Benjamin A. Lipsky

Diagnosis and Treatment of Diabetic Foot Infections

EXECUTIVE SUMMARY: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to 1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limbs arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III).

2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections a

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.

Chlorhexidine Compared with Povidone-Iodine Solution for Vascular Catheter–Site Care: A Meta-Analysis

Context Intravascular catheterrelated bloodstream infection is an important and potentially avoidable cause of morbidity. Various antiseptic solutions for skin disinfection and catheter-site care may help prevent catheter-related infections. Contribution This article summarizes data from eight randomized trials that compared antiseptic solutions. Approximately 1% of the patients with chlorhexidine gluconate disinfectant developed bloodstream infections from intravascular catheters. In the patients with disinfection by povidone-iodine, the rate was 2% (risk ratio, 0.49 [95% CI, 0.28 to 0.88]). Implications Chlorhexidine gluconate is more effective than povidoneiodine for intravascular catheter-site care. It is also more expensive. The Editors Intravascular catheters are commonly used in caring for hospitalized patients but can lead to serious infectious complications (1). Catheter-related bloodstream infection is associated with increased morbidity, mortality, length of hospitalization, and medical costs (2-6). Use of an antiseptic solution for skin disinfection at the catheter insertion site helps prevent catheter-related infections. Povidone-iodine solution is the most commonly used agent for this purpose (7, 8). Recently, several studies have compared the efficacy of povidone-iodine with that of chlorhexidine gluconate solutions for reducing vascular catheterrelated infections (7, 9-14; Knasinski V, Maki DG. A prospective, randomized, controlled trial of 1% chlorhexidine 75% alcohol vs. 10% povidone iodine for cutaneous disinfection and follow-up site care with central venous and arterial catheters [Presented paper]. San Diego: National Association of Vascular Access Network Conference; 2000). Unfortunately, because few clinical events have been observed in individual studies, it remains unclear which antiseptic solution is best, both statistically and clinically, for reducing the risk for catheter-related bloodstream infection, particularly in patients with central-line catheters. We sought to aid clinical decision making by evaluating the effectiveness of chlorhexidine gluconate versus povidone-iodine as a skin disinfectant for catheter-site care. We performed a meta-analysis of all available published and unpublished studies comparing chlorhexidine gluconate with povidone-iodine solution for vascular catheter-site care. Methods Study Selection We manually searched Index Medicus (1960 to 1965) and electronically searched MEDLINE (1966 to 2001), CINAHL: Nursing and Allied Health (1982 to 2001), Doctoral Dissertation Abstracts (1861 to 2001), International Pharmaceutical Abstracts (1970 to 2001), EMBASE, Lexis-Nexus, Web of Sciences, and Cochrane Library databases for publications in any language. For our search strategy, we used the Medical Subject Headings chlorhexidine and catheterization and the exploded key words chlorhexidine and catheter. We restricted the searches to clinical trials. To ensure that our search would be thorough, we consulted a research librarian at the University of Washington. To identify additional original studies, we reviewed the reference lists of the retrieved articles and any identified review articles. Studies presented at recent scientific meetings in the area of infection control were also identified by reviewing meeting programs and published meeting proceedings and by attending medical meetings on related topics. We contacted the manufacturer of chlorhexidine gluconate solution, the corresponding authors of relevant studies, and experts in the field to inquire about possible additional studies. To be included in the meta-analysis, a study needed 1) to be a randomized trial comparing any type of chlorhexidine gluconate solution with a povidone-iodine solution for vascular catheter-site care and 2) to report the incidence of catheter colonization or catheter-related bloodstream infection with sufficient data to calculate the risk ratio. Outcome Measures The primary outcome was catheter-related bloodstream infection, which we defined as isolation of the same organism (that is, identical species with the same antibiograms) from a peripheral blood culture and a semiquantitative or quantitative culture of a catheter segment. Our secondary outcome, catheter colonization, was defined as significant growth of microorganisms from a catheter segment, according to quantitative (>1000 colony-forming units [CFUs] per mL) or semiquantitative (>15 CFU) culture techniques (15, 16). Data Extraction Using a standardized data form, two investigators independently abstracted data on the size of the study sample, type of patient population, type of vascular catheter used, type of antiseptic used, anatomic site of insertion, use of catheter exchange