Develop. Med. Child Neurol. 1916, 18, 302-304
Prophylaxis in Urinary Tract Infection in Children with Myelomeningocele B. Hellstrom M. Jordahl-Carlsson A . Nergardh
Introduction It is well known that urinary tract infections constitute a serious problem in children with myelomeningocele. The reported incidence by the age of two years is around 50 per cent, although there has been considerable variation between different series (Thomas and Hopkins 1971). It is also a general experience that the bacterial flora in these persistent or recurrent infections largely consist of strains resistant to many chemotherapeutic agents and antibiotics. Despite this, relatively few systemic or controlled studies have been published concerning prophylaxis and therapy in these patients. In the present paper, a controlled trial of prophylaxis with nitrofurantoin is reported.
patient therefore served as his own control. The study was supervised in the outpatient department. The method was to obtain one urine culture each month. If significant bacteriuria occurred it was treated according to the pattern of resistance, and as soon as further urine culture had shown therapy to be effective the patients reverted to their current prophylaxis or non-prophylaxis period. In practice, the length of the periods were somewhat longer than planned but the total number of months observed in the non-prophylaxis periods was 320 and in the prophylaxis periods it was 299. The average length of surveillance for each patient was 15 months. The prophylactic dose of nitrofurantoin used was 2mg/kg/24 hours in two or three divided doses.
Material and Methods The study group comprised 39 infants and children with myelomeningocele (1 7 females, 22 males). They were born between 1957 and 1971 and were followed in the department of paediatrics, Karolinska hospital. It was intended to give the patients prophylaxis with nitrofurantoin for four-month periods, alternating with equal periods without prophylaxis. Each
Sampling and Bacteriological Technique The bacteriological examinations were carried out on urine which was either passed spontaneously or obtained after suprapubic compression; in both cases after careful washing of the external genitalia with sterile saline solution. On culture, the bacterial growth was quanti-
Correspondence to Dr. B. Hellstrom, Department of Paediatrics, Karolinska Hospital, S-104 01 Stockholm 60,Sweden
302
B. HELLSTR~M
M. JORDAHL-CARLSSON A. NERGARDH
42 per cent in the non-prophylaxis period. Comparing the periods, there were small hfferences in the incidence of different bacterial strains, but Ps. pyocyanea appeared in 20 per cent of the significant cultures in the prophylaxis period, compared with 10 per cent i n the non-prophylaxis period.
fied in the usual way and bacterial counts over lW,000cm3 was taken as indicating significant bacteriuria. The pattern of resistance was examined using the disc dlffusion method. Results The results of the trial with nitrofurantoin prophylaxis are shown in Figure 1. The frequency of positive cultures with significant bacteriuria was approximately 25 per cent, which is about half the frequency prior to starting t h s controlled series. However, the improved culture results cannot be attributed to nitrofurantoin prophylaxis, as the small difference in the frequency of positive cultures between the prophylaxis and non-prophylaxis groups was not statistically significant. There was an appreciable difference in the frequency of positive culture in boys compared with girls; the former were significantly more often culture-negative. Positive cultures were not equally distributed in all patients; a proportionately small number of patients accounted for a large number of positive cultures. In other words, certain patients were more or less constantly infected. A negative consequence of the nitrofurantoin prophylaxis was that those strains isolated in significant quantity during the period of prophylaxis were resistant to nitrofurantoin in 68 per cent of cases, compared with
Discussion Prior to this controlled study, sulphafurazole was the drug of choice in the treatment of sulphonamide-sensitive bacteriurias, and this drug was also used to a certain extent as 'long-term treatment prophylaxis' in an uncontrolled way. Among others, Lincoln et al. (1970, 1972) have shown such sulphonamide treatment, especially in cases with a tendency to recurrence, to result in colonisation with sulphonamide-resistant strains in the gut, which acts as a reservoir for reinfection. The problem of treatment in recurrent infections increases with increasing prevalence of the R factor, which promotes the development of resistance against several antibiotics and chemotherapeutic agents simultaneously. Considering these facts, it seems illogical to try to prevent recurrent infections with long-term prophylaxis using conventional sulphonamide drugs. Lorber et al. 1968, in a controlled study, have also shown that such treatment with sulphonamide is ineffective. On the other hand, in the same study a somewhat lesser tendency to infection was seen in a group on longterm nalidixic acid treatment compared with a control group, but the difference was not statistically significant. Conclusions The present trial gave no evidence that prophylactic treatment with nitrofurantoin is of value. Indeed, it may be of disadvantage because of a higher risk of re-infection with nitrofurantoin-resistant organisms.
