aziz,2pmthursantibiotics during pregnancy and … antibiotic use during pregnancy and lactation...

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Antibiotic Use During Antibiotic Use During

Pregnancy and LactationPregnancy and Lactation

Sorting Fact from Fiction Sorting Fact from Fiction

Natali Aziz, MD, MSNatali Aziz, MD, MS

Department of Obstetrics, Gynecology and Reproductive SciencesDepartment of Obstetrics, Gynecology and Reproductive Sciences

University of California at San FranciscoUniversity of California at San Francisco

Antepartum and Intrapartum ManagementAntepartum and Intrapartum Management

June 7, 2007June 7, 2007

Obstetric ChallengesObstetric Challenges

Infections: common in obstetrics Infections: common in obstetrics

Antibiotics: prescribed in pregnancy/lactation Antibiotics: prescribed in pregnancy/lactation

Limited studies in pregnant women Limited studies in pregnant women

Most safety data is observationalMost safety data is observational

Limited randomized trialsLimited randomized trials

Limited use of newer antibioticsLimited use of newer antibiotics

Perception that few antibiotics safe in pregnancyPerception that few antibiotics safe in pregnancy

Andrade 2004

OverviewOverview

Pharmacokinetics of PregnancyPharmacokinetics of Pregnancy

Drug Safety Classification SystemDrug Safety Classification System

Safety and use in PregnancySafety and use in Pregnancy

Safety and use in BreastfeedingSafety and use in Breastfeeding

Specific infections/treatmentsSpecific infections/treatments

–– Cystitis, pyelonephrititisCystitis, pyelonephrititis

–– Pneumonia, tuberculosisPneumonia, tuberculosis

–– BV, syphilis, GC, CTBV, syphilis, GC, CT

–– MastitisMastitis

Overview of AntibioticsOverview of Antibiotics

PenicillinsPenicillins

CephalosporinsCephalosporins

MacrolidesMacrolides

AminoglycosidesAminoglycosides

QuinolonesQuinolones

Other antibioticsOther antibiotics

––ChloramphenicolChloramphenicol

–– ClindamycinClindamycin

––NitrofurantoinNitrofurantoin

––RifampinRifampin

–– VancomycinVancomycin

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Physiologic changes on antibiotic PKPhysiologic changes on antibiotic PK

–– Serum and tissue levelsSerum and tissue levels

–– ExcretionExcretion

–– AccumulationAccumulation

Fall in plasma protein 1 g/100 mlFall in plasma protein 1 g/100 ml

–– Decreased drug binding Decreased drug binding

Intravascular volume increase Intravascular volume increase

–– Increased cardiac output and GFRIncreased cardiac output and GFR

–– ↑ drug ↑ drug clearance/lower serum levels clearance/lower serum levels

Antibiotics: lipid soluble and low molecular wtAntibiotics: lipid soluble and low molecular wt

–– Facilitate placental crossingFacilitate placental crossing

Pacifici 2006


Lower Serum LevelsLower Serum Levels

–– PenicillinsPenicillins

–– AmpicillinAmpicillin

–– AmoxicillinAmoxicillin

–– CephalosporinsCephalosporins

–– ErythromycinErythromycin

–– GentamicinGentamicin

–– Other aminoglycosidesOther aminoglycosides

–– NitrofurantoinNitrofurantoin

–– QuinolonesQuinolones

Unchanged Serum LevelsUnchanged Serum Levels


–– TMXTMX--SMXSMX

–– VancomycinVancomycin

Good 1971; Weinstein 1976; Phillipson 1977;

Bernard 1977; Landers1983; Nahum 2006

FDA Classification:FDA Classification:

Drug Safety in PregnancyDrug Safety in Pregnancy

A: No adverse effects in human pregnanciesA: No adverse effects in human pregnancies–– Safety established using wellSafety established using well--controlled human studiescontrolled human studies

B: Presumed safety in human pregnanciesB: Presumed safety in human pregnancies–– Limited human studies/no adverse effects in animal studiesLimited human studies/no adverse effects in animal studies

C: Uncertain safetyC: Uncertain safety–– Limited human studies/adverse effects in animal studiesLimited human studies/adverse effects in animal studies

D: Adverse effects in pregnanciesD: Adverse effects in pregnancies–– Benefits may outweigh associated risksBenefits may outweigh associated risks

