Published online October 31, 2008
PEDIATRICS Vol. 122 No. 5 November 2008, pp. 1039-1046 (doi:10.1542/peds.2007-3161)
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ARTICLE

Emergence of and Risk Factors for Methicillin-Resistant Staphylococcus aureus of Community Origin in Intensive Care Nurseries

Ulrich Seybold, MD, MSCRa,b,c, J. Sue Halvosa, MScc, Nancy White, RNc, Victoria Voris, RN, MPHc, Susan M. Ray, MDb,c and Henry M. Blumberg, MDb,c

a Medizinische Poliklinik, Ludwig Maximilians University, Munich, Germany
b Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
c Epidemiology Department, Grady Memorial Hospital, Atlanta, Georgia


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. The goal of this study was to define more clearly the impact of community-acquired methicillin-resistant Staphylococcus aureus clones (eg, USA300 and USA400) on colonization and infection in infants in intensive care nurseries and potential modes of transmission of community-acquired methicillin-resistant S aureus clones.

METHODS. Prospective surveillance for methicillin-resistant S aureus colonization and infection was performed among infants in the intensive care nurseries at Grady Memorial Hospital (Atlanta, GA) between 1993 and 2006. Beginning in September 2004, nares surveillance cultures were collected at admission. Methicillin-resistant S aureus isolates were genotyped by using pulsed-field gel electrophoresis and multiplex polymerase chain reaction assays for staphylococcal chromosomal cassette mec gene complex type and Panton-Valentine leukocidin genes. Prevalence of and risk factors for colonization with community-acquired versus health care-associated methicillin-resistant S aureus clones (eg, USA100) were assessed.

RESULTS. Between 1993 and 2006, 130 (3.5%) of 3707 infants were identified to be colonized with methicillin-resistant S aureus. Twelve (1.2%) of 996 admission nares cultures were positive for methicillin-resistant S aureus (since initiation of admission cultures in September 2004). Community-acquired methicillin-resistant S aureus clones were first recovered in 1998; the proportion of methicillin-resistant S aureus clones of community origin increased significantly between 1998 and 2004. Multivariate analysis identified vaginal delivery and maternal smoking, both among infants of mothers receiving systemic antibiotic treatment before delivery, as independent predictors for neonatal colonization with community-acquired methicillin-resistant S aureus. Systemic antibiotic therapy before delivery for nonsmoking mothers delivering through cesarean section and possibly endotracheal intubation were associated with the recovery of health care-associated methicillin-resistant S aureus clones.

CONCLUSIONS. Community-acquired methicillin-resistant S aureus clones have emerged as a major cause of methicillin-resistant S aureus colonization in high-risk newborns. Community-acquired methicillin-resistant S aureus recovery was associated with acquisition during birth, whereas health care-associated methicillin-resistant S aureus clones seemed to be transmitted nosocomially.

Key Words: Staphylococcus aureus • methicillin resistance • pulsed-field gel electrophoresis • colonization • NICU

Abbreviations: MRSA—methicillin-resistant Staphylococcus aureus • CA—community-associated • ICN—intensive care nursery • HA—health care-associated • PFGE—pulsed-field gel electrophoresis • SCCmec—staphylococcal chromosomal cassette mec gene complex • PVL—Panton-Valentine leukocidin • OR—odds ratio • CI—confidence interval • CDC—Centers for Disease Control and Prevention • PFT—pulsed-field type • aOR—adjusted odds ratio

The incidence of health care-associated (HA) methicillin-resistant Staphylococcus aureus (MRSA) infections in the United States and throughout the world has increased dramatically over the past 3 decades.1,2 MRSA has also emerged as an important cause of community-associated (CA) infections2,3 in both adult4–11 and pediatric12–16 populations. Novel MRSA clones of community origin (CA-MRSA clones, eg, USA300 and USA400, as opposed to HA-MRSA clones, eg, USA100 and USA2003) were first observed in the United States in 199712,15 and initially were recovered from patients without traditional HA-MRSA risk factors.3 More recently, CA-MRSA clones have been reported to cause HA infections, both at our institution5 and elsewhere.17

