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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 26 - Use of Prophylactic Antibiotics in Labor and Delivery

"If all of your self worth and esteem is invested in how much you consume, how many likes you get, or other quantifiable measures, the desire to simply possess things trumps our ability or capability to make moral connections with people around us." - Larry Harvey



PB#199 - Published September 2018

Five Pearls

  1. Cleaning the surgical site prior to incision using chlorhexidine or provo-iodine dramatically ↓ risk of skin infection

  2. Prepping the vagina may be additionally helpful in laboring patients who go for c-section or in patients with ruptured membranes at time of c-section

  3. Cefazolin 2 g administered by IV within 60 minutes of c-section will ↓ risk of infectious morbidity. Addition of Azithromycin may further ↓ the risk

  4. When considering an antibiotic, the benefits of infection prevention must be weighed against the risk of fostering multi-drug resistant organisms and messing with your patient's delicate microbiome

  5. To give or not to give: PPROM - YES!; Preterm labor - only if GBS unknown; cerclage? meh. Manual extraction of placenta? Sure.


Primer

- an ideal prophylactic agent is inexpensive, is long-acting, is narrowly-focused, and has few adverse effects

- what happens when you fire a shotgun at potential infection? You create multi-drug resistance bugs that kill grandmas (hey!...and grandpas)

- these bugs also harm neonates

- increases in neonatal E. coli sepsis correspond with increasing ampicillin-resistance patterns (preterm and low birth weight > term infants)

- up to 30% of GBS isolates are resistant to Clindamycin and Erythromycin

- Read Mountains Beyond Mountains by Tracy Kidder about Paul Farmer (hint: TB treatment in the developing world teaching us a valuable lesson)

- if a patient reports an allergy to a narrowly focused antibiotic, make sure it's a real allergy (a tummy ache is not a real allergy; laryngeal edema or shortness of breath may be, though)

- risk of adverse reaction with PCN is ~10%; 1:2500-25000 risk of anaphylactic reaction

- cross-reactive with cephalosporins in patients w/ reported PCN allergy is 10%, but much less (0.001-0.1%) of severe reaction

- skin testing in patients w/ reported "history of severe PCN allergy..." could save our system tons of money and lead to a huge reduction in MDR bugs



Skin prep/vaginal prep before c-section

- chlorhexidine cleansing of surgical site provides obvious benefit pre-surgery

- prepping the vagina prior to c-section in laboring patients and patients with ruptured membranes may provide some benefit

- meta-analysis from 2017 looked at the available literature and found ↓ risk of endometritis (8.8% → 4.5%), post-op fever (14.9% → 9.4%), but no ∆ in wound infection rate when vaginal prep was performed in women who went to c-section after laboring or in whom membranes were ruptured

- majority of studies included used a 10% provo-iodine solution for at least 30 sec

- little evidence to guide to this practice in non-laboring women or when membranes intact; though a 2017 RCT out of Egypt showed a ↓ in the rate of endometritis from 13.2% → 2.9% in the intervention group (n= 218; 0.25% chlorhexidine gluconate wipes used pre-op)

- there will be ∆ to vaginal flora with these practices, but the medical community hasn't evaluated clinical significance


Antibiotic prophylaxis before c-section

- Cochrane review (emergent and non-emergent c-section, labor or pre-labor): ↓ risk of fever, wound infection and endometritis

- administer within 60 minutes of incision (or as soon as possible after incision if c-section is emergent)

- antibiotic choice: need to cover Gram positive, Gram negative, and anaerobic organisms

- beta lactams and cephalosporins have comparable efficacy

- cefazolin (1st gen cephalosporin) and cefoxitin (2nd gen cephalosporin) equally efficacious, but the former is less expensive

- single-dose is best practice as you minimize risk of toxicity and risk of facilitating multi-drug resistance compared to multi-dose regimens

- cefazolin is the go-to; if severe PCN allergy, alternative is clindamycin 900 mg IV x1 PLUS gentamycin 4.5-5mg/kg IV x1 (limited data to guide alternatives)

- cefazolin 1 g likely OK if patient weighs ≤80 kg; 2 g otherwise is universal; 3g can be considered if patient weighs ≥120 kg


Should I add azithromycin?

- Reasonable to consider adding 500 mg to standard cefazolin regimen

- A review article concluded no added benefit; however, an RCT found a significant ↓ in endometritis (3.8% compared to 6.1% in patients who received cefazolin alone) and wound infection (2.4% compared to 6.6%) for non-elective c-section.


