Keys To Addressing MRSA In The Diabetic Foot
A Closer Look At Oral Antibiotics For MRSA
Trimethoprim/sulfamethoxazole (Bactrim, Roche). This is a dihydrofolate reductase inhibitor with a bactericidal, synergistic effect. It is contraindicated in patients with hepatic impairment and requires adjustment for renal dosing with CrCl of 15 to 30 mL/min. Indicated for CA-MRSA, trimethoprim/sulfamethoxazole is effective in deep infections and soft tissue infections with noted purulence. There is a concern for increasing resistance to trimethoprim/sulfamethoxazole. Therefore, cautious use and prescribing of the antibiotic is recommended. It is contraindicated in patients with folate deficiency, glucose-6-phosphate dehydrogenase deficiency, a history of anemia or thrombocytopenia. Exercise caution and make appropriate dosing adjustments when using this in elderly patients with renal insufficiency.
Doxycycline (Vibramycin, Pfizer). There has been growing use of doxycycline for CA-MRSA and it offers convenient twice per day dosing at 100 mg. There is no required renal adjustment to dosing but one must use caution with the drug and ensure monitoring in patients with hepatic impairment. Multiple reports have demonstrated successful outcomes with the use of doxycycline in SSTI.5 To date, research has shown doxycycline to be an effective monotherapy option in MRSA-associated SSTI.
Clindamycin (Cleocin, Pfizer). While clindamycin is effective in some MRSA infections, there has been increasing resistance in both the outpatient and hospital settings. It is critical to note that resistance to clindamycin is inducible but inked to macrolide resistance. Therefore, one should avoid clindamycin in patients with erythromycin isolates despite clindamycin sensitivity.
Clindamycin has bacteriostatic properties and does not require renal or hepatic adjustment in dosing. The manufacturer notes that possible side effects include diarrhea (noted in up to 20 percent of those taking the medication) and a risk of C. difficile. Clindamycin has excellent tissue, bone and abscess penetration. Further testing with the D-zone test is recommended for the detection of resistance although this would result in a one- to two-day delay in final confirmation.
Linezolid (Zyvox, Pfizer). Linezolid is an oxazolidinone drug that also inhibits the initiation of protein synthesis at the 50S ribosome. It has a specific indication for diabetic foot infections (skin and soft tissue infections) and is effective in targeting both MRSA and vancomycin resistant Enterococcus (VRE). It does not require renal adjustment with dosing and the dosage is 600 mg q12h. It is available as both an oral and parenteral agent with equal bioavailability. Accordingly, oral dosing is more desirable.
Use caution in all patients as there are associated risks of hematologic toxicity, thrombocytopenia and anemia. Therefore, monitoring of the complete blood cell count is required in patients on prolonged therapy.
Current Insights On Treating MRSA With IV Antibiotics
Vancomycin. While vancomycin is commonly perceived as the “gold standard” antibiotic and is often a first-line therapy for at-risk patients with MRSA, there have been reports of increased resistance or decreased efficacy.6 This resistance is often described as a “creeping resistance” given that isolates are still susceptible but require higher concentrations of vancomycin (therefore demonstrating higher minimum inhibitory concentrations). Vancomycin is a glycopeptide, bactericidal antibiotic and requires slow infusion over two hours. One must monitor peaks and troughs, and dose accordingly. Renal function is a concern and clinicians must carefully assess this when considering vancomycin. Tissue penetration is variable depending upon the extent of the inflammatory process present and the presence/absence of bone involvement.