The Coming Plague (75 page)
Authors: Laurie Garrett
Gonorrhea was also increasingly difficult to treat, having acquired widespread penicillin resistance during the 1970s and spectinomycin insensitivity by the mid-1980s.
46
The next drugs in line, then, were cefoxitin and tetracycline, and treatment was sufficiently complicated to require special guidelines from the CDC and WHO.
47
In addition to the penicillin-resistance plasmid
N
.
gonorrhoeae
strains had acquired during the late 1970s, gonorrhea also took on a plasmid around 1985 that gave it the ability to withstand tetracycline.
48
46
The next drugs in line, then, were cefoxitin and tetracycline, and treatment was sufficiently complicated to require special guidelines from the CDC and WHO.
47
In addition to the penicillin-resistance plasmid
N
.
gonorrhoeae
strains had acquired during the late 1970s, gonorrhea also took on a plasmid around 1985 that gave it the ability to withstand tetracycline.
48
So the New York Academy of Medicine in 1989 recommended that physicians inject the antibiotic ceftriaxone into their gonorrhea patients and give them oral doxycycline.
49
In addition to being considerably more expensive and available only in injectable form, ceftriaxone was a sulfur drug to which many people (up to 20 percent in the United States) were allergic.
49
In addition to being considerably more expensive and available only in injectable form, ceftriaxone was a sulfur drug to which many people (up to 20 percent in the United States) were allergic.
By 1990 physicians all over the world were using ciprofloxacin, ceftriaxone, or another member of the quinolone group of antibiotics to treat gonorrhea, finding the drugs highly effective. But in 1992, Australian physicians reported that the drugs were becoming less effective in treating patients who had recently traveled in Southeast Asia. By mutating changes in its cell wall, making itself less permeable to all the quinolone drugs,
N. gonorrhoeae
was, once again, outmaneuvering another line of human defense. A few resistant cases turned up in England as wellâagain, among recent travelers to Southeast Asia.
50
Presumably the widespread black-market availability of antibiotics in much of Southeast Asia contributed to selective emergence of quinolone-resistant gonorrhea.
N. gonorrhoeae
was, once again, outmaneuvering another line of human defense. A few resistant cases turned up in England as wellâagain, among recent travelers to Southeast Asia.
50
Presumably the widespread black-market availability of antibiotics in much of Southeast Asia contributed to selective emergence of quinolone-resistant gonorrhea.
The most dangerous emergences of resistance to antibiotics for people living in poor countries were those in bacteria that caused intestinal disease and diarrhea. In 1991, 80 percent of the people living in the world's poorest countries had no sanitary facilities for the disposal of human wastes. Even in the moderately developed countriesânations with middle-class populations
and some industrial capacityâabout half the people lacked sanitary toilet/sewage facilities.
51
Under such circumstances it was easy for a water- or food-borne microbe to enter the water supply, be ingested by a human, grow and thrive in the human's gastrointestinal tract, and then be expelled via human feces back into the community water supply.
and some industrial capacityâabout half the people lacked sanitary toilet/sewage facilities.
51
Under such circumstances it was easy for a water- or food-borne microbe to enter the water supply, be ingested by a human, grow and thrive in the human's gastrointestinal tract, and then be expelled via human feces back into the community water supply.
Not surprisingly, diarrheal diseases were a major cause of death among young children in poor countries. In 1991 the World Health Organization estimated that 3.2 million children annually died before reaching their fifth birthday, victims of diarrheal diseases.
Whether new antibiotic-resistant intestinal pathogens emerged first in the industrialized world or in poor countries made little difference on the net outcome: the microbes' greatest toll was taken among the world's poorest, weakest children. And as resistant strains pushed up the costs of treatment, forcing the use of more expensive antibiotics, doctors in poor countries had little choice but to ration the drugs, triaging access.
During the early 1960s,
Shigella dysenteriae
became the first diarrheal bacterium to emerge with resistance to penicillins. In the absence of antibiotic treatment
S. dysenteriae
killed up to 20 percent of the children in whom it caused disease, and fatality rates as high as 15 percent had been seen in adults. Even the less severe types of
Shigella (S. flexneri, S
.
sonnei,
and
S. boydii
) could be lethal diseases in up to 10 percent of those people who fell ill. And natural immunity to the organisms was weakânearly half the
Shigella
survivors suffered recurring disease.
