Antibiotic Resistance

The emergence of “superbugs”, bacteria resistant to multiple antibiotics, is shaping up as one of the greatest world-wide health-care challenges of the (still relatively) new century. Infectious Diseases (ID) Physicians warn of a coming “Red Plague” that threatens to effectively take us back to the pre-antibiotic era, when people died of what are currently considered minor infections, due to increasing Gram-negative resistance.

Gram-negative bacteria (including Enterobacteriaceae such as Escherichia coli [E.coli] & Klebsiella, and Pseudomonas and the Neisseriae) don’t retain crystal violet during the Gram stain process and so appear red under the microscope, hence the name “Red Plague”. Bacterial populations can develop resistance after exposure to particular antibiotics in humans, other animals or the environment, but they are also able to inherit resistance through “horizontal gene transfer” of plasmids (DNA molecules that exist within bacteria separate to their chromosomal DNA) which can be shared between species. A combination of widespread antibiotic use, both clinically and in agriculture, poor sanitation in developing countries that have relatively unrestricted access to antibiotics, and international travel have contributed to a dramatic increase in the incidence of dangerous multiple drug-resistant Gram-negative infections – Carbapenem-resistant Enterobacteriaceae (CRE) caused 17 infections in the UK in 2008, but 799 last year. And we are running out of antibiotics to use against them.

In this week’s Medical Journal of Australia (MJA), doctors in Brisbane reported the case of a man who experienced an horrific spread of infection due to multi-resistant E.coli after a procedure he required in order to diagnose his prostate cancer. He probably picked up the bacteria during a trip to South-East Asia, but was unaware of it as he didn’t get sick. Infection spread from his bowel to his prostate, and then to his sterno-clavicular joint (the joint between the collar-bone and breast-bone), and lumbar spine. He endured 10 weeks of IV antibiotics and 8 weeks of oral antibiotics.

Last week New Scientist reported that new antibiotics for multi-resistant bacteria are in the development pipeline, but aren’t being picked up by drug companies for development because with the high costs of bringing new drugs to market antibiotics are not considered a profitable investment. Unlike medications for chronic illness like heart disease or high cholesterol, antibiotics are used for short courses, and antibiotics for high-risk multi-resistant infections are deliberately used as infrequently as possible, so the opportunity to recoup on an investment by a pharmaceutical company that is ultimately answerable to its shareholders, rather than the public, its clients, isn’t seen to be there.

Again in the MJA this week, David Looke, Thomas Gottlieb, Cheryl Jones and David Paterson, highly respected ID Physicians in Brisbane and Sydney, authored an editorial in which they offered a series of recommendations to deal with this urgent problem:

1. implementation of national surveillance to follow these infections

2. implementation of  antibiotic stewardship in all health-care sectors so that antibiotic use is appropriate

3. support & funding for research (the US Congress and European authorities are revising the mechanisms for bringing new drugs to market so that antibiotics are not so costly to develop – there will be an inevitable trade-off in safety) 

4. embrace 

a.  innovative trials of preventive strategies, such as vaccines

b.  interventional radiology & minimalist surgical techniques 

c.  agriculture that doesn’t require antibiotics

5.  understand the importance of this “red-plague” as we do bird-flu.

This is a global problem and it requires a global response, but ultimately we doctors are primarily concerned with the patient in front of us. Endophthalmitis (intraocular infection) is the most feared complication of cataract surgery, and thankfully is very rare, and usually due to Gram-positive organisms. But as an ophthalmologist I treat patients with Gram-negative infections regularly and emerging resistance is a real threat.