Cephalosporins in pregnancy

Among all classes of antibacterial drugs intended for the treatment of inflammatory diseases caused by pathogenic and opportunistic microbes, cephalosporins are most often prescribed by doctors during pregnancy, since these antibiotics cause fewer side effects and do not have a teratogenic effect (unlike aminoglycoside antibiotics, lincosamides and fluoroquinolones).

In this case, in the treatment of pregnant women, semi-synthetic cephalosporins of the second and third generations are used, which are active against gram-negative bacteria and have a weaker toxic effect on the kidneys, which work under increased stress during pregnancy.

However, in any case, cephalosporins are used during pregnancy only as prescribed by the attending physician, who assesses the patient’s condition and decides that it is impossible to cope with the infection without antibiotics.

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Indications cephalosporins in pregnancy

Although the absolute safety of cephalosporins during pregnancy has not been clinically tested enough, these antibacterial drugs can be prescribed to pregnant women for infectious inflammations of the following: ENT organs and respiratory tract (tonsillitis, pharyngitis, otitis, sinusitis, bronchitis, pleurisy and pneumonia); abdominal and pelvic organs (endometritis); genital tract (chlamydia, gonorrhea, cervix, etc.); urinary tract and kidneys (cystitis, urethritis, nephritis, pyelonephritis); biliary tract (cholangitis); joints and periarticular tissues; pustular skin lesions (streptoderma, erysipelas, etc.).

Cephalosporins are very effective in treating hospital-acquired infections, bacterial meningitis (caused by pneumococci and meningococci) and endocarditis, as well as salmonella infections, peritonitis and sepsis.

Here are some names of cephalosporins used during pregnancy:

• Cefuroxime (Cefuroxime axetil, Cefumax, Ketocef, Novocef, Zinacef, Zinnat and other synonyms);
• Cefotaxime (Cefosin, Cefantral, Kefotex, Claforan, Clafotaxime, Talcef, etc.);
• Ceftriaxone (Cefaxone, Cefatrin, Betasporin, Lifaxon, Longacef, Rocephin);
• Cefixime (Cefix, Ceforal, Loprax, Suprax, Pancef).

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Release form

The drugs listed in the review are available in the following forms:

Cefuroxime - tablets (125, 250 and 500 mg); granules for suspension (in vials or sachets); powder for injection solution (in vials of 250, 750 and 1500 mg).

Cefotaxime and Ceftriaxone - powder for the preparation of parenteral solution (in bottles of 0.25-2 g).

Cefixime – capsules (100, 200 and 400 mg); powder for suspension and ready-to-use suspension for oral administration (in 5 ml vials).

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Pharmacodynamics

Like all beta-lactam antibiotics, cephalosporins during pregnancy (as well as cephalosporin group drugs used outside this condition) have a bactericidal effect on pathogens causing infectious inflammations, the essence of which lies in the disruption of the synthesis of oligopeptide components and the cross-linking of peptide glycan, the main substance of the murein wall of a bacterial cell. Changes in the structural integrity of cell membranes lead to lysis and death of microorganism cells: streptococci, staphylococci (except for strains of Staphylococcus aureus, resistant to penicillin), clostridia, erscherichia, proteus, gonococci, mycoplasma, chlamydia, fusobacteria, bacteroides.

However, cephalosporins do not act on the causative agents of pseudomembranous enterocolitis - Clostridium difficile; pseudomonas, listeria (Listeria monocytogenes), gastrointestinal campylobacter (Campylobacter spp.), legionella (Legionella spp.).

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Pharmacokinetics

Parenteral administration of Cefuroxime creates bacteria-killing concentrations in sputum, respiratory mucosa, cerebrospinal fluid and intercellular fluid of internal organ tissues within 25-45 minutes, providing a therapeutic effect for 5-8. The drug binds to plasma proteins by no more than 50% and is not transformed in the liver; it is excreted from the body by the kidneys (up to 90% unchanged). The use of Cefuroxime tablets increases the time before the onset of action of the drug by almost 3.5 and extends the half-life to 12 hours.

