Monday, 20 July 2015

Pediatric Bacterial Meningitis - Medication

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Antibiotics

Class Summary

Intravenous (IV) antibiotics are required for bacterial meningitis. If the causative organism is unknown, antibiotics regimens can be based on the child’s age, as follows:
- For infants younger than 30 days, ampicillin and an aminoglycoside or a cephalosporin (cefotaxime) are recommended
- For children aged 30-60 days, ampicillin and a cephalosporin (ceftriaxone or cefotaxime) can be used; because Streptococcus pneumoniae occasionally occurs in this age range, vancomycin should be considered instead of ampicillin
- In older children, a cephalosporin (cefotaxime or ceftriaxone) plus vancomycin (needs to be added secondary to the possibility of cephalosporin resistantStreptococcus pneumonia) can be used
The incidence of resistant S pneumoniae is increasing. If this organism is considered to be a potential cause of the meningitis, add vancomycin to the therapeutic regimen. Use of penicillin or ampicillin in the 3 months before illness is associated with increased risk of infection with resistant S pneumoniae.

Cefotaxime (Claforan)

Cefotaxime is a third-generation cephalosporin with a gram-negative spectrum; it has lower efficacy against gram-positive organisms. It arrests bacterial cell wall synthesis, which, in turn, inhibits bacterial growth.

Ceftazidime (Fortaz, Tazicef)

Ceftazidime is a third-generation cephalosporin with broad-spectrum gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to 1 or more penicillin-binding proteins (PBPs).

Ampicillin

Ampicillin has bactericidal activity against susceptible organisms. It is used as an alternative to amoxicillin when the patient is unable to take medication orally.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to 1 or more penicillin-binding proteins (PBPs).

Gentamicin

Gentamicin is an aminoglycoside used for gram-negative coverage. It is given intravenously (IV) or intramuscularly (IM) in combination with both an agent that covers gram-positive organisms and one that covers anaerobes. It is not the drug of choice but may be considered if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms. Dosing regimens are numerous. Adjust the dose on the basis of creatinine clearance and changes in volume of distribution.

Chloramphenicol

Since the introduction of third-generation cephalosporins, chloramphenicol has been less frequently used. It binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. It is effective against gram-negative and gram-positive bacteria.

Vancomycin

Vancomycin is a potent antibiotic directed against gram-positive organisms and active against Enterococcus species. It is indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or who have infections caused by resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora, anaerobes, or both.
To prevent toxicity, the current recommendation is to assay vancomycin trough levels after the third dose, 30 minutes before the next dose. Use the creatinine clearance to adjust dosing in patients diagnosed with renal impairment.

Meropenem (Merrem)

Meropenem is a carbapenem with slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared with imipenem. It is less likely to cause seizures and has superior penetration of blood-brain barrier compared with imipenem.

Penicillin G (Pfizerpen)

Penicillin G interferes with synthesis of cell-wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. It can be given alone to treat GBS meningitis when susceptibility of CSF isolates to the drug has been demonstrated.

Tobramycin

Tobramycin is used in skin, bone, and skin-structure infections caused by S aureus, P aeruginosa, Escherichia coli, and Klebsiella, Proteus, and Enterobacter species. It is indicated for staphylococcal infections when penicillin or potentially less toxic drugs are contraindicated and when bacterial susceptibility and clinical judgment justify its use. Dosing regimens are numerous and are adjusted on the basis of creatinine clearance and changes in the volume of distribution.

Amikacin

Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes; it blocks the recognition step in protein synthesis and causes growth inhibition. It is indicated for gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Amikacin is effective against P aeruginosa. Use patient's ideal body weight (IBW) for dosage calculation. The same principles of drug monitoring for gentamicin apply to amikacin.

Ticarcillin and clavulanate potassium (Timentin)

This drug combination inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active growth. It consists of an antipseudomonal penicillin plus a beta-lactamase inhibitor and provides coverage against most gram-positive, most gram-negatives, and most anaerobic organisms.

Oxacillin

Oxacillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is used in the treatment of infections caused by penicillinase-producing staphylococci. It may be given as initial therapy when a staphylococcal infection is suspected.

Rifampin (Rifadin)

Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It should be taken on an empty stomach. The use of rifampin, ceftriaxone, and ciprofloxacin has been effective as chemoprophylaxis.

Ciprofloxacin (Cipro, Proquin XR)

Ciprofloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, and most gram-negative organisms, but with no activity against anaerobes. It inhibits bacterial deoxyribonucleic acid (DNA) synthesis and, consequently, growth. The use of ciprofloxacin has been effective as chemoprophylaxis and, along with ceftriaxone, more effective against resistant strains of N meningitidis up to 4 weeks after treatment. It is used in patients older than 18 years.

Corticosteroids

Class Summary

In adults, corticosteroids, given before or along with the first dose of antibiotics, reduce morbidity and mortality (hearing loss, long-term neurologic sequelae, and death); these findings were applicable to high-income countries. In pediatric patients, however, it is uncertain whether corticosteroids are beneficial as adjuvant therapy for bacterial meningitis.

Dexamethasone (Baycadron)

Dexamethasone decreases inflammation by suppressing migration of polymorphonuclear leukocytes (PMNs) and reducing capillary permeability.

Vaccines, Inactivated, Bacterial

Class Summary

Vaccines with inactivated bacteria are used to induce active immunity against most common pathogens responsible for causing bacterial meningitis in the pediatric population. Prevention is an important aspect of the management of pediatric bacterial meningitis because it has been shown to reduce mortality and morbidity.

Meningococcal C and Y/haemophilus influenza type B tetanus conjugate vaccine (MenHibrix)

This vaccine contains antigenic capsular polysaccharides (ie, meningococcal serogroups A and C, H influenzae type b) that convey active immunity by stimulating endogenous antibody production; antibodies have been associated with protection from invasive meningococcal disease. It is approved by the US Food and Drug Administration (FDA) for use in infants. This combination vaccine is indicated in children aged 6 weeks to 18 months for active immunity against invasive disease. It is given as a 4-dose series, usually at well-baby checkups.

Haemophilus b conjugate vaccine (ActHIB, Hiberix, PedvaxHIB)

This vaccine is used for routine immunization of children against invasive diseases caused by H influenzae type b by decreasing nasopharyngeal colonization. The CDC Advisory Committee on Immunization Practices (ACIP) recommends that all children receive one of the conjugate vaccines licensed for infant use beginning routinely at age 2 months.

Meningitis group A C Y and W-135 vaccine diphtheria conjugate vaccine (Menactra, Menveo)

This vaccine is a diphtheria toxoid conjugate vaccine that induces the production of bactericidal antibodies specific to capsular polysaccharides of serogroups A, C, Y, and W-135. The meningococcal conjugate vaccine is recommended for high-risk groups, including patients with immunodeficiency, patients with functional or anatomic asplenia, and patients with deficiencies of terminal components of complement. It has been given to high-risk children as young as 9 months (Menactra) or 2 months (Menveo). The vaccine is also valuable in controlling epidemics of meningococcal disease.

Meningococcal polysaccharide vaccine (Menomune A/C/Y/W-135)

This is a quadrivalent vaccine for meningitis prophylaxis. It is considered an adjunct to antibiotic chemoprophylaxis. The meningococcal conjugate vaccine is recommended for high-risk groups, including patients with immunodeficiency, patients with functional or anatomic asplenia, and patients with deficiencies of terminal components of complement. It has been given to high-risk children as young as 9 months. The vaccine is also valuable in controlling epidemics of meningococcal disease.
 
 
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