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Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemase-producing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population- and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (

BackgroundCarbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in healthcare settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to trackblaKPC-carrying CRE (KPC-CRE) transmission across healthcare facilities in three U.S. states.MethodsClinical isolates were collected from Connecticut (CT; 2017-2018), Minnesota (MN; 2012-2018), and Tennessee (TN; 2016-2017) through the U.S. Centers for Disease Control and Prevention’s Multi-site Gram-negative Surveillance Initiative and additional surveillance. KPC-CRE isolates were whole-genome sequenced, and case report data on patient comorbidities, healthcare utilization, and interfacility patient transfer were extracted.FindingsIn CT, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In MN, cases were mainly from sporadic importation and transmission ofblaKPC-carryingKlebsiella pneumoniae(KPC-Kp) ST258, and clonal expansion of an imported epidemic lineage ofblaKPC-carryingEnterobacter hormaechei(KPC-Ec) ST171 primarily at a single focal facility and its satellite facilities. In TN, KPC-Kp ST258, and more recently emerged KPC-Kp ST307 and KPC-Eh ST114 were most common, with largely non-overlapping facility networks mediating the spread of ST258 versus ST307 and ST114.ConclusionsThe underlying processes driving KPC-CRE burden can differ substantially across regions, and different STs can spread via distinct pathways within a region. Integrating genomic and epidemiological data from regional surveillance, and information on interfacility patient transfers, can provide insights to target interventions.

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.

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.

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.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of healthcare-associated infections with limited treatment options and high mortality. To describe risk factors for mortality, we evaluated characteristics associated with 30-day mortality in patients with CRAB identified through the Emerging Infections Program (EIP). Methods: From January 2012 through December 2017, 8 EIP sites (CO, GA, MD, MN, NM, NY, OR, TN) participated in active, laboratory-, and population-based surveillance for CRAB. An incident case was defined as patient’s first isolation in a 30-day period of A. baumannii complex from sterile sites or urine with resistance to ≥1 carbapenem (excluding ertapenem). Medical records were abstracted. Patients were matched to state vital records to assess mortality within 30 days of incident culture collection. We developed 2 multivariable logistic regression models (1 for sterile site cases and 1 for urine cases) to evaluate characteristics associated with 30-day mortality. Results: We identified 744 patients contributing 863 cases, of which 185 of 863 cases (21.4%) died within 30 days of culture, including 113 of 257 cases (44.0%) isolated from a sterile site and 72 of 606 cases (11.9%) isolated from urine. Among 628 hospitalized cases, death occurred in 159 cases (25.3%). Among hospitalized fatal cases, death occurred after hospital discharge in 27 of 57 urine cases (47.4%) and 21 of 102 cases from sterile sites (20.6%). Among sterile site cases, female sex, intensive care unit (ICU) stay after culture, location in a healthcare facility, including a long-term care facility (LTCF), 3 days before culture, and diagnosis of septic shock were associated with increased odds of death in the model (Fig. 1). In urine cases, age 40–54 or ≥75 years, ICU stay after culture, presence of an indwelling device other than a urinary catheter or central line (eg, endotracheal tube), location in a LTCF 3 days before culture, diagnosis of septic shock, and Charlson comorbidity score ≥3 were associated with increased odds of mortality (Fig. 2). Conclusion: Overall 30-day mortality was high among patients with CRAB, including patients with CRAB isolated from urine. A substantial fraction of mortality occurred after discharge, especially among patients with urine cases. Although there were some differences in characteristics associated with mortality in patients with CRAB isolated from sterile sites versus urine, LTCF exposure and severe illness were associated with mortality in both patient groups. CRAB was associated with major mortality in these patients with evidence of healthcare experience and complex illness. More work is needed to determine whether prevention of CRAB infections would improve outcomes.Funding: NoneDisclosures: None

