Penicillin (penicillins) is a group of antibiotics produced by many types of moulds of the genus Penicillium, is active against most gram-positive and some gram-negative microorganisms (gonococci, meningococci, and spirochete). Penicillins belong to the so-called beta-lactam antibiotics (beta-lactams).
Beta-lactams — a large group of antibiotics, which is common for the presence in the structure of the molecules, four-membered beta-laktamnogo ring. To beta-lactams include penicillins, cephalosporins, carbapenems, monobactam. Beta-lactams are the most numerous group of used in clinical practice, antimicrobial drugs, which occupies a leading place in the treatment of most infectious diseases.
Historical information. In 1928, English scientist Alexander Fleming working at St.Mary’s Hospital in London, discovered the ability of filamentous fungus green mold (Penicillium notatum) cause the death of staphylococci in culture cells. The active substance of the fungus with antibacterial activity, A. Fleming called penicillin. In 1940 the Oxford group of researchers under the leadership of H. W. Florey and E. B. chain isolated in a pure form significant quantities of the first penicillin from culture of Penicillium notatum. In 1942 the eminent Russian researcher ZV ermoleva received penicillin from the fungus Penicillium crustosum. Since 1949 for clinical use became available a practically unlimited number of benzylpenicillin (penicillin G).
The group of penicillins include natural compounds produced by different types of fungi Penicillium, and a number of semisynthetic. Penicillins (and other beta-lactams) have a bactericidal effect on microorganisms.
the most General properties of penicillins include: low toxicity, wide range of dosages, cross-Allergy between all the penicillins and partially cephalosporins and carbapenems.
Antibacterial effects of beta-lactams is associated with their specific ability to disrupt the synthesis of bacterial cell walls.
Cell wall in bacteria has a rigid structure, it attaches the microorganisms form and protects it from destruction. It is based on heteropolymer — peptidoglycan, consisting of polysaccharides and polypeptides. Its mesh structure with cross-linking gives the cell wall strength. The composition of the polysaccharides include the amino sugar of N-acetylglucosamine and N-acetylmuramic acid is present only in bacteria. With amino sugars linked by short peptide chain that includes some L – and D-amino acids. In gram-positive bacteria cell wall contains 50-100 layers of peptidoglycan, gram-negative: 1-2 layers.
In the biosynthesis of peptidoglycan involves about 30 bacterial enzymes, this process consists of 3 stages. I believe that the penicillins disrupt late stages of cell wall synthesis, preventing the formation of peptide bonds by inhibiting an enzyme transpeptidaza. Transpeptidase is one of penitsillinazoy proteins, which interact with beta-lactam antibiotics. To penitsillinazou proteins — enzymes involved in the final stages of formation of bacterial cell walls, in addition to transpeptidase include carboxypeptidases and endopeptidazy. They have all the bacteria (for example, Staphylococcus aureus 4, Escherichia coli — 7). Penicillins bind to these proteins with different speed with the formation of covalent bonds. When this occurs inactivation penitsillinazoy proteins, the strength of the bacterial cell wall is disrupted and the cells undergo lysis.
Pharmacokinetics. the ingestion of penicillins are absorbed and distributed throughout the body. Penicillins penetrate well into tissues and body fluids (synovial, pleural, pericardial, bile) rapidly reaches therapeutic concentrations. The exception is cerebrospinal fluid, the internal environment of the eye and the prostate gland secretion and the concentration of penicillin is low. The concentration of penicillins in the cerebrospinal fluid may be different depending on conditions: normal — less than 1% of whey, inflammation may increase to 5%. Therapeutic concentrations in cerebrospinal fluid are created with meningitis and administration of drugs in high doses. Penicillins are rapidly excreted primarily by the kidneys by glomerular filtration and tubular secretion. The half-life they have a short (30-90 min), the concentration in urine is high.
There are several classifications drugs belonging to the group of penicillins: molecular structure, according to the sources, in their spectrum of activity.
