CHAPTER 3Antibiotics in pregnancyTim Weller, Conor JamiesonKey points There is little evidence regarding the safety of most antimicrobialtherapy in pregnancy Clinical experience indicates the safety of penicillins andcephalosporins Serious infections in pregnancy should be treated aggressivelyIntroductionThe use of antimicrobial agents during pregnancy often needs tobe considered as pregnant women are at the same risk of acquir-ing infectious diseases as anyone else. Indeed, they may be moreprone to certain infections, such as those of the urinary tract. Insome cases, such as asymptomatic bacteriuria, therapy is primarilyrequired to prevent fetal loss [1] rather than for the treatment ofthe mother. Regardless of who is the main beneficiary, it is impor-tant to know which compounds can be used with minimal risk inminor infections and to have some appreciation of the balance ofrisks for more serious cases.When the risk to the fetus is being assessed, several points shouldbe considered. With many antimicrobial agents, we now havemore than 40 years of experience of freedom from congenital ab-normality. The results of studies performed in animals should beviewed with caution. Sulphonamides, for example, can cause grossfetal malformations when given in high doses to rats and mice [2],but teratogenicity has not been recorded in humans despite use36Prescribing in Pregnancy, 4th edition. Edited by Peter Rubin and Margaret Ramsay,c 2008 Blackwell Publishing, ISBN: 978-1-4051-4712-5.Antibiotics in pregnancy 37for more than 50 years. One of the reasons why laboratory ani-mals make poor models for studying fetal damage is the profoundeffect antibiotics have on their normal gastrointestinal flora andconsequently on the animal’s metabolism.There are some drugs, however, with proven toxicity in hu-mans, which should definitely be avoided. Streptomycin, for ex-ample, has caused neonatal ototoxicity after long-term treatmentof tuberculosis [3,4]. By implication, the other aminoglycosidessuch as gentamicin, tobramycin, netilmicin and amikacin shouldbe avoided for minor infections, although there is no hard evidencethat they cause the same problem.Changes in the dynamics of blood flow and other physiologicaleffects of pregnancy can influence the pharmacokinetics of manydrugs. Philipson showed that serum concentrations of ampicillinin women who were 9–36 weeks pregnant were half the valuesfound in the same women when they were not pregnant [5]. Lowmaternal concentrations have been described after the ingestion ofmany antimicrobial agents, although the therapeutic implicationsof this are difficult to assess.Failure of antibiotic treatment may be blamed incorrectly on thewrong choice of antibiotic, and the drug might be replaced with apotentially more toxic agent. This could be particularly dangerouswhen concern for the fetus prevents the doctor from giving highdoses whilst treating a serious infection in the mother. In general,full adult doses should be used when treating infection in a preg-nant woman. Similarly, the length of therapy should be dictatedby the disease and not unduly influenced by the fact that the pa-tient is pregnant. Inadequate treatment, which may be followedby further courses of antibiotics, is likely to put the mother andfetus at greater risk than a full course of the appropriate drug.Antimicrobial agentsTable 3.1 lists most antimicrobial agents available in the UK to-gether with their possible toxic effects on the fetus during preg-nancy. Each is given a safety rating:‘Probably safe’ – controlled studies in women fail to demonstratea risk to the fetus in the first trimester or later trimesters. Afirst-choice drug if an antimicrobial agent has to be used.‘Caution’ – there are no controlled studies in pregnant womenand studies in animals have not demonstrated a risk to the38 Chapter 3Table 3.1 Antimicrobial agents and their possible adverse effectsAdverse effects on fetusAgent Use First trimester Second and third trimester CommentsPenicillinsPhenoxymethylpenicillin,penicillin G and long actingpenicillinsProbably safe Allergy; possibility ofsensitising the fetusNo adverse effects recordedduring decades of useAmpicillin and amoxicillin Probably safe Allergy; possibility ofsensitising the fetusNo adverse effects recordedduring decades of useAmpicillin pro drugs(talampicillin, pivampicillin,bacampicillin)Probably safe Allergy; possibility ofsensitising the fetusLimited data; no adverse effectsrecordedCo amoxiclav Probably safe Allergy; possibility ofsensitising the fetusLimited data; no adverse effectsrecordedTicarcillin,piperacillin/tazobactam andother antipseudomonalpenicillinsProbably safe Allergy; possibility ofsensitising the fetusNo adverse effects recordedduring decades of useFlucloxacillin and otherantistaphylococcalpenicillinsProbably safe Allergy; possibility ofsensitising the fetusNo adverse effects