Antibiotics for Cesarean:Update on Prophylaxis

T. Flint, MD MPH02/11/2019

Park City, Utah

Background• 1.2 million cesareans in US annually–1 in 3 deliveries

• Surgical site infection (SSI) is the most common complication

• SSI includes–Wound infection–Endometritis– Intrabdominal abscess

Risk Factors for SSI• Obesity• Chorioamnionitis (Triple I, IAI)• Cesarean with labor–Spontaneous– Induction

• Emergency cesarean without labor• Maternal comorbidities–Diabetes–Autoimmune conditions–Preeclampsia

Saed etal,AmJInfectCont,2019

SSI is expensive

•$3,400 - $4,000/SSI•$500 million/Year

Olsen. Infect Control Hosp Epidemiol. 2010

Prophylaxis• Preoperative vaginal prep• Pre-incision antibiotics• Gentle cord traction vs. manual removal• Subcutaneous closure > 2 cm• Suture skin closure• Antibiotics in special circumstances–CS after labor, ROM–Obesity–Chorioamnionitis (Triple I, etc.)

Sood,Curr Opin InfectDis2018,

TODAY’S FOCUS:ANTIBIOTIC PROPHYLAXIS

Pre-incision Antibiotics

• Therapeutic tissue levels at time of microbial contamination

• Agent of choice− Long acting − Narrow focus on likely

bacteria− Inexpensive− Few adverse effects

Genitourinary tract microbiology

Gram positiveaerobic

Gram negativeaerobic Anaerobic Mycoplasma Other

GBS E. coli Peptostreptococcus Mycoplasma Chlamydia

S. auerus Klebsiella Peptococcus Ureaplasma

Enterococcus Proteus Bacteroides

Pseudomonas Gardnerella

Enterobacter

Gibbs,AmJObstet Gynecol 1987

Choice of Antibiotic• Cover gram (+), gram (-), anaerobic bacteria• Cefazolin, cefotetan, cefuroxime, ampicillin,

piperacillin, cefoxitin, amp/sulfbactam• Cefazolin is equally effect as the others and

cheaper• Single dose as effective as multiple dose in

uncomplicated infections

Standard Antibiotic Prophylaxis for CS

ACOG,PB132,2018

Cefazolin 1 g IV for patients < 80 kgTiming < 60 min before incision

Re-dose Surgery more than 4 hoursBlood loss greater than 1500 ml

Allergy Clindamycin 900 mgGentamycin 5 mg/kg

Multi dose No

Prophylactic Antibiotics and Infectious Morbidity

0%2%4%6%8%10%12%14%16%18%

CompositeInfections

WoundInfections

NeonatalSepsis NICUAdmission

NoAbxAbxCordClampAbxPreop

Smail et al. Cochrane Database 2014.Mackeen et al. Cochrane Database 2014.

NR

*

*

*P<0.05

ADJUNCTIVE AZITHROMYCIN FOR NON-ELECTIVE CESAREAN

Cesarean Section/Optimal Antibiotic Prophylaxis Study (CSOAP)

• 60 to 70% of CS are non-elective–SSI 12-13% with standard single dose

• Azithromycin + standard prophylaxis reduce SSI?

• Multicenter RCT, multi-center (11 sites)• Non-elective CS during labor, +/- ROM• Antibiotic prophylaxis–Standard pre-incision cefazolin (clind/gent)–Azithromycin or placebo prior, during, after

incisionTita,A,etal,NEJM2016

Indications for Cesarean – no differences

Adjunctive Azithromycin Prophylaxisfor Cesarean DeliveryTita, A et al, NEJM 2016

CSOAP Primary OutcomesTita, A et al, NEJM 2016

Infectious MorbidityTita, A et al, NEJM 2016

12.0%

6.6%

8.2%

3.4%

6.1%

2.4%

5.0%4.4%

0%

2%

4%

6%

8%

10%

12%

14%

Infection (any) Wound Infxn Readmit/Visit NeonatalMorbidity

Standard+ Azithro*

* *

METHICILLIN RESISTANT STAPH AUREUS

MRSA• Increase in MRSA related SSI infections–16-21% over the last five years

• Asymptomatic pregnant women–10% positive rectovaginal–2% positive nasal swabs

• Oral antibiotics not effective in MRSA eradication or prevention of MRSA SSI

ACOG Recommendation for MRSA

• Routine MRSA screening not recommended during pregnancy

• Obstetric patients known to be positive with planned cesarean:–Single dose of vancomycin in addition to

