BACKGROUND: We investigated hospitalized carbapenem-resistant Enterobacterales (CRE) and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) cases with and without COVID-19, as identified through Emerging Infections Program surveillance in 10 sites from 2020 to 2022. METHODS: We defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K oxytoca, K pneumoniae, or K variicola resistant to any carbapenem. We defined an ESBL-E case as the first isolation of E coli, K pneumoniae, or K oxytoca resistant to any third-generation cephalosporin and nonresistant to all carbapenems tested. Specimens were drawn from a normally sterile site or urine among hospitalized residents of the surveillance area in a 30-day period. We defined COVID-19 as a positive SARS-CoV-2 test result (SC2(+)) within 14 days before CRE or ESBL-E specimen collection and performed multivariable logistic regression analyses. RESULTS: Of 1595 CRE and 1866 ESBL-E hospitalized cases, 38 (2.4%) and 60 (3.2%), respectively, had a SC2(+). Among these cases, a SC2(+) was associated with intensive care unit admission (adjusted odds ratio [aOR], 1.69 [95% CI, 1.14-2.50]; aOR, 1.48 [95% CI, 1.03-2.12]) and 30-day mortality (aOR, 1.79 [95% CI, 1.22-2.64]; aOR, 1.94 [95% CI, 1.39-2.70]). CONCLUSIONS: CRE and ESBL-E infections among hospitalized patients with preceding COVID-19 were uncommon but had worse outcomes when compared with cases without COVID-19. COVID-19 prevention in patients at risk of CRE and ESBL-E infections is needed, as well as continued infection control measures and antibiotic stewardship for patients with COVID-19.

BACKGROUND: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step towards informing better infection prevention and control practices and improving public health response. METHODS: Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1-December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS: Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly bla(OXA-23) or bla(OXA-24/40); however, an isolate with bla(NDM) was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS: Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.

BACKGROUND: We described changes in 2016─2020 carbapenem-resistant Enterobacterales (CRE) incidence rates in 7 US sites that conduct population-based CRE surveillance. METHODS: An incident CRE case was defined as the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to ≥1 carbapenem from a sterile site or urine in a surveillance area resident in a 30-day period. We reviewed medical records and classified cases as hospital-onset (HO), healthcare-associated community-onset (HACO), or community-associated (CA) CRE based on healthcare exposures and location of disease onset. We calculated incidence rates using census data. We used Poisson mixed effects regression models to perform 2016─2020 trend analyses, adjusting for sex, race/ethnicity, and age. We compared adjusted incidence rates between 2016 and subsequent years using incidence rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Of 4996 CRE cases, 62% were HACO, 21% CA, and 14% HO. The crude CRE incidence rate per 100 000 was 7.51 in 2016 and 6.08 in 2020 and was highest for HACO, followed by CA and HO. From 2016 to 2020, the adjusted overall CRE incidence rate decreased by 24% (RR, 0.76 [95% CI, .70-.83]). Significant decreases in incidence rates in 2020 were seen for HACO (RR, 0.75 [95% CI, .67-.84]) and CA (0.75 [.61-.92]) but not for HO CRE. CONCLUSIONS: Adjusted CRE incidence rates declined from 2016 to 2020, but changes over time varied by epidemiologic class. Continued surveillance and effective control strategies are needed to prevent CRE in all settings.

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of bla(KPC)-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of bla(KPC)-carrying Klebsiella pneumoniae ST258, and clonal expansion of bla(KPC)-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of bla(KPC)-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of bla(KPC) plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions.

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.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community. METHODS: 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 collected <3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing. RESULTS: 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. CONCLUSIONS: 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.