X: Adverse effects in pregnanciesX: Adverse effects in pregnancies–– Risks outweigh possible benefitRisks outweigh possible benefit

21 CFR 201.57

AntiAnti--Microbials: Microbials:

D and X FDA Drug CategoriesD and X FDA Drug Categories

D categoryD category

–– AminoglycosidesAminoglycosides

–– TetracyclinesTetracyclines

–– VoriconazoleVoriconazole

X categoryX category

–– QuinineQuinine

–– ThalidomideThalidomide

–– RibaviranRibaviran

–– MiltefosineMiltefosine

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Classifications:Classifications:

Drug Safety in LactationDrug Safety in Lactation

+: Generally accepted as safe+: Generally accepted as safe

?: Safety unknown or controversial?: Safety unknown or controversial

--: Generally regarded as unsafe: Generally regarded as unsafe

PenicillinsPenicillins and Pregnancyand Pregnancy

Examples: PCN G, PCN V, amoxicillin, ampicillinExamples: PCN G, PCN V, amoxicillin, ampicillin

General pharmacokinetics in pregnancyGeneral pharmacokinetics in pregnancy

–– Lower serum levelsLower serum levelsVol of dist/renal clearance increased in 2Vol of dist/renal clearance increased in 2ndnd&3&3rdrd trimesterstrimesters

Placental transfer: crossesPlacental transfer: crosses

Teratogenicity: noneTeratogenicity: none--unlikelyunlikely

–– No increased risk of congenital anomaliesNo increased risk of congenital anomalies

–– ?Association with NEC in preterm infants born to ?Association with NEC in preterm infants born to mothers on amoxicillinmothers on amoxicillin--clavulanic acid in 3clavulanic acid in 3rdrd trimester trimester

Philipson 1977; Heikkila 1993; Kullander 1976; Shar 1998; Czeizel 1998; Czeizel 2000;

Jepsen 2003; Colley 1983; Lovett 1997; Mercer 1997; Kenyon 2001

Cephalosporins and PregnancyCephalosporins and Pregnancy

Examples: cephalexin, cefazolinExamples: cephalexin, cefazolin


–– Lower serum levelsLower serum levels


Teratogenicity: unlikelyTeratogenicity: unlikely

–– Most studies demonstrate no increase in congenital Most studies demonstrate no increase in congenital defects or toxicity to newborndefects or toxicity to newborn

–– Few studies: ?small increase in congenital anomaliesFew studies: ?small increase in congenital anomaliesPoorly designed; no evaluation of confounders; recall biasPoorly designed; no evaluation of confounders; recall bias

Paterson 1972; Creatsas 1980; Pfau 1992; Rosa 1993

Macrolides and PregnancyMacrolides and Pregnancy

Examples: erythromycin, azithromycinExamples: erythromycin, azithromycin




Teratogenicity: noneTeratogenicity: none--unlikelyunlikely

––No association with congenital anomaliesNo association with congenital anomalies

––Estolate salt formulationEstolate salt formulation

Associated with hepatotoxicity in pregnant womenAssociated with hepatotoxicity in pregnant women

Jacobson 2001; Kacmar 2001; Rahangdale 2006; CDC 2006; Briggs 1998; McCormack 1977;

Collaborative Perinatal Project

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AminoglycosidesAminoglycosides and Pregnancyand Pregnancy

Examples: gentamicin, streptomycinExamples: gentamicin, streptomycin


–– Lower serum levels and decreased halfLower serum levels and decreased half--lifelife

–– Clearance decreased in preeclamptic patientsClearance decreased in preeclamptic patients

–– Check peak/trough levelsCheck peak/trough levels


Teratogenicity: undetermined/limited dataTeratogenicity: undetermined/limited data

–– Streptomycin: Case series of variable human ototoxic effects Streptomycin: Case series of variable human ototoxic effects

–– Gentamicin: No increase in congenital anomalies, ototoxicity, Gentamicin: No increase in congenital anomalies, ototoxicity,

nephrotoxicity in human studiesnephrotoxicity in human studies

–– Toxicity demonstrated in animal studies Toxicity demonstrated in animal studies

99--25X max recommended human doses (MRHD)25X max recommended human doses (MRHD)Weinstein 1976; Landers 1983; McNeeley 1985; Nahum 2006;

