Tag Archives: carbapenems

“Carbapenem Conundrums”

Antimicrobial Resistance, Antimicrobial Stewardship, The Science of Microbiology,

Last week, while on-call I recommended a carbapenem for three different patients within the space of 30 minutes. Yes, it happens sometimes! Most empiric antibiotic choices do not require the inclusion of a carbapenem, but key factors to consider are ESBL history, travel or hospitalisation in areas with high ESBL endemicity, and how sick the patient is.

It is interesting to look at the psychology of carbapenem prescribing. Some doctors prescribe carbapenems because they are afraid of giving treatment to their patients that might not cover all resistance profiles. Others are afraid of prescribing carbapenems because they are traditionally the top line treatment and scared of criticism from antimicrobial stewards like myself!

But if you have to use a carbapenem, which one should you use?

The main choice in New Zealand is generally between meropenem and ertapenem. Imipenem-cilastatin is rarely used now in New Zealand, mainly due to its seizure risk. (There is a little evidence that it is the optimal carbapenem for disseminated nocardiosis and a few other isoteric indications) Other carbapenems outside these three have limited availability in NZ hospitals, or at least the ones I work in. This may be different elsewhere in the world.

Choosing between meropenem and ertapenem:

Here are most of the key factors I take into account when choosing between the two

Organism coverage-If I need to empirically cover Pseudomonas or Enterococci or Acinetobacter spp., then meropenem is a better option than ertapenem due to its broader coverage.

CNS penetration-Meropenem is a better option than ertapenem due to better CNS penetration. I had a patient with E.coli meningitis recently who required meropenem until the susceptibilities were known.

Hypo-albuminaemia– Ertapenem is highly protein bound compared to meropenem, so in hypo-albuminaemic states, the free fraction of ertapenem is increased, and it is chucked out through the kidneys leading to a decreased half-life. Therefore, meropenem is preferred in hypo-albuminemia. I use 25 g/l as an arbitrary cut-off.

Dosing frequency– If reduced dosing frequency is preferred due to patient compliance/outpatient therapy etc, then once daily ertapenem is preferable to three times a day meropenem.

Penetration into biliary tissue-Ertapenem has poor penetration into biliary tissue compared to meropenem, so I prefer meropenem for biliary infections.

Duration of treatment- Meropenem is more stable than ertapenem against resistance mechanisms such as upregulation of efflux pumps or porin channel loss. These mechanisms can become an issue with prolonged treatment and should be taken into account when choosing between the two.

Although the above points might suggest otherwise, I actually recommend more ertapenem than meropenem. Ertapenem is absolutely fine for most straightforward cases of urosepsis where empiric ESBL coverage is required.

One other point. If you do need to utilise a carbapenem, then regular review and timely de-escalation based on the patient’s condition and/or susceptibility results is important to optimise antimicrobial stewardship.

Michael

“Too much knowledge…”

The Science of Microbiology, ,

shutterstock_knowledge

A little bit of knowledge can be a bad thing. So can too much…

The acronym  ESCHAPPM ( or something similar) will be familiar to most microbiologists. (a similar acronym SPICE, is sometimes used instead)

  • Enterobacter spp.
  • Serratia spp.
  • Citrobacter freundii
  • Hafnia spp.
  • Aeromonas spp.
  • Proteus spp.
  • Providencia spp.
  • Morganella morganii

Because we are clever microbiologists, we know this group of organisms may have inducible beta-lactamase activity, and we advise the clinicians of this, often provoking a reflex switch in anti-microbial therapy to carbapenems. Not only clinicians, but there are plenty of ID physicians who make this automatic transfer to carbapenems the moment the word ESCHAPPM is mentioned, my hospital included.

The thing is however, do all patients with infections by an ESCHAPPM organism require a carbapenem?

Almost certainly not…

If we use a carbapenem for every infection due to one of these organisms, then this amounts to a significant amount of carbapenems. This is therefore an important an important antimicrobial stewardship issue. We are supposed to be trying to decrease the use of broad spectrum antibiotics, not increase them.

But we have read the textbooks, and we are clever…

And yet, if we look at the literature, there is very little evidence to support the theoretical dangers of using a beta-lactam in such patients. In fact, there are several small studies out there that support the non-inferiority of beta-lactams in such patients, particularly in non-life threatening illnesses.

Not to mention there are other options out there, fluoroquinolones, sulphonamides, etc.

We are simply scared.

Here is what I generally do (rightly or wrongly):

  • In a patient with bacteraemia due to an ESCHAPPM organism, as long as they are clinically improving I am happy to continue therapy based on the phenotypic susceptibility results.
  • In patients with UTIs due to ESCHAPPM organisms, even if in hospital, I feel no need  whatsoever to move to carbapenems.
  • I reserve carbapenem use in “ESCHAPPM” patients to bacteraemic patients who are getting worse, and also for patients with chronic infections, e.g. prosthetic joint infection, on the rationale that the longer the treatment, the more chance you have of getting clinically relevant inducible beta-lactamase activity.

We need to take a more pragmatic approach to ESCHAPPM organisms and their treatment. We also need larger scale trials so we can be more confident in our decisions and adopt such approaches into guidelines.

and we need to be brave…

Michael

“Carbapenemases: As old as the Hills..”

History of Microbiology, The Science of Microbiology, , ,

There has been a lot in the press recently about carbapenem resistant enterobacteraciae (CRE).

As people with a professional interest in infection, it is important we know in detail the origins of carbapenems and carbapenemases. Such knowledge and understanding also focuses the mind when trying to control them.

"Meropenem molecule"
“Meropenem molecule”

Carbapenems are derived from Thienamycin, a naturally occuring substance found in Streptomyces cattleya, which is a bacteria found commonly in soil in the environment. Other bacteria residing close to these carbapenem like substances in the environment thus have to protect themselves to avoid being destroyed. Thus carbapenemases evolved in other environmental bacteria such as Bacillus cereus, Bacillus anthracis and Shewanella, amongst others.

What we have done is take these naturally occuring compounds, purified them (with only very minor modifications), concentrated them and started administering them to humans in the form of carbapenem antibiotics, thus ramping up the selection pressure on the human bacterial flora.

It is thus not surprising that human enterobacteraciae, faced with this selection pressure have decided that they want defences against carbapenems, and have “acquired” the resistance genes from the environmental bacteria, most likely by transfer on mobile genetic elements.

Many people still perceive carbapenemases as being a relatively new phenomenen. We know that they are not new however. Both carbapenems and carbapenemases have probably been around for millions of years. We have just moved the battle between carbapenems and carbapenemases from the “hills” into the human flora, where it really matters….

Michael

Off camping this weekend!, I will write a short article next week sometime on “protecting the carbapenems”.