BACKGROUND: Nursing homes (NHs) provide care in a congregate setting for residents at high risk of severe outcomes from SARS-CoV-2 infection. In spring 2020, NHs were implementing new guidance to minimize SARS-CoV-2 spread among residents and staff. OBJECTIVE: To assess whether telephone and video-based infection control assessment and response (TeleICAR) strategies could efficiently assess NH preparedness and help resolve gaps. DESIGN: We incorporated Centers for Disease Control and Prevention COVID-19 guidance for NH into an assessment tool covering 6 domains: visitor restrictions; health care personnel COVID-19 training; resident education, monitoring, screening, and cohorting; personal protective equipment supply; core infection prevention and control (IPC); and communication to public health. We performed TeleICAR consultations on behalf of health departments. Adherence to each element was documented and recommendations provided to the facility. SETTING AND PARTICIPANTS: Health department-referred NHs that agreed to TeleICAR consultation. METHODS: We assessed overall numbers and proportions of NH that had not implemented each infection control element (gap) and proportion of NH that reported making ≥1 change in practice following the assessment. RESULTS: During April 13 to June 12, 2020, we completed TeleICAR consultations in 629 NHs across 19 states. Overall, 524 (83%) had ≥1 implementation gaps identified; the median number of gaps was 2 (interquartile range: 1-4). The domains with the greatest number of facilities with gaps were core IPC practices (428/625; 68%) and COVID-19 education, monitoring, screening, and cohorting of residents (291/620; 47%). CONCLUSIONS AND IMPLICATIONS: TeleICAR was an alternative to onsite infection control assessments that enabled public health to efficiently reach NHs across the United States early in the COVID-19 pandemic. Assessments identified widespread gaps in core IPC practices that put residents and staff at risk of infection. TeleICAR is an important strategy that leverages infection control expertise and can be useful in future efforts to improve NH IPC.

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 (n = 349, 83%). Klebsiella pneumoniae was the most common organism (n = 265, 63%), followed by Enterobacter cloacae complex (n = 77, 18%) and Escherichia coli (n = 50, 12%). Of 419 isolates analyzed by whole genome sequencing, 307 (73%) harbored a carbapenemase gene; variants of bla(KPC) predominated (n = 299, 97%). The occurrence of carbapenemase-producing K. pneumoniae, E. cloacae complex, and E. coli varied by region; the predominant sequence type within each genus was ST258, ST171, and ST131, respectively. None of the carbapenemase-producing CRE isolates displayed resistance to all antimicrobials tested; susceptibility to amikacin and tigecycline was generally retained.

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: 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.

IMPORTANCE: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts. OBJECTIVE: To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas. DESIGN, SETTING, AND PARTICIPANTS: Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed. EXPOSURES: Demographics, comorbidities, health care exposures, and culture source and location. MAIN OUTCOMES AND MEASURES: Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics. Results: Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 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. CONCLUSIONS AND RELEVANCE: 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.

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: Case series have described severe lower respiratory tract infection (LRI) in healthy, community-dwelling persons caused by methicillin-resistant Staphylococcus aureus (MRSA). Evaluating populations at risk is needed. METHODS: Surveillance for patients aged 50 years or younger hospitalized with LRI who had S aureus isolated from blood or respiratory specimen during September 2008 to August 2010 was performed at 25 hospitals in 5 US metropolitan areas. Persons with recent health care exposure were excluded. Lower respiratory tract infection diagnosis required supporting radiographic or clinical evidence. Clinical characteristics of LRI were compared by methicillin resistance phenotype. RESULTS: In total, 94 hospitalized community-onset S aureus LRI cases were identified. Lower respiratory tract infection cases were identified in both young adults and children (60%, 35-50 years; and 19%, younger than 17 years), without any seasonality or association with influenza circulation. Among the 94 case patients with LRI, 34 patients (36%) had bacteremia, 36 patients (40%) required ICU admission, and 6 patients (6%) died; proportions were similar between cases with methicillin-susceptible S aureus and MRSA. Lower respiratory tract infection cases with MRSA had longer median length of stay compared with those with methicillin-susceptible S aureus (9 vs. 6 days; P = 0.04). Lower respiratory tract infection cases with evidence of influenza infection had higher mortality compared with LRI cases without influenza infection (31% vs. 2%; P = 0.003). During influenza circulation, 35 (55%) of 64 case patients with LRI were tested for influenza, and 9 (26%) of the 35 case patients tested positive. CONCLUSIONS: S aureus LRI occurred in both adults and children, without any seasonality or association with MRSA and with and without evidence of influenza infection, although case fatality was higher among those with evidence of influenza infection. 2013 by Lippincott Williams & Wilkins.

