Phenotypic and Genotypic Mupirocin Resistance among Staphylococci Causing Prosthetic Joint Infection
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微生物临床杂志 2005年第8期
Division of Infectious Diseases, Department of Internal Medicine
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota
ABSTRACT
Mupirocin MICs and mupA presence were determined in 108 staphylococci causing prosthetic joint infection. Zero of 35 isolates (0%) of methicillin-susceptible Staphylococcus aureus, 4/15 (27%) methicillin-resistant S. aureus isolates, 3/16 (19%) methicillin-susceptible coagulase-negative staphylococci, and 11/42 (26%) methicillin-resistant coagulase-negative staphylococci were mupirocin resistant. mupA was detected in all five high-level mupirocin-resistant staphylococci and one mupirocin-susceptible staphylococcus.
TEXT
Most Staphylococcus aureus infections appear to originate from endogenous nasal flora (1, 10, 24). Decolonization of nasal carriers prior to orthopedic surgery may reduce the incidence of surgical site infection caused by S. aureus and the subsequent development of prosthetic joint infection (PJI) (9, 26). Topical mupirocin is an effective S. aureus nasal decolonization agent (14, 21); however, mupirocin resistance may be associated with decolonization failure (4, 7, 25). Low-level resistance to mupirocin is associated with mutations in endogenous bacterial isoleucyl-tRNA synthetase; high-level mupirocin resistance is due to acquisition of mupA which encodes an exogenous isoleucyl-tRNA synthetase not inhibited by mupirocin (6, 8). Coagulase-negative staphylococci (CNS) may act as a reservoir for mupA, which may be transferred to S. aureus; transfer of mupA from CNS to S. aureus has been demonstrated in vitro (17, 23).
To determine the frequency of phenotypic and genotypic resistance to mupirocin, we collected staphylococci from patients who had infected knee or hip prostheses and were hospitalized at the Mayo Clinic, Rochester, Minn., between January 1999 and December 2002. One staphylococcal isolate per patient from the site of the infection was studied. PJI was defined by the presence of at least one of the following criteria: (i) growth of the same microorganism in two or more synovial fluid or intraoperative tissue cultures, (ii) synovial fluid or intraoperative tissue purulence, (iii) acute inflammation on histopathologic examination of intraoperative tissue, and (iv) a sinus tract communicating with the prosthesis (22, 28).
Mupirocin MICs were determined by broth microdilution according to Clinical and Laboratory Standards Institute (formerly NCCLS) guidelines (15). Mupirocin resistance was classified as low level (MIC, 8 to 256 μg/ml) or high level (MIC, >256 μg/ml) (3). S. aureus ATCC 29213 was used for assay control.
The presence of mupA was determined by using PCR with previously described primers Mup 1 (5' CCC ATG GCT TAC CAG TTG A) and Mup 2 (5' CCA TGG AGC ACT ATC CGA A) (8, 18). DNA was extracted from 108 bacterial cells by using DNA Stat DNA-60 (Tel-Test, Friendswood, TX). Cycling parameters consisted of 95°C for 10 min followed by 40 cycles of 1 min at 94°C, 2 min at 46°C, and 3 min at 72°C, with a final extension of 3 min at 72°C.
To evaluate differences in categorical variables between groups, the two-tailed Fisher's exact test was used. A P value of <0.05 was considered statistically significant. All calculations were performed using the statistical software package JMP (version 5.1; SAS Institute Inc., Cary, NC). The study was approved by the Mayo Clinic Institutional Review Board.
A total of 108 staphylococcal isolates from 57 men and 51 women (median age, 70 years; range, 17 to 90 years) with infected knee (n = 61) or hip (n = 47) prostheses were studied. Fifty isolates (46%) were S. aureus isolates and 58 isolates (54%) were CNS, including Staphylococcus epidermidis (n = 45), Staphylococcus lugdunensis (n = 6), Staphylococcus caprae/capitis (n = 2), Staphylococcus warneri (n = 2), Staphylococcus hominis (n = 1), Staphylococcus simulans (n = 1), and Staphylococcus saprophyticus (n = 1). Coagulase-negative staphylococci were identified to the species level by using conventional biochemical testing. For isolates for which identification was unclear by use of conventional biochemical testing, 16S ribosomal RNA gene PCR and bidirectional sequence analysis were performed, as previously described (11). Data were analyzed by use of Sequencher 3.1 (Gene Codes Corporation, Ann Arbor, MI) and GenBank.
