Table II.
In Vitro Studies on the Influence of Protein Binding on the Antimicrobial Activity of Different Classes of Antibiotics (January 1995–March 2008)
| Antibiotic class | Medium | Determination of PB in test medium (PB %) | In vitro model | Conclusion | Year | Reference |
|---|---|---|---|---|---|---|
| Cephalosporin | MHB+90% HS | Not performed, but cited from literature (cefditoren, 88%) | TKC | Presence of HA (4%) but not HS (90%) significantly reduces bactericidal activity of cefditoren against S. penumoniae, when compared to MHB. This corresponds to the bactericidal activity of the free fraction of cefditoren in MHB | 2007 | 47 |
| MHB+4 g/dL HA | ||||||
| MHB+calculated free fraction of antibiotic | ||||||
| Cephalosporin | Supplemented MHB+4 g/dL HA | Not performed | TKC | Presence of HA (4%) significantly reduces the bactericidal activity of ceftriaxone against S. aureus, when compared to ceftriaxone, cefepime, ceftazidime, and cefotaxime in MHB | 1995 | 46 |
| β-Lactam | MHB+4 g/dL HA | Not performed, but cited from literature (ampicillin, 20%; oxacillin, 60–94%) | TKC, MIC | Presence of HA (4%) significantly reduces the bactericidal activity of ampicillin, oxacillin against S. aureus, when compared to MHB. This corresponds to the bactericidal activity of the free fraction of both antibiotics in MHB | 2004 | 48 |
| MHB+calculated free fraction of antibiotic | ||||||
| Fluoroquinolone | MHB+HA (4–12 g/dL) | Performed in test medium (moxifloxacin, 38%; trovafloxacin, 77%) | TKC | Presence of HA (12%) (which has the same PB capacity for trovafloxacin and moxifloxacin as 100% HS) significantly reduces the bactericidal activity of both fluoroquinolones against S. aureus, but not against P. aeruginosa, when compared to MHB | 2008 | 9 |
| MHB+HS (20–70%) | ||||||
| Fluoroquinolone | MHB+4 g/dL HA | Not performed, but cited from literature (moxifloxacin, 26%) | TKC, MIC | Presence of HA (4%) significantly reduces the bactericidal activity of moxifloxacin against S. aureus, when compared to MHB. This corresponds to the bactericidal activity of the free fraction of moxifloxacin in MHB | 2004 | 48 |
| MHB+calculated free fraction of antibiotic | ||||||
| Fluoroquinolone | MHB+HA (10%, 30%, and 50%) | Not performed | TKC | Presence of HA (10%, 30%, and 50%) does not significantly reduce the bactericidal activity of moxifloxacin, trovafloxacin, and ciprofloxacin against S. aureus, S. penumoniae, and E. coli when compared to MHB | 2000 | 8 |
| Fluoroquinolone | Broth+20% HS | Performed in 100% HS (BAY 12-8039, 26.4–30%) | MIC | Presence of HS (20% and 70%) does not significantly reduce the bactericidal activity of BAY 12-8039 against gram-positive pathogens, when compared to pure broth | 1997 | 52 |
| Broth+70% HS | ||||||
| Iclaprim | MHB+50% HP | Not performed, but cited from literature (iclaprim, 93%) | MIC | Presence of HP (50%) does not significantly reduce the bactericidal activity of iclaprim against MSSA and MRSA, when compared to MHB | 2007 | 51 |
| Fusidic acid | MHB+50% HP | Not performed, but cited from literature (fusidic acid, 97%) | MIC | Presence of HP (50%) significantly reduces the bactericidal activity of fusidic acid against MSSA and MRSA | 2007 | 51 |
| Glycopeptide | MHB+50% HP | Not performed, but cited from literature (teicoplanin, 90%; vancomycin, 55%) | MIC | Presence of HP (50%) does not significantly reduce the bactericidal activity of teicoplanin and vancomycin against MSSA and MRSA | 2007 | 51 |
| Daptomycin | MHB+90% HS | Not performed, but cited from literature (daptomycin, 91.7%) | TKC | Presence of HA (4 g/dL) and HS (90%) significantly delays, but does not significantly reduce the bactericidal activity of daptomycin against E. faecium | 2007 | 49 |
| MHB+4 g/dL HA | ||||||
| MHB+calculated free fraction of antibiotic | ||||||
| Daptomycin | MHB+4 g/dL HA | Not performed, but cited from literature (daptomycin, 91–95%) | TKC, MIC | MIC values of daptomycin against MRSA and VREF increased twofold to eightfold in the presence of albumin (4 g/dL) and decreased twofold in the presence of serum (50%) | 2004 | 7 |
| MHB+50% HS | Presence of HA (4 g/dL) delays, but does not significantly reduce the bactericidal activity of daptomycin against MRSA and VREF | |||||
| MHB+calculated free fraction of antibiotic |
MHB Mueller Hinton broth, HA human albumin, HS human serum, HP human plasma, MSSA methicillin-susceptible S. aureus, MRSA methicillin-resistant S. aureus, VREF vancomycin-resistant E. faecium, MIC minimal inhibitory concentration, TKC time–kill curve