MRSA is an important pathogen in NICUs.14,18–20 Infants in the NICU are at increased risk for infectious complications in general,21 and low birth weight, peripherally inserted central catheters, parenteral nutrition, and endotracheal intubation are associated with increased risk for invasive MRSA disease.20,22 Despite neonates' exclusive exposure to a health care environment, CA-MRSA clones have been described as nosocomial pathogens among NICU patients.14,16,22–27 In addition, very early colonization was shown recently, which suggests a potential role for maternal transmission.20 The mechanisms of acquisition of CA-MRSA in this setting are incompletely defined. In addition, little is known about specific risk factors for colonization with CA-MRSA versus HA-MRSA clones or the molecular epidemiology of MRSA over a long period in the NICU setting. The purpose of this study was to determine the prevalence and molecular epidemiology of colonization with MRSA among infants in the intensive care nursery (ICN) between 1993 and 2006 and to assess risk factors for colonization with CA-MRSA versus HA-MRSA clones for these infants, to identify and ultimately to control potential pathways of CA-MRSA transmission.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Population and Data Abstraction
The study took place at Grady Memorial Hospital, a 1000-bed, university-affiliated, public hospital in downtown Atlanta, Georgia, which serves a predominantly minority and indigent patient population. In 2006, there were 1392 discharges from the 66-bed ICN. This study was approved by the Emory University institutional review board and the Grady Memorial Hospital research oversight committee.

An infection control protocol targeting MRSA in the ICN was initially implemented in January 1993, based on the daily surveillance of clinical microbiology records. Growth of MRSA from any patient-related specimen sent for culture by the treating physicians defined a clinical culture positive for MRSA. Measures taken after detection of MRSA in clinical cultures obtained from patients in the ICN included weekly culture surveillance of infants for MRSA; contact precautions28 and cohorting of nursing and respiratory therapy staff members caring for neonates colonized or infected with MRSA, until discharge; and an ongoing education program on hand hygiene and infection control measures. Surveillance cultures were routinely collected from infants' nares; through 1999, additional specimens (mostly perianal skin swabs and endotracheal aspirates) were cultured. Weekly surveillance cultures for MRSA were continued for patients in the ICN until 4 weeks after all known colonized or infected neonates were discharged from the unit. In addition, from September 2004 onward, nares surveillance cultures were collected from infants on the day of admission to the NICU, which usually was the day of birth. All infants with colonization and/or infection attributable to MRSA and detected between January 1, 1993, and December 31, 2006, were included in the study database.

The following infant-related data were collected: date and body site of the first surveillance culture positive for MRSA (defining the index culture) and consecutive cultures positive for MRSA, gender, race/ethnicity, admission and discharge dates, gestational age, birth weight, mode of delivery (ie, vaginal versus cesarean section), Apgar scores at 1 and 5 minutes after birth, date and type of surgery, presence of central vascular access devices (peripherally inserted central catheters, central venous catheters, or umbilical catheters), endotracheal intubation or tracheostomy, peripheral arterial catheters, systemic antibacterial drug treatment, and survival status at discharge. In addition, the following data on infants' mothers were collected: age, prenatal care visits, HIV and syphilis serological status (as determined during pregnancy or at delivery), detection of colonization or infection with Neisseria gonorrhoeae, Chlamydia trachomatis, or group B streptococcus during pregnancy, use of antibacterial drugs during pregnancy and in the peripartum period, and use of cocaine, ethanol, tobacco, or marijuana during pregnancy.

Clinical and Surveillance Cultures
Cultures of clinical specimens collected in the ICN were performed in the Grady Memorial Hospital clinical microbiology laboratory, according to standard methods.29 Surveillance cultures were performed by the Grady Memorial Hospital epidemiology department microbiology laboratory; swabs were plated on trypticase soy agar plates with 5% sheep blood and were incubated at 35°C for 24 hours. Colonies with morphologic features of Staphylococcus species were selected by an experienced microbiologist; identification of S aureus was performed with a commercial kit (BBL Staphyloslide; Becton-Dickinson, Franklin Lakes, NJ), and resistance to oxacillin was tested by culturing on oxacillin screen agar with 6 mg/L oxacillin (Becton-Dickinson).

Molecular Typing
MRSA isolates underwent genotyping with pulsed-field gel electrophoresis (PFGE) after digestion with SmaI, following a standard protocol established at the Centers for Disease Control and Prevention (CDC).3 Band patterns were compared with standard pulsed-field types (PFTs)3 by using BioNumerics software (Applied Maths, Austin, TX) for cluster analysis. A Dice similarity coefficient of ≥80% was used for demonstration of clonal relatedness.3 The staphylococcal chromosomal cassette mec gene complex (SCCmec) type was determined with polymerase chain reaction assays, as described elsewhere.30,31 The presence of the lukS-PV and lukF-PV genes for Panton-Valentine leukocidin (PVL) was demonstrated with polymerase chain reaction assays, as described elsewhere.10 The distribution of MRSA PFTs was determined for each calendar year.

