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Urinary tract infections UTIs are common in pregnant women and pose a great therapeutic challenge, since the risk of serious complications in both the mother and her child is high. Pregnancy is a state associated with physiological, structural and functional urinary tract changes which promote ascending infections from the urethra. Unlike the general population, all pregnant women should be screened for bacteriuria with urine culture, and asymptomatic bacteriuria must be treated in every case that is diagnosed, as it is an important risk factor for pyelonephritis in this population.
The antibiotic chosen should have a good maternal and fetal safety profile. In this paper, current principles of diagnosis and management of UTI in pregnancy are reviewed, and the main problems and controversies are identified and discussed. Urinary tract infections UTIs in pregnant women continue to pose a clinical problem and a great challenge for physicians. Although the incidence of bacteriuria in this population is only slightly higher than in non-pregnant women, its consequences for both the mother and the unborn child are more severe. That is related to profound structural and functional urinary tract changes, typical for pregnancy.
This may be due to high levels of circulating progesterone [ 17 ]. Simultaneously, the enlarged uterus compresses the urinary bladder, thus increasing the intravesical pressure, which may result in vesico-ureteral reflux and urine retention in the bladder after miction, commonly observed in pregnant women.
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Urinary stasis and impairment of the physiological anti-reflux mechanism create conditions favorable for bacterial growth and ascending infection. The additional predisposing factors include pregnancy-specific biochemical changes in urine, with higher amounts of glucose, amino acids and hormone degradation products, which increase urinary pH [ 78 ]. Similarly as in non-pregnant women, in pregnant women UTIs are classified either as asymptomatic bacteriuria ASBwhen the infection is limited to bacterial growth in urine, or symptomatic infections acute cystitis, acute pyelonephritiswhen bacteria invade urinary tract tissues, inducing an inflammatory response.
The UTIs in pregnancy are by definition considered complicated infections and require a special diagnostic approach and management. Urinary tract infections remain among the most common medical complications during pregnancy.
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The prevalence of acute pyelonephritis in most reports ranges from 0. Many women acquire bacteriuria before pregnancy [ 1819 ]. Other suggested risk factors for UTI during pregnancy are lower socioeconomic status, sexual activity, older age, multiparity, anatomical urinary tract abnormalities, sickle cell disease and diabetes, although the ificance of some of them age, parity or sickle cell trait remains a matter of controversy [ 11021 — 23 ]. The pathogens responsible for infections during pregnancy are similar to those in the general population.
The of the studies on perinatal outcomes of untreated ASB are controversial. The Cochrane Library meta-analysis revealed that antibiotic treatment was effective in reducing the incidence of low-birth-weight infants but not of preterm deliveries [ 27 ]. However, the authors stressed the poor methodological quality of the available studies, their different de, lack of sufficient information about the randomization methods, different definitions used, low statistical power and some substantial biases, urging caution in drawing conclusions.
A good example of these problems is presented by the Cardiff Birth Survey [ 33 ]. In a prospectively studied large cohort of 25 pregnancies, several demographic, social and medical factors including bacteriuria were ificantly associated with preterm birth in the initial univariable analyses.
However, after adjustments for other medical factors, bacteriuria retained an association of only borderline ificance, and after further adjustment for demographic and social factors, the relationship completely disappeared.
The of the second analysis of the same cohort, aimed to compare associations of studied factors with spontaneous vs. Two separate multiple logistic regression analyses revealed that spontaneous and indicated preterm births have different overall profiles of risk factors, and only the last of them was associated with bacteriuria. Maternal GBS bacteriuria in a pregnant woman is considered a marker for genital tract colonization with this organism which poses a ificant risk of preterm rupture of the membranes, premature delivery and early-onset severe neonatal infection [ 1242635 — 37 ].
