Cephalosporins are classified as beta-lactam drugs. They presented one of the largest classes of antibacterial drugs.
General information
Cephalosporins of 4 generations are considered relatively new. There are no oral forms in this group. The remaining three are represented by means for oral administration and parenteral use. Cephalosporins are highly effective and relatively low toxicity. Due to this, they occupy one of the leading positions in the frequency of use in clinical practice of all antibacterial agents.
Indications for use for each generation of cephalosporins depend on their pharmacokinetic properties and antibacterial activity. Medicines are structurally similar to penicillins. This determines a single mechanism of antimicrobial exposure, as well as cross-allergy in a number of patients.
Activity spectrum
Cephalosporins have a bactericidal effect. It is associated with a violation of the formation of cell walls of bacteria. In the series from the first to the third generation, there is a tendency to significantly expand the spectrum of action and enhance antimicrobial activity on gram-negative microbes with a slight decrease in the effect on gram-positive microorganisms. A common property for all agents is the absence of a significant effect on enterococci and some other microbes.
Many patients are interested in why 4-generation cephalosporins in tablets are not available. The fact is that these medicines have a special molecular structure. This does not allow the active components to penetrate into the structures of the cells of the intestinal mucosa. Therefore, cephalosporins 4 generations in tablets are not available. All medicines in this group are for parenteral administration. Cephalosporins of 4 generations are produced in ampoules with a solvent.
Cephalosporins 4 generations
Drugs in this group are prescribed exclusively by specialists. This is a relatively new category of drugs. Cephalosporins 3, 4 generations have a similar spectrum of effects. The difference is in fewer side effects in the second group. Cefepim, for example, is close to third-generation drugs in a number of ways. But due to some features in the chemical structure, it has the ability to penetrate through the outer wall of gram-negative microorganisms. Moreover, Cefepim is relatively resistant to hydrolysis by beta-lactamases (chromosomes) of the C-class. Therefore, in addition to the characteristics inherent to 3rd generation cephalosporins (Ceftriaxone, Cefotaxime), the drug exhibits such features as:
- influence on microbes-hyperproducers beta-lactamases (chromosome) C-class;
- high activity relative to non-fermentative microorganisms;
- higher resistance to extended-spectrum beta-lactamase hydrolysis (the significance of this feature is not completely clear).
Inhibitor-protected medicines
This drug includes one drug, “Cefoperazone / Sulbactam.” In comparison with a single agent, a combined medication has an extended spectrum of activity. It affects anaerobic microorganisms, most strains of enterobacteria that can produce beta-lactamases.
Pharmacokinetics
Parenteral cephalosporins 3, 4 generations are very well absorbed when introduced into the muscle. Medications for oral administration are characterized by high absorption in the digestive tract. Bioavailability will depend on the specific medication. It ranges from 40-50% (for Cefixime, for example) to 95% (for Cefaclor, Cefadroxil, Cephalexin). Absorption of certain oral medications may be slowed by food intake. But such a medication as “Cefuroxime ascetic” undergoes hydrolysis during absorption. A faster release of the active ingredient is facilitated by food.
Cephalosporins 4 generations are well distributed over many tissues and organs (except the prostate), as well as secrets. In high concentrations, medications are found in peritoneal and synovial, pericardial and pleural fluids, bones and skin, soft tissues, liver, muscles, kidneys and lungs. The ability to pass the BBB and form therapeutic concentrations in the cerebrospinal fluid is more pronounced in drugs of the third generation, such as Ceftazidime, Ceftriaxone, as well as Cefotaxime, and the representative of the fourth, Cefepim.
Metabolism and excretion
Most cephalosporins do not decompose. An exception is the medication "Cefotaxime". It is biotransfected with the subsequent formation of the active product. 4th generation cephalosporins are excreted, as are representatives of the rest, mainly by the kidneys. When excreted in the urine, fairly high concentrations are detected.
The cefoperazone and ceftriaxone medicines are distinguished by a double excretion route - by the liver and kidneys. For most cephalosporins, the elimination half-life is within one to two hours. A longer time is required for Ceftibuten, Cefixime (3-4 hours), and Ceftriaxone (up to 8.5 hours). This makes it possible to appoint them once a day. Against the background of renal failure, the dosage of medicines requires adjustment.
Side effects
Antibiotics - cephalosporins 4 generations - cause a number of negative consequences, in particular:
- An allergy. Patients may have erythema multiforme, rash, urticaria, serum sickness, eosinophilia. Side effects of this category also include anaphylactic shock and fever, Quincke's edema, bronchospasm.
- Hematologic reactions. Among them, it is worth highlighting a positive Coombs test, leukopenia, eosinophilia (rarely), hemolytic anemia, neutropenia.
- Nerve disorders. When using high doses in patients with renal dysfunction, convulsions are noted.
- From the liver: increased activity of transaminases.
- Digestive disorders. Among the negative consequences, diarrhea, pseudomembranous colitis, vomiting and nausea, pain in the abdomen are quite common. In the event of a loose stool with blood fragments, the drug is canceled.
- Local reactions. These include infiltration and soreness in the area of intramuscular injection and phlebitis with intravenous injection.
- Other consequences are expressed as candidiasis of the vagina and mouth.
Indications and contraindications
Cephalosporins of 4 generations are prescribed for severe, low-grade infections predominantly caused by multiresistant microflora. These include pleural empyema, lung abscess, pneumonia, sepsis, damage to joints and bones. Cephalosporins of 4 generations are indicated for infections of the complicated type in the urinary tract, against the background of neutropenia and other immunodeficiency states. Medicines are not prescribed for individual intolerance.
Precautionary measures
When used, a cross-type allergy is noted. In patients with penicillin intolerance, a similar reaction to first-generation cephalosporins is noted. Cross allergy when using the second or third category is less common (in 1-3% of cases). If there is an immediate type of reaction in the history (for example, anaphylactic shock or urticaria), first-generation drugs are prescribed with caution. Drugs in the following categories (especially the fourth) are safer.
Lactation and pregnancy
Cephalosporins are prescribed in the antenatal period without special restrictions. However, adequate controlled trials of drug safety studies have not been conducted. In low concentrations, cephalosporins can pass into milk. Against the background of the use of the drug during lactation, changes in the intestinal microflora, candidiasis, skin rash, and sensitization of the child are likely.
Pediatrics and Geriatrics
When used in newborns, an increase in half-life is likely due to delayed renal excretion. In elderly patients, a change in renal function is observed, in connection with which a slowdown in the elimination of medications is likely. This may require adjustment of the dosage regimen and dosage.
Kidney dysfunction
Since the elimination of most cephalosporins occurs through the kidney system mainly in the active form, the dosage regimen should be adjusted taking into account the characteristics of the body. When using high doses, especially in combination with loop diuretics or aminoglycosides, a nephrotoxic effect is likely.
Liver dysfunction
Some drugs are excreted with bile, and therefore, for patients with severe liver pathologies, the dosage should be reduced. In such patients, a high predisposition to bleeding and hypoprothrombinemia with the use of Cefoperazone is observed. For preventive purposes, vitamin K. is recommended.