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We describe 2 cases of extensively drug-resistant Pseudomonas aeruginosa infection caused by a strain of public health concern, as it was recently associated with a nationwide outbreak of contaminated artificial tears. Both cases were detected through database review of genomes in the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT), a routine genome sequencing–based surveillance program. We generated a high-quality reference genome for the outbreak strain from an isolate from our center and examined the mobile elements encoding bla VIM-80 and bla -GES-9 carbapenemases. We used publicly available Pseudomonas aeruginosa genomes to explore the genetic relatedness and antimicrobial resistance genes of the outbreak strain. [ABSTRACT FROM AUTHOR]

Persons with HIV (PWH) are at increased risk for bacterial infections, and previous publications document an increased risk for invasive meningococcal disease (IMD) in particular. This analysis provides evidence that PWH face a 6-fold increase in risk for IMD based on Active Bacterial Core surveillance data collected during 2009–2019. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) control on college campuses is challenging given communal living and student social dynamics. Understanding SARS-CoV-2 transmission among college students is important for the development of optimal control strategies. Methods SARS-CoV-2 nasal swab samples were collected from University of Pittsburgh students for symptomatic testing and asymptomatic surveillance from August 2020 through April 2021 from 3 campuses. Whole-genome sequencing (WGS) was performed on 308 samples, and contact tracing information collected from students was used to identify transmission clusters. Results We identified 31 Pangolin lineages of SARS-CoV-2, the majority belonging to B.1.1.7 (Alpha) and B.1.2 lineages. Contact tracing identified 142 students (46%) clustering with each other; WGS identified 53 putative transmission clusters involving 216 students (70%). WGS identified transmissions that were missed by contact tracing. However, 84 cases (27%) could not be linked by either WGS or contact tracing. Clusters were most frequently linked to students residing in the same dormitory, off-campus roommates, friends, or athletic activities. Conclusions The majority of SARS-CoV-2–positive samples clustered by WGS, indicating significant transmission across campuses. The combination of WGS and contact tracing maximized the identification of SARS-CoV-2 transmission on campus. WGS can be used as a strategy to mitigate, and further prevent transmission among students. [ABSTRACT FROM AUTHOR]

Background Nontypeable Haemophilus influenzae (NTHi) is the most common cause of invasive H. influenzae disease in the United States (US). We evaluated the epidemiology of invasive NTHi disease in the US, including among pregnant women, infants, and people with human immunodeficiency virus (PWH). Methods We used data from population- and laboratory-based surveillance for invasive H. influenzae disease conducted in 10 sites to estimate national incidence of NTHi, and to describe epidemiology in women of childbearing age, infants aged ≤30 days (neonates), and PWH living in the surveillance catchment areas. H. influenzae isolates were sent to the Centers for Disease Control and Prevention for species confirmation, serotyping, and whole genome sequencing of select isolates. Results During 2008–⁠2019, average annual NTHi incidence in the US was 1.3/100 000 population overall, 5.8/100 000 among children aged <1 year, and 10.2/100 000 among adults aged ≥80 years. Among 225 reported neonates with NTHi, 92% had a positive culture within the first week of life and 72% were preterm. NTHi risk was 23 times higher among preterm compared to term neonates, and 5.6 times higher in pregnant/postpartum compared to nonpregnant women. More than half of pregnant women with invasive NTHi had loss of pregnancy postinfection. Incidence among PWH aged ≥13 years was 9.5 cases per 100 000, compared to 1.1 cases per 100 000 for non-PWH (rate ratio, 8.3 [95% confidence interval, 7.1–9.7]; P <.0001). Conclusions NTHi causes substantial invasive disease, especially among older adults, pregnant/postpartum women, and neonates. Enhanced surveillance and evaluation of targeted interventions to prevent perinatal NTHi infections may be warranted. [ABSTRACT FROM AUTHOR]

Background Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the coronavirus disease 2019 (COVID-19) pandemic in the United States are limited. Methods We investigated changes in the incidence of IBD due to Streptococcus pneumoniae , Haemophilus influenzae , group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as 1 March to 31 December 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014 to February 2020 trends. We conducted secondary analysis of a health care database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic. Results Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae , H. influenzae , GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19–associated nonpharmaceutical interventions (NPIs). Significant declines were observed across all age and race groups, and surveillance sites for S. pneumoniae and H. influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years. Conclusions NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing. [ABSTRACT FROM AUTHOR]

Background Candidemia is a common healthcare-associated infection with high mortality. Estimates of recurrence range from 1% to 17%. Few studies have focused on those with recurrent candidemia, who often experience more severe illness and greater treatment failure. We describe recurrent candidemia trends and risk factors. Methods We analyzed population-based candidemia surveillance data collected during 2011–2018. Persons with >1 episode (defined as the 30-day period after a positive Candida species) were classified as having recurrent candidemia. We compared factors during the initial episode between those who developed recurrent candidemia and those who did not. Results Of the 5428 persons identified with candidemia, 326 (6%) had recurrent infection. Recurrent episodes occurred 1.0 month to 7.6 years after any previous episode. In multivariable logistic regression controlling for surveillance site and year, recurrent candidemia was associated with being 19–44 years old (vs ≥65 years; adjusted odds ratio [aOR], 3.05 [95% confidence interval {CI}, 2.10–4.44]), being discharged to a private residence (vs medical facility; aOR, 1.53 [95% CI, 1.12–2.08]), hospitalization in the 90 days prior to initial episode (aOR, 1.66 [95% CI, 1.27–2.18]), receipt of total parenteral nutrition (aOR, 2.08 [95% CI, 1.58–2.73]), and hepatitis C infection (aOR, 1.65 [95% CI, 1.12–2.43]). Conclusions Candidemia recurrence >30 days after initial infection occurred in >1 in 20 persons with candidemia. Associations with younger age and hepatitis C suggest injection drug use may play a modifiable role. Prevention efforts targeting central line care and total parenteral nutrition use may help reduce the risk of recurrent candidemia. [ABSTRACT FROM AUTHOR]

We evaluated healthcare facility use of International Classification of Diseases, Tenth Revision (ICD-10) codes for culture-confirmed candidemia cases detected by active public health surveillance during 2019–2020. Most cases (56%) did not receive a candidiasis code, suggesting that studies relying on ICD-10 codes likely underestimate disease burden. [ABSTRACT FROM AUTHOR]

Background: Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States after introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD.Methods: We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100 000 persons).Results: From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, whereas incidence of nonvaccine type (NVT) NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-2018, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes.Conclusions: Nonsusceptible IPD incidence decreased after PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis. Methods We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention's Emerging Infections Program during April–August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher's exact tests. Results Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit–level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%). Conclusions One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background Treatment of severe group A Streptococcus (GAS) infections requires timely and appropriate antibiotic therapy. We describe the epidemiology of antimicrobial-resistant invasive GAS (iGAS) infections in the United States (US). Methods We analyzed population-based iGAS surveillance data at 10 US sites from 2006 through 2017. Cases were defined as infection with GAS isolated from normally sterile sites or wounds in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. Antimicrobial susceptibility was determined using broth microdilution or whole genome sequencing. We compared characteristics among patients infected with erythromycin-nonsusceptible (EryNS) and clindamycin-nonsusceptible (CliNS) strains to those with susceptible infections. We analyzed proportions of EryNS and CliNS among isolates by site, year, risk factors, and emm type. Results Overall, 17 179 iGAS cases were reported; 14.5% were EryNS. Among isolates tested for both inducible and constitutive CliNS (2011–2017), 14.6% were CliNS. Most (99.8%) CliNS isolates were EryNS. Resistance was highest in 2017 (EryNS: 22.8%; CliNS: 22.0%). All isolates were susceptible to β-lactams. EryNS and CliNS infections were most frequent among persons aged 18–34 years and in persons residing in long-term care facilities, experiencing homelessness, incarcerated, or who injected drugs. Patterns varied by site. Patients with nonsusceptible infections were significantly less likely to die. The emm types with >30% EryNS or CliNS included types 77, 58, 11, 83, and 92. Conclusions Increasing prevalence of EryNS and CliNS iGAS infections in the US is predominantly due to expansion of several emm types. Clinicians should consider local resistance patterns when treating iGAS infections. [ABSTRACT FROM AUTHOR]

