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1.
Clin Infect Dis ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315890

RESUMO

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are extensively drug resistant bacteria. We investigated the source of a multistate CP-CRPA outbreak. METHODS: Cases were defined as a U.S. patient's first isolation of P. aeruginosa sequence type 1203 with the carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to CDC between January 1, 2022-May 15, 2023. We conducted a 1:1 matched case-control study at the post-acute care facility with the most cases, assessed exposures associated with case status for all case-patients, and tested products for bacterial contamination. RESULTS: We identified 81 case-patients from 18 states, 27 of whom were identified through surveillance cultures. Four (7%) of 54 case-patients with clinical cultures died within 30 days of culture collection, and four (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears compared to controls (crude matched OR: 5.0, 95% CI: 1.1, 22.8). Overall, artificial tears use was reported by 61 (87%) of 70 case-patients with information; 43 (77%) of 56 case-patients with brand information reported use of Brand A, an imported, preservative-free, over-the-counter (OTC) product. Bacteria isolated from opened and unopened bottles of Brand A were genetically related to patient isolates. FDA inspection of the manufacturing plant identified likely sources of contamination. CONCLUSIONS: A manufactured medical product serving as the vehicle for carbapenemase-producing organisms is unprecedented in the U.S. The clinical impacts from this outbreak underscore the need for improved requirements for U.S. OTC product importers.

2.
Emerg Infect Dis ; 28(1): 51-61, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34932447

RESUMO

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) producing the Verona integron‒encoded metallo-ß-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.


Assuntos
Farmacorresistência Bacteriana Múltipla , Turismo Médico , Infecções por Pseudomonas , Antibacterianos/uso terapêutico , Proteínas de Bactérias , Carbapenêmicos , Humanos , México/epidemiologia , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Estados Unidos/epidemiologia , beta-Lactamases/genética
4.
Antimicrob Agents Chemother ; 66(9): e0049622, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36066241

RESUMO

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 ß-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 ß-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Centers for Disease Control and Prevention, U.S. , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Porinas/genética , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Estados Unidos/epidemiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo
5.
J Clin Microbiol ; 60(3): e0215421, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-34985981

RESUMO

Carbapenems are antimicrobial drugs reserved for the treatment of severe multidrug-resistant Gram-negative bacterial infections. Carbapenem-resistant organisms (CROs) are an urgent public health threat and have been made reportable to public health authorities in many jurisdictions. Recent reports of CROs in companion animals and veterinary settings suggest that CROs are a One Health problem. However, standard practices of U.S. veterinary diagnostic laboratories (VDLs) to detect CROs are unknown. We assessed the capacity of VDLs to characterize carbapenem resistance in isolates from companion animals. Among 74 VDLs surveyed in 42 states, 23 laboratories (31%) from 22 states responded. Most (22/23, 96%) included ≥1 carbapenem on their primary antimicrobial susceptibility testing panel, and approximately one-third (9/23, 39%) performed phenotypic carbapenemase production testing or molecular identification of carbapenemase genes. Overall, 35% (8/23) of VDLs across eight states reported they would notify public health if a CRO was detected. Most (17/21, 81%) VDLs were not aware of CRO reporting mandates, and some expressed uncertainty about whether the scope of known mandates included CROs from veterinary sources. Although nearly all surveyed VDLs tested for carbapenem resistance, fewer had the capacity for mechanism testing or awareness of public health reporting requirements. Addressing these gaps is critical to monitoring CRO incidence and trends in veterinary medicine, preventing spread in veterinary settings, and mounting an effective One Health response. Improved collaboration and communication between public health and veterinary medicine is critical to inform infection control practices in veterinary settings and conduct a public health response when resistant isolates are detected.