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: Acute gastroenteritis (AGE) remains a common cause of clinic visits and hospitalizations in the United States, but the etiology is rarely determined. METHODS: We performed a prospective, multicenter emergency department-based study of adults with AGE. Subjects were interviewed on presentation and 3-4 weeks later. Serum samples, rectal swab specimens, and/or whole stool specimens were collected at presentation, and serum was collected 3-4 weeks later. Fecal specimens were tested for a comprehensive panel of viral, bacterial, and parasitic pathogens; serum was tested for calicivirus antibodies. RESULTS: Pathogens were detected in 25% of 364 subjects, including 49% who provided a whole stool specimen. The most commonly detected pathogens were norovirus (26%), rotavirus (18%), and Salmonella species (5.3%). Pathogens were detected significantly more often from whole stool samples versus a rectal swab specimen alone. Nine percent of subjects who provided whole stool samples had >1 pathogen identified. CONCLUSIONS: Viruses, especially noroviruses, play a major role as agents of severe diarrhea in adults. Further studies to confirm the unexpectedly high prevalence of rotaviruses and to explore the causes of illness among patients from whom a pathogen cannot be determined are needed. Studies of enteric pathogens should require the collection of whole stool samples.

BACKGROUND: Many assumed high morbidity and mortality would accompany the emergence of MRSA USA300 infections as a cause of healthcare-associated infections (HAIs). We evaluated patients with invasive MRSA infections to assess differences in outcomes between infections caused by USA100 and USA300. METHODS: Population-based data for invasive MRSA infections were used to identify two cohorts: (1) non-dialysis patients with central line-associated bloodstream infections (CLABSI); 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 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 (OR=2.6, P=.02). Independent predictors of CLABSI late complications included intensive care unit (ICU) admission before MRSA culture (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); while 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.

We describe clinical and laboratory characteristics of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections with vancomycin MICs of 2 mug/mL and compare hVISA to non-hVISA. Infections were most often healthcare-associated community-onset, demonstrated frequent complications and relapses. hVISA patients were more likely to have been hospitalized in the year prior to MRSA culture.

USA300 methicillin-resistant Staphylococcus aureus (MRSA) isolates are usually resistant only to oxacillin, erythromycin, and, increasingly, levofloxacin. Of these, oxacillin and levofloxacin resistances are chromosomally encoded. Plasmid-mediated clindamycin, mupirocin, and/or tetracycline resistance has been observed among USA300 isolates, but these descriptions were limited to specific patient populations or isolated occurrences. We examined the antimicrobial susceptibilities of invasive MRSA isolates from a national surveillance population in order to identify USA300 isolates with unusual, possibly emerging, plasmid-mediated antimicrobial resistance. DNA from these isolates was assayed for the presence of resistance determinants and the presence of a pSK41-like conjugative plasmid. Of 823 USA300 isolates, 72 (9%) were tetracycline resistant; 69 of these were doxycycline susceptible and tetK positive, and 3 were doxycycline resistant and tetM positive. Fifty-one (6.2%) isolates were clindamycin resistant and ermC positive; 22 (2.7%) isolates were high-level mupirocin resistant (mupA positive); 5 (0.6%) isolates were trimethoprim-sulfamethoxazole (TMP-SMZ) resistant, of which 4 were dfrA positive; and 7 (0.9%) isolates were gentamicin resistant and aac6'-aph2'' positive. Isolates with pSK41-like plasmids (n = 24) were positive for mupA (n = 19), dfrA (n = 6), aac6'-aph2'' (n = 6), tetM (n = 2), and ermC (n = 8); 20 pSK41-positive isolates were positive for two or more resistance genes. Conjugative transfer of resistance was demonstrated between four gentamicin- and mupirocin-resistant and three gentamicin- and TMP-SMZ-resistant USA300 isolates; transconjugants harbored a single pSK41-like plasmid, which was PCR positive for aac6'-aph2'' and either mupA and/or dfrA. USA300 and USA100 isolates from the same state with identical resistance profiles contained pSK41-like plasmids with indistinguishable restriction and Southern blot profiles, suggesting horizontal plasmid transfer between USA100 and USA300 isolates.