Background Incidence of invasive disease due to Haemophilus influenzae serotype a (Hia) increased an average of 13% annually from 2002 through 2015. We describe clinical characteristics and adverse clinical outcomes of US invasive Hia cases detected through multistate surveillance during 2011–2015. Methods Medical record data were abstracted for cases reported in 8 jurisdictions conducting active population- and laboratory-based surveillance for invasive Hia disease across the United States. Isolates from sterile sites were serotyped using real-time polymerase chain reaction. Adverse clinical outcomes were defined as any possible complication of meningitis, bacteremic pneumonia, or bacteremia (including hearing loss and developmental delay, but excluding death) and were assessed at hospital discharge and one-year post-disease onset. Results During 2011–2015, 190 Hia cases were reported to the 8 participating sites; 169 (88.9%) had data abstracted. Many patients were aged <5 years (42.6%). Meningitis was the most common clinical presentation among those aged <1 year (71.4%); bacteremic pneumonia was the most common presentation among persons aged ≥50 years (78.7%). Overall, 95.9% of patients were hospitalized. Among those hospitalized, 47.5% were admitted to an intensive care unit and 6.2% died during hospitalization. At hospital discharge and one-year post-disease onset, adverse outcomes were identified in 17.7% and 17.8% of patients overall and in 43.9% and 48.5% of patients with meningitis (primarily children). Conclusions Hia infection can cause severe disease that requires hospitalization and may also cause short- and long-term adverse clinical outcomes, especially among children. Novel vaccines could prevent morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background Reported outbreaks of invasive group A Streptococcus (iGAS) infections among people who inject drugs (PWID) and people experiencing homelessness (PEH) have increased, concurrent with rising US iGAS rates. We describe epidemiology among iGAS patients with these risk factors. Methods We analyzed iGAS infections from population-based Active Bacterial Core surveillance (ABCs) at 10 US sites from 2010 to 2017. Cases were defined as GAS isolated from a normally sterile site or from a wound in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. We categorized iGAS patients into four categories: injection drug use (IDU) only, homelessness only, both, and neither. We calculated annual change in prevalence of these risk factors using log binomial regression models. We estimated national iGAS infection rates among PWID and PEH. Results We identified 12 386 iGAS cases; IDU, homelessness, or both were documented in ~13%. Skin infections and acute skin breakdown were common among iGAS patients with documented IDU or homelessness. Endocarditis was 10-fold more frequent among iGAS patients with documented IDU only versus those with neither risk factor. Average percentage yearly increase in prevalence of IDU and homelessness among iGAS patients was 17.5% and 20.0%, respectively. iGAS infection rates among people with documented IDU or homelessness were ~14-fold and 17- to 80-fold higher, respectively, than among people without those risks. Conclusions IDU and homelessness likely contribute to increases in US incidence of iGAS infections. Improving management of skin breakdown and early recognition of skin infection could prevent iGAS infections in these patients. [ABSTRACT FROM AUTHOR]

Background Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non- albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. Methods During 2017–2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. Results Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29–3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non- albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. Conclusions A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non- albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed. [ABSTRACT FROM AUTHOR]

Background Since the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines in the United States, invasive H. influenzae disease epidemiology has changed, and racial disparities have not been recently described. Methods Active population- and laboratory-based surveillance for H. influenzae was conducted through Active Bacterial Core surveillance at 10 US sites. Data from 2008–2017 were used to estimate projected nationwide annual incidence, as cases per 100 000. Results During 2008–2017, Active Bacterial Core surveillance identified 7379 H. influenzae cases. Of 6705 patients (90.9%) with reported race, 76.2% were White, 18.6% were Black, 2.8% were Asian/Pacific Islander, and 2.4% were American Indian or Alaska Native (AI/AN). The nationwide annual incidence was 1.8 cases/100 000. By race, incidence was highest among AI/AN populations (3.1) and lowest among Asian/Pacific Islander populations (0.8). Nontypeable H. influenzae caused the largest incidence within all races (1.3), with no striking disparities identified. Among AI/AN children aged <5 years, incidence of H. influenzae serotype a (Hia) was 16.7 times higher and Hib incidence was 22.4 times higher than among White children. Although Hia incidence was lower among White and Black populations than among AI/AN populations, Hia incidence increased 13.6% annually among White children and 40.4% annually among Black children aged <5 years. Conclusions While nontypeable H. influenzae causes the largest H. influenzae burden overall, AI/AN populations experience disproportionately high rates of Hia and Hib, with the greatest disparity among AI/AN children aged <5 years. Prevention tools are needed to reduce disparities affecting AI/AN children and address increasing Hia incidence in other communities. [ABSTRACT FROM AUTHOR]

Background Traditional methods of outbreak investigations utilize reactive whole genome sequencing (WGS) to confirm or refute the outbreak. We have implemented WGS surveillance and a machine learning (ML) algorithm for the electronic health record (EHR) to retrospectively detect previously unidentified outbreaks and to determine the responsible transmission routes. Methods We performed WGS surveillance to identify and characterize clusters of genetically-related Pseudomonas aerugin osa infections during a 24-month period. ML of the EHR was used to identify potential transmission routes. A manual review of the EHR was performed by an infection preventionist to determine the most likely route and results were compared to the ML algorithm. Results We identified a cluster of 6 genetically related P. aeruginosa cases that occurred during a 7-month period. The ML algorithm identified gastroscopy as a potential transmission route for 4 of the 6 patients. Manual EHR review confirmed gastroscopy as the most likely route for 5 patients. This transmission route was confirmed by identification of a genetically-related P. aeruginosa incidentally cultured from a gastroscope used on 4of the 5 patients. Three infections, 2 of which were blood stream infections, could have been prevented if the ML algorithm had been running in real-time. Conclusions WGS surveillance combined with a ML algorithm of the EHR identified a previously undetected outbreak of gastroscope-associated P. aeruginosa infections. These results underscore the value of WGS surveillance and ML of the EHR for enhancing outbreak detection in hospitals and preventing serious infections. [ABSTRACT FROM AUTHOR]

Background Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008–2017. Methods Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated. Results From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN. Conclusions Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development. [ABSTRACT FROM AUTHOR]

Background Whole genome sequencing (WGS) surveillance and electronic health record data mining have the potential to greatly enhance the identification and control of hospital outbreaks. The objective was to develop methods for examining economic value of a WGS surveillance-based infection prevention (IP) program compared to standard of care (SoC). Methods The economic value of a WGS surveillance-based IP program was assessed from a hospital's perspective using historical outbreaks from 2011–2016. We used transmission network of outbreaks to estimate incremental cost per transmission averted. The number of transmissions averted depended on the effectiveness of intervening against transmission routes, time from transmission to positive culture results and time taken to obtain WGS results and intervene on the transmission route identified. The total cost of an IP program included cost of staffing, WGS, and treating infections. Results Approximately 41 out of 89 (46%) transmissions could have been averted under the WGS surveillance-based IP program, and it was found to be a less costly and more effective strategy than SoC. The results were most sensitive to the cost of performing WGS and the number of isolates sequenced per year under WGS surveillance. The probability of the WGS surveillance-based IP program being cost-effective was 80% if willingness to pay exceeded $2400 per transmission averted. Conclusions The proposed economic analysis is a useful tool to examine economic value of a WGS surveillance-based IP program. These methods will be applied to a prospective evaluation of WGS surveillance compared to SoC. [ABSTRACT FROM AUTHOR]

