P. Maureen Cassidy

Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013

IMPORTANCE Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts. OBJECTIVE To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas. DESIGN, SETTING, AND PARTICIPANTS Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed. EXPOSURES Demographics, comorbidities, health care exposures, and culture source and location. MAIN OUTCOMES AND MEASURES Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics. RESULTS Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100<000 population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20-2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York (1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95% CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95% CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]); 180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases, including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%) produced a carbapenemase. CONCLUSIONS AND RELEVANCE In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100<000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.

Distinguishing Tuberculosis from Nontuberculous Mycobacteria Lung Disease, Oregon, USA

To determine whether tuberculosis (TB) and nontuberculous mycobacteria (NTM) infection patients could be distinguished from one another with limited information, we compared pulmonary TB and NTM patients during 2005–2006. Our finding that age, birthplace, and presence of chronic obstructive pulmonary disease could differentiate TB and NTM disease could assist tuberculosis control efforts.

Pulmonary disease associated with nontuberculous mycobacteria, Oregon, USA.

To the Editor: Nontuberculous mycobacteria (NTM) are environmental organisms ubiquitous in soil and water, including municipal water supplies. When inhaled, these organisms cause chronic, severe lung disease in susceptible persons (1). Recent epidemiologic studies suggest NTM pulmonary disease is increasingly prevalent in North America, with annual incidence rates of 13 cases per 100,000 population in persons >50 years of age and 2–4-fold higher in older age groups (2–4). The current distribution of pulmonary NTM disease has been poorly characterized with regard to environment, climate, and other factors. We recently performed a statewide NTM surveillance project in Oregon, United States, where we documented higher pulmonary disease rates within the moister, temperate western regions of the state. Oregon is bisected north-south by mountains into 2 distinct climate zones. Western Oregon, where 87% of the state’s population lives, is temperate and wet; eastern Oregon is primarily rural, with an arid, high desert climate. Our goal was to evaluate whether disease clustering within the state could be explained by population density. For all Oregon residents who had newly diagnosed and existing pulmonary NTM disease during 2005 and 2006, we used case-patient home ZIP code and county of residence to construct statewide disease maps (4). We obtained state ZIP code and county-level census data for 2005 and 2006 from the Portland State University Population Research Center and used Oregon Office of Rural Health criteria to designate ZIP codes as urban or rural and counties as rural (nonmetropolitan), micropolitan, or metropolitan (5,6). Unlike ZIP code data, which lacked age information, county census data were age stratified and consisted of population numbers aggregated in 5-year age groups (e.g., 0–4 years, 5–9 years). Because nearly all pulmonary NTM disease occurred in persons >50 years of age, we calculated age-adjusted disease prevalence rates (by using 95% Poisson exact confidence intervals) for patients >50 years of age in the county census data. We used the Cochran-Armitage test for trend to evaluate differences in rates by rural, micropolitan, and metropolitan county designations. Statewide, 385 (94%) of 411 NTM cases occurred among residents of western Oregon, and the crude rate of annual disease prevalence was significantly higher in western than in eastern Oregon (6.0 vs. 2.7/100,000; p 50 years of age were similar (7.6 cases/100,000 population) to those in rural counties within western Oregon (6.5/100,000). Table Prevalence of pulmonary nontuberculous mycobacterial disease, by geographic region and population density, Oregon, USA, 2005 and 2006* In Oregon, where most pulmonary NTM disease is caused by Mycobacterium avium complex (MAC), our findings suggest that the higher rates of disease in the wet western portion of the state are best explained by differences in population density (4). Disease rates there were highly correlated with increasing population density, and in rural areas of western Oregon, disease rates were similar to those in the arid, primarily rural eastern portion of the state. Humans presumably are exposed to NTM daily through showering, bathing, and other activities where water or soil is aerosolized (7). Previous environmental studies suggest that persons living in urban areas could potentially have greater NTM exposure during these activities because NTM is more prevalent in piped networks of municipal water systems than in well-water systems primarily used in rural regions (8). A study in Japan in the 1980s found a similar association of pulmonary NTM disease (primarily MAC) with urban and wet environments compared with arid and rural regions in our study but unlike our study was not able to evaluate differences in disease rates between urban and rural areas independent of climate differences (9). A 1979 Texas study found an association of pulmonary NTM with rural living, although this result was driven by M. kansasii disease, and rates of MAC were actually higher in rural areas (10). These and other similar studies were conducted decades ago when the epidemiology of NTM was substantially different (i.e., predominantly a disease of male patients) and before the formulation of the 2007 American Thoracic Society/Infectious Diseases Society of America pulmonary NTM disease criteria (1). We were limited in drawing firm conclusions about why pulmonary NTM is more common in urban areas because we were not able to evaluate patients or regional water systems within our study. Persons living rurally might be less likely to seek medical care and thus have NTM diagnosed, which would account for the differences in our study. However, given the reasonably close proximity of western Oregon’s rural regions to major medical centers, we believe this scenario is unlikely. Our findings suggest that pulmonary NTM disease is closely associated with urban living. We suspect the difference in disease rates between urban and rural areas might reflect differences in host exposure to these pathogens. Further studies should be undertaken to elucidate the environmental exposures associated with pulmonary NTM.

