Benjamin A. Miko

Molecular Characterization of Methicillin-Susceptible Staphylococcus aureus Clinical Isolates in the United States, 2004 to 2010

ABSTRACT While much is known about the geographic distribution of different clonal types of methicillin-resistant Staphylococcus aureus (MRSA), few studies have assessed the molecular epidemiology of methicillin-susceptible S. aureus (MSSA), despite its continued clinical importance. In each U.S. Census region, reference laboratories collected successive MSSA isolates from patients with invasive or superficial staphylococcal infections for use in the Tigecycline Evaluation and Surveillance Trial. All isolates from the periods of 2004 to 2005 and 2009 to 2010 underwent antimicrobial susceptibility testing and characterization of their staphylococcal protein A (spa) type. Of the 708 isolates analyzed, 274 spa types were identified and divided into 15 genetic clusters. The most common clones were spa t002 (n = 63, 8.9%) and t008 (n = 56, 7.9%). While the distribution of the predominant spa types did not differ by U.S. Census region or time period, spa t008 was nearly twice as common in community skin and soft tissue infections than in nosocomial bloodstream infections (11.1% versus 5.6%, respectively; P = 0.008). Despite such differences, both community and nosocomial settings had diverse staphylococcal clonal types representing all major spa clusters. In contrast to those of MRSA, MSSA infectious isolates show wide genetic diversity without clear geographical or temporal clustering. Notably, the prevalent MSSA strains (spa t002 and spa t008) are analogous to the predominant MRSA clones, further demonstrating the importance of both lineages.

Emergence of Sequence Type 398 as a Community- and Healthcare-Associated Methicillin-Susceptible Staphylococcus aureus in Northern Manhattan

The methicillin-susceptible Staphylococcus aureus (MSSA) clone sequence type (ST) 398 has increasingly been identified as a pathogen in diverse geographic settings, yet its epidemiology remains incompletely understood. In this case-control study of MSSA infections, we identified ST398 MSSA as both a major community- and hospital-associated MSSA pathogen in the Dominican neighborhood of northern Manhattan.

Obesity as a Determinant of Staphylococcus aureus Colonization Among Inmates in Maximum-Security Prisons in New York State

Obesity increases a persons susceptibility to a variety of infections, including Staphylococcus aureus infections, which is an important cause of morbidity in correctional settings. Using a cross-sectional design, we assessed the association between obesity and S. aureus colonization, a risk factor for subsequent infection, in New York State maximum-security prisons (2011-2013). Anterior nares and oropharyngeal cultures were collected. Structured interviews and medical records were used to collect demographic, behavioral, and medical data. Body mass index (BMI; weight (kg)/height (m(2))) was categorized as 18.5-24.9, 25-29.9, 30-34.9, or ≥35. The association between BMI and S. aureus colonization was assessed using log-binomial regression. Thirty-eight percent of 638 female inmates and 26% of 794 male inmates had a BMI of 30 or higher. More than 40% of inmates were colonized. Female inmates with a BMI of 25-29.9 (prevalence ratio (PR) = 1.37, 95% confidence interval (CI): 1.06, 1.76), 30-34.9 (PR = 1.52, 95% CI: 1.17, 1.98), or ≥35 (PR = 1.49, 95% CI: 1.13, 1.96) had a higher likelihood of colonization than did those with a BMI of 18.5-24.9 after we controlled for age, educational level, smoking status, diabetes status, and presence of human immunodeficiency virus. Colonization was higher among male inmates with a BMI of 30-34.9 (PR = 1.27, 95% CI: 1.01, 1.61). Our findings demonstrate an association between BMI and S. aureus colonization among female prisoners. Potential contributory biologic and behavioral factors should be explored.

