Resistance to penicillin is usually due to Beta lactamase enzymes. Therefore adding a beta-lactamase inhibitor eg clavulanate (as found in co-amoxiclav) overcomes the resistance and extends the spectrum.
An alternative resistance mechanism however is production of defective Penicillin Binding Proteins – this is the mechanism of resistance in Pneumococci. Beta lactamase inhibitors therefore do not help.
Variable resistance seen; sometimes effective against penicillin resistant staphylococci including some MRSA, but poor activity against Haemophilus. Variable resistance seen in streptococcus, pneumococcus. Resistant mycoplasma are rare but do exist – try cipro, else tetracycline.
Using Azithromycin probably improves efficacy in Haemophilus (more active) but pneumococci that are resistant to erythromycin (approximately 5 to 20% of strains currently) will also be resistant to azithro, and no difference in in vitro activity between the newer and old macolides against other common respiratory pathogens.
In theory, you should use a combination of antibiotics (if possible) to treat a multiresistant organism, to prevent resistance developing (as in TB). However there is no good clinical data to support this, beyond TB treatment (which is slow growing, so probably different). On the contrary, meta-analyses demonstrate no difference in clinical outcomes between the two treatment strategies (for infections with Gram-negative bacteria), but there are well-documented increased toxicities with combination therapy.
Having said that, given the greater mortality associated with delays in appropriate and effective antimicrobial treatment, starting with combination therapy in critically ill patients seems sensible.
If there is poor response to treatment, rather than simply adding a second agent, consider:
- dose, frequency – are you achieving adequate time above MIC? Consider prolonged antibiotic infusion strategy
- route – give IV if not already
- duration – extended treatment course?
[doi: 10.1128/CMR.05041-11 Clin. Microbiol. Rev. July 2012 vol. 25 no. 3 450-470]