Oral clindamycin and ciprofloxacin therapy for diabetic foot infections

Infected foot ulcers are a common complication in persons with diabetes. In general, treatment consists of intravenous administration of antibiotics, for which the patients are customarily hospitalized. The average length of hospital stay for this therapy in our institution is 15.6 days. We evaluated a regimen of oral clindamycin plus ciprofloxacin, which patients could take at home, with respect to the clinical eradication of the infection and treatment cost savings. Our results demonstrated that with these oral agents, patients' length of hospital stay was greatly reduced, and the pharmacy realized significant cost avoidance.     

糖尿病足病合并感染的抗生素应用

糖尿病足病合并感染是糖尿病严重的并发症，其中尤以骨髓炎常见。最近的一项前瞻性流行病学研究，对1600名糖尿病患者观察2年，发现9．1％的患者发生感染。感染多发生在开放伤口和深部损伤。感染造成患者住院和截肢的危险分别是非感染者的56倍和154倍。当患者合并下肢血管病变时，感染发展迅速，威胁肢体和生命，增加了急诊截肢的比例。据统计，约20％的糖尿病足病患者发展成为骨髓炎。     

Ertapenem for diabetic foot infections

Foot infections are a common cause of hospitalization in people with diabetes. Diabetic foot infections are associated with increased risk of amputation and death. This monograph reviews the diagnosis and treatment of diabetic foot infections with particular attention to a new carbapenem antibiotic, ertapenem, which has the potential to reduce inpatient length of stay and hospital-associated costs.     

糖尿病足感染的处理

糖尿病足的严重感染会造成截肢,诊断并正确处理足部感染虽然是个难点,但也非常重要.它是创面修复、血管重建等其他治疗的基础.感染不解决,其他治疗都不可能成功,甚至连血糖都不能稳定控制.因此,在糖尿病足的各项处理中,首要的就是解决好糖尿病足的感染问题.     

利用蒙特卡洛模拟程序优化抗菌药物治疗

合理的抗菌药物应用是临床抗感染治疗成败的关键,由于抗菌药物在不同群体存在药物动力学差异,往往需要个体化用药.目前临床常用几种抗菌药物的给药剂量预估方法包括回归分析法、群体模型列线图以及蒙特卡洛模拟,本文综合比较3种方法的优劣,为临床安全合理使用抗菌药物提供参考.     

Optimising antimicrobial therapy through the use of Bayesian dosing programs

International Journal of Clinical Pharmacy - The optimisation of antibiotic dosing therapy with therapeutic drug monitoring is widely recommended. The aim of therapeutic drug monitoring is to help...     

Consensus document on treatment of infections in diabetic foot

Diabetic foot infection, particularly if it is associated to ischaemia,is the most common cause of lower limb amputation, in the general population, of hospital admissions, and a decrease in the quality of life in diabetics. Of all diabetics, 15% of them are going to suffer from a foot infection during their life, with an annual incidence of 1-4%, preceded by a foot ulcer in more than 80% of cases. They are complex infections and the prognosis is influenced by many factors, depending on the ulcer (location, extension, whether chronic or not, previous amputation, ischaemia grade), and the patient (age, renal impairment, time of onset of diabetes, associated comorbidity). All these must be taken into account when establishing its treatment. The infections must be classified according to their severity (mild, moderate-mild, moderatesevere, and severe). Their treatment is complex and must be multidisciplinary and must include debridement, discharge, adequate antibiotic therapy, revascularisation, and treatment of the ulcer. In this consensus document, produced in collaboration with the Spanish Angiology and Vascular Surgery Society (SEACV), the Spanish Society of Internal Medicine (SEMI), the Spanish Chemotherapy Society (SEQ), the Spanish Surgeons Association (AEC), the Spanish Society of Urgent Medicine and Emergencies (INFURG-SEMES) and the Spanish Society of Intensive and Critical Medicine and Coronary Care (SEMICYUC), the guidelines are developed based on the best available evidence on diabetic foot infections, aimed at achieving greater clinical efficacy.     

