WHEN, HOW AND WHY YOU MAY USE ANTIBIOTIC DURING PREGNANCY AND PHYSIOLOGIC AND PHARMACOLOGICAL FACTORS THAT AFFECT ITS USE.

1. Improving & UnderstandingImproving & Understanding
AntibioticAntibiotic PrescriptionPrescription DuringDuring
PregnancyPregnancy
Dr. Mamdouh SabryDr. Mamdouh Sabry
MD. Ain Shams, Ph.D. FranceMD. Ain Shams, Ph.D. France
Consultant Ob. & GynConsultant Ob. & Gyn..
EL Mataria Teaching Hospital, Nasser InstituteEL Mataria Teaching Hospital, Nasser Institute
Cairo, EgyptCairo, Egypt

2.  A significant number of women are exposed toA significant number of women are exposed to
antibiotics during their reproductive life.antibiotics during their reproductive life.
 The general principles of antibiotic therapy isThe general principles of antibiotic therapy is
applied to pregnant women as much as anyapplied to pregnant women as much as any
other patient.other patient.
 The physiologic changes which may alterThe physiologic changes which may alter
antibiotic effect during pregnancy and the effectantibiotic effect during pregnancy and the effect
of antibiotics on the embryo and mother areof antibiotics on the embryo and mother are
considered and has to be evaluated.considered and has to be evaluated.

3. I.I. Is it indicated.Is it indicated.
II.II. Gram stains, cultures → modification ofGram stains, cultures → modification of
therapy.therapy.
III.III. Infecting organism.Infecting organism.
IV.IV.Host factors.Host factors.
V.V. Antibiotic choices; spectrum, combination,Antibiotic choices; spectrum, combination,
dosing and intake.dosing and intake.
VI.VI.Duration of therapy → adequate but notDuration of therapy → adequate but not
unnecessary prolonged.unnecessary prolonged.
Sound principles of antibiotic therapySound principles of antibiotic therapy

4. HOST FACTORSHOST FACTORS
(Maternal pharmacokinetics)(Maternal pharmacokinetics)
1)1) Decrease overall serum concentrationDecrease overall serum concentration
of antibiotic.of antibiotic.
2)2) Increase excretion and clearance ofIncrease excretion and clearance of
antibiotic.antibiotic.
3)3) Increase incidence of infection.Increase incidence of infection.

5. HOST FACTORSHOST FACTORS
(Maternal pharmacokinetics)(Maternal pharmacokinetics)
1)1) Decrease overall serum concentration of antibiotic:.Decrease overall serum concentration of antibiotic:.
 GIT changes.GIT changes.
 ↓↓ serum albumin 20%.serum albumin 20%.
 Blood volume ↑→ ≤Blood volume ↑→ ≤ 45% (1500ml).45% (1500ml).
 Plasma volume ↑→ ≤ 50% (1300ml).Plasma volume ↑→ ≤ 50% (1300ml).
 ↑↑ Total body water → ≤ (2000ml).Total body water → ≤ (2000ml).

6. HOST FACTORSHOST FACTORS
(Maternal pharmacokinetics)(Maternal pharmacokinetics)
2)2) Increase excretion and clearance of antibiotic:.Increase excretion and clearance of antibiotic:.
 ↑↑ Renal blood flow ≤ 30%Renal blood flow ≤ 30%
 ↑↑ GFR ≤ 50%GFR ≤ 50%
 ↑↑ Creatinine clearance.Creatinine clearance.

7. HOST FACTORSHOST FACTORS
(Maternal pharmacokinetics)(Maternal pharmacokinetics)
3)3) ↑↑Incidence of infection:.Incidence of infection:.
 UTI.UTI.
 Vaginitis → PROM.Vaginitis → PROM.
 Gall bladder → stasis, emptying.Gall bladder → stasis, emptying.

8. Drug effects on FetusDrug effects on Fetus
 Congenital malformations among liveCongenital malformations among live
births represent about 5-6%.births represent about 5-6%.
 65% → unknown causes.65% → unknown causes.
 Drug induced → ≤ 1%Drug induced → ≤ 1% (Schardein. JL 2000)(Schardein. JL 2000)

9. FDA pregnancy risk categories:.FDA pregnancy risk categories:.
A.A. Controlled studies show no risk.Controlled studies show no risk.
B.B. +ve risk in animals & -ve risk in humans on+ve risk in animals & -ve risk in humans on
controlled studies, or –ve risk in animals ?!controlled studies, or –ve risk in animals ?!
C.C. Risk can not be ruled out; lacking wellRisk can not be ruled out; lacking well
controlled human studies or animal studies ascontrolled human studies or animal studies as
well, or even may show risk → benefits x riskwell, or even may show risk → benefits x risk
most drugs are category C;most drugs are category C; (aminoglycosides)(aminoglycosides)
D.D. +ve evidence of risk in humans but risk is+ve evidence of risk in humans but risk is
acceptable x potential benefits;acceptable x potential benefits; ttt of TB.ttt of TB.
X.X. Contraindicated; risk outweighs benefit.Contraindicated; risk outweighs benefit.

