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9433 the killers within

9433 The Killers Within 8/6/02 11:18 AM Page 291 acknowledgments
To embrace a field as broad and complex as drug-resistant bacteria,with all the microbiology it entails, then try to make it simple, clear,and compelling, we needed a lot of wise counsel. J. Glenn Morris Jr.
of the University of Maryland’s Baltimore Veterans Affairs MedicalCenter was one such guru; we are grateful not only for his consider-able help but for his commitment to fighting the war against drug-resistant bacteria on so many fronts. Like Morris, Fred Tenover andFred Angulo of the Centers for Disease Control both consented toseveral interviews, with much follow-up e-mailing, effortlessly tickingoff the subtleties of human and animal antibiotic resistance. Knowingthat two such capable experts are on the case for the U.S. govern-ment — committed public servants both — is one of the few cheeringaspects of this scary situation. Keiichi Hiramatsu of Tokyo’s JuntendoUniversity is another world-class expert in the field who was kindenough to offer considerable help, both in person and in long follow-up e-mail messages. Barry Kreiswirth of the New York Public HealthResearch Institute spent many hours with us; so did Chuck Ford, sen-ior scientist at Pharmacia & Upjohn. Henrik Wegener of the DanishZoonosis Center was a gracious host when we visited him inCopenhagen; he then kindly read and commented on our chapters onresistance in animal-use antibiotics. Christina Greko, in Stockholm,was just as gracious and helpful. Nina Chanishvili spoke with us atlength when we visited her at the Eliava Institute in Tbilisi, Georgia;she then responded to our follow-up queries with many long, veryhelpful e-mail messages.
9433 The Killers Within 8/6/02 11:18 AM Page 292 / A C K N O W L E D G M E N T S
Several other experts kept up a regular e-mail correspondence with us, alerting us to new studies, answering our queries, and then read-ing much or all of our manuscript. Jon Blum of the Harvard MedicalSchool was extraordinarily helpful in this regard, especially in guid-ing us through the thickets of Patrice Courvalin’s work with van-comycin-resistant enterococci, which made up the most scientificallycomplex chapter of our book. Yale Medical School’s ChristopherHerndon was just as valuable a guru — a real fount of scientific infor-mation, and never too busy, it seemed, to respond to our queries.
Susan Donelan, Director of Infection Control at Stony Brook Hospitalin Long Island, New York, gave us an insider’s tour, answered manyfollow-up queries, and read much of our manuscript with an eagle eyewhile somehow tending to newborn twins at the same time. HarrietteNadler of Rhone-Poulenc Rorer, Richard Goering of CreightonUniversity, Tamar Barlam of the Center for Science in the PublicInterest, and Steve Projan of Wyeth-Ayerst also answered manyqueries and offered much help along the way. Early on, we werebuoyed by a grant from Byron Waksman and the Foundation forMicrobiology.
In addition, we are indebted to the following for their considerable kindness and time in granting us interviews: Zamphira Alavidze,Evangeline Ames-Murray, Peter Applebaum, Thomas Aragon, JeffBand, Kiran Belani, Barry Bloom, François Bompart, Lori Boschetto,Daniel Bouanchaud, Steven Brooks, Gary Burke, Colin Campbell,Richard Carlton, Richard Carnevale, Henry Chambers, TeimurazChanishvili, David Cole, Patrice Courvalin, Robert Daum, Gary Doern,Michael Dowzicky, Paul Ewald, Paul Farmer, Barry Farr, CelineFeger, Dan Feiken, Vince Fischetti, Karen Florini, Claire Fraser,Terry Fredeking, Hank Fuchs, Alfred Gertler, Steven Gill, DonGillespie, Caisey Harlingten, William Haseltine, David Heymann,Richard Honour, Michael Jacobs, George Jacoby, Kathleen Jakob,William Jarvis, Judith Johnson, Wesley Kloos, Marin Kollef, DavidLandman, Marc Lappe, Robert Lehrer, Herminia de Lencastre,Bruce Levin, Richard Levins, Stuart Levy, Patty Lieberman, DonLow, Guido Majno, Nina Marano, Damien McDevitt, Don McGraw, 9433 The Killers Within 8/6/02 11:18 AM Page 293 A C K N O W L E D G M E N T S
Antone Medeiros, Amiran Meipariani, John Mekalanos, Carl Merril,George Miller, Linda Miller, Carol Moberg, Robert Moellering, TimNaimi, William Noble, Gary Noel, Tim Nolan, Richard Novick,Michael Osterholm, Lance Peterson, Sandy Pine, George Poste,Steve Quirk, James Rahal, Eric Reines, David Remy, Teri Remy, PeterReynolds, Louis Rice, Tim Rieser, Barbara Robinson-Dunn, MaryClaire Roghmann, Hugh Rosen, Marty Rosenberg, Dan Sahm,Patrick Schlievert, Dean Shinabarger, David Shrayer, Caroline Smithde Waal, Kirk Smith, Theresa Smith, Lord Soulsby of SwaffhamPrior, Steven Spiritas, Eric Spitzer, Dennis Stevens, Neal Steigbigel,Karen Stronsky, Alexander Sulakvelidze, Stephen Sundlof, FrankTalley, Michael Taylor, Judy Teppler, John Threlfall, Mona Tice, MarkTodd, Alexander Tomasz, Bill Trick, Carl Urban, Craig Venter, ChrisWalsh, Patrick Warren, Rob Williams, Rosamund Williams, MaryWilson, Wolfgang Witte, Rich Wood, Richard Wrangham, MichaelZasloff, Marcus Zervos, German Zuluaga, and Gary Zurenko.
At Little, Brown, Geoff Shandler adroitly edited the final manu- script, paring it and reshaping it to make it immeasurably better, andwe are very grateful for that. Thanks also to Sarah Crichton, who wasthe first editor to believe in this book. Thanks to our agents, JoniEvans and Rafe Sagalyn, for their help throughout. Thanks to LilianaMadrigal for her love and support, and to our friends for enduring anawful lot of talk about vancomycin-intermediate-resistant Staphylo-coccus aureus and many other such microbiological mouthfuls.
9433 The Killers Within 8/6/02 11:18 AM Page 295 Facts about Glenn Morris and his clinical rounds at Baltimore’s VA medical center are drawn from author interviews with Morris. 11 Every year, 1.2 million children around the world were estimated to die of S.
pneumo: Remarks by Anthony S. Fauci, M.D., director of the National Institute ofAllergy and Infectious Diseases, National Institutes of Health, before the SenateCommittee on Health, Education, Labor and Pensions Subcommittee on PublicHealth and Safety, February 25, 1999.
12 Now 45 percent of all S. pneumo strains were penicillin resistant:
“Antimicrobial Resistance with Streptococcus pneumoniae in the United States,1997–98,” by Gary V. Doern et al., Emerging Infectious Diseases 5, no. 6 (1999).
12 Bryan Alexander, eighteen, was found guilty: Arlington (TX) Morning News,
12 A few months later, talk show host Rosie O’Donnell: Rosie magazine, July
14 Stuart Levy, M.D., a Tufts University professor: “The Hunt Is On,” by Mary
Knudson, Technology Review, 100 ( January 11, 1998).
