It is becoming well known that the use of many antibiotics over several decades is beginning to backfire as some start to lose their efficacy.

With reference to a study in the online open-access journal of the American Society for Microbiology, bacteria that are resistant to the antibiotic colistin are also usually resistant to antimicrobial elements made by the human body. Host antimicrobials LL-37 and lysozyme assist the body in fighting bacteria. Cross-resistance to colistin could result in patients with life threatening and drug resistant infections also being burdened with an impaired immune response. As a last-resource drug, colistin is used to treat many types of drug-resistant infections. However, the recently discovered effects of the drug on bacterial resistance to immune attack, emphasises the necessity for more improved antibiotics. 

Despite being developed fifty years ago, colistin is still being prescribed today, not necessarily for its specific effectiveness or safety, but because the options for treating multi-drug resistant infections are becoming less and less. A patient’s last hope for survival can depend on colistin being administered when all other drugs have failed to produce the desired result. It was noted in the study that colistin operates by upsetting the inner and outer membranes that keep Gram-negative bacterial cells together. This is similar to the behaviour of LL-37 and lysozyme antimicrobials of the human immune system. At areas of inflammation the protein LL-37 will be found, but many different immune cells contain lysozyme including secretions such as breast milk, tears and mucous. These two antimicrobials are essential in defending any invading bacteria. Researchers aimed to find out whether resistance to colistin could create resistance to an attack by LL-37 or lysozyme. On inspection of A.baumannii isolates from numerous patients, observations revealed that all colistin-resistant strains contained mutations in pmrB.  This is a regulatory gene that induces the modification of polysaccharides on the outside of the cell in reaction to antibiotic exposure. Tests revealed a close relationship between the capability of single isolates to withstand high levels of colistin and to also prevent attacks by LL-37 or lysozyme. 

In order to get nearer to a linking source between treatment and cross-resistance, two pairs of A.baumannii isolates were studied. These were taken from two different patients, before and after treatment with colistin for three or six weeks. The outcome assisted in confirming the cross-resistance link, because before treatment neither strain was resistant to colistin, LL-37 or lysozyme. However, after treatment the strains displayed marked resistance to colistin and lysozyme. Similar to the resistant strains that were previously tested, both post-colistin isolates retained vital mutations in the pmrB gene that seem to grant the ability to oppose treatment. The colistin dilemma is indicative of much bigger problems, namely the ever increasing levels of drug resistance, a shortage of funding for antibiotic research and the absence of incentives for pharmaceutical companies to invest. It is important to promote increases in funding for further research and development of new antibiotics. Our complacency has led to the bugs becoming more resistant. If the right resources are available the situation can be reversed.