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Authors = Peter Rabinowitz

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9 pages, 449 KiB  
Article
Increased Odds of Antibiotic Resistance in E. coli Isolates from Recurrent Urinary Tract Infections
by Lauren Frisbie, Ann E. Salm, Jeff Radcliff, Scott J. Weissman, Hema Kapoor and Peter Rabinowitz
LabMed 2025, 2(2), 9; https://doi.org/10.3390/labmed2020009 - 22 May 2025
Viewed by 737
Abstract
This study included deidentified antibiotic susceptibility results from outpatient urinary Escherichia coli isolates from Washington state which were tested at a large clinical laboratory during 2013–2019. Isolates were categorized as representing the first, second, third, or fourth-or-greater occurrence of infection in data from [...] Read more.
This study included deidentified antibiotic susceptibility results from outpatient urinary Escherichia coli isolates from Washington state which were tested at a large clinical laboratory during 2013–2019. Isolates were categorized as representing the first, second, third, or fourth-or-greater occurrence of infection in data from individual patients. We used logistic regression with the outcome of resistance, adjusting for year of antimicrobial susceptibility test, patient sex, patient age, and facility type. In cases of subsequent infection, we found a significant risk of resistance to levofloxacin, ciprofloxacin, ceftriaxone, trimethoprim-sulfa, nitrofurantoin, ampicillin, gentamicin, and amoxicillin-clavulanate. Our findings suggest that Escherichia coli isolates from recurrent urinary tract infections have a higher rate of resistance to most tested antibiotics than isolates from the first urinary tract infection in a given year. However, susceptibility frequencies did not differ significantly between antibiograms constructed using only the first occurrence in a patient and those constructed using all subsequent occurrences. These findings suggest that the traditional approach of including only the first occurrence of urinary Escherichia coli in a patient may underestimate levels of antibiotic resistance in a community. Such underestimation could negatively affect empiric therapeutic choices, health outcomes, and treatment costs. Full article
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10 pages, 628 KiB  
Article
Regional Variation in Urinary Escherichia coli Resistance Among Outpatients in Washington State, 2013–2019
by Hannah T. Fenelon, Stephen E. Hawes, Hema Kapoor, Ann E. Salm, Jeff Radcliff and Peter M. Rabinowitz
Microorganisms 2024, 12(11), 2313; https://doi.org/10.3390/microorganisms12112313 - 14 Nov 2024
Viewed by 975
Abstract
Escherichia coli (E. coli) is a predominant pathogen of urinary tract infections (UTIs) in the United States. We analyzed resistance patterns by geographic location in Washington State to assess the need for regional antibiograms. The study included urinary E. coli antibiotic [...] Read more.
Escherichia coli (E. coli) is a predominant pathogen of urinary tract infections (UTIs) in the United States. We analyzed resistance patterns by geographic location in Washington State to assess the need for regional antibiograms. The study included urinary E. coli antibiotic susceptibility tests performed by Quest Diagnostics on Washington outpatient isolates from 2013 to 2019. We conducted logistic regressions with robust standard errors for five antibiotics (ceftriaxone, ciprofloxacin, gentamicin, trimethoprim-sulfamethoxazole), with isolates classified as “susceptible” or “resistant” for each antibiotic tested. Analyses were adjusted for sex, year of isolate collection, and age group (0–18, 19–50, >50). The state’s nine Public Health Emergency Preparedness Regions (PHEPRs) were used as the geographic level for the analysis. The analysis included 40,217 isolates (93% from females, mean age 47 years). Compared to the Central PHEPR (containing Seattle), most other regions had significantly lower adjusted prevalence ratios (aPORs) of antimicrobial resistance (AMR), with aPORs as low as 0.20 (95% CI: 0.06–0.63) for ceftriaxone in the North Central region. Additionally, no regions had significantly higher aPOR of resistance for any antibiotic. Differences in resistance between the Central and other regions varied by antibiotic with the largest difference for ceftriaxone and smallest for ampicillin. The finding of regional variation of E. coli AMR calls for more specific community antibiograms to enable a precise approach to antibiotic prescribing and stewardship. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Enterobacteriaceae and Enterococci)
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20 pages, 5810 KiB  
Article
Unraveling the Complexity of Chikungunya Virus Infection Immunological and Genetic Insights in Acute and Chronic Patients
by Hegger Fritsch, Marta Giovanetti, Luan Gaspar Clemente, Gabriel da Rocha Fernandes, Vagner Fonseca, Maricelia Maia de Lima, Melissa Falcão, Neuza de Jesus, Erenilde Marques de Cerqueira, Rivaldo Venâncio da Cunha, Marcos Vinicius Lima de Oliveira Francisco, Isadora Cristina de Siqueira, Carla de Oliveira, Joilson Xavier, Jorge Gomes Goulart Ferreira, Fábio Ribeiro Queiroz, Elise Smith, Jennifer Tisoncik-Go, Wesley C. Van Voorhis, Peter M. Rabinowitz, Judith N. Wasserheit, Michael Gale, Ana Maria Bispo de Filippis and Luiz Carlos Junior Alcantaraadd Show full author list remove Hide full author list
Genes 2024, 15(11), 1365; https://doi.org/10.3390/genes15111365 - 24 Oct 2024
Cited by 1 | Viewed by 3906
Abstract
Background: The chikungunya virus (CHIKV), transmitted by infected Aedes mosquitoes, has caused a significant number of infections worldwide. In Brazil, the emergence of the CHIKV-ECSA genotype in 2014 posed a major public health challenge due to its association with more severe symptoms. [...] Read more.