MRSA isolates with the PFTs USA300, USA400, USA1000, and USA1100, as well as novel clones most closely related to any of these 4 genotypes, were considered CA-MRSA.3,32 MRSA isolates of the PFTs USA100, USA200, and USA500 to USA800, as well as related novel clones, were considered HA-MRSA.3

Statistical Analyses
SAS 9.13 (SAS Institute, Cary, NC) was used for data analysis. Tests were 2-sided, at a significance level of {alpha} = .05. CA-MRSA clones first appeared in the Grady Memorial Hospital ICN in 1998, and the first reports in the United States described cases in 1997.12,15 Therefore, the analysis of risk factors for colonization with CA-MRSA versus HA-MRSA clones took into account only the time between January 1, 1997, and December 31, 2006. The measure of association in this prevalence study was the prevalence odds ratio (OR). Continuous variables were compared by using Student's t test or the Mann-Whitney-Wilcoxon test and proportions by using Pearson's {chi}2 test or Fisher's exact test.

Colinearity between gestational age and birth weight was resolved by dividing the observed birth weight by its expected value based on gender and gestational age, as described in the National Center for Health Statistics 1999 and 2000 Natality Data Sets33; this quotient defined the birth weight ratio. The main predictors of interest were mode of delivery and maternal smoking during pregnancy. Interactions between predictor variables and confounding of the effects of the main predictor variables by covariates were assessed. The final multivariate logistic regression model contained the main predictor variables as well as interaction terms and confounders.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Clinical and Patient Surveillance Cultures
Between January 1993 and December 2006, there were 67 infants with clinical cultures positive for MRSA in the ICN at Grady Memorial Hospital, 63 in the NICU (incidence density: 0.60 cases per 1000 patient-days) and 4 in the special care nursery (0.03 cases per 1000 patient-days). After the identification of these patients with clinical cultures positive for MRSA, 14981 weekly surveillance cultures (8867 nares, 4578 rectal, 1216 endotracheal aspirate, and 320 other cultures) were performed. A total of 266 surveillance cultures (1.7%) were positive for MRSA. Collection of surveillance cultures for MRSA in the ICN was triggered by the identification of patients with MRSA-positive clinical cultures and continued weekly for 4 weeks after discharge of the last infected or colonized patient in the unit. Between September 2004 and December 2006, 12 (1.2%) of 996 admission nares cultures were positive for MRSA. Overall, 130 (3.5%) of 3707 unique patients tested were identified as having MRSA colonization. The epidemiological curve for the first recovery of MRSA from weekly and admission surveillance cultures among neonates in the Grady Memorial Hospital ICN, in each 6-month period, is shown in Fig 1. There was a strong association between colonization and subsequent infection with MRSA (OR: 21.2; 95% confidence interval [CI]: 12.0–37.5).


Figure 1
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  		FIGURE 1 Epidemiological findings for patients' first surveillance cultures positive for MRSA (N = 130) per 6-month interval in the ICNs between 1993 and 2006. Admission surveillance cultures were implemented in September 2004.

 
Genotyping of MRSA Isolates From ICN Surveillance Cultures
One hundred twenty-nine of 130 MRSA isolates recovered from surveillance cultures for neonates between January 1993 and June 2006 were available for PFGE typing and 127 for PVL and SCCmec genotyping. PFGE typing results according to year are presented in Fig 2. MRSA isolates recovered during the initial MRSA outbreak in 1993, in the following years through 1997, and from another cluster of neonates in 2000 were all HA-MRSA clones, predominantly USA100. Beginning in 1998, CA-MRSA genotypes were recovered from neonates in the ICN. MRSA USA300 became the predominant genotype by 2004 (Fig 2), accounting for MRSA colonization in 13 (68%) of 19 patients that year. In 2005 and 2006, the number of USA300 isolates decreased, and 3 novel genotypes not contained in the initial national CDC database3 were recovered (designated types C, D, and E for this study). Type C accounted for 5 (25%) of 20 MRSA surveillance isolates in the ICN in 2005; it is PVL-negative, carries the SCCmecIV gene complex, and, among the PFTs described in the national database,3 is most closely related to USA800. Therefore, it was considered a HA-MRSA genotype. Types D and E appeared in 2006. Type D is PVL-negative and carries SCCmecII; it has also been detected in a NICU in North Carolina (L. K. McDougal, MS, personal communication, December 1, 2006) and therefore was considered a HA-MRSA genotype. Type E is PVL-negative and carries SCCmecV; because of its similarity to USA400, it was considered a CA-MRSA genotype. There was a significant increase in the proportion of CA-MRSA clones among all MRSA isolates recovered from infants in the ICN between 1997 and 2004 (P = .03, {chi}2 test for trend) (Fig 2).


