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Antibiotics for preventing complications in children with measles

  1. Sushil K Kabra1,*,
  2. Rakesh Lodha2

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 14 AUG 2013

Assessed as up-to-date: 24 MAY 2013

DOI: 10.1002/14651858.CD001477.pub4


How to Cite

Kabra SK, Lodha R. Antibiotics for preventing complications in children with measles. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD001477. DOI: 10.1002/14651858.CD001477.pub4.

Author Information

  1. 1

    All India Institute of Medical Sciences, Pediatric Pulmonology Division, Department of Pediatrics, Ansari Nagar, New Delhi, India

  2. 2

    All India Institute of Medical Sciences, Department of Pediatrics, Ansari Nagar, New Delhi, India

*Sushil K Kabra, Pediatric Pulmonology Division, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India. skkabra@hotmail.com. skkabra@rediffmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 14 AUG 2013

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Characteristics of included studies [ordered by study ID]
Anderson 1939

MethodsAlternate participants were allocated to control or treatment groups


Participants125 children with measles admitted to a hospital in Glasgow. 86% were under 6 years. Control group: 62 + 1 (withdrawn - measles not confirmed). Intervention group: 63. However, 13 participants in the control group and 16 participants in the intervention group already had pneumonia or empyema at the time of enrolment, therefore participants available for analysis of primary outcome (pneumonia) in the 2 groups were 49 and 47 patients respectively

On admission participants were:
- given diphtheria antitoxin 4000 units
- assessed for complications

Appearance of rash was considered first day of illness

Evaluation done by 1 person

Evenly balanced by age, sex and duration of illness before admission


InterventionsThe treatment group was given sulphanilamide 0.25 g to those under 5 and 0.5 g to those over 5

Children under 5 years were given 0.25 g 4-hourly for 10 days, followed by 0.25 g 3 times a day until discharge
Children over 5 years were given 0.5 g hourly for 10 days, followed by 0.25 g 3 times a day until discharge
All participants received the same nursing and general care


OutcomesThe duration in days of primary pyrexia
The duration in days until clinical cure of complications noted on admission
The incidence and nature of complications arising in hospital
The duration in days of clinical complications arising in hospital
The duration in days of residence in hospital. There were more complications in the sulphanilamide group


Notes1 control withdrawn (measles not confirmed)
Conclusion: sulphanilamide decreases duration of bronchopneumonia, but has no effect on other complications


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAlternate participants were allocated to 2 groups

Allocation concealment (selection bias)High riskAlternate participants received study drug with supportive care or only supportive care

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDetails of all the participants not mentioned in the text

Selective reporting (reporting bias)Unclear riskNot clear from paper

Other biasUnclear riskNo details about supporting agency

Garly 2006

MethodsRandomised, double-blind, placebo-controlled trial


Participants84 children (age range 0.49 to 24.8 years) with measles. Separate data for children below 18 years (81 children) were obtained from trial authors


InterventionsThe treatment group received co-trimoxazole. Children below 5 years of age and weighing < 18 kg received paediatric cotrimoxazole tablets 3 times a day and those above 5 years or > 18 kg received adult cotrimoxazole tablets twice a day. Control group received a placebo twice a day


OutcomesTreatment failure due to pneumonia, admission to hospital or both. Other morbidities


Notes2 participants in the treatment group and 1 patient in the control group received the wrong dose of the trial drug. A total of 87 participants were enrolled in the study. Follow-up of 1 and 2 participants, respectively, was not available in the treatment and control groups and these participants were not included in the intention-to-treat analysis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot clear from paper

Allocation concealment (selection bias)Low riskDouble-blind RCT

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blind randomized controlled trial

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blind randomized controlled trial

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll data shown

Selective reporting (reporting bias)Low riskNone

Other biasLow riskNone

Gibel 1942

MethodsParticipants were divided into 2 groups on admission


Participants401 children with measles admitted to King's Avenue Hospital, New York from December 1940 to June 1941. Separate data for those who already had pneumonia were not mentioned in the paper. However, data on uncomplicated cases (we presume children without pneumonia) in intervention and control groups at time of enrolment were 82 and 148 respectively. All aged under 6 years

