Volume 13, Issue 3 , Pages 399-402, May 2009
Prevention of urinary tract infection in six spinal cord-injured pregnant women who gave birth to seven children under a weekly oral cyclic antibiotic program
Article Outline
Summary
Background
Pregnancies in spinal cord-injured (SCI) patients present unique clinical challenges. Because of the neurogenic bladder and the use of intermittent catheterization, chronic bacteriuria and recurrent urinary tract infection (UTI) is common. During pregnancy the prevalence of UTI increases dramatically. Recurrent UTI requires multiple courses of antibiotics and increases the risks of abortion, prematurity, and low birth weight. A weekly oral cyclic antibiotic (WOCA) program was recently described for the prevention of UTI in SCI patients.
Objective
To test the impact of WOCA in six SCI pregnant women (four paraplegic, two tetraplegic).
Design
This was a prospective observational study. WOCA consists of the alternate administration of one of two antibiotics once per week.
Results
We observed a significant reduction of UTI (6 UTI/patient/year before pregnancy to 0.4 during pregnancy and under WOCA; p
<0.001) and no obstetric complications. Infant outcomes were good.
Conclusion
The WOCA regimen could be useful for UTI prophylaxis in SCI pregnant women.
Keywords: Antibiotic prophylaxis, Pregnancy, Preventive strategy, Spinal cord injury, Urinary tract infection
Introduction
The risk of urinary tract infection (UTI) associated with asymptomatic bacteriuria increases during pregnancy. Screening and treatment of asymptomatic bacteriuria is recommended to prevent pyelonephritis, which can initiate preterm labor and delivery.1 The annual incidence of spinal cord injury is approximately 40 per million persons worldwide.2 Asymptomatic bacteriuria is frequent (70%) in spinal cord-injured (SCI) patients using chronic intermittent catheterization (CIC), and is usually of no consequence to the integrity of the upper urinary tract when low pressure storage and complete voiding are obtained.3 However, UTI is the most frequent complication.4
Effective rehabilitation increases the number of SCI women considering pregnancy. Specific follow-up and treatments are mandatory.5 Prophylaxis for UTI during pregnancy in SCI patients is currently an unmet medical requirement. We recently described the safety and efficacy of a weekly oral cyclic antibiotic (WOCA) strategy to prevent UTI in SCI patients under CIC.6 The incidence of UTI was significantly reduced, antibiotic use decreased, no resistance to antibiotics occurred, no severe adverse events were reported, and no case of colonization with multidrug-resistant (MDR) bacteria was reported. However, the impact of WOCA on UTI is unknown in SCI pregnant women.
Materials and methods
This was a prospective observational single center study. Between 2004 and 2007, we enrolled six SCI women (four paraplegic, two tetraplegic) who intended to become pregnant. They were neurologically stable and more than 4 years post-SCI. Their mean age was 34 years (± 1 year). A complete medical history was obtained (level of SCI, surgery, co-existing medical conditions, allergies, catheterizations per day, mean volume per catheterization, history of UTI, hospitalizations, and courses of antibiotic therapy).
The definition of UTI in this specific population was established according to both culture results and clinical signs.2 Bacteriological analysis included a weekly urine culture from 6 weeks before until the end of the WOCA program, as well as the detection of possible MDR bacteria in anal and/or urinary samples. Susceptibility testing was done using both the disk diffusion method and an automated broth microdilution method. The breakpoints were those defined by the National Committee for Clinical Laboratory Standards.7
WOCA prophylaxis consists of the alternate administration of one of two antibiotics once per week. The antibiotics were chosen from the following list: amoxicillin 3000mg, cefixime 400mg, nitrofurantoin 300mg. During week A, the patient takes a single antibiotic (A), and the following week (B) the patient receives another antibiotic (B), and this is then repeated throughout the pregnancy. Each antibiotic was chosen according to the results of recent urine cultures. Quinolones were contraindicated due to their potential toxicity. The chosen antibiotic treatments are considered safe by the French reference center for teratogenesis.
The WOCA program was commenced at the start of the pregnancy. All the women were carefully followed in obstetrics units. The following parameters were evaluated weekly: patient compliance, fever, UTI with or without fever, and hospitalization. We noted the specific antibiotic dosage and duration of use, adverse effects, and the necessity to stop or change the antibiotic regimen. Urine cultures were performed weekly and sent to the medical staff in order to give a curative adapted treatment if necessary. The mothers and babies were followed up clinically for 10 days following delivery. The baby’s weight and perinatal progress were recorded. Screening was carried out for the presence of MDR bacteria.
Statistical analysis was performed with the SAS system using adapted different statistical tests. Results are expressed in terms of means and standard deviations. The Fisher’s exact test was used to determine significance.
Results
UTI, antibiotics, and bacteriological data (Table 1)
Before WOCA and despite excellent and observant care, the average number of UTIs was 6 per year, and the six women had a total history of 14 cases of pyelonephritis responsible for three hospitalizations (24 days). Each patient performed an average of 6 (± 1.4) CIC daily. Bladder compliance was good and there was no detrusor overactivity. The mean maximal bladder capacity was 450ml (± 50ml). There was no underlying upper urinary tract obstruction or stone disease and no severe co-morbidities. The mean length of time under antibiotic treatment for UTI was 69 (± 20) days/year/patient. The antibiotics were frequently self-prescribed and broad-spectrum (57%) such as fluoroquinolones.
Table 1. Evolution of UTI, antibiotic consumption, and bacteriological results in six pregnant SCI women before and after the WOCA regimen, and obstetric and neonatal characteristics.
| Patient | ||||||
|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | |
| Evolution of UTI before/after WOCA | ||||||
| UTI (n/year/person) | 3/0 | 12/0 | 3/1 | 6/0 | 4/1 | 8/0 |
| Pyelonephritis (n) | 1/0 | 0/0 | 9/0 | 1/0 | 2/0 | 1/0 |
| Total hospital (days) | 10/0 | 0/0 | 10/0 | 0/0 | 4/0 | 0/0 |
| Antibiotic consumption before/after WOCA | ||||||
| Antibiotic (days/year/person) | 60/50 | 80/50 | 70/55 | 60/50 | 70/55 | 70/50 |
| Broad-spectrum antibiotic use (%) | 70/0 | 60/0 | 50/0 | 40/0 | 60/0 | 60/0 |
| Bacteriological results before/after WOCA | ||||||
| Positive urine sample (%) | 75/40 | 80/40 | 85/40 | 100/40 | 80/30 | 80/50 |
| MDR colonization | Neg/Neg | Pos/Neg | Pos/Neg | Neg/Neg | Neg/Neg | Neg/Neg |
| Obstetric characteristics | 2 babies | |||||
| Gestational age (weeks) | 39, 40 | 38 | 38 | 39 | 39 | 38 |
| Labor and delivery complications | None | None | None | None | None | None |
| Method of delivery | V, F | CD | CD | V | F | V |
| Neonatal characteristics | 2 babies | |||||
| Birth weight (g) | 3250, 3150 | 3100 | 3000 | 3050 | 3250 | 3450 |
| Problems breathing | None | None | None | None | None | None |
| Infectious infant morbidity | None | None | None | None | None | None |
During pregnancy and under WOCA, there was a significant reduction in the occurrence of UTI. No occurrence of febrile UTI was noted and there was no hospitalization related to infection. Only two patients had a UTI (0.4 UTI/year/patient) compared to 6 UTI/year/patient before (p<0.001). They received amoxicillin 3g a day for 5 days. The mean total time under antibiotic treatment decreased to 55 (± 5) days/year/patient (p<0.05). Four patients did not take any curative antibiotics for UTI. The antibiotics were selected according to the recommendations, with 0% use of broad-spectrum type.
All patients were careful to take their prophylaxis as recommended and there was no severe adverse event. The most frequent pairs of antibiotics used were amoxicillin and cefixime (n=5) followed by cefixime and nitrofurantoin (n=1). The number of positive routine urine samples (bacteriuria >104 cfu/ml and pyuria >5×104 white blood cells/ml) decreased from 80% to 40%. The bacteria isolated from urine samples were Escherichia coli (60%), Enterococcus spp (20%), Streptococcus agalactiae (10%), and Klebsiella pneumoniae (10%). At inclusion, one patient was colonized with methicillin-resistant Staphylococcus aureus. This colonization disappeared during pregnancy. No new case of colonization with MDR bacteria was reported.
Obstetric and neonatal characteristics (Table 1)
The course of pregnancy was uneventful in all cases. We did not observe any diabetes, decubitus ulcer, or autonomic dysreflexia. The six women reported no specific complication related to their SCI. All women delivered at term with a mean gestational age at delivery of 39 weeks (range 38–40 weeks). Two women had a normal vaginal delivery. Another one delivered vaginally twice during the study period including one forceps delivery.
All newborns were born appropriate for gestational age and healthy, with a mean birth weight of 3180g (SD 80g). No respiratory distress or other neonatal complications were reported. None of the neonates were diagnosed with MDR bacteria colonization.
Discussion
Modern reproductive technology and effective rehabilitation may increase the number of SCI women considering pregnancy. Little attention has been given to reproductive health issues, and especially the management of pregnancy, in SCI women. SCI women experience a more severe and frequent rate of complications than women without SCI. During pregnancy, the incidence of UTI in SCI patients increases from 8% to 45.5%.8 Several complications arise as a result of UTI: 25% of women report the necessity to change their usual bladder management method. Neurogenic detrusor overactivity increases. The usual treatments can be contraindicated by pregnancy (some parasympatholytic drugs, botulinum toxin A). UTI can lead to specific complications for the fetus and the mother. The greater incidence of low birth weight infants born to these women underscores a need to focus attention on fetal and infant health.
