Use of Mupirocin in Controlling Methicillin-Resistant Staphylococcus Aureus Outbreaks in Long-Term Care Facilities

Mark Eggleston

Data Sources: Medical literature over the past 20 years on MRSA pertinent to LTC facilities.

Study Selection: Literature reviewed included case studies, prospective studies, and double-blind, randomized, placebo-controlled studies.

Data extraction: Predetermined criteria were established to obtain the data for study evaluation.

Data synthesis: MRSA is associated with inappropriate physician prescribing practices, an increasingly mobile patient population, and crowded institutional settings. MRSA, which is also resistant to all beta-lactam antibiotics, results from either bacterial production of beta-lactamase or low affinity of penicillin-binding protein. MRSA colonization of the nares is common, and nasal carriage is a serious health concern in patients at high risk of acquiring MRSA. Nasal eradication of MRSA using mupirocin is an effective means of controlling spread of MRSA in institutional populations. Consultant pharmacists should monitor proper use of this and all other antibiotics in long-term care facilities.

Conclusions: The outlook for MRSA control in the LTC setting rests primarily on future studies and somewhat unpredictable antimicrobial resistance development. Prudent use of mupirocin in this setting can aid in the prevention and control of MRSA outbreaks.

Key Words: Mupirocin, Methicillin-resistant Staphylococcus aureus, Antibiotic resistance, Long-term care facilities.

Abbreviations used: MRSA = Methicillin-resistant Staphylococcus aureus; LTC = Long-term care; MSSA = Methicillin-sensitive Staphylococcus aureus; HCW = Health care workers; MIC = Minimum inhibitory concentration.

Consult Pharm 1997; 12: 550-57.

MRSA is no more virulent than methicillin-susceptible S. aureus (MSSA), but it presents greater risk to infection control because of its invulnerability to most antibiotics. MRSA is one of the growing number of multiresistant organisms in the 1990s that represent threats to the continued effectiveness of antibiotic therapy.⁵ As pharmaceutical companies develop fewer new classes of antibiotics with tolerable safety profiles,⁶ currently available antibiotics become more of a precious resource for infection control. With infectious diseases now the third greatest underlying cause of death in the United States, ranking behind cardiovascular disease and malignancies,⁷ the possibility of super-resistant organisms becomes a greater threat.

In this paper, I review the use of mupirocin for nasal MRSA eradication during outbreaks in the long-term care setting and other potential actions to avoid MRSA antibiotic resistance.

MRSA in the Long-Term Care Setting

As with all community and hospital-acquired antimicrobial resistance, MRSA is associated with inappropriate physician prescribing practices, an increasingly mobile patient population, and crowded institutional settings that foster person-to-person and common-source transmission.⁸ Not surprisingly, LTC facilities provide such an environment for development of such resistance.⁹ LTC facilities (especially Veterans Affairs facilities) treat a highly transient patient population;¹⁰ in addition, LTC facilities focus on communal interaction as part of the rehabilitative process, with very few single-bed rooms.¹¹ Other factors associated with LTC facilities make them particularly prone to MRSA colonization and outbreaks (Table 1).^10,12-15

Table 1. Factors in Long-Term Care (LTC) Facilities That Contribute to MRSA Colonization

• A high-risk patient population
  Rates of infection with resistant organisms correlate with patients who are the most ill and require the most skilled care;¹⁰ this describes the majority of the LTC facility population. Other factors associated with MRSA and other nosocomial infections include: age-related immune system weakening;¹² causes of dementia; organic heart disease; malignancy; peripheral vascular disease; diabetes mellitus; chronic obstructive pulmonary disease; and frequent use of sedatives and hypnotics.¹³ MRSA rates specifically correlate with the presence of indwelling urinary catheters and decubitus ulcers,¹⁰ which are common in the LTC facility.

• Risk of urine contamination
  The prevalence of urinary incontinence in LTC facilities translates to a great environmental threat to LTC facility patients because urine is a typical MRSA reservoir.¹⁴ Misguided efforts to control incontinence with in-dwelling urinary catheters can exacerbate the problem because MRSA bacteriuria strongly correlates with the use of urinary catheters,¹⁴ which LTC facility personnel tend to overuse.¹⁵

• Poor health care worker compliance with infection-control procedures
  Full compliance with preventive measures among all HCWs, including physicians and nurses, is a persistent problem in health care and one that is particularly troublesome. Many LTC facility personnel are nonprofessional staff who may not fully understand the importance of infection control; in addition, high staff turnover rates create a need for continuous infection-control training.

