Treatment of lower urinary tract infection in pregnancy

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Abstract

Urinary tract infection (UTI) is a common complication of pregnancy. Approximately 20–40% of women with asymptomatic bacteriuria will develop pyelonephritis during pregnancy. All pregnant women, therefore, should have their urine cultured at their first visit to the clinic. In a clinical study comparing single-dose treatment with 3 g fosfomycin trometamol versus a 3-day course of 400 mg ceftibuten orally, the inclusion criteria were acute symptomatic lower UTI (acute cystitis), significant bacteriuria (≥103 CFU/ml), pyuria and confirmed pregnancy. Excluded were patients with asymptomatic bacteriuria or acute pyelonephritis. Predisposing factors comprised a history of recurrent UTI, diabetes mellitus, analgesic nephropathy, hyperuricaemia or Fanconi's syndrome. Escherichia coli was the most frequently isolated pathogen in both groups. Therapeutic success (clinical cure and bacteriological eradication of uropathogens) was achieved in 95.2% of the patients treated with fosfomycin-trometamol versus 90.0% of those treated with ceftibuten (P, non-significant). The treatment of acute cystitis in pregnant women using a single-dose of fosfomycin trometamol was equally effective as the 3-day course of oral ceftibuten. Both regimens were well tolerated with only minor adverse effects. Long-term chemoprophylaxis should be suggested in patients with recurrent UTI or following acute pyelonephritis during pregnancy.

Introduction

Urinary tract infection (UTI) is a common complication of pregnancy. It usually presents as bacterial cystitis in otherwise healthy women with a structurally normal urinary tract and intact voiding mechanisms [1]. In the majority of patients, infection appears to be confined to the lower urinary tract. It may be asymptomatic (asymptomatic bacteriuria), or symptomatic (acute cystitis). In pregnant patients, the most frequently isolated uropathogen is Escherichia coli. Other responsible microorganisms include other Enterobacteria (Klebsiella, Enterobacter, Proteus), Staphylococcus epidermidis or Staphylococcus saprophyticus, Enterococcus faecalis and group B Streptococcus [2].

The prevalence of asymptomatic bacteriuria in American, European and Australian studies varies between 2 and 13%; symptomatic infection develops in 1–2% of pregnant women [2], [3].

Factors predisposing to bacteriuria and UTI comprise hormonal changes and influence of mechanical factors during pregnancy which result in:

  • 1.

    relative stasis of urine in ureters;

  • 2.

    impaired emptying of urinary bladder;

  • 3.

    increased bladder residual volume and increased prevalence of vesicoureteral reflux; and

  • 4.

    increase of urine pH.

Pregnant patients may have difficulties in collecting a mid-stream clean catch of voided urine and to obtain an uncontaminated urine specimen. For asymptomatic patients, significant bacteriuria is defined as two consecutive positive cultures of >105 CFU/ml of midstream urine with growth of the same species [2], [4]. For pregnant women with symptoms, most authors suggest a diagnostic criterion of >103 organisms per ml of midstream urine in a single culture for significant bacteriuria [2], [3], [4].

Physicians recognised that 20–40% of pregnant women with asymptomatic bacteriuria will develop acute pyelonephritis [2], [5], [6]. In recent years, many controversial issues had been published. The debate continues whether screening for and treating asymptomatic bacteriuria (AB) is a useful way of preventing pyelonephritis during pregnancy, and whether this screening should be implemented for all patients or only for women at risk (i.e. diabetics or those with previous UTI) [2], [7], [8]. In a study by Gratacos et al., screening for AB was performed in 1652 pregnant women. AB was defined as two consecutive positive cultures with growth of the same species. AB was confirmed in 77 patients (70 were treated with a 7-day course of antibiotics, seven were not treated). In the 70 patients who were treated, 2.8% developed acute pyelonephritis before term. In the other seven patients who were not treated, the incidence of acute pyelonephritis was 28%. The authors observed that after implementing the screening programme for AB, the annual incidence of pyelonephritis in pregnancy decreased from 1.85 to 0.48% [2], [8]. All pregnant women should therefore have their urine examined at their first visit to the clinic. Evidence that infection causes pre-term labour has been reviewed by MacLean and it appears that locally or systemically released prostaglandins are important mediators of uterine activity [2], [9].

Because of altered pharmacokinetics, drug use in pregnancy may have unpredictable effects. Certain antibiotics are unsuitable for use due to their potential toxicity [2], [3]. Sulfonamides may increase the risk of kernicterus in neonates, tetracyclines cause dysplasia and discoloration of teeth and bones. Trimethoprim is an anti-folate agent and may interfere with neural tube development. Nitrofurantoin increases the risk of hemolysis and glucose-6-phosphate dehydrogenase (G6PD) deficiency in neonates. Aminoglycoside use may produce 8th nerve damage in the fetus, and fluoroquinolones have been associated with alterations in the joint cartilage of neonates [2], [7], [8].

Recommended antibiotics for the treatment of lower UTI during pregnancy include the FDA category — B antimicrobials, namely penicillins, oral cephalosporins and fosfomycin trometamol. Acute pyelonephritis should be treated preferably with parenteral cephalosporins, penicillins with beta-lactamase inhibitors or monobactams (aztreonam) [1], [2], [3], [4].

Section snippets

Patients and methods

Because of the superficial nature of cystitis, short-term therapy of acute uncomplicated lower UTI has gained wide acceptance as the preferred method of treatment, and many studies have confirmed that single-dose therapy can be as effective as conventional treatment [1], [6], [10], [11], [16], [17], [18]. The comparison with 3-, 5- and 7-day courses of antibiotic treatment of lower UTI in pregnant women show no advantages over single-dose therapy [2], [10], [15], [16], [18].

Various clinical

Results

A total of 41 pregnant patients with clinical symptoms of lower UTI were included in the study. Predisposing factors (history of recurrent UTI, diabetes mellitus, analgesic nephropathy, hyperuricaemia, Fanconi's syndrome) were found in ten patients in the fosfomycin group and in nine patients in the ceftibuten group (Table 1). Both treatment groups were comparable regarding age, weight and renal function.

The pathogens isolated are shown in Table 2. They were predominantly E. coli (17 in the

Discussion

Clinical and microbiological evaluation of fosfomycin trometamol for uncomplicated UTI is difficult. Published studies show large variations in the number of evaluated patients and variable comparative antibiotics were used in variable doses [1], [2], [8], [11], [12], [13], [14], [15], [16], [17], [18]. Evaluation of fosfomycin trometamol treatment in pregnant women is further complicated by the brevity of the two main reports [17], [18]. Altogether, 365 pregnant patients were treated with

Conclusions

UTI is a frequent event during pregnancy. Results of the study demonstrate that treatment of acute cystitis in pregnant women with a single-dose of fosfomycin trometamol and with a 3-day course of ceftibuten achieved comparable clinical and bacteriological cure rates and were well tolerated. In accordance with previously published studies single-dose or short-course treatment with an appropriate drug should be recommended for treatment of uncomplicated lower UTI in pregnant females [2], [6], [7]

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