International Journal of Infectious Diseases (2009) 13, 399—402

http://intl.elsevierhealth.com/journals/ijid

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
Jérôme Salomon a,b,*, Alexis Schnitzler c, Yves Ville d, Isabelle Laffont c,
Christian Perronne b, Pierre Denys c, Louis Bernard b

a
INSERM U657, PhEMI, Institut Pasteur, Paris, France
b
Department of Infectious Diseases, AP-HP, CHU Raymond Poincaré, Versailles University, 104 Boulevard Raymond Poincaré,
F-92 380 Garches, France
c
Department of Physical Medicine and Rehabilitation, AP-HP, Hôpital Poincaré, Versailles University, Garches, France
d
Department of Obstetrics and Gynecology, Hôpital de Poissy, Versailles University, Garches, France

Received 29 February 2008; received in revised form 23 July 2008; accepted 1 August 2008
Corresponding Editor: Michael Whitby, Brisbane, Australia

KEYWORDS
Antibiotic prophylaxis;
Pregnancy;
Preventive strategy;
Spinal cord injury;
Urinary tract infection
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 bacter-
iuria 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 tetra-
plegic).
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.
# 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

* Corresponding author. Tel.: +33 1 47 10 77 60; fax: +33 1 47 10 77 67.

E-mail addresses: jerome.salomon@rpc.aphp.fr, jsalomon@pasteur.fr (J. Salomon).

1201-9712/$36.00 # 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ijid.2008.08.006
400
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 world-
wide.2 Asymptomatic bacteriuria is frequent (70%) in spinal
cord-injured (SCI) patients using chronic intermittent cathe-
terization (CIC), and is usually of no consequence to the
integrity of the upper urinary tract when low pressure sto-
rage 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 treat-
ments 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 antibio-
tics occurred, no severe adverse events were reported, and
no case of colonization with multidrug-resistant (MDR) bac-
teria 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 preg-
nant. 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-exist-
ing medical conditions, allergies, catheterizations per day,
mean volume per catheterization, history of UTI, hospitali-
zations, and courses of antibiotic therapy).
The definition of UTI in this specific population was estab-
lished 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 3000 mg, cefixime
400 mg, nitrofurantoin 300 mg. 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 toxi-
city. 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 obste-
trics units. The following parameters were evaluated weekly:
J. Salomon et al.
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 per-
formed 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 450 ml ( 50 ml). There was
no underlying upper urinary tract obstruction or stone dis-
ease 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.
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 3 g 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 (bac-
teriuria >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 pneu-
moniae (10%). At inclusion, one patient was colonized with
methicillin-resistant Staphylococcus aureus. This coloniza-
tion disappeared during pregnancy. No new case of coloniza-
tion 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
Prevention of UTI in six spinal cord-injured pregnant women 401

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
UTI, urinary tract infection; SCI, spinal cord-injured; WOCA, weekly oral cyclic antibiotic program; MDR, multidrug-resistant bacteria; V,
spontaneous vaginal delivery; CD, cesarean delivery; F, forceps delivery.

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 3180 g (SD 80 g). 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 preg-
nancy. 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 preg-
nancy, 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, Westg-
ren 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 deliv-
eries. Problems included autonomic dysreflexia, decubitus
ulcers, and UTI.
Preconception consultation with obstetricians and physia-
trists may improve the quality of follow-up and the adapta-
tion 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 hos-
pital-related episodes.2 Urinary bacterial colonization is fre-
quent.14 Given the absence of controlled trials or prospective
data, it is difficult to make evidence-based recommenda-
tions. 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 asymp-
tomatic bacteriuria in SCI. Because of specific complications
due to UTI during pregnancy, screening and treatment of
asymptomatic bacteriuria is strongly recommended. The
402
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—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 anti-
biotic 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.
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