Antimicrobial interventions for the management of diabetic foot infections

Foot infections are the most common cause of hospitalisations and amputations in diabetic patients. They occur after skin ulcers or trauma in patients with peripheral neuropathy, sometimes together with vascular disease. Narrow-spectrum antibiotic agents should be prescribed for minor recent infections, and broader-spectrum agents for severe or chronic infections. When indicated, antibiotic therapy should be started early and be tailored to the individual patient. Diabetic foot osteomyelitis is a particularly controversial condition, especially regarding the need for reliable cultures, the type and duration of treatment, and the role of surgery. Recent data indicates that a medical approach might be effective and could reduce foot amputations among diabetic patients. Interdisciplinary cooperation with infectious disease specialists and orthopaedic surgeons should be considered in such situations.     

Novel antibiotics for the management of diabetic foot infections

Foot infections are a major cause of morbidity in diabetic patients. Staphylococcus aureus is the most important pathogen in mild infections; moderate to severe infections are frequently polymicrobial. Multidrug resistance is an increasing problem in isolates from diabetic feet. Worldwide, up to 30% of patients with diabetic foot infection (DFI) are colonised with methicillin-resistant S. aureus (MRSA), whilst extended-spectrum β-lactamase-producing Gram-negative bacteria are also common in some countries. This emergence of drug resistance has coincided with the launch or imminent availability of many new antibiotics. Most of these were developed to target multidrug-resistant Gram-positive bacteria, although some have a spectrum of activity that includes Gram-negative bacteria and anaerobes. There is a variable amount of experience with these agents in treating skin and skin-structure infections (SSSIs), especially for DFI. However, at least some have a spectrum of activity and/or pharmacological properties that suggest that they may be of value in managing DFIs. The aim of this paper is to review evidence for the efficacy of new antibiotics in the management of SSSIs, including any data relating specifically to the diabetic foot, and to consider where they might fit into the therapeutic armory against DFI.     

糖尿病足溃疡感染的病情判断和抗菌素治疗

本文通过对感染细菌与足溃疡特点的分析,进一步对糖尿病足溃疡病情的诊断和感染治疗过程中的抗菌素使用进行总结。     

Short-course antimicrobial therapy of respiratory tract infections

Accumulating evidence suggests that short-course (/=80%) of patients. However, more research is clearly needed in the subpopulations of children <2 years of age and in those with unresponsive/recurrent disease, since short-course therapy may not be successful in the majority of these patients.In sinusitis, most short-course therapy data have involved maxillary disease in adult patients. Regimens have included 3 days of azithromycin or cotrimoxazole (trimethoprim/sulfamethoxazole) or 5 days of cefpodoxime, telithromycin, gatifloxacin, gemifloxacin or amoxicillin/clavulanic acid. Preliminary results are encouraging but more study is clearly needed, especially in the paediatric population.In acute bacterial exacerbations of chronic bronchitis, short-course therapy with a variety of cephalosporins, second-generation fluoroquinolones and advanced generation macrolides/azalides/ketolides are all reasonable alternatives to traditional 7- to 14-day therapies.Cost containment in antimicrobial therapy should involve consideration of short-course therapy in the management of the most common types of respiratory tract infections.     