A new, less restrictive definition increases detection of Klebsiella pneumoniae carbapenemase producers., Preventing transmission of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based definition that reliably identifies CP-CRE while minimizing misclassification of non–CP-CRE could help prevention efforts. To assess possible definitions, we evaluated enterobacterial isolates that had been tested and deemed nonsusceptible to >1 carbapenem at US Emerging Infections Program sites. We determined the number of non-CP isolates that met (false positives) and CP isolates that did not meet (false negatives) the Centers for Disease Control and Prevention CRE definition in use during our study: 30% (94/312) of CRE had carbapenemase genes, and 21% (14/67) of Klebsiella pneumoniae carbapenemase–producing Klebsiella isolates had been misclassified as non-CP. A new definition requiring resistance to 1 carbapenem rarely missed CP strains, but 55% of results were false positive; adding the modified Hodge test to the definition decreased false positives to 12%. This definition should be considered for use in carbapenemase-producing CRE surveillance and prevention.

Background An increasing proportion of Clostridium difficile infections (CDI) in the United States are community-associated (CA). We conducted a case-control study to identify CA-CDI risk factors. Methods We enrolled participants from 10 US sites during October 2014–March 2015. Case patients were defined as persons age ≥18 years with a positive C. difficile specimen collected as an outpatient or within 3 days of hospitalization who had no admission to a health care facility in the prior 12 weeks and no prior CDI diagnosis. Each case patient was matched to one control (persons without CDI). Participants were interviewed about relevant exposures; multivariate conditional logistic regression was performed. Results Of 226 pairs, 70.4% were female and 52.2% were ≥60 years old. More case patients than controls had prior outpatient health care (82.1% vs 57.9%; P < .0001) and antibiotic (62.2% vs 10.3%; P < .0001) exposures. In multivariate analysis, antibiotic exposure—that is, cephalosporin (adjusted matched odds ratio [AmOR], 19.02; 95% CI, 1.13–321.39), clindamycin (AmOR, 35.31; 95% CI, 4.01–311.14), fluoroquinolone (AmOR, 30.71; 95% CI, 2.77–340.05) and beta-lactam and/or beta-lactamase inhibitor combination (AmOR, 9.87; 95% CI, 2.76–340.05),—emergency department visit (AmOR, 17.37; 95% CI, 1.99–151.22), white race (AmOR 7.67; 95% CI, 2.34–25.20), cardiac disease (AmOR, 4.87; 95% CI, 1.20–19.80), chronic kidney disease (AmOR, 12.12; 95% CI, 1.24–118.89), and inflammatory bowel disease (AmOR, 5.13; 95% CI, 1.27–20.79) were associated with CA-CDI. Conclusions Antibiotics remain an important risk factor for CA-CDI, underscoring the importance of appropriate outpatient prescribing. Emergency departments might be an environmental source of CDI; further investigation of their contribution to CDI transmission is needed.

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 Carbapenem-nonsusceptible Acinetobacter spp. (CNAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are recognized causes of severe and difficult to treat healthcare-associated infections. This study estimated and compared the incidence of CNAB and CRPA among patients admitted to US acute care hospitals in 2012–2017. Methods We measured the incidence of positive clinical cultures from inpatient encounters in a cohort of over 300 hospitals submitting data to the Premier Healthcare Database and Cerner Health Facts in 2012–2017. We included clinical cultures from any body site yielding Acinetobacter spp./P. aeruginosa non-susceptible/resistant to imipenem, meropenem, or doripenem. Cultures collected on days 1–3 of hospitalization were considered community-onset (CO) and cultures from later were hospital-onset (HO). Duplicate isolates identified within 14 days of an incident culture and surveillance cultures were excluded. For each year, a raking procedure generated weights to extrapolate the sample estimate to match the American Hospital Association distributions based on US census division, hospital bed capacity, teaching status, and urban designation. We compared estimated rates in 2017 vs. 2012 using weighted multivariable logistic regression adjusting for hospital characteristics and hospital-level clustering. Results In 2017, the estimated rates of HO and CO CNAB rates were 0.77 and 1.39/10,000 discharges, and HO and CO CRPA rates were 3.14 and 6.57, respectively. Compared with 2017, rates of HO CNAB decreased 49% (Odds Ratio (OR) 0.51; 95% CI: 0.34–0.75) and rates of CO CNAB decreased 29% (OR 0.71; 95% CI: 0.54–0.92). For CRPA, the incidence of HO decreased (OR 0.66; CI: 0.49–0.88) with no change in CO rates (OR 0.93; CI: 0.79–1.11). Assessment of cultures from sterile sites alone showed similar results, but they did not reach statistical significance, Figure 1. Conclusion We estimate significant national decreases in the rates of HO and CO CNAB, and HO CRPA. Risk factors and effective interventions to reduce CO CRPA might differ from CNAB and HO CRPA. Additional prevention strategies are needed to address CO CRPA. Disclosures All authors: No reported disclosures.