  MRSA = methicillin-resistant Staphylococcus aureus

Mechanisms of MRSA Antibiotic Resistance

MRSA is somewhat deceptive in name because its spectrum of resistance reaches beyond methicillin to encompass all beta-lactam antibiotics and penicillinase-resistant penicillins, including methicillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin.¹⁶ MRSA antibiotic resistance follows either of two mechanisms: beta-lactamase resistance or "intrinsic" resistance.¹⁷ Beta-lactamases are microbial enzymes, often coded for by extrachromosomal plasmids, that destroy antimicrobial agents with beta-lactam rings. Intrinsic resistance occurs when MRSA develops a penicillin-binding protein with an abnormally low drug affinity (penicillin-binding protein-2a), thus reducing the penicillin's ability to reach its active site.¹⁸ Of the two resistance mechanisms, intrinsic resistance is the mechanism responsible for most resistance to antistaphylococcal penicillins.¹⁷

Although several antibiotics show bacteriostatic and bactericidal activity against MRSA, vancomycin is the only consistently effective MRSA bactericidal antibiotic available. However, vancomycin treatment is far from ideal for many reasons. First, many experts believe that the emergence of vancomycin-resistant enterococci means that some MRSA strains will inevitably develop resistance to vancomycin, leaving patients defenseless against serious infections caused by MRSA. Second, the expense of both the antibiotic itself and subsequent serum monitoring makes vancomycin administration a cost-prohibitive treatment in many circumstances. Third, vancomycin is considerably toxic and commonly produces "red man" syndrome, generating erythema of the head and upper torso, pruritus, urticaria, and hypotension. Because this reaction is histamine-mediated, toxicity increases with added use of common perioperative treatments (e.g., opioids) and anesthetic agents that may release histamine.¹⁹

MRSA Control and Nasal Carriage Eradication

MRSA colonization in the nares is common, 20%-40% of the general population are intermittent or chronic MRSA nasal carriers. The colonization typically presents no threat to a healthy person. In a patient at high risk for nosocomial infection, though, nasal carriage of MRSA becomes a serious health concern. The nares are the body's primary MRSA reservoir, and nares colonization is largely responsible for colonization at other body sites. Subsequently, nasal carriage is strongly associated with eventual infection.

Results from one study of 140 patients beginning continuous ambulatory peritoneal dialysis showed that nasal S. aureus carriers were four times more likely to develop exit site wounds than noncarriers.²⁰ Primarily because of autoinfection, those with persistent nasal carriage are at a greater risk for recurrent furunculosis, exudative skin lesions, and surgical wound infections.²¹ MRSA nasal carriage has a high correlation with several other risk factors: intravenous drug use, chronic renal failure, diabetes mellitus, respiratory infection, and prolonged exposure to the hospital environment.²¹

Numerous studies support nasal eradication as a critical component to successful MRSA outbreak control.^22-28 This holds true not only in patients but also in health care workers (HCWs) who can transfer the bacteria by hand from their own colonized nares to patients,²⁹ representing another common method of MRSA transmission. For this reason, several studies show that nasal carriage elimination in HCWs may be required to remove a major potential reservoir of nosocomial infection.^25,30-32 Intranasal treatment also reduces MRSA hand carriage after treatment for two to three days, with lasting decreases compared with placebo for up to six months.²⁴

Nasal Carriage Eradication with Mupirocin

One of the first documented successes of nasal eradication of MRSA occurred during a hospital outbreak in London,³³ where infection-control practitioners applied mupirocin (Bactroban, SmithKline Beecham Pharmaceuticals)³⁴ intranasally to the colonized nares of patients and HCWs. Since its debut as an effective intranasal agent, mupirocin has been shown to eliminate nasal carriage during hospital MRSA outbreaks,^26,35,36 and its use for this purpose is well established in the United Kingdom.^23,26,36,37 Mupirocin was first formulated as a free acid in a polyethylene-glycol base and was approved by the U.S. Food and Drug Administration for the treatment of impetigo. Because of some reports of nasal mucosal irritation,³⁸ mupirocin was reformulated into mupirocin calcium (Bactroban Nasal³⁴ in a paraffin base for better toleration.²⁴ The most common adverse effects (reported by less than 2% of subjects) of mupirocin calcium include nasal irritation, sneezing, runny nose, or nasal congestion; abnormal taste; throat sensation or soreness; local pruritus; or local burning or stinging.³⁵