Assuntos
Anti-Infecciosos , Animais de Estimação , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Humanos , Laboratórios , Testes de Sensibilidade Microbiana , Estados Unidos , beta-Lactamases/genética
6.
Transpl Infect Dis ; 24(2): e13785, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34989092

RESUMO

BACKGROUND: Passive reporting to the Centers for Disease Control and Prevention has identified carbapenemase-producing organisms (CPOs) among solid organ transplant (SOT) recipients, potentially representing an emerging source of spread. We analyzed CPO prevalence in wards where SOT recipients receive inpatient care to inform public health action to prevent transmission. METHODS: From September 2019 to June 2020, five US hospitals conducted consecutive point prevalence surveys (PPS) of all consenting patients admitted to transplant units, regardless of transplant status. We used the Cepheid Xpert Carba-R assay to identify carbapenemase genes (blaKPC , blaNDM , blaVIM , blaIMP , blaOXA-48 ) from rectal swabs. Laboratory-developed molecular tests were used to retrospectively test for a wider range of blaIMP and blaOXA variants. RESULTS: In total, 154 patients were screened and 92 (60%) were SOT recipients. CPOs were detected among 7 (8%) SOT recipients, from two of five screened hospitals: four blaKPC , one blaNDM , and two blaOXA-23 . CPOs were detected in two (3%) of 62 non-transplant patients. In three of five participating hospitals, CPOs were not identified among any patients admitted to transplant units. CONCLUSIONS: Longitudinal surveillance in transplant units, as well as PPS in areas with diverse CPO epidemiology, may inform the utility of routine screening in SOT units to prevent the spread of CPOs.


Assuntos
Transplante de Órgãos , beta-Lactamases , Proteínas de Bactérias/genética , Hospitais , Humanos , Transplante de Órgãos/efeitos adversos , Prevalência , Estudos Retrospectivos , Transplantados , beta-Lactamases/genética
7.
Ann Intern Med ; 174(11): 1554-1562, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34487450

RESUMO

BACKGROUND: Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities. OBJECTIVE: To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC. DESIGN: Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019. SETTING: All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC. PARTICIPANTS: Current or recent patients in LTACHs and vSNFs in OC. INTERVENTION: In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided. MEASUREMENTS: Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness. RESULTS: Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019. LIMITATION: Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated. CONCLUSION: Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.


Assuntos
Candidíase/diagnóstico , Candidíase/prevenção & controle , Cuidados Semi-Intensivos , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Candida auris/genética , Candidíase/transmissão , Feminino , Humanos , Controle de Infecções , Assistência de Longa Duração , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Alta do Paciente , Instituições de Cuidados Especializados de Enfermagem , Sequenciamento Completo do Genoma
8.
Clin Infect Dis ; 72(3): 414-420, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32255490

RESUMO

BACKGROUND: Antibiotic resistance is often spread through bacterial populations via conjugative plasmids. However, plasmid transfer is not well recognized in clinical settings because of technical limitations, and health care-associated infections are usually caused by clonal transmission of a single pathogen. In 2015, multiple species of carbapenem-resistant Enterobacteriaceae (CRE), all producing a rare carbapenemase, were identified among patients in an intensive care unit. This observation suggested a large, previously unrecognized plasmid transmission chain and prompted our investigation. METHODS: Electronic medical record reviews, infection control observations, and environmental sampling completed the epidemiologic outbreak investigation. A laboratory analysis, conducted on patient and environmental isolates, included long-read whole-genome sequencing to fully elucidate plasmid DNA structures. Bioinformatics analyses were applied to infer plasmid transmission chains and results were subsequently confirmed using plasmid conjugation experiments. RESULTS: We identified 14 Verona integron-encoded metallo-ß-lactamase (VIM)-producing CRE in 12 patients, and 1 additional isolate was obtained from a patient room sink drain. Whole-genome sequencing identified the horizontal transfer of blaVIM-1, a rare carbapenem resistance mechanism in the United States, via a promiscuous incompatibility group A/C2 plasmid that spread among 5 bacterial species isolated from patients and the environment. CONCLUSIONS: This investigation represents the largest known outbreak of VIM-producing CRE in the United States to date, which comprises numerous bacterial species and strains. We present evidence of in-hospital plasmid transmission, as well as environmental contamination. Our findings demonstrate the potential for 2 types of hospital-acquired infection outbreaks: those due to clonal expansion and those due to the spread of conjugative plasmids encoding antibiotic resistance across species.