Background Carbapenemase-producing (CP-) carbapenem-resistant Enterobacteriaceae (CRE) have been almost exclusively linked to extensive healthcare exposure and are of significant concern due to limited treatment options and potential for plasmid-mediated spread of resistance. We report on CP-CRE in community-dwelling individuals. Methods We used 2012–2017 active, laboratory and population-based surveillance data for CRE from CDC’s Emerging Infections Program sites (9 sites by 2017). Cases were the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. from a normally sterile body specimen or urine in a surveillance site resident meeting a CRE phenotype (figure) in a 30 day period. Epidemiologic data were obtained from chart review. Cases were community-associated (CA) if not isolated after the first three days of a hospital stay; without inpatient healthcare, dialysis, or surgery in the year prior; and without indwelling medical devices within two days prior to culture. A convenience sample of isolates was tested at CDC by real-time PCR to detect blaKPC, blaNDM, blaOXA-48-like, blaVIM, or blaIMP. Results Of 4023 CRE cases, 699 (17%) were CA, from which 297 isolates were tested; 20 (7%) were CP-CRE, from 18 patients (2 had repeat isolation of the same gene/species). The median age was 68 years (range: 33–91), and 14 (78%) were female. Patients were from 7 sites (range: 1–4/site). Their CP-CRE (10 blaKPC, 6 blaNDM, and 2 blaOXA-48-like) were from three species (10 K. pneumoniae, 6 E. coli, 2 E. cloacae) and isolated from urine (n = 16) and blood (n = 2). Among those with CP-CRE from urine, 12 (75%) had clinical diagnoses of urinary tract infections and the rest had no infection documented. Overall, 7 (39%) were admitted to a hospital within 30 days of culture; none died during hospitalization. Most (n = 13; 72%) had underlying medical comorbidities, most commonly urinary tract abnormalities (n = 5; 28%) and diabetes mellitus (n = 5; 28%). Three (17%) had international travel within two months prior to culture. Conclusion CA CP-CRE were found in most surveillance sites but are rare, occurring primarily in older patients with underlying medical conditions. Patient interviews are planned to determine whether CA CP-CRE may be associated with distant or undocumented healthcare exposures. 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.

Background The majority of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in the United States are community-onset and occur in persons with recent health care exposure. Methods We performed a matched case-control study to identify risk factors for invasive MRSA infection among recently discharged patients. Cases had MRSA cultured from a normally sterile body site within 100 days following hospital discharge. Controls were matched on hospital, week of admission, and age. Results Among 77 cases, the most common types of invasive MRSA infection were bloodstream infection and osteomyelitis. Independent risk factors were a history of a MRSA-positive clinical culture from a superficial body site in the 12 months preceding the invasive infection (matched odds ratio [mOR], 23; 95% confidence interval [CI]: 3.7-142), hemodialysis (mOR, 21; 95% CI: 1.7-257), prior hospitalization length of stay >5 days (mOR, 4.5; 95% CI: 1.6-12), and male sex (mOR, 2.9; 95% CI: 1.1-7.9). Conclusion Risk factors for postdischarge invasive MRSA infections can be identified prior to discharge and remain with the patient after the hospitalization ends. Measures to prevent community-onset invasive MRSA infections might start in the hospital but should also be evaluated in postdischarge settings.

