Philip L. Graham

A U.S. Population-Based Survey of Staphylococcus aureus Colonization

Context Epidemiology and risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in the U.S. population are poorly understood. Contribution Extrapolation of 20012002 National Health and Nutrition Examination Survey (NHANES) data indicates that 84 million noninstitutionalized persons in the U.S. population are colonized with MSSA and 2 million are colonized with MRSA. Long-term care facility residence, diabetes, and age 65 years or older are associated with MRSA colonization. Men are at greater risk for MSSA colonization, and women are at greater risk for MRSA colonization. Black persons and those of Mexican birth are at decreased risk for colonization. Implications Risk for MRSA colonization differs according to previously unrecognized population characteristics. The Editors Although Staphylococcus aureus is one of the most common causes of community- and health careassociated infections, little is known about its effects on the U.S. population as a whole. We analyzed newly available data from the 20012002 National Health and Nutrition Examination Survey (NHANES) to expand our understanding of the national epidemiology of S. aureus colonization. This most recent version of the survey is the first to contain information about S. aureus nasal colonization. We aimed to describe the U.S. population epidemiology of S. aureus colonization, compare risk factors for colonization with methicillin-sensitive S. aureus (MSSA) versus methicillin-resistant S. aureus (MRSA), and compare genetic factors and toxin production genes in colonizing strains of both MSSA and MRSA and antibiotic resistance patterns for staphylococcal chromosomal cassette mec (SCCmec) type II (a methicillin resistance gene locus commonly seen in health careassociated MRSA) versus SCCmec type IV (a methicillin resistance gene locus commonly seen in community-associated MRSA). Methods Data Sources We undertook a secondary analysis of NHANES, 20012002 (1). Since the early 1960s, the National Center for Health Statistics has conducted NHANES to obtain representative information on the health and nutritional status of the U.S. population. The survey used a stratified, multistage probability design to sample the civilian, noninstitutionalized U.S. population. The sampling design allows calculation of estimates of the U.S. population (2). Beginning in 1999, NHANES became a continuous annual survey rather than a periodic survey. The data are released on public use data files every 2 years. The 20012002 NHANES is the most recent release of this cross-sectional national survey, which included in-home interview data, examination data from a mobile examination center, and laboratory data. Furthermore, NHANES included data on S. aureus colonization for the first time in this version. Study Sample Of 11039 persons interviewed, 10477 (94.9%) had physical examination data. Among them, 9622 (91.8%) had a nasal swab for S. aureus obtained, and we included these participants in our analysis. We compared the demographic characteristics (age, sex, and race or ethnicity) of those who were interviewed with those who had nasal swabs obtained. We found that they were essentially the same, and therefore, we considered patients who had swabs obtained to be representative of the national sample. Study Variables Microbiological Analysis Nasal swabs were first examined for proper labeling and integrity. They were then plated on mannitol salt agar (MSA), a selective medium for the isolation of S. aureus. The MSA plates were incubated at 37C for 48 hours. Mannitol-fermenting colonies were selected from the MSA plates and subcultured to trypticase soy agar and 5% sheep blood agar plates (BAPs) and incubated at 37C overnight. The MSA plates with little or no growth were reincubated at 37C overnight, and plates with nonmannitol-fermenting growth were held at room temperature. These plates were reexamined the next day, and any yellow or gold colonies were subcultured to BAPs. Overnight cultures on BAPs were first screened by using Staphaurex (Remel, Lenexa, Kansas), a rapid latex kit for identifying S. aureus. A tube coagulase test using rabbit plasma with EDTA was then performed on Staphaurex-negative isolates from BAPs with structure consistent with that of S. aureus and on Staphaurex-positive isolates with structure inconsistent with that of S. aureus (nonhemolytic). Staphaurex-positive isolates and Staphaurex-negative, tube coagulasepositive isolates were identified as S. aureus and were saved for further testing. Staphaurex-positive, tube coagulasenegative isolates were discarded. Staphylococcus aureus isolates were screened for methicillin resistance following the National Committee for Clinical Laboratory Standards (NCCLS) disk-diffusion method. Overnight cultures from BAP were plated on MuellerHinton agar, and a 1-g oxacillin disk was placed on the inoculated plate. Zone diameters were measured