14 Joshua Lederberg, M.D.: “Superbugs,” by Sheryl Gay Stolberg, New York
14 In 1954, 2 million pounds of antibiotics: “The Challenge of Antibiotic
Resistance,” by Stuart Levy, Scientific American, March 1998.
15 Yet researchers at the [CDC] judged that a full third: ibid.
15 Every year in U.S. medical institutions, 2 million patients: Centers for Disease
9433 The Killers Within 8/6/02 11:18 AM Page 296 16 the estimated $5 billion cost of treating drug-resistant infections: Fauci,
16 high incidence of pathogenic bacteria on computer keyboards: “Computer
Keyboards and Faucet Handles as Reservoirs of Nosocomial Pathogens in theIntensive Care Unit,” Sergio Bures, M.D., et al., American Journal of InfectionControl 28, no. 6 (December 2000).
16 Another had found the bugs in the cushions and fabric of chairs: “Persistent
Contamination of Fabric-Covered Furniture by Vancomycin-Resistant entero-cocci,” by Gary A. Noskin, M.D., et al., American Journal of Infection Control 28,no. 4 (August 2000).
16 A third had found them on rectal thermometers: “Hospital-Acquired
Infection with Vancomycin-Resistant Enterococcus faecium Transmitted byElectronic Thermometers,” by L. L. Livornese Jr. et al., Annals of Internal Medicine118, no. 2 ( January 15, 1993): 156; Annals of Internal Medicine 117, no. 2 ( July 15,1992), 112–16.
16 fourth on stethoscopes: “Contamination of Gowns, Gloves, and Stethoscopes
with Vancomycin-Resistant Enterococci,” by K. C. Zachary et al., Infection Control& Hospital Epidemiology 22, no. 9 (September 2001): 560–64.
16 In fact, one recent study conducted at Duke University: “Adverse Effects of
Contact Isolation,” by Kathryn B. Kirkland and Jill M. Weinstein, Lancet 354, no.
9185 (October 2, 1999).
18 “We can close the books on infectious diseases”: The Plague-Makers, by
Jeffrey A. Fisher, M.D. (New York: Simon & Schuster: 1994), 18.
19 Of those 50 million pounds of antibiotics: Levy, Scientific American, March
19 Each year, Salmonella infected: author interview with Fred Angulo of the
21 Treating a single case of multidrug-resistant tuberculosis: author interview
with Paul Farmer of Partners in Health.
21 “We are seeing a global resurgence”: U.S. Surgeon General David Satcher, in
For the general facts about bacteria at the start of this chapter, we are indebted principally to I. Edward Alcamo’s wonderfully readable textbook Fundamentals of 9433 The Killers Within 8/6/02 11:18 AM Page 297 Microbiology. Also very helpful was Stuart Levy’s The Antibiotic Paradox. For gen-eral facts about S. aureus, we relied on those sources, as well as “The GenusStaphylococcus,” a chapter by Wesley E. Kloos, Karl-Heinz Schleifer, andFriedrich Gotz, from A. Balows, H. G. Truper, M. Dworkin, et al., eds., TheProkaryotes, 2d ed. (New York: Springer-Verlag, 1991); and the Food and DrugAdministration’s online “Bad Bug Book” entry on S. aureus (http://vm.cfsan.
fda.gov), as well as the entry on same from the now-defunct Web site www.icanprevent.com, pioneered by former Minnesota state epidemiologist MichaelOsterholm (a regrettable loss!). Also helpful were Jeffrey A. Fisher’s The PlagueMakers and Geoffrey Cannon’s Superbug.
Author interviews with the following also informed this chapter: Jon Blum, Ph.D., Richard Goering, Ph.D., Wesley E. Kloos, Ph.D., Marc Lappe, Stuart Levy, M.D.,Guido Majno, M.D., Steve Projan, Ph.D., Patrick Schlievert, Ph.D., Fred Tenover,Ph.D. 31 In the Bible’s book of Exodus: from Exodus 9:10.
31 Girolamo Fracastoro propounded it: De contagione, Contagiosis morbus et eo-
31 Ogston went on to show: author interview with Wesley E. Kloos.
32 Christian Gram, a Danish doctor, declared: Alcamo, Fundamentals, 75.
32 British scientist Alexander Fleming discovered: The Fleming story is told well
in Miracle Cure: The Story of Penicillin and the Golden Age of Antibiotics, by MiltonWainwright, who discusses Ronald Hare’s contribution to the lore. It’s also dis-cussed in The Plague Makers and The Antibiotic Paradox. 34 began by successfully re-creating Fleming’s experiments: Florey and Chain’s
work is discussed in Miracle Cure, The Antibiotic Paradox, and The ForgottenPlague, by Frank Ryan, M.D. (Little, Brown, 1992).
35 “The greatest possibility of evil”: New York Times, June 26, 1945, 21.
36 By 1946, 14 percent of the S. aureus strains: “The Genus Staphylococcus,” by
37 Then in 1952 came a startling case in Japan: Why Antibiotics Fail, by Marc
Lappe (North Atlantic Books, 1986), 74.
39 Ever since the discovery of streptomycin: The story of vancomycin is drawn
from an unpublished Ph.D. thesis on the subject, “The Antibiotic Discovery Era(1940–1960): Vancomycin As an Example of the Era,” by Donald J. McGraw(Oregon State University, December 1975). Some details also drawn from author’sinterview with McGraw.
9433 The Killers Within 8/6/02 11:18 AM Page 298 The first part of this chapter is drawn principally from author interviews with Glenn Morris; the second part, on avoparcin and VRE, is based on an author interview withWolfgang Witte, Ph.D. Other sources interviewed for the chapter were BarryKreiswirth, Ph.D., Barry Farr, M.D., Donald Low, M.D., Fred Angulo, Ph.D., andWilliam Jarvis, M.D. 48 Dr. Don Low, chief of microbiology: Mark Witten, “Outbreak,” Saturday
48 Not long before . . . a patient at the Toronto Hospital: ibid.
4 : T H E G E N E T I C D E T E C T I V E This chapter was drawn principally from author interviews with Patrice Courvalin, Ph.D., of the Pasteur Institute, Christopher Walsh, Ph.D., of Harvard University med-ical school, Peter Reynolds, Ph.D., of Cambridge University, and William Noble, Ph.D. 58 A grateful public underwrote it: François Jacob, “The Pasteur Institute,” at
the Nobel e-Museum Web Site, www.nobel.se/medicine/articles/jacob.
70 Noble’s article, published in a scholarly journal: “Co-transfer of Vancomycin
and Other Resistant Genes from Enterococcus faecalis NCTC 12201 toStaphylococcus aureus,” by W. C. Noble, Z. Virani, and R. G. Cree, FEMS Microbiol.
Lett.
93 (1992): 195–98.
