CEF CLAVE TABLETS

Indications

• Bacterial infections due to sensitive Gram-positive and Gram-negative bacteria
• Surgical prophylaxis
• Haemophilus influenzae epiglottitis
• Acute infections
• Meningitis (emergency treatment)
• Uncomplicated gonorrhoea
• Disseminated gonococcal infection

Dosage

Children: In children aged 1 month to 11 years

Adults: For adults, the typical dosage is 1 g every 12 hours for severe infections, or 400 mg for a single dose in cases of uncomplicated gonorrhoea.

Mechanism of action

Cefixime binds to penicillin-binding proteins (PBPs) located in the bacterial cell wall. This binding inhibits the transpeptidase activity essential for peptidoglycan cross-linking, thereby disrupting cell wall synthesis and integrity, which ultimately leads to bacterial cell lysis, especially in rapidly growing bacteria.

Pharmacodynamics

Cefixime exhibits bactericidal activity by preventing the final stages of bacterial cell wall synthesis. It is stable against certain beta-lactamases, making it effective against some resistant bacterial strains. The drug can cause hypersensitivity reactions and is associated with a risk of Clostridium difficile-associated diarrhea. It may also lead to a decrease in prothrombin activity, necessitating caution in susceptible populations.

Pharmacokinetics

Cefixime is well-absorbed after oral administration, with a bioavailability of approximately 40-50%. Peak plasma concentrations occur within 2-6 hours post-dose. It is widely distributed in body tissues and fluids, including urine. The drug is primarily eliminated via the kidneys, with dose adjustments required in patients with renal impairment. Cefixime has a half-life of about 3-4 hours, necessitating multiple doses for sustained therapeutic effect.

Contra-indications

• Hypersensitivity to cefixime or other cephalosporins
• Severe renal impairment

Adverse effects

• Acute kidney injury
• Arthralgia
• Drug fever
• Dyspepsia
• Dyspnoea
• Edema
• Flatulence
• Genital pruritus
• Hypereosinophilia
• Jaundice
• Serum sickness-like reaction
• Thrombocytosis

Interactions

• Probenecid may increase cefixime levels
• Cephalosporins may interact with anticoagulants and increase bleeding risk
• Certain antibiotics may have additive effects

Precautions

• Caution in patients with a history of gastrointestinal disease, particularly colitis
• Monitor renal function in patients with renal impairment
• Use with caution in patients on dialysis

Pregnancy

Not known to be harmful.

Breast-feeding

Present in milk in low concentrations; use with caution.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• Oral tablets
• Injection (intravenous and intramuscular)

Indications

• Bacterial infections caused by beta-lactamase producing organisms
• Community-acquired pneumonia
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections

Dosage

Children: Paediatric dosing of clavulanate should be determined based on the specific indication and the formulation used. Refer to the BNF for

Adults: The usual adult dose of clavulanate varies depending on the specific antibiotic it is combined with, generally ranging from 125 mg to 250 mg, taken every 8 hours when combined with amoxicillin.

Mechanism of action

Clavulanate works by irreversibly binding to the active site of beta-lactamase enzymes. By inhibiting these enzymes, clavulanate protects beta-lactam antibiotics from degradation, allowing them to exert their antibacterial effects effectively. This mechanism enhances the spectrum of activity of the co-administered antibiotic, thereby improving clinical outcomes in infections caused by beta-lactamase producing organisms.

Pharmacodynamics

Clavulanate exhibits a time-dependent antibacterial effect, characterized by its ability to maintain effective concentrations against beta-lactamase producing bacteria. Its pharmacodynamic properties are mainly influenced by its interaction with beta-lactam antibiotics, enhancing their efficacy in treating infections. The overall effect is a synergistic relationship that increases the potency of the antibiotic treatment.

Pharmacokinetics

Clavulanate is usually administered orally or parenterally, and it is rapidly absorbed from the gastrointestinal tract. It reaches peak plasma concentrations within 1 to 2 hours after administration. The drug is widely distributed in body tissues, with a volume of distribution indicative of good tissue penetration. Clavulanate undergoes hepatic metabolism, primarily by conjugation, and is excreted largely in the urine as metabolites. The elimination half-life is approximately 1 hour, necessitating frequent dosing for optimal therapeutic effect.

Contra-indications

• Hypersensitivity to clavulanate or any component of the formulation
• History of jaundice or hepatic impairment related to previous use of beta-lactam antibiotics

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Hepatic dysfunction
• Allergic reactions

Interactions

• Probenecid may increase concentrations of clavulanate
• Anticoagulants may have altered effects due to changes in gut flora

Precautions

• Monitor liver function during prolonged therapy
• Use cautiously in patients with renal impairment
• Assess for history of allergy to penicillins or cephalosporins

Pregnancy

Clavulanate is classified as category B. Animal studies have not shown teratogenic effects, but adequate and well-controlled studies in pregnant women are lacking.

Breast-feeding

Clavulanate is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• Clavulanate potassium 125 mg/5 mL
• Clavulanate potassium 250 mg/5 mL

Mechanism of action

The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan. Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as "penicillin-binding proteins" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal. Cefixime is a cephalosporin and cephalosporins work by using their beta-lactam rings to inhibit bacterial cell wall synthesis by binding to the penicillin-binding proteins transpeptidases on bacteria. The inhibition of synthesis of the bacteria cell wall will cause lysis, particularly in fast growing organisms such as bacteria. Specifically, cephalosporins inhibit penicillin-sensitive enzymes responsible for the final 3D structure of the bacterial cell wall which in turn inhibit bacterial cell wall peptidoglycan synthesis.

Pharmacodynamics

Cefixime, a broad-spectrum antibiotic, is an orally-active third-generation semisynthetic cephalosporin. Like other cephalosporins, the antibacterial action of cefixime results from inhibition of cell wall synthesis. Also like other cephalosporins, cefixime is stable when in the presence of certain beta-lactamase enzymes, which means certain organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases could be susceptible to cefixime. Use of cefixime can result in hypersensitivity reactions including anaphylactic/anaphylactoid reactions and _Clostridium difficile_-associated diarrhea (CDAD); it may also be associated with a fall in prothrombin activity. Cefixime doses should be adjusted for patients that have renal impairment and patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD), while patients on dialysis should be monitored while taking cefixime.