Ampisulbin® [Ampicillin, Sulbactam]

Pharmacological properties

Ampisulbin is a combination of a beta-lactam inhibitor - sulbactam and a bactericidal beta-lactam antibiotic - ampicillin.

Ampicillin belongs to the group of penicillins with a wide spectrum of action and is active against gram-positive and gram-negative microorganisms. Ampicillin exhibits a bactericidal effect, inhibiting the biosynthesis of cell membranes of microorganisms in the proliferation phase.

Sulbactam inhibits the beta-lactamases of bacteria that inactivate penicillins, thus enhancing the effect of ampicillin on penicillin-resistant microorganisms. Sulbactam exhibits antibacterial activity only against Neisseriaceae, Acinetobacter calcoaceticus, Bacteroides spp., Moraxella Branhamella catarrhalis and Burkholderia cepacia.

Sulbactam / ampicillin resistance can be based on the following mechanisms:

• inactivation of beta-lactamases, as a result of which sulbactam / ampicillin does not have a sufficient effect on bacteria producing beta-lactamase;
• a decrease in the affinity of penicillin-binding proteins (PSB) due to a mutation of existing PSB or in connection with the production of additional PSB with reduced affinity for ampicillin;
• insufficient suppression of PSB due to poor penetration of ampicillin into the outer wall of the cell.

Usually sensitive species of microorganisms

Aerobic gram-positive bacteria: Staphylococcus aureus (methicillin-sensitive), Enterococcus faecalis, Streptococcus pneumonia and other streptococci.

Aerobic gram-negative bacteria: Haemophilus influenzae and parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae and meningitidis.

Anaerobic bacteria: Bacteroides fragilis and other species of this genus.

Species acquiring resistance in isolated cases

Aerobic gram-positive bacteria: Enterococcus faecium, Staphylococcus epidermidis.

Aerobic gram-negative bacteria: E. coli, bacteria of the genus Klebsiella and Proteus.

Congenital resistant microorganisms

Aerobic gram-positive bacteria: Staphylococcus aureus (methicillin-resistant).

Aerobic gram-negative bacteria: Psuedomonas aeruginosa, Enterobacter cloacae, species of Citrobacter, Morganella morganii, Serratia and all enterobacteria producing type I beta-lactamase.

Benchmarks

For sulbactam / ampicillin, the following MPC benchmarks are recommended (μg / ml according to EUCAST): sensitive ≤2, resistant ≥8.

The level of resistance may vary depending on geographical location and time, therefore, for treatment of severe infections, it is desirable to have local information on resistance for selected species. If necessary, you should seek the advice of an expert if the local level of resistance reaches values ​​at which the benefits of the drug are called into question, at least in the case of certain types of infections. A microbiological diagnosis is recommended, including identification of the pathogen and determination of sensitivity to clindamycin during treatment of severe infections or in case of resistance to therapy.

Pharmacokinetics

Suction / distribution

Both after i / v and after i / m administration, high plasma concentrations of ampicillin / sulbactam are achieved. After iv administration of ampicillin / sulbactam, higher concentrations are achieved than after i / m, but the bioavailability of ampicillin / sulbactam after i / m administration is almost complete. In addition, sulbactam / ampicillin is well distributed in most tissues, body fluids, and secretions.

Metabolism

The metabolites of sulbactam and ampicillin have not yet been determined.

Breeding

T_½ both sulbactam and ampicillin in adults is ≈1 hours. In patients over the age of 65, T_½ fluctuates between 2 and 3 hours. At the age of 1 to 1.5 years T_½ slightly shorter (≈50 min), while it is much longer (8–9 h) in newborns and premature babies. About 80% of both substances are excreted unchanged in the urine within 8 hours after the administration of a single dose of sulbactam / ampicillin.

The simultaneous use of sulbactam and ampicillin does not lead to clinically important deviations from the kinetic parameters observed with the introduction of a single dose of individual substances.

Indications

Treatment for infections caused by microorganisms sensitive to the components of the drug:

• infections of the upper and lower respiratory tract, including sinusitis, otitis media, epiglottitis and bacterial pneumonia;
• urinary tract infections and pyelonephritis;
• intraperitoneal infections, including peritonitis, cholecystitis, endometritis and pelvic inflammation;
• bacterial septicemia;
• infections of the skin, soft tissues, bones and joints;
• gonococcal infection.