How Antibiotics Work
According to the medical classification, the penicillins have been divided as follows (the classification is based on several grounds, including differences in ways of receipt):
I. Preparations of penicillin obtained by biological synthesis (biosynthetic penicillins):
I. 1. For parenteral administration (destroyed in the acidic environment of the stomach):
Short lasting action:
- Benzylpenicillin (sodium salt),
- Benzylpenicillin (potassium salt);
Long lasting action:
- Benzylpenicillin (procaine salt)
- Bicillin 5.
I. 2. For enteral introduction (acid-fast):
- phenoxymethylpenicillin (penicillin V).
II. Semisynthetic penicillins
II.1. For parenteral and enteral introduction (acid-fast):
Is resistant to penicillinase:
- oxacillin (sodium salt),
II.2. For parenteral administration (destroyed in the acidic environment of stomach)
- broad spectrum, including Pseudomonas aeruginosa
- carbenicillin (disodium salt)
II.3. For enteral introduction (acid-fast):
- carbenicillin (indanyl sodium)
According to the classification penicillins can be divided into 6 groups:
- Natural penicillins (benzylpenicillin, bicillin, dentists).
- Isoxazolylpenicillins (oxacillin, cloxacillin, Flucloxacillin).
- Amidinoproline (amdinocillin, pivampicillin, bacardimartini, azidocillin).
- Aminopenicilline (ampicillin, amoxicillin, talampicillin, bacampicillin, pivampicillin).
- Carboxypenicillins (carbenicillin, carfecillin, carindacillin, tikarcillina).
- Ureidopenicillin (azlocillin, mezlocillin, piperacillin).
Source, action spectrum, as well as a combination with beta-lactamase consider when creating the classification contained in the medical guide.
- benzylpenicillin (penicillin G)
- phenoxymethylpenicillin (penicillin V)
- benzathine benzylpenicillin
- penicillin procaine
- benzathine phenoxymethylpenicillin.
3. Extended-spectrum (aminopenicilline):
4. Active against Pseudomonas aeruginosa:
5. Combined with beta-lactamase inhibitors (inhibitorsdisease):
Natural penicillin is the antibiotics of a narrow spectrum of activity affecting gram-positive bacteria and cocci. Biosynthetic penicillins is obtained from culture medium on which to grow certain strains of fungi (Penicillium).There are several types of natural penicillins, one of the most active and persistent of these is the penicillin. In medical practice used benzylpenicillin in the form of various salts — sodium, potassium and novocaine.
Natural penicillins have similar antimicrobial activity. The natural penicillins are destroyed by beta lactamases, therefore, ineffective for the treatment of staphylococcal infections, because in most cases staphylococci produce beta-lactamases. They are effective primarily against gram-positive microorganisms (including Streptococcus spp., including Streptococcus pneumoniae Enterococcus spp.),Bacillus spp. Listeria monocytogenes, Erysipelothrix rhusiopathiae, gram negative cocci (Neisseria meningitidis, Neisseria gonorrhoeae), some anaerobes (Peptostreptococcus spp. Fusobacterium spp.), spirochaetes (Treponema spp., Borrelia spp. Leptospira spp.). Gram-negative bacteria normally resistant, with the exception of Haemophilus ducreyi and Pasteurella multocida. against viruses (pathogens influenza, polio, smallpox, etc.), Mycobacterium tuberculosis, the causative agent of amebiasis, Rickettsia, fungi, penicillin is ineffective.
Benzylpenicillin is mainly active against gram-positive cocci. Spectra of antibacterial action of penicillin and phenoxymethylpenicillin are almost identical. However, benzylpenicillin 5-10 times more active than penicillin against a sensitive Neisseria spp. and some anaerobes. Dentists prescribed for infections of moderate severity. The activity of penicillin determined by biological in antimicrobial effect on a certain strain of Staphylococcus aureus. Per unit (1 U) take activity 0,5988 g of chemically pure crystalline sodium salt of benzylpenicillin.
Significant disadvantages of benzylpenicillin are its instability to beta-lactamases (by enzymatic cleavage of beta-laktamnogo ring beta-lactamase (penicillinase) with the formation of penitsillanovoy acid antibiotic loses its antimicrobial activity), slight absorption in the stomach (necessitates injecting routes of administration) and relatively low activity against most gram-negative microorganisms.
