Treatment of staphylococcal infections in children

Issue: November 2013

ByC. Buddy Creech, MD, MPH

The management of staphylococcal infections in children, although relatively straightforward, is riddled with nuance.

Given the wide array of Staphylococcus aureus infection phenotypes, one must take several factors into account when choosing the most appropriate therapy, such as the age of the patient, the site of infection, the presence or absence of bacteremia and recent antimicrobial usage. Taken together, the treatment of staphylococcal infections has become much more difficult in recent years.

Treatment of staphylococcal abscesses

Surely, the management of a staphylococcal skin and soft tissue infection (SSTI) must be the most straightforward of all staphylococcal phenotypes; however, this is not always the case. In their classic work published in the Annals of Emergency Medicine, Llera and Levy established that abscess drainage was the sine qua non of SSTI treatment. Although this was before the community-acquired methicillin-resistant S. aureus era, abscess drainage is likely still to be the most important aspect of abscess management. Lee and colleagues, in a retrospective study of pediatric abscesses in Dallas, found that for abscesses less than 5 cm in greatest diameter, the choice of antibiotic agent was largely immaterial.

Even if an agent to which S. aureus was resistant and prescribed, those with smaller, drained abscesses had favorable outcomes. This suggests that the importance of drainage has not diminished in the CA-MRSA era. Yet, there remains considerable debate in the field: Should topical anesthetics be used since the acidic environment of the abscess cavity renders most agents ineffective; is spontaneous drainage an adequate surrogate for surgical drainage; and should abscess cavities be packed to facilitate ongoing drainage? Ongoing, prospective studies are needed to inform these important clinical questions.

C. Buddy
Creech

Even more nuanced than abscess drainage is the choice of antimicrobial agent. Some studies indicate that the choice of antimicrobial is less critical for small abscesses in otherwise healthy children. This is, of course, predicated on adequate drainage and appropriate follow-up. An NIH-sponsored, randomized, placebo-controlled trial of SSTI treatment (DMID 07-0051) is currently underway that will establish whether drainage alone is indeed sufficient. For now, the majority of us treat with one of a variety of agents, including clindamycin, trimethoprim-sulfamethoxazole and doxycycline. Each of these has particular advantages and disadvantages.

Clindamycin

Clindamycin is a highly bioavailable lincosamide antibiotic that is highly active against staphylococcal strains. Although resistance is an issue in some communities in the United States, susceptibility rates in excess of 85% are enjoyed by most. As a result, clindamycin is an excellent first-line agent for SSTI management, although a few disadvantages should be mentioned. The first is the liquid suspension’s remarkably unpalatable taste and smell. Various techniques have been devised to mask this characteristic, including the addition of cherry flavoring and pre-administration of chocolate syrup. Although these certainly improve matters, they do not completely avoid the unpleasant nature of the drug. We have had reasonable success with simply emptying the contents of clindamycin capsules into a small amount of chocolate syrup, applesauce or yogurt when the dosing range can be achieved. The second potential disadvantage is the risk for Clostridium difficile infection; however, it is not completely clear in children that the magnitude of risk is greater than for other broad-spectrum antibacterials (such as cephalosporins) and should not realistically affect treatment decisions.

Trimethoprim-sulfamethoxazole

TMP-SMX is a combination agent directed at inhibiting folate metabolism in S. aureus. In vitro susceptibilities are consistently more than 90% to 95%, and both anecdotal and clinical trial data suggest it is an effective treatment for many S. aureus infections, including SSTI. However, some data, including a study published in Pediatrics in 2011 by Williams and colleagues, suggest that treatment failures and recurrence risk may be higher in patients receiving TMP-SMX vs. clindamycin.

In a large retrospective study we conducted in Tennessee, we evaluated 41,094 patients who were diagnosed with an SSTI and received antibiotics. Approximately 6,000 of these children underwent incision and drainage of the abscess; among these, there were 568 treatment failures (9%) and 994 recurrences of SSTI (23%). The odds of treatment failure were higher among children receiving beta-lactam therapy or TMP-SMX (OR=1.92; 95% CI, 1.49-2.47) than clindamycin. Even more interesting was that the risk of recurrent SSTI disease within 1 year was higher among those receiving beta-lactams (OR=1.42; 95% CI, 1.19-1.69) or TMP/SMX (OR=1.26; 95%, 1.06-1.49) vs. clindamycin (OR=1.00). Whether these retrospective data can be corroborated by prospective, randomized clinical trial data remains unknown.

