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Table 1 Characteristics of included studies

From: Systematic review: the bioavailability of orally administered antibiotics during the initial phase of a systemic infection in non-ICU patients

Study Setting Disease
Phase of infection
Study design Study drug
Dosage regimen
Sample size
Age (y)
  Predefined outcomes Conclusion Risk of bias score
  Serum Concentrations or Cmax ( mg/l)
Tmax (h)
AUC (mg/l*h)
Bioavailability (F in %)
Farid et al, 1975
[25]
Hospitalized patients (Egypt) Salmonella bacteraemia associated with Schistosomiasis
Acute enteric fever/febrile
Cross-sectional
PK after first dose on the first and second day of therapy
amoxicillin
PO: 250mg qd
N=5
Age: 20-29
(N total:12, 7 with age<18 y)
  Day 1 Day 2 Cserum day 2 adequate for the treatment of the Salmonellae isolated from the urine and blood. 4/10
  2h 3h 4h 2h 3h 4h
Cserum       
Pat 7 0.12 4.1 3.1 3.5 - 2.4
Pat 8 2.0 1.1 - 3.3 - 0.7
Pat 9 7.1 - 2.1 8.5 - 1.15
Pat 10 3.1 3.25 1.0 0.63 - 2.0
Pat 11 3.5 3.95 3.65 1.57 - 3.9
Davies et al, 1979
[22]
Hospitalized patients (The Netherlands) Acute exacerbations of chronic bronchitis
Initial phase
Cross-sectional
PK after first dose of different antibiotics
1. amoxicillin
PO: 750mg
2. ampicillin
PO: 1000mg
1. N=23
2. N=17
Age: -
  Amoxicillin Ampicillin Amoxicillin measured serum concentrations generally satisfactory to treat H. influenza and S. pneumoniae
Ampicillin does not yield satisfactory concentrations in serum and sputum.
1/10
Cmax 11 (6-15 visual inspection) 8.3 (4-13 visual inspection)
Tmax 1.5 2
AUC 30.19 26.34
Bohte et al, 1995
[21]
Hospitalized patients (The Netherlands) CAP
Initial phase
Cross-sectional
PK around first and second dose
azithromycin
PO: 500 mg bd on day 1, thereafter od during 4 days
N=8
Age: 32-75
  3h 12h 15h Low Cserum during the first 12h of treatment as compared to healthy volunteers. 3/10
Cserum 0.06-0.25 0.03-0.12 0.28-0.55
Offman et al, 2000
[26]
Hospitalized patients (Canada) CAP
Acutely ill
Longitudinal cohort
PK after first dose acutely ill vs. convalescent phase
clarithromycin
PO: 500mg single dose
N= 12
Age: 77±2
  Acutely ill Ca Convalescent C No impaired oral absorption in acutely ill patients with CAP.
During acute phase of significantly decreased Cmax and AUC of 14-hydroxy clarithromycin.
9/10
Cmax 4.32 ± 0.63 3.57 ± 0.46
Tmax 3.50 ± 0.5 2.83 ± 0.59
AUC 47.37 ± 8.51 36.22 ± 6.09*
  Acutely ill 14-OHb Convalescent 14-OH
Cmax 0.42 ± 0.08 0.76 ± 0.23*
Tmax 4.83 ± 1.29 3.08 ± 0.51
AUC 5.84 ± 1.08 8.84 ± 1.92*
Patel et al, 1995
[27]
Hospitalized patients (USA) Acute infectious illnesses
Acute febrile phase (oral T>38.9;rectal T>38.3)
Longitudinal cohort
PK after first dose acutely ill vs. convalescent phase
ciprofloxacin
PO: 500mg single dose
N=12
Age: 36 (20-62)
  Acutely ill Convalescent No significant PK differences between acutely ill and convalescent phase. 8/10
Cmax 2.45 (±0.77) 2.31 (±1.26)
Tmax 1.48 (±0.75) 2.48 (±1.46)
AUC 10.91 (± 3.64) 11.05 (± 4.41)
Ramirez et al, 1985
[28]
Hospitalized patients (Guatemala) Selected susceptible gram-negative or gram-positive infections
Initial febrile phase, or febrile phase after inadequate treatment
Cross-sectional
PK at first, fourth and last day of therapy
ciprofloxacin
PO: 500mg bd
N= 71
(N total = 100)
Age: 38.1 (18-84)
  Day 1: Day 4: Last day: Drug levels in blood lower than previously reported 4/10
Cpeak 0.77 ± 0.43 0.79 ± 0.49 0.80 ± 0.41
Cthrough 0.29 ± 0.24 0.34 ± 0.32 0.29 ± 0.24
Guay et al, 1987
[29]
Hospitalized patients (USA) Lower respiratory tract infections
Acutely ill
Longitudinal cohort
PK after first dose acutely ill vs. convalescent phase
ciprofloxacin
PO: 750mg bd
Febrile
N= 7
Afebrile
N=4
Age: 77.7 (71-89)
(N total = 13, but 6 with renal/hepatic impairment)
  Acutely ill Convalescent No significant PK differences between acute illness and convalescent phase. 6/10
PK n= 4:c  
Cmax 6.11 ± 2.67 9.9 ± 3.65
Tmax 1.6 ± 0.45 1.3 ± 0.6 h
  PK n=7:  
Cmax: 6.83 ± 3.39  
Tmax: 1.8 ± 0.7  
Davies et al, 1986
[23]
Hospitalized patients (The Netherlands) Acute purulent exacerbations of chronic bronchitis
Initial phase
Cross-sectional
PK after first dose of 3 different doses
ciprofloxacin
PO:
Group 1: 500mg bd
Group 2A: 750mg bd (badge 1)
Group 2B: 750mg bd (badge 2)
Group 3: 1000mg bd
N=80 (8)
Group 1: 20
Age: 66.2
Group 2A: 20
Age: 66.8
Group 2B: 20
Age: 60.3
Group 3: 20
Age: 65.9
  Group 1 Group 2A Group 2B Group 3 Measured serum concentrations were generally satisfactory to treat H. influenza or B. catarrhalis. 3/10
Cmax 3.36 (range 1-6) 2.3 (range 1.4-3.4) 3.13 (range 1.3-5) 3.76 (range 2.5-6)
Tmax 2.4 1.68 2.25 1.95
AUC 12.9 (range 6-20.7) 11.1 (range 7-15.6) 14.7 (range 6.8-25.6) 17.9 (range 9.9-25.8)
Davies et al, 1984
[24]
Hospitalized patients (The Netherlands) Acute exacerbations of chronic bronchitis
Initial phase
Cross-sectional
PK after first dose
enoxacin
PO: 600mg bd
N= 15
Age: 66.4 (50-81)
Cmax
Tmax
AUC0-7
AUC0-12
3.7 (± 1.2 visual inspection)
2.3
17.03
25.02
Good GI-absorption. However, unclear comparator. The interpatient serum concentrations did not differ widely. 1/10
  1. *Statistically significant differences: AUCa, bp < 0.10 for normally distributed values; Cmaxbp < 0.05 for non-normally distributed values
  2. aC Clarithromycin, b14-hydroxy-clarithromycin
  3. cMean PK of the 4 patients who were also evaluated during the convalescent phase