Multidrug-Resistant Organisms Are A Major Focus For Microbiologists

Reemerging infections and drug-resistant microbes are topics that are capturing considerable attention among microbiologists these days. And evidence of their interest is by no means confined to such microbiology journals as the Journal of Virology or the Journal of Clinical Microbiology. Indeed, these topics dominated the entire August 21 issue of Science magazine last year. Writing in that issue, for example, was Harold Neu, a medical pharmacologist at Columbia University's College of Physicians and Surgeons. Neu tells The Scientist that physicians in the United States have a tendency to throw antibiotics at too many illnesses. "I think it's going to be almost impossible to totally end this," he says. "What will happen is we'll breed many antibiotic-resistant microorganims." And unless the pharmaceutical industry keeps ahead of this trend, he warns, "there will be a lot of problems for the future." In the Science article (257:1064, 1992), Neu pointed out that the worrisome situation is not confined to the U.S.: "The stunning success of the pharmaceutical industry in the United States, Japan, the United Kingdom, France, and Germany in creating new antibiotics over the past three decades has caused society to become complacent about the potential of bacterial resistance." Neu points to the 50 types of penicillins, 70 cephalosporins, 12 tetracyclines, and so on, that are currently available. But despite all these antibiotics, he says, "a person could die in a hospital in New York, San Francisco, Paris, Barcelona, Tokyo, or Singapore as a result of a resistant bacterial infection." Especially troubling to microbiologists at the Centers for Disease Control in Atlanta is reemergent tuberculosis. Until the early 1980s, this disease was in a rapid decline, but now it's bouncing back. Its incidence rose by 15 percent from 1985 to 1990, and now new, multidrug-resistant versions of this disease have arrived. To knock out TB requires the use of several drugs because there are strains that are resistant to at least one drug. What's happening now is the emergence of strains that are resistant to several of the leading drugs. "If you have an organism that's resistant, it means the patients are in effect getting mono therapy," says CDC microbiologist Robert Good. He points to a paper from a group of other CDC researchers (M.L. Pearson, et al., Annals of Internal Medicine, 117[3]:191, 1992) reporting an outbreak of multidrug-resistant TB at a New York City hospital that killed people with AIDS so fast that most cases were not even identified as TB before the victims died. The CDC researchers also found that, apparently as a result of this outbreak, up to 50 percent of the health-care workers at this hospital tested positive in a skin test for TB. "Our results show that health-care workers are also at risk for nosocomial [hospital] acquisition of tuberculosis," according to the paper's authors. "Although urban institutions providing care to large numbers of patients with HIV infection and tuberculosis are likely to bear the greatest burden of these epidemics, multi- drug-resistant tuberculosis is not likely to be confined to these institutions." Good says to fight the disease, "we're looking for new drugs, that's No. 1." And he cites important work going on into understanding the molecular biology of drug resistance, being conducted by Ying Zhang at Hammersmith Hospital in London, along with Stewart Cole at the Laboratorie de Gentique Moleculaire Bacterienne in Paris. These researchers have succeeded in cloning the katG catalase-peroxidase gene in Mycobacterium tuberculosis, which they believe may be the culprit in resistance to isoniazid, the core drug in the TB arsenal. The authors speak to the relevance of their work in a 1992 article in Nature (Y. Zhang, et al., 358:591, 1992): "An improved understanding of the mechanism of drug resistance will enable rapid tests for drug-resistant isolates to be developed and should facilitate the design of antituberculosis drugs." Highlights in Microbiology While the topics of reemerging infections and drug-resistant microbes seem to be capturing the microbiology spotlight, there are countless other significant developments in the field. To feature these new and exciting research findings, the American Society for Microbiology recently began publishing a section entitled "Journal Highlights" in its monthly publication, ASM News. The purpose of the section is to "alert readers to interesting developments reported in ASM journals that they otherwise might not see." What follows is a selection of some of the recently highlighted papers. J.L. Gallarda, et al., "Early detection of antibody to human immunodeficiency virus type 1 by using an antigen conjugate immunoassay correlates with the presence of immunoglobulin M antibody," Journal of Clinical Microbiology, 30:2379-84, 1992. The new test reduces the likelihood of sending someone home during the acute infection phase without a clue that he or she is harboring the virus, which may not be discovered for years, according to the report. S.R. Gogu, et al., "Amelioration of zidovudine-induced fetal toxicity in pregnant mice," Antimicrobial Agents and Chemotherapy, 36:2370-4, 1992. The adverse effects of AZT can be demonstrated and reversed in mice with the simultaneous administration of vitamin E, erythropoietin, or interleukin-3. P.B. Eisenhauser, et al., "Cryptidins: antimicrobial defensins of the murine small intestine," Infection and Immunology, 60: 3556-65, 1992. The small intestine, although warm, moist, and nutrient-rich, has an unexpectedly small population of bacteria. The researchers point to endogenous antimicrobial peptides and proteins secreted by intestinal epithelial cells as the explanation. J.N. Engel, "Azithromycin-induced block of elementary body formation in Chlamydia trachomatis," Antimicrob. Agents Chemother., 36:2304-9, 1992. Azithromycin rapidly blocks chlamydial growth in the life cycle and prevents vacuole formation. G.P. Leonardi, et al., "Evaluation of three immunoassays for detection of Chlamydia trachomatis in urine specimens from asymptomatic males," Journal of Clinical Microbiology, 30:2793- 96, 1992. Contrary to previous reports, chlamydia can be detected in urine of asymptomatic men through the use of available immunoassays, according to these authors. L.C. Madoff, et al., "Protection of neonatal mice from group B streptococcal infection by maternal immunization with beta C protein," Infect. Immun., 60:4989-94, 1992. "Transplacental antibodies conferred protection from group B streptococcal infection in newborn mice whose mothers had been immunized with a beta C protein vaccine. . . . Comparable results in humans would eradicate one of the leading causes of neonatal sepsis and mortality in the United States," ASM News says of the research. J.L. Whitton, et al., "A string-of-beads vaccine, comprising linked minigenes, confers protection from lethal-dose virus challenge," Journal of Virology, 67:348-52, 1993. "Foreign-DNA space limitations on the use of attenuated live virus as a vaccine vector may be overcome by the minigene strategy, whereby several eptitopes inducing antiviral cytotoxic T lymphocytes (CTLs) can be expressed in a recombinant vaccine," says ASM. The researchers used small segments of genetic material strung together to evoke a response from the major histocompatibility complex. M.-L. Johansson, et al., "Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora," Applied and Environmental Microbiology, 59:15- 20, 1993. "In healthy volunteers, 10 days' worth of fermented oatmeal soup enhanced by 19 strains of Lactobacillus produced a jejunal bacterial mix that would be desirable in patients at risk of complications arising from antibiotic suppression of normal intestinal flora," ASM says of the work. --S.V.

Multidrug-Resistant Organisms Are A Major Focus For Microbiologists

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