Background: The chikungunya virus (CHIKV), transmitted by infected Aedes mosquitoes, has caused a significant number of infections worldwide. In Brazil, the emergence of the CHIKV-ECSA genotype in 2014 posed a major public health challenge due to its association with more severe symptoms. Objectives/Methods: This study aimed to shed new light on the host immune response by examining the whole-blood transcriptomic profile of both CHIKV-acute and chronically infected individuals from Feira de Santana, Bahia, Brazil, a region heavily affected by CHIKV, Dengue, and Zika virus epidemics. Results: Our data reveal complex symptomatology characterized by arthralgia and post-chikungunya neuropathy in individuals with chronic sequelae, particularly affecting women living in socially vulnerable situations. Analysis of gene modules suggests heightened metabolic processes, represented by an increase in NADH, COX5A, COA3, CYC1, and cap methylation in patients with acute disease. In contrast, individuals with chronic manifestations exhibit a distinct pattern of histone methylation, probably mediated by NCOA3 in the coactivation of different nuclear receptors, KMT2 genes, KDM3B and TET2, and with alterations in the immunological response, majorly led by IL-17RA, IL-6R, and STAT3 Th17 genes. Conclusion: Our results emphasize the complexity of CHIKV disease progression, demonstrating the heterogeneous gene expression and symptomatologic scenario across both acute and chronic phases. Moreover, the identification of specific gene modules associated with viral pathogenesis provides critical insights into the molecular mechanisms underlying these distinct clinical manifestations. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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12 pages, 1640 KiB  
Article
Associations between Isolation Source, Clonal Composition, and Antibiotic Resistance Genes in Escherichia coli Collected in Washington State, USA
by Mary Jewell, Erica R. Fuhrmeister, Marilyn C. Roberts, Scott J. Weissman, Peter M. Rabinowitz and Stephen E. Hawes
Antibiotics 2024, 13(1), 103; https://doi.org/10.3390/antibiotics13010103 - 20 Jan 2024
Cited by 3 | Viewed by 2358
Abstract
Antimicrobial resistance (AMR) is a global health problem stemming from the use of antibiotics in humans, animals, and the environment. This study used whole-genome sequencing (WGS) of E. coli to explore patterns of AMR across sectors in Washington State, USA (WA). The WGS [...] Read more.
Antimicrobial resistance (AMR) is a global health problem stemming from the use of antibiotics in humans, animals, and the environment. This study used whole-genome sequencing (WGS) of E. coli to explore patterns of AMR across sectors in Washington State, USA (WA). The WGS data from 1449 E. coli isolates were evaluated for isolation source (humans, animals, food, or the environment) and the presence of antibiotic resistance genes (ARGs). We performed sequence typing using PubMLST and used ResFinder to identify ARGs. We categorized isolates as being pan-susceptible, resistant, or multidrug-resistant (MDR), defined as carrying resistance genes for at least three or more antimicrobial drug classes. In total, 60% of isolates were pan-susceptible, while 18% were resistant, and 22% exhibited MDR. The proportion of resistant isolates varied significantly according to the source of the isolates (p < 0.001). The greatest resistance was detected in isolates from humans and then animals, while environmental isolates showed the least resistance. This study demonstrates the feasibility of comparing AMR across various sectors in Washington using WGS and a One Health approach. Such analysis can complement other efforts for AMR surveillance and potentially lead to targeted interventions and monitoring activities to reduce the overall burden of AMR. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: What Can We Learn from Genomics?)
