Appendix: Details of cited studies

 

Outcomes

Author

Date

Country

Antibiotics

Sample size

Level of evidence

Proportion of meningococcal cases

Mortality

Auditory or Neurological Sequelae

CSF Sterilisation

Adverse effects

Barson

1985

USA

Ceftriaxone vs chloramphenicol-ampicillin

 

50 children

 

1b[1]

 

6% (n=3)

 

No deaths occurred

 

No significant difference

Sterility at 10.5-18h:

ceftriaxone 67%

chloram-amp 60%

(p>0.05)

diarrhoea:

ceftriaxone 59% chloram-amp 22%

(p<0.01)

Congeni

1984

USA

Ceftriaxone vs chloramphenicol-ampicillin

 

45 children

 

1b

 

9% (n=4)

 

 ceftriaxone 2 (9%)

chlor-amp 1 (4%)

p>0.05

 

ceftriaxone 13%

chlor-amp 22%

(p>0.05)

sterility at 24h:

ceftriaxone 95%

chlor-amp 78%

(p>0.05)

transient eosinophilia neutropenia, anaemia or diarrhoea:

ceftriaxone 23%

chlor-amp 9%

 

Del Rio

1983

Texas

Ceftriaxone vs chloramphenicol + ampicillin

 

78 children

 

1b- [2]

 

11.5% (n=9)

 

No deaths occurred

 

ceftriaxone 13%

chlor-amp 15%

(p>0.05)

Reduced colony count at 4-12h:

ceftriaxone 54%

chor-amp 49%

(p=0.58)

All sterile at 24h

 

diarrhoea:

ceftriaxone 41%

chor-amp 21%

p<0.05

Girgis

1988

Cairo

Ceftriaxone vs chloramphenicol + ampicillin

 

70 children

 

1b

 

38.6% (n=27)

ceftriaxone 6 (17%)

chlor-amp 9 (26%)

(p>0.05)

No sequelae developed in any surviving patient

CSF sterile in all surviving patients at 6 days

diarrhoea: with ceftriaxone 5.7%

chlor-amp 0%

(p>0.05)

 

Hassan

1976

Egypt

 

Epicillin vs ampicillin

96 adults and children

 

1b-

 

78% (n=75)

 

total deaths 13 (13%)

comparable rates between groups (data not presented)

7 day follow up showed comparable rates of good recovery (data not presented)

Response rate non-significantly slower with epicillin (data not presented)

 

 

no adverse drug reactions

Jacobs

1985

USA

Cefotaxime vs chloramphenicol-ampicillin

 

50 children

 

1b- 2

 

16% (n=8)

 

chlor-amp 1 (4%)

cefotaxime 0 (0%)

 

chlor-amp 5 (19%)

cefotaxime 5 (22%)

Sterile by day 2:

cefotaxime 100%

chlor-amp:data not presented

 

no adverse drug reactions

Manios

1969

Greece

Ampicillin vs combined sulphadimidine-penicillin G

 

159 children

 

1b

 

100% (n=159)

 

ampicillin 3 (4%)

sulph-penG 3 (3.6%)

 

(p>0.05)

ampicillin 1 (1.5%)

sulph-penG 3 (3.6%)

(p>0.05)

 

No long-term follow-up for sequelae

Time to normal CSF:

ampicillin 12.4 days

sulph-penG 13.4days

 

CSF sterility:

all sterile by 48h

severe drug reaction (thrombocytopenia or haematuria): ampicillin 0 (0%)

sulph-penG 3 (3.6%)

 

Outcomes

Author

Date

Country

Antibiotics

Sample size

Level of evidence

Proportion of meningococcal cases

Mortality

Auditory or Neurological Sequelae

CSF Sterilisation

Adverse effects

 

Marks

1985

USA

 

Cefuroxime vs chloramphenicol-ampicillin

 

107 children

 

1b

 

6.5% (n=7)

 

cefuroxime 1 (2%)

chlor-amp 1 (1.8%)

