Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
Records 1-30 (of 119 Records) |
Query Trace: Halpin A[original query] |
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Sentinel Surveillance reveals phylogenetic diversity and detection of linear plasmids harboring vanA and optrA among enterococci collected in the United States
Kent AG , Spicer LM , Campbell D , Breaker E , McAllister GA , Ewing TO , Longo C , Balbuena R , Burroughs M , Burgin A , Padilla J , Johnson JK , Halpin AL , McKay SL , Rasheed JK , Elkins CA , Karlsson M , Lutgring JD , Gargis AS . Antimicrob Agents Chemother 2024 e0059124 Enterococcus faecalis and Enterococcus faecium are frequent causes of healthcare-associated infections. Antimicrobial-resistant enterococci pose a serious public health threat, particularly vancomycin-resistant enterococci (VRE), for which treatment options are limited. The Centers for Disease Control and Prevention's Division of Healthcare Quality Promotion Sentinel Surveillance system conducted surveillance from 2018 to 2019 to evaluate antimicrobial susceptibility profiles and molecular epidemiology of 205 E. faecalis and 180 E. faecium clinical isolates collected from nine geographically diverse sites in the United States. Whole genome sequencing revealed diverse genetic lineages, with no single sequence type accounting for more than 15% of E. faecalis or E. faecium. Phylogenetic analysis distinguished E. faecium from 19 E. lactis (previously known as E. faecium clade B). Resistance to vancomycin was 78.3% among E. faecium, 7.8% among E. faecalis, and did not occur among E. lactis isolates. Resistance to daptomycin and linezolid was rare: E. faecium (5.6%, 0.6%, respectively), E. faecalis (2%, 2%), and E. lactis (5.3%, 0%). All VRE harbored the vanA gene. Three of the seven isolates that were not susceptible to linezolid harbored optrA, one chromosomally located and two on linear plasmids that shared a conserved backbone with other multidrug-resistant conjugative linear plasmids. One of these isolates contained optrA and vanA co-localized on the linear plasmid. By screening all enterococci, 20% of E. faecium were predicted to harbor linear plasmids, whereas none were predicted among E. faecalis or E. lactis. Continued surveillance is needed to assess the future emergence and spread of antimicrobial resistance by linear plasmids and other mechanisms.IMPORTANCEThis work confirms prior reports of E. faecium showing higher levels of resistance to more antibiotics than E. faecalis and identifies that diverse sequence types are contributing to enterococcal infections in the United States. All VRE harbored the vanA gene. We present the first report of the linezolid resistance gene optrA on linear plasmids in the United States, one of which co-carried a vanA cassette. Additional studies integrating epidemiological, antimicrobial susceptibility, and genomic methods to characterize mechanisms of resistance, including the role of linear plasmids, will be critical to understanding the changing landscape of enterococci in the United States. |
Burkholderia multivorans infections associated with use of ice and water from ice machines for patient care activities - four hospitals, California and Colorado, 2020-2024
Vazquez Deida AA , Spicer KB , McNamara KX , Arduino MJ , Gable P , Halpin AL , Caverly LJ , LiPuma JJ , Bardach B , Mayle C , Baird SN , Czaja CA , Chinn R , Siegel JD , Perkins KM . MMWR Morb Mortal Wkly Rep 2024 73 (39) 883-887 Ice machines can harbor water-related organisms, and the use of ice or tap water for clinical care activities has been associated with infections in health care settings. During 2021-2022, a total of 23 cases of infection by Burkholderia multivorans (sequence type ST659) were reported at two southern California hospitals and linked to contaminated ice and water from ice machines. In addition to these 23 cases, this report also includes 23 previously unreported cases of B. multivorans ST659 infections that occurred during 2020-2024: 13 at a northern California hospital, eight at a hospital in Colorado, and two additional cases at one of the southern California hospitals. The same brand of ice machine and brands of filters, descaling, and sanitizing products were used by all four hospitals; B. multivorans was isolated from samples collected from ice machines in two of the hospitals. Whole genome sequencing indicated that all clinical and ice machine isolates were highly genetically similar (0-14 single nucleotide variant differences across 81% of the selected reference genome). Recommendations from public health officials to halt the outbreak included avoiding ice and tap water during clinical care activities. An investigation is ongoing to determine possible sources of ice machine contamination. During outbreaks of water-related organisms in health care facilities, health care personnel should consider avoiding the use of tap water, including ice and water from ice machines, for patient care. |
Public health case for microbiome-sparing antibiotics and new opportunities for drug development
