaerobes, were isolated in 219/271 patients (80.8%) by culturing debrided tissue (71.2%) or purulent material (28.8%). Infections were polymicrobial in 33.8% of patients. The most common pathogens were Staphylococcus aureus (27.3%) and Pseudomonas spp. (20.4%); enterobacteriaceae, enterococci, streptococci and anaerobes accounted for 11.5, 7.6, 6.9 and 1.9%, respectively. Antibiotics were frequently administered by parenteral route and frequently in combination. Piperacillin/tazobactam was the parenteral antibiotic most frequently utilized (21.1%). Cure/improvement was observed in 93.4% of patients.
CONCLUSIONS: Foot ulcers in diabetes are common and serious; the aetiology is often polymicrobial, often including S. aureus and Pseudomonas spp. Treatment in the out-patient setting is safe and effective, and penicillins together with beta-lactamase inhibitors and fluoroquinolones are the most frequent choice.
Introduction: The prevalence of diabetes mellitus is high in Singapore. Infections of the lower limb are significant causes of morbidity in this population. Although the aerobic bacteriology of these infections is well-documented, there is less data available on the anaerobic pathogens involved. This study sets out to describe the anaerobic bacteria associated with diabetic foot infections, and evaluates the susceptibility to 3 antimicrobials with anaerobic activity. Materials and Methods: Anaerobic culture was performed on operative samples taken from diabetic foot infections. Organisms were identified through standard microbiological methods and commercial identification kits. Antimicrobial susceptibility testing to clindamycin, metronidazole and imipenem was performed by agar dilution. Results: One hundred and two strains of strict anaerobic bacteria were isolated from 30 unique specimens. The predominant anaerobic isolates were Peptostreptococcus spp. (46%) and Bacteroides fragilis group (19%). Antibiotic resistance was detected for clindamycin (18%), metronidazole (1%) and imipenem (2%). Conclusion: Multiple anaerobic species can be isolated from diabetic foot infections. A significant proportion of isolates are resistant to clindamycin, while resistance to imipenem and metronidazole remains low.
Aims. One proposed method to diagnose diabetic foot ulcers (DFUs) for infection is clinical examination. Twelve different signs of infection have been reported. The purpose of this study was to examine diagnostic validity of each individual clinical sign, a combination of signs recommended by the Infectious Disease Society of America (IDSA), and a composite predictor based on all signs of localized wound infection in identifying DFU infection, among a sample of DFUs.
Methods. A cross-sectional research design was used. Sixty-four individuals with DFUs were recruited from a Department of Veterans Affairs Medical Center and an academic-affiliated hospital. Each DFU was independently assessed by 2 research team members using the clinical signs and symptoms checklist. Tissue specimens were then obtained via wound biopsy and quantitatively processed. Ulcers with more than 10(6) organisms per gram of tissue were defined as having high microbial load. Individual signs and the IDSA combination were assessed for validity by calculating sensitivity, specificity, and concordance probability. The composite predictor was analyzed using c-index and receiver operating curves.
Results. Twenty-five (39%) of the DFUs had high microbial loads. No individual sign was a significant predictor of high microbial load. The IDSA combination was not a significant predictor either. The c-index of the composite predictor was .645 with a 95% confidence interval of .559-.732.
Conclusions. Individual signs of infection do not perform well nor does the IDSA combination of signs. However, a composite predictor based on all signs provides a moderate level of discrimination, suggesting clinical use. Larger sample sizes and alternate reference standards are recommended.
Our aim was to evaluate the role of SPECT/CT for the diagnosis of diabetic foot infection by labeled leukocytes.
METHODS: Seventeen patients with 19 clinically suspected sites of infection were included. After leukocyte labeling and administration, planar scans were acquired at 30 min, 4 h, and 24 h for 18 consecutive patients. SPECT/CT was obtained at 6 h. The final diagnosis was established by clinical follow-up (24 mo) in all cases and by bone biopsy for 14 sites.
RESULTS: Leukocyte scanning was positive in 16 of 19 lesions and negative in 3. SPECT/CT changed the interpretation of the planar and SPECT images for 10 of 19 suspected sites (52.6%): it excluded osteomyelitis in 6 cases, revealed bone infection in 1 case, and revealed both bone and soft-tissue infection in 3 cases. The hybrid device did not significantly contribute to the evaluation of patients with negative scan results.
CONCLUSION: SPECT/CT can be useful for a more accurate diagnosis of diabetic foot infection by labeled leukocyte imaging.
AIMS/HYPOTHESIS: In 2003, guidelines for management of diabetic foot infection (DFI) were written by the authors' team according to the guidelines of the International Working Group on the Diabetic Foot. The effects of implementing these guidelines on the microbiology and costs of infected diabetic foot ulcers were assessed.
METHODS: From 2003 to 2007, potential beneficial effects of implementing these guidelines were assessed by comparison over time of bacteriological data (number of bacterial samples, number of microorganisms isolated in cultures, prevalence of multidrug-resistant organisms [MDRO] and colonising flora), and costs related to use of antimicrobial agents and microbiology laboratory workload.
RESULTS: The study included 405 consecutive diabetic patients referred to the Diabetic Foot Unit for a suspected DFI. From 2003 to 2007, a significant decrease was observed in the median number of bacteria species per sample (from 4.1 to 1.6), prevalence of MDRO (35.2% vs 16.3%) and methicillin-resistant Staphylococcus aureus (52.2% vs 18.9%) (p < 0.001). Moreover, prevalence of pathogens considered as colonisers dramatically fell from 23.1% to 5.8% of all isolates (p < 0.001). In parallel, implementation of guidelines was associated with a saving of <euro>14,914 (US$20,046) related to a reduced microbiology laboratory workload and <euro>109,305 (US$147,536) due to reduced prescription of extended-spectrum antibiotic agents.
