Monthly Archives: October 2014

“Adding meaning to methicillin”


You will all be familiar with the acronym MRSA (Methicillin Resistant Staphylococcus aureus), but you probably won’t be so familar with the methicillin part, unless you are even older than me.

Methicillin was the first semi-synthetic beta-lactam and was manufactured by Beecham and released commercially in 1959. This antibiotic was a marked improvement on the original penicillins such as Penicillin G (benzylpenicillin). Scientists had discovered that by making the side chain of the beta-lactam ring bulkier, the “steric hindrance” produced made the antibiotic more stable to penicillinases. At that time at least 50% already of all Staph aureus isolates produced penicillinase and were thus resistant to straightforward penicillin.

However a major problem with methicillin is that it is poorly absorbed when given orally and it is broken down rapidly by acid in the stomach. In 1961, Beecham released newer penicillinase stable beta-lactams called oxacillin and cloxacillin (flucloxacillin was first used commercially in the early seventies). These newer antibiotics were much more stable when given orally.

And as with all antibiotics, it did not take long before resistance to methicillin in the human population became prevalent. The first Staphylococcus aureus isolate resistant to methicillin (MRSA) was described in 1961 in the UK.

Clinical use of methicillin tapered off during the 1980s and as far as I am aware the antibiotic is no longer available commercially, but the name Methicillin Reistant Staphylococcus aureus continues to this day.

Maybe we should change the name of MRSA to BRSA… The mechanism of resistance in MRSA (mecA gene encoding for altered PBP2a) confers resistance to not just methicillin, but all beta-lactams. For me, the acronym BRSA makes it clear what antibiotics can be excluded for starters in treatment of an MRSA infection.


p.s. The taxonomical establishment have since changed the name of methicillin to meticillin, for reasons which are best known to themselves….

“Endemicity and the Environment”

MDR Tuberculosis is highly prevalent in countries such as India, South Africa and Ukraine, but virtually non-existent in others.

Metallo-beta-lactamases, such NDM1, are imported into New Zealand, but so far have not become endemic.

Measles is a major killer in sub-Saharan Africa but reduced to the odd sporadic case in other parts of the world.

Just because a micro-organism is successful in one environment, it does not mean it will thrive in another. Like everything else in life, they look for niches.

…and when I talk about environment, I am thinking about everything from Infection Control, Antibiotic Stewardship, Public Health infrastructure, vaccination coverage, even population density.

I think as a microbiologist, using the expertise and experience that has been acquired, you get a feel about how an emerging disease would “cope” in your local environment.

Which leads us onto the major topic of the moment, Ebola. Ebola transmission is currently intense in Liberia, Sierra Leone & Guinea, but struggles to gain a foothold in other countries, despite the importation of sporadic cases.

I think NZ has an environment that Ebola would struggle to become endemic in, although as with other countries, we are always at risk of imported cases and even secondary infections, as experienced in the USA.

However that is not the whole story. Zoonotic micro-organisms, and particularly those ones that are relatively naive in the human host (such as Ebola), have the ability to adapt and change, and make fools of us all….


“Beware the trapdoors”

Experience can often count for quite a bit, it can allow you to avoid pitfalls and focus down on whether you can actually make a difference or not.

Take for example a seemingly simple scenario: a case of Campylobacter jejuni isolated from the stool sample of a hospitalised patient. New Zealand has a high incidence of Campylobacter infection so I would encounter this scenario once every couple of weeks.

This result reflexively makes me think of three trap doors I don’t want to fall through 

1) How long has the patient been in hospital for? Campylobacteriosis almost always has an incubation period of less than 7 days. If the patient has been in hospital for longer than this, think about hospital acquired infection. Get Infection Control to investigate further and look for other cases.

2) Get the Campylobacter result to the clinician quickly. Often campylobacteriosis presents with bloody diarrhoea, and often the laboratory result becomes available at just about the same time as the patient is getting teed up for invasive investigations such as a colonoscopy. During my career I have seen a few patients subjected to colonoscopy when a laboratory diagnosis of Campylobacter has been made but not communicated to the clinicians. Campylobacter results in hospitalised patients do not traditionally require a telephone call, but I generally tend to, in order to avoid this scenario.

3) Does this patient warrant treatment? Treatment for campylobacter gastroenteritis is generally of limited benefit and usually not indicated. However the fact that this patient is in hospital puts them straightaway at the more severe end of the scale. These patients are often immunocompromised or have had prolonged diarrhoea and to be honest my threshold for treating is fairly low. 

Campylobacter jejuni infection is generally not as exciting as some of its more extrovert siblings like Campylobacter fetus. However you still need to be careful. You could have a PhD in Campylobacter but unless you know where the trapdoors are you can still get caught.