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Pneumococcus: How to choose the right antibiotic
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Streptococcus pneumoniae is an important bacterial pathogen of many infectious diseases affecting infants and children. S. pneumoniae is a leading cause of common pediatric infections, including acute otitis media and rhinosinusitis, as well as lower respiratory tract infections such as pneumonia.
Two vaccines directed at S. pneumoniae have had significant results in disease caused by this pathogen in recent years; yet, S. pneumoniae remains an important pathogen. The 13-valent pneumococcal conjugate vaccine (Prevnar13, Pfizer) was introduced in 2010 and replaced the 7-valent conjugate vaccine (Prevnar, Pfizer). PCV13 includes additional serotypes (eg, serotype 19A) that have increased as important causes of infection in recent years. The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is indicated for some children aged 2 years and older who are at higher risk for infection and illness, such as children with underlying cardiac, pulmonary or metabolic conditions. These vaccines have altered the serotypes causing infection and disease and also have allowed other bacterial pathogens, such as Haemophilus influenzae, to have increasing roles.
Edward A. Bell
Antibiotic choice
Antibiotic choice for respiratory infections can depend upon local microbial sensitivity patterns, severity of infection, patient age and drug allergies, among others. Within recent years, guidelines on diagnosis and treatment of common pediatric infectious diseases have been published, including AOM, rhinosinusitis and community-acquired pneumonia (CAP).
A review of the mechanism of action of antibiotics commonly used for pediatric respiratory tract infections, such as the beta-lactam antibiotics (eg, amoxicillin) is helpful when discussing antibiotic choice and use. A common term used in the published literature is PK-PD target, or breakpoint. This term relates to the concentration of the antibiotic (PK; pharmacokinetics) obtainable with a specific dose at the site of infection, and the pharmacodynamics of the antibiotic (ie, the pharmacology). For amoxicillin and other beta-lactam antibiotics, it is the time that the antibiotic concentration at the site of infection remains above the minimum inhibitory concentration of the pathogen that is important (ie, time-dependent). For maximal efficacy, this time must be 40% to 50% of the dosing interval.
For other antibiotics (such as fluoroquinolones), it is the maximal concentration at the site of the infection, as it relates to the pathogen MIC, that is important. Researchers are then able to apply antibiotic concentrations obtainable in a population of children and relate these to MIC values obtained from numerous samples of bacteria, to predict susceptibility profiles for specific antibiotics.
Most common pathogens
Harrison and colleagues recently assessed the antimicrobial susceptibilities of three clinically important pathogens in children — S. pneumoniae, H. influenzae and Moraxella catarrhalis. All tested isolates were obtained from children. A total of 208 S. pneumoniae isolates, including 42 19A serotypes, were evaluated. Of these, 41% were penicillin-susceptible and 30% were penicillin-resistant (using 2007 laboratory breakpoint definitions). Overall, the antibiotics with the highest activity (PK-PD percentage susceptible) were ceftriaxone (95%), high-dose amoxicillin, 90 mg/kg/day (89%), clindamycin (85%), and standard-dose amoxicillin, 45 mg/kg/day (74%). Oral cephalosporins had moderate activity (about 59% to 69% PK-PD susceptible). Activity of azithromycin was slightly lower (57%).
Information obtained from bacterial susceptibility studies, such as that described above, and consideration of the favorable characteristics of amoxicillin (good pharmacokinetic profile, good taste, inexpensive cost, low adverse effect profile) led to inclusion of amoxicillin and amoxicillin/clavulanate as initial choices for treatment of otherwise healthy, appropriately immunized, ambulatory infants and children in recently published guidelines for rhinosinusitis, CAP and AOM.
When treating children with mild-moderate CAP in an area with higher rates of pneumococcal resistance, recently published guidelines suggest dividing high-dose amoxicillin over three dosing intervals instead of twice-daily dosing. This dosing schedule is more likely to achieve antibiotic concentrations above the MIC at the site of infection (eg, pulmonary tissue).
When prescribing high-dose amoxicillin-clavulanate (Augmentin, Dr. Reddy’s Laboratories), a useful reminder for clinicians relates to the differences in the amoxicillin-clavulanate products. Using other amoxicillin-clavulanate products at 90 mg/kg/day will increase a risk for diarrhea because of a higher amount of clavulanate given.
Thus, when prescribing high-dose amoxicillin-clavulanate, only the 600 mg/5 mL formulation should be used.
References:
Bradley JS. Clin Infect Dis. 2011;53:e25-e76.For more information:
Edward A. Bell, PharmD, BCPS, is a professor of clinical sciences at Drake University College of Pharmacy, Blank Children’s Hospital, in Des Moines, Iowa. He is also a member of the Infectious Diseases in Children Editorial Board. He can be reached at: Drake University College of Pharmacy, 2507 University Ave, Des Moines, IA 50311; email: ed.bell@drake.edu.Disclosure: Bell reports no relevant financial disclosures.