Sikhymbaev M.D., Myrzagulova A.O.

KAZAKHSTAN MEDICAL UNIVERSITY "KSPH"

Solutions to the early detection of asymptomatic bacteriuria in pregnancy

 (literature review)

Annotation: The Asymptomatic bacteriuria (ASB) is found in 2.5–15 % of pregnant women and when it is untreated, often complicated by the development of obstetric, urological and perinatal pathology. The effective diagnosis and treatment of ASB  leads to the significant reduction in the frequency of these complications. The standard diagnosis of ABS is two-fold  urine culture with the definition of susceptibility of microorganisms to antibiotics.

Keywords: asymptomatic bacteriuria, pregnancy.

It is common knowledge the problem of urinary tract infection remains one of the leading in obstetric practice. This is due to the high frequency of occurrence among pregnant women, which can reach 8%, the peculiarity of the clinical course, diagnosis and therapy of urinary tract infections during pregnancy [1, 2]. Being the preclinical form of different of diseases of the urinary tract, asymptomatic bacteriuria is characterized by persistent recurrent course with a low percentage of self-healing, high risk development of women and newborn, complications and high probability of manifestation in the form of symptomatic urinary tract infections [3].

It is known that asymptomatic bacteriuria, is also called as asymptomatic infection of the urinary tract, by implication, the basis of the number of bacteria from properly collected urine sample obtained from persons without symptoms or signs of urinary tract infection [4]. One of the first researchers dedicated to the study of asymptomatic bacteriuria, was Whalley P., who gave the definition of ASB as persistent bacterial colonisation of the urinary tract in the absence of specific clinical symptoms [5]. The guantitative criteria for the diagnosis of ASB were first presented in the writings of Kass in 1960 [6]. Currently, indicator and  standard for diagnosis is the detection of ASB in 1.0 ml of urine of 105 bacteria or more [7].

The asymptomatic bacteriuria is widely distributed in the population. The occurrence of this phenomenon among  healthy female population depends an age (increases from 1% among schoolgirls to 20% or more among women over 80  and older [8]) and sexual activity (married women of eligibility age, the incidence rate is 6-7 times higher than that of the nuns the similar age [9]).

According to the literature the ASB  prevalence among pregnant women is presented in a very wide range: from 2,5 to 15% [ 10]. Ķą÷ąėī ōīšģū

The risk of ASB in pregnant women depends on a number of factors. So, when you were pregnant the ASB develops in 6.0% of cases, while among primigravidae only 3.2%. In developing countries, ASB is the most common in pregnant women from low social class in 6.5% of cases, among the middle class are much less likely to 2.5%. During gestation, gestosis, the ASB is found significantly more often in 19% of cases, whereas in healthy pregnant women, the frequency of ASB is  6%. Episodes of UTI in the medical history and low education level also increases the risk of ASB during pregnancy. It should be noted that women with malformations of the kidneys and urinary tract, urolithiasis, inflammatory diseases of the genital organs, diabetes, HIV and patients with urinary catheters are at high risk for development of urinary tract infections (both symptomatic and asymptomatic) [11, 12, 13]. The escherichia coli is the most frequent uropathogens associated with ASB (50 to 80%). Also quite common are a number of other microorganisms: Klebsiella pneumoniae, Proteus mirabilis, Streptococcus group b, Enterococcus and Staphylococcus saprophyticus [14].

In 2008 V. A. Kaptilnyi, by diagnosing ABS in 120 pregnant women, presented the structure of pathogens: Escherichia coli (55,9%); gram (+)  bacteria of the family Enterobacteriaceae (12,5%); gram (+)  strepto-, and staphylococci (26.6 %) other microorganisms not included in the first two groups: Pseudomonas spp. Corynebacterium., Candida spp. and others (5,0%) [14]. In the practical guidelines of the American society of infectious diseases represents one of the most complete characteristics on the diagnosis and treatment of ASB in adults.

