Antibiotics 2
Antibiotics
Are the products of life activity of microorganisms (most often fungi) and their synthetic derivatives.
- Aminoglycosides
- Macrolides
- Tetracyclines
- Lincosamides
- Antibiotics of a peptide group: Polymyxins, glycopeptides.
- Other antibiotics.
- Quinolones/fluoroquinolones
Aminoglycosides (AG)
- AG of the 1st generation: streptomycin, neomycin, monomycin, kanamycin.
- AG of the 2nd generation: gentamicin, sisomicin, netilmicin, tobramycin.
- AG of the 3rd generation: Amikacin, dibekacin, isepamicin etc.
Mechanism of action and range of activity
- AG exert bactericidal effect associated with the disturbance of protein synthesis by ribosomes.
- The level of antibacterial action depends on the dose.
- AG – drugs of a wide range of action.
- They are of high-performance in terms of the majority of gram-negative bacteria (colon bacillus, salmonella, shigella, proteus, Klebsiella, enterobacteria, serratia) and staphylococci.
Pharmacokinetics: Administered p/o, AG is almost not absorbed, that’s why it is used parenterally.
After i/v administration Сmax is in 30 min and in 0,5 – 1,5 h after i/m administration.
AG are not metabolized, excreted by kidneys unchanged by way of glomerular filtration (it is stored in renal tissue for up to 30 days). Т1/2 1,5 – 4 h, in case of renal failure – up to 70 hours and more.
Indications
- Empirical therapy (gentamicin, Amikacin, netilmicin in combination with β-lactams, glycopeptides and antianaerobic drugs);
- hospital (nosocomial) pneumonia (they are effective for pneumonia caused by aerobic gram-negative flora);
- sepsis of unknown etiology (in combination with β-lactams and antianaerobic drugs: lincosamides, metronidazole);
- infective endocarditis (in combination with penicillins);
The drug for empirical therapy in urgent cases is amikacin because more than 90 % of microorganisms (gram-negative and gram-positive) maintain sensitivity to it.
Streptomycin sulfate (streptomycin) is a derivative of ray fungus – Streptomycesglobisporusstreptomycini or related microorganisms. The doses are calculated in mass or in units of activity (UA); 1 UA = 1 microgram of chemically pure streptomycin.
Wide range of antimicrobial action. It is effective to mycobacteria of tuberculosis, most gram-negative bacteria (colon bacillus, Friedländer's bacillus, Pfeiffer's bacillus, causative agents of plague, tularemia, brucellosis) and some gram-positive (staphylococci) aerobic microorganisms.
Pharmacokinetics: taken p/o, it is poorly absorbed and almost completely excreted by intestines in an unchanged form. Administered i/m, it is well-absorbed, Сmax is in 1-2 h after a single administration in a therapeutic dose and is maintained for 6-8 hours. Excreted mainly by kidneys. It is used as a main antituberculous drugs when pulmonary TB or TB of other organs have been diagnosed for the first time. The drug is also used for the pyoinflammatory processes of various localization. Prescriprion: i/m, in the form of sprays, intratracheal and intracavernous (for adults) administrations. Single i/m dose for adults – 0.5-1 g, daily – 1 g or 25-30 mg/kg (max. 1.5 g) 2-3 times a week. The course of treatment – up to 2 months. Side effects: allergic, toxic; convulsions, gait disorder, nausea, vomiting, dizziness, headaches, rapid heartbeat, albuminuria, hematuria, diarrhea, the disorder of the VIII pair of cranial nerves, vestibular disorders, hearing impairment. If used for a long time, the development of deafness is possible. Contraindications: diseases of hearing and vestibular apparatus associated with neuritis of the VIII pair of cranial nerves, otoneuritis; тяжелая степень НК (??), renal failure, cerebral circulation disorder, obliterating endarteritis, myasthenia. Drug interaction: must not be used together with antibiotics possessing an ototoxic action (kanamycin, florimicin, Ristomycin, gentamicin, monomicin) as well as with furosemide and curariform drugs. Dosage form: powder for injection solutions in 0.25, 0.5, 1 g vials. Gentamicin sulfate
Gentamicin sulfate (Gentamycinisulfas) is an antibiotic produced by Micromonosporаpurpurea. The combination of С1, С2, С1а exerts a bacteriostatic action towards numerous gram-positive and gram-negative microorganisms including blue pus bacillus, colon bacillus, proteus, salmonella etc; affects the strains of staphylococci resistant to neomycin and kanamycin. Pharmacokinetics: after i/m administration it is rapidly absorbed; in GIT – poorly absorbed. Cmax – 1 h, bacteriostatic concentrations in blood are maintained for 8-12 hours; excreted by kidneys unchanged reaching its high concentration in urine. It is used for various infection diseases. Administration – i/m, i/v (IV drip), locally. Parenteral – 3-5 mg/kg/day for 1-2 administrations. Locally – into the involved eye 1-2 drops 3-4 times a day. Side effects: Ototoxic and nephrotoxic, disturbances of neuromuscular conduction. Sometimes – nausea, vomiting, renal dysfunction, anemia, leukopenic, thrombocytopenia, rarely – allergic reactions. Contraindications: inflammation of acoustic nerve, myasthenia, pregnancy. It mustn’t be prescribed in combination with other antibiotics performing oto- and nephrotoxic actions. It is not prescribed in case of uraemia. Dosage forms: powder (porous mass) for injection solutions in 1%, 2%, 4%, 6%, 8% and 10 thousand,20 thousand, 40 thousand, 60 thousand and 80 thousand IU – 2 ml. Amikacin sulphate
Amikacin sulphate (Amikacinsulfate, Mikacin, Amikin) is obtained by the semisynthetic method out of Kanamycin A. It is effective in relation to gram-positive (staphylococci) and, especially, gram-negative (blue pus and colon bacilli, salmonella, shigella, klebsiella) bacteria (including resistant to other aminoglycoside antibiotics). It is not effective in relation to enterococci. Indications: see AG administered parenterally. Prescription: i/m, i/v – 15 mg/kg/day in 1-2 administrations. Most likely used for empirical therapy of hospital infections as a part of combination treatment. Applied locally in the form of gel. Side effects: hearing and balance impairments, renal and hepatic dysfunction, nausea, vomiting, anemia, leucopenia, thrombocytopenia, allergic reactions. Contraindications: vestibular apparatus disorder, neuritis of acoustic nerve, renal dysfunction, pregnancy. Dosage form: powder for injection solutions in 0,1, 0,25, 0,5 g vials; 5%, 12,5% and 25% solutions for injections in amp. (vials) – 2 ml; and 25% - 4 ml; 5% gel in 30 g tubes.Tetracyclines (Т)
Classification
- Short action (tetracycline), prescribed to be used 3-4 times a day.
- Average action (Metacycline) – prescribed twice a day.
- Long action – doxycycline, minocycline – once a day.
Mechanism of action and range of action:
T is a group of bacteriostatic antibiotics of a wide range of action. Binding to the receptors of ribosome subunits, they disturb the synthesis of proteins by pathogenic microorganisms.
