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

Abstract

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.

Diagnosis and Treatment of Diabetic Foot Infections

“…Overall, expect a good clinical response (i.e., resolution of clinical evidence of infection) to appropriate therapy in 80%-90% of mild-to-moderate infections [84,121,130,263] and in 60%-80% of severe infections or cases of osteomyelitis [130,145,147,237,283]. Factors associated with a poor outcome include signs of systemic infection [237], inadequate limb perfusion, osteomyelitis [273,[283][284][285], the presence of necrosis or gangrene [276], an inexperienced surgeon [286], and proximal location of the infection [287].…”

“…Some patients with apparently mild infections and more patients with moderate infections may also need hospitalization; this may be for observation, urgent diagnostic testing, or because complicating factors are likely to affect their wound care or adherence to antibiotic treatment. In the absence of these complicating features, most patients with mild or moderate infections can be treated as outpatients (A-II) [84,121].…”

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

“…Most guidelines recommend vancomycin for MRSA infections and antistaphylococcal penicillins for MSSA, with or without adjunctive rifampin (543). Because vancomycin has poor bone penetration and low clinical cure rates, there is increasing interest in the use of alternative agents for MRSA osteoarticular infections, including linezolid (560,561), daptomycin (562), and rifampin in combination with either quinolones or fusidic acid (549,563). The only reported RCT addressing antibiotic choice for staphylococcal PJI in patients undergoing 2-stage replacement compared daptomycin with the "standard of care" (vancomycin, teicoplanin, or nafcillin) for 6 weeks in between the 2 stages in 75 adults with staphylococcal PJI (562).…”

Diabetic foot osteomyelitis: a progress report on diagnosis and a systematic review of treatment

“…Antibiotics with activity predominantly against Gram positive organisms (staphylococci and streptococci) [52] and broad-spectrum antibiotics with increased activity against Gram negative organisms and obligate anaerobes [53] appear equally effective. These findings confirm the results of a recent review of the antibiotic management of all types of osteomyelitis [54].…”

“…A single randomized study compared results with oral and intravenous antibiotics [52]. No studies in DFO have compared the outcome of administering the same agents by different routes, or have assessed the efficacy of locally administered antibiotics, such as antibiotic-impregnated polymethylmethacrylate or calcium sulfate beads.…”