Table 1 shows the distribution of mupirocin resistance among staphylococcal isolates. Phenotypic mupirocin resistance was more common among CNS (14 of 58 isolates, 24%) than among S. aureus isolates (4 of 50 isolates, 8%) (P = 0.037). Among the 35 methicillin-susceptible S. aureus isolates, no mupirocin resistance was detected, whereas 4 of 15 (27%) methicillin-resistant S. aureus (MRSA) isolates were resistant to mupirocin (P = 0.006). Three MRSA isolates exhibited low-level mupirocin resistance (mupirocin MICs were 8, 32, and 32 μg/ml), and one exhibited high-level mupirocin resistance. Among CNS, 3 of 16 (19%) methicillin-susceptible isolates and 11 of 42 (26%) methicillin-resistant isolates exhibited mupirocin resistance (P = 0.736). Two methicillin-susceptible CNS exhibited low-level mupirocin resistance (mupirocin MICs were 32 and 64 μg/ml), and one exhibited high-level mupirocin resistance. In contrast, eight methicillin-resistant CNS exhibited low-level mupirocin resistance (mupirocin MICs were 32 μg/ml [six isolates] and 64 μg/ml [two isolates]), and three exhibited high-level mupirocin resistance.
mupA was detected in all isolates exhibiting high-level mupirocin resistance, as well as in one mupirocin-susceptible (mupirocin MIC, 2 μg/ml) S. epidermidis isolate. PCR amplification and product sequence analysis confirmed the presence of a mupA-specific sequence in this mupirocin-susceptible S. epidermidis isolate (GenBank accession number X75439) (8).
In our study, mupirocin resistance was more prevalent in CNS than in S. aureus (24% versus 8%), as was previously shown in studies with bloodstream, nosocomial pneumonia, skin and soft tissue infection, environmental, and carriage isolates (12, 13, 16, 20, 27). We also found that the mupirocin resistance rate among methicillin-resistant staphylococci causing PJI was higher than that of methicillin-susceptible staphylococci causing PJI, especially among S. aureus isolates (i.e., 27% in MRSA isolates versus 0% in methicillin-susceptible S. aureus isolates). This finding has been previously reported (2, 12, 20, 27); however, our study is the first to include a defined group of individuals with PJI. The presence of mupA in our study did not consistently correlate with high-level mupirocin resistance. mupA has been previously reported among S. aureus isolates exhibiting low-level mupirocin resistance (5, 18, 19) but not (as reported herein) in mupirocin-susceptible S. epidermidis. mupA may be present but not expressed, potentially as a result of mutations outside of the region sequenced herein or inadequate gene copy (18).
In conclusion, mupirocin resistance was found in 27% of MRSA isolates causing hip or knee PJI. This finding is important because mupirocin is used for decolonization of MRSA carriers, including the prevention of infection after implantation of prosthetic devices. Mupirocin susceptibility testing of S. aureus isolates to be treated with mupirocin is advised. New strategies for MRSA nasal decolonization are warranted.
(This work was presented in part at the 43rd Interscience Conference of Antimicrobial Agents and Chemotherapy, Chicago, Ill., 14 to 17 September 2003.)
ACKNOWLEDGMENTS
This study was supported in part by the Spanish Society of Infectious Diseases and Clinical Microbiology (Madrid, Spain) and the Mayo Foundation.
REFERENCES
Chang, F. Y., N. Singh, T. Gayowski, S. D. Drenning, M. M. Wagener, and I. R. Marino. 1998. Staphylococcus aureus nasal colonization and association with infections in liver transplant recipients. Transplantation 65:1169-1172.
Chaves, F., J. Garcia-Martinez, S. de Miguel, and J. R. Otero. 2004. Molecular characterization of resistance to mupirocin in methicillin-susceptible and -resistant isolates of Staphylococcus aureus from nasal samples. J. Clin. Microbiol. 42:822-824.
Cookson, B. D. 1998. The emergence of mupirocin resistance: a challenge to infection control and antibiotic prescribing practice. J. Antimicrob. Chemother. 41:11-18.
