Ampicillin

Pharmacological properties

ampicillin has a wide spectrum of antibacterial (bactericidal) action. active against gram-positive microorganisms (staphylococcus spp., with the exception of penicillinase-producing strains; streptococcus spp., including s. pneumoniae; corynebacterium diphtheriae, bacillus anthracis, clostridium spp., most enterococci, and shrimp , salmonella spp., neisseria meningitidis, n. gonorrhoeae, proteus mirabilis, some strains of klebsiella pneumoniae, haemophilus influenzae) microorganisms.

The drug is destroyed by penicillinase and therefore does not affect penicillin-forming bacteria strains. The drug inhibits peptidoglycan polymerase and transpeptidase, prevents the formation of peptide bonds and disrupts the late stages of the synthesis of the cell wall of microorganisms that divide. The resulting defects in the membrane reduce the osmotic resistance of the bacterial cell, which leads to its death (lysis).

Pharmacokinetics When i / m or / in the introduction of circulates in high concentrations in the blood. C_max in the blood manifests itself after 15 minutes with a / in the introduction and after 0.5-1 hours - after a / m. With a / m administration of 0.5-1 g of ampicillin with an interval between doses of 4-6 hours in the blood, the therapeutic concentration is maintained.

It penetrates well into tissues and body fluids, manifests itself in therapeutic concentrations in the pleural, peritoneal and synovial fluids. In bile, it can manifest itself in concentrations 4–100 times higher than in blood. A relatively small (10–30%) portion binds to plasma proteins. Through the BBB does not penetrate. Almost no biotransformation. It is excreted mainly by the kidneys, partly with bile, in women who are breastfeeding, it penetrates into milk. Within 12 hours, 45–70% of the administered dose is excreted in the urine. In case of impaired renal excretory function, the level of the drug in the blood rises and its excretion slows down. With creatinine clearance of 10 ml / min, the level of antibiotic in the blood can be 10 times higher than in patients with normal renal function. T_½ lengthens from 1-2 hours normally to 10-12 hours. Ampicillin does not accumulate upon repeated administration, which makes it possible to use it in high doses and for a long time.

Indications

Sepsis, septic endocarditis, meningitis, respiratory tract infections (pneumonia, chronic bronchitis, lung abscess); urinary and biliary tract infections (pyelitis, pyelonephritis, cystitis, cholangitis, cholecystitis); infections of the skin and soft tissues and diseases caused by microorganisms sensitive to the action of the antibiotic (caused by beta-hemolytic group A streptococcus or coagulase-positive staphylococcus sensitive to penicillin); reorganization of carriers of typhoid (carriers of salmonella typhi and paratyphi).

Application

The dose of the drug and the duration of treatment are set individually, depending on the severity of the disease, the location of the infection and the sensitivity of the pathogen to the drug. a skin test is required for hypersensitivity to the antibiotic. the drug is administered in / m or / in (drip or stream).

The recommended dose for adults is 250–500 mg 4 times a day, daily - up to 1-3 g. In severe infections, the daily dose can be increased to ≥10 g.

For newborns, the drug is prescribed in a daily dose of 20-40 mg / kg body weight, for children of other age groups - 50-100 mg / kg. In severe infections, these doses can be doubled. The daily dose is administered in 4-6 doses with an interval of 4-6 hours.

In case of meningitis in children: at the age of 1 month, 100–500 mg / kg in a daily dose is prescribed; at the age of 1 month, in a daily dose of 200–300 mg / kg for 6–8 administrations. The daily dose is administered in 4-6 doses.

The duration of treatment is 7-14 days or more. Treatment with ampicillin should be continued for at least 48–72 hours after normalization of body temperature and the disappearance of the symptoms of the disease. In infections caused by hemolytic streptococcus, the duration of treatment should be at least 10 days.

A solution for i / m administration should be prepared immediately before use, adding 5 ml of sterile water for injection to the contents of the vial. For iv injection, a single dose of the drug (no more than 2 g) is dissolved in 5–10 ml of water for injection or 0.9% sodium chloride solution and administered slowly for 3-5 minutes (administration at a dose of 1-2 g is carried out for 10-15 minutes).At a single dose exceeding 2 g, the drug is administered intravenously. For iv drip, a single dose of the drug (2–4 g) is dissolved in a small volume of water for injection (7.5–15 ml, respectively), then the resulting antibiotic solution is added to 125–250 ml of 0.9% r- ra of sodium chloride or 5-10% r-ra of glucose and administered at a rate of 60-80 drops per minute. When administered dropwise to children, 5-10% glucose solution is used as a solvent. Use solutions immediately after preparation.