Doxycycline

Doxycycline is an effective anti staphylococcal antimicrobial whose utility is limited primarily by age; children younger than 8 years should not routinely receive doxycycline due to tetracycline-associated enamel staining. In older children and young adults, however, doxycycline is a reasonable alternative, particularly in areas with high clindamycin resistance and for those with specific allergies (eg, TMP-SMX hypersensitivity).

Other agents

For the management of SSTI, other agents are rarely required, particularly in the outpatient setting. Vancomycin is the drug of choice for hospitalized patients with presumed or proven clindamycin-resistance in the setting of severe disease. Vancomycin is also the drug of choice for patients with suspected bacteremia or other intravascular sources of infection. Linezolid is highly active against staphylococci, including MRSA, but its role in SSTI therapy is limited by high cost, adverse effect profile (seen nearly exclusively with usage longer than 14 days), and a desire to limit unnecessary exposure. Fluoroquinolones, although often susceptible in vitro, can be effective, but resistance can occur very quickly, thus limiting any recommendation to use quinolones for uncomplicated SSTI. Newer parenteral agents, such as daptomycin or ceftaroline (Teflaro, Cerexa), are typically unnecessary for SSTI management, and pediatric data on dosing are only now becoming available.

Management of recurrent SSTI

Sometimes, more challenging than the initial management of staphylococcal SSTIs is the avoidance of future events. Our group and others have demonstrated the frequency of recurrence to be 20% to 30%, although in some series, as many as 50% to 72% may experience recurrence. It remains unclear what the best prevention strategy may be, but approaches that alter the microbial ecology in the entire household rather than the index case alone appear to be more effective.

Stephanie A. Fritz, MD, and colleagues in St. Louis have established that twice-daily nasal application of mupirocin and chlorhexidine body washes are more effective when administered to all household members vs. index patients alone. In their study, 72% of patients in the index-decolonization group experienced recurrent SSTI compared with 52% in the household-decolonization group (P=.02). Interestingly, overall S. aureus carriage was not significantly different between groups, implying that “decolonization” is difficult to accomplish, but strain replacement may occur, thus reducing the risk of subsequent disease. Due to these results, our local practice is to offer decolonization therapy for patients experiencing recurrent disease or for families with multiple family members who are developing infections. Our typical regimen includes nasal decolonization (twice-daily mupirocin for 5 days), cutaneous decolonization (chlorhexidine washes or dilute bleach baths), and environmental decolonization (eg, washing of bed linens, decontamination of high-touch surfaces). These are done at the household level. When this fails, we typically repeat these processes because we have had reasonable success with a second application of these maneuvers.

Additional studies needed

Staphylococcal SSTIs are a dime a dozen in most of our clinics and EDs; however, these infections can be incredibly difficult to manage initially and even more difficult to prevent. Additional prospective data, which we can expect to come from the DMID 07-0051 study, will be critical in determining best practices in both the adult and pediatric population until a primary prevention strategy, such as vaccination, can be achieved.

References:

Fritz SA. Clin Infect Dis. 2012;54:743-751.
Lee MC. Pediatr Infect Dis J. 2004;23:123-127.
Llera JL. Ann Emerg Med. 1985;14:15-19.
Williams DJ. Pediatrics. 2011;128:e479-487.

For more information:

C. Buddy Creech, MD, MPH, is assistant professor of pediatric infectious diseases and associate director of the Vanderbilt Vaccine Research Program, as well as program co-director of the Pediatric Infectious Diseases Fellowship at Vanderbilt University School of Medicine and Monroe Carell Jr. Children’s Hospital. Creech is also a member of the Infectious Diseases in Children Editorial Board.

Disclosures: Creech reports no relevant financial disclosures.