Note: Remember that all decisions to administer prophylactic antibiotics should be judicious. More is not always better. Benefits of infection prevention must be weighed against the risk of fosters multi-drug resistant organisms and messing with your patient's delicate microbiome


When do I re-dose?

- re-dose when two half-lives for your antibiotic have past from time of initial administration

- cefazolin has a serum half life of ~2 hrs after IV administration; therefore, re-dose 4 hrs after initial administration

- also re-dose if you estimate that you have lost ≥ 1.5L of blood


How do physiologic changes in pregnancy affect antibiotic dosing?

- ↑ GFR in the kidneys may increase clearance of the drug from serum

- ↑ plasma volume may dilute the serum drug concentration

- ↑ binding proteins in pregnancy may further decrease serum drug concentration

- ↓ gastric emptying rate may slow oral absorption in pregnancy

- for these reason, higher doses of antibiotics may be required


How does obesity affect antibiotic dosing?

- most antibiotics are lipophilic (fat-soluble)

- for example, cefazolin is commonly prescribed as prophylaxis pre-cesarean delivery; 2 g is generally ordered universally for any BMI, though 1 g can be considered for patients weighing ≤80kg

- consensus guidelines in non-obstetric patients are now recommending cefazolin 3 g for patients weighing ≥120 kg (2015 RCT in obstetric patients found no difference in adipose tissue concentration when 3 g were used compared to 2 g, but this study is flawed in that it presumes that higher adipose concentration is an indicator of effective improvements in prophylaxis)

- Follow Jeffrey Sperling, MD on Twitter for MFM literature updates


Should I be screening my pregnant patient for MRSA?

- No. there's insufficient evidence to guide management of MRSA concerns in pregnant women

- Usually MRSA does not develop into invasive disease

- if your patient is a known MRSA carrier AND she is undergoing c-section, a single dose of vancomycin is reasonable to consider as an addition to the standard regimen prior to incision


What about antibiotics in PPROM?

- when ROM is diagnosed at <34 wga, "latency" antibiotics have been found to delay the onset of labor and ↓ risk of chorio, neonatal infection, and need for neonatal oxygen therapy (Cochrane Review)

- the regimen:

2x days ampicillin 2 g IV q6hr PLUS erythromycin 250 mg IV q6hr THEN 5x days amoxicillin 250 mg PO q8hr PLUS erythromycin 333 mg PO q8hr

- erythromycin and azithromycin are equally efficacious, but the latter is cheaper and better tolerated from GI standpoint

- amoxicillin-clavulanic acid (augmentin) associated with higher risk of neonatal necrotizing enterocolitis (NEC) in some studies, therefore not recommended

- if PCN allergic:

Azithromycin 1 g PO x1 at time of admission PLUS 2x days cefazolin 1g IV q8hr THEN 5x days cephalexin 500 mg PO four times daily

- if severe PCN allergy, substitute cephalosporins for gentamicin/clindamycin


What if my patient presents with preterm labor, intact membranes?

- latency antibiotics aren't indicated if membranes are intact

- if you think a baby might deliver, you should consider GBS status

- if <37 wks and GBS status is unknown, it is recommended to start antibiotics for GBS prophylaxis

- collect a swab, start antibiotics; if you think labor has "cooled off", it's reasonable to hold antibiotics to minimize excess exposure

- if culture comes back negative, then you can discontinue altogether


What is bacterial endocarditis and why should I be concerned?

- Some patients are at risk of seeding their heart valves in the event of systemic bacterial infection

- Per ACOG, antibiotic prophylaxis isn't warranted outside of gingival manipulation, but ACOG still considers it reasonable to initiate prophylactic antibiotics for those highest risk patients (cyanotic heart disease, prosthetic heart valves, or history of infective endocarditis) within 30-60 min of delivery

Should I give antibiotics after I repair a 3rd or 4th degree perineal laceration?

- Evidence of mixed. May be reasonable

- Give 1x dose of cefazolin 1-2 g (clindamycin if severe PCN allergy)


Should I give antibiotics for a cervical cerclage procedure?

- Insufficient evidence


How about for manual removal of placenta, postpartum dilation and curettage, or intrauterine Bakri balloon placement?

- insufficient evidence. Personally? I give cefazolin 1-2 g IV.

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