Contraindications

Hypersensitivity to ampicillin and other β-lactam antibiotics (penicillins, cephalosporins, carbapenems); severe violations of the liver and kidneys; Infectious mononucleosis; leukemia; HIV infection digestive tract diseases / colitis associated with the use of antibiotics.

Side effects

On the part of the immune system: allergic reactions, including rash, itching, hyperemia, urticaria, rhinitis, conjunctivitis, fever, joint pain, eosinophilia, exfoliative dermatitis, purpura, multiforme exudative erythema, Stevens-Johnson syndrome, Quinckes edema, anapha, Quincke edema, Anapha.

From the digestive system: nausea, vomiting, diarrhea, taste changes, abdominal pain, stomatitis, glossitis, dry mouth, intestinal dysbiosis, gastritis, enterocolitis, hemorrhagic colitis. During treatment or within a few weeks after the end of antibiotic therapy, there is a likelihood of developing pseudomembranous colitis.

From the hepatobiliary system: hepatitis, cholestatic jaundice.

From the side of the central nervous system and peripheral nervous system: when using the drug in high doses in patients with renal failure, dizziness, headache, tremor, convulsions, neuropathy are possible.

Local reactions: including swelling, itching, hyperemia at the injection site.

Laboratory indicators: increased activity of hepatic transaminases, LDH, alkaline phosphatase, creatinine, false-positive results of non-enzymatic glucosuric tests and Coombs reaction.

Other: reversible hemopoiesis disorders (leukopenia, thrombocytopenia, hemolytic anemia, agranulocytosis), interstitial nephritis, superinfection, candidiasis. When using Ampicillin in patients with bacteremia (sepsis), a bacteriolysis reaction (Yarish-Herxheimer reaction) is possible.

special instructions

In the process of treatment, systematic monitoring of the function of the kidneys, liver and peripheral blood is necessary. in patients with renal failure, the dose of the drug must be reduced; in patients with severe renal failure (creatinine clearance 10 ml / min), use the drug in half dose with an interval of 12 hours

Caution should be used in the treatment of sick children if there is evidence in the mother’s history of her increased sensitivity to penicillins.

In AD, hay fever and other allergic diseases, the drug should be used while prescribing desensitizing agents.

With prolonged treatment with weakened patients, superinfection caused by microorganisms resistant to the drug may develop.

It is necessary to stop taking the drug if a skin rash occurs.

Patients with lymphocytic leukemia have an increased risk of developing a skin rash.

Use during pregnancy and lactation. No teratogenic effect of Ampicillin. However, the use of Ampicillin during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus.

Ampicillin passes into breast milk in low concentrations. During treatment, breast-feeding should be discontinued.

Children. Ampicillin is used in pediatric practice.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. During treatment, some patients may experience adverse reactions from the central nervous system (seeADVERSE EFFECTS), therefore, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Interactions

Ampicillin increases the effect of anticoagulants, antibiotics of the aminoglycoside series, reduces the effect of oral contraceptives. with the simultaneous use of ampicillin with oral estrogen-containing drugs, there is a decrease in their effectiveness due to weakening of the hepatic circulation of estrogen.

Probenecid reduces the tubular secretion of ampicillin, resulting in an increased risk of developing its toxic effect.

Allopurinol is more likely to cause a skin rash.

Ampicillin in high doses reduces the level of atenolol in blood plasma, therefore it is recommended to use these drugs separately, atenolol first, and after it - ampicillin.

Ampicillin reduces clearance and increases the toxicity of methotrexate, enhances the absorption of digoxin.

The interaction of ampicillin with macrolides, paromomycin, tetracyclines, chloramphenicol reduces the effect of both drugs. Ampicillin may reduce the effect of sodium benzoate.

With the simultaneous use of beta-adrenoreceptor blockers, the likelihood of anaphylactic reactions increases.

Overdose

In case of an overdose, toxic effects on the central nervous system (dizziness, headache), dyspeptic symptoms (nausea, vomiting, loose stools), allergic reactions in the form of a skin rash are possible. in case of overdose symptoms, the drug should be stopped immediately and symptomatic treatment should be carried out: gastric lavage, intake of activated carbon, saline laxatives, correction of water-electrolyte balance, hemodialysis. with allergies, antihistamines and desensitizing agents are indicated.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.