Ten Clostridioides difficile isolates representing the top 10 ribotypes collected in 2016 through the Emerging Infections Program underwent long-read sequencing to obtain high-quality reference genome assemblies. These isolates are publicly available through the CDC & FDA Antibiotic Resistance Isolate Bank.

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.

We thank Gonzales-Luna and colleagues [1] for their comments. We agree that laboratories must have access to accurate and standardized methods for antimicrobial susceptibility testing (AST) results to be clinically meaningful. The reference method for performing Clostridioides difficile AST is agar dilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines [2]. The CLSI method for performing AST for anaerobic bacteria recommends that 5 μg/mL of hemin be incorporated into agar dilution plates and that the hemin stock solution should be protected from light and stored at 4°C–8°C for no longer than 1 month [2]. The susceptibility testing done by Gargis et al [3] was performed according to these guidelines, and the hemin stock solution was protected from light. | | Nevertheless, we read with interest the research in recent years [4–6] related to heme-dependent metronidazole resistance, including the reported association between isolates characterized as heme dependent and metronidazole resistant and the presence of a T to G mutation (PnimBG) in the −10 promoter region of the nitroimidazole reductase gene, nimB [5]. While Olaitan et al [5] found that not all heme-dependent metronidazole-resistant isolates contained the PnimBG mutation, Olaitan et al [5] indicate that most do; therefore, the presence of PnimBG may be predictive of resistance. We determined that the nimB mutation was present in 20% of our study isolates (116 of 593), of which 99% (115 of 116) belonged to RT027 (Table 1). The remaining isolate was RT014, the only RT014 isolate containing the PnimBG mutation among the 65 evaluated.

Importance: There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. Objective(s): To evaluate the quantitative titers and durability of binding antibodies detected after SARSCoV-2 infection and subsequent COVID-19 vaccination. Design(s): A prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOWTM COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. Setting(s): A nursing home during and after a SARS-CoV-2 outbreak. Participant(s): 11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and Measures: SARS-CoV-2 testing (BinaxNOWTM, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). Result(s): Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive but none were culture positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation <=90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Conclusions and Relevance: Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. We conducted a prospective longitudinal evaluation of 11 consenting SARS-CoV-2-positive nursing home residents to evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. The evaluation included nine visits over 150 days from October 25, 2020, through April 1, 2021. Visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW™ COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. We evaluated quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). The median age among participants was 74 years; one participant was immunocompromised. Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies, and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive, but none were culture- positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation ≤90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

BACKGROUND: Antimicrobial susceptibility testing (AST) is not routinely performed for Clostridioides difficile and data evaluating minimum inhibitory concentrations (MICs) are limited. We performed AST and whole genome sequencing (WGS) for 593 C. difficile isolates collected between 2012-2017 through the Centers for Disease Control and Prevention's Emerging Infections Program. METHODS: MICs to six antimicrobial agents (ceftriaxone, clindamycin, meropenem, metronidazole, moxifloxacin, and vancomycin) were determined using the reference agar dilution method according to Clinical and Laboratory Standards Institute guidelines. WGS was performed on all isolates to detect the presence of genes or mutations previously associated with resistance. RESULTS: Among all isolates, 98.5% displayed a vancomycin MIC ≤ 2 μg/mL and 97.3% displayed a metronidazole MIC ≤ 2 μg/mL. Ribotype 027 (RT027) isolates displayed higher vancomycin MICs (MIC50: 2 μg/mL; MIC90: 2 μg/mL) than non-RT027 isolates (MIC50: 0.5 μg/mL; MIC90: 1 μg/mL) (P < 0.01). No vanA/B genes were detected. RT027 isolates also showed higher MICs to clindamycin and moxifloxacin and were more likely to harbor associated resistance genes or mutations. CONCLUSIONS: Elevated MICs to antibiotics used for treatment of C. difficile infection were rare and there was no increase in MICs over time. The lack of vanA/B genes or mutations consistently associated with elevated vancomycin MICs suggests there are multifactorial mechanisms of resistance. Ongoing surveillance of C. difficile using reference AST and WGS to monitor MIC trends and the presence of antibiotic resistance mechanisms is essential.