Assuntos
Infecção Hospitalar , Integrons , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo
9.
Clin Infect Dis ; 72(11): e753-e760, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32984882

RESUMO

BACKGROUND: Candida auris is an emerging, multidrug-resistant yeast that spreads in healthcare settings. People colonized with C. auris can transmit this pathogen and are at risk for invasive infections. New York State (NYS) has the largest US burden (>500 colonized and infected people); many colonized individuals are mechanically ventilated or have tracheostomy, and are residents of ventilator-capable skilled nursing facilities (vSNF). We evaluated the factors associated with C. auris colonization among vSNF residents to inform prevention interventions. METHODS: During 2016-2018, the NYS Department of Health conducted point prevalence surveys (PPS) to detect C. auris colonization among residents of vSNFs. In a case-control investigation, we defined a case as C. auris colonization in a resident, and identified up to 4 residents with negative swabs during the same PPS as controls. We abstracted data from medical records on patient facility transfers, antimicrobial use, and medical history. RESULTS: We included 60 cases and 218 controls identified from 6 vSNFs. After controlling for potential confounders, the following characteristics were associated with C. auris colonization: being on a ventilator (adjusted odds ratio [aOR], 5.9; 95% confidence interval [CI], 2.3-15.4), receiving carbapenem antibiotics in the prior 90 days (aOR, 3.5; 95% CI, 1.6-7.6), having ≥1 acute care hospital visit in the prior 6 months (aOR, 4.2; 95% CI, 1.9-9.6), and receiving systemic fluconazole in the prior 90 days (aOR, 6.0; 95% CI, 1.6-22.6). CONCLUSIONS: Targeted screening of patients in vSNFs with the above risk factors for C. auris can help identify colonized patients and facilitate the implementation of infection control measures. Antimicrobial stewardship may be an important factor in the prevention of C. auris colonization.


Assuntos
Candida , Instituições de Cuidados Especializados de Enfermagem , Antifúngicos/uso terapêutico , Fluconazol , Humanos , New York , Ventiladores Mecânicos
10.
Emerg Infect Dis ; 27(9): 2475-2479, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34424168

RESUMO

Reports of organisms harboring multiple carbapenemase genes have increased since 2010. During October 2012-April 2019, the Centers for Disease Control and Prevention documented 151 of these isolates from 100 patients in the United States. Possible risk factors included recent history of international travel, international inpatient healthcare, and solid organ or bone marrow transplantation.


Assuntos
Proteínas de Bactérias , beta-Lactamases , Proteínas de Bactérias/genética , Bactérias Gram-Negativas , Humanos , Estados Unidos/epidemiologia , beta-Lactamases/genética
11.
J Clin Microbiol ; 59(6)2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33762362

RESUMO

Detection of carbapenem-resistant Pseudomonas aeruginosa (CRPA) with carbapenemase-producing (CP) genes is critical for preventing transmission. Our objective was to assess whether certain antimicrobial susceptibility testing (AST) profiles can efficiently identify CP-CRPA. We defined CRPA as P. aeruginosa with imipenem or meropenem MICs of ≥8 µg/ml; CP-CRPA was CRPA with CP genes (blaKPC/blaIMP/blaNDM/blaOXA-48/blaVIM). We assessed the sensitivity and specificity of AST profiles to detect CP-CRPA among CRPA isolates collected by CDC's Antibiotic Resistance Laboratory Network (AR Lab Network) and the Emerging Infections Program (EIP) during 2017 to 2019. Three percent (195/6,192) of AR Lab Network CRPA isolates were CP-CRPA. Among CRPA isolates, adding not susceptible (NS) to cefepime or ceftazidime to the definition had 91% sensitivity and 50% specificity for identifying CP-CRPA; adding NS to ceftolozane-tazobactam had 100% sensitivity and 86% specificity. Of 965 EIP CRPA isolates evaluated for CP genes, 7 were identified as CP-CRPA; 6 of the 7 were NS to cefepime and ceftazidime, and all 7 were NS to ceftolozane-tazobactam. Among 4,182 EIP isolates, clinical laboratory AST results were available for 96% of them for cefepime, 80% for ceftazidime, and 4% for ceftolozane-tazobactam. The number of CRPA isolates needed to test (NNT) to identify one CP-CRPA isolate decreased from 138 to 64 if the definition of NS to cefepime or ceftazidime was used and to 7 with NS to ceftolozane-tazobactam. Adding not susceptible to cefepime or ceftazidime to CRPA carbapenemase testing criteria would reduce the NNT by half and can be implemented in most clinical laboratories; adding not susceptible to ceftolozane-tazobactam could be even more predictive once AST for this drug is more widely available.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Compostos Azabicíclicos , Proteínas de Bactérias , Carbapenêmicos/farmacologia , Cefalosporinas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , beta-Lactamases/genética
12.
MMWR Morb Mortal Wkly Rep ; 70(2): 56-57, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33444298

