Profile

Scott J. Weissman, MD

Scott J. Weissman, MD

Infectious Disease

On staff since November 2003

Academic Title: Assistant Professor

Research Center: Center for Global Infectious Disease Research

Scott Weissman, MD: Assistant Professor of Pediatric Infectious Diseases. Despite being one of the most exhaustively studied free-living organisms in biology, the Escherichia coli bacterium continues to produce a massive burden of disease, including extraintestinal syndromes such as urinary tract infections (UTI) and bloodstream infections.

Since the initiation of intrapartum antimicrobial prophylaxis for group B streptococcus during pregnancy, E. coli has become the leading bacterial cause of early-onset sepsis (EOS) in newborns. Now, with ampicillin-resistant rates >80% among E. coli isolates, it remains unclear whether contemporary EOS isolates represent antibiotic-resistant derivatives of the traditional K1-encapsulated clones described in the 1970s (which would facilitate rapid point-of-care screening tests) or a more diverse array of novel antibiotic-resistant clones like those that have complicated empiric treatment of community-acquired UTI (e.g., Bactrim-resistant "clonal group A"). My lab uses PCR- and sequence-based molecular typing techniques to characterize clinical isolate collections gathered through active and passive surveillance by the NICHD Neonatal Research Network and the Minnesota Department of Health.

With the appearance of EOS-associated clones resistant to standard ampicillin/gentamicin combination therapy, this project will inform guidelines for the empiric treatment of early-onset sepsis. My lab is also using molecular techniques to characterize the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL) enzymes among Enterobacteriaceae. Since 2000, we have witnessed the worldwide emergence of Gram-negative "superbugs" such as E. coli ST131 and Klebsiella pneumoniae ST258which not only encode multiple virulence factors associated with extraintestinal disease, but also Class A enzymes that hydrolyze third-generation cephalosporins and carbapenem antibiotics (CTX-M-15 and KPC, respectively). Our molecular typing methods will characterize the dynamics of antibiotic resistance, to distinguish epidemics of resistance genes that spread between plasmids, plasmids that spread between strains, and strains that spread across continents.

Overview

Board Certification(s)

Pediatrics
Pediatric Infectious Diseases

Medical/Professional School

University of California, California College of Medicine, Irvine

Residency

Pediatrics, Kaiser Permanente Health Care, Los Angeles

Fellowship

Pediatric Infectious Disease, Seattle Children's Hospital, Seattle

Research Description

Despite being one of the most exhaustively studied free-living organisms in biology, Escherichia coli continues to produce a massive burden of disease, including extraintestinal syndromes such as urinary tract infections (UTI) and bloodstream infections. Since 2000, we have witnessed the worldwide emergence of Gram-negative "superbugs," such as E. coli ST131 and Klebsiella pneumoniae ST258 - which not only encode multiple virulence factors associated with extraintestinal disease, but also Class A enzymes that hydrolyze third-generation cephalosporins and carbapenem antibiotics (CTX-M-15 and KPC, respectively). The subsequent appearance of the New Delhi Metallo-beta-lactamase (NDM) enzyme has accentuated the highly dynamic nature of spreading antibiotic resistance, as travelers abroad have become colonized with pan-resistant bacteria and brought them back to their countries of origin and then experienced virtually untreatable infections. Through collaborations with other free-standing children's hospitals and the Washington State Department of Health, Dr. Weissman's lab uses molecular and sequence-based techniques to characterize the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL) and carbapenemase enzymes among Enterobacteriaceae. Their molecular typing methods characterize the molecular dynamics of antibiotic resistance, distinguishing epidemics of resistance genes that spread between plasmids, plasmids that spread between strains, and strains that spread across continents.

