rifampin and Diabetic-Foot

The prevalence of diabetes mellitus continues to inexorably rise in the United States and throughout the world. Lower limb amputations are a devastating comorbid complication of diabetes mellitus. Osteomyelitis increases the risk of amputation fourfold and commonly presages death. Antimicrobial therapy for diabetic foot osteomyelitis (DFO) varies greatly, indicating that high quality data are needed to inform clinical decision making. Several small trials have indicated that the addition of rifampin to backbone antimicrobial regimens for osteomyelitis outside the setting of the diabetic foot results in 28 to 42% higher cure rates.. This is a prospective, randomized, double-blind investigation of the addition of 6 weeks of rifampin, 600 mg daily, vs. matched placebo (riboflavin) to standard-of-care, backbone antimicrobial therapy for DFO. The study population are patients enrolled in Veteran Health Administration (VHA), ages ≥18 and ≤ 89 years with diabetes mellitus and definite or probable osteomyelitis of the foot for whom an extended course of oral or intravenous antibiotics is planned. The primary endpoint is amputation-free survival. The primary hypothesis is that using rifampin as adjunctive therapy will lower the hazard rate compared with the group that does not use rifampin as adjunctive therapy. The primary hypothesis will be tested by means of a two-sided log-rank test with a 5% significance level. The test has 90% power to detect a hazard ratio of 0.67 or lower with a total of 880 study participants followed on average for 1.8 years.. VA INTREPID will test if a rifampin-adjunctive antibiotic regimen increases amputation-free survival in patients seeking care in the VHA with DFO. A positive finding and its adoption by clinicians would reduce lower extremity amputations and their associated physical and emotional impact and reduce mortality for Veterans and for the general population with diabetic foot osteomyelitis. Given that rifampin-adjunctive regimens are currently employed for therapy for the majority of DFO cases in Europe, and only in a small minority of cases in the United States, the trial results will impact therapeutic decisions, even if the null hypothesis is not rejected.. Registered January 6, 2017 at ClinicalTrials.gov, NCT03012529.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amputation, Surgical; Anti-Bacterial Agents; Antibiotic Prophylaxis; Diabetic Foot; Double-Blind Method; Female; Foot; Humans; Male; Middle Aged; Osteomyelitis; Placebos; Prospective Studies; Rifampin; Secondary Prevention; Veterans; Young Adult

Little is known about the optimal duration of antibiotic therapy for diabetic foot osteomyelitis (DFO). This study sought to compare the effectiveness of 6 versus 12 weeks of antibiotic therapy in patients with DFO treated nonsurgically (i.e., antibiotics alone).. This was a prospective randomized trial comparing 6- versus 12-week duration of antibiotic treatment. Remission of osteomyelitis during the monitoring period was defined as complete and persistent (>4 weeks) healing of the wound (if present initially), absence of recurrent infection at the initial site or that of adjacent rays, and no need for surgical bone resection or amputation at the end of a follow-up period of at least 12 months after completion of antibiotic treatment.. Forty patients followed at five French general hospitals were randomized between January 2007 and January 2009, with 20 treated for 6 weeks and 20 treated for 12 weeks with antibiotics. The two groups were comparable for all variables recorded at inclusion in the study. Remission was obtained in 26 (65%) patients, with no significant differences between patients treated for 6 versus 12 weeks (12/20 vs. 14/20, respectively; P = 0.50). We did not identify any significant parameters associated with patient outcome. Fewer patients treated for 6 weeks experienced gastrointestinal adverse events related to antimicrobial therapy compared with patients treated for 12 weeks (respectively, 15 vs. 45%; P = 0.04).. The present multicenter prospective randomized study provides data suggesting that 6-week duration of antibiotic therapy may be sufficient in patients with DFO for whom nonsurgical treatment is considered.

