Search

Background Nontuberculous mycobacteria (NTM) cause pulmonary (PNTM) and extrapulmonary (ENTM) disease. Infections are difficult to diagnose and treat, and exposures occur in healthcare and community settings. In the United States, NTM epidemiology has been described largely through analyses of microbiology data from health departments, electronic health records, and administrative data. We describe findings from a multisite pilot of active, laboratory- and population-based NTM surveillance. Methods The Centers for Disease Control and Prevention’s Emerging Infections Program conducted NTM surveillance at 4 sites (Colorado, 5 counties; Minnesota, 2 counties; New York, 2 counties; and Oregon, 3 counties [PNTM] and statewide [ENTM]) from 1 October 2019 through 31 March 2020. PNTM cases were defined using published microbiologic criteria. ENTM cases required NTM isolation from a nonpulmonary specimen, excluding stool and rectal swabs. Patient data were collected via medical record review. Results Overall, 299 NTM cases were reported (PNTM: 231, 77%); Mycobacterium avium complex was the most common species group. Annualized prevalence was 7.5/100 000 population (PNTM: 6.1/100 000; ENTM: 1.4/100 000). Most patients had signs or symptoms in the 14 days before positive specimen collection (ENTM: 62, 91.2%; PNTM: 201, 87.0%). Of PNTM cases, 145 (62.8%) were female and 168 (72.7%) had underlying chronic lung disease. Among ENTM cases, 29 (42.6%) were female, 21 (30.9%) did not have documented underlying conditions, and 26 (38.2%) had infection at the site of a medical device or procedure. Conclusions Active, population-based NTM surveillance will provide data for monitoring the burden of disease and characterize affected populations to inform interventions.

Stroke, Alzheimer's Disease, and other neurological pathologies are not only among the leading causes of death in the United States but also account for a huge portion of national healthcare expenditure (National Center for Health Statistics, 2016 report). Advancing our understanding of the bodily response to neural injury and the mechanisms that might be used to prevent or heal that injury is of paramount importance. This dissertation is a presentation of work aimed at understanding the molecular cascades that govern regeneration after neural injury using the olfactory neuroepithelium (OE) - one of the few locations in the adult where such regeneration is naturally able to occur - as a model.Throughout the human lifespan, the OE is continually subject to chemotoxic and mechanical insult. Remarkably, the epithelium has the ability to fully regenerate all cell types, both neurons and supporting cells after minor or extensive injury. Understanding the biological regulation that allows for this regeneration serves two purposes: One, these mechanisms may be usefully employed in the development of translational methods for treating neurological diseases. Two, the cells and stem cells of the OE constitute a rich potential source of cells for possible transplantation in translational approaches to pathologies where neural death has occurred. In this dissertation, we evaluated the functional importance of the Stem Cell Factor growth factor (SCF) and C-Kit, the receptor tyrosine kinase SCF binds to, in neural regeneration.The regenerative capability of the human epithelium is faithfully recapitulated by the murine OE, making it an ideal model of the human system for use in researching regenerative mechanisms. Using transgenic mouse models, we examined the expression of SCF and C-Kit in the OE via a combination of molecular imaging and single-cell transcriptional sequencing, and we discovered that SCF is expressed by all sustentacular (SUS) supporting cells and all horizontal basal stem cells, both in the uninjured and in the injured/regenerating OE. C-Kit is expressed by a large fraction of the globose basal cells, a population which is heterogeneous and consists both of stem and committed progenitor cells, and some microvillous cells, a population which is the subject of much current research. Interestingly, during regeneration after experimentally induced injury, the majority of cells express SCF or C-Kit. These striking expression patterns led us to look for deficits in SCF knock-out transgenic mice with the hope of better understanding the function of this growth factor. We found that SCF is critical to production of normal numbers of neurons and microvillous cells during regeneration. Extensive assessment of the expression patterns and impact of the ablation of SCF function in the OE led us to a novel understanding of the role of this growth factor/receptor pair in neural recovery after injury: SCF is critical for OE stem cells to make neuronal fate decisions during regeneration from injury.

