Table 2.
Summary of microbiological data from included experimental studies (author, year; in vitro: drug concentration in the surface, drug release (related immersion period); microbiological assessments: quantitative test, mean and median of bacterial load (standard deviance); % reduction by authors calculated; infection rate; statistical significance)
| Author |
In vitro |
Microbiological assessments |
||||||
|---|---|---|---|---|---|---|---|---|
| Drug concentration in the surface | Drug release (immersion period) | Quantitative test | Bacterial load |
% Reduction | Infection rate | p value | ||
| Control | Experimental | |||||||
| Adams et al. (2009) | 23.5 μg | 70% (6 d) | CFU/implant + Rolled out on agar plates test (Infection rate) | 1w: 11,230.67 (±299.5) 2w: 2,186.33 (±204.2) 3w: 17,7891.0 (±27,220.1) 4w: 18,765.0 (±4,493.75) |
1w: 3.00 (±1.27) 2w: 1.57 (±0.57) 3w: 12,989.0 (±822.07) 4w: 4,531.5 (±221.2) | ~75.8% | NR | NR |
| Alt et al. (2014) | 307 μg rifampicin and 1,522 μg fosfomycin | NR | Rolled out on agar plates test | NR | NR | NR | C: 100% (5/5) T: 16.7% (1/6) | 0.015 |
| Antoci et al. (2007) | NR | NR | CFU/implant | 1w:1,43,814.43 (±10,051.54) 2w: 87,951.81 (±7,831.33) 3w: 22,6315.79 (±11,403.51) |
1w: 10,458.17 (±1,494.02) 2w: 25,903.61 (±1,807.23) 3w: 1,33,333.33 (±14,912.28) |
~58.9% | NR | 0.046 (1-w follow-up) |
| Auñón et al. (2020) | 1.45 mg of gentamicin and 1.4 mg of vancomycin | 56% gentamicin and 10.66% vancomycin (240 min) | CFU/cm2 (Log10) | 1.52 (±1.5) | 0.15 (±0.47) | ~90.1% | NR | 0.0074 |
| Aykut et al. (2010) | NR | NR | Positive or negative culture | NR | NR | NR | C: 100% (10/10) TEI: 0% (0/10) CLIN: 10% (1/10) |
<.001 (C versus TEI, and C versus CLIN) |
| Badar et al. (2015) | 1.2 mg/cm2 | NP | Bioluminescence intensity | 1w: 100.56 (±28.4) 2w: 99.40 (±37.64) 3w: 289.88 (±21.30) |
1w: 26.47 (±4.67) 2w: 68.45 (±28.03) 3w: 276.19 (±47.43) |
~4.8% | NR | NR |
| Croes et al. (2018) | NR | NR | CFU/implant (Log10) | Uncoated: 5.01 (NR) CS control: 5.87 (NR) |
5.63 (NR) | ~4.4% (no difference) | C: 40% (2/5) CS control: 100% (8/8) T: 40% (2/5) |
0.035 (CS control versus T for infection rate) |
| Darouiche et al. (2007) | 35 μg/cm2 (noncovalently bound) | 94% minocycline and 95% rifampin (6 h) | Positive or negative culture | NR | NR | NR | C: 100% (12/12) T: 38.46% (5/13) | 0.0016 |
| Diefenbeck et al. (2016) | 0.59 mg of G-SDS and 1.11 mg of G-TA | 54.2 μg and 424.9 μg G from G-SDS and G-TA, respectively. (24 h) | Positive or negative culture | NR | NR | NR | C: 100% (10/10) G-SDS: 0% (0/10) G-TA: 10% (1/10) | NR |
| Ghimire et al. (2019) | 90 μg/mm³ hydrogel | ~100% (24 h) | CFU/implant | 3w: 520.0 (±40.0) | 3w: 0 | 100% | NR | ≤.01 |
| Grohmann et al. (2019) | (PL-PGA)-20G = 0.32 (PL-PGA)-30G = 0.45 (PL-HEP)-20G = 0.15 (PL-HEP)-30G = 0.51 Data presented as referenced loads |
(PL-PGA)-20G = 5.52 μg/cm2 (PL-PGA)-30G = 18.62 μg/cm2 (PL-HEP)-20G = 46.89 μg/cm2 (PL-HEP)-30G = 86.21 μg/cm2 (14 d) |
CFU/implant (1/mm2) (rolled over agar) |
