Patrick Duff, M.D. University of Florida

Transcription

1 Patrick Duff, M.D. University of Florida

2 DISCLOSURE I have no conflict of interest with respect to any of the material presented in this lecture.

3 GBS INFECTION LEARNING OBJECTIVES At the conclusion of this presentation, the practitioner will be able to: Describe the epidemiology of early-onset GBS infection Describe the maternal and neonatal complications associated with GBS infection Describe the most effective strategy for reducing the frequency of early-onset neonatal GBS infection

4 GBS INFECTION KEY REFERENCE Prevention of Perinatal Group B Streptococcal Disease MMWR November 19, 2010

5 GBS INFECTION MICROBIOLOGY S. agalactiae Gram-positive Encapsulated Beta-hemolytic Type III is dominant pathogen

6 GBS INFECTION PREVALENCE Prevalence in pregnancy is 20-30% Frequency of invasive neonatal infection now is 0.3 to 0.4/1000 births 1000 to 1200 new cases each year 70% occur in term infants Case fatality rate has decreased from 50% to 4 to 6 %

7 GBS INFECTION CLASSIFICATION Early Late Amenable to obstetric intervention

8 EARLY ONSET GBS INFECTION Exclusively vertical transmission Usual manifestations Pneumonia Sepsis

9 MORTALITY OF EARLY-ONSET INFECTION GESTATIONAL AGE MORTALITY Term 4 to 6 % weeks 10 to 20 % < 33 weeks 30 %

10 LATE ONSET GBS INFECTION Occurs predominantly through horizontal transmission Mortality is about 5 % for both preterm and term infants Usual manifestations Sepsis Pneumonia Meningitis

11 RISK FACTORS FOR EARLY ONSET GBS INFECTION Preterm PROM Preterm labor Maternal fever ROM > 18 hours Previous infected infant

12 RISK FACTORS FOR EARLY-ONSET GBS INFECTION Young age African-American and Hispanic ethnicity Low levels of antibody to typespecific capsular antigens

13 EFFECT OF RISK FACTORS ON NEONATAL MORTALITY OUTCOME RISK FACTOR POSITIVE Attack rate 40 to 50 % < 5 % Mortality 30 to 35 % < 5 % RISK FACTOR NEGATIVE

14 RAPID DIAGNOSTIC TESTS FOR GBS Gram stain Antigen detection Optical immunoassay DNA probe Insufficiently sensitive in patients with low levels of colonization

15 NUCLEIC ACID AMPLIFICATION TESTS May not be sufficiently sensitive if do not grow the organism first in an enriched broth Not rapidly available if time is taken to grow organism in enriched broth Relatively complex test Not all laboratories can perform this test 24 hours a day, 7 days a week

16 DIAGNOSIS OF GBS NUCLEIC ACID AMPLIFICATION Type of Sample Sensitivity (Range %) Specificity (Range %) Non-enriched 63 to to 97 Enriched 93 to to 99

17 DIAGNOSIS OF GBS NUCLEIC ACID AMPLIFICATION TESTS TEST SENSITIVITY TIME REQUIRED IDI Strep % 40 to 100 minutes Xpert GBS Assay 91 99% < 75 minutes Most recent dataà more promising

18 DIAGNOSIS OF GBS INFECTION CURRENT STANDARD OF CARE Culture of the lower third of the vagina, perineum, and rectum Culture in nutrient broth Lim Broth TransVag Broth Carrot Broth Subculture onto solid agar

19 DIAGNOSIS OF GBS ACCELERATED CULTURE-BASED ASSAY Faro et al. Infect Dis Obstet Gynecol 6 hour cultureà immunoblot-based test (QuickTest, Nanologix, Inc) Identified organism and allowed sensitivity testing Compared to conventional culture Sensitivity 97% Specificity 88%

20 PREVENTION OF GBS INFECTION

21 PREVENTION OF GBS INFECTION HISTORICAL TIMELINE YEAR PUBLICATION INTERVENTION 1992 ACOG/AAP Statement 1996 First CDC Guidelines Culture at 28 weeks Treat colonized patients who have risk factors Screening vs riskfactor based approach

22 PREVENTION OF GBS INFECTION HISTORICAL TIMELINE YEAR PUBLICATION INTERVENTION nd CDC Guidelines Universal antenatal screening at weeks rd CDC Guidelines Elimination of erythromycin Optimal timing of antibiotics 4 h 2011 ACOG Committee Opinion Reinforcement of CDC guidelines

23 PREVENTIVE STRATEGIES CDC PROTOCOL Selective screening of high risk preterm patients Universal screening at weeks Intrapartum treatment of ALL colonized patients If colonization status unknown treatment on basis of risk factors

24 PREDICTIVE VALUE OF GBS CULTURES AT WEEKS OUTCOME PERCENT 95 % CI Sensitivity Specificity Positive PV Negative PV Yancey et al. Obstet Gynecol 1996; 88:

25 PREDICTIVE VALUE OF GBS CULTURES PRIOR POSITIVE CULTURE Antenatal genital 68 % Antenatal urine 61 % Prior pregnancy 48 % POSITIVE CULTURE IN LABOR Edwards et al. Obstet Gynecol 2002; 100:

26 EFFECT OF CDC PROTOCOL Reduced rate of neonatal sepsis Reduced rate of maternal infection Level II evidence

27 EFFECT OF CDC PROTOCOL STRATEGY Treatment on basis of risk factors Treatment on basis of universal screening % NEONATAL INFECTIONS PREVENTED Rosenstein et al. Obstet Gynecol 1997; 90: Level II Evidence

