Mechanism of Action and Physicochemical Properties
Like all beta-lactam antibiotics, carbenicillin inhibits bacterial cell wall peptidoglycan synthesis. A structural feature of carboxypenicillins is the presence of a carboxyl group on the side chain, which confers a negative charge to the molecule and provides some resistance to beta-lactamases.
At the same time, the absence of an amino group in carbenicillin hinders its diffusion through porin channels of Gram-negative bacteria ($G-$). The compound is classified as a hydrophilic broad-spectrum agent, though high doses are required to achieve the necessary bactericidal concentration inside the microbial cell.
Pharmacokinetics and Administration
The drug is acid-labile—it is completely destroyed by gastric hydrochloric acid and is practically unabsorbed when taken orally. For this reason, carbenicillin is administered exclusively parenterally: intramuscularly or intravenously.
In the body, the drug is approximately 50% bound to plasma proteins, does not cross the blood-brain barrier (BBB), and is excreted primarily by the kidneys. Due to its short half-life, injections are prescribed 4–6 times a day. The intravenous solution is prepared ex tempore (extemporaneously, immediately before use): 1.0 g of powder is dissolved in 10 mL of 0.9% sodium chloride solution and administered at a rate of about 60 drops per minute.
Spectrum of Antimicrobial Activity
Carbenicillin is active against many members of the Enterobacteriaceae family, as well as bacteria of the genera Pseudomonas and Enterobacter (due to resistance to their chromosomal beta-lactamases).
Among carboxypenicillins, carbenicillin exhibits the lowest efficacy against Pseudomonas aeruginosa, ranking behind ticarcillin, mezlocillin, azlocillin, and piperacillin. Intrinsic gaps in its spectrum (resistant microorganisms) include Klebsiella spp., Proteus vulgaris, Citrobacter diversus, and Enterococcus faecalis.
Side Effects and Therapy Risks
Treatment with carbenicillin can cause standard penicillin-associated allergic reactions (urticaria, angioedema, anaphylactic shock) as well as specific toxic effects:
- Hypernatremia: caused by the drug being formulated as a disodium salt. This poses a serious risk for patients with chronic heart failure (CHF).
- Hypokalemia: occurs due to the accelerated excretion of potassium ions ($K^+$) alongside the non-reabsorbed negatively charged antibiotic anion in the distal renal tubules.
- Bleeding disorders: develop as a result of inhibited platelet aggregation.