405
2. Koudstaal PJ, van Gijn J, Staal A, Duivenoorden HJ, Gerritsma JGM, Kraaijeveld CL. Diagnosis of transient ischemic attacks: improvement of interobserver agreement by a check-list in ordinary language. Stroke 1986; 17: 723-28. 3. Fisher CM. Lacunar strokes and infarcts. Neurology 1982; 32: 871-76. 4. Hodges JR, Warlow CP. The aetiology of transient global amnesia: a case-control study of 114 cases with prospective follow-up. Brain 1990; 113: 639-57. 5. Meissner I, Wiebers DO, Swanson JW, O’Fallon WM. The natural history of drop attacks. Neurology 1986; 36: 1029-34. 6. Dennis MS, Bamford JM, Sandercock PAG, Warlow CP. Lone bilateral blindness: a transient ischaemic attack. Lancet 1989; i: 185-88. 7. Yanigahara T, Piepgras D, Klass DW. Repetitive involuntary movements associated with episodic cerebral ischemia. Ann Neurol
1985;18: 244-50. 8. Lee H, Lerner A. Transient inhibitory seizures mimicking crescendo TIAs. Neurology 1990; 40: 165-66. 9. Portenoy RK, Abissi CJ, Lipton RB, et al. Headache in cerebrovascular disease. Stroke 1984; 15: 1009-12. 10. Larsen BH, Sorensen PS, Marquardsen J. Transient ischaemic attacks in young patients: a thromboembolic or migrainous manifestation? A 10 year follow up study of 46 patients. J Neurol Neurosurg Psychiatry 1990; 53: 1029-33. 11. Fisher CM. Late-life migraine accompaniments: further experience. Stroke 1986; 17: 1035-42. 12. Calanchini PR, Swanson PD, Gotshall RA, et al. Cooperative study of hospital frequency and character of transient ischemic attacks IV: the reliability of diagnosis. JAMA 1977; 238: 2029-33. 13. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325: 445-53.
14. Waxman SG, Toole JF. Temporal profile resembling TIA in the setting of cerebral infarction. Stroke 1983; 14: 433-37. 15. Shinar D, Gross CR, Hier DB, et al. Interobserver reliability in the interpretation of computed tomographic scans of stroke patients. Arch Neurol 1987; 44: 149-55. 16. Dennis M, Bamford J, Sandercock P, Molyneux A, Warlow C. Computed tomography in patients with transient ischaemic attacks: when is a transient ischaemic attack not a transient ischaemic attack but a stroke? J Neurol 1990; 237: 257-61. 17. Tomasello F, Mariani F, Fieschi C, et al. Assessment of inter-observer differences in the Italian multicenter study on reversible cerebral ischemia. Stroke 1982; 13: 32-35. 18. Wiebers DO, Whisnant JP, O’Fallon WM. Reversible ischemic neurologic deficit (RIND) in a community: Rochester, Minnesota, 1955-1974. Neurology 1982; 32: 459-65. 19. Dennis MS, Bamford JM, Sandercock PAG, Warlow CP. A comparison of risk factors and prognosis for transient ischemic attacks and minor ischemic strokes: the Oxfordshire Community Stroke Project. Stroke 1989; 20: 1494-99. 20. Caplan LR. Are terms such as completed stroke or RIND of continued usefulness? Stroke 1983; 14: 431-33. 21. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991; 337: 1521-26. 22. Kappelle LJ, van Latum JC, Koudstaal PJ, van Gijn J. Transient ischaemic attacks and small-vessel disease. Lancet 1991; 337: 339-41. 23. Landi G, Candelise L, Cella E, Pinardi G. Interobserver reliability of the diagnosis of lacunar transient ischemic attack (TIA with lacunar syndrome). Cerebrovasc Dis (in press). 24. Hankey GJ, Warlow CP. Lacunar transient ischaemic attacks: a clinically useful concept? Lancet 1991; 337: 335-38.