Essentials for selecting antimicrobial therapy for intra-abdominal infections

Intra-abdominal infection (IAI) is a complex disease entity in which different aspects must be balanced in order to select the proper antimicrobial regimen and determine duration of therapy. A current classification indicates different faces of peritonitis. Primary peritonitis implies an intact gastrointestinal tract without overt barrier disruption. Secondary peritonitis refers to localized or diffuse peritoneal inflammation and abscess formation due to disruption of the anatomical barrier. Tertiary peritonitis includes cases that cannot be solved by a single or even sequential surgical intervention, often in combination with sequential courses of antimicrobial therapy. The most frequently used classification distinguishes 'uncomplicated' and 'complicated' IAI. In uncomplicated IAI, the infectious process is contained within a single organ, without anatomical disruption. In complicated IAI, disease is extended, with either localized or generalized peritonitis. However, there exists more than a single dimension of complexity in IAI, including severity of disease expression through systemic inflammation. As the currently used classifications of IAI often incite confusion by mixing elements of anatomical barrier disruption, severity of disease expression and (the likelihood of) resistance involvement, we propose an alternative for the current widely accepted classification. We suggest abandoning the terms 'uncomplicated' and 'complicated' IAI, as they merely confuse the issue. Furthermore, the term 'tertiary peritonitis' should likewise be discarded, as this simply refers to treatment failure of secondary peritonitis resulting in a state of persistent infection and/or inflammation. Hence, anatomical disruption and disease severity should be separated into different phenotypes for the same disease in combination with either presence or absence of risk factors for involvement of pathogens that are not routinely covered in first-line antimicrobial regimens (Pseudomonas aeruginosa, enterococci, Candida species and resistant pathogens). Generally, these risk factors can be brought back to recent exposure to antimicrobial agents and substantial length of stay in healthcare settings (5-7 days). As such, we developed a grid based on the different components of the classification: (i) anatomical disruption; (ii) severity of disease expression; and (iii) either community-acquired/early-onset healthcare-associated origin or healthcare-associated origin and/or recent antimicrobial exposure. The grid allows physicians to define the index case of IAI in a more unequivocal way and to select the most convenient empirical antimicrobial regimens. The grid advises on the necessity of covering nosocomial Gram-negative bacteria (including P. aeruginosa), enterococci and yeasts. The basis of antimicrobial therapy for IAI is that both Gram-negative and anaerobic bacteria should always be covered. In recent years, some newer agents such as doripenem, moxifloxacin and tigecycline have been added to the antimicrobial armamentarium for IAI. For patients in whom the source can be adequately controlled, antimicrobial therapy should be restricted to a short course (e.g. 3-7 days in peritonitis).     

负压伤口疗法在糖尿病足中的运用

近年来,国内外采用负压伤口疗法治疗糖尿病足溃疡,积累了一定的经验,现本文对此作一综述。     

Consensus statement on antimicrobial therapy of intra-abdominal infections in Asia

The selection of antimicrobial agents in the 2006 Guidelines (consensus statement) on Empiric Therapy for Complicated Intra-Abdominal Infections (IAIs) in Asia was based on resistance and epidemiological data from the Asian region. In these 2006 guidelines, single agent therapy using the beta-lactam/beta-lactamase inhibitors ampicillin/sulbactam or cefoperazone-sulbactam is recommended for mild-to-moderate cases, while piperacillin-tazobactam is recommended for high-severity cases. When using carbapenems, ertapenem is recommended for mild-to-moderate cases, while imipenem and meropenem are recommended for high-severity cases. For combination regimes, two types of agents are recommended: cephalosporin-based and monobactam-based. For mild-to-moderate cases, a third generation cephalosporin plus metronidazole is recommended. For high-severity cases, a third or fourth generation cephalosporin plus metronidazole+/-amikacin is recommended. For the monobactam-based regimen, aztreonam plus metronidazole is recommended for high-severity cases only.     

Pharmacokinetics and penetration of linezolid into inflamed soft tissue in diabetic foot infections