and recorded after 24-hour incubation at 37C as sensitive (13 mm), intermediate (11 mm to 12 mm), or resistant (10 mm). Isolates that were resistant to oxacillin (MRSA), those that were intermediate to oxacillin (MSSA), and every tenth isolate that was sensitive to oxacillin (MSSA) by disk diffusion were saved for additional testing of organism characteristics. These tests included antibiotic susceptibility testing (minimal inhibitory concentration [MIC]) using broth microdilution according to NCCLS reference methods; strain typing by pulsed-field gel electrophoresis using SmaI enzyme; singleplex polymerase chain reaction (PCR) for detection of genes encoding enterotoxins, toxic shock syndrome toxin-1, and PantonValentine leukocidin toxin; and SCCmec typing by PCR (3). The NHANES quality control and quality assurance protocols meet the 1988 Clinical Laboratory Improvement Act mandates. Detailed quality control and quality assurance instructions are discussed in the NHANES Laboratory Procedures Manual (4). Risk Factors We examined potential risk factors associated with MSSA and MRSA available in the NHANES data set. These were demographic variables (age, sex, race or ethnicity, education, and birthplace), insurance coverage, health or disease status, and hospitalization or long-term care. We expected that older people would have more chronic conditions and more exposure to antibiotic therapy and hospitalization and, therefore, could be at higher risk for acquiring MRSA. We arbitrarily defined older age groups as age 65 years or older and all other age groups as age less than 65 years. Statistical Analysis We estimated the prevalence of MRSA and MSSA colonization in the U.S. population by using appropriate weighting variables provided with the data set (2). We estimated the prevalence of S. aureus and MRSA, categorized by risk factor, by using weighted samples. We first performed bivariate analyses to examine the association of each individual risk factor with S. aureus and with MRSA. Then, we performed logistic regression analyses to examine risk factors for S. aureus and MRSA, respectively. The multivariate models allowed us to examine the effect of each potential risk factor while controlling for other variables. We ran a series of stepwise regressions, and the final models only included the statistically significant independent variables. We used Wald statistics to test the statistical significance of each independent variable. We calculated odds ratios and 95% CIs. We used weighted samples in chi-square tests and logistic regressions. We compared antimicrobial resistance profiles and genes for toxin production in a subset of MSSA versus MRSA and in a subset of SCCmec type II versus SCCmec type IV by using chi-square tests. We used unweighted samples because of the small size of these subsamples. We performed data analyses by using SUDAAN-callable SAS, version 9 (Research Triangle Institute, Research Triangle Park, North Carolina), which is often used to analyze data collected from surveys with complex sampling designs. Role of the Funding Sources Dr. Graham received salary support from a National Institutes of Health Mentored Clinical Research Scholar Grant, and Drs. Larson and Lin received salary support from the Center for Interdisciplinary Research on Antimicrobial Resistance, National Center for Research Resources, and National Institutes of Health. The funding sources were not involved in the design, analysis, and interpretation of data or in the decision to submit the manuscript for publication. Results Population Epidemiology A total of 9622 participants had cultures for S. aureus obtained. Of these participants, 2889 (31.6% [95% CI, 29.8% to 33.4%]) and 75 (0.84% [CI, 0.4% to 1.2%]) were colonized with MSSA and with MRSA, respectively. On the basis of these data, approximately 84 million and 2 million noninstitutionalized persons in the U.S. population are colonized with MSSA and MRSA, respectively. Prevalence of S. aureus was as low as 26.8% among black persons and was as high as 38% among men (Table 1). The highest prevalence of MRSA was among people who had been in a long-term care facility in the past 12 months (30.9%), people with diabetes (8.5%), and people 65 years of age or older (8.3%) (Table 2). Of persons with MRSA, half are estimated to be colonized with SCCmec type II and half with SCCmec type IV. Table 1. Colonization withStaphylococcus aureus(Methicillin-Sensitive and Methicillin-Resistant) by Risk Factor among the U.S. Population Table 2. Methicillin Resistance among Persons Colonized withStaphylococcus aureusby Risk Factor Staphylococcal Colonization Risks In a multivariate logistic regression model, persons younger than 65 years of age, men, those with less than a high school education, and those with asthma were more likely to have acquired staphylococcal colonization. Black persons and those of Mexican birth were at lower risk than white persons and than those born in the United Stat