Czeizel 2000; Wing 1998; Wuarez 2001; Hulton 1995; Nishio 1987; Deguine 1996; Gilbert 1990

TetracyclinesTetracyclines and Pregnancyand Pregnancy

Examples: tetracycline, doxycyline, minocyclineExamples: tetracycline, doxycyline, minocycline


–– UnknownUnknown


Teratogenicity: unlikely Teratogenicity: unlikely

–– May induce hepatic necrosis in pregnant womenMay induce hepatic necrosis in pregnant women

–– May cause teeth staining, enamel hypoplasia, and reversible May cause teeth staining, enamel hypoplasia, and reversible

depression of fetal bone growth depression of fetal bone growth

–– Skeletal anomalies in animals (17x MRHD)Skeletal anomalies in animals (17x MRHD)

–– Doxycycline: No association with congenital anomaliesDoxycycline: No association with congenital anomalies

–– Doxycycline: No reports of teeth staining in humans!Doxycycline: No reports of teeth staining in humans!Nahum 2006; Rosa 1993; Czeizel 1997; Horne 1980; Bastianini 1970;

Schultz 1963; Wenk 1981; Kunelis 1965; Genot 1970; Rebich 1985; Cohlan 1963

Quinolones and PregnancyQuinolones and Pregnancy

Examples: ciprofloxacin, levofloxacin, ofloxacin Examples: ciprofloxacin, levofloxacin, ofloxacin

General pharmacokinetics in pregnancyGeneral pharmacokinetics in pregnancy–– Lower serum levelsLower serum levels


Teratogenicity: unlikelyTeratogenicity: unlikely–– No significant increase or trends in congenital anomalies in No significant increase or trends in congenital anomalies in human studies (cipro, oflox)human studies (cipro, oflox)

–– Cipro: No adverse effects in animal studiesCipro: No adverse effects in animal studies

–– Levo: Fetal skeletal ossification retardation, skeletal Levo: Fetal skeletal ossification retardation, skeletal variations, decreased weight, increased mortality in rats variations, decreased weight, increased mortality in rats

810 mg/kg/day dose (>9x MRHD)810 mg/kg/day dose (>9x MRHD)

–– Levofloxacin human studies limitedLevofloxacin human studies limitedVon Rosenstiel 1994; Loebstein 1998; Wolfson 1991; Schaefer 1996;

Daniscovicova 1994; Schluter 1989; CDC 2001; Watanabe 1992; ENTIS

Other Antibiotics and PregnancyOther Antibiotics and Pregnancy

ChloramphenicolChloramphenicol

ClindamycinClindamycin

NitrofurantoinNitrofurantoin

RifampinRifampin

VancomycinVancomycin

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Chloramphenicol and PregnancyChloramphenicol and Pregnancy





–– No significant risk of congenital anomaliesNo significant risk of congenital anomalies

–– Potential bone marrow suppression in infantPotential bone marrow suppression in infant

Avoid near term, during labor, and in breastfeedingAvoid near term, during labor, and in breastfeeding

Numah 2006; Weiss 1960; Czeizel 2000; Heinonen 1977;

Courtney 1968; Fritz 1971: Prochazka 1964

Clindamycin and PregnancyClindamycin and Pregnancy


–– No changeNo change


Teratogenicity: undetermined/unlikelyTeratogenicity: undetermined/unlikely

–– No increased risk of congenital anomalies No increased risk of congenital anomalies

–– Causative factor for development of C. diffCausative factor for development of C. diff

No difference in pregnant versus nonNo difference in pregnant versus non--pregnant womenpregnant women

Numah 2006; Rosa 1993; McGready 2001; McCormack 1987; Ou 2001; Rothman 1988

Nitrofurantoin and PregnancyNitrofurantoin and Pregnancy





–– Rare adverse effect: pulmonary hypersensitivityRare adverse effect: pulmonary hypersensitivity


–– May induce hemolytic anemia in G6PD deficiencyMay induce hemolytic anemia in G6PD deficiencyNo case of hemolytic anemia of newborn due to inNo case of hemolytic anemia of newborn due to in--utero utero exposure!exposure!

