Methods

Quasi‐randomised controlled trial using alternate group assignment. Placebo was not used.
Allocation concealment: no
Blinding of intervention: no
Completeness of follow up: yes
Blinding of outcome measurement: no

Participants

Single unit study in Montreal, Canada. Subjects recruited from 1 April 1971 to 31 March 1972. Infants with respiratory distress syndrome and having umbilical arterial catheters inserted were considered eligible for inclusion. Catheters were inserted under sterile conditions, within 24 hours of birth. There were 37 infants in the treatment group and 38 in the control group. Birth weight range was 720 ‐ 3500 grams and gestational age at birth ranged from 25 to 40 weeks.

Interventions

Ampicillin 25 mg/kg intravenously every 6 hours plus kanamycin 7.5 mg/kg intramuscularly every 12 hours versus no treatment. At catheter insertion and daily thereafter 1.5‐3 mL of blood for culture was collected from the catheter. Just prior to catheter removal, blood for culture was collected from a cleansed peripheral site on an upper limb (or in the event of death, via a cardiac puncture) and from the catheter. The distal 1‐2 cm of catheter was collected for culture in 33 treated infants and 35 control infants. The following organisms were considered contaminants: coagulase‐negative Staphylococci, Micrococcus species, alpha‐haemolytic Streptococcus, and diphtheroids.

Outcomes

Mortality: 11 of 37 treated infants and 10 of 38 control infants died. All deaths were judged to be due to hyaline membrane disease. Catheter‐drawn blood cultures just prior to catheter removal: positive in 8 of 37 treated infants (all considered contaminants) and 19 of 38 control infants (16 considered contaminants). Peripherally‐drawn blood cultures: positive in no treated infants and 3 of 38 control infants (one considered a contaminant). Of the two considered pathogens, one was Pseudomonas aeruginosa and the other was Staphylococcus aureus. The Pseudomonas was isolated from a post‐mortem cardiac puncture specimen, and also from a catheter‐drawn specimen collected prior to the infant's death. It was not isolated from the catheter tip, and blood cultures (both catheter‐drawn and peripherally‐drawn) 24 hours prior to death were negative. The Staphylococcus aureus was isolated in a blood culture specimen drawn 2 days after catheter removal. Catheter‐tip colonisation: organisms were isolated from the tips of catheters of 8 of 33 treated infants (6 were considered contaminants) and 19 of 35 control infants (13 were considered contaminants). Two infants (one from each group) had localised umbilical infection.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

Quasi‐randomised controlled trial using alternate group assignment. Placebo was not used.

Allocation concealment?

High risk

Allocation concealment: no

Blinding?
All outcomes

High risk

Blinding of intervention: no
Blinding of outcome measurement: no

Incomplete outcome data addressed?
All outcomes

Unclear risk

Completeness of follow up: yes

Methods

Quasi‐randomised controlled trial using group assignment based on date of birth (odd dates vs even dates). Placebo was not used.
Allocation concealment: no
Blinding of intervention: no
Completeness of follow up: yes
Blinding of outcome measurement: no

Participants

Single unit study in Rhode Island, United States. Subjects recruited from 15 January 1974 to 15 April 1975. Infants requiring insertion of an umbilical arterial catheter in the first 24 hours of life as part of their management were considered eligible for inclusion. All infants were catheterised for respiratory distress. Catheters were inserted using an aseptic technique. One hundred and thirty‐seven infants were enrolled. Eighty‐three were given antibiotics (58 as prophylaxis; 25 at treating physician request) and 54 were not.

Interventions

Infants born on even days were allocated to Group 1: penicillin 25,000 U/kg intravenously every 12 hours and kanamycin 5 mg/kg intramuscularly every 8 hours. Infants born on odd days were allocated to Group 2 or Group 3, at treating physician discretion. Those who were given antibiotics at the request of the treating physician were in Group 3. The remainder (Group 2) were given no antibiotics. Enrolled infants had blood for culture collected from a peripheral vein just prior to catheter insertion and at the time of catheter removal, and from the catheter at insertion and just prior to removal. The volume of blood collected for culture was 0.5 to 1 mL. At catheter removal, the tip was sent for culture.

Outcomes

Mean (standard deviation) birth weight was 1835 (644) grams in Group 1, 2036 (696) grams in Group 2, and 1686 (819) grams in Group 3. Mean (standard deviation) gestational age was 33 (3) weeks in Group 1, 33 (7) weeks in Group 2, and 32 (4) weeks in Group 3. Mean (standard deviation) duration of catheterisation was 76 (53) hours in Group 1, 76 (48) hours in Group 2, and 94 (63) hours in Group 3. Mortality was 9 of 58 in Group 1 (15.5%), 6 of 54 in Group 2 (11.1%) and 2 of 25 in Group 3 (8.0%). No death was attributed to infection. Peripherally‐collected blood cultures, taken at catheter removal, were obtained from 89 infants (65%); catheter blood cultures, taken just prior to catheter removal, were obtained from 87 infants (64%); catheter tip cultures were obtained from 98 catheters (72%). Rates of positive peripheral blood cultures were 0 of 36 in Group 1, 3 of 35 in Group 2 (two were considered pathogens), and 0 of 18 in Group 3. Catheter blood cultures were positive in 0 of 37 Group 1 infants, 14 of 34 Group 2 infants (four were considered pathogens), and 0 of 16 Group 3 infants. Catheter tip cultures were positive in 8 of 37 in Group 1 (none were considered pathogens), 12 of 36 in Group 2 (one was considered a pathogen), and 1 of 25 in Group 3 (not considered a pathogen). The two pathogens isolated in peripheral blood cultures were Proteus mirabilis and Escherichia coli. In both cases the same organism was isolated from catheter blood cultures but not from the catheter tip. Of the two infants concerned, one (positive for Proteus mirabilis) was clinically unwell, whereas the other was not. Two other infants, also in Group 2, had Escherichia coli isolated in catheter blood cultures but peripheral blood culture was either negative or not taken ‐ both infants were clinically well.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

Quasi‐randomised controlled trial using group assignment based on date of birth (odd dates vs even dates). Placebo was not used.

Allocation concealment?

High risk

Allocation concealment: no

Blinding?
All outcomes

High risk

Blinding of intervention: no
Blinding of outcome measurement: no

Incomplete outcome data addressed?
All outcomes

Low risk

Completeness of follow up: yes