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Ryan K Shields, Liang Chen, Shaoji Cheng, Kalyan D Chavda, Ellen G Press, Avin Snyder, Ruchi Pandey, Yohei Doi, Barry N Kreiswirth, M Hong Nguyen, Cornelius J Clancy
Ceftazidime-avibactam is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase (KPC). We report the first cases of ceftazidime-avibactam resistance to develop during treatment of CRE infections, and identify resistance mechanisms. Ceftazidime-avibactam resistant K. pneumoniae emerged in three patients after ceftazidime-avibactam treatment for 10-19 days. Whole genome sequencing (WGS) of longitudinal ceftazidime-avibactam susceptible and resistant K...
December 28, 2016: Antimicrobial Agents and Chemotherapy
Kalyan D Chavda, Liang Chen, Derrick E Fouts, Granger Sutton, Lauren Brinkac, Stephen G Jenkins, Robert A Bonomo, Mark D Adams, Barry N Kreiswirth
: Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regions to decipher the molecular origins of carbapenem resistance and to understand the changing phylogeny of these emerging and drug-resistant pathogens. Of the carbapenem-resistant isolates, 30 possessed blaKPC-2, 40 had blaKPC-3, 2 had blaKPC-4, and 2 had blaNDM-1 Twenty-three isolates were carbapenem susceptible...
December 13, 2016: MBio
Tyler S Brown, Apurva Narechania, John R Walker, Paul J Planet, Pablo J Bifani, Sergios-Orestis Kolokotronis, Barry N Kreiswirth, Barun Mathema
BACKGROUND: Whole genome sequencing (WGS) has rapidly become an important research tool in tuberculosis epidemiology and is likely to replace many existing methods in public health microbiology in the near future. WGS-based methods may be particularly useful in areas with less diverse Mycobacterium tuberculosis populations, such as New York City, where conventional genotyping is often uninformative and field epidemiology often difficult. This study applies four candidate strategies for WGS-based identification of emerging M...
21, 2016: BMC Genomics
R S Robbins, B R Perri, S D Ahuja, H A Anger, J Sullivan Meissner, E Shashkina, B N Kreiswirth, D C Proops
Comparing genotype results of tuberculosis (TB) isolates from individuals diagnosed with TB can support or refute transmission; however, these conclusions are based upon the criteria used to define a genotype match. We used a genotype-match definition which allowed for variation in IS6110 restriction fragment length polymorphism (RFLP) to support transmission between epidemiologically linked persons. Contacts of individuals with infectious TB (index cases) diagnosed in New York City from 1997 to 2003 who subsequently developed TB (contact cases) from 1997 to 2007 were identified...
November 21, 2016: Epidemiology and Infection
Scott R Evans, Andrea M Hujer, Hongyu Jiang, Carol B Hill, Kristine M Hujer, Jose R Mediavilla, Claudia Manca, Thuy Tien T Tran, T Nicholas Domitrovic, Paul G Higgins, Harald Seifert, Barry N Kreiswirth, Robin Patel, Michael R Jacobs, Liang Chen, Rangarajan Sampath, Thomas Hall, Christine Marzan, Vance G Fowler, Henry F Chambers, Robert A Bonomo
The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp...
January 2017: Journal of Clinical Microbiology
Jingnan Lv, Xiuqin Qi, Dan Zhang, Zhou Zheng, Yuehui Chen, Yinjuan Guo, Shanshan Wang, Liang Chen, Barry N Kreiswirth, Yi-Wei Tang, Zengqiang Chen, Longhua Hu, Liangxing Wang, Fangyou Yu
Since the first report of blaNDM-1, 16 blaNDM variants have been identified among Gram-negative bacteria worldwide. Recently, a novel blaNDM variant, blaNDM-13, was identified in the chromosome of an ST101 Escherichia coli isolate from Nepal. Here we first reported plasmid-mediated blaNDM-13 in a carbapenem-resistant E. coli ST5138 clinical isolate associated with hospital-acquired urinary tract infection from China. blaNDM-13 and blaSHV-12 coexisted on the a ~54 Kb self-transferable plasmid. Compared with NDM-1, NDM-13, NDM-3, and NDM-4 had two amino acid substitutions (D95N and M154L), one amino acid substitution (D95N) and one amino acid substitutions (M154L), respectively...
2016: Frontiers in Cellular and Infection Microbiology
Apurva Narechania, Richard Baker, Rob DeSalle, Barun Mathema, Sergios-Orestis Kolokotronis, Barry Kreiswirth, Paul J Planet
BACKGROUND: Collective animal behavior, such as the flocking of birds or the shoaling of fish, has inspired a class of algorithms designed to optimize distance-based clusters in various applications, including document analysis and DNA microarrays. In a flocking model, individual agents respond only to their immediate environment and move according to a few simple rules. After several iterations the agents self-organize, and clusters emerge without the need for partitional seeds. In addition to its unsupervised nature, flocking offers several computational advantages, including the potential to reduce the number of required comparisons...
October 24, 2016: GigaScience
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...
November 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.
December 15, 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: Unlike tuberculosis, nontuberculous mycobacterial disease is not reportable to public health authorities in the United States, and the total burden of disease is uncertain. OBJECTIVES: To estimate the mortality of nontuberculous mycobacterial disease in the United States over a 15-year period and to identify temporal trends. METHODS: The U.S. Multiple Cause of Death Files from 1999 through 2014 were searched for a listing of nontuberculous mycobacterial disease by International Classification of Diseases, Tenth Revision code as either the underlying or a contributing cause of death...
November 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 6 h. 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 on chromogenic agar...
November 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...
August 30, 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 methicillin-resistant Staphylococcus aureus (MRSA) via regulation of principal virulence factors (eg, adhesins and toxins) and biofilm formation. Resistance of S. aureus strains to β-lactam antibiotics (eg, 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...
November 1, 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
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