Cefotaxime in Gram-negative meningitis

Journal of Infection (I98Z)

5, IOI-IO2

Letter to the Editor

C e f o t a x i m e in G r a m - n e g a t l v e m e n i n g i t i s

In adults, Gram-negative bacillary meningitis is generally a complication of cranial trauma and neurosurgical procedures. Spontaneously occurring meningitis is much less common, affecting chiefly immunocompromised hosts. T h e high mortality rate in these patients is undoubtedly related to factors such as senility and serious underlying disease besides the fact that at present we lack an effective form of therapy 1. Here we describe two patients with spontaneous Gram-negative meningitis treated successfully with cefotaxime. Case one

A 5e-year-old man was admitted on I7 March I98o for the treatment of multiple myeloma. Because of the presence of a hyperviscosity syndrome, hypercalcaemia and renal failure, he was treated with melphalan, corticosteroids, furosemide and fluids. Plasmapheresis was begun. Thirteen days after admission he suddenly developed chills, fever and became obtunded. Neck stiffness was found. C S F was mildly cloudy and contained 256 × Io9/1 mononuclear, protein o'69/1 and glucose 2.0 mmol/1 (blood sugar 7"5 mm/1). A Gram stain was unhelpful. A chest film showed pneumonia. Cefotaxime I g every eight hours and gentamicin 8o mg as a single dose were started. Klebsiella pneumoniae ( M I C for cefotaxime o-oo6 mg/1) was isolated from blood and CSF cultures. T h e patient became alert, fever disappeared and three days later the C S F was clear and contained o-I × Io9/1 cells, protein 0"45 g/1 and glucose 3"4 mm/1. A Gram stain and culture were negative. Cefotaxime was continued during two weeks and finally he was discharged from hospital without any neurological damage. Case two

A 68-year-old woman was admitted on 8 June I98I because of fever and drowsiness. She had had several bouts of renal colic and urinary tract infection. In the emergency ward she was febrile, hyporeactive and a neck stiffness was noted. A chest film showed pneumonia. A lumbar puncture was done and cefotaxime z g/I.V, every four hours was immediately begun. Escherichia coli ( M I C for cefotaxime 0.006 mg/1) was isolated from blood and CSF cultures. Table I shows chemical and microbiological studies done on CSF, four hours after cefotaxime administration. T w o days after admission she was afebrile and alert and after two weeks course of treatment, she was discharged from the hospital. T h e treatment of Gram-negative bacillary meningitis in adults has been until now disappointing and approximately 75 per cent of the patients died. 1 T h e third generation cephalosporins, cefotaxime and moxalactam, have some

Letter to the Editor

102

Table I

CSF Cells (IOa/1) protein/mmol/1 CSF sugar/Serum sugar Gram stain Culture Cefotaxime levels CSF Serum Bactericidal titre: CSF Serum

8 June

IO June

15 June

13"o (PMN) 3"9

4.25 (PMN) 2.2

I'2/22

7/I8

Gram -- ve bacilli

negative negative

o.i 9 (PMN) 2-2 6/16 negative negative

15 mg/l 4 mg/l

5"4 mg/l 2 mg/l

i :I28 i :32

i :64 I :i6

E coli m

u n i q u e advantages t hat make t h e m suitable for the t r e a t m e n t o f G r a m - n e g a t i v e meningitis. T h e y show an e x p a n d e d s p e c t r u m o f action against m a n y G r a m negative bacillV and have good p e n e t r a t i o n into C S F . a In the pat i ent in w h o m we could d e t e r m i n e C S F levels o f cefotaxime, it was 3 3 - 2 5 o times h i g h e r t h a n M I C and bactericidal capacity o f C S F was also a p p r o p r i a t e . W h e t h e r such bactericidal activity was m a i n t a i n e d is u n k n o w n . F o u r h o u r s after i.v. injection o f th e d r u g , its values in C S F w er e c o n s i d e r a b l y h i g h e r t h a n c o n c e n t r a t i o n s in s e r u m and as could be e x p e c t e d , C S F levels seem ed to d e p e n d on the stage o f t r e a t m e n t an d on t he n u m b e r o f cells in t he C S F . S o m e investigators in E u r o p e a nd U n i t e d States have d e v e l o p e d p r e l i m i n a r y data d e m o n s t r a t i n g t he efficacy o f cefotaxime and m o x a l a c t a m in a limited n u m b e r o f patients. 4 T h i s b r i e f r e p o r t sustains such experience. It is possible t h a t in th e n ear f u t u r e , t he i n t r o d u c t i o n o f these n e w drugs will change t he p a n o r a m a o f these devastating infections.

Fundacion Jimenez Diaz, Universidad Autonoma, M a d r i d

M . L. Fernandez-Guerrero, Angeles Tortes and Francisco Soriano

References

I. Fernandez-Guerrero ML, Diaz Fernandez JL, Gomez Garc6s JL, Soriano F. Meningitis espont~inea por bacilos gram-negativos. Rev Clin Esp I98I ; I63: 263-268. 2. Hall WH, Opfer BJ, Gerding DN. Comparative activities of the oxa-b-lac-tam LY 127935, cefotaxime, cefoperazone, cefamandole and ticarcillin against multiply resistant gramnegative bacilli. Antimicrob Agents Chemother 198o; x7: 272-279. 3. Schaad VB, McCracken GH, Loock CA. Pharmacokinetics and bacteriologic efficacy of moxalactam, cefotaxime, cefoperazone and rocephin in experimental bacterial meningitis. J Infect Dis 1981; I43 : 156-I 63. 4. Landesman SH, Shah PM, Armengaud M, Barza M, Cherubin CE. Past and current roles for cephalosporin antibiotics in treatment of meningitis. Emphasis on use in Gram-negative bacillary meningitis. Am J ivied 1981; 71 : 693-703 •