This first part of this chapter is based chiefly on author interviews with Keiichi Hiramatsu, M.D., Ph.D. The Michigan section is based on interviews with FredTenover, Ph.D., Theresa Smith, M.D., William Jarvis, M.D., Barbara Robinson-Dunn,Ph.D., Jeff Band, M.D., and Marcus Zervos, M.D. The New Jersey VISA story is basedon interviews with Theresa Smith, Gary Burke, M.D., Rob Williams, M.D., LoriBoschetto, and Karen Stronsky. 77 Hiramatsu’s report appeared, belatedly: “Characterization of Staphylococci
with Reduced Susceptibilities to Vancomycin and other Glycopeptides,” by F. C.
Tenover et al., Journal of Clinical Microbiology 36, no. 4: 1020–27. See also“Dissemination in Japanese Hospitals of Strains of Staphylococcus aureusHeterogeneously Resistant to Vancomycin,” by Keiichi Hiramatsu et al., Lancet,December 6, 1997, and “Contribution of a Thickened Cell Wall and Its GlutamineNonamidated Component to the Vancomycin Resistance Expressed by Staphylococcus 9433 The Killers Within 8/6/02 11:18 AM Page 299 aureus Mu50,” by Longzhu Cui et al., Antimicrobial Agents and Chemotherapy 44,no. 9 (September 2000): 2276–85. In addition, Hiramatsu has written chapters of ac-ademic texts on VISA, including “Vancomycin Resistance in Staphylococci,” fromDrug Resistance Updates (Harcourt Brace & Co., 1998), 135–50 and “Mechanisms ofMethicillin and Vancomycin Resistance in Staphylococcus aureus,” by Hiramatsu,Teruyo Ito, Ph.D., and Hideaki Hanaki, Ph.D., from Balliere’s Clinical InfectiousDiseases 5, no. 2 (July 1999): 221–42.
78 The call came one day in late July: author interview with Barbara Robinson-
83 In her hotel room, Smith laid out all the charts: “Update: Staphylococcus au-
reus with Reduced Susceptibility to Vancomycin —United States, 1997,” MMWR46, no. 33 (August 22, 1997), 765–66.
Theresa Smith’s more complete report on the Michigan cases appeared in the New England Journal of Medicine on February 18, 1999, as “Emergence ofVancomycin Resistance in Staphylococcus aureus” (340, no. 7, 493–501).
84 Campbell wanted her to call him on arriving: author interview with Colin
6 : T W O N O T- Q U I T E - M A G I C B U L L E T S The story of Synercid is based chiefly on author interviews with Rhone-Poulenc Rorer’s Daniel Bouanchaud, M.D., François Bompart, M.D., Michael Dowzicky,Ph.D., Celine Feger, and Harriette Nadler, Ph.D. The story of linezolid is based chieflyon author interviews with Pharmacia & Upjohn’s Chuck Ford, Gary Zurenko, MarkTodd, and Dean Shinabarger. 91 On March 20, 1998: “Staphylococcus aureus with reduced susceptibility to
vancomycin isolated from a patient with fatal bacteremia,” by Sharon S. Rotun et al.,Emerging Infectious Diseases 5, no. 1 ( January–March 1999). See also “Superbugs,”by Sheryl Gay Stolberg, New York Times Magazine, August 2, 1998.
92 Alexander Tomasz and Krzysztof Sieradzki demonstrated: “The Develop-
ment of Vancomycin Resistance in a Patient with Methicillin-ResistantStaphylococcus aureus Infection,” by Sieradzki et al., New England Journal ofMedicine 340, no. 7 (February 18, 1999).
92 Sixteen-year-old Teresa Miltonberger’s ordeal began: The Seattle Times,
May 22, 1998, 1, has a good initial report on the tragedy. A medical update on TeresaMiltonberger appears in an Associated Press dispatch of December 18, 1998. A ret-rospective piece, pegged to the sentencing of the school shooter, appears in theOregonian, November 11, 1999, 1.
9433 The Killers Within 8/6/02 11:18 AM Page 300 97 Etienne and Bompart’s team conducted phase one trials: Several details from
this stage of the story are adopted from “Germ Warfare,” by Dan Greenburg, NewYork Magazine, October 1993.
99 Synercid, Moellering conceded in his report: “In Vitro Activity of RP 59500,
an Injectable Streptogramin Antibiotic, Against Vancomycin-Resistant Gram-Positive Organisms,” by Linda A. Collins et al., Antimicrobial Agents andChemotherapy, 37, no. 3, March 1993, 598–601.
100 The patient, a forty-six-year-old woman: “Quinupristin/Dalfopristin (RP
59500) Therapy for Vancomycin-Resistant Enterococcus faecium Aortic GraftInfection: Case Report,” by Vivek S. Sahgal et al., Microbial Drug Resistance 1, no. 3(1995): 245–47.
102 Some 2,000 patients in all were given Synercid: Associated Press report,
September 21, 1999; also, Pittsburgh Post-Gazette, September 9, 1997, sec. A, p. 3.
102 Even Robert Moellering found reason: “The Efficacy and Safety of
Quinupristin/Dalfopristin for the Treatment of Infections Caused by Vancomycin-Resistant Enterococcus faecium,” by R. C. Moellering et al., Journal of AntimicrobialChemotherapy 44 (August 1999): 251–61.
111 One remarkable story came from Orlando, Florida: “County Lines Cancer
Patient Refuses to Lose Her Zest for Life,” by Jim Toner, Orlando Sentinel, July 15,2001.
111 In one typical trial study of 200 patients: “New Antibiotics to Fight
Superbug,” Independent, September 28, 1998, 10.
111 In an MRSA trial of 460 patients: “FDA Advisers Recommend Approval of
Linezolid,” Reuters Health, March 27, 2000.
111 In a study of forty-four patients: ibid.
111 One of the many doctors: Independent, September 28, 1998.
113 Zyvox, by contrast, cost about $140 a day: “FDA Approves New Drug to
Attack Resistant Germs,” by Sheryl Gay Stolberg, New York Times, April 19, 2000,sec. A, p. 19.
114 Pharmacia & Upjohn had dutifully reported: “Linezolid: First of a New
Drug Class for Gram-Positive Infections,” Drug & Therapeutic Perspectives 17,no. 9 (2001): 1–6.
114 Quinn used Zyvox on five patients: “Infections Due to Vancomycin-
Resistant Enterococcus faecium Resistant to Linezolid,” by Ronald D. Gonzales et al.,Lancet, April 14, 2001.
9433 The Killers Within 8/6/02 11:18 AM Page 301 114 Dr. Cameron Durrant: Adam Marcus, “Resistance Found to Potent New
Antibiotic,” HealthScout (a publication of MDchoice.com at www.healthscout.com).
115 In a follow-up study to Synercid trials, RPR had duly noted: “Characterization
of Isolates Associated with Emerging Resistance to Quinupristin/Dalfopristin(Synercid) During a Worldwide Clinical Program,” by M. Dowzicky et al., DiagnosticMicrobiology and Infectious Disease 37 (2000): 57–62.