Fig. 1. Results of a trial with nitrofurantoin prophylaxis.
303
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY.
1976, 18
in girls. Collecting specimens by bladderpuncture might be of value in order to study this aspect more closely.
On average, compared with the figures in the period preceding the study, the frequency of bacteriuria was halved, but this can be related to more regular superVision and earlier detection of significant bacteriuria, and a change from sulphafurazole to co-trimoxazole in the treatment of sensitive infections during the study period. The markedly fewer infections in the boys in this study may reflect a higher incidence of colonisation of the urethra
Acknowledgements: This study was supported by grants from Kronprinsessan Lovisas Forening f6r Barnasjukvgrd, Sallskapet Barnasjukvird and the Swedish Medical Research Council (4492), Stockhoim, Sweden. AUTHORS’ APPOINTMENTS
Dr. B. Hellstrom, Head, Section of Habilitation; Dr. M. Jordahl-Carlsson, member of staff; Dr. A. Negkrdh, Paediatric Neurologist; Paediatric Department, Karolinska Hospital, Stockholm, Sweden.
SUMMARY
In 39 infants and children with myelomeningocele, no lower incidence of urinary tract infection was obtained by a trial of prophylaxis treatment with nitrofurantoin. Instead, nitrofurantoin-resistant strains appeared in some children, with the accompanying higher risk of re-infection. RI?SUMI?
Chez 39 enfants atteints de spina bifida, il n’a pas ete observk de baisse de frequence des infections du tractus urinaire par un essai de traitement prophylactique avec le nitrofuranto’ine. En revanche, des colonies rksistantes B la nitrofurantohe sont apparues chez quelques enfants avec le haut risque de rkinfection que cela prksente. ZUSAMMENFASSUNC
Bei 39 Kindern mit Spina bifida wurde die Zahl der Harnwegsinfekte durch eine Prophylaxe mit Nitrofurantoin nicht herabgesetzt. Im Gegenteil, bei einigen Kindern traten Nitrofurantoin-resistente Stamme auf, durch die ein vie1 hoheres Risiko einer Reinfektion gegeben war. RESUMEN
En 39 niiios con espina bifida no se obtuvo una incidencia menor de infecci6n de vias urinarias con el ensayo de un tratamiento profilactico con nitrofurantoina. En carnbio, en algunos niiios aparecieron capas resistentes a la nitrofurantoina, con el mayor riesgo acompaiiante de una reinfeccih. REFERENCES Lincoln, K., Lidin-Janson, G., Winberg, J. (1970) ‘Resistant urinary infections resulting from cnanges in resistance pattern of faecal flora induced by sulphonamide and hospital environment.’ Brifish Medical Journal, iii, 305. - - - (1972) ‘Faecal and periurethral flora after oral administration of sulphonamide, nitrofurantoin and nalidixic acid.’ Acru Paediatrica Scandinavica, 61,643. Lorber, J., Menneer, P.C., Allott, D.C. (1968) ‘An investigation into prophylactic treatment of urinary tract infections in infants born with spina bifida cystica.’ Developmental Medicine and Child Neurology, 10, Suppl. 15,30. Thomas, M., Hopkins, J. (1971) ‘A study of the renal tract from birth in children with myelomeningocele.‘ Developmental Medicine and Child Neurology, 13, Suppl. 25, 96.