McDonald LC , Young VB , Wilcox MH , Halpin AL , Chaves RL . mSphere 2024 e0041724 Although antibiotics remain a cornerstone of modern medicine, the issues of widespread antibiotic resistance and collateral damage to the microbiome from antibiotic use are driving a need for drug developers to consider more tailored, patient-directed products to avoid antibiotic-induced perturbations of the structure and function of the indigenous microbiota. This perspective summarizes a cascade of microbiome health effects that is initiated by antibiotic-mediated microbiome disruption at an individual level and ultimately leads to infection and transmission of multidrug-resistant pathogens across patient populations. The scientific evidence behind each of the key steps of this cascade is presented. The interruption of this cascade through the use of highly targeted, microbiome-sparing antibiotics aiming to improve health outcomes is discussed. Further, this perspective reflects on some key clinical trial design and reimbursement considerations to be addressed as part of the drug development path. |
Measures to prevent and treat Nipah virus disease: research priorities for 2024-29
Moore KA , Mehr AJ , Ostrowsky JT , Ulrich AK , Moua NM , Fay PC , Hart PJ , Golding JP , Benassi V , Preziosi MP , Broder CC , de Wit E , Formenty PBH , Freiberg AN , Gurley ES , Halpin K , Luby SP , Mazzola LT , Montgomery JM , Spiropoulou CF , Mourya DT , Parveen S , Rahman M , Roth C , Wang LF , Osterholm MT . Lancet Infect Dis 2024 Nipah virus causes highly lethal disease, with case-fatality rates ranging from 40% to 100% in recognised outbreaks. No treatments or licensed vaccines are currently available for the prevention and control of Nipah virus infection. In 2019, WHO published an advanced draft of a research and development roadmap for accelerating development of medical countermeasures, including diagnostics, therapeutics, and vaccines, to enable effective and timely emergency response to Nipah virus outbreaks. This Personal View provides an update to the WHO roadmap by defining current research priorities for development of Nipah virus medical countermeasures, based primarily on literature published in the last 5 years and consensus opinion of 15 subject matter experts with broad experience in development of medical countermeasures for Nipah virus or experience in the epidemiology, ecology, or public health control of outbreaks of Nipah virus. The research priorities are organised into four main sections: cross-cutting issues (for those that apply to more than one category of medical countermeasures), diagnostics, therapeutics, and vaccines. The strategic goals and milestones identified in each section focus on key achievements that are needed over the next 6 years to ensure that the necessary tools are available for rapid response to future outbreaks of Nipah virus or related henipaviruses. |
Decolonization and pathogen reduction approaches to prevent antimicrobial resistance and healthcare-associated infections
Mangalea MR , Halpin AL , Haile M , Elkins CA , McDonald LC . Emerg Infect Dis 2024 30 (6) 1069-1076 Antimicrobial resistance in healthcare-associated bacterial pathogens and the infections they cause are major public health threats affecting nearly all healthcare facilities. Antimicrobial-resistant bacterial infections can occur when colonizing pathogenic bacteria that normally make up a small fraction of the human microbiota increase in number in response to clinical perturbations. Such infections are especially likely when pathogens are resistant to the collateral effects of antimicrobial agents that disrupt the human microbiome, resulting in loss of colonization resistance, a key host defense. Pathogen reduction is an emerging strategy to prevent transmission of, and infection with, antimicrobial-resistant healthcare-associated pathogens. We describe the basis for pathogen reduction as an overall prevention strategy, the evidence for its effectiveness, and the role of the human microbiome in colonization resistance that also reduces the risk for infection once colonized. In addition, we explore ideal attributes of current and future pathogen-reducing approaches. |
Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient Hemodialysis
Bardossy AC , Korhonen L , Schatzman S , Gable P , Herzig C , Brown NE , Beshearse E , Varela K , Sabour S , Lyons AK , Overton R , Hudson M , Hernandez-Romieu AC , Alvarez J , Roman K , Weng M , Soda E , Patel PR , Grate C , Dalrymple LS , Wingard RL , Thornburg NJ , Halpin ASL , Folster JM , Tobin-D'Angelo M , Lea J , Apata I , McDonald LC , Brown AC , Kutty PK , Novosad S . Kidney360 12/28/2021 2 (12) 1917-1927 BACKGROUND: Patients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity. METHODS: From August to November 2020, we enrolled patients on maintenance dialysis with SARS-CoV-2 infections from outpatient dialysis facilities in Atlanta, Georgia. We followed participants for approximately 42 days. We assessed COVID-19 symptoms and collected specimens. Oropharyngeal (OP), anterior nasal (AN), and saliva (SA) specimens were tested for the presence of SARS-CoV-2 RNA, using RT-PCR, and sent for viral culture. Serology, including neutralizing