Background: The USA300 methicillin-resistant Staphylococcus aureus (MRSA) strain, which initially emerged as a cause of community-associated infections, has recently become an important pathogen in healthcare-associated infections (HAIs). However, its impact on patient outcomes has not been well studied. We evaluated patients with invasive MRSA infections to assess differences in outcomes between infections caused by USA100 and those caused by USA300. Methods: Population-based data for invasive MRSA infections were used to identify 2 cohorts: (1) nondialysis patients with central line-associated bloodstream infections (CLABSIs) and (2) patients with community-onset pneumonia (PNEUMO) during 2005-2007 from 6 US metropolitan areas. Medical records of patients with confirmed MRSA USA100 or USA300 infection were reviewed. Logistic regression and, when appropriate, survival analysis was performed to evaluate mortality, early and late complications, and length of stay. Results: A total of 236 and 100 patients were included in the CLABSI and PNEUMO cohorts, respectively. USA300 was the only independent predictor of early complications for PNEUMO patients (odds ratio [OR], 2.6; P = .02). Independent predictors of CLABSI late complications included intensive care unit (ICU) admission before MRSA culture (adjusted OR [AOR], 2.1; P= .01) and Charlson comorbidity index (AOR, 2.6; P = .003), but not strain type. PNEUMO patients were significantly more likely to die if they were older (P = .02), black (P < .001), or infected with USA100 strain (P = .02), whereas those with CLABSI were more likely to die if they were older (P < .001), had comorbidities (P < .001), or had an ICU admission before MRSA culture (P = .001). Conclusions: USA300 was associated with early complications in PNEUMO patients. However, it was not associated with mortality for either PNEUMO or CLABSI patients. Concerns regarding higher mortality from HAIs caused by USA300 may not be warranted.

Objectives. The role of noroviruses in both foodborne and person-to-person outbreaks of acute gastroenteritis (AGE) has been difficult to determine in the U.S. because of lack of routine norovirus testing and of national reporting of person-to-person outbreaks. We conducted a prospective study in one state in which enhanced testing for noroviruses was performed to better understand the relative contribution of all gastroenteric pathogens. Methods. During the two-year period, 2000–2001, we took all fecal specimens from AGE outbreaks reported in Georgia that were negative for bacteria and tested these for norovirus. Results. We investigated 78 AGE outbreaks, from which suitable fecal samples were collected from 57 of them. Norovirus was identified in 25 (44%) outbreaks, bacteria in 20 (35%) outbreaks, and parasites in one (2%) outbreak. Forty-three (75%) of the outbreaks tested were foodborne, of which 17 (40%) were attributable to norovirus and 18 (42%) were attributable to bacteria. Adjusting for incomplete testing, we estimated that 53% of all AGE outbreaks were attributable to norovirus. A total of 2,674 people were reported ill in the 57 outbreaks, and norovirus infections accounted for 1,735 (65%) of these cases. Norovirus outbreaks tended to be larger than bacterial outbreaks, with a median number of 30 vs. 16 cases per outbreak, respectively ( p=0.057). Conclusions. This study provides further evidence that noroviruses are, overall, the most common cause of AGE outbreaks in the U.S. Improved specimen collection, reporting person-to-person outbreaks, and access to molecular assays are needed to further understand the role of these viruses and methods for their prevention.

