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Paul J Planet, Apurva Narechania, Liang Chen, Barun Mathema, Sam Boundy, Gordon Archer, Barry Kreiswirth
A deluge of whole-genome sequencing has begun to give insights into the patterns and processes of microbial evolution, but genome sequences have accrued in a haphazard manner, with biased sampling of natural variation that is driven largely by medical and epidemiological priorities. For instance, there is a strong bias for sequencing epidemic lineages of methicillin-resistant Staphylococcus aureus (MRSA) over sensitive isolates (methicillin-sensitive S. aureus: MSSA). As more diverse genomes are sequenced the emerging picture is of a highly subdivided species with a handful of relatively clonal groups (complexes) that, at any given moment, dominate in particular geographical regions...
October 14, 2016: Trends in Microbiology
G Ralph Corey, Francis F Arhin, Matthew A Wikler, Daniel F Sahm, Barry N Kreiswirth, José R Mediavilla, Samantha Good, Claude Fiset, Hai Jiang, Greg Moeck, Heidi Kabler, Sinikka Green, William O'Riordan
Oritavancin is a lipoglycopeptide antibiotic with bactericidal activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The phase 3 studies SOLO I and SOLO II demonstrated comparable efficacy and safety of a single dose of oritavancin compared with 7-10 days of twice-daily vancomycin in adults with acute bacterial skin and skin-structure infections (ABSSSIs). The present analysis assessed clinical responses by pathogen at 48-72 h and at study days 14-24 in SOLO patients within the pooled data set...
September 13, 2016: International Journal of Antimicrobial Agents
Ryan K Shields, Brian A Potoski, Ghady Haidar, Binghua Hao, Yohei Doi, Liang Chen, Ellen G Press, Barry N Kreiswirth, Cornelius J Clancy, M Hong Nguyen
Thirty-seven carbapenem-resistant Enterobacteriaceae (CRE)-infected patients were treated with ceftazidime-avibactam. Clinical success and survival rates at 30-days were 59% (22/37) and 76% (28/37), respectively. In 23% (5/22) of clinical successes, CRE infections recurred within 90-days. Microbiologic failure rate was 27% (10/37). Ceftazidime-avibactam resistance was detected in 30% (3/10) of microbiologic failures.
September 13, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Christopher Vinnard, Sarah Longworth, Alyssa Mezochow, Amee Patrawalla, Barry N Kreiswirth, Keith Hamilton
RATIONALE: Nontuberculous mycobacteria are a diverse group of organisms related to M. tuberculosis and cause a wide range of human disease. Unlike tuberculosis, nontuberculous mycobacterial disease is not reportable to public health authorities in the United States (US), and the total burden of disease is uncertain. OBJECTIVES: To estimate the mortality burden of nontuberculous mycobacterial disease in the US over a 15-year period, and to identify temporal trends...
September 8, 2016: Annals of the American Thoracic Society
Kalyan D Chavda, Michael J Satlin, Liang Chen, Claudia Manca, Stephen G Jenkins, Thomas J Walsh, Barry N Kreiswirth
We developed and evaluated multiplexed molecular beacon probes in a real-time PCR assay to identify prominent extended-spectrum β-lactamase, plasmid-mediated AmpC β-lactamase (pAmpC), and carbapenemase genes directly from perianal swab specimens within six hours. We evaluated this assay on 158 perianal swabs collected from hematopoietic stem cell transplant recipients and found that this assay was highly sensitive and specific for detection of CTX-M-, pAmpC-, and KPC-producing Enterobacteriaceae, compared to culture onto chromogenic agar...
September 6, 2016: Antimicrobial Agents and Chemotherapy
José R Mediavilla, Amee Patrawalla, Liang Chen, Kalyan D Chavda, Barun Mathema, Christopher Vinnard, Lisa L Dever, Barry N Kreiswirth
UNLABELLED: Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States...
2016: MBio
Liang Li, Ambrose Cheung, Arnold S Bayer, Liang Chen, Wessam Abdelhady, Barry N Kreiswirth, Michael R Yeaman, Yan Q Xiong
BACKGROUND:  The global regulator, sarA, modulates virulence of MRSA via regulation of principal virulence factors (e.g., adhesins; toxins) and biofilm formation. Resistance of S. aureus strains to β-lactam antibiotics (e.g., oxacillin) depends on the production of penicillin-binding protein 2a (PBP2a), encoded by mecA METHODS:  In the present study, we investigated the impact of sarA on the phenotypic and genotypic characteristics of oxacillin resistance both in vitro and in an experimental endocarditis model using prototypic healthcare- and community-associated MRSA parental and their respective sarA mutant strain sets...
August 19, 2016: Journal of Infectious Diseases
Michael J Satlin, Nina Cohen, Kevin C Ma, Zivile Gedrimaite, Rosemary Soave, Gülce Askin, Liang Chen, Barry N Kreiswirth, Thomas J Walsh, Susan K Seo
OBJECTIVES: To determine the prevalence, risk factors, treatments, and outcomes of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) in adult neutropenic patients with hematologic malignancies. METHODS: We reviewed all BSIs between 2008 and 2012 in this population at two New York City oncology centers. A case-control study was conducted to identify CRE BSI risk factors, using three controls of non-CRE BSIs per case. RESULTS: CRE caused 43 (2...
