HA-MRSA cases were defined as follows: 1 an MRSA infection identified after 48 hours of hospital admission; 2 a history of hospitalization, surgery, dialysis, or residence in a long-term care facility within 1 year of the MRSA culture date; 3 a permanent indwelling catheter or percutaneous medical device present at the time of culture; or 4 a known positive culture for MRSA before the study period.
To treat MRSA keratitis, empirical or fortified antibiotics were administered hourly. Subsequent modifications to the antibiotic treatment regimens were made according to the culture results, susceptibility testing, and clinical response. Surgical interventions, such as amniotic membrane transplantation, tarsorrhaphy, patch graft, or therapeutic penetrating keratoplasty, were indicated in some cases based on the clinical conditions.
The healing time was also recorded once the infiltration had subsided and the epithelial defect had healed. Where data were available, visual acuity was recorded at least 2 months after the keratitis had subsided and stabilized. For the purpose of statistical analysis, Snellen visual acuity values were converted into logMAR units.
The schedule reported by Scott et al. The criteria proposed by Tenover et al. The SCC mec typing was determined using a previously described multiplex polymerase chain reaction PCR strategy [ 24 ]. Statistical significance was defined as. Twenty-six cases of MRSA keratitis were identified, including 12 Table 1 shows the demographic data of the patients with MRSA keratitis. Table 2 presents the clinical findings of MRSA keratitis.
There was no difference in the location, infiltration size, and presence of hypopyon between the 2 groups. Table 3 lists the predisposing factors for MRSA keratitis. Additionally, a higher percentage of the patients with HA-MRSA keratitis had a recent history of using topical antibiotics or corticosteroids. No difference was observed between the 2 groups for other local risk factors, such as contact lens wear, trauma, and previous ocular surgery.
Table 4 lists the antibiotic susceptibility of MRSA. All MRSA isolates were susceptible to vancomycin and teicoplanin, but resistant to clindamycin, erythromycin, and penicillin. Table 5 presents treatment and outcome of MRSA keratitis. All patients with MRSA keratitis were treated with topical antibiotics. Three patients were refractory to medical treatment; 2 patients one in each group underwent patch grafts with glycerol-preserved cornea; one patient with severe CA-MRSA keratitis, who had no light perception at presentation and responded poorly to medical treatment, underwent evisceration.
Other 6 patients received amniotic membrane transplantation or tarsorrhaphy to promote reepithelialization. There were no significant differences in the rate of surgical intervention, admission, severe complications including corneal perforation and endophthalmitis , or healing time between the 2 groups. In addition, there was no significant difference between the 2 groups in terms of the final visual outcomes.
Eight MRSA isolates were available for the genotyping analysis. Shanmuganathan et al. Khan et al. Compared with previously reported cases of MRSA keratitis, the infections observed in our study appeared to be more severe.
Previous reports indicated that ocular surface disease was a significant risk factor for MRSA keratitis [ 27 — 29 ]. Hori et al. Fukuda et al. In addition, local immunocompromised status could promote colonized MRSA to be pathogenic.
In our patients with MRSA keratitis, the associated ocular surface diseases included dry eye, exposure keratitis, trichiasis, Stevens-Johnson syndrome, and ocular pemphigoid. Such patients frequently had a compromised integrity of ocular surface and corneal epithelial defect; they were typically treated with topical corticosteroids and antibiotics, and they occasionally wore therapeutic contact lenses.
All of these factors might predispose the patients to MRSA corneal infection. The higher rate of systemic comorbidities and previous use of topical antibiotics or corticosteroids in the patients with HA-MRSA keratitis in this study was probably because these patients might require frequent hospital visits; hence, they were more exposed to HA-MRSA.
Recently, Hong et al. We did not test fluoroquinolones in our microbiology laboratory because they were not included in the recommended list of antibiotics published by the CLSI. Because fluoroquinolones are effective broad-spectrum antibiotics and are commonly used as an empirical monotherapy for bacterial keratitis, we would extend the antibiotic susceptibility profiles to include fluoroquinolones to determine whether there are any differences between CA-MRSA and HA-MRSA isolates in future studies.
