Cephalosporins are classified as beta-lactam drugs. They represent one of the largest classes of antibacterial drugs.
General information
4th generation cephalosporins are considered relatively new. There are no oral forms in this group. The remaining three are oral and parenteral agents. Cephalosporins have high efficiency and relatively low toxicity. As a result, they are one of the most frequently used 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 predetermines a single mechanism of antimicrobial action, 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 bacterial cell walls. In the series from the first to the third generation, there is a tendency to significantly expand the spectrum of action and increaseantimicrobial activity on gram-negative microbes with a slight decrease in the effect on gram-positive microorganisms. The common property for all means is the absence of a significant effect on enterococci and some other microbes.
Many patients are wondering why 4th generation cephalosporins are not available in tablets? 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, 4th generation cephalosporins are not available in tablets. All medicines in this group are intended for parenteral administration. 4th generation cephalosporins are available in solvent ampoules.
4th generation cephalosporins
Drugs of this group are prescribed exclusively by specialists. This is a relatively new category of medicines. Cephalosporins 3, 4 generations have a similar spectrum of effects. The difference is in fewer side effects in the second group. The drug "Cefepime", for example, is close to third-generation drugs in a number of parameters. But due to some features in the chemical structure, it has the ability to penetrate the outer wall of gram-negative microorganisms. At the same time, Cefepime is relatively resistant to hydrolysis by beta-lactamases (chromosomal) of the C-class. Therefore, in addition to the characteristics characteristic of 3rd generation cephalosporins (Ceftriaxone, Cefotaxime), the drug exhibits suchfeatures like:
- effect on microbes-hyperproducers of beta-lactamase (chromosomal) C-class;
- high activity relative to non-fermenting microorganisms;
- higher resistance to hydrolysis of extended-spectrum beta-lactamases (the meaning of this feature is not fully understood).
Inhibitorprotected drugs
This group includes one drug "Cefoperazone/Sulbactam". In comparison with a mono-drug, the combined drug has an extended spectrum of activity. It has an effect on anaerobic microorganisms, most strains of enterobacteria capable of producing beta-lactamases.
Pharmacokinetics
3rd and 4th generation parenteral cephalosporins are very well absorbed when injected into the muscle. Medications for oral administration are highly absorbed in the gastrointestinal tract. Bioavailability will depend on the specific drug. It ranges from 40-50% (for Cefixime, for example) to 95% (for Cefaclor, Cefadroxil, Cefalexin). The absorption of some oral medications may be slowed down by food intake. But such a drug as "Cefuroxime asketil" undergoes hydrolysis during absorption. Faster release of the active ingredient is facilitated by food.
4th generation cephalosporins are well distributed in many tissues and organs (except for the prostate), as well as secretions. In high concentrations, drugs are found in the peritoneal and synovial, pericardial and pleuralfluids, 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 third-generation drugs such as Ceftazidime, Ceftriaxone, and Cefotaxime, and the representative of the fourth, Cefepime.
Metabolism and excretion
Most of the cephalosporins are not degraded. An exception is the drug "Cefotaxime". It biotransforms with the subsequent formation of an active product. The 4th generation cephalosporins, like the rest, are excreted mainly by the kidneys. When excreted in the urine, rather high concentrations are found.
Medications "Cefoperazone" and "Ceftriaxone" are distinguished by a double route of excretion - by the liver and kidneys. For most cephalosporins, the 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 assign them once a day. Against the background of renal failure, the dosage of medications requires adjustment.
Side effects
Antibiotics - 4th generation cephalosporins - cause a number of negative consequences, in particular:
- Allergy. Patients may present with erythema multiforme, rash, urticaria,serum sickness, eosinophilia. Side effects in this category also include anaphylactic shock and fever, Quincke's edema, bronchospasm.
- Hematological reactions. Among them, it is worth highlighting a positive Coombs test, leukopenia, eosinophilia (rarely), hemolytic anemia, neutropenia.
- Nervous disorders. Seizures have been reported at higher doses in patients with renal dysfunction.
- From the side of the liver: increased activity of transaminases.
- Digestive disorders. Among the negative consequences, diarrhea, pseudomembranous colitis, vomiting and nausea, and abdominal pain are quite common. In case of loose stools with blood fragments, the drug is canceled.
- Local reactions. These include infiltration and soreness at the site of intramuscular injection and phlebitis with intravenous injection.
- Other effects expressed as vaginal and oral candidiasis.
Indications and contraindications
4th generation cephalosporins are prescribed for severe, predominantly low-grade infections caused by multiresistant microflora. These include pleural empyema, lung abscess, pneumonia, sepsis, joint and bone lesions. 4th generation cephalosporins are indicated for complicated infections in the urinary tract, against the background of neutropenia and other immunodeficiency conditions. Medications are not prescribed for individual intolerance.
Precautions
Cross-type allergy noted when used. In patientswith intolerance to penicillins, a similar reaction to first-generation cephalosporins is noted. Cross-allergy with the use of the second or third category is less common (in 1-3% of cases). If there is a history of immediate-type reactions (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 prenatal period without special restrictions. However, adequate controlled studies of the safety of drugs 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 against the background of delayed renal excretion. In elderly patients, there is a change in renal function, and therefore a slowdown in the elimination of drugs is likely. This may require adjustment of the dosage regimen and dosage.
Kidney dysfunction
Because most cephalosporins are excreted via the renal system predominantly in the active form, the dosage regimen must be adjusted to suit the body. When using high doses, especially in combination with loop diuretics oraminoglycosides, a nephrotoxic effect is likely.
Liver dysfunction
Some drugs are excreted in the bile, and therefore for patients with severe liver pathologies, the dosage should be reduced. In such patients, there is a high predisposition to bleeding and hypoprothrombinemia when using Cefoperazone. Vitamin K is recommended for preventive purposes.