CONCLUSIONS/INTERPRETATION: Implementation of guidelines for obtaining specimens for culture from patients with DFI is cost-saving and provides interesting quality indicators in the global management of DFI.
BACKGROUND: A study has found that major amputations are necessary on 69% of ischemic diabetic foot patients treated with conventional therapy. An uncontrolled study of 31 patients showed that only 33% needed major amputation after treatment with conventional therapy plus De Marco Formula (DMF), a novel formulation of procaine and Polyvinylpyrrolidone.
OBJECTIVE: To assess the tolerability and safety of the combination of conventional therapy and De Marco Formula for infected ischemic diabetic foot.
METHODS: Adult patients, 10 male/24 female, were treated with the conventional therapy for diabetic foot plus DMF (0.15ml/kg/day IM) during ten days and then twice a week until healing of the lesions or completion of a 52-day period. Required amputations, lesion areas, adverse events occurrence and clinical laboratory parameters (hemoglobin, blood cell counts, glycosilated hemoglobin, total proteins, creatinine, alanine transaminase and alkaline phosphatase) were determined during the treatment period.
RESULTS: Two slight (5.88%) and one moderate (2.94%) adverse events (mainly cutaneous rash) were reported. The last one was reported on the 15th day of treatment and DMF dosing was discontinued by patient's request. Clinical laboratory mean values remained within normal ranges during treatment except for blood leukocyte counts that pathologically elevated at baseline and decreased to normality by treatment end. This study has found that 18.08% of patients (N=6) needed a lower limb amputation with the combined treatments. The standard reported rate in Cuba is 25-29%. Furthermore, a progressive reduction of the mean lesion area from 51.29cm(2) at the beginning to 1.89cm(2) at the end of the treatment (p=0.000001) was observed.
CONCLUSION: The treatment with De Marco Formula for 52 days as an adjuvant for the conventional therapy for infected ischemic diabetic foot was well tolerated and safe. These findings are consistent with those of a randomized prospective controlled study performed later.
Beneficial effects of implementing guidelines on microbiology and costs of infected diabetic foot ulcers
A. Sotto, J.-L. Richard, C. Combescure, N. Jourdan, S. Schuldiner, N. Bouziges and J.-P. Lavigne Diabetologia; Volume 53, Number 10, 2249-2255
In 2003, guidelines for management of diabetic foot infection (DFI) were written by the authors’ team according to the guidelines of the International Working Group on the Diabetic Foot. The effects of implementing these guidelines on the microbiology and costs of infected diabetic foot ulcers were assessed.
From 2003 to 2007, potential beneficial effects of implementing these guidelines were assessed by comparison over time of bacteriological data (number of bacterial samples, number of microorganisms isolated in cultures, prevalence of multidrug-resistant organisms [MDRO] and colonising flora), and costs related to use of antimicrobial agents and microbiology laboratory workload.
The study included 405 consecutive diabetic patients referred to the Diabetic Foot Unit for a suspected DFI. From 2003 to 2007, a significant decrease was observed in the median number of bacteria species per sample (from 4.1 to 1.6), prevalence of MDRO (35.2% vs 16.3%) and methicillin-resistant Staphylococcus aureus (52.2% vs 18.9%) (p < 0.001). Moreover, prevalence of pathogens considered as colonisers dramatically fell from 23.1% to 5.8% of all isolates (p < 0.001). In parallel, implementation of guidelines was associated with a saving of €14,914 (US$20,046) related to a reduced microbiology laboratory workload and €109,305 (US$20,046)relatedtoareducedmicrobiologylaboratory workloadand€109,305(US 147,536) due to reduced prescription of extended-spectrum antibiotic agents.
Implementation of guidelines for obtaining specimens for culture from patients with DFI is cost-saving and provides interesting quality indicators in the global management of DFI.
Changing microbiological profile of pathogenic bacteria in diabetic foot infections: time for a rethink on which empirical therapy to choose?
Ramakant P, Verma AK, Misra R, Prasad KN, Chand G, Mishra A, Agarwal G, Agarwal A, Mishra SK. Diabetologia. 2010 Sep 11. [Epub ahead of print]
AIMS/HYPOTHESIS: We studied the bacterial aetiology and antibiotic sensitivity pattern of diabetic foot ulcers in India.
METHODS: Records of 447 hospitalised patients between 1991 and 2008 were retrospectively analysed between two time periods (before and after 1999) to compare bacterial aetiology and antimicrobial sensitivity patterns. The first three consecutive cultures from the same wound during treatment were evaluated.
RESULTS: Of 1,632 cultures, 66% were polymicrobial, 23% monomicrobial and 11% sterile. In the monomicrobial group, 14% (n = 228) of cultures were Gram-negative, whereas 9% (n = 147) were Gram-positive. The most common pathogens in the first culture were Pseudomonas aeruginosa (20.1%), Staphylococcus aureus (17.2%) and Escherichia coli (16.3%). Results for the third cultures showed persistence of P. aeruginosa (15.3%) and E. coli (14.2%). Gram-negative isolates dominated over Gram-positive ones (25.3% vs 15.1%, p < 0.05). Antibiotic sensitivity patterns before and after 1999 were: piperacillin-tazobactam 74% vs 66% (p < 0.005), imipenem 77% vs 85% (NS), cefoperazone-sulbactam 47% vs 44% (p < 0.005), amikacin 62% vs 78% (NS), ceftriaxone 41% vs 36% (p < 0.005), amoxicillin-clavulanate 51% vs 43% (p < 0.05) and clindamycin 43% vs 36% (p < 0.005), respectively.