Figure 2
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  		FIGURE 2 Distribution of PFTs among 130 MRSA isolates from surveillance cultures in the ICNs between 1993 and 2006. Types A, C, D, and E are PFTs with <80% similarity to any of the PFTs USA100 to USA1100. USA300, USA400, and type E are considered CA-MRSA clones. PFTs USA100, USA500, USA700, and USA800 and types A, C, and D are considered HA-MRSA clones. No isolates with PFTs USA200, USA600, USA1000, or USA1100 were recovered from infants in our ICN. There was a statistically significant trend for an increase in the proportion of CA-MRSA isolates over time (1997–2004; P = .03, Cochran-Armitage exact test for trend). a One isolate was not available for PFGE analysis.

 
No MRSA isolates recovered before 2001 carried the genes for PVL. Starting in 2001, the PVL genes were detected in MRSA USA300 isolates; in 2002 and 2003, all USA300 isolates carried the PVL genes. From 2004 through 2006, there were PVL-negative and PVL-positive USA300 isolates. The PVL genes were not found in any isolates other than PFT USA300.

Epidemiological Characteristics
Because CA-MRSA strains in the United States were first described in 1997,12,15 the analysis of risk factors for CA-MRSA included the time period between 1997 and 2006. Demographic and epidemiological characteristics for the 99 infants colonized with MRSA in the Grady Memorial Hospital ICN between 1997 and 2006 are presented in Table 1. Fifty-five infants (56%) were female and 44 (44%) were male; 79 infants (80%) were black, 14 (14%) Hispanic, 3 (3%) Native American, and 3 (3%) white. Forty-seven infants (47%) were delivered vaginally and 52 (53%) by cesarean section. Mothers of 86 infants (87%) received systemic antibacterial therapy at any time during pregnancy, including mothers of 75 infants (76%) who received antimicrobial agents immediately before delivery (during the peripartum hospitalization). For mothers of 24 infants (24%), substance abuse during pregnancy was documented; mothers of 22 infants (22%) smoked either tobacco or marijuana during pregnancy.


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  		TABLE 1 Univariate Analyses of Risk Factors for Colonization With CA-MRSA Versus HA-MRSA Genotypes in 99 Infants Hospitalized in ICNs Between 1997 and 2006

 
Univariate Analyses of Risk Factors for Colonization With CA-MRSA Versus HA-MRSA Clones
Characteristics of 45 infants with CA-MRSA colonization and 54 infants with HA-MRSA colonization hospitalized in the ICN in 1997–2006, as well as the univariate analysis results demonstrating associations with colonization with CA-MRSA versus HA-MRSA clones, also are shown in Table 1. Statistically significant risk factors for colonization with CA-MRSA genotypes included vaginal delivery (OR: 3.03; 95% CI: 1.33–6.90; P = .01), maternal smoking of tobacco or marijuana during pregnancy (OR: 3.36; 95% CI: 1.23–9.19; P = .02), greater gestational age (P = .007), and higher birth weight (P = .03). Colonization with HA-MRSA clones was associated with maternal receipt of systemic antibacterial therapy during the peripartum hospitalization (OR: 0.32 for CA-MRSA colonization; 95% CI: 0.12–0.83; P = .02) and neonates requiring endotracheal intubation or tracheostomy (OR: 0.29 for CA-MRSA colonization; 95% CI: 0.12–0.71; P = .005).