Application of mupirocin to the anterior nares with a cotton swab twice daily for five days has resulted in nasal-carriage clearance in as soon as four to five hours of initial application and clearance among nearly all subjects within two days.^36,38 Overall, efficacy rates in initial elimination are high, and the nares typically remain free of MRSA in follow-up studies.^17,37,38 When and if recolonization occurs following MRSA nasal eradication with mupirocin, it occurs regardless of the MRSA strain's resistance pattern.^35,36 Phage types from recolonized strains often differ from the original colonizing strain type, suggesting that recolonization is not related to mupirocin resistance.³⁸ Oftentimes, nasal-clearance failure relates to MRSA colonization or infection at other body sites.³⁷ Compared with other topical treatments for MRSA, including hexachlorophene, chlorhexidine, bacitracin, bacitracin and polymixin B, bacitracin with oral rifampin, iodophors, triclosan, neomycin, and gentamicin, mupirocin has shown to be the most effective.³⁶ Results from studies of rifampicin, cotrimoxazole with rifampin or with ciprofloxacin, chlorhexidine with or without neomycin, and topical vancomycin show that none was as reliable or as effective at initial eradication and preventing recolonization as mupirocin.³⁶

Mupirocin is an ideal agent for topical use in eradicating MRSA. It is unsuitable as a systemic antibiotic because it is susceptible to gastric acidity,³⁶ is metabolized by the body into inactive monoic acid,³⁵ and has a plasma half-life of less than 30 minutes.³⁹ However, topical antibiotics are preferred over systemic ones for nasal eradication for several reasons. No systemic antibiotic has the same sustained efficacy demonstrated by topical agents for eradication of MRSA, plus systemic agents would cause more toxicity and adverse effects. More importantly, minimal topical use of systemic agents helps to preserve their efficacy by decreasing the opportunity for developing resistance^36,38 and cross-resistance, as has been seen with ciprofloxacin and rifampin.³⁸

Basis of Mupirocin Activity

Mupirocin is a 9-hydroxy-nonanionic acid produced by natural Pseudomonas fluorescens fermentation. It maintains its high level of in vitro activity, regardless of methicillin susceptibility of an MRSA strain, by reversibly inhibiting isoleucyl-tRNA synthases.⁴⁰ Mupirocin has a unique chemical structure among antibiotics,⁴¹ which places it into its own antibiotic class and eliminates cross-resistance with other antibiotics, including chloramphenicol, erythromycin, fusidic acid, gentamicin, lincomycin, methicillin, neomycin, novobiocin, penicillin, streptomycin, and tetracycline⁴² (Figure 1).³⁴

Mupirocin is bacteriostatic at concentrations near its minimum inhibitory concentration (MIC) of 0.12 to 1.0 mg/mL but becomes bactericidal at higher concentrations.⁴³ Mupirocin's scope of in vitro applications includes a broad range of gram-positive staphylococci (including MRSA and lactamase-producing strains of S. aureus, S. epidermidis, and S. saprophyticus), some gram-negative bacteria (such as Neisseria gonorrhoeae and Haemophilus influenzae), and most streptococci (such as Streptococcus pyogenes)^38,44 (Table 2).^44-49

Table 2. Antibacterial Activity of Mupirocin Against Gram-Positive Organisms (adapted, with permission, from Parenti, 1987)^44-49

Organism	Mupirocin MIC (g/mL)a	No. Isolates
Staphylococcus aureus	0.06 - 0.15	40
	0.04 - 0.32	159
	0.06 - 0.125	33
	0.06 - 0.25	310
Methicillin-resistant Staphylococcus aureus	0.04 - 0.96	219
Multiple-resistant Staphylococcus aureus	0.12 - 0.25	N.A.
Beta-hemolytic streptococci	0.05 - 0.5	N.A.
Streptococcus agalactiae	0.5	1
Streptococcus pyogenes	0.03 - 0.12	1
Streptococcus pneumoniae	0.12	1
Streptococcus viridans	0.25 - 2.0	1
Listeria monocytogenes	8	1
Corynebacterium species	>128	1
Micrococcus luteus	>128	1
Clostridium difficile	32	1
Peptococcus prevotii	>128	1
Propionibacterium acnes	>128	1

a Not specified whether or not MIC50 or MIC90 (minimum concentration needed to inhibit 50% to 90% of tested isolates, respectively) was used. In reference 19, a test strain of the organism was used. MIC = minimum inhibitory concentration; NA = not applicable.