28 ANTIBIOTIC SENSITIVITY OF GBS ANTIBIOTIC SENSITIVITY (%) Penicillin and 100 ampicillin Cefazolin and 100 vancomycin Clindamycin 80 to 87 Erythromycin 68 to 75

29 GBS PROPHYLAXIS FOR PENICILLIN- ALLERGIC PATIENTS TYPE OF ALLERGY Mild Severe DRUG Cefazolin Clindamycin (if testing has been done for inducible resistance) Vancomycin * * 56% of patients with allergy inappropriately receive vancomycin

30 ANTIBIOTIC DOSING REGIMENS DRUG Penicillin DOSE 5 million units initially, then 2.5 to 3.0 million units q 4 hours Ampicillin 2 grams initially, then 1 gram q 4 hours Cefazolin 2 grams initially, then 1 gram q 8 hours

31 ANTIBIOTIC DOSING REGIMENS DRUG Clindamycin Vancomycin DOSE 900 mg q 8 hours 1 gram q 12 hours

32 EFFECTS OF INTRAPARTUM PROPHYLAXIS No evidence that intrapartum antibiotics could cause an anaphylactic reaction in the fetus/neonate No evidence that intrapartum antibiotics select for resistant organisms GBS E. coli

33 GBS INFECTION TIMING OF ANTIBIOTIC ADMINISTRATION

34 TIMING OF ANTIBIOTIC PROPHYLAXIS (DeCueto et al) Optimal protective effect occurs when antibiotics are administered 4 h prior to delivery Level II evidence

35 TIMING OF ANTIBIOTIC ADMINISTRATION (Barber et al) Prospective cohort study (Level II evidence) N = 98 5 million units of penicillin initially, then 2.5 million units Q 4 h Fetuses exposed to < 4 h of antibiotics actually had higher serum concentrations than those exposed for > 4 h

36 TIMING OF ANTIBIOTIC PROPHYLAXIS (McNanley et al) Prospective cohort study Penicillin used for prophylaxis Mean vaginal GBS counts decreased 5-fold within 2 hours, 50-fold within 4 hours, and almost 1000-fold within 6 hours Level II evidence

37 TIMING OF ANTIBIOTIC PROPHYLAXIS (Fairlie et al) TREATMENT REGIMEN PCN or Amp > 4 h (term) 91 % PCN or Amp > 4 h (preterm) 86 % Clindamycin (overall) 22 % PCN or Amp 2-4 h (overall) 38 % PCN or Amp < 2 h (overall) 47 % CLINICAL EFFECTIVENESS

38 GBS PROPHYLAXIS ADDITIONAL ISSUES Patients who previously had a baby with invasive GBS infection should always be considered colonized and should be treated intrapartum in a subsequent pregnancy Level III Evidence

39 GBS PROPHYLAXIS ADDITIONAL ISSUES Patients with GBS bacteriuria earlier in pregnancy should be considered colonized at the time of labor and should receive intrapartum prophylaxis. Level II Evidence

40 GBS PROPHYLAXIS ADDITIONAL ISSUES Patients who were colonized with GBS in a previous pregnancy should be recultured in a subsequent pregnancy. Their risk of being colonized is only 48 % Level II Evidence

41 GBS PROPHYLAXIS ADDITIONAL ISSUES Patients who are colonized with GBS and who are scheduled for cesarean delivery do not need GBS prophylaxis Even in setting of PROM and labor, the usual prophylaxis for cesarean delivery should provide appropriate prophylaxis for GBS Level III Evidence

42 GBS INFECTION UNANSWERED QUESTIONS

43 GBS PROPHYLAXIS UNANSWERED QUESTIONS Sweeping the membranes in a colonized patient Antepartum treatment in a patient with a prior stillbirth Vaccine

44 CONCLUSIONS A perfect outcome for all patients is not possible despite our fervent wishes and our best efforts

45 CONCLUSIONS LEVEL A RECOMMENDATION The best preventive strategy is the CDC protocol Key outcomes Decreased frequency of neonatal infection Decreased frequency of maternal infection Overall effectiveness 86 to 89 %

46 AREAS FOR IMPROVEMENT Only 85% of women in U.S. are now screened correctly Timing Culture method Only 87% of colonized women receive prophylaxis Appropriate drug Appropriate dose

47 AREAS FOR IMPROVEMENT Only 63% of women delivering preterm with unknown GBS status receive prophylaxis Testing for clindamycin resistance is only rarely performed When performed, test is not always done optimally Inherent versus induced resistance

48 CONCLUSIONS LEVEL A RECOMMENDATIONS Culture all patients at weeks Alternativeà NAAT at onset of labor Treat all colonized patients intrapartum with prophylactic antibiotics Treat on the basis of risk factors if colonization status is unknown Administer prophylaxis for at least 4 hours prior to delivery

49 GBS INFECTION REFERENCES Bergeron. NEJM 2000;343: CDC. MMWR(Suppl) 1996;45:1-24. DeCueto. Obstet Gynecol 1998;91: Locksmith. AJOG 1999;180: Yancey. Obstet Gynecol 1992;80: Edwards & Duff. Obstet Gynecol 2002;100:534-9 and

50 REFERENCES Jamie. Obstet Gynecol 2004; 104: Gibbs. Obstet Gynecol 2004;104: McNanley. Am J Obstet Gynecol 2007;197:583 e1-583e4. Barber. Obstet Gynecol 2008; 112: Verani. MMWR 2010; 59 (RR10): Fairlie. Obstet Gynecol 2012; 121: Verani. Obstet Gynecol 2014; 123: Briody. Obstet Gynecol 2016; 127: