Pharmacology of GBS drugs

Presented by Vicki Penwell, CPM, LM, MSM, MA

Indications for Drug Prophyaxis

Positive GBS culture in current pregnancy

GBS bacteria cultured in urine during the current

pregnancy

Any woman who had a previous baby develop

group B strep disease

Signs and symptoms indicating risk in labor

When GBS status unknown

Signs and symptoms indicating risk if status

unknown

Labor starting at less than 37 weeks

Prolonged membrane rupture ( 18 or more

hours before delivery)

Fever during labor

Practices unsupported by research

Informal survey found that many different

treatment modalities are used by midwives for

preventing Early-Onset Group B Strep Disease in

the babies born to GBS positive women.

They include using a variety of treatments,

different antibiotics than what is recommended,

and administering antibiotics in timing other than

recommended

(Penwell et al)

Chlorhexidine Rinse

Birth canal washes with the disinfectant

chlorhexidine (Hibiclens) does not seem to

reduce the risk of a mother spreading group B

strep bacteria to her baby.

Although chlorhexadine reduces the risk of a

newborn being colonized with GBS, it has not

been shown to decrease the risk of actual GBS

infections in newborns.

(Stade et al. 2004)

Treatment before labor

Giving penicillin to women before labor does

not work. Although penicillin temporarily lowered

GBS levels, by the time women went into labor

the GBS levels were back up again.

(Gardner et al. 1979).

Oral or IM Antibiotics

Antibiotics taken by mouth or IM instead of

through IV are not effective at preventing group

B strep disease in babies.

(Easmon,Hastings 1983, CDC 2016)

Treatment after illness has begun

Due to treatment in labor, there has been a large drop in early GBS infection rates in the U.S.—from 1.7 cases per 1,000 births in 1990, to 0.25 cases per 1,000 births today

If a mother who carries GBS is not treated with antibiotics during labor, the baby’s risk of developing a serious, life- threatening GBS infection is 1 to 2%

(Boyer & Gotoff 1985; CDC 2012; Feigin, Cherry et al. 2009)

GBS and antibiotics

. To date, receiving antibiotics through IV during

labor, at least 4 hours before the birth, is the

only proven strategy to protect a baby from

early-onset group B strep disease.

Antibiotics for treating GBS during

labor, in order of recommendation

Penicillin

Ampicillin

If Penicillin allergy, may use:

Cefazolin

Alternative antibiotics include Clindaymycin and Vancomycin (not recommended except in rare cases of Penicillin anaphylaxis)

Know and Follow CDC Guidelines

Again, here we see a wide variance of actual

practice among midwives who treat GBS

positive women in labor with antibiotics.

Various reasons are given…including personal

preference, fear of drug reactions, how often

drug has to be administered, and availability of

drugs

Which Antibiotic to use?

The efficacy of Penicillin and Ampicillin as intravenously administered intrapartum agents for the prevention of early-onset neonatal GBS disease has been demonstrated in clinical trials and large observational studies. The efficacy of alternatives has not been evaluated. However, cefazolin has similar pharmacokinetics and dynamics to penicillin and ampicillin and achieves high intra-amniotic concentrations.

(CDC May 2016)

Microbiome Concerns

Penicillin is the anitbiotic of choice because it is

very specific to kill GBS and less likely to kill other

good bacteria.

Penicillin is recommended by CDC and ACOG

as first line drug to prevent early onset GBS

infections

Serious reactions to Penicillin are actually rare

(about 1 out of every 10,000 women)

Allergy or Anaphylaxis

Women who have a known allergy to Penicllin

can take Cefazolin instead. Cefazolin (like

Penicillin and Ampicillin) crosses the placenta

and reaches the fetus's bloodstream.

If woman has high risk for anaphylaxis with

penicillin, CDC recommends alternative

antibiotics include Clindaymycin and

Vancomycin.

Drawbacks of alternative drugs

Clindamycin and Vancomycin have never been tested in clinical trials for the prevention of early GBS infection.

Clindamycin and Vancomycin barely reach the fetal bloodstream, if at all.

GBS must be specifically tested to know that Clindamycin or Vancomycin will work on a woman’s particular strain of GBS.

Erythromycin should never be used at any time(CDC, 2010; Pacifici 2006)

Timing is everything

The CDC recommends that antibiotics be given every 4 hours, starting more than 4 hours before birth.