October 2016: Journal of Infection
Guillermo Madico, Moses Mpeirwe, Laura White, Solange Vinhas, Beverley Orr, Patrick Orikiriza, Nancy S Miller, Mary Gaeddert, Juliet Mwanga-Amumpaire, Moises Palaci, Barry Kreiswirth, Joe Straight, Reynaldo Dietze, Yap Boum, Edward C Jones-López
RATIONALE: Rapid diagnosis of pulmonary tuberculosis (TB) is critical for timely initiation of treatment and interruption of transmission. Yet, despite recent advances, many patients remain undiagnosed. Culture, usually considered the most sensitive diagnostic method, is sub-optimal for paucibacillary disease. METHODS: We evaluated the Totally Optimized PCR (TOP) TB assay, a new molecular test that we hypothesize is more sensitive than culture. After pre-clinical studies, we estimated TOP's per-patient sensitivity and specificity in a convenience sample of 261 HIV-infected pulmonary TB suspects enrolled into a TB diagnostic study in Mbarara, Uganda against MGIT culture, Xpert MTB/RIF and a composite reference standard...
2016: PloS One
C Tkaczyk, M M Hamilton, A Sadowska, Y Shi, C S Chang, P Chowdhury, R Buonapane, X Xiao, P Warrener, J Mediavilla, B Kreiswirth, J Suzich, C K Stover, B R Sellman
UNLABELLED: Staphylococcus aureus produces numerous virulence factors, each contributing different mechanisms to bacterial pathogenesis in a spectrum of diseases. Alpha toxin (AT), a cytolytic pore-forming toxin, plays a key role in skin and soft tissue infections and pneumonia, and a human anti-AT monoclonal antibody (MAb), MEDI4893*, has been shown to reduce disease severity in dermonecrosis and pneumonia infection models. However, interstrain diversity and the complex pathogenesis of S...
2016: MBio
Xiaohong Zeng, Hui Li, Rongrong Zheng, Natalia Kurepina, Barry N Kreiswirth, Xilin Zhao, Ye Xu, Qingge Li
We report here a ligation-based spoligotyping that can identify unamplified spacers in membrane-based spoligotyping due to asymmetric insertion of IS6110 in the direct repeat locus. Our typing yielded 84.4% (411/487) concordance with traditional typing and 100% (487/487) accuracy when confirmed by DNA sequencing.
September 2016: Journal of Clinical Microbiology
Tarah Lynch, Liang Chen, Gisele Peirano, Dan B Gregson, Deirdre L Church, John Conly, Barry N Kreiswirth, Johann D Pitout
During 2013, ST278 Klebsiella pneumoniae with blaNDM-7 was isolated from the urine (KpN01) and rectum (KpN02) of a patient in Calgary, Canada. The same strain (KpN04) was subsequently isolated from another patient in the same unit. Interestingly, a carbapenem-susceptible K. pneumoniae ST278 (KpN06) was obtained 1 month later from the blood of the second patient. Next-generation sequencing (NGS) revealed that the loss of carbapenem-resistance in KpN06 was due to a 5-kb deletion on the blaNDM-7-harboring IncX3 plasmid...
September 1, 2016: Journal of Infectious Diseases
Hua Yu, Fen Qu, Bin Shan, Bin Huang, Wei Jia, Cha Chen, Aiqing Li, Minhui Miao, Xin Zhang, Chunmei Bao, Yunmin Xu, Kalyan D Chavda, Yi-Wei Tang, Barry N Kreiswirth, Hong Du, Liang Chen
The spread of the plasmid-mediated colistin resistance gene, mcr-1, into carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates poses a significant threat to global health. Here we report the identification of three mcr-1-harboring carbapenem-resistant Escherichia coli strains, collected from three patients in two provinces in China. Our results show that mcr-1-harboring CRE strains have started to spread in different hospitals in China. In addition, this report presents the first description of chromosomal integration of mcr-1 into a carbapenem-resistant E...
August 2016: Antimicrobial Agents and Chemotherapy
Scott R Evans, Gene Pennello, Norberto Pantoja-Galicia, Hongyu Jiang, Andrea M Hujer, Kristine M Hujer, Claudia Manca, Carol Hill, Michael R Jacobs, Liang Chen, Robin Patel, Barry N Kreiswirth, Robert A Bonomo
The medical community needs systematic and pragmatic approaches for evaluating the benefit-risk trade-offs of diagnostics that assist in medical decision making. Benefit-Risk Evaluation of Diagnostics: A Framework (BED-FRAME) is a strategy for pragmatic evaluation of diagnostics designed to supplement traditional approaches. BED-FRAME evaluates diagnostic yield and addresses 2 key issues: (1) that diagnostic yield depends on prevalence, and (2) that different diagnostic errors carry different clinical consequences...