304
Prophylaxis in Urinary Tract Infection in Children with Myelomeningocele B. Hellstrom M. Jordahl-Carlsson A . Nergardh
Introduction It is well known that urinary tract infections constitute a serious problem in children with myelomeningocele. The reported incidence by the age of two years is around 50 per cent, although there has been considerable variation between different series (Thomas and Hopkins 1971). It is also a general experience that the bacterial flora in these persistent or recurrent infections largely consist of strains resistant to many chemotherapeutic agents and antibiotics. Despite this, relatively few systemic or controlled studies have been published concerning prophylaxis and therapy in these patients. In the present paper, a controlled trial of prophylaxis with nitrofurantoin is reported.
patient therefore served as his own control. The study was supervised in the outpatient department. The method was to obtain one urine culture each month. If significant bacteriuria occurred it was treated according to the pattern of resistance, and as soon as further urine culture had shown therapy to be effective the patients reverted to their current prophylaxis or non-prophylaxis period. In practice, the length of the periods were somewhat longer than planned but the total number of months observed in the non-prophylaxis periods was 320 and in the prophylaxis periods it was 299. The average length of surveillance for each patient was 15 months. The prophylactic dose of nitrofurantoin used was 2mg/kg/24 hours in two or three divided doses.
Material and Methods The study group comprised 39 infants and children with myelomeningocele (1 7 females, 22 males). They were born between 1957 and 1971 and were followed in the department of paediatrics, Karolinska hospital. It was intended to give the patients prophylaxis with nitrofurantoin for four-month periods, alternating with equal periods without prophylaxis. Each
Sampling and Bacteriological Technique The bacteriological examinations were carried out on urine which was either passed spontaneously or obtained after suprapubic compression; in both cases after careful washing of the external genitalia with sterile saline solution. On culture, the bacterial growth was quanti-
Correspondence to Dr. B. Hellstrom, Department of Paediatrics, Karolinska Hospital, S-104 01 Stockholm 60,Sweden
302
B. HELLSTR~M
M. JORDAHL-CARLSSON A. NERGARDH
42 per cent in the non-prophylaxis period. Comparing the periods, there were small hfferences in the incidence of different bacterial strains, but Ps. pyocyanea appeared in 20 per cent of the significant cultures in the prophylaxis period, compared with 10 per cent i n the non-prophylaxis period.
fied in the usual way and bacterial counts over lW,000cm3 was taken as indicating significant bacteriuria. The pattern of resistance was examined using the disc dlffusion method. Results The results of the trial with nitrofurantoin prophylaxis are shown in Figure 1. The frequency of positive cultures with significant bacteriuria was approximately 25 per cent, which is about half the frequency prior to starting t h s controlled series. However, the improved culture results cannot be attributed to nitrofurantoin prophylaxis, as the small difference in the frequency of positive cultures between the prophylaxis and non-prophylaxis groups was not statistically significant. There was an appreciable difference in the frequency of positive culture in boys compared with girls; the former were significantly more often culture-negative. Positive cultures were not equally distributed in all patients; a proportionately small number of patients accounted for a large number of positive cultures. In other words, certain patients were more or less constantly infected. A negative consequence of the nitrofurantoin prophylaxis was that those strains isolated in significant quantity during the period of prophylaxis were resistant to nitrofurantoin in 68 per cent of cases, compared with
Discussion Prior to this controlled study, sulphafurazole was the drug of choice in the treatment of sulphonamide-sensitive bacteriurias, and this drug was also used to a certain extent as 'long-term treatment prophylaxis' in an uncontrolled way. Among others, Lincoln et al. (1970, 1972) have shown such sulphonamide treatment, especially in cases with a tendency to recurrence, to result in colonisation with sulphonamide-resistant strains in the gut, which acts as a reservoir for reinfection. The problem of treatment in recurrent infections increases with increasing prevalence of the R factor, which promotes the development of resistance against several antibiotics and chemotherapeutic agents simultaneously. Considering these facts, it seems illogical to try to prevent recurrent infections with long-term prophylaxis using conventional sulphonamide drugs. Lorber et al. 1968, in a controlled study, have also shown that such treatment with sulphonamide is ineffective. On the other hand, in the same study a somewhat lesser tendency to infection was seen in a group on longterm nalidixic acid treatment compared with a control group, but the difference was not statistically significant. Conclusions The present trial gave no evidence that prophylactic treatment with nitrofurantoin is of value. Indeed, it may be of disadvantage because of a higher risk of re-infection with nitrofurantoin-resistant organisms.