antibodies, was measured in blood specimens. RESULTS: Fifteen participants, with a median age of 58 (range, 37‒77) years, were enrolled. Median duration of RT-PCR positivity from diagnosis was 18 days (interquartile range [IQR], 8‒24 days). Ten participants had at least one, for a total of 41, positive RT-PCR specimens ≥10 days after symptoms onset. Of these 41 specimens, 21 underwent viral culture; one (5%) was positive 14 days after symptom onset. Thirteen participants developed SARS-CoV-2-specific antibodies, 11 of which included neutralizing antibodies. RT-PCRs remained positive after seroconversion in eight participants and after detection of neutralizing antibodies in four participants; however, all of these samples were culture negative. CONCLUSIONS: Patients with ESKD on maintenance dialysis remained persistently and intermittently SARS-CoV-2-RT-PCR positive. However, of the 15 participants, only one had infectious virus, on day 14 after symptom onset. Most participants mounted an antibody response, including neutralizing antibodies. Participants continued having RT-PCR-positive results in the presence of SARS-CoV-2-specific antibodies, but without replication-competent virus detected. |
Differentiation of hypervirulent and classical Klebsiella pneumoniae with acquired drug resistance
Russo TA , Alvarado CL , Davies CJ , Drayer ZJ , Carlino-MacDonald U , Hutson A , Luo TL , Martin MJ , Corey BW , Moser KA , Rasheed JK , Halpin AL , McGann PT , Lebreton F . mBio 2024 e0286723 Hypervirulent Klebsiella pneumoniae (hvKp) is a concerning pathogen that can cause life-threatening infections in otherwise healthy individuals. Importantly, although strains of hvKp have been acquiring antimicrobial resistance, the effect on virulence is unclear. Therefore, it is of critical importance to determine whether a given antimicrobial resistant K. pneumoniae isolate is hypervirulent. This report determined which combination of genotypic and phenotypic markers could most accurately identify hvKp strains with acquired resistance. Both logistic regression and a machine-learning prediction model demonstrated that biomarker count alone was the strongest predictor. The presence of all five of the biomarkers iucA, iroB, peg-344, rmpA, and rmpA2 was most accurate (94%); the presence of ≥4 of these biomarkers was most sensitive (100%). Accurately identifying hvKp is vital for surveillance and research, and the availability of biomarker data could alert the clinician that hvKp is a consideration, which, in turn, would assist in optimizing patient care. |
Concurrent transmission of multiple carbapenemases in a long-term acute-care hospital
Rankin DA , Walters MS , Caicedo L , Gable P , Moulton-Meissner HA , Chan A , Burks A , Edwards K , McAllister G , Kent A , Laufer Halpin A , Moore C , McLemore T , Thomas L , Dotson NQ , Chu AK . Infect Control Hosp Epidemiol 2024 1-10 OBJECTIVE: We investigated concurrent outbreaks of Pseudomonas aeruginosa carrying bla(VIM) (VIM-CRPA) and Enterobacterales carrying bla(KPC) (KPC-CRE) at a long-term acute-care hospital (LTACH A). METHODS: We defined an incident case as the first detection of bla(KPC) or bla(VIM) from a patient's clinical cultures or colonization screening test. We reviewed medical records and performed infection control assessments, colonization screening, environmental sampling, and molecular characterization of carbapenemase-producing organisms from clinical and environmental sources by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. RESULTS: From July 2017 to December 2018, 76 incident cases were identified from 69 case patients: 51 had bla(KPC,) 11 had bla(VIM,) and 7 had bla(VIM) and bla(KPC). Also, bla(KPC) were identified from 7 Enterobacterales, and all bla(VIM) were P. aeruginosa. We observed gaps in hand hygiene, and we recovered KPC-CRE and VIM-CRPA from drains and toilets. We identified 4 KPC alleles and 2 VIM alleles; 2 KPC alleles were located on plasmids that were identified across multiple Enterobacterales and in both clinical and environmental isolates. CONCLUSIONS: Our response to a single patient colonized with VIM-CRPA and KPC-CRE identified concurrent CPO outbreaks at LTACH A. Epidemiologic and genomic investigations indicated that the observed diversity was due to a combination of multiple introductions of VIM-CRPA and KPC-CRE and to the transfer of carbapenemase genes across different bacteria species and strains. Improved infection control, including interventions that minimized potential spread from wastewater premise plumbing, stopped transmission. |
Reply to Gonzales-Luna et al
Gargis AS , Karlsson M , Kamile Rasheed J , Kent AG , McKay SL , Paulick AL , Anderson KF , Adamczyk M , Campbell D , Korhonen LC , McAllister G , Vlachos N , Halpin AL , Lutgring JD , Guh AY , Clifford McDonald L , Elkins CA . Clin Infect Dis 2023 76 (11) 2039-2041 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. |
Evidence review and recommendations for the implementation of genomics for antimicrobial resistance surveillance: reports from an international expert group