CONCLUSIONS/INTERPRETATION: Unlike in the West, in India Gram-negative bacteria were found to have always been dominant in the wounds of patients with diabetic foot infections. Infection with polymicrobial multidrug-resistant Gram-negative bacilli is common. The policy of empirical antimicrobial therapy at tertiary care needs to be changed.
The Optimized Evaluation of Diabetic Foot Infection by Dual Isotope SPECT/CT Imaging Protocol.
Heiba SI, Kolker D, Mocherla B, Kapoor K, Jiang M, Son H, Rangaswamy B, Kostakoglu L, Savitch I, Dacosta M, Machac J. J Foot Ankle Surg. 2010 Sep 16. [Epub ahead of print]
Sequential Tc-99m hydroxymethylene-diphosphonate (HDP) 3-phase bone (BS) and In-111 leukocyte scanning (WBCS) have been frequently used to evaluate the diabetic foot, as nonosteomyelitis BS uptake is repeatedly observed and osteomyelitis (OM) in WBCS is often uncertain without BS correlation. Additionally, both modalities are limited in lesion localization because of low resolution and lack of anatomic details. We investigated a method that combined BS/WBCS, and if needed, WBCS/bone marrow scanning (BMS) using SPECT/CT to accurately diagnose/localize infection in a practical protocol. Blood flow/pool images were obtained followed by WBC reinjection and next day dual isotope (DI) BS/WBCS planar and SPECT/CT. BMS/WBCS SPECT/CT (step 2 DI) was obtained on the following day when images were suspicious for mid/hindfoot OM. Diagnosis accuracy and confidence were judged for the various imaging combinations. Diagnosis was classified as OM, soft tissue infection (STI), both OM/STI, and other/no bony pathology by microbiology/pathology or follow-up. Distinction between various diagnostic categories and overall OM diagnostic accuracy in 213 patients were higher for DI than WBCS or BS alone, and for DI SPECT/CT than DI planar or SPECT only. Diagnostic confidence/lesion site was significantly higher for DI SPECT/CT than other comparative imaging methods. In a group of 97 patients with confirmed microbiologic/pathologic diagnosis, similar results were attained. Step 2 DI SPECT/CT performed in 67 patients further improved diagnostic accuracy/confidence. DI SPECT/CT is a highly accurate modality that considerably improves detection and discrimination of STI and OM while providing precise anatomic localization in the diabetic foot. This combined imaging technique promises to beneficially impact diabetic patient care.
Pharmacokinetics and penetration of moxifloxacin into infected diabetic foot tissue in a large diabetic patient cohort.
Majcher-Peszynska J, Sass M, Schipper S, Czaika V, Gussmann A, Lobmann R, Mundkowski RG, Luebbert C, Kujath P, Ruf BR, Koch H, Schareck W, Klar E, Drewelow B; for the Moxifloxacin-DFI Study Group. Eur J Clin Pharmacol. 2010 Sep 25. [Epub ahead of print]
OBJECTIVES: Physiological changes occurring in patients with diabetes may affect the pharmacokinetics and penetration of antimicrobial agents into peripheral tissue. We examined the pharmacokinetics and the penetration of moxifloxacin into perinecrotic tissue of diabetic foot lesions in patients with diabetic foot infections (DFI).
PATIENTS AND METHODS: Adult patients suffering from type 2 diabetes mellitus and hospitalized for DFI (Texas classification of at least B2) were treated with 400 mg moxifloxacin intravenously (IV) or orally (PO) once daily. The pharmacokinetics of moxifloxacin and its concentration 3 h after administration in samples of perinecrotic tissue resected from infected diabetic foot wounds were determined at steady state (days 4-8).
RESULTS: A total of 53 patients with diabetes mellitus type 2 (mean age 69.4 ± 10.8 years) were included in the study, of whom 28 received PO and 25 IV moxifloxacin therapy for a median of 8 days. In the PO and IV subgroups, the mean maximum observed plasma concentration (C (max)) in plasma was 2.69 and 4.77 mg/l at a median of 2 [time to reach C (max) (T (max)) range 1.0-8.0 h] and 1 h after administration, respectively. A mean area under the plasma concentration-time curve from time 0 until the last quantifiable plasma concentration (AUC(0-24 h)) of 29.36 mg h/l (PO) and 27.09 mg h/l (IV) was achieved. Mean moxifloxacin concentrations in perinecrotic tissue of infected diabetic foot wounds following PO or IV administration were 1.79 ± 0.82 and 2.20 ± 1.54 μg/g, thus exceeding the MIC(90) (minimum inhibitory concentration required to inhibit growth of 90% of organisms) for Staphylococcus aureus (0.25 mg/l) by seven- and eightfold and the MIC(90) for Escherichia coli (0.06 mg/l) by 29-fold and 36-fold, respectively. The mean tissue-to-plasma ratios of moxifloxacin concentration 3 h after administration were 1.01 ± 0.57 (PO) and 1.09 ± 0.69 (IV). Significant differences between the routes of administration were observed for T (max) and C (max) (P < 0.01), but not for other clinically relevant parameters (AUC(0-24); moxifloxacin DFI tissue concentration).