115 In Michigan, however, a more ominous study: “Antimicrobial Resistance in
Enterococci Isolated from Turkey Flocks Fed Virginiamycin,” by L. A. Welton et al.,Antimicrobial Agents and Chemotherapy 42, no. 3 (March 1998): 705–8.
7 : A D E A D LY T H R E AT I N L I V E S T O C K This chapter is based chiefly on author interviews with Marcus Zervos, M.D., Fred Angulo, D.V.M., Ph.D., Richard Carnevale, D.V.M., and Stephen Sundlof, D.V.M.,Ph.D. 117 he spent a whole year studying turkey feces: “Antimicrobial Resistance in
Enterococci Isolated from Turkey Flocks Fed Virginiamycin,” by Welton et al.,Antimicrobial Agents and Chemotherapy 42, no. 3 (March 1998): 705–8.
118 In 1996, he and his researchers had gone to test fecal droppings: “Survey for
Multiply Resistant Enterococci from Livestock and Associated Feed,” by S. White,S. Qaiyumi, R. J. Johnson, and R. S. Schwalbe, presented at the Ninety-SeventhAmerican Society of Microbiology General Meeting, May 1997.
119 CDC investigators purchased chickens from twenty-six grocery stores: au-
122 America supported a livestock population of 7.5 billion chickens, 293 million
turkeys: Online fact sheet at the Animal Health Institute Web Site, www.ahi.org.
122 A pig, for example, received an average of ten different antibiotics: from a re-
port on the Soil Association on the British Broadcasting Corporation, October 8,1999.
123 Growth promoters, usually mixed in with food: “Hogging It,” a report by
the Union of Concerned Scientists, as recounted in the UCS magazine Nucleus,Spring 2001.
123 American farmers used seventeen different antibiotics on their livestock:
Center for Science in the Public Interest.
124 In September 1999, a three-year-old girl had died: “An Outbreak of Bacteria
Kills a Child,” New York Times, September 6, 1999, sec. B, p. 5.
9433 The Killers Within 8/6/02 11:18 AM Page 302 124 The following summer, another three-year-old girl died: Reuters Health,
124 North of the border in Walkerton, Ontario: Reuters, May 31, 2000.
124 the CDC estimated that 73,000 Americans incurred diarrhea each year: “The
Antimicrobial Resistance Patterns of Escherichia coli 0157:H7—NARMS, 1996–1999,”by K. Johnson et al., a report from the National Antimicrobial Resistance MonitoringSystem to the International Conference on Emerging Infectious Diseases, 2000.
125 it accounted for some 2.4 million infections each year: author interview with
125 About 100 Americans died each year from Campylobacter: author interview
125 Rare in the United States a generation ago, it still affected fewer: author in-
126 Together, Campylobacter and Salmonella accounted for 80 percent: Centers
129 Ashley Mulroy, of Wheeling, West Virginia, read a shocking story: “Teen-
ager’s Science Project Reveals Issues About the Water Some People Drink,” CBSEvening News, February 23, 2001.
This chapter is based chiefly on author interviews with Henrik C. Wegener, C.V.M., Ph.D., Christina Greko, C.V.M., Fred Angulo, C.V.M., Ph.D., and Kirk Smith,D.V.M., Ph.D. 143 retail prices for meat stayed about the same: “The Consequences of
Discontinued Use of Antimicrobial Growth Promoters (AGPs) for Food ProducingAnimals in Denmark,” by H. C. Wegener et al., International Conference onEmerging Infectious Diseases 2000, Abstract: Antimicrobial Resistance, 2.
143 “I’m sure VRE can transfer from animals to people”: author interview with
144 Sundlof had been advised by CVM’s chief counsel: author interview with
145 “New animal drugs,” he would explain: ibid.
147 In all, Smith and his team looked at 6,674 human cases: Quinolone Resistant
Campylobacter jejuni Infections in Minnesota, 1992–1998,” Kirk E. Smith et al.,New England Journal of Medicine 340 (May 20, 1999): 1525–32.
9433 The Killers Within 8/6/02 11:18 AM Page 303 149 In 1997, just one year after the introduction of fluoroquinolones: author in-
150 On June 18, 1998, Henrik Wegener and his colleagues: “An Outbreak of
Multidrug-Resistant, Quinolone-Resistant Salmonella Enterica Serotype TyphimuriumDT104,” by Kare Molbak et al., New England Journal of Medicine 341, no. 19(November 4, 1999): 1420–25.
152 a British researcher named John Threlfall: “Increasing Spectrum of
Resistance in Multiresistant Salmonella typhimurium,” by E. J. Threlfall et al., Lancet347 (1996): 1053–54. Also, author interview with John Threlfall.
152 By 1996, 16 percent of the DT104 in animals was quinolone resistant:
“Protecting the Crown Jewels of Medicine,” an overview published by the Centerfor Science in the Public Interest, Washington, D.C., 1998.
152 But the percentage of DT104 in people: author interview with Fred Angulo;
also, “Emergence of Multidrug-Resistant Salmonella enterica Serotype TyphimuriumDT104 Infections in the United States,” by M. Kathleen Glynn et al., New EnglandJournal of Medicine 338, no. 19 (May 7, 1998): 1333–38.
153 A first documented outbreak in the United States had arisen: Reported by G.
Hosek, et al., “Multidrug-Resistant Salmonella Serotype Typhimurium —UnitedStates,” 1996, MMWR 46, no. 14 (April 11, 1997): 308–10.
153 The next U.S. outbreak was both more widespread and more easily traced:
“Two Outbreaks of Multidrug-Resistant Salmonella Typhimurium DT104Infections Linked to Raw-Milk Cheese in Northern California,” by Sara H. Cody etal., Journal of the American Medical Association 281, no. 19 (May 19, 1999):1805–15.
154 For Cynthia Hawley, forty-five, a brutal acquaintance with DT104 began:
“Outbreak,” by Amanda Spake, U.S. News & World Report, November 24, 1997, 71.
155 By 1998, Fred Angulo and colleagues at the CDC had determined:
“Emerging Quinolone-Resistant Salmonella in the United States,” HallgeirHerikstag et al., Emerging Infectious Diseases 3, no. 3 (1997): 371–72.
156 In the Philippines: ibid.
156 “We have gotten away from talking about zero risk”: author interview with
157 In Oregon, a patient who appeared to have incurred this infection:
“Emergence of Fluoroquinolone-Resistant Salmonella Infections in the UnitedStates: Nosocomial Outbreaks Suggest a Changing Epidemiology,” by S. Olsen etal., National Antimicrobial Resistance Monitoring System, Presentations, 2000, theCenters for Disease Control.
9433 The Killers Within 8/6/02 11:18 AM Page 304 This chapter is based chiefly on author interviews with Mona Tice, Tim Naimi, M.D., M.P.H., and Patrick Schlievert, Ph.D. 162 Dr. Belani murmured that she would do her best: author interview with Dr.
169 a fourth child succumbed: “Four Pediatric Deaths from Community-
Acquired Methicillin-Resistant Staphylococcus aureus — Minnesota and NorthDakota, 1997–1999,” by C. Hunt et al., Morbidity and Mortality Weekly Review 48,no. 32 (August 20, 1999): 707–10.
