ACTA FAC. MED. NAISS. 2003; 20 (2): 137-141

Original article

THE TREATMENT OF ASYMPTOMATIC BACTERIURIA IN PREGNANCY

¹Milena Veljković,  ²Radmila Veličković-Radovanović

¹Health Centre, Nis

²Institute of Nephrology and Hemodialysis, Nis

SUMMARY

             Asymptomatic bacteriuria (ASB) is defined as the presence of significant bacteriuria without  any obvious symptoms of the urinary tract infection (UTI). The found incidence ASB in the first trimester of pregnancy is 4.13%, in the second 7.42%, and in the third trimester 8.38%.  The most frequent cause is E. coli (86.97%). The presence of ASB in pregnancy requires antibiotic or uro antiseptic treatment. The first- generation cephalosporins were used in 62.45%, ampicillin in 18.77%, nitrofurantoin in 11.88% and sulphapreparations in 6.9%. The initial treatment was successful in 87.74%, but 28.3% of pregnant women who had ASB during the first trimester of pregnancy had recidive or relapse later.

Kay words: pregnancy, asymptomatic bacteriuria, treatment.

INTRODUCTION

             There are some changes in the urinary tract during the pregnancy which are suitable for urinary tract infections (UTI). A dilatation of the renal calices, pelvis and ureters is noticed in the sixth week of gestation. The maximum dilatation is from 22-24 weeks of gestation and is present in 90% of pregnant women (1). The right ureter is usually stronger dilatated (2). Dilatation together with hyperplasia of the smooth muscular fibers of the urinary tract accounts for the appearance of urinary stasis (2).  The bladder increases its capacity and decreases its tonus and as a result, the vesicourethral reflux appears. The urine of the pregnant women is less concentrated and in 70% the glycosuria is present (1).

              Risk factors for the appearance of UTI in the pregnancy are: low socioeconomic status (3), low educational level (4), and the presence of sickle cell anemia, diabetes mellitus or gestational diabetes (5, 6) bacterial vaginosis (7), former presence of UTI (5).

              Asymptomatic bacteriuria (ASB) is defined as the presence of significant bacteriuria without obvious symptoms of UTI. Significant bacteriuria represents 100 000 or more bacterias per milliter of urine provided that one uropathogen bacteria is isolated from the middle stream of morning urine after cleaning vulvae. The presence of a minor number of bacteria or the presence of mixed bacterial flora is generally a sign of urinary contamination (5, 8).

A sign of UTI (8) can be the presence of less than 100 000 bacteria per ml of urine with some infection symptoms.

AIM OF WORK

              The aim of work is to estimate the appearance of the incidence of ASB in pregnancy, the most frequent causes and the efficiency of the treatment.

METHOD OF WORK

              The pregnant women's morning urine was checked during the first antenatal control. Mass bacteria result was an indication of a quantitative microbiological control and anti biogram determination before starting an antibiotic therapy. Detailed instructions were given about necessity of careful vulvar cleaning, taking a middle stream of the morning urine and its transportation to the laboratory (within one hour). A test examination was done 10 days after finishing the therapy. The prospective analysis was done in the period from February 2000 to October 2002.

THE RESULTS OF THE WORK

Table 1. The presence of bacteriuria in three month periods

Incidence ASB is 4.13-8.38%.

Table 2. Distribution of  ASB causes

The most frequent cause of ASB was E. coli (86.97%).

Table 3. Treatment of pregnant women with ASB

Cephalosporins were most frequently used (62.45%).

Discussion

              The ASB incidence within female population increases during lifetime: among schoolgirls 1-2%, among women of reproductive age 5% (2) and the incidence among pregnant women 5-10% (1, 9).

              The ASB incidence in our testing was: 4.3% among pregnant women in the first trimester, 7.42% in the second trimester and 8.38% in the third trimester of pregnancy. The manifested UTI was 2.26% in the first trimester, 0.78% in the second and 1.25% in third trimester of pregnancy.

              ASB causes in pregnancy are similar to those seen in non-pregnant women. The most frequent cause is E. coli (80-90%), then Proteus mirabilis, Klebsiella, Streptococcus type B, Staphylococcus. Rare causes are Gardnerella vaginalis and Ureaplasma ureolyticum (10, 11). In our material E. coli was isolated in 86.97% of pregnant women with ASB.

              ASB therapy is necessary in specific population such as pregnant women (6). The medicine that is used is primarily secreted in the urinary tract achieving prolongation of its high concentrations in urine and vaginal secretion (12).

               A traditional ASB treatment in literature is considered to be the one lasting 3 to 7 days. Cephalexin 250 mg, erythromycin 250-500 mg, nitrofurantoin 50-100mg, sulfisoxazole 1 g or amoxicillin- clavulanic acid 250 mg are given for times a day. Trimethoprim-sulfamethoxazole 160/180 mg is given twice a day. (1).

                Other authors recommended as a three-day treatment the following: amoxicillin 500 mg three times a day; ampicillin 250 mg four times a day; first-generation cephalosporins 250 mg four times a day, nitrofurantoin 100 mg twice a day, sulfonamide 500 mg four times a day (5).