RESUMO

In July 2020, the Florida Department of Health was alerted to three Candida auris bloodstream infections and one urinary tract infection in four patients with coronavirus disease 2019 (COVID-19) who received care in the same dedicated COVID-19 unit of an acute care hospital (hospital A). C. auris is a multidrug-resistant yeast that can cause invasive infection. Its ability to colonize patients asymptomatically and persist on surfaces has contributed to previous C. auris outbreaks in health care settings (1-7). Since the first C. auris case was identified in Florida in 2017, aggressive measures have been implemented to limit spread, including contact tracing and screening upon detection of a new case. Before the COVID-19 pandemic, hospital A conducted admission screening for C. auris and admitted colonized patients to a separate dedicated ward.


Assuntos
COVID-19/terapia , Candida/isolamento & purificação , Candidíase/epidemiologia , Surtos de Doenças , Unidades Hospitalares , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Feminino , Florida/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade
13.
MMWR Morb Mortal Wkly Rep ; 70(36): 1242-1244, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34499630

RESUMO

Wastewater surveillance, the measurement of pathogen levels in wastewater, is used to evaluate community-level infection trends, augment traditional surveillance that leverages clinical tests and services (e.g., case reporting), and monitor public health interventions (1). Approximately 40% of persons infected with SARS-CoV-2, the virus that causes COVID-19, shed virus RNA in their stool (2); therefore, community-level trends in SARS-CoV-2 infections, both symptomatic and asymptomatic (2) can be tracked through wastewater testing (3-6). CDC launched the National Wastewater Surveillance System (NWSS) in September 2020 to coordinate wastewater surveillance programs implemented by state, tribal, local, and territorial health departments to support the COVID-19 pandemic response. In the United States, wastewater surveillance was not previously implemented at the national level. As of August 2021, NWSS includes 37 states, four cities, and two territories. This report summarizes NWSS activities and describes innovative applications of wastewater surveillance data by two states, which have included generating alerts to local jurisdictions, allocating mobile testing resources, evaluating irregularities in traditional surveillance, refining health messaging, and forecasting clinical resource needs. NWSS complements traditional surveillance and enables health departments to intervene earlier with focused support in communities experiencing increasing concentrations of SARS-CoV-2 in wastewater. The ability to conduct wastewater surveillance is not affected by access to health care or the clinical testing capacity in the community. Robust, sustainable implementation of wastewater surveillance requires public health capacity for wastewater testing, analysis, and interpretation. Partnerships between wastewater utilities and public health departments are needed to leverage wastewater surveillance data for the COVID-19 response for rapid assessment of emerging threats and preparedness for future pandemics.


Assuntos
COVID-19/prevenção & controle , Pandemias/prevenção & controle , Vigilância em Saúde Pública/métodos , SARS-CoV-2/isolamento & purificação , Águas Residuárias/virologia , COVID-19/epidemiologia , Centers for Disease Control and Prevention, U.S. , Humanos , Estados Unidos/epidemiologia
14.
MMWR Morb Mortal Wkly Rep ; 70(23): 846-850, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34111060