Control group: 201 participants
Treatment group: 153 participants

Duration of illness similar at the time of admission


InterventionsThe treatment group received sulfathiazole according to body weight
Dose 215 mg/kg for the first 24 hours, then 143 mg/kg daily until discharge
Controls were treated symptomatically
Otherwise the participants received the same nursing care and were admitted to the same ward


OutcomesDuration in days of primary pyrexia
Duration in days until clinical cure of complications noted on admission
Incidence and nature of complications arising in hospital
Duration in days of clinical complications arising in hospital
Duration in days of residence in hospital
Death rate of measles complicated by bronchopneumonia as compared to previous years
A comparison of the death rate in this hospital in previous years and the death rate this year with sulfathiazole


NotesOne case of bronchopneumonia and 1 case of otitis media were excluded


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot mentioned in the text

Allocation concealment (selection bias)High riskParticipants who had pneumonia were not allocated to the no antibiotics group

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen-label trial

Blinding of outcome assessment (detection bias)
All outcomes
High riskOpen-label trial

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskParticipants who had pneumonia and other complications were allocated to intervention and control groups. Outcome of those who did not have pneumonia at time of enrolment are not very clearly mentioned

Selective reporting (reporting bias)Unclear riskDetails of all the enrolled participants are not very clear

Other biasUnclear riskNo mention of supporting agency

Hogarth 1939

MethodsAlternate participants were assigned to treatment and control groups


Participants329 children admitted to a hospital with measles from December 1937 to July 1938
74% were under 4 years of age. No withdrawals

158 received proseptasine

Cases were graded into mild, moderate and severe on admission
The participants were stratified in the 2 groups by degree of severity (toxemia, intensity of rash, condition of the mouth)
Prophylactic dose of diphtheria antitoxin given at the time of admission
The control group had more younger children
These differences were considered slight and did not preclude comparison

All participants assessed by 1 person at the time of admission


InterventionsThe treatment group received para-benzylaminobenzenesulphonamide (proseptasine) for a period of 10 days after admission to hospital:
< 1 year, 0.5 g 3 times a day for 5 days, then 0.5 g twice a day for 5 days
1 to 5 years, 1 g 3 times a day for 5 days, then 0.5 g 3 times a day for 5 days
> 5 years, 1 g 4 times a day for 5 days, then 0.5 g 4 times a day for 5 days

Duration of treatment 10 days

Controls received no antibiotic or placebo but got the same nursing care


OutcomesComplications observed for 12 days after admission

Bronchopneumonia - clinical or X-ray
Acute otitis media
Cervical adenitis
Enteritis
Other complications (tonsillitis, conjunctivitis, boils, styes)


NotesConclusion: proseptasine is of value in reducing the incidence of complications such as bronchopneumonia, acute otitis media and cervical adenitis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAlternate participants received intervention or no treatment

Allocation concealment (selection bias)High riskAlternate participants were assigned to intervention and control group

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen-label trial

Blinding of outcome assessment (detection bias)
All outcomes
High riskOpen-label trial

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDetails of all the enrolled participants available

Selective reporting (reporting bias)Unclear riskNot clear from data

Other biasUnclear riskNo mention of financial support

Karelitz 1951

MethodsFirst 15 participants were given chlortetracycline, then subsequent participants were treated with chlortetracycline or penicillin or remained untreated


ParticipantsChildren all aged under 9 years admitted from 15 February to 15 May 1950 to the Willard Parker Hospital, New York

Chlortetracycline: 45 participants
Penicillin: 44 participants
No therapy: 43

Onset of illness: appearance of rash
All seen by trial author soon after admission
Seen daily for severity and complications
Chest X-ray done in 35 cases assigned penicillin or chlortetracycline groups


InterventionsChlortetracycline, procaine penicillin

First 15 cases were treated with chlortetracycline, later alternate cases were given chlortetracycline or penicillin or left untreated

Dose: chlortetracycline: oral 60 mg/kg 4 times a day
Penicillin: IM 300,000 units

3/4 of the chlortetracycline treated participants started therapy in the pre-eruptive period or at the beginning of the rash
3/5 of the penicillin treated participants were given their first dose of penicillin at the beginning of the rash


OutcomesDuration and intensity of the rash, temperature, rhinorrhea, photophobia, cough and complications
Pneumonia
Death

None of the participants developed complications in the chlortetracycline group, 1 in the penicillin group and 10 in the untreated group


