JAC Advance Access originally published online on April 8, 2008
Journal of Antimicrobial Chemotherapy 2008 62(1):109-115; doi:10.1093/jac/dkn149
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Original research |
Susceptibility of Staphylococcus aureus isolated from skin and wound infections in the United States 2005–07: laboratory-based surveillance study
1 Replidyne Inc., 1450 Infinite Drive, Louisville, CO 80027, USA 2 Eurofins Medinet Inc, 13665 Dulles Technology Drive, Herndon, VA 20171, USA
* Correspondence address. Replidyne Inc., 472 Wheelers Farms Road, Milford, CT 06460, USA. Tel: +1-203-301-2166; Fax: +1-203-301-2199; E-mail: gtillotson{at}replidyne.com
Received 24 January 2008; returned 25 January 2008; revised 11 March 2008; accepted 11 March 2008
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Abstract |
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Objectives: The aim of this study was to describe the rates of antimicrobial susceptibility of Staphylococcus aureus from skin and wound infections reported from nine regions of the USA during 2005–07 and to identify the regional variation in patterns of resistance.
Methods: The Surveillance Network (TSN) comprises 296 laboratories across the nine census regions of the USA. TSN laboratories reported the susceptibility data for six antimicrobials by isolate with source and other relevant data. Antimicrobial susceptibility data were analysed by individual drug resistance, multidrug resistance and geographical distribution of resistance phenotypes.
Results: There were over 380 000 isolates of S. aureus tested and reported for the period 2005–07. Methicillin resistance was observed in 57.8% in 2007, with little change from 2005. There was little difference in rates of methicillin resistance between community and hospital strains, although strains from intensive care units (ICUs) tended to be slightly more resistant overall. Resistance to other antimicrobials was also reported. A regional variation in resistance rates was noted with the highest rates in the Central states and lowest in the New England and Mid-Atlantic regions. There was high activity observed with trimethoprim/sulfamethoxazole and gentamicin. Linezolid resistance was rare. Oxacillin resistance was similar among paediatric and elderly cohorts, whereas ciprofloxacin and clindamycin resistance was significantly (P < 0.01) more common in elderly patients when compared with both paediatric and adult populations. Less than a third of all isolates showed no resistance mechanism, 30.3%. Three distinct resistance phenotypes accounted for 46% of all resistant strains. Overall, there were more highly drug-resistant isolates from the ICU with four, five or six drug-resistant phenotypes accounting for over a third of all strains.
Conclusions: S. aureus has become methicillin-resistant in both the community and hospital settings; however, little change has been seen in the past 3 years. Multiresistant strains now are seen in all settings, but due to regional variation, empirical therapy should be guided by local susceptibility patterns. Currently, among the agents studied, only trimethoprim/sulfamethoxazole, gentamicin and linezolid exhibit susceptibility rates of >95%.
Keywords: S. aureus , methicillin resistance , multidrug resistance , skin infections , community-acquired , inpatient , ICU
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Introduction |
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Staphylococcus aureus has recently gained significant notoriety in both the medical and lay press and media principally through an apparent increase in the proportion of fatal infections, notably among children. The awareness of physicians and public alike has been elevated, and changes in clinical practice may be driven by panic and concern. The increase in strains of S. aureus producing Panton–Valentine leucocidin (PVL) seems most apparent in community-acquired infections, although little longitudinal data exist to support this perception. Nevertheless, PVL-positive methicillin-resistant S. aureus (MRSA) are an increasing cause of infections, a number of which have rapidly progressed to hospitalization or fatality.1–3 This article presents data from a large-scale laboratory-based surveillance programme over the period 2005–07 from almost 300 hospitals across the USA.
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Methods |
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The Surveillance Network (TSN®) was the data source for this investigation. It comprises an electronic database of strain-specific, qualitative and quantitative antimicrobial susceptibility test data reported by clinical laboratories in the USA that has been previously used to evaluate trends concerning antimicrobial susceptibility.4–6 The TSN database contains over 120 million susceptibility results collected from 296 US institutions. Susceptibility was determined according to CLSI breakpoints that were current in the year of testing.7–9 Besides in vitro susceptibility data, TSN gathers profiles from other queries that can be used individually or in any combination for the analysis of susceptibility data including organism identification, national and regional geography, such as the nine regions of the US Bureau of Census, institution demographics (type and number of beds), patient demographics (age, gender and location) and specimen source.