Landers 1983; Philipson 1982; Briggs 1998; Prytherch 1989; Rosa 1993

Rifampin and PregnancyRifampin and Pregnancy






Numah 2006; Stevenson 1959; Steen 1977; Bhargava 1996; Khan 2001

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Vancomycin and PregnancyVancomycin and Pregnancy


–– UnchangedUnchanged


Teratogenicity: undetermined/unlikelyTeratogenicity: undetermined/unlikely

–– No significant risk of congenital anomaliesNo significant risk of congenital anomalies

–– No change in risk of ototoxicity or nephrotoxicity in No change in risk of ototoxicity or nephrotoxicity in

pregnant versus nonpregnant versus non--pregnant womenpregnant women

–– Risk of toxicities to fetus considered lowRisk of toxicities to fetus considered low

Pearl et al, IDSOG 2006; Reyes 1989; Bourget 1991; Friedman 2000; MacCulloch 1981

Breastfeeding and Antibiotics:Breastfeeding and Antibiotics:PharmacodynamicsPharmacodynamics

Factors affecting medication transfer into milkFactors affecting medication transfer into milk–– Medication dose timingMedication dose timing

–– BioavailabilityBioavailability

–– Maternal Clearance Maternal Clearance

Drugs most likely to be transferredDrugs most likely to be transferred–– NonNon--ionized ionized

–– NonNon--protein bound protein bound

–– Low molecular weight Low molecular weight

–– High lipid solubility High lipid solubility

–– High pH High pH

Antibiotics Antibiotics DO NOTDO NOT affect breast milk supplyaffect breast milk supply

Breastfeeding and AntibioticsBreastfeeding and Antibiotics

Most antibiotics compatible with breastfeedingMost antibiotics compatible with breastfeeding

Many used therapeutically in infants Many used therapeutically in infants

Potential adverse effects in infants Potential adverse effects in infants

–– Changes in intestinal floraChanges in intestinal flora

Common antimicrobials safe in breastfeedingCommon antimicrobials safe in breastfeeding

–– Penicillins Penicillins

–– Cephalosporins Cephalosporins

–– Macrolides Macrolides

–– AminoglycosidesAminoglycosides

Use controversial???Use controversial???

–– Ofloxacin/QuinolonesOfloxacin/Quinolones

–– MetronidazoleMetronidazole

Breastfeeding and Antibiotics:Breastfeeding and Antibiotics:OfloxacinOfloxacin

Found in breast milkFound in breast milk

Associated with arthropathy in juvenile animalsAssociated with arthropathy in juvenile animals

Risk of arthropathy in infants extremely lowRisk of arthropathy in infants extremely low

–– Case series >7000 children on chronic quinolonesCase series >7000 children on chronic quinolones

ONLY 10/7000 developed arthropathyONLY 10/7000 developed arthropathy--like syndromelike syndrome

Bottom line: Bottom line: Compatible with breastCompatible with breast--feedingfeeding

Ingham 1977; Burkhardt 1997; AAP Committee on Drugs 2001

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Breastfeeding and Antibiotics:Breastfeeding and Antibiotics:Metronidazole/TinidazoleMetronidazole/Tinidazole

Association with carcinogenesis in rodents Association with carcinogenesis in rodents

No cancer association in humansNo cancer association in humans

No significant increase in adverse eventsNo significant increase in adverse events

–– Trend toward loose stools and candidal Trend toward loose stools and candidal

colonization in metronidazolecolonization in metronidazole--exposed infantsexposed infants

Bottom line:Bottom line: Compatible with breastfeedingCompatible with breastfeeding

–– Express/discard milk x 24 hours when 2 gm dosingExpress/discard milk x 24 hours when 2 gm dosing

Passmore 1988; Einarson 2000

Breastfeeding and Antibiotics:Breastfeeding and Antibiotics:Medications to AvoidMedications to Avoid

ChloramphenicolChloramphenicol

–– Breastfeeding safety unknownBreastfeeding safety unknown

–– Concern for potential bone marrow suppressionConcern for potential bone marrow suppression

–– “Gray“Gray--baby” syndromebaby” syndrome

–– Use not recommended in breastfeeding by AAPUse not recommended in breastfeeding by AAP

TetracyclineTetracycline

–– Chronic useChronic use NOT recommended NOT recommended

–– May cause staining of immature teeth in infantsMay cause staining of immature teeth in infants

–– ShortShort--termterm use compatible with breastfeeding!use compatible with breastfeeding!