TetracyclineTetracycline (Tetracyclin) is an AB produced by Streptomycesaureofaciens or related microorganisms. It has a wide range of action towards the most gram-positive and gram-negative bacteria, as well as spirochaetes, leptospiras, rickettsia and major viruses. Pharmacokinetics: administered p/o, it is partly absorbed (up to 66% of the dose), it penetrates tissues, fluids and organs well (accumulated in bones, liver, spleen and teeth); excreted unchanged with urine and bile. Indications: p/o for acute courses of chronic bronchitis, community-acquired pneumonia, acne, Chlamydia infections, mycoplasmal infections, ricketsiosis, leptospirosis, actinomycosis, gangrenous infections (plaque, cholera, anthrax), brucellosis, glanders, tularemia, syphilis, for eradication of Н. Pylori, for the prevention of infectious complications in operated patients. It is also used locally for the infection diseases of eyes, burns, phlegmons, mastitis etc. Presciption: p/o (in tab.) during orimmediately after the meal taking water with 1-2 g/day for 4 ingestions. The course of treatment is 5-7 days. After the symptoms of the disease are gone, one still continues using the drug for 1-3 more days. Side effects: loss of appetite, nausea, vomiting, diarrhea, glossitis, stomatitis, gastritis, proctitis, disbacteriosis, allergic skin reactions, Quincke's edema etc. Photosensitization is possible. Contraindications: hypersensitivity, fungus disease, leukopenia, systemic lupus erythematosus, renal and hepatic diseases, pregnancy, lactation, chilfren under 8 years of age. Dosage forms: tabs. – 0,05 g (50 000 IU), 0,1 g (100 000 IU) and 0,25 g (250 000 IU); caps. – 0,1 g (100 000 IU), 0,2 g (200 000 IU) and 0,25 g (250 000 IU) (N20).
Metacycline hydrochlorideMetacycline hydrochloride (Metacyclinihydrochloride, Rondomycine, Rondomycini) is a semi-synthetic derivative of tetracycline. By its antibacterial activity it is similar to other tetracyclines.Pharmacokinetics: it is better absorbed in GIT and stored in blood longer. Cmax – 2-4 h, Т1/2 – 6-10 h. It penetrates organs and tissues easily, reaches high concentrations in liver, kidneys, pleural, ascitic fluids, gets through placenta. It undergoes biotransformation in liver, excreted slowly mainly with urine and bile. Side effects and contraindications are the same as for tetracycline. Prescription: during or immediately after the meal 0,3 g 2 times a day, for serious states – 0.9 g/day. The course of treatment – 7-10 days. Dosage form: caps. – 0,15 and 0,3 g (N8,16).
Doxycycline hydrochlorideDoxycycline hydrochloride (Doxycyclinehydrochloridum, Vibramycin, Unidox Solutab) is a semi-synthetic derivative of oxytetracycline. It has a wide range of action. It is effective towards the most gram-positive and gram-negative microorganisms including the ones resistant to other antibiotics as well as other tetracyclines. It has a bactericidal activity towards protozoan: amoeba, malaria plasmodium. Pharmacokinetics: it is rapidly and completely absorbed in GIT, Cmax – around 2.6 hours, Т1/2 - 10-20 h. Depending on the administered dose, the therapeutic concentration is maintained in blood for 18-20 hours. It penetrates into organs and tissues quite well, but badly – into cerebrospinal fluid. It undergoes biotransformation in liver (partly) (30-60%), excreted slowly – with urine and feces. Unlike tetracycline, doxycycline has higher bioavailability, longer action and is tolerated better. Cumulation is possible. Indications are the same as for other T. It is specifically indicated for the acute courses of bronchitis, infections of the small pelvis, infections caused by Chlamydia, mycoplasma, Rickettsia, for acne, gonorrhea, syphilis, chronic prostatitis, proctitis, urethritis, cholera, plaque, anthrax, leptospirosis, for the prevention of topical malaria. It is highly effective for brucellosis. Prescription: p/o – on the first day – 0,2 g, then – 0,1 g/day for 7-10 days. I/v and i/m – 0.1 g/day. Side effects: dyspepsia, vascular collapse, disbacteriosis, neutropenia, allergic reactions.Contraindications: serious renal failure, leucopenia, porphyria, pregnancy, lactation, age under 8. Dosage form: caps. – 0,05, 0,1. 0,2 g; tabs. – 0,1, 0,2 g; frozen-dried powder or porous mass for injection solutions in 0.1 and 0.2 g amp; 2% solution for injections in 5 ml vials. Macrolides (ML)
Classification
- Natural: erythromycin, oleandomycin, spiramycin, Josamycin, Midecamycin.
- Prodrugs: erythromycin ethers – propionyl, ethylsuccinate; erythromycin salts – stearate; Oleandomycin ethers – troleandomycin, Triacetyloleandomycin; Rokitamycin – propyl ether of leucomycin А5.
- Semisynthetic: Azithromycin, Miocamycin, Dirithromycin, Clarithromycin, flurithromycin, Roxithromycin.
Mechanism of action and range of activity.
ML possess a bacteriostatic action. In high concentrations they are capable of acting bactericidally on β-hemolytic streptococcus of group A, pneumococcus, causative agents of pertussis and diphtheria. The mechanism is in the inhibition of protein synthesis in the cells of sensitive microorganisms.
AzitromycinAzitromycin (Sumamed) is a semi-synthetic derivative of erythromycin. It is highly effective in relation to gram-positive bacteria (staphylococci, streptococci, pneumococci) including the ones producing β-lactamase, as well as gram-negative (enterococci, colon bacillus and hemophilic bacteria, gonococci, legionella, shigella, salmonella) microorganisms, anaerobes (bacteroids, clostridia, peptococci), chlamydia, mycoplasma and spirochete. Unlike erythromycin, it is more active towards gram-negative microbes, more resistant to the acid medium of the stomach, it is excreted out of the body slowly and lasts longer; it is better tolerated, and less likely to be inhibited by the hepatic cytochrome P-450. Pharmacokinetics: it is rapidly absorbed in GIT (resistant to the acid medium), bioavailability – around 37%, Cmax – 2.5-3 hours, Т1/2 – 14-68 h. It penetrates tissues and organs well. The bactericidal concentration is maintained in the focus of infective inflammation for 5-7 days after the last dose. The biotransformation is in liver, excretion – with bile. Indications: tonsillitis, pharyngitis, pneumonia, bronchitis, sinusitis, otitis, scarlet fever, erysipelas, acne, chlamidia urethritis, cervicitis, gonorrheal and non-gonorrheal borreliosis (Lyme disease), atypical bacteriosis in case of AIDS etc. It is used for eradication of H.pylori. Prescription: p/o – 1 hour before or 2 hours after meal. 0.5 g – once a day for 3 days; or 0.5 g once on the first day, starting with the 2nd till 5th days – 0.25 g once a day. Side effects: Allergic reactions, nausea, vomiting, cholestasis, jaundice.Contraindications: serious renal and hepatic dysfunctions. With caution – at cardiac arrhythmias. Dosage forms: tabs. – 0,125 g (N6) and 0,5 g (N 3); caps. – 0,25 g (N 6).