Baker KS , Jauneikaite E , Nunn JG , Midega JT , Atun R , Holt KE , Walia K , Howden BP , Tate H , Okeke IN , Carattoli A , Hsu LY , Hopkins KL , Muloi DM , Wheeler NE , Aanensen DM , Mason LCE , Rodgus J , Hendriksen RS , Essack SY , Egyir B , Halpin AL , MacCannell DR , Campos J , Srikantiah P , Feasey NA , Peacock SJ . Lancet Microbe 2023 4 (12) e1035-e1039 Nearly a century after the beginning of the antibiotic era, which has been associated with unparalleled improvements in human health and reductions in mortality associated with infection, the dwindling pipeline for new antibiotic classes coupled with the inevitable spread of antimicrobial resistance (AMR) poses a major global challenge. Historically, surveillance of bacteria with AMR typically relied on phenotypic analysis of isolates taken from infected individuals, which provides only a low-resolution view of the epidemiology behind an individual infection or wider outbreak. Recent years have seen increasing adoption of powerful new genomic technologies with the potential to revolutionise AMR surveillance by providing a high-resolution picture of the AMR profile of the bacteria causing infections and providing real-time actionable information for treating and preventing infection. However, many barriers remain to be overcome before genomic technologies can be adopted as a standard part of routine AMR surveillance around the world. Accordingly, the Surveillance and Epidemiology of Drug-resistant Infections Consortium convened an expert working group to assess the benefits and challenges of using genomics for AMR surveillance. In this Series, we detail these discussions and provide recommendations from the working group that can help to realise the massive potential benefits for genomics in surveillance of AMR. |
Genomics for antimicrobial resistance surveillance to support infection prevention and control in health-care facilities
Jauneikaite E , Baker KS , Nunn JG , Midega JT , Hsu LY , Singh SR , Halpin AL , Hopkins KL , Price JR , Srikantiah P , Egyir B , Okeke IN , Holt KE , Peacock SJ , Feasey NA . Lancet Microbe 2023 4 (12) e1040-e1046 Integration of genomic technologies into routine antimicrobial resistance (AMR) surveillance in health-care facilities has the potential to generate rapid, actionable information for patient management and inform infection prevention and control measures in near real time. However, substantial challenges limit the implementation of genomics for AMR surveillance in clinical settings. Through a workshop series and online consultation, international experts from across the AMR and pathogen genomics fields convened to review the evidence base underpinning the use of genomics for AMR surveillance in a range of settings. Here, we summarise the identified challenges and potential benefits of genomic AMR surveillance in health-care settings, and outline the recommendations of the working group to realise this potential. These recommendations include the definition of viable and cost-effective use cases for genomic AMR surveillance, strengthening training competencies (particularly in bioinformatics), and building capacity at local, national, and regional levels using hub and spoke models. |
Comparison of carbapenem-susceptible and carbapenem-resistant Enterobacterales at nine sites in the USA, 2013-2016: a resource for antimicrobial resistance investigators
Lutgring JD , Kent AG , Bowers JR , Jasso-Selles DE , Albrecht V , Stevens VA , Pfeiffer A , Barnes R , Engelthaler DM , Johnson JK , Gargis AS , Rasheed JK , Limbago BM , Elkins CA , Karlsson M , Halpin AL . Microb Genom 2023 9 (11) Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat. Genomic sequencing is an important tool for investigating CRE. Through the Division of Healthcare Quality Promotion Sentinel Surveillance system, we collected CRE and carbapenem-susceptible Enterobacterales (CSE) from nine clinical laboratories in the USA from 2013 to 2016 and analysed both phenotypic and genomic sequencing data for 680 isolates. We describe the molecular epidemiology and antimicrobial susceptibility testing (AST) data of this collection of isolates. We also performed a phenotype-genotype correlation for the carbapenems and evaluated the presence of virulence genes in Klebsiella pneumoniae complex isolates. These AST and genomic sequencing data can be used to compare and contrast CRE and CSE at these sites and serve as a resource for the antimicrobial resistance research community. |
Posttransfusion sepsis attributable to bacterial contamination in platelet collection set manufacturing facility, United States
