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Original Research: CYSTIC FIBROSIS |

Complex Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Isolates From Children With Cystic Fibrosis in the Era of Epidemic Community-Associated Methicillin-Resistant S aureus* FREE TO VIEW

Daniel Glikman, MD; Jane D. Siegel, MD; Michael Z. David, MD; Ngozi M. Okoro, MPH; Susan Boyle-Vavra, PhD; Maria L. Dowell, MD; Robert S. Daum, MD
Author and Funding Information

Affiliations: *From the Sections of Infectious Diseases (Drs. Glikman, David, Boyle-Vavra, and Daum) and Pulmonary Medicine (Dr. Dowell), Department of Pediatrics, University of Chicago, Chicago, IL; and the Department of Pediatrics (Dr. Siegel and Ms. Okoro), University of Texas Southwestern Medical Center, Dallas, TX.,  Current affiliation: Department of Pediatrics and Infectious Diseases Unit, Western Galilee Hospital, Nahariya, Israel.

Correspondence to: Robert S. Daum, MD, University of Chicago, Pediatrics, Section of Infectious Diseases, 5841 S Maryland Ave, MC 6054, Chicago, IL 60637; e-mail: rdaum@peds.bsd.uchicago.edu



Chest. 2008;133(6):1381-1387. doi:10.1378/chest.07-2437
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Background: Limited data exist about the molecular types of methicillin-resistant Staphylococcus aureus (MRSA) strains found in children with cystic fibrosis (CF). We sought to characterize MRSA strains from these patients and compare them with MRSA strains from non-CF pediatric patients.

Methods: All MRSA isolates were collected prospectively at Children’s Medical Center in Dallas, TX, and the University of Chicago Comer Children’s Hospital in 2004 to 2005. All CF MRSA isolates underwent susceptibility testing, multilocus sequence typing, Panton-Valentine leukocidin gene detection (pvl+), and staphylococcal chromosome cassette mec (SCCmec) typing.

Results: A total of 22 of 34 MRSA isolates (64.7%) from patients with CF belonged to clonal complex (CC) 5 and contained SCCmec II, so-called health-care associated MRSA (HA-MRSA) strains. Nine of 34 MRSA strains (26.5%) were CC 8, and contained SCCmec IV, so-called community-associated MRSA (CA-MRSA) strains. The CA-MRSA strains tended to be isolated from newly colonized CF patients. In contrast, CC8 isolates predominated among the non-CF patients (294 of 331 patients; 88.8%). MRSA isolates from children with CF were more likely to be resistant to clindamycin (65% vs 19%, respectively) and ciprofloxacin (62% vs 17%, respectively) compared with strains from non-CF patients (p < 0.001). There was no difference in the rate of pvl+ isolate recovery from children with CF undergoing a surveillance culture (7 of 23 children) compared with those with pulmonary exacerbation (3 of 11 children; p = 1.0).

Conclusions: Both CA-MRSA (CC8) isolates and HA-MRSA (CC5) isolates populate the respiratory tracts of children with CF. HA-MRSA isolates predominated, but CA-MRSA strains predominated among CF patients with newly acquired MRSA strains and among the non-CF patients. The presence of CA-MRSA strains in children with CF was not associated with exacerbation or necrotizing pneumonia.

Figures in this Article

Staphylococcus aureus is an important pathogen that is commonly isolated from the respiratory tracts of patients with cystic fibrosis (CF).1Many S aureus isolates are resistant to methicillin, although this antibiotic is no longer used clinically. Nevertheless, the term methicillin-resistant S aureus (MRSA) has persisted and implies cross-resistance to all available β-lactam antibiotics including penicillins and cephalosporins. The rate of recovery of MRSA from the respiratory tract of patients with CF is increasing.2 In 1995, only 0.1% of patients who reported to the Cystic Fibrosis Foundation Patient Registry had MRSA recovered from a respiratory tract culture, although a data field for MRSA was not included in the registry at that time. In 2001 and 2005, the percentages were 7.3% and 17.2%, respectively.35 This increase has paralleled a similar increase in the incidence of community-associated MRSA (CA-MRSA) in the general population in many areas in the United States69 and elsewhere in the world.10The MRSA isolates responsible for this CA-MRSA epidemic are novel and differ from the so-called health-care–associated MRSA (HA-MRSA) isolates that have been described for many decades. CA-MRSA isolates contain small mobile genetic elements, called staphylococcal chromosome cassette mec (SCCmec) type IV or V, that mediate methicillin resistance. They also usually carry the genes for the Panton-Valentine leukocidin (PVL), a pore-forming exotoxin carried on bacteriophages, and other virulence factors usually not found in HA-MRSA strains.13 In the United States, most CA-MRSA isolates belong to the pulsotype designated USA300 and to multilocus sequence type (ST) 8.14CA-MRSA isolates have been implicated in skin and soft tissue infections, and in serious infections including necrotizing pneumonia and severe sepsis.1517