Mupirocin-Resistant MRSA

Mupirocin-resistant MRSA strains are uncommon,³⁵ but they have developed both in vivo and in vitro.³⁶ Most resistant strains produce chromosomally encoded, modified isoleucyl-tRNA synthase, which destroys mupirocin activity.⁵⁰ These low-level resistance strains (MIC 8 to 256 mg/L) are usually susceptible to a 2% mupirocin preparation, given its concentration of approximately 20,000 mg/L.³⁵ For this reason, low-level mupirocin resistance may not interfere with nasal clearance.^37,51 Studies of isolates from nasal recolonizations show no evidence of resistance from intranasal mupirocin.

Extended mupirocin use can lead to the genetic selection of MRSA strains carrying a mupirocin-resistant plasmid,^10,36 resulting in high-level mupirocin-resistant strains (MIC 512 mg/L). One study of high-level resistant strains⁵² detected two different isoleucyl-tRNA synthase enzymes; this verifies the viability of plasmid-mediated resistance. Although in vitro resistance emerges in a slow and stepwise fashion,⁵³ in vivo strains of MRSA with high-level resistance may show no stepwise development. Such strains are associated with mupirocin use in dermatology wards or for extended treatment periods,^54-56 making extended topical use an imprudent practice.⁴⁵

Consultant Pharmacists' Role in Mupirocin Therapy

Nasal clearance with mupirocin is one part of a multicomponent plan for managing MRSA in the LTC setting. As effective as mupirocin is for nasal eradication, eradication efforts are pointless without efforts to minimize or eliminate patient-to-patient contact.¹¹ A comprehensive MRSA management plan also requires early identification of carriers, skin and mouth antiseptics, isolation policies,³⁷ and surveillance.⁵⁷ The chief responsibility of the consultant pharmacist in this plan is overseeing appropriate use of all antibiotics. The first step in this process is reviewing antibiotic orders for appropriate indications.

All antibiotic administration merits careful consideration, control, and monitoring and should entail the most narrow-spectrum antibiotics possible,¹⁴ such as first-generation cephalosporins.⁸ Therefore, the consultant pharmacist's first step is to review the appropriateness of all antibiotic prescriptions. Despite the wide availability of antibiotic-prescribing guidelines and hospital policies, many physicians continue to misprescribe and overprescribe antibiotics. To meet the concomitant goals of cost containment and resistance control, some hospital pharmacies have set up systems to identify and flag antibiotic-prescribing trends or programs, authorizing the pharmacist's automatic conversion of certain drug regimens to more economic and logical ones. Of course, the key to such programs is a positive educational relationship between pharmacists and physicians.^58,59

Because of the possibility of resistance to mupirocin, its extensive use without appropriate clinical indication is not recommended.³⁶ For this reason, nasal eradication with mupirocin can be reasonably recommended for eliminating MRSA colonization in patients and HCWs under selective circumstances. The pharmacist can assist with reducing the potential for resistance by monitoring mupirocin use and assuring its administration only for appropriate decolonization purposes.

One appropriate situation for mupirocin use is during an MRSA outbreak.^35,51,60 Another valid use is in high-risk patient populations or in HCWs serving such populations,^10,35 such as those with diabetes mellitus, peripheral vascular disease,¹⁰ in-dwelling tubes, decubitus ulcers, or multiple functional disabilities.⁶¹ Another instance is when MRSA contributes to an appreciable morbidity from nosocomial infections, including bacteremias, pneumonia, or deep-wound infections.⁶²

Although numerous studies demonstrate the benefits of decolonization in controlling infection rates in the acute-care hospital, the few studies that do address efficacy in LTC facilities present mixed results.⁶¹ Further investigation is needed to determine if LTC facilities have unique MRSA transmission patterns and to establish MRSA prevalence and incidence in LTC facilities.⁶¹ For this reason, mupirocin decolonization is not recommended for endemic situations.⁵¹

After confirming the appropriateness of an antibiotic prescription, the pharmacist's next step is to monitor antibiotic administration. LTC staff responsible for drug administration should receive explicit directions for administration of both systemic and topical antibiotics. They should be instructed to avoid unintended, extended treatment periods that could lead to development of resistance to mupirocin. Prolonged exposure, especially on skin surfaces, should be avoided. The consultant pharmacist should maintain open communications with all HCWs.