Claritromycin (Klacid, Fromilid, Клеримед) is prescribed for p/o use – 205-500 mg every 12 hours (regardless of the food intake) or 1 g once a day (Klacid) or with an IV drip (for 45-60 min) every 12 hours – 500 mg. It is used in the schemes for eradication of H.pylori in ulcer and gastritis patients (the regular dose of the drug is used), for atypical mycobacteriosis (in combination with ethambutol and Rifabutine). In case of serious renal dysfunctions (creatinine clearance ≤ 30 ml/min) the dose must be reduced by half.Roxitrovycin (Rulid) is prescribed 150 mg 2 times/day, in the morning and evening or 300 mg – once a day 1 hour before meal. In case of serious hepatic failure – 150 mg/day. For the prevention of infections at AIDS – 300 mg 3 times a week every other day.Lincosamides (LA)
Mechanism of action and range of activity.
LA inhibit the intracellular protein synthesis by ribosomes of the microorganisms. They exert bacteriostatic action against gram-positive bacteria (except enterococci and methicillin resistant staphylococci), asporous anaerobes, hemophilic bacillus. Pharmacokinetics: Clindamycin is well-absorbed in GIT, bioavailability – 90% regardless of the food intake. Taken on an empty stomach, lincomycin is absorbed to 30%, after meal – 5%. Cmax – 2-4 hours after p/o use and in 1-2 hours if administered i/m. The therapeutic concentration is maintained up to 12 hours. LAs are well-distributed if administered both enterally or parenterally. They can be accumulated in bones and joints (75% of the concentration in blood plasma), in pleural fluid (90%), bronchopulmonary secretion, bile. It doesn’t go through BBB well, but it does get through placenta well enough and gets to mother’s milk. The metabolism is in liver. Excretion – by GIT. Half-life period of lincomycin – 46 hours, clindamycin – 0.5-3 hours. Indications and dosing regimen: they are used as an additional antibiotics. Indications: Lower respiratory tract infections (aspiration pneumonia, lung abscess, pleural empyema.
Small pelvis infections. Peritonitis.
Clindamycin is also used for toxoplasmosis and chloroquine resistant malaria. In case of severe infections they are better to be combined with aminoglycosides affecting gram-negative aerobic flora. They shouldn’t be used for staphylococcal infection because of its bacteriostatic action.
Clindamycin (Dalacin C, Clindacin) is prescribed for p/o use – 150-600 mg (regardless of the food intake) every 6 hours and 600-900 mg i/v or i/m every 8 hours. Contraindications: myasthenia; hypersensitivity; bronchial asthma; GIT diseases in anamnesis (nonspecific ulcerative colitis, enteritis or colitis caused by the use of antibiotics); serious hepatic and/or renal dysfunctions; pregnancy and lactation period.Side effects: GIT dysfunctions, pseudomembranous colitis, neutropenia, thrombocytopenic purpura, excessive growth of fungi, block of neuromuscular conduction, allergic reactions. If administered rapidly – AP fall, cardiac arrest, apnoae.Drug interactions: The absorption of the drugs is reduced if taken together with adsorbents and antidiarrheal drugs. The antidiarrheal drugs worsen the course of pseudomembranous colitis (slow the removal of toxins down). Levomycetin and erythromycin reduce the effects of LAs because they displace them out of the connections with 50S ribosomes. The drugs for inhalation anesthesia, myorelaxants and anesthetics increase the block of neuromuscular transmission, induce the weakness of skeletal muscles, respiratory arrest.Antibiotics of peptide structure
Polymyxins
Mechanism of action and range of activity.
They perform bactericidal action, disturbing the integrity of cytoplasmic membrane of a microbe cell. They are characterized by narrow range of activity and high toxicity. They are active to blue pus bacillus, shigella, hemolytic influenza, salmonella, enterobacteria.
Pharmacokinetics: they are not absorbed in GIT and applied locally. Administered parenterally. Polymyxini M sulfate (PolymixiniMsulfas) is produced by the sporeforming soil bacteria Bacilluspolymyxa or close microorganisms. It mostly affects gram-negative bacteria: inhibits the growth of colon bacillus, salmonella, shigella, klibsiella, effective to the blue pus bacillus; it is not effective to proteus, gram-positive and gram-negative cocci, mycobacteria, fungi. When taken p/o, it is poorly-absorbed in GIT and is not toxic. Applied locally is almost non-toxic.Indications: p/o – for GIT diseases caused by gram-negative bacteria and blue pus bacillus; it is recommended for dysentery if other AB are not effective and for the preparation of patients for the surgery. Locally: low-intensity purulent ptocesses: wounds, burns, necrotic ulcers, bedsores, inflammatory diseases of eyes and ears, abscesses caused by Pseudomonasaeruginosa and other gram-negative microorganisms. The drug can be combined with other antibiotics acting on gram-positive microbes. Prescription: for the external and internal use. Parenteral administration is not allowed.P/o – in tabs. – 500 000 IU 4-6 times a day. The average course of treatment – 5-10 days. In case of recurrences – repeated course is required after the 3-4 days break. Side effects are not normally noticed. Sometimes at the longer use one might develop changes in kidneys. Allergy is possible. Contraindications: renal and hepatic dysfunctions.Dosage forms: tabs. – 500 000 IU; ointment (20 000 IU/g) in 5, 10, 15, 25, 30 and 50 g tubes and in 10, 15, 25, 30 and 50 g jars; liniment (10 000 IU/ml) in 30 g jars of dark glass.Glycopeptides (GP)
Vancomycin, Teicoplanine
The mechanism of action and range of activity.
They inhibit the biosynthesis of the cell wall, disturb the penetrability of the cytoplasmic membrane and inhibit the RNA synthesis what hampers the development of bacterial resistance.
They are active to the majority of gram-positive cocci and bacteria including enterococci, resistant strains of staphylococci, causative agents of diphtheria and anthrax, clostridia, actinomycete. Gram-negative microorganisms are resistant to glycopeptides. Pharmacokinetics: they are not absorbed if taken p/o, that’s why they are administered parenterally. They are not metabolized, excreted by kidneys, that’s why a correction of the dose is needed in case of renal failure. The half-life period of Vancomycin – 6-8 hours, Teicoplanine – 40-70 hours, that’s why the drugs are prescribed to be taken once a day. Indications and dosing regimen: drugs of reserve.Vancomycin (Vancocin, Vanmixan, Vancoled, Edicin) is an antibiotic of a narrow range of action. It is indicated for septicemia and endocarditis caused by staphylococcus and enterococcus, infections of bones and joints (osteomyelitis included), brain abscess, erysipelas, staphylococcal and streptococcal meningitis that can’t be treated with other antibacterial drugs. Sometimes in case of enterococcal endocarditis Vancomycin should be combined with aminoglycosides or Rifampicin (considering the nephrotoxicity). Administration: i/v – 1 g (infusion 2 hours) 2 times a day. P/o – 0,125 g 4 times a day; for the treatment of pseudomembranous colitis – 0,5 g 4 times a day). In case of meningitis – as an addition to the i/v infusion – intrathecally 0.005-0.01 g every 48-72 hours. In surgery – for the prevention: i/v 1 g 60 min before surgery.Other antibiotics
Chloramphenicol (Levomycetin, synthomycin)
The mechanism of action and range of activity.
It’s a natural antibiotic. It exerts a bacteriostatic action, disturbing the protein synthesis in ribosomes. It is active to gram-positive and gram-negative bacteria, anaerobes, rickettsia, spirochaete, Chlamydia.