Decousser, J. W., P. Pina, J. C. Ghnassia, J. P. Bedos, and P. Y. Allouch. 2003. First report of clinical and microbiological failure in the eradication of glycopeptide-intermediate methicillin-resistant Staphylococcus aureus carriage by mupirocin. Eur. J. Clin. Microbiol. Infect. Dis. 22:318-319.
Fujimura, S., A. Watanabe, and D. Beighton. 2001. Characterization of the mupA gene in strains of methicillin-resistant Staphylococcus aureus with a low level of resistance to mupirocin. Antimicrob. Agents Chemother. 45:641-642.
Gilbart, J., C. R. Perry, and B. Slocombe. 1993. High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-tRNA synthetases. Antimicrob. Agents Chemother. 37:32-38.
Harbarth, S., S. Dharan, N. Liassine, P. Herrault, R. Auckenthaler, and D. Pittet. 1999. Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 43:1412-1416.
Hodgson, J. E., S. P. Curnock, K. G. Dyke, R. Morris, D. R. Sylvester, and M. S. Gross. 1994. Molecular characterization of the gene encoding high-level mupirocin resistance in Staphylococcus aureus J2870. Antimicrob. Agents Chemother. 38:1205-1208.
Kalmeijer, M. D., E. van Nieuwland-Bollen, D. Bogaers-Hofman, and G. A. de Baere. 2000. Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery. Infect. Control Hosp. Epidemiol. 21:319-323.
Kluytmans, J., A. van Belkum, and H. Verbrugh. 1997. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin. Microbiol. Rev. 10:505-520.
Kolbert, C., P. Rys, M. Hopkins, D. Lynch, J. Germer, C. O'Sullivan, A. Trampuz, and R. Patel. 2004. 16S ribosomal DNA sequence analysis for identification of bacteria in a clinical microbiology laboratory. In D. Persing, F. Tenover, J. Versalovic, Y. Tang, E. Unger, D. Relman, and T. White (ed.), Molecular microbiology: diagnostic principles and practice. ASM Press, Washington, D.C.
Kresken, M., D. Hafner, F. J. Schmitz, and T. A. Wichelhaus. 2004. Prevalence of mupirocin resistance in clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis: results of the Antimicrobial Resistance Surveillance Study of the Paul-Ehrlich-Society for Chemotherapy, 2001. Int. J. Antimicrob. Agents 23:577-581.
Leski, T. A., M. Gniadkowski, A. Skoczynska, E. Stefaniuk, K. Trzcinski, and W. Hryniewicz. 1999. Outbreak of mupirocin-resistant staphylococci in a hospital in Warsaw, Poland, due to plasmid transmission and clonal spread of several strains. J. Clin. Microbiol. 37:2781-2788.
Mody, L., C. A. Kauffman, S. A. McNeil, A. T. Galecki, and S. F. Bradley. 2003. Mupirocin-based decolonization of Staphylococcus aureus carriers in residents of 2 long-term care facilities: a randomized, double-blind, placebo-controlled trial. Clin. Infect. Dis. 37:1467-1474.
NCCLS. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 6th ed. Approved standard M7-A6. NCCLS, Wayne, Pa.
Petinaki, E., I. Spiliopoulou, F. Kontos, M. Maniati, Z. Bersos, N. Stakias, H. Malamou-Lada, C. Koutsia-Carouzou, and A. N. Maniatis. 2004. Clonal dissemination of mupirocin-resistant staphylococci in Greek hospitals. J. Antimicrob. Chemother. 53:105-108.
Rahman, M., S. Connolly, W. C. Noble, B. Cookson, and I. Phillips. 1990. Diversity of staphylococci exhibiting high-level resistance to mupirocin. J. Med. Microbiol. 33:97-100.
Ramsey, M. A., S. F. Bradley, C. A. Kauffman, and T. M. Morton. 1996. Identification of chromosomal location of mupA gene, encoding low-level mupirocin resistance in staphylococcal isolates. Antimicrob. Agents Chemother. 40:2820-2823.
Ramsey, M. A., S. F. Bradley, C. A. Kauffman, T. M. Morton, J. E. Patterson, and D. R. Reagan. 1998. Characterization of mupirocin-resistant Staphylococcus aureus from different geographic areas. Antimicrob. Agents Chemother. 42:1305. (Letter.)