Background: The mechanisms by which Neisseria meningitidis cause persistent human carriage and transition from carriage to invasive disease have not been fully elucidated.Methods: Georgia and Maryland high school students were sampled for pharyngeal carriage of N. meningitidis during the 2006-2007 school year. A total of 321 isolates from 188 carriers and all 67 invasive disease isolates collected during the same time and from the same geographic region underwent whole-genome sequencing. Core-genome multilocus sequence typing was used to compare allelic profiles, and direct read mapping was used to study strain evolution.Results: Among 188 N. meningitidis culture-positive students, 98 (52.1%) were N. meningitidis culture positive at 2 or 3 samplings. Most students who were positive at >1 sampling (98%) had persistence of a single strain. More than a third of students carried isolates that were highly genetically related to isolates from other students in the same school, and occasional transmission within the same county was also evident. The major pilin subunit gene, pilE, was the most variable gene, and no carrier had identical pilE sequences at different time points.Conclusion: We found strong evidence of local meningococcal transmission at both the school and county levels. Allelic variation within genes encoding bacterial surface structures, particularly pilE, was common. [ABSTRACT FROM AUTHOR]

Background Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. Methods Using whole genome sequencing, a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6340 invasive GBS isolates recovered during 2015–2017 through population-based Active Bacterial Core surveillance (ABCs) in 8 states. Results Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in 11 clonal complexes (CCs) comprised of multilocus sequence types identical or closely related to sequence types 1, 8, 12, 17, 19, 22, 23, 28, 88, 452, and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with nonsusceptibility to 1 or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin nonsusceptible (minimum inhibitory concentration = 2 µg/mL). Nearly all isolates possessed capsule genes, 1–2 of the 3 main pilus gene clusters, and 1 of 4 homologous alpha/Rib family determinants. Presence of the hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. Conclusions This first comprehensive, population-based quantitation of strain features in the United States suggests that current vaccine candidates should have good coverage. The β-lactams remain appropriate for first-line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring. [ABSTRACT FROM AUTHOR]

Background Invasive group B Streptococcus (iGBS) isolates with mutations in the pbp2x gene that encodes penicillin binding protein 2x can have reduced beta-lactam susceptibility (RBLS) when susceptible by Clinical and Laboratory Standards Institute (CLSI) criteria. We assessed the emergence and characteristics of RBLS strains in US iGBS isolates. Methods We analyzed iGBS isolates from 8 multistate population-based surveillance sites from 1998 to 2018. During 1998–2014, phenotypic antimicrobial susceptibility was determined by broth microdilution; criteria for 6 antibiotics were used to identify RBLS, followed by whole-genome sequencing (WGS). WGS for all isolates was added in 2015; we used phenotypic and genotypic results of >2000 isolates to validate phenotypic RBLS criteria and genotypic predictions. Since 2016, WGS has been used to screen for RBLS with broth microdilution confirmation of predicted RBLS isolates. Results Of 28 269 iGBS isolates, 28 (0.1%) were nonsusceptible by CLSI criteria; 137 (0.5%) met RBLS criteria. RBLS isolates were detected in all Active Bacterial Core surveillance sites. The RBLS proportion increased, especially since 2013 (odds ratio, 1.17; 95% CI, 1.03–1.32); the proportion that were nonsusceptible remained stable. Conclusions The RBSL proportion was low but increasing among US iGBS isolates. Ongoing monitoring is needed to detect emerging threats to prevention and treatment of GBS infections. [ABSTRACT FROM AUTHOR]

Background Candidemia is a common healthcare-associated bloodstream infection with high morbidity and mortality. There are no current estimates of candidemia burden in the United States (US). Methods In 2017, the Centers for Disease Control and Prevention conducted active population-based surveillance for candidemia through the Emerging Infections Program in 45 counties in 9 states encompassing approximately 17 million persons (5% of the national population). Laboratories serving the catchment area population reported all blood cultures with Candida , and a standard case definition was applied to identify cases that occurred in surveillance area residents. Burden of cases and mortality were estimated by extrapolating surveillance area cases to national numbers using 2017 national census data. Results We identified 1226 candidemia cases across 9 surveillance sites in 2017. Based on this, we estimated that 22 660 (95% confidence interval [CI], 20 210–25 110) cases of candidemia occurred in the US in 2017. Overall estimated incidence was 7.0 cases per 100 000 persons, with highest rates in adults aged ≥ 65 years (20.1/100 000), males (7.9/100 000), and those of black race (12.3/100 000). An estimated 3380 (95% CI, 1318–5442) deaths occurred within 7 days of a positive Candida blood culture, and 5628 (95% CI, 2465–8791) deaths occurred during the hospitalization with candidemia. Conclusions Our analysis highlights the substantial burden of candidemia in the US. Because candidemia is only one form of invasive candidiasis, the true burden of invasive infections due to Candida is higher. Ongoing surveillance can support future burden estimates and help assess the impact of prevention interventions. [ABSTRACT FROM AUTHOR]

Background Injection drug use (IDU) is a known, but infrequent risk factor on candidemia; however, the opioid epidemic and increases in IDU may be changing the epidemiology of candidemia. Methods Active population-based surveillance for candidemia was conducted in selected US counties. Cases of candidemia were categorized as IDU cases if IDU was indicated in the medical records in the 12 months prior to the date of initial culture. Results During 2017, 1191 candidemia cases were identified in patients aged >12 years (incidence: 6.9 per 100 000 population); 128 (10.7%) had IDU history, and this proportion was especially high (34.6%) in patients with candidemia aged 19–44. Patients with candidemia and IDU history were younger than those without (median age, 35 vs 63 years; P <.001). Candidemia cases involving recent IDU were less likely to have typical risk factors including malignancy (7.0% vs 29.4%; relative risk [RR], 0.2 [95% confidence interval {CI},.1–.5]), abdominal surgery (3.9% vs 17.5%; RR, 0.2 [95% CI,.09–.5]), and total parenteral nutrition (3.9% vs 22.5%; RR, 0.2 [95% CI,.07–.4]). Candidemia cases with IDU occurred more commonly in smokers (68.8% vs 18.5%; RR, 3.7 [95% CI, 3.1–4.4]), those with hepatitis C (54.7% vs 6.4%; RR, 8.5 [95% CI, 6.5–11.3]), and in people who were homeless (13.3% vs 0.8%; RR, 15.7 [95% CI, 7.1–34.5]). Conclusions Clinicians should consider injection drug use as a risk factor in patients with candidemia who lack typical candidemia risk factors, especially in those with who are 19–44 years of age and have community-associated candidemia. [ABSTRACT FROM AUTHOR]

Background The 13-valent pneumococcal vaccine (PCV13) was introduced for US children in 2010 and for immunocompromised adults ≥19 years old in series with the 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated PCV13 indirect effects on invasive pneumococcal disease (IPD) among adults with and without PCV13 indications. Methods Using Active Bacterial Core surveillance and the National Health Survey, using Active Bacterial Core surveillance and the National Health Interview Survey, we estimated and compared IPD incidence in 2013–2014 and 2007–2008, by age and serotype group (PCV13, PPSV23-unique, or nonvaccine types [NVTs]), among adults with and without PCV13 indications. Results IPD incidence declined among all adults. Among adults 19–64 years, PCV13-type IPD declined 57% (95% confidence interval [CI], −68% to −43%) in adults with immunocompromising conditions (indication for PCV13 use), 57% (95% CI, −62% to –52%) in immunocompetent adults with chronic medical conditions (CMCs, indications for PPSV23 use alone), and 74% (95% CI, −78% to −70%) in adults with neither vaccine indication. Among adults aged ≥65 years, PCV13-type IPD decreased 68% (95% CI, −76% to −60%) in those with immunocompromising conditions, 68% (95% CI, −72% to −63%) in those with CMCs, and 71% (95% CI, −77% to −64%) in healthy adults. PPSV23-unique types increased in adults 19‒64 years with CMCs, and NVTs did not change among adults with or without PCV13 indications. From 2013 to 2014, non-PCV13 serotypes accounted for 80% of IPD. Conclusions IPD incidence among US adults declined after PCV13 introduction in children. Similar reductions in PCV13-type IPD in those with and without PCV13 indications suggest that observed benefits are largely due to indirect effects from pediatric PCV13 use rather than direct use among adults. [ABSTRACT FROM AUTHOR]

