COMBICILLIN CAPSULE

Indications

• Bacterial infections
• Listerial meningitis
• Bronchitis
• Urinary tract infections
• Community-acquired pneumonia
• Salmonellosis

Dosage

Children: Refer to the BNF for Children for specific dosing: Neonate up to 7 days: 30 mg/kg every 12 hours; Neonate 7 to 20 days: 30 mg/kg every 8 hours; Neonate 21 to 28 days: 30 mg/kg every 6 hours.

Adults: 500 mg to 1 g every 6 hours, depending on the severity of the infection.

Mechanism of action

Ampicillin works by inhibiting bacterial cell wall synthesis, leading to cell lysis and death in susceptible bacteria.

Pharmacodynamics

Ampicillin exhibits bactericidal activity against a broad spectrum of gram-positive and some gram-negative bacteria, including Streptococcus spp., Enterococcus spp., and certain E. coli strains.

Pharmacokinetics

Ampicillin is well absorbed from the gastrointestinal tract, with a bioavailability of approximately 50-70%. It is distributed widely in body tissues and fluids, including the central nervous system. It is primarily eliminated by the kidneys through glomerular filtration and tubular secretion.

Adverse effects

• Colitis haemorrhagic
• Skin rash

Interactions

• Allopurinol (increases risk of skin rash)

Precautions

• Caution in renal impairment
• Potential for electrolyte accumulation with intravenous use

Pregnancy

Not known to be harmful.

Breast-feeding

Trace amounts in milk, but appropriate to use.

Storage

Store in a cool, dry place, protected from light.

Formulations

• Ampicillin 500 mg capsules
• Ampicillin 125 mg/5 ml oral suspension
• Ampicillin 25 mg per 1 ml oral suspension
• Ampicillin powder for injection

Indications

• Skin and soft tissue infections
• Bone infections (osteomyelitis)
• Endocarditis
• Pneumonia caused by susceptible strains
• Urinary tract infections caused by susceptible organisms

Dosage

Children: Refer to the BNF for Children for appropriate dosing based on age and weight.

Adults: Refer to specific guidelines based on the type and severity of infection, as well as patient-specific factors.

Mechanism of action

Cloxacillin works by inhibiting bacterial cell wall synthesis. It binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, disrupting the transpeptidation process necessary for cross-linking peptidoglycan layers. This leads to cell lysis and death, particularly in actively dividing bacteria.

Pharmacodynamics

The pharmacodynamics of cloxacillin involve its bactericidal activity against susceptible strains of bacteria. The drug's effectiveness is enhanced by its stability against hydrolysis by beta-lactamases produced by certain bacteria. The minimum inhibitory concentration (MIC) is crucial in determining its effectiveness, with susceptibility typically assessed using standard laboratory methods.

Pharmacokinetics

Cloxacillin is absorbed well from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours post-administration. It is widely distributed in body tissues and fluids, with good penetration into bone and soft tissues. The drug is metabolized in the liver and primarily excreted unchanged in urine, with a half-life of approximately 30 minutes to 1 hour in healthy adults.

Contra-indications

• Hypersensitivity to cloxacillin or any component of the formulation
• History of severe allergic reactions to penicillins or cephalosporins

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Rash
• Urticaria
• Anaphylaxis
• Clostridium difficile-associated diarrhea
• Hepatic dysfunction
• Nephrotoxicity

Interactions

• Probenecid may increase serum concentrations of cloxacillin
• Aminoglycosides may have additive effects on nephrotoxicity
• Oral contraceptives may have reduced efficacy

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of anaphylaxis after the first dose
• Consider potential for superinfection with prolonged use

Pregnancy

Cloxacillin is classified as category B. Animal studies have not shown any fetal harm, but caution is advised when prescribing during pregnancy.

Breast-feeding

Cloxacillin is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

Store in a cool, dry place away from direct sunlight. Reconstituted solutions should be refrigerated and used within the specified timeframe.

Formulations

• Capsules
• Oral suspension
• Injectable solution

Mechanism of action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, Ampicillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Ampicillin interferes with an autolysin inhibitor. SINCE PENICILLIN HAS NO EFFECT ON EXISTING CELL WALLS, BACTERIA MUST BE MULTIPLYING FOR BACTERICIDAL ACTION OF PENICILLIN TO BE MANIFEST. /PENICILLINS/ 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/ Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin binding proteins located on the inner membrane of the bacterial cell wall. Penicillin binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/

Pharmacodynamics

Ampicillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Ampicillin has <i>in vitro</i> activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Ampicillin results from the inhibition of cell wall synthesis and is mediated through Ampicillin binding to penicillin binding proteins (PBPs). Ampicillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.