Pharmacokinetics: completely absorbed if administered p/o. Half-life period – 1.5-3.5 h (in children – 6.5 hours). Excretion – by kidneys. Administered i/m in an inactive form (succinate). Before the moment of activation a part of the drug is eliminated by kidneys and the concentration of Chloramphenicol in blood can be lower than after the oral ingestion. Indications and dosing regimen: meningitis caused by meningococci, pneumococci, hemophilic influenza, typhoid fever and paratyphoid fever A, Q fever, epidemic (louse-borne) typhus, brain abscess. It is also used locally for bacterial eye infections. It should be used as an antibiotic of reserve. Prescription: p/o and i/v – 0,0125-0,025 g/kg 4 times a day. Maximum dose is 4 g a day. Locally: eye drops – 1-2 drops every 1-4 hours. Contraindications: pregnancy, lactation, hepatic dysfunction, allergic reaction to chloramphenicol, inhibition of bone-marrow blood formation skin diseases (psoriasis, eczema, fungal involvements), young age (children), porphyria. Side effects: dose-dependent and reversible inhibition of the bone marrow’ GIT dysfunction; “gray syndrome” in newborns («серый синдром» у новорожденных (bloating, blue-grayish skin color, hypothermia, dyspnea, hypotension); neurotoxic reactions; bleeding out of gums. Drugs interactions: barbiturates, Rifampicin, Phenytoin decrease the concentration of chloramphenicol in blood. Levomycetin intensifies the effect of peroral antidiabetic drugs, Phenytoin, Warfarin, iron drugs, B12, folic acid. Cimetidine and cytostatics increase the risk of aplastic anemia development. It mustn’t be combined with erythromycin, lincosamides (antagonism).Quinolones/Fluoroquinolones
Quinolones – a big group of antimicrobial drugs united by one mechanism of action: inhibition of DNA synthesis. Classification of quinolones
First generation: non-fluoridized quinolones – nalidixic acid, oxolinic acid, pipemidic acid.Second generation: «gram-negative» fluoroquinolones – Lomefloxacin, Norfloxacin, Ciprofloxacin, Ofloxacin, Pefloxacin.Third generation: «respiratory» fluoroquinolones – Levofloxacin, Sparfloxacin.Fourth generation: «respiratory» + «antianaerobic» fluoroquinolones and non- fluoridized quinolones – Moxifloxacin, Gemifloxacin, garenoxacin. Fluoroquinolones (FQ)
The mechanism of action and range of activity.
FQ get through the protein layer of the membrane inside the cell and selectively bind to DNAse and topoisomer IV and almost completely paralyzes their work. As a result the replication of DNA and its binding into a spiral is stopped and lysis of a bacterium occurs. The drugs are accumulated in macrophages and neutrophils in the concentration 4-8 times higher than in the outer environment causing the intracellular antibacterial effect.
The true resistance to FQ can be developed. It is caused by the loss of the external membrane protein by the microbe cell and it decreases the penetration of the drug into the system. Pharmacokinetics: All the FQ are well-absorbed in GIT. The maximum concentration in blood is achieved in 1-3 hours. The absorption can be slowed down by the simultaneous use of antacids and vitamins containing zinc. All the Qs are well-distributed in the body; in organs and tissues the concentrations are created close to serum-like or even exceeding them. FQs are eliminated slowly out of the body. The half-life period – 3-4 hours (Norfloxacin) – 18-21 hours (Sparfloxacin). In case of severe renal failure a dose correction of all the FQs is required and in case of hepatic failure – of Pefloxacin.
Indications and dosing regimen: The advantage of FQs is the possibility of an effective empirical therapy in case of severe forms of generalized infection before the microbiological diagnosis. Infections of respiratory tracts: sinusitis, especially caused by resistant strains, malignant external otitis. The drugs are very useful for the treatment of lower respiratory tracts infections (pneumonia, bronchitis, multiple bronchiectasis, in patients with mucoviscidosis). Infections of urine-excreting tracts: effectiveness in case of complicated and non-complicated infections – 70-100%. Sexually transmitted infections (STIs): in case of acute non-complicated gonorrhea of various localizations the effectiveness of FQs at the single administration – 97-100%. In case of Chlamydia infection – 45-100%, mycoplasma – 33-100%. Enteric infections: they are effective for salmonellosis, dysentery, various forms of bacterial diarrhea, including the travellers’ diarrhea, cholera, campilobacteriosis. Surgical infections: FQs are effective for the treatment of serious forms of pyoinflammatory processes in skin, soft tissues, purulent arthritis, chronic osteomyelitis caused by gram-negative aerobic bacteria. They are used in the complex treatment of infections at burns. Gynaecological infections: the drugs are successfully used for the treatment of the inflammatory diseases of the small pelvis. Septicemia, bacteremia: FQs are effective in case of septic processes accompanied by bacterimia caused by aerobic gram-negative and gram-positive bacteria (effectiveness – 73-96%). They are very effective for the patients with neutropenia and immunodeficiency states. Tuberculosis: FQs are successfully used for the treatment of severe complicated forms of TB and bacterial (non-mycobacterial) complications. Levofloxacin
Levofloxacin (Tavanic, Eleflox) are used p/o on an empty stomach – 250-500 mg 1-2 times a day without chewing, drinking much water. In case of acute sinusitis – 0.5 g once a day; pneumonia, skin and soft tissues infections – 0.5 g 2 times a day; acute pyelonephritis – 0.25 g once a day. I/v – 0.25-0.5 g 2-1 times a day (slow infusion – 1 hour). The course of treatment – 7-10 days. Cystitis – 0.1 g 2 times a day for 3 days or 0.2 g in a single dose. Moxifloxacin (Avelox) is taken p/o regardless of the food intake – 0.4 g once a day for 5-10 days. Ciprofloxacin (Neofloxin, Ciprobay, Ciprolet, Цифлоцин) are ingested p/o without chewing drinking enough water – 0.25 g (at the serious infections 0.5-0.75 g) 2-3 times a day. I/v – 0.2 g (in case of serious infections – 0.4 g) 2 times a day for 1 hour. The course of treatment – 7-14 days, in case salmonellosis - up to 4-6 weeks. Acute gonorrhea – 0.25-0.5 g in a single dose p/o or 0.1 g i/v. Locally – 1-2 drops into an eye every 4 hours. Contraindications: hypersensitivity, pregnancy, lactation, young age (danger of disturbance of cartilaginous tissue), epilepsy (relative contraindication). Side effects: FQs are usually well-tolerated and considered to be ones of the safest antimicrobial drugs. The following side effects are possible: nausea, vomiting, diarrhea, anorexia, stomach pains, insomnia, vertigo, skin rash, photosensitization, arthralgia, hallucinations, taste disorder, vision disorder, lab tests changes. FQs almost do not cause allergies. Drug interactions: non-absorbed chelates are formed at the simultaneous use of antacids, iron, zinc and bismuth drugs. Neurotoxicity increases if taken together with NSAIDs, Theophylline, caffeine. It is not recommended to prescribe them together with indirect anticoagulants (the risk of bleeding), derivatives of nitrofurans (antagonism), the drugs alkalizing urine (nephrotoxicity).
