Table 91Summary of included studies for antimicrobials for pulmonary exacerbations with P aeruginosa

StudyIntervention/ComparisonPopulationOutcomesComments
Cochrane systematic reviews
Hurley 2015
Cochrane SR		Comparison 1. Single IV agents compared Comparison 2. Single IV (with placebo) vs combination of IV antibiotics Comparison 3. Single IV vs combination of IV antibiotics Comparison 4. Combination of antibiotics vs combination of antibiotics Participants diagnosed with cystic fibrosis using the Cystic Fibrosis Foundation diagnostic consensus statement, of all ages and all levels of severity. All studies that explicitly aimed to trial an IV antibiotic for the treatment of pulmonary exacerbation were considered.
  • Lung function (FEV1)
  • Time to next exacerbation
  • Quality of life (CFQ-R)
  • Mortality (cystic fibrosisrelated and all causes)
  • Adverse events
AMSTAR score: 11/11
Primary studies included in the Cochrane SR
Blumer 2005
(USA)
RCT		Intervention 1: IV meropenem 40 mg/kg up to a maximum dose of 2 g and IV tobramcyin (given for a mean of 13.5 days)
Intervention 2: IV ceftazidime 50 mg/kg up to a maximum dose of 2 g and IV tobramycin (given for a mean of 14.1 days)
  • Tobramycin dose adjusted to give a peak serum concentration of>= 8 µg/mL and trough concentration of < 2 µg/mL
N=121 participants with a recent (usually < 1 month) culture of P aeruginosa or B cepacia complex recruited at a protocol-de fined exacerbation.
  • Age: ≥ 5 years of age
  • Lung function (FEV1)
Included in Cochrane SR Hurley 2015
Conway 1997
(UK)
RCT		Intervention 1: IV colistin (2 MU 3× daily).
Intervention 2: IV colistin (2 MU 3× daily) and a second anti-pseudomonal antibiotic		N=71 adults with cystic fibrosis and chronic P aeruginosa experiencing a protocol-defined exacerbation.
  • Mean age (SD): 21 (4.2) years.
  • FEV1
  • Mortality
  • Adverse effects
Included in Cochrane SR Hurley 2015
De Boeck 1989
(Belgium
RCT		Intervention 1: IV ceftazidime 50 mg/kg 3× daily.
Intervention 2: IV piperacillin 75 mg/kg 4× daily and IV tobramycin 10 mg/kg/day in3 doses		N=21 participants with cystic fibrosis and a protocol-defined pulmonary exacerbation, chronically infected with P aeruginosa that was sensitive to piperacillin, tobramycin and ceftazidime
  • Mean age 14.8 years
  • FEV1
  • Time to readmission
  • Mortality
Included in Cochrane SR Hurley 2015
Elborn 1992
(UK)
RCT		Intervention 1: IV ceftazidime 2 g 3× daily.
Intervention 2: IV aztreonam 2 g 3× daily.		N=24 participants with cystic fibrosis and chronic P aeruginosa infection experiencing exacerbations.
Mean (range) age: 20 (14 to 48) years
  • FEV1
Included in Cochrane SR Hurley 2015
Gold 1985
(Canada)
RCT		Intervention 1: IV ceftazidime 200 mg/kg/day in 4 doses.
Intervention 2: IV ticarcillin 300 mg/kg/day in 4 doses and IV tobramycin 10 mg/kg/day in 3 doses		N=30 participants with cystic fibrosis and P aeruginosa infection present at the previous clinic visit, experiencing an acute respiratory exacerbation.
  • Age >12 years. Mean age (SD): 18.9 (1.1) in group 1; 17.8 (0.8) in group 2
  • FEV1
  • Adverse effects
Included in Cochrane SR Hurley 2015
Macystis fibrosisarlane 1985
(Australia)
RCT		Intervention 1: IV piperacillin 50 mg/kg 4-hourly.
Intervention 2: IV placebo 5% dextrose 4-hourly
Intervention 3: IV piperacillin 100 mg/kg 8-hourly.
Intervention 4: IV placebo 5% dextrose 8-hourly.
All participants received IV tobramycin 2.5 mg/kg 3× daily, oral flucloxacillin 25 mg/kg/day in 4 doses and oral probenecid (suggested to increase antibiotic concentrations) 250 - 500 mg 3× daily
Duration: 14 days.		N=19 participants aged over 8 years with cystic fibrosis with P aeruginosa in sputum admitted to hospital for worsening respiratory status.
  • Mean age: 13.7 to 15.6 years
  • FEV1
  • Adverse effects
Included in Cochrane SR Hurley 2015 Pseudomonas was not eradicated from the sputum in any of the patients
Master 2001
(Australia)
RCT		Intervention 1: IV ceftazidime 50 mg/kg/dose 3× daily and IV tobramycin 3 mg/kg/dose 3× daily
