Antibiotic Resistance: Germs Fighting Back

The development of antibiotics is, arguably, the greatest achievement of modern medicine. However, with time those antibiotics have started to become less effective through inappropriate and excessive usage. In this article I will discuss the origins of this problem, how bad the situation has become, and the strategies that we need to follow. But first, let’s take a brief look at how antibiotics developed, and their evolution during the early years.

A Brief History Of Antibiotics

Many people have come to believe that antibiotics were first discovered by Alexander Fleming, but that is not actually the case. In fact, a German physician named Paul Ehrlich developed an antibiotic called Salvarsan in 1909, for the treatment of syphilis.

It wasn’t until 1928 that Alexander Fleming MD “accidentally” discovered penicillin. Dr. Fleming was studying bacteria grown in petri dishes in his laboratory. The dishes became contaminated with mold, but he noticed that there was a halo around each spot of mold, a clear area in which bacteria wouldn’t grow. That mold he named penicillin. It was a history-changing, event. By the 1940s, penicillin was the drug of choice for Staphylococcus aureus, a type of bacteria that can cause food poisoning, pneumonia, bacteremia, and more.

Antibiotics were widely used in World War II and countless lives were saved from diseases and infections that might previously have been fatal. However, by the 1950s S. aureus had developed resistance to penicillin. This led to the development of methicillin, which replaced penicillin as the drug of choice for S. aureus. However, pathogens have since developed resistance to methicillin and other antibiotics.

The Scope Of Antibiotic Resistance

“We need to end our love affair with antibiotics.”
Kristi L. Koenig, MD, Director, Disaster Medical Sciences, University of California

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One of the most pressing problems faced in health care is the increasing prevalence of antibiotic (also called antimicrobial) resistance, exacerbated by a decreasing number of new antimicrobials available for the treatment of patients. This increasing resistance is a significant threat to public health. Antibiotics have been used so widely, and for so long, that the infectious organisms they were designed to kill have adapted to them. Some common infections are becoming increasingly difficult to treat, and may now take much longer to resolve. (1)

Antibiotic resistance is evolving among common community-acquired infections such as childhood ear infections and infections of the respiratory and urinary tracts. Healthcare-associated (nosocomial) infections have also been increasing over the last two decades. Significant factors in this change include:

  • An increase in immunocompromised and elderly patients
  • Increasing use of invasive in-dwelling devices such as catheters
  • More complex hospital environments
  • Failures of infection-control measures

Worryingly, antimicrobial resistance has emerged in virtually all healthcare-associated infectious pathogens. The most common nosocomial infections in the United States are Staphlococcus, Enterococcus, and Candida, but there are a number of others that are also becoming increasingly diffficult to treat. Diseases like tuberculosis, gonorrhea, and malaria, usually community-acquired, are becoming more difficult to treat due to the emergence of resistance. Many fungi, viruses, and parasites are also becoming resistant.

Some microorganisms may develop resistance to a single antimicrobial agent (or related class of agents), while others develop resistance to several antibiotic agents or classes. These organisms are referred to as multi-drug-resistant or MDR strains. In some cases, the microorganisms have become so resistant that no currently available antibiotics are effective against them. (2)

Approximately 1.7 million patients in the United States acquire an infection in the hospital each year; about 99,000 of those will die from that infection. Seventy percent of the bacteria causing nosocomial infections are resistant to at least one drug commonly used to treat such infections.

Strains of S. aureus resistant to methicillin, the “MRSA” that is often reported in the news, have become standard inhabitants of hospitals. In addition, they are increasingly prevalent in community settings such as locker rooms, college dormitories, and day care centers. Recently, even more concerning cases of S. aureus have been reported in the United States and other countries. In these cases, S. aureus developed resistance to vancomycin, a very powerful antibiotic that is usually reserved for the most intractable bacterial infections. (3)

Inappropriate Use Of Antibiotics

Appropriate prescribing of antibiotics may slow the rate at which resistance is developing. A study in Finland evaluated resistance of a strain of streptococci to erythromycin, one of the earliest antibiotics, widely used for respiratory infections. They established national guidelines for prescribing, to limit the use of erythromycin. After four years, the resistance of streptococci decreased from 16.5 to 8.6 percent. (4)

