Foot infections are a serious complication of diabetes associated with substantial morbidity and occasional mortality. Antibiotic therapy for mild infections in patients who have not recently received antibiotic therapy can often be directed at just staphylococci and streptococci. Empiric therapy for infections that are chronic, moderate or severe, or that occur in patients who have failed previous antibiotic treatment, should usually be more broad spectrum. Bone infection also complicates a substantial percentage of diabetic foot wounds and increases the likelihood of treatment failure, requiring lower extremity amputation. An increasing body of evidence supports the effectiveness of nonsurgical treatment of diabetic foot osteomyelitis in selected patients, although the optimal choice of agent, route of administration and duration of therapy have yet to be defined. This article examines the potential role of standard and newer antibiotics that may be appropriate for treating diabetic foot infections, including ertapenem, vancomycin, moxifloxacin, daptomycin, telavancin and tigecycline, as well as several investigational agents, such as dalbavancin, ceftobiprole and nemonoxacin.
Introduction

People with diabetes are at high risk for developing infections of the foot. It is estimated that in the USA, 15% of diabetic patients will develop a foot ulcer in their lifetime[1] and diabetics have at least a tenfold greater risk of hospitalization for foot infections compared with individuals without diabetes.[2] More than 60% of non-traumatic lower-limb amputations occur in people with diabetes, the majority of which are preceded by an infected foot wound.[3–5] The likelihood of adverse outcomes is even higher in developing countries where access to medical care, especially advanced treatment modalities, is often limited. Morbidity and mortality associated with diabetic foot infections (DFIs) can be expected to increase in light of the fact that the number of people with diabetes worldwide is projected to double, reaching approximately 366 million by 2030.[6]

Diabetic foot infections result from a complex interplay among three main complications of long-term diabetes: immunopathy, neuropathy and arterial disease. In vitro evidence suggests that in the diabetic patient neutrophil function is compromised, with impaired chemotaxis and phagocytosis.[7–9] Diabetic neuropathy leads to foot deformity, which results in high pressure areas, leading to calluses and eventually breaks in the protective skin envelope. Sensory neuropathy leads to a decreased awareness on the part of the patient of potential risks to the foot, or failure to recognize that a foot wound, especially if infected, requires urgent treatment. Peripheral arterial disease jeopardizes the viability of soft tissue and bone, and facilitates the spread of infection by compromising the penetration of leukocytes and antibiotics to the infected site.

Bacteria most commonly gain entry to subcutaneous tissues by a disruption of the normal cutaneous barrier. This may occur through small fissures between the toes, acute traumatic wounds, burns or chronic pressure-related ulcers. Infection may remain mild and localized, or spread rapidly along tendon sheaths and fascial planes. An infection that begins under a metatarsal head, for example, may quickly progress to an abscess in the plantar space, which requires urgent surgical intervention.

Properly treating DFIs requires knowledge in several fields and often special surgical skills. Thus, a multidisciplinary approach, including specialists in infectious diseases, foot surgeons (orthopedic or podiatric), endocrinologists, vascular surgeons and wound care experts, can optimize treatment outcomes. Assembling such a team, ensuring that it follows evidence-based guidelines and regularly audits its results are processes that are likely to provide the best outcomes for patients with DFI.

Specific Antibiotic Agents:

Ertapenem
Vancomycin
Linezolid
Daptomycin
Tigecycline
Moxifloxacin
Telavancin

Anti-infective Therapy:

Empiric therapy of DFIs should ideally be guided by the severity of the infection and the likely microbiology of the wound. Acute, relatively mild infections in patients who have not recently received antibiotic therapy can often be solely directed at aerobic Gram-positive cocci. Infections that are chronic, moderate or severe, or that occur in patients who have failed previous antibiotic treatment should usually be more broad spectrum. The need to cover MRSA (or ESBL) isolates depends on the likelihood of these pathogens in any given patient. Definitive therapy, to complete the appropriate course, should be based on both the clinical response to empiric therapy and the results of the culture and sensitivity report. In polymicrobial infections, some organisms may represent contaminants or colonizers, and may therefore not need to be specifically covered by the antibiotic regimen.