The Coming Plague

by Laurie Garrett

  In Denmark, where national medical registries are excellent because all the nation’s citizens receive their health care from the federal government, a review of the country’s meningitis cases from 1986 to 1989 revealed that 104 people had suffered the severe ailment as a result of staphylococcal infection. Sixty-one of the cases were acquired in the hospital following surgery. Fortunately, none of the Danish cases was MRSA, but all involved some degree of penicillin resistance. See A. G. Jensen, F. Esperson, P. Skinhøj, et al., “Staphylococcus aureus Meningitis,” Archives of Internal Medicine 153 (1993): 1902–8.

  9 Bacterial subtypes 29/52/80/95 in Detroit; 29/77/83A/85 in Boston. See L. R. Crane, D. P. Levine, M. J. Zervos, and G. Cummings, “Bacteremia in Narcotic Addicts at the Detroit Medical Center: I. Microbiology, Epidemiology, Risk Factors, and Empiric Therapy,” Review of Infectious Diseases 8 (1986): 364–73; and D. E. Craven, A. I. Rixinger, T. A. Goularte, and W. R. McCabe, “Methicillin-Resistant Staphylococcus aureus Bacteremia Linked to Intravenous Drug Abusers Using a ‘Shooting Gallery,’” American Journal of Medicine 80 (1986): 770–76.

  10 Udo and Grubb (1990), op. cit.

  11 B. Kreiswirth, J. Kornblum, R. D. Arbeit, et al., “Evidence for a Clonal Origin of Methicillin Resistance in Staphylococcus aureus,” Science 259 (1993): 227–30.

  12 For an overview of the global penicillin resistance trends, for example, see C. C. Sanders and W. E. Sanders, Jr., “Beta-Lactam Resistance in Gram-Negative Bacteria: Global Trends and Clinical Impact,” Clinical Infectious Diseases 15 (1992): 824–39.

  13

  14 Cohen (1992), op. cit.

  15 C. E. Phelps, “Bug/Drug Resistance: Sometimes Less Is More,” Medical Care 27 (1989): 194–203.

  16 D. L. Stevens, M. H. Tanner, J. Winship, et al., “Severe Group A Streptococcal Infections Associated with a Toxic Shock-like Syndrome and Scarlet Fever Toxin,” New England Journal of Medicine 321 (1989): 1–7.

  17 K. Wright, “Bad News Bacteria,” Science 249 (1990): 22–24.

  18 H. C. Dillon, and C. W. Derrick, Jr., “Streptococcal Complications: The Outlook for Prevention,” Hospital Practice, September 1972: 93–101.

  19 S. P. Gotoff, “Emergence of Group B Streptococci as Major Perinatal Pathogens,” Hospital Practice, September 1977: 85–90.

  20 Neu (1992), op. cit.

  21 Centers for Disease Control, “Prevalence of Penicillin-Resistant Streptococcus pneumoniae—Connecticut, 1992–1993,” Morbidity and Mortality Weekly Report 43 (1994): 216–23.

  22 A survey of 748 cardiac patients treated in Johannesburg, South Africa—all of whom were poor blacks who had suffered childhood bouts of rheumatic fever—illustrated the severity of heart disease produced by the bacteria. Under the apartheid state, black South Africans lived in conditions of acute squalor and health care deprivation. As a result, during the 1980s rheumatic fever was about as common among black South Africans as it had been among white urban Americans in 1920. And like their 1920s counterparts in the United States, black South Africans who survived rheumatic fever during early childhood had a better than 50 percent chance of facing life-threatening heart disease before their twentieth birthday. The primary cause of their cardiac difficulties was mitral valve damage which required open-heart surgery. R. H. Marcus, P. Sareli, W. A. Pocock, and J. B. Barlow, “The Spectrum of Severe Rheumatic Mitral Valve Disease in a Developing Country,” Annals of Internal Medicine 120 (1994): 177–83.

  Dealing surgically with rheumatic fever heart damage has been likened to “attempting to mop up the water on the floor while leaving the faucet open,” particularly in the context of poor countries. WHO during the 1990s instituted a trial program of rheumatic fever prevention in sixteen developing countries that involved training local paramedics to recognize streptococcal throat infections in children and treat the kids prophylactically with benzathine penicillin to prevent recurrent infections. M. J. McLaren, M. Markowitz, and M. A. Gerber, “Rheumatic Heart Disease in Developing Countries: The Consequence of Inadequate Prevention,” Annals of Internal Medicine 120 (1994): 243–44.

  23 L. G. Veasy, S. E. Wiedneier, G. S. Orsmond, et al., “Resurgence of Acute Rheumatic Fever in the Intermountain Area of the United States,” New England Journal of Medicine 316 (1987): 421–27.