RESUMO

SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants (1). Variants have the potential to affect transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. In November 2020, CDC established national surveillance for SARS-CoV-2 variants using genomic sequencing. As of May 6, 2021, sequences from 177,044 SARS-CoV-2-positive specimens collected during December 20, 2020-May 6, 2021, from 55 U.S. jurisdictions had been generated by or reported to CDC. These included 3,275 sequences for the 2-week period ending January 2, 2021, compared with 25,000 sequences for the 2-week period ending April 24, 2021 (0.1% and 3.1% of reported positive SARS-CoV-2 tests, respectively). Because sequences might be generated by multiple laboratories and sequence availability varies both geographically and over time, CDC developed statistical weighting and variance estimation methods to generate population-based estimates of the proportions of identified variants among SARS-CoV-2 infections circulating nationwide and in each of the 10 U.S. Department of Health and Human Services (HHS) geographic regions.* During the 2-week period ending April 24, 2021, the B.1.1.7 and P.1 variants represented an estimated 66.0% and 5.0% of U.S. SARS-CoV-2 infections, respectively, demonstrating the rise to predominance of the B.1.1.7 variant of concern† (VOC) and emergence of the P.1 VOC in the United States. Using SARS-CoV-2 genomic surveillance methods to analyze surveillance data produces timely population-based estimates of the proportions of variants circulating nationally and regionally. Surveillance findings demonstrate the potential for new variants to emerge and become predominant, and the importance of robust genomic surveillance. Along with efforts to characterize the clinical and public health impact of SARS-CoV-2 variants, surveillance can help guide interventions to control the COVID-19 pandemic in the United States.


Assuntos
COVID-19/virologia , SARS-CoV-2/genética , COVID-19/epidemiologia , Monitoramento Epidemiológico , Humanos , SARS-CoV-2/isolamento & purificação , Estados Unidos/epidemiologia
15.
Proc Natl Acad Sci U S A ; 115(11): E2604-E2613, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29483266

RESUMO

Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that is the target of several classes of herbicides. Malaria parasites contain a plant-like ACC, and this is the only protein predicted to be biotinylated in the parasite. We found that ACC is expressed in the apicoplast organelle in liver- and blood-stage malaria parasites; however, it is activated through biotinylation only in the liver stages. Consistent with this observation, deletion of the biotin ligase responsible for ACC biotinylation does not impede blood-stage growth, but results in late liver-stage developmental defects. Biotin depletion increases the severity of the developmental defects, demonstrating that parasite and host biotin metabolism are required for normal liver-stage progression. This finding may link the development of liver-stage malaria parasites to the nutritional status of the host, as neither the parasite nor the human host can synthesize biotin.


Assuntos
Biotina/metabolismo , Interações Hospedeiro-Parasita/fisiologia , Fígado/parasitologia , Malária/metabolismo , Plasmodium/metabolismo , Acetil-CoA Carboxilase/metabolismo , Animais , Apicoplastos/metabolismo , Carbono-Nitrogênio Ligases/metabolismo , Células Hep G2 , Humanos , Fígado/metabolismo , Malária/parasitologia , Camundongos , Proteínas de Protozoários/metabolismo
16.
Clin Infect Dis ; 70(3): 388-394, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30919885

RESUMO

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recently published interim guidance for a public health response to contain novel or targeted multidrug-resistant organisms (MDROs). We assessed the impact of implementing the strategy in a US state using a mathematical model. METHODS: We used a deterministic compartmental model, parametrized via a novel analysis of carbapenem-resistant Enterobacteriaceae data reported to the National Healthcare Safety Network and patient transfer data from the Centers for Medicare and Medicaid Services. The simulations assumed that after the importation of the MDRO and its initial detection by clinical culture at an index hospital, fortnightly prevalence surveys for colonization and additional infection control interventions were implemented at the index facility; similar surveys were then also implemented at those facilities known to be connected most strongly to it as measured by patient transfer data; and prevalence surveys were discontinued after 2 consecutive negative surveys. RESULTS: If additional infection-control interventions are assumed to lead to a 20% reduction in transmissibility in intervention facilities, prevalent case count in the state 3 years after importation would be reduced by 76% (interquartile range: 73-77%). During the third year, these additional infection-control measures would be applied in facilities accounting for 42% (37-46%) of inpatient days. CONCLUSIONS: CDC guidance for containing MDROs, when used in combination with information on transfer of patients among hospitals, is predicted to be effective, enabling targeted and efficient use of prevention resources during an outbreak response. Even modestly effective infection-control measures may lead to a substantial reduction in transmission events.


