Carbapenems Antibiotics Used in Children
Introduction to Carbapenems in Pediatrics
Carbapenems are a class of β-lactam antibiotics with broad-spectrum activity against gram-positive, gram-negative, and anaerobic bacteria. They are considered a last-line defense against serious bacterial infections in children due to their potency and ability to overcome many resistance mechanisms.
The most commonly used carbapenems in pediatric practice include:
- Meropenem
- Imipenem (usually combined with cilastatin)
- Ertapenem
Doripenem is another carbapenem, but its use in children is less common and not as well-studied.
Pharmacology of Carbapenems
Mechanism of Action:
- Carbapenems inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).
- They are highly resistant to most β-lactamases, including extended-spectrum β-lactamases (ESBLs).
Pharmacokinetics in Children:
- Distribution: Good penetration into most body tissues and fluids, including the cerebrospinal fluid.
- Metabolism: Primarily renal excretion; imipenem is co-administered with cilastatin to inhibit renal metabolism.
- Half-life: Generally shorter in children compared to adults, necessitating more frequent dosing.
Indications for Carbapenem Use in Children
Carbapenems are typically reserved for serious infections caused by multidrug-resistant organisms or in situations where broad-spectrum coverage is crucial. Common indications include:
- Severe nosocomial infections
- Complicated intra-abdominal infections
- Complicated urinary tract infections
- Severe pneumonia, including ventilator-associated pneumonia
- Septicemia
- Febrile neutropenia
- Meningitis (meropenem)
- Infections caused by ESBL-producing organisms
The choice of specific carbapenem depends on the suspected pathogens, site of infection, and local resistance patterns.
Dosing of Carbapenems in Children
Dosing varies based on the specific carbapenem, the child's age, weight, and renal function. General guidelines:
- Meropenem:
- Infants > 3 months and children: 20-40 mg/kg/dose every 8 hours
- Maximum dose: 2 g every 8 hours
- Imipenem-cilastatin:
- Children > 3 months: 15-25 mg/kg/dose every 6 hours
- Maximum dose: 1 g every 6 hours
- Ertapenem:
- Children 3 months to 12 years: 15 mg/kg twice daily
- Children > 12 years: 1 g once daily
Note: Dosing should be adjusted for renal impairment. Always consult current guidelines and product information for the most up-to-date dosing recommendations.
Adverse Effects of Carbapenems in Children
While generally well-tolerated, carbapenems can cause several adverse effects:
- Gastrointestinal disturbances: nausea, vomiting, diarrhea
- Skin reactions: rash, pruritus
- Hematological effects: eosinophilia, thrombocytopenia
- Hepatic: transient elevations in liver enzymes
- Central nervous system: seizures (more common with imipenem, especially in patients with CNS disorders or renal impairment)
- Electrolyte imbalances
- Injection site reactions
Rare but serious adverse effects include anaphylaxis and Clostridioides difficile-associated diarrhea.
Precautions and Considerations
When using carbapenems in children, consider the following:
- Antimicrobial Stewardship: Use carbapenems judiciously to prevent the development of resistance.
- Cross-reactivity: Patients with severe penicillin allergies may also react to carbapenems (though cross-reactivity is lower than previously thought).
- Renal Function: Adjust doses in patients with renal impairment.
- CNS Disorders: Use imipenem with caution in patients with CNS disorders due to increased seizure risk.
- Drug Interactions: Carbapenems may decrease valproic acid levels.
- Pregnancy and Lactation: Limited data available; use only when clearly needed.
Regular monitoring of clinical response, renal function, and potential adverse effects is essential during carbapenem therapy in children.
Meropenem in Pediatrics
Overview
Meropenem is often the preferred carbapenem in pediatrics due to its broad spectrum of activity, good safety profile, and CNS penetration.