Under normal conditions, the drug penicillin is poorly penetrates into the cerebrospinal fluid, but the inflammation of the meninges the BBB penetration increases.
Benzylpenicillin, used in the form of highly soluble sodium and potassium salts, acts short — 3-4 hours, as rapidly excreted from the body, and it requires frequent injections. In this regard, for application in medical practice were offered a sparingly soluble salt of benzylpenicillin (including novocaine salt) and benzathine benzylpenicillin.
Long-acting forms of penicillin, or depo-penicillin: Bicillin 1 (benzathine benzylpenicillin), as well as combined drugs based on them — Bitsillin-3 (benzathine benzylpenicillin + benzylpenicillin sodium + benzylpenicillin novocaine salt), Bitsillin-5 (benzathine benzylpenicillin + benzylpenicillin novocaine salt), constitute a suspension, you can enter only intramuscularly. They are slowly absorbed from the injection site, creating a depot in the muscle tissue. This allows to maintain the concentration of antibiotic in the blood for a considerable time and reduce, thus, the frequency of drug administration.
All salts of penicillin used parenterally, because they are destroyed in the acidic environment of the stomach. Natural penicillins kislotostabilen properties, although to a lesser degree, has only phenoxymethylpenicillin (penicillin V). Dentists on chemical structure differs from penicillin by the presence in the molecule phenoxymethyl group instead of a benzyl.
Penicillin used for infections caused by streptococci, including Streptococcus pneumoniae (community acquired pneumonia, meningitis),Streptococcus pyogenes (streptococcal tonsillitis, impetigo, erysipelas, scarlet fever, endocarditis), in meningococcal infections. Benzylpenicillin is the antibiotic of choice in the treatment of diphtheria, gas gangrene, leptospirosis, Lyme disease.
Bicillin shown, in the first place, the long-term maintenance of effective concentrations in the body. They are used in syphilis and other diseases caused by a pale Treponema (yaws), streptococcal infections (except infections caused by streptococci In acute tonsillitis, scarlet fever, wound infections, erysipelas, rheumatism, leishmaniasis.
In 1957, of the natural penicillins were allocated to 6-aminopenicillanic acid and on its basis have been developed semi-synthetic drugs.
6-Aminopenicillanic acid — based molecules all of penicillin (“penicillin nucleus”) — a complex heterocyclic compound consisting of two rings: tiazolidinovogo and beta-laktamnogo. With a beta-lactam ring connected the radical side, which determines the essential pharmacologic properties of the resulting molecule drug. Natural penicillins structure of the radical is dependent on the composition of the environment where you grow Penicillium spp.
Semisynthetic penicillins are produced by chemical modification, adding different radicals to the molecule 6-aminopenicillanic acid. Thus was obtained the penicillins, have certain properties:
- resistant to the penicillinase (beta-lactamase);
- acid-fast, effective upon appointment inside;
- with a broad spectrum of action.
Isoxazolylpenicillins (isoxazolyl penicillins, penicillinsusceptible, antistaphylococcal penicillins). Most staphylococci produce a specific enzyme beta-lactamase (penicillinase) and resistant to benzylpenicillin (penitsillinazoobrazuyuschih are 80-90% of strains of Staphylococcus aureus).
Major antistaphylococcal drug is oxacillin. Group penicillinase-resistant drugs also includes cloxacillin, Flucloxacillin, methicillin, nafcillin and dicloxacillin that due to the high toxicity and/or low efficiency not found clinical application.
Spectrum antibacterial action oxacillin similar range benzylpenicillin actions, but due to resistance to oxacillin penicillinase and is active against penitsillinazoobrazuyuschih staphylococci resistant to benzylpenicillin and phenoxymethylpenicillin, and also resistant to other antibiotics.
Activity against gram-positive cocci (including staphylococci do not produce beta-lactamases) isoxazolylpenicillins, including oxacillin, significantly inferior to the natural penicillins, so when disease agents which are sensitive to benzylpenicillin microorganisms, they are less effective than the last. Oxacillin does not show activity against gram-negative bacteria (except for Neisseria spp.), anaerobes. In this regard, drugs of this group are shown only in those cases when it is known that infection caused by penitsillinazoobrazuyuschih strains of staphylococci.