Shigella dysenteriae
became the first diarrheal bacterium to emerge with resistance to penicillins. In the absence of antibiotic treatment
S. dysenteriae
killed up to 20 percent of the children in whom it caused disease, and fatality rates as high as 15 percent had been seen in adults. Even the less severe types of
Shigella (S. flexneri, S
.
sonnei,
and
S. boydii
) could be lethal diseases in up to 10 percent of those people who fell ill. And natural immunity to the organisms was weakânearly half the
Shigella
survivors suffered recurring disease.
In September 1983 a middle-aged Hopi woman living on her tribe's national lands in Arizona was hospitalized with
Shigella
dysentery. Doctors soon realized that she suffered from an altogether new mutant strain of the microbe that was resistant to ampicillin, carbenicillin, streptomycin, trimethoprim, sulfamethoxazole, sulfisoxazole, and tetracycline. It turned out the woman had a long history of urinary tract infections, for which she had taken trimethoprim and sulfamethoxazole off and on for at least three years.
Shigella
dysentery. Doctors soon realized that she suffered from an altogether new mutant strain of the microbe that was resistant to ampicillin, carbenicillin, streptomycin, trimethoprim, sulfamethoxazole, sulfisoxazole, and tetracycline. It turned out the woman had a long history of urinary tract infections, for which she had taken trimethoprim and sulfamethoxazole off and on for at least three years.
Her intestines had become a breeding colony for resistant bacteria. Subjected repeatedly to antibiotic assaults, the microbes shared resistance plasmids. Colonies of
Escherichia coli
were apparently already in possession of a plasmid bearing genes that conferred resistance to trimethoprim and sulfamethoxazole, and they shared that plasmid with
Shigella
in the Hopi woman's gastrointestinal tract.
52
Though health authorities did what they could to limit the spread of the super-bug, by 1987 up to 21 percent of all
Shigella
infections among the Hopi and nearby Navajo were caused by the mutant strain. Nationwide, 7 percent of all
Shigella
infections in 1986 involved the super-bug, and a third of all cases were also ampicillin-resistant.
Escherichia coli
were apparently already in possession of a plasmid bearing genes that conferred resistance to trimethoprim and sulfamethoxazole, and they shared that plasmid with
Shigella
in the Hopi woman's gastrointestinal tract.
52
Though health authorities did what they could to limit the spread of the super-bug, by 1987 up to 21 percent of all
Shigella
infections among the Hopi and nearby Navajo were caused by the mutant strain. Nationwide, 7 percent of all
Shigella
infections in 1986 involved the super-bug, and a third of all cases were also ampicillin-resistant.
In Ontario, Canada, even higher levels of
Shigella
resistance were apparent by 1990: eight out of every ten human illnesses with the organism involved resistant strains. And
half
of all
Shigella
infections were caused by bacteria that were resistant to
four or more antibiotics.
53
Shigella
resistance were apparent by 1990: eight out of every ten human illnesses with the organism involved resistant strains. And
half
of all
Shigella
infections were caused by bacteria that were resistant to
four or more antibiotics.
53
Again, the most devastating impact of such multiply resistant
Shigella
was felt in the world's poorest nations. When a new multiply resistant strain reached the African country of Burundi, for example, the nation's Ministry of Health was unable to come up with enough foreign exchange to purchase alternative drugs from wealthy-nation pharmaceutical companies. So untold numbers of people died of dysentery.
54
Shigella
was felt in the world's poorest nations. When a new multiply resistant strain reached the African country of Burundi, for example, the nation's Ministry of Health was unable to come up with enough foreign exchange to purchase alternative drugs from wealthy-nation pharmaceutical companies. So untold numbers of people died of dysentery.