19.17∗ | (PL-PGA)-20G = 3.33∗ (PL-PGA)-30G = 12.50∗ (PL-HEP)-20G = 19.17∗ (PL-HEP)-30G = 3.33∗ | (PL-PGA)-20G = ~83.1% (PL-PGA)-30G = ~34.8% (PL-HEP)-20G = ~0% (PL-HEP)-30G = ~82.7% | NR | NR (No difference) |
| Janson et al. (2019) | NR | 758 μg (15 min) | CFU/implant | (BC-104): 3.43 (±2)×105 (BC-105): 2.85 (±1.4)×105 |
(BC-104): 0.48×105 (BC-105): 0 | (BC-104): ~85.9% (BC-105): 100% | C (BC-104): 100% (3/3) C (BC-105): 100% (2/2) T (BC-104): 33% (1/3) T (BC-105): 0% (0/2) |
NR |
| Jennings et al. (2016) | 25% | NR | CFU/implant | 600,000 (NR) | 20 (±21) | ~99.9% | NR | <.001 |
| Kälicke et al. (2006) | 3% Rifampicin and 7% fusidic acid | ~80% (42 d) | Harvesting | NR | NR | NR | C: 83% (10/12) PLLA-C: 83%(10/12) T: 17% (2/12) |
0.033 (controls versus test) |
| Kucharíková et al. (2016) | 35 pmol/cm2 | NR | CFU/implant (Log10) |
S. aureus: 5.37 (±0.41) C. albicans: 4.47 (±0.15) |
S. aureus: 2.92 (±0.25) C. albicans: 3.00 (±0.24) | S. aureus: ~45.6% C. albicans: ~32.9% | NR | <.05 (S. aureus) NR (C. albicans) |
| Liu et al. (2017) | NR | NR | Rolled out on agar plates test | Ti-C: >1000 CFU NTATi-C: >1000 CFU |
Ti-G: 473.75 (±10.69) NTATi-G: 40.5 (±12.36) |
Ti-G: ~52.6% NTATi-G: ~95.9% |
C: 100% (4/4) NTATi-C: 100% (4/4) Ti-G: 100% (4/4) NTATi-G: 100% (4/4) |
<.05 |
| Lucke et al. (2003) | 10% | NR | Rolled out on agar plates test | Ti-C: >1,000 CFU PDLLA-C: >1,000 CFU | 182 (±101) | ~81.8% | Ti-C: 100% (10/10) PDLLA-C: 100% (10/10) T: 70% (7/10) |
<.05 |
| Lucke et al. (2005) | 10% | 60% (24 h) | Rolled out on agar plates test | Ti-C: >1,000 CFU PDLLA-C: >1,000 CFU | NR (range 7–136 colonies) | NR | Ti-C: 100% (10/10) PDLLA-C: 100% (10/10) T: 10% (1/10) | NR |
| Ma et al. (2017) | NR | - NIR: 2.8 mg/mL + NIR: 6.5 mg/mL (25 min) |
Antibacterial ratio (%) | 1d – Ti + NIR: 0.92% (±7.32) 3d – Ti + NIR: 82.42% (±2.75) 1w – Ti + NIR: 88.22% (±4.58) 1d – Ti – NIR: 0% (±6.14) 3d – Ti - NIR: 70% (±4.91) 1w – Ti – NIR: 81.05% (±3.68) |
1d – T + NIR: 99.15% (±1.83) 3d – T + NIR: 99.67% (±0.91) 1w – T + NIR: 99.97% (±0.91) 1d – T – NIR: 60.75% (±4.91) 3d – T – NIR: 88.59% (±2.45) 1w – T – NIR: 99.42% (±1.23) | NR | NR | <.001 (1d and 3d for + NIR; 1d for −NIR); <.01 (7d for –NIR); <.05(1w + NIR; 3d for –NIR) |
| Metsemakers et al. (2015) | 3.4 mg | ~95% (4 w) | CFU/implant (Log10) | MSSA: 5.10∗ MRSA: 4.89∗ |
MSSA: 0∗ MRSA: 0∗ |
At least 3-log lower median numbers of CFUs (no significant difference) | MSSA - C: 80% (4/5) MSSA - T: 0% (0/6) MRSA - C: 100% (8/8) MRSA - T: 43% (3/7) |
<.05 (infection rate) |
| Moskowitz et al. (2010) | 550 μg/cm2 | ~100% (5.5 w) | Rolled out on agar plates test | 4d: >200 CFU 1w: >200 CFU |
4d: <22 CFU 1w: <190 CFU | 4d: ~89.0% 1w: ~5.0% |
4d - C: 83% (5/6) 4d - T: 0% (0/6) 7d - C: 71% (5/7) 7d - T: 0% (0/8) | NR |
| Neut et al. (2015) | 1 mg/cm2 | ~100% (168 h) | CFU/implant (Log10) | 2d: 4.82 (±1.32) 1w: 3.60 (±2.64) |
2d: 0 1w: 0 | 100% | C: 100% (7/7) T: 0% (0/7) | 0.001 |