Although the rate of admission, complications, and surgical intervention was higher in the patients with CA-MRSA keratitis, there was no statistically significant difference between the 2 groups.
Additionally, we did not detect a difference in the visual outcomes between the 2 groups. Rutar et al. The authors of that study acknowledged that severe MRSA infections may have been overrepresented because only isolates from cultures were included in that study.
Sueke et al. Our clinical microbiology laboratories retain only isolates from blood for long-term storage; only 8 isolates were available for genotyping analysis, so it was difficult for us to determine whether there were interspecies differences in the CA-MRSA keratitis cases observed in this study. Moreover, the statistical power of our study was limited by the small sample size.
This study was limited by its retrospective nature and small sample. The treatment protocols varied among the physicians, and there were inherent flaws of visual acuity with variable interval as an outcome measure. In addition, we used oxacillin testing as a surrogate to identify the resistant species of S.
Moreover, the patient selection criteria may have influenced the data interpretation because our patients came from a referral-based tertiary-care institution. Therefore, caution should be applied when generalizing the results.
Nevertheless, larger studies are warranted to further evaluate this association. The authors declare that there is no conflict of interests regarding the publication of this paper.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the paper. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles.
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Results were computed using SAS statistical software Version 8. During , unique patients with a S aureus isolate from a clinical culture were identified from 10 participating facilities data on total S aureus infections were not available at 2 facilities Table 1. The distribution of clinical infections differed between community-associated and health care—associated MRSA cases Table 4.
Compared with health care—associated cases, community-associated case infections were more likely to involve skin and soft tissue OR, 4. Susceptibility and PFGE testing were performed on community-associated isolates 25 isolates were unavailable from participating facilities and a representative sample of health care—associated isolates see "Methods" section.
Oxacillin resistance a surrogate for methicillin resistance was confirmed in all MRSA isolates. Among community-associated isolates, susceptibilities did not differ between pediatric and adult isolates. Community-associated isolates from skin sites were more likely to be susceptible to ciprofloxacin OR, 1. Community-associated MRSA isolates were also more likely than health care—associated MRSA isolates to be susceptible to all 4 of the following antimicrobial agents: ciprofloxacin, clindamycin, gentamicin, and trimethoprim-sulfamethoxazole OR, 5.
In a logistic regression model adjusted for age, sex, surrogate income, laboratory location Minneapolis-St Paul metropolitan vs greater Minnesota , and culture site skin vs other , susceptibility to all 4 antimicrobials was an independent predictor of having a community-associated case definition adjusted OR, 2. Overall, distinct PFGE subtype patterns were identified. A third clonal group, designated clonal group H, was strongly associated with health care—associated isolates.
In another multivariate model adjusted for age, sex, surrogate income, laboratory facility Minneapolis-St Paul metropolitan area vs greater Minnesota , and culture site skin vs other , PFGE clonal groups A and B adjusted OR, 2. Both exotoxin genes eg, Panton Valentine leukocidin genes , and gene alleles SCC mec alleles and accessory gene regulator alleles were disproportionately distributed between community-associated and health care—associated isolates Table 6.
Of 25 genes tested, 8 genes were not identified in any isolates listed in Table 6. Of the 16 exotoxin genes that were present in at least some MRSA isolates, 6 Panton Valentine leukocidins, staph enterotoxins A, C, and K, accessory gene regulator 3, and SCC mec IV were significantly more likely to be found among community-associated isolates, and 7 were significantly more likely to be found among health care—associated isolates.
Only 3 exotoxin genes were found in the majority of case isolates from both groups. Even though the mecA gene, which confers methicillin resistance, and the accessory gene regulator alleles were present in all isolates, SCC mec IV allele and agr 3 allele were statistically more likely to be present in community-associated isolates than in health care—associated isolates. Conversely, SCC mec II and agr 2 were more commonly identified among health care—associated isolates.
