Antibiotics – Back to the Future
Antibiotics were the drugs -that were going to take the human race into the next millennium.
Now, more than 60 years after the discovery of penicillin, we find ourselves back to the future. It may as well be 1930 again, because many of the strains of bacteria we sought to eliminate, and indeed for a while seemed to have beaten, have re-emerged with a vengeance. Throughout the medical press you will find the concept of the “emergence” of new strains of superbugs. But emergence is really regression, a frustrating return to the standard which prevailed universally in the previous century (JAMA, 1996; 75(3): 243-6).
In theory antibiotics are a good thing—and in life-threatening situations they still are. When all goes well an antibiotic quells an infection by attacking and destroying the organism’s protective cell wall; by blocking its production of essential proteins; by interfering with chemical messages essential for reproduction; or by some other equally effective method or combination of methods.
But through a number of factors, largely involving misuse and overuse of antibiotics, some “bugs” have developed defence mechanisms to repel these attacks. They undergo genetic mutations which allow them to produce stronger cell walls, for example, or to change chemical messages.
Penicillin was already being associated with resistant organisms when it was introduced in the 1930s. Today, 25 per cent of patients are suffering from a drug-resistant strain of pneumonococcus. This figure shoots up to 40 per cent among white children under six (N Eng J Med, August 24,1995). This alarming rise came to light when re-searchers at the Centers for Disease Control and Prevention
in Atlanta examined 431 patients (adults and children). They found that 25 per cent were penicillin
resistant (7 per cent were highly resistant); 26 per cent were resistant to trimethoprirn/sulphamethoxazole (Septrin); 15 per cent were resistant to erythromycin; 9 per cent to cefotaxime and 25 per cent to multiple drugs. In the UK, the frequency of penicillin-resistant pneumonococci doubled between 1990 and 1995; the microbe’s resistance to erythromycin trebled in that same time (BMJ, 1996; 312: 1454-6). This is a picture which is repeated throughout the world.
In 1992 in the United States some 23 million people underwent surgery, and nearly every one of them received prophylactic antibiotics. Up to 920,000 of them developed post-surgical bacterial infections, the majority of which were due to staphylococcus, in particular methicillin-resistant staphylococcus aureus or MRSA (N Eng J Med, 1992; 326:337-9). MRSA was first reported in 1961 just after methicillin was introduced {BMJ, 1993; 307: 1049-54). Despite evidence, a curious mixture of complacency and arrogance allowed us to continue widespread use for another 30 years.
That same year 15 per cent of-all Staph strains in the US and nearly 40 per cent of those strains isolated from patients in American hospitals were MRSA (Infect Control & Hospital Epidemiol, 1992; 13: 582-6). Significant problems were occurring elsewhere. In New York a tuberculosis strain resistant to seven different types of antibiotic was discovered (J Clin Microbiol, 1994; 32: 1542-6). In England one man had an escherichia coli strain resistant to 20 different antibiotics (Lancet, 1993; 342:177). In one extreme case in Australia a staph virus contracted by one patient was immune to 31 different types of antibiotics (J Med Microbiol, 1990; 35: 72-9). By 1993 it was thought that nearly every common pathogenic bacterial species had developed some degree of clinically significant drug resistance. And over two dozen of these emergent strains could outwit most commonly available antibiotic treatment (Science, 1992; 257: 1066-7).
Super-resistant bugs are no respecters of class. You are just as likely to get a case of Salmonella from a Caesar salad in a high class restaurant as you are from a hot food cart in an underdeveloped country.
Since 1993 salmonella has been an essentially untreatable disease—there is now nothing which will relieve the three or four days of agony it brings (J Infect Dis, 1993; 168: 1304-7).
Resistant bacteria are not checked by national or natural barriers, and it’s likely that greater mobility is contributing as much to the spread of resistant microbes as are crowded, unhygenic hospital clinics and wards (JAMA, 1990; 263: 2569-70).