CONCLUSIONS: The plasma concentration-time curve of moxifloxacin in diabetic patients is similar to that of healthy volunteers. We also observed a good penetration of moxifloxacin into inflamed DFI tissue which taken together with the possibility of sequential IV/PO therapy suggest that moxifloxacin 400 mg once daily is a therapeutic option in the treatment of DFI caused by susceptible organisms.
Isolation of bacteriophages to multi-drug resistant Enterococci obtained from diabetic foot: A novel antimicrobial agent waiting in the shelf?
Vinodkumar CS, Srinivasa H, Basavarajappa KG, Geethalakshmi S, Bandekar N. Indian J Pathol Microbiol. 2011 Jan-Mar;54(1):90-5.
Introduction: While foot infections in persons with diabetes are initially treated empirically, therapy directed at known causative organisms may improve the outcome. Many studies have reported on the bacteriology of diabetic foot infections (DFIs), but the results have varied and have often been contradictory. The purpose of the research work is to call attention to a frightening twist in the antibiotic-resistant Enterococci problem in diabetic foot that has not received adequate attention from the medical fraternity and also the pharmaceutical pipeline for new antibiotics is drying up. Materials and Methods: Adult diabetic patients admitted for lower extremity infections from July 2008 to December 2009 in the medical wards and intensive care unit of medical teaching hospitals were included in the study. The extent of the lower extremity infection on admission was assessed based on Wagner's classification from grades I to V. Specimens were collected from the lesions upon admission prior to the initiation of antibiotic therapy or within the first 48 h of admission. Results: During the 18-month prospective study, 32 strains of Enterococcus spp. (26 Enterococcus faecalis and 06 E. faecium) were recovered. Antibiotic sensitivity testing was done by Kirby-Bauer's disk diffusion method. Isolates were screened for high-level aminoglycoside resistance (HLAR). A total of 65.6% of Enterococcus species showed HLAR. Multidrug resistance and concomitant resistance of HLAR strains to other antibiotics were quite high. None of the Enterococcus species was resistant to vancomycin. Conclusion: Multidrug-resistant Enterococci are a real problem and continuous surveillance is necessary. Today, resistance has rendered most of the original antibiotics obsolete for many infections, mandating the development of alternative anti-infection modalities. One of such alternatives stemming up from an old idea is the bacteriophage therapy. In the present study, we could able to demonstrate the viable phages against MDR E. faecali
The aim of our study was to analyse the foot infections in diabetic patients. We analysed foot ulcerations in 124 diabetics who attended outpatient foot clinic, or were hospitalized in the period from 1996 to 2006. Basic neuropathy screening examination was made with cotton wisp, pin-prick, tuning fork, and monofilament. For evaluation of leg ischemia, besides the evaluation of the presence of pedal pulses, the ankle-brachial pressure index was measured. If the infection of foot ulceration was clinically present, bacteriology examinations was performed. In the case of deep wound infection, x-ray examination was made. If bone destruction was present, osteomyelitis was diagnosed by technecium bone scanning and by technecium-labelled leukocyte scan. Deformation and destruction of the bone without infection was appoited as Charcot neuroarthropathy. Foot ulcer infection was found in 58 % diabetic patients, wounds were more often deep (80 %). Infection was not associated with special location of foot ulcer. Two-third of the total infected wounds were associated with leg ischemia and 30.6 % of infected ulcer ended with leg amputation. More foot ulcer infections were found in the diabetics with HbAlc over 8 %. Infection was coupled with diabetic retinopathy (in 63 % patients) (p=0.023), and also with diabetic nephropathy (in 66 % patients) (p=0.012). Bacteriology examination revealed most often Staphylococci (45.8 %), antibiotic therapy was made most often with chinolones. Osteomyelitis was present in 34.7 % of foot ulcer infections. In 14 diabetics (56 %) after antibiotic therapy it was not necessary to perform a leg amputation. HbAlc seems to be a significant predictor of osteomyelitis (p<0.02; OR=1.76). In conclusion, we confirmed that diabetic foot infections, especially on ischemic leg, in diabetics with poor metabolic control and chronic diabetic microvascular complications, are associated with a higher risk of leg amputations. Further, it is possible to cure osteomyelitis successfully without surgery in more than half the cases
Diabetic foot infection: a critical review of recent randomized clinical trials on antibiotic therapy
Crouzet J, Lavigne JP, Richard JL, Sotto A; on behalf of the Nîmes University Hospital Working Group on the Diabetic Foot (GP30). Int J Infect Dis. 2011 Jul 5. [Epub ahead of print]
Controlled clinical trials are essential tools for evaluating the efficacy of antibiotic treatment against infection, but the results of such trials critically depend on sensitive, reproducible, and feasible outcome measures. We reviewed randomized controlled trials on the antibiotic treatment of diabetic foot infection published between 1999 and 2009 in terms of quality and endpoints. Discrepancies in study design, inclusion criteria, statistical methodology, and the varying definitions of both clinical and microbiological endpoints between the published studies, make it difficult to compare them, as well as to determine which regimen may be the most appropriate for patients with diabetic foot infection.
Microbiology at first visit of moderate-to-severe diabetic foot infection with antimicrobial activity and a survey of quinolone monotherapy.