The binding of the antibiotic Cefotaxime to plasma proteins is lower (on average about 35%), but the concentration required for treatment remains in the blood for 12 hours. This drug passes through the BBB. Metabolism is carried out by liver enzymes, with a third of the breakdown products active against bacteria. Cefotaxime is eliminated by the kidneys and partly by the intestines, with a half-life in the range of 1-2.5 hours.

The drug Ceftriaxone - due to rapid absorption, high degree of binding to plasma proteins (up to 90-95%) and 100% bioavailability - after intramuscular injection reaches maximum concentration on average after 2.5 hours, accumulating in tissues and interstitial fluids and cerebrospinal fluid with subsequent injections. About 45-55% of the drug is excreted from the body unchanged, excretion with urine and partially with bile; the half-life lasts up to 8-9 hours.

Absorption is absorbed Cefixime after taking capsules or suspension is quite fast, but the bioavailability of this drug is about 40%, and the highest concentration in the blood plasma is noted 4 hours after administration. The main part of Cefixime is eliminated by the kidneys with a half-life of about 3.5 hours.

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Dosing and administration

The cephalosporin antibiotics included in this review are used as follows:

Cefuroxime in tablets is prescribed at 0.25-0.5 g every 12 hours (during meals), for a 10-day course. For pneumonia, the drug is used in the form of intramuscular injections - twice a day, 1.5 g for two to three days, after which they switch to the tablet drug, taking another 5-7 days twice a day, 0.5 g.

Cefotaxime is administered both intravenously and intramuscularly, three to four times a day at a daily dose in the range of 3-8 g (the specific dosage is determined by the doctor).

The daily dose of Ceftriaxone for injection is lower and ranges from one to two grams (divided into two injections per day).

Cefixime capsules can be prescribed to pregnant women at 200 mg twice a day.

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Contraindications

Cephalosporin antibiotics are contraindicated in patients with a history of severe immediate allergic reactions (urticaria, anaphylactic shock, interstitial nephritis, etc.).

It is not recommended to use drugs of this pharmacological group if there is a history of enteritis, ulcerative colitis, functional liver failure, or difficult-to-stop bleeding (associated with hypoprothrombinemia).

Contraindicated cephalosporins in early pregnancy (up to 4-5 months) are first-generation drugs (Cefazolin, Cephalexin, Cephradine, etc.), as well as the third-generation cephalosporin drug - Ceftriaxone (Cefaxone, Cefatrin, Betasporin, etc. trade names).

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Side effects cephalosporins in pregnancy

The main side effects of cephalosporins during pregnancy are:

• epidermal rashes such as dermatitis, purpura;
• leukopenia, thrombocytopenia, eosinophilia, thrombocytosis;
• fever, hyperhidrosis and anaphylactic reactions;
• general weakness and rapid fatigue;
• nausea, dry mouth, vomiting, flatulence, diarrhea, indigestion, abdominal pain;
• increased levels of bilirubin, liver transaminases and alkaline phosphatase in the blood;
• increased levels of urea and creatinine in the blood;
• formation of gallstones.

Overdose

Overdosing on cephalosporin antibiotics can cause increased side effects, primarily nausea and diarrhea. There is a high risk of seizures. Dose reduction and symptomatic treatment are recommended.

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Interactions with other drugs

The use of cephalosporin antibiotics simultaneously with non-steroidal anti-inflammatory drugs, including acetylsalicylic acid, increases the negative impact of antimicrobial drugs on the kidneys.

Cephalosporins should not be combined during pregnancy with antibacterial drugs of other groups, for example, aminoglycosides.

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Storage conditions

The indicated cephalosporin antibiotics should be stored in a dark place at a temperature of up to +25°C, and the prepared emulsions for oral administration should be stored in the refrigerator (no longer than 7 days).

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Shelf life

The shelf life of drugs in sealed packaging is 24 months.

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