54
Similarly, between 1960 and 1993 several other enteric bacteriaâspecies that infected the human gastrointestinal tractâacquired profound genetic abilities to resist
Homo sapiens
weaponry. These included
E. coli, Klebsiella, Proteus, Salmonella, Serratia marcescens, Pseudomonas, Enterococcus faecium, Enterobacteriaceae
, and cholera. The situation by 1990 was quite grave, particularly in poor countries that lacked sufficient resources or capital to eliminate the unsanitary conditions responsible for the transmission of the microbes from humans to the water supply and from food to humans.
55
Homo sapiens
weaponry. These included
E. coli, Klebsiella, Proteus, Salmonella, Serratia marcescens, Pseudomonas, Enterococcus faecium, Enterobacteriaceae
, and cholera. The situation by 1990 was quite grave, particularly in poor countries that lacked sufficient resources or capital to eliminate the unsanitary conditions responsible for the transmission of the microbes from humans to the water supply and from food to humans.
55
Salmonella
, the leading cause of food poisoning, was appearing in the Caesar salads served up in restaurants on Manhattan's posh Upper East Side, or in taco stands along the border
caminos
of Juarez, Mexico.
56
By 1993 it was an essentially untreatable diarrheal disease, as no known antibiotic seemed capable of reducing the three to four days of agony a typical
Salmonella
infection produced in
Homo sapiens
.
57
Fortunately, the microbe rarely caused anything more dangerous in its human hosts than headaches, acute stomach pain, diarrhea, nausea, and dehydration.
, the leading cause of food poisoning, was appearing in the Caesar salads served up in restaurants on Manhattan's posh Upper East Side, or in taco stands along the border
caminos
of Juarez, Mexico.
56
By 1993 it was an essentially untreatable diarrheal disease, as no known antibiotic seemed capable of reducing the three to four days of agony a typical
Salmonella
infection produced in
Homo sapiens
.
57
Fortunately, the microbe rarely caused anything more dangerous in its human hosts than headaches, acute stomach pain, diarrhea, nausea, and dehydration.
One of the most disturbing prospects for physicians worldwide was the emergence around 1988 of vancomycin-resistant
Enterococcus faecium
and
faecalis
. With vancomycin the only remaining reliable treatment for staph and strep infections, there was great concern that resistant enterococcal bacteria could share their resistance genes with the other, otherwise untreatable microbes.
Enterococcus faecium
and
faecalis
. With vancomycin the only remaining reliable treatment for staph and strep infections, there was great concern that resistant enterococcal bacteria could share their resistance genes with the other, otherwise untreatable microbes.
“It hasn't happened yet, but everybody thinks it will,” CDC bacteriologist Bill Jarvis said.
Such a bacterial strain, if it did emerge, would be virtually incurable and extremely dangerous, for it would possess not only special drug-resistant genes but also those for heightened virulence.
Physicians and scientists working outside the field of bacteriology in the 1990s generally assumed that, as had been the case before, another class of antibiotics would be developed and the problem would go away.
But they were wrong.
“There's nothing on the shelf. Nothing in the pipeline. If we lose vancomycin we're going to be back to the 1930s with staph,” Jarvis said. The same could be true for
Streptococcus
.
Streptococcus
.
“That would be the real nightmare,” predicted the CDC's Bill Jarvis.
The nightmare began unfolding in 1988 with first reports of vancomycin-resistant
E. faecium
strains surfacing all over the world, usually appearing first inside hospitals.
58
E. faecium
strains surfacing all over the world, usually appearing first inside hospitals.
58
For example, a handful of hospitalized patients in New York City hospitals fell ill with vancomycin-resistant strains during 1988: their cases were isolated, and there was no evidence of bacterial spread to other patients or into the community. Between September 1989 and March 1991, however, vancomycin-resistant strains of enterococci emerged in twenty different New York City hospitals. A survey of the first hundred of those New York cases revealed that ninety-eight people became infected while in the hospital; two acquired their infections in the community.
Forty-two of the hundred patients died; incurable enterococci was the direct cause of death for nineteen of them, a contributor in the remaining terminal cases. Most of the dead were elderly individuals.
When laboratory molecular studies were done on bacterial samples from twenty-one of the patients, New York City Health Department researchers found that nineteen were resistant to
all
available drugs. And individuals who were infected with the super-resistant strains also progressed to full-blown blood disease (septicemia) more quickly.
