What Does Inducible Clindamycin Resistance Mean for a Culture?
Inducible clindamycin resistance means the bacteria appear susceptible to clindamycin on standard testing but will develop resistance during treatment, leading to therapeutic failure—therefore, clindamycin should NOT be used for these isolates. 1
Mechanism of Resistance
Inducible clindamycin resistance occurs when bacteria are resistant to erythromycin but appear susceptible to clindamycin on routine susceptibility testing. 1
The bacteria carry genes (typically erm genes) that can be "turned on" by exposure to macrolides like erythromycin, causing the bacteria to produce enzymes that modify the ribosomal binding site, conferring resistance to clindamycin during therapy. 2
This is called inducible macrolide-lincosamide-streptogramin B (MLSBi) resistance. 3, 4
Detection: The D-Test
The double-disk diffusion test (D-test) is the standard method to detect inducible clindamycin resistance. 1
The test involves placing erythromycin and clindamycin disks 15-21 mm apart on an agar plate. 1
A positive D-test (D-zone positive) shows a flattening of the clindamycin zone of inhibition adjacent to the erythromycin disk, creating a characteristic "D" shape. 1
According to CDC guidelines, laboratories must perform D-zone testing for all isolates that are erythromycin-resistant and clindamycin-susceptible, particularly for Group B Streptococcus in penicillin-allergic patients. 1
Clinical Significance
When Inducible Resistance is Detected:
If the D-test is positive (inducible resistance detected), clindamycin MUST NOT be used for treatment, as it will fail clinically. 1
For penicillin-allergic patients at high risk for anaphylaxis with GBS infections showing inducible clindamycin resistance, vancomycin should be used instead. 1
Prevalence Considerations:
Inducible clindamycin resistance is common in MRSA, with rates ranging from 20-63% depending on the population studied. 3, 5
Hospital-associated MRSA (HA-MRSA) has higher rates of inducible resistance compared to community-associated MRSA (CA-MRSA). 4
Coagulase-negative staphylococci show even higher rates of inducible resistance (34.3%) compared to S. aureus (7.1%). 6
Treatment Implications
For Staphylococcal Infections:
Clindamycin can only be used if the isolate is susceptible to BOTH clindamycin AND erythromycin, OR if it is clindamycin-susceptible, erythromycin-resistant, but D-test NEGATIVE. 1
Approximately 50% of MRSA strains may have inducible or constitutive clindamycin resistance, making susceptibility testing critical. 7
For Group B Streptococcus:
In penicillin-allergic pregnant women, clindamycin may be used if the isolate is sensitive to clindamycin but resistant to erythromycin ONLY when the D-test is negative. 1
If inducible resistance is present, vancomycin becomes the alternative agent. 1
Common Pitfalls
Standard broth microdilution testing may miss inducible resistance, making the D-test essential for accurate detection. 1
Using clindamycin without performing the D-test in erythromycin-resistant, clindamycin-susceptible isolates risks treatment failure. 3, 8
Some laboratories may not routinely perform D-testing—clinicians must specifically request antimicrobial susceptibility testing with D-test for penicillin-allergic patients. 1
The inter-disk distance matters: using 15 mm edge-to-edge distance detects 14% more inducible resistance cases than the standard 21 mm distance. 5