Background Vancomycin-resistant enterococci (VRE) are a major cause of hospital-acquired infections. The risk of infection from interventional radiology (IR) procedures is not well documented. Whole-genome sequencing (WGS) surveillance of clinical bacterial isolates among hospitalized patients can identify previously unrecognized outbreaks. Methods We analyzed WGS surveillance data from November 2016 to November 2017 for evidence of VRE transmission. A previously unrecognized cluster of 10 genetically related VRE (Enterococcus faecium) infections was discovered. Electronic health record review identified IR procedures as a potential source. An outbreak investigation was conducted. Results Of the 10 outbreak patients, 9 had undergone an IR procedure with intravenous (IV) contrast ≤22 days before infection. In a matched case-control study, preceding IR procedure and IR procedure with contrast were associated with VRE infection (matched odds ratio [MOR], 16.72; 95% confidence interval [CI], 2.01 to 138.73; P =.009 and MOR, 39.35; 95% CI, 7.85 to infinity; P <.001, respectively). Investigation of IR practices and review of the manufacturer's training video revealed sterility breaches in contrast preparation. Our investigation also supported possible transmission from an IR technician. Infection prevention interventions were implemented, and no further IR-associated VRE transmissions have been observed. Conclusions A prolonged outbreak of VRE infections related to IR procedures with IV contrast resulted from nonsterile preparation of injectable contrast. The fact that our VRE outbreak was discovered through WGS surveillance and the manufacturer's training video that demonstrated nonsterile technique raise the possibility that infections following invasive IR procedures may be more common than previously recognized. [ABSTRACT FROM AUTHOR]

Background Few data on intracranial group A Streptococcus (GAS) infection in children are available. Here, we describe the demographic, clinical, and diagnostic characteristics of 91 children with intracranial GAS infection. Methods Cases of intracranial GAS infection in persons ≤18 years of age reported between 1997 and 2014 were identified by the Centers for Disease Control and Prevention's population- and laboratory-based Active Bacterial Core surveillance (ABCs) system. Medical charts were abstracted using a active, standardized case report form. All available isolates were emm typed. US census data were used to calculate rates. Results ABCs identified 2596 children with invasive GAS infection over an 18-year period; 91 (3.5%) had an intracranial infection. Intracranial infections were most frequent during the winter months and among children aged <1 year. The average annual incidence was 0.07 cases per 100000 children. For 83 patients for whom information for further classification was available, the principal clinical presentations included meningitis (35 [42%]), intracranial infection after otitis media, mastoiditis, or sinusitis (34 [41%]), and ventriculoperitoneal shunt infection (14 [17%]). Seven (8%) of these infections progressed to streptococcal toxic shock syndrome. The overall case fatality rate was 15%. GAS emm types 1 (31% of available isolates) and 12 (13% of available isolates) were most common. Conclusions Pediatric intracranial (GAS) infections are uncommon but often severe. Risk factors for intracranial GAS infection include the presence of a ventriculoperitoneal shunt and contiguous infections in the middle ear or sinuses. [ABSTRACT FROM AUTHOR]

Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology. [ABSTRACT FROM AUTHOR]

Candidemia and Clostridium difficile infection (CDI) are important healthcare-associated infections that share certain risk factors. We sought to describe candidemia-CDI coinfection using population-based surveillance data. We found that nearly 1 in 10 patients with candidemia had CDI coinfection. [ABSTRACT FROM AUTHOR]

Background Despite substantial attention to the individual topics, little is known about the relationship between racial disparities and antimicrobial-resistant and/or healthcare-associated infection trends, such as for methicillin-resistant Staphylococcus aureus (MRSA). Methods We analyzed Emerging Infections Program 2005–2014 surveillance data (9 US states) to determine whether reductions in invasive MRSA incidence (isolated from normally sterile body sites) affected racial disparities in rates. Case classification included hospital-onset (HO, culture >3 days after admission), healthcare-associated community onset (HACO, culture ≤3 days after admission and dialysis, hospitalization, surgery, or long-term care residence within 1 year prior), or community-associated (CA, all others). Negative binomial regression models were used to evaluate the adjusted rate ratio (aRR) of MRSA in black patients (vs in white patients) controlling for age, sex, and temporal trends. Results During 2005–2014, invasive HO and HACO (but not CA) MRSA rates decreased. Despite this, blacks had higher rates for HO (aRR, 3.20; 95% confidence interval [CI], 2.35–4.35), HACO (aRR, 3.84; 95% CI, 2.94–5.01), and CA (aRR, 2.78; 95% CI, 2.30–3.37) MRSA. Limiting the analysis to chronic dialysis patients reduced, but did not eliminate, the higher HACO MRSA rates among blacks (aRR, 1.83; 95% CI, 1.72–1.96), even though invasive MRSA rates among dialysis patients decreased during 2005–2014. These racial differences did not change over time. Conclusions Previous reductions in healthcare-associated MRSA infections have not affected racial disparities in MRSA rates. Improved understanding of the underlying causes of these differences is needed to develop effective prevention interventions that reduce racial disparities in MRSA infections. [ABSTRACT FROM AUTHOR]

Background Following Haemophilus influenzae serotype b (Hib) conjugate vaccine introduction in the 1980s, Hib disease in young children dramatically decreased, and epidemiology of invasive H. influenzae changed. Methods Active surveillance for invasive H. influenzae disease was conducted through Active Bacterial Core surveillance sites. Incidence rates were directly standardized to the age and race distribution of the US population. Results During 2009–2015, the estimated mean annual incidence of invasive H. influenzae disease was 1.70 cases per 100000 population. Incidence was highest among adults aged ≥65 years (6.30) and children aged <1 year (8.45); many cases in infants aged <1 year occurred during the first month of life in preterm or low-birth-weight infants. Among children aged <5 years (incidence: 2.84), incidence was substantially higher in American Indian and Alaska Natives AI/AN (15.19) than in all other races (2.62). Overall, 14.5% of cases were fatal; case fatality was highest among adults aged ≥65 years (20%). Nontypeable H. influenzae had the highest incidence (1.22) and case fatality (16%), as compared with Hib (0.03; 4%) and non-b encapsulated serotypes (0.45; 11%). Compared with 2002–2008, the estimated incidence of invasive H. influenzae disease increased by 16%, driven by increases in disease caused by serotype a and nontypeable strains. Conclusions Invasive H. influenzae disease has increased, particularly due to nontypeable strains and serotype a. A considerable burden of invasive H. influenzae disease affects the oldest and youngest age groups, particularly AI/AN children. These data can inform prevention strategies, including vaccine development. [ABSTRACT FROM AUTHOR]