The LTC facility is not an isolated epidemiologic unit in the context of infection control; thus, patients transferring between facilities increase the risk of nosocomial infection transmission. As a health care professional who often maintains regular contact with several institutions within the same community, a consultant pharmacist is in a unique position to foster a continuum of careful and conservative antibiotic administration. Addressing MRSA as a community issue makes infection control more feasible and can inevitably prolong the efficacy of all antibiotics, thereby improving health care outcomes for the general patient population.

Conclusion

Since research into the use of mupirocin for MRSA control in the LTC setting has produced variable results, its ultimate utility will be determined in future studies. An unknown factor in this situation is the possibility of development of antimicrobial resistance to the drug. Most studies on MRSA control have been conducted in acute-care hospitals. Thus, further studies are needed to identify possible MRSA patterns unique to LTC facilities; MRSA incidence and prevalence in free-standing LTC facilities; and the frequency with which MRSA leads to hospitalization of LTC patients.⁶³ Diligent and universal adherence to strict antibiotic prescribing practices will help to stem the march of antibiotic-resistant pathogens until researchers find new ways to combat infectious diseases.

References

1. Conly JM, Hill S, Ross J et al. Handwashing practices in an intensive care unit: the effects of an educational program and its relationship to infection rates. Am J Infect Control 1989; 17:330-9.

2. Eykyn SJ. Staphylococcal sepsis: the changing pattern of disease and therapy. Lancet 1988; 1:100-4.

3. Horan T, Culver D, Jarvis W et al. Pathogens causing nosocomial infections: preliminary data from the National Nosocomial Infections Surveillance System. Antimicrob Newslett 1988; 5:65-7.

4. Shanson DC, Johnstone D, Midgley J. Control of a hospital outbreak of methicillin-resistant Staphylococcus aureus infections: value of an isolation unit. J Hosp Infect 1985; 6:285-92.

5. Cohen ML. Epidemiology of drug resistance: implications for a post-antimicrobial era. Science 1992; 257:1050-5.

6. Travis J. Reviving the antibiotic miracle? Science 1994; 264:360-2.

7. Pinner RW, Teutsch SM, Simonsen L et al. Trends in infectious diseases mortality in the United States. JAMA 1996; 275:189-93.

8. Goldmann DA, Weinstein RA, Wenzel RP et al. Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals: a challenge to hospital leadership. JAMA 1996; 275:234-40.

9. Jones SR, Parker DF, Liebow ES et al. Appropriateness of antibiotic therapy in long-term care facilities. Am J Med 1987; 83:499-502.

10. Terpenning MS, Bradley SF, Wan JY et al. Colonization and infections with antibiotic-resistant bacteria in a long-term care facility. J Am Geriatr Soc 1994; 42:1062-9.

11. Strausbaugh LJ, Jacobson C, Sewell DL, Potter S et al. Antimicrobial therapy for methicillin-resistant Staphylococcus aureus colonization in residents and staff of a veterans affairs nursing home care unit. Infect Control Hosp Epidemiol 1992; 13:151-9.

12. Kenney RA. Physiology of aging: a synopsis. Chicago: Year Book Medical Publishers, 1989.

13. Satterfield N. Infection control in long-term care facilities: the hospital-based practitioner's role. Infect Control Hosp Epidemiol 1993; 14:40-7.

14. Coll PP, Crabtree BF, O'Connor PJ et al. Clinical risk factors for methicillin-resistant Staphylococcus aureus bacteriuria in a skilled-care nursing home. Arch Fam Med 1994; 3:357-60.

15. Ribeiro BJ, Smith SR. Evaluation of urinary catheterization and urinary incontinence in a general nursing home population. J Am Geriatr Soc 1985; 33:478-82.

16. Wenzel RP, Nettleman MD, Jones RN et al. Methicillin-resistant Staphylococcus aureus: implications for the 1990s and effective control measures. Am J Med 1991; 91(Suppl 3B):221S-227S.