Topics: Amputation, Surgical; Anti-Bacterial Agents; Diabetic Foot; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Male; Middle Aged; Osteomyelitis; Prospective Studies; Rifampin; Treatment Outcome; Wound Healing

We retrospectively evaluated the safety and effectiveness of colistin alone or in combination with other antimicrobials in eight diabetic patients with severe diabetic foot infections due to multidrug resistant (MDR) Pseudomonas aeruginosa, complicated in 4 cases by osteomyelitis. All patients received colistin after other ineffective antimicrobial treatment, when MDR P. aeruginosa strains were isolated by cultural examination and together with a multidisciplinary care approach including revascularization, surgical debridement and adequate offloading. The mean duration of therapy was 72 +/- 52.9 days. Six out of 8 patients (75%) successfully benefited from colistin therapy, while 2 patients failed and/or experienced side effects that led to discontinuation of therapy. Serious adverse events (i.e. acute renal failure and pulmonary edema) were observed in 1 patient. Our data allow us to conclude that colistin, alone or in combination with other antimicrobials, is safe and effective when administered as part of a multidisciplinary approach, to promote healing of diabetic foot infection due to MDR P. aeruginosa.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Debridement; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Osteomyelitis; Pseudomonas Infections; Retrospective Studies; Rifampin; Treatment Outcome

Topics: Clindamycin; Diabetes Mellitus; Diabetic Foot; Drug Monitoring; Humans; Osteomyelitis; Rifampin

BACKGROUND Foot ulcers are high-morbidity and debilitating complications of diabetes mellitus, and carry significantly increased rates of associated major amputations. They contribute to significantly worse quality of life. Osteomyelitis is a frequent complication of diabetic foot ulcers, since bacteria can contiguously spread from soft tissues to the bone, involving the cortex first and then the bone marrow. Unfortunately, clinically unsuspected osteomyelitis is frequent in persisting diabetic foot ulcers. It is associated with limb amputations and increased mortality. CASE REPORT We describe a 76-year-old man with long-standing insulin-treated type 2 diabetes, who experienced extensively drug-resistant Enterococcus faecalis diabetic foot myositis and osteomyelitis associated with sepsis. He was successfully treated with surgical debridement combined with the administration of teicoplanin plus rifampicin in the outpatient setting, completing, in total, a twelve-week course of antibiotic therapy. CONCLUSIONS Clinically unsuspected osteomyelitis in patients with persisting diabetic foot ulcers has been associated with infections from highly resistant bacteria. Early and accurate diagnosis of diabetic foot osteomyelitis, as well as proper therapeutic approach (antimicrobial and surgical), is of great importance to reduce the risk of minor and major amputations, septic shock leading to multiple organ failure, and overall mortality.

Topics: Aged; Anti-Bacterial Agents; Diabetes Mellitus, Type 2; Diabetic Foot; Enterococcus faecalis; Humans; Male; Myositis; Osteomyelitis; Outpatients; Pharmaceutical Preparations; Quality of Life; Rifampin; Teicoplanin

Topics: Agar; Anti-Bacterial Agents; Bacteria; Calcium Sulfate; Diabetes Mellitus; Diabetic Foot; Floxacillin; Gentamicins; Humans; Microbial Sensitivity Tests; Rifampin; Vancomycin

The prevalence of diabetes continues to rise around the world. Diabetic foot is a serious complication of diabetes, and diabetic patients with diabetic foot osteomyelitis (DFO) have a fourfold increased risk of amputation, usually indicating death. Therefore, it is particularly important to seek a more effective treatment for DFO. The treatment of DFO varies from person to person, and antimicrobial therapies vary widely. A large number of clinical studies have shown that rifampicin adjuvant therapy can reduce the rate of amputation and mortality in DFO patients. However, there is no systematic summary of clinical evidence, which limits the clinical application of rifampicin. Therefore, we attempted to provide high-quality evidence for the clinical efficacy and safety of rifampin in the adjuvant treatment of DFO through this meta-analysis.. English literature is mainly searched in Cochrane Library, PubMed, EMBASE and Web of Science, while Chinese literature is from CNKI, CBM, VIP and Wangfang databases. At the same time, we will search clinical registration tests and gray literature. Two methodologically trained researchers will read the title, abstract, and full text, and independently select qualified literature based on inclusion and exclusion criteria. Binary data is expressed as relative risk, continuous data is expressed as mean difference or standard mean difference. The final data are synthesized using a fixed effect model or a random effect model, depending on the presence of heterogeneity. In the end, the patient's amputation rate and mortality were the main research indicators. Survival rate, HbA1c, serum creatinine, changes in ulcer area, and SF-36 quality of life assessment were used as secondary indicators. We will perform a sensitivity analysis to assess the stability of the results. Then the publication bias was evaluated by funnel plot analysis and Egger test. Finally, we will use a "recommendation grading, evaluation, formulation and evaluation" system to assess the quality of the evidence. All data analysis will be meta-analyzed by the statistical software RevMan software version 5.3.. This study will provide a high-quality comprehensive report on the effectiveness and safety of rifampicin in the treatment of DFO, and our findings will be published in peer-reviewed journals.. This systematic review and meta-analysis will provide a comprehensive summary and careful evaluation of rifampicin as an adjuvant treatment of DFO with a view to providing multiple options for clinical treatment of the disease. REGISTRATION NUMBER:: is INPLASY202040084.

