Asymptomatic

bacteriuria in pregnancy Brenda Kazemier

AIOS gynaecologie Amsterdam UMC

Physiologic changes in pregnancy

UTI in pregnancy more often complicated

Pregnancy

Change immune system woman

Urinary stasis

Vesicoureteral reflux

Diabetes

Puerperium

Decreased bladder sensitivity

Bladder overdistension

Catheterization

What is ASB?

ASB = ASymptomatic Bacteriuria

Presence of bacteria in urine without complaints of UTI

Cutoff ≥ 10e5 colony forming units per ml

Incidence in pregnancy around 2-10%

Some even report up to 40%

Risk ASB in pregnancy?

Pyelonephritis Placebo: 197/959= 21%

Antibiotics: 55/996 = 5%

Preterm birth<38 weeks Placebo: 37/174= 21%

Antibiotics: 31/238= 13%

Low birthweight <2500g Placebo: 96/738= 13%

Antibiotics: 65/764= 8.5%

Cochrane review 2009

Why repeat trials?

Existing data outdated, trials published between 1960 and1987

No ultrasound for dating pregnancy, diagnosis preterm birth?

Incidence ASB and pyelonephritis unknown in the Netherlands

Other countries allready screen and treat routinely

Netherlands relatively conservative with antibiotics

Study design

Screen study with embedded randomised controlled trial

Population: low risk women between 16-21 weeks of pregnancy

Exclusion criteria:

Symptomatic or use of antibiotics

Previous preterm delivery <34wks

Diabetes Mellitus

Known structural anomalies urinary tract

Allergy to nitrofurantoin

Multiple pregnancy

ASB screening

Gold standard is urinary culture

Low risk pregnant women are seen in midwifery practices

Midwifery practices/ultrasound centers no direct access to microbiology lab urinary culture not feasible

Alternative: Uricult dipslide technique

CLED + MacConkey medium

Sensitivity: 98 *

Specificity: 99.6 *

* Mignini 2009 obstetrics and gynaecology

Interpretation of dipslides

Dipslides were sent to one central laboratory (Laboratory for infectious

diseases, Groningen)

The isolates of positive dipslides were determined by standard methods and

VITEC automated systems (BioMerieux) and if the culture is positive, only the

dominant phenotype (two types at most) will be analyzed.

Resistance of all uropathogens for the most commonly used antimicrobial

agents will be determined following EUCAST guidelines and breakpoints.

ASB treat

Randomized controlled trial

Intervention: 2x100mg nitrofurantoin for 5 days or placebo

1 week after end of treatment follow up culture

Outcomes ASB trial

Composite primary outcome:

• Pyelonephritis &/or preterm birth <34 wk

Secondary outcomes

- Neonatal outcomes (preterm birth, growth restriction)

- Maternal morbidity (UTI)

ASB 5%

ASB 5%

Baseline table

5,3

0,5 0,5

5,1

0,8 0,5

0

1

2

3

4

5

6

Preterm birth <37weeks

Preterm birth <32weeks

Preterm birth <28weeks

Preterm birth in women with and without ASB

ASB No ASB

Van de 15 persisterend positieve vrouwen hadden 13 dezelfde verwekker (11 E. coli en 2 GBS)

Twee vrouwen hadden de 2e keer een andere verwekker (CNS E. coli en Enterococcus E.coli )

Subanalyses cohort

Symptomatische UWI vs geen symptomatische UWI

Klachten passen bij UWI + behandeling met antibiotica

Klinische diagnose, geen kweken bekend

Maternale en neonatale uitkomsten

8,2

5,4

0,86 1,5

0,43

3,7

2,9

0,31 0,2 0,31

0

1

2

3

4

5

6

7

8

9

Totalspontaneouspreterm birth

Pretermbirth 34-37

weeks

Pretermbirth 32-34

weeks

Pretermbirth 28-32

weeks

Pretermbirth <28 weeks

PER

CEN

TA

GE

Spontaneous preterm birth in women with and without UTI in pregnancy

UTI No UTI

Conclusion

• Prevalence ASB in the Netherlands is 5%

• Uropathogens conform literature

• Women with untreated ASB are at increased risk of pyelonephritis and symptomatic UTI during

pregnancy.

• The absolute risk of pyelonephritis with untreated ASB is small (2%) and much lower than

currently reported in literature (21%)

• Most women with pyelonephritis did not have ASB around 20 weeks of gestation (83%)

Conclusion • 50% of women receiving placebo were ASB negative 1 week after end of treatment

• 11% of women receiving nitrofurantoin were persistent ASB positive 1 week after end of treatment

• Compliance? Length of treatment?

• Women with ASB are not at increased risk for preterm birth or low birth weight

• Women with symptomatic UTI are at increased risk for preterm birth

• And at increased risk for endometritis and mastitis after birth

Discussion The biggest challenge remains differentiating between significant (disease) and

insignificant colonisation (not related to symptoms or adverse events)

Symptoms in pregnancy very difficult

Not clear which microorganisms are considered uropathogens and which are contaminants resulting in a wide range of reported incidences of ASB

Can differences in virulence explain difference in preterm birth risk between ASB and symptomatic UTI?

Do women with UTI represent a subtype of pregnant women at high risk for complications in general?

Not only increased preterm birth but also mastitis and endometritis

Perhaps not UTI leading to preterm birth but other common risk factors?

Consequences ASB in high risk women?

Questions?

GBS bacteriuria

Any amount of GBS was present in 77 women (1.5%)

None had GBS present in at least 10e5 CFU/ml or more.

GBS was found as an isolated micro-organism (less than 10e5 CFU/ml) in 58 women and on

contaminated dipslides in 19 women.

Analysis on outcomes of these pregnancies will be performed in future