Assuntos
Infecção Hospitalar , Farmacorresistência Bacteriana Múltipla , Idoso , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Instalações de Saúde , Humanos , Medicare , Estados Unidos/epidemiologia
17.
Clin Infect Dis ; 71(11): e718-e725, 2020 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-32291441

RESUMO

BACKGROUND: Since the identification of the first 2 Candida auris cases in Chicago, Illinois, in 2016, ongoing spread has been documented in the Chicago area. We describe C. auris emergence in high-acuity, long-term healthcare facilities and present a case study of public health response to C. auris and carbapenemase-producing organisms (CPOs) at one ventilator-capable skilled nursing facility (vSNF-A). METHODS: We performed point prevalence surveys (PPSs) to identify patients colonized with C. auris and infection-control (IC) assessments and provided ongoing support for IC improvements in Illinois acute- and long-term care facilities during August 2016-December 2018. During 2018, we initiated a focused effort at vSNF-A and conducted 7 C. auris PPSs; during 4 PPSs, we also performed CPO screening and environmental sampling. RESULTS: During August 2016-December 2018 in Illinois, 490 individuals were found to be colonized or infected with C. auris. PPSs identified the highest prevalence of C. auris colonization in vSNF settings (prevalence, 23-71%). IC assessments in multiple vSNFs identified common challenges in core IC practices. Repeat PPSs at vSNF-A in 2018 identified increasing C. auris prevalence from 43% to 71%. Most residents screened during multiple PPSs remained persistently colonized with C. auris. Among 191 environmental samples collected, 39% were positive for C. auris, including samples from bedrails, windowsills, and shared patient-care items. CONCLUSIONS: High burden in vSNFs along with persistent colonization of residents and environmental contamination point to the need for prioritizing IC interventions to control the spread of C. auris and CPOs.


Assuntos
Candida , Instituições de Cuidados Especializados de Enfermagem , Chicago/epidemiologia , Seguimentos , Humanos , Illinois/epidemiologia , Ventiladores Mecânicos
18.
MMWR Morb Mortal Wkly Rep ; 69(48): 1827-1831, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33270611

RESUMO

Carbapenem-resistant Acinetobacter baumannii (CRAB), an opportunistic pathogen primarily associated with hospital-acquired infections, is an urgent public health threat (1). In health care facilities, CRAB readily contaminates the patient care environment and health care providers' hands, survives for extended periods on dry surfaces, and can be spread by asymptomatically colonized persons; these factors make CRAB outbreaks in acute care hospitals difficult to control (2,3). On May 28, 2020, a New Jersey hospital (hospital A) reported a cluster of CRAB infections during a surge in patients hospitalized with coronavirus disease 2019 (COVID-19). Hospital A and the New Jersey Department of Health (NJDOH) conducted an investigation, and identified 34 patients with hospital-acquired multidrug-resistant CRAB infection or colonization during February-July 2020, including 21 (62%) who were admitted to two intensive care units (ICUs) dedicated to caring for COVID-19 patients. In late March, increasing COVID-19-related hospitalizations led to shortages in personnel, personal protective equipment (PPE), and medical equipment, resulting in changes to conventional infection prevention and control (IPC) practices. In late May, hospital A resumed normal operations, including standard IPC measures, as COVID-19 hospitalizations decreased, lessening the impact of personnel and supply chain shortages on hospital functions. CRAB cases subsequently returned to a pre-COVID-19 baseline of none to two cases monthly. The occurrence of this cluster underscores the potential for multidrug-resistant organisms (MDROs) to spread during events when standard hospital practices might be disrupted; conventional IPC strategies should be reinstated as soon as capacity and resources allow.


Assuntos
Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Carbapenêmicos/farmacologia , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana , COVID-19/epidemiologia , COVID-19/terapia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , New Jersey/epidemiologia , Admissão do Paciente/estatística & dados numéricos
20.
Clin Infect Dis ; 68(8): 1327-1334, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30204838

RESUMO

BACKGROUND: Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1-harboring bacteria in the United States. METHODS: A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. RESULTS: Two patients had highly related mcr-1-positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. Klebsiella pneumoniae and Escherichia coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. CONCLUSIONS: We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of a US Food and Drug Administration-cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings.


Assuntos
Farmacorresistência Bacteriana Múltipla , Duodenoscópios/microbiologia , Contaminação de Equipamentos , Klebsiella pneumoniae/isolamento & purificação , Colistina , Humanos , Testes de Sensibilidade Microbiana , Estados Unidos
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