Epidemiologic Associations Between Short-Bowel Syndrome and Bloodstream Infection Among Hospitalized Children

BACKGROUND Children with short bowel syndrome (SBS) suffer from strikingly high rates of morbidity and mortality, due in part to their susceptibility to life-threatening infectious diseases. Few large, multisite studies have evaluated patient-specific factors associated with bacteremia in hospitalized children with and without SBS. METHODS We conducted a case-control study to examine the epidemiological associations between SBS and bloodstream infections (BSI) in hospitalized children. Pediatric BSI cases and controls were selected from a prospective cohort study conducted at 3 New York City hospitals. RESULTS Among 40 723 hospital admissions of 30 179 children, 1047 diagnoses of BSI were identified. A total of 64 children had a diagnosis of SBS. BSI was identified frequently among hospitalizations for children admitted with SBS (n = 207/450, 46%) compared to hospitalizations for children without the condition (n = 840/40 273, 2.1%, P < .001). While this population represented only 0.2% of our overall cohort, it accounted for nearly 20% of all hospital admissions with BSI. Multivariable analysis identified 8 factors significantly associated with pediatric hospitalizations with BSI. These included a diagnosis of SBS (odds ratio [OR] 19.0), ages 1-5 years (OR 1.33), presence of a non-Broviac-Hickman central venous catheter (OR 6.36), immunosuppression (OR 0.53), kidney injury (OR 6.67), organ transplantation (OR 4.44), admission from a skilled nursing facility (OR 2.66), and cirrhosis (OR 7.23). CONCLUSIONS While several clinical characteristics are contributory to the risk of BSI in children, SBS remains the single strongest predictor. Further research into the mediators of this risk will be essential for the development of prevention strategies for this vulnerable population.

Epidemiological and Biological Determinants of Staphylococcus aureus Clinical Infection in New York State Maximum Security Prisons

BACKGROUND Large outbreaks of Staphylococcus aureus (SA) infections have occurred in correctional facilities across the country. We aimed to define the epidemiological and microbiological determinants of SA infection in prisons to facilitate development of prevention strategies for this underserved population. METHODS We conducted a case-control study of SA infection at 2 New York State maximum security prisons. SA-infected inmates were matched with 3 uninfected controls. Subjects had cultures taken from sites of infection and colonization (nose and throat) and were interviewed via structured questionnaire. SA isolates were characterized by spa typing. Bivariate and multivariable analyses were conducted using conditional logistic regression. RESULTS Between March 2011 and January 2013, 82 cases were enrolled and matched with 246 controls. On bivariate analysis, the use of oral and topical antibiotics over the preceding 6 months was strongly associated with clinical infection (OR, 2.52; P < .001 and 4.38, P < .001, respectively). Inmates with clinical infection had 3.16 times the odds of being diabetic compared with inmates who did not have clinical infection (P < .001). Concurrent nasal and/or oropharyngeal colonization was also associated with an increased odds of infection (OR, 1.46; P = .002). Among colonized inmates, cases were significantly more likely to carry the SA clone spa t008 (usually representing the epidemic strain USA300) compared to controls (OR, 2.52; P = .01). CONCLUSIONS Several inmate characteristics were strongly associated with SA infection in the prison setting. Although many of these factors were likely present prior to incarceration, they may help medical staff identify prisoners for targeted prevention strategies.

Is Environmental Contamination Associated with Staphylococcus aureus Clinical Infection in Maximum Security Prisons

