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When the D-test is key.

We recently saw a 4-month-old infant with a severe cellulitis that began as a tiny pacifier blister under his lower lip. Purulent exudate from the wound yielded methicillin-resistant Staphylococcus aureus that was erythromycin resistant but clindamycin susceptible.

Clindamycin was initiated intravenously, and a good clinical response was noted by day 2. He was sent home on day 3, where he continued the 10-day course of treatment. One month later, the infant was readmitted with clinical relapse of his infection. Wound culture again confirmed S. aureus. This time it was resistant to both erythromycin and clindamycin.

This child's course is remarkable for illustrating the importance of recognizing community acquisition of methicillin-resistant S. aureus (MRSA) and for highlighting the situation where inducible macrolide resistance can lead to clinical relapse.

This latest twist in the evolution of MRSA will impact the way you treat all staphylococcal infections in children.

Reports of infection caused by community-acquired MRSA proliferated in the last decade, and led us to conclude that clindamycin would be an ideal agent for a case such as ours. Now, however, before you prescribe clindamycin, it's critical to find out whether your local lab is using the "D-test'" and how it is reporting the results to you. A positive D-test means that the S. aureus strain, although initially susceptible to clindamycin, carries a gene that may mutate and induce resistance soon after the initiation of treatment.

The D-test involves placing a 2-mg clindamycin disk 15-26 mm apart from a 15-mg erythromycin disk on agar that has been inoculated with the S. aureus strain. The presence of the inducible macrolide lincosamide-streptogramin B resistance gene will result in a D-shaped blunting of the circular zone of inhibition surrounding the clindamycin disk, on the side facing the erythromycin disk. (See photo.)

Many clinical labs are now simply reporting D-test-positive strains as clindamycin resistant, but not all. Some have simply stopped reporting clindamycin susceptibility results altogether unless you ask for them specifically.

How often you're likely to encounter this phenomenon may depend on where you practice. In a recent study in Baltimore, 90 of 161 (56%) erythromycin-resistant / clindamycin-susceptible S. aureus strains isolated from children with surgical site infections were D-test-positive (Clin. Infect. Dis. 37[9]: 1257-60, 2003). In Chicago, D-tests were positive in 31 of 33 (94%) MRSA strains with the erythromycin-resistant/clindamycin-susceptible discrepancy (Pediatr. Infect. Dis. J. 21[6]:530-34, 2002).

Here in Kansas City, approximately one-third of our MRSA strains with the discrepancy have been D test-positive. Importantly, this phenomenon also can occur with methicillin-sensitive strains. In fact, in the Baltimore study, the rate was higher among the methicillin-susceptible isolates than among the methicillin-resistant strains (78% vs. 43%).

Based on what we know now, here's what I recommend: For simple skin infections in a well-appearing child, an antistaphyloccoca113lactam like cephalexin is fine. In cases of clinical failure, culture the wound. If S. aureus is identified and the organism is MRSA, check for the erythromycin / clindamycin susceptibility discordance and make sure your lab is doing the D-test. If it's positive, an alternative choice of therapy would be trimethoprim-sulfamethoxazole and rifampin. Clindamycin is still appropriate for D-test-negative MRSA strains.

It is not clear how often clinical relapse would occur if clindamycin were used in cases with inducible resistance, but I would advise against it for serious infections. Intravenous vancomycin is the drug of choice for serious invasive staphylococcal infections, pending culture results.

The newer antistaphylococcal agent linezolid also may play a role, but it's very expensive--in the ballpark of $1,000 for a full 10-day treatment. Still, we did use it in our 4-month-old after he had completed 4 days of intravenous vancomycin, as it was still cheaper than keeping him in the hospital.

Interestingly, this isn't really new. It was actually described in 1969 in a paper entitled "Erythromycin-Inducible Resistance in Staphylococcus aureus: Survey of Antibiotic Classes Involved" (J. Bacteriol. 98[2]:447-52, 1969). The entire text of the article is available free online.

And it isn't the end. Both vancomycin intermediate-susceptible and vancomycin- resistant S. aureus strains have been reported in the United States, and more are likely to be forthcoming.

DR. MARY ANNE JACKSON is chief of pediatric infectious diseases at Children's Mercy Hospital, Kansas City, and professor of pediatrics at the University of Missouri-Kansas City.
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Title Annotation:ID Consult
Author:Jackson, Mary Anne
Publication:Pediatric News
Geographic Code:1USA
Date:Apr 1, 2004
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