Multivariate Analysis of Risk Factors for Colonization With CA-MRSA Versus HA-MRSA Clones
Results of a multivariate logistic regression model with estimates of the stratum-specific adjusted ORs (aORs) are shown in Table 2. This analysis takes into account interaction of systemic antibiotic therapy during the peripartum period with both vaginal delivery and maternal smoking. Vaginal delivery (aOR: 5.44; 95% CI: 1.69–17.6; P = .005) and maternal tobacco or marijuana use (aOR: 6.91; 95% CI: 1.58–30.2; P = .01) were significant predictors for CA-MRSA colonization among infants whose mothers had received systemic antibacterial therapy immediately before delivery (Table 2). Among neonates who were delivered through cesarean section and had mothers who did not smoke, those whose mothers received systemic antibacterial therapy immediately before delivery (aOR: 0.06; 95% CI: 0.004–0.93; P = .04) were significantly less like to have CA-MRSA recovered and more likely to have positive cultures for HA-MRSA genotypes. There was a trend toward less CA-MRSA colonization for neonates who required endotracheal intubation or tracheostomy (aOR: 0.31 for CA-MRSA; 95% CI: 0.09–1.07; P = .06). This model controlled for gestational age, birth weight ratio, and systemic antibacterial therapy during pregnancy, excluding the peripartum hospitalization (Table 2).


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  		TABLE 2 Multivariate Logistic Regression Analysis of Risk Factors for Neonatal Colonization With CA-MRSA Versus HA-MRSA Genotypes

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
MRSA has become an important cause of nosocomial infections for infants cared for in the NICU setting.14,18–20 In adult patients cared for at Grady Memorial Hospital, CA-MRSA (ie, USA300) emerged as an important cause of community-onset as well as HA staphylococcal infections4,5 by 2004. We now demonstrate the emergence and recovery of CA-MRSA genotypes from infants in the Grady Memorial Hospital ICN beginning in 1998.

Between 1993 and 2006, 130 (3.5%) of 3707 neonates in the ICN were identified as being colonized with MRSA. In addition, between September 2004 and December 2006, 12 (1.2%) of 996 infants were shown to be colonized with MRSA at the time of admission to the ICN (generally immediately after birth). These admission surveillance cultures were implemented because of an increased frequency of recovery of MRSA in 2003–2004 and enabled health care workers in the ICN to institute appropriate infection control measures (eg, contact precautions) at the earliest time possible. Between 1993 and 2000, MRSA USA100 (a traditional HA-MRSA clone) was the predominant genotype detected among neonates colonized with MRSA in the ICN. MRSA USA300, a CA-MRSA clone, emerged as the predominant genotype by 2004. During the time between the first description of CA-MRSA in the United States in 199712,15 and the end of the study period in 2006, 45 (45%) of 99 MRSA isolates recovered from surveillance cultures from neonates in our ICN were CA-MRSA genotypes. These findings are both noteworthy and concerning, given that these infants had never been outside the health care system; this indicates that CA-MRSA genotypes had entered the hospital environment and were subsequently transmitted to the infants. Multivariate analysis identified vaginal delivery (aOR: 5.44; P = .005) and maternal smoking (aOR: 6.91; P = .01) as independent risk factors for colonization with CA-MRSA among infants of mothers who had received systemic antibiotic therapy immediately before delivery. Conversely, systemic antibiotic therapy immediately before delivery (aOR: 0.06 for infants delivered through cesarean section to nonsmoking mothers; P = .04) and possibly endotracheal intubation (AOR: 0.31; P = .06) were associated with decreased risk of recovery of CA-MRSA and thus increased risk of recovery of HA-MRSA genotypes.

With prospective laboratory surveillance for MRSA isolates from ICN patients and collection of surveillance cultures starting in 1993, this study represents the longest prospective, longitudinal investigation of the evolution of MRSA in a NICU/ICN setting to date. The emergence of CA-MRSA genotypes in the ICN parallels the paradigm shift of CA-MRSA clones causing HA disease, as observed in adult patients.5,17

Molecular typing studies were conducted by using PFGE and cluster analysis methods, as established by the CDC for the national MRSA database,3 complemented by polymerase chain reaction assays for identification of the SCCmec gene type30,31 and detection of PVL genes.10 Combining these methods resulted in the identification of clones not found among the major clusters in the CDC national database and detection of a significant proportion of USA300 isolates not carrying the PVL genes, which is rarely seen.34 The reasons for the increasing degree of clonal heterogeneity among MRSA isolates recovered in 2005 and 2006 (after emergence of MRSA USA300 as the predominant ICN clone), along with a decrease in the number of MRSA USA300 isolates in those years, is unclear.

MRSA transmission to infants from health care workers,23,35,36 as well as from family members,25,27,37–41 has been documented. Similarly, the detection of CA-MRSA in NICU or nursery settings has been described.14,16,22–27,42,43 However, findings suggesting that CA-MRSA transmission occurred during transit through the birth canal have not been reported previously. Vaginal colonization with MRSA was observed for 0.3% to 1.3% of pregnant women from a limited number of series,40,44,45 and intrapartum MRSA transmission from vaginally colonized mothers to neonates was systematically addressed only once, before the emergence of CA-MRSA.40 Although it could not be demonstrated then,40 there are reports20,41,46 suggesting such a possibility. Clearly, more and larger prospective studies are needed to address this question.

