VAIL, COLO. – A major theme running through the latest guidelines for management of community-acquired pneumonia in children is that Streptococcus pneumoniae is the most common bacterial pathogen – and the best target for empiric therapy.
"It’s really all about pneumococcus," declared Dr. Mark J. Abzug, professor of pediatrics at the University of Colorado, Denver.
Dr. Mark J. Abzug
The guidelines put forth jointly by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America endorse high-dose amoxicillin as first-line therapy for previously healthy, appropriately immunized infants, preschoolers, school-aged children, and adolescents with mild to moderate community-acquired pneumonia (CAP) of suspected bacterial origin (Clin. Infect. Dis. 2011; 53: e25-76).
High-dose oral amoxicillin at 90 mg/kg per day covers 87%-95% of S. pneumoniae isolates nationally, whereas most second- and third-generation oral cephalosporins cover only 60%-70%. Azithromycin isn’t recommended for suspected pneumococcal CAP because of an associated resistance rate of up to 40%. Amoxicillin/clavulanic acid offers no incremental benefit over amoxicillin alone for pneumococcus, Dr. Abzug observed at the conference, which was sponsored by Children’s Hospital Colorado.
The guidelines recommend b.i.d. dosing of amoxicillin based largely on extrapolation from experience in acute otitis media. But Dr. Abzug takes issue with that guidance.
"I’m going to beg to differ with that recommendation and suggest that for pneumonia, which is a bit different from otitis, dividing t.i.d. is going to be better," the pediatrician asserted.
Modeling studies indicate b.i.d. dosing of amoxicillin at 90 mg/kg per day is effective for 99% of highly susceptible (minimal inhibitory concentration of 0.5 mcg/mL) S. pneumococcus isolates, but only for 65% of strains with a minimum inhibitory concentration (MIC) of 2 mcg/mL, whereas t.i.d. dosing is sufficient for 90% of such strains. And at Children’s Hospital Colorado, nearly 20% of S. pneumoniae isolates in 2011 were intermediately susceptible (MIC = 4 mcg/mL) or resistant (MIC = 8 mcg/mL) to penicillin.
"For the 20% or so that are intermediate or resistant, b.i.d. dosing is not going to be the answer," Dr. Abzug stressed.
For patients with nonserious amoxicillin allergies, the guidelines recommend cefuroxime, cefprozil, or cefpodoxime as oral alternatives; nationally, 67%-80% of S. pneumoniae strains are susceptible to these agents. Clindamycin is an alternative option. Levofloxacin and linezolid are effective for close to 100% of isolates, but are best reserved for second- or third-line therapy.
It may come as a surprise to many physicians that the guidelines deem routine chest x-rays "not necessary" for suspected CAP in the outpatient setting.
"Will this encourage antibiotic overuse? The guidelines don’t address this," the pediatrician noted.
The guidelines also recommend against routine complete blood counts, blood cultures, and urinary antigen detection tests in outpatients.
In fully immunized children with suspected bacterial CAP sufficiently serious for hospitalization, the recommendation is for parenteral ampicillin or penicillin G so long as local epidemiologic data indicate a lack of substantial resistance for invasive pneumococci as defined by an MIC greater than 8 mcg/mL and the patient doesn’t have empyema or other potentially life-threatening complications. When those conditions aren’t met, however, the guidelines endorse the third-generation cephalosporins ceftriaxone or cefotaxime.
Dr. Abzug applauded a recent study by pediatricians at Children’s Mercy Hospitals and Clinics in Kansas City, Mo., that provided support in everyday clinical practice for the ampicillin-first management strategy recommended in the national guidelines. The retrospective study included 1,033 patients admitted with CAP to the tertiary referral hospital during the 12 months before and after the 2008 introduction of a clinical practice guideline encouraging the use of ampicillin as the first-line empiric antibiotic in previously healthy children with uncomplicated CAP.
The Kansas City pediatricians noted that the use of ampicillin as first-line therapy has historically been uncommon at tertiary children’s hospitals, as evidenced by a mere 5.5% rate in a study using the Pediatric Hospital Information Systems database (Pediatrics 2011;127:e255-63). The goal was to turn that situation around at Children’s Mercy Hospitals and Clinics, since ampicillin is a narrower-spectrum antibiotic than the third-generation cephalosporins, and hence less likely to promote antibiotic resistance.
Prior to introduction of the hospital guideline, ceftriaxone was prescribed as empiric therapy for CAP in 72% of cases, with ampicillin being the second most commonly prescribed antibiotic at 13%. In the year after the guideline was introduced, ampicillin was the most common antibiotic, prescribed in 63% of cases, with ceftriaxone prescribed in 21%. And even though the prevalence of S. pneumoniae isolates with intermediate susceptibility or resistance to penicillin was 24% at the hospital during that time period, the change in therapy didn’t result in an increase in adverse outcomes: The preguideline treatment failure rate was 1.5% and the postguideline rate was similar at 1% (Pediatrics 2012;129:e597-604).