SELECTION OF ANTIBIOTICS IN

OBSTETRICS
 Antibiotic
Definition:
Chemical produced by a microorganism
that kills or inhibits the growth of another
microorganism
 OBJECTIVES
Use only drugs which are extensively used in past
Do not use new or untried drug
Use smallest effective dose
No drug is safe beyond all doubts in early pregnancy
Recognize factors which determine drug passage
across the placenta and into breast milk.
Identify aspects of medications that determine safety
during lactation.
GENERAL CONSIDERATIONS IN
OBSTETRICS

I. Ante partum-Teratogenic effects

II. Post partum-effects on the breast feeding

neonate
EFFECTS OF ANTIBIOTICS IN OBSTETRICS
Ante partum Postpartum

 TRIMESTER FIRST
LACTATION

-congenital malformations  GI – diarrhea, constipation, vomiting,

(teratogenesis) feeding intolerance, hypoglycemia
 SECOND & THIRD TRIMESTER
 CNS – lethargy, sedation, poor
- affect growth & fetal development
suckling, muscle hypotonia, tremors,
or restlessness, withdrawal upon
discontinuation
- toxic effects on fetal tissues

 NEAR TERM  Other – possible sensitization or

allergic reaction
- adverse effects on Labour or neonate
after delivery
 Drug Transfer to the Fetus
Drug Transfer through Drug Passage through
the Placenta Breast Milk
 Diffusion from maternal
 Placental transfer may plasma into milk
occur by:  Higher maternal plasma
 Passive diffusion levels mean higher
breast milk
 Facilitated diffusion
concentrations
 Active transport  Equilibrium will be
 Placental surface area established with most
 Placental metabolism drugs between milk
 CRITERA FOR DRUG TRANSFER
 Molecular weight
 Lipid solubility
 Ionization
 Protein binding
 Chemical Structure
 Drug concentration
 Drug equilibrium
Drugs in the mother's blood can cross the placental
membrane into blood vessels in the villi and pass through
the umbilical cord to the fetus.
 CHOICE OF ANTIBIOTIC AGENT

 Pregnancy- first trimester

-second trimester
-third trimester
 Others -Renal functions
-hepatic functions
-drug allergy
-genetic factors(G-6-PD deficiency)
Drug Category In Pregnancy - FDA
Classification
A: No risk to the fetus
B: No risk to the fetus But there are no adequate and well-
controlled studies in pregnant women
C: Adverse effect on the fetus on animals, but there are no
adequate and well-controlled studies in humans.
Consider Potential benefits v. potential risks
D: Positive evidence of human fetal risk based on adverse
reaction data from investigational or marketing experience or
studies in humans. Consider Potential benefits v. potential
risks
X: Studies in humans or animals have demonstrated fetal
abnormalities and/or there is positive evidence of human fetal
risk based on adverse reaction data from investigational or
marketing experience, and the risks involved in use of the agent
in pregnant women clearly outweigh the potential benefits.
WHO categorization for drugs used in
breastfeeding
I - Compatible for breast feeding(no known or
theoretical contraindication considered safe)
II - Compatible with breastfeeding. Monitor infant for
side effects- (may theoretically cause side effects
but has not been observed to do so)
III- Avoid if possible. Monitor fetal side effects(side
effects reported in infants)
IV- Avoid if possible. May inhibit lactation
V- Avoid (cause serious side effects)
 Teratogens
• A substance, organism, physical agents capable of
inducing abnormal structure or function such as:
– Gross structural abnormalities
– Functional deficiencies
– Intrauterine growth restriction
– Behavioral aberrations
– Demise
 Teratogenic Factors