Tascini C, Piaggesi A, Tagliaferri E, Iacopi E, Fondelli S, Tedeschi A, Rizzo L, Leonildi A, Menichetti F. Diabetes Res Clin Pract. 2011 Aug 6. [Epub ahead of print]
Samples from 1295 patients with diabetic foot infection were evaluated; 4332 samples were collected with an average of 3.3 samples per patient. Fifty-seven percent of patients had a 2B ulcer and 23% had a 3B ulcer according to Texas University Classification. In 64.2% of samples collected at first visit an etiologic agent was identified. About 40% of the positive samples were polymicrobial. Gram positive bacteria were more frequently isolated (52.6%), Staphylococcus aureus was the most frequently isolated single agent (29.9%) and MRSA was 22% of S. aureus. Enterococcus spp., mainly Enterococcus faecalis, were 9.9%, all vancomycin susceptible except 2 isolates. Streptococci were 4.6%, more than 60% Streptococcus agalactiae. Gram negative rods were 40.6%, with enterobacteria 23.5% and Pseudomonas aeruginosa 10.3%. Anaerobes were only 0.3%, probably due to culture methods applied in our laboratory. Cotrimoxazole, rifampin and doxycycline were still active against S. aureus. ESBL producers, among enterobacteria, were 10%, mainly Escherichia coli and Proteus spp. Only colistin had a rate of susceptibility against P. aeruginosa above 90%. Levofloxacin had the best clinical activity with respect to the other quinolones, but when it failed, selected more resistant strains with respect to moxifloxacin among S. aureus and with respect to ciprofloxacin among P. aeruginosa.
This retrospective analysis included intent-to-treat control patient data from two published, randomised, diabetic foot ulcer (DFU) trials in an effort to differentiate ulcers that are unlikely to heal by 12 weeks despite early healing progress [≥50% percent area reduction (PAR) at 4 weeks]. Predicted and actual wound area trajectories in DFUs that achieved early healing progress were analysed from weeks 5 to 12 and compared for ulcers that did and did not heal at 12 weeks. In 120 patients who achieved ≥50% PAR by week 4, 62 (52%) failed to heal by 12 weeks. Deviations from the predicted healing course were evident by 6 weeks for non healing ulcers. A 2-week delay in healing significantly lowered healing rates (P = 0·001). For DFUs with ≥50% PAR at 4 weeks, those achieving ≥90% versus <90% PAR at 8 weeks had a 2·7-fold higher healing rate at 12 weeks (P = 0·001). A PAR of <90% at 8 weeks provided a negative predictive value for DFU healing at 12 weeks of 82%. For ulcers that fail to progress or worsen from weeks 4 to 6, and those that fail to achieve 90% PAR at 8 weeks, reevaluation of the wound and its treatment is recommended.
A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot.
Peters EJ, Lipsky BA, Berendt AR, Embil JM, Lavery LA, Senneville E, Urbančič-Rovan V, Bakker K, Jeffcoate WJ. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:142-62.
The International Working Group on the Diabetic Foot expert panel on infection conducted a systematic review of the published evidence relating to treatment of foot infection in diabetes. Our search of the literature published prior to August 2010 identified 7517 articles, 29 of which fulfilled predefined criteria for detailed data extraction. Four additional eligible papers were identified from other sources. Of the total of 33 studies, 29 were randomized controlled trials, and four were cohort studies. Among 12 studies comparing different antibiotic regimens in the management of skin and soft-tissue infection, none reported a better response with any particular regimen. Of seven studies that compared antibiotic regimens in patients with infection involving both soft tissue and bone, one reported a better clinical outcome in those treated with cefoxitin compared with ampicillin/sulbactam, but the others reported no differences between treatment regimens. In two health economic analyses, there was a small saving using one regimen versus another. No published data support the superiority of any particular route of delivery of systemic antibiotics or clarify the optimal duration of antibiotic therapy in either soft-tissue infection or osteomyelitis. In one non-randomized cohort study, the outcome of treatment of osteomyelitis was better when the antibiotic choice was based on culture of bone specimens as opposed to wound swabs, but this study was not randomized, and the results may have been affected by confounding factors. Results from two studies suggested that early surgical intervention was associated with a significant reduction in major amputation, but the methodological quality of both was low. In two studies, the use of superoxidized water was associated with a better outcome than soap or povidone iodine, but both had a high risk of bias. Studies using granulocyte-colony stimulating factor reported mixed results. There was no improvement in infection outcomes associated with hyperbaric oxygen therapy. No benefit has been reported with any other intervention, and, overall, there are currently no trial data to justify the adoption of any particular therapeutic approach in diabetic patients with infection of either soft tissue or bone of the foo
This update of the International Working Group on the Diabetic Foot incorporates some information from a related review of diabetic foot osteomyelitis (DFO) and a systematic review of the management of infection of the diabetic foot. The pathophysiology of these infections is now well understood, and there is a validated system for classifying the severity of infections based on their clinical findings. Diagnosing osteomyelitis remains difficult, but several recent publications have clarified the role of clinical, laboratory and imaging tests. Magnetic resonance imaging has emerged as the most accurate means of diagnosing bone infection, but bone biopsy for culture and histopathology remains the criterion standard. Determining the organisms responsible for a diabetic foot infection via culture of appropriately collected tissue specimens enables clinicians to make optimal antibiotic choices based on culture and sensitivity results. In addition to culture-directed antibiotic therapy, most infections require some surgical intervention, ranging from minor debridement to major resection, amputation or revascularization. Clinicians must also provide proper wound care to ensure healing of the wound. Various adjunctive therapies may benefit some patients, but the data supporting them are weak. If properly treated, most diabetic foot infections can be cured. Providers practising in developing countries, and their patients, face especially challenging situations
Distinguishing Colonization From Infection With Staphylococcus aureus in Diabetic Foot Ulcers With Miniaturized Oligonucleotide Arrays: A French multicenter study.