Limited data exist, however, about the genetic backgrounds of the MRSA strains found in the respiratory tract of patients with CF, so it is not clear whether HA-MRSA or CA-MRSA strains are responsible for the increase in the incidence of MRSA in the CF population. Furthermore, the clinical impact of MRSA on the status of a patient with CF, both in the short term and the long term, has not been defined.2

Recently, it has been suggested18 that the likelihood of hospitalization and the requirement for treatment with antimicrobial agents were significantly increased in patients with CF and MRSA in the respiratory tract compared with those with methicillin-susceptible S aureus. Patients with CF and MRSA also had significantly greater airflow obstruction. However, the molecular characteristics of the infecting MRSA strains were not investigated, and it was not clear whether these findings were associated with CA-MRSA or HA-MRSA isolates with their different antimicrobial resistance and virulence gene repertoires.

To further investigate the role of MRSA in patients with CF, we sought to characterize the MRSA strains obtained from children with CF and compare those isolates with MRSA strains from non-CF pediatric patients from the same community. To accomplish this, we prospectively collected MRSA isolates from two urban tertiary care children’s hospitals in the United States that experienced epidemics of MRSA infections in the previous decade. We compared the molecular characteristics and antimicrobial susceptibilities of these MRSA isolates and MRSA-associated clinical syndromes in patients with CF with those observed in non-CF pediatric patients.

Setting

The University of Chicago Comer Children’s Hospital (UCCCH) is a tertiary care medical center in Chicago, IL, with 155 inpatient beds. The CF center at UCCCH had cared for 56 children and adolescents at the time of the study. Children’s Medical Center Dallas (CMCD) is a tertiary care medical facility in Dallas, TX, with 411 inpatient beds. The CF center at CMCD had cared for 256 children and adolescents at the time of the study. The percentage of patients with MRSA isolates in 2005 and 2006 was derived from the Epidemiologic Study of Cystic Fibrosis Center report that was forwarded to the Cystic Fibrosis Foundation and was calculated from a review of medical records.

CF patients were seen routinely every 3 months in both centers and at any time when an acute exacerbation occurred. From each patient, an expectorated respiratory tract specimen or an oropharyngeal swab from patients too young to expectorate was obtained at least annually, and usually quarterly, and during any acute exacerbation as recommended by the Cystic Fibrosis Foundation in their infection control recommendations2 and clinical practice guidelines.19 Among hospitalized CF patients, BAL fluid specimens were occasionally obtained from the more severely ill patients. All specimens were transported to the clinical microbiology laboratory for culture and antimicrobial susceptibility testing.

Microbiological Studies and MRSA Surveillance

At both institutions, we prospectively collected all MRSA isolates identified between July 1, 2004 (November 1 at CMCD), and June 30, 2005, from patients in all clinical settings (emergency department, outpatient clinics, and hospitalized patients). At both institutions, the antimicrobial susceptibility profile of each isolate was determined. At the UCCCH, this was done (Vitek 2 system; BioMérieux Vitek, Inc; Durham, NC) for oxacillin, erythromycin, clindamycin, ciprofloxacin, rifampin, gentamicin, linezolid, and vancomycin. All isolates identified by automated testing as being susceptible to oxacillin underwent confirmation by cefoxitin disk susceptibility testing. For isolates that tested resistant to erythromycin but susceptible to clindamycin by single-agent testing, a D-zone test to detect inducible clindamycin resistance was performed. Only those isolates scheduled for D-zone testing were tested for trimethoprim (TMP)/sulfamethoxazole (SMX) susceptibility by disk diffusion. At CMCD, isolates were routinely tested (MicroScan WalkAway system; Siemens; Deerfield, IL) for the above- mentioned antimicrobial agents and TMP/SMX susceptibility. All assays were performed in accord with the Clinical Laboratory Standards Institute guidelines.20 Isolates tested as having intermediate resistance were considered to be resistant.