(p>0.05)

 

cefuroxime 5 (10%)

chlor-amp 4 (7%)

 

No long-term follow-up for sequelae

sterility at day 2: 100% meningococcal cases

No difference between treatment groups (p>0.05)

mild rash or diarrhoea:

cefuroxime 4 (8%)

chlor-amp 3 (5%)

Nathan

2005

Niger

Ceftriaxone

Vs chloramphenicol

 

308 children

 

1b-[3]

 

100%

 

ceftriaxone 6 (4%)

chloramph 5 (3%)

(p>0.05)

at 72h:

ceftriaxone 14 (9%)

chloramph 9 (6%)

(p>0.05)

 

not measured in this trial

 

no adverse effects

 

Overturf

1977

California

 

Carbenicillin vs ampicillin

 

86

(62 children)

 

1b

 

8%

(n=7 children)

 

 

ampicillin 3 (6.5%)

carbenicillin 0 (0%)

(p>0.05)

significant sequelae:

 

ampicillin 8 (17%)

carbenicillin 5 (13%)

(p>0.05)

sterility at 24h:

 100% patients

No significant differences between treatment groups

eosinophilia, rash, diarrhoea or fever:

carbenicillin 27%

ampicillin 17.5%

 

Pecoul

1991

Mali, Niger

 

Chloramphenicol vs

Ampicillin

 

528 children

 

1b-3

 

30.5% (n=161)

case fatality rate at day 4:

chloram 28%

ampicillin 24.5%

(95%CI = 0.86-1.52)

deaths or serious sequelae at discharge

chloram 45.3%

ampicillin 39.1%

(95%CI = 0.95-1.42)

 

not measured in this trial

 

no adverse effects reported

 

Peltola

1989

Finland

 

Chloramphenicol vs ampicillin vs cefotaxime vs ceftriaxone

 

197 children

 

1b

 

16% (n=32)

 

chloram 3 (5.6%)

ampicillin 1 (2%)

cefotaxime 4 (7.8%)

ceftriaxone 1 (2%)

 

(not significant)

 

chloram 2 (3.7%)

ampicillin 2 (4.3%)

ceftriaxone 8 (16%)

 

(no significant differences)

sterile significantly earlier in Mnc4 meningitis than Hib[4] (p<0.01)

day 4 sterility all cases except 1 case of Hib treated with chloramphenicol

mild diarrhoea:

chloram 9 (17%)

ampicillin 7 (15%)

cefotaxime 6 (12%)

ceftriaxone 19 (38%)

significantly increased risk with ceftriaxone (p<0.05)

 

Rodriguez

1985

Dominican Republic

 

Ceftazidime vs chloramphenicol-ampcillin

 

100 children

 

2b[5]

 

18% (n=14)

 

ceftazidime 12(20%)

chlor-amp 8 (21%)

 

gross neurological sequelae:

ceftazidime 2 (5%)

chlor-amp 1 (4%)

CSF normalised by end of therapy in all patients

ceftazidime 10.2days

chor-amp 9.5 days

(mean duration)

diarrhoea, reactive arthritis:

ceftazidime 2 (3%)

diarrhoea, fever, leukopenia+anaemia chlor-amp 3 (8%)

 

Outcomes

Author

Date

Country

Antibiotics

Sample size

Level of evidence

Proportion of meningococcal cases

Mortality

Auditory or Neurological Sequelae

CSF Sterilisation

Adverse effects

 

Rodriguez

1986

Sulbactam-ampicillin vs chloramphenicol-ampicillin

 

81 children

 

2b

 

10% (n=8)

 

chlor-amp 6(18%) sulbactam-amp 1(3%)

 

chlor-amp 18% sulbactam-amp 12%

 

 

not measured

 

no significant difference

Rodriguez

1986

Ceftazidime vs chloramphenicol-ampicillin

100 chilren

 

1b

 

18% (n=14)

ceftazidime 12