Schmitz, F. J., E. Lindenlauf, B. Hofmann, A. C. Fluit, J. Verhoef, H. P. Heinz, and M. E. Jones. 1998. The prevalence of low- and high-level mupirocin resistance in staphylococci from 19 European hospitals. J. Antimicrob Chemother. 42:489-495.
Tomic, V., P. Svetina Sorli, D. Trinkaus, J. Sorli, A. F. Widmer, and A. Trampuz. 2004. Comprehensive strategy to prevent nosocomial spread of methicillin-resistant Staphylococcus aureus in a highly endemic setting. Arch. Intern. Med. 164:2038-2043.
Trampuz, A., D. R. Osmon, A. D. Hanssen, J. M. Steckelberg, and R. Patel. 2003. Molecular and antibiofilm approaches to prosthetic joint infection. Clin. Orthop. Relat. Res. 2003:69-88.
Udo, E. E., L. E. Jacob, and E. M. Mokadas. 1997. Conjugative transfer of high-level mupirocin resistance from Staphylococcus haemolyticus to other staphylococci. Antimicrob. Agents Chemother. 41:693-695.
von Eiff, C., K. Becker, K. Machka, H. Stammer, G. Peters, et al. 2001. Nasal carriage as a source of Staphylococcus aureus bacteremia. N. Engl. J. Med. 344:11-16.
Walker, E. S., J. E. Vasquez, R. Dula, H. Bullock, and F. A. Sarubbi. 2003. Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective Infect. Control Hosp. Epidemiol. 24:342-346.
Wilcox, M. H., J. Hall, H. Pike, P. A. Templeton, W. N. Fawley, P. Parnell, and P. Verity. 2003. Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections. J. Hosp. Infect. 54:196-201.
Yun, H. J., S. W. Lee, G. M. Yoon, S. Y. Kim, S. Choi, Y. S. Lee, E. C. Choi, and S. Kim. 2003. Prevalence and mechanisms of low- and high-level mupirocin resistance in staphylococci isolated from a Korean hospital. J. Antimicrob. Chemother. 51:619-623.
Zimmerli, W., A. Trampuz, and P. E. Ochsner. 2004. Prosthetic-joint infections. N. Engl. J. Med. 351:1645-1654.(Margalida Rotger, Andrej )
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota
ABSTRACT
Mupirocin MICs and mupA presence were determined in 108 staphylococci causing prosthetic joint infection. Zero of 35 isolates (0%) of methicillin-susceptible Staphylococcus aureus, 4/15 (27%) methicillin-resistant S. aureus isolates, 3/16 (19%) methicillin-susceptible coagulase-negative staphylococci, and 11/42 (26%) methicillin-resistant coagulase-negative staphylococci were mupirocin resistant. mupA was detected in all five high-level mupirocin-resistant staphylococci and one mupirocin-susceptible staphylococcus.
TEXT
Most Staphylococcus aureus infections appear to originate from endogenous nasal flora (1, 10, 24). Decolonization of nasal carriers prior to orthopedic surgery may reduce the incidence of surgical site infection caused by S. aureus and the subsequent development of prosthetic joint infection (PJI) (9, 26). Topical mupirocin is an effective S. aureus nasal decolonization agent (14, 21); however, mupirocin resistance may be associated with decolonization failure (4, 7, 25). Low-level resistance to mupirocin is associated with mutations in endogenous bacterial isoleucyl-tRNA synthetase; high-level mupirocin resistance is due to acquisition of mupA which encodes an exogenous isoleucyl-tRNA synthetase not inhibited by mupirocin (6, 8). Coagulase-negative staphylococci (CNS) may act as a reservoir for mupA, which may be transferred to S. aureus; transfer of mupA from CNS to S. aureus has been demonstrated in vitro (17, 23).
To determine the frequency of phenotypic and genotypic resistance to mupirocin, we collected staphylococci from patients who had infected knee or hip prostheses and were hospitalized at the Mayo Clinic, Rochester, Minn., between January 1999 and December 2002. One staphylococcal isolate per patient from the site of the infection was studied. PJI was defined by the presence of at least one of the following criteria: (i) growth of the same microorganism in two or more synovial fluid or intraoperative tissue cultures, (ii) synovial fluid or intraoperative tissue purulence, (iii) acute inflammation on histopathologic examination of intraoperative tissue, and (iv) a sinus tract communicating with the prosthesis (22, 28).