In the United States, a single pulsed-field type (PFT), USA300 (multilocus sequence type [MLST] 8), is the predominant cause of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections (26, 35). A subset of isolates with the pulsed-field gel electrophoresis (PFGE) pattern USA300-0114 and other closely related strains have disseminated clonally throughout the United States (25, 35) and typically carry Panton-Valentine leukocidin (PVL) toxin genes, the arginine catabolic mobile element (ACME), and staphylococcal cassette chromosome mec (SCCmec) type IVa (13). Although PFT USA100 (MLST 5) is the most common PFT isolated in cases of health care-associated MRSA infections in the United States (23), USA300 isolates have now emerged as a cause of health care-associated infections (22, 23, 32). Whereas traditional health care-associated MRSA strains are usually resistant to multiple antimicrobial classes, USA300 isolates are typically susceptible to most classes of antimicrobial agents and are resistant only to oxacillin and erythromycin (12, 17, 35). However, resistance to other antimicrobial agents has been sporadically reported in USA300 isolates (i.e., resistance to fluoroquinolones, tetracycline, clindamycin, and mupirocin) (10, 16, 35). Treatment options for MRSA skin and soft-tissue infections include trimethoprim-sulfamethoxazole (TMP-SMZ), clindamycin, and tetracyclines (6, 9, 14); the emergence of resistance to these agents in USA300 strains will pose a challenge for treating both community- and health care-associated S. aureus infections. Since 2001, when USA300 isolates were first recognized (25), these isolates have become increasingly resistant to the fluoroquinolones; 54% of the Active Bacterial Core surveillance (ABCs) isolates from 2005 to 2006 were resistant to levofloxacin (23). Fluoroquinolone resistance in S. aureus arises via chromosomal mutations in the DNA gyrase gene gyrA (18). Most other antimicrobial resistance in staphylococci emerges by acquisition of resistance determinants residing on plasmids and is often associated with transposons or insertion sequences (33). In previous analyses of USA300 isolates, several plasmids were identified. Among isolates with a typical susceptibility pattern (resistance to penicillin, oxacillin, and erythromycin), two plasmids were described: a small, 3.1-kb cryptic plasmid and a 27-kb mosaic plasmid that harbors several resistance determinants, including resistance to erythromycin (msrA) and penicillin (blaZ) (17, 35). Among USA300 isolates with resistance to tetracycline but susceptibility to doxycycline and minocycline, a 4.4-kb plasmid with the tetK determinant was reported (11, 30, 35), and isolates with clindamycin resistance carried a small, 2.6-kb plasmid harboring ermC (35). For USA300 isolates with both clindamycin and high-level mupirocin resistance, Diep et al. (10, 11) described a large conjugative plasmid, pUSA03, which carried two resistance determinants, ermC and mupA. The pUSA03 plasmid is related to a plasmid family that was first detected in gentamicin-resistant staphylococcal strains isolated in the mid-1970s (1, 2) and includes pGO1, pSK41, and pLW1043 (4, 5, 36). These plasmids are defined in this study as “pSK41-like” plasmids. They contain a highly conserved, transfer-associated region consisting of 15 tra genes. The plasmids also typically have multiple copies of the insertion element IS257, which act as preferred sites for integration of mobile elements that can carry resistance genes (4, 5). Antimicrobial resistance determinants described on pSK41-like plasmids include aac6′-aph2″, which confers resistance to aminoglycosides (4, 5, 36, 37); dfrA, which confers high-level trimethoprim resistance (5); mupA, which confers high-level mupirocin resistance (11, 27); and vanA, which confers vancomycin resistance (36). Previously, reports of USA300 isolates with plasmid-mediated resistance have been single events or restricted to specific geographical areas (10, 16). Here we describe USA300 isolates with unusual plasmid-mediated antimicrobial resistance patterns, including resistance to clindamycin, mupirocin (high level), gentamicin, trimethoprim (high level), and/or doxycycline. Outside of the ABCs collection (23), gentamicin and trimethoprim resistance have not been previously reported for USA300 isolates.

