Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections
Abstract
:1. Introduction
2. Mechanisms of Drug Resistance
2.1. Carbapenemase-producing CRE
2.2. Non-Carbapenemase-producing CRE
3. Current Resistance Status
4. Treatment Options
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Species | Class A | Class B (MBLs) | Class D | Ref. |
---|---|---|---|---|
Klebsiella pneumoniae | KPC-3 | NDM-1, VIM-1 | OXA-48 | Okoche et al. Boutal et al. |
Klebsiella oxytoca | OXA-48, OXA-181 | Okoche et al. Boutal et al. | ||
Escherichia coli | KPC | NDM-1, NDM-5, NDM-9, VIM | OXA-48, OXA-181, OXA-244 | Okoche et al. Boutal et al. |
Proteus mirabilis | KPC | OXA-48 | Okoche et al. Boutal et al. | |
Serratia marcescens | KPC | VIM | Okoche et al. Boutal et al. | |
Enterobacter cloacae | KPC, IMI-1 | VIM-4 | OXA-48 | Okoche et al. Boutal et al. |
Enterobacter aerogenes | KPC | OXA-48 | Okoche et al. Boutal et al. | |
Citrobacter freundii | VIM | OXA-48 | Okoche et al. Boutal et al. | |
Citrobacter koseri | OXA-48 | Okoche et al. Boutal et al. | ||
Salmonella enterica | KPC-2 | NMD-1, NMD-5, VIM-1, VIM-2, IMP-4 | OXA-48 | Fernández et al. |
Morganella morganii | NDM-1 | OXA-48 | Boutal et al. | |
Providencia stuartii | KPC-2 | VIM-1 | Abdallah et al. | |
Providencia rettgeri | IMP-1 | OXA-72 | Abdallah et al. |
Antibiotic | Guidelines | Disk Content (µg) | Disk Diffusion (mm) | Dilution (µg/mL) | ||||
---|---|---|---|---|---|---|---|---|
S | I | R | S | I | R | |||
Ertapenem | EUCAST 1 CLSI 2 | 10 | ≥25 ≥23 | - 19–21 | ≤25 ≤18 | ≤0.5 ≤0.5 | - 1 | 0.5 ≥2 |
Imipenem | EUCAST 1 CLSI 2 | 10 | 22 ≥23 | 21–18 20–22 | ≤17 ≤19 | ≤2 ≤1 | 3 2 | 4 ≥4 |
Meropenem | EUCAST 1 CLSI 2 | 10 | 22 ≥23 | 21–17 20–22 | 16 ≤19 | ≤2 ≤1 | 3–7 2 | 8 ≥4 |
Doripenem | EUCAST 3 CLSI 2 | 10 10 | 22 ≥23 | 21–17 20–22 | ≤16 ≤19 | ≤1 ≤1 | 2–3 2 | 4 ≥4 |
Drug (Pharmaceutical Company) | Action Mechanism | Structure | Limitations | Ref. | |
---|---|---|---|---|---|
“Old Antibiotics” | Fosfomycin (Merck) | Cell wall synthesis inhibitor | Appearance of resistance | Vardakas et al. | |
Aminoglycosides | Protein synthesis inhibitor | Appearance of resistance | Rodriguez-Bano et al. Satlin et al. | ||
Colistin (Kobayashi Bacteriological Laboratory) | Cell membrane disruptor | Nephrotoxicity and other severe adverse effects | Karaiskos et al. Daikos et al. | ||
Tigecycline (Pfizer) | Protein synthesis inhibitor | Low concentration in tissue | Ni et al. | ||
Dual Therapies | Ertapenem + Meropenem/Doripenem | Cell wall synthesis inhibitor | - | Bulik et al. | |
Ceftazidime/Avibactam (Allergan) | Cell wall synthesis inhibitor/ß-lactamase inhibitor | Appearance of resistance | De Jonge et al. | ||
Meropenem/Vaborbactam (Melinta) | Cell wall synthesis inhibitor/ß-lactamase inhibitor | Insufficient clinical data | Karaiskos et al. | ||
Novel Drugs | Plazomicin (Achaogen) | Protein synthesis inhibitor | Ineffective against MBL-producers | Landman et al. | |
Eravacycline (Tetraphase) | Protein synthesis inhibitor | Currently in clinical trials | Zhanel et al. | ||
Imipenem/Relebactam (Merck) | Cell wall synthesis inhibitor/ß-lactamase inhibitor | Currently in clinical trials | Blizzard et al. | ||
Cefiderocol (Shionogi) | Cell wall synthesis inhibitor | Currently in clinical trials | Saisho et al. | ||
Zidebactam (Wockhardt) | ß-lactamase inhibitor | Currently in clinical trials | Karaiskos et al. | ||
Nacubactam (Roche) | ß-lactamase inhibitor | Currently in clinical trials | Papp-Wallace et al. |
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Suay-García, B.; Pérez-Gracia, M.T. Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections. Antibiotics 2019, 8, 122. https://doi.org/10.3390/antibiotics8030122
Suay-García B, Pérez-Gracia MT. Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections. Antibiotics. 2019; 8(3):122. https://doi.org/10.3390/antibiotics8030122
Chicago/Turabian StyleSuay-García, Beatriz, and María Teresa Pérez-Gracia. 2019. "Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections" Antibiotics 8, no. 3: 122. https://doi.org/10.3390/antibiotics8030122