Antibiotics in Necrotizing Soft Tissue Infections
Abstract
:1. Introduction
2. Microbiology of NSTIs
3. Microbial Documentation of NSTIs: A Challenge for Microbiologists
4. Antibiotic Treatment
4.1. Available Data Regarding Choice of Molecules Specifically in NSTIs
4.2. Specificities for GAS Infections: Anti-Toxinic Molecules
4.3. Perspectives on Other NSTI Specificities
4.4. Duration of Treatment and De-Escalation
5. Pharmacokinetics (PK) and Pharmacodynamics (PD) Targets and Optimization
6. Tissue Diffusion of Antibiotics
6.1. Available Data from Uncomplicated SSTI
Molecule | Guidelines | Pharmacokinetic Parameters | Tissue Penetration (Tissue/Blood Ratio) | Antimicrobial Spectrum/Anti-Toxinic Activity and other Specific Aspects | Dosing Regimen § | ||||
---|---|---|---|---|---|---|---|---|---|
Distribution (Vd) | Protein Binding | PK/PD Targets in Severe Infections | Soft Tissue of Healthy Subjects | Impact of Necrosis on Tissue Diffusion | Impact of Altered Tissue Perfusion on Tissue Diffusion [84,94,95,96,97,98] | ||||
Piperacillin + tazobactam | USA 2014 (IDSA) World 2018 (WSES/SIS-E) Germany 2018 South Korea 2017 | Hydrophilic (0.24 L/kg) | Low (16%) | fT > 4−8 × MIC = 100% | Low (0.27) [81] * | Medium to low impact (tissue concentrations appear sufficient to achieve PK/PD targets) | No data | Methicillin-susceptible S. aureus, S. pyogenes, Enterobacteriaceae, nonfermenting bacilli, anaerobic bacteria | 4 g q6h IV Consider prolonged (4 h) or continuous infusion with loading dose |
Cefotaxime | USA 2014 Norway 2013 South Korea 2017 | Hydrophilic (0.28 L/kg) | Low (30–51%) | fT > 4−8 × MIC = 100% | Medium (0.54) [99] π | Medium to low impact (tissue concentrations appear sufficient to achieve PK/PD targets) | No data (but high decrease of tissue concentration with others cephalosporins: cefepime [100] and ceftazidime [101]) | Methicillin-susceptible S. aureus, S. pyogenes, Enterobacteriaceae | 2 g q6–8h IV |
Meropenem | USA 2014 World 2018 Germany 2018 South Korea 2017 | Hydrophilic (0.25 L/kg) | Very low (2%) | fT > 4−8 × MIC = 100% | Low (0.35–0.48) [87] * | Medium to high decrease in drug concentration (tissue concentrations could not be sufficient to achieve PK/PD targets) | Low impact | Methicillin-susceptible S. aureus, S. pyogenes, Enterobacteriaceae, nonfermenting bacilli anaerobic bacteria activity on multi-drug resistant gram-negative bacilli | 1–2 g q8h IV Consider prolonged infusion 3 h |
Gentamycin | Norway 2013 | Hydrophilic (0.26 L/kg) | Very low (0–3%) | Cmax/MIC > 8–10 | Medium (0.60) [81] * | High decrease in drug concentration | No data | S. aureus, S. pyogenes, Enterobacteriaceae, nonfermenting bacilli Rapid bactericidal action Should be added in cases of septic shock | 5–8 mg/kg over 30 min, q24h |
Amikacin | France 2018 | Hydrophilic (0.26 L/kg) | Very low (< 10%) | Cmax/MIC > 8–10 | High (1.03) [86] π | High decrease in drug concentration | No data | S. aureus, S. pyogenes, Enterobacteriaceae, nonfermenting bacilli Rapid bactericidal action Should be added in cases of septic shock | 25–30 m/kg over 30 min, q24h |
Metronidazole | USA 2014 Norway 2013 South Korea 2017 | Lipophilic (0.65 L/kg) | Very low (< 10%) | AUC24/MIC Cmax/MIC No target defined | High (0.67) [85] * | No or low impact | No impact [102] | Anaerobic bacteria | 500 mg q8h IV |
Vancomycin | USA 2014 South Korea 2017 | Hydrophilic (0.70 L/kg) | Medium (55%) | AUC24/MIC > 400–600 | Low (0.30) [81] * | Medium to high decrease in drug concentration | High impact [103] | Methicillin-resistant S. aureus | Consider continuous infusion of 30 mg/kg/24 h with loading dose of 30 mg/kg and TDM |
Daptomycin | World 2018 | Hydrophilic (0.10 L/kg) | High (92%) | AUC24/MIC > 666 [104] | High (0.74–0,93) [81] * | No data | No impact | Methicillin-resistant S. aureus | 8–12 mg/kg q24h |
Linezolid | USA 2014 World 2018 South Korea 2017 | Lipophilic (0.65 L/kg) | Low (31%) | AUC24/MIC > 80–120 fT > 1 × MIC = 85% [105] | High (0.75–1.32) [81] * | No data | No impact | Methicillin-resistant S. aureus In vitro evidence of anti-toxinic action | 600 mg q12h IV (higher doses might be needed in obese patients [80]) |
Clindamycin | World 2018 Germany 2018 | Lipophilic (1.1 L/kg) | High (90%) | AUC24/MIC No target defined | High (1.06) [106] x | No data | No impact | S. aureus, S. pyogenes Anaerobic bacteria (but with high proportion of resistant strains), High evidence of in vivo and in vitro anti-toxinic action | 600–900 mg q8h IV |
6.2. Available Data on Antibiotic Diffusion in Necrotic Tissue
6.3. Available Data on Antibiotic Diffusion in the Presence of Altered Perfusion
7. Suggested Empiric Treatment for Suspected NSTI Based on Basic Microbiology
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type of Pathogens | Primary | Secondary | Polymicrobial | Commensals |
---|---|---|---|---|
Pathogenicity | May cause NSTI in patients without known risk factors | May cause infection in patients with risk factors | Rarely pathogen in the absence of a primary or secondary pathogen | Do not cause NSTI although sometimes identified with other pathogens |
Species | Group A Streptococcus Staphylococcus aureus Vibrio vulnificus Clostridium perfringens | Other Streptococcus (group B, C, G, anginosus) Pneumococcus Haemophilus influenzae Neisseria meningitidis Enterobacteriaceae Nonfermenting gram-negative bacilli Other anaerobes (Bacteroides, Prevotella, Fusobacterium) | Enterococcus | Bacillus Corynebacterium Micrococcus Coagulase negative Staphylococci |
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Urbina, T.; Razazi, K.; Ourghanlian, C.; Woerther, P.-L.; Chosidow, O.; Lepeule, R.; de Prost, N. Antibiotics in Necrotizing Soft Tissue Infections. Antibiotics 2021, 10, 1104. https://doi.org/10.3390/antibiotics10091104
Urbina T, Razazi K, Ourghanlian C, Woerther P-L, Chosidow O, Lepeule R, de Prost N. Antibiotics in Necrotizing Soft Tissue Infections. Antibiotics. 2021; 10(9):1104. https://doi.org/10.3390/antibiotics10091104
Chicago/Turabian StyleUrbina, Tomas, Keyvan Razazi, Clément Ourghanlian, Paul-Louis Woerther, Olivier Chosidow, Raphaël Lepeule, and Nicolas de Prost. 2021. "Antibiotics in Necrotizing Soft Tissue Infections" Antibiotics 10, no. 9: 1104. https://doi.org/10.3390/antibiotics10091104