  24 See “Streptococcal Diseases,” in A. S. Benenson, ed., Control of Communicable Diseases in Man (Washington, D.C.: American Public Health Association, 1990), 411–18.

  25 L. A. Haglund, G. R. Istre, D. A. Pickett, et al., “Invasive Pneumococcal Disease in Central Oklahoma: Emergence of High-Level Penicillin Resistance and Multiple Antibiotic Resistance,” Journal of Infectious Diseases 168 (1993): 1532–35.

  26 F. Shan, S. Germer, and D. Hazell, “Aetiology of Pneumonia in Children in Goroka Hospital, Papua New Guinea,” Lancet II (1981): 537–41.

  27 World Health Organization, “Implementation of the Global Strategy for Health for All by the Year 2000, Second Evaluation; and Eighth Report on the World Health Situation,” report to the 45th World Health Assembly, Provisional Agenda Item 17, Geneva, 1992.

  28 J. S. Spika, M. H. Munshi, B. Wojtyniak, et al., “Acute Lower Respiratory Infections: A Major Cause of Death in Children in Bangladesh,” Annals of Tropical Pediatrics 9 (1989): 33–39; and B. J. Selwyn and BOSTID, “The Epidemiology of Acute Respiratory Tract Infection in Young Children: Comparison of Findings from Several Developing Countries,” Review of Infectious Diseases 12 (1990): S870–S888.

  29 World Health Organization, “Acute Respiratory Infections in Children: Case Management in Small Hospitals in Developing Countries,” Program for the Control of Acute Respiratory Infections, Geneva, 1990.

  30 Ibid.; and M. Harari, F. Shann, V. Spooner, et al., “Clinical Signs of Pneumonia in Children,” Lancet 338 (1991): 928–30.

  31 M. R. Pandey, N. M. P. Dawlaire, E. S. Starbuck, et al., “Reduction in Total Under-Five Mortality in Western Nepal Through Community-Based Antimicrobial Treatment of Pneumonia,” Lancet 338 (1991): 993–97.

  32 B. Sutrisna, R. R. Frerichs, and A. L. Reingold, “Randomised, Controlled Trial of Effectiveness of Ampicillin in Mild Acute Respiratory Infections in Indonesian Children,” Lancet 338 (1991): 471–74.

  33 Ibid.

  34 X. Carne, J. M. Arnau, and J. R. Laporte, “Erythromycin Resistance in Streptococci,” Lancet II (1989): 444–45; Centers for Disease Control, “Penicillin-Resistant Streptococcus pneumoniae—Minnesota,” Morbidity and Mortality Weekly Report 26 (1977): 345; Centers for Disease Control, “Drug-Resistant Streptococcus pneumoniae—Kentucky and Tennessee, 1993,” Morbidity and Mortality Weekly Report 43 (1994): 23–25; A. Marton, M. Gulyas, R. Munoz, and A. Tomasz, “Extremely High Incidence of Antibiotic Resistance in Clinical Isolates of Streptococcus pneumoniae in Hungary,” Journal of Infectious Diseases 163 (1991): 542–48; L. K. McDougal, R. Facklam, M. Reeves, et al., “Analysis of Multiply Antimicrobial-Resistant Isolates of Streptococcus pneumoniae from the United States,” Antimicrobial Agents and Chemotherapy 36 (1992): 2176–84; and J. Versalovic, V. Kapur, E. O. Mason, Jr., et al., “Penicillin-Resistant Streptococcus pneumoniae Strains Recovered in Houston: Identification and Molecular Characterization of Multiple Clones,” Journal of Infectious Diseases 167 (1993): 850–56.

  35 R. Munoz, A. Marton, and A. Tomasz, Thirtieth International Conference on Antimicrobial Agents and Chemotherapy, 1990, Abstract No. 173; and A. Tomasz, “Multiple-Antibiotic-Resistant Pathogenic Bacteria,” New England Journal of Medicine 330 (1994): 1247–51.

  36 Centers for Disease Control, “Multiple Antibiotic Resistance of Pneumococci—So
uth Africa,” Morbidity and Mortality Weekly Report 26 (1977): 285–86.

  37 H. J. Koornhof, M. Jacobs, M. Isaacson, et al., “Follow-up on Multiple Antibiotic-Resistant Pneumococci,” South African Morbidity and Mortality Weekly Report 21 (1978): 1–7.

  38 A. Tomasz, “Disease Causing Bacteria Resistant to Antibiotics,” Annual Meeting of the American Association for the Advancement of Science, San Francisco, February 19, 1994.