The CDC's Emerging Infections Program (EIP) conducted population- and laboratory-based surveillance of US carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 2016 through 2018. To characterize the pathotype, 1,019 isolates collected through this project underwent antimicrobial susceptibility testing and whole-genome sequencing. Sequenced genomes were classified using the seven-gene multilocus sequence typing (MLST) scheme and a core genome (cg)MLST scheme was used to determine phylogeny. Both chromosomal and horizontally transmitted mechanisms of carbapenem resistance were assessed. There were 336 sequence types (STs) among the 1,019 sequenced genomes, and the genomes varied by an average of 84.7% of the cgMLST alleles used. Mutations associated with dysfunction of the porin OprD were found in 888 (87.1%) of the genomes and were correlated with carbapenem resistance, and a machine learning model incorporating hundreds of genetic variations among the chromosomal mechanisms of resistance was able to classify resistant genomes. While only 7 (0.1%) isolates harbored carbapenemase genes, 66 (6.5%) had acquired non-carbapenemase β-lactamase genes, and these were more likely to have OprD dysfunction and be resistant to all carbapenems tested. The genetic diversity demonstrates that the pathotype includes a variety of strains, and clones previously identified as high-risk make up only a minority of CRPA strains in the United States. The increased carbapenem resistance in isolates with acquired non-carbapenemase β-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa.

Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community.Active, population-based surveillance was conducted to identify case-patients with cultures positive for Enterobacterales not susceptible to a carbapenem (excluding ertapenem) and resistant to all third-generation cephalosporins tested at 8 US sites from January 2012 to December 2015. Medical records were used to classify cases as health care-associated, or as community-associated (CA) if a patient had no known health care risk factors and a culture was collected3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing.We identified 1499 CRE cases in 1194 case-patients; 149 cases (10%) in 139 case-patients were CA. The incidence of CRE cases per 100,000 population was 2.96 (95% CI: 2.81, 3.11) overall and 0.29 (95% CI: 0.25, 0.35) for CA-CRE. Most CA-CRE cases were in White persons (73%), females (84%) and identified from urine cultures (98%). Among the 12 sequenced CA-CRE isolates, 5 (42%) harbored a carbapenemase gene.Ten percent of CRE cases were CA; some isolates from CA-CRE cases harbored carbapenemase genes. Continued CRE surveillance in the community is critical to monitor emergence outside of traditional health care settings.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) producing the Verona integron‒encoded metallo-β-lactamase (VIM) are highly antimicrobial drug-resistant pathogens that are uncommon in the United States. We investigated the source of VIM-CRPA among US medical tourists who underwent bariatric surgery in Tijuana, Mexico. Cases were defined as isolation of VIM-CRPA or CRPA from a patient who had an elective invasive medical procedure in Mexico during January 2018‒December 2019 and within 45 days before specimen collection. Whole-genome sequencing of isolates was performed. Thirty-eight case-patients were identified in 18 states; 31 were operated on by surgeon 1, most frequently at facility A (27/31 patients). Whole-genome sequencing identified isolates linked to surgeon 1 were closely related and distinct from isolates linked to other surgeons in Tijuana. Facility A closed in March 2019. US patients and providers should acknowledge the risk for colonization or infection after medical tourism with highly drug-resistant pathogens uncommon in the United States.

Background: Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods: During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacter spp (E. cloacae complex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results: Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli (62.2% of E. coli isolates tested) and Enterobacter spp (61.4% of Enterobacter isolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions: Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coli and Enterobacter spp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.Funding: NoneDisclosures: None

In 2014, Oregon implemented an interfacility transfer communication law requiring notification of multidrug-resistant organism status on patient transfer. Based on 2015 and 2016 statewide facility surveys, compliance was 77% and 87% for hospitals, and 67% and 68% for skilled nursing facilities. Methods for complying with the rule were heterogeneous, and fewer than half of all facilities surveyed reported use of a standardized interfacility transfer communication form to assess a patient's multidrug-resistant organism status on transfer.

Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. During July-October 2015 in the United States, we piloted laboratory-based surveillance for carbapenem-resistant P. aeruginosa (CRPA) at sentinel facilities in Georgia, New Mexico, Oregon, and Tennessee, and population-based surveillance in Monroe County, NY. An incident case was the first P. aeruginosa isolate resistant to antipseudomonal carbapenems from a patient in a 30-day period from any source except the nares, rectum or perirectal area, or feces. We found 294 incident cases among 274 patients. Cases were most commonly identified from respiratory sites (120/294; 40.8%) and urine (111/294; 37.8%); most (223/280; 79.6%) occurred in patients with healthcare facility inpatient stays in the prior year. Genes encoding carbapenemases were identified in 3 (2.3%) of 129 isolates tested. The burden of CRPA was high at facilities under surveillance, but carbapenemase-producing CRPA were rare.

We investigated a cluster of Mycobacterium fortuitum and M. goodii prosthetic joint surgical site infections occurring during 2010–2014. Cases were defined as culture-positive nontuberculous mycobacteria surgical site infections that had occurred within 1 year of joint replacement surgery performed on or after October 1, 2010. We identified 9 cases by case finding, chart review, interviews, surgical observations, matched case–control study, pulsed-field gel electrophoresis of isolates, and environmental investigation; 6 cases were diagnosed >90 days after surgery. Cases were associated with a surgical instrument vendor representative being in the operating room during surgery; other potential sources were ruled out. A tenth case occurred during 2016. This cluster of infections associated with a vendor reinforces that all personnel entering the operating suite should follow infection control guidelines; samples for mycobacterial culture should be collected early; and postoperative surveillance for

Nontuberculous mycobacteria (NTM), ubiquitous in soil and water, usually infect immunocompromised persons. However, even healthy persons are susceptible to infection through percutaneous inoculation. Although 77% of NTM diseases manifest as primarily pulmonary illnesses (1), NTM also infect skin, bones, joints, the lymphatic system, and soft tissue. NTM infections can have incubation periods that exceed 5 years (2), often require prolonged treatment, and can lead to sepsis and death. Extrapulmonary NTM outbreaks have been reported in association with contaminated surgical gentian violet (3), nail salon pedicures (4), and tattoos received at tattoo parlors (5), although few surveillance data have been available for estimating the public health burden of NTM.* On January 1, 2014, the Oregon Health Authority designated extrapulmonary NTM disease a reportable condition. To characterize extrapulmonary NTM infection, estimate resources required for surveillance, and assess the usefulness of surveillance in outbreak detection and investigation, 2014–2016 extrapulmonary NTM surveillance data were reviewed, and interviews with stakeholders were conducted. During 2014–2016, 134 extrapulmonary NTM cases (11 per 1 million persons per year) were reported in Oregon. The age distribution was bimodal, with highest incidence among persons aged

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.

OBJECTIVETo determine the scope, source, and mode of transmission of a multifacility outbreak of extensively drug-resistant (XDR)Acinetobacter baumannii.DESIGNOutbreak investigation.SETTING AND PARTICIPANTSResidents and patients in skilled nursing facilities, long-term acute-care hospital, and acute-care hospitals.METHODSA case was defined as the incident isolate from clinical or surveillance cultures of XDRAcinetobacter baumanniiresistant to imipenem or meropenem and nonsusceptible to all but 1 or 2 antibiotic classes in a patient in an Oregon healthcare facility during January 2012–December 2014. We queried clinical laboratories, reviewed medical records, oversaw patient and environmental surveillance surveys at 2 facilities, and recommended interventions. Pulsed-field gel electrophoresis (PFGE) and molecular analysis were performed.RESULTSWe identified 21 cases, highly related by PFGE or healthcare facility exposure. Overall, 17 patients (81%) were admitted to either long-term acute-care hospital A (n=8), or skilled nursing facility A (n=8), or both (n=1) prior to XDRA. baumanniiisolation. Interfacility communication of patient or resident XDR status was not performed during transfer between facilities. The rare plasmid-encoded carbapenemase geneblaOXA-237was present in 16 outbreak isolates. Contact precautions, chlorhexidine baths, enhanced environmental cleaning, and interfacility communication were implemented for cases to halt transmission.CONCLUSIONSInterfacility transmission of XDRA. baumanniicarrying the rare blaOXA-237was facilitated by transfer of affected patients without communication to receiving facilities.Infect Control Hosp Epidemiol2017;38:1335–1341

