antistaphylococcal

Antistaphylococcal refers to antibiotics that are effective against Staphylococcus species, particularly strains that produce beta-lactamase. In clinical use, the term most often designates penicillinase-resistant penicillins, a subgroup developed to withstand staphylococcal penicillinases. The principal agents are nafcillin, oxacillin, dicloxacillin, and flucloxacillin.

Mechanism of action and rationale: these drugs are beta-lactam antibiotics that inhibit bacterial cell wall synthesis by binding penicillin-binding proteins. Their bulky side chains protect the beta-lactam ring from hydrolysis by staphylococcal penicillinases, enabling activity against susceptible staphylococci while remaining less active against many other bacteria.

Spectrum and limitations: antistaphylococcal penicillins have good activity against Staphylococcus aureus that is methicillin-susceptible, as well as many streptococci. They show limited activity against most gram-negative bacteria and have no activity against methicillin-resistant Staphylococcus aureus (MRSA) or many enterococci. They are not reliable for infections caused by organisms producing broad-spectrum beta-lactamases or by MRSA.

Clinical use and resistance: these agents are used for infections caused by methicillin-susceptible Staphylococcus aureus, including certain skin and soft tissue infections, bone and joint infections, and some pneumonias, where beta-lactamase production is a concern. Resistance can arise through altered penicillin-binding proteins or the acquisition of additional resistance mechanisms; MRSA remains resistant to these drugs.

Pharmacokinetics and adverse effects: formulations are available for oral or parenteral administration, with tissue distribution suitable for many soft tissue and skeletal infections. Adverse effects are similar to other beta-lactams and include hypersensitivity reactions, rash, and, less commonly, gastrointestinal upset or liver and kidney toxicity in susceptible individuals.