Today only one antibiotic, vancomycin, is thought to be effective against most MRSA. But even ^^^^ this drug is becoming increasingly ineffective, especially against the enterococci bacterium (JAMA, 1993; 270: 1796; Lancet, 1996; 347: 252). It has also been shown that transfer resistance (one organism passing its resistance on to another) can occur between enterococci and the staph virus (FEMS Microbial Health, 1992; 93:195-8; Antimicrobial Agents and Chemotherapy, 1989; 33: 10-15), and it is now believed that within a few years both staph and strep viruses will have acquired widespread vancomycin resistance. This process is thought to be helped along by the practice of giving poultry and livestock antibiotics in their feed (see box, pi). New antibiotics are costly and time consuming to produce—there have been no new antibiotics for more than a decade. It is unlikely that newer, stronger drugs such as Upjohn’s proposed oxazolidinone or the proposed new class of peptide antibiotics (Lancet, 1997; 349: 418-22) are the final answer to this dilemma.
In addition to creating more resistant bugs, antibiotics have also been implicated in a rising number of unrelated diseases and disease-like states. The most well known of these is fatigue, mild to moderate gastrointestinal upsets, candida overgrowth (which can lead to other problems) and antibiotic allergy. However these are just the tip of the iceberg.
Antibiotic use has been associated with severe skin rashes (Contact Derm, 1996; 35: 116-7), seizures (Lancet, 1991; 338: 259), psychosis (Am J Med, 1991; 90: 528-9) facial paralysis (BMJ, 1994; 309: 1411); metabolic abnormalities mimicking Bartter’s syndrome (Cancer, 1984; 54: 808-10; Am J Kidney Dis, 1986; 7: 245-9) and other renal abnormalities (Lancet, 1995; 345: 732-3; Nephrol Dialysis Transplant, 1994; 9(Suppl 4): 130-4; Am Fam Phys, 1996; 53(1): 227-32); severe diarrhea and pseudomembranous colitis (Gut, 1987; 28: 1467-73; J Infect Dis, 1985; 151: 476-81; Clin Ther, 1991; 13: 270-80; BMJ, 1985; 290: 1112). Only recently MRSA has been found in the stools of those with post-antibiotic entercolitis (Lancet, 1993; 342: 804).
Australian doctors report that flu-doxacillin, a semi-synthetic penicillin, can cause cholestatic jaundice (Med J Aust, 1989; 151:701-5), though it is thought that its relation to the drug may largely go unrecognized because of a delayed onset (Lancet, 1992; 339: 679). Older patients and those receiving flucioxacillin for more than two weeks are most at risk (BMJ, 1993; 306:233-5). These are not new findings. Liver damage associated with this antibiotic was first noticed in the Netherlands and reported in 1982 (NethJMed, 1982; 25:47-8) and has been reported again and again (Drug Safety, 1996:15(1): 79-85).
Newer combination antibiotics such as Septrin, a combination of trimethoprim and sulphamethoxazole, sometimes known as co-trimoxazole, have been linked with disfiguring skin rashes and blisters (Ind J Derm, 1982; 48: 207-8; Br J Dermatol, 1987; 116: 241-2; Dermatol, 1986; 172: 230-1), and a host of HIV-like symptoms including anemia, loss of appetite, nausea, vomiting, numbness, convulsions, chills, fever, swollen glands and ulcers in the mouth, eyes and urethra. Its use has also been associated with adverse effects on kidney function in renal transplant patients (Lancet, 1984; i: 394-5).
There has been a suggested link between antibiotic use, particularly the penicillins, and the development of diabetes (Lisa Landymore-Lim, Poisonous Prescriptions, 1992, PODD), epileptic seizures (J Neurosurg, 1993; 78(6): 938-43) and Crohn’s disease (Hepato-Gasteroenterol, 1994; 41(6): 549-51). Antibiotic eyedrops have been shown to cause aplastic anemia (Drug Safety, 1996; 14(5): 273-6; Br J Opthamol, 1996; 80(2): 182-4).
