Issue 3 / 31 January 2011

THE alphabet of antibiotic resistance is proceeding apace.

Most clinicians are aware of VRE and MRSA, but few are aware of new menaces ― multiresistant β-lactamases circulating under acronyms such as CTX-M, NDM-1 and KPC.

These enzymes are produced by enteric organisms which are part of the normal intestinal flora — mainly Escherichia coli and Klebsiella pneumoniae.

Only occasionally do the organisms cause clinical illness such as urinary tract infections (UTIs), so the incidence of antibiotic resistance detected in patients presenting with associated clinical conditions grossly underestimates the level of resistance that may be developing in the community.

By the time community-acquired infections develop, they are already widespread.

Yet, because of a lack of surveillance systems (and hence foresight), we currently have no knowledge of the spread in Australia.

CTX-M (cefotaxime) -type extended-spectrum β-lactamases (ESBLs), first isolated in Munich, have been documented in more than 50% of faecal specimens in China, up to 80% of specimens in India and increasingly in returned travellers in Australia, particularly those from Asia.

But, in most cases, it is the elderly, particularly long-term care facility patients, who are affected in Australia.

So this is not just an index of travel; these enzymes are well and truly entrenched here.

As with MRSA, ESBLs are a sleeper for ongoing dissemination in nursing homes, with the potential to fuel back-and-forth transmission between hospitals and nursing homes.

ESBLs are seen in hospital infections in Australia but it is the threat of insidious community spread that is most concerning.

This is exactly what happened with KPC (Klebsiella pneumoniae carbapemase) enzymes in the United States. “Wildfire” spread occurred not only between health care sectors and the community but across the nation from its origin in the north-east of the country.

The first clinical case of KPC in Australia was detected in Sydney in December.

Multiresistant organisms are resistant to virtually all oral antibiotics used in the community as well as to main-stay parenteral antibiotics such as third-generation cephalosporins.

This results in:

  • a delay in treatment for 48 hours or more which, for some patients with a UTI, can be life-threatening
  • hospitalisation of patients who cannot be treated with conventional drugs in the community — tying up resources and exposing otherwise well patients to potential nosocomial cross-infection — plus the huge economic costs to the health system (for antibiotics) and to the workplace (in lost production)
  • a considerable impact on other medical specialties, for example, rectal biopsies may become unsafe, and haematology or transplantation services could be affected.

NDM-1 (New Delhi metallo-beta-lactamase 1) is the most worrying cause for concern.

These are highly promiscuous enzymes that are coding for resistance to virtually all known antibiotics.

The spread has been rapid and alarming considering that it is less than 2 years since it was first recognised in India.

Three clinical cases have been noted so far in Australia — in Queensland, New South Wales and the Australian Capital Territory — all following travel.

A similar enzyme (VIM-1) has been spreading rapidly through hospitals in Greece, and we have seen another (IMP-4) cause outbreaks in some Victorian and NSW hospitals.

Unfortunately, we have once again absolutely no idea of IMP-4’s prevalence because we have no monitoring systems.

Unlike MRSA and community-associated MRSA ― where medical use of antibiotics is suspected of being the cause ― with these enzymes, especially CTX-M, the cause is, without doubt, profligacy in antimicrobial use in agriculture and animals.

We must recognise antibiotic resistance as a true epidemic, in the same way that we think of avian flu as a potential epidemic, and treat it as a public health crisis and a social challenge.

This is something the Australasian Society for Infectious Diseases and the Australian Society for Antimicrobials is trying to address, by bringing together all interested parties at the forthcoming Antimicrobial Summit in Sydney, NSW.

We must promote and coordinate surveillance, research and education for antibiotic resistance at all levels, and ensure the government is engaged in these issues.

Without a concerted effort at government level ― across all health care sectors, veterinary practice and the agricultural sector ― our individual efforts are doomed to failure.

Associate Professor Tom Gottlieb is the president of the Australasian Society for Infectious Diseases and president-elect of the Australian Society for Antimicrobials.

Posted 31 January 2011

One thought on “Tom Gottlieb: Antibiotic crisis is here

  1. Dr Attila Danko says:

    “Unlike MRSA and community-associated MRSA ― where medical use of antibiotics is suspected of being the cause ― with these enzymes, especially CTX-M, the cause is, without doubt, profligacy in antimicrobial use in agriculture and animals.”
    I always found the emphasis on doctors being the main cause of antibiotic resistance to be bizarre. We know bacteria can exchange plasmids and the overall level of resistance is largely an ecological phenomenon. What we do is give a short course of a high dose of old fashioned antibiotics. Unlikely to produce much resistance. What intensive livestock farmers do is give constant low levels of often very advanced antibiotics (quinolones and the like) simply to increase the meat yield and feed efficiency by decreasing gut flora! I’m glad this issue is being raised as it is commonly and wrongly believed that doctors are the main cause of resistance. Of course, in this post-modern age we have status and power so we must be the targets.

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