Introduction
Carbenicillin is a semisynthetic, broad-spectrum penicillin antibiotic belonging to the carboxypenicillin subclass. First introduced in the 1960s, it was among the first penicillins developed with activity against Gram-negative bacteria, particularly Pseudomonas aeruginosa. While its clinical use has significantly declined in favor of newer antibiotics with improved spectra and safety profiles, understanding carbenicillin remains important for historical context and in certain specialized applications.
Mechanism of Action
Carbenicillin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. Like other beta-lactam antibiotics, it binds to penicillin-binding proteins (PBPs) located in the bacterial cell wall, disrupting the final transpeptidation step of peptidoglycan synthesis. This action leads to activation of autolytic enzymes and subsequent cell lysis. Carbenicillin demonstrates activity against many Gram-negative organisms due to its enhanced ability to penetrate the outer membrane of these bacteria compared to earlier penicillins.
Indications
Carbenicillin is indicated for the treatment of:
- Serious infections caused by susceptible strains of Pseudomonas aeruginosa
- Proteus species infections (particularly indole-positive strains)
- Enterobacter species infections
- Complicated urinary tract infections
- Septicemia
- Respiratory tract infections
Note: Current clinical use is limited due to the availability of more potent and better-tolerated antipseudomonal penicillins and other antibiotic classes.
Dosage and Administration
Adults:- Systemic infections: 200-300 mg/kg/day IV in divided doses every 4-6 hours (typically 2-5 g every 4-6 hours)
- Urinary tract infections: 382-764 mg PO four times daily (as carbenicillin indanyl sodium)
- Maximum daily dose: 30-40 g
- CrCl >30 mL/min: No dosage adjustment typically needed
- CrCl 10-30 mL/min: Reduce dose by 25-50%
- CrCl <10 mL/min: Reduce dose by 50-75%
- IV infusion: Reconstitute with sterile water or NaCl 0.9%; dilute in 50-100 mL of compatible fluid; infuse over 30-60 minutes
- IM administration: Painful; not recommended
- Oral: Administer with food to enhance absorption of the indanyl ester form
Pharmacokinetics
Absorption: Poor oral bioavailability (<5%) as the free acid; carbenicillin indanyl sodium (oral prodrug) has approximately 30-40% bioavailability Distribution: Widely distributed to body tissues and fluids; achieves therapeutic concentrations in urine, bile, and bronchial secretions; CSF penetration is poor (<10% of serum levels) Protein binding: 50% Metabolism: Hepatic hydrolysis to active drug (oral form) Elimination: Primarily renal (80-90% unchanged); half-life: ~1 hour in normal renal function Excretion: Urine (active drug)Contraindications
- Hypersensitivity to carbenicillin, other penicillins, or beta-lactam antibiotics
- History of severe allergic reactions (anaphylaxis) to any penicillin
Warnings and Precautions
- Hypersensitivity reactions: Cross-reactivity with cephalosporins possible
- Electrolyte imbalance: Contains approximately 4.7 mEq sodium per gram; monitor in patients with heart failure, hypertension, or renal impairment
- Bleeding tendencies: May cause platelet dysfunction and prolong bleeding time
- Superinfection: May result in bacterial or fungal overgrowth
- Renal impairment: Requires dosage adjustment; may accumulate in patients with renal dysfunction
- Seizure risk: High doses may cause neurotoxicity, particularly in patients with renal impairment
Drug Interactions
- Probenecid: Decreases renal tubular secretion of carbenicillin, increasing serum levels and prolonging half-life
- Aminoglycosides: Physically incompatible when mixed together; may inactivate aminoglycosides
- Oral contraceptives: May decrease effectiveness due to altered gut flora
- Warfarin: May potentiate anticoagulant effect and increase bleeding risk
- Methotrexate: May decrease renal clearance of methotrexate
Adverse Effects
Common:- Gastrointestinal: Nausea, vomiting, diarrhea
- Hypersensitivity: Rash, urticaria, fever
- Local: Pain at injection site, phlebitis
- Anaphylaxis
- Bleeding complications
- Electrolyte imbalances (hypernatremia, hypokalemia)
- Interstitial nephritis
- Seizures (with high doses in renal impairment)
- Hematologic: Neutropenia, thrombocytopenia
- Hepatic enzyme elevations
Monitoring Parameters
- Clinical response to therapy
- Renal function (BUN, creatinine)
- Electrolytes (sodium, potassium)
- Complete blood count with differential
- Coagulation parameters in high-risk patients
- Signs of hypersensitivity reactions
- Culture and susceptibility results
Patient Education
- Complete the full course of therapy even if feeling better
- Report any signs of allergic reaction (rash, itching, difficulty breathing)
- Notify healthcare provider of any unusual bleeding or bruising
- Oral form should be taken with food
- Maintain adequate hydration during therapy
- Inform all healthcare providers of carbenicillin use, especially before surgical procedures
- Report severe diarrhea, as it may indicate C. difficile infection
References
1. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition 2. Antimicrobial Therapy: A Guide to the Use of Antibacterial, Antiviral, Antifungal, and Antiparasitic Agents 3. Sanford Guide to Antimicrobial Therapy 4. Carbenicillin prescribing information (historical) 5. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases 6. Clinical Pharmacology of Antibiotics. Clin J Am Soc Nephrol. 2019 7. Beta-Lactam Antibiotics: Mechanisms of Action and Resistance. Antibiotics (Basel). 2020 8. Historical review of carboxypenicillins. J Antimicrob Chemother. 1989
Note: This monograph provides historical and educational information. Clinical use of carbenicillin has been largely superseded by newer antimicrobial agents with improved safety and efficacy profiles.