September 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Kalyan D Chavda, Liang Chen, Michael R Jacobs, Robert A Bonomo, Barry N Kreiswirth
The emergence and spread of Klebsiella pneumoniae carbapenemase (KPC) among Enterobacteriaceae presents a major public health threat to the world. Although not as common as in K. pneumoniae, KPC is also found in Escherichia coli strains. Here, we genetically characterized 9 carbapenem-resistant E. coli strains isolated from six hospitals in the United States and completely sequenced their blaKPC-harboring plasmids. The nine strains were isolated from different geographical locations and belonged to 8 different E...
July 2016: Antimicrobial Agents and Chemotherapy
Aiqing Li, Yong Yang, Minhui Miao, Kalyan D Chavda, José R Mediavilla, Xiaofang Xie, Ping Feng, Yi-Wei Tang, Barry N Kreiswirth, Liang Chen, Hong Du
Here we completely sequenced four mcr-1-haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1-harboring plasmids from an E. coli sequence type 2448 (ST2448) isolate and two K. pneumoniae ST25 isolates were identical (all pMCR1-IncX4), belonging to the IncX4 incompatibility group, while the plasmid from an E. coli ST2085 isolate (pMCR1-IncI2) belongs to the IncI2 group. A nearly identical 2...
July 2016: Antimicrobial Agents and Chemotherapy
Kelly Stinson, Natalia Kurepina, Amour Venter, Mamoru Fujiwara, Masanori Kawasaki, Juliano Timm, Elena Shashkina, Barry N Kreiswirth, Yongge Liu, Makoto Matsumoto, Lawrence Geiter
The increasing global burden of multidrug-resistant tuberculosis (MDR-TB) requires reliable drug susceptibility testing that accurately characterizes susceptibility and resistance of pathogenic bacteria to effectively treat patients with this deadly disease. Delamanid is an anti-TB agent first approved in the European Union in 2014 for the treatment of pulmonary MDR-TB in adults. Using the agar proportion method, delamanid MIC was determined for 460 isolates: 316 from patients enrolled in a phase 2 global clinical trial, 76 from two phase 2 early bactericidal activity trials conducted in South Africa, and 68 isolates obtained outside clinical trials (45 from Japanese patients and 23 from South African patients)...
June 2016: Antimicrobial Agents and Chemotherapy
Deanna J Buehrle, Ryan K Shields, Liang Chen, Binghua Hao, Ellen G Press, Ammar Alkrouk, Brian A Potoski, Barry N Kreiswirth, Cornelius J Clancy, M Hong Nguyen
We compared ceftazidime-avibactam, ceftolozane-tazobactam, ceftazidime, cefepime, and piperacillin-tazobactam MICs for 38 meropenem-resistant Pseudomonas aeruginosa isolates. No isolates harbored carbapenemases; 74% were oprD mutants. Ceftazidime-avibactam and ceftolozane-tazobactam were active against 92% of the isolates, including 80% that were resistant to all three β-lactams. Forty-three percent of ceftazidime-avibactam-susceptible isolates and 6% of ceftolozane-tazobactam-susceptible isolates exhibited MICs at the respective breakpoints...
May 2016: Antimicrobial Agents and Chemotherapy
Maha R Farhat, Razvan Sultana, Oleg Iartchouk, Sam Bozeman, James Galagan, Peter Sisk, Christian Stolte, Hanna Nebenzahl-Guimaraes, Karen Jacobson, Alexander Sloutsky, Devinder Kaur, James Posey, Barry N Kreiswirth, Natalia Kurepina, Leen Rigouts, Elizabeth M Streicher, Tommie C Victor, Robin M Warren, Dick van Soolingen, Megan Murray
RATIONALE: The development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance-conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of antituberculosis drugs. OBJECTIVES: To determine the optimal molecular approach needed, we sought to create a comprehensive catalog of resistance mutations and assess their sensitivity and specificity in diagnosing drug resistance...
September 1, 2016: American Journal of Respiratory and Critical Care Medicine
Nishant Prasad, Georges Labaze, Joanna Kopacz, Sophie Chwa, Dimitris Platis, Cynthia X Pan, Daniel Russo, Vincent J LaBombardi, Giuliana Osorio, Simcha Pollack, Barry N Kreiswirth, Liang Chen, Carl Urban, Sorana Segal-Maurer
BACKGROUND: Residents of long-term care facilities (LTCFs) are at increased risk for colonization and development of infections with multidrug-resistant organisms. This study was undertaken to determine prevalence of asymptomatic rectal colonization with Clostridium difficile (and proportion of 027/NAP1/BI ribotype) or carbapenem-resistant Enterobacteriaceae (CRE) in an LTCF population. METHODS: Active surveillance was performed for C difficile and CRE rectal colonization of 301 residents in a 320-bed (80-bed ventilator unit), hospital-affiliated LTCF with retrospective chart review for patient demographics and potential risk factors...
May 1, 2016: American Journal of Infection Control
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