Kracalik I , Kent AG , Villa CH , Gable P , Annambhotla P , McAllister G , Yokoe D , Langelier CR , Oakeson K , Noble-Wang J , Illoh O , Halpin AL , Eder AF , Basavaraju SV . Emerg Infect Dis 2023 29 (10) 1979-1989 During May 2018‒December 2022, we reviewed transfusion-transmitted sepsis cases in the United States attributable to polymicrobial contaminated apheresis platelet components, including Acinetobacter calcoaceticus‒baumannii complex or Staphylococcus saprophyticus isolated from patients and components. Transfused platelet components underwent bacterial risk control strategies (primary culture, pathogen reduction or primary culture, and secondary rapid test) before transfusion. Environmental samples were collected from a platelet collection set manufacturing facility. Seven sepsis cases from 6 platelet donations from 6 different donors were identified in patients from 6 states; 3 patients died. Cultures identified Acinetobacter calcoaceticus‒baumannii complex in 6 patients and 6 transfused platelets, S. saprophyticus in 4 patients and 4 transfused platelets. Whole-genome sequencing showed environmental isolates from the manufacturer were closely related genetically to patient and platelet isolates, indicating the manufacturer was the most probable source of recurrent polymicrobial contamination. Clinicians should maintain awareness of possible transfusion-transmitted sepsis even when using bacterial risk control strategies. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines (preprint)
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Hossain J , Lin X , Lester S , Pusch E , Jones J , Cui D , Chatterjee P , Jenks HM , Morantz E , Larson G , Hatta M , Harcourt J , Tamin A , Li Y , Tao Y , Zhao K , Burroughs A , Wong T , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Laufer Halpin AS , Lee JS , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan V , Wentworth DE , Zhou B , Batra D , Beck A , Caravas J , Cintron-Moret R , Cook PW , Gerhart J , Gulvik C , Hassell N , Howard D , Knipe K , Kondor RJ , Kovacs N , Lacek K , Mann BR , McMullan LK , Moser K , Paden CR , Martin BR , Schmerer M , Shepard S , Stanton R , Stark T , Sula E , Tymeckia K , Unoarumhi Y . bioRxiv 2021 30 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic. |
Containment of a Verona integron-encoded metallo-beta-lactamase-producing pseudomonas aeruginosa outbreak associated with an acute care hospital sink-Tennessee, 2018-2020
Chan A , Thure K , Tobey K , Shugart A , Schmedes S , Burks JAth , Hardin H , Moore C , Carpenter T , Brooks S , Gable P , Moulton Meissner H , McAllister G , Lawsin A , Laufer Halpin A , Spalding Walters M , Keaton A . Open Forum Infect Dis 2023 10 (5) ofad194 BACKGROUND: Contaminated healthcare facility wastewater plumbing is recognized as a source of carbapenemase-producing organism transmission. In August 2019, the Tennessee Department of Health (TDH) identified a patient colonized with Verona integron-encoded metallo-beta-lactamase-producing carbapenem-resistant Pseudomonas aeruginosa (VIM-CRPA). A record review revealed that 33% (4 of 12) of all reported patients in Tennessee with VIM had history of prior admission to acute care hospital (ACH) A intensive care unit (ICU) Room X, prompting further investigation. METHODS: A case was defined as polymerase chain reaction detection of bla(VIM) in a patient with prior admission to ACH A from November 2017 to November 2020. The TDH performed point prevalence surveys, discharge screening, onsite observations, and environmental testing at ACH A. The VIM-CRPA isolates underwent whole-genome sequencing (WGS). RESULTS: In a screening of 44% (n = 11) of 25 patients admitted to Room X between January and June 2020, we identified 36% (n = 4) colonized with VIM-CRPA, resulting in 8 cases associated with Room X from March 2018 to June 2020. No additional cases were identified in 2 point-prevalence surveys of the ACH A ICU. Samples from the bathroom and handwashing sink drains in Room X grew VIM-CRPA; all available case and environmental isolates were found to be ST253 harboring bla(VIM-1) and to be closely related by WGS. Transmission ended after implementation of intensive water management and infection control interventions. CONCLUSIONS: A single ICU room's contaminated drains were associated with 8 VIM-CRPA cases over a 2-year period. This outbreak highlights the need to include wastewater plumbing in hospital water management plans to mitigate the risk of transmission of antibiotic-resistant organisms to patients. |
Erratum: Vol. 71, No. 6.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (14) 528 The report “Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants — United States, June 2021–January 2022” contained several errors. |
Unintended consequences: Renaming botulinum neurotoxin-producing species of clostridium and related species
Lúquez C , Halpin JL , Dykes J . Toxicon 2023 224 107036 Botulinum neurotoxin-producing species of Clostridium are highly diverse. Clostridium botulinum could represent at least four different species of Clostridium. In addition, strains that do not produce botulinum neurotoxin are closely related to toxigenic strains, probably representing the same species. Although reclassification of these organisms has been proposed in the past, their species names have remained unchanged, mainly because of the premise that changing names of medically relevant organisms might cause confusion in the healthcare and scientific community. In this review, we discuss the possible unintended consequences of reclassifying botulinum neurotoxin-producing species of Clostridium, which are of public health, medical, and biodefense interest. |
Draft Genome Sequences of 20 Clostridium botulinum Type A Isolates from Foodborne Botulism Outbreaks.
