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Prevalence of high-level mupirocin resistance among meticillin-resistant Staphylococcus aureus isolates in a tertiary care hospital in Singapore
Journal of Hospital Infection 82 (2012) 56e57 Available online at www.sciencedirect.com
Journal of Hospital Infection journal homepage: www.elsevierhealth.com/journals/jhin
Short report
Prevalence of high-level mupirocin resistance among meticillin-resistant Staphylococcus aureus isolates in a tertiary care hospital in Singapore S. Choudhury a, *, P.U. Krishnan a, B. Ang b a b
Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore
A R T I C L E
I N F O
Article history: Received 29 February 2012 Accepted 2 July 2012 Available online 31 July 2012 Keywords: Hospital Meticillin-resistant Staphylococcus aureus Mupirocin Resistance
S U M M A R Y
High-level resistance to mupirocin in meticillin-resistant Staphylococcus aureus (MRSA) jeopardizes its role in nasal decolonization protocols. We carried out a study in 2010 to determine the prevalence of high-level mupirocin resistance in our tertiary-care hospital. The prevalence of high-level resistance to mupirocin in MRSA in this hospital was 11%. There was also complete agreement between the genotypic and phenotypic methods of detection of high-level mupirocin resistance in 24 of the screening isolates. ª 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Introduction Mupirocin or pseudomonic acid is a topical antimicrobial agent used empirically in this 1500-bed multi-specialty hospital for the eradication of nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA). Although it is well known that MRSA exhibits both low-level and high-level resistance to this drug, most hospitals have been using this agent in their MRSA decolonization protocols without determining susceptibility to the drug as there were no commercially available test methods or US Food and Drug Administration interpretive breakpoints until recently. It has been reported that emerging resistance to this topical agent has compromised its effectiveness in eradicating MRSA from the anterior nares of colonized patients.1
* Corresponding author. Address: Department of Laboratory Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. Tel.: þ65 91183117; fax: þ65 63578967. E-mail address: [email protected] (S. Choudhury).
The anti-bacterial activity of mupirocin is due to competitive inhibition with isoleucine for bacterial isoleucyl-tRNA synthetase (IRS) resulting in inhibition of bacterial protein synthesis.2 Mupirocin-resistant MRSA isolates are grouped into two distinct categories: low-level resistant isolates have minimum inhibitory concentrations (MICs) ranging from 8 to 256 mg/mL, and high-level resistant isolates have MICs 512 mg/mL.3 Low-level resistance to mupirocin is due to mutations in the endogenous gene coding for IRS and the clinical significance of this type of resistance is unclear. Isolates resistant to a high level of mupirocin contain two distinct IRS enzymes: an endogenous IRS similar to that in lowlevel resistant isolates plus an additional IRS mediated by the plasmid-encoded ileS-2 gene; high-level mupirocin resistance has been associated with MRSA nasal decolonization failure.4 Although mupirocin was introduced into this hospital’s formulary in 1996, strict controls for its use have been in place and the drug is used almost exclusively for nasal decolonization of MRSA carriers. Neither a pre- nor post-introductory surveillance for mupirocin resistance in MRSA has been conducted at
0195-6701/$ e see front matter ª 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jhin.2012.07.002
S. Choudhury et al. / Journal of Hospital Infection 82 (2012) 56e57 our hospital. This study was carried out in 2010 with the aim of determining the prevalence of high-level mupirocin resistance in this hospital. We also wanted to estimate the degree of concordance between the two different methods of detecting mupirocin resistance available in our laboratory.
Methods During the period 2009e2010, screening for MRSA carriage was done for certain high-risk groups, i.e. patients admitted in intensive care and renal dialysis units. All isolates obtained from MRSA screening as well as the first clinical MRSA isolate from patients were stored in this laboratory. For this study, a total of 307 MRSA isolates were obtained from distinct patients over this period, 94 from screening samples and 213 from clinical cultures. In all, 122 patients (39%) had documentation of recent treatment with mupirocin 2% nasal ointment (Bactroban, GlaxoSmithKline, Research Triangle Park, NC, USA) according to the hospital’s pharmacy electronic records. Disc diffusion tests were performed according to the guidelines of the Clinical and Laboratory Standards Institute.5 The presence of any zone of inhibition with the 200 mg disc indicates absence of high-level mupirocin resistance; S. aureus ATCC 25923 and S. aureus ATCC BAA 1708 were used as negative and positive controls respectively. Twenty-four isolates from screening samples were tested genotypically for high-level mupirocin resistance. NucliSens easyMAG extraction kit (bioMe ´rieux, Marcy l’Etoile, France) was used to purify genomic DNA from these isolates. A 456 bp region in the ileS-2 gene was amplified by polymerase chain reaction using published primers.2 The reaction products were analysed using 1.5% agarose gel electrophoresis with S. aureus ATCC BAA 1708 and distilled water as positive and negative controls respectively.
