Sultamicillin

Ampicillin is an aminopenicillin which exerts its bactericidal activity by interfering with the synthesis of the bacterial cell wall. It inhibits transpeptidase, an enzyme responsible for the synthesis of the peptidoglycan layer of the bacterial cell wall. This results in the interruption of peptidoglycan synthesis causing spheroplast formation and bacterial lysis.

Sulbactam is a penicillanic acid sulfone with beta-lactamase inhibitory properties. It is an irreversible inhibitor of many plasmid-mediated and some chromosomal beta- lactamases and has a similar spectrum of beta-lactamase inhibition as clavulanic acid. Sulbactam can therefore enhance the activity of penicillins and cephalosporins against many strains of bacteria.

Antimicrobial spectrum of activity

Sultamicillin has demonstrated bactericidal activity against the following microorganisms:

Aerobic Gram-positive:

Staphylococcus aureus penicillin-resistant and some methicillin-resistant Haemophilus parainfluenzae (both beta-strains)
Staphylococcus epidermidis (including penicillin-resistant and some methicillin-resistant strains)
Streptococcus pneumoniae
Streptococcus faecalis
Other Streptococcus spp.

Aerobic Gram-negative:

Haemophilus influenzae (both beta-lactamase positive and negative strains)
Haemophilus parainfluenzae (both beta-lactamase positive and negative strains)
Moraxella catarrhalis
Escherichia coli
Klebsiella spp.
Proteus spp. (both indole-positive and indole-negative)
Enterobacter spp.
Morganella morganii
Citrobacter spp.
Neisseria meningitidis
Neisseria gonorrhoeae

Anaerobes:

Bacteroides fragilis and related species

Oral administration

After oral administration, sultamicillin is hydrolyzed during absorption to equivalent molar quantities (1:1) of ampicillin and sulbactam. The bioavailability of an oral dose of sultamicillin is 80% of an equal intravenous (IV) dose of ampicillin and sulbactam.

Food does not affect the systemic bioavailability of sultamicillin. After sultamicillin administration, peak serum levels of ampicillin are approximately twice those of an equal dose of oral ampicillin. Elimination half-lives are about 1 hour and 0.75 hour for ampicillin and sulbactam, respectively, in healthy volunteers, with 50-75% of each drug being excreted unchanged in the urine. The elimination half-lives are increased in the elderly and in patients with renal impairment. Probenecid decreases the renal tubular secretion of both ampicillin and sulbactam.

IV / IM administration

Immediately after completion of a 15-minute intravenous infusion of sulbactam, peak serum concentrations of ampicillin and sulbactam are attained. Ampicillin serum levels are similar to those produced by the administration of equivalent amounts of ampicillin alone. Peak ampicillin serum levels ranging from 109 to 150 mcg/mL are attained after administration of 2000 mg of ampicillin plus 1000 mg sulbactam and 40 to 71 mcg/mL after administration of 1000 mg ampicillin plus 500 mg sulbactam. The corresponding mean peak serum levels for sulbactam range from 48 to 88 mcg/mL and 21 to 40 mcg/mL, respectively. After an intramuscular injection of 1000 mg ampicillin plus 500 mg sulbactam, peak ampicillin serum levels ranging from 8 to 37 mcg/mL and peak sulbactam serum levels ranging from 6 to 24 mcg/mL are attained.

The mean serum half-life of both drugs is approximately 1 hour in healthy volunteers.

Approximately 75 to 85% of both ampicillin and sulbactam are excreted unchanged in the urine during the first 8 hours after administration of sulbactam to individuals with normal renal function. Somewhat higher and more prolonged serum levels of ampicillin and sulbactam can be achieved with the concurrent administration of probenecid.

In patients with impaired renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin.

Ampicillin has been found to be approximately 28% reversibly bound to human serum protein and sulbactam approximately 38% reversibly bound.

The following average levels of ampicillin and sulbactam were measured in the tissues and fluids listed:

Concentration of sulbactam in Various Body Tissues and Fluids:

Penetration of both ampicillin and sulbactam into cerebrospinal fluid in the presence of inflamed meninges has been demonstrated after IV administration of sulbactam.

The pharmacokinetics of ampicillin and sulbactam in pediatric patients receiving sulbactam are similar to those observed in adults. Immediately after a 15-minute infusion of 50 to 75 mg sulbactam/kg body weight, peak serum and plasma concentrations of 82 to 446 mcg ampicillin/mL and 44 to 203 mcg sulbactam/mL were obtained. Mean half-life values were approximately 1 hour.

While reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in man.