| Nie et al. (2016) | NR | “the covalent modification of the Ti surfaces does not allow the release of any antibiotic” | CFU/implant (Log10) | 6.20 (±0.18) | 4.56 (±0.16) | ~26.5% | NR | <.05 |
| Nie et al. (2017) | NR | NR | CFU/implant (Log10) | 4.67 (±2.34)×105 | 3.3 (1.67)×103 | ~99.3% | NR | <.05 |
| Song et al. (2017) | NR | NR | Washout of implants (O.D. values) | 4w: 0.17 (±0.24) 8w: 0.29 (±0.30) 16w: 0.64 (±0.06) |
4w: 0.04 (±0.02) 8w: 0.04 (±0.01) 16w: 0.29 (±0.29) |
~54.7% | 8w - C: 100% (5/5) 8w - T: 0% (0/5) 16w - C: 100% (5/5) 16w - T: 40% (2/5) | <.005 |
| Stavrakis et al. (2019) | NR | ~23μg vancomycin (1 w) | CFU/implant (Log10) | 2.8 (±1.5)×102 | Vanco: 2 (±2) Tig: 1.8 (±1.8)×101 | Vanco: ~99.3% Tig: ~93.6% |
NR | NR |
| Thompson et al. (2019) | 311.32 μg/mL | >95% (15 min) | CFU/implant (Log10) | 1.76×106 (NR) | 6.43 ×101 (NR) | ~99.9% | C: 100% (9/9) T: 12.5% (1/8) | <.01 |
| Yang et al. (2016) | NR | 91.45 μg (57 h) | CFU/implant | Ti-C: 6.7×105 (±7.55×104) NT-C: 4.6×105 (±6.24×104) |
1.57×104 (±2.08×103) | NT: ~97.7% T: ~96.6% |
NR | <.01 |
| Yuan et al. (2018) | NR | 81.7% (24 h in the presence of S. aureus) | CFU/implant (Log10) | 3.43 (±0.12) | 0.90 (±0.43) | ~73.8% | NR | <.01 |
| Zeng et al. (2020) | 634.6 μg | 408.3 μg (14 d) | CFU/implant | Ti-C - NIR: 192.5 (±12.5) Ti-C + NIR: 182.5 (±22.5) |
T - NIR: 82.5 (±10.0) T + NIR: 5.00 (±2.5) |
NIR−: ~57.1% NIR+: ~97.3% |
NR | <.01 (Ti-C versus T) <.05 (T - NIR versus T + NIR) |
| Zhang et al. (2018) | NR | NR | CFU/implant | 8.42 (±0.68)×105 | 4.04 (±0.89)×104 | ~95.2% | NR | <.05 |
| Zhang et al. (2019) | NR | NR | CFU/implant | 1,478.26 (±521.74) | 65.22 (±65.21) | ~95.6% | NR | <.05 |
| Zhou et al. (2017) | 25% (4 mg) | 26.03 ng/mL (released in the blood after 2 h implant installation) | CFU/implant | >104 | <10³ | ~90.0% | C: 100% (6/6) T: 16.7% (1/6) | <.05 (infection rate) |
Notes: In vitro (NR, not reported; NP, not possible to extract data from the graph; G, gentamicin; SDS, sodium dodecyl sulfate; TA, tannic acid; PL, polycation; PGA, polyanion; HEP, heparin; d, days; min, minutes; h, hours; w, weeks); Quantitative test (CFU, colony forming unit; O.D., optical density); Microbiological assessments (NR, not reported; d, day; w, week; CS, chitosan; ∗ = median; PL, polycation; PGA, polyanion; HEP, heparin; G, gentamicin; BC, bacterial concentration; CFU, colony forming unit; Ti, titanium; C, control group; NTA, nanotubular anodized surface; PDLLA, poly(D,L-lactide); +NIR, with near-infrared light; −NIR, without near-infrared light; T, test group; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; Vanco, vancomycin; Tig, tigecycline; NT, nanotubes); Infection ratio (NR, not reported; C, control group; T, test group; TEI,teicoplanin; CLIN, clindamycin; CS, chitosan; G, gentamicin; SDS, sodium dodecyl sulfate; TA, tannic acid; BC, bacterial concentration; PLLA, poly-L-lactide; Ti, titanium; C, control group; NTA, nanotubular anodized surface; PDLLA, poly(D,L-lactide); MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin.