“Exam room 3 is a sign out, 23 yo F, here for nausea, found to be pregnant. US shows IUP, good heart rate. No VB, has outside PMD. Got Zofran, tolerating PO. No urinary complaints, but we are waiting for her to give urine for the Urinalysis (UA). Discharge with antibiotics if she has a UTI.”
Pretty easy sign-out right? But then she can’t urinate for hours…and keeps asking to leave…then she finally goes. The result: few bact, 5 wbcs, 10-15 epi’s, 1+LE, neg nitrite. Do you treat? Insist she send another sample? Have her follow-up with her primary ob/gyn doctor?
Background
I have been told that we need UA’s on all pregnant women to evaluate for asymptomatic bacteriuria (ASB). With rates ranging from 2-15%, ASB is described as increasing the incidence of pyelonephritis, preterm delivery and low birth-weight (LBW), but what are the exact rates? One paper estimated that 40% of spontaneous premature births are due to infection. A meta-analysis concluded that non-infected women had 0.65 chance of LBW and 0.50 chance of premature labor compared to their counter-parts with ASB. Even worse, ASB is more likely to lead to pyelonephritis in pregnant women compared to non-pregnant women.
Interestingly, LBW and premature labor are both more common in women from lower socioeconomic class, and when corrected for that variable, some studies showed no difference in LBW/premature labor with and without infection. Oddly, the data consistently reports that if you treat ASB with antibiotics, you decrease the rate of pyelo/LBW/premature labor. Our current conclusion is: asymptomatic bacteriuria in pregnancy causes harm, should be investigated and eradicated. How to screen though, turns out to be slightly more complicated.
ACOG, USPTF, IDSA and AFP actually recommend a clean catch urine culture in pregnant women, though the timing varies. Per ACOG and USPTF: at 12-16 weeks gestation or during their first prenatal visit. Per IDSA: early in pregnancy, as appropriate. Per AFP: at least once as a screen for ASB. The definition of a positive culture here is at least 10^5 CFUs/ml. Notice there is no mention of testing for this in the ED in pregnant women outside of 12-16 weeks gestation. Additionally, IDSA reports there is no evidence for or against re-screening culture negative women.
What about Urinalysis?
Turns out, it is not a good test for ASB, but let’s look at the data.
A large meta-analysis on urinalysis vs urine culture as gold standard reports:
Nitrite highly heterogeneous between studies
Sens 45-60% (lowest sens in pregnant population) Spec 85-98%
Leukocyte Esterase
Sens 48-96% Spec 17-93%
One or both pos Nitrite/LE
Sens 68-88% Spec (none given due to so much heterogeneity)
They conclude that negative LE and nitrite rules out UTI in pregnant patients, but that any positive result must be evaluated with a culture.
A better meta-analysis by our own Dr. Meister and Dr. Sinert reports the following likelihood ratios for women with symptomatic UTI:
positive nitrite (+LR 24.6), no LE/blood (-LR 0.2), no LE/nitrite/protein/blood (LR 0), no urine WBC on microscopy (–LR 0.1), >2+ organisms (+LR 21.9). Even with an LR of 0.1, the UA is such an imprecise test, that Dr. Meister and Dr. Sinert still recommend a urine culture. With an LR > 4, they recommend antibiotics. Keep in mind that these numbers came from symptomatic women who probably had much higher rates of actual infection than in our ASB population.But how good is culture?
While a negative culture rules out UTI, a positive culture has an 80% PPV. Two positive urine cultures for the same organism increases the PPV to 95%. This means that 1 out of 5 patients treated for ASB did not need antibiotics!
Lastly, good old Cochrane
If you treat asymptomatic bacteriuria in pregnancy, there is a NNT of 7 to prevent pyelonephritis. Treating ASB does reduce incidence of low birth-weight, but the data supporting this conclusion is poor. There is no evidence that treating ASB reduces incidence of pre-term birth. No studies looked at adverse outcomes from antibiotics. The optimal time to do the urine culture is unknown. The optimal duration of therapy is unknown. Urine microscopy and urine dipstick “have not been shown to perform satisfactorily in this population.”
Conclusions
1. If a Urinalysis shows anything other than negative leukocyte esterase AND negative nitrite, then it is useless and a culture should be done. It’s like the D-dimer of asymptomatic bacteriuria. If it’s negative, it’s negative. If it’s positive, do another test.
2. Sending a urine culture in the ED is not clearly indicated by the guidelines.
Interesting Counter-Point
Our own Chief DiMare eloquently described a hypothetical environment where the patients do not follow-up as instructed. In this imaginary ER, what should the doctor do to screen for ASB? We know that a “positive” UA has a very poor PPV for actual ASB, but it is the only test we can get back during a patient’s visit. If we draw a culture and hold off on antibiotics, patients lost to follow-up will not be treated or subsequently screened by their Ob.
If you get a UA and treat, you are undoubtedly treating people that do not need antibiotics. You are not following the guidelines or the evidence. You are increasing resistance while exposing your patients to potential side effects and allergic reactions. You’re in/Urine trouble (get it?). If you don’t get a UA/treat and the patient doesn’t follow up, you may have missed decreasing their risk of pyelonephritis, while possibly increasing their risk of pre-term delivery and low birth weight babies. You’re in/Urine trouble(get it on the second try?).
What would you do in an ideal world and this bizarre one described by soon-to-be attending DiMare?
Perhaps a better solution would be a hospital system that flags Urine Cultures from pregnant women and contacts them with the results.
Any other ideas from the audience?
References
Lettieri L, Vintzileos AM, Rodis JF, Albini SM, Salafia CM. Does “idiopathic” preterm labor resulting in preterm birth exist? Am J Obstet Gynecol. 1993 May;168(5):1480-5.
Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC, Bracken M. Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth-weight. Obstet Gynecol. 1989 Apr;73(4):576-82.
Cram LF, Zapata MI, Toy EC, Baker B 3rd. Genitourinary infections and their association with preterm labor. Am Fam Physician. 2002 Jan 15;65(2):241-8.
http://www.uspreventiveservicestaskforce.org/uspstf08/asymptbact/asbactrs.htm
American Academy of Family Physicians. Summary of recommendations for clinical preventive services. Revision 6.4. August 2007
Nicolle LE et al. IDSA guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40:643-54
American Academy of Pediatrics, American College of Obstretricians and Gynecologists. Guidelines for Perinatal Care. 6th ed. Elk Grove Village, IL, and Washington, DC: American Academy of Pediatrics, American College of Obstretricians and Gynecologists; 2007:100-1
Tukur Ado Jido. Urinary Tract Infection in Pregnancy: Evaluation of Diagnostic Framework. Saudi J Kidney Dis Transpl 2014;25(1):85-90
Lumbiganon et al. Screening and Treating Asymptomatic Bacteriuria in Pregnancy. Curr Opin Obstet Geynecol 2010;22:95-99
Deville et al. The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy. BMC urology. 2004,4:4.
Meister et al. History and Physical Examination Plus Laboratory Testing for the Diagnosis of Adult Female Urinary Tract Infections. Acad Emerg Med. 2013; 20: 632-645
Smaill et al. Antibiotics for asymptomatic bacteruria in pregnancy (review). The Cochrane Library;2007. Issue 4
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