recordedduring decades of useAntibiotics in pregnancy 39CephalosporinsOral (cefalexin, cefadroxil,cefradine, cefaclor,cefixime, cefpodoxime,cefprozil, cefuroxime)Probably safe Allergy; possibility ofsensitising the fetusLimited data; no adverse effectsrecordedIntravenous (cefuroxime,ceftazidime, cefotaxime,ceftriaxone, cefpirome,cefoxitin)Probably safe Allergy; possibility ofsensitising the fetusLimited data; no adverse effectsrecordedCarbapenemsImipenem AvoidToxicity in animalsMeropenem, ertapenem Caution Limited data; use only if benefitoutweighs riskOther β lactamsAztreonam Caution Limited data; use only if benefitoutweighs riskMecillinam Probably safeMacrolides/lincosamidesErythromycin Probably safe No adverse effects recordedduring decades of useAzithromycin, clarithromycin Caution Limited data; alternatives areusually available
Clindamycin Probably safe Beware of maternal
pseudomembranous colitis
(Continued )40 Chapter 3
Table 3.1 (Continued)
Adverse effects on fetus
Agent Use First trimester Second and third trimester Comments
Tetracyclines
Tetracycline, demeclocycline,
doxycycline, lymecycline,
minocycline, oxytetracycline
Avoid Effect on development
in animals
Discolouration and dysplasia
of bones and teeth,
cataracts
Possible maternal hepatotoxicity
Aminoglycosides
Amikacin, gentamicin,
neomycin, netilmicin,
tobramycin
Caution Theoretical risk of ototoxicity Use in serious sepsis if benefit
outweighs risk
Quinolones
Ciprofloxacin, levofloxacin,
moxifloxacin, nalidixic acid,
norfloxacin, ofloxacin
Avoid Arthropathy in animal
studies
Arthropathy in animal studies May be used if no alternative
available
Other antibacterial agents
Chloramphenicol Avoid No evidence of adverse
effects to the fetus in
early pregnancy, but
a safer alternative is
usually available
Grey baby syndrome Safe if given topically as
absorption is minimalAntibiotics in pregnancy 41
Colistin Avoid Possible fetal toxicity
Fusidic acid Probably safe Limited data; no adverse effects
recorded
Metronidazole, tinidazole Probably safe Theoretical teratogenic
risk
No adverse effects recorded,
confirmed by meta analysis
Nitrofurantion Caution Risk of haemolysis at term Safe, except during labour and
delivery
Vancomycin, teicoplanin Caution Limited data; use only if
benefits outweigh risk
Trimethoprim Caution Theoretical teratogenic
risk
No adverse events recorded; use
if benefits outweigh risk
Co trimoxazole Avoid Theoretical teratogenic
risk
Neonatal haemolysis and
methaemoglobinaemia
Antituberculous agents
Capreomycin Caution Use only if benefits outweigh
risk; teratogenic in animal
studies
Cycloserine Caution Use only if benefit outweighs
risk
Rifampicin Caution Teratogenic at high
doses in animals
Possible increased risk of
neonatal bleeding
Use only if benefit outweighs
risk; vitamin K should be given
to mother and neonate; avoid
in mothers with liver disease
(Continued )42 Chapter 3
Table 3.1 (Continued)
Adverse effects on fetus
Agent Use First trimester Second and third trimester Comments
Isoniazid Probably safe
Ethambutol Caution Teratogenic in animals No adverse effects reported but
teratogenic in animals
Pyrazinamide Caution Limited data; use only when
benefit outweighs risk
Streptomycin Avoid Ototoxicity Safer agents always available
Antifungal agents
Amphotericin Caution Limited data; use only if benefit
outweighs risk
Caspofungin Caution Toxicity in animal
studies
Use only if benefit outweighs
risk
Fluconazole Caution Limited data; toxicity at high
doses in animals; use only if
benefit outweighs risk
Itraconazole, ketoconazole Avoid Teratogenic in animals
Miconazole, clotrimazole Caution Absorbed from vaginal topical
use, but no adverse effects
recordedAntibiotics in pregnancy 43
Flucytosine Avoid Teratogenic in animals
Terbinafine Caution Limited data; treatment may be
postponed until after
pregnancy
Griesofulvin Avoid Fetotoxic and
teratogenic
Women should avoid pregnancy
for 1 mo following treatment
Nystatin Probably safe Minimal absorption
Voriconazole Caution Use only if benefit outweighs
risk; toxicity in animal studies
Antiparasitic agents
Albendazole, mebendazole,
thiabendazole
Avoid Teratogenic in animals
Atovaquone Caution Limited data; use if benefit
outweighs risk
Piperazine Probably safe Limited data; treatment may be
postponed until after
pregnancy
Pentamidine Caution Limited experience; use if
benefit outweighs risk
Antiviral agents
Aciclovir, famciclovir,
valaciclovir
Caution Limited data; use if benefit
outweighs risk
(Continued )44 Chapter 3
Table 3.1 (Continued)
Adverse effects on fetus
Agent Use First trimester Second and third trimester Comments
Cidofovir Avoid Teratogenic in animals
Ganciclovir, valganciclovir Avoid Teratogenic in animals
Foscarnet Avoid
Manufacturer advises avoidance
in pregnancy
Adefovir Caution Toxicity in animal studies; use
only if ben
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