Aminoglycosides (AG)
- AG of the 1st generation: streptomycin, neomycin, monomycin, kanamycin.
- AG of the 2nd generation: gentamicin, sisomicin, netilmicin, tobramycin.
- AG of the 3rd generation: Amikacin, dibekacin, isepamicin etc.
Mechanism of action and range of activity
- AG exert bactericidal effect associated with the disturbance of protein synthesis by ribosomes.
- The level of antibacterial action depends on the dose.
- AG – drugs of a wide range of action.
- They are of high-performance in terms of the majority of gram-negative bacteria (colon bacillus, salmonella, shigella, proteus, Klebsiella, enterobacteria, serratia) and staphylococci.
Pharmacokinetics: Administered p/o, AG is almost not absorbed, that’s why it is used parenterally.
After i/v administration Сmax is in 30 min and in 0,5 – 1,5 h after i/m administration.
AG are not metabolized, excreted by kidneys unchanged by way of glomerular filtration (it is stored in renal tissue for up to 30 days). Т1/2 1,5 – 4 h, in case of renal failure – up to 70 hours and more.
Indications
- Empirical therapy (gentamicin, Amikacin, netilmicin in combination with β-lactams, glycopeptides and antianaerobic drugs);
- hospital (nosocomial) pneumonia (they are effective for pneumonia caused by aerobic gram-negative flora);
- sepsis of unknown etiology (in combination with β-lactams and antianaerobic drugs: lincosamides, metronidazole);
- infective endocarditis (in combination with penicillins);
The drug for empirical therapy in urgent cases is amikacin because more than 90 % of microorganisms (gram-negative and gram-positive) maintain sensitivity to it.
Streptomycin sulfate (streptomycin) is a derivative of ray fungus – Streptomycesglobisporusstreptomycini or related microorganisms. The doses are calculated in mass or in units of activity (UA); 1 UA = 1 microgram of chemically pure streptomycin.
Wide range of antimicrobial action. It is effective to mycobacteria of tuberculosis, most gram-negative bacteria (colon bacillus, Friedländer's bacillus, Pfeiffer's bacillus, causative agents of plague, tularemia, brucellosis) and some gram-positive (staphylococci) aerobic microorganisms.
Pharmacokinetics: taken p/o, it is poorly absorbed and almost completely excreted by intestines in an unchanged form. Administered i/m, it is well-absorbed, Сmax is in 1-2 h after a single administration in a therapeutic dose and is maintained for 6-8 hours. Excreted mainly by kidneys.
It is used as a main antituberculous drugs when pulmonary TB or TB of other organs have been diagnosed for the first time. The drug is also used for the pyoinflammatory processes of various localization.
Prescriprion: i/m, in the form of sprays, intratracheal and intracavernous (for adults) administrations. Single i/m dose for adults – 0.5-1 g, daily – 1 g or 25-30 mg/kg (max. 1.5 g) 2-3 times a week. The course of treatment – up to 2 months.
Side effects: allergic, toxic; convulsions, gait disorder, nausea, vomiting, dizziness, headaches, rapid heartbeat, albuminuria, hematuria, diarrhea, the disorder of the VIII pair of cranial nerves, vestibular disorders, hearing impairment. If used for a long time, the development of deafness is possible.
Contraindications: diseases of hearing and vestibular apparatus associated with neuritis of the VIII pair of cranial nerves, otoneuritis; тяжелая степень НК (??), renal failure, cerebral circulation disorder, obliterating endarteritis, myasthenia.
Drug interaction: must not be used together with antibiotics possessing an ototoxic action (kanamycin, florimicin, Ristomycin, gentamicin, monomicin) as well as with furosemide and curariform drugs.
Dosage form: powder for injection solutions in 0.25, 0.5, 1 g vials.
Gentamicin sulfate
Gentamicin sulfate (Gentamycinisulfas) is an antibiotic produced by Micromonosporаpurpurea. The combination of С1, С2, С1а exerts a bacteriostatic action towards numerous gram-positive and gram-negative microorganisms including blue pus bacillus, colon bacillus, proteus, salmonella etc; affects the strains of staphylococci resistant to neomycin and kanamycin.
Pharmacokinetics: after i/m administration it is rapidly absorbed; in GIT – poorly absorbed. Cmax – 1 h, bacteriostatic concentrations in blood are maintained for 8-12 hours; excreted by kidneys unchanged reaching its high concentration in urine. It is used for various infection diseases.
Administration – i/m, i/v (IV drip), locally. Parenteral – 3-5 mg/kg/day for 1-2 administrations. Locally – into the involved eye 1-2 drops 3-4 times a day.
Side effects: Ototoxic and nephrotoxic, disturbances of neuromuscular conduction. Sometimes – nausea, vomiting, renal dysfunction, anemia, leukopenic, thrombocytopenia, rarely – allergic reactions.
Contraindications: inflammation of acoustic nerve, myasthenia, pregnancy. It mustn’t be prescribed in combination with other antibiotics performing oto- and nephrotoxic actions. It is not prescribed in case of uraemia.
Dosage forms: powder (porous mass) for injection solutions in 1%, 2%, 4%, 6%, 8% and 10 thousand,20 thousand, 40 thousand, 60 thousand and 80 thousand IU – 2 ml.
Amikacin sulphate
Amikacin sulphate (Amikacinsulfate, Mikacin, Amikin) is obtained by the semisynthetic method out of Kanamycin A. It is effective in relation to gram-positive (staphylococci) and, especially, gram-negative (blue pus and colon bacilli, salmonella, shigella, klebsiella) bacteria (including resistant to other aminoglycoside antibiotics). It is not effective in relation to enterococci.
Indications: see AG administered parenterally.
Prescription: i/m, i/v – 15 mg/kg/day in 1-2 administrations. Most likely used for empirical therapy of hospital infections as a part of combination treatment. Applied locally in the form of gel.
Side effects: hearing and balance impairments, renal and hepatic dysfunction, nausea, vomiting, anemia, leucopenia, thrombocytopenia, allergic reactions. Contraindications: vestibular apparatus disorder, neuritis of acoustic nerve, renal dysfunction, pregnancy.
Dosage form: powder for injection solutions in 0,1, 0,25, 0,5 g vials; 5%, 12,5% and 25% solutions for injections in amp. (vials) – 2 ml; and 25% - 4 ml; 5% gel in 30 g tubes.
Tetracyclines (Т)
Classification
- Short action (tetracycline), prescribed to be used 3-4 times a day.
- Average action (Metacycline) – prescribed twice a day.
- Long action – doxycycline, minocycline – once a day.
Mechanism of action and range of action:
T is a group of bacteriostatic antibiotics of a wide range of action. Binding to the receptors of ribosome subunits, they disturb the synthesis of proteins by pathogenic microorganisms.
Tetracycline
Tetracycline (Tetracyclin) is an AB produced by Streptomycesaureofaciens or related microorganisms. It has a wide range of action towards the most gram-positive and gram-negative bacteria, as well as spirochaetes, leptospiras, rickettsia and major viruses.
Pharmacokinetics: administered p/o, it is partly absorbed (up to 66% of the dose), it penetrates tissues, fluids and organs well (accumulated in bones, liver, spleen and teeth); excreted unchanged with urine and bile.
