Drug Criteria & Outcomes

Nasal mupirocin to prevent S. aureus infections

By Stacey Breeding, PharmD Candidate McWhorter School of Pharmacy Samford University, Birmingham, AL

Staphylococcus aureus causes 25% of nosocomial infections and is the most frequent cause of surgical site infections. The organism can be found colonized on the skin and nasopharynx and is transmitted via person-to-person contact or through inhalation of the organism. Approximately 30% of the population at one time is colonized with S. aureus in the anterior nares.1 Colonization is an important risk factor for developing staphylococcal infections. Multiple studies have shown eradication of nasal S. aureus colonization resulted in decreased rates of S. aureus infections. In various patient populations, intranasal mupirocin has been administered to eliminate nasal carriage of S. aureus.

Mupirocin calcium (Bactroban) is a naturally occurring antibiotic produced by fermentation of Pseudomonas fluorescens. It binds to bacterial isoleucyl transfer-RNA synthetase, resulting in the inhibition of protein and RNA synthesis. In vitro studies show it to be highly active against S. aureus and various other staphylococci and streptococci. The intranasal ointment is U.S. Food and Drug Administration (FDA)-approved for eradication of nasal colonization with methicillin-resistant S. aureus (MRSA) in adult patients and health care workers during institutional outbreaks. The recommended dosage is 0.5 g inserted into each nostril twice daily for five days.2

Mupirocin is most often administered during MRSA outbreaks in combination with infection control measures. Some of these measures include enforcing hand washing, wearing gloves while caring for MRSA-infected or -colonized patients, isolating infected and colonized patients, performing laboratory-based surveillance, and maintaining barrier precautions. In observational studies, mupirocin has eliminated nasal colonization and controlled MRSA outbreaks. Results from these studies indicate negative MRSA cultures at the end of therapy in at least 90% of patients and health care workers. Similar results are shown in placebo-controlled studies of health care workers with nasal carriage of S. aureus. In these studies, long-term follow-up confirmed that eradication persisted for months (> 50% at three months) after a five-day course of therapy.2 Because decolonization has been used in combination with other infection control measures, it is hard to determine the precise efficacy of mupirocin.

Prophylactic mupirocin has been studied most extensively in postoperative, peritoneal dialysis, and hemodialysis patients. The results from these studies have been variable. Two studies that involved prophylactic use of mupirocin in cardiac surgery reported a 60% reduction in surgical site infections.3 In both studies, a historical control group was used, which may lead to false conclusions.

Multiple studies have established mupirocin as the agent of choice for eradication of nasal and pericatheter colonization by S. aureus in hemodialysis and peritoneal dialysis patients. A placebo-controlled study with preoperative use of mupirocin in orthopedic surgery showed an eradication rate of 80% with S. aureus colonization in the anterior nares.4 However, this did not significantly reduce the surgical site infection rate in this patient population. Another placebo-controlled trial involving 3,864 preoperative patients receiving prophylactic treatment of mupirocin also failed to significantly reduce the overall rate of surgical site infections. This study did significantly reduce the rate of all nosocomial S. aureus infections in carriers (high-risk group) compared to placebo (7.9% vs. 4.0%).1

A major concern is that prophylactic use of mupirocin can lead to resistance. Studies show resistance rates increase with prolonged or wide-spread use of the antibiotic within an institution. Also, resistance has been seen in patients who have not been treated with mupirocin suggesting cross-transmission from person to person. In one hospital administering prophylactic mupirocin to all patients to decrease rising MRSA infections, the institution reported 60% mupirocin resistance during the first year of practice. Seventy-three percent of those resistant strains were highly resistant, rendering the antibiotic ineffective.5 Smaller short-term studies involving prophylactic mupirocin report minimal resistance.

Nasal carriage of S. aureus is a risk factor for developing this infection. Mupirocin has demonstrated efficacy in decolonization, but results vary among studies regarding decreased rates of infection. Studies report that long-term and wide-spread use within a facility can lead to resistance. Therefore, conservative use of mupirocin should be employed. Mupirocin has shown the most benefit in reducing infections in patients with confirmed nasal colonization of S. aureus, including MRSA. Experts suggest prophylaxis be administered only to patients with culture proven colonization of S. aureus or MRSA using a short-course regimen (twice a day for five to seven days).

References

1. Perl TM, Cullen JJ, Wenzel RP, et al. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N Engl J Med 2002;346:1871-1877.

2. Bertino, JS. Intranasal mupirocin for outbreaks of methicillin-resistant Staphylococcus aureus. Am J Health Syst Pharm 1997;54:2185-2191.

3. Cimochowski GE, Harostock MD, Brown R, et al. Intranasal mupirocin reduces sternal wound infection after open-heart surgery in diabetics and nondiabetics. Ann Thorac Surg 2001;71:1572-1579.

4. Kulmeijer MD, Coertjens H, Nieuwland-Bollen PM, et al. Surgical site infections in orthopedic surgery: The effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study. CID 2002;35:353-358.

5. Farr BM. Mupirocin to prevent S. aureus infections. N Engl J Med 2002;346:1905-1906.