  39 Dillon and Derrick (1972), op. cit.

  40 J. Casal, A. Fenoll, M. D. Vicioso, and R. Munoz, “Increase in Resistance to Penicillin in Pneumococci in Spain,” Lancet I (1989): 735.

  41 G. M. Caputo, P. C. Appelbaum, and H. H. Liu, “Infections Due to Penicillin-Resistant Pneumococci,” Archives of Internal Medicine 153 (1993): 1301–10.

  42 A. Tomasz, “Multiple-Antibiotic-Resistant Pathogenic Bacteria,” New England Journal of Medicine 330 (1984): 1247–51; and B. E. Murray, “Can Antibiotic Resistance Be Controlled?” New England Journal of Medicine 330 (1994): 1229–30.

  43 J. M. H. Pearson, G. S. Haile, and R. J. W. Rees, “Primary Dapsone-resistant Leprosy,” Leprosy Review 48 (1977): 129–32.

  44 C. Jia-Kun, W. Si-Yu, H. Yu-Hong, et al., “Primary Dapsone Resistance in China,” Leprosy Review 60 (1989): 263–66.

  45 N. Honore and S. T. Cole, “Molecular Basis of Rifampin Resistance in Mycobacterium leprae,” Antimicrobial Agents and Chemotherapy 37 (1993): 414–18; and C. Fox, personal communication, 1993.

  46 J. W. Boslego, E. C. Tramont, E. T. Takafuji, et al., “Effect of Spectinomycin Use on the Prevalence of Resistant and of Penicillinase-Producing Neisseria gonorrhoeae,” New England Journal of Medicine 317 (1987): 272–77.

  47 Centers for Disease Control, “Antibiotic Resistant Strains of Neisseria gonorrhoeae: Policy Guidelines for Detection, Management and Control,” Morbidity and Mortality Weekly Report 36 (1987): Supplement 1S—18S.

  48 Centers for Disease Control, “Tetracycline-Resistant Neisseria gonorrhoeae—Georgia. Pennsylvania, New Hampshire,” Morbidity and Mortality Weekly Report 34 (1985): 563–65; Centers for Disease Control, “Plasmid-Mediated Tetracycline-Resistant Neisseria gonorrhoeae—Georgia, Massachusetts, Oregon,” Morbidity and Mortality Weekly Report 35 (1986): 304–6; and J. S. Knapp, J. M. Zenilman, J. W. Biddle, et al., “Frequency and Distribution in the United States of Strains of Neisseria gonorrhoeae with Plasmid-Mediated, High-Level Resistance to Tetracycline,” Journal of Infectious Diseases 155 (1987): 819–22.

  49 Committee on Public Health, “Statement on Treatment of Gonorrhea: Penicillin Is Passe,” Bulletin of the New York Academy of Medicine 65 (1989): 243–46.

  50 J. W. Tapsall, T. R. Shultz, and E. A. Phillips, “Characteristics of Neisseria gonorrhoeae Isolated in Australia Showing Decreased Sensitivity to Quinolone Antibiotics,” Pathology 24 (1992): 27–31.

  51 World Health Organization, “Implementation of the Global Strategy for Health” (1992), op. cit.

  52 Wright (1990), op. cit.

  53 N. Harnett, “High Level Resistance to Trimethoprim, Cotrimoxazole and Other Antimicrobial Agents Among Clinical Isolates of Shigella Species in Ontario, Canada—An Update,” Epidemiology of Infection 109 (1992): 463–72.

  54 A. A. Ries, Abstract, Thirty-first Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 29—October 2, 1991.

  55 One of the clearest examples of the dangers that resistant diarrhea-producing organisms pose to poor countries was Guatemala’s 1969 outbreak of antibiotic-resistant Shigella. The mutant bacteria were resistant to chloramphenicol, tetracycline, streptomycin, and sulfonamide, then the most commonly used anti-Shigella drugs. The epidemic that resulted from the emergence of the new bug sickened 112,000 Guatemalans and killed 12,500, most of them children.

  56 According to CDC statistics, acute Salmonella food poisoning episodes in the United States skyrocketed. For example, between 1950 and 1980 the number of reported cases jumped from fewer than 1,000 to over 36,000, and the agency felt that physicians reported only one out of every 100 cases. So by 1980 there were probably about 3.5 million Salmonella food poisoning incidents in the United States annually. A decade later the CDC would estimate that 5 million Americans came down with Salmonella food poisoning annually, and outbreaks that debilitated up to 200,000 at a time were reported throughout the late 1980s.

  57 C. Sanchez, E. García-Restoy, J. Garau, et al., “Ciprofloxacin and Trimethoprim-Sulfamethoxazole Versus Placebo in Acute Uncomplicated Salmonella Enteritis: A Double-Blind Trial,” Journal of Infectious Diseases 168 (1993): 1304–7.