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.Funding: NoneDisclosures: None

Background: Due to limited therapeutic options and potential for spread, carbapenem-resistant Enterobacteriaceae (CRE)-producing New Delhi metallo-β-lactamases (NDMs) are a public health priority. We investigated the epidemiology of NDM-producing CRE reported to the CDC to clarify its distribution and relative prevalence. Methods: The CDC’s Antibiotic Resistance Laboratory Network supports molecular testing of CRE for 5 carbapenemases nationally. Although KPC is the most common carbapenemase in the United States, non-KPC carbapenemases are a growing concern. We analyzed CRE with any of 4 non-KPC plasmid-mediated carbapenemases (NDM, VIM, IMP, or OXA-48 type) isolated from specimens collected from January 1, 2017, through June 30, 2019; only a patient’s first isolate per organism–carbapenemase combination was included. We excluded isolates from specimen sources associated with colonization screening (eg, perirectal). We compared the proportion of NDM-producing CRE to all non-KPC–producing CP-CRE between period A (January to June 2018) and period B (January to June 2019). Health departments and the CDC collected additional exposure and molecular information in selected states to better describe current NDM-producing CRE epidemiology. Results: Overall, 47 states reported 1,013 non–KPC-producing CP-CRE (range/state, 1–109 isolates; median, 11 isolates); 46 states reported 631 NDM-producing CRE (range/state, 1–84; median, 6). NDM-producing CRE increased quarterly from the third quarter of 2018 through the second quarter of 2019; CP-CRE isolates with other non-KPC carbapenemases remained stable (Fig. 1). In period A, 124 of 216 emerging CP-CRE had NDM (57.1%), compared with 255 of 359 emerging CP-CRE (71.0%) during period B (P = .1179). Among NDM-producing CRE, the proportion of Enterobacter spp increased from 10.5% in 2018 to 18.4% in 2019 (P = .0467) (Fig. 2). In total, 18 states reported more NDM-producing CRE in the first 6 months of 2019 than in all of 2018. Connecticut, Ohio, and Oregon were among states that conducted detailed investigations; these 3 states identified 24 NDM-producing CRE isolates from 23 patients in period B. Overall, 5 (21.7%) of 22 patients with history available traveled internationally ≤12 months prior to culture; 17 (73.9%) acquired NDM-producing CRE domestically. Among 15 isolates sequenced, 8 (53.3%) carried NDM-5 (6 E. coli, 1 Enterobacter spp and 1 Klebsiella spp) and 7 (46.7%) carried NDM-1 (6 Enterobacter spp and 1 Klebsiella spp). Species were diverse; no single strain type was shared by >2 isolates. Conclusions: Detection of NDM-producing CRE has increased across the AR Lab Network. Among states with detailed information available, domestic acquisition was common, and no single variant or strain predominated. Aggressive public health response and further understanding of current US NDM-CRE epidemiology are needed to prevent further spread.Disclosures: NoneFunding: None

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.

