Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies
Abstract
:1. Introduction
2. Results
2.1. Ceftazidime
Synthesis of the Findings concerning Drug Regimens for Ceftazidime
2.2. Cefepime
Synthesis of the Findings concerning Drug Regimens for Cefepime
2.3. Piperacillin-Tazobactam
Synthesis of the Findings concerning Drug Regimens for Piperacillin-Tazobactam
2.4. Meropenem
Synthesis of the Findings concerning Drug Regimens for Meropenem
2.5. Imipenem-Cilastatin
Synthesis of the Findings concerning Drug Regimens for Imipenem-Cilastatin
2.6. Aztreonam
Synthesis of the Findings concerning Drug Regimens for Aztreonam
2.7. New Beta-Lactam-Beta-Lactamase Inhibitor Combinations, Ceftaroline, Ceftobiprole and Cefiderocol
Synthesis of the Findings concerning Drug Regimens for New Beta-Lactam-Beta-Lactamase Inhibitor Combinations, Ceftaroline, Ceftobiprole and Cefiderocol
3. Discussion
4. Materials and Methods
5. Conclusions
6. Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A. Search Strings
Search Strings | Number of Hits | Paper after TIAB and Full-Text Analysis * |
---|---|---|
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “piperacillin” [tiab] | 127 | 10 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “ceftazidime” [tiab] | 168 | 7 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “cefepime" [tiab] | 51 | 5 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “meropenem” [tiab] | 131 | 11 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “imipenem” [tiab] | 270 | 8 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “aztreonam” [tiab] | 48 | 2 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “avibactam” [tiab] | 5 | 1 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “vaborbactam” [tiab] | 2 | 0 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “ceftolozane” [tiab] | 2 | 0 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “relebactam” [tiab] | 1 | 0 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “ceftaroline” [tiab] | 3 | 0 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “ceftobiprole” [tiab] | 2 | 0 |
(“burn” [tiab] or “burns” [tiab] or “burned” [tiab]) and “cefiderocol” [tiab] | 3 | 0 |
Total * | 813 | 44 |
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First Author | Target Antibiotic(s) | Country of the First Author | Year of Publication | Study Design | Number of Patients | Control Group | Mean % of Burned TBSA | Mean CLCR (mL/m) | Mean Body Weight (Kg) | Suggested PK/PD Target(s) |
---|---|---|---|---|---|---|---|---|---|---|
Alshaer [22] | FEP, TZP, MEM | USA | 2022 | Before/after study | 23 (post-intervention) | 19 (pre-intervention) | 25 | 119 | Na | Cmin > MIC; Cmin > 4 × MIC |
Aoki [23] | FEP | Japan | 2010 | Case report | 1 | Nap | 46 | 163 | Na | 60–70% fT > MIC |
Bonapace [11] | FEP | USA | 1999 | Clinical PK study + population PK model | 12 | Nap | 36 | 135 | 84 | 60% T > MIC |
Boucher [24] | IPM | USA | 1990 | Clinical PK study | 11 | Nap | 43 | 105 | 71 | None |
Boucher [12] | IPM | USA | 2016 | Clinical PK study | 10 | Nap | 23 | In CRRT | Na | None |
Bourget [25] | TZP | France | 1995 | Clinical PK study | 10 | Nap | 41 | 120 | 78 | 100% T > MIC |
Conil [26] | CAZ, FEP | France | 2007 | Clinical PK study | 30 | Nap | Na | Na | Na | Cmin > 4 × MIC |
Conil [27] | CAZ | France | 2007 | Clinical PK study + population PK model | 50 | Nap | 23 | 105 | 71 | None |
Conil [28] 05 | CAZ | France | 2007 | Randomized controlled trial with clinical PK study | 15 | 15 | Na | Na | Na | Cmin > 4 × MIC |
Conil [29] | CAZ | France | 2013 | Clinical PK study + population PK model | 70 | Nap | 32 | 118 | 74 | Steady state concentration of 40–100 mg/L |
Corcione [16] | MEM | Italy | 2020 | Clinical PK study + population PK model | 17 | 34 | 134 | Na | BMI: 25 kg/m2 | 75% fT > MIC |