Molecular Typing of MRSA Isolates

Multilocus sequence typing (MLST) was performed on MRSA isolates as described.21ST types were assigned to clonal complexes (CCs) using the eBURST algorithm, as has been described elsewhere.22The presence of mecA was assessed, and the SCCmec type of each strain was determined by the molecular architecture of the ccr and mec complexes using the polymerase chain reaction, as has been previously described.23 The presence of lukF-PV and lukS-PV encoding the PVL toxin (pvl+) was performed by polymerase chain reaction as described.,23 All MRSA isolates from children with CF, at both centers, underwent molecular typing, as did all non-CF MRSA isolates from UCCCH and a 20% randomly selected sample of the non-CF isolates from CMCD.

Patient Information

For each MRSA patient-isolate, the medical records were reviewed to determine the date of hospital admission, prespecified demographic information, the date of specimen procurement, the anatomic site of the culture, the clinical indication for the culture, antimicrobial susceptibility, radiographic and other testing results, and any history of MRSA isolation since 1994 (1998 at the CMCD). For the CF patient isolates, data were also obtained from the CF clinic databases. For each patient visit, a CF exacerbation was defined by a change from baseline in three or more of the following symptoms: cough; exercise tolerance; sputum production; fever; weight loss; absenteeism from work or school; respiratory rate; physical examination of the lung fields; chest radiograph findings; and spirometry and oximetry results.19 In the absence of an exacerbation, cultures were performed for CF patients as routine surveillance.

Definitions of CA-MRSA and HA-MRSA

Patient-isolates were designated as CA-MRSA or HA-MRSA based on the SCCmec type, and the ST. SCCmec IV-bearing isolates and isolates belonging to CC8 or CC1 were designated as CA-MRSA strains, as these traits are highly correlated with the USA 300 and 400 pulsotypes, respectively.1415 SCCmec-II bearing isolates and/or CC5 isolates were designated as HA-MRSA strains.,1415

Statistical Analysis

Bacteriologic and patient data were compiled in electronic databases (Access; Microsoft; Redmond, WA; and Epi-Info; Centers for Disease Control and Prevention; Atlanta, GA). Only the first isolate collected from each patient during the surveillance period was included. Data were analyzed with a statistical software package (Stata SE, version 9.2; StataCorp; College Station, TX). Comparisons between groups were performed using the χ2 test or Fisher exact test. All hypotheses were evaluated by two-tailed tests and were considered significant at p < 0.05. The study was approved by the institutional review boards of the Biological Sciences Division of the University of Chicago and the University of Texas Southwestern Medical Center.

Study Population

The percentages of patients with an MRSA isolate among patients with CF in 2005 were 27% and 17%, respectively, at CMCD and UCCCH. In 2006, the corresponding percentages were 35% and 23%, respectively.

At UCCCH, 225 unique-patient MRSA isolates were collected during the study period. Seven isolates were from CF patients. At CMCD, 644 MRSA isolates were identified from a prospective review of laboratory records performed during the study period; 57 were from patients with CF. A total of 543 isolates were available and were subjected to antimicrobial susceptibility testing. Of the 543 isolates, 27 were from CF patients. All MRSA isolates from patients with CF and 113 of the non-CF isolates from CMCD underwent molecular typing. In summary, 34 isolates from CF patients and 331 isolates from non-CF patients from both centers combined underwent molecular typing.

The mean ages of the non-CF patients were 5.0 and 5.6 years, respectively, at CMCD and UCCCH (age range, 0.02 to 24.0 years). The mean age of the non-CF patients whose isolates underwent molecular testing was 5.2 years. The mean ages of the patients with CF were 13.1 and 14 years, respectively, at CMCD (age range, 3 to 27 years) and UCCCH (age range, 6 to 20 years).