Background. Invasive community-associated methicillin-resistant Staphylococcus aureus (MRSA) incidence in the United States is higher among black persons than white persons. We explored the extent to which socioeconomic factors might explain this racial disparity. Methods. A retrospective cohort was based on the Centers for Disease Control and Prevention's Emerging Infections Program surveillance data for invasive community-associated MRSA cases (isolated from a normally sterile site of an outpatient or on hospital admission day ≤3 in a patient without specified major healthcare exposures) from 2009 to 2011 in 33 counties of 9 states. We used generalized estimating equations to determine census tract-level factors associated with differences in MRSA incidence and inverse odds ratio-weighted mediation analysis to determine the proportion of racial disparity mediated by socioeconomic factors. Results. Annual invasive community-associated MRSA incidence was 4.59 per 100 000 among whites and 7.60 per 100 000 among blacks (rate ratio [RR], 1.66; 95% confidence interval [CI], 1.52-1.80). In the mediation analysis, after accounting for census tract-level measures of federally designated medically underserved areas, education, income, housing value, and rural status, 91% of the original racial disparity was explained; no significant association of black race with community-associated MRSA remained (RR, 1.05; 95% CI, .92-1.20). Conclusions. The racial disparity in invasive community-associated MRSA rates was largely explained by socioeconomic factors. The specific factors that underlie the association between census tract-level socioeconomic measures and MRSA incidence, which may include modifiable social (eg, poverty, crowding) and biological factors (not explored in this analysis), should be elucidated to define strategies for reducing racial disparities in community-associated MRSA rates. [ABSTRACT FROM AUTHOR]

Background. Invasive group A Streptococcus (GAS) infections are associated with significant morbidity and mortality rates. We report the epidemiology and trends of invasive GAS over 8 years of surveillance. Methods. From January 2005 through December 2012, we collected data from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance, a population-based network of 10 geographically diverse US sites (2012 population, 32.8 million). We defined invasive GAS as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis (NF) or streptococcal toxic shock syndrome (STSS). Available isolates were emm typed.We calculated rates and made age- and race-adjusted national projections using census data. Results. We identified 9557 cases (3.8 cases per 100 000 persons per year) with 1116 deaths (case-fatality rate, 11.7%). The casefatality rates for septic shock, STSS, and NF were 45%, 38%, and 29%, respectively. The annual incidence was highest among persons aged ≥65 years (9.4/100 000) or <1 year (5.3) and among blacks (4.7/100 000). National rates remained steady over 8 years of surveillance. Factors independently associated with death included increasing age, residence in a nursing home, recent surgery, septic shock, NF, meningitis, isolated bacteremia, pneumonia, emm type 1 or 3, and underlying chronic illness or immunosuppression. An estimated 10 649-13 434 cases of invasive GAS infections occur in the United States annually, resulting in 1136-1607 deaths. In a 30-valent Mprotein vaccine, emm types accounted for 91% of isolates. Conclusions. The burden of invasive GAS infection in the United States remains substantial. Vaccines under development could have a considerable public health impact. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis is an important cause of meningococcal disease globally. Sequence type (ST)-11 clonal complex (cc11) is a hypervirulentmeningococcal lineage historically associated with serogroupCcapsule and is believed to have acquired theWcapsule through a C toWcapsular switching event.We studied the sequence of capsule gene cluster (cps) and adjoining genomic regions of 524 invasiveWcc11 strains isolated globally.We identified recombination breakpoints corresponding to two distinct recombination events withinWcc11: A 8.4-kb recombinant region likely acquired fromWcc22 including the sialic acid/glycosyl-transferase gene, csw resulted in a C→W change in capsular phenotype and a 13.7-kb recombinant segment likely acquired from Y cc23 lineage includes 4.5 kbof cps genes and8.2 kbdownstreamof the cps cluster resulting in allelic changes in capsule translocation genes.Avast majority ofWcc11strains (497/524,94.8%) retainbothrecombination events as evidencedby sharing identicalor very closely related capsular allelic profiles. These data suggest that theW cc11 capsular switch involved two separate recombination events and that current globalWcc11 meningococcal disease is caused by strains bearing this mosaic capsular switch. [ABSTRACT FROM AUTHOR]

Background. Antibiotic-nonsusceptible invasive pneumococcal disease (IPD) decreased substantially after the US introduction of the pediatric 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. However, rates of antibiotic-nonsusceptible non-PCV7- type IPD increased during 2004-2009. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7.We assessed the impact of PCV13 on antibiotic-nonsusceptible IPD rates. Methods. We defined IPD as pneumococcal isolation from a normally sterile site in a resident from 10 US surveillance sites. Antibiotic-nonsusceptible isolates were those intermediate or resistant to ≥1 antibiotic classes according to 2012 Clinical and Laboratory Standards Institute breakpoints. We examined rates of antibiotic nonsusceptibility and estimated cases prevented between observed cases of antibiotic-nonsusceptible IPD and cases that would have occurred if PCV13 had not been introduced. Results. From 2009 to 2013, rates of antibiotic-nonsusceptible IPD caused by serotypes included in PCV13 but not in PCV7 decreased from 6.5 to 0.5 per 100 000 in children aged <5 years and from 4.4 to 1.4 per 100 000 in adults aged ≥65 years. During 2010-2013, we estimated that 1636 and 1327 cases of antibiotic-nonsusceptible IPD caused by serotypes included in PCV13 but not PCV7 were prevented among children aged <5 years (-97% difference) and among adults aged ≥65 years (-64% difference), respectively. Although we observed small increases in antibiotic-nonsusceptible IPD caused by non-PCV13 serotypes, no non-PCV13 serotype dominated among antibiotic-nonsusceptible strains. Conclusions. After PCV13 introduction, antibiotic-nonsusceptible IPD decreased in multiple age groups. Continued surveillance is needed to monitor trends of nonvaccine serotypes. Pneumococcal conjugate vaccines are important tools in the approach to combat antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background. Invasive group A Streptococcus (iGAS) infections cause significant morbidity and mortality worldwide. We analyzed whether obesity and diabetes were associated with iGAS infections and worse outcomes among an adult US population. Methods. We determined the incidence of iGAS infections using 2010-2012 cases in adults aged ≥18 years from Active Bacterial Core surveillance (ABCs), a population-based surveillance system, as the numerator. For the denominator, we used ABCs catchment area population estimates from the 2011 to 2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. The relative risk (RR) of iGAS was determined by obesity and diabetes status after adjusting for age group, gender, race, and other underlying conditions through binomial logistic regression. Multivariable logistic regression was used to determine whether obesity or diabetes was associated with increased odds of death due to iGAS compared to normal weight and nondiabetic patients, respectively. Results. Between 2010 and 2012, 2927 iGAS cases were identified. Diabetes was associated with an increased risk of iGAS in all racial groups (adjusted risk ratio [aRR] ranged from 2.71 to 5.08). Grade 3 obesity (body mass index [BMI] ≥40) was associated with an increased risk of iGAS for whites (aRR = 3.47; 95% confidence interval [CI], 3.00-4.01). Grades 1-2 (BMI = 30.0-<40.0) and grade 3 obesity were associated with an increased odds of death (odds ratio [OR] = 1.55, [95% CI, 1.05, 2.29] and OR = 1.62 [95% CI, 1.01, 2.61], respectively) when compared to normal weight patients. Conclusions. These results may help target vaccines against GAS that are currently under development. Efforts to develop enhanced treatment regimens for iGAS may improve prognoses for obese patients. [ABSTRACT FROM AUTHOR]