There are certain limitations to this study. (1) Epidemiological data were collected retrospectively; however, both laboratory surveillance for clinical MRSA cultures and surveillance culture collection were prospective. (2) Collection of surveillance cultures was not continuous over the 14-year study period. This was attributable to the protocol implemented in 1993, which required surveillance cultures after detection of MRSA in a clinical culture, and this could lead to underestimation of the number of neonates with MRSA colonization. (3) The study design for the assessment of risk factors in a cross-sectional prevalence study with the mutually exclusive outcomes of CA-MRSA versus HA-MRSA colonization requires caution for interpretation of the findings, because absolute risks cannot be assessed in this study population; however, the hypothesis of an increased risk for CA-MRSA with vaginal delivery is supported by the fact that CA-MRSA clones were recovered from 6 of 8 infants colonized with MRSA on the day of birth. (4) Finally, the sample size of 99 infants for the analysis of specific risk factors for CA-MRSA versus HA-MRSA is a relative limitation; however, confirming the risk factors identified in univariate analyses (with the exception of birth weight and gestational age, both markers for comorbidity) with multivariate analyses demonstrated the robustness of the findings and supported their validity.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
CA-MRSA clones, specifically USA300, emerged as the predominant cause of MRSA colonization in high-risk newborns from 1998 through 2004. Important risk factors for colonization by CA-MRSA versus HA-MRSA clones include maternal smoking during pregnancy and vaginal delivery, both in infants of mothers receiving systemic antibacterial therapy immediately before delivery. This suggests vertical transmission of CA-MRSA genotypes at birth, whereas HA-MRSA clones seem to have been acquired nosocomially. The complex interactions between maternal factors (such as smoking status, prenatal care, and mode of delivery), infant-related factors (such as comorbidity and medical treatment), and MRSA strain-related factors (such as the presence of PVL genes), all potentially affecting MRSA colonization, clearly warrant further investigation. Effectively addressing important risk factors for MRSA transmission in the era of CA-MRSA will be a continuing challenge for infection control programs, including those in ICNs.


   ACKNOWLEDGMENTS
 
We thank Fred C. Tenover and Linda K. McDougal for their invaluable help and advice with PFT assignment and classification.


   FOOTNOTES
 
Accepted Feb 25, 2008.

Address correspondence to Ulrich Seybold, MD, MSCR, Division of Infectious Diseases, Medizinische Poliklinik, University Hospital-Downtown Campus, Ludwig Maximilians University Munich, Pettenkoferstrasse 8a, D-80336 Munich, Germany. E-mail: useybold{at}med.uni-muenchen.de

The authors have indicated they have no financial relationships relevant to this article to disclose.


What's Known on This Subject

MRSA is an important pathogen in intensive care nurseries. CA-MRSA has been described in this setting.

 

What This Study Adds

The emergence of CA-MRSA in our institution's intensive care nurseries over time is described. Risk factors for CA-MRSA versus HA-MRSA colonization are identified, suggesting different modalities of transmission for CA-MRSA and HA-MRSA.

 


