aerobic bacterium, can be very difficult to treat because they are often resistant to a number of antibiotics (see earlier blog). Let me illustrate with a recent patient of mine...
The patient initially responded to the treatment but nearly two weeks after starting the Meropenem the osteomyelitis got worse and a further operative washout was performed. These samples also grew a P. aeruginosa but this time it was resistant to Meropenem and sensitive to Piptazobactam, Ceftazidime, Ciprofloxacin and Gentamicin. Weird huh!?
The Meropenem was stopped and Piptazobactam was started instead.
After a further two weeks, having shown another initial
response, the patient deteriorated again. Superficial samples continued to grow a P. aeruginosa but it is now resistant to Piptazobactam and sensitive to Meropenem again. Sound familiar? Argh, what’s going on!! The team rang the microbiologist for advice; they think there must be two bacteria and want an antibiotic to treat both. So what does the Microbiologist do? Are there really two bacteria?
The problem isn’t that there are two bacteria, the problem is
that there is one bacterium which is switching on and off resistance depending upon which antibiotic the patient is given. This is often given as a trick question in microbiology exams (Registrars take note!).
How do Microbiologists know this will happen? To my knowledge P. aeruginosa is one of only a few bacteria that use such a fluctuating and complex arsenal of resistance
mechanisms against antibiotics.
Like a castle there is more than one method of defence: the moat, the portcullis and the unscalable walls.
The bacterium could be employing one of two mechanisms of resistance, involving reduced entry of the antibiotic into the bacterium through the loss of a porin (holes) in the cell membrane PLUS one of the following:
- Over expression of a chromosomal AmpC enzyme which breaks down the small amount of antibiotic which does manage to enter the cell
- A multi-efflux pump which removes any antibiotic
which manages to enter the cell
Beta-lactams tested will be active against this bacterium. Knowing that this bacterium has this ability to change its sensitivity pattern means that resistance is predictable from the first isolate, even though the bacterium appeared sensitive in the laboratory.
In order to treat this patient it is necessary to use different
classes of antibiotics and preferably a combination of two which prevent P. aeruginosa becoming resistant because it cannot fight off both forms of attack, one antibiotic will usually succeed.
In this case a combination of Ciprofloxacin and Gentamicin were chosen, but it is important to continue to monitor the sensitivity patterns. If the sensitivity pattern shows resistance to Ciprofloxacin, the bacterium is using a multi-efflux pump. The antibiotic will need changing to Colistin;
however this is not given initially as it is nephrotoxic. Remember: few anti-pseudomonal antibiotics exist.
P. aeruginosa is described as being “competent” due to its ability to develop new mechanisms of resistance through the acquisition of additional genetic material. This in addition to its inherent resistance to antibiotics makes P. aeruginosa infections very difficult to treat.