‘Antibiotics: handle with care’

The aim of the first annual World Antibiotic Awareness Week, held in November, was to raise recognition of the growing problem of bacterial resistance to antimicrobials and to disseminate information on how these drugs can be used more prudently. Is it still possible, though, to prevent an antibiotic apocalypse?
The development of drug-resistant bacteria is the inevitable result of natural selection, but formerly the discovery of novel compounds kept pace with microbial evolution; this is no longer the case. During the past decade numerous academic articles have reported alarming examples of antibiotic resistance in microorganisms, including multidrug-resistant Staphylococcus aureus and Mycobacterium tuberculosis, as well as extensively drug-resistant tuberculosis, and the mass media has duly disseminated this information to the general public. Around 5 years ago the NDM-1 gene, which confers resistance to the potent carbapenem antibiotics used against multi-resistant strains of Gram-negative bacilli, was found in Enterobacteriaceae including the ubiquitous Escherichia coli. The latest catastrophe is the emergence of the MCR-1 mechanism that allows polymixin-resistance plasmids to be transferred between strains of Enterobacteriaceae. And polymixins are (or should be) the drugs of last resort to treat infections with bacteria that are multidrug resistant, including carbapenem-resistant strains.
As well as over-liberal medical prescription of unnecessary antibiotics without prior diagnostic testing, premature cessation of treatment and unregulated sources of drugs enabling “self-prescription”, the routine use of antimicrobials in industrialized agriculture has greatly exacerbated the resistance problem. The recently reported polymixin resistance was first observed in China during routine testing of commensal E. coli in food animals, prompting a robust study that discovered the MCR-1 mechanism in 15% of E. coli isolates from raw meat, 21% of isolates from livestock and 1% of isolates from infected patients. Although the problem is currently confined to China, this type of mechanism spreads resistance so easily between bacteria that it will soon become a global problem. Should polymixin-resistance plasmids be transferred to Enterobacteriaceae that are already multidrug-resistant, truly untreatable Gram-negative bacterial infections would result.
Initiatives to prevent the further squandering of antibiotics coupled with rigorous infection control procedures are highly unlikely to prevent an antibiotic apocalypse now. But a worldwide ban on the veterinary use of medical antimicrobials might just stem the tide until new drugs (such as teixobactin for multidrug-resistant Gram-positive pathogens) have been approved.