Halpin JL , Gómez GA , Dykes JK , Lúquez C . Microbiol Resour Announc 2023 12 (1) e0086822 Here, we present 20 draft genome sequences of Clostridium botulinum type A isolates originating from foodborne outbreaks in the United States and Ethiopia. Publicly available genomes enhance our understanding of C. botulinum genomics and are an asset in bioterrorism preparedness. |
Dialysis Water Supply Faucet as Reservoir for Carbapenemase-Producing Pseudomonas aeruginosa
Prestel C , Moulton-Meissner H , Gable P , Stanton RA , Glowicz J , Franco L , McConnell M , Torres T , John D , Blackwell G , Yates R , Brown C , Reyes K , McAllister GA , Kunz J , Conners EE , Benedict KM , Kirby A , Mattioli M , Xu K , Gualandi N , Booth S , Novosad S , Arduino M , Halpin AL , Wells K , Walters MS . Emerg Infect Dis 2022 28 (10) 2069-2073 During June 2017-November 2019, a total 36 patients with carbapenem-resistant Pseudomonas aeruginosa harboring Verona-integron-encoded metallo-β-lactamase were identified in a city in western Texas, USA. A faucet contaminated with the organism, identified through environmental sampling, in a specialty care room was the likely source for infection in a subset of patients. |
Reference Susceptibility Testing and Genomic Surveillance of Clostridioides difficile, United States, 2012-17.
Gargis AS , Karlsson M , Paulick AL , Anderson KF , Adamczyk M , Vlachos N , Kent AG , McAllister GA , McKay SL , Halpin AL , Albrecht V , Campbell D , Korhonen L , Elkins CA , Rasheed JK , Guh AY , McDonald LC , Lutgring JD . Clin Infect Dis 2022 76 (5) 890-896 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. |
Whole-Genome Sequencing Reveals Diversity of Carbapenem-Resistant Pseudomonas aeruginosa Collected through CDC's Emerging Infections Program, United States, 2016-2018.
Stanton RA , Campbell D , McAllister GA , Breaker E , Adamczyk M , Daniels JB , Lutgring JD , Karlsson M , Schutz K , Jacob JT , Wilson LE , Vaeth E , Li L , Lynfield R , Snippes Vagnone PM , Phipps EC , Hancock EB , Dumyati G , Tsay R , Cassidy PM , Mounsey J , Grass JE , Bulens SN , Walters MS , Halpin AL . Antimicrob Agents Chemother 2022 66 (9) e0049622 The CDC's Emerging Infections Program (EIP) conducted population- and laboratory-based surveillance of US carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 2016 through 2018. To characterize the pathotype, 1,019 isolates collected through this project underwent antimicrobial susceptibility testing and whole-genome sequencing. Sequenced genomes were classified using the seven-gene multilocus sequence typing (MLST) scheme and a core genome (cg)MLST scheme was used to determine phylogeny. Both chromosomal and horizontally transmitted mechanisms of carbapenem resistance were assessed. There were 336 sequence types (STs) among the 1,019 sequenced genomes, and the genomes varied by an average of 84.7% of the cgMLST alleles used. Mutations associated with dysfunction of the porin OprD were found in 888 (87.1%) of the genomes and were correlated with carbapenem resistance, and a machine learning model incorporating hundreds of genetic variations among the chromosomal mechanisms of resistance was able to classify resistant genomes. While only 7 (0.1%) isolates harbored carbapenemase genes, 66 (6.5%) had acquired non-carbapenemase β-lactamase genes, and these were more likely to have OprD dysfunction and be resistant to all carbapenems tested. The genetic diversity demonstrates that the pathotype includes a variety of strains, and clones previously identified as high-risk make up only a minority of CRPA strains in the United States. The increased carbapenem resistance in isolates with acquired non-carbapenemase β-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines.