Over the past decade, large outbreaks of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have occurred in correctional facilities across the country.1,2 Although many have been managed with aggressive interventions, response to standard infection control procedures has been variable, highlighting our incomplete understanding of staphylococcal transmission in this setting.2 Environmental contamination has recently emerged as a possible target for novel prevention and control strategies.3,4 This study sought to characterize the relationship between environmental contamination and clinical infection in this vulnerable population. We conducted a case-control study of S. aureus environmental contamination at 2 New York State (NYS) maximum security prisons: Sing Sing (men) and Bedford Hills (women). Prisoners with documented S. aureus skin infections were identified by medical personnel at each prison. For every case, 2 uninfected controls—1 nasally and/or oropharyngeally colonized with S. aureus and 1 noncolonized—were selected from the same prison in a contemporaneous fashion. These were identified through our research group’s ongoing study of S. aureus colonization in NYS prisons.5 Consenting study participants had a standardized set of environmental surfaces cultured within 1 week of infection diagnosis (cases) or selection (controls). These included bed sheets, sink handles, toilet flushes, toilet seats, cell bars, light switches, soap dishes, window handles, locker handles, and radios but varied on the basis of the prisoner’s cell contents. Cultures were also obtained from shared gymnasiums in each prison at study initiation. All samples were collected using premoistened rayon-tipped swabs and qualitatively cultured as described else-where.5 S. aureus isolates were typed by polymerase chain reaction sequencing of the spa (staphylococcal protein A) gene.6 SAS (ver. 9.2; SAS Institute) was utilized for data analysis. The study was approved by the Columbia University and NYS Department of Corrections Institutional Review Boards. Ten cases were enrolled in this study. Twenty controls were selected, but 2 did not meet inclusion criteria. There were no significant associations between case status and the demographic and exposure variables assessed (sex, age, race/ ethnicity, self-perceived health, shower frequency, and gym use). The proportion of subjects with S. aureus contamination on 1 or more surfaces did not vary appreciably on the basis of infection status (3/10 cases [30%] vs 6/18 controls overall [33.3%]; Table 1). Despite this, environmental contamination of controls varied depending on their colonization status. Surface contamination, when present, was more frequent among cases than among controls (13/18 surfaces from 3 cases [72.2%] vs 20/43 surfaces from 6 controls [46.5%]; P = .07). Six clonal types were identified on surfaces of the 9 contaminated cells; only 1 cell had more than 1 clone present. None of the infectious, colonization, or personal environmental isolates were methicillin resistant. TABLE 1 Environmental Contamination of Cases and Controls Of the 20 items sampled in the Sing Sing gymnasium, 8 (40%) were positive for S. aureus. These included the gym door handle, boxing gloves, basketballs, abdominal crunch machine, seated and upright leg presses, and hand sanitizer dispenser. Among these surfaces, 6 clonal types were found (spa t002, t008, t334, t701, t1510, and t2334), and all were methicillin susceptible. The Bedford Hills gymnasium was not heavily contaminated; 2 (7.7%) of 26 surfaces were positive, 1 with methicillin-resistant spa t008. Few studies have assessed the prevalence and significance of bacterial surface contamination in jails or prisons. In 2009, Felkner et al7 cultured 132 surfaces from a Texas jail in a nonoutbreak setting. S. aureus was recovered from 10 surfaces (7.6%), with the majority of isolates (8/10) resistant to methicillin. A subset of isolates (6/10) underwent pulsed-field gel electrophoresis, and two-thirds were found to be identical to the USA300 epidemic strain (spa t008). Inmates at Sing Sing and Bedford Hills are known to have high rates of asymptomatic colonization with MRSA (11.2% and 11.1%, respectively) and USA300 (10% and 12.4%, respectively).5 Although this study documented a high prevalence of staphylococcal contamination, only 1 (0.4%) of the 283 environmental cultures was positive for MRSA. The etiology of this discrepancy is unclear. As previous studies have shown effective survival of USA300 and MRSA in the environment,6, 8 the comparatively low prevalence of surface contamination with these clones may be related to infection control strategies within the prison. Since USA300 is a common cause of skin abscesses, systemic antibiotics administered to those with active infection may reduce asymptomatic carriage and subsequent environmental contamination with this clone. Similarly, aggressive environmental hygiene may be differentially applied to locations highly contaminated with this strain if they are associated with purulent skin infections. Prisoners are responsible for disinfecting their own environments using quaternary ammonium products on a weekly basis. Despite this, the true frequency and intensity of cleaning may vary on the basis of prisoner preferences. Our finding of increased environmental contamination among colonized controls compared with that among noncolonized controls suggests that asymptomatic nasal and/or oropharyngeal carriage correlates with environmental reservoirs. Although every effort was made to culture cases’ cells immediately after an infection was identified, antimicrobials and disinfection administered immediately after ascertainment may have limited our ability to capture environmental contamination. Our study is further impaired by its small sample size, limited largely by a low incidence of infections over our study period. It is possible that investigations of environmental contamination during prison-based outbreaks could yield different results. Prospective studies with larger enrollments may be more effective in demonstrating small but significant trends in environmental colonization. While mounting evidence suggests a linkage between S. aureus surface contamination and clinical infection, data remain conflicting.3,4,6 Further research into prison-based infectious reservoirs will be essential to effectively protect this important population and the communities in which they reside.