Results and discussion The overall prevalence of high-level mupirocin resistance in this hospital was 11%, 14% in screening samples and 10% in clinical isolates. In a study conducted in a neighbouring hospital in this country and others from Trinidad and China, the prevalence of high-level mupirocin resistance in MRSA was 31.3%, 26.1% and 6.6% respectively (http://www.apsic2011. com/abstract/60.asp).6e8 The prevalence of high-level mupirocin resistance appears to vary considerably in different parts of the world as well as between hospitals in the same region.
57
There was complete concordance between the genotypic and phenotypic (disc diffusion) methods of detection of highlevel mupirocin resistance in these 24 isolates; the ileS-2 gene was detected in 21 of the 24 isolates which were also resistant by the disc diffusion method. The remaining three were negative for high-level mupirocin resistance by both methods. With the high and variable rate of resistance to mupirocin in MRSA in hospitals worldwide, institutions should consider routine detection of resistance to this drug prior to its use in nasal decolonization protocols. Conflict of interest statement None declared. Funding sources None.
References 1. de Oliveira NE, Cardozo AP, Marques Ede A, dos Santos KR, Giambiagi-deMarval M. Interpretive criteria to differentiate lowand high-level mupirocin resistance in Staphylococcus aureus. J Med Microbiol 2007;56:937e939. 2. Yun HJ, Lee SW, Yoon GM, et al. Prevalence and mechanisms of low- and high-level mupirocin resistance in staphylococci isolated from a Korean hospital. J Antimicrob Chemother 2003;51:619e623. 3. Cookson BD. The emergence of mupirocin resistance: a challenge to infection control and antibiotic prescribing practice. J Antimicrob Chemother 1998;41:11e18. 4. Morton TM, Johnston JL, Patterson J, Archer GL. Characterization of a conjugative staphylococcal mupirocin resistance plasmid. Antimicrob Agents Chemother 1995;39:1272e1280. 5. Clinical and Laboratory Standards Institute/NCCLS. Performance standards for antimicrobial susceptibility testing; 20th informational supplement. CLSI document M100eS20. Wayne, PA: CLSI; 2010. 6. Ling ML, Goh SS, Tan AL. Increasing mupirocin resistance in Singapore. In: 5th International Congress of the Asia Pacific Society of Infection Control, Melbourne Convention Centre, Melbourne, Australia, 2011. 7. Orrett FA. The emergence of mupirocin resistance among clinical isolates of methicillin-resistant Staphylococcus aureus in Trinidad: a first report. Jpn J Infect Dis 2008;61:107e110. 8. Liu QZ, Wu Q, Zhang YB, et al. Prevalence of clinical meticillinresistant Staphylococcus aureus (MRSA) with high-level mupirocin resistance in Shanghai and Wenzhou, China. Int J Antimicrob Agents 2010;35:114e118.
Journal of Hospital Infection journal homepage: www.elsevierhealth.com/journals/jhin
Short report
Prevalence of high-level mupirocin resistance among meticillin-resistant Staphylococcus aureus isolates in a tertiary care hospital in Singapore S. Choudhury a, *, P.U. Krishnan a, B. Ang b a b
Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore
A R T I C L E
I N F O
Article history: Received 29 February 2012 Accepted 2 July 2012 Available online 31 July 2012 Keywords: Hospital Meticillin-resistant Staphylococcus aureus Mupirocin Resistance
S U M M A R Y
High-level resistance to mupirocin in meticillin-resistant Staphylococcus aureus (MRSA) jeopardizes its role in nasal decolonization protocols. We carried out a study in 2010 to determine the prevalence of high-level mupirocin resistance in our tertiary-care hospital. The prevalence of high-level resistance to mupirocin in MRSA in this hospital was 11%. There was also complete agreement between the genotypic and phenotypic methods of detection of high-level mupirocin resistance in 24 of the screening isolates. ª 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Introduction Mupirocin or pseudomonic acid is a topical antimicrobial agent used empirically in this 1500-bed multi-specialty hospital for the eradication of nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA). Although it is well known that MRSA exhibits both low-level and high-level resistance to this drug, most hospitals have been using this agent in their MRSA decolonization protocols without determining susceptibility to the drug as there were no commercially available test methods or US Food and Drug Administration interpretive breakpoints until recently. It has been reported that emerging resistance to this topical agent has compromised its effectiveness in eradicating MRSA from the anterior nares of colonized patients.1
* Corresponding author. Address: Department of Laboratory Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. Tel.: þ65 91183117; fax: þ65 63578967. E-mail address: [email protected] (S. Choudhury).
