Antimicrobials have transformed our ability to treat many infectious diseases that were fatal only a few decades ago. The increasing use of antibiotics in humans, animals, and agriculture has resulted in many germs developing resistance to these powerful drugs. All major groups of pathogens [viruses, fungi, parasites and bacteria] can become resistant to antimicrobials.
Many diseases are increasingly difficult to treat because of the emergence of drug-resistant organisms including HIV and other viruses. Bacteria such as staphylococci, enterococci, and E. coli, respiratory infections, such as tuberculosis and influenza, food-borne pathogens such as Salmonella and Campylobacter, sexually transmitted organisms such as Neisseria Gonorrhoeae; Candida and other fungal infections and parasites such as Plasmodium falciparum, the cause of malaria.
Antimicrobial-resistant infectious germs [those that are not killed or inhibited by these medications] are an increasingly important public health concern. Tuberculosis, gonorrhea, malaria and childhood ear infections are just a few of the diseases that have become more difficult to treat due to the emergence of drug-resistant pathogens. Antimicrobial resistance is becoming a factor in virtually all hospital acquired infections.
In addition to its adverse effect on public health, antimicrobial resistance contributes to higher health care costs. Treating resistant infections often requires the use of more expensive or more toxic drugs and can result in longer hospital stays for infected patients.
A key factor in the development of antimicrobial resistance is the ability of infectious organisms to adapt quickly to new environmental conditions. Microbes generally are unicellular creatures that, compared with multicellular organisms, have a small number of genes. Even a single random gene mutation can have a large impact on their disease causing properties; and since most microbes replicate very rapidly, they can evolve rapidly.
Thus, a mutation that helps a microbe survive in the presence of an antibiotic will quickly become predominant throughout the microbial population.
Microbes also commonly acquire genes, including those encoding for resistance by direct transfer from members of their own species or from unrelated microbes.
The innate adaptability of microbes is complemented by the widespread and sometimes inappropriate use of antimicrobials. Ideal conditions for the emergence of drug resistant microbes result when drugs are prescribed for the common cold and other conditions for which they are not indicated or when individuals do not complete their prescribed treatment regimen.
Hospitals also provide a fertile environment for drug resistant pathogens. Close contact among sick patients and extensive use of antimicrobials force pathogens to develop resistance.
Antimicrobial resistance has been recognized since the introduction of penicillin nearly fifty years ago when resistant infections caused by Staphylococcus Aureus rapidly appeared. Today, hospitals worldwide are facing unprecedented problems from the rapid emergence and dissemination of other microbes resistant to one or more antimicrobial agents.
Strains of Staphylococcus Aureus resistant to methicillin and other antibiotics are endemic in some hospitals. Infections with methicillin resistant S. Aureus strains may also be increasing in non-hospital settings. A limited number of drugs remain effective against these infections.
S. Aureus strains with reduced susceptibility to vancomycin have emerged recently in Japan and the US. The emergence of these resistant strains is becoming a very serious problem.
Increasing reliance on vancomycin has led to the emergence of resistant enterococci, a bacterium that infects wounds, the urinary tract and other sites. Until a few years ago, such resistance had not been reported in U.S. hospitals.
Streptococcus pneumoniae causes thousands of cases of meningitis and pneumonia in the US and seven million cases of ear infections each year. Currently, about thirty percent of S. pneumoniae strains are resistant to penicillin, the primary drug used to treat this infection. Many penicillin resistant strains are also resistant to other antimicrobial drugs.
In sexually transmitted disease clinics that monitor outbreaks of drug resistant infections, doctors have found that more than a third of gonorrhea strains are resistant to penicillin or tetracycline, or both.
An estimated three to five hundred million people worldwide are infected with parasites that cause malaria. Resistance to chloroquine, once widely used and highly effective for preventing and treating malaria, has emerged in most parts of the world.
Resistance to other antimalaria drugs also is widespread and growing. Strains of multidrug resistant tuberculosis have emerged over the last decade and pose a particular threat to people infected with HIV. Drug resistant strains are as contagious as those that are susceptible to drugs. Resistant tuberculosis is more difficult and vastly more expensive to treat, and patients may remain infectious longer due to inadequate treatment.
Diarrheal diseases cause almost three million deaths a year, mostly in developing countries, where resistant strains of highly pathogenic bacteria such as Shigella dysenteriae, Campylobacter, Vibrio Cholerae, Escherichia coli and Salmonella are emerging. Recent outbreaks of Salmonella food poisoning have occurred in the US; a potentially dangerous strain known as Salmonella Typhimurium, resistant to ampicillin, sulfa, streptomycin, tetracycline and chloramphenicol, has caused illness in Europe, Canada and the US.
Fungal pathogens account for a growing proportion of hospital infections. Diseases such as candidiasis and Pneumocystis Carinii pneumonia are common among AIDS patients, and isolated outbreaks of other fungal diseases in people with normal immune systems have occurred recently in the US. Scientists and clinicians are concerned that the increasing use of antifungal drugs will lead to drug resistant fungi; in fact, recent studies have documented resistance of Candida species to fluconazole, a drug used widely to treat patients with systemic fungal diseases.
At present, we have powerful new drugs and drug combinations against HIV. Although treatments that combine new protease inhibitor drugs with other anti-HIV medications often effectively suppress its production in infected individuals, results from recent clinical studies suggest that many treatment failures occur due to the development of resistance by the virus.
Scientists and health care professionals agree that decreasing the incidence of antimicrobial resistance will require improved systems for monitoring outbreaks of drug resistant infections and a more judicious use of antimicrobial drugs.
They also recognize the critical role that basic research plays in responding to this problem. For example, studies of microbial physiology help scientists understand the biological processes that pathogens use to resist drug treatment. This knowledge can lead to the development of new strategies to overcome or reverse these processes.
Investigations in molecular genetics and biochemistry identify critical pathways and functions in how microbes replicate. Rapid improvements in gene sequencing technology are making it faster and easier to pinpoint the actual molecules involved in these pathways, which in turn could serve as targets for new antimicrobial drugs.
Basic research has already yielded practical results. For example, studies of the molecular basis of drug resistance have led to the development of molecular tools to identify drug resistant parasites. Also, to the identification of the genetic basis of resistance and resulting biochemical alterations in several parasite species,
the identification of methods to reverse resistance and the synthesis of drugs that are effective against drug resistant strains of malaria.
Alice M. Crawford, MD
Health & Life® MedixNet®
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