Teaser Appetizer: Super Bugs

by Shiban Ganju

Super bugs excel in defying therapy just like super star Britney. Though antibiotic resistant bugs or ‘super bugs’ thrived before the super stars, yet unlike them they lay unnoticed – that is, till recently.

Microbes inhabited this planet long before humans. They were already experts in the game of ‘natural selection’ – an evolutionary survival strategy - before we learned the game of antibiotic attack. Microbes, like other organisms, mutate genetically and they do it often because they multiply fast – sometimes with a gap of only 15 minutes between generations. One random mutation would bestow the luck of antibiotic resistance.

When we vanquish the vulnerable microbes with an onslaught of antibiotics, the resistant mutated bugs thrive and proliferate with impunity. It is not that the bacteria ‘acquire’ resistance but the mutated bacteria have a survival advantage over the non-mutated bacteria. And that is evolution in action.

Bacteria interfere with the antibiotic action by altering themselves. For example, penicillin disrupts the cell wall of susceptible bacteria; the resistant microbes modify the structure of the cell wall so penicillin cannot bind to it.

Bacteria may mutate naturally to evolve such resistance, but more sinister is the way of the plasmid – a small circle of DNA, which can move between bacteria conferring resistance. A single altered plasmid can cause havoc. Over 12,000 people died of diarrhea in Guatemala in 1968 due to a strain of Shigella, which carried a plasmid resistant to four antibiotics.

The first super bug to exhibit antibiotic resistance was Staphylococcus aureus (SA), which often lives on our skin and inside our noses but can also inflict serious infections like boils, abscesses and toxic shock. The resistant variant of SA declared its existence just a few years after the mass production of penicillin in 1943. (Alexander Fleming, the discoverer of penicillin had forewarned this a few years earlier.) Trying to be one up, we invented methicillin to banish SA, which in its turn evolved into MRSA - methicillin resistant staphylococcal aureus. When we shot more antibiotics in vengeance against SA, unscathed MRSA proliferated. CDC claims that in 1974 only 2% SA infections was due to MRSA; by 1995 it was 22% and in 2004 it was 63%. Now MRSA is endemic in health care institutions and has made inroads into normal healthy population also. But we have hope in vancomycin - a drug of last resort for many infections, which is still lethal against MRSA. What will happen if MRSA becomes resistant to vancomycin?

One group of bacteria – enterococci, which reside in the normal intestines – has already rapidly turned resistant to vancomycin in the past 20 years. No vancomycin resistant enterococcus was reported in the US before 1989. What if this resistance is transmitted to MRSA? ‘Alarming’ is what some have called this scenario. The first two cases of vancomycin resistant SA were reported in 2002 from Michigan and Pennsylvania and the a third one, in 2004, from New York. Some more have been reported since. The crisis has just begun.

All microbes have potential to develop resistance to any antibiotic, any where in the world. Tuberculosis, malaria, ear infections are now less susceptible to old antibiotics. Another super bug, Streptococcus pneumoniae, a pneumonia-causing microbe, first exhibited its resistance to penicillin in 1967 in Papua New Guinea. Up to 1987 only 0.02 % of the strains of this bug were penicillin resistant, but by 1994, CDC reported it had climbed to 6.6%. In Hungary it got even worse: by 1976 more than 50% strains of this bug turned resistant because of unabashed use of penicillin in the prior decade.

Consider Japan: between 1953 and 1965, Shigella - a dysentery provoking bug - escalated its population resistant to streptomycin, tetracycline, sulfanilamide and chloramphenicol, from 0.2% to 58%.

The super bugs became ‘globalized’ much before we did. Southeast Asia exported its new strain of penicillin resistant gonorrhea bug to the USA when American soldiers returned home by 1976 carrying the bug with them

(Many centuries ago, syphilis had traveled in reverse direction on ships)

By now, globalization of infectious diseases is not a headline grabbing news. Antibiotic resistant bugs erupt frequently in remote parts of the world and travel to distant locations. That is because we have gone antibiotic crazy!

We shower our agriculture with ten times and stuff our animals with thirty times more antibiotics than we consume as humans. It is estimated, that we inundate the planet with 100 to 180 million kilos of antibiotics every year, which is probably enough for 25 billion courses of full treatment for every human four times a year.

We have reached a stage, where - if you watched TV lately – super bugs have replaced superstars at prime time. But there is a difference between a super bug and Britney Spears: she is merely self-destructive.

About 90,000 patients die every year in the USA of infections acquired in the hospitals and 70% of these microbes are resistant to at least one antibiotic. Our response: newer, more expensive, perhaps more toxic antibiotics and longer hospital stay.

We are lucky; this problem is not amenable to bipartisan-republican-democratic health care reform or we will never find a solution. Wisdom supplementing our scientific knowledge can control the crisis.

* Doctors should not prescribe antibiotics unless absolutely needed and should attempt to prescribe a specific antibiotic for the suspected pathogen as opposed to a ‘broad spectrum’ antibiotic, which targets many pathogens. A survey by the National Center for Health Statistics showed that the prescription of ‘broad spectrum’ antibiotics has increased even though the number of prescription has not.

* Parents should not demand antibiotics for their children. One study showed that doctors prescribe antibiotics five times more often, if they feel that the parents expect them. Indiscriminate use of antibiotics has made children the commonest target of resistant pathogens.

* Hospitals should have better internal surveillance systems and linkages with the other public health institutions. We really don’t have a grip on emerging resistance in the world. International reporting system and surveillance needs cooperation between nations

* Health care workers in hospitals should wash their hands between touching patients. This has been proven to be the single most effective way of controlling transmission in the hospitals.

* We need to curtail excessive antibiotic use in animals.

* Pharmaceutical companies need to build a pipeline of dugs against evolving infection. We were complacent 20 years ago, thinking that we had conquered infections and did not pursue the development of antimicrobials with vigor. In the mean time resistant pathogens multiplied and we have no drugs to counter some of them.

* Scientists need to look at new ways of handling infections: probiotics to build normal flora which can suppress the pathogens; phages which are pathogen specific and not broad spectrum like antibiotics; drugs that target molecules on bacteria to rener them ineffective without killing them; and above all prophylactic vaccines.

While we are pondering and planning, there is profit to be made. Gadget peddlers are cashing on the frenzy of fear – real and perceived.

Here are some products: special hand soaps like hands2go; nose cleaner – nasopore nasal wash; personalized ‘life saver’ pacifier for the kids and silver and copper dressings for wounds. Then there are special cleaning services that are ready to rush their swat teams to debug your office!

With recent flurry in the media, the time is right to capture public attention. We need ‘super star’ power to educate people. I vote for Britney; she will be a perfect model to tout these gadgets and be an ambassador for a campaign against super bugs. She personifies the destructive power of resistance to therapy.