They may develop various complications, such as acute kidney injury, anemia, hypertension, preeclampsia, sepsis and septic shock, hemolysis, thrombocytopenia, and acute respiratory distress syndrome, particularly if treatment is initiated too late [ 172738 — 44 ]. Although these associations have not always been proved to be causal, most of the complications seem to be due to renal or other tissue damage caused by bacterial endotoxins and a systemic inflammatory response with endothelial injury [ 4245 ].
A of observational studies have demonstrated the relationship between maternal symptomatic UTI and the risk of premature delivery and lower birth weight [ 28 — 3046 ].
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However, again, a substantial heterogeneity between these studies, together with many possible biases, makes it difficult to establish the overall contribution of UTI to preterm birth [ 48 ]. A rare but severe complication is the transmission of the infection onto the newborn baby [ 49 ]. Very often the transmitted infection Two from a heavily colonized birth canal, usually with GBS [ 26 ]. Nearly all antimicrobials cross the placenta, and some of them may exert teratogenic effects.
Commonly accepted antibiotics used in treating UTIs during pregnancy, regardless of its period, include derivatives of penicillin and cephalosporins, particularly those with low protein-binding ability such as cephalexinall of FDA pregnancy category B Table I [ 50 ]. A — Well-controlled studies available in humans with no adverse effects observed in human pregnancies; B — No adverse effects in well-controlled studies of human pregnancies with 8th effects seen in animal pregnancies OR no adverse effects in animal pregnancies without well-controlled human pregnancy data available; C — Human data lacking with adverse pregnancy effects seen in animal studies OR no pregnancy data available in either animals or humans; D — Adverse effects demonstrated in human women benefits of drug use may outweigh the associated risks.
In the large American population-based National Birth Defects Prevention Study, maternal use of sulfonamides and nitrofurantoin 1 month before pregnancy to the end of the first trimester was associated with more serious defects than any other antibacterial classes [ 51 ]. However, this study has been criticized for several ificant limitations including recall bias women were asked about antibiotic use after pregnancy and it was not confirmed by medical recordsinability to determine whether the birth defect was due to the antibiotic itself, the infection for which the antibiotic was and, or other confounding factors.
Recently Nordeng et al. Among pregnancies between andwomen filled prescriptions for nitrofurantoin in the first trimester. The arch concerns other antimicrobials with very high protein binding e.
One should also remember that trimethoprim FDA pregnancy category C is a folic acid antagonist; thus, supplementation of this agent and monitoring of its serum concentration are required during treatment [ 5657 ]. Nitrofurantoin can be theoretically associated with a risk of fetal or neonatal hemolytic anemia if the mother has glucosephosphate deficiency, and although this complication in pregnancy has not been reported, the drug should be used with caution, particularly in areas of disease prevalence [ 105859 ].
The use of fluoroquinolones FDA pregnancy category C is essentially contraindicated throughout pregnancy, since fetal cartilage development disorders have been reported in experimental animals, although not in human studies [ 2760 — 63 ]. The rate of major congenital malformations did not differ between the group exposed to quinolones in the first trimester and the control group 2.
A systemic review of prospective, controlled studies showed that the use of fluoroquinolones during the first trimester of pregnancy does not appear to be associated with an increased risk of major malformations recognized after birth, stillbirths, preterm births or low birth weight [ 64 ]. Apparently more data are needed to establish safety of fluoroquinolones in pregnancy before they may be routinely prescribed.
However, in some cases of complicated symptomatic UTI, resistant to other antibiotics, their benefits may outweigh the risks [ 60 ].
Gentamicin and other aminoglycosides are FDA pregnancy category D, because of their potential nephro- and neurotoxicity eighth nerve damage to the fetus [ 16566 ]. Although these drugs are used in pregnancy relatively often, the data on their embryotoxicity and teratogenicity are limited.
Earlier reports suggested an association between prenatal exposure to macrolides and congenital heart defects or pyloric stenosis, whereas the of some recent studies are rather reassuring [ 5167 — 71 ].