NotesConclusion: very few of the untreated control cases were observed by the trial authors. Information was obtained from hospital records. There were problems with ascertaining duration of cough, photophobia and rhinorrhea
The main difference was in the complications that developed in the untreated group and the prolonged course in these cases
Children receiving chlortetracycline or penicillin had reduced fever duration
Neither chlortetracycline nor penicillin given to children with pre-eruptive rubeola or begun on the first day of rash seem to have had any definite therapeutic effect on the course of the primary disease
Temperature from appearance of rash lasted 2.2, 2.8 and 4.4 days in the chlortetracycline, penicillin and control groups, respectively
An earlier drop in temperature in the treated cases was statistically significant
Chlortetracycline and penicillin were effective against otitis media and pneumonia present on admission, and for the complications which developed during the course of the disease
Chlortetracycline and penicillin are useful in the prevention and cure of secondary infection in measles


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskFirst 15 participants were given chlortetracycline, then subsequent participants were treated with chlortetracycline or penicillin or remained untreated

Allocation concealment (selection bias)Unclear riskNo details about allocation concealment mentioned in the paper

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen-label

Blinding of outcome assessment (detection bias)
All outcomes
High riskOpen-label

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot clear from data

Selective reporting (reporting bias)Unclear riskNot clear from data

Other biasUnclear riskNot clear from paper

Karelitz 1954

MethodsConsecutive inpatients; children with complications were alternated into the 2 penicillin groups while children without complications were left untreated


ParticipantsChildren with measles admitted to William Parker Hospital, New York
98% aged < 10 years

Benzethacil: 61 participants
Procaine penicillin: 67 participants
No treatment : 41 participants

Additional 87 participants were observed in April and May 1953

Ages of the 2 groups were well-balanced


InterventionsAqueous benzethacil 600,000 units single injection in children under 5 years
Aqueous procaine penicillin 300,000 units on admission and daily for a total of 4 doses
Aqueous procaine penicillin 600,000 units on admission and repeated on the third and sixth days


OutcomesPneumonia - diagnosed clinically and also confirmed by X-ray

Discharged within 2 to 3 days. Could not observe late complications


NotesFever in treatment groups was of a shorter duration
No complications observed in the group receiving 4 doses of aqueous penicillin
2 children developed bacterial complications in the benzathine penicillin group


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot mentioned

Allocation concealment (selection bias)Unclear riskNot used

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen-label

Blinding of outcome assessment (detection bias)
All outcomes
High riskOpen-label

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot clear from paper

Selective reporting (reporting bias)Unclear riskNot clear from paper

Other biasUnclear riskUnclear

Prasad 1967

MethodsParticipants were given placebo or tetracycline. Patient allocation not clear


ParticipantsInpatients and outpatients at SN Medical College, Agra, India

90% < 5 years
27 cases > 5 years of age

158 children were randomized:
- 78 to tetracycline
- 80 to placebo


InterventionsTetracycline 33 mg/kg for 7 days or placebo


OutcomesComplications
Clinical improvement, i.e. temperature, cough and general condition

216 cases had an X-ray examination. 16 were Mantoux-positive and showed radiological changes - hilar gland enlargement, infiltration, increased lung marking. These participants were excluded from the study


NotesRadiological changes were 50% less with tetracycline and serious complications like bronchopneumonia and lobar type were completely absent

Use of tetracycline reduces the incidence of serious complications like consolidation and lung collapse and perhaps subsequent sequelae like bronchiectasis and pulmonary fibrosis
81 cases were followed for 6 to 7 months


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot mentioned

Allocation concealment (selection bias)Unclear riskDouble-blind randomized trial

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blind

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blind randomized trial

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskAll enrolled participants accounted for

Selective reporting (reporting bias)Unclear riskAll enrolled participants accounted for

Other biasUnclear riskFunding not mentioned

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Samb 1995Cohort study comparing the development of respiratory symptoms and case-fatality rates with historical controls. Not a controlled trial

Thompson 1938Children hospitalised with severe measles treated with sulphonamide or benzyl sulphonamide were compared to children with a milder form of measles (who did not receive antibiotics) for development of bronchopneumonia, otitis media, laryngitis, rhinitis and skin infections. Not a controlled trial

Weinstein 1955Children with measles without obvious secondary infections. Compared children who received antibiotics prescribed by their primary care physicians and those who did not receive antibiotics for development of pneumonia, otitis media, laryngitis and laryngotracheobronchitis. Not a controlled trial

