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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)