Ampicillin/flucloxacillin

Co-fluampicil capsules and container

Co-fluampicil capsules

Ampicillin/flucloxacillin is a combination antibiotic therapy used in the treatment of a variety of bacterial infections. This combination harnesses the antibacterial effects of both ampicillin and flucloxacillin, broadening the spectrum of bacteria it can effectively combat. Ampicillin is a beta-lactam antibiotic that is effective against a wide range of Gram-positive bacteria and some Gram-negative bacteria. Flucloxacillin, on the other hand, is a penicillinase-resistant penicillin, which makes it particularly effective against Staphylococcus aureus, including strains that produce beta-lactamase, an enzyme that confers resistance to many other beta-lactam antibiotics.

Indications

Ampicillin/flucloxacillin is indicated for the treatment of infections caused by susceptible organisms where a broad spectrum of activity is required. This includes respiratory tract infections, urinary tract infections, skin and soft tissue infections, and septicemia. It is particularly useful in treating infections known or suspected to involve mixed bacterial populations, where ampicillin's efficacy against Gram-negative bacteria complements flucloxacillin's activity against penicillin-resistant Staphylococcus aureus.

Mechanism of Action

The mechanism of action of ampicillin/flucloxacillin involves the inhibition of bacterial cell wall synthesis. Both ampicillin and flucloxacillin bind to penicillin-binding proteins (PBPs) on the bacterial cell wall. This binding inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. The result is the weakening of the bacterial cell wall and ultimately cell lysis.

Pharmacokinetics

The pharmacokinetics of ampicillin and flucloxacillin when administered together generally reflect the characteristics of each agent. Ampicillin is well absorbed from the gastrointestinal tract but its bioavailability can be reduced by food. It is eliminated primarily through the kidneys. Flucloxacillin has a similar absorption profile but is more acid-stable, allowing for better oral absorption. It is also primarily excreted by the kidneys. When combined, the two drugs do not significantly affect each other's absorption or elimination.

Adverse Effects

The combination of ampicillin and flucloxacillin is generally well tolerated, but adverse effects can occur. These may include allergic reactions, ranging from rash to anaphylaxis, gastrointestinal disturbances such as nausea, vomiting, and diarrhea, and changes in blood parameters, including neutropenia and thrombocytopenia. As with all antibiotics, prolonged use may lead to the overgrowth of non-susceptible organisms, including fungi.

Resistance

The use of ampicillin/flucloxacillin, as with all antibiotics, can lead to the development of resistance. Bacterial resistance mechanisms include the production of beta-lactamase enzymes that degrade the antibiotic, alterations in PBPs that reduce drug binding, and changes in membrane permeability that decrease drug uptake. The inclusion of flucloxacillin in this combination is specifically aimed at overcoming resistance by beta-lactamase-producing strains of Staphylococcus aureus.

Conclusion

Ampicillin/flucloxacillin is a valuable combination antibiotic for the treatment of mixed bacterial infections, offering a broad spectrum of activity against both Gram-positive and Gram-negative organisms. Its use should be guided by susceptibility testing and clinical judgment to minimize the risk of resistance development.