In the United States, the adverse effects of inappropriate and/or excessive use of antibiotics, especially resistance, is only increasing. A national, office-based study showed an increase of 48 percent in antibiotic prescribing for children between 1980 and 1992. (5) The use of antibiotics is especially high in the very young and the elderly. In one study, 37 and 70 percent of children, by three and six months of age respectively, had received at least one antibiotic prescription. (6)

A significant amount of the overuse of antibiotics appears to be for viral or bacterial infections which usually resolve spontaneously. The Center for Disease Control and Prevention (CDC) estimates that about 100 million prescriptions for antibiotics are prescribed by office-based physicians annually, and as many as half of those are unnecessary. Most antibiotic prescriptions in the ambulatory setting (i.e. not hospitalized) are for respiratory infections. Studies evaluating physicians’ prescribing patterns have found that almost half of office visits for colds and upper respiratory infections (URIs), and 80 percent of cases of acute bronchitis, were treated with antibiotics. That prescribing pattern persists despite the fact that antibacterial agents do not have effects on viral infections such as the common cold. Other studies have shown that antibacterial agents do not shorten the length of illness in cases of acute bronchitis. (7)

Despite acknowledging the association of antimicrobial use and bacterial resistance, physicians continue to prescribe antibiotics when nonessential. In one study, 97 percent of physicians surveyed agreed that overuse of antibiotics is a major factor contributing to antibiotic resistance. However, an evaluation of the practice patterns of the same physicians revealed continued prescribing of antimicrobials for viral illnesses. Other potential effects of indiscriminate antibiotic prescribing include allergic reactions, long-term damage to the immune system, development of gut dysbiosis or Candida overgrowth, adverse reactions and drug-drug interactions. (8)

Why Are Antibiotics Still Wrongly Prescribed?

Many patients want antibiotics, and physicians continue to prescribe them in situations where antibiotics should be withheld for a number of reasons. It should be remembered that the act of prescribing an antibiotic has social and medical implications. From the patient’s point of view, the prescribing of an antibiotic validates that the patient has an illness, that a diagnosis has been made, and that the illness is amenable to treatment. The fact that there is a “cure” for their problem reassures them that the illness is not serious. (9) However, prescribing antibiotics unnecessarily has other effects on society as a while, namely the fact that this practice leads to antibiotic resistance among dangerous pathogens.

Patients are accustomed to receiving antibiotics for benign respiratory infections and have come to believe, sometimes strongly, that antibiotics demonstrate efficacy and are necessary for treatment of these illnesses. In fact, patients are so convinced of the effectiveness of antibiotics that in one clinical trial of acute bronchitis, 60 percent of the patients screened for the study refused to participate because they did not wish to be randomized to the placebo arm of the trial. (10)

Patients frequently seek medical help to relieve the symptoms of common infections, and around one-half will have been urged to see a physician by family or friends. Many visits to a physician’s office are triggered by a persistent cough, and about two-thirds will complain of disturbed sleep. However, we know that antibiotics do not provide relief for a persistent cough or disturbed sleep.

Some clinical features of disease influence physicians’ treatment decisions. The presence of purulent nasal discharge is more likely to result in a physician prescribing an antibiotic for a patient with acute bronchitis. However the purulent nasal discharge does not adequately differentiate between a viral and a bacterial cause, and is not associated with a worse outcome.

The presence of a cough for more than three days will trigger some physicians to prescribe antibiotics. The natural history of acute bronchitis is for a cough to last 2-3 weeks; it is not a sign of more-severe or persistent infection. With the exception of a patient with chronic obstructive pulmonary disease, fever and a smoking history are not indications to prescribe antibiotics for patients with acute bronchitis. Sometimes, physicians prescribe antibiotics with the intention of preventing a more severe infection, but studies on antibiotic use in upper respiratory infections (URIs) failed to note a decrease in the incidence or severity of the disease.

