Antibiotic resistance

Look out: resistance outbreaks about!

Jon Otter (@jonotter) Antibiotic resistance , ,

We are all familiar with the idea of outbreaks. A noteworthy pathogen rears its ugly head leaving a trail of destruction in its wake (as in ‘Contagion’, or before that, ‘Outbreak’). (I credit ‘Outbreak’ with getting me into microbiology and epidemiology as an impressionable 15 year old by the way.) Or more commonly in hospitals, a ward experiences an increased incidence of a particularly resistant or virulent clone. But a recent study from some colleagues at the Centre for Clinical Infection and Diagnostics Research at St. Thomas’ Hospital in London turns the idea of ‘outbreak’ on its head by identifying surprisingly common outbreaks of resistance to a particular antibiotic across different species.

The horizontal transfer of resistance genes is generally considered to be a rare event relative to horizontal, clonal transmission of an outbreak pathogen (see Figure below). But the findings of this study suggest more promiscuous spread of resistance genes than you may expect.

ICU resistance

Figure: Horizontal transfer of resistance genes is generally considered to be the least common cause of ICU resistance.  

The team used some outbreak scanning software to interrogate laboratory reports from two ICUs between 2002 and 2009. Analysis of the large dataset, comprising almost 90,000 patient days, found that outbreaks occurred for two thirds of the 26 ‘species-groups’ studied. Only three of these were recognized at the time. Thirty-nine outbreaks of resistance were detected, the majority of which (87%) did not coincide with an increase in a particular ‘species-group’, supporting the fact that these were due to horizontal gene transfer between species.

The clustering of individual species into ‘species-groups’ is somewhat problematic, and may serve to over-emphasize the number of outbreaks that occurred. Quite a number of the outbreaks of the same ‘species-group’ and of resistance were very small – with 2 cases over a day or two. Also, clustering of the same species does not necessarily mean clonal transmission has occurred – you’d need to do molecular typing to prove that. Similarly, clustering of resistance across species to the same antibiotic does not necessarily mean horizontal gene transfer has occurred; multiple mechanisms could be involved. Notwithstanding these limitations, this is an important study and has changed the way that I think about hospital outbreaks.

Infection control interventions implemented to control recognized outbreaks on the ICU appeared to reduce the overall number of outbreaks of the same ‘species-group’, but did not affect the number of resistance outbreaks. So, it seems that different measures are necessary to control outbreaks of resistance. Perhaps the best weapon we have to combat outbreaks of resistance is to restrict our use of antibiotics. If we can reduce the selective pressure driving resistance, we should see less clonal outbreaks of resistant bacteria and less resistance outbreaks across species.

Article citation: Vlek AL, Cooper BS, Kypraios T, Cox A, Edgeworth JD, Auguet OT. Clustering of antimicrobial resistance outbreaks across bacterial species in the intensive care unit. Clin Infect Dis 2013; 57: 65-76.

Eight solutions from the G8 summit to curb antibiotic resistance

Jon Otter (@jonotter) Antibiotic resistance , ,

G8

As effective therapy using antibiotics becomes increasingly difficult due to resistance, the emphasis must move from cure to prevention of bacterial infection. There is an urgent need to take internationally coordinated action to curb the further development of antibiotic resistance. The steps required are complex and will require engagement on a national and international level. So, it’s encouraging to see antibiotic resistance on the G8 agenda. Here’s eight solutions that have been discussed by G8 summit science ministers:

  1. Get antibiotic resistance on the agenda. The fact that the issue is being discussed at all demonstrates that the problem is being recognized. The recent rhetoric from Dame Sally Davies (“antibiotic resistance as big a risk as terrorism”) and the US CDC (“deadly, untreatable superbugs”) will help.
  2. Reduce overuse (abuse) of antibiotics in medical, veterinary and other applications. Antibiotics simply should not be used to fatten up animals and stop barnacles attaching to ship hulls!
  3. Restrict the availability of antibiotics where they are currently available over the counter. According to Dame Sally Davies, 83% of Russian families use antibiotics inappropriately at home.
  4. Stimulate the discovery of new antibiotics, and streamline the testing and approvals required to bring a new antibiotic to market. Drugs are expensive to discover and then bring to market. Pharmaceutical companies are not currently focused on developing new antibiotics and need to be incentivized.
  5. Improve and share surveillance efforts. National and international surveillance systems should be established for emerging resistant strains.
  6. Highlight the financial burden of antibiotic resistance ($21bn-$34bn a year in the US, £10bn a year in the UK).
  7. Stop selling antibiotics at the cost of Smarties. Otherwise they will be consumed like Smarties. Generic antibiotics can be very cheap indeed; increasing the price of generic antibiotics will provide a financial barrier to inappropriate over-the-counter use.
  8. Develop rapid diagnostics to reduce the universal or empiric use of inappropriate / ineffective agents. This does not sit well with the proposed universal use of antibiotics.