 Timing of exposure
 Developmental stage during exposure
 Maternal dose and duration
 Maternal pharmacokinetics
 Genetic factors/phenotypes
 Interactions between agents
 Known Teratogenic Antibiotics
 Aminoglycosides
 Streptomycin
 Polymyxins
 Colistin
 Gentamycin
 Polymyxin
 Tobramycin etc.
 Tetracyclines  Antimycotics
 Amphoteracin B
 Doxycycline
 5 flucytosine
 Minocycline
 Grisiofulvin etc.
 Tetracycline
 5- nitroimidazoles
 Metronidazole etc.
 ANTIBIOTICS
 Beta Lactams -Penicillins
-Cephalosporins
-Carbepenems
-Monobactams
 Flouroquinolones
 Tetracyclines & Chloramphenicol
 Macrolides
 Aminoglycosides
 Sulfonamides
 Miscellaneous Antibiotics
 Penicillins
 Active against gram positive bacteria newer penicillin
active against both gram positive and gram negative
bacteria.
 In Pregnancy:
 Category B drugs
 Cross the placenta easily and rapidly
 Lactation:
 Crosses in low concentrations
 Compatible with breastfeeding
 May cause diarrhea in neonates
I. Narrow-spectrum:
II. Moderate-spectrum:
A. β-lactamase sensitive:
 amoxicillin
 benzathine penicillin
 Ampicillin
 benzylpenicillin(penicillin G)
 Phenoxymethylpenicillin III. Broad-spectrum
(penicillin V)  co-amoxiclav
 procaine penicillin (amoxicillin+clavulanic acid)
IV. Extended-spectrum
B. Penicillinase-resistant  azlocillin
penicillins:  carbenicillin
 methicillin  ticarcillin
 oxacillin  mezlocillin
 nafcillin  piperacillin
 cloxacillin
 dicloxacillin
 flucloxacillin
C. β-lactamase-resistant
penicillins:
 Temocillin
Penicillin
 These group of drugs belong to category B
 Considered safe in pregnancy
 No drug so far has been found to have any effect on rat
fetus.
 Cephalosporins

 In Pregnancy:
 Category B drugs
 Cross the placenta during pregnancy
 Some reports of increased anomalies with specific
cephalosporins (cephalexin, cephradrine)
 Primarily cardiac defects….
 (..\Documents\cephelexin.docx
 ..\Documents\Cephradine.docx

 Lactation:
 Excreted into breastmilk in low concentrations
 Considered compatible with breastfeeding
 Classifications of Cephalosporins
First Generation:
 Cephalexin
 Cefazolin
 Cephalothin
 Cephradine

 Active against G+ cocci (except.enterococci & MRSA):

s.pneumoniae, s.pyogenes,s. aureus, s.
epidermidis
 Indicated for streptococcal pharyngitis ( e.g.cephalexin)
 Commonly used ( eg. Cefazolin) as prophylacic for
surgical procedures.
 Modest activity against G- bacteria
 Second Generation
Cefoxitin
Cefuroxime
Cefprozil
Mainly effective against G- bacteria
Modest activity against G+ bacteria

Cefoxitin: active against bowel anaerobes (B. fragilis )

Cefuroxim: active against H. influenzae, M. catarrhalis,
S.pneumoniae
Cef. Axetil: oral form of cefuroxime
Cefaclor: active against H. influenzae, M. catarrhalis &E.coli
Cefprozil: similar to cefaclor, c. axetil and augmentin- Liked by
children
Second Generations are used primarily for URTIs ( acute otitis
media, sinusitis ) and Lower RTIs ( acute exacerbation
 Third Generation

 Ceftriaxone
 Cefotaxime
 Cetazidime
 Cefoperazone
 Cefixime

 They have enhanced G- activity, H. influenzae, N.

meningitidis, N.gonorrhea, P. aeruginosae, M.
catarrhalis, E.coli, most Klebsiella
 Ceftriaxone: has long half-life . Not advised in
neonates (interferes with bilirubin metabolism )
 Cefotaxime: preferred in neonate ( does not interfere
with bilirubin metabolism ), as may ceftriaxone.
Ceftriaxone
 In vitro studies have shown that Ceftriaxone can
displace bilirubin from its binding to serum albumin
and bilirubin encephalopathy can possibly develop in
neonates with hyperbilirubinemia especially
prematures.
 Hence,its should be avoided in mothers who are
lactating premature neonate or hyperbilirubinemic.
 ..\Documents\ceftriaxone.pdf
 Fourth Generation

Cefipime:
Active against G+ bacteria than cefazolin against s.
pyogenes, s.pneumoniae but lower against s. aureus.
Similar to cefotaxime against E.coli & K. pneumoniae
but for p. aeruginosa
 Carbapenems

Ertapenem, Imipenem, Meropenem

 Category B/C/B in pregnancy
 Likely cross the placenta
 Very little human data
 Lactation
 Excreted into breast milk in low amounts
 Unknown effects but likely low clinical
significance
 Monobactams

 Aztreonam
 Tigemonam
 Nocardicin
 A.tabtoxinine-β-lactam
 Pregnancy Category B, likely safe in pregnancy, little
human data
 Lactation – Compatible
 Fluoroquinolones