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Deresinski S. Methicillin-resistant Staphylococcus aureus: an evolutionary, epidemiologic, and therapeutic odyssey. Clin Infect Dis. 2005;40 (4):562 –573[CrossRef][Web of Science][Medline]
  2. Zetola N, Francis JS, Nuermberger EL, Bishai WR. Community-acquired meticillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis. 2005;5 (5):275 –286[CrossRef][Web of Science][Medline]
  3. McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, Tenover FC. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol. 2003;41 (11):5113 –5120[Abstract/Free Full Text]
  4. King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med. 2006;144 (5):309 –317[Abstract/Free Full Text]
  5. Seybold U, Kourbatova EV, Johnson JG, et al. Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections. Clin Infect Dis. 2006;42 (5):647 –656[CrossRef][Web of Science][Medline]
  6. Centers for Disease Control and Prevention. Methicillin-resistant Staphylococcus aureus infections in correctional facilities: Georgia, California, and Texas, 2001–2003. MMWR Morb Mortal Wkly Rep. 2003;52 (41):992 –996[Medline]
  7. Centers for Disease Control and Prevention. Methicillin-resistant Staphylococcus aureus infections among competitive sports participants: Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000–2003. MMWR Morb Mortal Wkly Rep. 2003;52 (33):793 –795[Medline]
  8. Fridkin SK, Hageman JC, Morrison M, et al. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med. 2005;352 (14):1436 –1444[Abstract/Free Full Text]
  9. Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med. 2005;352 (14):1445 –1453[Abstract/Free Full Text]
  10. Lina G, Piemont Y, Godail-Gamot F, et al. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis. 1999;29 (5):1128 –1132[CrossRef][Web of Science][Medline]
  11. Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003;290 (22):2976 –2984[Abstract/Free Full Text]
  12. Centers for Disease Control and Prevention. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus: Minnesota and North Dakota, 1997–1999. JAMA. 1999;282 (12):1123 –1125[Free Full Text]
  13. Buckingham SC, McDougal LK, Cathey LD, et al. Emergence of community-associated methicillin-resistant Staphylococcus aureus at a Memphis, Tennessee, children's hospital. Pediatr Infect Dis J. 2004;23 (7):619 –624[Web of Science][Medline]
  14. Healy CM, Hulten KG, Palazzi DL, Campbell JR, Baker CJ. Emergence of new strains of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. Clin Infect Dis. 2004;39 (10):1460 –1466[CrossRef][Web of Science][Medline]
  15. Herold BC, Immergluck LC, Maranan MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA. 1998;279 (8):593 –598[Abstract/Free Full Text]
  16. Regev-Yochay G, Rubinstein E, Barzilai A, et al. Methicillin-resistant Staphylococcus aureus in neonatal intensive care unit. Emerg Infect Dis. 2005;11 (3):453 –456[Web of Science][Medline]
  17. Klevens RM, Morrison MA, Fridkin SK, et al. Community-associated methicillin-resistant Staphylococcus aureus and healthcare risk factors. Emerg Infect Dis. 2006;12 (12):1991 –1993[Web of Science][Medline]
  18. Saiman L. Hospital-acquired infections in the neonatal intensive care unit: introduction. Semin Perinatol. 2002;26 (5):313 –314[CrossRef][Web of Science][Medline]
  19. Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110 (2):285 –291[Abstract/Free Full Text]
  20. Huang Y-C, Chou Y-H, Su L-H, Lien R-I, Lin T-Y. Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units. Pediatrics. 2006;118 (2):469 –474[Abstract/Free Full Text]
  21. Saiman L. Risk factors for hospital-acquired infections in the neonatal intensive care unit. Semin Perinatol. 2002;26 (5):315 –321[CrossRef][Web of Science][Medline]
  22. Gerber SI, Jones RC, Scott MV, et al. Management of outbreaks of methicillin-resistant Staphylococcus aureus infection in the neonatal intensive care unit: a consensus statement. Infect Control Hosp Epidemiol. 2006;27 (2):139 –145[CrossRef][Web of Science][Medline]
  23. Sax H, Posfay-Barbe K, Harbarth S, et al. Control of a cluster of community-associated, methicillin-resistant Staphylococcus aureus in neonatology. J Hosp Infect. 2006;63 (1):93 –100[CrossRef][Web of Science][Medline]
  24. David MD, Kearns AM, Gossain S, Ganner M, Holmes A. Community-associated meticillin-resistant Staphylococcus aureus: nosocomial transmission in a neonatal unit. J Hosp Infect. 2006;64 (3):244 –250[CrossRef][Web of Science][Medline]
  25. Al-Tawfiq JA. Father-to-infant transmission of community-acquired methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. Infect Control Hosp Epidemiol. 2006;27 (6):636 –637[CrossRef][Web of Science][Medline]
  26. Kuint J, Barzilai A, Regev-Yochay G, Rubinstein E, Keller N, Maayan-Metzger A. Comparison of community-acquired methicillin-resistant Staphylococcus aureus bacteremia to other staphylococcal species in a neonatal intensive care unit. Eur J Pediatr. 2007;166 (4):319 –325[CrossRef][Web of Science][Medline]