Intervention 2: IV tobramycin 9 mg/kg/day 1× daily.
Duration: at least 10 days.		N=51 participants with cystic fibrosis experiencing a protocol-defined exacerbation with P aeruginosa isolated from sputum. Participants with an FVC lower than 40% predicted were excluded.
  • Mean age (SD): 16 (7) years in group 1; 14 (5) years in group 2
  • FEV1
  • Adverse effects
Included in Cochrane SR Hurley 2015
McCarty 1988
(USA)
RCT		Intervention 1: IV piperacillin 600 mg/kg/day (regimen not detailed)
Intervention 2: IV piperacillin 600 mg/kg/day and tobramycin 8 - 10 mg/kg/day (regimen not detailed
Duration: at least 10 days.		N=17 children with cystic fibrosis admitted for treatment of pulmonary exacerbations with P aeruginosa.
  • Age range: 2 to 12 years.
  • FEV1
  • Eradication of pseudomonas
  • Adverse effects
Included in Cochrane SR Hurley 2015
Richard 1997
(Switzerland)
RCT		Intervention 1: oral ciprofloxacin 15 mg/kg 2× daily.
Intervention 2: IV ceftazidime 50 mg/kg 3× daily and IV tobramycin 3 mg/kg 3× daily
Duration: 14 days.		N=108 children with cystic fibrosis and P aeruginosa infection and experiencing a protocol-defined pulmonary exacerbation with P aeruginosa.
  • Mean age: 10.2 years in group 1; 11 years in group 2. Age range: 5 to <17.
  • Eradication of pseudomonas
  • Adverse effects
Included in Cochrane SR Hurley 2015
Salh 1992
(UK)
RCT		Intervention 1; IV aztreonam 8 g/day in 4 doses.
Intervention 2: IV ceftazidime 8 g/day in 4 doses.
Duration: 2 weeks		N=22 participants with cystic fibrosis and P aeruginosa sensitive to the study drugs who were admitted to hospital due to an infective exacerbation
  • Age range: 16 to 32 years.
  • FEV1
Included in Cochrane SR Hurley 2015
Schaad 1987
(Switzerland)
RCT		Intervention 1: IV ceftazidime 250 mg/kg/day in 4 doses and IV amikacin 33 mg/kg/day in 3 doses
Intervention 2: IV ceftazidime 250 mg/kg/day in 4 doses and IV amikacin 33 mg/kg/day in 3 doses and nebulised amikacin 100 mg 2× daily
Duration: 15 days		N=62 participants with cystic fibrosis admitted with an acute pulmonary exacerbation who had P aeruginosa isolated on admission. Those who had been admitted to hospital in the recent 6 months were excluded
  • (n=87 courses of therapy by random assignment)
  • Age range: 3 to 24 years.
  • Adverse effects
Included in Cochrane SR Hurley 2015
Schaad 1989
(Switzerland)
RCT		Intervention 1: IV aztreonam 300 mg/kg/day in 4 doses and IV amikacin 36 mg/kg/day in 3 doses
Intervention 2: IV ceftazidime 300 mg/kg/day in 4 doses and IV amikacin 36 mg/kg/day in 3 doses for 2 weeks followed by oral ciprofloxacin 30 mg/kg/day for 4 weeks
Duration: 2 weeks IV treatment, with oral treatment extended for a further 4 weeks in1 group		N=42 participants with cystic fibrosis admitted with a protocol-defined pulmonary exacerbation and P aeruginosa isolated at admission. Those who had been admitted to hospital in previous 4 months were excluded
  • (n=56 treatment courses by random assignment)
  • Mean age (SD): 15.4 (6) years (range 2.3 to 25.4 years).
  • Eradication of Pseudomonas
  • FEV1
  • Adverse effects
Included in Cochrane SR Hurley 2015
Wesley 1988
(New Zealand)
RCT		Intervention 1: IV ceftazidime 150 mg/kg/day (regimen not detailed) Intervention 2: IV tobramycin 7.5 mg/kg/day and IV ticarcillin 300 mg/kg/day (regimen not detailed)
Duration: 14 days		N=13 children with cystic fibrosis and severe chest disease with pseudomonas chest exacerbation.
  • Age range: 9 to 15 years.
  • Number of admission requiring iv antibiotics or death
  • Adverse effects
Included in Cochrane SR Hurley 2015 Conference abstract

FEV1: Forced Expiratory volume. Information provided in the table is adapted from Hurley 2015.

From: 9, Pulmonary monitoring, assessment and management

Cover of Cystic Fibrosis
Cystic Fibrosis: Diagnosis and management.
NICE Guideline, No. 78.
National Guideline Alliance (UK).
Copyright © NICE 2017.

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