CLINICAL PRACTICE therapy in penicillin-resistant pneumococcal meningitis Failure of chloramphenicol
First-line therapy for meningitis is often penicillin Penicillin-resistant chloramphenicol. plus Streptococcus pneumoniae (PRSP) infections are increasing world wide, but the efficacy of chloramphenicol for PRSP meningitis is unknown. We therefore prospectively assessed children with pneumococcal meningitis treated with penicillin plus
chloramphenicol over 27 months to compare outcome of penicillin-susceptible S pneumoniae (PSSP) meningitis with that of PRSP meningitis. 68 children with pneumococcal meningitis who survived 24 hours were evaluated, of whom 25 had chloramphenicol-susceptible PRSP meningitis that was treated initially with chloramphenicol. 20 (80%) of these 25 children had an unsatisfactory outcome (death, serious neurological deficit, or poor clinical response). By contrast, 14 (33%) of 43 children with PSSP meningitis (treated with benzylpenicillin) had an adverse outcome (p 1 ’0 jg/ml). Chloramphenicol MICs and minimum bactericidal concentrations (MBCs) for PRSP strains that were susceptible to chloramphenicol as judged by disc testing were done at the end of the study without knowledge of clinical outcome. MICs and MBCs of chloramphenicol were not available during the patients’ hospital stay and did not influence patient management. Isolates with a chloramphenicol MIC of less than 8 )ig/ml are usually regarded as chloramphenicol susceptible! and this cut-off was used in subsequent analyses. Isolates were serogrouped according to the Danish nomenclature with antisera from the Statens Seruminstitut, Copenhagen, Denmark. Pneumococci
Susceptibility Kirby-Bauer
were
to
Statistical analysis
shown in table 11. The most frequently isolated serogroups 6, 14, and 19 (together accounting for 60% of all isolates and for 91 % of penicillin-resistant isolates, table 111).
were
Management of PRSP meningitis During the study, cases were treated with benzylpenicillin (400000 U/kg per day) and chloramphenicol (75-100 mg/kg per day) pending CSF culture results. If a PSSP was isolated, benzylpenicillin alone was continued. After identification of a PRSP (usually 24-48 h after admission), chloramphenicol alone was continued if the patient was progressing satisfactorily. In 12 (48%) of 25 infections due to S pneumoniae that was chloramphenicol susceptible but moderately penicillin resistant, initial treatment with chloramphenicol was either changed (to ceftriaxone in 10 children) or supplemented (with vancomycin in 2) because of unsatisfactory clinical response. In 3 children who did not respond adequately to chloramphenicol, a lumbar puncture was repeated before changing treatment-ie, 24-48 h after starting treatment and 1-2 h after an intravenous dose of chloramphenicolbut pneumococci were not reisolated from CSF. However, in all 3 cases, CSF chloramphenicol bactericidal activity was no more than 1 in 4. Despite a change in therapy, all 3 children died. 3 children
whose treatment was changed from chloramphenicol had been on phenobarbital for convulsions. Chloramphenicol blood concentrations, measured in 2, were in the therapeutic range (16 and 20 TABLE II-CHARACTERISTICS OF CHILDREN WITH PENICILLIN-SENSITIVE AND PENICILLIN-RESISTANT PNEUMOCOCCAL MENINGITIS
Differences between children with PRSP and those with PSSP analysed with Fisher’s exact test. The t test and the Mann-Whitney U-test were used to assess differences in measured outcomes depending on distribution. were
Results 84
children
with
were assessed.