Topics: Adjuvants, Pharmaceutic; Anti-Bacterial Agents; Diabetic Foot; Humans; Meta-Analysis as Topic; Osteomyelitis; Rifampin; Systematic Review as Topic

Among patients diagnosed with diabetes, the lifetime incidence of foot ulcers is 15%. Infection is a common complication of foot ulcers, and 20% to 60% of infections result in diabetic foot osteomyelitis (DFO). Current treatment guidelines do not endorse any specific antibiotic agent for DFO, but small clinical trials suggest the addition of rifampin to antimicrobial regimens results in improved cure rates for osteomyelitis.. To compare the clinical outcomes of patients treated for DFO in the Veterans Health Administration (VHA) with and without adjunctive rifampin.. This observational cohort study used VHA databases to identify index DFO cases from January 1, 2009, through December 31, 2013, and analyzed patients alive and without high-level amputation at 90 days after diagnosis in whom antibiotic therapy was initiated within 6 weeks of diagnosis. Patients with death or major amputation within 90 days of diagnosis, who were not treated with systemic antibiotics dispensed by the VHA within 6 weeks of diagnosis, or who were treated at facilities where rifampin was not dispensed for DFO were excluded. The retrospective cohort to inform the planning of a multisite randomized clinical trial was first investigated in spring 2015; retrospective analysis was performed from February 2017 through September 2019.. Patients initiating rifampin therapy within 6 weeks of the DFO diagnosis and receiving the drug for at least 14 days within 90 days of diagnosis were considered treated with rifampin. Patients not administered rifampin within 90 days of diagnosis served as the comparator group.. A combined end point of mortality or amputation within 2 years of diagnosis was analyzed. Differences in times to event were evaluated using log-rank tests. Differences in event rates were compared using χ2 tests and multivariable logistic regression.. The analysis population included 130 patients treated with rifampin and 6044 treated without rifampin (total of 6174; 6085 men [98.6%]; mean [SD] age, 64.9 [9.7] years). Lower event rates were observed among the rifampin group (35 of 130 [26.9%] vs 2250 of 6044 [37.2%]; P = .02). Patients treated with rifampin were younger (mean [SD] age, 62.2 [9.4] vs 64.9 [9.6] years), had fewer comorbidities (mean [SD] Charlson comorbidity index score, 3.5 [1.8] vs 4.0 [2.2]), had more infectious disease specialty consultations (63 of 130 [48.5%] vs 1960 of 6044 [32.4%]), and more often had Staphylococcus aureus identified in cultures (55 of 130 [42.3%] vs 1755 of 6044 [29.0%]) than patients not treated with rifampin. A logistic regression estimating the odds of events and controlling for these and other covariates yielded a significant association of rifampin (odds ratio, 0.65; 95% CI, 0.43-0.96; P = .04).. In this cohort study, patients administered rifampin experienced lower rates of death and amputation than patients not treated with rifampin, which remained significant after adjustment for confounders. These results coupled with existing evidence from small clinical trials suggest the addition of rifampin to current treatment regimens may be a useful antimicrobial option in the treatment of DFO.

Topics: Amputation, Surgical; Anti-Bacterial Agents; Diabetic Foot; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Osteomyelitis; Rifampin; Treatment Outcome; United States; Veterans Health Services

Staphylococcus aureus is the main cause of diabetic foot infection with the patient's endogenous flora as the principal source. Nasal carriage of S. aureus has been identified as an important risk factor for the acquisition of diabetic foot infections.. The study assessment the associations of S. aureus with methicillin resistant S. aureus were isolation from diabetic foot infection and nasal carriage of the same patients and their antibiotic susceptibility profile.. Diagnosis of S. aureus and methicillin resistant S. aureus were carried out by using standard procedures. Antibiotic sensitivity profiles were determent by breakpoint dilution method.. Out of 222 S. aureus isolation, 139 (62.61%) were isolated from the diabetic foot and 83 (37.39%) from the nasal carriage. Seventy one (30.87%) of the patients were S. aureus infection diabetic foot with nasal carriage. Among diabetic foot infection and nasal carriage patients, 40.85% of S. aureus were considered as methicillin resistant S. aureus. Rifampicin (96.40%) and Levofloxacin (91.44%) were active against S. aureus.. Patients at strong risk for methicillin resistant S. aureus nasal carriage and subsequent diabetic foot infection with high resistance to antibiotics.

