How Australia and other developed countries have ended up in their current predicament of infections showing increasing resistance to antibiotics is addressed in a session at the Australasian Society for Infectious Diseases (ASID) Gram Negative Superbug meeting on the Gold Coast.
The role of doctors is explored by Dr Krispin Hajkowicz, Infectious Diseases Physician, and Senior Lecturer, University of Queensland, QLD. “The loss of effective antibiotics to antimicrobial resistance within two generations of their discovery is one of the great tragedies of human history. The people of the world want to hold someone accountable. Should it be doctors? Using the approach of a medical litigation claim, it can be shown that the current crisis was largely foreseeable, that doctors had a duty of care to the world to preserve the precious resource of effective antimicrobials and that they breached this duty of care,” says Dr Hajkowicz.
He points to evidence from studies showing that up to 50% of all antimicrobial prescribing by doctors is inappropriate, and that reducing inappropriate prescribing is largely unsuccessful by current interventions. “So my view is yes, doctors are to blame. Our penance is to develop and enforce national consensus guidelines for antimicrobial use, based on evidence, enshrined in legislation and involving both hospital and community prescribers. Additionally, doctors must promote the development of new antibiotics and then use these responsibly. Perhaps a new generation of doctors will undo what we have so foolishly done.”
Addressing the role of airlines, Joshua Freeman, of the Auckland District Health Board, New Zealand, says: “Over the last 15 years, international air travel has increased to the point where in 2010 alone, a total of 940 million international tourist arrivals were recorded globally. This phenomenon, along with a concurrent increase in the international movement of migrant workers has provided an unprecedented opportunity for the transfer of antimicrobial resistant organisms across international borders, usually from countries with a high prevalence to those with a low prevalence of antibiotic resistance.”
He discusses dissemination of extended-spectum ß-lactamase gene blaCTX-M-15 and the emergence of a carbapenemase gene known as blaNDM. (New Delhi metallo-beta-lactamase 1), both thought to originate on the Indian subcontinent. Since its first description as recently as 2009 in a returned traveler from India to Sweden, numerous case reports have described the dissemination of blaNDM to low prevalence countries worldwide (including the USA, Canada, Australia, New Zealand, and the UK among others), mostly among patients with a previous history of hospitalisation somewhere in the Indian subcontinent. “For NDM, unlike CTX-M-15, even the last line carbapenem antibiotics cannot be used effectively, which in many cases leaves virtually no treatment options,” says Freeman,
“These examples demonstrate that at the individual patient level, international travel to high prevalence countries, and in particular hospitalisation within those countries, should be viewed as an important risk factor for colonisation and subsequent infection with highly resistant gram negative organisms. Recognising the importance of this risk factor in the hospital setting is critical, because it has direct practical implications - both for the infection control measures that ought to be used and for the choice of appropriate empiric antibiotic therapy in critically ill patients,” concludes Freeman.
Addressing the possible role of nursing homes, Dr Paul Ingram (PathWest Laboratory, Royal Perth Hospital, and University of Western Australia, Perth, WA) says: “Nursing home residents are at risk of acquiring carbapenem resistant Enterobacteriaceae (CRE) as they have numerous co-morbidities, are frequently hospitalised and experience high rates of inappropriate antibiotic use.”
He adds that difficulty applying standard and transmission based precautions, proximity to other residents and faecal incontinence may facility secondary transmission. “Thus, nursing home may act as reservoirs and/or propagators of CRE,” says Ingram. He highlights that overseas, for example in the UK and USA, the rates of multi-resistant gram negative bacteria in nursing homes is often greater than that of methicillin resistant
Staphylococcus aureus (MRSA) or vancomycin resistant enterococcus (VRE). He concludes: “The prevalence and transmission dynamics of CRE in Australian nursing homes has not been widely studied, although nursing homes have been associated with endemic CRE cases in Australia. Studies into the prevalence and transmission of these organisms in nursing homes should be pursued.”
Looking at the possible role drug companies have had both in the development of and combating the problem, Dr David Grolman, Surgeon, intensivist and Associate Medical Director: Anti-Infectives Specialty Care, Pfizer Australia & New Zealand, says: “There is little doubt that the discovery and development of antimicrobial drugs has been the single therapeutic drug area that has contributed most to the dramatic improvement in life expectancy achieved by medical science over the past century. Whilst the majority of antimicrobial agents have been developed by drug companies, it is not the development of the drugs per se that has resulted in accelerating the rate of bacterial antibiotic resistance, but the inappropriate and excessive usage of the drugs.”
Dr Grolman highlights that there is global consensus that we need many more antibiotic agents in our armamentarium in order to deal with new, emerging and re-emerging pathogens. He says: “We need a concerted effort by all players in healthcare and governments to develop new antibiotics and achieve the discovery of novel antibiotic mechanisms of action.”
He also discusses his concern over the enormous use of antibiotics to promote growth of livestock in agriculture as a key factor in developing resistance. He concludes: “The key aspects to enable the medical scientific community to improve antibiotic usage in the short term revolve around improvements in the diagnosis of bacterial infection and improvements in rapid identification of the offending pathogen and its potential virulence factors and inherent resistance mechanisms. Rapid confirmation of definite bacterial sepsis and identification of the culprit will allow for limitation of antibiotic therapy to when genuinely needed and will ensure appropriate selection of the correct antibiotic therapy.”
Finally, referring to the role of animals (or more specifically agriculture), Dr Ben Rogers University of Queensland Centre for Clinical Research, says: “For many decades animals have been suggested as a source of antimicrobial resistant bacteria in humans. This observation is based on recognition of the large volume of antimicrobials administered to food producing animals, and the frequent isolation of resistant bacteria from such animals and their retail meat products.”
He says that contemporary molecular epidemiology techniques have allowed a greater understanding of the dynamics of this sharing of resistance. Of particular research interest, in the last decade, has been resistance of E. coli to extended spectrum cephalosporin antimicrobials, encoded by ESBL and AmpC genes. Review of currently published literature demonstrates geographically and temporally limited instances of transmission, from food producing animals to humans, of E. coli clones harbouring ESBL or AmpC genes. “These have almost exclusively been described as occurring amongst poultry. Although less well defined, the transmission or ‘leakage’ of smaller mobile resistance elements between food producing animals and humans appears to be more wide spread in time, place, and animal species involved,” concludes Dr Rogers. “A number of factors impact on variation in these phenomena including differences in farming techniques, food supply chains and significant regional variation in the practice and regulations governing use of antimicrobials in animals.”