Main pharmacokinetic differences isoxazolylpenicillins from benzylpenicillin:
- quick, but not complete (30-50%) absorption from the gastrointestinal tract. You can apply these antibiotics such as parenteral (V/m, in/in), and inside, but 1-1,5 hour before meals, because they have low resistance to hydrochloric acid;
- high degree of binding to plasma albumin (90-95%) and the inability to remove isoxazolylpenicillins from the body with hemodialysis;
- not only renal but hepatic excretion, no need of dosage adjustment in mild renal failure.
Main clinical value of oxacillin — treatment of staphylococcal infections caused by penicillinresistant strains of Staphylococcus aureus (except infections caused by methicillin-resistant Staphylococcus aureus, MRSA). Note that in hospitals prevalent strains ofStaphylococcus aureus resistant to oxacillin and methicillin (methicillin — first penicillinaseproducing penicillin, discontinued). Nosocomial and community-acquired strains of Staphylococcus aureus resistant to oxacillin/methicillin, are usually multidrug resistant — they are resistant to all other beta-lactams and often to macrolides, aminoglycosides, fluoroquinolones. The drugs of choice in infections caused by MRSA, vancomycin or linezolid.
Nafcillin slightly more active than oxacillin and other penicillinase-resistant penicillins (but less active than benzylpenicillin). Nafcillin permeates through the GEB (its concentration in the cerebrospinal fluid sufficient for the treatment of staphylococcal meningitis), is excreted primarily in the bile (maximum concentration in bile is much higher than whey), to a lesser extent by the kidneys. Perhaps the use of orally and parenterally.
Amidinoproline is penicillin narrow spectrum of action, but with a predominant activity against gram-negative enterobacteria. Drugs amidinoproline (amdinocillin, pivampicillin, bacardimartini, azidocillin) is not registered in Europe.
Penicillins with extended spectrum activity
In accordance with the classification provided by D. A. Kharkevich, a semi-synthetic broad-spectrum antibiotics are divided into the following groups:
I. Drugs that do not affect Pseudomonas aeruginosa:
- Aminopenicillin: ampicillin, amoxicillin.
II. Preparations active against Pseudomonas aeruginosa:
- Carboxypenicillins: carbenicillin, tikarcillina, carfecillin;
- Ureidopenicillin: piperacillin, azlocillin, mezlocillin.
Aminopenicilline broad — spectrum antibiotics. All of them are destroyed by beta-lactamases both gram-positive and gram-negative bacteria.
In medical practice widely used amoxicillin, ampicillin. Ampicillin — the founder of the group aminopenicillins. Against gram-positive bacteria ampicillin, like all semi-synthetic penicillins, inferior to the activity of benzylpenicillin, but is superior to oxacillin.
Ampicillin and amoxicillin have similar spectra of action. Compared with the natural penicillins antimicrobial spectrum of ampicillin and amoxicillin apply to sensitive strains of enterobacteria, Escherichia coli, Proteus mirabilis, Salmonella spp., Shigella spp. Haemophilus influenzae; better natural penicillins act on Listeria monocytogenes and sensitive enterococci.
Of all oral beta-lactams amoxicillin has the greatest activity against Streptococcus pneumoniae are resistant to natural penicillins.
Ampicillin is not effective against penitsillinazoobrazuyuschih strains of Staphylococcus spp strains Pseudomonas aeruginosa most strains of Enterobacter spp., Proteus vulgaris (indispositions).
Available combined preparations such as Ampiox (ampicillin + oxacillin). The combination of ampicillin or penicillin by oxacillin is rational, because the spectrum of action of this combination becomes more widespread.
Difference between amoxicillin (which is one of the leading oral antibiotic) of ampicillin is its pharmacokinetic profile when administered amoxicillin is more rapidly and well absorbed in the intestinal tract (75-90%) than ampicillin (35-50%), bioavailability is not dependent on food intake. Amoxicillin penetrates better into some tissues, including the respiratory system, where its concentration is 2 times higher than blood concentration.
