GRAMOCEF-CV

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

• Infections caused by beta-lactamase-producing bacteria
• Acute bacterial sinusitis
• Acute otitis media
• Lower respiratory tract infections
• Urinary tract infections

Dosage

Children: Refer to the BNF for Children for specific dosing according to age and weight; adjustments may be necessary based on the clinical scenario.

Adults: Refer to specific product guidelines for dosing; typical regimens depend on the combination antibiotic used and the severity of the infection.

Mechanism of action

Clavulanic acid works by irreversibly binding to the active site of beta-lactamase enzymes that are produced by certain bacteria to inactivate beta-lactam antibiotics. By inhibiting these enzymes, clavulanic acid protects the penicillin antibiotic from degradation, allowing it to exert its antibacterial effects.

Pharmacodynamics

Clavulanic acid has a synergistic effect when combined with other antibiotics, particularly amoxicillin. The presence of clavulanic acid allows for the effective treatment of infections caused by bacteria that would otherwise be resistant to penicillins. Its antibacterial activity is generally weak on its own but significantly enhances the efficacy of other beta-lactam antibiotics.

Pharmacokinetics

Clavulanic acid is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 hour. It is widely distributed throughout the body and has a half-life of approximately 1 hour. The drug is primarily excreted unchanged in the urine. In the presence of renal impairment, dosage adjustment may be necessary, as the elimination of clavulanic acid can be affected.

Contra-indications

• Hypersensitivity to clavulanic acid or any of the excipients
• History of jaundice or hepatic impairment associated with previous use of penicillins or beta-lactam antibiotics

Adverse effects

• Nausea
• Diarrhea
• Rash
• Elevated liver enzymes
• Allergic reactions including anaphylaxis
• Superinfection

Interactions

• May enhance the effects of anticoagulants such as warfarin
• Probenecid may increase plasma concentrations of clavulanic acid
• May reduce the efficacy of oral contraceptives

Precautions

• Caution in patients with renal impairment
• Monitor liver function in patients receiving prolonged therapy
• Use with caution in patients with a history of allergic reactions to beta-lactams

Pregnancy

Clavulanic acid is categorized as pregnancy category B. Animal studies have not shown any harm to the fetus, but there are no adequate and well-controlled studies in pregnant women.

Breast-feeding

Clavulanic acid is excreted in breast milk, but it is generally considered safe for use during breastfeeding. Monitor for potential effects in the infant.

Storage

Store at room temperature, away from moisture and heat. Protect from light. Keep out of reach of children.

Formulations

• Oral tablets
• Oral suspension
• Injectable forms

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.