Lab URL

http://www.seattlechildrens.org/research/global-infectious-disease-research/weissman-lab/

Research Focus Area

Infectious Disease

Awards and Honors

Award Name Award Description Awarded By Award Date
U.S. News Top Doctor U.S. News and World Report 2012
Seattle Magazine Top Doctor - 2012 Seattle Magazine Top Doctor - 2012 Seattle Magazine 2012

Publications

  • Zerr DM, Qin X, Oron AP, Adler AL, Wolter DJ, Berry JE, Hoffman L, Weissman SJ
    Pediatric Infection and Intestinal Carriage Due to Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae.
    Antimicrobial agents and chemotherapy , 2014 July : 58(7)3997-4004
  • Kronman MP, Zerr DM, Qin X, Englund J, Cornell C, Sanders JE, Myers J, Rayar J, Berry JE, Adler AL, Weissman SJ
    Intestinal decontamination of multidrug-resistant Klebsiella pneumoniae after recurrent infections in an immunocompromised host.
    Diagnostic microbiology and infectious disease , 2014 June
  • Little ML, Qin X, Zerr DM, Weissman SJ
    Molecular epidemiology of colonizing and disease-causing Klebsiella pneumoniae in paediatric patients.
    Journal of medical microbiology , 2014 Apr, : 63(Pt 4)610-6
  • Drekonja DM, Beekmann SE, Elliott S, Mukundan D, Polenakovik H, Rosenthal ME, Tamma PD, Polgreen PM, Weissman SJ
    Challenges in the management of infections due to carbapenem-resistant Enterobacteriaceae.
    Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America , 2014 Apr, : 35(4)437-9
  • Sick AC, Tschudin-Sutter S, Turnbull AE, Weissman SJ, Tamma PD
    Empiric Combination Therapy for Gram-Negative Bacteremia.
    Pediatrics , 2014 Apr,
  • Newland JG, Gerber JS, Weissman SJ, Shah SS, Turgeon C, Hedican EB, Thurm C, Hall M, Courter J, Brogan TV, Maples H, Lee BR, Hersh AL
    Prevalence and characteristics of antimicrobial stewardship programs at freestanding children's hospitals in the United States.
    Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America , 2014 Mar. : 35(3)265-71
  • Tchesnokova V, Billig M, Chattopadhyay S, Linardopoulou E, Aprikian P, Roberts PL, Skrivankova V, Johnston B, Gileva A, Igusheva I, Toland A, Riddell K, Rogers P, Qin X, Butler-Wu S, Cookson BT, Fang FC, Kahl B, Price LB, Weissman SJ, Limaye A, Scholes D, Johnson JR, Sokurenko EV
    Predictive diagnostics for Escherichia coli infections based on the clonal association of antimicrobial resistance and clinical outcome.
    Journal of clinical microbiology , 2013 Sept. : 51(9)2991-9
  • Chattopadhyay S, Taub F, Paul S, Weissman SJ, Sokurenko EV
    Microbial variome database: point mutations, adaptive or not, in bacterial core genomes.
    Molecular biology and evolution , 2013 June : 30(6)1465-70
  • Weissman SJ, Adler A, Qin X, Zerr DM
    Emergence of extended-spectrum -lactam resistance among Escherichia coli at a US academic children's hospital is clonal at the sequence type level for CTX-M-15, but not for CMY-2.
    International journal of antimicrobial agents , 2013 May : 41(5)414-20
  • Kisiela DI, Chattopadhyay S, Tchesnokova V, Paul S, Weissman SJ, Medenica I, Clegg S, Sokurenko EV
    Evolutionary analysis points to divergent physiological roles of type 1 fimbriae in Salmonella and Escherichia coli.
    mBio , 2013 Mar. : 4(2)
  • Johnson JR, Tchesnokova V, Johnston B, Clabots C, Roberts PL, Billig M, Riddell K, Rogers P, Qin X, Butler-Wu S, Price LB, Aziz M, Nicolas-Chanoine MH, Debroy C, Robicsek A, Hansen G, Urban C, Platell J, Trott DJ, Zhanel G, Weissman SJ, Cookson BT, Fang FC, Limaye AP, Scholes D, Chattopadhyay S, Hooper DC, Sokurenko EV