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16 pages, 2435 KiB  
Article
Detection of SARS-CoV-2 in Terrestrial Animals in Southern Nigeria: Potential Cases of Reverse Zoonosis
by Anise N. Happi, Akeemat O. Ayinla, Olusola A. Ogunsanya, Ayotunde E. Sijuwola, Femi M. Saibu, Kazeem Akano, Uwem E. George, Adebayo E. Sopeju, Peter M. Rabinowitz, Kayode K. Ojo, Lynn K. Barrett, Wesley C. Van Voorhis and Christian T. Happi
Viruses 2023, 15(5), 1187; https://doi.org/10.3390/v15051187 - 17 May 2023
Cited by 9 | Viewed by 3136
Abstract
Since SARS-CoV-2 caused the COVID-19 pandemic, records have suggested the occurrence of reverse zoonosis of pets and farm animals in contact with SARS-CoV-2-positive humans in the Occident. However, there is little information on the spread of the virus among animals in contact with [...] Read more.
Since SARS-CoV-2 caused the COVID-19 pandemic, records have suggested the occurrence of reverse zoonosis of pets and farm animals in contact with SARS-CoV-2-positive humans in the Occident. However, there is little information on the spread of the virus among animals in contact with humans in Africa. Therefore, this study aimed to investigate the occurrence of SARS-CoV-2 in various animals in Nigeria. Overall, 791 animals from Ebonyi, Ogun, Ondo, and Oyo States, Nigeria were screened for SARS-CoV-2 using RT-qPCR (n = 364) and IgG ELISA (n = 654). SARS-CoV-2 positivity rates were 45.9% (RT-qPCR) and 1.4% (ELISA). SARS-CoV-2 RNA was detected in almost all animal taxa and sampling locations except Oyo State. SARS-CoV-2 IgGs were detected only in goats from Ebonyi and pigs from Ogun States. Overall, SARS-CoV-2 infectivity rates were higher in 2021 than in 2022. Our study highlights the ability of the virus to infect various animals. It presents the first report of natural SARS-CoV-2 infection in poultry, pigs, domestic ruminants, and lizards. The close human–animal interactions in these settings suggest ongoing reverse zoonosis, highlighting the role of behavioral factors of transmission and the potential for SARS-CoV-2 to spread among animals. These underscore the importance of continuous monitoring to detect and intervene in any eventual upsurge. Full article
(This article belongs to the Section SARS-CoV-2 and COVID-19)
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12 pages, 1757 KiB  
Article
Genomic Epidemiology of Clinical Brucella melitensis Isolates from Southern Israel
by Bar Zilberman, Yair Motro, Orli Sagi, David Kornspan, Shalom Ben-Shimol, Michael Gdalevich, Yael Yagel, Nadav Davidovitch, Boris Khalfin, Peter Rabinowitz, Lior Nesher, Itamar Grotto, Svetlana Bardenstein and Jacob Moran-Gilad
Microorganisms 2022, 10(2), 238; https://doi.org/10.3390/microorganisms10020238 - 22 Jan 2022
Cited by 8 | Viewed by 3216
Abstract
Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products, is endemic in Southern Israel, mainly among the Bedouin Arab population. However, the genomic epidemiology of B. melitensis in this region has not yet been elucidated. A cohort of brucellosis cases ( [...] Read more.
Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products, is endemic in Southern Israel, mainly among the Bedouin Arab population. However, the genomic epidemiology of B. melitensis in this region has not yet been elucidated. A cohort of brucellosis cases (n = 118) diagnosed between 2017–2019 was studied using whole-genome sequencing (WGS). Phylogenetic analyses utilized core genome MLST (cgMLST) for all local isolates and core genome SNPs for 347 human-associated B. melitensis genomes, including Israeli and publicly available sequences. Israeli isolates formed two main clusters, presenting a notable diversity, with no clear dominance of a specific strain. On a global scale, the Israeli genomes clustered according to their geographical location, in proximity to genomes originating from the Middle East, and formed the largest cluster in the tree, suggesting relatively high conservation. Our study unveils the genomic epidemiology of B. melitensis in Southern Israel, implicating that rather than a common source, the transmission pattern of brucellosis among Bedouin communities is complex, predominantly local, and household-based. Further, genomic surveillance of B. melitensis is expected to inform future public health and veterinary interventions and clinical care. Full article
(This article belongs to the Special Issue Rapid and Novel Diagnostics for Infectious Diseases)
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18 pages, 1890 KiB  
Article
Surveillance for Antibiotic-Resistant E. coli in the Salish Sea Ecosystem
by Alexandria Vingino, Marilyn C. Roberts, Michelle Wainstein, James West, Stephanie A. Norman, Dyanna Lambourn, Jeffery Lahti, Ryan Ruiz, Marisa D’Angeli, Scott J. Weissman and Peter Rabinowitz
Antibiotics 2021, 10(10), 1201; https://doi.org/10.3390/antibiotics10101201 - 2 Oct 2021
Cited by 14 | Viewed by 3974
Abstract
E. coli was isolated from the Salish Sea (Puget Sound) ecosystem, including samples of marine and fresh water, and wildlife dependent on this environment. E. coli isolates were assessed for phenotypic and genotypic resistance to antibiotics. A total of 305 E. coli isolates [...] Read more.
E. coli was isolated from the Salish Sea (Puget Sound) ecosystem, including samples of marine and fresh water, and wildlife dependent on this environment. E. coli isolates were assessed for phenotypic and genotypic resistance to antibiotics. A total of 305 E. coli isolates was characterized from samples collected from: marine water obtained in four quadrants of the Salish Sea; select locations near beaches; fresh water from streams near marine beaches; and fecal samples from harbor porpoises (Phocoena phocoena), harbor seals (Phoca vitulina), river otters (Lontra canadensis), and English sole (Parophrys vetulus). Isolates were evaluated using antimicrobial susceptibility typing, whole-genome sequencing, fumC, and multilocus sequence typing. Resistance and virulence genes were identified from sequence data. Of the 305 isolates from Salish Sea samples, 20 (6.6%) of the E. coli were intermediate, and 31 (10.2%) were resistant to ≥1 class of antibiotics, with 26.9% of nonsusceptible (resistant and intermediate resistant) E. coli isolates from marine mammals and 70% from river otters. The proportion of nonsusceptible isolates from animals was significantly higher than samples taken from marine water (p < 0.0001). A total of 196 unique STs was identified including 37 extraintestinal pathogenic E. coli (ExPEC)-associated STs [ST10, ST38, ST58, ST69, ST73, ST117, ST131, and ST405]. The study suggests that animals may be potential sentinels for antibiotic-resistant and ExPEC E. coli in the Salish Sea ecosystem. Full article
(This article belongs to the Special Issue 10th Anniversary of Antibiotics—Feature Papers)
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13 pages, 3009 KiB  
Article
Whole Genome Sequence Analysis of Brucella melitensis Phylogeny and Virulence Factors
by Peter Rabinowitz, Bar Zilberman, Yair Motro, Marilyn C. Roberts, Alex Greninger, Lior Nesher, Shalom Ben-Shimol, Yael Yagel, Michael Gdalevich, Orly Sagi, Nadav Davidovitch, David Kornspan, Svetlana Bardenstein and Jacob Moran-Gilad
Microbiol. Res. 2021, 12(3), 698-710; https://doi.org/10.3390/microbiolres12030050 - 24 Aug 2021
Cited by 10 | Viewed by 5640
Abstract
Brucellosis has a wide range of clinical severity in humans that remains poorly understood. Whole genome sequencing (WGS) analysis may be able to detect variation in virulence genes. We used Brucella melitensis sequences in the NCBI Sequence Read Archive (SRA) database to assemble [...] Read more.