Background. Echinocandins are first-line treatment for Candida glabrata candidemia. Echinocandin resistance is concerning due to limited remaining treatment options. We used data from a multisite, population-based surveillance program to describe the epidemiology and risk factors for echinocandin nonsusceptible (NS) C glabrata candidemia. Methods. The Centers for Disease Control and Prevention's Emerging Infections Program conducts populationbased laboratory surveillance for candidemia in 4 metropolitan areas (7.9 million persons; 80 hospitals). We identified C glabrata cases occurring during 2008-2014; medical records of cases were reviewed, and C glabrata isolates underwent broth microdilution antifungal susceptibility testing. We defined echinocandin-NS C glabrata (intermediate or resistant) based on 2012 Clinical and Laboratory Standards Institute minimum inhibitory concentration breakpoints. Independent risk factors for NS C glabrata were determined by stepwise logistic regression. Results. Of 1385 C glabrata cases, 83 (6.0%) had NS isolates (19 intermediate and 64 resistant); the proportion of NS isolates rose from 4.2% in 2008 to 7.8% in 2014 (P < .001). The proportion of NS isolates at each hospital ranged from 0% to 25.8%; 3 large, academic hospitals accounted for almost half of all NS isolates. In multivariate analysis, prior echinocandin exposure (adjusted odds ratio [aOR], 5.3; 95% CI, 2.6-1.2), previous candidemia episode (aOR, 2.5; 95% CI, 1.2-5.1), hospitalization in the last 90 days (aOR, 1.9; 95% CI, 1.0-3.5, and fluconazole resistance [aOR, 3.6; 95% CI, 2.0-6.4]) were significantly associated with NS C glabrata. Fifty-nine percent of NS C glabrata cases had no known prior echinocandin exposure. Conclusion. The proportion of NS C glabrata isolates rose significantly during 2008-2014, and NS C glabrata frequency differed across hospitals. In addition to acquired resistance resulting from prior drug exposure, occurrence of NS C glabrata without prior echinocandin exposure suggests possible transmission of resistant organisms. [ABSTRACT FROM AUTHOR]

Background. Meningococcal conjugate vaccines against serogroups A, C, W, and Y (MenACWY) are recommended for routine use in adolescents aged 11-18 years. The impact of these vaccines on the meningococcal population structure in the United States have yet to be evaluated. Methods. Meningococcal isolates recovered during 2006-2010 (ie, after introduction of MenACWY) collected through Active Bacterial Core surveillance (ABCs) were characterized; serogroup distribution and molecular features of these isolates were compared to previously published data on ABCs isolates recovered from 2000 to 2005 (ie, before introduction of MenACWY). P values were generated using χ2 statistics and exact methods. Results. There was a significant change (P < .05) in serogroup distribution among all age groups between the 2 periods. A small proportion of isolates showed evidence of capsular switching in both periods. Between the 2 periods, significant changes were observed in the distribution of porin A, ferric enterobactin transport, and strain genotypes among vaccine and nonvaccine serogroups. Conclusions. The population structure of US meningococcal isolates is dynamic; some changes occurred over time, but the basic structure remained. Vaccine-induced serogroup replacement was not observed, although a small proportion of isolates had undergone capsule switching, possibly driven by non-vaccine-mediated selection. Changes in the distribution of molecular features are likely due to horizontal gene transfer and changes in serogroup distribution. [ABSTRACT FROM AUTHOR]

Background. Meningococcal disease incidence in the United States is at an all-time low. In a previous study of Georgia high school students, meningococcal carriage prevalence was 7%. The purpose of this study was to measure the impact of a meningococcal conjugate vaccine on serogroup Y meningococcal carriage and to define the dynamics of carriage in high school students. Methods. This was a prospective cohort study at 8 high schools, 4 each in Maryland and Georgia, during a school year. Students at participating schools received quadrivalent meningococcal conjugate vaccine that uses diphtheria toxoid as the protein carrier (MCV4-DT). In each state, 2 high schools were randomly assigned for MCV4-DT receipt by students at the beginning of the study, and 2 were randomly assigned for MCV4-DT receipt at the end. Oropharyngeal swab cultures for meningococcal carriage were performed 3 times during the school year. Results. Among 3311 students, the prevalence of meningococcal carriage was 3.21%--4.01%. Phenotypically nongroupable strains accounted for 88% of carriage isolates. There were only 5 observed acquisitions of serogroup Y strains during the study; therefore, the impact of MCV4-DT on meningococcal carriage could not be determined. Conclusions. Meningococcal carriage rates in US high school students were lower than expected, and the vast majority of strains did not express capsule. These findings may help explain the historically low incidence of meningococcal disease in the United States. [ABSTRACT FROM AUTHOR]

Introduction of 7-valent pneumococcal conjugate vaccine (PCV7) resulted in elimination of racial disparities in PCV7-type invasive pneumococcal disease (IPD) rates. New conjugate vaccines and strategies to address underlying etiologies behind racial disparities are needed to eliminate disparities in non-PCV7-type IPD.Background. Before the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), invasive pneumococcal disease (IPD) rates among blacks were twice the rates in whites. We measured the effects of trends in PCV7-type and non-PCV7-type IPD rates on racial disparities in overall IPD and estimated the proportion of IPD caused by serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13).Methods. We analyzed data from the Active Bacterial Core surveillance system, which performs active, laboratory- and population-based surveillance for IPD for 29.2 million people in the United States, for the period 1998–2009. For patients with unknown race, we multiplied imputed race to calculate age-, race-, and serotype-specific IPD incidence rates.Results. During 1998–2009, 47 449 IPD cases were identified; race was unknown for 5419 (11%). After multiple imputation, 31 981 (67%) patients were considered white and 13 750 (29%) black. PCV7-type IPD rates in all ages in both races decreased to <1 case per 100 000, whereas there were no decreases in overall IPD rates after 2002. By 2009, PCV13 serotypes caused 71% of cases among whites aged <5 years compared with 58% among blacks (P < .01). PCV13 serotypes caused 50% of IPD cases in whites aged ≥5 years compared with 43% among blacks (P < .01).Conclusions. Despite near elimination of PCV7-type IPD in both races, overall disparities in IPD rates persisted because non-PCV7-type IPD rates are higher among blacks. Whereas PCV13 introduction may reduce racial disparities in IPD, higher valency conjugate vaccines and strategies to directly address underlying causes are needed to eliminate IPD disparities. [ABSTRACT FROM PUBLISHER]

Incidence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections decreased substantially among dialysis patients during 2005–2011 based on surveillance data from 9 metropolitan areas. Despite decreases, an estimated 15 169 invasive MRSA infections occurred in US dialysis patients in 2011.Background. Approximately 15 700 invasive methicillin-resistant Staphylococcus aureus (MRSA) infections occurred in US dialysis patients in 2010. Frequent hospital visits and prolonged bloodstream access, especially via central venous catheters (CVCs), are risk factors among hemodialysis patients. We describe the epidemiology of and recent trends in invasive MRSA infections among dialysis patients.Methods. We analyzed population-based data from 9 US metropolitan areas from 2005 to 2011. Cases were defined as MRSA isolated from a normally sterile body site in a surveillance area resident who received dialysis, and were classified as hospital-onset (HO; culture collected >3 days after hospital admission) or healthcare-associated community-onset (HACO; all others). Incidence was calculated using denominators from the US Renal Data System. Temporal trends in incidence and national estimates were calculated controlling for age, sex, and race.Results. From 2005 to 2011, 7489 cases were identified; 85.7% were HACO infections, and 93.2% were bloodstream infections. Incidence of invasive MRSA infections decreased from 6.5 to 4.2 per 100 dialysis patients (annual decrease, 7.3%) with annual decreases of 6.7% for HACO and 10.5% for HO cases. Among cases identified during 2009–2011, 70% of patients were hospitalized in the year prior to infection. Among hemodialysis cases, 60.4% of patients were dialyzed through a CVC. The 2011 national estimated number of MRSA infections was 15 169.Conclusions. There has been a substantial decrease in invasive MRSA infection incidence among dialysis patients. Most cases had previous hospitalizations, suggesting that efforts to control MRSA in hospitals might have contributed to the declines. Infection prevention measures should include improved vascular access and CVC care. [ABSTRACT FROM AUTHOR]