Most significant differences of pharmacokinetic parameters of benzylpenicillin aminopenicillins:
- ability to assign inside;
- insignificant binding to plasma proteins — 80% aminopenicillins remain in the blood in free form and good penetration into tissues and body fluids (with meningitis concentrations in cerebrospinal fluid can be 70-95% of the concentrations in the blood);
- multiplicity of purposes of the combined drugs 2-3 times a day.
Main indications for prescribing aminopenicillin infection of the upper respiratory tract and ENT-organs, infections of urinary tract, infections of the gastrointestinal tract, the eradication of Helicobacter pylori (amoxicillin), meningitis.
Feature undesirable actions aminopenicillins is the development of “ampicillinbuy rash, which is a non-allergic maculopapular rash nature, which passes quickly to remove the drug.
One of the contraindications to the appointment aminopenicillins is infectious mononucleosis.
These include carboxypenicillins (carbenicillin, tikarcillina) and ureidopenicillin (azlocillin, piperacillin).
Carboxypenicillins is the antibiotic that has a spectrum of antimicrobial action similar to that aminopenicilline (with the exception of the action for Pseudomonas aeruginosa). Carbenicillin — first enticingly penicillin activity antipseudomonal inferior to other penicillins. Carboxypenicillins act on Pseudomonas aeruginosa Pseudomonas aeruginosa) and indolpologitiona species of Proteus (Proteus spp.) resistant to ampicillin and other aminopenicillins. Clinical significance carboxypenicillins currently reduced. Although they have a broad spectrum but inactive against a large part of the strains of Staphylococcus aureus, Enterococcus faecalis, Klebsiella spp., Listeria monocytogenes. Almost did not pass through GEB. Multiplicity of destination 4 times a day. Rapidly develop secondary resistance of microorganisms.
Ureidopenicillin is also enticingly antibiotics, their spectrum of action coincides with carboxypenicillins. The most active drug of this group — piperacillin. Of the drugs of this group only azlocillin retains its value in medical practice.
Ureidopenicillin more active than carboxypenicillins against Pseudomonas aeruginosa. They are used in the treatment of infections caused by Klebsiella spp.
Enticingly penicillins are destroyed by beta-lactamases.
Pharmacokinetic features ureidopenicillins:
- is administered only parenterally (I/m and in/in);
- excretion involves not only the kidneys but also the liver;
- the multiplicity of application 3 times a day;
- rapidly develop secondary resistance of bacteria.
Due to the emergence of strains with high resistance to penicillins and antidiagonal no advantages over other antibiotics penicillins enticingly almost lost its value.
Main indications for these two groups enticingly penicillins are nosocomial infections caused by sensitive strains of Pseudomonas aeruginosa in combination with aminoglycosides and fluoroquinolones.
Penicillins and other beta-lactam antibiotics have a high antimicrobial activity, but many of them can develop resistance of microorganisms.
This resistance is due to the ability of microorganisms to produce specific enzymes — beta-lactamase (penicillinase) that destroy (hydrolyze) beta the β-lactam ring of penicillins, which deprives them of antibacterial activity and leads to the development of resistant strains of microorganisms.
Some semisynthetic penicillins are resistant to beta-lactamase. In addition, to overcome the acquired resistance was developed compounds able to irreversibly inhibit the activity of these enzymes, called beta-lactamase inhibitors. They are used when creating inhibitorsdisease penicillins.
Beta-lactamase Inhibitors, like penicillins, are beta-lactam compounds, but, by themselves, have minimal antibacterial activity. These substances are irreversibly associated with beta-lactamases and inactivate these enzymes, thereby protecting beta-lactam antibiotics from hydrolysis. The beta-lactamase inhibitors are most active against beta-lactamase encoded by plasmid genes.