Of the 34 children with CF and available MRSA isolates, 3 came from specimens obtained during bronchoscopy; the remainder were from sputum or oropharyngeal swabs. Eleven of the 34 patients (32.4%) had MRSA isolated for the first time during the surveillance period. The mean ages of those acquiring MRSA for the first time and those known to be colonized with an MRSA strain prior to the study period were identical (12.6 years of age). However, those acquiring MRSA for the first time were more likely to have an isolate bearing SCCmec IV (7 of 11 vs 4 of 22 children, respectively; p = 0.02 [Fisher exact test]).

For 10 of the CF patients (29.4%) with a MRSA isolate, a specimen was recovered in a pure culture. The concomitant pathogens in the 24 other patients were Pseudomonas aeruginosa (n = 15), Aspergillus spp (n = 4), methicillin-susceptible S aureus (n = 3), Haemophilus influenzae (n = 2), Mycobacterium chelonae-abscessus, Stenotrophomonas maltophilia, Penicillium spp, Achromobacter xylosoxidans, and Burkholderia cepacia complex (1 each) [some patients had more than one concomitant pathogen].

Molecular Typing of MRSA Isolates

The 34 MRSA isolates from children with CF contained SCCmec II or SCCmec IV in, roughly, a 2:1 ratio; one isolate contained an untypable SCCmec element. In contrast, among the non-CF patients, 91% had SCCmec IV and 9% had SCCmec II; one isolate contained SCCmec V (Fig 1 , top).

Not unexpectedly, there were strong associations between SCCmec II and CC5, and between SCCmec IV and CC8. Thus, the stratification of MRSA isolates from CF and non-CF patients by CC (Fig 1, bottom) produced results similar to those when MRSA isolates were stratified by SCCmec type. Among the CF isolates, 71% belonged to CC5, 26% belonged to CC8, and 3% belonged to CC1. The non-CF isolates were heavily weighted toward CC8 (89%), and only 4% were CC5; 7% were CC1, and CC20, CC22, and CC59 were represented by one isolate each.

pvl Genes

Among the MRSA isolates from CF patients, 10 of 34 patients (29.4%) were pvl+. Seven of these 10 patients had MRSA isolated from the respiratory tract for the first time. The percentage of pvl+ strains among the non-CF isolates was higher (85%; 283 of 331 isolates; p < 0.001). This is explained by the nearly universal carriage of pvl genes by CC8 (256 of 264 isolates; 97%) and CC1 (20 of 23 isolates; 87%) MRSA isolates carrying SCCmec IV. Four of 38 of the CC5 isolates (11%) and 3 of 6 isolates (50%) representing other CCs were pvl+.

Antimicrobial Susceptibility

A total of 331 non-CF MRSA isolates and 34 MRSA isolates from children with CF underwent antimicrobial susceptibility testing. After ensuring that there were no significant differences in the rates of resistance to any tested antimicrobial agent when the non-CF isolates obtained from UCCCH and CMCD were compared or when the CF isolates obtained at each center were compared, we pooled the data from the two centers.

Among the MRSA isolates from both the CF and non-CF patients, no tested isolate was resistant to TMP/SMX, linezolid, or vancomycin. MRSA isolates from CF patients were more frequently resistant to clindamycin (Table 1 ) whether by single-agent testing or by classifying D-zone test-positive isolates as resistant. Ciprofloxacin resistance was also more frequent among the patients with CF.

However, the differences in non-β-lactam resistance rates can be accounted for by the differences in the MRSA genetic backgrounds themselves. Isolates harboring SCCmec II, often termed HA-MRSA isolates, have a higher rate of resistance to non-β-lactam antibiotics like clindamycin and ciprofloxacin when compared with isolates harboring SCCmec IV, often termed CA-MRSA isolates. This difference holds true for both the CF and the non-CF MRSA patient isolates (Table 1). Thus, the apparent differences in susceptibility rates between CF and non-CF MRSA isolates are best explained by the higher rate of non-β-lactam resistance among SCCmec II-containing isolates. Put differently, SCCmec IV-containing MRSA isolates have similar resistance profiles whether they were obtained from CF or non-CF patients. The same can be said for MRSA isolates containing SCCmec II.