The drug can be prescribed in the perioperative period in order to reduce the incidence of postoperative infections in patients undergoing surgery on the abdominal and pelvic cavity and in which infection in the abdominal cavity is possible. With caesarean section or termination of pregnancy, the drug can be used for prevention to reduce the incidence of postoperative sepsis.

It should be noted that sulbactam / ampicillin is ineffective against Pseudomonas aeruginosa.

When using the drug, it is necessary to take into account official recommendations regarding the appropriate use of antimicrobial agents.

Application

Before starting therapy with the use of the drug ampisulbin and lidocaine or another anesthetic, it is necessary to conduct skin tests to determine the individual sensitivity to these drugs (in case of taking the latter, information about the safety of use should be taken into account).

The drug is administered in / in and / m (in the form of a bolus injection or infusion).

To prepare for use, the drug should be diluted with sterile water for injection or another compatible solution. After adding the solvent, wait a few minutes until the foam disappears completely, and then visually assess the completeness of dissolution.

Dissolve the drug with at least 3.2 ml of water for injection (or other compatible solution), respectively. Intramuscularly administered as a bolus injection (at least 3 minutes). With greater dilution, the dose can be administered both bolus and in the form of infusion (within 15-30 minutes).

With i / m use, the drug should be injected deep into the muscle; if the injections are painful, then a 0.5% sterile injection solution of lidocaine hydrochloride or another suitable local anesthetic can be used to reconstitute the powder.

The maximum final concentration of sulbactam / ampicillin is 125 mg / 250 mg in 1 ml.

Treatment for infections caused by microorganisms sensitive to sulbactam and ampicillin

Use in adults. Depending on the severity of the infection, the daily dose of the drug from 1.5 to 12 g should be used in divided doses every 6–8 hours (every 12 hours for less severe infections); the maximum daily dose should not exceed 12 g for the drug (4 g for sulbactam) (table. 1).

Use in children. For newborns in the 1st week of life (especially premature), the drug is usually prescribed at a dose of 75 mg / kg / day (which corresponds to 25 mg / kg / day of sulbactam and 50 mg / kg / day of ampicillin) in divided doses every 12 hours .

In newborns over the age of 1 week and children under 1 year old, the daily dose of the drug is 150 mg / kg (which corresponds to 50 mg / kg / day of sulbactam and 100 mg / kg / day of ampicillin) and should be used in divided doses with an interval of 12 hours .

In children over the age of 1 year, the daily dose of the drug is 150 mg / kg (which corresponds to 50 mg / kg / day of sulbactam and 100 mg / kg / day of ampicillin). The drug is usually administered every 6-8 hours.

For the prevention of surgical infections, the dose of the drug is 1.5–3 g; it should be administered during induction of anesthesia, which provides sufficient time to achieve effective concentrations in blood plasma and tissues during surgery. The dose can be reintroduced every 6-8 hours; the use of the drug, as a rule, is stopped 24 hours after the operation, except in cases where the use of the drug is intended for therapeutic purposes.

For treatment of uncomplicated gonorrhea, the drug can be administered 1 time at a dose of 1.5 g iv or IM.In order to prolong the time to maintain the concentration of sulbactam and ampicillin in blood plasma, probenecid at a dose of 1 g orally should be used simultaneously.

Use in patients with impaired renal function. In patients with severe renal failure (creatinine clearance of 30 ml / min), the excretion of sulbactam and ampicillin is reduced equally, so their ratio in blood plasma does not change. For such patients, the intervals between doses of the drug should be prolonged in accordance with the usual practice of the use of ampicillin (table. 2).

Dialysis patients. Both sulbactam and ampicillin are equally eliminated by hemodialysis. Therefore, it should be applied immediately after dialysis and then, before the next dialysis begins, apply at intervals of 48 hours.

Use in patients with impaired liver function. For patients with impaired liver function, dose adjustment is not required.

Use in the elderly. In the absence of renal failure, dose adjustment in elderly patients is not required.

The duration of treatment depends on the severity of the infection and is usually 5-14 days, however, in more severe cases, it can be increased or ampicillin may be additionally prescribed. As a rule, treatment is continued for an additional 48 hours after normalization of body temperature and the disappearance of other symptoms of a bacterial infection.

The duration of treatment for infections caused by hemolytic streptococcus should be at least 10 days in order to avoid rheumatoid fever and glomerulonephritis.

Breeding instructions

Concentrated solution for v / m use should be used within 1 h after recovery.

The use of the drug for infusion, depending on the type of solvent chosen, is shown in table. 3.