Inhibitorsdisease penicillin is a combination antibiotic of penicillin with a specific inhibitor of beta-lactamase (clavulanic acid, sulbactam, tazobactam). The beta-lactamase inhibitors are not used independently, but are used in combination with beta-lactams. This combination allows to increase the stability of the antibiotic and its activity against organisms producing these enzymes (beta-lactamases): Staphylococcus aureus, Haemophilus influenza Moraxella catarrhalis, Neisseria gonorrhoeae, Escherichia coli, Klebsiella spp., Proteus spp., anaerobes, including Bacteroides fragilis. As a result, resistant to penicillin strains of microorganisms become sensitive to the combination of drugs. The spectrum of antibacterial activity inhibitorsdisease beta-lactams matches the spectrum of contained in the composition of penicillins, varies only in the level of acquired resistance. Inhibitorsdisease penicillins are used to treat infections of different localization and for perioperative prophylaxis in abdominal surgery.
Inhibitorsdisease penicillins include amoxicillin/clavulanate, ampicillin/sulbactam, amoxicillin/sulbactam, piperacillin/tazobactam, tikarcillina/clavulanate. Ticarcillin/clavulanate has antidiagonal activity and active against Stenotrophomonas maltophilia. Sulbactam has its own antibacterial activity against gram-negative cocci of the family Neisseriaceae and the family of non-fermenting bacteria Acinetobacter.
Indications for use of penicillin
Penicillin used for infections caused by susceptible pathogens to it. Mostly they are used for infections of the upper respiratory tract, in the treatment of angina, scarlet fever, otitis media, sepsis, syphilis, gonorrhoea, infections of the gastrointestinal tract, urinary tract infections etc.
Apply penicillins should only by prescription and under medical supervision. It must be remembered that the use of insufficient doses of penicillin (and other antibiotics) or too early termination of treatment can lead to the development of resistant strains of microorganisms (especially natural penicillins). When the resistance should continue therapy with other antibiotics.
Use of penicillins in ophthalmology. ophthalmic penicillins are applied topically in the form of instillation, subconjunctival and intravitreal injections. Penicillins are poorly pass through gematoentsefalichesky barrier. On the background of inflammatory process of their penetration into the inner structures of the eye increases and concentrations in them are therapeutically important. So, with instillation into the conjunctival SAC of therapeutic concentrations of penicillins are determined in the stroma of the cornea, the local application in the anterior chamber practically does not penetrate. When subconjunctival administration of medications are defined in the cornea and anterior chamber of the eye, in the vitreous — concentration below therapeutic.
Solutions for topical application serves ex tempore Used penicillins for the treatment of gonococcal conjunctivitis (benzylpenicillin), keratitis (ampicillin, benzylpenicillin, oxacillin, piperacillin, etc.), canaliculata, especially caused by actinomycetes (benzylpenicillin, phenoxymethylpenicillin), abscess and phlegmon of the orbit (ampicillin/clavulanate, ampicillin/sulbactam, penicillin, etc.) and other eye diseases. In addition, penicillins are used to prevent infectious complications in trauma of the eyelids and orbit, especially when the penetration of a foreign body into the tissues of the orbit (ampicillin/clavulanate, ampicillin/sulbactam, etc.).
Use of penicillins in urological practice. In urological practice from antibiotics-penicillins are widely used inhibitorsdisease drugs (the use of natural penicillins and semisynthetic penicillins use as drugs of choice is not considered to be justified due to the high level of resistance of uropathogenic strains.
Side and toxic effects of penicillin. Penicillins have low toxicity in several antibiotics and a large breadth of therapeutic action (especially natural). The most serious side effects associated with hypersensitivity to them. Allergic reactions have been reported in a significant number of patients (according to different sources, from 1 to 10%). Penicillins more common than other drugs pharmaceutical groups, are the cause of drug Allergy. In patients who had allergic reactions to the introduction of penicillins in history, the subsequent application of these reactions are observed in 10-15% of cases. Less than 1% of people who have not previously noted such reactions, allergic reaction to penicillin with repeated administration.
Penicillins can cause an allergic reaction at any dose and any dosage form.