Association Between SCCmec Types, MLST, pvl, and Clinical Syndromes Among Patients With CF

Eleven patients had MRSA isolated from a specimen obtained during an exacerbation. These so-called exacerbation isolates did not differ significantly from the surveillance MRSA CF isolates in terms of the percentage that were pvl+ (3 of 11 isolates [27.3%] vs 7 of 23 isolates [30.4%], respectively; p = 1.0), the percentage that carried SCCmec IV (2 of 11 isolates [18.2%] vs 9 of 23 isolates [39.1%], respectively; p = 0.27), the percentage that carried SCCmec II (8 of 11 isolates [72.7%] vs 14 of 23 isolates [60.8%], respectively; p = 0.71), or the percentage that belonged to CC8 (2 of 11 isolates [18.2%] vs 7 of 23 isolates [30.4%], respectively; p = 0.68).

MRSA isolates increasingly populate the respiratory tracts of children with CF.45 Data from the Cystic Fibrosis Foundation Patient Registry taken together with the prevalence data obtained from our chart reviews document that the rate of recovery of MRSA from the respiratory tracts of patients with CF has continued to increase. We may have even underestimated the prevalence of MRSA in our CF population since we did not optimally culture for S aureus small-colony variants, which are known to be present in the sputum of patients with CF.,2425

The reasons for the increase in MRSA colonization are not clear. MRSA disease has been epidemic in the United States, usually occurring among otherwise healthy patients in many communities, including those at UCCCH and CMCD. The isolates causing epidemic MRSA disease in otherwise healthy individuals typically contain SCCmec IV and carry the pvl genes.26

We found that the molecular epidemiology of the MRSA isolates populating the respiratory tract of our patients with CF is complex. The majority of the MRSA isolates from CF patients that we typed are the so-called HA-MRSA strains. They contain SCCmec II and nearly always lack the pvl genes. Finding these HA-MRSA isolates among patients with CF comes as no surprise since patients with CF have frequent contact with the health-care system. The substantial frequency with which we identified CA-MRSA isolates that contained SCCmec IV and the pvl genes among these patients is also noteworthy. The pvl+ isolates have been implicated in the pathophysiology of necrotizing pneumonia, although the specific role in pathogenicity attributed to this toxin is controversial.2728 Of particular interest was the higher percentage of CA-MRSA isolates found among those persons acquiring MRSA colonization during the study interval. Should this trend continue, it is possible that these CA-MRSA isolates may become the predominant MRSA genetic backgrounds among CF patients in the United States in the future.

We found no association with CA-MRSA or HA-MRSA and pulmonary exacerbation. Even among patients with CF and pvl+ MRSA, we encountered no patients with focal lung infiltrates, necrotizing pneumonia, or lung abscesses. Our findings contrast with those of a recent report29 from St. Louis in which six children with CF and pvl+ MRSA strains were more likely to have a focal pulmonary infiltrate (including two patients with lung abscess), a greater decline in lung function at the time of MRSA detection, and a requirement for hospitalization and IV antibiotic therapy. However, our study design included only the first MRSA isolate from each patient during the study period. A longitudinal study may have been more informative.

MRSA isolates from children with CF were more often resistant to non-β-lactams such as clindamycin and ciprofloxacin than those from non-CF patients. When stratified by SCCmec type, however, this difference reflected the genotype of the isolate. HA-MRSA isolates are often resistant to multiple antibiotics, whereas CA-MRSA isolates are typically broadly susceptible to non-β-lactam antimicrobial agents. This is because SCCmec II-containing, clindamycin-resistant, pvl-negative isolates (HA-MRSA strains) predominated among the CF patients, although CA-MRSA isolates were not rare. In contrast, the otherwise healthy non-CF patients seldom had such HA-MRSA isolates; thus, among their isolates, SCCmec IV, clindamycin- and ciprofloxacin-susceptible, pvl+ isolates predominated.

Other investigators30 have suggested that the epidemiology of MRSA among CF patients is complex. Among 21 adults with CF and MRSA in Brisbane, QLD, Australia, 11 patients (52%) had one of the two MRSA strains that were endemic at the local hospital; the rest had genetically distinct MRSA strains. Among nine CF centers in Belgium, 32 MRSA strains were identified; 66% belonged to one of the epidemic clones disseminated in Belgian hospitals. SCCmec I or III, which are the types usually associated with HA-MRSA, were found in 55% of the MRSA isolates, whereas 45% carried SCCmec IV, which is usually associated with CA-MRSA strains.,25 Data were not presented from these two reports to allow comparison with MRSA isolates circulating among non-CF patients in the community. In the report from St. Louis,29 among 40 MRSA isolates obtained from children with CF, 75% had SCCmec II and 25% had SCCmec IV; MLST data were not available for the majority of the isolates.