with guide wire, concurrent use of other interventions, and incidence of catheter colonization and catheter-related bloodstream infection. We also evaluated the following methodologic components of each study: randomization procedure, extent of blinding, and description of eligible participants. The authors of studies that did not contain sufficient data were contacted for additional information. Statistical Analysis We separately analyzed the incidences of catheter colonization and catheter-related bloodstream infection. The summary risk ratios and 95% CIs were calculated by using the DerSimonian and Laird method under a random-effects model (17). A statistical test of heterogeneity was performed by using the Mantel-Haenszel method (18). To explore potential clinical sources of heterogeneity, we conducted sensitivity analyses according to characteristics of the study, the study participants, the types of catheters used, outcome definitions, and concentrations of antiseptics used. We explored publication bias using the funnel-plot method by graphing the effect size of trials on the horizontal axis and the number of participants in each trial on the vertical axis (19); asymmetry in the funnel plot suggested publication bias. Because some studies allowed patients to receive more than one vascular catheter during the study period, the within-patient correlation could underestimate the standard error of the effect measure. To investigate this effect, we inflated the variance of the risk ratio for each study by multiplying it by the average number of catheters per patient (20). To perform all statistical analyses, we used Stata software, version 6.0 (Stata Corp. College Station, Texas), by employing the command METAN. Results Study Selection We located 302 articles from our manual and computerized searches (Figure 1). Reviews of the titles and abstracts from the computerized search, followed by review of the full manuscripts of potentially relevant articles, identified 6 published studies that met our inclusion criteria. Of the 296 remaining studies, 285 were excluded because chlorhexidine gluconate was not used for catheter-site care (n = 268), use of the disinfectants was not determined by random allocation (n = 13), povidone-iodine was not used as a comparator (n = 2), or colonization or catheter-related bloodstream infection was not recorded (n = 2). The other 11 excluded studies were duplicate studies retrieved from different databases. In addition to the 6 studies identified from searches, 1 published abstract (9) and 1 published study (10) were identified from the reference list of a review article (21). Thus, our meta-analysis comprised 8 total studies. Studies were reviewed by two investigators, and there were no discrepancies in the abstracted data. Figure 1. Trial flow depicting the selection process of studies included in the meta-analysis. Study Characteristics Table 1 shows the characteristics of the eight included studies. These trials used 4143 catheters (1493 central venous, 1361 peripheral venous, 704 peripheral arterial, 395 pulmonary arterial, 75 peripherally inserted central venous, 62 introducer sheaths, and 53 hemodialysis). Five studies included only patients from intensive care units (7, 9, 11, 12, 14); three studies included patients from any unit in the hospital (10, 13; Knasinski V, Maki DG [Presented paper]). One study was a multicenter clinical trial (10). Among the included studies that reported patient age, the average age ranged from 50 to 65 years (7, 10-12, 14). The mean duration of catheterization for the chlorhexidine gluconate and povidone-iodine groups was similar in all studies that provided this information, except one in which the chlorhexidine gluconate group was catheterized longer (9.9 vs. 5.9 days) (14). There was no significant difference in the anatomic sites (such as subclavian or femoral) in which catheters were inserted between the chlorhexidine gluconate and povidone-iodine groups. One study allowed catheter exchange via a guide wire (7). Only one study noted adverse effects from the use of either antiseptic solution: Maki and colleagues (7) found erythema at the insertion site in 28.3% of catheters in the povidone-iodine group and in 45.3% of catheters in the chlorhexidine gluconate group (P < 0.001). However, there was no statistically significant difference in erythema among these two groups and patients whose sites were disinfected with alcohol (7). Table 1. Characteristics of Studies Comparing Chlorhexidine Gluconate Solutions with Povidone-Iodine Solutions for Vascular Catheter-Site Care The included studies used several formulations of chlorhexidine gluconate. Five studies (10, 13, 14; Knasinski V, Maki DG [Presented paper]) used an alcoholic solution, and three studies (7, 9, 11) used an aqueous solution. All studies used 10% povidone-iodine solution for the control group. However, only one study specified the sequence of applications of 70% alcohol and 10% povidone-iodine (13). Five studies clearly described their procedures for care of the catheter site (7, 10-12, 14); in these studies, the dressing was changed and the insertion site was typically cleansed every 48 to 72 hours (7). Sterile gau