Indications: p/o for acute courses of chronic bronchitis, community-acquired pneumonia, acne, Chlamydia infections, mycoplasmal infections, ricketsiosis, leptospirosis, actinomycosis, gangrenous infections (plaque, cholera, anthrax), brucellosis, glanders, tularemia, syphilis, for eradication of Н. Pylori, for the prevention of infectious complications in operated patients. It is also used locally for the infection diseases of eyes, burns, phlegmons, mastitis etc.
Presciption: p/o (in tab.) during orimmediately after the meal taking water with 1-2 g/day for 4 ingestions. The course of treatment is 5-7 days. After the symptoms of the disease are gone, one still continues using the drug for 1-3 more days.
Side effects: loss of appetite, nausea, vomiting, diarrhea, glossitis, stomatitis, gastritis, proctitis, disbacteriosis, allergic skin reactions, Quincke's edema etc. Photosensitization is possible.
Contraindications: hypersensitivity, fungus disease, leukopenia, systemic lupus erythematosus, renal and hepatic diseases, pregnancy, lactation, chilfren under 8 years of age.
Dosage forms: tabs. – 0,05 g (50 000 IU), 0,1 g (100 000 IU) and 0,25 g (250 000 IU); caps. – 0,1 g (100 000 IU), 0,2 g (200 000 IU) and 0,25 g (250 000 IU) (N20).
Metacycline hydrochloride
Metacycline hydrochloride (Metacyclinihydrochloride, Rondomycine, Rondomycini) is a semi-synthetic derivative of tetracycline. By its antibacterial activity it is similar to other tetracyclines.
Pharmacokinetics: it is better absorbed in GIT and stored in blood longer. Cmax – 2-4 h, Т1/2 – 6-10 h. It penetrates organs and tissues easily, reaches high concentrations in liver, kidneys, pleural, ascitic fluids, gets through placenta. It undergoes biotransformation in liver, excreted slowly mainly with urine and bile.
Side effects and contraindications are the same as for tetracycline.
Prescription: during or immediately after the meal 0,3 g 2 times a day, for serious states – 0.9 g/day. The course of treatment – 7-10 days.
Dosage form: caps. – 0,15 and 0,3 g (N8,16).
Doxycycline hydrochloride
Doxycycline hydrochloride (Doxycyclinehydrochloridum, Vibramycin, Unidox Solutab) is a semi-synthetic derivative of oxytetracycline. It has a wide range of action. It is effective towards the most gram-positive and gram-negative microorganisms including the ones resistant to other antibiotics as well as other tetracyclines. It has a bactericidal activity towards protozoan: amoeba, malaria plasmodium.
Pharmacokinetics: it is rapidly and completely absorbed in GIT, Cmax – around 2.6 hours, Т1/2 - 10-20 h. Depending on the administered dose, the therapeutic concentration is maintained in blood for 18-20 hours. It penetrates into organs and tissues quite well, but badly – into cerebrospinal fluid. It undergoes biotransformation in liver (partly) (30-60%), excreted slowly – with urine and feces. Unlike tetracycline, doxycycline has higher bioavailability, longer action and is tolerated better. Cumulation is possible.
Indications are the same as for other T. It is specifically indicated for the acute courses of bronchitis, infections of the small pelvis, infections caused by Chlamydia, mycoplasma, Rickettsia, for acne, gonorrhea, syphilis, chronic prostatitis, proctitis, urethritis, cholera, plaque, anthrax, leptospirosis, for the prevention of topical malaria. It is highly effective for brucellosis.
Prescription: p/o – on the first day – 0,2 g, then – 0,1 g/day for 7-10 days. I/v and i/m – 0.1 g/day.
Side effects: dyspepsia, vascular collapse, disbacteriosis, neutropenia, allergic reactions.
Contraindications: serious renal failure, leucopenia, porphyria, pregnancy, lactation, age under 8.
Dosage form: caps. – 0,05, 0,1. 0,2 g; tabs. – 0,1, 0,2 g; frozen-dried powder or porous mass for injection solutions in 0.1 and 0.2 g amp; 2% solution for injections in 5 ml vials.
Macrolides (ML)
Classification
- Natural: erythromycin, oleandomycin, spiramycin, Josamycin, Midecamycin.
- Prodrugs: erythromycin ethers – propionyl, ethylsuccinate; erythromycin salts – stearate; Oleandomycin ethers – troleandomycin, Triacetyloleandomycin; Rokitamycin – propyl ether of leucomycin А5.
- Semisynthetic: Azithromycin, Miocamycin, Dirithromycin, Clarithromycin, flurithromycin, Roxithromycin.
Mechanism of action and range of activity.
ML possess a bacteriostatic action. In high concentrations they are capable of acting bactericidally on β-hemolytic streptococcus of group A, pneumococcus, causative agents of pertussis and diphtheria. The mechanism is in the inhibition of protein synthesis in the cells of sensitive microorganisms.
Azitromycin
Azitromycin (Sumamed) is a semi-synthetic derivative of erythromycin.
It is highly effective in relation to gram-positive bacteria (staphylococci, streptococci, pneumococci) including the ones producing β-lactamase, as well as gram-negative (enterococci, colon bacillus and hemophilic bacteria, gonococci, legionella, shigella, salmonella) microorganisms, anaerobes (bacteroids, clostridia, peptococci), chlamydia, mycoplasma and spirochete.
Unlike erythromycin, it is more active towards gram-negative microbes, more resistant to the acid medium of the stomach, it is excreted out of the body slowly and lasts longer; it is better tolerated, and less likely to be inhibited by the hepatic cytochrome P-450.
Pharmacokinetics: it is rapidly absorbed in GIT (resistant to the acid medium), bioavailability – around 37%, Cmax – 2.5-3 hours, Т1/2 – 14-68 h. It penetrates tissues and organs well. The bactericidal concentration is maintained in the focus of infective inflammation for 5-7 days after the last dose. The biotransformation is in liver, excretion – with bile.
Indications: tonsillitis, pharyngitis, pneumonia, bronchitis, sinusitis, otitis, scarlet fever, erysipelas, acne, chlamidia urethritis, cervicitis, gonorrheal and non-gonorrheal borreliosis (Lyme disease), atypical bacteriosis in case of AIDS etc. It is used for eradication of H.pylori.
Prescription: p/o – 1 hour before or 2 hours after meal. 0.5 g – once a day for 3 days; or 0.5 g once on the first day, starting with the 2nd till 5th days – 0.25 g once a day.
Side effects: Allergic reactions, nausea, vomiting, cholestasis, jaundice.
Contraindications: serious renal and hepatic dysfunctions. With caution – at cardiac arrhythmias.
Dosage forms: tabs. – 0,125 g (N6) and 0,5 g (N 3); caps. – 0,25 g (N 6).
Claritromycin (Klacid, Fromilid, Клеримед) is prescribed for p/o use – 205-500 mg every 12 hours (regardless of the food intake) or 1 g once a day (Klacid) or with an IV drip (for 45-60 min) every 12 hours – 500 mg. It is used in the schemes for eradication of H.pylori in ulcer and gastritis patients (the regular dose of the drug is used), for atypical mycobacteriosis (in combination with ethambutol and Rifabutine). In case of serious renal dysfunctions (creatinine clearance ≤ 30 ml/min) the dose must be reduced by half.