There’s no simple solution to the problem of increasing antibiotic resistance. The problem is long-standing, multi-factorial and global. However, international collaboration can make real progress is curbing the increase in antibiotic resistance rates and perhaps even begin to reverse the trend.

Is treating surfaces rather than patients with colistin a good idea?

Jon Otter (@jonotter) Antibiotic resistance, Antimicrobial surfaces , , , ,

PillsAntimicrobial resistance is a worldwide problem and the emergence of multi-drug resistant (MDR) bacteria and the lack of therapeutic options have led to the revival of old antibiotics such as colistin.1 This antibiotic is now considered as a “last line” antibiotic used to treat infection with MDR strains especially those cause by Gram-negative pathogens.2 Unfortunately, resistance to colistin has already been documented among a number of problematic pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, although the exact mechanism of resistance is not yet well defined.3

Within this context, I was surprised to come across a study4 presented at the 23nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) conference held in Berlin in April 2013, by a Portuguese group aimed at covalently immobilizing colistin on biomaterials to prevent biomaterial-associated infection.

The use of antimicrobial materials and materials coated or impregnated with antimicrobial agents in healthcare settings is a flourishing field of research. This is driven by an increased recognition of the role of environmental surfaces in the transmission of nosocomial pathogens5 as well as the age old problem of bacterial colonisation of indwelling medical devices.6  With few exceptions, such materials have yet to be proven effective in reducing infection in practice. In addition, the possibility of the development of resistance to the active agents within these materials and surfaces has not yet been well investigated.

The Portuguese study,4 successfully covalently immobilized colistin onto a polycarbonate surface using a polydopamine dip-coating methodology. They used two strains of P. aeruginosa to test for the ability of the bacteria to attach to these colistin coated surfaces and the antimicrobial activity of these surfaces. The results showed that colistin coated surfaces had no effect on bacterial attachment and that the majority (but not all) of the bacterial cells were killed. So, some cells were still viable after 24 hr incubation on the colistin coated surfaces. The concentration of colistin used was not reported, but it is clearly not sufficient to inactivate all the cells on the surfaces which can potentially lead to the development of resistance to the drug, especially in a versatile organism such as P. aeruginosa.

I believe that in an era of MDR and pan-resistant strains and virtually untreatable bacterial infections, the idea of using one of our last line antibiotics to coat biomedical surfaces potentially breading colistin and other antimicrobial resistant strains is the last thing the healthcare community needs.

References

  1. Bergen PJ, Landersdorfer CB, Lee HJ, Li J, Nation RL. ‘Old’ antibiotics for emerging multidrug-resistant bacteria.Curr Opin Infect Dis. 2012 Dec;25(6):626-33
  2. Biswas S, Brunel JM, Dubus JC, Reynaud-Gaubert M, Rolain JM. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect Ther. 2012 Aug;10(8):917-34.
  3. Lim LM, Ly N, Anderson D, Yang JC, Macander L, Jarkowski A 3rd, Forrest A, Bulitta JB, Tsuji BT. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy. 2010 Dec;30(12):1279-91
  4. Alves D, Lopes S, Pereira MO. A colistin coating to prevent biomaterial-associated infections. ECCMID. 2013. Berlin. Abstract P1105.
  5. Otter JA, Yezli S, French GL. The role played by contaminated surfaces in the transmission of nosocomial pathogens. Infect Control Hosp Epidemiol. 2011 Jul;32(7):687-99
  6. Nicolle LE. Urinary catheter-associated infections. Infect Dis Clin North Am. 2012 Mar;26(1):13-27.