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Adverse events increased among children treated with TMP-SMX for SSTI
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Adverse events associated with trimethoprim-sulfamethoxazole use is becoming more commonplace as the mediation is more frequently used to treat skin and soft tissue infection in children, according to the findings in a report published online.
Jennifer L. Goldman, MD, of the University of Missouri, and colleagues reported on data from a retrospective chart review that analyzed adverse events in children in one hospital and compared them with children who were recorded in the Pediatric Health Information System database.
The number of TMP-SMX adverse events climbed at one hospital from five cases between 2000 and 2004 to 104 cases from 2005 to 2009, and about 60% of these patients were being treated for a skin and soft tissue infection (SSTI).
The researchers reported a similar finding nationwide, with adverse events related to TMP-SMX doubling between 2004 and 2009 from five patients per 100,000 admissions to 13 per 100,000 admissions.
Because there are relatively few oral options for the empirical treatment of SSTIs caused by methicillin-resistant Staphylococcus aureus in the outpatient setting (clindamycin, TMP-SMX, tetracycline, and linezolid), coupled with the increasing rate of clindamycin resistance reported in areas of the United States, treatment with TMP-SMX is likely, according to the study authors, adding that clinicians must be more vigilant for adverse drug reactions associated with TMP-SMX.
“A 20-fold increase in observed adverse drug reactions to TMP-SMX was not totally unexpected and was driven by the increase usage in the era of MRSA,” Goldman told Infectious Diseases in Children. “This is a reminder that all medications have an associated risk and potential adverse drug reactions must be considered and discussed with patients. Judicious usage of TMP-SMX may result in a decrease in these undesired reactions and additional research is needed to better understand who is at greatest risk of developing these often unpredictable responses.”
Disclosure: The researchers reported no relevant financial disclosures.
Jennifer L. Goldman, MD, can be reached at jlgoldman@cmh.edu.
Perspective
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James H. Brien, DO
This excellent retrospective study over a 10-year period at a very large and busy children’s hospital adds some clarity to a couple of concerning problems: pharmaceutical management of skin and soft tissue infections (SSTI) due to MRSA; and the growing number of adverse drug reactions to one of the main options for therapy, trimethoprim/sulfamethoxazole (TMP/SMX).
Anyone in a busy primary care practice for more than a few years has probably had at least a couple of patients with a potentially severe skin reaction to TMP/SMX therapy, ranging from Stevens-Johnson syndrome to toxic epidermal necrolysis. This can be particularly problematic for patients with HIV.
Many years ago, a boxed warning was placed in the package insert about this possible complication. This occurred around the same time the indication for TMP/SMX as an option for prophylaxis of recurrent otitis media was removed. However, TMP/SMX remains a good combination antimicrobial choice for certain infections, including SSTIs caused by MRSA. But we may need to be a bit more selective in whom it is used as empiric therapy.
I favor using doxycycline in children aged 8 years and older. Also, in our central Texas community, clindamycin remains sensitive to more than 85% of outpatient MRSA isolates, which makes this a reasonable empiric alternative in our younger patients (if they can stand the taste). You would need to decide if the same is true where you practice.
An added benefit of empiric clindamycin is its activity against group A strep (Streptococcus pyogenes - GAS); a major deficiency of TMP/SMX. If the physician guesses wrong and uses TMP/SMX in a GAS soft-tissue infection, the infection may rapidly progress to an advanced stage, including sepsis. While one may guess the underlying cause of a SSTI based on appearance, speed of onset, progression and statistical likelihood, one can never second guess the sensitivities.
In our setting, methicillin-sensitive S. aureus (MSSA) seems to be making a comeback, with more treatment options. For all these reasons, I favor culturing all new soft-tissue abscesses, which is a practice many experts will argue against, considering that drainage alone may be all that is needed to resolve the infection. Therefore, perhaps holding off empiric antimicrobial treatment, as suggested in the paper, would be best. However, if empiric treatment is to be used, why not use clindamycin, pending sensitivities. Even if the organism turns out to be resistant to clindamycin, it will likely resolve anyway, and if not, then culture-directed therapy can be started at the follow-up visit.
Lastly, as the authors pointed out, linezolid (Zyvox, Pharmacia & Upjohn) would be an excellent option for presumed MRSA infection in areas of high clindamycin resistance, except for the cost. I was recently quoted $3,000 from two different pharmacies for a 2-week course of linezolid to switch a 10-year-old ,who was being treated for an MRSA osteomyelitis, who lost his PICC line. Until the cost comes down, linezolid is not a practical choice for most SSTIs. However, if the patient has a sulfa allergy, this could be the only choice.
In any case, it is desirable to reduce the use of TMP/SMX where possible to reduce the growing frequency of severe adverse drug reactions.
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