ANTIBIOTICS USE

IN PREGNANCY
DWI ARIS AGUNG NUGRAHANINGSIH

INTRODUCTION
Antibiotics account for nearly 80% of all
prescription medications during pregnancy.
Approximately 20-25% of pregnant women receive
antibiotics.
The most common infection during pregnancy:
urinary tract infection (pyelonephritis; sexually
transmitted infections) and upper respiratory tract
infection.
Untreated infection fetal risks (low birth weight,
prematurity, abortion, etc)
No efficacy and safety data from clinical trial due to
standard to exclude pregnant women from study.

INTRODUCTION
Increae total body water, blood volume (40-50%) and
plasma volume (40-50%) increase Vd of some
antibiotics.
50% increase in renal blood flow (vasodilation of afferent
and efferent arterioles) increase antibiotics excretion
Alterations of GIT motility changes in absorption, oral
bioavalilability, delayed onset of certain antibiotics
Changes in hepatic enzymes significant drugs
metabolism changes drugs dose adjustment
Decrease albumin and alterations of plasma pH increase
concentration of unbound drug

http://antibiotics-list.com/

AMINOGLYCOSIDES
Aminoglycoside: Serum T1/2 is shorter, clearance is
increased, larger Vd in pregnancy lower serum peak
concentration
Aminoglycoside cross the placenta Can cause toxicity
especially during first trimester
Example: bilateral congenital deafness related to
streptomycin
Aminoglycoside can be used for short term during
pregnancy if the benefit out weight the risk.

BETA LACTAMS AND

RELATED ANTIBIOTICS
Penicillins and their newer derivatives are the most widely
prescribed antimicrobial class during pregnancy.
Penicillin iv 1st line prophylaxis if the patient is colonized
with group B streptococcus ampicillin is recommeded
alternative.
Penicillin highly crossed placental, if highly bind to protein
(anti staphylococcal penicillin) produce lower fetal tissue
concentration, if low protein binding (penicillin G, ampicilin)
high fetal tissue concentration.
Increase plasma volume, creatinin clearance decrease
serum penicillin concentration.
Penicillin group including those in combination with beta
lactamase inhibitor pregnancy category B

CEPHALOSPORINS
AND CEPHAMYCINS
Cephalosporins remain as the first line option for
many infection in pregnancy (allergic to penicillin).
All cephalosporins cephamycins are classified as
pregnancy category B.
Ceftriaxone remains as the treatment of choice for
GO during pregnancy.
Ceftriaxone should be used cautiously at term due
to the potential risk of kern icterus in neonate.
Newer drugs from this group should be used
carefully since lack of data for pregnancy used.

CARBAPENEMS
Ertapenem, meropenem and doripenem are
pregnancy category B while imipenem-cilastatin
is pregnancy category C.
In pregnancy there is data of decrease imipenem
concentration.
Carbapenem therapy should be reserved for
pregnant women with infections that are
resistant to penicillin and cephalosporin therapy
with limited alternatives.

MONOBACTAMS
Monobactams lack of cross reactivity with
penicilline and cephalosporine.
There are inconclusive data regarding its safety.
Aztreonam should be used with caution during
1st trimester due to lack of data, however safety
data during perinatal periode showed that its
pregnancy category B.
Should only used for patient with penicillin
allergy for whom beta lactam therapy is
contraindicated.

FLUOROQUINOLONE
Although its categorized as pregnancy category C,
they are generally contraindicated in pregnancy.
There are suggested relation between
fluoroquinolone with renal toxicity, cardiac defects
and central nervous system toxicity in the fetus.
Animal study have showed bone and cartilage
damage in fetus.
Because of the current evidence, fluoroquinolone
use in pregnancy is only recommended if there is
no alternatives.

GLYCOPEPTIDES AND
LIPOPEPTIDES
Vancomycin is a glycopeptide classified as
pregnancy category B safe for use in pregnancy
in the case of serious gram positive infections
(particularly during 2nd and 3rd trimester).
Vancomycin is widely distributed in the body tissue,
primary eliminated by glomerular filtration in the the
kidney and 55% protein bind alteration kinetics
during pregnancy
Vancomycin crosses the placenta and has been
found in the umbilical cord blood after intravenous
administration.