The anti-bacterial activity of mupirocin is due to competitive inhibition with isoleucine for bacterial isoleucyl-tRNA synthetase (IRS) resulting in inhibition of bacterial protein synthesis.2 Mupirocin-resistant MRSA isolates are grouped into two distinct categories: low-level resistant isolates have minimum inhibitory concentrations (MICs) ranging from 8 to 256 mg/mL, and high-level resistant isolates have MICs 512 mg/mL.3 Low-level resistance to mupirocin is due to mutations in the endogenous gene coding for IRS and the clinical significance of this type of resistance is unclear. Isolates resistant to a high level of mupirocin contain two distinct IRS enzymes: an endogenous IRS similar to that in lowlevel resistant isolates plus an additional IRS mediated by the plasmid-encoded ileS-2 gene; high-level mupirocin resistance has been associated with MRSA nasal decolonization failure.4 Although mupirocin was introduced into this hospital’s formulary in 1996, strict controls for its use have been in place and the drug is used almost exclusively for nasal decolonization of MRSA carriers. Neither a pre- nor post-introductory surveillance for mupirocin resistance in MRSA has been conducted at
0195-6701/$ e see front matter ª 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jhin.2012.07.002
S. Choudhury et al. / Journal of Hospital Infection 82 (2012) 56e57 our hospital. This study was carried out in 2010 with the aim of determining the prevalence of high-level mupirocin resistance in this hospital. We also wanted to estimate the degree of concordance between the two different methods of detecting mupirocin resistance available in our laboratory.
Methods During the period 2009e2010, screening for MRSA carriage was done for certain high-risk groups, i.e. patients admitted in intensive care and renal dialysis units. All isolates obtained from MRSA screening as well as the first clinical MRSA isolate from patients were stored in this laboratory. For this study, a total of 307 MRSA isolates were obtained from distinct patients over this period, 94 from screening samples and 213 from clinical cultures. In all, 122 patients (39%) had documentation of recent treatment with mupirocin 2% nasal ointment (Bactroban, GlaxoSmithKline, Research Triangle Park, NC, USA) according to the hospital’s pharmacy electronic records. Disc diffusion tests were performed according to the guidelines of the Clinical and Laboratory Standards Institute.5 The presence of any zone of inhibition with the 200 mg disc indicates absence of high-level mupirocin resistance; S. aureus ATCC 25923 and S. aureus ATCC BAA 1708 were used as negative and positive controls respectively. Twenty-four isolates from screening samples were tested genotypically for high-level mupirocin resistance. NucliSens easyMAG extraction kit (bioMe ´rieux, Marcy l’Etoile, France) was used to purify genomic DNA from these isolates. A 456 bp region in the ileS-2 gene was amplified by polymerase chain reaction using published primers.2 The reaction products were analysed using 1.5% agarose gel electrophoresis with S. aureus ATCC BAA 1708 and distilled water as positive and negative controls respectively.
Results and discussion The overall prevalence of high-level mupirocin resistance in this hospital was 11%, 14% in screening samples and 10% in clinical isolates. In a study conducted in a neighbouring hospital in this country and others from Trinidad and China, the prevalence of high-level mupirocin resistance in MRSA was 31.3%, 26.1% and 6.6% respectively (http://www.apsic2011. com/abstract/60.asp).6e8 The prevalence of high-level mupirocin resistance appears to vary considerably in different parts of the world as well as between hospitals in the same region.
57
There was complete concordance between the genotypic and phenotypic (disc diffusion) methods of detection of highlevel mupirocin resistance in these 24 isolates; the ileS-2 gene was detected in 21 of the 24 isolates which were also resistant by the disc diffusion method. The remaining three were negative for high-level mupirocin resistance by both methods. With the high and variable rate of resistance to mupirocin in MRSA in hospitals worldwide, institutions should consider routine detection of resistance to this drug prior to its use in nasal decolonization protocols. Conflict of interest statement None declared. Funding sources None.
References 1. de Oliveira NE, Cardozo AP, Marques Ede A, dos Santos KR, Giambiagi-deMarval M. Interpretive criteria to differentiate lowand high-level mupirocin resistance in Staphylococcus aureus. J Med Microbiol 2007;56:937e939. 2. Yun HJ, Lee SW, Yoon GM, et al. Prevalence and mechanisms of low- and high-level mupirocin resistance in staphylococci isolated from a Korean hospital. J Antimicrob Chemother 2003;51:619e623. 3. Cookson BD. The emergence of mupirocin resistance: a challenge to infection control and antibiotic prescribing practice. J Antimicrob Chemother 1998;41:11e18. 4. Morton TM, Johnston JL, Patterson J, Archer GL. Characterization of a conjugative staphylococcal mupirocin resistance plasmid. Antimicrob Agents Chemother 1995;39:1272e1280. 5. Clinical and Laboratory Standards Institute/NCCLS. Performance standards for antimicrobial susceptibility testing; 20th informational supplement. CLSI document M100eS20. Wayne, PA: CLSI; 2010. 6. Ling ML, Goh SS, Tan AL. Increasing mupirocin resistance in Singapore. In: 5th International Congress of the Asia Pacific Society of Infection Control, Melbourne Convention Centre, Melbourne, Australia, 2011. 7. Orrett FA. The emergence of mupirocin resistance among clinical isolates of methicillin-resistant Staphylococcus aureus in Trinidad: a first report. Jpn J Infect Dis 2008;61:107e110. 8. Liu QZ, Wu Q, Zhang YB, et al. Prevalence of clinical meticillinresistant Staphylococcus aureus (MRSA) with high-level mupirocin resistance in Shanghai and Wenzhou, China. Int J Antimicrob Agents 2010;35:114e118.