Megan McArdle has a rather grim post about bacterial antibiotic resistance:
The superbugs have not only gotten bad fast–from “not really an issue” in 1980 to a major problem today–but they seem to be getting badder faster, as they merrily borrow resistance-conferring genes from each other. Researchers now say they’re seeing resistance show up in the lab, before they even put the stuff into people.
Of course, the most worrying thing is not the effect on the budget. It’s the effect on the people. A world without antibiotics is a world of vast suffering and early death.
Unfortunately, there is no easy solution to this problem and a consideration of the history of antibiotics and methicillin-resistant Staphylococcus aureus (MRSA) may explain why.
The penicillin antibiotics have been known for more than a century but didn’t come into widespread use until 70 years ago. Their effectivceness in treating staph rendered them invaluable during World War II. 2.3 million doses were produced for the invasion of Normandy in 1944. After the war it made its way into widespread civilian use.
The first known case of MRSA was identified in 1961 in the UK. There is epidemiological reason to believe that it originated in the UK and its eradication there has proved elusive. It took 20 years for MRSA to spread from the UK to the USA to any great degree. Since its emergence the incidence in the US has grown to 31.8 cases per 100,000 and about 20% of those are fatal. See here for the rise in MRSA cases among hospital patients.
I would suggest that the emergence and spread of resistant variants of bacteria can be traced to the following causes:
- Widespread availability of relatively inexpensive antibiotics.
- Abuse of antibiotics. I speculate that the urge to overtreat may be a contributing factor.
- Increased travel. Without travel resistant varieties would just stay where they originated.
Now consider the antibiotic linezolid:
When linezolid (Zyvox) received federal approval in early 2000, it was the first completely new antibiotic compound to reach the pharmaceutical market in 35 years. The synthetic compound even proved effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) bacteria, for which no other line of defense existed. Its creator, New Jersey-based Pharmacia, sounded confident that few people would become resistant to the drug. It was not to be. Within months, patients infected with MRSA and VRE were not responding to linezolid.1,2
Such quick resistance epitomizes the dilemma of antibiotics development: Drugs cost hundreds of millions of dollars and take at least a decade to develop, and then become increasingly less effective. (see ‘Renewing the Fight Against Bacteria,’).
In the past, a classic screening approach, which tests in vitro the inhibitory effect of synthetic and natural compounds or extracts, led to the discovery of many current antibacterial drugs. Linezolid, for example, was developed in this way: thousands of compounds were reviewed to find one that kills bacteria. Today, this method yields few, novel, promising structures. The related method of developing second and third generation drugs based on existing pharmaceuticals is no longer considered an option because cross resistance reduces the effectiveness of macrolides (based on erythromycin), rifapentine (based on penicillin), and carbapenems (based on imipenim).
In many places in the world antibiotics are available over the counter and here in United States incentives to do more, effective or not, lead to over-prescription. It has been suggested that the routine use of antibiotics in animal feed contributes to the development of resistant bacterial strains as well.
Modern travel, the wide availability of antibiotics, and misuse both of patients and physicians create an evnironment in which the development of resistant strains of bacteria is inevitable and once established, these strains have proved very difficult to uproot. The increasing cost (even in the absence of regulatory barriers, a frequent target) makes it unlikely that the development of new antibiotics will keep up with the evolution of new resistant bacterial strains.
Barring some development to fight bacteria other than the development of new antibiotics we may well be entering a post-antibiotic age. I don’t look forward to this eventuality. Antibiotics have been very good to my family—without them I probably wouldn’t be here. In the 1880s nearly every adult male in my lineage died from bacterial disease (tuberculosis, staph). Puerperal fever (septicemia following childbirth) was a common cause of death among my female ancestors. As late as 1930 people in my family were dying of tuberculosis but since 1940 nobody in my family has died of bacterial disease. We may be returning to those days.