Background. We examined whether observed increases in antibiotic nonsusceptible nonvaccine serotypes after introduction of pneumococcal conjugate vaccine in the United States in 2000 were driven primarily by vaccine or antibiotic use.Methods. Using active surveillance data, we evaluated geographic and temporal differences in serotype distribution and within-serotype differences during 2000–2009. We compared nonsusceptibility to penicillin and erythromycin by geography after standardizing differences across time, place, and serotype by regressing standardized versus crude proportions. A regression slope (RS) approaching zero indicates greater importance of the standardizing factor.Results. Through 2000–2006, geographic differences in nonsusceptibility were better explained by within-serotype prevalence of nonsusceptibility (RS 0.32, 95% confidence interval [CI], .08–.55 for penicillin) than by geographic differences in serotype distribution (RS 0.71, 95% CI, .44–.97). From 2007–2009, serotype distribution differences became more important for penicillin (within-serotype RS 0.52, 95% CI, .11–.93; serotype distribution RS 0.57, 95% CI, .14–1.0).Conclusions. Differential nonsusceptibility, within individual serotypes, accounts for most geographic variation in nonsusceptibility, suggesting selective pressure from antibiotic use, rather than differences in serotype distribution, mainly determines nonsusceptibility patterns. Recent trends suggest geographic differences in serotype distribution may be affecting the prevalence of nonsusceptibility, possibly due to decreases in the number of nonsusceptible serotypes. [ABSTRACT FROM PUBLISHER]

Multilocus variable number of tandem repeats analysis genotyping of Clostridium difficile isolates from screening tests and patients with symptomatic C. difficile infection reveals that asymptomatic carriers and environmental transmission from both carriers and patients with C. difficile infection contribute to new hospital-acquired cases.Background. Previous studies have suggested that asymptomatic carriers of toxigenic Clostridium difficile are a source of hospital-associated (HA) infections. Multilocus variable number of tandem repeats analysis (MLVA) is a highly discriminatory molecular subtyping tool that helps to determine possible transmission sources.Methods. Clostridium difficile isolates were recovered from perirectal swabs collected for vancomycin-resistant Enterococcus (VRE) surveillance as well as from clinical C. difficile toxin–positive stool samples from July to November 2009 at the University of Pittsburgh Medical Center Presbyterian (UPMC). MLVA was performed to determine the genetic relationships between isolates from asymptomatic carriers and patients with HA C. difficile infection (HA-CDI). Asymptomatic carriage and HA-CDI isolates were considered to be associated if the carriage isolate was collected before the HA-CDI isolate and if the MLVA genotypes had a summed tandem-repeat difference of ≤2.Results. Of 3006 patients screened, 314 (10.4%) were positive for toxigenic C. difficile, of whom 226 (7.5%) were detected only by VRE surveillance cultures. Of 56 incident cases of CDI classified as HA at UPMC during the study with available isolates, 17 (30%) cases were associated with CDI patients, whereas 16 (29%) cases were associated with carriers. Transmission events from prior bed occupants with CDI (n = 2) or carriers (n = 2) were identified in 4 of 56 cases.Conclusions. In our hospital with an established infection control program designed to contain transmission from symptomatic CDI patients, asymptomatic carriers appear to have played an important role in transmission. Identification and isolation of carriers may be necessary to further reduce transmission of C. difficile in such settings. [ABSTRACT FROM AUTHOR]

Background. Because pneumococcal pneumonia was prevalent during previous influenza pandemics, we evaluated invasive pneumococcal pneumonia (IPP) rates during the 2009 influenza A(H1N1) pandemic.Methods. We identified laboratory-confirmed, influenza-associated hospitalizations and IPP cases (pneumococcus isolated from normally sterile sites with discharge diagnoses of pneumonia) using active, population-based surveillance in the United States. We compared IPP rates during peak pandemic months (April 2009–March 2010) to mean IPP rates in nonpandemic years (April 2004–March 2009) and, using Poisson models, to 2006–2008 influenza seasons.Results. Higher IPP rates occurred during the peak pandemic month compared to nonpandemic periods in 5–24 (IPP rate per 10 million: 48 vs 9 (95% confidence interval [CI], 5–13), 25–49 (74 vs 53 [CI, 41–65]), 50–64 (188 vs 114 [CI, 85–143]), and ≥65-year-olds (229 vs 187 [CI, 159–216]). In the models with seasonal influenza rates included, observed IPP rates during the pandemic peak were within the predicted 95% CIs, suggesting this increase was not greater than observed with seasonal influenza.Conclusions. The recent influenza pandemic likely resulted in an out-of-season IPP peak among persons ≥5 years. The IPP peak's magnitude was similar to that seen during seasonal influenza epidemics. [ABSTRACT FROM PUBLISHER]

We describe marked shifts in candidemia epidemiology over the past 2 decades. Adults aged ≥65 years replaced infants as the highest incidence group; adjusted incidence has declined significantly in infants. Efforts to determine effective prevention strategies are needed.Background. Candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported.Methods. We conducted active, population-based surveillance in metropolitan Atlanta, Georgia, and Baltimore City/County, Maryland (combined population 5.2 million), during 2008–2011. We calculated candidemia incidence and antifungal drug resistance compared with prior surveillance (Atlanta, 1992–1993; Baltimore, 1998–2000).Results. We identified 2675 cases of candidemia with 2329 isolates during 3 years of surveillance. Mean annual crude incidence per 100 000 person-years was 13.3 in Atlanta and 26.2 in Baltimore. Rates were highest among adults aged ≥65 years (Atlanta, 59.1; Baltimore, 72.4) and infants (aged <1 year; Atlanta, 34.3; Baltimore, 46.2). In both locations compared with prior surveillance, adjusted incidence significantly declined for infants of both black and white race (Atlanta: black risk ratio [RR], 0.26 [95% confidence interval {CI}, .17–.38]; white RR: 0.19 [95% CI, .12–.29]; Baltimore: black RR, 0.38 [95% CI, .22–.64]; white RR: 0.51 [95% CI: .29–.90]). Prevalence of fluconazole resistance (7%) was unchanged compared with prior surveillance; 32 (1%) isolates were echinocandin-resistant, and 9 (8 Candida glabrata) were multidrug resistant to both fluconazole and an echinocandin.Conclusions. We describe marked shifts in candidemia epidemiology over the past 2 decades. Adults aged ≥65 years replaced infants as the highest incidence group; adjusted incidence has declined significantly in infants. Use of antifungal prophylaxis, improvements in infection control, or changes in catheter insertion practices may be contributing to these declines. Further surveillance for antifungal resistance and efforts to determine effective prevention strategies are needed. [ABSTRACT FROM AUTHOR]

Background. Streptococcus pneumoniae (pneumococcus) caused approximately 44 000 US invasive pneumococcal disease (IPD) cases in 2008. Antibiotic nonsusceptibility complicates IPD treatment. Using penicillin susceptibility breakpoints adopted in 2008, we evaluated antibiotic-nonsusceptible IPD trends in light of the introductions of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 and a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010. Methods. IPD cases were defined by isolation of pneumococcus from a normally sterile site in individuals residing in Active Bacterial Core surveillance (ABCs) areas during 1998-2008. Pneumococci were serotyped and tested for antibiotic susceptibility using broth microdilution. Results. During 1998-2008, ABCs identified 43 198 IPD cases. Penicillin-nonsusceptible strains caused 6%-14% of IPD cases, depending on age. Between 1998-1999 and 2008, penicillin-nonsusceptible IPD rates declined 64% for children aged <5 years (12.1-4.4 cases per 100 000), and 45% for adults aged ≥65 (4.8-2.6 cases per 100 000). Rates of IPD nonsusceptible to multiple antibiotics mirrored these trends. During 2007-2008, serotypes in PCV13 but not PCV7 caused 78%-97% of penicillin-nonsusceptible IPD, depending on age. Conclusions. Antibiotic-nonsusceptible IPD rates remain below pre-PCV7 rates for children <5 and adults ≥65 years old. PCV13 vaccines hold promise for further nonsusceptibility reductions. [ABSTRACT FROM AUTHOR]