The burden of diabetic foot ulcers

Lower extremity ulcers represent a major concern for patients with diabetes and for those who treat them, from both a quality of life and an economic standpoint. Studies to evaluate quality of life have shown that patients with foot ulcers have decreased physical, emotional, and social function. Analyses of economic impact have shown (1) the majority of costs occur in the inpatient setting, (2) a lack of financial benefit when comparing primary amputation with an aggressive approach to limb salvaging including vascular reconstruction, and (3) private insurance provides greater reimbursement for inpatient care than does Medicare. Results of etiologic studies suggest that hyperglycemia induces diabetes-related complications through sorbitol accumulation and protein glycation, and the resultant nerve damage manifests as peripheral neuropathy, which predisposes to ulcer development. Patients with diabetes also have an increased incidence of peripheral vascular disease, impaired wound healing, and decreased ability to fight infection. In light of these factors, it is sometimes difficult to determine the optimal course for patient management. This review is aimed at helping healthcare providers make better decisions about treatment, resource use, and strategies for future foot ulcer prevention.

Fluoroquinolone Toxicity Profiles: A Review Focusing on Newer Agents

For 2 decades fluoroquinolones have been found to be generally well-tolerated and safe. Adverse events may be inherent to the class or influenced by structural modifications. The commonest adverse events are gastrointestinal tract (GI) and central nervous system (CNS) reactions; nephrotoxicity and tendinitis are infrequent, but agents differ greatly in phototoxic potential. Fluoroquinolones are safe in elderly, human immunodeficiency virus-infected, and neutropenic patients, but because of possible effects on articular cartilage, they are not currently recommended for children or pregnant women. Four new agents have recently been licensed. Levofloxacin causes few GI or CNS adverse events and is minimally phototoxic. Sparfloxacin infrequently causes GI or CNS effects but is associated with relatively high rates of phototoxicity and prolongation of the electrocardiographic QTc interval (Q-T interval, corrected for heart rate). Grepafloxacin causes relatively high rates of GI effects, taste perversion, and QTc interval prolongation, but it is minimally phototoxic. Trovafloxacin is associated with a moderate rate of GI effects and a relatively high incidence of dizziness but has low phototoxic potential.

Osteomyelitis of the Foot in Diabetic Patients

Osteomyelitis of the foot, a common and serious problem in diabetic patients, results from diabetes complications, especially peripheral neuropathy. Infection generally develops by spread of contiguous soft-tissue infection to underlying bone. The major diagnostic difficulty in diabetic patients is distinguishing bone infection from noninfectious neuropathic bony lesions. Certain clinical signs suggest osteomyelitis, but imaging tests are usually needed. The 111In-labeled leukocyte scan and magnetic resonance imaging are the most diagnostically useful. Staphylococcus aureus is the most common etiologic agent, followed by other aerobic gram-positive cocci. Aerobic gram-negative bacilli and anaerobes are occasionally isolated, often in mixed infections. Antimicrobial therapy is best directed by cultures of the infected bone, obtained percutaneously or at surgery. Antibiotic therapy should usually be given parenterally, at least initially, and continued for at least 6 weeks. Surgical debridement or resection of the infected bone, when feasible, improves the outcome. With appropriate therapy most cases of osteomyelitis can be successfully managed.

Coryneform bacteria in infectious diseases: clinical and laboratory aspects.

Coryneform isolates from clinical specimens frequently cannot be identified by either reference laboratories or research laboratories. Many of these organisms are skin flora that belong to a large number of taxonomic groups, only 40% of which are in the genus Corynebacterium. This review provides an update on clinical presentations, microbiological features, and pathogenic mechanisms of infections with nondiphtheria Corynebacterium species and other pleomorphic gram-positive rods. The early literature is also reviewed for a few coryneforms, especially those whose roles as pathogens are controversial. Recognition of newly emerging opportunistic coryneforms is dependent on sound identification schemes which cannot be developed until cell wall analyses and nucleic acid studies have defined the taxonomic groups and all of the reference strains within each taxon have been shown by molecular methods to be authentic members. Only then can reliable batteries of biochemical tests be selected for distinguishing each taxon.

Urinary Tract Infections in Men: Epidemiology, Pathophysiology, Diagnosis, and Treatment

