Carbenicillin - Dosage, Indications, Contraindications, and Side Effects

Overview

Carbenicillin belongs to the penicillin group of drugs. It is a broad-spectrum antibiotic having a 6-beta-2-carboxy-2-phenyl acetamido side chain. Carbenicillin is a prescription medicine used alone or with other medications to treat infections of the upper and lower urinary tract and also in asymptomatic bacteriuria. It must be used only to treat or prevent infections strongly suspected or proven to be caused by the bacteria. Though Carbenicillin was approved by the United States Food and Drug Administration in 1972, its use has been discontinued.

How Does Carbenicillin Work?

Carbenicillin is an antibiotic that is effective against a variety of gram-positive and gram-negative microorganisms. Carbenicillin works by preventing the formation of the cell wall, which is required for survival, and thus destroys the bacteria.

What Are the Indications of Carbenicillin?

The indications of Carbenicillin include;

• It is used for acute as well as chronic infections of the upper and lower urinary tract.

• It is used to treat asymptomatic bacteriuria (the presence of bacteria in the urine sample, but the patient has no symptoms of a urinary infection) due to microorganisms such as Escherichia coli, Pseudomonas, Enterobacter, Enterococci species, etc.

• It is used in the treatment of prostatitis (inflammation of the prostate gland) as a result of an infection caused by E. coli, Proteus mirabilis, Enterobacter, Enterococci species, etc.

What Are the Contraindications of Carbenicillin?

Carbenicillin is contraindicated in patients with a known history of penicillin allergy.

What Is the Dosage of Carbenicillin?

The recommended dose of Carbenicillin is as follows:

• For patients suffering from urinary tract infections caused by E.coli, Proteus species and Enterobacter is recommended at the dose of one to two tablets, four times a day.

• Pseudomonas and Enterococcus - two tablets; four times a day.

• Prostatitis - two tablets; four times a day.

Overdose of Carbenicillin can lead to mild gastrointestinal irritation, but the symptoms are transitory. Anaphylactic reactions may occur in hypersensitive individuals.

What Are the Warnings and Precautions Regarding Carbenicillin?

• The penicillin group of drugs may cause serious and occasionally fatal anaphylactic reactions on oral or parenteral therapy. It is mainly seen in patients with a history of hypersensitivity to penicillin or a history of sensitivity to various allergens. Therefore, a thorough history is obtained before the initiation of treatment with Carbenicillin. If an allergic reaction is reported, the drug must be discontinued, and a suitable treatment must be advised.

• Serious hypersensitivity reactions require immediate treatment with Epinephrine. If necessary, oxygen therapy, intravenous steroids, airway management, and intubation must be performed.

• Clostridium difficile can produce toxins A and B, which can lead to diarrhea, with the severity ranging from mild to fatal colitis. Antibacterial agents can affect the normal flora of the intestine and can cause an overgrowth of Clostridium difficile. Hence, Clostridium difficile-associated diarrhea (CDAD) must be considered in patients with diarrhea following antibiotic therapy. A careful medical history is taken before starting treatment with Carbenicillin. If CDAD is suspected during the treatment, the drug must be discontinued, and appropriate fluid and electrolyte therapy, along with supplementation of proteins and antibiotic treatment for C. difficile, must be considered.

• Long-term use of Carbenicillin can result in the overgrowth of nonsusceptible microorganisms, and appropriate measures must be taken if superinfection occurs during the treatment with Carbenicillin.

• Patients with severe renal impairment may not achieve therapeutic urine levels as the kidneys primarily excrete Carbenicillin. Dose adjustment must be made in patients with mild to moderate renal impairment to prevent the accumulation of the drug.

• Carbenicillin can increase the risk of drug-resistant bacterial development in the absence of proven or strongly suspected bacterial infection or a prophylactic indication.

• Similarly to other penicillin groups of drugs, during prolonged treatment with Carbenicillin, a regular assessment of organ system function, including hepatic, renal, and hematopoietic systems, is recommended.

• The penicillin group of drugs can be distributed in low concentrations into breast milk. However, significant problems have not been documented, but the use of these drugs by nursing mothers is contraindicated because it may cause diarrhea, skin rash, candidiasis, etc; in the breastfed infant.

What Are the Adverse Effects of Carbenicillin?