Cotta [30] | MEM | Australia | 2015 | Case report | 1 | Nap | 50 | 129 | 100 | 54% fT > MIC; 10% fT > 4–6 MIC |
Dailly [31] | IPM | France | 2003 | Clinical PK study + population PK model | 47 | Nap | 28 | Na | 75 | None |
Dailly [32] | CAZ | France | 2003 | Clinical PK study + population PK model | 41 | Nap | 34 | Na (mean serum creatinine: 75 mmol/l) | 74 | None |
Doh [33] | MEM | South Korea | 2010 | Clinical PK study + population PK model | 59 | 0 | 49 | 138 | 66 | 40% fT > MIC |
Falcone [34] | ATM; CZA | Italy | 2021 | Clinical PK study + population PK model | 8 burn patients, 41 total patients | Nap | Na | Na | BMI: 24 kg/m2 | 100% fT > MIC |
Fournier [14] | TZP; MEM | Switzerland | 2018 | Monocentric, unblinded, randomized, controlled trial | 19 | 19 | 20 | Na | Na | 100% fT > MIC |
Friedrich [13] | ATM | USA | 1991 | Clinical PK study | 8 | Nap | 49 | Na | 83 | None |
Gomez [35] | IPM | Brazil | 2015 | Clinical PK study + population PK model | 51 | 36 | Not specified, 36 patients with normal renal function and 15 with renal failure | 68 | Na | 40% fT > MIC |
Hallam [36] | MEM | UK | 2010 | Case report | 1 | Nap | 52 | Na | Na | 100% fT > MIC |
Jeon [37] | TZP | South Korea | 2014 | Clinical PK study + population PK model | 5 | Nap | 35 | 132 | 67 | 50% fT > MIC |
Le Floch [38] | CAZ, IPM | France | 2009 | Clinical PK study | Number of patients not specified; 120 samples | Nap | 32 | 153 | 76 | 100% fT > 4xMIC |
Li [17] | IPM | Belgium | 2018 | Clinical PK study + population PK model | 20 | Nap | Na | Na | Na | 40% fT > MIC |
Machado [15] | TZP, IPM, MEM | Brazil | 2017 | Before/after study | 77 | 63 | 31 | Na | 81 | 100% fT > MIC for TZP; 60% fT > MIC for IPM and MEM |
Messiano [39] | MEM | Brazil | 2022 | Clinical PK study | 15 | Nap | 33 | 100 | BMI: 24 kg/m2 | 100% fT > MIC |
Olbrisch [40] | TZP | Germany | 2018 | Prospective cohort study with PK study + population PK model | 20 | 16 | 31 | Na | 80 | 100% fT > 4xMIC |
Patel [41] | TZP; MEM | Australia | 2012 | Clinical PK study | 50 (6 on TZP, 1 on MEM) | Nap | 17 | 86 | Na | 100% fT > MIC; 100% fT > 4 × MIC |
Por [42] | IPM | USA | 2021 | Clinical PK study + population PK model | 12 in CRRT | 11 not in CRRT | 43 | 132 | 98 | 40% fT > MIC |
Ramon-Lopez [43] | MEM | UK | 2015 | Clinical PK study + population PK model | 12 | Nap | 41 | 137 | 83 | 40% T > MIC; 60% T > MIC; 80% T > MIC |
Sampol [44] | FEP | France | 2000 | Clinical PK study | 6 | Nap | 32 | 123 | Na | None |
Selig [45] | TZP | USA | 2022 | Case-control study + population PK model | 5 | 14 | 38 | 210 | 103 | 50% fT > MIC; 100% fT > MIC; 100% ft > 4 × MIC |
Selig [46] | MEM | USA | 2022 | Case-control study + population PK model | 11 | 12 | 33 | 150 | 88 | 40% fT > MIC; 99% fT > MIC |
Shikuma [47] | TZP | USA | 1990 | Clinical PK study | 9 | Nap | Na | 90–120 | Na | Not specified |
Torian [48] | TZP | USA | 2023 | Case report | 1 | Nap | 3.2 | >120 | Na | 100% T > MIC |
Walstad [49] | CAZ | Norway | 1998 | Clinical PK study with measurement of tissue concentration | 8 | Nap | 20–80 | Na | Na | None |
Antibiotic | Advisable Drug Regimens in Burn Patients without Renal Impairment | Suggested Modalities of Preparation and Administration [50] |
---|---|---|
Ceftazidime | At least 1 g every 4 h or CI of 6 g/24 h (with loading dose) | Using syringe pump: 2 g in 50 mL of normal saline (0.9%) or glucose solution (5%), over 8 h, 3 times a day |
Cefepime | 2 g every 8 h; consider CI of 6 g/24 h (with loading dose), particularly for severe infections or high MICs | Using syringe pump: 2 g in 50 mL of normal saline (0.9%) or glucose solution (5%), over 8 h, 3 times a day |