PURPOSE To review the epidemiology, pathophysiology, diagnosis, and treatment of urinary tract infections in men, especially insofar as they differ from those in women. DATA IDENTIFICATION Studies published between 1954 and 1988 were identified using MEDLINE (1981-1988) and Index Medicus (1981-1988), and through extensive manual searching of textbooks, symposia, monographs, and bibliographies of identified articles. STUDY SELECTION More than 200 studies were reviewed; those studies most pertinent to the topics reviewed were cited. Unpublished data from the authors studies were also cited. DATA EXTRACTION Study quality and descriptive information about prevalence, evaluations, interventions, and outcomes were assessed. Quantitative synthesis was not done. RESULTS OF DATA ANALYSIS Most men with urinary tract infection have a functional or anatomic abnormality of the genitourinary tract. Prostatic hypertrophy and genitourinary instrumentation are the major predispositions to infection in men. Signs and symptoms of bacteriuria in men are similar to those in women. Diagnosis rests on a properly collected specimen yielding 10(3) or more colony-forming units/mL of a single or predominant species. Eschericia coli is the most frequent uropathogen, but other gram-negative and gram-positive species cause up to one half of cases. Treatment of men with single-dose therapy is inadequate; men with recurrent infections require at least 6 weeks of appropriate treatment. Asymptomatic bacteriuria is common in elderly men, but does not usually necessitate treatment. Although genitourinary abnormalities are frequent in bacteriuric male patients, a diagnostic evaluation is probably indicated only in young boys and in men with recurrent or complicated infections. CONCLUSIONS Several important aspects of the epidemiology, pathophysiology, diagnosis, and treatment of urinary tract infections differ in male populations from those in the much better studied female populations. Knowledge of recently available data will help clinicians develop a rational approach to caring for bacteriuric men.

Bacteriology of Moderate-to-Severe Diabetic Foot Infections and In Vitro Activity of Antimicrobial Agents

ABSTRACT As part of a United States-based multicenter clinical trial, conducted from 2001 to 2004, that compared ertapenem to piperacillin-tazobactam for the treatment of moderate-to-severe diabetic foot infections (DFIs), we obtained 454 pretreatment specimens from 433 patients. After debridement, the investigators collected wound specimens, mostly by curettage or biopsy, and sent them to the R. M. Alden Research Laboratory for aerobic and anaerobic culture. Among the 427 positive cultures, 83.8% were polymicrobial, 48% grew only aerobes, 43.7% had both aerobes and anaerobes, and 1.3% had only anaerobes. Cultures yielded a total of 1,145 aerobic strains and 462 anaerobic strains, with an average of 2.7 organisms per culture (range, 1 to 8) for aerobes and 2.3 organisms per culture (range, 1 to 9) for anaerobes. The predominant aerobic organisms were oxacillin-susceptible Staphylococcus aureus (14.3%), oxacillin-resistant Staphylococcus aureus (4.4%), coagulase-negative Staphylococcus species (15.3%), Streptococcus species (15.5%), Enterococcus species (13.5%), Corynebacterium species (10.1%), members of the family Enterobacteriaceae (12.8%), and Pseudomonas aeruginosa (3.5%). The predominant anaerobes were gram-positive cocci (45.2%), Prevotella species (13.6%), Porphyromonas species (11.3%), and the Bacteroides fragilis group (10.2%). Pure cultures were noted for 20% of oxacillin-resistant Staphylococcus aureus cultures, 9.2% of Staphylococcus epidermidis cultures, and 2.5% of P. aeruginosa cultures. Two or more species of Staphylococcus were present in 13.1% of the patients. Ertapenem and piperacillin-tazobactam were each active against >98% of the enteric gram-negative rods, methicillin-sensitive S. aureus, and anaerobes. Among the fluoroquinolones, 24% of anaerobes, especially the gram-positive cocci, were resistant to moxifloxacin; 27% of the gram-positive aerobes but only 6% of the members of the family Enterobacteriaceae were resistant to levofloxacin. Moderate-to-severe DFIs are typically polymicrobial, and almost half include anaerobes. Our antibiotic susceptibility results can help to inform therapeutic choices.

Treating Foot Infections in Diabetic Patients: A Randomized, Multicenter, Open-Label Trial of Linezolid versus Ampicillin-Sulbactam/Amoxicillin-Clavulanate

Foot infections in diabetic patients are predominantly caused by gram-positive cocci, many of which are now antibiotic resistant. Because linezolid is active against these pathogens, we compared the efficacy and safety of intravenous and oral formulations with that of intravenous ampicillin-sulbactam and intravenous and oral amoxicillin-clavulanate given for 7-28 days in a randomized, open-label, multicenter study of all types of foot infection in diabetic patients (ratio of linezolid to comparator drug recipients, 2:1). Among 371 patients, the clinical cure rates associated with linezolid and the comparators were statistically equivalent overall (81% vs. 71%, respectively) but were significantly higher for linezolid-treated patients with infected foot ulcers (81% vs. 68%; P=.018) and for patients without osteomyelitis (87% vs. 72%; P=.003). Cure rates were comparable for inpatients and outpatients and for both oral and intravenous formulations. Drug-related adverse events were significantly more common in the linezolid group, but they were generally mild and reversible. Linezolid was at least as effective as aminopenicillin/beta-lactamase inhibitors for treating foot infections in diabetic patients.