17. Mulligan ME, Murray-Leisure KA, Ribner BS et al. Methicillin-resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management. Am J Med 1993:94:313-328.

18. Malouin F, Bryan LE. Modification of penicillin-binding proteins as mechanisms of -lactam resistance. Antimicrob Agents Chemother 1986; 30:1-5.

19. Flaherty JF. Central nervous system infections. In: Young LY, Koda-Kimble MA, eds. Applied therapeutics: the clinical use of drugs. 6th ed. 1995: Vancouver, WA: Applied Therapeutics, Inc., 56-18.

20. Luzar MA, Coles GA, Faller B et al. Staphylococcus aureus nasal carriage and infection in patients on continuous ambulatory peritoneal dialysis. N Engl J Med 1990; 322:505-9.

21. Waldvogel FA. Staphylococcus aureus (including toxic shock syndrome). In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and practices of infectious diseases. 3rd ed. New York: Churchill Livingstone, 1990:1489-510.

22. Redhead RJ, Lamb YJ, Roswell RB. The efficacy of calcium mupirocin in the eradication of Staphylococcus aureus carriage. Br J Clin Pharmacol 1991; 45:252-4.

23. Hill RLR, Duckworth GJ, Casewell MW. Elimination of nasal carriage of methicillin-resistant Staphylococcus aureus with mupirocin during a hospital outbreak. J Antimicrob Chemother 1988; 22:377-84.

24. Reagan DR, Doebbeling BN, Pfaller MA et al. Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment. Ann Intern Med 1991; 114:101-6.

25. Fernandez C, Gaspar C, Torrellas A et al. A double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of mupirocin calcium ointment for eliminating nasal carriage of Staphylococcus aureus among hospital personnel. J Antimicrob Chemother 1995; 35:399-408.

26. Doebbeling BN, Breneman DL, Neu HC et al. Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. Clin Infect Dis 1993; 17:466-74.

27. Casewell MW, Hill RLR. Elimination of nasal carriage of Staphylococcus aureus with mupirocin ('pseudomonic acid')a controlled trial. J Antimicrob Chemother 1986; 17:365-72.

28. Haddad Q, Sobayo EI, Basit OBA et al. Outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. J Hosp Infect 1993; 23:211-21.

29. Neu HC. The use of mupirocin in controlling methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol 1990; 11:31-2.

30. Boyce JM, Potter-Bynoe G, Opal SM et al. Common source outbreak of methicillin-resistant Staphylococcus aureus associated with respiratory therapy and nursing personnel. Presented at the Second Annual Meeting of the Society for Hospital Epidemiology of America; 1992 Apr 12-14; Baltimore, MD.

31. Klimek JJ, Marsik FJ, Bartlett RC et al. Clinical, epidemiologic and bacteriologic observations of an outbreak of methicillin-resistant Staphylococcus aureus at a large community hospital. Am J Med 1976; 61:340-5.

32. Coovadia YM, Bhana RH, Johnson AP et al. A laboratory-confirmed outbreak of rifampicin-methicillin resistant Staphylococcus aureus (RMRSA) in a newborn nursery. J Hosp Infect 1989; 14:303-12.

33. Dacre JE, Emmerson AM, Jenner EA. Nasal carriage of gentamicin and methicillin-resistant Staphylococcus aureus in a special care baby unit: value of topical mupirocin and traditional methods of infection control. J Hosp Infect 1987; 10:120-8.

34. Bactroban Nasal Prescribing Information. SmithKline Beecham Pharmaceuticals, Philadelphia, PA; 1995 November.

35. Hudson IRB. The efficacy of intranasal mupirocin in the prevention of staphylococcal infections: a review of recent experience. J Hosp Infect 1994; 27:81-98.

36. Hill RLR, Casewell MW. Nasal carriage of MRSA: the role of mupirocin and outlook for resistance. Drugs Exp Clin Res 1990; 16:397-402.

37. Coello R, Jimnez J, Garcia M et al. Prospective study of infection, colonization and carriage of methicillin-resistant Staphylococcus aureus in an outbreak affecting 990 patients. Eur J Clin Microbiol Infect Dis 1994; 13(1):74-81.

38. Scully BE, Briones F, Gu J et al. Mupirocin treatment of nasal staphylococcal colonization. Arch Intern Med 1992; 152:353-6.