                 There is a daily therapeutic treatment for ASB therapy. Masterson (13) achieved cure in 88% of pregnant women using only one dosage of 3 g of amoxicillin provided that the cause of infection is sensitive to this medicine. Other authors have noted efficiency (50-78%) by using one dosage of amoxicillin, cephalexin and nitrofurantoin (10, 14-16). For a daily treatment one can use: 3 g amoxicillin, 2 g ampicillin, first-generation cephalosporins 2 g, sulfisoxazole 2 g, trimethoprim-sulfamethoxazole 320/ 1600 mg (5) and fosfomycin 3 g (1).

              As a special treatment 100 mg of nitrofurantoin is recommended for 10 days before bedtime, and if it is a recurrent IUT there is a need for a continuing therapy until delivery (5).

              In our research of ASB therapy which we conducted in accordance with the received anti-biogram taking into account the period of pregnancy evading the potential harmful effect on the embryo. The pregnant women also got instructions for taking enough liquid and frequently emptying urinary bladder (approximately every 3 hours). We used most frequently first-generation cephalosporins 500 mg four times a day. The therapy was carried out on 163 pregnant women (62, 45%). The second medicine was ampicillin 500 mg, used four times a day. It was used on 49 pregnant women (18, 77%). A considerate frequency of resistance to ampicillin (35%) was noticed by E. coli.  Nitrofurantoin and sulfipreparations were not used in the last two weeks before the delivery term or, if there was a danger for preterm delivery. The treatment lasted 7-10 days. The treatment was successful in 229 pregnant women (87.74%). In 15 pregnant women with ASB in the first trimester (28.3%) who had successful initial therapeutic treatment a reinfection occurred later. A considerate number of pregnant women (45%) had some kind of risk factors for the appearance of UTI: earlier infections (cystitis, pyelitis, and pyelonephritis), lowered or movable kidney, and cystic changes of kidneys, calculosis or nephrectomy)

The use of antibiotics in pregnancy can bear certain risks.

               The use of sulfopreparations is possible in the first and second pregnancy trimester because no teratogenic effect was observed. There is a contraindication of its use in the third trimester especially close to the term of delivery and if they are combined with trimethoprim there is even a contraindication in the first trimester (1). Sulfapreparations compete with bilirubin binding with fetal plasma proteins. The surplus of nonbinding bilirubin is removed during the pregnancy from circulation of embryo through the placenta. After the delivery this placenta "help" disappears and there is a possibility of hyperbilirubinemia in the newborn, especially if it is immature (5,17).

             Although nitrofurantoin is a good choice for treatment of UTI due to its high urine concetration (1), its use in pregnancy can be followed by hemolytical anemia when a deficit of glucose-6-phosphate dehydrogenase is present in pregnant women. There is a rare appearance of pneumonitis and pulmonal reaction (18), an extensive rarity is the appearance of fetal hemolytic anemia (5).

              The use of tetracycline in pregnancy leads to the incorporation of this medicine into fetal teeth and bones that are in calcification phase disturbing the normal development of these tissues and baby teeth get light-yellow color that gradually turns into light-brown. As baby teeth calcification in utero teeth overcolouring will appear when taking tetracycline after 20 weeks of gestation. There is no clear clinical proof of teratogenic effect of tetracycline applied in the first pregnancy trimester (17).

                Aminoglycosides may lead to material nephrotoxicity and fetal ototoxicity which arises doubt in its use. However, this occurs rarely if the dosage is appropriate (19).

              The application of quinolone may lead to atrophic changes in immature animals and are not acceptable as routine use during pregnancy although this effect hasn't been proved in humans (5).

            Prolonged use of antibiotics, especially ampicillin and cephalosporins may interfere with normal gastrointestinal flora and may be associated with chronic vulvovaginitis secondary to overgrowth of Candida albicans (20).

               For a long time ampicillin has been the choice for ASB treatment. The resistance of E. coli to this medicine has grown in the last years.  It occurs in 20-30% of cases (21). The resistance to cephalosporins and sulfopreparations is present.  Resistance to trimethoprim-sulfamethoxazole exists in some parts of USA 18-22%, but the resistance to nitrofurantoin and fluoroquinolone is still below 2% (12).

              There is a low rate of spontaneous ASB disappearance during the pregnancy, and a high rate of acute pyelonephritis. This requires a strict ASB treatment during pregnancy (22). The acute pyelonephritis appears in 20-30% of untreated ASB cases in pregnancy (19, 23, 24), and only in 3-4% of treated patients (25). Untreated ASB may lead to anemia and hypertension (8, 26), and there hasn't been estimated a clear effect on the low-birth-weight infants (27, 28). Approximately 1/3 of pregnant women will encounter reinfection or relapse during the pregnancy (5) which influences their life quality.

              There is a need for screening for bacteriuria during the pregnancy. The American College of Obstetricians and Gynecology (29) recommends a test of urino culture in the first antenatal control of pregnant women, and is recommendable to be retested in the third trimester of pregnancy, and US. Preventive Services Task Force (30) recommends screening for the presence of bacteriuria between the twelfth and sixteenth week of gestation. If the initial urino culture is sterile and there are no risk factors for UTI only in 1% cases may be expected to have pathological urino culture result later during pregnancy (31).

CONCLUSION

              There is a need for screening for bacteriuria during the pregnancy. There is a low rate of spontaneous ASB disappearance. Treatment is necessary. We recommend first generation cephalosporins, ampicillin, sulfapreparations or nitrofurantoin if the cause of ASB is sensitive to the medicine. The medicine was given 7-10 days and treatment was successful in 87, 74 % of pregnancy.

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