According to the data presented in this work, ASB is a microbiological diagnosis based on urine collected with the observance of sterility and transported to the laboratory in a very short period of time that allows for the greatest degree limit the growth of bacteria. For the diagnosis of ASB it is recommended to use the following criteria: isolation of the same bacteria in a quantity ≥ 105 CFU/ml in 2 consecutive urine culture with an interval of more than 24 hours, obtained from pregnant women with no signs of UTI, a single selection of bacteria in an amount of ≥ 102 CFU/ml in the urine culture obtained by bladder catheterization, the absence of clinical signs of infection, leukocyturia [15].

Nowadays, standard ASB – the selection of microorganisms in a quantity ≥ 105 CFU/ml has been criticized as overly restrictive for pregnant women. This approach is justified by the results of the studies, according to which already during the isolation of bacteria from urine in the amount of 102-104 CFU/ml, there is increased frequency of obstetric, neonatal and urological complications.

So, the bacteriuria with the separation of small quantities of microorganisms compared to women without ASB, there is an increase development in pregnant of acute inflammatory diseases of the urinary system 4 times, anemia 5,8 times, inflammatory infiltration in the fetal membranes in 5,8 times, premature rupture of membranes – 4,3 times, the frequency of birth full-term newborns with signs of morphofunctional immaturity - 5 times, the birth of children with low Apgar score of 7 points and below – by 5,2 times, the birth of children with a decrease in the mass-growth rate is below 60 in 5,7 times [15].

The pyuria accompanies bacteriuria in asymptomatic 30-70% of pregnant women [16, 17]. The increase in the number of polymorphonuclear leukocytes in the urine is a sign of inflammation of the urinary tract of various etiologies. So, renal tuberculosis, sexually transmitted diseases, non-infectious interstitial nephritis accompanied by severe leukocyturia with negative urine culture.

Thus, pyuria is still insufficient for diagnosis of ASB, and its presence or absence allows to differentiate asymptomatic or clinically manifest urinary infection [17]. Nowadays, the "gold standard" diagnosis of bacteriuria is twice urine culture  (method urinoculture) determining the sensitivity of isolated microorganisms to antibiotics.

But due to the cost, complexity and duration of implementation, this method is not always available in countries with limited health care resources and may not be screening. It should be noted that in the Russian Federation culture screening of all pregnant women on ASB are still not carried out, but it is made is used in Kazakhstan. The rapid methods  of  the urinary tract diagnosis are widespread among the USA and European specialists and practitioners.

The basis of the most common is the use of diagnostic strips (Urine dipstick), immersion of the slides (Dipslide culture), bioluminescence of different variants of smear examinations [18].

In clinical practice for the diagnosis of bacteriuria and leukocyturia are widely used simple and inexpensive rapid tests in the form immersed in the urine sample is specially prepared strips in a few minutes changes color in the presence of the test agent. The indicator strip is an inert white material performing the function of a substrate on which there are a different number of reagent zones.

The express Ķą÷ąėī ōīšģū

test for bacteriuria is based on the detection of urine nitrites indicate the presence in the urine of some species of microorganisms (Escherichia coli, Klebsiella, Proteus, Staphylococcus, Pseudomonas), reducing the nitrate to nitrite. It should be noted that the study may be falsely negative if the urine is not enough concentrated  and if the microorganism is not reduced nitrates (Ånterococcii, S. saprophyticus, Acinetobacter, etc.).

The express test on leukocyturia is based on the determination in urine of granulocyte esterases. The sensitivity of the test is 10-25 leukocytes / 10-6 L. The number of the authors speak out against their use, citing the low sensitivity of the method, in some studies up to 30%. Meanwhile, other researchers point to the widespread availability of rapid tests data, low cost and speed of testing, allowing their use in view of the limited sensitivity [18]. It should be noted that the simultaneous rapid test for bacteriuria and rapid test for pyuria can increase their diagnostic efficacy. Submersible slides (uricult) - is a plate on which culture medium coated on both sides (2 to 3). Method for detection of microorganisms in the urine when cultured using submerged slides have ease of use and relative cheapness and speed, compared with the standard sowing urine, and also has high precision. Thus, according Mignini L. et al. (2009) likelihood ratio for a positive result urikulta was 225 (95% CI 113-449), increasing the likelihood of ASB to 98%. On the other hand, the likelihood ratio for a negative result - 0.02 (95% CI 0.01-0.05), reducing the likelihood of bacteriuria in less than 1%. Given the accuracy, ease of use, portability, speed and relative cheapness urikultov, many authors tend to think of this test is very promising and the most suitable as a rapid method of diagnosis ASB [19].

It is know that, pregnant women with untreated asymptomatic bacteriuria in 20-30% develop acute pyelonephritis [19, 20, 21]. Some studies indicate higher frequency of this complication up to 40% [22]. 50% of children born with low body weight. Significantly increases the risk of preterm birth [22], preeclampsia [23], hypertension, and anemia [24] and postpartum endometritis [25].

In a recent survey, published by Smaill F. in Cochran library, it is shown that the use of antibiotics effectively sanitizes ASB in pregnant women, reduces the risk of developing pyelonephritis (up to 1% -4%) and low birth weight. [25]. Reduction of frequency of premature birth as a result of antibiotic therapy according to some literature data has been observed, other sources (more recent) were identified [26].

Thus, the feasibility of ASB treatment of pregnant women with traditional microbiological criterion (≥105 CFU/ml) has no doubt. To sum up everything, nowadays, relevant question concerning the "low" of bacteriuria. IS commonly used I\individual work indicates the high significance of bacteriuria in pregnant women with microbiological criteria 102-104 CFU/ml, accompanied by a high frequency of obstetric, neonatal and urological complications [26].

So the peculiarities of a female organism during  the pregnancy, childbirth and the postpartum period make the choice of therapeutic effects very important due to the possible transplacental transition, getting into the  milk and adverse effects on the fetus and newborn [27].

Thus, a review of available literature demonstrates the high significance of asymptomatic bacteriuria in pregnant women in the obstetric, urological and perinatal pathology. It should be noted the absence of wide clinical practice timely microbiological diagnosis and, consequently, adequate treatment of this infection. The standard of diagnosis in pregnant ASB — bacteriological methods of urine with the definition of sensitivity  microorganisms dedicated to antibiotics. For screening ASB is the most preferred test system using the submersible slide, given the accuracy, ease of use, portability, speed and relative cheapness urikultov.

References and recommended reading

Delzell J.E., Lefevre M.L. Urinary tract infections during pregnancy // Am. Fam. Physician. – 2000. – Vol. 61, N 3. – P. 713–721

Mikhail M.S., Anyaegbunam A. Lower urinary tract disfunction in pregnancy // Obstet. Gynecol. Surv. – 1995. – Vol. 50. – P. 675-683.

 – S. 1-4 of 4. Captainy V. A. Course and outcome of pregnancy in patients with asymptomatic bacteriuria: author. dis. kand. med. Sciences. – M. – 2008

      4. Rubin R.H., Shapiro E.D., Andriole V.T., Davis RJ, Stamm W.E. Evaluation of new anti-infective drugs for the treatment of urinary tract infection // Clin. Infect. Dis. – 1992. – Vol. 15, N 1. – P 216-227.

      5.  Whalley P. Bacteriuria of pregnancy // Amer. J Obstet. and Gynecology. – 1967. – Vol. 97. – P. 723–738.

   6.  Kass E.H. The role of asymptomatic bacteriuria in the pathogenesis of pyelonephritis // In: Biology of pyelonephritis, ed. by Quinn E.L., Kass E.H. – Boston: Little, Brown, 1960. – p. 399.

   7. McNair R.D., MacDonald S.R., Dooley S.L., Peterson L.R. Evaluation of the centrifuged and Gram-stained smear, urinalysis, and reagent strip  testing to detect asymptomatic bacteriuria in obstetric patients // Am. J. Obstet. Gynecol. – 2000. – Vol. 182, N 5. – P. 1076-1079.

   8.  Nicolle L.E. Asymptomatic bacteriuria: when to screen and when to treat // Infect. Dis. Clin. North. Am. – 2003. – Vol. 17. – P. 367–394.

