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. 2021 Jun 23;2021(6):CD002007. doi: 10.1002/14651858.CD002007.pub5

Summary of findings 1. Summary of findings: single compared with combination intravenous anti‐pseudomonal antibiotic therapy for people with cystic fibrosis ‐ short‐term effects.

Single compared with combination intravenous anti‐pseudomonal antibiotic therapy for people with cystic fibrosis ‐ short‐term effects
Patient or population: children and adults with cystic fibrosis
Settings: inpatient or outpatient
Intervention: combination IV antibiotic therapy
Comparison: single IV antibiotic
Outcomes Illustrative comparative risks* (95% CI) Relative effect
(95% CI) No of Participants
(trials) Quality of the evidence
(GRADE) Comments
Assumed risk Corresponding risk
Single IV antibiotic therapy Combined IV antibiotic therapy
Change in FEV1 % predicted at end of antibiotic course: absolute post‐treatment values
 
Follow‐up: 10 ‐ 14 days
The mean FEV1 (% predicted) ranged across control groups from
46% to 50.9%. The mean FEV1 (% predicted) in the intervention groups was
5.25% higher (9.14% lower to 19.64% higher). MD 5.25 (95% CI ‐9.14 to 19.64) 93
(2) ⊕⊕⊝⊝
lowa,b
 
3 further trials reported on this outcome, but it was not possible to include the data in our analyses.
Master reported that the combination antibiotic group had a significantly higher FEV1 % predicted after 10 days of treatment (P < 0.05) (Master 1997).
McCarty reported a "similar improvement" in FEV1 in both groups but no further detail (McCarty 1988).
The elective trial reported higher median values for FEV1 % predicted in the combination group at baseline and Day 14, but at Day 90 the median was higher in the single antibiotic group (Pedersen 1986).
Change in sputum P aeruginosa density at end of treatment (cfu/g)
 
Follow‐up: 10 ‐ 14 days
The mean (SD) sputum P aeruginosa density was 6.9 cfu/g (15.5) in the control group. The mean sputum P aeruginosa density in the intervention groups was
1.60 cfu/g lower.
(9.51 cfu/g lower to 6.31 cfu/g higher). MD ‐1.60 cfu/g (95% CI ‐9.51 to 6.31) 76
(1) ⊕⊕⊕⊝
moderateb
 
2 further trials looked at bacterial concentration, but used different measures and reported within‐group differences only. McLaughlin reported a significant decrease in bacterial concentration (cfu/mL) in the combination group and a non‐significant decrease in the single antibiotic group (McLaughlin 1983).
McCarty reported 5/19 P aeruginosa isolates in the single therapy group decreased in titre by more than 10² cfu/mL compared to 12/19 P aeruginosa isolates in the combination group (McCarty 1988).
Additional treatment required
 
This outcome was not measured in the short term.  
Time to next course of antibiotics
 
This outcome was not reported in the short term.  
Adverse events during treatment
 
Follow‐up: 10 ‐ 14 days
There were no differences between single or combination IV antibiotic therapy:
  • erythema at injection site, RR 0.46 (95% CI 0.09 to 2.36);

  • generalised rash, RR 6.16 (95% CI 0.12 to 316.67);

  • fever, RR 0.81 (95% CI 0.05 to 14.14);

  • renal impairment, RR 1.54 (95% CI 0.15 to 15.56);

  • auditory impairment, RR 5.86 (95% CI 0.11 to 305.44); and

  • proteinuria, RR 3.62 (95% CI 0.68 to 19.30).


 
N/A 131
(2) ⊕⊕⊝⊝
lowb,c
 
4 further trials provided narrative information on adverse events.
Master reported tinnitus in 2 participants (1 in each group) which was thought to be related to tobramycin (Master 1997).
Parry reported phlebitis in 6 participants, eosinophilia in 5 participants and urticaria in 1 participant, all in the single antibiotic group (Parry 1977).
 
The two remaining trials reported no serious adverse events or incidences of auditory problems or nephrotoxicity in either group (Costantini 1982Pedersen 1986).
Quality of life
 
This outcome was not measured in the short term.  
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
cfu: colony forming units; CI: confidence interval; FEV1: forced expiratory volume in 1 second; IV: intravenous; MD: mean difference; RR: risk ratio; SD: standard deviation.
GRADE Working Group grades of evidence
High certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low certainty: we are very uncertain about the estimate.

a. Downgraded once as there was an unclear risk of bias across some domains across the two trials. In one trial the randomisation methods weren't described adequately and both trials had a high dropout rate.

b. Downgraded once due to small sample size or low event rate, or both.

c. Downgraded once due to risk of bias within one of the included trials, particularly in the domains of sequence generation and blinding.