This is the first prospective comparison of community-associated and health care—associated MRSA cases in the United States, to our knowledge, and it is the first study performed at multiple sites. In fact, a previous study in Minnesota showed that there were actually strong similarities eg, age distribution, infection characteristics between community-associated methicillin-sensitive S aureus infections and community-associated MRSA patients.
This speculation is further strengthened by a recent report documenting this event in a clinical isolate, and by the fact that SCC mec IV is probably more mobile than other SCC mec alleles. Another unique feature of our investigation was our attempt to collect MRSA isolates from all reported cases. Community-associated MRSA isolates were more likely to be susceptible to multiple antimicrobial classes and to have distinct molecular features based on PFGE compared with health care—associated isolates.
These findings further support our contention that most community-associated MRSA infections in Minnesota are not due to casual health care exposures or to MRSA strains that originated in health care settings, although this remains controversial.
The differences in exotoxin genes between community-associated and health care—associated isolates also suggest that the pathogenesis of these MRSA infections may differ.
Recent evidence indicates that Panton Valentine leukocidins and the SCC mec IV allele, which are rarely found in health care—associated MRSA strains globally, are common among community-associated MRSA strains from 3 different continents, even though community-associated strains from these continents do not share a common genetic lineage. In Europe, Panton Valentine leukocidin genes are associated with community-associated staphylococcal skin infections and necrotizing pneumonia.
Furthermore, the community-associated MRSA strains responsible for severe cases of necrotizing pneumonia in Minnesota and North Dakota 7 all had Panton Valentine leukocidin genes.
Our study had several limitations. Misclassification, however, would only have minimized the observed differences between community-associated and health care—associated MRSA patients and isolates.
Because our study was not population-based, it is possible that MRSA cases identified through sentinel site surveillance were not representative of all cases that occurred throughout Minnesota.
However, to date there have been no published population-based studies of MRSA patients and isolates. We also believe that our study is more representative than previous studies because we identified cases from multiple laboratory facilities in both urban and rural areas from different geographic locations statewide.
Finally, because we have not studied MRSA colonization in Minnesota, we cannot determine the prevalence of MRSA among those colonized with S aureus , and therefore we do not know whether community-associated MRSA strains are more likely than other S aureus strains to cause disease. Because there are epidemiological and microbiological differences between community-associated and health care—associated MRSA infections, strategies to prevent and treat these infections likely differ as well.
To prevent clinical complications from community-associated MRSA infections, clinicians working in outpatient or emergency department settings should consider practice modifications in areas where such infections are known to be prevalent.
Because most community-associated MRSA isolates were susceptible to several already-available antimicrobial agents, and because most patients had noninvasive infections, the treatment of community-associated MRSA infections should not routinely require the use of vancomycin.
However, patients with MRSA infections should be evaluated and treated appropriately and receive follow-up evaluation to ensure resolution of their infection. To improve prevention strategies, more work is needed to characterize specific risk factors for community-associated MRSA infections.
However, at least one study has implicated prior exposure to antimicrobial agents as an independent risk factor for community-associated MRSA infection. Currently, there are no data to suggest that decolonization protocols for MRSA patients or their families are necessary or have long-term effectiveness. Resistance to antimicrobial agents used for decolonization has evolved rapidly in settings in which such strategies have been attempted. Because community-associated infection is frequently identified in children, questions have arisen regarding transmission in group settings.
Future strategies such as vaccination to prevent S aureus infections in both community and health care settings hold greater promise. However, it is likely that antimicrobial-resistant strains of S aureus will continue to evolve and that S aureus will remain an important and adaptive human pathogen. Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue.
Figure 1. Figure 2. The reference strain was MR14, which was the most commonly identified pattern among Minnesota methicillin-resistant S aureus isolates with a community-associated case definition. Figure 3.
Isolates from clonal group H were statistically associated with health care—associated case status. Isolates from clonal groups B and A were statistically associated with community-associated case status. NCTC represents a molecular weight standard. Table 1. Table 2. Table 3. Table 4. Table 5. Table 6.
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