OBJECTIVE: Without timely screening, diagnosis, and intervention, hearing loss can cause significant delays in a child's speech, language, social, and emotional development. In 2019, Texas had nearly twice the average rate of loss to follow-up (LFU) or loss to documentation (LTD; i.e., missing documentation of services received) among infants who did not pass their newborn hearing screening compared to the United States overall (51.1% vs. 27.5%). We aimed to identify factors contributing to LFU/LTD among infants who do not pass their newborn hearing screening in Texas. STUDY DESIGN: Data were collected through semi-structured qualitative interviews with 56 providers along the hearing care continuum, including hospital newborn hearing screening program staff, audiologists, primary care physicians, and early intervention (EI) program staff located in three rural and urban public health regions in Texas. Following recording and transcription of the interviews, we used qualitative data analysis software to analyze themes using a conventional content analysis approach. RESULTS: Frequently cited barriers included problems with family access to care, difficulty contacting patients, problems with communication between providers and referrals, lack of knowledge among providers and parents, and problems using the online reporting system. Providers in rural areas more often mentioned problems with family access to care and contacting families compared to providers in urban areas. CONCLUSION: These findings provide insight into strategies that public health professionals and health care providers can use to work together to help further increase the number of children identified early who may benefit from EI services.

TO THE EDITORWe read with concern the report by Darkoh and colleagues describing vancomycin resistance in Clostridioides difficile isolates recovered from patients in Houston, Texas, and Nairobi, Kenya [1]. The authors suggested that vancomycin resistance, which they found to be common, may lead to therapeutic failure for patients infected with C. difficile and that routine antimicrobial susceptibility testing (AST) should be expanded. The authors report that 26% of C. difficile toxin gene-positive patients in Houston and 67% of sequential hospitalized patients in Nairobi with acute diarrhea had growth on primary screening media containing 4g/mL vancomycin. This alarmingly high proportion of a vancomycin resistant phenotype exceeds initial treatment failure rates reported in the literature [2], calling into question the reliability of these findings.

Healthcare-associated carbapenem-resistant Acinetobacter baumannii (CRAB) infections are a serious threat associated with global epidemic clones and a variety of carbapenemase gene classes. In this study, we describe the molecular epidemiology, including whole-genome sequencing analysis and antimicrobial susceptibility profiles of 92 selected, nonredundant CRAB collected through public health efforts in the United States from 2013 to 2017. Among the 92 isolates, the Oxford (OX) multilocus sequence typing scheme identified 30 sequence types (STs); the majority of isolates (n = 59, 64%) represented STs belonging to the international clonal complex 92 (CC92(OX)). Among these, ST208(OX) (n = 21) and ST281(OX) (n = 20) were the most common. All isolates carried an OXA-type carbapenemase gene, comprising 20 alleles. Ninety isolates (98%) encoded an intrinsic OXA-51-like enzyme; 67 (73%) harbored an additional acquired bla(OXA) gene, most commonly bla(OXA-23) (n = 45; 49%). Compared with isolates harboring only intrinsic oxacillinase genes, acquired bla(OXA) gene presence was associated with higher prevalence of resistance and a higher median minimum inhibitory concentration to the carbapenem imipenem (64 μg/mL vs. 8 μg/mL), and antibiotics from other drug classes, including penicillin, aminoglycosides, cephalosporins, and polymyxins. These data illustrate the wide distribution of CC92(OX) and high prevalence of acquired bla(OXA) carbapenemase genes among CRAB in the United States.

Repeated antigen testing of 12 SARS-CoV-2-positive nursing home residents using Abbott BinaxNOW™ identified 9/9 (100%) culture-positive specimens up to 6 days after initial positive test. Antigen positivity lasted 2-24 days. Antigen positivity might last beyond the infectious period, but was reliable in residents with evidence of early infection.

BACKGROUND: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people. OBJECTIVE: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak. DESIGN: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results. SETTING: A nursing home with an ongoing SARS-CoV-2 outbreak. PARTICIPANTS: 532 paired specimens collected from 234 available residents and staff. MEASUREMENTS: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture. RESULTS: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively). LIMITATION: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff. CONCLUSION: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes. PRIMARY FUNDING SOURCE: None.