The use of penicillin is possible allergic reactions of immediate type and delayed. I believe that an allergic reaction to the penicillins is connected, mainly, with intermediate product of their metabolism — penitsillanovoy group. It’s called the great antigenic determinant and is formed with the gap beta laktamnogo ring. To small antigenic determinants penitsillinov include, in particular, the unmodified molecules of penicillins, benzylpenicillin. They are formed in vivo, but also sets in solutions of penicillin prepared for injection. Believe that early allergic reactions to penicillins is mediated mainly IgE-antibodies to small antigenic determinants, delayed and late (urticaria) — usually IgE-antibodies to antigenic determinants of the large.
Hypersensitivity Reaction due to formation in the body of antibodies and usually occur a few days after the beginning of use of penicillin (the terms can fluctuate from several minutes to several weeks). In some cases, allergic reactions manifest as skin rashes, dermatitis, fever. In more severe cases, these reactions are manifested by edema of the mucous membranes, arthritis, arthralgia, renal and other disorders. Possible anaphylactic shock, bronchospasm, pain in the abdomen, swelling of the brain and other manifestations.
Severe allergic reaction is an absolute contraindication to the introduction of penicillin in the future. The patient may need to explain that even a small amount of penicillin, taken into the body with food or when carrying out skin tests may be deadly.
Sometimes the only symptom of an allergic reaction to the penicillins is the fever (the nature is continuous, remittent or intermittent, sometimes accompanied by chills). Fever usually disappears within 1-1. 5 hours after drug withdrawal, but can sometimes last for several days.
For all penicillins characteristic cross-sensitization and cross-allergic reactions. Any products containing penicillin, including cosmetics, food products, can cause sensitisation.
Penicillins can cause various side and toxic effects of non-allergic nature. These include: ingestion — irritant effect, including glossitis, stomatitis, nausea, diarrhea; when I/m administration — pain, infiltration, aseptic necrosis of the muscles; the on/in the introduction — phlebitis, thrombophlebitis.
May increase reflex excitability of the CNS. With the use of high doses may experience neurotoxic effects: hallucinations, delusions, impaired regulation of BP, seizures. Seizures more likely in patients receiving high-dose penicillin and/or patients with severe liver dysfunction. Due to the risk of severe neurotoxic reactions penicillins endolyumbalno you can not enter (with the exception of benzylpenicillin sodium salt, which is introduced very carefully, for health reasons).
In the treatment of penicillin to the development of superinfection, candidiasis of the oral cavity, vagina, and intestinal dysbiosis. Penicillin (often ampicillin) can cause antibiotic-associated diarrhea.
Ampicillin introduces ampicillinbuy rash (5-10% of the patients), accompanied by itching, fever. This side effect occurs more frequently on 5-10th day of application of large doses of ampicillin in children with lymphadenopathy and viral infections or with concomitant ingestion of allopurinol and nearly all patients with infectious mononucleosis.
Specific adverse reactions when using bicillin are local infiltrates and vascular complications in the form of Dew syndromes (ischemia and gangrene of the limbs in case of accidental introduction into the artery) or Nicolau (pulmonary embolism and cerebral vessels when injected into the vein).
If you are using oxacillin possible hematuria, proteinuria, interstitial nephritis. Application enticingly penicillins (carboxypenicillins, ureidopenicillins) may be accompanied by allergic reactions, symptoms of neurotoxicity, acute interstitial nephritis, dysbiosis, thrombocytopenia, neutropenia, leukopenia, eosinophilia. When using carbenicillin possible hemorrhagic syndrome. Combination drugs containing klavulanova acid, can cause severe liver damage.
Pregnancy. Penicillins cross the placenta. Although adequate and well-controlled studies of safety in humans is not conducted, the penicillins, including inhibitorsdisease, widely used in pregnant women, while no complications were recorded.
In studies on laboratory animals when administered penicillins in doses 2-25 (for different penicillins) exceeding therapeutic, disorders of fertility and effects on reproductive function are not detected. Teratogenic, mutagenic, embryotoxic properties with the introduction of penicillins animals have not been identified.
In accordance with universally recognised recommendations of the FDA (Food and Drug Administration) that determine the possibility of using drugs during pregnancy, drugs of the penicillin group of the action to the child belong to the category B by the FDA (study of reproduction in animals showed adverse effects of medicines and adequate and well-controlled studies in pregnant women have been conducted).