This analysis focused specifically on S. aureus and used TSN to investigate S. aureus isolated from January 2005 to September 2007. The overall prevalence of S. aureus isolates taken from skin and wound specimen sources was studied according to patient location including inpatient, intensive care unit (ICU) and outpatient. Strains of S. aureus isolated from skin or wound infections were used as the source most likely to yield the highest incidence of this species as per Styers et al.10 MRSA rates for the study period were estimated by year. In addition, S. aureus and MRSA specifically were analysed by US Bureau of Census region. Susceptibility to erythromycin, trimethoprim/sulfamethoxazole and levofloxacin were examined as well as multidrug-resistant (MDR), defined as concurrent resistance to three or more of the following agents: ciprofloxacin, clindamycin, erythromycin, gentamicin, oxacillin and trimethoprim/sulfamethoxazole. Only strains tested simultaneously against each of these agents were included in the MDR analysis of prevalence and distribution of resistance. All incidence rates were compared statistically using 
2 analysis, with a P value of less than 0.05 being significant.
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Results |
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The rate of resistance among S. aureus over the period 2005–07 is shown in Table 1. Overall MRSA rates in the USA showed little change between 2005 and 2006, but there was a significant difference in oxacillin resistance between 2006 and 2007 (P < 0.05). In 2007, the overall rate of MRSA was 57%, with significant differences between outpatient (56.0%), inpatient (58.9%) and ICU isolates (61.5%) (Table 2).
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Erythromycin resistance increased from 64.2% in 2005 to 64.8% in 2007, whereas levofloxacin resistance increased from 37.1% in 2005 to 39.5% in 2007. In contrast, trimethoprim/sulfamethoxazole resistance showed a slight decrease from 2.0% in 2005 to 1.6% in both 2006 and 2007. For all the agents, the rates of resistance were lower in isolates from outpatients when compared with isolates from inpatients or ICU patients (Table 2).
The regional differences in resistance among S. aureus in 2007 are shown in Figure 1. The lowest rate of MRSA was observed in the New England region (48.1%) and in the Mid-Atlantic region (48.9%), compared with the highest rates observed in the East South Central region (67.3%) and in the West South Central region (67.0%); these differences were statistically significant (P < 0.05). The West South Central region also showed the highest erythromycin resistance rate (72.3%), when compared with New England, which retained the lowest resistance rate of 56.8% (P < 0.05). Levofloxacin, as a representative of the fluoroquinolones used to treat skin infections when compared with other oral antibiotics, showed a lower overall resistance rate of 39.5% in 2007, but still regional differences were reported, with New England showing the lowest resistance rate of 23.4% when compared with the Mountain region showing a statistically significantly higher resistance rate of 52.4%. Of note, the lowest resistance rates were seen with trimethoprim/sulfamethoxazole (for which the rates ranged from 0.7% in West North Central and East South Central to 3.7% in East North Central) and vancomycin, for which no resistance was detected. Linezolid resistance was reported in 13 of 80 527 isolates in 2007 (Table 1), although these have not been confirmed. Although increasingly used to manage superficial skin infections, mupirocin was not tested in any laboratory. Thus, we are unable to comment on resistance emergence to this agent.
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Among MDR isolates, the most commonly observed resistances were to erythromycin (99.4%), oxacillin (95.1%) and ciprofloxacin (95.6%), whereas resistance to gentamicin and trimethoprim/sulfamethoxazole was seen in 5.7% and 3.9% of the MDR isolates, respectively (Table 3). The analysis of the database by patient age showed that the proportion of S. aureus isolates that were MRSA was approximately the same in those aged
16 years and the elderly (
65 years) (52.5% versus 51.3%, respectively, P = 0.2), whereas the rate seen among those aged 17–64 years was significantly higher (56.5%; P < 0.01) compared with both the paediatric and elderly populations (Table 4). Another interesting observation was the significantly lower proportion of S. aureus strains resistant to ciprofloxacin in patients aged 16 years (19.4%) when compared with isolates from patients aged 17–64 (34.7%) or 65 years (49.2%) (P < 0.01 for both comparisons). A similar trend was also noted with clindamycin with resistance seen in 8.9%, 15.7% and 33.8% of the isolates for the three respective cohorts (P < 0.01 for 16 year group compared with both 17–64 year and 65 year cohorts).
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In 2007, less than a third (30.3%) of all strains of S. aureus were pan-susceptible, whereas 11.6% expressed a single resistance phenotype (Table 5). MDR was noted in 32% of the isolates. The distribution of these phenotypes by patient location among skin or wound infections is shown in Table 6. Generally, the isolates from outpatient specimens were more susceptible than either inpatient or ICU sources. More strains carried two resistance mechanisms in the outpatient cohort, ~30% compared with ~10% among the ICU strains. Strains having four or more resistance mechanisms were seen more often in the ICU and inpatient strains than community S. aureus.
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Discussion |
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Despite the current publicity surrounding MRSA, the overall rate of methicillin (oxacillin) resistance did not alter markedly in the 3 year study period, with almost two-thirds of all S. aureus, the most common cause of skin infections, being resistant to methicillin and macrolides. Concurrently, resistance to levofloxacin and other fluoroquinolones exceeded 20%, a threshold previously considered by the Infectious Disease Society of America to be suggestive of likely poorer outcomes.