  58 L. M. Bush, J. Calmon, C. L. Cherney, et al., “High-Level Penicillin Resistance Among Isolates of Enterococci,” Annals of Internal Medicine 110 (1990): 515–20; J. M. Boyce, S. M. Opal, G. Potter-Bynow, et al., “Emergence and Nosocomial Transmission of Ampicillin-Resistant Enterococci,” Antimicrobial Agents and Chemotherapy 36 (1992): 1032–39; and F. Caron, J. F. Lemeland, G. Humbert, et al., “Triple Combination Penicillin-Vancomycin-Gentamicin for Experimental Endocarditis Caused by a Highly Penicillin- and Glycopeptide-Resistant Isolate of Enterococcus faecium,” Journal of Infectious Diseases 168 (1993): 681–86.

  Even ampicillin and vancomycin couldn’t kill the bacteria. They were bacteriostatic, meaning they controlled the growth of enterococci colonies and prevented their spread throughout the human body. By 1975 no drug could actually kill the bacteria.

  59 T. R. Frieden, S. S. Munsiff, D. E. Low, et al., “Emergence of Vancomycin-Resistant Enterococci in New York City,” Lancet 342 (1993): 76–79; and R. V. Spera and B. F. Farber, “Multiply-Resistant Enterococcus faecium: The Nosocomial Pathogen of the 1990s,” Journal of the American Medical Association 268 (1992): 2563–64.

  60 B. E. Murray, “Can Antibiotic Resistance Be Controlled?” New England Journal of Medicine 330 (1994): 1229–30; L. Garrett, “Superbugs,” Newsday, May 8, 1994: Al, A46, and A47; L. Garrett, “The Ebbing Miracle,” Newsday, May 8, 1994: A5, A46; and L. Garrett, “Infection Fighters,” Newsday, May 10, 1994: B25, B28–B29.

  61 A. H. C. Uttley, N. Woodford, A. P. Johnson, et al., “Vancomycin-Resistant Enterococci,” Lancet 342 (1993): 615.

  62 M. H. Wilcox, R. C. Spencer, and G. R. Weeks, “Vancomycin-Resistant Enterococci,” Lancet 342 (1993): 615–16.

  63 E. Manso, G. DeSio, F. Biarasco, et al., “Vancomycin-Resistant Enterococci,” Lancet 342 (1993): 616–17.

  64 Centers for Disease Control, “Nosocomial Enterococci Resistant to Vancomycin in United States, 1989–1993,” Morbidity and Mortality Weekly Report 42 (1993): 597–98.

  65 L. L. Livornese, Jr., S. Dias, C. Samel, et al., “Hospital-Acquired Infection with Vancomycin-Resistant Enterococcus faecium Transmitted by Electronic Thermometers,” Annals of Internal Medicine 117 (1992): 112–16.

  66 A. H. C. Uttley and R. C. George, “Nosocomial Enterococcal Infection,” Current Opinions in Infectious Diseases 4 (1991): 525–29.

  67 R. Pallares, M. Pujol, C. Pena, et al., “Cephalosporins as Risk Factor for Nosocomial Enterococcus faecalis Bacteremia,” Archives of Internal Medicine 153 (1993): 1581–86.

  68 R. Leclerq, E. Derlot, M. Weber, et al., “Transferable Vancomycin and Teicoplanin Resistance in Enterococcus faecium,” Antimicrobial Agents and Chemotherapy 33 (1989): 10–15; and W. C. Noble, Z. Virani, and R. G. A. Cree, “Co-transfer of Vancomycin and Other Resistance Genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus,” FEMS Microbial Letter 93 (1992): 195–98.

  69 L. Garrett, “Superbugs” (1994), op. cit.; and L. Garrett,
“Infection Fighters” (1994), op. cit.

  70 S. B. Levy, G. B. Fitzgerald, and A. B. Macone, “Escherichia coli Transmission from Poultry to Human,” Nature 260 (1976): 40–42.

  71 A very thorough analysis of agricultural and livestock use of antibiotics and the emergence of dangerous bacteria can be found in Levy’s book: Levy (1992), op. cit. Levy has dedicated his professional life to the problem, and the reader would be hard pressed to find a more detailed accounting of the multitudinous ways in which overuse and misuse of antibiotics are dooming the drugs to failure and granting victory to the microbes.

  72 H. P. Endtz, R. P. Mouton, T. van der Reyden, et al., “Fluoroquinolone Resistance in Campylobactr spp. Isolated from Human Stools and Poultry Products,” Lancet 335 (1990): 787.