Nonclinical factors influence a physician’s choice about prescribing an antibiotic at least 50 percent of the time. In a managed-care environment, there is insufficient time for a physician to educate his or her patients about the ineffectiveness of antibiotics. In short, prescribing an antibiotic is an effective way to end an office visit. Although some physicians believe that prescribing an antibiotic will decrease return office visits, up to 25 percent of patients with URIs make a return visit within a month, regardless of the prescription of antibiotics. (7)

Although physicians often feel compelled to prescribe an antibiotic to satisfy patient demands, patient satisfaction surveys indicate that patients do not acknowledge such pressure on their physicians. One survey that indicated that while 65 percent of patients expected to receive an antibiotic for treatment of a URI, there was no correlation between patient satisfaction and receipt of an antibiotic prescription. Patient satisfaction correlated highest with the quality of the patient-physician interaction. Results from focus groups indicate that patients would be satisfied if an antibiotic is not prescribed, as long as the physician explained the reasoning behind that decision. (8)

A physician can usually distinguish between a viral and bacterial illness using just the patient history and physical examination. However, more important than determining the pathogen is knowing if an antibiotic will have a favorable effect on the duration of the disease. For example, erythromycin is often prescribed for acute bronchitis caused by mycoplasma pneumoniae, but research shows that it does not alter the natural course of the illness.

Other factors should also be considered when deciding whether to prescribe or withhold an antibiotic. These factors include side effects, potential allergic reactions, and drug-to-drug interactions. The least expensive drug, which has shown efficacy for that particular illness-causing microbe, should generally be prescribed.

There are alternatives too. Supplements like probiotics can improve immunity and bolster resistance against pathogenic infections. For fungal infections, prescription or natural antifungals are a good alternative.

Trends In Antimicrobial Resistance

Here are some recent trends that have been noted in antimicrobial resistance:

  • Reports of MRSA in people with no link to the healthcare system are increasing, both in the United States and many parts of the world.
  • The agricultural use of antibiotics in food-producing animals contributes to the evolving and persistence of resistant bacteria. Resistant bacteria can be transmitted to humans through the foods eaten.
  • Antimicrobial resistance is emerging among fungi, particularly the fungi that cause infections in transplant patients with weakened immune systems.
  • Antimicrobial resistance is being found among the drugs used to treat human immunodeficiency virus (HIV) and influenza.
  • Antibiotic resistance is developing among the drugs used to treat malaria, in many parts of the world.
  • Antimicrobial resistance has developed to a variety of parasites that cause infection.

The Centers for Disease Control and Prevention (CDC) has a number of educational programs designed to prevent the development and transmission of infections, and promote the proper use of antibiotics. Everyone has a role in limiting the development and spread of antimicrobial-resistant pathogens.

“An untreated cold will last for a week, but a cold treated with an antibiotic will last only seven days.” – Anonymous

Further Reading

1) National Institutes of Health Fact Sheet, “Antibiotic Resistance”, http://www.niaid.nih.gov/topics/antimicrobialresistance/Pages/default.aspx.

2) Alliance for the Prudent Use of Antibiotics, “Science of Resistance: Ecology”, http://www.tufts.edu/med/apua/about_issue/ecology.shtml.

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References

1) Kristi L. Koenig, University of California, Antibiotics Are Rarely Indicated for Respiratory Tract Infections, http://www.jwatch.org/em200712140000001/2007/12/14/antibiotics-are-rarely-indicated-respiratory.

2) National Institutes of Health Fact Sheet, Antibiotic Resistance, http://www.niaid.nih.gov/topics/antimicrobialresistance/Pages/default.aspx.

3) Centers for Disease Control and Prevention, About Antimicrobial Resistance: A Brief Overview, http://www.cdc.gov/drugresistance.html.

4) Seppala, et al (1997), The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland, http://www.ncbi.nlm.nih.gov/pubmed/9250845.

5) McCaig, et al (1995), Trends in antimicrobial drug prescribing among office-based physicians in the United States, http://www.ncbi.nlm.nih.gov/pubmed/7807660.

6) Bergus, et al (1996). Antibiotic use during the first 200 days of life, http://www.ncbi.nlm.nih.gov/pubmed/8930223.

7) Fahey, et al (1998), Quantitative systematic review of randomized controlled trials comparing antibiotics and placebo for acute cough in adults, http://www.bmj.com/content/316/7135/906.

8) Watson, et al (1999), Antimicrobial use for pediatric upper respiratory infections: reported practice, actual practice, and patient beliefs, http://www.ncbi.nlm.nih.gov/pubmed/10585974.

9) Avorn, et al (2000), Cultural and economic factors that (mis)shape antibiotic use: the nonparmacologic basis of therapeutics, http://www.ncbi.nlm.nih.gov/pubmed/10896639.

10) Frank, et al (1984), The treatment of acute bronchitis with trimethoprim and sulfamethoxazole, http://www.ncbi.nlm.nih.gov/pubmed/0006611385.

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