Antibiotics 1
Antibiotics
Are the products of life activity of microorganisms (most often fungi) and their synthetic derivatives.
By the peculiarities of antimicrobial action antibiotics can be classified into:
- bactericidal antibiotics (they cause the death of bacteria): penicillins, cephalosporins, aminoglycosides, polymyxins;
- bacteriostatic antibiotics (they prevent bacteria from growing and reproducing): tetracyclines, chloramphenicol, macrolides, lincosamides.
One and the same antibiotic can act as a bactericidal one on some bacteria and as a bacteriostatic one – on other bacteria. For example, chloramphenicol acts on many bacteria bacteriostaticly, while on hemophilic bacteria – as a bactericidal antibiotic.
By the range of antimicrobial action antibiotics are classified into:
- Antibiotics affecting mainly gram-positive bacteria (cocci), for example, benzylpenicillins;
- Antibiotics affecting mainly gram-negative bacteria (bacilli), for example, fluoroquinolones of the 1st and 2nd generations (Ciprofloxacin).
- Antibiotics of a wide range of action affecting both gram-positive and gram-negative microflora – aminopenicillins, cephalosporins, aminoglycosides, tetracyclines etc.
By the mechanisms of antimicrobial action one distinguishes antibiotics that destroy the following structures and processes in a bacterium:
- The wall of a cell;
- permeability of cytoplasmic membrane;
- synthesis of proteins;
- synthesis of RNA.
β – lactam antibiotics
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
Penicillins
One differentiates biosynthetic (natural) and semisynthetic penicillins.
Biosynthetic ones:
- Benzylpenicillins;
- Phenoxymethylpenicillins.
Semisynthetic penicillins are subdivided into:
- Penicillins resistant to penicillinase – an enzyme splitting penicillin;
- Penicillins of a wide range of action;
- Aminopenicillins;
- Carboxypenicillins;
- Ureidopenicillins.
Benzylpenicillins
Pharmacodynamics. They inhibit transpeptidases participating in the synthesis of peptidoglycan of the cellular wall of bacteria and destroying it. They exert a bactericidal action on mainly gram-positive bacteria. Among gram-negative – on meningococci and gonococci. The majority of strains of staphylococci possess resistance to benzylpenicillins because they release β- lactamase (penicillinase) – an enzyme splitting benzylpenicillins.
Pharmacokinetics. In stomach penicillins are destroyed by HCl, that is why they are administered parenterally. Many penicillins are not metabolized and excreted by kidneys in an unchanged form. The half-life period of the majority of penicillins (except “depot-P”) – 1 hour and it gets longer in case of renal failure.
Benzylpenicillin (BP) (Benzylpenicillinum) is produced in the form of sodium and potassium salts for parenteral administration. Sodium salt can be administered i/m, i/v and endolumbally. Potassium salt – only i/m (injections are very painful!).
Pharmacokinetics: Сmax in blood – in 30-60 min after i/m administration. The duration of action – 4 hours independent on the administered dose. The number of administrations – 4-6 times a day. If the clearance of creatinine is less than 30 ml/min – 3 times a day. For i/v administration sodium salt of BP is mixed with 100-200 ml of physiological solution.
Pharmacodynamics. They inhibit transpeptidases participating in the synthesis of peptidoglycan of the cellular wall of bacteria and destroying it. They exert a bactericidal action on mainly gram-positive bacteria. Among gram-negative – on meningococci and gonococci. The majority of strains of staphylococci possess resistance to benzylpenicillins because they release β- lactamase (penicillinase) – an enzyme splitting benzylpenicillins.
Pharmacokinetics. In stomach penicillins are destroyed by HCl, that is why they are administered parenterally. Many penicillins are not metabolized and excreted by kidneys in an unchanged form. The half-life period of the majority of penicillins (except “depot-P”) – 1 hour and it gets longer in case of renal failure.
Benzylpenicillin (BP) (Benzylpenicillinum) is produced in the form of sodium and potassium salts for parenteral administration. Sodium salt can be administered i/m, i/v and endolumbally. Potassium salt – only i/m (injections are very painful!).
Pharmacokinetics: Сmax in blood – in 30-60 min after i/m administration. The duration of action – 4 hours independent on the administered dose. The number of administrations – 4-6 times a day. If the clearance of creatinine is less than 30 ml/min – 3 times a day. For i/v administration sodium salt of BP is mixed with 100-200 ml of physiological solution.
Dose regimen
- Large doses of BP (20-30 mln IU/day) are used for the treatment of severe infections: meningitis, infective endocarditis, gas gangrene. With a daily dose more than 30 mln IU toxic effects from the side of CNS are possible (convulsions).
- Medium doses of BP (10-18 mln IU/day) are used for the treatment of aspiration pneumonia or lung abscess caused by group A streptococci or by anaerobic cocci, in combination with aminoglycosides – for the treatment of enterococcal endocarditis.
- Small doses of BP (4-8 mln IU/day) are used for the treatment of pneumococcal pneumonia.
Prolonged penicillin drugs (bicillins 1,3,5) are used for the prevention of rheumatism, scarlet fever and recurrent erysipelas. They are administered in the form of suspension only i/m.