Sotto A, Richard JL, Messad N, Molinari N, Jourdan N, Schuldiner S, Sultan A, Carrière C, Canivet B, Landraud L, Lina G, Lavigne JP; the French Study Group on the Diabetic Foot. Diabetes Care. 2012 Feb 1.
OBJECTIVE: To extend our previous work on evaluating the use of oligonucleotide arrays to discriminate colonization from infection owing to Staphylococcus aureus in diabetic foot ulcers (DFUs).
RESEARCH DESIGN AND METHODS: Patients admitted to 14 French diabetic foot departments for a DFU were screened for entry into the study. At admission, ulcers were classified based on clinical examination according to the Infectious Diseases Society of America system. Only patients with monomicrobial culture for S. aureus were included. In persons with an uninfected ulcer, a second wound bacterial specimen was obtained 1 month later. Using oligonucleotide arrays, S. aureus resistance and virulence genes were determined, and each isolate was affiliated to a clonal complex (CC).
RESULTS: S. aureus was initially isolated from 75 uninfected and 120 infected ulcers; 35 were methicillin resistant. A total of 44 (59%) strains from uninfected DFUs belonged to CC5/CC8 clones vs. 6 (5%) from infected DFUs (P < 0.001). During follow-up, 57 (76%) of uninfected DFUs healed or had a favorable outcome; the strain in 49 (86%) of them belonged to CC5/CC8. Conversely, 18 (24%) had a poor outcome but not a single strain belonged to CC5/CC8 clone. Moreover, lukDE was significantly associated with a favorable outcome of the wound.
CONCLUSIONS: As suggested by our previous study, the use of DNA arrays appears to be a promising technique that might help distinguishing uninfected from infected wounds, predicting ulcer outcome and then contributing to a more adequate use of antibiotics.
Photodynamic inactivation of drug-resistant bacteria isolated from diabetic foot ulcers.
Kashef N, Esmaeeli Djavid G, Siroosy M, Taghi Khani A, Hesami Zokai F, Fateh M. Iran J Microbiol. 2011 Mar;3(1):36-41.
BACKGROUND AND OBJECTIVES : Due to the extensive use of antibiotics, the spread of drug-resistant bacteria is one of the most worrisome threats to public health. One strategy that can be used to overcome potential shortcomings might be the inactivation of these organisms by photodynamic therapy. In this study, we have investigated whether drug-resistant wound-associated organisms (Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli) are sensitive to lethal photosensitization using the dye methylene blue coupled with laser light of 660 nm.
MATERIALS AND METHODS : Effect of photosensitizer concentration (25, 50, 100 µg/ml) and laser light dose (27.3, 54.6 and 109.2 J/cm(2)) on lethal photosensitization was investigated. RESULTS : All species were susceptible to killing by photodynamic inactivation. The bactericidal effect was not dependent on the concentration of methylene blue but it was dependent on the light dose. Methylene blue photosensitization using red laser light (109.2 J/cm(2)) was able to achieve reductions of 99.03% and 98.95% in the viable counts of S. aureus and S. epidermidis (using starting concentrations of 10(4)-10(5) CFU/ml). Eradication of 92.23% were obtained for E. coli (initial concentration 10(4)-10(5) CFU/ml) photosensitized by the red light (109.2 J/cm(2)).
CONCLUSION : These findings imply that MB in combination with red light may be an effective means of eradicating drug- resistant bacteria from wounds.
The purpose of this study was to determine the microbiological profile of diabetic foot infections (DFIs) and assess the antibiotic susceptibility of the causative agents. Data were obtained from a retrospective analysis of DFI samples collected from June 2007 to July 2008. Specimens were cultured using optimal aerobic and anaerobic microbiological techniques, and antibiotic susceptibility testing was performed according to the methods recommended by the Clinical and Laboratory Standards Institute (CLSI). Extended-spectrum β-lactamase (ESBL) production was measured using the double disk synergy test and the ESBL Etest. A total of 440 patients were diagnosed with DFIs during this period, and a total of 777 pathogens were isolated from these patients with an average of 1.8 pathogens per lesion. We isolated more Gram-negative pathogens (51.2%) than Gram-positive pathogens (32.3%) or anaerobes (15.3%). Polymicrobial infection was identified in 75% of the patients. The predominant organisms isolated were members of the Enterobacteriaceae family (28.5%), Pseudomonas aeruginosa (17.4%), Staphylococcus aureus (11.8%), methicillin-resistant S. aureus (7.7%), anaerobic Gram-negative organisms (10.8%), and Enterococcus spp. (7%). Vancomycin was the most effective treatment for Gram-positive bacteria, and imipenem, piperacillin-tazobactam and amikacin were the most effective treatments for the Gram-negative bacteria. In conclusion, DFI is common among diabetic patients in Kuwait, and most of the cases evaluated in this study displayed polymicrobial etiology. The majority of isolates were multi-drug resistant. The data gathered in this study will be beneficial for future determinations of empirical therapy policies for the management of DFIs
A prospective, multi-center study: factors related to the management of diabetic foot infections.