10. pregnancy risk categoriespregnancy risk categories
Pregnancy CategoryPregnancy Category
AnimalAnimal
ExposureExposure
HumanHuman
ExposureExposure
AA -- --
BB ++
--
--
??
CC ++
??
??
??
DD (benefit may outweigh risk)(benefit may outweigh risk) ++ ++
XX (contraindicated)(contraindicated) ++ ++
- No risk; + known risk; ? No information available.- No risk; + known risk; ? No information available.

11. Exposure Time & RiskExposure Time & Risk
 Conception →Conception → 2020 days (days (55thth
. Week) (complete. Week) (complete
repair x fetal wastage).repair x fetal wastage).
 Critical periodCritical period → organogenesis→ organogenesis 20-6020-60 days,days,
((5-105-10 weeks) during which embryo is mostweeks) during which embryo is most
vulnerable to insult. (Refampin → renal tubularvulnerable to insult. (Refampin → renal tubular
defects, facial clefts).defects, facial clefts).
 Second trimester → avoid agents withSecond trimester → avoid agents with
antimetabolic action (trimethoprim; anti-folate).antimetabolic action (trimethoprim; anti-folate).
 Third trimester → (near term), affect newbornThird trimester → (near term), affect newborn
babies (chloramephinicol, sulfonamides).babies (chloramephinicol, sulfonamides).

12. Antibiotic selectionAntibiotic selection
 Penicillins: category (B)Penicillins: category (B)
 Bactericidal, relatively safe for mother and fetus,
despite extensive use still very active and cost
effective.
 Cephalosporins: category (B)Cephalosporins: category (B)
 Generally safe during pregnancy.
 Cefoperazone, Cofotetan and Cefomanadol → ±
platelet dysfuncton or hypoprothrombinemia.

13. Antibiotic selectionAntibiotic selection
 Macrolides: category (B)Macrolides: category (B)
 Spiramycin, Erythromycin, Azithromycin…….
 Erythromycin Esteolate → cholostatic jaundice.
 Used in upper & lower respiratory tract infection,
uncomplicated skin infection, STD, CAP.
 Metronidozole: category (B)Metronidozole: category (B)
 Affects anaerobic organisms, TV, GL and EH.
 Pseudomembranous cotitis → cl. difficile.

14. Antibiotic selectionAntibiotic selection
 Clindamycin: category (B)Clindamycin: category (B)
 Macrolide, generally bacteriostatic and
bactericidal for some organisms on increase
concentration. ( Gonorrhea, Typhoid )
 Affects Gm. +ve aerobes strept., most staph.
And anaerobes Gm. +ve, Gm. –ve, 300 mg
orally, 4 times daily in mastitis
 Local cream for vaginitis.
 Nitrofurantion: category (B)Nitrofurantion: category (B)
 Bactericidal, excreted in urine. G6PD def.
 Active against common uropathogen.

15. Antibiotic selectionAntibiotic selection
 Aminoglycosides: category (C)Aminoglycosides: category (C)
 Gentamycin, Amikacin, Netilimycin, Tobramycin,
(x Streptomycin x).
 Affects Gm. –ve bacilli, N.gonorrhoea and staph.
Species.
 Nephrotoxic and ototoxic?
 Used in UTI.
 Trimethoprim, SMX: category (C)Trimethoprim, SMX: category (C)
 UTI → ?! Sinusitis otitis media, traveller’s
diarrhea (Shigella organisms), N.N. Jaundice.

16. Antibiotic selectionAntibiotic selection
 Aztreonam: category (B)Aztreonam: category (B)
 IV, IM. Only → Gm. –ve organisms.
 Vancomycin, linezolid (zyvox..?!): category (C)Vancomycin, linezolid (zyvox..?!): category (C)
 Ouinupristim / Dalfopristin (synercid):Ouinupristim / Dalfopristin (synercid):
category (B)category (B)
 Carbapenams: category (C)Carbapenams: category (C)
 Impienem – cilastatin, Meropenam cover broad
range of organisms; -ve on MRSA.
 Tetracyclines: category (D)Tetracyclines: category (D)
 Fluoraquinolones: category (C)Fluoraquinolones: category (C)
 ≥ 11 different drugs.

17. Conclusion
-Cautious use of antibiotics is especially important
during pregnancy because they can affect both the
mother and the fetus.
-Without exception, antimicrobials cross the
placenta; thus, the fetus is exposed to the adverse
effects of every antibiotic taken by the mother.
-Although prescription drugs account for less than
1% of all congenital malformations, potential
teratogenic effects must be considered since
antimicrobials are so commonly prescribed

18. ConclusionConclusion contcont ..
 Antibiotic use around pregnancy requiresAntibiotic use around pregnancy requires
consideration of maternal physiology and fetalconsideration of maternal physiology and fetal
risk.risk.
 For less serious infections, the safest antibioticFor less serious infections, the safest antibiotic
should be selected.should be selected.
 In life-threatening infections, the risk ofIn life-threatening infections, the risk of
morbidity or mortality may overshadow themorbidity or mortality may overshadow the
possibility of teratogenic side effects.possibility of teratogenic side effects.
 However, once microbial sensitivity is knownHowever, once microbial sensitivity is known
the safest antibiotic should be used.the safest antibiotic should be used.