  27. Gastelum DT, Dassey D, Mascola L, Yasuda LM. Transmission of community-associated methicillin-resistant Staphylococcus aureus from breast milk in the neonatal intensive care unit. Pediatr Infect Dis J. 2005;24 (12):1122 –1124[CrossRef][Web of Science][Medline]
  28. Siegel JD, Rhinehart E, Jackson M, Chiarello L, Healthcare Infection Control Practices Advisory Committee (HICPAC). Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006. Atlanta, GA: Centers for Disease Control and Prevention; 2006. Available at www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf. Accessed September 4, 2008
  29. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically: Approved Standard M7-A6. 6th ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2003
  30. Oliveira DC, de Lencastre H. Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2002;46 (7):2155 –2161[Abstract/Free Full Text]
  31. Zhang K, McClure JA, Elsayed S, Louie T, Conly JM. Novel multiplex PCR assay for characterization and concomitant subtyping of staphylococcal cassette chromosome mec types I to V in methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2005;43 (10):5026 –5033[Abstract/Free Full Text]
  32. Diep BA, Carleton HA, Chang RF, Sensabaugh GF, Perdreau-Remington F. Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus. J Infect Dis. 2006;193 (11):1495 –1503[CrossRef][Web of Science][Medline]
  33. Oken E, Kleinman KP, Rich-Edwards J, Gillman MW. A nearly continuous measure of birth weight for gestational age using a United States national reference. BMC Pediatr. 2003;3 :6[CrossRef][Medline]
  34. Tenover FC, McDougal LK, Goering RV, et al. Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol. 2006;44 (1):108 –118[Abstract/Free Full Text]
  35. Bertin ML, Vinski J, Schmitt S, et al. Outbreak of methicillin-resistant Staphylococcus aureus colonization and infection in a neonatal intensive care unit epidemiologically linked to a healthcare worker with chronic otitis. Infect Control Hosp Epidemiol. 2006;27 (6):581 –585[CrossRef][Web of Science][Medline]
  36. Stein M, Navon-Venezia S, Chmelnitsky I, et al. An outbreak of new, nonmultidrug-resistant, methicillin-resistant Staphylococcus aureus strain (SCCmec type IIIA variant-1) in the neonatal intensive care unit transmitted by a staff member. Pediatr Infect Dis J. 2006;25 (6):557 –559[CrossRef][Web of Science][Medline]
  37. Behari P, Englund J, Alcasid G, Garcia-Houchins S, Weber SG. Transmission of methicillin-resistant Staphylococcus aureus to preterm infants through breast milk. Infect Control Hosp Epidemiol. 2004;25 (9):778 –780[CrossRef][Web of Science][Medline]
  38. Shiojima T, Ohki Y, Nako Y, Morikawa A, Okubo T, Iyobe S. Immediate control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit. J Infect Chemother. 2003;9 (3):243 –247[CrossRef][Medline]
  39. Eckhardt C, Halvosa JS, Ray SM, Blumberg HM. Transmission of methicillin-resistant Staphylococcus aureus in the neonatal intensive care unit from a patient with community-acquired disease. Infect Control Hosp Epidemiol. 2003;24 (6):460 –461[CrossRef][Web of Science][Medline]
  40. Mitsuda T, Arai K, Fujita S, Yokota S. Demonstration of mother-to-infant transmission of Staphylococcus aureus by pulsed-field gel electrophoresis. Eur J Pediatr. 1996;155 (3):194 –199[CrossRef][Web of Science][Medline]
  41. Morel AS, Wu F, Della-Latta P, Cronquist A, Rubenstein D, Saiman L. Nosocomial transmission of methicillin-resistant Staphylococcus aureus from a mother to her preterm quadruplet infants. Am J Infect Control. 2002;30 (3):170 –173[CrossRef][Web of Science][Medline]
  42. Bratu S, Eramo A, Kopec R, et al. Community-associated methicillin-resistant Staphylococcus aureus in hospital nursery and maternity units. Emerg Infect Dis. 2005;11 (6):808 –813[Web of Science][Medline]
  43. Centers for Disease Control and Prevention. Community-associated methicillin-resistant Staphylococcus aureus infection among healthy newborns: Chicago and Los Angeles County, 2004. MMWR Morb Mortal Wkly Rep. 2006;55 (12):329 –332[Medline]
  44. Altoparlak U, Kadanali A, Kadanali S. Genital flora in pregnancy and its association with group B streptococcal colonization. Int J Gynaecol Obstet. 2004;87 (3):245 –246[CrossRef][Medline]
  45. Chen KT, Huard RC, Della-Latta P, Saiman L. Prevalence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in pregnant women. Obstet Gynecol. 2006;108 (3):482 –487[CrossRef][Web of Science][Medline]
  46. L'Hériteau F, Lucet JC, Scanvic A, Bouvet E. Community-acquired methicillin-resistant Staphylococcus aureus and familial transmission. JAMA. 1999;282 (11):1038 –1039[Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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