“My understanding has always been that Gentamicin provides mainly Gram-negative cover with some Gram-positive cover (Staphylococcus spp., Streptococcus spp. and maybe Enterococcus spp.) and better Gram-positive cover is provided when combined with a beta-lactam or glycopeptide. I've recently been told that the combination of Aztreonam, Gentamicin and Metronidazole provides a similar cover to Amoxicillin, Gentamicin and Metronidazole which is what we recommend for intra-abdominal infections. What are suitable penicillin alternatives for intra-abdominal infections?”
- What is the spectrum of activity of Gentamicin?
- Is the combination of Aztreonam, Gentamicin and Metronidazole equivalent to Amoxicillin, Gentamicin and Metronidazole for intra-abdominal infections?
- What are suitable penicillin-free alternatives to Amoxicillin, Gentamicin and Metronidazole?
In order to answer these questions effectively it is first necessary to understand the bacteria involved in intra-abdominal infections. Most intra-abdominal infections are endogenous, they occur when the patient’s normal bowel flora leaks out of their bowel and into the normally sterile peritoneum or surrounding tissues. The normal flora of the bowel includes:
- Anaerobes, either Gram-positive or Gram-negative
- Enterobacteriaceae (e.g. E. coli, Klebsiella spp., Enterobacter spp.), Gram-negative
- Enterococcus spp., Gram-positive
- Streptococcus spp. (e.g. Streptococcus anginosus group), Gram-positive
Therefore any antibiotic or combination of antibiotics used to treat intra-abdominal infections has to cover the normal flora of the bowel.
So will Gentamicin cover these?
Gentamicin is an aminoglycoside antibiotic which works by interfering with mRNA translation at the ribosome thereby preventing protein synthesis.
Gentamicin has excellent bactericidal activity against Gram-negative bacilli including the Enterobacteriaceae (e.g. E. coli, Klebsiella spp., Enterobacter spp.) as well as Pseudomonas spp. but unfortunately it’s Gram-positive activity is limited to Staphylococcus spp. In the context of an intra-abdominal infection, Gentamicin should only be used to cover the Gram-negative bacteria; as it has no activity against the anaerobes (even the Gram-negative ones) or the Gram-positive bacteria present. Using Gentamicin alone would still leave the Streptococcus spp., Enterococcus spp. and the anaerobes to continue to cause havoc. Therefore Gentamicin has to be combined with other antibiotics for the treatment of intra-abdominal infections.
Some of the confusion about the spectrum of activity of Gentamicin occurs because there are times when Gentamicin is added to another antibiotic in order to provide more activity against Enterococcus spp. and Streptococcus spp. (which it is not actually active against!). What, I hear you cry!?! The most common situation where this occurs is in the treatment of infective endocarditis. But the important point is that the Gentamicin is being added to an antibiotic which already has excellent activity against these bacteria e.g. Benzylpenicillin, Amoxicillin, Teicoplanin and Vancomycin. Although Gentamicin on its own is not active, after the penicillin or glycopeptide has damaged the cell wall the Gentamicin is then able to enter the bacterium and act on the ribosome. The combination of a cell wall active agent and Gentamicin provides synergy; the combination of the two antibiotics is more active than either antibiotic alone. Clever hey! Well I think so.
Is the combination of Aztreonam, Gentamicin and Metronidazole equivalent to Amoxicillin, Gentamicin and Metronidazole for intra-abdominal infections?
Essentially the question is are Aztreonam and Amoxicillin equivalent as in both regimens the patient is on Gentamicin and Metronidazole (an anti-anaerobic antibiotic).
Amoxicillin has excellent bactericidal activity against Streptococcus spp., most Enterococcus spp., and most E. coli and some anaerobes. It is an ideal antibiotic to use with Gentamicin and Metronidazole for the treatment of intra-abdominal infections.
So what about Aztreonam? Aztreonam is only active against Gram-negative bacteria such as the Enterobacteriaceae and Pseudomonas spp. In fact it’s spectrum of activity tends to overlap with Gentamicin. It doesn’t provide any additional benefit to using Gentamicin alone; the Gram-positive bacteria are still not covered in intra-abdominal infections. The combination of Aztreonam, Gentamicin and Metronidazole is therefore not suitable for intra-abdominal infections. Aztreonam only tends to be used for the treatment of Pseudomonas spp. in cystic fibrosis patients, usually in other infections there are more suitable antibiotics.
What are suitable penicillin-free alternatives to Amoxicillin, Gentamicin and Metronidazole?
So what do you use to treat an intra-abdominal infection instead of Amoxicillin when a patient has a severe beta-lactam allergy? Probably the most commonly used antibiotics to replace Amoxicillin are the glycopeptides e.g. Teicoplanin or Vancomycin. These antibiotics only have Gram-positive activity but that’s fine in this situation as the Gentamicin will deal with the Gram-negatives. Many hospitals prefer to use Teicoplanin over Vancomycin on the basis that it is less nephrotoxic and at normal therapeutic doses you do not need to monitor serum antibiotic levels of Teicoplanin.
However there are a number of alternative antibiotics that could also be used instead of amoxicillin. The table below (taken from the book) can be used to identify what antibiotics are active against each bacterium e.g. follow the column down from the bacterium name Enterococcus spp. to see what would be active. The table shows the potential alternatives to Amoxicillin or Teicoplanin or Vancomycin are:
My own order of preference is below with the reasons why I would use it over the next antibiotic in the list:
- Tigecycline (less interactions or serious potential side-effects than Linezolid, also has some Gram-negative activity which may be of extra benefit)
- Linezolid (better tolerated by patients in my experience than Daptomycin)
- Daptomycin (I have more experience with this antibiotic than Fosfomycin)
- Fosfomycin (I have never used it in this situation therefore I would come to it last!)
In summary the choice of antibiotic for intra-abdominal infections has to cover the common microorganisms causing that type of infection: Gram-positive, Gram-negative and anaerobic bacteria. This usually requires a combination of antibiotics.
So in order to answer the specific questions:
- YES - Gentamicin provides mainly Gram-negative cover and is also active against Gram-positive Staphylococcus spp., but NOT Streptococcus spp. or Enterococcus spp.
- YES - Gram-positive cover is provided when Gentamicin is combined with a beta-lactam or glycopeptide
- NO - Aztreonam, Gentamicin and Metronidazole does NOT provide a similar cover to Amoxicillin, Gentamicin and Metronidazole
- Amoxicillin, Gentamicin and Metronidazole is a good combination for intra-abdominal infections
- You can use the table to find all suitable penicillin alternatives
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