Hospital Transmission of Community-Acquired Methicillin-Resistant Staphylococcus aureus among Postpartum Women

Infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are being increasingly observed in patients who lack traditional risk factors. We described 8 postpartum women who developed skin and soft-tissue infections caused by MRSA at a mean time of 23 days (range, 4-73 days) after delivery. Infections included 4 cases of mastitis (3 of which progressed to breast abscess), a postoperative wound infection, cellulitis, and pustulosis. The outbreak strains were compared with the prototype CA-MRSA strain MW2 and found to be indistinguishable by pulsed-field gel electrophoresis. All were spa type 131, all contained the staphylococcal chromosomal cassette mec type IV, and all expressed Panton-Valentine leukocidin and staphylococcal enterotoxins C and H. The route of transmission was not discovered: the results of surveillance cultures of samples obtained from employees of the hospital, the hospital environment, and newborns were negative for the outbreak strain. We report that MW2, which was previously limited to the midwestern United States, has spread to the northeastern United States and has become a health care-associated pathogen.

Risk factors for late onset gram-negative sepsis in low birth weight infants hospitalized in the neonatal intensive care unit.

Background: Gram-negative bloodstream infections (BSIs) cause 20–30% of late onset sepsis in neonatal intensive care unit (NICU) patients and have mortality rates of 30–50%. We investigated risk factors for late onset Gram-negative sepsis in very low birth weight (<1500 g) NICU patients. Methods: We performed a case-control study as part of a larger 2-year clinical trial that examined the effects of hand hygiene practices on hospital-acquired infections. In this substudy, a case was a very low birth weight infant with a hospital-acquired Gram-negative BSI; control subjects, matched on study site and hand hygiene product, were chosen randomly from the patients who did not have Gram-negative BSIs. Potential risk factors were analyzed by Mantel-Haenszel methods and conditional logistic regression. Results: There were 48 cases of Gram-negative BSI. In multivariate analysis, we found that the following variables were significantly associated with Gram-negative BSI: central venous catheterization duration of >10 days; nasal cannula continuous positive airway pressure use; H2 blocker/proton pump inhibitor use; and gastrointestinal tract pathology. Conclusions: These analyses provide insights into potential strategies to reduce Gram-negative BSIs. Catheters should be removed as possible and H2 blockers/proton pump inhibitors should be used judiciously in NICU patients. The association between nasal cannula continuous positive airway pressure and Gram-negative BSIs requires further investigation. The association of gastrointestinal tract pathology with Gram-negative BSIs identifies a high risk group of neonates who may benefit from enhanced preventative strategies.

Concordance of Gastrointestinal Tract Colonization and Subsequent Bloodstream Infections With Gram-negative Bacilli in Very Low Birth Weight Infants in the Neonatal Intensive Care Unit.