Objective  Physiological changes and local and systemic inflammation may affect plasma and tissue pharmacokinetics of antimicrobial agents in diabetics. The aim of the study was to investigate the penetration of linezolid into inflamed areas of infected diabetic foot wounds and the pharmacokinetics in the risk population of diabetics. Methods  Pharmacokinetics and tissue penetration of linezolid into inflamed diabetic foot infection (DFI) tissue were determined at steady state in 15 patients with diabetes type 2 and DFI following administration of multiple oral doses of 600 mg given every 12 h. Second debridement was performed on days 4–6, 3 h after linezolid administration. Linezolid concentrations were determined in perinecrotic wound tissue of inflamed diabetic foot by high-performance liquid chromatography (HPLC). Results  A mean maximum plasma concentration (C_max) in plasma of 14.3 mg/L was attained at a median of 2.0 h [time to reach C_max (T_max) range 0.5–6.0 h). Area under the concentration time curve from zero to 12 h (AUC_0–12 h) with a mean of 114.1 mg∙h/L and C_min of 5.4 mg/L were achieved in patients with diabetes mellitus type 2. Penetration of linezolid into inflamed areas of DFI with tissue/plasma ratios of mean 101.7% [95% confidence interval (CI) 56; 148%] produced a mean concentration of 9.6 μg/g (95% CI 7.4; 11.8 μg/g) greater than those predicted to be effective against methicillin-resistant staphylococci [minimum concentration that inhibits 90% of organisms (MIC₉₀) of 4 mg/L]. Tissue/plasma ratios correlated positive with systemic inflammation. Conclusion  Plasma pharmacokinetics of linezolid in diabetics and adequate levels in inflamed areas of diabetic foot wound suggest that an oral dose of 600 mg bd of linezolid provides effective concentrations for treating methicillin-resistant Staphylococcus aureus (MRSA) in DFI. Presented in part at the 41th Annual Meeting of the European Association for Study of Diabetes, September 2005 in Athens, Greece, and at the 7th Annual Congress of the German Clinical Pharmacology, November 2005 in Dresden, Germany     

The major clinical outcomes of diabetic foot infections: One center experience

Diabetes mellitus with its limb and life-threatening complications such as diabetic foot infection and amputation are increasing at epidemic rates all over the world. The objective of this study was to determine the rate of lower extremity amputation, the risk factors and the bacteriologic profile for diabetic foot lesions. The records of all 84 patients with diabetic foot infections of a large general hospital over a 4-year period were retrospectively included. The most commonly isolated pathogens were Staphylococcus aureus (39%), Pseudomonas aeruginosa (14%), Proteus mirabilis (14%), Escherichia coli (14%), Group B streptococci (12%), and Klebsiella pneumonia (8%). The variables, independently associated with higher foot infections, were inadequate diabetic regulation (93%), peripheral neuropathy (88.1%), peripheral vascular disease (73.8%), smoking (56%), past history of ulcer (28.5%), penetrating injury (20.3%), inadequate foot wear (15%) and Charcot osteoartropathy (10.7%). The general amputation rate was 38.1%. Diabetic foot ulcers and its complication rates including infection, gangrene and lower extremity amputation in Turkey are still high. Preventive care of the foot in patients with diabetes mellitus is extremly important. Therefore early diagnosing of risk factors for diabetic foot infections in the primary care setting and their adequate therapy under multidisciplinary approach should not be neglected.     

Comparative costs of ertapenem and piperacillin-tazobactam in the treatment of diabetic foot infections.

PURPOSE: To evaluate potential cost savings, trial data were used to determine the clinical outcomes for i.v. ertapenem given once daily and i.v. piperacillin-tazobactam given every six hours daily in treating diabetic foot infections. METHODS: A cost-minimization analysis (CMA) was conducted on the drug-dosing data of the subset of patients enrolled in a recent double-blind randomized trial who were treated solely as inpatients and were clinically evaluable at fi nal assessment (n = 99). Cost per dose was calculated from (a) average hospital acquisition price per dose for ertapenem ($40.52) or piperacillin-tazobactam ($13.58), (b) average U.S. wages and benefits for labor, based on nine published time-and-motion studies of i.v. antibiotic preparation and administration ($3.10), and (c) consumable supplies, using a 40% discount off the manufacturer list price ($2.90). For each patient, the actual number of antibiotic doses given was multiplied by total cost per dose. RESULTS: There were no significant differences between antibiotic groups with respect to patient demographics, percentage with a severe wound, and mean days of i.v. therapy. Compared with piperacillin-tazobactam, patients treated with ertapenem received significantly fewer mean doses (25.5 versus 7.5; p < 0.0001) and lower antibiotic-related costs ($502.76 versus $355.55, respectively; p < 0.001). The $147.21 difference between groups accounts for approximately 3% of total hospital Medicare reimbursements for these infections. CONCLUSION: A CMA of treatment of diabetic foot infections showed that, compared with piperacillin-tazobactam given four times daily i.v., ertapenem given once daily i.v. was associated with lower drug acquisition and supply costs and less time and labor devoted to preparation and administration of i.v. therapy.     