    Abrupt emergence of a single dominant multidrug-resistant strain of Escherichia coli.
    The Journal of infectious diseases , 2013 Mar. : 207(6)919-28
  • Tamma PD, Newland JG, Pannaraj PS, Metjian TA, Banerjee R, Gerber JS, Weissman SJ, Beekmann SE, Polgreen PM, Hersh AL
    The use of intravenous colistin among children in the United States: results from a multicenter, case series.
    The Pediatric infectious disease journal , 2013 Jan. : 32(1)17-22
  • Newland JG, Banerjee R, Gerber JS, Hersh AL, Steinke L, Weissman SJ
    Antimicrobial stewardship in pediatric care: strategies and future directions.
    Pharmacotherapy , 2012 Aug. : 32(8)735-43
  • Johnson JR, Urban C, Weissman SJ, Jorgensen JH, Lewis JS 2nd, Hansen G, Edelstein PH, Robicsek A, Cleary T, Adachi J, Paterson D, Quinn J, Hanson ND, Johnston BD, Clabots C, Kuskowski MA, AMERECUS Investigators
    Molecular epidemiological analysis of Escherichia coli sequence type ST131 (O25:H4) and blaCTX-M-15 among extended-spectrum--lactamase-producing E. coli from the United States, 2000 to 2009.
    Antimicrobial agents and chemotherapy , 2012 May : 56(5)2364-70
  • Johnson JR, Nicolas-Chanoine MH, DebRoy C, Castanheira M, Robicsek A, Hansen G, Weissman S, Urban C, Platell J, Trott D, Zhanel G, Clabots C, Johnston BD, Kuskowski MA, MASTER Investigators
    Comparison of Escherichia coli ST131 pulsotypes, by epidemiologic traits, 1967-2009.
    Emerging infectious diseases , 2012 Apr, : 18(4)598-607
  • Weissman SJ, Johnson JR, Tchesnokova V, Billig M, Dykhuizen D, Riddell K, Rogers P, Qin X, Butler-Wu S, Cookson BT, Fang FC, Scholes D, Chattopadhyay S, Sokurenko E
    High-resolution two-locus clonal typing of extraintestinal pathogenic Escherichia coli.
    Applied and environmental microbiology , 2012 Mar. : 78(5)1353-60
  • Scott J. Weissman, MD
    Antibiotic options for treatment of pediatric infections with Enterobacteriaceae producing broad spectrum beta-lactamases
    Anti-Infective Agents , 2012 : 10(2)130-135
  • Little ML, Qin X, Zerr DM, Weissman SJ
    Molecular diversity in mechanisms of carbapenem resistance in paediatric Enterobacteriaceae.
    International journal of antimicrobial agents , 2012 Jan. : 39(1)52-7
  • Jaspan HB, Brothers AW, Campbell AJ, McGuire JK, Browd SR, Manley TJ, Pak D, Weissman SJ
    Multidrug-resistant Enterococcus faecium meningitis in a toddler: characterization of the organism and successful treatment with intraventricular daptomycin and intravenous tigecycline.
    The Pediatric infectious disease journal , 2010 Apr, : 379-81
  • Stahlhut SG, Tchesnokova V, Struve C, Weissman SJ, Chattopadhyay S, Yakovenko O, Aprikian P, Sokurenko EV, Krogfelt KA
    Comparative structure-function analysis of mannose-specific FimH adhesins from Klebsiella pneumoniae and Escherichia coli.
    Journal of bacteriology , 2009 Nov. : 6592-601
  • Chattopadhyay S, Weissman SJ, Minin VN, Russo TA, Dykhuizen DE, Sokurenko EV
    High frequency of hotspot mutations in core genes of Escherichia coli due to short-term positive selection.
    Proceedings of the National Academy of Sciences of the United States of America , 2009 July : 12412-7
  • Stahlhut SG, Chattopadhyay S, Struve C, Weissman SJ, Aprikian P, Libby SJ, Fang FC, Krogfelt KA, Sokurenko EV