Roxitrovycin (Rulid) is prescribed 150 mg 2 times/day, in the morning and evening or 300 mg – once a day 1 hour before meal. In case of serious hepatic failure – 150 mg/day. For the prevention of infections at AIDS – 300 mg 3 times a week every other day.
Lincosamides (LA)
Mechanism of action and range of activity.
LA inhibit the intracellular protein synthesis by ribosomes of the microorganisms. They exert bacteriostatic action against gram-positive bacteria (except enterococci and methicillin resistant staphylococci), asporous anaerobes, hemophilic bacillus.
Pharmacokinetics: Clindamycin is well-absorbed in GIT, bioavailability – 90% regardless of the food intake. Taken on an empty stomach, lincomycin is absorbed to 30%, after meal – 5%. Cmax – 2-4 hours after p/o use and in 1-2 hours if administered i/m. The therapeutic concentration is maintained up to 12 hours. LAs are well-distributed if administered both enterally or parenterally. They can be accumulated in bones and joints (75% of the concentration in blood plasma), in pleural fluid (90%), bronchopulmonary secretion, bile. It doesn’t go through BBB well, but it does get through placenta well enough and gets to mother’s milk. The metabolism is in liver. Excretion – by GIT. Half-life period of lincomycin – 46 hours, clindamycin – 0.5-3 hours.
Indications and dosing regimen: they are used as an additional antibiotics. Indications: Lower respiratory tract infections (aspiration pneumonia, lung abscess, pleural empyema.
Small pelvis infections. Peritonitis.
Clindamycin is also used for toxoplasmosis and chloroquine resistant malaria. In case of severe infections they are better to be combined with aminoglycosides affecting gram-negative aerobic flora.
They shouldn’t be used for staphylococcal infection because of its bacteriostatic action.
Clindamycin (Dalacin C, Clindacin) is prescribed for p/o use – 150-600 mg (regardless of the food intake) every 6 hours and 600-900 mg i/v or i/m every 8 hours.
Contraindications: myasthenia; hypersensitivity; bronchial asthma; GIT diseases in anamnesis (nonspecific ulcerative colitis, enteritis or colitis caused by the use of antibiotics); serious hepatic and/or renal dysfunctions; pregnancy and lactation period.
Side effects: GIT dysfunctions, pseudomembranous colitis, neutropenia, thrombocytopenic purpura, excessive growth of fungi, block of neuromuscular conduction, allergic reactions. If administered rapidly – AP fall, cardiac arrest, apnoae.
Drug interactions: The absorption of the drugs is reduced if taken together with adsorbents and antidiarrheal drugs. The antidiarrheal drugs worsen the course of pseudomembranous colitis (slow the removal of toxins down). Levomycetin and erythromycin reduce the effects of LAs because they displace them out of the connections with 50S ribosomes. The drugs for inhalation anesthesia, myorelaxants and anesthetics increase the block of neuromuscular transmission, induce the weakness of skeletal muscles, respiratory arrest.
Antibiotics of peptide structure
Polymyxins
Mechanism of action and range of activity.
They perform bactericidal action, disturbing the integrity of cytoplasmic membrane of a microbe cell. They are characterized by narrow range of activity and high toxicity. They are active to blue pus bacillus, shigella, hemolytic influenza, salmonella, enterobacteria.
Pharmacokinetics: they are not absorbed in GIT and applied locally. Administered parenterally.
Polymyxini M sulfate (PolymixiniMsulfas) is produced by the sporeforming soil bacteria Bacilluspolymyxa or close microorganisms.
It mostly affects gram-negative bacteria: inhibits the growth of colon bacillus, salmonella, shigella, klibsiella, effective to the blue pus bacillus; it is not effective to proteus, gram-positive and gram-negative cocci, mycobacteria, fungi.
When taken p/o, it is poorly-absorbed in GIT and is not toxic. Applied locally is almost non-toxic.
Indications: p/o – for GIT diseases caused by gram-negative bacteria and blue pus bacillus; it is recommended for dysentery if other AB are not effective and for the preparation of patients for the surgery.
Locally: low-intensity purulent ptocesses: wounds, burns, necrotic ulcers, bedsores, inflammatory diseases of eyes and ears, abscesses caused by Pseudomonasaeruginosa and other gram-negative microorganisms.
The drug can be combined with other antibiotics acting on gram-positive microbes.
Prescription: for the external and internal use. Parenteral administration is not allowed.
P/o – in tabs. – 500 000 IU 4-6 times a day. The average course of treatment – 5-10 days. In case of recurrences – repeated course is required after the 3-4 days break. Side effects are not normally noticed. Sometimes at the longer use one might develop changes in kidneys. Allergy is possible.
Contraindications: renal and hepatic dysfunctions.
Dosage forms: tabs. – 500 000 IU; ointment (20 000 IU/g) in 5, 10, 15, 25, 30 and 50 g tubes and in 10, 15, 25, 30 and 50 g jars; liniment (10 000 IU/ml) in 30 g jars of dark glass.
Glycopeptides (GP)
Vancomycin, Teicoplanine
The mechanism of action and range of activity.
They inhibit the biosynthesis of the cell wall, disturb the penetrability of the cytoplasmic membrane and inhibit the RNA synthesis what hampers the development of bacterial resistance.
They are active to the majority of gram-positive cocci and bacteria including enterococci, resistant strains of staphylococci, causative agents of diphtheria and anthrax, clostridia, actinomycete. Gram-negative microorganisms are resistant to glycopeptides.
Pharmacokinetics: they are not absorbed if taken p/o, that’s why they are administered parenterally.
They are not metabolized, excreted by kidneys, that’s why a correction of the dose is needed in case of renal failure. The half-life period of Vancomycin – 6-8 hours, Teicoplanine – 40-70 hours, that’s why the drugs are prescribed to be taken once a day.
Indications and dosing regimen: drugs of reserve.
Vancomycin (Vancocin, Vanmixan, Vancoled, Edicin) is an antibiotic of a narrow range of action. It is indicated for septicemia and endocarditis caused by staphylococcus and enterococcus, infections of bones and joints (osteomyelitis included), brain abscess, erysipelas, staphylococcal and streptococcal meningitis that can’t be treated with other antibacterial drugs. Sometimes in case of enterococcal endocarditis Vancomycin should be combined with aminoglycosides or Rifampicin (considering the nephrotoxicity).
Administration: i/v – 1 g (infusion 2 hours) 2 times a day. P/o – 0,125 g 4 times a day; for the treatment of pseudomembranous colitis – 0,5 g 4 times a day). In case of meningitis – as an addition to the i/v infusion – intrathecally 0.005-0.01 g every 48-72 hours. In surgery – for the prevention: i/v 1 g 60 min before surgery.
Other antibiotics
Chloramphenicol (Levomycetin, synthomycin)
The mechanism of action and range of activity.
It’s a natural antibiotic. It exerts a bacteriostatic action, disturbing the protein synthesis in ribosomes. It is active to gram-positive and gram-negative bacteria, anaerobes, rickettsia, spirochaete, Chlamydia.
