Int Urogynecol J (2007) 18:525–529 DOI 10.1007/s00192-006-0190-y
ORIGINAL ARTICLE
Is single-dose fosfomycin trometamol a good alternative for asymptomatic bacteriuria in the second trimester of pregnancy? Ömer Bayrak & Ersin Çimentepe & İlknur İnegöl & Ali Fuat Atmaca & Candan İltemir Duvan & Akif Koç & Nilgün Öztürk Turhan
Received: 6 October 2005 / Accepted: 2 July 2006 / Published online: 29 August 2006 # International Urogynecology Journal 2006
Abstract Untreated asymptomatic bacteriuria has been associated with acute pyelonephritis, which may have a role in many maternal and fetal complications. Acute pyelonephritis in pregnancy is related to anemia, septicemia, transient renal dysfunction, and pulmonary insufficiency. A randomized study was conducted to assess the clinical and microbiological efficacy of a single dose of fosfomycin trometamol for the treatment of asymptomatic bacteriuria in the second trimester of pregnancy compared with a 5-day regimen of cefuroxime axetyl. Forty-four women received fosfomycin trometamol and 40 women received cefuroxime axetyl. There were no statistically significant differences between both groups regarding the mean age and mean duration of pregnancy. Therapeutic success was achieved in 93.2% of the patients treated with fosfomycin trometamol vs 95% of those treated with cefuroxime axetyl. A single dose of fosfomycin trometamol is a safe and effective alternative in the treatment of asymptomatic urinary tract infections in the second trimester of pregnancy. Keywords Fosfomycin trometamol . Cefuroxime axetyl . Asymptomatic urinary tract infection Ö. Bayrak (*) : E. Çimentepe : A. Koç Department of Urology, Fatih University School of Medicine, Alpaslan Türkeş cad., 06510 Emek, Ankara, Turkey e-mail:
[email protected] İ. İnegöl : C. İ. Duvan : N. Ö. Turhan Department of Obstetric and Gynecology, Fatih University School of Medicine, Ankara, Turkey A. F. Atmaca 1st Urology Clinic, Atatürk Education and Training Hospital, Ankara, Turkey
Introduction Asymptomatic bacteriuria refers to persistent, actively multiplying bacteria within the urinary tract without symptoms. The reported prevalence in pregnancy varies from 2 to 7% and depends on parity, race, and socioeconomic status [1]. If asymptomatic bacteriuria is not treated, approximately 25% of women will subsequently develop acute symptoms of an infection during pregnancy [2]. Untreated asymptomatic bacteriuria has been associated with acute pyelonephritis, which may have a role in many maternal and fetal complications. Acute pyelonephritis in pregnancy is related to anemia (23%), septicemia (17%), transient renal dysfunction (2%), and pulmonary insufficiency (7%) [3]. About one in five pregnant women with pyelonephritis will develop evidence of multiple-system derangement from endotoxemia and sepsis [3–6]. The most common manifestation of sepsis is acute respiratory distress syndrome, which has been reported in approximately 1 in 50 women with acute pyelonephritis [4, 7, 8]. Asymptomatic bacteriuria has been associated in some studies with a number of adverse pregnancy outcomes such as low birth weight, prematurity, preterm low birth weight, premature labor, hypertension /preeclampsia, maternal anemia, and amnionitis [9, 10]. Since the first report of an association between asymptomatic bacteriuria and low birth weight (less than 2,500 g) in 1962, many studies on the same subject have been published [11]. Some of these confirmed this association while others disputed it. Gilstrap et al. [6] found no association with anemia, hypertension, or low birth weight infants. However, Mittendorf et al. [12], by using meta-analysis, concluded that true associations between asymptomatic bacteriuria and preterm delivery (less than 37 weeks of gestation) and asymptomatic bacteriuria and low birth weight do exist.