Background Testing for urinary tract infection (UTI) and Clostridiodes difficile infection (CDI) poses diagnostic and antimicrobial stewardship challenges. Both diagnoses hinge on local microbiology laboratory algorithms. For UTI testing, the definition of “abnormal” urinalysis and the use of reflex urine cultures, both of which alter the frequency of bacteriuria detection, likely differs between laboratories. For CDI, pretest probability, choice and sequence of diagnostic tests are likely variable and impact the chances of accurate diagnosis. Methods To understand laboratory practices and determine variations in local testing algorithms, we deployed a self-administered survey to microbiology laboratories serving Oregon healthcare facilities via SurveyMonkey in September 2018. Responses were collected through April 2019. We analyzed a subset of questions focused on UTI and CDI diagnosis. Results Of 51 surveyed laboratories, response rate was 86% (n = 44). 91% of respondents (n = 40) process bacterial cultures. 47.5% (n = 19) primarily perform urine culture when ordered, whereas the remainder primarily perform cultures in a reflex algorithm when ordered (n = 12; 30%) or a reflex algorithm automatically (n = 9; 22.5%) (Figure 1). The definition of an abnormal urinalysis varied widely (Figure 2). 15% (n = 6) of laboratories reported considering changes to their workflow; two cited a goal of reducing unnecessary testing. Of the 32 laboratories that perform in-house C. difficile testing, the assays and sequence in which they were implemented in testing algorithms varied substantially (Figure 3) and most commonly included NAAT testing. Seven (21.8%) laboratories reported recently changed practices; these changes did not favor any particular algorithm. 84.2% (n = 32) reported stool rejection criteria to limit unnecessary testing, but these criteria varied (Figure 4). Conclusion Wide variation exists in laboratory workflows for UTI and CDI diagnoses in Oregon, suggesting lack of consensus on optimal practices. Encouragingly, multiple labs described recently implemented or planned interventions to reduce unnecessary testing for both infections. This snapshot will inform statewide education and interventions to optimize testing and help prevent patient and population harm. Disclosures All authors: No reported disclosures.

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 bla OXA carbapenemase gene, later identified as bla OXA-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 bla OXA-237 , flanked on either side by IS Aba1 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 bla OXA-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.

Background Carbapenem-resistant Enterobacteriacae (CRE) are an urgent US public health threat. CDC reported CRE incidence to be 2.93/100,000 population in 2012–2013 in selected sites but changed the CRE surveillance case definition in 2016 to improve sensitivity for detecting carbapenemase-producing (CP) CRE. We describe CRE epidemiology before and after the change. Methods Eight CDC Emerging Infections Program sites (CO, GA, MD, MN, NM, NY, OR, TN) conducted active, population-based CRE surveillance in selected counties. A case was defined as having an isolate of E. coli, Enterobacter, or Klebsiella meeting a susceptibility phenotype (figure) at a clinical laboratory from urine or a normally sterile body site in a surveillance area resident in a 30-day period. We collected data from medical records and defined cases as community-associated (CA) if no healthcare risk factors were documented. A convenience sample of isolates were tested for carbapenemase genes at CDC by real-time PCR. We calculated incidence rates (per 100,000 population) by using US Census data. Case epidemiology and the proportion of CP-CRE isolates in 2015 versus 2016 were compared. Results In total, 442 incident CRE cases were reported in 2015, and 1,149 cases were reported in 2016. Most isolates were cultured from urine: 87% in 2015 and 92% in 2016 (P < .001). The crude overall pooled mean incidence in 2015 was 2.9 (range by site: 0.45–7.19) and in 2016 was 7.48 (range: 3.13–15.95). The most common CRE genus was Klebsiella (51%) in 2015, and in 2016 was Enterobacter (41%, P < 0.001). Of the subset of CRE isolates tested at CDC, 109/227 (48%) were CP-CRE in 2015 and 109/551 (20%) were CP-CRE in 2016. In 2015, 52/442 (12%) of cases were CA CRE, and in 2016, 267/1,149 (23%) were CA CRE (P < 0.001). In 2016, 3/111 (2.7%) of CA CRE isolates tested were CP-CRE. Conclusion A large increase in reported CRE incidence was observed after the change in the case definition. The new case definition includes a substantially larger number of Enterobacter cases. A decrease in CP-CRE prevalence appears to be driven by an increase in non-CP-CRE cases. Although CP-CRE in the community still appear to be rare, a substantial proportion of phenotypic CRE appear to be CA, and CDC is undertaking efforts to further investigate CA CRE, including CP-CRE. Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