Is it safe to leave an ECMO circuit primed

Extracorporeal membrane oxygenation (ECMO) is a means of life support for failing patients who require extreme life-saving measures due to failure of their heart, lungs or both organs. In a patient suffering cardiac arrest, the faster circulation via cardiopulmonary resuscitation (CPR) can be instituted the better the outcome is. If an ECMO circuit needs to be built and primed it may add significant minutes to the response time. The purpose of this study is to test for any growth in primed ECMO circuits at given time intervals to prove the safety of leaving an ECMO circuit primed. This, in turn, may lead to decreased response time, with an arrest and the placement of the arresting patient on ECMO. Five ECMO circuits were set up, primed and sampled for bacterial growth at 0, 24, 48 and 72 hours and then at one-week intervals, with an end point of four weeks. No bacterial growth was found at any point during the sampling process.

Clinical Significance of Human Herpesvirus 6 Positivity on the FilmArray Meningitis/Encephalitis Panel

Abstract A review of 15 patients who tested positive for human herpesvirus 6 (HHV-6) on the FilmArray Meningitis/Encephalitis panel revealed that the majority were unlikely to have HHV-6 encephalitis. Criteria to assist interpretation of HHV-6 positive results are presented.

Outcomes for Potential Kidney Transplant Recipients Offered Public Health Service Increased Risk Kidneys: A Single Center Experience

Discard rate of Public Health Service Increased Risk (PHS‐IR) organs is high despite the absence of worse kidney transplant outcomes.

Genomic Surveillance Reveals Diversity of Multidrug-Resistant Organism Colonization and Infection: A Prospective Cohort Study in Liver Transplant Recipients

Background Multidrug-resistant organisms (MDROs) are an important cause of morbidity and mortality after solid organ transplantation. We aimed to characterize MDRO colonization dynamics and infection in liver transplant (LT) recipients through innovative use of active surveillance and whole-genome sequencing (WGS). Methods We prospectively enrolled consecutive adult patients undergoing LT from March 2014 to March 2016. Fecal samples were collected at multiple timepoints from time of enrollment to 12 months posttransplant. Samples were screened for carbapenem-resistant Enterobacteriaceae (CRE), Enterobacteriaceae resistant to third-generation cephalosporins (Ceph-RE), and vancomycin-resistant enterococci. We performed WGS of CRE and selected Ceph-RE isolates. We also collected clinical data including demographics, transplant characteristics, and infection data. Results We collected 998 stool samples and 119 rectal swabs from 128 patients. MDRO colonization was detected in 86 (67%) patients at least once and was significantly associated with subsequent MDRO infection (0 vs 19.8%, P = .002). Child-Turcotte-Pugh score at LT and duration of post-LT hospitalization were independent predictors of both MDRO colonization and infection. Temporal dynamics differed between MDROs with respect to onset of colonization, clearance, and infections. We detected an unexpected diversity of CRE colonizing isolates and previously unrecognized transmission that spanned Ceph-RE and CRE phenotypes, as well as a cluster of mcr-1-producing isolates. Conclusions Active surveillance and WGS showed that MDRO colonization is a highly dynamic and complex process after LT. Understanding that complexity is crucial for informing decisions regarding MDRO infection control, use of therapeutic decolonization, and empiric treatment regimens.