What is the role of medications in the treatment of pediatric pneumococcal infections?

Updated: Jan 14, 2019
  • Author: Meera Varman, MD; Chief Editor: Russell W Steele, MD  more...
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Answer

Many pneumococcal strains are resistant to penicillin (8-40%, depending on geographic location), and resistance to ceftriaxone is also increasing. Therapy must be altered accordingly. Nonsusceptibility to penicillin and trimethoprim/sulfamethoxazole has increased from 25% and 18%, respectively, in the prepneumococcal vaccine era (ie, prior to availability of pneumococcal vaccine 7 [PCV7]) to 39% and 29%, respectively, in the postvaccination period.

When a strain is resistant to penicillin and cephalosporins, it is often also resistant to erythromycin, trimethoprim-sulfamethoxazole, and tetracyclines. Resistance is seen most often in serotypes 6, 9, 14, 19, and 23.

Penicillin-resistant strains are defined as intermediately resistant (minimum inhibitory concentration [MIC] >0.1-1 mcg/mL) or highly resistant (MIC ≥ 2 mcg/mL). The susceptibility to cefotaxime or ceftriaxone is based on location of isolation of the organism.

Table. Drug Comparison (Open Table in a new window)

Drug

Sensitive, MIC mcg/mL

Resistant isolate, MIC mcg/mL

Intermediate resistance

Resistant

Penicillin/amoxicillin

≤0.06

0.1-1

≥2

Cefotaxime or ceftriaxone

Nonmeningeal ≤1, meningeal ≤0.5

Nonmeningeal 2, meningeal 1

Nonmeningeal ≥4, meningeal ≥2

The key to successful antibiotic therapy of pneumococcal disease is achieving drug concentrations in the affected area of the body that are several times higher than the MIC of the organism.

Beta-lactam antibiotics (eg, amoxicillin, cefuroxime) achieve high levels in middle ear fluid and in the respiratory tract. For this reason, they remain the drugs of choice for otitis media and sinusitis, even when these infections are caused by penicillin-resistant pneumococci. Amoxicillin is the drug of choice for susceptible strains causing most noninvasive disease (eg, otitis media, sinusitis) and for outpatient treatment of pneumonia. High-dose amoxicillin (80-90 mg/kg/d) can also be used for otitis media, sinusitis, and pneumonia caused by penicillin-resistant pneumococci with intermediate resistance. If otitis media fails to respond after high-dose amoxicillin, the next options include amoxicillin/clavulanate (Augmentin), cefdinir, cefpodoxime, or intramuscular ceftriaxone. If the patients fail with these regimens myringotomy may be required.

Eradication of meningitis requires a drug concentration of 8-fold to 15-fold higher than the minimum bactericidal concentration (MBC) in the CNS. Initial empiric therapy should include cefotaxime (225-300 mg/kg/d divided every 8 h) or ceftriaxone (100 mg/kg/d divided every 12-24 h) along with vancomycin (60 mg/kg/d divided every 6 h). Vancomycin should be discontinued if the organism is susceptible to ceftriaxone. Ceftriaxone is the drug of choice for meningitis caused by ceftriaxone-susceptible pneumococci (MIC < 0.5 mcg/mL).

Meropenem may be an alternative to ceftriaxone for ceftriaxone-resistant pneumococcal meningitis. If the MIC to meropenem is more than 0.12 mcg/mL, vancomycin should be used in addition to meropenem.

For nonmeningeal invasive pneumococcal disease including disease caused by penicillin- and ceftriaxone-resistant pneumococci, ceftriaxone is the drug of choice if the organism's MIC to ceftriaxone is less than 4 mcg/mL. For organisms with an MIC of 4 mcg/mL or higher, vancomycin probably should be used in addition to ceftriaxone.


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