Children are on the receiving end of so many antibiotics these days. One of the most disturbing links are those between antibiotic use and possible brain damage. Recently a survey of youngsters between the age of 1 and 12 years by the Developmental Delay Registry has found that those who had taken more than 20 cycles of antibiotics in their lifetime were 50 per cent more likely to suffer developmental delays. Children who have had three rounds or fewer were half as likely to become developmentally delayed (Townsend Letter for Doctors, October 1995).
In the same vein, an American doctor has discovered a link between high functioning autism and at least three doses of broad spectrum antibiotics such as Augmentin and Ceclor. Normal development can be arrested overnight at between 18 to 30 months (Townsend Letter for Doctors, January 1995).
While the medical profession may remain sceptical about such a link, the experience of parents says otherwise. Sally Smith wrote to WDDTY to say that her son Luke fell ill with a respiratory infection when he was 17 months old and was prescribed amoxycillin. After taking the drug he “lost his vocabulary. In fact he did not speak again for almost eight years.” She now runs the Tomatis listening therapy centre specifically for children with developmental delays or similar problems and says in the last three years she has encountered at least 200 other children who have been similarly affected.
Another reader from Kilmarnock wrote that when her 4-year-old daughter was given antibiotics as a precaution, “Her fat metabolism went haywire. Her heart was affected. After six months she was skin and bones, and I feared the worse. Later her adult teeth were affected, as was her liver. I could go on at length.”
In one study from Iceland among children aged 7, researchers found a close link between the level of antibiotic prescribing and antibiotic-resistant pneumococci. Of 919 children recruited for the study, nearly 50 were carrying either penicillin-resistant or multi-resistant pneumonococci (BMJ, 1996; 313: 897-91). Pneumonococcus is the bug responsible for pneumonia, meningitis, sinusitis and otis media (middle ear infection).
Doctors first made the connection between antibiotic use and hearing loss in children in the 1980s. By 1990 about a third of all ear infections in young American children were due to pneu-monococcus, and nearly half those cases involved strains which were resistant to penicillins (Morbidity and Mortality Weekly Report, 1994; 43:216-23). Today it is thought that up to two-thirds of all cases are caused by the overuse of antibiotics such as streptomycin and gentamicin (BMJ, 1996; 313: 648). There has also been a marked increase in the incidence of hearing loss among children in the developing world, and it is thought that up to two-thirds of cases are caused by the indiscriminate use of antibiotics (BMJ, 1996; 313:648).
Unfortunately stopping the use of antibiotics is not necessarily the answer. Although it is commonly assumed that once “antibiotic pressure” is taken away, most organisms will lose their resistance, a research team from Emory University has shown otherwise. They tested this hypothesis on a strain of streptomycin-resistant E coli. After 135 generations the researchers found that offspring still had a high degree of streptomycin resistance (Nature, 1996; 381: 1204).
As a cause of death, infectious diseases are still outranked by heart disease and cancer, but the numbers are rising (JAMA, 1996; 275(3): 243-6). The big questions are no longer those pondered in movies such as Outbreak. If s not Ebola, Machupo or Lassa which are like-
ly to do us in. The bugs which will be our downfall are more likely to be less glamorous: pneumonococcus, tuberculosis, streptococcus and staphylococcus, escherichia coli, salmonella—all bugs which, 20 years ago, our microbiologists were confidently predicting would be eradicated by the end of the century.
Medical literature about antibiotics is infused with the language of war. We “fight”, “combat”, “vanquish” and “annihilate”. We are involved in a “chemical arms race”. We require “more effective strategies” and draw “battle lines” (and, almost inevitably, we “lose”).
There is no easy answer to the problems which antibiotic over-use throw at us. But, for those who wish to maintain the “miracle” for when it’s most needed the issue is very simple: the more you use it, the faster you will lose it.