Background. With the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines, there has been a dramatic reduction of Hib disease in young children and the epidemiological trends of invasive H. influenzae have shifted. Methods. Data were collected from active surveillance for invasive H. influenzae disease conducted through Active Bacterial Core surveillance sites during 1989-2008. Results. During 1999-2008, the estimated mean annual incidence of H. influenzae infection was 1.62 cases per 100 000 population; 15.3% of cases were fatal. Incidence was higher among adults aged ≥65 years, compared with other age groups. The largest burden of disease among children aged <5 years was in infants aged <1 year; many of these cases occurred during the first month of life in preterm or low-birth weight infants. An estimated 10% of the total burden of disease among children aged <5 years occurred in American Indian and Alaska Native children. During 1989-2008, 7559 cases of H. influenzae disease were reported from Active Bacterial Core surveillance sites. Small increases in the incidence of serotypes a, e, and f were observed during 1989-2008. The largest of these increases was in serotype f and was primarily among adults aged ≥18 years. Conclusions. Since the introduction of Hib conjugate vaccines, the incidence of invasive disease caused by H. influenzae in the United States has decreased dramatically; however, a considerable burden of non-Hib disease is still present in the oldest and youngest age groups. There is no evidence of substantial replacement disease with non-b serotypes in young children in the United States. [ABSTRACT FROM AUTHOR]

Background. Rates of invasive pneumococcal disease (IPD) varied among the United States before pneumococcal conjugate vaccine (PCV7) introduction. We compared trends in IPD rates among diverse US sites over 10 years since PCV7 introduction. Methods. Patients with IPD of all ages were identified through active population and laboratory-based surveillance in 8 geographic areas under continuous surveillance during 1998-2009. Isolates were serotyped. IPD incidence rates and percent changes were calculated by site, serotype group, age, and year. Results. Reductions in rates of IPD ranged, by site, from 19 to 29.9 cases per 100,000 population during 1998- 1999 to 11.2-18.0 cases per 100,000 population during 2009 (rate reduction, 5.1-15.3 cases per 100,000 population). Reductions in IPD rates among children aged <5 years ranged from 35.7 to 117.2 cases per 100,000 population across the sites. Reductions in rates of IPD due to PCV7 serotypes were seen in all age groups at all sites, ranging from 12 to 21.4 cases per 100,000 population during 1998-1999 to <2 cases per 100,000 population during 2009 (92%-98% reductions). Serotype 19A rates ranged from 0.4 to 1.5 cases per 100,000 population during 1998-1999 to 1.3 to 3.4 cases per 100,000 population during 2009 (rate difference, 0.9-2.8 cases per 100,000 population); modest increases were observed for most age groups across the sites. Rates of IPD due to all other serotypes ranged from 6.3 to 10.3 cases per 100,000 population during 1998-1999 to 8.3-13.6 cases per 100,000 population during 2009 (rate difference,20.4 to 5.7 cases per 100,000 population). Across the sites, the greatest rate increases were seen in the 50-64 and >65 year age groups. Conclusions. Reductions in IPD due to vaccine serotypes were consistent across sites. Changes in serotype 19A and all other serotypes were variable. Although relative increases in non-vaccine type serotypes were large in some sites, absolute rate increases were small. [ABSTRACT FROM AUTHOR]

Background. A quadrivalent meningococcal conjugate vaccine (MCV4) was licensed in the United States in 2005; no serogroup B vaccine is available. Neisseria meningitidis changes its capsular phenotype through capsular switching, which has implications for vaccines that do not protect against all serogroups. Methods. Meningococcal isolates from 10 Active Bacterial Core surveillance sites from 2000 through 2005 were analyzed to identify changes occurring after MCV4 licensure. Isolates were characterized by multilocus sequence typing (MLST) and outer membrane protein gene sequencing. Isolates expressing capsular polysaccharide different from that associated with the MLST lineage were considered to demonstrate capsular switching. Results. Among 1160 isolates, the most common genetic lineages were the sequence type (ST)-23, ST-32, ST- 11, and ST-41/44 clonal complexes. Of serogroup B and Y isolates, 8 (1.5%) and 3 (0.9%), respectively, demonstrated capsular switching, compared with 36 (12.9%) for serogroup C (P < .001); most serogroup C switches were from virulent serogroup B and/or serogroup Y lineages. Conclusions. A limited number of genetic lineages caused the majority of invasive meningococcal infections. A substantial proportion of isolates had evidence of capsular switching. The high prevalence of capsular switching requires surveillance to detect changes in the meningococcal population structure that may affect the effectiveness of meningococcal vaccines. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis is a leading cause of bacterial meningitis and other serious infections worldwide. The epidemiological profile of N. meningitidis is highly changeable, with great differences in disease incidence and serogroup distribution. Six serogroups (namely serogroups A, B, C, W-135, X, and Y) are responsible for most cases of meningococcal disease worldwide; the epidemiological profile of disease caused by each serogroup is unique. No vaccine is available for endemic disease caused by serogroup B strains. Two tetravalent (A/C/Y/ W-135) meningococcal vaccines are licensed in the United States: a purified polysaccharide product and a polysaccharide-protein conjugate vaccine. The conjugate vaccine is recommended for all adolescents, although vaccine coverage remains low, and other groups at high risk of infection. A comprehensive program to prevent invasive meningococcal disease in the United States will require vaccination of infants; several conjugate vaccines for infants may become available in the near future. Broadly protective vaccines for endemic serogroup B disease are also needed. [ABSTRACT FROM AUTHOR]

Background. In January 2005, a quadrivalent (serogroups A, C , Y, and W-135) meningococcal conjugate vaccine was licensed for use in adolescents. This report describes the epidemiologic features of meningococcal disease in the United States from January 1998 through December 2007, before and during implementation of adolescent quadrivalent meningococcal conjugate vaccination. Methods. Data were collected from active surveillance for invasive Neisseria meningitidis conducted through the Active Bacterial Core surveillance (ABCs) sites during 1998-2007. Isolates from cases were serogrouped at the ABCs site and confirmed at the Centers for Disease Control and Prevention. Estimates of the incidence and number of cases in the 50 states were calculated, standardizing for race and age group. Results. In the period 1998-2007, a total of 2262 cases of meningococcal disease were reported from ABCs sites; 11.3% of these cases were fatal. The estimated United States average annual incidence of meningococcal disease was 0.53 cases per 100,000 population (95% confidence interval, 0.51-0.55), and an estimated 1525 (95% confidence interval, 1470-1598) cases occurred annually. The annual incidence decreased 64.1%, from 0.92 cases per 100,000 population in 1998 to 0.33 cases per 100,000 population in 2007. Infants aged <1 year have the highest incidence of meningococcal disease (5.38 cases per 100,000 population). After introduction of the quadrivalent meningococcal conjugate vaccine, no significant decrease in serogroup C or Y meningococcal disease was seen among those aged 11-19 years in 2006-2007, compared with 2004-2005. Conclusions. Before the introduction of the quadrivalent meningococcal conjugate vaccine, the incidence of meningococcal disease in the United States decreased to a historic low. However, meningococcal disease still causes a substantial burden of disease among all age groups. Future vaccination strategies may include targeting infants and preventing serogroup B meningococcal disease. [ABSTRACT FROM AUTHOR]