Group B streptococcal disease is one of the most common infections in the first week after birth. In 2002, national guidelines recommended universal late antenatal screening of pregnant women for colonization with group B streptococcus to identify candidates for intrapartum chemoprophylaxis.We evaluated the implementation of the guidelines in a multistate, retrospective cohort selected from the Active Bacterial Core surveillance, a 10-state, population-based system that monitors invasive group B streptococcal disease. We abstracted data from the labor and delivery records of a stratified random sample of live births and of all cases in which the newborn had early-onset group B streptococcal disease (i.e., disease in infants7 days of age) in 2003 and 2004. We compared our results with those from a study with a similar design that evaluated screening practices in 1998 and 1999.We abstracted records of 254 births in which the infant had group B streptococcal disease and 7437 births in which the infant did not. The rate of screening for group B streptococcus before delivery increased from 48.1% in 1998-1999 to 85.0% in 2003-2004; the percentage of infants exposed to intrapartum antibiotics increased from 26.8% to 31.7%. Chemoprophylaxis was administered in 87.0% of the women who were positive for group B streptococcus and who delivered at term, but in only 63.4% of women with unknown colonization status who delivered preterm. The overall incidence of early-onset group B streptococcal disease was 0.32 cases per 1000 live births. Preterm infants had a higher incidence of early-onset group B streptococcal disease than did term infants (0.73 vs. 0.26 cases per 1000 live births); however, 74.4% of the cases of group B streptococcal disease (189 of 254) occurred in term infants. Missed screening among mothers who delivered at term accounted for 34 of the 254 cases of group B streptococcal disease (13.4%). A total of 61.4% of the term infants with group B streptococcal disease were born to women who had tested negative for group B streptococcus before delivery.Recommendations for universal screening were rapidly adopted. Improved management of preterm deliveries and improved collection, processing, and reporting of culture results may prevent additional cases of early-onset group B streptococcal disease.

We documented transmission by food and person-to-person contact; persistence of virus despite sanitization onboard, including introductions of new strains; and seeding of an outbreak on land., We describe an investigation of a norovirus gastroenteritis outbreak aboard a cruise ship affecting 6 consecutive cruises and the use of sequence analysis to determine modes of virus transmission. Noroviruses (NoV), are the most common cause of infectious acute gastroenteritis and are transmitted feco-orally through food and water, directly from person to person and by environmental contamination (1). These viruses are often responsible for protracted outbreaks in closed settings, such as cruise ships, nursing homes, and hospitals (2,3).

Analysis of foodborne outbreaks shows how advances in viral diagnostics are clarifying the causes of foodborne outbreaks and determining the high impact of norovirus infections., Efforts to prevent foodborne illness target bacterial pathogens, yet noroviruses (NoV) are suspected to be the most common cause of gastroenteritis. New molecular assays allow for better estimation of the role of NoV in foodborne illness. We analyzed 8,271 foodborne outbreaks reported to the Centers for Disease Control and Prevention from 1991 to 2000 and additional data from 6 states. The proportion of NoV-confirmed outbreaks increased from 1% in 1991 to 12% in 2000. However, from 1998 to 2000, 76% of NoV outbreaks were reported by only 11 states. In 2000, an estimated 50% of foodborne outbreaks in 6 states were attributable to NoV. NoV outbreaks were larger than bacterial outbreaks (median persons affected: 25 versus 15), and 10% of affected persons sought medical care; 1% were hospitalized. More widespread use of molecular assays will permit better estimates of the role of NoV illness and help direct efforts to control foodborne illness.