Fig. 1. Results of a trial with nitrofurantoin prophylaxis.
303
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY.
1976, 18
in girls. Collecting specimens by bladderpuncture might be of value in order to study this aspect more closely.
On average, compared with the figures in the period preceding the study, the frequency of bacteriuria was halved, but this can be related to more regular superVision and earlier detection of significant bacteriuria, and a change from sulphafurazole to co-trimoxazole in the treatment of sensitive infections during the study period. The markedly fewer infections in the boys in this study may reflect a higher incidence of colonisation of the urethra
Acknowledgements: This study was supported by grants from Kronprinsessan Lovisas Forening f6r Barnasjukvgrd, Sallskapet Barnasjukvird and the Swedish Medical Research Council (4492), Stockhoim, Sweden. AUTHORS’ APPOINTMENTS
Dr. B. Hellstrom, Head, Section of Habilitation; Dr. M. Jordahl-Carlsson, member of staff; Dr. A. Negkrdh, Paediatric Neurologist; Paediatric Department, Karolinska Hospital, Stockholm, Sweden.
SUMMARY
In 39 infants and children with myelomeningocele, no lower incidence of urinary tract infection was obtained by a trial of prophylaxis treatment with nitrofurantoin. Instead, nitrofurantoin-resistant strains appeared in some children, with the accompanying higher risk of re-infection. RI?SUMI?
Chez 39 enfants atteints de spina bifida, il n’a pas ete observk de baisse de frequence des infections du tractus urinaire par un essai de traitement prophylactique avec le nitrofuranto’ine. En revanche, des colonies rksistantes B la nitrofurantohe sont apparues chez quelques enfants avec le haut risque de rkinfection que cela prksente. ZUSAMMENFASSUNC
Bei 39 Kindern mit Spina bifida wurde die Zahl der Harnwegsinfekte durch eine Prophylaxe mit Nitrofurantoin nicht herabgesetzt. Im Gegenteil, bei einigen Kindern traten Nitrofurantoin-resistente Stamme auf, durch die ein vie1 hoheres Risiko einer Reinfektion gegeben war. RESUMEN
En 39 niiios con espina bifida no se obtuvo una incidencia menor de infecci6n de vias urinarias con el ensayo de un tratamiento profilactico con nitrofurantoina. En carnbio, en algunos niiios aparecieron capas resistentes a la nitrofurantoina, con el mayor riesgo acompaiiante de una reinfeccih. REFERENCES Lincoln, K., Lidin-Janson, G., Winberg, J. (1970) ‘Resistant urinary infections resulting from cnanges in resistance pattern of faecal flora induced by sulphonamide and hospital environment.’ Brifish Medical Journal, iii, 305. - - - (1972) ‘Faecal and periurethral flora after oral administration of sulphonamide, nitrofurantoin and nalidixic acid.’ Acru Paediatrica Scandinavica, 61,643. Lorber, J., Menneer, P.C., Allott, D.C. (1968) ‘An investigation into prophylactic treatment of urinary tract infections in infants born with spina bifida cystica.’ Developmental Medicine and Child Neurology, 10, Suppl. 15,30. Thomas, M., Hopkins, J. (1971) ‘A study of the renal tract from birth in children with myelomeningocele.‘ Developmental Medicine and Child Neurology, 13, Suppl. 25, 96.
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