COLIMOX WATER SOLUBLE POWDER

Indications

• Bacterial infections
• Urinary tract infections
• Sinusitis
• Uncomplicated community-acquired pneumonia
• Salmonellosis
• Oral infections
• Lyme disease (under expert supervision)
• Acute exacerbation of bronchiectasis
• Anthrax (treatment and post-exposure prophylaxis)

Dosage

Children: 1 month–11 years: 30 mg/kg 3 times a day for 21 days; children 1–4 years: 250 mg 3 times a day; children 5–11 years: 500 mg 3 times a day.

Adults: 500 mg 3 times a day; increased if necessary up to 1 g 3 times a day in severe infections.

Mechanism of action

Amoxicillin works by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, interfering with the transpeptidation process necessary for cell wall integrity.

Pharmacodynamics

Amoxicillin exhibits bactericidal activity against susceptible bacteria. Its action is time-dependent, meaning that its effectiveness is related to the duration of time that the drug concentration remains above the minimum inhibitory concentration (MIC) for the target pathogen.

Pharmacokinetics

Amoxicillin is well absorbed from the gastrointestinal tract, with peak plasma concentrations achieved within 1-2 hours after oral administration. It is widely distributed in body tissues and fluids, and it is excreted primarily via the kidneys. The elimination half-life is approximately 1 hour, and renal impairment may necessitate dosage adjustments.

Adverse effects

• Skin rash
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Allergic reactions (including anaphylaxis)
• Superinfection (due to resistant organisms)

Interactions

• Allopurinol (increases risk of skin rash)

Precautions

• History of penicillin allergy
• Renal impairment (reduce dose)
• Use with caution in patients with mononucleosis

Pregnancy

Use only if clearly needed; no adequate studies in pregnant women.

Breast-feeding

Amoxicillin is excreted in breast milk; use with caution.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Phenoxymethylpenicillin 250mg/5ml oral solution
• Phenoxymethylpenicillin 250 mg tablets

Indications

• Serious infections caused by multidrug-resistant Gram-negative bacteria
• Pneumonia caused by Pseudomonas aeruginosa
• Complicated urinary tract infections
• Bacteremia
• Meningitis caused by susceptible organisms

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Refer to specific clinical guidelines or the BNF for appropriate dosing information.

Mechanism of action

Colistin exerts its antibacterial effects by binding to the lipopolysaccharide (LPS) of the bacterial outer membrane, leading to disruption of the membrane integrity. This results in leakage of intracellular contents and ultimately cell death. The interaction with LPS alters membrane permeability and causes destabilization of the membrane structure, which is critical for bacterial survival.

Pharmacodynamics

Colistin's primary action is bactericidal against Gram-negative bacteria. It shows concentration-dependent killing, meaning that higher concentrations lead to a more significant antibacterial effect. Resistance to colistin can occur through modifications of the bacterial outer membrane, particularly through the addition of 4-amino-4-deoxy-L-arabinose to the lipid A component of LPS, which reduces colistin's binding affinity.

Pharmacokinetics

Colistin is administered intravenously or intramuscularly, as it is poorly absorbed from the gastrointestinal tract. After administration, it is rapidly distributed into body tissues, but it has a variable volume of distribution. Colistin is primarily eliminated by the kidneys, and its half-life is influenced by renal function. Renal impairment can lead to accumulation and increased risk of toxicity, necessitating dosage adjustments.

Contra-indications

• Hypersensitivity to colistin or any component of the formulation
• Renal impairment (caution advised in patients with moderate to severe renal impairment)

Adverse effects

• Nephrotoxicity
• Neurotoxicity (including dizziness, vertigo, and neuromuscular blockade)
• Allergic reactions (including rash and anaphylaxis)
• Gastrointestinal disturbances (such as diarrhea and nausea)

Interactions

• Concurrent use of other nephrotoxic agents (e.g., aminoglycosides, vancomycin)
• Potential for increased neuromuscular blockade when used with neuromuscular blockers

Precautions

• Monitor renal function during treatment
• Use with caution in patients with neuromuscular disorders
• Ensure adequate hydration to reduce nephrotoxic effects

Pregnancy

Colistin should be used in pregnancy only if clearly needed, as there is limited safety data available.

Breast-feeding

Caution is advised when administering colistin to nursing mothers, as it is unknown if it is excreted in human milk.

Storage

Store in a cool, dry place, protected from light. Reconstituted solutions should be used promptly and discarded after 24 hours if not used.

Formulations

• Colistin sulfate for oral use
• Colistimethate sodium for injection

Mechanism of action

Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action. The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/ Amoxicillin is similar to penicillin in its bactericidal action against susceptible bacteria during the stage of active multiplication. It acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria.

Pharmacodynamics

Amoxicillin competitively inhibit penicillin binding proteins, leading to upregulation of autolytic enzymes and inhibition of cell wall synthesis. Amoxicillin has a long duration of action as it is usually given twice daily. Amoxicillin has a wide therapeutic range as mild overdoses are not associated with significant toxicity. Patients should be counselled regarding the risk of anaphylaxis, _Clostridium difficile_ infections, and bacterial resistance.