AAP Committee on Drugs 1994, 2001; Weiss 1960

Breastfeeding and Antibiotics:Breastfeeding and Antibiotics:Compatible MedicationsCompatible Medications

AcyclovirAcyclovir CiprofloxacinCiprofloxacin OfloxacinOfloxacin

AmoxicillinAmoxicillin ClindamycinClindamycin QuinidineQuinidine

AztreonamAztreonam DapsoneDapsone QuinineQuinine

CefazolinCefazolin ErythromycinErythromycin RifampinRifampin

CefotaximeCefotaxime EthambutolEthambutol StreptomycinStreptomycin

CefoxitinCefoxitin FluconazoleFluconazole SulbactamSulbactam

CefprozilCefprozil GentamicinGentamicin SulfadiazineSulfadiazine

CeftazidimeCeftazidime IsoniazidIsoniazid SulfisoxazoleSulfisoxazole

CeftriaxoneCeftriaxone KanamycinKanamycin TetracyclineTetracycline

ChloroquineChloroquine NitrofurantoinNitrofurantoin TMXTMX--SMXSMXAAP Committee on Drugs, Pediatrics 2001

Cystitis TreatmentCystitis TreatmentNitrofurantoin Nitrofurantoin –– Rare adverse effect: pulmonary hypersensitivityRare adverse effect: pulmonary hypersensitivity

CephalosporinsCephalosporins


TrimethoprimTrimethoprim--sulfamethoxazole (TMXsulfamethoxazole (TMX--SMX)SMX)–– SulfonamidesSulfonamides

Theoretical risk: displaces bilirubin Theoretical risk: displaces bilirubin �� ?kernicterus?kernicterus

No cases of human kernicterus!No cases of human kernicterus!

No association with birth defectsNo association with birth defects

–– Trimethoprim: Folic acid antagonist Trimethoprim: Folic acid antagonist Ensure folic acid supplementation if used in first trimesterEnsure folic acid supplementation if used in first trimester

Quinolones?Quinolones?

Duration: 3Duration: 3--7 days7 daysBoggess 1996; Patterson 1997

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Pyelonephritis TreatmentPyelonephritis Treatment


Cephalosporins Cephalosporins

GentamicinGentamicin


DurationDuration

–– IV x 48 hours afebrileIV x 48 hours afebrile

––Change to POChange to PO

––1010--14 days total treatment14 days total treatment

Pneumonia TreatmentPneumonia Treatment

AzithromycinAzithromycin

AmoxicillinAmoxicillin

AmoxicillinAmoxicillin--clavulanic acidclavulanic acid

Ceftriaxone Ceftriaxone

Doxycycline? Doxycycline?


Tuberculosis:Tuberculosis:

Preventive TherapyPreventive Therapy

Isoniazid (INH)Isoniazid (INH)

–– Crosses placentaCrosses placenta

–– No increased toxicity to fetusNo increased toxicity to fetus

–– Breastfeeding compatibleBreastfeeding compatible

–– Possible increase in hepatic toxicity in womenPossible increase in hepatic toxicity in women

Bottom line: Bottom line: Postponed until after deliveryPostponed until after delivery

–– ExceptionsExceptions

HIV infectionHIV infection

Recent PPD conversion with known TB contact Recent PPD conversion with known TB contact

Snider 1992; Brost 1997

Bacterial Vaginosis TreatmentBacterial Vaginosis Treatment

Recommended regimensRecommended regimens–– Metronidazole (500 mg po BID x 7 days)Metronidazole (500 mg po BID x 7 days)

–– Metronidazole (250 mg po TID x 7 days)Metronidazole (250 mg po TID x 7 days)

–– Clindamycin (300 mg po BID x 7 days)Clindamycin (300 mg po BID x 7 days)

MetronidazoleMetronidazole–– No teratogenic association demonstrated! No teratogenic association demonstrated!

–– Single 2 gram dose not effective for BV txSingle 2 gram dose not effective for BV tx

Oral therapy preferred over vaginalOral therapy preferred over vaginal

Clindamycin cream use in 2Clindamycin cream use in 2ndnd and 3and 3rdrd trimesterstrimesters–– Associated with increased adverse eventsAssociated with increased adverse events

–– LBW, neonatal infectionsLBW, neonatal infections

CDC 2006; Caro-Paton 1997; Burtin 1995; Piper 1993;

Lamont 2003; McGregor 1994; Joesoef 1995; Vermeulen 1999

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Bacterial STD Treatment:Bacterial STD Treatment:

SyphilisSyphilis

Benzathine Penicillin G Benzathine Penicillin G

No proven alternatives during pregnancy!No proven alternatives during pregnancy!