Piperacillin-tazobactam | 18 g/24 h CI (with loading dose). Higher doses may be needed for patients with ARC or high MICs | Using syringe pump: 4.5 g in 50 mL of normal saline (0.9%) or glucose solution (5%), over 6 h, 4 times a day |
Meropenem | 6 g/24 h CI (with loading dose). Higher doses may be needed for patients with ARC | Using syringe pump: 2 g in 50 mL of normal saline (0.9%), over 8 h, 3 times a day |
Imipenem-cilastatin | 500 mg every 6 h; 1 g every 6 h if ARC or MIC > 2 mg/dL | 500 mg in 100 mL of normal saline (0.9%), in 30 min, 4 times a day; 1 g in 250 mL of normal saline (0.9%), over 1 h, 4 times a day. Continuous infusion not recommended due to stability issues |
Aztreonam | 2 g every 8 h or 6–8 g in CI (particularly for high CLCR or high MICs) | 2 g in 100 mL of normal saline (0.9%), in 30 min, 3 times a day; Using syringe pump: 3 g in 50 mL of normal saline (0.9%), over 12 h, 2 times a day |
Ceftaroline, ceftobiprole, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol | No specific data on burn patients. Standard regimens:
|
|
Ceftazidime-avibactam | Insufficient data. Standard regimen: 2.5 g every 8 h | 2.5 g in 50 mL of normal saline (0.9%), over 2 h, 3 times a day. Continuous infusion may be proposed. |
Antibiotic | Dosages Used by EUCAST to Define Breakpoints [65] | EUCAST Clinical Breakpoint Tables v. 13.1 (mg/L) | Suggested PK/PD Target [21] | |||
---|---|---|---|---|---|---|
Standard Dosage | High Dosage | S≤ | R> | Pre-Clinical PK/PD Target for Efficacy | Clinical PK/PD Target for Efficacy | |
Ceftazidime | 1 g × 3 | 2 g × 3 or 1 g × 6 | Ent: 1 Pa: 0.001 | Ent: 4 Pa: 8 | 60–70% fT > MIC | 40–100% fT > MIC |
Cefepime | 1 g × 3 or 2 g × 2 | 2 g × 3. For severe P. aeruginosa infections: 2 g in 4 h × 3 | Ent: 1 Pa: 0.001 | Ent: 4 Pa: 8 | 60–70% fT > MIC | 40–100% fT > MIC |
Piperacillin-tazobactam | 4.5 g × 4 or 4.5 g in 4 h × 3 | 4.5 g in 3 h × 4 | Ent: 8 Pa: 0.001 | Ent: 8 Pa: 16 | 50% fT > MIC | 50–100% fT > MIC |
Meropenem | 1 g × 3 | 2 g in 3 h × 3 | Ent: 2 Pa: 2 | Ent: 8 Pa: 8 | 40% fT > MIC | 50–100% fT > MIC |
Imipenem-clinastatin | 0.5 g × 4 | 1 g × 4 | Ent: 2 Pa: 0.001 | Ent: 4 Pa: 4 | 40% fT > MIC | 50–100% fT > MIC |
Aztreonam | 1 g × 3 | 2 g × 4 | Ent: 1 Pa: 0.002 | Ent: 4 Pa: 16 | / | 50–100% fT > MIC [34] |
Ceftolozane-tazobactam | 1.5 g × 3 | 3 g × 3 | Ent: 2 Pa: 4 | Ent: 2 Pa: 4 | / | / |
Ceftazidime-avibactam | 2.5 g in 2 h × 3 | Ent: 8 Pa: 8 | Ent: 8 Pa: 8 | / | / | |
Meropenem-vaborbactam | 4 g in 3 h × 3 | Ent: 8 Pa: 8 | Ent: 8 Pa: 8 | / | / | |
Imipenem-cilastatin-relebactam | 0.75 g × 4 | none | Ent: 2 Pa: 2 | Ent: 2 Pa: 2 | / | / |
Ceftaroline | 0.6 g × 2 | 0.6 g × 3 | Ent: 0.5 | Ent: 0.5 | / | / |
Ceftobiprole | 0.5 in 2 h × 3 | none | Ent: 0.25 | Ent: 0.25 | / | / |
Cefiderocol | 2 g in 3 h × 3 | none | Ent: 2 Pa: 2 | Ent: 2 Pa: 2 | / | / |
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Tebano, G.; la Martire, G.; Raumer, L.; Cricca, M.; Melandri, D.; Pea, F.; Cristini, F. Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies. Antibiotics 2023, 12, 1737. https://doi.org/10.3390/antibiotics12121737
Tebano G, la Martire G, Raumer L, Cricca M, Melandri D, Pea F, Cristini F. Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies. Antibiotics. 2023; 12(12):1737. https://doi.org/10.3390/antibiotics12121737
Chicago/Turabian StyleTebano, Gianpiero, Giulia la Martire, Luigi Raumer, Monica Cricca, Davide Melandri, Federico Pea, and Francesco Cristini. 2023. "Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies" Antibiotics 12, no. 12: 1737. https://doi.org/10.3390/antibiotics12121737
APA StyleTebano, G., la Martire, G., Raumer, L., Cricca, M., Melandri, D., Pea, F., & Cristini, F. (2023). Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies. Antibiotics, 12(12), 1737. https://doi.org/10.3390/antibiotics12121737