Procainibenzylpenicillin. After the i/m administration novocain salt of benzylpenicillin is absorbed slowly; the concentration in blood is lower in comparison with the administered sodium salt but the duration of action is longer – up to 12 hours. It is mainly used in case of chronic course of the disease – syphilis, anthrax, diphtheria, oral cavity infections.
Bicillins (1,3,5)
Prolonged penicillin drugs (bicillins 1,3,5) are used for the prevention of rheumatism, scarlet fever and recurrent erysipelas. They are administered in the form of suspension only i/m.
- Benzathine benzylpenicillin (Bicillin-1, Retarpen, Extencilline) is administered in case of tonsillopharyngitis and erysipelas i/m – 1.2-2.4 mln IU in a single dose (for the prevention of rheumatism and recurrent erysipelas – once a month), in case of syphilis – 2.4 mln IU every 5-7 days (2-3 injections).
- Benzathine benzylpenicillin + Benzathine benzylpenicillin procaine + Benzylpenicillin (Bicillin-3) unlike Bicillin-1 reaches higher concentration in blood within first 3-6 hours and undergoes rapid elimination out of the body. It is administered more frequently – 300 000 IU once in 3 days or 600 000 IU in 6 days or 1.2 mln IU in a single dose. In case of syphilis one administers 900 000 IU in 6 days or 1.2 mln IU according to the instructions.
- Benzathine benzylpenicillin + Benzathine benzylpenicillin procaine (Bicillin-5) is administered i/m – 1.5 mln IU in a single dose and once a month for the prevention of rheumatism.
- Side effects: allergic reactions, fever, rarely hemolytic anemia, convulsions when administered i/v rapidly. The potassium salt of BP is not recommended to be used in case of renal failure. When administered i/m in large doses, it can cause aseptic necrosis.
- Contraindications: allergic reactions to penicillins and for benzylpenicillin procaine – to novocaine. Potassium salt of BP is strictly contraindicated to be administered endolumbally at meningitis.
- Drug interactions: penicillins mustn’t be combined with aminoglycosides because of their physicochemical incompatibility. Potassium salt of BP combined with ACE inhibitors, potassium-sparing diuretics and K drugs can cause hyperaemia. At the simultaneous administration with sulfanilamides bactericidal action of penicillins is decreased.
Penicillinase resistant
They have less antimicrobial activity than BP. The advantage of the drug is its stability to staphylococcal β-lactamase. They are the drugs of choice for the treatment of staphylococcal skin infection, infections of soft tissues, bones, joints, in case of infective endocarditis, pneumonia, sepsis and brain abscess.
- Sodium salt of oxacillin is recommended for parenteral use (i/m, i/v) in case of light infections – 1 g, in case of serious ones – 2 g every 4 hours or p/o 2-4 g/day divided into 4 intakes 1-1.5 hours before meal. Do not combine with aminoglycosides!
- Side effects: nausea, vomiting, diarrhea, allergic reactions.
- Sodium salt of Cloxacillin and Dicloxacillin – p/o use. Maximum concentration in blood – in 1-2 hours. One prescribes Cloxacillin 0.25-0.5 g, Dicloxacillin – 0.125-0.5 g every 6 hours before meal.
Name | Average therapeutic dose, administration rout | Dosage form |
Sodium salt of Oxacillin (Oxacillinumnatrium) | P/o - 2-4 g/day for 4 ingestions.I/m,i/v 4-12 g/day for 4-6 ingestions | Tab. – 0,25 and 0,5 g; caps. – 0,25 g; powder for injection solutions in 25 and 0.5 g vials. |
Aminopinicillins
Pharmacodynamics. Antibiotics of a wide range. They act on gram-positive and aerobic gram-negative bacteria (E.coli, salmonella, Shigella) and H.influenzae.
Ampicillin
Pharmacokinetics: mainly used parenterally because of the low bioavailability (20-40%). After the meal it is less by half.
Prescription: p/o – only for the treatment of bacillary dysentery. It is used in 6 hours an hour before the meal – 0.5 g.
I/v – 20-40 mg/kg/day for the treatment of acute simple out-of-hospital infections of respiratory and urine excreting tracts.
Side effects: allergy symptoms – skin rash, кожная сыпь, hives, Quincke's edema, rarely anaphylactic shock, nausea, diarrhea. If take for a longer period of time the development of superinfection is possible (yeastlike fungi, gram-negative microbes).
Contraindications: high sensitivity to penicillins, infectious mononucleosis.
Amoxicillin
Pharmacokinetics: an ampicillin derivative. Only for the oral use. Bioavailibility – 75-93%. Food intake does not affect the absorption.
The first drug to be used for out-patient treatment of acute infections of ENT-organs (sinusitis, otitis media), lower respiratory tracts (acute bacterial bronchitis, community-acquired bacterial pneumonia), urine-excreting tracts (acute cystitis, acute pyelonephritis, asymptomatic bacteriuria), some intestinal infections (typhoid fever, salmonellosis), in dental procedures, for the treatment of bacterial endocarditis. It is also used for eradication of H.pylori.