Evaluation of the Carba NP test in Oregon, 2013

ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health threat. We evaluated the capacity of the Carba NP test to detect carbapenemase production in 206 isolates: 143 Enterobacteriaceae identified by Oregons CRE surveillance program in 2013 and 63 known carbapenemase-positive organisms. Overall, test sensitivity and specificity were 89% (59/66 isolates; 95% confidence interval [CI], 81 to 97%) and 100% (140/140 isolates; 95% CI, 98 to 100%), respectively. All KPC, NDM-1, VIM, and IMP producers but no (0/7 isolates) OXA-48-like strains were Carba NP positive prior to a post hoc protocol modification. We subsequently incorporated Carba NP into Oregons CRE screening algorithm.

Carbapenem-Nonsusceptible Acinetobacter baumannii, 8 US Metropolitan Areas, 2012-2015.

In healthcare settings, Acinetobacter spp. bacteria commonly demonstrate antimicrobial resistance, making them a major treatment challenge. Nearly half of Acinetobacter organisms from clinical cultures in the United States are nonsusceptible to carbapenem antimicrobial drugs. During 2012–2015, we conducted laboratory- and population-based surveillance in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee to determine the incidence of carbapenem-nonsusceptible A. baumannii cultured from urine or normally sterile sites and to describe the demographic and clinical characteristics of patients and cases. We identified 621 cases in 537 patients; crude annual incidence was 1.2 cases/100,000 persons. Among 598 cases for which complete data were available, 528 (88.3%) occurred among patients with exposure to a healthcare facility during the preceding year; 506 (84.6%) patients had an indwelling device. Although incidence was lower than for other healthcare-associated pathogens, cases were associated with substantial illness and death.

New Delhi Metallo-β-lactamase-1 (NDM-1) Escherichia coli isolated from household vacuum cleaner — Oregon, 2013

The first Oregon case of New Delhi metallo-β-lactamase-1 (NDM-1)-producing Escherichia coli was reported during November 2013. Epidemiologic investigation revealed only local outpatient medical care and no travel outside Oregon for both the patient and his household contact. Environmental sampling discovered a matching isolate from the patient’s household vacuum cleaner, suggesting environmental persistence.

Nosocomial Outbreak of Extensively Drug-Resistant Acinetobacter baumannii Isolates Containing blaOXA-237 Carried on a Plasmid

ABSTRACT Carbapenem antibiotics are among the mainstays for treating infections caused by Acinetobacter baumannii, especially in the Northwest United States, where carbapenem-resistant A. baumannii remains relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant A. baumannii occurred in 16 patients from five health care facilities in the state of Oregon. All isolates were defined as extensively drug resistant. Multilocus sequence typing revealed that the isolates belonged to sequence type 2 (international clone 2 [IC2]) and were >95% similar as determined by repetitive-sequence-based PCR analysis. Multiplex PCR revealed the presence of a blaOXA carbapenemase gene, later identified as blaOXA-237. Whole-genome sequencing of all isolates revealed a well-supported separate branch within a global A. baumannii phylogeny. Pacific Biosciences (PacBio) SMRT sequencing was also performed on one isolate to gain insight into the genetic location of the carbapenem resistance gene. We discovered that blaOXA-237, flanked on either side by ISAba1 elements in opposite orientations, was carried on a 15,198-bp plasmid designated pORAB01-3 and was present in all 16 isolates. The plasmid also contained genes encoding a TonB-dependent receptor, septicolysin, a type IV secretory pathway (VirD4 component, TraG/TraD family) ATPase, an integrase, a RepB family plasmid DNA replication initiator protein, an alpha/beta hydrolase, and a BrnT/BrnA type II toxin-antitoxin system. This is the first reported outbreak in the northwestern United States associated with this carbapenemase. Particularly worrisome is that blaOXA-237 was carried on a plasmid and found in the most prominent worldwide clonal group IC2, potentially giving pORAB01-3 great capacity for future widespread dissemination.