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 Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an important cause of healthcare-associated infections. We characterized the molecular epidemiology of CRE in isolates collected through the Emerging Infections Program (EIP) at the Centers for Disease Control and Prevention (CDC). Methods From 2011–2015, 8 U.S. EIP sites (CO, GA, MD, MN, NY, NM, TN and OR) collected CRE (Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, and Klebsiella oxytoca) isolated from a normally sterile site or urine. Isolates were sent to CDC for reference antimicrobial susceptibility testing and real-time PCR detection of carbapenemase genes (blaKPC, blaNDM, blaOXA-48). Phenotypically confirmed CRE were analyzed by whole genome sequencing (WGS) using an Illumina MiSeq benchtop sequencer. Results Among 639 Enterobacteriaceae evaluated, 414 (65%) were phenotypically confirmed as CRE using CDC’s current surveillance definition (resistant to ertapenem, imipenem, doripenem, or meropenem). Among isolates confirmed as CRE, 303 (73%) were carbapenemase-producers (CP-CRE). The majority of CP-CRE originated from GA (39%), MD (35%) and MN (11%); most non-CP-CREs originated from MN (27%), CO (25%) and OR (17%). K. pneumoniae was the predominant carbapenemase-producing species (78%) followed by E. cloacae complex spp (12%), E. coli (7.9%), E. Aerogenes (0.9%) and K. oxytoca (0.6%). The most common carbapenemase genes detected were blaKPC-3 (76%) and blaKPC-2 (19%); blaNDM and blaOXA-48-like genes were detected in 1.6% and 0.3% of isolates, respectively. For carbapenemase-producing K. pneumoniae, Enterobacter spp, and E. coli, the predominant sequence types (ST) were ST258 (65%), ST171 (35%) and ST131 (29%), respectively. Conclusion The distribution of CP and non-CP-CRE varied across the catchment sites. Among CP-CRE, KPC-producing K. pneumoniae predominated; other carbapenemases were rarely identified in the locations under surveillance. Strain types known to have increased epidemic potential (ST258 and ST131) were common among carbapenemase-producing K. pneumoniae and E. coli isolates, respectively. Disclosures All authors: No reported disclosures.

An infant with diarrhea attended a community playgroup. In the subsequent 48 hours, 6 of the 7 mothers and children reported gastroenteritis; fecal specimens from 5 persons tested positive for norovirus, with identical sequences. No breach of hygiene or contact with fecal matter was identified. Excluding the child with gastroenteritis from the playgroup could have prevented this outbreak.

We describe clinical and laboratory characteristics of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections with vancomycin MICs of 2 μg/ml and compare heteroresistant-intermediate S. aureus (hVISA) to non-hVISA. Health care-associated community-onset infections were the most common and resulted in frequent complications and relapses. hVISA-infected patients were more likely to have been hospitalized in the year prior to MRSA culture.

Typhoid fever in the United States has increasingly been due to infection with antimicrobial-resistant Salmonella ser Typhi. National surveillance for typhoid fever can inform prevention and treatment recommendations.To assess trends in infections with antimicrobial-resistant S. Typhi.Cross-sectional, laboratory-based surveillance study.We reviewed data from 1999-2006 for 1902 persons with typhoid fever who had epidemiologic information submitted to the Centers for Disease Control and Prevention (CDC) and 2016 S. Typhi isolates sent by participating public health laboratories to the National Antimicrobial Resistance Monitoring System Laboratory at the CDC for antimicrobial susceptibility testing.Proportion of S. Typhi isolates demonstrating resistance to 14 antimicrobial agents and patient risk factors for antimicrobial-resistant infections.Patient median age was 22 years (range,1-90 years); 1295 (73%) were hospitalized and 3 (0.2%) died. Foreign travel within 30 days of illness was reported by 1439 (79%). Only 58 travelers (5%) had received typhoid vaccine. Two hundred seventy-two (13%) of 2016 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant S. Typhi [MDRST]); 758 (38%) were resistant to nalidixic acid (nalidixic acid-resistant S. Typhi [NARST]) and 734 NARST isolates (97%) had decreased susceptibility to ciprofloxacin. The proportion of NARST increased from 19% in 1999 to 54% in 2006. Five ciprofloxacin-resistant isolates were identified. Patients with resistant infections were more likely to report travel to the Indian subcontinent: 85% of patients infected with MDRST and 94% with NARST traveled to the Indian subcontinent, while 44% of those with susceptible infections did (MDRST odds ratio, 7.5; 95% confidence interval, 4.1-13.8; NARST odds ratio, 20.4; 95% confidence interval, 12.4-33.9).Infection with antimicrobial-resistant S. Typhi strains among US patients with typhoid fever is associated with travel to the Indian subcontinent, and an increasing proportion of these infections are due to S. Typhi strains with decreased susceptibility to fluoroquinolones.