Adverse reactions of Carbenicillin include;

• Gastrointestinal: The most common adverse reactions associated with Carbenicillin include symptoms related to the gastrointestinal tract. Commonly reported adverse reactions include diarrhea, nausea, vomiting, taste changes, glossitis (inflammation of the tongue), and flatulence (accumulation of gas). Rare symptoms include anorexia (eating disorder), dry mouth, furry tongue, abdominal cramps, rectal bleeding, etc.

• Dermatological: Skin rash, urticaria (itchy rash), and pruritus (itchy skin).

• Hematological: Anemia, thrombocytopenia (low platelet count), leukopenia (reduced white blood cell levels), eosinophilia (increased eosinophils), and neutropenia (low neutrophils) have been rarely observed.

• Other Reactions: Headache, hyperthermia (high body temperature), itchy eyes, loose stools, and vaginitis (inflammation of the vagina). Mild elevations were observed in the serum glutamic-oxaloacetic transaminase (SGOT) levels following an administration of Carbenicillin.

For Patients

What Are Urinary Tract Infections?

Infection in any organ of the urinary system, such as the ureters, kidneys, urinary bladder, or urethra, is referred to as a urinary tract infection (UTI). Women are at a higher risk of developing a UTI compared to men. Bacteria most commonly cause these infections; however, rarely, a UTI can also occur from a fungal infection. The symptoms of UTI include;

• Persistent urge to urinate and frequently passing small amounts of urine.

• Burning sensation while urinating.

• Cloudy appearance or red or bright-pink-colored urine.

• Pain in the pelvic area.

What Is Carbenicillin?

Carbenicillin is a prescription medicine used to treat different types of infections caused by bacteria. It is an antibiotic medication used alone or in combination with other medicines.

How Should Carbenicillin Be Stored?

Carbenicillin tablets must be protected from moisture and stored at temperatures not exceeding 30 degrees Celsius and must be kept away from children.

What Are the Steps to Be Followed Before Taking Carbenicillin?

• Carbenicillin must be used only for recommended infections; this medication should not be used for viral infections or the common cold.

• Carbenicilin must be taken exactly as prescribed by the doctor.

• Patients might feel better during the early course of therapy; missing or skipping the doses may decrease the effectiveness of the treatment, and also, the bacteria may develop resistance, and the drug may not be effective when the same medicine is taken in the future.

• Carbenicillin must not be taken by others, even if they have similar symptoms.

• Antibiotics commonly cause diarrhea and may stop after discontinuation of the treatment.

• If the patients experience watery stools, fever, or stomach cramps as late as two or more months after the last dose, a doctor must be consulted as soon as possible.

What Must the Patients Inform the Doctor Before Taking Carbenicillin?

• The patient must inform the healthcare professional in case of allergies to Carbenicillin or any other medications.

• Female patients must tell the doctor if they are pregnant, breastfeeding, or taking any birth control pills.

• Patients must inform the doctor if they are suffering from kidney disease or have a history of diarrhea, asthma, etc.

What Are the Side Effects of Carbenicillin?

Some of the side effects of Carbenicillin include;

• Nausea and vomiting.

• Stomach pain.

• Diarrhea.

• Headache.

• Vaginal itching.

• Changes in taste.

• Difficulty breathing.

• Dry mouth.

• Fever.

• Skin rash.

• Bodyache.

For Doctors

Description

Carbenicillin is a semisynthetic penicillin, a sodium salt of carbenicillin disodium. It is available in the form of a tablet and is freely soluble in water. Each tablet contains 382 mg (milligram) of Carbenicillin, 23 mg of sodium, 118 mg of indanyl sodium ester along with other inert ingredients such as magnesium stearate, glycine, sodium lauryl sulfate, hydroxypropyl cellulose, hypromellose, etc. Microbial susceptibility to Carbenicillin was performed using standard methods advised by the National Committee for Clinical Laboratory Standards. A lab report of ‘susceptible’ indicated that the microorganism would most likely respond to the treatment with Carbenicillin, and the report as ‘resistant’ indicated that the microorganism would not respond to treatment with Carbenicillin.