meningitis 20 days and died.9
culture-positive
pneumococcal
1 child had a probable relapse after
Microbiology The antimicrobial resistance of the strains is shown in table I. Overall penicillin resistance rate was 42 %; in 1989, it was 37% (16/43) and in 1990/91 it increased to 46% (19/41). Of 35 PRSP isolated, 32 (91 %) were community acquired. Clinical details of cases of PRSP and PSSP meningitis are
Data given as no of children with feature unless otherwise indicated *Median (Interquartile range), tMedlan (range), tMean (SD), §One
excluded’, "p
2. Koudstaal PJ, van Gijn J, Staal A, Duivenoorden HJ, Gerritsma JGM, Kraaijeveld CL. Diagnosis of transient ischemic attacks: improvement of interobserver agreement by a check-list in ordinary language. Stroke 1986; 17: 723-28. 3. Fisher CM. Lacunar strokes and infarcts. Neurology 1982; 32: 871-76. 4. Hodges JR, Warlow CP. The aetiology of transient global amnesia: a case-control study of 114 cases with prospective follow-up. Brain 1990; 113: 639-57. 5. Meissner I, Wiebers DO, Swanson JW, O’Fallon WM. The natural history of drop attacks. Neurology 1986; 36: 1029-34. 6. Dennis MS, Bamford JM, Sandercock PAG, Warlow CP. Lone bilateral blindness: a transient ischaemic attack. Lancet 1989; i: 185-88. 7. Yanigahara T, Piepgras D, Klass DW. Repetitive involuntary movements associated with episodic cerebral ischemia. Ann Neurol
1985;18: 244-50. 8. Lee H, Lerner A. Transient inhibitory seizures mimicking crescendo TIAs. Neurology 1990; 40: 165-66. 9. Portenoy RK, Abissi CJ, Lipton RB, et al. Headache in cerebrovascular disease. Stroke 1984; 15: 1009-12. 10. Larsen BH, Sorensen PS, Marquardsen J. Transient ischaemic attacks in young patients: a thromboembolic or migrainous manifestation? A 10 year follow up study of 46 patients. J Neurol Neurosurg Psychiatry 1990; 53: 1029-33. 11. Fisher CM. Late-life migraine accompaniments: further experience. Stroke 1986; 17: 1035-42. 12. Calanchini PR, Swanson PD, Gotshall RA, et al. Cooperative study of hospital frequency and character of transient ischemic attacks IV: the reliability of diagnosis. JAMA 1977; 238: 2029-33. 13. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325: 445-53.
14. Waxman SG, Toole JF. Temporal profile resembling TIA in the setting of cerebral infarction. Stroke 1983; 14: 433-37. 15. Shinar D, Gross CR, Hier DB, et al. Interobserver reliability in the interpretation of computed tomographic scans of stroke patients. Arch Neurol 1987; 44: 149-55. 16. Dennis M, Bamford J, Sandercock P, Molyneux A, Warlow C. Computed tomography in patients with transient ischaemic attacks: when is a transient ischaemic attack not a transient ischaemic attack but a stroke? J Neurol 1990; 237: 257-61. 17. Tomasello F, Mariani F, Fieschi C, et al. Assessment of inter-observer differences in the Italian multicenter study on reversible cerebral ischemia. Stroke 1982; 13: 32-35. 18. Wiebers DO, Whisnant JP, O’Fallon WM. Reversible ischemic neurologic deficit (RIND) in a community: Rochester, Minnesota, 1955-1974. Neurology 1982; 32: 459-65. 19. Dennis MS, Bamford JM, Sandercock PAG, Warlow CP. A comparison of risk factors and prognosis for transient ischemic attacks and minor ischemic strokes: the Oxfordshire Community Stroke Project. Stroke 1989; 20: 1494-99. 20. Caplan LR. Are terms such as completed stroke or RIND of continued usefulness? Stroke 1983; 14: 431-33. 21. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991; 337: 1521-26. 22. Kappelle LJ, van Latum JC, Koudstaal PJ, van Gijn J. Transient ischaemic attacks and small-vessel disease. Lancet 1991; 337: 339-41. 23. Landi G, Candelise L, Cella E, Pinardi G. Interobserver reliability of the diagnosis of lacunar transient ischemic attack (TIA with lacunar syndrome). Cerebrovasc Dis (in press). 24. Hankey GJ, Warlow CP. Lacunar transient ischaemic attacks: a clinically useful concept? Lancet 1991; 337: 335-38.