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Mann BR , Hossain J , Lin X , Lester S , Pusch EA , Jones J , Cui D , Chatterjee P , Jenks MH , Morantz EK , Larson GP , Hatta M , Harcourt JL , Tamin A , Li Y , Tao Y , Zhao K , Lacek K , Burroughs A , Wang W , Wilson M , Wong T , Park SH , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Halpin AL , McMullan LK , Lee JS , Xia H , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan VG , Wentworth DE , Zhou B . Nat Commun 2022 13 (1) 4350 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic. |
Carbapenem-Resistant enterobacterales in individuals with and without health care risk factors -Emerging infections program, United States, 2012-2015.
Bulens SN , Reses HE , Ansari UA , Grass JE , Carmon C , Albrecht V , Lawsin A , McAllister G , Daniels J , Lee YK , Yi S , See I , Jacob JT , Bower CW , Wilson L , Vaeth E , Lynfield R , Vagnone PS , Shaw KM , Dumyati G , Tsay R , Phipps EC , Bamberg W , Janelle SJ , Beldavs ZG , Cassidy PM , Kainer M , Muleta D , Mounsey JT , Laufer-Halpin A , Karlsson M , Lutgring JD , Walters MS . Am J Infect Control 2022 51 (1) 70-77 BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community. METHODS: Active, population-based surveillance was conducted to identify case-patients with cultures positive for Enterobacterales not susceptible to a carbapenem (excluding ertapenem) and resistant to all third-generation cephalosporins tested at 8 US sites from January 2012 to December 2015. Medical records were used to classify cases as health care-associated, or as community-associated (CA) if a patient had no known health care risk factors and a culture was collected <3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing. RESULTS: We identified 1499 CRE cases in 1194 case-patients; 149 cases (10%) in 139 case-patients were CA. The incidence of CRE cases per 100,000 population was 2.96 (95% CI: 2.81, 3.11) overall and 0.29 (95% CI: 0.25, 0.35) for CA-CRE. Most CA-CRE cases were in White persons (73%), females (84%) and identified from urine cultures (98%). Among the 12 sequenced CA-CRE isolates, 5 (42%) harbored a carbapenemase gene. CONCLUSIONS: Ten percent of CRE cases were CA; some isolates from CA-CRE cases harbored carbapenemase genes. Continued CRE surveillance in the community is critical to monitor emergence outside of traditional health care settings. |
Are vancomycin non-susceptible clostridioides difficile strains emerging
Lutgring JD , McKay SL , Gargis AS , Halpin AL , McDonald LC . Clin Infect Dis 2022 75 (9) 1677-1678 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. |
Draft Genome Sequence of Clostridium botulinum Subtype bont/A5(B2').
Kruemmel AR , Halpin JL , Foltz V , Dykes J , Lquez C . Microbiol Resour Announc 2022 11 (7) e0034822 Here, we report the draft genome sequence of Clostridium botulinum strain CDC76130, which harbors a rare botulinum toxin gene (bont) complex arrangement of bont/A5 and truncated bont/B2 within the same ha toxin gene cluster. |
Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii in the United States, 2013-2017.
McKay SL , Vlachos N , Daniels JB , Albrecht VS , Stevens VA , Rasheed JK , Johnson JK , Lutgring JD , Sjölund-Karlsson M , Halpin AL . Microb Drug Resist 2022 28 (6) 645-653 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. |
Sentinel Surveillance Reveals Emerging Daptomycin-Resistant ST736 Enterococcus faecium and Multiple Mechanisms of Linezolid Resistance in Enterococci in the United States.
