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September 13th, 2013

Clindamycin vs. TMP/SMX for Soft Tissue Infections: A Clinical Trial That Needs Some Marketing

What is this tree doing in this light bulb?At ICAAC this week — the ID conference with the most inscrutable acronym out there — Loren Miller from UCLA presented a clinical trial on treatment of skin and soft tissue infections that has widespread clinical applications, yet may receive little if any attention.

And why is that?

Simply because the drugs (clindamycin and trimethoprim/sulfamethoxazole) have been off-patent for years. Cripes, they’re so cheap that some pharmacies give them away. That’s right — they’re free!

So allow me to market the study a bit.

Here’s the clinical question:

Which is better for uncomplicated skin and soft tissue infections — clindamycin or TMP/SMX?

Clearly the best way to get the answer is to do a randomized, double-blind trial, which is what we have here: Eligible subjects had a skin infection (abscess and/or cellulitis), were not systemically ill, diabetic, or needing hospitalization. If abscesses were present, they were drained.

Participants were then randomized to clindamycin 300 mg three-times daily or TMP/SMX 1 DS tablet twice daily for 10 days, along with matching placebos.  (Note:  Meets length of therapy rules.)

524 study subjects enrolled at 4 US sites; they had a mean age of 27, with 30% younger than 13. 45% had purulent drainage, and virtually all had I and D as part of their management; the remainder had cellulitis alone. Among those who had cultures, more than half had MRSA; 14% of the Staph aureus isolates had resistance to clindamycin.

14 days after enrollment, 80% of the clinda and 78% of the TMP/SMX group were cured. (About half of the “failures” were really loss to follow-up.) Diarrhea was more common in the clindamycin arm; there were no cases of C diff, and no severe rashes to TMP/SMX.

So to conclude, they’re basically the same.

How to choose? Here are some pros and cons.

  • Clindamycin is famously good for beta strep, and active against most (but not all) Staph aureus, including MRSA. But, there’s that diarrhea nastiness, with or without C diff.
  • TMP-SMX is active against virtually all Staph aureus, but whether it’s a beta-strep drug depends on whom you ask (many think it isn’t). And of course, it rarely can cause severe rashes and systemic hypersensitivity reactions.

One possible explanation for the near-equal outcomes is that the two treatments failed in different ways — the clindamycin versus resistant staph, and the TMP/SMX for the strep. Since most would get better with no antibiotics anyway (especially those with drained abscesses), these small differences offset each other.

And some might quibble at the dosing of the TMP/SMX — I’ve heard an awful lot of people say with confidence that the right dose for cellulitis is 2 DS tablets twice daily, though far as I know there are no data confirming this (surprisingly) strongly held opinion.

Regardless, kudos to the investigators for getting this study done. It may not yield a glossy advertisement in a medical journal, but undoubtedly will be very useful, cited by numerous primary care, ID, and emergency room providers all over the world.

16 Responses to “Clindamycin vs. TMP/SMX for Soft Tissue Infections: A Clinical Trial That Needs Some Marketing”

  1. Josh says:

    See Bowen et al (http://www.ncbi.nlm.nih.gov/pubmed/23052313) for an interesting perspective on the mantra that TMP-SMX doesn’t treat strep…

  2. Sali says:

    Very good news for Primary Care in my part of the world where cost is a big factor. We use TMP-SMX a great deal in the treatment of UTI, 2 tablets twice daily for 3 days and I find better compliance in patients compared to Amoxycillin 500mg po TDS for 5days. The only drawback is the risk of hemolysis to patients with G6PD deficiency which is slightly more prevalent here.

  3. Gilbert vergara says:

    Clindamcin is very effective againsta MRSA especially community acquired, we must always cinsider CDI After treatment. What i would like to point out as a microbiologist we must always think the most common pathogen causing the skin infection. Most of my colleagues would agree that majority of skin infections are caused by members of the Staphylococcus family wether MRSA or MSSA or even coagulase negative Staph. So co-trimoxazole is ok as a primary drug for skin infections. Clindamycin on the other hand must be reserved in case of MRSA isolate resistant to co-trimoxazole

  4. RL says:

    Dear Dr. Sax,

    Could the results of the study be a signal that in a population without diabetes that is not systemicly ill and does not require hospitalization with a SSTI > 5cm I&D is enough? I understand that this is not what the study aimed for given that there was no placebo arm which I do not know if it is feasible/ethical given that the current recommendations are to treat if antibiotics if the lesion is > 5cm. I just wonder….