 
Comparison 1. Antibiotic versus placebo or no antibiotic (excluding children with pneumonia or sepsis on admission)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Development of pneumonia (7 studies)71263Odds Ratio (M-H, Random, 95% CI)0.35 [0.12, 1.01]

 2 Development of diarrhoea4766Odds Ratio (M-H, Random, 95% CI)0.53 [0.23, 1.22]

 3 Development of conjunctivitis2212Odds Ratio (M-H, Random, 95% CI)0.39 [0.15, 1.00]

 4 Development of otitis media51033Odds Ratio (M-H, Random, 95% CI)0.34 [0.16, 0.73]

 5 Development of croup1130Odds Ratio (M-H, Random, 95% CI)0.16 [0.01, 4.06]

 6 Development of tonsillitis2256Odds Ratio (M-H, Random, 95% CI)0.08 [0.01, 0.72]

 7 Death71482Odds Ratio (M-H, Random, 95% CI)3.04 [0.47, 19.63]

 
Comparison 2. Baseline characteristics of participants

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Median age184Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 Male sex3607Odds Ratio (M-H, Random, 95% CI)1.15 [0.69, 1.91]

 3 Weight for age z-score < -2175Odds Ratio (M-H, Random, 95% CI)2.73 [0.97, 7.71]

 4 Children below age of two years51243Odds Ratio (M-H, Random, 95% CI)1.50 [1.18, 1.92]

 5 Age less than one year4914Odds Ratio (M-H, Random, 95% CI)1.23 [0.81, 1.85]

 
Comparison 3. Sensitivity analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Development of pneumonia (without Prasad 1967)61106Odds Ratio (M-H, Random, 95% CI)0.34 [0.07, 1.52]

 2 Development of pneumonia (without Karelitz 1951)61131Odds Ratio (M-H, Random, 95% CI)0.41 [0.13, 1.26]

 3 Development of pneumonia (without Karelitz 1954)61026Odds Ratio (M-H, Random, 95% CI)0.48 [0.17, 1.36]

 4 Development of pneumonia (without Hogarth 1939)6934Odds Ratio (M-H, Random, 95% CI)0.33 [0.09, 1.22]

 5 Development of pneumonia (without Gibel 1942)61033Odds Ratio (M-H, Random, 95% CI)0.26 [0.12, 0.60]

 6 Development of pneumonia (without Garly 2006)61181Odds Ratio (M-H, Random, 95% CI)0.40 [0.12, 1.32]

 7 Development of pneumonia (without Anderson 1939)61167Odds Ratio (M-H, Random, 95% CI)0.30 [0.08, 1.14]

 8 Death (without Gibel 1942)61021Odds Ratio (M-H, Random, 95% CI)3.05 [0.31, 30.15]

 9 Death (without Anderson 1939)61357Odds Ratio (M-H, Random, 95% CI)2.06 [0.21, 19.94]

 10 Diarrhoea (without Karelitz 1954)3510Odds Ratio (M-H, Random, 95% CI)0.57 [0.23, 1.44]

 11 Diarrhoea (without Hogarth 1939)3437Odds Ratio (M-H, Random, 95% CI)0.32 [0.13, 0.78]

 12 Diarrhoea (without Garly 2006)3685Odds Ratio (M-H, Random, 95% CI)0.58 [0.20, 1.71]

 13 Diarrhoea (without Anderson 1939)3685Odds Ratio (M-H, Random, 95% CI)0.58 [0.20, 1.71]

 14 Development of otitis media (without Garly 2006)4952Odds Ratio (M-H, Random, 95% CI)0.34 [0.15, 0.75]

 15 Development of otitis media (without Anderson 1939)4914Odds Ratio (M-H, Random, 95% CI)0.33 [0.13, 0.80]

 16 Development of otitis media (without Gibel 1942)4658Odds Ratio (M-H, Random, 95% CI)0.34 [0.16, 0.73]

 17 Development of otitis media (without Karelitz 1951)4904Odds Ratio (M-H, Random, 95% CI)0.41 [0.19, 0.92]

 18 Development of otitis media (without Hogarth 1939)4704Odds Ratio (M-H, Random, 95% CI)0.28 [0.10, 0.80]