Background Pseudomonas aeruginosa is intrinsically resistant to many commonly used antimicrobials and carbapenems are often required to treat infections. We describe the epidemiology and crude incidence of carbapenem-resistant P. aeruginosa(CRPA) in the EIP catchment area. Methods From August 1, 2016 through July 31, 2017, we conducted laboratory- and population-based surveillance for CRPA in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. We defined an incident case as the first isolate of P. aeruginosa-resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period. Patient charts were reviewed. A random sample of isolates was screened at CDC for carbapenemases using the modified carbapenem inactivation method (mCIM) and real-time PCR. Results During the 12-month period, we identified 3,042 incident cases among 2,154 patients. The crude incidence rate was 21.2 (95% CI, 20.4–21.9) per 100,000 persons and varied by site (range: 7.7 in Oregon to 31.1 in Maryland). The median age of patients was 64 years (range: Conclusion The burden of CRPA varied by EIP site. Most cases occurred in persons with healthcare exposures and underlying conditions. The majority of isolates were susceptible to at least one first-line antimicrobial. Carbapenemase producers were rare; a more specific phenotypic definition would greatly facilitate surveillance for these isolates. Disclosures All authors: No reported disclosures.

Background Pseudomonas aeruginosa is intrinsically resistant to many commonly used antimicrobials, and carbapenems are often required to treat infections. We describe the crude incidence, epidemiology, and molecular characteristics of carbapenem-resistant P. aeruginosa (CRPA) in the EIP catchment area. Methods From August 1, 2016 through July 31, 2018, we conducted laboratory- and population-based surveillance for CRPA in selected areas in eight sites. We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period. Patient charts were reviewed. Analysis excluded cystic fibrosis patients. A random sample of isolates was collected. Real-time PCR to detect carbapenemase genes and whole-genome sequencing are in progress. Results We identified 4,209 cases in 3373 patients. The annual incidence was 14.50 (95% CI, 14.07–14.94) per 100,000 persons and varied among sites from 4.89 in OR to 25.21 in NY. The median age of patients was 66 years (range: < 1–101), 42.1% were female, and nearly all (97.5%) had an underlying condition. Most cases were identified from urine (42.8%) and lower respiratory tract (35.7%) cultures. Nearly all (93.3%) occurred in patients with inpatient healthcare facility stay, surgery, chronic dialysis, or indwelling devices in the prior year; death occurred in 7.2%. Among 937 isolates tested, 847 (90.4%) underwent PCR; six (0.7%) harbored a carbapenemase, from four sites (CO, MD, NY, and OR): blaVIM (3), blaKPC (2), and blaIMP (1). Of 612 (65.3%) isolates sequenced, the most common ST types were ST235 (9.2%) and ST298 (4.9%). Conclusion Carbapenemases were rarely the cause of carbapenem resistance but were found at EIP sites with high and low CRPA incidence. The emergence of mobile carbapenemases in P. aeruginosa has the potential to increase the incidence of CRPA. Increased detection and early response to carbapenemase-producing CRPA is key to prevent further emergence. Disclosures All authors: No reported disclosures.

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.

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 Oregon's 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 Oregon's CRE screening algorithm.

Community-specific antimicrobial susceptibility data may help monitor trends among drug-resistant Streptococcus pneumoniae and guide empiric therapy. Because active, population-based surveillance for invasive pneumococcal disease is accurate but resource intensive, we compared the proportion of penicillin-nonsusceptible isolates obtained from existing antibiograms, a less expensive system, to that obtained from 1 year of active surveillance for Georgia, Tennessee, California, Minnesota, Oregon, Maryland, Connecticut, and New York. For all sites, proportions of penicillin-nonsusceptible isolates from antibiograms were within 10 percentage points (median 3.65) of those from invasive-only isolates obtained through active surveillance. Only 23% of antibiograms distinguished between isolates intermediate and resistant to penicillin; 63% and 57% included susceptibility results for erythromycin and extended-spectrum cephalosporins, respectively. Aggregating existing hospital antibiograms is a simple and relatively accurate way to estimate local prevalence of penicillin-nonsusceptible pneumococcus; however, antibiograms offer limited data on isolates with intermediate and high-level penicillin resistance and isolates resistant to other agents.