MACROLIDES AND
KETOLIDES
Erythromycin was persistently associated with
cardiovascular defects any product containing
erythromycin should be used with caution in
pregnancy and only when benefit outweighs risk.
Azithromycin has generally been considered safe for
use in pregnancy (pregnancy category B).
Clarithromycin exposure has not been associated
with increase incidence of major malformation
however the data have been conflicting (category C)

TETRACYCLINE
Labeled as pregnancy category D
They are associated with congenital defects,
with large doses being linked to maternal liver
toxicity.
Tetracycline penetrate into tissue and body
fluids with the degree of penetration correlated
to lipid solubility (mynocycline> doxycycline>
tetracycline).
Tetracycline cross the placenta and when used
beyond the second trimester, they can bind to
calcium in the developing fetus and cause
permanent discoloration of bones and teeth.

METRONIDAZOLE
Metronidazole is classified as pregnancy
category B; however it is contraindicated in the
first trimester of pregnancy.
Metronidazole remains as a a recommended
therapy for vaginosis and trichomonas
infections in pregnancy
However repeat exposure during pregnancy is
unknown and reduced risk of preterm birth has
not been clearly established.

SULFAMETHOXAZOLETRIMETHOPRIM
Both are categorized FDA pregnancy category C.
Both should be avoided during 1st trimester due to the
mechanism of trimethophrim as folate antagonist
increase the risk of major congenital malformation,
primarily neural tube and cardiac defect folate
supplementation seem to reduce the risk.
Sulfonamide should not be used during 3rd trimester as
they theoretically result in an increase of unbound
bilirubin due to competitive protein binding.
Trimethoprim-sulfametoxazole use in the 1st trimester
related with urinary tract defects, 2nd & 3rd trimester realte
with small for gestation age newborn.

ANTITUBERCULOSIS
1st line therapy for TB in pregnant women is the
same with non pregnant population.
Isoniazid (pregnancy category C) increase
hepatitis especially for those with prexisting
liver disease or HIV infection monitoring liver
enzymes is important elevation of 3-5 times of
the upper limit of normal may prompt
discontinuation of anti TB therapy.
Pridoxine (B6) daily oral supplementation (25-50
mg/day) is advised for all pregnant women
receiving INH to mitigate neurologic
complications in the mother and newborn.

ANTITUBERCULOSIS
Rifampicin has pregnancy category C.
INH coupled with rifampicin is known to increase liver
enzymes additively needed carefull monitoring.
Rifampicin exposure related to newborn bleeding
therefore vit K prophylaxis may be necessary.
Ethambutol is pregnancy category B considered to
be safe in pregnancy.
Pyrazinamide is pregnancy category C.
Fluoroquinolone which may be used in multidrug
resitant TB, should be generally avoided in pregnancy.
The newest anti TB agent, bedaquiline, is considered
pregnancy category B.

CLORAMPHENICOL
Cloramphenicol is relatively toxic and can cause
the agranulocytosis.
It crosses the placenta well and can reach
therapeutic concentration in the fetus.
It should not be used in the last weeks of
pregnancy as owing to inadequate metabolism
in the neonate, toxic concentration can be
reached which may cause gray baby syndrome
(feeding problems, vomiting, ash-gary skin,
respiratory distress and cardiovascular
colapse).

CONCLUSION
Assessment of risk-benefit to mother and fetus
both short and long term.
Many antibiotics are considered safe in
pregnancy, especially beta lactams, macrolides,
clindamycin, etc.
Given the lack of evidence for safety in
pregnancy, common practice is to avoid
prescribing antibiotics wherever possible or if
considered absolutely necessary, then to
prescribe in such a way as to minimise potential
fetal exposure to antibiotics (oral as much as
possible, short term).

REFERENCE
Bookstaver PB et al., 2015. A review of antibiotic use in
pregnancy. Pharmacotherapy 35 (11): 1052-1062.
Sipos S et al., 2011. Infections, antibiotics and pregnancy.
TMJ 61 (3-4): 225-231.