Mohamed contacted me through the website and asked “what is the clinical benefit of cidal versus static antibiotics?” It’s a great question, and one which often causes confusion.
In order to know when you shouldn’t use a static antibiotic and why a static antibiotic might fail you need to know which antibiotics are static and which are cidal. This information is available deep within 1000s of pages of reference texts like Mandell or Kucers! Alternatively it is easily accessible in Microbiology Nuts and Bolts clearly under each antibiotic and there are only 310 pages in our little book :-) P.S. you can buy it here
A bactericidal (“cidal”) antibiotic is one that kills bacteria without reliance on the patient’s immune system to help. A bacteriostatic (“static”) antibiotic is one that prevents the organism multiplying but it is the patient’s own immune system which kills off the bacteria and leads to recovery from the infection. So why does this matter?
In these specific scenarios either there is insufficient time for a static antibiotic to work before permanent damage occurs or the patient dies, or the patient does not have a properly functioning immune system to work with a static antibiotic. These scenarios include:
- Sepsis – the infection has become severe despite a functioning immune system and is so aggressive that the patient will die before a static antibiotic is able to help
- Meningitis and encephalitis – the infection will cause death or irreversible brain damage before a static antibiotic will help
- Endocarditis – the infection is in a site where the patient’s own immune system is unable to deal with the bacteria and therefore a static antibiotic won’t eliminate the bacteria as it is working alone
- Primary and secondary immunodeficiency – the patient doesn’t have a properly functioning immune system to work with a static antibiotic e.g. febrile neutropaenia
You should never use a static antibiotic in these clinical scenarios, you should always use cidal antibiotics.
Cidal antibiotics are:
- Beta-lactams e.g. penicillins, cephalosporins and carbapenems
- Macrolides e.g. Erythromycin, Clarithromycin
- Lincosamides e.g. Clindamycin
- Aminoglycosides e.g. Gentamicin
- Quinolones e.g. Ciprofloxacin
- Glycopeptides e.g. Teicoplanin, Vancomycin
These antibiotics are the mainstay of treatment for most infections in hospital. They work in severe infections and immunodeficiency. Hospital patients with infections are usually there because their infection is severe or their own immune system is unable to deal with the infection without help, so cidal antibiotics are the most appropriate.
Why have static then?
Static antibiotics still have a value, they still treat infections and sometimes there is not always something better; they can be the best treatment available. Why is this? Because they can target a specific bacterium or at least provide some cover when no other antibiotic will work.
If a patient in the community has MRSA they may be prescribed Doxycycline even though this is static. As the patient is not too sick their immune system can help eradicate the bacteria. Added to this is that it is an oral preparation; if a cidal antibiotic was used, e.g. Teicoplanin, the patient would have to be admitted to hospital for IVs. This exposes the patient to additional risk of hospital acquired infection and worse side effects let alone an increased cost. Is there no other cidal antibiotic which is oral in this situation? Well...not exactly...you may come across the odd MRSA which tests sensitive to erythromycin or ciprofloxacin but the majority are resistant to these cidal antibiotics and it would be unwise to choose them empirically.
Whilst static antibiotics do not kill bacteria they still have their uses. Doxycycline is really useful for treating skin and soft tissue infections and pneumonia, especially in primary care, and Tigecycline is a good antibiotic for resistant Gram-positive bacteria such as Glycopeptide resistant enterococci (GRE). The main clinical drawback to using static antibiotics in hospitals is they are not as effective in very unwell patients, they may however be used in combination with cidal antibiotics when there is no other choice.
Static antibiotics are:
- Tetracyclines e.g. Doxycycline
- Glycylcyclines e.g. Tigecycline
- Sulphonamides e.g. Sulphamethoxazole
- Fusidic acid
So let’s muddle it up...and see how confusion occurs:
- What we commonly consider to be cidal antibiotics are actually static at lower concentrations
- A small number of antibiotics are cidal against some bacteria but static against others!
Cidal antibiotics are only cidal if enough of the antibiotic is given; at low levels or doses they are actually static. For example low levels might inadvertently occur if inadequate doses are used to treat patients (e.g. an incorrect low dose or missing doses etc). I am also becoming increasingly concerned about the impact of obesity on our ability to achieve cidal antibiotic levels in these patients and I wonder if normal dosing in these large body masses is actually producing low levels and therefore only providing bacteriostatic therapy.
For the cidal antibiotics we sometimes measure their effectiveness in the laboratory using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). If the MIC or MBC was always the same for any given combination and bacteria we wouldn’t need to measure it. However “Joe Blogg’s” and “Paul Smith’s” S. aureus will have different MICs and MBCs with Flucloxacillin. The MIC and MBC are specific to each antibiotic and the bacterium it is tested against. For more about the difference between MIC and MBC see the website Microbiology Nuts & Bolts Testing Antibiotic Resistance. Traditionally we haven’t worried too much about MIC and MBC as the original work in the 1940s-1960s on these antibiotics showed we could easily reach cidal levels with normal dosing regimens. However, obesity may change this.
So we have established that some antibiotics can be static or cidal depending on the concentration of antibiotic but added to this is that some antibiotics can be either cidal or static depending upon which bacteria you are treating. Confused? Let me elaborate…
These mixed cidal and static antibiotics are unusual in that they are cidal against certain bacterial species but static against other bacterial species. It is the combination of antibiotic and bacteria that is important (e.g. antibiotic + bacteria A = antibiotic is cidal, antibiotic + bacteria B = antibiotic is static, antibiotic + bacteria C = antibiotic is cidal etc).
The group of antibiotics that are cidal against some bacteria but static against others include:
Let’s look at two situations:
- Chloramphenicol is second line therapy for meningitis in patients with a history of severe allergy to beta-lactams. It is cidal against the common causes of meningitis, Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae; however it is static against all other bacterial species. It is a good choice for the severe infection meningitis as we want to kill off the bacteria quickly and without the need for the patient’s immune response to act. It may be used as a static agent in non-severe pneumonia where the patient has time to launch their own response.
- Linezolid is usually used as static antibiotic against infections caused by Gram-positive bacteria such as MRSA and GRE. However it is actually cidal against streptococci e.g. Streptococcus pneumoniae. NB It has no activity against Gram-negative bacteria.
So back to Mohamed’s original question; what is the clinical benefit of cidal versus static antibiotics? The simple answer is cidal antibiotics are of benefit when treating severe infections or infections in patients with immunodeficiency, but as I’ve explained it’s not always as simple as we would like.
Great question! Thanks Mohamed. If you have a question about something to do with microbiology that you think would make a good blog let me know, I’m always on the lookout for new topics.