169 A short walk from Naimi’s office: author interview with Patrick Schlievert.
See also “Exotoxins of Staphylococcus aureus,” by Martin M. Dinges, Paul M.
Orwin, and Patrick M. Schlievert, Clinical Microbiology Reviews 13, no. 1 ( January2000): 16–34.
170 But Schlievert’s bold explanation of toxic shock syndrome: A thorough ac-
count of Schlievert’s investigation of TSS is found in The Coming Plague, by LaurieGarrett (Penguin Books, 1994), 402–5.
1 0 : T H E O L D M A N ’ S F R I E N D This chapter is based chiefly on interviews with Susan Donelan, M.D., Peter Applebaum, M.D., Michael Jacobs, M.D., and Alexander Tomasz, Ph.D. 173 it accounted for the lion’s share of 500,000 cases: statement by Anthony S.
Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases,National Institutes of Health, before the Senate Committee on Health, Education,Labor, and Pensions Subcommittee on Public Health and Safety, February 25, 1999.
174 Globally, S. pneumo was estimated: ibid.
174 Indeed, 70 percent of all respiratory infections were viral: author interview
175 Among hospital patients who had contracted pneumonia: “Penicillin-
Resistant Pneumococci: New-Generation Fluoroquinolones and Lower RespiratoryTract Infections,” by Julio Ramirez, M.D., Hospital Medicine 35, no. 6 (1999):43–49.
175 Up to 61 percent of the children in some daycare centers: ibid.
177 One day in the spring of 1977, Peter Applebaum: author interview with
Applebaum. See also Applebaum’s “Streptococcus pneumoniae Resistant to Penicillin 9433 The Killers Within 8/6/02 11:18 AM Page 305 and Chloramphenicol,” Lancet, November 12, 1977, 995–97. Michael Jacobs’s ac-count of the South Africa outbreak is reported, with colleagues, as “Emergence ofMultiply Resistant Pneumococci,” New England Journal of Medicine 299, no. 14(October 5, 1978): 735–40.
180 He had come as a young man to America from Hungary in 1956: author in-
182 Soon de Lencastre realized there were two closely related clones: author in-
terview with Lencastre. Also, see “Carriage of Internationally Spread Clones ofStreptococcus pneumoniae with Unusual Drug Resistance Patterns in ChildrenAttending Day Care Centers in Lisbon, Portugal,” by Raquel Sa-Leao, AlexanderTomasz, Ilda Santo Sanches, Antonio Brito-Avo, Sigurdur E. Vilhelmsson, Karl G.
Kristinsson, and Herminia de Lencastre, Journal of Infectious Diseases 182 (October2000): 1153–60.
182 Iceland, where strict government health protocols: “Evidence for the
Introduction of a Multiresistant Clone of Serotype 6B Streptococcus pneumoniaefrom Spain to Iceland in the Late 1980s,” by Sonia Soares, Karl G. Kristinsson,James M. Musser, and Alexander Tomasz, Journal of Infectious Diseases 168 ( July1993): 158–63.
183 A national survey by the CDC from 1979 to 1986: discussed in
“Antimicrobial Resistance in Streptococcus pneumoniae: Implications for Treatmentin the New Century,” by Joseph P. Lynch III and Fernando J. Martinez, M.D.,C.M.E., the Medical Education Collaborative, Ortho-McNeil.
183 Then, in 1993, reports began to appear: “Drug-Resistant Streptococcus pneu-
moniae — Kentucky and Tennessee, 1993,” Morbidity and Mortality Report 43, no. 2( January 21, 1994): 23–25, 31. See also “Prevalence of Penicillin-ResistantStreptococcus pneumoniae — Connecticut, 1992–1993,” MMWR 43, no. 12 (April 1,1994): 216–17, 223.
183 The CDC would determine that by the late 1990s: “Increasing Prevalence of
Multidrug-Resistant Streptococcus pneumoniae in the United States,” by Cynthia G.
Whitney et al., New England Journal of Medicine 343, no. 26 (December 28, 2000):1917–24.
183 But Don Low, who had fought so hard: “Decreased Susceptibility of
Streptococcus pneumoniae to Fluoroquinolones in Canada,” by Danny K. Chen,Allison McGeer, Joyce C. de Azavedo, and Donald E. Low, New England Journal ofMedicine 341, no. 4 ( July 22, 1999): 233–39.
184 Clinical isolates of S. pneumo had been identified: “Mechanisms of Tolerance
to Vancomycin in Streptococcus pneumoniae,” by Robyn M. Atkinson et al.,Infectious Medicine 17, no. 12 (2000): 793–801.
9433 The Killers Within 8/6/02 11:18 AM Page 306 184 Bill Jarvis of the CDC assumed: author interview with Jarvis.
185 Perhaps, as Tomasz mused: author interview with Tomasz.
This chapter was drawn chiefly from author interviews with Don Low, M.D., Dennis Stevens, M.D., and Vince Fischetti, Ph.D. General facts on necrotizing fasciitis can befound through the National Necrotizing Fasciitis Foundation (dbatdorff@aol.com). 187 For Evangeline Ames Murray: author interview with Murray.
190 That, apparently, was the case with George Poste: author interview with Poste.
192 Dr. Dennis Stevens, an Idaho-based infectious diseases specialist: author in-
194 If Stevens and Schlievert’s paper: “Severe Group A Streptococcal Infections
Associated with a Toxic Shock-like Syndrome and Scarlet Fever Toxin A,” by D. L.
Stevens et al., New England Journal of Medicine 321, no. 1 ( July 6, 1989): 1–7.
194 Henson, fifty-three, was at the pinnacle of an extraordinary career:
Entertainment Weekly, May 16, 1997, 132.
195 On the coffee table of his hospital office: Two of Don Low’s seminal papers
on Group A strep infections are “Invasive Group A Streptococcal Infections inOntario, Canada,” by H. Dele Davies and others including Low, New EnglandJournal of Medicine 335 (August 22, 1996): 547–54; and “Clinical Experience with20 Cases of Group A Streptococcus Necrotizing Fasciitis and Myonecrosis: 1995 to1997,” by Catherine T. Haywood and others including Low, Plastic andReconstructive Surgery 103, no. 6 (May 1999).
195 One Monday in the fall of 1994, Bouchard was admitted: “The Fight of His
Life,” by Barry Came, Maclean’s 107 (December 12, 1994).
197 In Queens, New York, an eight-year-old boy died of it: New York Times,
197 In Chicago, a seventy-year-old: Chicago Sun Times, December 1, 1999, 72.
197 That same year, a sixty-one-year-old Cuban American man: Miami Herald,
197 In San Francisco, also in 1999: San Francisco Chronicle, June 18, 1999, sec. A,
197 “When a person is admitted”: author interview with Dr. Thomas Aragon.
