The Post-Antibiotic Era: Emerging Deadly Superbugs
“With more than 40 diseases in existence today that were unknown a generation ago, and about 1,100 epidemic events verified by the WHO [World Health Organization] in the past five years, it’s nearly impossible to keep up on the emergence of infectious disease events as they break…”
—Larry Madoff, MD, International Society for Infectious Diseases
“Our communities aren’t safe from these kinds of organisms, which creep in and go from person to person. Many of these threats are more important, more real, and more possible than the threats of bioterrorism. We are trying to alert both the scientific and the lay community, and especially our own government, to this threat to the homeland.”
—Stuart B. Levy, MD, Director, Center for Adaptation Genetics and Drug Resistance Tufts University School of Medicine
“Over the decades the bacteria that antibiotics control have developed resistance to these drugs. Today, virtually all important, bacterial infections in the United States and throughout the world are becoming resistant.”
—Centers for Disease Control (CDC) [Emphasis ours]
“ The global increase in resistance to antimicrobial drugs, including the emergence of bacterial strains that are resistant to all available antibacterial agents, has created a public health problem of potentially crisis proportions.”
—American Medical Association (AMA) [Emphasis ours]
The discovery of antibiotics and their introduction into medical practice was hailed as one of the most important events in the struggle against human infectious diseases. The “Antibiotic Era” began in earnest in the early 1940s, Penicillin being the first antibiotic introduced into clinical practice. Discovery after discovery of effective anti-bacterial drugs then followed and optimism ran high in anticipation of the soon conquest of infectious disease. So high, in fact, that in 1969, William H. Stewart, then Surgeon General of the United States, testified in Congress that, “the time has come to close the book on infectious diseases”. Since that premature, overconfident assertion there has been a powerful resurgence of infectious diseases, the single most threatening component of which has been the appearance of disease-causing bacteria which have become resistant to antibiotics. Scientists began noticing that each time they developed a new class of antibiotics, it wasn’t long before pathogens developed resistance to them.
In 1964, physicians began using new drugs called Cephalosporins, which were effective against many infections, including pneumonia; but E. coli, Klebsiella pneumoniae, and a genus of bacteria called Enterobacter soon developed a way to fend them off. Out of pharmaceutical labs then came the Carbapenem and Fluoroquinolone drugs and, within a matter of just a few years, they began to lose their effectiveness against Acinetobacter species and other microbes (see “The Frightening Emergence of NDM-1, KPC”, below). The first penicillin-resistant Pneumococcus was discovered two years before the above-quoted “Mission Accomplished” statement by the U.S. Surgeon General. It was found in Papua, New Guinea.
By 1977, an epidemic disease caused by Pneumococcus was being reported by South African hospitals. The bug had not only become resistant to Penicillin but other antibiotics as well and an increase in its level of resistance by more than several thousandfold was reported. Since the early 1990s, this Multi Drug-Resistant (“MDR”) Pneumococcus has demonstrated its ability to spread from one country to another, reaching extremely high levels in some countries. Pneumococcus is the culprit behind outbreaks of pneumonia in various communities worldwide. This bacterium is a major threat to public safety because it can be life-threatening to certain ill or elderly patients (40,000‑50,000 Americans die from exposure to Pneumoccus each year; there’s no telling what will happen if MDR Pneumoccus should gain a foothold). It also causes life-threatening infections of the bloodstream, and meningitis. It is the major causative agent of middle ear infections in children. The bugs have spread through day care centers “like a chain letter,” says one reporter and, according to the highly-respected, infectious disease researcher Dr. Alexander Tomasz, young children under age two are at high risk of acquiring diseases caused by Pneumococcus. He reported that “several day-care centers in the U.S. were shown to have particularly high frequency of carriage of multi drug-resistant pneumococcal strains.” Pneumococcus is responsible for nearly half of the visits to pediatricians each year.
The development of MDR (again, “multi drug-resistant”) Staphylococcus aureus well illustrates the battle between the agile pathogens and drugs. S. aureus is a bacterium that lives harmlessly in the human body but can cause various kinds of infections. After the clinical application of Penicillin in the 1940s, S. aureus soon adapted to the treatment mechanism of penicillin, and by the 1950s, almost half of Staph strains had become resistant to Penicillin. A new antibiotic, Methicillin, was developed in the 1960s. Methicillin kills S. aureus by interfering with the bacterium’s ability to form a cell wall. But somewhere along the line, the staph germ picked up a gene called mecA, and mecA reduced Methicillin’s ability to interfere with the S. aureus cell wall by a thousandfold. Once the pathogen had mecA, it had become what is now known as MRSA (pronounced “Mersa”), or “Methicillin Resistant Staphylococcus aureus”. No one knows how S. aureus managed to develop this genetic augmentation. By the late 1970s MRSA became widespread. Today, MRSA has managed to transform itself into a major infectious agent that can only be effectively treated with Vancomycin, one of the few last killers of Superbugs. Unfortunately, in 1996, a Japanese hospital reported the first case of Vancomycin-resistant S. aureus (VRSA) during surgery on a four-month-old boy. The U.S., France and Hong Kong subsequently all reported VRSA incidents. A few years later in 2000, Linezolid was launched as a new antibiotic to combat both MRSA and VRSA. But only one year later, Boston researchers reported the first case of Linezolid-resistant MRSA in an 85-year-old man undergoing peritoneal dialysis. After failing to contain his MRSA by Linezolid, researchers tried five antibiotics (Ampicillin, Azithromycin, Gentamicin, Levofloxacin, and Quinupristin-Dalfopristin) but the unfortunate man eventually died from the uncontrollable infection.
As more and more physicians have prescribed more and more antibiotics, the number and variations of resistant pathogens have multiplied. Many bacteria have now clearly demonstrated their capacity to develop sophisticated mechanisms of resistance against almost every antibiotic invented thus far. They possess a remarkable ability to adapt to their environments and defend themselves against drugs by a variety of means. What’s worse, bacteria possess a deadly ability to swap DNA not only between “family members” but also between different “tribes”, as it were. For example, after Enterococci bacteria developed resistance to Vancomycin, British researchers in 1992 watched in the lab as the Enterococci bugs passed this resistance to S. aureus. At that point, these differing species of Enterococcus and Staphylococcus became “pathogenic allies” (see the post, “A Continuing Conversation”). Dr. Tomasz comments, “…these resistance mechanisms can find their way from one bacterium to another through a variety of efficient microbial gene transfer mechanisms.
Bacteria resistant to many of our drugs can also travel over large geographic distances and reach high incidence in certain parts of the world. A bacterial pathogen resistant to all chemotherapeutic agents is no longer science fiction.” We are now at a critical juncture where any number of deadly human pathogens have become resistant to multiple antibiotic agents. Medical science is, at present, able to do nothing more than the equivalent of scrambling around trying to plug holes in a dike which is now showing signs of some very significant stress fractures all over the world. What’s more, because of the extremely long time which elapses between the discovery of a new, more powerful antibiotic substance (assuming any have been recently discovered) and its development, testing and subsequent delivery to the marketplace, the prospects for an antibiotic solution to this coming microbial nightmare are grim indeed. It is therefore our considered opinion that we must look elsewhere for help and we’ll get to that a bit later in this blog. First, though, make sure you’ve looked over some of the dangerous Superbugs which are posing such a growing threat by clicking “A Rogues Gallery“…