Sidebar: Antibiotics in the environment
Genetically modified organisms, animals who either eat GM food or who are given growth hormones or antibiotics to treat the diseases inherent in high density food production, and human consumption of animals and/or foods made from products containing these organisms are contributing to our unknowing consumption of antibiotics. Transfer resistance, from animals to humans, is an ongoing problem (Lancet, 1994; 344: 323) and one which has been proven again and again to be a reality (Nature;1976; 260: 40-2; Lancet, 1993; 342: 1371-2; Scand J Infect Dis, 1988; 20: 573). It is also thought that what we call food allergies may, in some cases, be an allergy to the antibiotic residue in common foods (Vet Microbiol, 1993; 35: 213-26).
The medical press has been rife with arguments for banning antibiotics as growth promoting agents in animals (Lancet, 1996; 348: 619). Salmonella drug resistance can be passed on through poultry products (N Eng J Med, 1984; 311: 617-22). Avoparcin and vancomycin are both used throughout Europe to improve the digestibility of feeds for cows, pigs and poultry. In Germany, strains of vancomycin resistant enterococci have been found in minced meat from separate butchers as well as in human fecal samples (Lancet, 1996; 347: 1047).In the US milk is full of a growth hormone known as BST. American dairy products are shipped quite legally to Europe. While US farmers argue that BST is destroyed in the pasteurizing process, antibiotics and resistant strains of bacteria have been found in both hamburger and dairy products (N Eng J Med, 1987; 316: 565-70).
Sidebar: Antibiotic resistance
Streptococcus pneumoniae
Diseases caused
Meningitis, pneumonia
Antibiotics that don’t work
Aminoglycosides, cephalosporins, chloramphenicol, erythromycin, penicillins, tetracycline, trimethoprim/sulphamethoxazole
Staphylococcus aureus
Diseases caused
Blood poisoning, surgical infections, pneumonia
Antibiotics that don’t work
All but vancomycin
Enterococcus
Diseases caused
Blood poisoning, surgical infections
Antibiotics that don’t work
Aminoglycosides, cephalosporins, erythromycin, penicillins, tetracycline, vancomycin
Haemophilus influenzae
Diseases caused
Meningitis, ear infections, pneumonia, sinusitis
Antibiotics that don’t work
Chloramphenicol, penicillins, tetracycline, trimethoprim/sulphamethoxazole
Microbacterium tuberculosis
Diseases caused
Tuberculosis
Antibiotics that don’t work
Aminoglycosides, ethambutol, isoniazid, pyrazinamide, rifampin
Shigella dysenteriae
Diseases caused
Severe diarrhea
Antibiotics that don’t work
Ampicillin, chloramphenicol, tetracycline, trimethoprim/sulphamethoxazole
Plasmodium falciparum
Diseases caused
Malaria
Antibiotics that don’t work
Chloroquine
Neisseria gonorrhoea
Diseases caused
Gonorrhea
Antibiotics that don’t work
Penicillins, spectinomycin, tetracycline
Sidebar: Kicking the antibiotic habit
At the front line of this battle are ,GPs. Although most GPs are aware of the wider implications of over-prescribing, it is still very difficult to find ways of helping them break the antibiotic “habit” (GP, February 26,1993).
There is a disturbing trend towards blaming patients for antibiotic overuse. It’s the fault of the overanxious mother whose child has an ear infection or the businessman with the common cold who does not wish to take valuable days off work who are pressurizing overworked doctors into doing “something”.
There is no doubt that patients can work with doctors in a kind of unholy alliance, but pointing the finger of blame is a little too simplistic and ignores the fact that as much as two thirds of antibiotic prescribing is “entirely irrational” (see Harris Coulter, The Divided Legacy—A History of the Schism in Medical Thought, The Centre for Empirical Medicine, 1995).
There is evidence that our doctors (like many of us) are creatures of habit and simply overwhelmed by the sheer number of antibiotics on the market and far too reliant on drug companies for “education” about their efficacy (N Eng J Med 1993; 328:1047).