1726What Defines Carbapenem-Resistant Enterobacteriaceae (CRE) in a Low Prevalence State? Oregon, 2010 — 2013

Background. Preventing the spread of carbapenem-resistant Enterobacteriaceae (CRE) is important to public health because of high infection-related morbidity, mortality, and cost. Carbapenemase producing (CP)-CRE are most concerning because of their rapid global dissemination. In 2013, CRE in Oregon were defined as Enterobacteriaceae with non-susceptibility to ≥1 carbapenem, including ertapenem, and resistance to any 3generation cephalosporin. Review of surveillance data raised concerns of poor definition specificity for CP-CRE creating burden for laboratories and public health investigators. Methods. We analyzed all CRE isolates reported in Oregon December 2010 – October 2013. We reviewed surveillance data from other states and published literature, focusing on CRE minimal inhibitory concentration breakpoints. Results. Of our 125 unique isolates, 75 (60%) were Enterobacter cloacae, 13 (10%) Enterobacter aerogenes, 11 (9%) Escherichia coli, 11 (9%) Klebsiella pneumoniae, and 14 (11%) were other species. Non-susceptibility only to ertapenem was demonstrated by 66 (53%), of which 47 (72%) were E. cloacae. Of the 34 isolates non-susceptible to multiple carbapenems, 18 (53%) were E. cloacae, 5 (15%) E. aerogenes, 4 (12%) E. coli, and 6 (18%) K. pneumoniae. Ninety-nine (81%) isolates were resistant to all 3 generation cephalosporins tested. Three were CP-CRE; all were K. pneumoniae producing K. pneumoniae carbapenemases. Review of literature and other states’ data confirmed carbapenemases were present in E. cloacae. Excluding ertapenem from the definition for laboratories using the updated Clinical Laboratory Standard Institute (CLSI) breakpoints did not greatly reduce sensitivity for the most common carbapenemases. Finally, retaining the cephalosporin-resistance requirement enhanced specificity. The new definition decreased the number of cases to investigate by 57%, without missing any CP-CRE. Conclusion. Wemodified our case definition to increase CP-CRE specificity, without losing sensitivity, thus decreasing investigation burden. For laboratories using current CLSI breakpoints, the new definition includes all Enterobacteriaceae, removes ertapenem, and requires resistance to all 3 generation cephalosporins tested. Disclosures. All authors: No reported disclosures.

351NDM-1-producing Escherichia coli Isolated from a Case Patient's Environment

351. NDM-1-producing Escherichia coli Isolated from a Case Patient’s Environment Genevieve L. Buser, MDCM, MSHP; P. Maureen Cassidy, MPH; Christopher Pfeiffer, MD; John M. Townes, MD; Karim E. Morey, MS, M(ASCP); Jaipreet Rayar, MS; Kirthi K. Kutumbaka, PhD; Sukkyun Han, PhD; Cesar Nadala, PhD; Mansour Samadpour, PhD; Scott Weissman, MD; Robert Vega, MS, SM (AAM); Zintars G. Beldavs, MS; Acute and Communicable Disease Prevention, Oregon Health Authority, Portland, OR; Infectious Diseases, Portland VA Medical Center, Portland, OR; Oregon Health and Science University, Portland, OR; Oregon State Public Health Laboratory, Hillsboro, OR; Seattle Children’s Research Institute, Seattle, WA; Molecular Epidemiology Inc., Lake Forest Park, WA