Background: Gram-negative bacilli (GNB) cause as many as 20% of episodes of late-onset sepsis among very low birth weight (VLBW, birth weight ≤1500 g) infants in the neonatal intensive care unit. As the gastrointestinal (GI) tract can serve as a reservoir for GNB, we hypothesized that VLBW infants with prior GI tract colonization with gentamicin-susceptible GNB who developed bloodstream infections (BSI) would do so with gentamicin-susceptible GNB. Methods: A prospective cohort study of VLBW infants was performed in 2 level III neonatal intensive care units from September 2004 to October 2007. GI tract surveillance cultures were obtained weekly. Risk factors for GNB BSI and for GI tract colonization with GNB were assessed. Results: Fifty-one (7.3%) of 698 subjects experienced 59 GNB BSIs of which 34 occurred by 6 weeks of life and 625 (90%) of 698 subjects were colonized with GNB. Overall, 25% of BSI and 16% of GI tract isolates were nonsusceptible to gentamicin and colonization with the same species and same gentamicin susceptibility profile preceded 98% of GNB BSIs. Vaginal delivery, birth weight ≤750 g, GI tract pathology, increased use of central venous catheters, use of vancomycin, mechanical ventilation, and H2 blockers/proton pump inhibitors were associated with GNB BSI. Vaginal delivery, birth weight >1000 g, and treatment with carbapenem agents were associated with GNB colonization. Conclusions: These data support the use of empiric gentamicin to treat late-onset sepsis in infants colonized with gentamicin-susceptible GNB. Targeted GI tract surveillance cultures of infants with specific risk factors during weeks 2 to 6 of life could be used to guide empiric therapy for late-onset sepsis.

Novel Influenza A(H1N1) in a Pediatric Health Care Facility in New York City During the First Wave of the 2009 Pandemic

OBJECTIVE To describe the burden of care experienced by our pediatric health care facility in New York, New York, from May 3, 2009, to July 31, 2009, during the novel influenza A(H1N1) pandemic that began in spring 2009. DESIGN Retrospective case series. SETTING Pediatric emergency departments and inpatient facilities of New York-Presbyterian Hospital. Patients Children presenting to the emergency departments with influenza-like illness (ILI) and children aged 18 years or younger hospitalized with positive laboratory test results for influenza A from May 3, 2009, to July 31, 2009. MAIN OUTCOME MEASURES Proportion of children with ILI who were hospitalized and proportion of hospitalized children with influenza A with respiratory failure, bacterial superinfection, and mortality. RESULTS When compared with the same period in 2008, the pediatric emergency departments experienced an excess of 3750 visits (19.9% increase). Overall, 27.7% of visits were for ILI; 2.5% of patients with ILI were hospitalized. Of the 115 hospitalized subjects with confirmed influenza A (median age, 4.3 years), 93 (80.9%) had underlying conditions. Four (3.5%) had identified bacterial superinfection, 1 (0.9%) died, and 35 (30.4%) were admitted to a pediatric intensive care unit; of these 35 patients, 11 had pneumonia and required mechanical ventilation, including high-frequency oscillatory ventilation (n = 3). CONCLUSIONS At our center, 2.5% of children with ILI presenting to the emergency departments during the first wave of the 2009 novel influenza A(H1N1) pandemic were hospitalized. Of the 115 hospitalized children with confirmed influenza A, 9.6% had respiratory failure and 0.9% died. These findings can be compared with the disease severity of subsequent waves of the 2009 novel influenza A(H1N1) pandemic.

Linezolid treatment of vancomycin-resistant Enterococcus faecium ventriculitis.

The successful treatment of a 7-month-old infant with shunt-associated ventriculitis caused by vancomycin-resistant Enterococcus faecium is presented. Linezolid was administered intravenously every 8 h; children have a greater volume of distribution and total body clearance than adults and therefore require more frequent dosing. The patient tolerated the therapy without adverse effects.

The gastrointestinal tract serves as the reservoir for Gram-negative pathogens in very low birth weight infants.

We report a pilot study testing the hypothesis that Gram-negative bacilli colonizing the gastrointestinal tracts of infants with birth weights <1500 g are the source of subsequent bloodstream infections. Ninety-five percent (18 of 19) of paired bloodstream infection or antecedent rectal cultures were genotypically concordant. The gastrointestinal tract is the reservoir for most cases of Gram-negative sepsis in this population.