regular antibiotic prophylaxis (cefazolin)–Vancomycin by itself not adequate

ANTIBIOTIC PROPHYLAXIS ASSOCIATED WITH CESAREAN

SECTION IN BMI > 30

Obesity in pregnancy

CDC Data, 2018

University of UtahDelivery type by BMI

BMI <2950%

BMI 30-3428%

BMI 35-3913%

BMI >409%

PERCENTAGE OF DELIVERIES BY BMI

Obesity & Wound Complications

0%

5%

10%

15%

20%

Wound complication Wound infectionBMI<30 BMI 30-45 BMI >45

Stamilio andScifres..2014.

Cefazolin dosing for BMI > 30• Standard dose recommendation: 2g

cefazolin within 60 minutes of incision• Some hospital/systems give 2 gm to all

patients • Additional dosing for weight > 120kg–Mostly bariatric literature–Based on pharmacokinetic data–Recent cesarean related studies, but

minimal clinical dataBratzler et al. Am J Health Syst Pharm 2013ACOG PB 132, 2018

Cefazolin concentration: prospective cohort

• Swank et al, 2015

0%

20%

40%

60%

80%

100%

BMI20-30 BMI30-40 BMI>40

AdequateOpeningAdiposeSamples

2g 3g

0%

20%

40%

60%

80%

100%

BMI20-30 BMI30-40 BMI>40

AdequateClosingAdiposeSamples

2g 3g

RCT of Cefazolin DosingMaggio et al. Obstet Gynecol 2015

0%

20%

40%

60%

80%

100%

Opening Closing

Adequate adipose concentration to inhibit Staphylococcus among women with BMI > 30

2g cefazolin

3g cefazolin

Cefazolin dosage and SSIAhmadzia HK et al. Obstet Gynecol 2015

• Retrospective cohort (2015) from Johns Hopkins and Duke

• Compared SSI after cesarean in women receiving 2 and 3 gm cefazolin preoperatively

• 355 patients included• SSI– 13% in 2 g group– 13.1% in 3 g group

• Problems–Not adequately powered– Included women in labor

Post-cesarean extended oral antibiotic prophylaxis among

obese women

Post-cesarean Oral AntibioticsValent, AM, et al, JAMA, 2017

• RCT of PO cephalexin & metronidazole vs placebo for prevention of SSI in women with BMI > 30–Cefazolin 500 mg + metronidazole 500 mg or

placebo Q 8hours for 48 hours–Standard preoperative IV antibiotics

• Primary outcome–superficial incisional, deep incisional, or

organ space infections• Stratified by membrane status• Mean BMI 40

Post-Cesarean Cephalexin and Metronidazole

Outcomes

C/M

(n = 202)

Placebo

(n = 201)

RR

(95% CI) P

SSI 13 (6.4) 31 (15.4) 0.41 (.22-.77) .01

Incision morbidity 20 (9.9) 32 (15.9) 0.61 (0.37-2.1) .18

FUO 9 (4.5) 10 (5.0) 0.89 (0.37-2.14) .94

Wound

Separation16 (7.9) 22 (10.9) 0.72 (0.39-1.33) .56

Cellulitis 12 (5.9) 27 (13.4) 0.44 (0.23-0.84) .04

Endometritis 2 (1.0) 8 (4.0) 0.24 (0.53-1.16) .05

Valentetal.JAMA2017

Post-Cesarean Cephalexin and Metronidazole

Ruptured Membranes

C/M (n = 63)