9433 The Killers Within 8/6/02 11:18 AM Page 307 197 Richard Novick, one of the most distinguished researchers: author interview
198 Possibly as a harbinger of trouble to come: “Outbreak of Drug-Resistant
Strep Bacteria,” by Laurie Tarkan, New York Times, April 18, 2002, sec. A, p. 23;“Erythromycin-Resistant Group A Streptococci in Schoolchildren in Pittsburgh,”by Judith M. Martin, M.D. et al., New England Journal of Medicine 346, no. 16(April 18, 2002): 1200–06.
This chapter is based chiefly on author interviews with James Rahal, M.D., and his staff at New York Hospital Queens. 204 Unfortunately, he began seeing resistance to the drug: “Nosocomial
Outbreak of Klebsiella Infection Resistant to Late-Generation Cephalosporins,” byKenneth S. Meyer et al., Annals of Internal Medicine 119, no. 5 (September 1, 1993):353–57.
204 Within two years, Rahal had an epidemic of ceftazidime-resistant Klebsiella:
author interview with Rahal. Also, see “Identification of TEM-26 B-lactamaseResponsible for a Major Outbreak of Ceftazidime-Resistant Klebsiella pneumoniae,”by Carl Urban et al., Antimicrobial Agents and Chemotherapy 38, no. 2 (February1994): 392–95.
204 He’d just seen his first Klebsiella resistant to imipenem: “Clinical
Characteristics and Molecular Epidemiology Associated with Imipenem-ResistantKlebsiella pneumoniae,” by Muhammad Ahmad et al., Clinical Infectious Diseases 29(August 1999): 352–55.
205 The answer was to stop using ceftazidime and all other cephalosporins:
“Class Restriction of Cephalosporin Use to Control Total Cephalosporin Resistancein Nosocomial Klebsiella,” by James J. Rahal et al., Journal of the American MedicalAssociation 280, no. 14 (October 14, 1998): 1233–37.
206 a pharmaceutical nightmare called polymyxin: “Clinical and Molecular
Epidemiology of Acinetobacter Infections Sensitive Only to Polymyxin B andSulbactam,” by Eddie S. Go et al., Lancet 344 (November 12, 1994): 1329–32.
207 They found that 44 percent of the Klebsiella pneumo isolates: “Antimicrobial
Resistance in Enterobacteriaceae in Brooklyn, NY: Epidemiology and Relation toAntibiotic Usage Patterns,” by Guillermo Saurina et al., Journal of AntimicrobialChemotherapy 45 (2000): 895–98.
9433 The Killers Within 8/6/02 11:18 AM Page 308 207 Acinetobacter’s story was particularly chilling: “Endemic Carbapenem-
Resistant Acinetobacter Species in Brooklyn, New York: Citywide Prevalence,Interinstitutional Spread, and Relation to Antibiotic Usage,” by Vivek M. Manikalet al., Clinical Infectious Diseases 31 ( July 2000): 101–6.
207 In Zurich, Switzerland: Drs. R. Fleisch and Christian Ruef of University
Hospital of Zurich, reporting to the fortieth annual Interscience Conference onAntimicrobial Agents and Chemotherapy, hosted by the American Society ofMicrobiology, September 17–20, 2000, Metro Toronto Convention Centre, Ontario,Canada.
208 In the fall of 2001: author interview with Louis Rice, M.D. Also see
“Ceftazidime-Resistant Klebsiella pneumoniae Isolates Recovered at the ClevelandDepartment of Veterans Affairs Medical Center,” by Louise B. Rice, Elizabeth C.
Eckstein, Jerome DeVente, and David M. Shlaes, Clinical Infectious Diseases 23( July 23, 1996): 118–24.
208 At Brown University’s Miriam Hospital in Providence: author interview with
208 At the Lahey Clinic in Burlington, Massachusetts: author interview with
208 At the Baltimore VA medical center: author interview with Judith Johnson.
209 At nearby Kingsbrook Jewish Medical Center: author interview with Steven
E. Brooks, M.D. Also see “Are We Doing Enough to Contain AcinetobacterInfections?” by Steven E. Brooks, Ph.D., letter to the editor, Infection Control andHospital Epidemiology, May 2000, 304.
210 In a study published in the fall of 2001: “Widespread Distribution of Urinary
Tract Infections Caused by a Multidrug-Resistant Escherichia coli Clonal Group,”by Amee R. Manges, et al., New England Journal of Medicine 345, no. 14 (October4, 2001): 1007–13.
211 Here, in 1995, Marc Galimand: “Multidrug Resistance in Yersinia pestis
Mediated by a Transferable Plasmid,” by Marc Galimand et al., New EnglandJournal of Medicine 337, no. 10 (September 4, 1997): 677–80.
212 In the roughly 2,000 years since it had appeared as a human pathogen: A suc-
cinct history of plague appears in Laurie Garrett’s The Coming Plague (Penguin,1994), 237–39.
214 But according to Dr. Ken Alibek: See Biohazard: The Chilling True Story of the
Largest Covert Biological Weapons Program in the World—Told from Inside by theMan Who Ran It, by Ken Alibek with Stephen Handelman (Random House, 1999).
9433 The Killers Within 8/6/02 11:18 AM Page 309 215 In October 2001, for example: Jaime R. Torres, CNN Health, October 11,
215 Four years after their initial finding: “Transferable Plasmid-Mediated
Resistance to Streptomycin in Clinical Isolate of Yersinia pestis,” by Annie Guiyouleet al., Emerging Infectious Diseases 7, no. 1 (2001), 43–48.
1 3 : H O P E I N F R O G S A N D D R A G O N S The story of Magainin is based chiefly on author interviews with Michael Zasloff. Also helpful was Zasloff’s unpublished account of the magainin story, “TheCommercial Development of the Antimicrobial Peptide Pexigainin,” January 2000.
One of the best general-audience overviews of peptides is “Ancient System Gets NewRespect,” by Trisha Gura,
Science 291, no. 5511, 2068. The account of searching forpeptides in Komodo dragons is based chiefly on author interviews with TerryFredeking, Jon Arnett, and Don Gillespie. 218 So promising was Zasloff’s finding: “Magainins, a Class of Antimicrobial
Peptides from Xenopus Skin: Isolation, Characterization of Two Active Forms, andPartial cDNA Sequence of a Precursor,” by Michael Zasloff, Proceedings of theNational Academy of Science, USA 84 (August 1987): 5449–53.
218 “If only part of their laboratory promise is fulfilled”: Editorial, New York
219 In 1981, a Swedish researcher named Hans Boman: H. Steiner et al., Nature
292, pp. 246–48. See also Boman’s review “Antibacterial Peptides: Key ComponentsNeeded in Immunity,” Cell 65 (April 19, 1991): 205–7.
219 In the 1960s, a researcher at New York’s Rockefeller University: M. C.
Modrzakowski and J. K. Spitznagel, Infect. Immun. 25 (1979): 597–602.
220 A decade later, Robert Lehrer: author interview with Robert Lehrer.
223 Robert E. W. Hancock: For starters, see “Peptide Antibiotics,” a review by
Robert E. W. Hancock, Lancet 349, no. 9049 (February 8, 1997).
