Bacterial resistance to penicillin on the rise

Published in The Hindu on September 21, 2006

The consequences of a drug being used and misused on a large scale are once again beginning to emerge. Only this time, the drug involved is one of the most potent to fight bacterial infections responsible for killing nearly one million young children every year.

The drug in question is penicillin, one of the wonder drugs of the last Century. And the bacterial infections being discussed are pneumococcal infections – pneumonia, meningitis and sepsis. These infections are caused by two bacteria (Streptococcus pneumoniae and Haemophilus influenza).

“When we started the ‘Invasive Bacterial Infectious Surveillance’ (IBIS) in 1993, no resistance to penicillin was seen. Intermediate resistance was seen in 1998. It has been gradually increasing since then,” said Dr. Kurien Thomas. Dr. Thomas is the Principal Investigator of IBIS and also a Professor in the Department of Medicine II & Clinical Epidemiology Unit, CMC, Vellore.

The IBIS is a multicentric project involving seven cities and is an ongoing surveillance that was started in 1993. The study was undertaken in teaching hospitals in southern, northern and central regions of the country.

There was a compelling need for surveillance to understand the antimicrobial resistance pattern and decide on an alternative strategy. A commonly used drug – cotrimoxazole (Septran) – was no longer working due to the resistance developed by the bacteria. Used for all kinds of upper respiratory infections, there is more than 85 per cent resistance to Septran.

“The second objective was to understand the seroepidemiology of the invasive pneumococcal disease for the development of a preventive vaccine,” he said.

High mortality rate

According to WHO, pneumococcal infections are becoming difficult to treat as bacteria are turning more resistant to the commonly used antibiotics. Currently, the mortality rate due to severe pneumonia in hospitals has been found to be 3-5 per cent.

The mortality rate due to meningitis is even more alarming – 35-50 per cent. Even if children escape death, morbidity is severe. They very often develop residual damage such as paralysis of the limbs.

What is more appalling is that, with both types of bacteria (S. pneumoniae and H. influenza) causing pneumonia, meningitis and sepsis, and mere clinical observations sans laboratory testing difficult to identify the causative bacteria, treatment is based purely on the age of the patients.

“Across India, laboratory facilities are poor. So age is the determining factor,” he said, explaining the rationale behind the choice of medication for treating the infections. H. influenza affects the very young children – a few months old, and infrequently, the adults.

Treating patients based more on the age factor and not on confirmed laboratory findings is a sure bet for bacteria developing resistance to drugs. “The large antimicrobial pressure – use and misuse of penicillin compounds in the society, has led to the development of resistance to penicillin,” he said. “There was no resistance when the surveillance was started in 1993. Some resistance, about 1 per cent, was seen in 1998. It increased to 7-8 per cent in 2002.”

Already, H. influenza is resistant to penicillin. So using it to treat the same infections caused by this class of bacteria is now not possible. The recourse has been to use third generation cephalosporin to treat the infections caused by both types of bacteria in young children.

Herein lies a big danger. While cephalosporin is the only drug that can currently treat H. influenza, its wide use, and use in children who are infected with S. pneumoniae and not H. influenza is bound to cause serious problems in the future.

The danger

“There is a possibility of Streptococcus [bacteria] developing resistance to cephalosporin,” Prof. Thomas warned. “And that is the real danger.”

Already, the third generation cephalosporin is expensive. A fourth generation drug will not only be more expensive but will be more toxic too.

Even when properly treated, the drug gets into the environment and in due course helps the bacteria develop resistance to it. Its misuse only aggravates and hastens the process.

In the case of penicillin, its wide use for veterinary purposes increased its presence in the environment many fold. H. influenza developing resistance to penicillin was thus bound to happen. And the findings of IBIS of increasing resistance to penicillin should come as no surprise.

While a vaccine for H. influenza already exists and is equally potent in India, it is not the same with pneumococcal infections caused by S. pneumoniae. The vaccine currently used in the developed countries can offer only about 50 per cent protection when used here. “We have 3-4 serotypes not present in the already available vaccine,” he noted.

“To offer 70-80 per cent protection, we need a different vaccine,” Prof. Thomas explained. And efforts to this end are already under way. A vaccine for pneumococcal infections that is specifically meant for children needs to have the ability to produce antibodies targeting the bacteria.

S. pneumoniae is a capsulated bacterium. With the capsule being made of polysaccharide, the young children’s immune system is not powerful enough to produce antibodies to attack the bacteria. The vaccine, therefore, needs to address this issue.

“At this point of time, we are expecting a 13 valent vaccine to be available in India for Rs.5 in two years’ time,” Prof. Thomas said optimistically.

Whether or not we have one at that price in two years’ time, there is a compelling need to put in place proper systems that will ensure that drug resistance does not set in.

And for that to happen, equal responsibility rests with all stakeholders – government, doctors and patients. The government for strengthening the laboratory facilities in hospitals, doctors for prescribing correct drugs and in correct dosages and only when required, and finally the patients who should adhere to and complete the regimen.

There are several instances to amply demonstrate that we have failed in preventing drug resistance in the past and are paying a huge price for our negligence.