Ampicillin 250 mg, Cloxacillin 250 mg Hard-gelatin capsules

Cloxacillin binds penicillin-binding proteins and inhibits bacterial cell-wall synthesis. It resists many staphylococcal penicillinases, but altered PBP2a associated with mecA-mediated resistance prevents that property from establishing activity against resistant staphylococci.

The capsule reference describes broad distribution into body fluids and tissues, protein binding of approximately 95–97% and a distribution volume around 0.1 L/kg. Renal elimination includes filtration and tubular secretion; about 30–45% is recovered unchanged in urine, with partial hepatic metabolism and smaller biliary and fecal losses. The reported half-life is 0.5–1.1 hours and increases with impaired renal function. No quantitative oral absorption estimate is supplied in this section.

Ampicillin is bactericidal at low concentrations and is clinically effective not only against the gram-positive organisms usually susceptible to penicillin G but also against a variety of gram-negative organisms. It is stable in the presence of gastric acid and is well absorbed from the gastrointestinal tract. It diffuses readily into most body tissues and fluids; however, penetration into the cerebrospinal fluid and brain occurs only with meningeal inflammation. Ampicillin is excreted largely unchanged in the urine; its excretion can be delayed by concurrent administration of probenecid which inhibits the renal tubular secretion of ampicillin. In blood serum, ampicillin is the least bound of all the penicillins; an average of about 20 percent of the drug is bound to plasma proteins as compared to 60 to 90 percent of the other penicillins. The administration of 500 mg dose of ampicillin capsules results in an average peak blood serum level of approximately 3.0 mcg/mL.

Mechanism of Action — Ampicillin 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.

Mechanism of Resistance — Resistance to ampicillin is mediated primarily through enzymes called beta-lactamases that cleave the beta-lactam ring of ampicillin, rendering it inactive.

Antimicrobial Activity — Ampicillin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections, as described in the INDICATIONS AND USAGE section.

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to 0.12 mcg/mL for ampicillin. However the efficacy of ampicillin in treating clinical infections due to these bacteria has not been established in adequate and well-controlled trials.

Susceptibility Testing — For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.