Preventive strategies for central line–associated bloodstream infections in pediatric hematopoietic stem cell transplant recipients

BACKGROUND Few studies have described preventive strategies for central line-associated bloodstream infections (CLABSIs) in pediatric hematopoietic stem cell transplantation (HSCT) recipients. METHODS We performed a pilot intervention study in our pediatric HSCT population in 2006-2008 and compared CLABSI rates before and after implementation of preventive strategies (ie, training staff and caregivers in procedures for dressing changes and drawing blood) in the inpatient, outpatient, and non-health care (ie, home) settings. We also studied the pathogens associated with hospital-onset versus community-onset CLABSIs. RESULTS During the study period, 90 children (median age, 10 years) underwent HSCT. Fifty-nine children (66%) developed a CLABSI; 18 in the hospital, 27 in the community, and 14 in both settings. After implementation of central line (CL) maintenance care strategies, the overall CLABSI rate declined from 10.03 to 3.00 CLABSIs per 1,000 CL-days (rate ratio, 0.3; 95% confidence interval, 0.2-0.5, P < .0001) and rates declined for both hospital- and community-onset CLABSIs. Gram negative pathogens caused more community-onset (45/65, 69%) than hospital-onset (22/46, 48%) CLABSIs (odds ratio, 2.5; 95% confidence interval, 1.1-5.4; P = .02). CONCLUSIONS Standardization of care practices for CL maintenance was associated with a reduction of CLABSIs in our pediatric HSCT population. A multicenter study is needed to confirm these observations.

Epidemiology of Enterococci in a Neonatal Intensive Care Unit

We performed an epidemiological investigation of a 62-bed neonatal intensive care unit in response to 2 infants with clinical cultures positive for vancomycin-resistant enterococci (VRE). Surveillance cultures detected 11 infants colonized with VRE. Surveillance triggered by even a single clinical culture positive for VRE may be justified in the neonatal intensive care unit, because a single culture result may represent a large hidden reservoir of VRE-colonized infants.

Live vaccine use and safety in DiGeorge syndrome.

OBJECTIVE: Live vaccines are generally contraindicated in patients with DiGeorge syndrome (DGS), a congenital disorder characterized by cellular immune deficiency. Vaccine utilization and safety in this population are not well described. This study examined vaccination patterns and adverse events following live immunization (AEFLI) in these individuals. METHODS: A multicenter retrospective cohort study was conducted in subjects with DGS confirmed by fluorescence in situ hybridization assay (chromosome 22q11.2 microdeletion). Live vaccine-preventable illnesses, vaccination coverage and timeliness, and AEFLIs in the 56-day window after live vaccination were examined. Bivariate and multivariable analyses assessed the impact of demographics medical history, timing of diagnostic confirmation, and preceding immune function on vaccination patterns and AEFLIs. RESULTS: Of 194 subjects, 77% and 75% received measles-mumps-rubella (MMR) and varicella vaccines, respectively; 58% completed recommended vaccinations by age 19 to 35 months. Adverse events occurred after 14% and 20% of MMR and varicella vaccine doses, respectively. Most events were minor, few were serious, and no deaths were reported in post–live vaccination windows. Although early diagnostic confirmation negatively affected live vaccination coverage and timeliness (P < .001), baseline CD4% did not differ between subjects who did or did not receive live vaccines by 12 to 18 months. Among varicella vaccine recipients, those with a subsequent adverse event had a lower preceding CD4% (24.8% ± 7.3%) than those without (35.5% ± 11.7%) (P < .05); no CD4% differences were observed with MMR vaccination. Fourteen unvaccinated subjects experienced live vaccine–preventable illnesses. CONCLUSIONS: Live vaccines were frequently given and generally well-tolerated among patients with DGS with mild-to-moderate immunosuppression.