Pharmacokinetics: completely absorbed if administered p/o. Half-life period – 1.5-3.5 h (in children – 6.5 hours). Excretion – by kidneys. Administered i/m in an inactive form (succinate). Before the moment of activation a part of the drug is eliminated by kidneys and the concentration of Chloramphenicol in blood can be lower than after the oral ingestion.
Indications and dosing regimen: meningitis caused by meningococci, pneumococci, hemophilic influenza, typhoid fever and paratyphoid fever A, Q fever, epidemic (louse-borne) typhus, brain abscess. It is also used locally for bacterial eye infections. It should be used as an antibiotic of reserve.
Prescription: p/o and i/v – 0,0125-0,025 g/kg 4 times a day. Maximum dose is 4 g a day. Locally: eye drops – 1-2 drops every 1-4 hours.
Contraindications: pregnancy, lactation, hepatic dysfunction, allergic reaction to chloramphenicol, inhibition of bone-marrow blood formation skin diseases (psoriasis, eczema, fungal involvements), young age (children), porphyria.
Side effects: dose-dependent and reversible inhibition of the bone marrow’ GIT dysfunction; “gray syndrome” in newborns («серый синдром» у новорожденных (bloating, blue-grayish skin color, hypothermia, dyspnea, hypotension); neurotoxic reactions; bleeding out of gums.
Drugs interactions: barbiturates, Rifampicin, Phenytoin decrease the concentration of chloramphenicol in blood. Levomycetin intensifies the effect of peroral antidiabetic drugs, Phenytoin, Warfarin, iron drugs, B12, folic acid. Cimetidine and cytostatics increase the risk of aplastic anemia development. It mustn’t be combined with erythromycin, lincosamides (antagonism).
Quinolones/Fluoroquinolones
Quinolones – a big group of antimicrobial drugs united by one mechanism of action: inhibition of DNA synthesis.
Classification of quinolones
First generation: non-fluoridized quinolones – nalidixic acid, oxolinic acid, pipemidic acid.
Second generation: «gram-negative» fluoroquinolones – Lomefloxacin, Norfloxacin, Ciprofloxacin, Ofloxacin, Pefloxacin.
Third generation: «respiratory» fluoroquinolones – Levofloxacin, Sparfloxacin.
Fourth generation: «respiratory» + «antianaerobic» fluoroquinolones and non- fluoridized quinolones – Moxifloxacin, Gemifloxacin, garenoxacin.
Fluoroquinolones (FQ)
The mechanism of action and range of activity.
FQ get through the protein layer of the membrane inside the cell and selectively bind to DNAse and topoisomer IV and almost completely paralyzes their work. As a result the replication of DNA and its binding into a spiral is stopped and lysis of a bacterium occurs. The drugs are accumulated in macrophages and neutrophils in the concentration 4-8 times higher than in the outer environment causing the intracellular antibacterial effect.
The true resistance to FQ can be developed. It is caused by the loss of the external membrane protein by the microbe cell and it decreases the penetration of the drug into the system.
Pharmacokinetics: All the FQ are well-absorbed in GIT. The maximum concentration in blood is achieved in 1-3 hours. The absorption can be slowed down by the simultaneous use of antacids and vitamins containing zinc. All the Qs are well-distributed in the body; in organs and tissues the concentrations are created close to serum-like or even exceeding them. FQs are eliminated slowly out of the body. The half-life period – 3-4 hours (Norfloxacin) – 18-21 hours (Sparfloxacin). In case of severe renal failure a dose correction of all the FQs is required and in case of hepatic failure – of Pefloxacin.
Indications and dosing regimen: The advantage of FQs is the possibility of an effective empirical therapy in case of severe forms of generalized infection before the microbiological diagnosis.
Infections of respiratory tracts: sinusitis, especially caused by resistant strains, malignant external otitis. The drugs are very useful for the treatment of lower respiratory tracts infections (pneumonia, bronchitis, multiple bronchiectasis, in patients with mucoviscidosis).
Infections of urine-excreting tracts: effectiveness in case of complicated and non-complicated infections – 70-100%.
Sexually transmitted infections (STIs): in case of acute non-complicated gonorrhea of various localizations the effectiveness of FQs at the single administration – 97-100%. In case of Chlamydia infection – 45-100%, mycoplasma – 33-100%.
Enteric infections: they are effective for salmonellosis, dysentery, various forms of bacterial diarrhea, including the travellers’ diarrhea, cholera, campilobacteriosis.
Surgical infections: FQs are effective for the treatment of serious forms of pyoinflammatory processes in skin, soft tissues, purulent arthritis, chronic osteomyelitis caused by gram-negative aerobic bacteria. They are used in the complex treatment of infections at burns.
Gynaecological infections: the drugs are successfully used for the treatment of the inflammatory diseases of the small pelvis.
Septicemia, bacteremia: FQs are effective in case of septic processes accompanied by bacterimia caused by aerobic gram-negative and gram-positive bacteria (effectiveness – 73-96%). They are very effective for the patients with neutropenia and immunodeficiency states.
Tuberculosis: FQs are successfully used for the treatment of severe complicated forms of TB and bacterial (non-mycobacterial) complications.
Levofloxacin
Levofloxacin (Tavanic, Eleflox) are used p/o on an empty stomach – 250-500 mg 1-2 times a day without chewing, drinking much water. In case of acute sinusitis – 0.5 g once a day; pneumonia, skin and soft tissues infections – 0.5 g 2 times a day; acute pyelonephritis – 0.25 g once a day. I/v – 0.25-0.5 g 2-1 times a day (slow infusion – 1 hour). The course of treatment – 7-10 days. Cystitis – 0.1 g 2 times a day for 3 days or 0.2 g in a single dose.
Moxifloxacin (Avelox) is taken p/o regardless of the food intake – 0.4 g once a day for 5-10 days.
Ciprofloxacin (Neofloxin, Ciprobay, Ciprolet, Цифлоцин) are ingested p/o without chewing drinking enough water – 0.25 g (at the serious infections 0.5-0.75 g) 2-3 times a day. I/v – 0.2 g (in case of serious infections – 0.4 g) 2 times a day for 1 hour. The course of treatment – 7-14 days, in case salmonellosis - up to 4-6 weeks. Acute gonorrhea – 0.25-0.5 g in a single dose p/o or 0.1 g i/v. Locally – 1-2 drops into an eye every 4 hours.
Contraindications: hypersensitivity, pregnancy, lactation, young age (danger of disturbance of cartilaginous tissue), epilepsy (relative contraindication).
Side effects: FQs are usually well-tolerated and considered to be ones of the safest antimicrobial drugs. The following side effects are possible: nausea, vomiting, diarrhea, anorexia, stomach pains, insomnia, vertigo, skin rash, photosensitization, arthralgia, hallucinations, taste disorder, vision disorder, lab tests changes. FQs almost do not cause allergies.
Drug interactions: non-absorbed chelates are formed at the simultaneous use of antacids, iron, zinc and bismuth drugs. Neurotoxicity increases if taken together with NSAIDs, Theophylline, caffeine. It is not recommended to prescribe them together with indirect anticoagulants (the risk of bleeding), derivatives of nitrofurans (antagonism), the drugs alkalizing urine (nephrotoxicity).