Ertugrul BM, Oncul O, Tulek N, Willke A, Sacar S, Tunccan OG, Yilmaz E, Kaya O, Ozturk B, Turhan O, Yapar N, Ture M, Akin F. Eur J Clin Microbiol Infect Dis. 2012 Feb 22.
The Turkish Association of Clinical Microbiology and Infectious Diseases, Diabetic Foot Infections Working Group conducted a prospective study to determine the factors affecting the outcomes of diabetic foot infections. A total of 96 patients were enrolled in the study. Microbiological assessment was performed in 86 patients. A total of 115 causative bacteria were isolated from 71 patients. The most frequently isolated bacterial species was Pseudomonas aeruginosa (n = 21, 18.3%). Among cases with bacterial growth, 37 patients (43%) were infected with 38 (33%) antibiotic-resistant bacteria. The mean (±SD) antibiotics cost was 2,220.42 (±994.59) USD in cases infected with resistant bacteria, while it was 1,206.60 (±1,160.6) USD in patients infected with susceptible bacteria (p < 0.001). According to the logistic regression analysis, the risk factors related to the growth of resistant bacteria were previous amputation (p = 0.018, OR = 7.229) and antibiotics administration within the last 30 days (p = 0.032, OR = 3.796); that related to the development of osteomyelitis was wound size >4.5 cm(2) (p = 0.041, OR = 2.8); and that related to the failure of the treatment was the growth of resistant bacteria (p = 0.016, OR = 5.333). Diabetic foot osteomyelitis is usually a chronic infection and requires surgical therapy. Amputation is the accepted form of treatment for osteomyelitis. Limited limb-saving surgery and prolonged antibiotic therapy directed toward the definitive causative bacteria are most appropriate. This may decrease limb loss through amputations. As a result the infections caused by resistant bacteria may lead to a high cost of antibiotherapy, prolonged hospitalization duration, and failure of the treatment.
To examine the distribution patterns of pathogens isolated from the patients with diabetic foot ulcers and explore the risk factors for infections of methicillin-resistant S. aureus (MRSA) or methicillin-resistant S. epidermidis (MRSE).
A total of 388 diabetic-foot patients hospitalized at Tianjin Metabolic Diseases Hospital between January 2008 and June 2010 were recruited. The distribution profiles of pathogens isolated from diabetic foot ulcers were summarized. The patients with S. aureus infections were divided into MRSA and MSSA groups while those with S. epidermidis infections into MRSE and MSSE groups. The clinical features of these patients were compared between all groups. Logistic regression was employed to identify the risk factors for the MRSA/MRSE infections.
A total of 362 pathogens were isolated from them. And the Gram-positive bacteria were the most predominant (57.2%, 207/362), followed by Gram-negative bacilli (39.2%, 142/362) and true fungi (3.6%, 13/362). The three most frequently isolated pathogens were S. aureus (27.1%), S. epidermidis (18.8%) and Pseudomonas aeruginosa (15.5%). Statistically significant differences existed in antibiotic usage in 6 months prior to hospitalization, course of ulcer, ulcer size, deep ulcer, osteomyelitis, hypertension, anemia, hypoproteinemia and erythrocyte sedimentation rate between the patients infected with MRSA and MSSA (P < 0.05). The MRSE infection was correlated with recurrent ulcer, osteomyelitis, hypoproteinemia, HbA1c and lower total serum protein (P < 0.05). Multiple Logistic regression analysis revealed that antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis, hypertension and hypoproteinemia were risk factors for the MRSA infection. And HbA1c was a risk factor for the MRSE infection.
In the present study, the Gram-positive cocci are the main pathogens isolated from diabetic foot ulcers. And S. aureus and S. epidermidis are the most frequently isolated pathogens. Antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis, hypertension and hypoproteinemia are risk factors for the MRSA infection. And HbA1c is a risk factor for the MRSE infection.
India has the largest diabetic population of 50.8 million that could reach an epidemic proportion by 2030. Diabetic foot infection is one of the dreaded complications of diabetes. Only a few studies that focus on patterns of diabetic foot infection in our region, where diabetic foot care is inadequate, are available. This study evaluated microbial and clinical characteristics of diabetic foot infections that will be helpful in taking appropriate measures for their management.
In this prospective study conducted during 2008-2009, sixty-two diabetic foot patients underwent detailed history, clinical examination, and laboratory investigations including parameters of systemic infections. Microbial culture and sensitivity were performed at the time of presentation.
Among 62 cases, 43.5% had mono-microbial infection, 35.5% had poly-microbial infections, and 21% had sterile culture. Among 82 bacteria isolated, 68% were Gram negative and 32% were Gram positive. Leukocyte counts were higher (16928±9642 versus 14593±6687 cells/mm(3)) and haemoglobin (7.9±2.4 versus 9.2±2.2 mg/dl) lower in poly-microbial compared to mono-microbial infections. Haemoglobin counts were lower and leukocyte counts higher in Gram-negative compared to Gram-positive infections. Patients with sterile cultures also had clinical evidence of persistent infection. Escherichia coli were the most common isolate and piperacillin/tazobactam showed highest sensitivity.
Gram-negative bacteria were most prevalent in diabetic foot infection. It is not uncommon to have culture reports negative despite clinical evidence of infection. This study suggests that piperacillin/tazobactam should be the treatment of choice on an empirical basis prior to a definitive bacteriological study and in cases with negative culture reports.