When Penicillin or Ampicillin was given more than 4 hours before birth, it was effective 89% of the time.

Giving antibiotics 2-4 hours before birth was effective 38% of the time.

(Fairlie et al., 2013)

Every 4 hours, for more than 4 hours

In another study, more infants whose mothers

received less than 4 hours of antibiotics had a

discharge diagnosis of sepsis when compared to

infants whose mothers received 4 hours or more

of antibiotics (1.4% versus 0.4%.)

(Turrentine et al., 2013)

Antibiotic Details

Indication

Dose

Route

Half Life

Storage

Why (Reason for use)

PenicillinRecommended by CDC, ACOG

Indication: Group B Strep Prophylaxis

Dose: 5 million units initial dose, then 2.5 million

units every 4 hours till birth.

Route: IV in .≥100 ml LR, NS, or D5LR

Half life: 42 minutes

Storage: Below 86 F

Why: Most specific, less “collateral damage”

AmpicillinAlternative if Penicillin not available

Indication: Group B Strep Prophylaxis

Dose: 2 grams initial dose, then 1 gram every 4

hours until birth

Route: IV in ≥ 100 ml NS or LR

Half life: 1 hour

Storage: 68-77 F

Why: Tolerated well if Penicillin not available

CefazolinOnly if Allergy to Penicillin exists

Indication: Group B Strep Prophylaxis

Dose: 2 grams initial dose, then 1 gram every 8

hours until birth

Route: IV in ≥ 100 ml LR, NS, or D5LR

Half life: 2 hours

Storage: 68-77 F

Why: drug of choice for Penicillin allergy with low

risk for anaphylaxis

ClindamycinOnly if anaphylaxis exits

Indication: Group B Strep Prophylaxis only if

absolutely necessary, and test GBS type first

Dose: 900 mg every 8 hours

Route IV in ≥ 100 ml NS only

Half Life: 2-3 hours

Storage: 68-77 F

Why: drug for use when severe penicillin

anaphylaxis exists and there is no other choice

VancomycinOnly if anaphylaxis exits

Indication: Group B Strep Prophylaxis only if

nothing else is possible, and test GBS type first

Dose: 1 g every 12 hours

Route: IV in LR or NS

Half Life: 4-6 hours

Storage: (59° to 86°F)

Why: Rarely ever used; does not seem to work

Anaphylaxis

Characterized by sudden onset of:

Rash/Hives; Flushing; Tissue swelling; Airway

obstruction; Hypotension; Diarrhea;

Brochospasm and Circulatory collaspe

Death from edema obstructing airway

Management of Anaphylactic

Shock

Stop the drug and call for help

Maintain airway, or start CPR

Adrenaline IM in lateral thigh

Repeat dose as necessary while urgently seeking

help from EMS

Epinephrine HCl

1:1000 ( EpiPen)

Indications: Treatment of severe allergic

reactions

Dose: 0.3 ml pre-metered dose

Route of Administration: Subcutaneously or

intramuscularly

Epinephrine HCl

1:1000 ( EpiPen), cont.

Duration of Treatment : Every 20 minutes or until EMS arrives.

Action time or half life : Works in Seconds. Lasts only 20 minutes or less.

Storage: Protect from light. 59-86 F (77 best). Do not refrigerate OR leave in car

Call 911 after administering

New Vaccine on the horizon

Pfizer is set to test a potential vaccine to prevent

GBS infections in Newborns

The Bill & Melinda Gates Foundation has

awarded a grant to support a study evaluating

a vaccine to protect newborns against group B

Streptococcus infection (GBS). The vaccine, still

in early stage development, t is designed to

protect newborns by immunizing their mothers.

Possible future vaccine

Evidence from studies has shown that a

potential conjugate vaccine, incorporating at

least five serotypes of GBS, could prevent

around 95 percent of group B streptococcal

disease in infants younger than three months.

Possible future vaccine, cont.

“We are looking to determine whether our

investigational vaccine could generate levels of

protective antibodies in the mother that, when

passed to her unborn baby, will protect the

baby against deadly GBS infection during a time

when the infant is most vulnerable to infection.”

Kathrin U. Jansen, PhD, head of Vaccine

Research & Development, Pfizer. Oct 2016

In closing– Important to keep

updating our knowledge on GBS

Thank you