120例糖尿病足感染患者病原菌分布特点及药敏分析

目的 了解青岛地区糖尿病足(DF)合并感染的病原菌分布及药物敏感情况.方法 选取2013年12月至2015年12月于青岛内分泌糖尿病医院住院的120例糖尿病足感染患者,分析其病原菌分布特点及药物敏感性,及病原菌分布与DF严重性的关系.结果 120例DF患者足部分泌物培养出病原菌103株,阳性率为85.83％.其中,革兰阳性球菌65株,占63.11％(65/103),革兰阴性杆菌38株,占36.89％(38/103).混合菌感染患者24例,占20.00％(24/120),其中16例Wagner分级≥3级,占66.67％(16/24).感染的病原菌主要有金黄色葡萄球菌、表皮葡萄球菌、变形杆菌、大肠埃希菌.革兰阴性杆菌对泰能、阿米卡星、哌拉西林较为敏感;对头孢唑林、氨苄西林大多耐药.革兰阳性球菌对庆大霉素、替考拉宁、莫西沙星较敏感,而对青霉素、大环内酯类大多耐药.结论 糖尿病足感染的病原菌分布广泛,耐药率高,且随着感染加重,革兰阴性杆菌逐渐占据主导地位.临床治疗中,在积极降糖治疗的同时,尽早、多次行分泌物病原学检查及早期联合选择敏感抗菌药物治疗至关重要.     

糖尿病足分离的铜绿假单胞菌对氨基糖苷类抗生素耐药机制探讨

【摘要】 目的 通过对天津地区糖尿病足感染主要革兰氏阴性致病菌,铜绿假单胞菌（PA）对氨基糖苷类抗生素耐药的表型和基因型分析,旨在指导临床抗生素用药的选择,减少耐药菌株的增加。方法 采集本院209例糖尿病足溃疡患者的细菌学报告以及药敏结果,筛选出41株PA菌株,萃取菌株DNA后,以聚合酶链反应（PCR）检测氨基糖苷类修饰酶aac (3’)-Ⅱ、aac (6’) -Ⅰb、aac (6’) -Ⅱ、ant (2″) -Ⅰ、ant (3″) -Ⅰ及aac (3’) -Ⅰ,结合所选患者的临床资料和对耐药报告,对耐药基因型及耐药表型的进行相关分析。结果 结果显示,糖尿病足溃疡创面分离出的致病菌以革兰氏阳性（G+）菌为主,为51.67%;PA的总检出率为19.62%,是革兰氏阴性菌（G-）的首位致病菌;在感染较深、较重创面中PA的检出率明显增高;感染PA患者的溃疡面积明显高于感染其他G-菌和G+菌患者。PA菌株对所检测的氨基糖苷类抗菌素的耐药率高达73.17,检出氨基糖苷类修饰酶基因最多的为ant (3″) -Ⅰ（65.85%）,aac (3’) -Ⅱ,aac(6’) -Ⅱ,aac (6’)-Ⅰb及ant (2″) -Ⅰ分别为63.41%,48.78%,12.2%及7.32%,aac(3’)-Ⅰ未检出。结论 研究提示在创面较深较大、感染较重的创面PA感染几率大;氨基糖苷类抗菌素的耐药现象非常严重; ant(3″)-Ⅰ是最为常见的氨基糖苷类抗菌素耐药基因。