Placebo (n = 63)

RR(95% CI) P

SSI 6 (9.5) 19 (30.2) 0.31(0.13-0.71) .008

Valent et al. JAMA 2017

Intact Membranes

C/M (n = 138)

Placebo (n = 139)

RR(95% CI) P

SSI 7 (5.0) 12 (8.7) 0.58 (0.24-1.44) .47

Post-cesarean Oral AntibioticsValent, AM, et al, JAMA, 2017

• Single center– Is this generalizable to the rest of the country–Confounders–HIGH rate of SSI in placebo group compared

to rest of the country• Implemented before current standards– Added azithromycin for labor/rupture–Higher doses of cefazolin

• May be alternative for obese women who have not received azithromycin

Peri-operative antibiotics for Cesarean in the setting of Triple

I, IAI, Chorioamnionitis

Treatment for Chorio, IAI, Triple IACOG CO 712, 2017

Recommended Abx

Ampicillin 2g IV Q 6 hours

Gentamicin 2 mg/kg followed by 1.5 mg/kg Q 8 hours or5 mg/kg Q 24 hours

Mild PCN Allergy*Cefazolin 2g IV Q8 hours

Severe PCN Allergy*Clindamycin or 900 mg IV Q8 hoursVancomycin 1 g IV Q12 hours

*Substitute for ampicillin. Gentamicin in all of these regimens

Treatment for Chorio, IAI, Triple IACOG CO 712, 2017

Alternative Regimens

Ampicillin/Sulbactam 3 g IV Q 6 hoursPiperacillin-tazobactam 3.375 Q 6 hours or 4.5 g Q 8 hours

Cefotetan 2 g IV Q 12 hoursCefoxitin 2 g IV Q 8 hoursErtapenum 1 g IV Q 24 hours

Cesarean Prophylaxis and IAI• If the patient is already receiving broad

spectrum antibiotics for another indication (IAI, pyelo, etc), additional cefazolin is not necessary• One additional dose of chosen regimen

should be given after cesarean• PLUS Clindamycin 900 mg IV or

metronidazole 500 mg IV for at least one dose

ACOG CO 712, 2017ACOG PB 199, 2018

Antibiotics for Cesarean• 1st generation cephalosporin is first line for all

patients undergoing CS– < 60 mins prior to incision– 1 g for patients < 80 kg– 2 g for patients > 80 kg– 3 g considered for patients > 120 kg

• Azithromycin for non-elective CS• MRSA – add vancomycin to preop abx• IAI–Give one dose after CS–Add clindamycin or metronidazole

Skin AntisepsisTuuli MG, NEJM, 2016

• RCT of chlorhexidine alcohol vs iodine-alcohol–572 women in CXH group–575 in IOD group

• Primary outcome–Superficial or deep wound infection within 30

days

Skin AntisepsisTuuli MG, NEJM, 2016

7.3%

2.4%

12.5%

4.0%

1.0%

7.9%

0%

2%

4%

6%

8%

10%

12%

14%

SSI Deep SSI MD Visit

IODCHX

*

Vaginal CleansingMeta-analysis and Systematic Review, 2017• Assess the efficacy of vaginal cleansing

before cesarean delivery in reducing PPE• RCTs comparing vaginal cleansing vs placebo

or no intervention– 15 RCTs with 4,744 women included

• Subgroup analysis– Labor vs. no labor–Membrane status–Type of antiseptic solution–Time of preop antibiotics

Vaginal CleansingMeta-analysis and Systematic Review, 2017

• Vaginal cleansing resulted in less endometritis among subgroups–Laboring patients–Patients with ROM–Povidone-iodine solution (not CHX)–Preoperative antibiotics

OutcomesVaginal

Cleansing ControlsRR

(95% CI)

Endometritis 4.5% 8.8% 0.52 (0.37–0.72)

Postoperative fever 9.4% 14.9% 0.65 (0.50–0.86)