   9.  Kunin C.M., McCormack R.C. An epidemiologic study of bacteriuria and blood pressure among nuns and working women. // N. Engl. J. Med. – 1968. – Vol. 278. – P. 635–642.

10.  Mignini L., Carroli G., Abalos E., et al. Accuracy of diagnostic tests to detect asymptomatic bacteriuria during pregnancy. // Obstet. Gynecol. – 2009. – Vol. 113. – P. 346–352.

11.  Fatima N., Ishrat S. Frequency and risk factors of asymptomatic bacteriuria during pregnancy // J. Coll. Physicians. Surg. Pak. – 2006. – Vol. 16, N 4. – P. 273–275

12. Kovavisarach E., Vichaipruck M., Kanjarahareutai S. Risk factors related to asymptomatic bacteriuria in pregnant women. // J. Med. Assoc. Thai. – 2009. – Vol. 92. – P. 606–610.

13. Schnarr J., Smaill F. Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy // Eur. J. Clin. Invest. – 2008. – Vol. 38. – P. 50-57.

14. Sheiner E., Mazor-Drey E., Levy A. Asymptomatic bacteriuria during pregnancy // J. Matern. Fetal. Neonatal. Med. – 2009. – Vol. 22. – P. 423-427.1. Abramchenko V. V., Bashmakova M. A., Korkhov V. Antibiotics in obstetrics and gynecology // Manual for doctors. 2-e Izd., Rev. and additional – SPb.: Specla – 2001. – 239 p. 

15. Nicolle L.E., Bradley S., Colgan R. et al. Infectious diseases society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults // Clin. Infect. Dis. – 2005. – Vol. 40. – P.643-654.

16.  Bachman J.W., Heise R.H., Naessons J.M., Timmerman M.G. A study of various tests to detect asymptomatic urinary tract infections in an obstetric population // JAMA. – 1993. – Vol. 270. – P. 1971–1974.

17. Kincaid-Smith P., Bullen M. Bacteriuria in pregnancy // Lancet. – 1965. – Vol. 1. – P. 395–399.

18. Lumbiganon P., Laopaiboon M., Thinkhamrop J. Screening and treating asymptomatic bacteriuria in pregnancy // Curr. Opin. Obstet. Gynecol. – 2010. – Vol. 22, N 2. – P. 95-99.

19. Deville W.L., Yzermans J.C., van Duijn N.P., et al. The urine dipstick test useful to rule out infections. A metaanalysis of the accuracy // BMC Urol. – 2004. – Vol. 4. – P. 4.

20. Kass E. H. Pyelonephritis and bacteriuria. A major problem in preventative medicine // Annals of internal Medicine. – 1962. – Vol. 56. – P. 46–53

21.  Smaill F., Vazquez J.C. Antibiotics for asymptomatic bacteriuria in pregnancy // Cochrane Database Syst. Rev. – 2007. – Vol. 18, N 2. – CD000490.

22.  Canadian Communication Group. Screening for asymptomatic bacteriuria in pregnancy, 1994, Ottawa.

23.  Savage W.E., Hajj S.N., Kass E.H. Demographic and prognostic characteristics of bacteriuria in pregnancy // Medicine. – 1967. – Vol. 46. – P. 385-407.

24. Robertson J.G., Livingstone J.R., Isdale M.H. The management and complications of asymptomatic bacteriuria during pregnancy. J. Obstet. Gynec. Br. Commonw. – 1968. – Vol. 75, N 1. – P. 59-65.

25. Romero R., Oyarzun E., Mazor M., Sirtori M., Hobbins J.C., Bracken M. Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight // Obstet. Gynecol. – 1989. – Vol. 73. – P. 576582.

26. Karpov O. I., Zaitsev A. And the risk of the use of medications during pregnancy and lactation. – SPB., 2003. – 352 p.

27. Abramchenko V. V., Bashmakova M. A., Korkhov V. Antibiotics in obstetrics and gynecology // Manual for doctors. 2-e Izd., Rev. and additional – SPb.: Specla – 2001. – 239 p.