Pharmacology
- Mechanism: Inhibits cell wall synthesis by binding to PBPs
- Spectrum: Broad-spectrum activity against gram-positive, gram-negative, and anaerobic bacteria
- CNS Penetration: Good penetration into cerebrospinal fluid
- Elimination: Primarily renal
Indications
- Severe nosocomial infections
- Meningitis
- Complicated intra-abdominal infections
- Febrile neutropenia
- Severe pneumonia
- Infections caused by ESBL-producing organisms
Dosing
For infants > 3 months and children:
- Standard dose: 20 mg/kg every 8 hours
- Severe infections: 40 mg/kg every 8 hours
- Meningitis: 40 mg/kg every 8 hours
- Maximum dose: 2 g every 8 hours
Note: Dosing intervals may need to be adjusted in renal impairment.
Adverse Effects
- Generally well-tolerated
- Common: Diarrhea, nausea, vomiting, rash
- Less common: Headache, thrombocytopenia, neutropenia
- Rare: Seizures (lower risk compared to imipenem)
Special Considerations
- Preferred over imipenem for CNS infections due to lower seizure risk
- Dosage adjustment required in renal impairment
- Monitor liver function during prolonged therapy
Imipenem-cilastatin in Pediatrics
Overview
Imipenem is co-formulated with cilastatin, which inhibits renal metabolism of imipenem, increasing its bioavailability and reducing nephrotoxicity.
Pharmacology
- Mechanism: Imipenem inhibits cell wall synthesis; cilastatin inhibits renal metabolism of imipenem
- Spectrum: Very broad spectrum, including many gram-positive, gram-negative, and anaerobic bacteria
- CNS Penetration: Moderate
- Elimination: Primarily renal
Indications
- Severe polymicrobial infections
- Complicated intra-abdominal infections
- Nosocomial pneumonia
- Septicemia
- Empiric therapy in febrile neutropenia
Dosing
For children > 3 months:
- Standard dose: 15-25 mg/kg every 6 hours
- Severe infections: Consider 25 mg/kg every 6 hours
- Maximum dose: 1 g every 6 hours
Note: Dosing should be adjusted in renal impairment.
Adverse Effects
- Common: Nausea, vomiting, diarrhea
- Less common: Rash, thrombocytopenia
- Important: Higher risk of seizures compared to other carbapenems, especially in patients with CNS disorders or renal impairment
Special Considerations
- Use with caution in patients with CNS disorders due to increased seizure risk
- Not recommended for meningitis due to inadequate CNS penetration and higher seizure risk
- Dosage adjustment required in renal impairment
- Monitor for electrolyte imbalances, particularly in young infants
Ertapenem in Pediatrics
Overview
Ertapenem has a narrower spectrum compared to meropenem and imipenem but offers the advantage of once-daily dosing.
Pharmacology
- Mechanism: Inhibits cell wall synthesis by binding to PBPs
- Spectrum: Active against many gram-positive, gram-negative, and anaerobic bacteria, but less active against Pseudomonas and Acinetobacter species
- CNS Penetration: Limited
- Elimination: Primarily renal
Indications
- Complicated intra-abdominal infections
- Complicated skin and soft tissue infections
- Community-acquired pneumonia
- Complicated urinary tract infections
- Acute pelvic infections
Dosing
- Children 3 months to 12 years: 15 mg/kg twice daily
- Children > 12 years: 1 g once daily
- Maximum daily dose: 1 g
Note: Once-daily dosing is possible in children > 12 years and adults due to the drug's long half-life.
Adverse Effects
- Generally well-tolerated
- Common: Diarrhea, nausea, headache
- Less common: Vomiting, altered taste, injection site reactions
- Rare: Seizures (lower risk compared to imipenem)
Special Considerations
- Not recommended for hospital-acquired infections or suspected Pseudomonas infections due to lack of activity
- Convenient once-daily dosing in older children and adults
- Dosage adjustment required in renal impairment
- Limited data on use in young infants
External Resources
- Carbapenems: Past, Present, and Future - Comprehensive review of carbapenems in the Journal of Antimicrobial Chemotherapy
- Meropenem in children: safety and efficacy - Detailed review of meropenem use in pediatrics
- Ertapenem in Pediatrics - Recent study on ertapenem use in children
- Carbapenems in Pediatrics - Comprehensive review article from the Journal of Pediatric Pharmacology and Therapeutics
- WHO Carbapenem Review - World Health Organization's review on the use of carbapenems
- Meropenem in Pediatric Patients - Clinical practice guidelines for meropenem use in children