Gargis AS , Spicer LM , Kent AG , Zhu W , Campbell D , McAllister G , Ewing TO , Albrecht V , Stevens VA , Sheth M , Padilla J , Batra D , Johnson JK , Halpin AL , Rasheed JK , Elkins CA , Karlsson M , Lutgring JD . Front Microbiol 2021 12 807398 Enterococcus faecalis and faecium with resistance to daptomycin and/or linezolid are emerging globally. We present the genomic characterization of daptomycin- and linezolid-resistant E. faecalis and E. faecium surveillance isolates from the United States, 2013-2016. Daptomycin resistance was low among E. faecalis (2/364, 0.5%) and E. faecium (17/344, 5%). The majority (71%, 12/17) of daptomycin-resistant E. faecium isolates belonged to the emerging ST736 clone and contained mutations in liaFSR and cls previously associated with resistance. However, 1/2 E. faecalis and 3/17 E. faecium did not contain these mutations previously associated with daptomycin resistance. Linezolid resistance was rare among E. faecalis (1/364, 0.3%) and E. faecium (2/344, 0.6%). These two E. faecium isolates, one of which was also resistant to daptomycin and vancomycin, contained the 23S rRNA nucleotide mutation (G2576T) associated with linezolid resistance. Long-read sequencing revealed the linezolid-resistant E. faecalis isolate contained chromosomal- and plasmid-encoded copies of optrA. The chromosomal optrA was located on the recently described Tn6674 multiresistance transposon. The second copy of optrA was encoded on an ∼65 kb mosaic plasmid, with component regions sharing high sequence identity to optrA-encoding multiresistance plasmids of animal origin. The optrA-encoding plasmid contained open reading frames predicted to encode proteins associated with a pheromone-responsive plasmid transfer system, and filter mating experiments confirmed the plasmid was conjugative. Continued surveillance of enterococci is necessary to assess the prevalence and trends of daptomycin and linezolid resistance in the United States, characterize resistance mechanisms and how they transfer, and monitor for emerging sequence types associated with resistance. |
Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants - United States, June 2021-January 2022.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (6) 206-211 Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.(†) The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice. |
Acceptance of Saliva-Based Specimen Collection for SARS-CoV-2 Testing Among K-12 Students, Teachers, and Staff.
McLaughlin HP , Worrell MC , Malone S , Dawson P , Maricque B , Halpin JL , Lee S , Fritz SA , Tinker SC , Neidich JA , Towns K , Lee JS , Barrios LC , Neatherlin JC , Newland JG , Salzer JS . Public Health Rep 2022 137 (3) 333549221074395 OBJECTIVE: Saliva specimens collected in school populations may offer a more feasible, noninvasive alternative to nasal swabs for large-scale COVID-19 testing efforts in kindergarten through 12th grade (K-12) schools. We investigated acceptance of saliva-based COVID-19 testing among quarantined K-12 students and their parents, teachers, and staff members who recently experienced a SARS-CoV-2 exposure in school. METHODS: We surveyed 719 participants, in person or by telephone, who agreed to or declined a free saliva-based COVID-19 reverse-transcription polymerase chain reaction test as part of a surveillance investigation about whether they would have consented to testing if offered a nasal swab instead. We conducted this investigation in 6 school districts in Greene County (n = 3) and St. Louis County (n = 3), Missouri, from January 25 through March 23, 2021. RESULTS: More than one-third (160 of 446) of K-12 students (or their parents or guardians), teachers, and staff members who agreed to a saliva-based COVID-19 test indicated they would have declined testing if specimen collection were by nasal swab. When stratified by school level, 51% (67 of 132) of elementary school students or their parents or guardians would not have agreed to testing if a nasal swab was offered. CONCLUSIONS: Some students, especially those in elementary school, preferred saliva-based COVID-19 testing to nasal swab testing. Use of saliva-based testing might increase voluntary participation in screening efforts in K-12 schools to help prevent the spread of SARS-CoV-2. |
Extensively Drug-Resistant Carbapenemase-Producing Pseudomonas aeruginosa and Medical Tourism from the United States to Mexico, 2018-2019.
Kracalik I , Ham DC , McAllister G , Smith AR , Vowles M , Kauber K , Zambrano M , Rodriguez G , Garner K , Chorbi K , Cassidy PM , McBee S , Stoney RJ , Moser K , Villarino ME , Zazueta OE , Bhatnagar A , Sula E , Stanton RA , Brown AC , Halpin AL , Epstein L , Walters MS . Emerg Infect Dis 2022 28 (1) 51-61 Carbapenem-resistant Pseudomonas aeruginosa (CRPA) producing the Verona integron‒encoded metallo-β-lactamase (VIM) are highly antimicrobial drug-resistant pathogens that are uncommon in the United States. We investigated the source of VIM-CRPA among US medical tourists who underwent bariatric surgery in Tijuana, Mexico. Cases were defined as isolation of VIM-CRPA or CRPA from a patient who had an elective invasive medical procedure in Mexico during January 2018‒December 2019 and within 45 days before specimen collection. Whole-genome sequencing of isolates was performed. Thirty-eight case-patients were identified in 18 states; 31 were operated on by surgeon 1, most frequently at facility A (27/31 patients). Whole-genome sequencing identified isolates linked to surgeon 1 were closely related and distinct from isolates linked to other surgeons in Tijuana. Facility A closed in March 2019. US patients and providers should acknowledge the risk for colonization or infection after medical tourism with highly drug-resistant pathogens uncommon in the United States. |
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