History of PCN allergyHistory of PCN allergy

–– Skin testing Skin testing

–– PCN desensitizationPCN desensitization

CDC 2006


ChlamydiaChlamydiaFirst LineFirst Line

Azithromycin (1 gram po single dose)Azithromycin (1 gram po single dose)

Amoxicillin (500 mg po TID x 7 days) Amoxicillin (500 mg po TID x 7 days)

Second LineSecond LineErythromycin base/ethylsuccinate Erythromycin base/ethylsuccinate

GI symptomsGI symptoms�� nonnon--compliancecompliance

Less favored or avoidedLess favored or avoidedDoxycycline Doxycycline


Erythromycin estolateErythromycin estolate

––Associated with hepatotoxicity in pregnancyAssociated with hepatotoxicity in pregnancy

Jacobson 2001; Kacmar 2001; Rahangdale 2006; CDC 2006


Gonorrhea Gonorrhea

33rdrd generation Cephalosporingeneration Cephalosporin

–– Ceftriaxone 125 mg IM Ceftriaxone 125 mg IM

–– Cefixime 400 mg POCefixime 400 mg PO

HighHigh--risk PCN allergy risk PCN allergy

–– Spectinomycin 2g IM Spectinomycin 2g IM (CDC)(CDC)

–– Azithromycin 2 g POAzithromycin 2 g PO

If unknown Chlamydia statusIf unknown Chlamydia status

–– Treat presumptively for coTreat presumptively for co--infection infection


–– No longer recommended in US due to resistance!No longer recommended in US due to resistance!CDC 2006; CDC 2007

Mastitis TreatmentMastitis Treatment

First lineFirst line

–– DicloxacillinDicloxacillin

No response in 24No response in 24--48 hours48 hours

–– CephalexinCephalexin

–– AugmentinAugmentin

Mild PCN allergyMild PCN allergy

–– Cephalexin Cephalexin

HighHigh--risk PCN allergy or MRSA infectionsrisk PCN allergy or MRSA infections

–– TMXTMX--SMXSMX


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SummarySummary

Significant PK changes in pregnancy Significant PK changes in pregnancy

Dose antibiotics on upper limits if possibleDose antibiotics on upper limits if possible

Virtually all antibiotics cross placentaVirtually all antibiotics cross placenta

Virtually all antibiotics found in breast milkVirtually all antibiotics found in breast milk

Many abx are overall safe for use in pregnancyMany abx are overall safe for use in pregnancy

Quinolones and doxycycline Quinolones and doxycycline

–– May be considered for treatment in pregnancy if May be considered for treatment in pregnancy if

other alternatives not availableother alternatives not available

SummarySummary

Most abx may be used in breastfeedingMost abx may be used in breastfeeding

Avoid chronic tetracyclines use in breastfeeding Avoid chronic tetracyclines use in breastfeeding

Avoid use of chloramphenicol in breastfeedingAvoid use of chloramphenicol in breastfeeding

Quinolones compatible with breastfeedingQuinolones compatible with breastfeeding

Metronidazole compatible with breastfeedingMetronidazole compatible with breastfeeding

Review actual risks versus benefits w/ patientReview actual risks versus benefits w/ patient

Utilize risk vs. benefit for management decisionUtilize risk vs. benefit for management decision

UCSF Reproductive Infectious DiseaseUCSF Reproductive Infectious Disease

Consult ServiceConsult Service

11--415415--719719--87268726

FreeFree

2424--hour availabilityhour availability

For medical providers seeking assistance For medical providers seeking assistance

in management of reproductive infectious in management of reproductive infectious

disease and perinatal HIV issuesdisease and perinatal HIV issues

AcknowledgementsAcknowledgements

Robin Field, MDRobin Field, MD

Tekoa King, CNM, MPHTekoa King, CNM, MPH

Julian Parer, MD, PhDJulian Parer, MD, PhD

IrenIrenéé Merry and UCSF CME officeMerry and UCSF CME office

Deborah Cohan, MD, MPHDeborah Cohan, MD, MPH

aziz,2pmthursantibiotics during pregnancy and … antibiotic use during pregnancy and lactation...

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