Since 2003, there has been an increasing number of reports of transmission within hospitals, in the United States and other countries, of SCCmec IV MRSA strains, which are commonly considered to be CA-MRSA strains. USA300 strains are now the predominant MRSA strains causing hospital- acquired infections at some centers.3134 It will be of interest and importance to continue to monitor MRSA strains in patients with CF in view of the rapidly changing epidemiology of CA-MRSA disease.

As a first step, our data provide an important basis for monitoring trends in the evolving epidemiology of MRSA both among the general pediatric patient population and among children with CF. They also provide guidance for the treatment for MRSA, and support the need for consistent implementation of recommended infection control strategies for patients with CF in inpatient units and ambulatory clinics.

Abbreviations: CA-MRSA = community-associated methicillin-resistant Staphylococcus aureus; CC = clonal complex; CF = cystic fibrosis; CMCD = Children’s Medical Center Dallas; HA-MRSA = health-care–associated methicillin-resistant Staphylococcus aureus; MLST = multilocus sequence typing; MRSA = methicillin-resistant Staphylococcus aureus; PVL = Panton-Valentine leukocidin; SCCmec = staphylococcal chromosome cassette mec; SMX = sulfamethoxazole; ST = sequence type; TMP = trimethoprim; UCCCH = University of Chicago Comer Children’s Hospital

Dr. Glikman is a recipient of a Children’s Research Foundation Grant. Dr. Daum and Dr. Boyle-Vavra are supported by RO1 CCR 523379 and RO1 CI000373-01 from the CDC, and RO1 AI40481-01A1 and RO1 AI067584-01A2 from NIAID, as well by the Grant HealthCare Foundation and grants from GeneOhm, Pfizer, and Clorox. Dr. David is supported by RO1 CI000373-01 from the CDC.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Figure Jump LinkFigure 1. Comparison of SCCmec types (top, A) and MLST clonal complexes (bottom, B) for isolates of patients with CF (n = 34) and for isolates of non-CF patients (n = 331). The non-CF isolates total 101% due to rounding.Grahic Jump Location
Table Graphic Jump Location
Table 1. Comparison Between CF and Non-CF MRSA Isolates When Stratified by SCCmec Type*
* 

Values are given as No./total No. of patients (%), unless otherwise indicated. NS = not significant.

 

Proportion of isolates with SCCmec II vs the proportion of isolates containing SCCmec IV that are resistant to the specific antibiotic (χ2 test or Fisher exact test).

 

SCCmec II, n = 22; SCCmec IV, n = 11; Untypable SCCmec, n = 1.

§ 

Percentage resistant or percentage positive (D-zone test) is in parentheses.

 

Single-agent testing.

# 

SCCmec II, n = 30; SCCmec IV, n = 300 (two isolates were not tested); Untypable SCCmec, n = 1.

The authors wish to thank Jie Peng and Kimberly King for performing molecular studies and maintaining the patient database, and Sophie Miller for helping to generate the graphs and assisting in editing the manuscript. We thank the staff of the Clinical Microbiology Laboratories for their cooperation.

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Figures

Figure Jump LinkFigure 1. Comparison of SCCmec types (top, A) and MLST clonal complexes (bottom, B) for isolates of patients with CF (n = 34) and for isolates of non-CF patients (n = 331). The non-CF isolates total 101% due to rounding.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Comparison Between CF and Non-CF MRSA Isolates When Stratified by SCCmec Type*
* 

Values are given as No./total No. of patients (%), unless otherwise indicated. NS = not significant.

 

Proportion of isolates with SCCmec II vs the proportion of isolates containing SCCmec IV that are resistant to the specific antibiotic (χ2 test or Fisher exact test).

 

SCCmec II, n = 22; SCCmec IV, n = 11; Untypable SCCmec, n = 1.

§ 

Percentage resistant or percentage positive (D-zone test) is in parentheses.

 

Single-agent testing.

# 

SCCmec II, n = 30; SCCmec IV, n = 300 (two isolates were not tested); Untypable SCCmec, n = 1.

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