Better Monitoring, Ban on Farm Animal Use Needed
The Japanese government monitors resistance to fluoroquinolones (FQs). These important antibiotics are called "New quinolones" or "Neoquinolones" in Japan, referring to the second or third generation of fluoroquinolones. The Japanese Veterinary Antimicrobial Resistance Monitoring System and the Infectious Diseases Surveillance Center monitor resistance in animals and humans respectively. Better monitoring of resistance is needed to get a better idea about the seriousness of the resistance problem in Japan.
JVARM: Antibiotic Resistance in Animals
JVARM, the Japanese Veterinary Antimicrobial Resistance Monitoring System, that was established in 1999. 1)
The Japanese reports and the data (in pdf files) are available only in Japanese. 2)
JOF looked at the data that is published annually since 1999. We made the following observations:
JVARM checks for two fluoroquinolones: Ofloxacin and Enrofloxacin. Salmonella and Enterecoccus do not seem to show significant resistance to these antibiotics. For E Coli the situation is worse:
E Coli - average for all animals: 2.2 % show resistance to ERFX and
2.7 show resistance to OFLX.
Campylobacter jejuni - 16 % are resistant to ERFX and about 16 % are resistant to OFLX (data from 2002). That is an average of all animals tested, including broilers, cattle and pigs. It is interesting to note that the rate hasn't changed since monitoring started 1999. These are rather high rates, and the JVARM report indicates that it is a cause of some concern.
Also JVARM monitors nalidixan (nalidixic acid). This is a quinolone that is very important for humans, so finding bacteria that are resistant to nalidixan is regarded as a serious issue. JVARM 2003 found that 20 % of salmonella and 24.3 % of campylobacter in samples from animals were resistant to nalidixan. Experts JOF has consulted with agree that nalidixan resistance levels are the most worrying. There is documentation that strains of bacteria with such resistance lead to failure in humans, when they need to be treated with fluoroquinolones.
IDSC: Antibiotic Resistance in Humans
It was tricky to find data on resistance to fluoroquinolones in humans. We found it on a website from a government center called IDSC (Infectious Diseases Surveillance Center) that is a branch of the Health and Welfare Ministry. 3)
IDSC refers to two studies on campylobacter. One is in English, from May, 1999 that looks at resistance in humans, and especially resistance to Ofloxacin and Enrofloxacin. They conclude that 31 % of the isolates from humans at a hospital (214 patients) proved resistant to OFLX in 1998. 4)
The other campylobacter study comes from a Tokyo hospital, and is only published in Japanese. They found that resistance to Neoquinolones (FQs) increased generally from 15% in the time period of 1993-94 to 26.5% in the time period of 1998-99. That is quite a large increase, and the authors are expressing concern. 4)
A recent study from Shizuoka showed that 44.6% of human isolates of Campylobacter jejuni were resistant to Ciprofloxacin. 5)
On PubMed, we also found a Japanese study on FQ-resistance in salmonella.
The authors note that there is evidence that the incidence of strains
that exhibit decreased susceptibilities to the most recent fluoroquinolones
used for the treatment of typhoid fever is increasing. The study examines
Cipro-resistant strains found in patients in regional public health
offices in Japan between 1995 and 2001.
Fluoroquinolones are approved for farm animals in the U.S., EU and Japan. What is worse, FQs can also be used for pets such as dogs and cats. The most common product for farm animals is Enrofloxacin, a fluoroquinolone sold by the Bayer Corporation under the name Baytril. In the U.S., the Food and Drug Administration has tried to ban all fluoroquinolones in animal use. The only other product on the U.S. market was Sara Flox made by Abbott Laboratories. In 2000, Abbott immediately declared that it would comply with the FDA decision and withdraw its product. Bayer, a German multinational drug-company, has refused to cooperate and still, five years later, still sells its product that Michael Shnayerson and Mark Plotkin in their book The Killer Within calls "very profitable product". According to published data, quinolone resistance in poultry has increased from 1 % to more than 19 % in the first four years it was used in the U.S. That is not an acceptable trend.
Why can companies still sell important antibiotics like fluoroquinolones for farm animals? Clearly, sick animals need treatment, but it is better to improve conditions, for example with better animal welfare and hygiene training for the workers, than to use the so-called drugs of last resort. As many other diseases are no longer responding to older antibiotics, many people will increasingly be at risk as bacteria become resistant. Without proper monitoring, it is also very difficult to get a better idea about the seriousness of the resistance problem. Japan Offspring Fund wants better monitoring, but also a ban on fluoroquinolones for farm animals without delay, based on the precautionary principle.
Japan - data of use in animals
Total use of Fluoroquinolone in 2001 was 6.3 ton
Approved fluoroquinolones for humans
Currently, there are seven fluoroquinolones approved and available for humans in the United States. These are:
Ciprofloxacin (Cipro) is the most well-known and widely used fluoroquinolone. Ofloxacin and lomefloxacin also are useful in a wide variety of infections. These antimicrobials belong to the second generation of fluoroquinolones.
The third generation includes levofloxacin, sparfloxacin, clinafloxacin, grepafloxacin, DU-6859a, and trovafloxacin of which only two are approved in the U.S.
Sparfloxacin is one of the newest compounds and carries indications for infections mostly of the respiratory tract.
Fluoroquinolone Brand Names
In the U.S.
In Japan 8)
1) About JVARM (in English)
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