268 Quinolones

Pharmacology and toxicology

Quinolones impair bacterial DNA metabolism by inhibiting DNA gyrase. They have bactericidal activity at normal doses; at higher doses they have also bacteriostatic properties by inhibiting bacterial RNA and protein synthesis. Quinolones have a high affinity for cartilage and bone tissue; this affinity is highest in immature cartilage.

Pipemidic acid, cinoxacin, and nalidixic acid belong to the group of older quinolones. They concentrate in the urinary tract. Few data on their safety during pregnancy are available.

The newer fluoroquinolones have more favorable efficacy and pharmacokinetic properties, and are therefore suitable for the treatment of systemic infections. Ciprofloxacin, enoxacin, fleroxacin, gat-ifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, rosoxacin, and sparfloxacin belong to the fluoroquinolones group.

Quinolones cross the placenta and are found in the amniotic fluid at low concentrations. Umbilical cord concentrations of ciprofloxacin, pefloxacin, and ofloxacin have been found to be lower than maternal blood concentrations (Giamarellou 1989).

The use of fluoroquinolones in the first trimester of pregnancy has not been associated with an increased risk of major malformations or other adverse effects on pregnancy outcome (Larsen 2001,

2.6.9 Nitrofurantoin and other drugs for urinary tract infections

Loebstein 1998, Schaefer 1996. Berkovitch 1994). Most data are available for norfloxacin and ciprofloxacin and, to a lesser extent, for ofloxacin and pefloxacin. There are no or few data for the other fluoroquinolones. Quinolones have not been found to be teratogenic in animals.

Animal experiments have shown that quinolones can cause damage to the cartilage of immature animals and the fetus, resulting in arthropathy. The sensitivity is highest in the dog. The effects arc dependent on the dose and duration of treatment, and occur only in the sensitive period.

Musculoskeletal dysfunctions have so far not been found after prenatal exposure in humans (Loebstein 1998, Berkovitch 1994, Peled 1991). Wogelius (2005) expressed concern that prenatal use of fluoroquinolones may be associated with an increased risk of bone malformations. However, the study on 130 women who redeemed a prescription for fluoroquinolones during the first trimester or 30 days before conception did not find a significant increase of (such) birth defects (Wogelius 2005).

Recommendation. Quinolones should only be used in case of complicated infections resistant to the antibiotics of choice in pregnancy. Ciprofloxacin and norfloxacin should then be chosen, because of their relatively large documented experience. Even the first-trimester use of a quinolone antibiotic is not an indication for termination of pregnancy, but detailed fetal ultrasonography can be offered in such cases.

2.6.9 Nitrofurantoin and other drugs for urinary tract infections

Pharmacology and toxicology

Nitrofurantoin is an antiseptic drug which has been used for many decades as an effective agent for the treatment and prophylaxis of urinary tract infections and asymptomatic bacteriuria in pregnancy. High concentrations appear only in the urinary tract; maternal and fetal serum concentrations are low; marked placental transfer does not occur. Nitrofurantoin has not been associated with an increased risk of congenital malformations (Briggs 2005, Ben-David 1994).

Nitrofurantoin may cause hemolytic reactions, especially in patients with glucose-6-phosphatase dehydrogenase deficiency, but except for one case (Bruel 2000) hemolytic anemia in the newborn has never been reported after in utero exposure to nitrofurantoin (Gait 1990).

Fosfomycbi is a broad-spectrum antibiotic which inhibits cell-wall synthesis and is indicated for the treatment of uncomplicated urinary tract infections, especially acute cystitis. A single dose produces therapeutic concentrations in the urine which may last for 1-3 days (Stein 1998). Fosfomycin appears to be safe for use during pregnancy (Reeves 1992).

Methenamine mandelate and methenamine hippurate are antiseptic agents for the treatment of urinary tract infections. In urine, formaldehyde is produced from methenamine. In general, they are controversially discussed drugs. Adverse effects on pregnancy outcome have not been reported, but documented experience is very limited.

Recommendation. Nitrofurantoin and fosfomycin can be given during pregnancy to treat urinary tract infections when the antibiotics of choice have been ineffective. Methenamine is contraindicated during pregnancy. Inadvertent use is not an indication for termination of pregnancy or for invasive prenatal diagnostic procedures.

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Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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  • ruby
    Is pipemidic acid safe during lectation?
    5 years ago

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