223 John Forrest, a professor at Yale: “Biotech Discovers the Shark,” by Judith
Masslo Anderson, MD, October 1993, 43–55.
224 Eventually, Zasloff found a way to purify shark squalamine: “Squalamine: An
Aminosterol Antibiotic from the Shark,” by Karen S. Moore et al., Proceedings of theNational Academy of Sciences USA 90 (February 1993): 1354–58.
226 The panel, composed of seven experts: Zasloff’s unpublished account, “The
Commercial Development of the Antimicrobial Peptide Pexigainin,” January 2000.
9433 The Killers Within 8/6/02 11:18 AM Page 310 The account of Felix d’Herelle’s life is drawn in part from William C. Summers’s scholarly biography, Felix d’Herelle and the Origins of Molecular Biology (YaleUniversity Press, 1999). Many details about George Eliava and the Eliava Institute aredrawn from interviews with the institute’s Nina Chanishvili. 234 On a frigid day in January 2001: author interview with Alfred Gertler.
237 Phages are viruses: Good factual descriptions of phages can be found in
“Phage Therapy: Past History and Future Prospects,” by Richard M. Carlton,Archivum Immunologiae et Therapiae Experimentalis 47 (1999): 267–74; “TheReturn of the Phage,” by Julie Wakefield, Smithsonian, October 2000, 43–46;“Return of a Killer,” by Brendan I. Koerner, U.S. News & World Report, Novem-ber 2, 1998; and “The Good Virus,” by Peter Radetsky, Discover, November 1996.
238 Born in 1873 in Montreal: This and subsequent details of d’Herelle’s early
life are in Summers’s Felix d’Herelle. 241 In a crisp, two-page paper that startled the scientific world: “Sur un microbe
invisible antagoniste des bacilles dysenteriques,” by Felix d’Herelle. Comptes rendusAcad. Sciences 1917: 373–75.
243 Eliava was as brash and dramatic a character: Many details of Eliava’s life and
career are drawn from author interviews with Nina Chanishvili of the Eliava Institute.
248 D’Herelle and his wife arrived by ship in October 1933: This and other de-
tails of d’Herelle’s time in Russia are drawn from Summers’s Felix d’Herelle, as wellas “Felix d’Herelle in Russia,” by D. P. Shrayer, Bulletin of the Institut Pasteur 94(1996): 91–96.
250 An article in the Journal of the American Medical Association: Journal of the
American Medical Association 100, no. 3 (1933): 110–13.
250 One product called Enterofagos: Dr. Paul Barrow in “The Virus That
251 Early preparations were often impure: “Phage Therapy,” by Richard
Carlton, Archivum Immunologiae et Therapiae Experimentalis 47 (1999): 267–74.
252 Crucial work was also done: “Results of Bacteriophage Treatment of
Suppurative Bacterial Infection in the Years 1981–1986,” by Stefan Slopek et al.,Archivum Immunologiae et Therapiae Experimentalis 35 (1987): 569–83. See also anappraisal of Slopek’s work in “Bacteriophages Show Promise As AntimicrobialAgents,” by J. Alisky et al., Journal of Infection 36 (1998): 5–15.
253 Beginning in 1982, British researchers: “Successful Treatment of Experimental
Escherichia coli Infections in Mice Using Phage: Its General Superiority over 9433 The Killers Within 8/6/02 11:18 AM Page 311 Antibiotics,” by H. Williams Smith and M. B. Huggins, Journal of GeneralMicrobiology 1238 (1982): 307–18. Also, “The Control of Experimental Escherichiacoli Diarrhoea in Calves by Means of Bacteriophages,” by H. Williams Smith, MichaelB. Huggins, and Kathleen M. Shaw, Journal of General Microbiology 133 (1987):1111–26.
253 To researchers who had worked with George Eliava: author interview with
254 Dr. Nina Chanishvili and her colleagues would hurry: Along with author in-
terviews with Dr. Chanishvili, some details about the institute’s recent history aredrawn from “A Stalinist Antibiotic Alternative,” by Lawrence Osborne, New YorkTimes Magazine, February 6, 2000, 50–55.
256 Carl Merril had learned of bacteriophages: author interview with Merril.
256 In 1945, Salvador Luria and Max Delbruck had studied: “1969: Max
Delbruck, Salvador Luria and Alfred Hershey,” a Nobel chronicle by Tonsei N.K.
Raju, Lancet 354, no. 9180 (August 28, 1999), 784.
259 With that, Carlton staked $50,000: author interview with Carlton.
259 Merril, Adhya, and Carlton published their findings on serial passage:
“Long-Circulating Bacteriophage As Antibacterial Agents,” by Carl R. Merril et al.,Proceedings of the National Academy of Sciences USA 93 (April 1996): 3188–92.
260 In a signed commentary: “Smaller Fleas: Ad Infinitum,” by Joshua Lederberg
260 “The Good Virus,” by medical writer Peter Radetsky: Discover, November
260 Two respected scientists: “Phage Therapy Revisited: The Population Biology
of a Bacterial Infection and Its Treatment with Bacteriophage and Antibiotics,” byBruce R. Levin and J. J. Bull, American Naturalist 147, no. 6 ( June 1996).
261 He had made millions by licensing: author interview with Caisey Harlingten.
262 Eventually the Georgians would use an intravenous phage: author interview
263 Honour explained that he’d just spent: author interview with Richard Honour.
265 “We gave the Americans access to all this background research”: Lawrence
Osborne, “A Stalinist Antibiotic Alternative,” New York Times Magazine, Febru-ary 6, 2000, 50.
266 Soon, however, this potential alliance fizzled: author interview with Sandro
9433 The Killers Within 8/6/02 11:18 AM Page 312 268 Honour got a desperate call: author interview with Richard Honour. Also,
“Defeat of a Superbug?” ABC News.com, September 16, 1999.
1 5 : P E E R I N G I N T O T H E A B Y S S 274 Historically, the Soviet Union had controlled TB with ruthless effectiveness:
Abigail Zuger, “Russia Has Few Weapons as Infectious Diseases Surge,” New YorkTimes, December 5, 2000, F1.
275 Each year, 300,000 new prisoners were incarcerated: Yevgenia Borisova,
“Crossing Borders” and “Kemerovo: One Region’s TB Profile,” Moscow Times,January 29, 2000. Also, New York Times, December 5, 2000.
275 Paul Farmer, a forty-one-year-old Harvard-trained doctor: author interviews
with Farmer. Also, see “The Good Doctor,” by Tracy Kidder, The New Yorker, July10, 2000, 40–58.
276 One day in the fall of 1998: John Donnelly and Dave Montgomery, “TB from
Ex-Soviet States Resists Most Drugs,” Arizona Republic, March 21, 1999, sec. A, p. 27.
277 one new study suggested it was actually lowering hospital costs: Reuters
277 In July 2001, an eighty-five-year-old man in London: “Linezolid Resistance
in a Clinical Isolate of S. aureus,” by S. Tsiodras et al., Lancet 358 (2001): 207–8.