Clearly, education of doctors and consumers is the best way to break the cycle. Doctors need to be motivated to keep their knowledge of resistance up to date and, as one journal suggests, improve their communication skills in order to better explain the relatively small gain to be had from antibiotic use. For instance, with a sore throat you have a 90 per cent chance of being symptom-free in seven days whether or not you take antibiotics; with antibiotics you have a 50 per cent chance of being symptom-free on day 3 rather than on day 3 1/2. (Med J Aus, 1992; 156: 644-9).
Patients need to be given reliable information like this and encouraged to trust that they will get better by themselves, albeit a little bit more slowly Antibiotic drug abuse may be a world-wide problem, but it is still best tackled at the local, individual level.
Sidebar: Avoiding antibiotics
Prevention is better than cure. The stronger your immune system is, the less likely it is that you will succumb to any kind of bug. Following a good daily programme of a wholefood diet, with antioxidant supplements, stress reduction through good-qualify sleep, relaxation techniques such as yoga, meditation and visualization will make you less prone to viral illness. Also make sure that “infections” like ear ache are not the result of allergies.
If you do get an infection:
Consider herbal alternatives. Many botanical preparations have significant antibiotic actions against bacteria, viruses and fungi. These preparations generally enhance our own body’s natural defence mechanisms. There are three widely used herbs which naturopaths rely on:
Echinacea angustifolia {purple concflower) perhaps the most well known herb and one which has been shown to have profound immunostimulatory effects. Its use can activate T lymphocytes and other white blood cells and promote the increased production and secretion of interferon.
Hydrastis canadensis (goldenseal) has also shown remarkable immunostimulatory activity. It can increase blood supply to the spleen. Berberine, one of its components, can activate the macrophages which are responsible for engulfing and destroying bacteria, viruses, fungi and tumour cells. Berberis vulgaris (barberry) also contains berberine and has long demonstrated its antibiotic activity and immunostimulatory effect. It may prove especially useful against staphylococcus.
Glycyrrhiza glabra (liquorice) is very useful in treating infections. It also increases interferon production and can prevent immunosupression caused by stress and cortisone. It has displayed antibiotic activity against staphylococcus, streptococcus and Candida albicans and antiviral activity against herpes simplex type 1.
For parasites
If you are suffering from the gastrointestinal effects of the cryptosporidium parasite which has made its
way into London’s water supply the NutriCentre (0171-436-5122) advise us that a mixture of Artemesia annua (wormwood), clove and black walnut tincture may be effective.
If it’s a virus…
Antibiotics will be useless. A herbal preparation called Viracin, composed of acerin, babul bark and canaigre root, may prove effective against viruses which cause flu-like symptoms, particularly of the digestive tract, as well as chronic fatigue and the Epstein Barr virus. Available through the Nutricentre.
If you must take antibiotics:
Your general level of health will influence how well you respond to both illness and the scattergun mechanism of many broad spectrum antibiotics. So, in addition to the above, consider these points for safer antibiotic use.
- Make sure you actually have a bacterial infection. It is unlikely that your condition will worsen while you await test results and don’t let your doctor pressure you into taking antibiotics which you do not want or may not need.
- Ask your doctor to show you the Data Sheet Compendium information on his chosen antibiotic so that you can see for yourself the possible side effects. Steer clear of combination antibiotics which seem to have more side effects. If possible, go for the oldest and most tried and tested variety, which also are less likely to cause mutation in the environment.
- Take plenty of probiotics. While you are taking antibiotics and for a time afterwards make sure you take high levels of lactobacillus which will replace friendly bacteria destroyed by the antibiotics.
- Finish your prescribed course of antibiotics. If you break off treatment prematurely, you may only have killed off a proportion of those microbes sensitive to your antibiotic. This alters the balance between sensitive and resistant microbes, giving resistant microbes the upperhand. Eventually these will multiply and dominate the culture in your gut (or wherever). The next time you get ill it will be much harder to treat the infection.
- This article first appeared in the April 1997 (volume 8 number 1) edition of What Doctors Don’t Tell You
