OBJECTIVETo investigate the antibacterial activity of silver sulfadiazine (SD-Ag), mupirocin, and clotrimazole used alone or in combination against methicillin-resistant Staphylococcus aureus (MRSA) isolated from burn wounds.

METHODSEighteen MRSA isolates from wound excretion of 18 burn patients hospitalized in our unit from July to December 2011 were collected continuously and non-repetitively. (1) Minimum inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of SD-Ag, mupirocin, and clotrimazole used alone, those of SD-Ag and mupirocin used in combination, and those of SD-Ag, mupirocin, and clotrimazole used in combination to MRSA were determined by checkerboard agar dilution method. (2) Fractional inhibitory concentration (FIC) index was calculated to determine the combined effect of SD-Ag plus mupirocin, and SD-Ag plus mupirocin and clotrimazole. Synergy with FIC index less than or equal to 0.5 or additivity with FIC index more than 0.5 and less than or equal to 1.0 was regarded as effective, and indifference with FIC index more than 1.0 and less than or equal to 4.0 or antagonism with FIC index more than 4.0 was regarded as ineffective. The effective ratio was compared with overall ratio (assumed as 0) by unilateral binomial distribution test.

RESULTSThe MIC, MIC50, and MIC90 of SD-Ag, mupirocin, and clotrimazole used alone against 18 MRSA isolates were respectively 8, 8, 16 µg/mL; 2, 16, 64 µg/mL; 2, 2, 2 µg/mL. MIC of antimicrobial agents used in combination decreased from 3.1% to 50.0% as compared with that of individual agent used alone. Compared with those of single application of SD-Ag and mupirocin, MIC50 of SD-Ag and that of mupirocin both decreased 75.0%, and MIC90 of them decreased 87.5% when SD-Ag and mupirocin were used in combination. Compared with those of single application of SD-Ag, mupirocin, and clotrimazole, MIC50 of SD-Ag, mupirocin, and clotrimazole respectively decreased 75.0%, 87.5%, and 50.0%; MIC90 of them respectively decreased 87.5%, 96.9%, and 50.0% when SD-Ag, mupirocin, and clotrimazole were used in combination. Among the 18 MRSA isolates, the combined effect of SD-Ag and mupirocin was synergic in 9 isolates, additive in 7 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate; the combined effect of SD-Ag, mupirocin, and clotrimazole was additive in 16 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate. There were statistically significant differences between effective ratio and overall ratio of 18 MRSA isolates treated with combined antimicrobial agents (P values all above 0.01).

CONCLUSIONSFor burn wounds at middle and late stages infected with Staphylococcus aureus or Staphylococcus aureus and Fungus, low dose of SD-Ag or combination of above-mentioned antimicrobial agents can effectively control infection and decrease the adverse effect of antimicrobial agents on wound healing.

Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; administration & dosage ; adverse effects ; pharmacology ; Burns ; microbiology ; Child ; Child, Preschool ; Clotrimazole ; administration & dosage ; adverse effects ; pharmacology ; Drug Therapy, Combination ; Female ; Humans ; Infant ; Male ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; isolation & purification ; Middle Aged ; Mupirocin ; administration & dosage ; adverse effects ; pharmacology ; Silver Sulfadiazine ; administration & dosage ; adverse effects ; pharmacology ; Young Adult

BACKGROUND/AIMS: Intranasal mupirocin and chlorhexidine bathing are candidate strategies to prevent healthcare-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In Korea, intranasal mupirocin is not available, and mupirocin ointment, an over-the-counter drug, has been used indiscriminately. Furthermore, because it is covered by health insurance, mupirocin is easy to prescribe within hospitals. METHODS: We performed a mupirocin drug utilization review (DUR) within Hallym University Sacred Heart Hospital. Annual use of mupirocin was investigated between 2003 and 2013, and monthly consumption of mupirocin was assessed during the final 2-year period. The DUR focused on August 2012, the period of highest use of mupirocin. Also, we investigated trends in mupirocin resistance in MRSA between 2011 and 2013. RESULTS: Annual consumption of mupirocin increased from 3,529 tubes in 2003 to 6,475 tubes in 2013. During August 2012, 817 tubes were prescribed to 598 patients; of these, 84.9% were prescribed to outpatients, and 77.6% at the dermatology department. The most common indication was prevention of skin infections (84.9%), and the ointment was combined with systemic antibiotics in 62.9% of cases. The average duration of systemic antibiotic administration was about 7.8 days. The rate of low-level mupirocin resistance in MRSA increased from 8.0% to 22.0%, and that of high-level mupirocin resistance increased from about 4.0% to about 7.5%. CONCLUSIONS: Inappropriate use of mupirocin is prevalent. Considering the increase in resistance and the future application of intranasal mupirocin, prophylactic use of mupirocin in dermatology departments should be reconsidered.
Administration, Cutaneous ; Anti-Bacterial Agents/*administration & dosage/adverse effects ; Drug Prescriptions ; Drug Resistance, Multiple, Bacterial ; Drug Utilization Review ; *Hospitals, University ; Humans ; Inappropriate Prescribing/*trends ; Methicillin-Resistant Staphylococcus aureus/*drug effects ; Microbial Sensitivity Tests ; Mupirocin/*administration & dosage/adverse effects ; Ointments ; Practice Patterns, Physicians'/*trends ; Predictive Value of Tests ; Republic of Korea ; Retrospective Studies ; Staphylococcal Skin Infections/diagnosis/*drug therapy/microbiology ; Time Factors