Mupirocin MICs were determined by broth microdilution according to Clinical and Laboratory Standards Institute (formerly NCCLS) guidelines (15). Mupirocin resistance was classified as low level (MIC, 8 to 256 μg/ml) or high level (MIC, >256 μg/ml) (3). S. aureus ATCC 29213 was used for assay control.
The presence of mupA was determined by using PCR with previously described primers Mup 1 (5' CCC ATG GCT TAC CAG TTG A) and Mup 2 (5' CCA TGG AGC ACT ATC CGA A) (8, 18). DNA was extracted from 108 bacterial cells by using DNA Stat DNA-60 (Tel-Test, Friendswood, TX). Cycling parameters consisted of 95°C for 10 min followed by 40 cycles of 1 min at 94°C, 2 min at 46°C, and 3 min at 72°C, with a final extension of 3 min at 72°C.
To evaluate differences in categorical variables between groups, the two-tailed Fisher's exact test was used. A P value of <0.05 was considered statistically significant. All calculations were performed using the statistical software package JMP (version 5.1; SAS Institute Inc., Cary, NC). The study was approved by the Mayo Clinic Institutional Review Board.
A total of 108 staphylococcal isolates from 57 men and 51 women (median age, 70 years; range, 17 to 90 years) with infected knee (n = 61) or hip (n = 47) prostheses were studied. Fifty isolates (46%) were S. aureus isolates and 58 isolates (54%) were CNS, including Staphylococcus epidermidis (n = 45), Staphylococcus lugdunensis (n = 6), Staphylococcus caprae/capitis (n = 2), Staphylococcus warneri (n = 2), Staphylococcus hominis (n = 1), Staphylococcus simulans (n = 1), and Staphylococcus saprophyticus (n = 1). Coagulase-negative staphylococci were identified to the species level by using conventional biochemical testing. For isolates for which identification was unclear by use of conventional biochemical testing, 16S ribosomal RNA gene PCR and bidirectional sequence analysis were performed, as previously described (11). Data were analyzed by use of Sequencher 3.1 (Gene Codes Corporation, Ann Arbor, MI) and GenBank.
Table 1 shows the distribution of mupirocin resistance among staphylococcal isolates. Phenotypic mupirocin resistance was more common among CNS (14 of 58 isolates, 24%) than among S. aureus isolates (4 of 50 isolates, 8%) (P = 0.037). Among the 35 methicillin-susceptible S. aureus isolates, no mupirocin resistance was detected, whereas 4 of 15 (27%) methicillin-resistant S. aureus (MRSA) isolates were resistant to mupirocin (P = 0.006). Three MRSA isolates exhibited low-level mupirocin resistance (mupirocin MICs were 8, 32, and 32 μg/ml), and one exhibited high-level mupirocin resistance. Among CNS, 3 of 16 (19%) methicillin-susceptible isolates and 11 of 42 (26%) methicillin-resistant isolates exhibited mupirocin resistance (P = 0.736). Two methicillin-susceptible CNS exhibited low-level mupirocin resistance (mupirocin MICs were 32 and 64 μg/ml), and one exhibited high-level mupirocin resistance. In contrast, eight methicillin-resistant CNS exhibited low-level mupirocin resistance (mupirocin MICs were 32 μg/ml [six isolates] and 64 μg/ml [two isolates]), and three exhibited high-level mupirocin resistance.
mupA was detected in all isolates exhibiting high-level mupirocin resistance, as well as in one mupirocin-susceptible (mupirocin MIC, 2 μg/ml) S. epidermidis isolate. PCR amplification and product sequence analysis confirmed the presence of a mupA-specific sequence in this mupirocin-susceptible S. epidermidis isolate (GenBank accession number X75439) (8).