However, what is not clear from this surveillance is the incidence of PVL-positive S. aureus, regardless of methicillin resistance. Although there is controversy over the exact role of PVL in serious staphylococcal disease, it still serves as a good marker of potentially difficult-to-treat staphylococcal infections based on the many reports of rapidly fulminant infections.11
One clear trend observed was the inter-regional difference in staphylococcal resistance; the New England and Mid-Atlantic regions generally had the lowest resistance rates, whereas the Central regions usually showed higher resistance rates. Other interesting differences included the higher incidence of MDR phenotypes in both inpatient and ICU isolates when compared with outpatient strains and the lack of age difference in terms of methicillin resistance, although both clindamycin and ciprofloxacin resistances were lower in isolates from those aged 16 years. This latter difference may be due to less drug exposure as children are rarely treated with fluoroquinolones.
Ellingson et al.12 recently reported management approaches of skin infections in the USA where 13.3% of the patients had incision and drainage, whereas only 7% of the patients with skin infections had a culture performed with 4% having both incision and drainage and culture. Overall, almost >75% had neither incision and drainage nor culture performed. Recent analysis of over 50 million US patient visits due to skin infections requiring an antibiotic highlighted the continued use of cefalexin and other β-lactams as initial empirical therapy with topical agents only being used for impetigo or furuncles. There was very little use of agents such as trimethoprim/sulfamethoxazole or doxycycline.13
Thus, on the basis of these habits and trends, the local application of TSN data may help improve the management of these infections most recently highlighted in both medical and lay media. However, only prospective and more expansive surveillance including isolates from infections not previously examined, such as impetigo, minor abrasions, or simple wounds, will continue to guide empirical management and therapy. In addition, testing of a sample of these strains for virulence factors will also assist in the education of both primary care and hospital health providers as MRSA from the community seemingly merges with the more antibiotic-resistant hospital-acquired strains.
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The work was internally funded and not supported by any grant, contract or other financial incentive.
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G. S. T. and I. A. C. are employees of Replidyne Inc., D. C. D., K. M. T., T. d. F. and D. F. S. are employees of Eurofins-Medinet. Replidyne is a biopharmaceutical company that conducts research & development in the anti-infective field. Both G. S. T. and I. A. C. hold stock in the company. Eurofins Medinet is a full service global central laboratory that owns the TSN® database. None of the authors will benefit financially from this work or related data.
Author contributions. Acquisition of the data: D. F. S., D. C. D. and K. M. T. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis; study design: G. S. T., I. A. C. and D. C. D.; data collation: D. C. D., K. M. T. and T. d. F.; data analysis: G. S. T. and D. C. D.; statistical analysis: Vaishali Joshi; drafting of the manuscript: D. C. D. and G. S. T.; critical review of the manuscript for important intellectual content: D. F. S., I. A. C., T. d. F., K. M. T., G. S. T. and D. C. D.; funding: no specific funding; administrative, technical or material support: T. d. F. and K. M. T.; study supervision: G. S. T.
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1 Fridkin SK, Hageman JC, Morrison M, et al. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med (2005) 352:1436–44.
2 Anon. Severe methicillin-resistant Staphylococcus aureus community acquired pneumonia associated with influenza—Louisiana and Georgia, December 2006–January 2007. MMWR Morb Mortal Wkly Rep (2007) 56:325–9.[Medline]
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5 Jones RN, Fritsche TR, Sader HS, et al. LEADER surveillance program results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from the United States (50 medical centers). Diagn Microbiol Infect Dis (2007) 59:309–17.[Web of Science][Medline]
6 Pillar CM, Draghi DC, Sheehan DJ, et al. Prevalence of multi-drug resistant, methicillin-resistant Staphylococcus aureus in the United States: findings of the stratified analysis of the 2004–2005 LEADER surveillance programs. Diagn Microbiol Infect Dis (2008) 60:221–4.[CrossRef][Web of Science][Medline]
7 Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Fifteenth Informational Supplement M100-S15 (2005) Wayne, PA, USA: CLSI.
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10 Styers D, Sheehan DJ, Hogan P, et al. Laboratory-based surveillance of current antimicrobial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States. Ann Clin Microbiol Antimicrob (2007) 5:2.
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12 Ellingson K, Gorwitz RJ, Pearson ML. Variability in practice patterns for out-patient management of staphylococcal skin and soft tissue infections. In: Abstracts of the Forty-fifth Annual IDSA Meeting, San Diego, CA, 2007. Abstract 299.
13 International Medical Statistics, National Data Trends Information, USA Audit data for oral antibiotic prescriptions, 2006. IMS, Plymouth Meeting, PA, USA.
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