59
all
available drugs. And individuals who were infected with the super-resistant strains also progressed to full-blown blood disease (septicemia) more quickly.
59
By 1994 all of the Greater New York City large hospitals had cases of vancomycin-resistant enterococci, and infection control had become a major crisis for facilities throughout eastern New Jersey, New York City, and neighboring suburban counties.
60
Similarly grim outbreaks of vancomycin-resistant super-bugs were seen in London,
61
Sheffield, England,
62
and Ancona, Italy.
63
60
Similarly grim outbreaks of vancomycin-resistant super-bugs were seen in London,
61
Sheffield, England,
62
and Ancona, Italy.
63
A CDC survey of key U.S. hospitals found that by 1994 some 7.9 percent of all reported
Enterococcus
infections involved vancomycin-resistant strains. On the nation's intensive-care units, where the risk of infection was highest, vancomycin-resistant strains accounted for just 0.4 percent of all enterococcal infections in 1989, and 13.6 percent by 1993. The highest incidence of the problem was in New York City hospitals, where 8.9 percent of
all
enterococcal infections were of vancomycin-resistant strains.
64
Enterococcus
infections involved vancomycin-resistant strains. On the nation's intensive-care units, where the risk of infection was highest, vancomycin-resistant strains accounted for just 0.4 percent of all enterococcal infections in 1989, and 13.6 percent by 1993. The highest incidence of the problem was in New York City hospitals, where 8.9 percent of
all
enterococcal infections were of vancomycin-resistant strains.
64
Inside American hospitals the emergence of super-enterococci was facilitated by practices that allowed the organism to instantly spread from one susceptible human to another: electronic thermometers,
65
catheters and surgical instruments,
66
intravenous lines, mechanical ventilation, and overuse of cephalosporin-type antibiotics.
67
The latter increased the risk of hospital-acquired enterococcal infection because the cephalosporin-type antibiotics had no effect on enterococcal bacteria but did devastate colonies of rival microbes, rendering the treated human especially vulnerable.
65
catheters and surgical instruments,
66
intravenous lines, mechanical ventilation, and overuse of cephalosporin-type antibiotics.
67
The latter increased the risk of hospital-acquired enterococcal infection because the cephalosporin-type antibiotics had no effect on enterococcal bacteria but did devastate colonies of rival microbes, rendering the treated human especially vulnerable.
By the end of 1993, with vancomycin-resistant enterococci reports coming in from all over the world, CDC and WHO scientists waited anxiously for the seemingly inevitableâexchange of the
vanA
or other resistance plasmids from the
E. faecalis or E. faecium to Staphylococcus
or
Streptococcus
. It had been done experimentally. European scientists had proven the microbial species capable of such a feat.
68
It only remained for nature to take its course.
69
vanA
or other resistance plasmids from the
E. faecalis or E. faecium to Staphylococcus
or
Streptococcus
. It had been done experimentally. European scientists had proven the microbial species capable of such a feat.
68
It only remained for nature to take its course.
69
The human gastrointestinal tract was an ideal ecology for such microbial events as plasmid exchanges because it was densely populated with dozens of species of both pathogenic and helpfulâcommensalâorganisms. More bacteria lived on a single square inch of the human intestine than there were humans on the entire planet. There were more microbes colonizing a given human's body than there were human tissue cells.
As anybody who had ever taken antibiotics knew, many microbial residents of the gastrointestinal tract performed beneficial functions. As they digested food for their own purposes, these bacteria assisted in the task of breaking down the fats, sugars, proteins, and unwanted chemicals that regularly flowed through the human body. In their absence, human digestion was a difficult, often painful process, as signaled by the constipation, cramps, and gas that often resulted from antibiotic treatment. Antibiotics disrupted the balance of both commensal and pathogenic microbes.
Not long after the advent of the antibiotic medical revolution, an equally radical change in veterinary and livestock practices took place. Expensive livestock lived longer when their ailments were treated with antibiotics. Prophylactic treatment seemed even wiser, as animal husbandry soon included routine antibiotic dosing of chickens, cattle, and dairy cows. The shelf life of meat, poultry, eggs, and dairy products was extended through antibiotic treatment of the animals.
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