  5. Loretta S says:

    I had read about this study last week and it basically confirmed what I normally do in practice for patients who fit the study group profile. I tend to avoid clindamycin because of the diarrhea side effect. Good to get some solid evidence supporting TMP-SMX as Tx for skin infections. I don’t use 2 DS tabs BID, mainly because there isn’t good evidence to support it, as Paul notes. I did, however, recently have a patient develop an all-over body rash on Day 10 of TMP-SMX therapy (1 DS tab BID). She was not happy that I insisted on seeing the rash. No S-J Syndrome, thank goodness. But she sure was miserable for a few days.

  6. Abigail says:

    Clindamycin is most certainly NOT cheap. Even in generic form, it can cost my patients $50-$150 dollars for treatment, when paying out-of-pocket. Hence, they are not equivalents. My ED uses Bactrim almost exclusively, reserving Clinda for Sulfa allergies or failures.

  7. Paul Sax says:

    >>Clindamycin is most certainly NOT cheap.

    Abigail, good point, it’s generally more than TMP/SMX. But it’s still 10-20 fold less than linezolid!

    Paul

  8. Thomas J Rush says:

    Where’s the placebo arm? The treatment for MRSA boils or abscesses is drainage and, in most cases antibiotics add nothing. No wonder the two drugs are the same!!

  9. Barry Smith says:

    I’m both a research scientist (neurophysiological aspects of cardiovascular physiology and related topics) and a CLL patient with a recent skin infection. I agree with others that the Miller et al. study is an important first double-blind trial in this area. I would also hope that the Miller group and others will replicate and extend this investigation. I think it would be important to add a placebo arm to obtain data on treatment-free remission. In addition, topical treatments, such as clindamycin gel and mupirocin, appear to be effective in some cases, and I think it might be important to study topical vs. systemic approaches.. Finally, dose-response studies may also be needed. For example, I developed the skin infection in the context of ongoing prophylaxis with Bactrim DS (b.i.d on MWF). This suggests that a higher dose is needed (and routinely used) once an infection develops, but we need more data to determine minimum effective dose.

  10. Ryan says:

    Abigail, not sure where you are located, but Costco online prescription checker has Clindamycin 150 mg capsules #100 as costing $22.55. #100 of Bactrim DS is $11.35. Certainly cheaper, but I have no idea how anybody could be charging $50-150 for a course of therapy of clindamycin.

  11. Martin Smukler says:

    Clindamycin 300 mg is the expensive form. The 150 mg is much cheaper. Also exercise caution prescribing high dose TMP/SMX. There is a risk of hyperkalemia esp. with renal insufficiency and ACEI, ARB, K sparing diuretics, etc.

  12. Ryan says:

    #100 of the 300 mg clindamycin is $66, just as a FYI.

  13. Dr n says:

    is tmpsmx bacteriocidal or static?
    i beleive clinda is bacteriostatic,
    how does this affect us clinically?

  14. BJ says:

    clindamycin 150 mg is a $4 antibiotic in many places.

  15. Dr. H says:

    Is there a website or phone app that compares prices for drugs by pharmacy?

  16. Jonathan says:

    I have not seen the study, but from Paul’s description, it combined purulent and nonpurulent cellulitis. Another recent study showed that for nonpurulent cellulitis, adding TMP/SMZ to cephalexin did not have a benefit. That is not surprising, since most nonpurulent cellulitis is not due to MRSA. Most patients with nonpurulent cellulitis who fail to respond to cephalexin seem to respond to IV cefazolin (and time, and elevation). I am curious to see if there was a subgroup analysis of the purulent vs nonpurulent cases. It would also be interesting to see if clindamycin resistance predicted clindamycin failure, but there probably were not enough cases for that. Anyway, for nonpurulent cellulitis, I would consider both of these drugs second-line to a beta-lactam. I look forward to publication of the trial.

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HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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Infectious Diseases

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