In our study, mupirocin resistance was more prevalent in CNS than in S. aureus (24% versus 8%), as was previously shown in studies with bloodstream, nosocomial pneumonia, skin and soft tissue infection, environmental, and carriage isolates (12, 13, 16, 20, 27). We also found that the mupirocin resistance rate among methicillin-resistant staphylococci causing PJI was higher than that of methicillin-susceptible staphylococci causing PJI, especially among S. aureus isolates (i.e., 27% in MRSA isolates versus 0% in methicillin-susceptible S. aureus isolates). This finding has been previously reported (2, 12, 20, 27); however, our study is the first to include a defined group of individuals with PJI. The presence of mupA in our study did not consistently correlate with high-level mupirocin resistance. mupA has been previously reported among S. aureus isolates exhibiting low-level mupirocin resistance (5, 18, 19) but not (as reported herein) in mupirocin-susceptible S. epidermidis. mupA may be present but not expressed, potentially as a result of mutations outside of the region sequenced herein or inadequate gene copy (18).
In conclusion, mupirocin resistance was found in 27% of MRSA isolates causing hip or knee PJI. This finding is important because mupirocin is used for decolonization of MRSA carriers, including the prevention of infection after implantation of prosthetic devices. Mupirocin susceptibility testing of S. aureus isolates to be treated with mupirocin is advised. New strategies for MRSA nasal decolonization are warranted.
(This work was presented in part at the 43rd Interscience Conference of Antimicrobial Agents and Chemotherapy, Chicago, Ill., 14 to 17 September 2003.)
ACKNOWLEDGMENTS
This study was supported in part by the Spanish Society of Infectious Diseases and Clinical Microbiology (Madrid, Spain) and the Mayo Foundation.
REFERENCES
Chang, F. Y., N. Singh, T. Gayowski, S. D. Drenning, M. M. Wagener, and I. R. Marino. 1998. Staphylococcus aureus nasal colonization and association with infections in liver transplant recipients. Transplantation 65:1169-1172.
Chaves, F., J. Garcia-Martinez, S. de Miguel, and J. R. Otero. 2004. Molecular characterization of resistance to mupirocin in methicillin-susceptible and -resistant isolates of Staphylococcus aureus from nasal samples. J. Clin. Microbiol. 42:822-824.
Cookson, B. D. 1998. The emergence of mupirocin resistance: a challenge to infection control and antibiotic prescribing practice. J. Antimicrob. Chemother. 41:11-18.
Decousser, J. W., P. Pina, J. C. Ghnassia, J. P. Bedos, and P. Y. Allouch. 2003. First report of clinical and microbiological failure in the eradication of glycopeptide-intermediate methicillin-resistant Staphylococcus aureus carriage by mupirocin. Eur. J. Clin. Microbiol. Infect. Dis. 22:318-319.
Fujimura, S., A. Watanabe, and D. Beighton. 2001. Characterization of the mupA gene in strains of methicillin-resistant Staphylococcus aureus with a low level of resistance to mupirocin. Antimicrob. Agents Chemother. 45:641-642.
Gilbart, J., C. R. Perry, and B. Slocombe. 1993. High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-tRNA synthetases. Antimicrob. Agents Chemother. 37:32-38.
Harbarth, S., S. Dharan, N. Liassine, P. Herrault, R. Auckenthaler, and D. Pittet. 1999. Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 43:1412-1416.
Hodgson, J. E., S. P. Curnock, K. G. Dyke, R. Morris, D. R. Sylvester, and M. S. Gross. 1994. Molecular characterization of the gene encoding high-level mupirocin resistance in Staphylococcus aureus J2870. Antimicrob. Agents Chemother. 38:1205-1208.
Kalmeijer, M. D., E. van Nieuwland-Bollen, D. Bogaers-Hofman, and G. A. de Baere. 2000. Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery. Infect. Control Hosp. Epidemiol. 21:319-323.
Kluytmans, J., A. van Belkum, and H. Verbrugh. 1997. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin. Microbiol. Rev. 10:505-520.
Kolbert, C., P. Rys, M. Hopkins, D. Lynch, J. Germer, C. O'Sullivan, A. Trampuz, and R. Patel. 2004. 16S ribosomal DNA sequence analysis for identification of bacteria in a clinical microbiology laboratory. In D. Persing, F. Tenover, J. Versalovic, Y. Tang, E. Unger, D. Relman, and T. White (ed.), Molecular microbiology: diagnostic principles and practice. ASM Press, Washington, D.C.