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Asymptomatic urinary tract infections and their adverse effects on pregnancy remain prevalent and preventable. Stenqvist et al. [13] reported that the risk of onset of bacteriuria is highest between the 9th and 17th gestational weeks and suggested the 16th gestational week as the optimal time for a single screening for bacteriuria calculated as the number of bacteriuria-free gestational weeks gained by treatment. Therefore, screening the pregnant women at their antenatal visits, particularly in the second trimester of pregnancy where the asymptomatic bacteriuria is the highest, is a rationale approach. The recommendation of the US Preventative Services Task Force [14] is to obtain a urine culture between 12 and 16 weeks of gestation (an “A” recommendation). Reassessment of this important subject to search for more effective and shorter treatment modalities to increase the patient compliance is relevant at this time. Antibiotic treatment compared to placebo or no treatment is effective in clearing asymptomatic bacteriuria and in reducing the risk of pyelonephritis in pregnancy. Antibiotic treatment is associated with a reduction in the incidence of preterm delivery or low birth weight babies [15, 16], but the antibacterial agent chosen in pregnancy must be well-tolerated, empirically known to be harmless to the mother and the fetus, and have a low level of bacterial resistance. When selecting drugs to use in pregnancy, wellestablished agents with well-known properties are generally preferred to newer ones. For obvious ethical reasons, research on the effects of drugs on the fetus is mainly restricted to retrospective studies and case reports. βLactam antibiotics including, penicillins (ampicillin, amoxicillin, and mecillinam) and cephalosporins are some of the oldest antibiotics used to treat some bacterial infections. No β-lactam antibiotic is known to be teratogenic. However, the greatest limitation to its use in urinary tract infection is the increasing level of resistance to Escherichia coli. In the past two decades, several new antibacterial agents have been developed in response to the worldwide problem of increasing bacterial resistance. Before these agents are widely used in pregnancy, it is essential to ensure that they are safe for both the pregnant women and for the fetus. Cephalosporins and fosfomycin trometamol are recommended antibiotics for the treatment of urinary tract infection (UTI) during pregnancy and are under the Food and Drug Administration category B [6]. We screened all women attending our clinic in the second trimester of their pregnancy, where the incidence of asymptomatic bacteriuria is the highest. The aim of this randomized controlled study was to assess the clinical efficacy of single-dose fosfomycin trometamol vs cefuroxime axetyl in the treatment of asymptomatic urinary tract infections in pregnancy.
Int Urogynecol J (2007) 18:525–529
Materials and methods Pregnant women attending the Department of Urology and antenatal clinics of the Obstetrics and Gynecology Department of Fatih University between the period of November 2004–May 2005, with no signs and symptoms of urinary tract infections in the second trimester of their gestations, were screened for asymptomatic urinary tract infection. Approval for this study was obtained from the Institutional Review Board of the University of Fatih School of Medicine. Asymptomatic bacteriuria was defined as the presence of two consecutive clean-catch urine specimens yielding positive cultures (100,000 cfu/ml) of the same uropathogens in a patient without urinary symptoms. Gravidas exhibiting leukocytosis, fever, urolithiasis, lower back pain, or women giving a history of previous urologic surgery and known abnormalities of the urinary tract were excluded from the study. Midstream urine specimen of the women with asymptomatic bacteriuria were collected using the clean-catch method after given written instruction and were tested for microscopic analysis before standard quantitative cultures and antibiotic sensitivity tests were also performed. After written informed consent had been obtained, the patients were randomized to receive either a single dose fosfomycin trometamol or a 5-day course of cefuroxime axetyl. To ensure an equal number of patients in each group, a block randomization method was used. The blocks were numbered, placed into a bag, and a staff member blinded to the research protocol selected the patients into the treatment groups. Group I received a single-dose of 3 g fosfomycin trometamol of one sachet in a glass of water taken at night on an empty stomach. Group II was treated with oral 250 mg cefuroxime axetyl twice a day for 5 days. Based on the literature, we expected a urinary tract infection to be eradicated in about 97% of the patients treated with oral 250 mg cefuroxime axetyl twice a day for 5 days [17]. Cure rates for a single course of therapy are usually reported in the range 70–94% [18, 19]. We considered a 19% decrease in short-term effectiveness of the fosfomycin trometamol treatment (78% eradication) to still be acceptable, taking into account the reduced development of resistant microorganisms, greater compliance, and fewer side effects of the single-dose therapy. Power analysis identified 90 patients (45 for group A, 45 for group B) as the total sample size required to detect the difference between 97 and 78% efficacy in therapeutic success (bacteriological eradication of uropathogens) with a power of 79% at 5% significance level. One week after completion of therapy, the patients were called to the hospital for a repeat urine analysis and urine
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culture, and any possible drug-associated adverse effect was recorded by their physicians. Negative culture test results were accepted as eradication of bacteriuria. Analysis of data was performed by SPSS package program for windows, version 11.5, as well as Mann– Whitney U tests and chi-square test where appropriate. A p value of
