364
VOL.
5
NO.
4
~
Acknowledgements
We are grateful to Mr. R. van Raalte and stalT of the Mcdical Illustrations Department of Royal Perth Hospital for preparing the figures; and to Ms Tanya Roberts and Ms Ms Christine Christine Hopkins Hopkins for secretarial secretarial assistance.
References References II. . POLANI. P. POL.AI*I. P E. t and and Mi)usAHA\. M o \ \ & H A \E. E. J.J . (19721: (19721 Progresrive Propcicl\c cardiom!opathic cdrd!om!irchow was repeatedly isolated from the CSF while on antibiotic treatment, an attempt was made to obtain therapeutic antibiotic levels in the CSF for a prolonged period. Administration of chloramphenicol was ceased after one month treatment and the dose of ampicillin was increased to 1 g/kg/24 hours. Sulphadiazine 200 mg/kg/24 hours was introduced at the same time (1 g fourth hourly). On this regime the CSF showed antibacterial activity at il one in twelve dilution against the Salmonella. However, thc CSF concentration of Ampicillin was only 2 pgirnl whereas the minimal inhibitory concentration (MIC) of ampicillin in
TABLE 1 CSF concentration (2 hours after administration] 20 pg:ml Sulphadiazine Trimethoprim 0 . 6 pg:ml Ratio sulphadiazine/trimethoprim: 33;l
1 1
~
i
r i m was 6 pgiml. Thus despite the high dose of ampicillin used. the CSF penetration was inadequate. The antibacterial activity of the CSF was due principally to the sulphadiazine, and the administration of ampicillin was ceased three weeks after treatment was commenced. P a r e n t e d Trimethoprim was obtained from BurroughsWcllcome and this was commenced in combination with sulphadiazine. I n nirro tests revealed syncrgisni between trinicthoprimisulphadiazine against the Salmonella. with the MIC of trimethoprim and sulphadiazinc being 0.125 pg:ml and 2.5 &in1 respectively. Initial therapy consisted of intravenous (IV) trimethoprim 10 mg/kg/24 hours (30 mg bd) and sulphadiazine 200 mg/kg;24 hours (300 mg sixth hourly). Following thc initiation of this therapy the lumbar CSF levels of sulphadiazineitrimethoprim were measured two hours aftcr thcir administration and are represented in Table 1. Some authors4* have recommended that for maximum synergistic effect the drugs should be present in the ratio of the MIC’s, i.e. 20/1. In order to achieve this the dose of trimethoprim was
’
1000-
-
I!lot
I level: 1 4 . 1
-
_r
, ,
I
I
I I
VOL.
5
NO.
4
~
Acknowledgements
We are grateful to Mr. R. van Raalte and stalT of the Mcdical Illustrations Department of Royal Perth Hospital for preparing the figures; and to Ms Tanya Roberts and Ms Ms Christine Christine Hopkins Hopkins for secretarial secretarial assistance.
References References II. . POLANI. P. POL.AI*I. P E. t and and Mi)usAHA\. M o \ \ & H A \E. E. J.J . (19721: (19721 Progresrive Propcicl\c cardiom!opathic cdrd!om!irchow was repeatedly isolated from the CSF while on antibiotic treatment, an attempt was made to obtain therapeutic antibiotic levels in the CSF for a prolonged period. Administration of chloramphenicol was ceased after one month treatment and the dose of ampicillin was increased to 1 g/kg/24 hours. Sulphadiazine 200 mg/kg/24 hours was introduced at the same time (1 g fourth hourly). On this regime the CSF showed antibacterial activity at il one in twelve dilution against the Salmonella. However, thc CSF concentration of Ampicillin was only 2 pgirnl whereas the minimal inhibitory concentration (MIC) of ampicillin in
TABLE 1 CSF concentration (2 hours after administration] 20 pg:ml Sulphadiazine Trimethoprim 0 . 6 pg:ml Ratio sulphadiazine/trimethoprim: 33;l
1 1
~
i
r i m was 6 pgiml. Thus despite the high dose of ampicillin used. the CSF penetration was inadequate. The antibacterial activity of the CSF was due principally to the sulphadiazine, and the administration of ampicillin was ceased three weeks after treatment was commenced. P a r e n t e d Trimethoprim was obtained from BurroughsWcllcome and this was commenced in combination with sulphadiazine. I n nirro tests revealed syncrgisni between trinicthoprimisulphadiazine against the Salmonella. with the MIC of trimethoprim and sulphadiazinc being 0.125 pg:ml and 2.5 &in1 respectively. Initial therapy consisted of intravenous (IV) trimethoprim 10 mg/kg/24 hours (30 mg bd) and sulphadiazine 200 mg/kg;24 hours (300 mg sixth hourly). Following thc initiation of this therapy the lumbar CSF levels of sulphadiazineitrimethoprim were measured two hours aftcr thcir administration and are represented in Table 1. Some authors4* have recommended that for maximum synergistic effect the drugs should be present in the ratio of the MIC’s, i.e. 20/1. In order to achieve this the dose of trimethoprim was
’
1000-
-
I!lot
I level: 1 4 . 1
-
_r
, ,
I
I
I I
