This is a Staphyococcus aureus isolate from a patient presenting with cellulitis.

The disc on the left contains erythromycin (a macrolide) and the disc on the right contains clindamycin (a lincosamide)

1) What phenomenen is shown here?

This is a D-zone showing that the erythromycin has induced the Staph. aureus to be resistant to clindamycin

2) What is the molecular basis of this phenomenen?

Mediated by the erm gene, which codes for a methylase enzyme which alters the antibiotic binding site for the following three antibiotic groups: macrolides, lincosamides and group B streptogrammins.

When the erm gene expression is constitutive (always turned on), the bacteria will be resistant phenotypically to the three closely related classes of antibiotics; Macrolides (including erythromycin), lincosamides (including clindamycin), and Group B streptogrammins).

When the erm gene expression is inducible (present with potential to be turned on), then the phenotype shows macrolide (including erythromycin) resistance but susceptibility to lincosamides (including clindamycin) and Group B streptogrammins. The resistance can then be induced by demonstrating the D zone as above.

The phenotype produced on the plate as above is sometimes thus referred to as the iMLSB phenotype.

If the phenotype shows erythromycin resistance but clindamycin susceptibility which is not inducible then the resistance mechanism is likely to be mediated through genes coding for efflux pumps such as msrA

3) What bacterial species can this phenomenen be present in?

Can be present in all types of streptococci and staphylococci. However clearly more clinically relevant in bacteria which are more commonly pathogenic to humans such as Staphylococcus aureus, beta-haemolytic streptococci and Streptococcus pneumoniae.

4) What implications does this have for treatment of the patient?

The literature has described successful treatment with clindamycin, infections caused by Staphylococcus aureus strains that produce the iMLSB phenotype. It has also described not surprisingly treatment failures.

CLSI recommends that isolates showing the iMLSB phenotype be reported resistant to clindamycin, due to the potential for in-vivo resistance to develop due to erm gene induction.

I personally don’t write off clindamycin completely in this situation, particularly if the patient is doing well or there are limited other options.

 

All this takes a bit of digestion! It is explained in a bit more detail in the following article, which takes about 10 minutes to read through.