Background Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat in the United States because of high morbidity and mortality, few treatment options, and potential for rapid spread among patients. To assess for changes in CRE epidemiology and risk among populations, we analyzed CDC Emerging Infections Program (EIP) 2012–2015 surveillance data for CRE. Methods Active, population-based CRE surveillance was initiated in January 2012 at 3 EIP sites (GA, MN, OR) and expanded to 5 additional sites (CO, MD, NM, New York, TN) by 2014. An incident case was the first Escherichia coli, Enterobacter, or Klebsiella isolate (non-susceptible to at least one carbapenem and resistant to all third-generation cephalosporins tested) collected from urine or a normally sterile body site from a patient during a 30-day period. Data were collected from patients’ medical records. Cases were hospital-onset (HO) or long-term care facility (LTCF) onset if patients were in the respective facility ≥3 days prior to culture or at the time of culture; and community-onset (CO) otherwise. We calculated incidence rates based on census data for EIP sites and described by type of infection onset. Results A total of 1,582 incident CRE cases were reported in 2012–2015. Most cases (88%) were identified through urine cultures; 946 (60%) were female, and median age was 66 years (interquartile range: 55–77). The median incidence by site was 2.95 per 100,000 population (range: 0.35–8.98). Among the three sites with four full years of data, a different trend was seen in each (Figure). Trends in GA and MN were statistically significant, and no significant trend was seen in OR. Overall, 480 cases (30%) were HO, 524 (33%) were LTCF onset, and 578 (37%) were CO. Of CO cases, 308 (53%) had been hospitalized, admitted to a long- term acute care hospital or were a LTCF resident in the prior year. Conclusion CRE incidence varied more than 20-fold across surveillance sites, with evidence of continued increases in MN. Measuring impact of programs aimed at reducing CRE transmission in other regions will require obtaining local data to identify cases occurring during and after healthcare facility discharge. Further study of changes in incidence in some settings and areas might offer opportunities to refine and expand effective control strategies. Disclosures All authors: No reported disclosures.

Background Nontuberculous mycobacteria (NTM) are important human pathogens, yet little is known about disease prevalence in the United States. Reports suggest prevalence has increased, particularly in women, but population-based data to substantiate this are lacking. We sought to estimate NTM disease prevalence in Oregon, and describe disease by site, species, and patient demographic characteristics. Methods We contacted laboratories that performed mycobacterial cultures on Oregon residents in 2005-2006. For each isolate, we obtained source, collection date, species, and patient demographics. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease. Results We identified 933 patients with > or =1 NTM isolate. Of these, 527 (56%) met the case definition (annualized prevalence, 7.2 cases per 100,000 persons). Pulmonary cases predominated (5.6 cases per 100,000 persons), followed by skin/soft-tissue cases (0.9 cases per 100,000 persons). Mycobacterium avium complex was the most common species identified in pulmonary cases (4.7 cases per 100,000 persons). Pulmonary disease prevalence was significantly higher in women (6.4 cases per 100,000 persons) than men (4.7 cases per 100,000 persons) and was highest in persons aged >50 years (15.5 cases per 100,000 persons). Conclusions NTM are frequently isolated from Oregon residents; more than one-half of all isolates likely represent true disease. Pulmonary NTM is most common among elderly women, and M. avium causes most disease. Future efforts to monitor disease trends should be undertaken, and efforts made to validate the use of the ATS/IDSA microbiologic criteria alone to predict pulmonary NTM disease.

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.To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas.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.Demographics, comorbidities, health care exposures, and culture source and location.Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics.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 100000 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.In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100000 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.