Jackson and Wadley observed ruptured membranes, increased spasticity, and autonomic dysreflexia. Pregnancies were more likely to produce low birth weight babies (14%), and some babies with fever required antibiotics (4.5%). There was a trend towards having infants who had more dyspnea at birth (15%).8 Baker et al.9 reviewed pregnancy in 11 SCI women. Ten of the mothers experienced UTI and three experienced pyelonephritis. In a retrospective study, Westgren et al.10 reported the outcomes of 29 SCI women who experienced 49 pregnancies and gave birth to 52 children. Nine of the infants were born preterm and two were small for gestational age. The perinatal mortality rate was 3.8%. Cross et al.11 reported on 22 SCI women who had 32 pregnancies. Three pregnancies aborted. Abnormal presentations occurred in over 10%. Complications included autonomic hyperreflexia and frequent UTI. Charlifue et al.12 collected data relating to 47 women, of whom half had vaginal deliveries. Problems included autonomic dysreflexia, decubitus ulcers, and UTI.
Preconception consultation with obstetricians and physiatrists may improve the quality of follow-up and the adaptation of treatments for such patients. The prevention and management of UTI in SCI individuals is challenging.13 Urinary complications are responsible for a large proportion of hospital-related episodes.2 Urinary bacterial colonization is frequent.14 Given the absence of controlled trials or prospective data, it is difficult to make evidence-based recommendations. Daily antibiotic prophylaxis has yielded discordant results and is not recommended because of the risk of the emergence of bacterial resistance and a decreasing effect over time.15 There is currently a consensus to respect asymptomatic bacteriuria in SCI. Because of specific complications due to UTI during pregnancy, screening and treatment of asymptomatic bacteriuria is strongly recommended. The efficacy of continuous long-term antimicrobial prophylaxis is uncertain and it can cause severe adverse reactions in the mother and/or the fetus as well as increasing antimicrobial resistance.16, 17, 18 A recent study has shown the efficacy and safety of WOCA in the prevention of UTI in SCI patients.6
In this prospective study of six SCI pregnant women under WOCA, we observed a significant reduction in UTI and antibiotic consumption with no severe adverse events. We noted no abortion or obstetric complications. All seven babies were born at term, of normal weight, and healthy. Infant outcomes were uniformly good. The findings of our study are limited by the small sample size but add to the literature. A larger study could confirm the safety and efficiency of the WOCA regimen as UTI prophylaxis in this specific high-risk population.
Ethical approval: This study was approved by the research committee of the hospital. The protocol was explained to each patient and an informed consent was obtained.
Conflict of interest: No conflict of interest to declare.
References
- Vazquez JC, Villar J. Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev 2003(4):CD002256.
- . Urinary tract infection in persons with spinal cord injury. Arch Phys Med Rehabil. 1995;76:272–280
- . Potential preventive strategies and therapies in urinary tract infection. World J Urol. 1999;17:359–363
- . Epidemiology and risk factors for urinary tract infection in patients with spinal cord injury. J Urol. 2000;164:1285–1289
- ACOG Committee Opinion No. 275. Obstetrics care of patients with spinal cord injuries. Obstet Gynecol 2002;100:625–7.
- Prevention of urinary tract infection in spinal cord-injured patients: safety and efficacy of a weekly oral cyclic antibiotic (WOCA) program with a 2 year follow-up: an observational prospective study. J Antimicrob Chemother. 2006;57:784–788
- National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing. 7th ed. Approved standard M2-A7. Wayne, PA, USA: National Committee for Clinical Laboratory Standards; 2000.
- . A multicenter study of women’s self-reported reproductive health after spinal cord injury. Arch Phys Med Rehabil. 1999;8:1420–1428
- . Risks associated with pregnancy in spinal cord-injured women. Obstet Gynecol. 1992;80(3 Pt 1):425–428
- . Pregnancy and delivery in women with a traumatic spinal cord injury in Sweden, 1980–1991. Obstet Gynecol. 1993;81:926–930
- . Pregnancy, labor and delivery post spinal cord injury. Paraplegia. 1992;30:890–902
- . Sexual issues of women with spinal cord injuries. Paraplegia. 1992;30:192–199
- Antimicrobial prophylaxis for urinary tract infection in persons with spinal cord dysfunction. Arch Phys Med Rehabil. 2002;83:129–138
- . Prevention of urinary tract infection in patients with spinal cord injury—a microbiological review. Spinal Cord. 1997;35:198–204
- . Asymptomatic bacteriuria: review and discussion of the IDSA guidelines. Int J Antimicrob Agents. 2006;28(Suppl 1):S42–S48
- . Epidemiology and risk factors for urinary tract infection following spinal cord injury. Arch Phys Med Rehabil. 1993;74:691–695
- . Impact of nosocomial infection on length of stay and functional improvement among patients admitted to an acute rehabilitation unit. Infect Control Hosp Epidemiol. 2001;22:83–87
- . Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women. JAMA. 1999;281:736–738
PII: S1201-9712(08)01503-8
doi:10.1016/j.ijid.2008.08.006
© 2008 International Society for Infectious Diseases. Published by Elsevier Inc. All rights reserved.
Volume 13, Issue 3 , Pages 399-402, May 2009