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.

Between July 2000 and June 2004, fecal specimens from 270 outbreaks of acute gastroenteritis were sent to the Centers for Disease Control and Prevention by local or state health departments for calicivirus testing. Of the 226 outbreaks that met the criteria for inclusion in the present study, caliciviruses were detected in 184 (81%) by reverse-transcription polymerase chain reaction and nucleotide sequencing. Nursing homes, retirement centers, and hospitals were the most frequently reported settings, and person-to-person contact was the most common mode of transmission, followed by foodborne spread. Overall, genogroup II norovirus (NoV) strains were the most abundant (79%), followed by genogroup I NoV strains (19%) and sapovirus (2%). Nucleotide-sequence analysis indicated a great diversity of NoV strains and implicated the emergence of one particular sequence variant in outbreaks occurring between July 2002 and June 2003. The public health impact of caliciviruses will not be fully appreciated, nor will interventions be completely evaluated, until methods to detect these viruses are more routinely used.

BACKGROUND In 68% of foodborne disease outbreaks, no etiologic pathogen is identified. In two-thirds of outbreaks with no identified etiology, no stool specimens are submitted for testing. METHODS From April 2001 to March 2003, we pilot-tested use of prepackaged, self-contained stool specimen collection kits in 3 states, delivered to and from patients by courier or mail, to improve rates of specimen collection in the outbreak setting. Specimens were tested for bacterial and viral pathogens at health department laboratories, and results were correlated with epidemiological investigation data. RESULTS Specimens were returned by > or =1 person in 52 (96%) of 54 outbreaks in which kits were deployed; in total, 263 (76%) of 347 persons who received kits returned specimens. Resolution of symptoms was the most commonly cited reason for nonsubmission of kits. An etiology was confirmed in 37 (71%) of 52 outbreaks with specimens returned; 28 (76%) were attributable to norovirus, and 9 (24%) were attributed to bacterial pathogens. Stool kits were well received and cost an average of approximately 43 dollars per specimen returned. CONCLUSIONS In two-thirds of foodborne disease outbreaks in which delivered stool collection kits were successfully deployed, an etiologic organism was identified. Delivery of kits to and from patients to improve rates of stool collection in outbreaks in which specimens might otherwise not be submitted could substantially reduce the number of outbreaks with an unknown etiology.

In 2002, a sharp increase in outbreaks of norovirus-associated illness, both on cruise ships and on land, encouraged us to examine the molecular epidemiology of detected noroviruses, to identify a common strain or source. Of 14 laboratory-confirmed outbreaks on cruise ships, 12 (86%) were attributed to caliciviruses; among these 12, outbreak characteristics included continuation on successive cruises in 6 (50%), multiple modes of transmission in 7 (58%), and high (>10%) attack rates in 7 (58%). Eleven of the 12 calicivirus outbreaks were attributed to noroviruses, 7 (64%) of which were attributed to a previously unreported lineage, provisionally named "the Farmington Hills strain." From May 2002 to December 2002, 10 (45%) of 22 land-based outbreaks also were attributed to this strain. Nucleotide-sequence analysis provided insights into norovirus transmission, by documenting links among outbreaks, the introduction of strains onto ships, and viral persistence on board (despite cleaning). Control measures for outbreaks should address all routes of transmission. Better outbreak surveillance and collection of data on sequences will help to monitor norovirus strains and to identify common sources.