 Synthetic broad spectrum antibiotics

 In Pregnancy:
 Category C
 Not recommended in pregnancy
 Cartilage damage in animals
 Safer alternatives usually exist
 Lactation:
 Excreted into breast milk
 Limited human data
 Should also be avoided in breastfeeding as they have been
reported to cause arthropathies in immature animals
 Macrolides
 Azithromycin
 Clarithromycin
 Erythromycin
 Inhibit protein synthesis
 They are effective against penicillin-resistant strains
 Macrolides are effective against most of the G(+) bacteria, cocci or bacillus
 They are less effective against G(-) bacteria
 In Pregnancy:
 Categories B
 Cross the placenta in low amounts
 Limited data with azithromycin and clarithromycin
 Lactation:
 Erythromycin compatible
 Others probably compatible
 Aminoglycosides
 Amikacin
 Gentamicin
 Tobramycin
 Inhibit protein synthesis
 Serious infections caused by aerobic gram (-) bacteria
 Pregnancy: Category C
 Rapidly cross placenta
 Enter amniotic fluid through fetal circulation
 Associated defects and complications: Some neonates have had hearing
defects, whereas others have had vestibular problems. Some offspring had
inner ear damage, whereas others did not.
 Lactation
 Compatible with breastfeeding
 Not absorbed through GI tract
 Sulfonamides
 They are bacteriostatic because it inhibits bacterial synthesis of folic acid
 Clinical usefulness has decreased because of the effectiveness of other
antibiotics
 Pregnancy Category C
 Readily cross the placenta
 Concerns of use at term
 Lactation
 Excreted into breast milk in low levels
 Use should be avoided in premature infants.
 Sulphonamides are best avoided in infants with glucose-6-
phosphate dehydrogenase deficiency.
 Precipitates kernicterus in newborn.
 Tetracyclines
(doxycycline, minocycline, tetracycline)
 In Pregnancy:
 Category D
 Contraindicated in pregnancy
 Antibiotic crosses the placenta , chelates with calcium and is
deposited in the developing teeth and bones of the fetus.
Causes discoloration of the teeth and enamel hypoplasia can
occur from the end of the first trimester.
 Have been linked to maternal liver toxicity(acute fatty liver)
 Can cause temporary suppression of bone growth
 Lactation:
 Transfer of tetracycline into breast milk is low but possible
risks of inhibiting bone growth or causing dental staining.
 Serum levels in infants undetectable
 Chloramphenicol

 Inhibits protein synthesis in bacteria.

 Avoided in late pregnancy and during labour because of the
potential for the “grey baby syndrome” in the newborn infant.
 The syndrome usually starts 2–9 days after therapy has begun,
causing vomiting, suck refusal, rapid irregular respiration,
abdominal distension, followed by flaccidity, an ashen grey
colour and hypothermia. About 40% of these neonates die from
circulatory collapse on about the fifth day. Therefore, it should
only be used in pregnancy in life-threatening conditions, when
no alternative is available.
 Miscellaneous Antibiotics

 Clindamycin
 Pregnancy Category B, commonly used
 Lactation – Compatible per AAP
 Miscellaneous Antibiotics

 Linezolid
 Pregnancy Category C, no human data available
 Lactation – unknown, myelosuppression in animals

 Vancomycin
 Pregnancy Category B, compatible
 Lactation – likely compatible, not absorbed
 Miscellaneous Antibiotics

 Nitrofurantoin
 Pregnancy Category B, possible hemolytic anemia with
use at term
 Low levels of glutathione may predispose the fetus to
haemolytic anaemia if it is exposed to nitrofurantoin
 Lactation – Compatible, avoid with G-6-PD deficiency

 Trimethoprim
 Pregnancy Category C, potentially problematic early in
pregnancy
 Lactation – Compatible as combination drug
 Miscellaneous Antibiotics

 Metronidazole:
 Pregnancy Category C, carcinogenic in animals, avoid in
1st trimester if possible
 Causes ongenital malformations including coronal
hypospadias, syndactyly, calcaneous valgus, hydrocele
and pyloric stenosis, which may not necessarily be
related to the first trimester.
 Lactation – may cause lactose intolerance, and since the
drug may be teratogenic.Low dose 200-400mg TDS can
be given.
 ..\Documents\metronidazole.docx
 Topical Antibiotics