Mechanism of Action

Carbenicillin, in a free state, is pharmacologically active and exerts antibacterial activity by interfering with the cell wall synthesis of susceptible bacteria. Carbenicillin acylates the penicillin-sensitive transpeptidase C-terminal domain by opening the lactam ring. This, in turn, prevents the crosslinking of peptidoglycan strands, thus inhibiting bacterial cell wall synthesis.

The majority of Klebsiella species and various strains of Pseudomonas have developed resistance to Carbenicillin.

Pharmacokinetics

• Absorption: After an oral administration, Carbenicillin is acid stable and rapidly absorbed from the small intestine, and the oral bioavailability is around 30 to 40 percent. It exhibits low plasma concentrations and is excreted through the urine.

• Following absorption, the drug gets converted to its active form by the hydrolysis of the ester linkage after an administration of a single 500 mg tablet of Carbenicillin; a peak plasma concentration reached in one hour is 6.5 mcg/ml.

• Excretion: Approximately 30 percent of the dose of Carbenicillin is excreted unchanged in the urine within 12 hours, and another six percent is excreted over the next 12 hours.

Pharmacodynamics

Carbenicillin is a semisynthetic penicillin; it has antipseudomonal and antiprotease activity. It provides in vitro activity against various gram-positive and gram-negative microorganisms. Due to the high urine levels observed following administration, clinical efficacy has been demonstrated in urine infections due to susceptible species of E. coli, Proteus mirabilis, P. vulgaris, Enterobacter, and Enterococci species, etc.

Drug Interactions

• Aminoglycosides: The broad-spectrum penicillin group of drug Carbenicillin is often combined with aminoglycoside antibiotics such as Gentamicin, Amikacin, and others to obtain coverage against gram-negative bacteria. This combination is proven to be synergistic against gram-negative bacilli, especially Enterobacteriaceae and Pseudomonas aeruginosa.

• Ambroxol: Ambroxol and its active metabolite Bromhexine have been widely used as expectorants. The risk, as well as the severity of developing methemoglobinemia, is found to be increased when penicillins are co-administered with Ambroxol.

• Probenecid: Carbenicillin levels in the blood may be increased due to the concurrent administration of Carbenicillin with Probenecid.

• Atracurium: Neuro-muscular blocker Atracurium is used to relax muscles under general anesthesia for mechanical ventilation. It has been noted that the efficacy of Atracurium increases therapeutically when co-administered with Carbenicillin.

• Acenocoumarol: The anticoagulant activity of Acenocoumarol is increased when co-administered with Carbenicillin, leading to a risk of bleeding diathesis.

• Acyclovir: The excretion of the antiretroviral drug Acyclovir can be reduced when it is combined with Carbenicillin.

Clinical Studies

Studies were conducted on 74 patients with serious infections treated with one gram of Carbenicillin, which was found to be more effective when administered intramuscularly four times a day for seven days. Significant results were obtained in infections caused by the strains of Proteus species and E. coli. During the in vitro studies, no effect of serum was observed on the minimal concentration of the drug. Resistance was observed to develop rapidly in vitro to Pseudomonas species. For patients with severe Pseudomonas pyocyanea infections, Carbenicillin must be used in larger doses, and intravenous administration may be recommended.

Nonclinical Toxicology

Long-term animal or human studies have not been conducted to evaluate the carcinogenic potential of Carbenicillin. Rats who were fed around 250 to 1000 mg/kg/day for 18 months demonstrated mild liver pathology (bile duct hyperplasia), and there was no evidence of drug-related neoplasia. Administration of Carbenicillin at daily doses of approximately 1000 mg/kg did not show any significant effect on the fertility or reproductive ability of rats.

Use of Carbenicillin in Specific Populations

• Pregnancy: Adequate and well-controlled studies have not been conducted in pregnant women with respect to Carbenicillin. However, animal reproduction studies have been conducted. At dose levels of 1000 mg or 500 mg/kg (milligram/kilogram) in rats, 500 mg/kg in monkeys, and 200 mg/kg in mice showed no significant harm to the fetus. As animal reproduction studies may not always predict the human response, the drug must be used in pregnancy only if needed and after consultation with the doctor.

• Nursing Mothers: Carbenicillin is excreted in human milk; however, the exact amount of the drug is unknown; therefore, caution must be exercised if the drug is administered to the nursing mother.

• Pediatric Use: The safety and effectiveness of Carbenicillin in children are not established.