Given the availability of an effective and safe vaccine, the World Health Organization (WHO) declared that global measles eradication is achievable, and measles elimination goals have since been established as interim steps toward eradication. As part of a strategy to maintain elimination, the Pan American Health Organization (PAHO) and WHO stipulate a minimum annual reporting rate of discarded non-measles cases of ≥2 per 100,000 population, in order to ensure sensitive surveillance and adequate investigative effort. With its effective vaccination program, the United States in 2000 was among the first countries to verify elimination, although subsequently, it has not routinely reported discarded rates. We estimated MLI investigation rates among insured individuals during 2010-2017, using data from the MarketScan® databases. We defined "MLI investigations" as measles serologic testing within 5 days following diagnostic codes for measles-compatible symptoms and conditions. We provide a rationale for pre-specifying three subgroups for analysis: children aged ≤15 years; males aged 16-22 years excluding data from summer months; and males aged ≥23 years. MLI investigation rates ranged from 6.6─26.4 per 100,000, remaining stable over time except during the 2015 measles outbreaks when rates increased, particularly among young children. In addition to high vaccine uptake, measles elimination requires ongoing vigilance by clinicians and high-quality, case-based surveillance. Estimated rates of MLI investigations in this U.S. population suggesting that the quality of measles surveillance is sufficiently sensitive to detect endemic measles circulation if it were to be occurring.

BACKGROUND: The primary reported risk factors for herpes zoster (HZ) are increasing age and immunodeficiency yet estimates of HZ risk by immunocompromising condition have not been well characterized. We undertook a systematic review of the literature to estimate HZ risk in five categories of immunocompromised patients. METHODS: We systematically reviewed studies examining risk of HZ and its complications in adult patients with hematopoietic cell transplants (HCT), cancer (hematologic and solid tumor), HIV, and solid organ transplant (SOT; kidney and other). We identified studies in Pubmed, Embase, Cochrane, Scopus, and clinicaltrials.gov that presented original data from studies in the United States published after 1992 (1996 for HIV). We assessed risk of bias with Cochrane or GRADE methods. RESULTS: We identified and screened 3,765 records and synthesized 34 studies with low or moderate risk of bias. The majority of studies included (32/34) reported at least one estimate of HZ cumulative incidence (range=0%-41%). Twelve studies reported HZ incidence, which varied widely within and between immunocompromised populations. Incidence estimates ranged between 9 and 92 HZ cases/1,000 patient-years and were highest in HCT, followed by hematologic malignancies, SOT, solid tumor malignancies, and lowest in HIV patients. Among 17 studies of HCT patients, absent or <1 year of post-transplant antiviral prophylaxis were associated with higher HZ cumulative incidence. CONCLUSIONS: HZ is common among all immunocompromised populations studied-exceeding expected HZ incidence among immunocompetent adults >/=60 years. Better evidence of incidence of HZ complications and severity in immunocompromised populations are needed to inform economic and HZ vaccine policy analyses.

On August 6, 2017, the Kosrae Department of Health Services (KDHS) in the Federated States of Micronesia identified a confirmed case of mumps in a Kosrae resident who had 2 documented doses of measles-mumps-rubella (MMR) vaccine. The patient aged 18 years had recently traveled to Seattle, Washington, which was experiencing a mumps outbreak among members of its Pacific Islander population. Other Pacific Islands were concurrently experiencing large mumps outbreaks (1,2), in some places exceeding 500 cases, raising concern about the possibility of a similar outbreak in Kosrae. By October 6, KDHS had identified 17 cases (nine laboratory confirmed and eight suspected [clinically diagnosed as parotitis]) on the island (population 6,600) (Figure), with an attack rate of 14 cases per 1,000 residents in the primary affected municipality. At the request of KDHS, CDC deployed a team on October 17 to assist KDHS in investigation and control activities. The KDHS-CDC team conducted active surveillance to assess outbreak magnitude, interviewed mumps patients, collected specimens for laboratory testing, and reviewed patients’ vaccination records. KDHS conducted islandwide awareness campaigns about the outbreak and mumps prevention measures, and highlighted the importance of vaccination.

In August 2018, CDC noted an increased number of reports of patients having symptoms clinically compatible with acute flaccid myelitis (AFM), a rare condition characterized by rapid onset of flaccid weakness in one or more limbs and spinal cord gray matter lesions, compared with August 2017. Since 2014, CDC has conducted surveillance for AFM using a standardized case definition (1,2). An Epi-X* notice was issued on August 23, 2018, to increase clinician awareness and provide guidance for case reporting.