CLINICAL PRACTICE therapy in penicillin-resistant pneumococcal meningitis Failure of chloramphenicol
First-line therapy for meningitis is often penicillin Penicillin-resistant chloramphenicol. plus Streptococcus pneumoniae (PRSP) infections are increasing world wide, but the efficacy of chloramphenicol for PRSP meningitis is unknown. We therefore prospectively assessed children with pneumococcal meningitis treated with penicillin plus
chloramphenicol over 27 months to compare outcome of penicillin-susceptible S pneumoniae (PSSP) meningitis with that of PRSP meningitis. 68 children with pneumococcal meningitis who survived 24 hours were evaluated, of whom 25 had chloramphenicol-susceptible PRSP meningitis that was treated initially with chloramphenicol. 20 (80%) of these 25 children had an unsatisfactory outcome (death, serious neurological deficit, or poor clinical response). By contrast, 14 (33%) of 43 children with PSSP meningitis (treated with benzylpenicillin) had an adverse outcome (p 1 ’0 jg/ml). Chloramphenicol MICs and minimum bactericidal concentrations (MBCs) for PRSP strains that were susceptible to chloramphenicol as judged by disc testing were done at the end of the study without knowledge of clinical outcome. MICs and MBCs of chloramphenicol were not available during the patients’ hospital stay and did not influence patient management. Isolates with a chloramphenicol MIC of less than 8 )ig/ml are usually regarded as chloramphenicol susceptible! and this cut-off was used in subsequent analyses. Isolates were serogrouped according to the Danish nomenclature with antisera from the Statens Seruminstitut, Copenhagen, Denmark. Pneumococci
Susceptibility Kirby-Bauer
were
to
Statistical analysis
shown in table 11. The most frequently isolated serogroups 6, 14, and 19 (together accounting for 60% of all isolates and for 91 % of penicillin-resistant isolates, table 111).
were
Management of PRSP meningitis During the study, cases were treated with benzylpenicillin (400000 U/kg per day) and chloramphenicol (75-100 mg/kg per day) pending CSF culture results. If a PSSP was isolated, benzylpenicillin alone was continued. After identification of a PRSP (usually 24-48 h after admission), chloramphenicol alone was continued if the patient was progressing satisfactorily. In 12 (48%) of 25 infections due to S pneumoniae that was chloramphenicol susceptible but moderately penicillin resistant, initial treatment with chloramphenicol was either changed (to ceftriaxone in 10 children) or supplemented (with vancomycin in 2) because of unsatisfactory clinical response. In 3 children who did not respond adequately to chloramphenicol, a lumbar puncture was repeated before changing treatment-ie, 24-48 h after starting treatment and 1-2 h after an intravenous dose of chloramphenicolbut pneumococci were not reisolated from CSF. However, in all 3 cases, CSF chloramphenicol bactericidal activity was no more than 1 in 4. Despite a change in therapy, all 3 children died. 3 children
whose treatment was changed from chloramphenicol had been on phenobarbital for convulsions. Chloramphenicol blood concentrations, measured in 2, were in the therapeutic range (16 and 20 TABLE II-CHARACTERISTICS OF CHILDREN WITH PENICILLIN-SENSITIVE AND PENICILLIN-RESISTANT PNEUMOCOCCAL MENINGITIS
Differences between children with PRSP and those with PSSP analysed with Fisher’s exact test. The t test and the Mann-Whitney U-test were used to assess differences in measured outcomes depending on distribution. were
Results 84
children
with
were assessed.
meningitis 20 days and died.9
culture-positive
pneumococcal
1 child had a probable relapse after
Microbiology The antimicrobial resistance of the strains is shown in table I. Overall penicillin resistance rate was 42 %; in 1989, it was 37% (16/43) and in 1990/91 it increased to 46% (19/41). Of 35 PRSP isolated, 32 (91 %) were community acquired. Clinical details of cases of PRSP and PSSP meningitis are
Data given as no of children with feature unless otherwise indicated *Median (Interquartile range), tMedlan (range), tMean (SD), §One
excluded’, "p
