Table 1 Characteristics of included studies
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 | |||||