CONTEXT: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of public health importance; MRSA prevention programs that may affect MRSA transmission and infection are increasingly common in health care settings. Whether there have been changes in MRSA infection incidence as these programs become established is unknown; however, recent data have shown that rates of MRSA bloodstream infections (BSIs) in intensive care units are decreasing. OBJECTIVE: To describe changes in rates of invasive health care-associated MRSA infections from 2005 through 2008 among residents of 9 US metropolitan areas. DESIGN, SETTING, AND PARTICIPANTS: Active, population-based surveillance for invasive MRSA in 9 metropolitan areas covering a population of approximately 15 million persons. All reports of laboratory-identified episodes of invasive (from a normally sterile body site) MRSA infections from 2005 through 2008 were evaluated and classified based on the setting of the positive culture and the presence or absence of health care exposures. Health care-associated infections (ie, hospital-onset and health care-associated community-onset), which made up 82% of the total infections, were included in this analysis. MAIN OUTCOME MEASURES: Change in incidence of invasive health care-associated MRSA infections and health care-associated MRSA BSIs using population of the catchment area as the denominator. RESULTS: From 2005 through 2008, there were 21,503 episodes of invasive MRSA infection; 17,508 were health care associated. Of these, 15,458 were MRSA BSIs. The incidence rate of hospital-onset invasive MRSA infections was 1.02 per 10,000 population in 2005 and decreased 9.4% per year (95% confidence interval [CI], 14.7% to 3.8%; P = .005), and the incidence of health care-associated community-onset infections was 2.20 per 10,000 population in 2005 and decreased 5.7% per year (95% CI, 9.7% to 1.6%; P = .01). The decrease was most prominent for the subset of infections with BSIs (hospital-onset: -11.2%; 95% CI -15.9% to -6.3%; health care-associated community-onset: -6.6%; 95% CI -9.5% to -3.7%). CONCLUSION: Over the 4-year period from 2005 through 2008 in 9 diverse metropolitan areas, rates of invasive health care-associated MRSA infections decreased among patients with health care-associated infections that began in the community and also decreased among those with hospital-onset invasive disease.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has rapidly emerged in the USA as a cause of severe infections in previously healthy persons without traditional risk factors. We describe the epidemiology of severe CA-MRSA disease in the state of Georgia, USA and analyse the risk of death associated with three different clinical syndromes of CA-MRSA disease - pneumonia, invasive disease, and skin and soft-tissue infections (SSTIs). A total of 1670 cases of severe CA-MRSA disease were reported during 2005-2007. The case-fatality rate was 3.4%; sex and race of fatal and non-fatal cases did not differ significantly. While CA-MRSA pneumonia and invasive disease were less common than SSTIs, they were about 15 times more likely to result in death [risk ratio 16.69, 95% confidence interval (CI) 10.28-27.07 and 13.98, 95% CI 7.74-25.27, respectively]. When controlling for age and the presence of other clinical syndromes the odds of death in patients manifesting specific severe CA-MRSA syndromes was highest in those with pneumonia (odds ratio 11.34). Possible risk factors for severe CA-MRSA SSTI and pneumonia included the draining of lesions without medical assistance and an antecedent influenza-like illness.

We evaluated the potential effects of a hypothetical vaccine in preventing invasive methicillin-resistant Staphylococcus aureus (MRSA) disease in the United States. Using an active, population-based surveillance program, we estimated baseline disease rates in the United States and compared three distinct vaccination strategies which targeted adults > or =65 years of age, persons at risk for recurrent invasive infection, and patients at hospital discharge. The strategies were projected to reduce the burden of invasive MRSA disease by 12.1%, 13.9% and 17.6%, respectively; with the strategy of vaccinating both adults > or =65 years of age and all adults at hospital discharge having the greatest impact per dose. Our data suggest that availability of an effective S. aureus vaccine could result in substantial reductions in invasive MRSA disease incidence. As candidate vaccines are evaluated, these data will be important in determining the optimal vaccination strategy.

CONTEXT: 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. OBJECTIVE: To assess trends in infections with antimicrobial-resistant S. Typhi. DESIGN: Cross-sectional, laboratory-based surveillance study. SETTING AND PARTICIPANTS: 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. MAIN OUTCOME MEASURES: Proportion of S. Typhi isolates demonstrating resistance to 14 antimicrobial agents and patient risk factors for antimicrobial-resistant infections. RESULTS: 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). CONCLUSION: 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.