When assigning the penicillins during pregnancy should be (as for any other funds) to take into account the duration of pregnancy. In the process of therapy it is necessary to strictly monitor the condition of mother and child.
Use in breastfeeding. Penicillins penetrate into breast milk. Although significant complications in a person not registered, use of penicillins by nursing mothers may lead to sensitization of the child, changing the intestinal microflora, diarrhoea, development of candidiasis and skin rash in infants.
Pediatrics. the use of penicillins in children pediatric-specific problems was not, however, keep in mind that not enough developed renal function in neonates and young children may lead to accumulation of penicillin (in this regard, it is noted an increased risk of neurotoxic action with the development of seizures).
Geriatrics. Specific geriatric problems in the application of penicillin is not registered. However, it should be remembered that older people are more likely age-related renal dysfunction, and therefore may require dose adjustment.
Impaired renal function and liver. the kidney/liver failure the accumulation is possible. At moderate and severe insufficiency of the kidney and/or liver dose adjustment is required and the periods between administration of the antibiotic.
Interaction of penicillins with other medicines. Bactericidal antibiotics (including cephalosporins, cycloserine, vancomycin, rifampicin, aminoglycosides) have a synergistic effect, bacteriostatic antibiotics (including macrolides, chloramphenicol, lincosamides, tetracyclines) — antagonistic. Care must be taken with the combination of penicillins active against Pseudomonas aeruginosaPseudomonas aeruginosa), with anticoagulants and antiplatelet agents (potential risk of increased bleeding). Do not combine with penicillins with thrombolytic drugs. When combined with sulfonamides may weaken bactericidal effect. Oral penicillins can decrease the effectiveness of oral contraceptives due to violation of enterohepatic circulation of estrogens. Penicillins can slow down the excretion of methotrexate (inhibit its tubular secretion). The combination of ampicillin with allopurinol increases the likelihood of skin rashes. The use of high doses of the potassium salt of benzylpenicillin in combination with potassium-sparing diuretics, potassium supplements or ACE inhibitors increases risk of hyperkalemia. Penicillins farmatsevticeski incompatible with aminoglikozidami.
Due to the fact that long-term oral antibiotics may be suppressed intestinal microflora, produce vitamins b1 In6 In12 and PP patients for the prevention of IMR designate b vitamins.
In conclusion it should be noted that the penicillins are a large group of natural and semisynthetic antibiotics having bactericidal effect. Antibacterial action is due to disruption of synthesis of peptidoglycan cell wall. The effect is due to inactivation of the enzyme transpeptidaza one of penitsillinazoy proteins located on the inner membrane of the bacterial cell wall, involved in the late stages of its synthesis. The differences between the penicillins are associated with the characteristics of their spectrum of action, pharmacokinetic properties and spectrum of adverse effects.
For several decades successful use of penicillins having problems associated with their incorrect application. Thus, the prophylactic purpose of penicillins at risk of bacterial infection is often unfounded. Wrong mode of treatment wrong dose (too high or too low) and frequency of injections can lead to adverse effects, reduce the effectiveness and development of drug resistance.
So, currently, most strains of Staphylococcus spp. are resistant to natural penicillins. In recent years, increased frequency of detecting resistant strains of Neisseria gonorrhoeae.
Main mechanism of acquired resistance to penicillins is associated with the production of betalactamases. To overcome widespread among microorganisms acquired resistance was developed compounds able to irreversibly inhibit the activity of these enzymes, called beta-lactamase inhibitors — clavulanic acid (clavulanate), sulbactam and tazobactam. They are used in the creation of combined (inhibitorsdisease) penicillins.
It Should be remembered that the choice of antibacterial drugs, including penicillin, should be primarily due to sensitivity to the agent that caused the disease, and no contraindications to its destination.
Penicillins the first antibiotics were introduced in clinical practice. Despite the diversity of modern antimicrobial agents, including cephalosporins, macrolides, fluoroquinolones, penicillins still remain one of the major groups of antibacterial drugs used in the treatment of infectious diseases.