Aminopenicillins shouldn’t be prescribed for the treatment of chronic and hospital infections.
Side effects: dyspepsia, insomnia, excitation, dizziness, convulsive reactions, tachycardia, pain in joints, interstitial nephritis, disbacteriosis, candidosis, allergic reactions.
Contraindications: allergic diathesis, bronchial asthma, hay fever, infectious mononucleosis, lymphatic leukemia, GIT diseases in anamnesis.
Prescription – 0.5-1 g every 8 hours; for the prevention of bacterial endocarditis – 3 g in a single dose. Rarely it causes intestinal disbacteriosis and diarrhea.
Combination drugs containing β-lactams and β-lactamase inhibitors
Inhibitors do not perform antimicrobial action but they irreversibly bind to the enzymes (lactamases) and inactivate them. 3 inhibitors of β-lactamase are used: Sulbactam, clavulanic acid and Tazobactam. The combination of AB with β-lactamase inhibitors restores their activity in relation to the majority of staphylococci, gram-negative bacteria, asporous anaerobes, as well as widens their antimicrobial range.
Amoxicillin/clavulanic acid (Amoksiklav, Augmentin, Клавоцин) is the major drug for the treatment of out-of-hospital infections of respiratory tracts (otitis media, sinusitis, acute condition of chronic bronchitis, pneumonia), urine-excreting tracts, small pelvis organs, gonorrhea. It doesn’t affect blue pus bacillus. One prescribes it for the oral use – 0,375 and 0,625 g 3 times/day (during meal); i/v – 1.2 g 3-4 times/day.
Dosage form: tab. – 0,25 and 0,5 g Amoxicillin and 0,125 g of clavulanic acid; frozen-dried powder for injection solutions in 0.6 and 1.2 g vials (respectively, 0.5 and 1 g of amoxicillin and 0.1 and 0.2 g of clavulanic acid).
Amoxicillin/sulbactam (Sultamicillin, Unasyn) is effective in case of a mixed aerobic-anaerobic infection (intraabdominal, gynaecological, traumatic, osteomyelitis, sepsis), meningitis caused by Н.influenzae. One prescribes orally 0,375-0,75 g 2 times/day.; i/m, i/v starting with 1,5 to 12 g/day in 2-4 intakes.
Antipseudomonal P
(Carboxypenicillins, Ureidopenicillins)
They are most effective to the blue pus bacillus, streptococci, enterococci, bacteroids. They are destroyed by β-lactamases. Resistance is rapidly developed. It is not recommended to prescribe them as monotherapy. They should be prescribed together with aminoglycosides or fluoroquinolones.
Pharmacokinetics: after i/m and i/v administration Сmax is 30 min. – 1 h, it penetrates into tissues and liquids of the body; it doesn’t undergo the biotransformation in liver. It is excreted by kidneys, reaching high concentration in urine.
Indications: serious hospital infections of various localization (respiratory tracts, urine-excreting tracts, intraabdominal, gynaecological etc.), caused by the blue pus infection
Side effects: hypernatremia (all the drugs contain sodium – 1.85 mEq in 1 g in Mezlocillin up to 5,2 mEq in Ticarcillin), hypokalemia, thrombocytopenia caused by membrane dysfunction in thrombocytes manifested by hemorrhage.
Contrindications: Carboxi- and ureidopenicillins are contraindicated in case of hepatic and renal failure. Relative contraindications: colitis caused by the use of antibiotics.
Cephalosporins (CP)
They are active in relation to all microorganisms except enterococci, clamydia, mycoplasma. They act bactericidally. Well-tolerated.
CP of the 1st generation
Parenteral: Cefazolins (Kefzol), Сеfaloridine (Ceporine), Cefalotine, Cefapirine sodium salt, Cefradine.
Oral: Cefradine, Cefalexine, Cefadroxil.
They are most active to gram-positive cocci (staphylococci, streptococci, pneumococci).
Indications: skin and soft tissues infections (furunculosis, phlegmon, pyoderma), infections of bones (osteomyelitis) and joints, mastitis, sepsis and endocarditis (stable to staphylococcal β-lactamase). Noncomplicated pyelonephritis caused by colon bacillus, cystitis, urethritis, prostatitis, gonorrhea, streptococcic tonsilopharingitis, otitis, pneumonia. For the prevention of infectious complications during surgeries on bile ducts, stomach and small intestine, small pelvis organs, in traumatology and orthopaedics, vascular and cardiac surgery.
Cefasolin sodium salt
Pharmacokinetics: if administered i/m, rapidly absorbed, Сmax – 1 h, Т1/2 – about 2 h; effective concentration in plasma is maintained for 8-12 hours. Excretion by kidneys (90%) in an unchanged form.
Side effects: allergy, leukopenia, eosinophilia, neutropenia, agranulocytosis, thrombocytopenia, hemolytic anemia, candidosis, pseudomembranous colitis, nausea, vomiting, anorexia, diarrhea. Local painfulness is possible if administered i/m.
Contraindications: pregnancy, lactation.