How reliable are cultures of specimens from superficial swabs compared with those of deep tissue in patients with diabetic foot ulcers?
Mutluoglu M, Uzun G, Turhan V, Gorenek L, Ay H, Lipsky BA. J Diabetes Complications. 2012 Apr 18.
To assess the reliability of cultures of superficial swabs (SS) by comparing them with cultures of concomitantly obtained deep tissue (DT) specimens in patients with diabetic foot ulcers.
We reviewed clinical and microbiological data from patients with diabetes who presented during a two-year period to our hyperbaric medicine center with a foot ulcer. We identified patients who had at least one concomitantly collected SS and DT pair of specimens sent for culture.
A total of 89 culture pairs were available from 54 eligible patients, 33 (61.1%) of whom were hospitalized. Wounds were infected in 47 (87.0%) of the patients and 28 (51.9%) patients had received antibiotic therapy within the previous month. Overall, 65 (73%) of the SS and DT pairs had identical culture results, but in 11 (16.9%) cases the cultures were sterile; thus, only 54 (69.2%) of the 78 culture-positive pairs had identical results. Compared with DT, SS cultures yielded ≥1 extra organism in 10 (11.2%) cases, missed at least one organism in 8 (9.0%), and were completely different in 6 (6.7%). When compared to DT culture results, SS cultures had a positive predictive value of 84.4%, negative predictive value of 44.0%, and overall accuracy of 73.0%.
In patients with diabetic foot ulcers, results of specimens for culture taken by SS did not correlate well with those obtained by DT. This suggests that SS specimens may be less reliable for guiding antimicrobial therapy than DT specimens.
A Molecular and Culture-Based Assessment of the Microbial Diversity of Diabetic Chronic Foot Wounds and Contralateral Skin Sites.
Oates A, Bowling FL, Boulton AJ, McBain AJ. J Clin Microbiol. 2012 May 2.
Wound debridement samples and contralateral (healthy) skin swabs, acquired from 26 patients attending a specialist foot clinic were analysed by differential isolation and eubacterial-specific PCR-DGGE, in conjunction with DNA sequencing. Thirteen out of twenty-six wounds harboured pathogens according to culture analyses, of which Staphylococcus aureus was the most common (13/13). Candida (1/13), pseudomonas (1/13) and streptococci (7/13) were less prevalent. Contralateral skin was associated with comparatively low densities of bacteria and overt pathogens were not detected. According to DGGE analyses, all wounds were associated with significantly greater eubacterial diversity than contralateral skin (p<0.05), although no significant difference in total eubacterial diversity was detected between wounds from which known pathogens had been isolated and those that were putatively uninfected. DGGE amplicons with homology to Staphylococcus sp. (8/13) and S. aureus (2/13) were detected in putatively infected wound samples, whilst Staphylococcus sp. amplicons were detected in 11/13 non-infected wounds; S. aureus was not detected in these samples. Whilst a majority of skin-derived DGGE consortial fingerprints could be differentiated from wound profiles through principal component analysis (PCA), a large minority could not. Furthermore, wounds from which pathogens had been isolated could not be distinguished from putatively uninfected wounds on this basis. In conclusion, whilst chronic wounds generally harboured greater eubacterial diversity than healthy skin, the isolation of known pathogens was not associated with qualitatively distinct consortial profiles or otherwise altered diversity. Data generated support the utility of both culture and DGGE for the microbial characterization of chronic wounds.
2012 infectious diseases society of america clinical practice guideline for the diagnosis and treatment of diabetic foot infections.
Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS, Senneville E. Clin Infect Dis. 2012 Jun;54(12):e132-73.
Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.
Topical Application of a Gentamicin-Collagen Sponge Combined with Systemic Antibiotic Therapy for the Treatment of Diabetic Foot Infections of Moderate Severity
A Randomized, Controlled, Multicenter Clinical Trial
Benjamin A. Lipsky, Michael Kuss, Michael Edmonds, Alexander Reyzelman, Felix Sigal J Am Podiatr Med Assoc 102(3): 223-232, 2012
Background: The aim of this pilot study was to determine the safety and potential benefit of adding a topical gentamicin-collagen sponge to standard of care (systemic antibiotic therapy plus standard diabetic wound management) for treating diabetic foot infections of moderate severity.
Methods: We randomized 56 patients with moderately infected diabetic foot ulcers in a 2:1 ratio to receive standard of care plus the gentamicin-collagen sponge (treatment group, n = 38) or standard of care only (control group, n = 18) for up to 28 days of treatment. Investigators performed clinical, microbiological, and safety assessments at regularly scheduled intervals and collected pharmacokinetic samples from patients treated with the gentamicin-collagen sponge. Test of cure was clinically assessed 14 days after all antibiotic therapy was stopped.
Results: On treatment day 7, we noted clinical cure in no treatment patients and three control patients (P = .017). However, for evaluable patients at the test-of-cure visit, the treatment group had a significantly higher proportion of patients with clinical cure than did the control group (22 of 22 [100.0%] versus 7 of 10 [70.0%]; P =.024). Patients in the treatment group also had a higher rate of eradication of baseline pathogens at all visits (P ≤ .038) and a reduced time to pathogen eradication (P < .001). Safety data were similar for both groups.
Conclusions: Topical application of the gentamicin-collagen sponge seems safe and may improve clinical and microbiological outcomes of diabetic foot infections of moderate severity when combined with standard of care. These pilot data suggest that a larger trial of this treatment is warranted.