Topics: Adult; Aged; Anti-Bacterial Agents; Carrier State; Diabetic Foot; Female; Humans; Levofloxacin; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Nose; Ofloxacin; Rifampin; Risk Factors; Staphylococcal Infections

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.

Topics: Anti-Infective Agents; Candida; Diabetic Foot; Doxycycline; Enterococcus; Enterococcus faecalis; Escherichia coli; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Quinolones; Rifampin; Staphylococcus aureus; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

The evaluation of the safety and effectiveness of colistin in association with rifampin and imipenem in 1 diabetic patient with severe diabetic foot infection (DFI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by osteomyelitis, is presented in this "Case Report". The patient received colistin after other ineffective antimicrobial treatment when an MDR P aeruginosa strain was isolated by cultural examination, together with a multidisciplinary care approach including surgical debridement and adequate offloading. The efficacy of combination colistin plus rifampin plus imipenem was observed with a checkerboard method and bactericidal activity of the serum. The patient received colistin combination therapy for 6 weeks with cure of the infection and without renal toxicity. These data suggest that colistin, in combination with rifampin and imipenem, is safe and effective, in promoting healing in DFI due to MDR P aeruginosa and suggest the need for controlled clinical studies.

Topics: Aged; Anti-Bacterial Agents; Colistin; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Follow-Up Studies; Humans; Imipenem; Male; Metatarsal Bones; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

The interest of the management of bone infections in the diabetic foot, inspired by the recommendations for the treatment of chronic osteitis, was assessed in this study.. Twenty bone infections in 17 diabetic patients with moderate to mild infections of the feet were confirmed by the results of X-ray and/or scintigraphic studies and bone surgery biopsy cultures revealing one or more bacteria sensitive to standard osteitis treatment (rifampicine + fluoroquinolone). The patients had received this treatment per os for a median duration of 6 months (3 to 10 months). Clinical follow-up was carried out during a consultation at 1, 3 and 6 months during treatment and then by telephone every six months after the end of treatment. Clinical success was defined as the disappearance of any local sign of infection and by the absence of relapse during the post-treatment follow-up period. The evolution of the bone infection was also assessed by the results of a control conducted 3 to 6 months after initiation of the antibiotic treatment.. At the end of the treatment, all signs of infection had disappeared in 15/17 patients (88.2%) and no relapse had occurred in 14 (82.3%) patients at the end of a median post-treatment period of 22 months (12 to 41 months). Resection of necrotic bone was performed at the same time as the bone biopsy in 2 patients. The median duration of hospitalisation was of 14 days (3 to 53 days). During the study, a multi-resistant germ was isolated in 4 patients (1 Pseudomonas aeruginosa, 3 Staphylococcus aureus). During the post-treatment follow-up, 3 patients dies from causes unrelated to the infection treated. No serious adverse event was reported during the study.. The results of this pilot study support the rationale of applying the treatment regimens of chronic osteitis to diabetic lesions of the feet, but are only applicable to comparable patients presenting with non-severe lesions of the feet. Moreover, the use of antibiotics with potent selection of resistance such as rifampicine and fluoroquinolone, requires that bone biopsies be taken, which is not easy in all the diabetic foot care centres. We are presently conducting a study to identify the sub-populations of diabetic patients who could benefit from such treatment.

Topics: Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Biopsy; Chronic Disease; Diabetic Foot; Drug Resistance, Multiple; Female; Fluoroquinolones; Humans; Male; Middle Aged; Osteitis; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Seventeen diabetic patients with moderate to mild foot lesions associated with 20 osteomyelitic bones diagnosed by both bone scan and bone biopsy received rifampicin plus ofloxacin for a median duration of 6 months. Cure was defined as disappearance of all signs and symptoms of infection at the end of the treatment and absence of relapse during follow up. At the end of the treatment period, cure was achieved in 15 patients (88.2%) and was maintained in 13 patients (76.5%) at the end of an average post-treatment follow-up of 22 months. No serious drug-related adverse events were recorded.

Topics: Administration, Oral; Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Bacterial Infections; Chronic Disease; Diabetic Foot; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ofloxacin; Osteomyelitis; Rifampin; Treatment Outcome