39. Baines PJ, Jackson D, Mellows G, et al. In: Wilkinson DS, Price JD eds. "Mupirocina novel topical antibiotic." London: Royal Society of Medicine, 1984:13.

40. Slocombe B, Perry C. The antimicrobial activity of mupirocin: an update on resistance. J Hosp Infect 1991; 19(Suppl B):19-25.

41. Parenti MA, Hatfield SM, Leyden JJ. Mupirocin: a topical antibiotic with unique structure and mechanism of action. Clin Pharm 1987; 6:761-70.

42. McEvoy GK, ed. [American Hospital Formulary Service] AHFS drug information. Bethesda, MD: American Society of Health-System Pharmacists, 1993:2164.

43. Leyden JJ, Kligman AM. Rationale for topical antibiotics. Cutis 1978; 22:515-28.

44. Sutherland R, Boon RJ, Griffin KE et al. Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob Agents Chemother 1985; 27:495-8.

45. Casewell MW, Hill RLR. In vitro activity of mupirocin against clinical isolates of Staphylococcus aureus. J Antimicrob Chemother 1985; 15:523-31.

46. Wuite J, Davies BI, Go MJ et al. Pseudomonic acid, a new antibiotic for topical therapy. J Am Acad Dermatol 1985; 12:1026-31.

47. Evans LH, Townsend DE. Mupirocin activity against methicillin-resistant Staphylococcus aureus [letter]. Med J Aust 1986; 145:55-6.

48. Leigh DA, Tighe C. The antibacterial activity of mupirocin. In:Wilkinson T, Price JD, eds. Mupirocin: a novel topical antibiotic. London: Royal Society of Medicine, 1984:65-7.

50. Farmer TH, Gilbart J, Elson SW. Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus. J Antimicrob Chemother 1992; 30:587-96.

51. Kauffman CA, Terpenning MS, He X et al. Attempts to eradicate methicillin-resistant Staphylococcus aureus from a long-term-care facility with the use of mupirocin ointment. Am J Med 1993; 94:371-8.

52. Gilbart J, Perry CR, Slocombe B. High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-tRNA synthetases. Antimicrob Agents Chemother 1993; 37:32-8.

53. Kaye ET, Kaye KM. Topical antibacterial agents. Infect Dis Clin North Am 1995; 9(3):547-59.

54. Cookson BD, Lacey RW, Noble WC et al. Mupirocin-resistant Staphylococcus aureus. Lancet 1990; 335:1095-6.

55. Smith GE, Kennedy CTC. Staphylococcus aureus resistant to mupirocin [letter]. J Antimicrob Chemother 1988; 21:141-2.

56. Layton MC, Perez M, Heald P et al. An outbreak of mupirocin-resistant Staphylococcus aureus on a dermatology ward associated with an environmental reservoir. Infect Control Hosp Epidemiol 1993; 14:369-75.

57. Cederna JE, Terpenning MS, Ensberg Met al. Staphylococcus aureus nasal colonisation in a nursing home: eradication with mupirocin. Infect Control Hosp Epidemiol 1990; 11:13-6.

58. Berman JR, Zaran FK, Rybak MJ. Pharmacy-based antimicrobial-monitoring service. Am J Hosp Pharm 1992; 49:1701-6.

59. Manzo J, Amodio-Groton MA, Kleinmann K. Antibiotic cost control measures in a hospital pharmacy. Clin Ther 1993; 15(Suppl A):37-43.

60. Casewell MW. Important epidemiological features of methicillin-resistant Staphylococcus aureus and the role of mupirocin for successful control. Intern Clin Pract Series 1992:83-6.

61. Boyce JM, Jackson MM, Pugliese G et al. Methicillin-resistant Staphylococcus aureus (MRSA): a briefing for acute care hospitals and nursing facilities. Infect Control Hosp Epidemiol 1994; 15:105-15.

62. Boyce JM. Should we vigorously try to contain and control methicillin-resistant Staphylococcus aureus? Infect Control Hosp Epidemiol 1991; 12:46-54.

63. Boyce JM. Methicillin-resistant Staphylococcus aureus in hospitals and long-term care facilities: microbiology, epidemiology, and preventive measures. Infect Control Hosp Epidemiol 1992; 13:725-37.

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