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No ificant teratogenic effect of erythromycin was identified in a Hungarian case-control study, a nationally based registry of cases with congenital abnormalities [ 69 ]. The main limitations of this data set were: a relatively low response rate, retrospective collection of data recall biasinability to exclude the effect of other drugs, and a restriction of the study to the second and third trimester. However, in a large prospective observational study, performed in women exposed to macrolides during the first trimester, Bar-Oz et al.
Recently, Lin et al. In logistic regression analysis they found no association of exposure to the drugs and increased risk of both types of birth defects. Again, these should be interpreted with caution, since the power of the study was limited and — as the authors underline — modest associations could be missed. So further studies are needed before the macrolides become accepted for wide use.
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Until then, this group of antibiotics should be reserved for the treatment of serious or life-threatening conditions, unresponsive to standard antibiotic therapy. The study sought follow-up information for children at age 7 in the UK using a parent-report postal questionnaire.
The cause of this neurological dysfunction is unclear, but it could be a result of subclinical perinatal infection as well as a direct effect of the antibiotics on the fetal brain or cerebral blood flow. Alternatively the antibiotic might have negatively influenced microbial colonization of newborn children, with long-lasting consequences.
There are some suggestions that antibiotics alter immune tolerance by changing the fetal gut flora, thus contributing to the substantial increase in the incidence of asthma, allergies, autoimmune diseases, autism, ADHD and other chronic conditions [ 73 — 75 ].
The main conclusion from all these interesting studies is that we should be very cautious in prescribing antibiotics to pregnant women in the absence of proven benefit e. The criteria for diagnosis and treatment of UTI are more restrictive compared with the general population, since the potential risks concern not only an expectant mother but also her unborn.
Given the evidence that effective antimicrobial therapy of ASB in pregnancy ificantly reduces the risk of pyelonephritis and possibly also adverse fetal outcomes, routine screening for the presence of clinically ificant bacteriuria in all pregnant women has become necessary. Urine culture remains the most reliable test allowing the diagnosis of ASB. Due to this high rate of false positivein some centers women with a positive urine culture are asked to return within 1 week for the second testing, to avoid unnecessary treatment [ 11 ].
A question which remains unanswered is: should women in whom no ASB was detected upon the first examination have additional screening in later pregnancy? To date, repeated tests have been recommended only in high-risk women with diabetes, sickle cell anemia, immunological defects, urinary tract abnormalities or a history of recurring infections before pregnancy [ 238 ]. However, the more recent reports suggest that repeating the urine culture in each trimester improves the detection rate of ASB [ 7879 ].
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McIsaac et al. A total of 49 cases of ASB were detected prevalence 4. In a much smaller Turkish study, ASB prevalence distribution in the first, second, and third trimesters was 0. That suggests that many women with no bacteriuria in their initial examination in the first trimester may develop bacteriuria during the later trimesters. The authors of these studies conclude that it would be prudent to screen pregnant women for bacteriuria also in the second and third trimesters [ 7879 ].
However, until large, prospective, randomized clinical trials RCTs are available and a clear benefit of this routine additional screening is observed, no recommendation can be made for or against it. The presence of ASB in a pregnant woman is an absolute indication for initiation of the treatment. The benefits of such a strategy with bacteriological follow-up were summarized by Smaill and Vazquez for the Cochrane Library, on the basis of the of 14 RCTs, embracing pregnant women with ASB, in which the effects of different antibiotics given for different duration were compared to placebo or untreated groups [ 27 ].
Management of ASB in pregnancy consists of short-term, usually 5—7 days, oral antibiotic therapy [ 76 ]. Basic principles of management are presented in Table II. In the face of the rapidly developing antibiotic resistance, the current position is that the treatment should be based on microbial sensitivity testing.
Recently, a growing of authors suggest that a reasonable first choice drug in the second and third trimester is the old and almost forgotten nitrofurantoin [ 80 — 82 ]. Kashanian et al. Out of 10 cultures in which E. The same approach is recommended for women who had a infant with invasive GBS disease.