 There is no evidence the topical anti-infective creams,

ointments, gels sufficiently get absorbed into breast milk
 Any visible cream should be wiped off prior to breastfeeding
 PROPHYLACTIC ANTIBIOTIC IN C-SECTION
 Women scheduled for caesarean section should receive the first
dose of the antibiotic an hour before delivery.
 Such strategy is associated with lower risk of wound infection
and total postoperative infection
 This however, did not reduce the rate of neonatal sepsis or their
admission to a neonatal intensive care unit
 First-generation cephalosporin are the first prophylactic choice
in the caesarean setting. Clindamycin and gentamicin are the
alternative recommended for women with reported allergy to
beta-lactam antibiotics.
Drugs in breastfeeding

1. Safe for administration: 2. Effects not known/to be used

 Aminoglycosides. with caution:
 Amoxycillin.  Clindamycin.
 Amoxycillin-clavulanate.  Metronidazole (low dose).
 Cephalosporins.  Nalidixic acid.
 Macrolides.  Nitrofurantoin.
 Trimethoprim-  Tetracyclines.
sulphamethoxazole.

3. Not recommended:
 Metronidazole (single high
dose).
 Quinolones
 Chloramphenicol.
DRUGS WITH ADVERSE EFFECTS ON FETUS
 Chloramphenicol:
 Gray baby syndrome
 In women or fetuses with glucose-6-phosphate
dehydrogenase (G6PD) deficiency, the breakdown of red
blood cells
 Fluoroquinolones:
 Possibility of joint abnormalities (seen only in animals)
 Kanamycin:
 Damage to the fetus's ear, resulting in deafness
 Nitrofurantoin:
 In women or fetuses with G6PD deficiency, the breakdown
of red blood cells
 contd

 Streptomycin:
 Damage to the fetus's ear, resulting in deafness
 Sulfonamides:
 When the drugs are given late in pregnancy, jaundice
and possibly brain damage in the newborn
(sulfasalazine)
 In women or fetuses with G6PD deficiency, the
breakdown of red blood cells
 Tetracycline:
 Slowed bone growth, permanent yellowing of the teeth,
and increased susceptibility to cavities in the baby
 Occasionally, liver failure in the pregnant woman
Questions to Ask
 Is this drug used in neonates?
 How old is the infant?
 What is the duration of therapy?
 What are the pharmacokinetics of the agent?
 What is the risk/benefit for the mother?
 Does this medicine cause problems in G6PD
deficiency?
Considerations in Breastfeeding

 Withhold or delay therapy if possible

 Use a drug with poor penetration into milk
 Use an alternate route of administration
 Avoid nursing at peak drug concentrations
 Give drug before infants longest sleep
 Pump and dump milk
 Discontinue breastfeeding
Sensitivity
 S.aureus- vancomycin ,
erythromycin, Linezolid
 S.epidermis- vancomycin,
linezolid, pipzo.
 Pseudomonas- Aztreonam,
Pipzo, Amikacin.
 E.coli & Klebsiella- pipzo,
amikacin, astreonam,
cefotaxime.
Resistance
 Pipzo, Cefpodoxime,
penicillin
 Cipro, Cefpodoxime,
penicillin
 Ceftriaxone, Cefipime,
cefoperaxone, oflox
 Cipro,cefuroxime, cotrimox,
nalidixic acid, nitrofurantoin.
Inappropriate Antimicrobial Use
 Prescription not taken correctly
 Antibiotics for viral infections
 Antibiotics sold without medical supervision
 Spread of resistant microbes in hospitals due to
lack of hygiene
 Lack of quality control in manufacture or outdated
antimicrobial
 Inadequate surveillance or defective susceptibility
assays
 These leads to development of resistant strains
Consequences of Antimicrobial
Resistance
Infections
resistant to
available
antibiotics

Increased cost
of treatment
 Conclusions
No antibiotic is safe beyond all doubts in early pregnancy

According to FDA classification, no antibiotic is classified

as group A

Effect of an antibiotic on the fetus depends upon its

gestational age and drug pharmacokinetics

Use of unnecessary antibiotics in pregnancy & lactation

should be avoided

Very little human data is available on the safety of

antibiotics in pregnancy and lactation
 contd
Penicillins, Cephalosporins, Macrolides, Monobactams,
Clindamycin, etc fall under group B according to FDA.
Penicillins and Macrolides should be the first
choice(considering safety and cost effective)
Cephalosporins should be used with precaution.

Aminoglycosides, Fluroquinolones, Sulphonamides,

Linezolid, Metronidazole fall under group C.

Tetracyclines, Chloramphenicol fall under the group D

drugs
THANK YOU……..