Brucellosis has a wide range of clinical severity in humans that remains poorly understood. Whole genome sequencing (WGS) analysis may be able to detect variation in virulence genes. We used Brucella melitensis sequences in the NCBI Sequence Read Archive (SRA) database to assemble 248 whole genomes, and additionally, assembled 27 B. melitensis genomes from samples of human patients in Southern Israel. We searched the 275 assembled genomes for the 43 B. melitensis virulence genes in the Virulence Factors of Pathogenic Bacteria Database (VFDB) and 10 other published putative virulence genes. We explored pan-genome variation across the genomes and in a pilot analysis, explored single nucleotide polymorphism (SNP) variation among the ten putative virulence genes. More than 99% of the genomes had sequences for all Brucella melitensis virulence genes included in the VFDB. The 10 other virulence genes of interest were present across all the genomes, but three of these genes had SNP variation associated with particular Brucella melitensis genotypes. SNP variation was also seen within the Israeli genomes obtained from a small geographic region. While the Brucella genome is highly conserved, this novel and large whole genome study of Brucella demonstrates the ability of whole genome and pan-genome analysis to screen multiple genomes and identify SNP variation in both known and novel virulence genes that could be associated with differential disease virulence. Further development of whole genome techniques and linkage with clinical metadata on disease outcomes could shed light on whether such variation in the Brucella genome plays a role in pathogenesis. Full article
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11 pages, 710 KiB  
Article
Contribution and Interaction of Shiga Toxin Genes to Escherichia coli O157:H7 Virulence
by Gillian A.M. Tarr, Taryn Stokowski, Smriti Shringi, Phillip I. Tarr, Stephen B. Freedman, Hanna N. Oltean, Peter M. Rabinowitz and Linda Chui
Toxins 2019, 11(10), 607; https://doi.org/10.3390/toxins11100607 - 18 Oct 2019
Cited by 24 | Viewed by 4939
Abstract
Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes [...] Read more.
Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes encode differ in their in vitro and experimental phenotypes, but the human population-level impact of these differences is poorly understood. Using Shiga toxin-encoding bacteriophage insertion typing and real-time polymerase chain reaction, we genotyped isolates from 936 E. coli O157:H7 cases and verified HUS status via chart review. We compared the HUS risk between isolates with stx2a and those with stx2a and another gene and estimated additive interaction of the stx genes. Adjusted for age and symptoms, the HUS incidence of E. coli O157:H7 containing stx2a alone was 4.4% greater (95% confidence interval (CI) −0.3%, 9.1%) than when it occurred with stx1a. When stx1a and stx2a occur together, the risk of HUS was 27.1% lower (95% CI −87.8%, −2.3%) than would be expected if interaction were not present. At the population level, temporal or geographic shifts toward these genotypes should be monitored, and stx genotype may be an important consideration in clinically predicting HUS among E. coli O157:H7 cases. Full article
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10 pages, 2085 KiB  
Article
Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy
by Errol R. Norwitz, Gabriel McNeill, Akshita Kalyan, Elizabeth Rivers, Ebad Ahmed, Ling Meng, Phikhanh Vu, Melissa Egbert, Marlene Shapira, Katie Kobara, Sheetal Parmar, Shruti Goel, Sarah A. Prins, Israel Aruh, Nicola Persico, Jared C. Robins, Brian Kirshon, Zachary P. Demko, Allison Ryan, Paul R. Billings, Matthew Rabinowitz, Peter Benn, Kimberly A. Martin and Herman L. Hedrianaadd Show full author list remove Hide full author list
J. Clin. Med. 2019, 8(7), 937; https://doi.org/10.3390/jcm8070937 - 28 Jun 2019
Cited by 43 | Viewed by 8908
Abstract
We analyzed maternal plasma cell-free DNA samples from twin pregnancies in a prospective blinded study to validate a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for zygosity, fetal sex, and aneuploidy. Zygosity was evaluated by looking for either one or two fetal genome [...] Read more.
We analyzed maternal plasma cell-free DNA samples from twin pregnancies in a prospective blinded study to validate a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for zygosity, fetal sex, and aneuploidy. Zygosity was evaluated by looking for either one or two fetal genome complements, fetal sex was evaluated by evaluating Y-chromosome loci, and aneuploidy was assessed through SNP ratios. Zygosity was correctly predicted in 100% of cases (93/93; 95% confidence interval (CI) 96.1%–100%). Individual fetal sex for both twins was also called with 100% accuracy (102/102; 95% weighted CI 95.2%–100%). All cases with copy number truth were also correctly identified. The dizygotic aneuploidy sensitivity was 100% (10/10; 95% CI 69.2%–100%), and overall specificity was 100% (96/96; 95% weighted CI, 94.8%–100%). The mean fetal fraction (FF) of monozygotic twins (n = 43) was 13.0% (standard deviation (SD), 4.5%); for dizygotic twins (n = 79), the mean lower FF was 6.5% (SD, 3.1%) and the mean higher FF was 8.1% (SD, 3.5%). We conclude SNP-based NIPT for zygosity is of value when chorionicity is uncertain or anomalies are identified. Zygosity, fetal sex, and aneuploidy are complementary evaluations that can be carried out on the same specimen as early as 9 weeks’ gestation. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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