    Population variability of the FimH type 1 fimbrial adhesin in Klebsiella pneumoniae.
    Journal of bacteriology , 2009 Mar. : 1941-50
  • Qin X, Zerr DM, Weissman SJ, Englund JA, Denno DM, Klein EJ, Tarr PI, Kwong J, Stapp JR, Tulloch LG, Galanakis E
    Prevalence and mechanisms of broad-spectrum beta-lactam resistance in Enterobacteriaceae: a children's hospital experience.
    Antimicrobial agents and chemotherapy , 2008 Nov. : 3909-14
  • Gomez-Duarte OG, Chattopadhyay S, Weissman SJ, Giron JA, Kaper JB, Sokurenko EV
    Genetic diversity of the gene cluster encoding longus, a type IV pilus of enterotoxigenic Escherichia coli.
    Journal of bacteriology , 2007 Dec. : 9145-9
  • Weissman SJ, Beskhlebnaya V, Chesnokova V, Chattopadhyay S, Stamm WE, Hooton TM, Sokurenko EV
    Differential stability and trade-off effects of pathoadaptive mutations in the Escherichia coli FimH adhesin.
    Infection and immunity , 2007 July : 3548-55
  • Chattopadhyay S, Feldgarden M, Weissman SJ, Dykhuizen DE, van Belle G, Sokurenko EV
    Haplotype diversity in "source-sink" dynamics of Escherichia coli urovirulence.
    Journal of molecular evolution , 2007 Feb. : 204-14
  • Johnson JR, Owens KL, Clabots CR, Weissman SJ, Cannon SB
    Phylogenetic relationships among clonal groups of extraintestinal pathogenic Escherichia coli as assessed by multi-locus sequence analysis.
    Microbes and infection / Institut Pasteur , 2006 June : 1702-13
  • Weissman SJ, Chattopadhyay S, Aprikian P, Obata-Yasuoka M, Yarova-Yarovaya Y, Stapleton A, Ba-Thein W, Dykhuizen D, Johnson JR, Sokurenko EV
    Clonal analysis reveals high rate of structural mutations in fimbrial adhesins of extraintestinal pathogenic Escherichia coli.
    Molecular microbiology , 2006 Feb. : 975-88
  • Sokurenko EV, Feldgarden M, Trintchina E, Weissman SJ, Avagyan S, Chattopadhyay S, Johnson JR, Dykhuizen DE
    Selection footprint in the FimH adhesin shows pathoadaptive niche differentiation in Escherichia coli.
    Molecular biology and evolution , 2004 July : 1373-83
  • Qin X, Weissman SJ, Chesnut MF, Zhang B, Shen L
    Kirby-Bauer disc approximation to detect inducible third-generation cephalosporin resistance in Enterobacteriaceae.
    Annals of clinical microbiology and antimicrobials , 2004 July : 13
  • Weissman SJ, Moseley SL, Dykhuizen DE, Sokurenko EV
    Enterobacterial adhesins and the case for studying SNPs in bacteria.
    Trends in microbiology , 2003 Mar. : 115-7
  • Qin X, Abe PM, Weissman SJ, Manning SC
    Extrapulmonary Legionella micdadei infection in a previously healthy child.
    The Pediatric infectious disease journal , 2002 Dec. : 1174-6

Research Funding

Grant Title Grantor Amount Award Date
Differences in infecting and colonizing Enterobacteriaceae from short-course vs standard therapy of pediatric UTI - R21AI099930 NIH/NIAID $125,000 annual DC April 1, 2012 - Feb. 28, 2015
Resistance and relatedness: Molecular features of Klebsiella pneumoniae as a colonizer and pathogen in pediatric patients in Seattle, WA Institute of Translational Health Sciences/UW June 3, 2010 - April 30, 2012
National surveillance of emerging MDR in pediatric Enterobacteriaceae infections - R01 AI083413 (Co-PI with Zerr) NIH/NIAID $420,236 annual DC June 1, 2010 - May 31, 2015
Multi-drug resistance and virulence patterns in canine and feline urinary E. coli American College of Veterinary Medicine Jan. 1, 2008 - March 31, 2011