Kresken, M., D. Hafner, F. J. Schmitz, and T. A. Wichelhaus. 2004. Prevalence of mupirocin resistance in clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis: results of the Antimicrobial Resistance Surveillance Study of the Paul-Ehrlich-Society for Chemotherapy, 2001. Int. J. Antimicrob. Agents 23:577-581.
Leski, T. A., M. Gniadkowski, A. Skoczynska, E. Stefaniuk, K. Trzcinski, and W. Hryniewicz. 1999. Outbreak of mupirocin-resistant staphylococci in a hospital in Warsaw, Poland, due to plasmid transmission and clonal spread of several strains. J. Clin. Microbiol. 37:2781-2788.
Mody, L., C. A. Kauffman, S. A. McNeil, A. T. Galecki, and S. F. Bradley. 2003. Mupirocin-based decolonization of Staphylococcus aureus carriers in residents of 2 long-term care facilities: a randomized, double-blind, placebo-controlled trial. Clin. Infect. Dis. 37:1467-1474.
NCCLS. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 6th ed. Approved standard M7-A6. NCCLS, Wayne, Pa.
Petinaki, E., I. Spiliopoulou, F. Kontos, M. Maniati, Z. Bersos, N. Stakias, H. Malamou-Lada, C. Koutsia-Carouzou, and A. N. Maniatis. 2004. Clonal dissemination of mupirocin-resistant staphylococci in Greek hospitals. J. Antimicrob. Chemother. 53:105-108.
Rahman, M., S. Connolly, W. C. Noble, B. Cookson, and I. Phillips. 1990. Diversity of staphylococci exhibiting high-level resistance to mupirocin. J. Med. Microbiol. 33:97-100.
Ramsey, M. A., S. F. Bradley, C. A. Kauffman, and T. M. Morton. 1996. Identification of chromosomal location of mupA gene, encoding low-level mupirocin resistance in staphylococcal isolates. Antimicrob. Agents Chemother. 40:2820-2823.
Ramsey, M. A., S. F. Bradley, C. A. Kauffman, T. M. Morton, J. E. Patterson, and D. R. Reagan. 1998. Characterization of mupirocin-resistant Staphylococcus aureus from different geographic areas. Antimicrob. Agents Chemother. 42:1305. (Letter.)
Schmitz, F. J., E. Lindenlauf, B. Hofmann, A. C. Fluit, J. Verhoef, H. P. Heinz, and M. E. Jones. 1998. The prevalence of low- and high-level mupirocin resistance in staphylococci from 19 European hospitals. J. Antimicrob Chemother. 42:489-495.
Tomic, V., P. Svetina Sorli, D. Trinkaus, J. Sorli, A. F. Widmer, and A. Trampuz. 2004. Comprehensive strategy to prevent nosocomial spread of methicillin-resistant Staphylococcus aureus in a highly endemic setting. Arch. Intern. Med. 164:2038-2043.
Trampuz, A., D. R. Osmon, A. D. Hanssen, J. M. Steckelberg, and R. Patel. 2003. Molecular and antibiofilm approaches to prosthetic joint infection. Clin. Orthop. Relat. Res. 2003:69-88.
Udo, E. E., L. E. Jacob, and E. M. Mokadas. 1997. Conjugative transfer of high-level mupirocin resistance from Staphylococcus haemolyticus to other staphylococci. Antimicrob. Agents Chemother. 41:693-695.
von Eiff, C., K. Becker, K. Machka, H. Stammer, G. Peters, et al. 2001. Nasal carriage as a source of Staphylococcus aureus bacteremia. N. Engl. J. Med. 344:11-16.
Walker, E. S., J. E. Vasquez, R. Dula, H. Bullock, and F. A. Sarubbi. 2003. Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective Infect. Control Hosp. Epidemiol. 24:342-346.
Wilcox, M. H., J. Hall, H. Pike, P. A. Templeton, W. N. Fawley, P. Parnell, and P. Verity. 2003. Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections. J. Hosp. Infect. 54:196-201.
Yun, H. J., S. W. Lee, G. M. Yoon, S. Y. Kim, S. Choi, Y. S. Lee, E. C. Choi, and S. Kim. 2003. Prevalence and mechanisms of low- and high-level mupirocin resistance in staphylococci isolated from a Korean hospital. J. Antimicrob. Chemother. 51:619-623.
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