277 In December 2001, researchers at Minnesota’s Mayo Clinic reported: A pres-
entation by Immaculada Herrero and colleagues at the Forty-first InterscienceConference on Antimicrobial Agents and Chemotherapy, December 17, 2001.
278 “It’s the most cidal drug anyone’s every seen”: author interview with Frank
278 Eli Lilly was out. . . . So were Roche and DuPont: author interviews with
278 That fall, a group of researchers from Tufts concluded: New York Times,
281 “The world of Synercid”: author interview with François Bompart.
281 The other boost to the field: New York Times, July 25, 2001, sec. C, p. 17.
282 In February 1997: author interviews with William Jarvis and Steve Quirk.
Also see “Control of Vancomycin-Resistant Enterococcus in Health Care Facilitiesin a Region,” by Belinda E. Ostrowsky et al., New England Journal of Medicine 344,no. 19 (May 10, 2001): 1427–33.
9433 The Killers Within 8/6/02 11:18 AM Page 313 283 “Hey, what if John Paul Jones”: author interview with Barry Farr.
284 The oft-cited case was Communist Hungary: author interview with Marc
284 Immunologist Marc Lappe agreed: author interview with Lappe.
284 But Bruce Levin, a prominent population biologist: author interview with
285 In October 2001, Fred Angulo and Henrik Wegener both contributed: New
England Journal of Medicine 345, no. 16 (October 18, 2001).
285 Angulo and colleagues tested chicken carcasses: “Quinupristin-Dalfopristin-
Resistant Enterococcus faecium on Chicken and in Human Stool Specimens,” byL. C. McDonald, et al., New England Journal of Medicine 345, no. 16 (October 18,2001): 1155–60.
285 Wegener and other researchers: “Transient Intestinal Carriage After
Ingestion of Antibiotic-Resistant Enterococcus faecium from Chicken and Pork,” byT. L. Sorenson et al., New England Journal of Medicine 345, no. 16 (October 18,2001): 1161–66.
285 Very possibly, the growing public clamor: New York Times, February 10,
286 with profits of about $1.6 billion: New York Times, November 13, 2001, sec.
286 Richard Levins, a population biologist at Harvard: author interview with
9433 The Killers Within 8/6/02 11:18 AM Page 315 a selected bibliography
Alcamo, Edward. Fundamentals of Microbiology. 4th Ed. New York: Benjamin/ Cummings Publishing, 1994. A marvelously readable college textbook.
Cannon, Geoffrey. Superbug. London: Virgin Publishing, 1995. A ruminative and compelling overview of antibiotic resistance.
de Kruif, Paul. Microbe Hunters. New York: Harcourt Brace/Harvest, 1954.
Originally published in 1926, this classic compendium of stories of microbehunters before the antibiotic era inspired countless teenagers to become scien-tists. Still great fun.
Fisher, Jeffrey A. The Plague Makers. New York: Simon & Schuster, 1994. A handy overview of the history of antibiotics — and of antibiotic resistance.
Garrett, Laurie. Betrayal of Trust. New York: Hyperion, 2000. Fascinating investi- gations of recent outbreaks of plague, Ebola, multidrug-resistant tuberculosis,and more.
———. The Coming Plague. New York: Penguin, 1994. A definitive, Pulitzer Prize–winning overview of global infectious disease threats, including drug-resistant bacteria.
Lappe, Marc. When Antibiotics Fail. Berkeley, Calif.: North Atlantic Books, 1995. A prescient and passionate work first published in 1986.
Levy, Stuart. The Antibiotic Paradox. New York: Plenum Press, 1992. Though now a decade old, Levy’s elegantly succinct work remains the seminal study of antibi-otic resistance. It explains the science of the subject in considerable detail, yet re-mains a book for the layperson, readable and compelling. Available throughLevy’s Alliance for the Prudent Use of Antibiotics (see Web Sites on page 317).
Miller, Judith, Stephen Engelberg, and William Broad. Germs. New York: Simon & Schuster, 2001. A fascinating history of germ warfare in the United States andthe U.S.S.R. that discusses the engineering of drug-resistant plague.
9433 The Killers Within 8/6/02 11:18 AM Page 316 S E L E C T E D
B I B L I O G R A P H Y
Osterholm, Michael. Living Terrors. New York: Delacorte Press, 2001. Another fascinating look at germ warfare from the well-known former Minnesota stateepidemiologist.
Schell, Orville. Modern Meat. New York: Random House, 1984. This ground-break- ing work was the first to report on the history and consequences of growth pro-moters in agriculture.
Summers, William C. Felix d’Herelle and the Origins of Molecular Biology. New Haven, Conn.: Yale University Press, 1999. A painstaking history of the greatphage pioneer and his work.
Wainwright, Milton. Miracle Cure. Oxford: Basil Blackwell, 1990. An entertaining and cogent history of the development of penicillin and other essential antibiotics.
9433 The Killers Within 8/6/02 11:18 AM Page 317 web sites
Several Web sites now offer a wealth of information on antibiotic resistance, in- cluding recommendations for doctors and patients. The first two listings are perhapsthe most comprehensive; the others follow in no particular order.
www.keepantibioticsworking.com —Several consumer groups, among them Environmental Defense, the Union of Concerned Scientists, and the Sierra Club,have banded together to make this a one-stop-shopping site for all the latest newsand links on antibiotic resistance. An amazing resource that covers all aspects of thesubject but focuses on agricultural antibiotic use.
www.apua.com —This is the site for Stuart Levy’s Alliance for the Prudent Use of Antibiotics, also a cornucopia of news, recommendations, and links.
in.fullcoverage.yahoo.com/fc/India/Antibiotics_and_Microbiology/— the Yahoo site for antibiotics and microbiology. Loads of good stuff.
www.evergreen.edu/phage — the best Web site devoted to bacteriophages, estab- lished and maintained by Betty Kutter of Evergreen State College.
www.intralytix.com — the Web site for Glenn Morris’s phage start-up, with good www.expobio.com—the site for Exponential Biotherapies, another phage start-up.
www.phagetx.com—the site for Phage Therapeutics, the third U.S. phage start-up.
www.cdc.gov —This is the opening page of the Centers for Disease Control’s Web site, which affords access to a number of other important sites, including the CDC’sregular publications, like the Morbidity and Mortality Weekly Report, as well asEmerging Infectious Diseases. The site has a section on drug-resistant bacteria.
www.public.iastate.edu/~fuchs/abr/antib.html — a fascinating and quirky com- pendium of articles on antibiotic resistance.
www.virology.net/garryfavwebjournals.html — an amazing (and exhaustive) list of scores of microbiology journals, with links to all.
www.scirus.com/?h — an overall medical information Web site, with lots of links

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Rayons X et gamma et rayonnements particulaires 2010-11 Question 9 Rayons X et gamma et rayonnements particulaires Cochez la (ou les) proposition(s) vraie(s) A- Les protons et les neutrons sont les particules fondamentales constituant le noyau atomique. B- Deux isotopes d’un élément se différencient par leur nombre de neutrons. C- Cobalt-60 (Z = 27) et le nickel-60

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