Efficacy of Novel Combinations of Antibiotics against Multidrug-Resistant—New Delhi Metallo-Beta-Lactamase-Producing Strains of Enterobacterales
Abstract
:1. Introduction
2. Results and Discussion
2.1. Minimum Inhibitory Concentration
2.2. Synergistic Effect of Antibiotic Combinations
3. Materials and Methods
3.1. Strain, Antibiotics and Chemicals
3.2. Combination of Antibiotics and MIC
3.3. D-Checkerboard Microdilution Assay to Determine FICI
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Cherak, Z.; Loucif, L.; Moussi, A.; Bendjama, E.; Benbouza, A.; Rolain, J.M. Emergence of Metallo-β-Lactamases and OXA-48 Carbapenemase Producing Gram-Negative Bacteria in Hospital Wastewater in Algeria: A Potential Dissemination Pathway Into the Environment. Microb. Drug Resist. 2022, 28, 23–30. [Google Scholar] [CrossRef] [PubMed]
- Bush, K. Past and present perspectives on β-lactamases. Antimicrob. Agents Chemother. 2018, 62, e01076-18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khan, A.U.; Maryam, L.; Zarrilli, R. Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): A threat to public health. BMC Microbiol. 2017, 17, 101. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yong, D.; Toleman, M.A.; Giske, C.G.; Cho, H.S.; Sundman, K.; Lee, K.; Walsh, T.R. Characterization of a new metallo-β-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob. Agents Chemother. 2009, 53, 5046–5054. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Almutairi, M.M. Synergistic activities of colistin combined with other antimicrobial agents against colistin-resistant Acinetobacter baumannii clinical isolates. PLoS ONE 2022, 17, e0270908. [Google Scholar] [CrossRef] [PubMed]
- Scudeller, L.; Righi, E.; Chiamenti, M.; Bragantini, D.; Menchinelli, G.; Cattaneo, P.; Giske, C.G.; Lodise, T.; Sanguinetti, M.; Piddock, L.J.; et al. Systematic review and meta-analysis of in vitro efficacy of antibiotic combination therapy against carbapenem-resistant Gram-negative bacilli. Int. J. Antimicrob. Agents 2021, 57, 106344. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, N.; Ali, S.M.; Khan, A.U. Co-existence of blaNDM-1 and blaVIM-1 producing Moellerella wisconsensis in NICU of North Indian Hospital. J. Infect. Dev. Ctries. 2020, 14, 228–231. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, N.; Khalid, S.; Ali, S.M.; Khan, A.U. Occurrence of blaNDM variants among Enterobacteriaceae from a neonatal intensive care unit in a northern India hospital. Front. Microbiol. 2018, 9, 407. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khalid, S.; Ahmad, N.; Ali, S.M.; Khan, A.U. The outbreak of efficiently transferred carbapenem-resistant blaNDM producing gram-negative bacilli isolated from the neonatal intensive care unit of an Indian hospital. Microb. Drug Resist. 2020, 26, 284–289. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, N.; Ali, S.M.; Khan, A.U. Molecular characterization of novel sequence type of carbapenem-resistant New Delhi Metallo-β-lactamase-1-producing Klebsiella pneumoniae in the neonatal intensive care unit of an Indian hospital. Int. J. Antimicrob. Agents 2019, 53, 525–529. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, N.; Ali, S.M.; Khan, A.U. Detection of New Delhi metallo-β-lactamase variants NDM-4, NDM-5, and NDM-7 in Enterobacter aerogenes isolated from a neonatal intensive care unit of a North India Hospital: A first report. Microb. Drug Resist. 2018, 24, 161–165. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, N.; Ali, S.M.; Khan, A.U. First reported New Delhi metallo-β-lactamase-1-producing Cedecea lapagei. Int. J. Antimicrob. Agents 2017, 49, 118–119. [Google Scholar] [CrossRef] [PubMed]
- Parvez, S.; Khan, A.U. Hospital sewage water: A reservoir for variants of New Delhi metallo- β-lactamase (NDM) and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Int. J. Antimicrob. Agents 2018, 51, 82–88. [Google Scholar] [CrossRef] [PubMed]
- Maryam, L.; Khalid, S.; Ali, A.; Khan, A.U. Synergistic effect of doripenem in combination with cefoxitin and tetracycline in inhibiting NDM-1-producing bacteria. Future Microbiol. 2019, 14, 671–689. [Google Scholar] [CrossRef] [PubMed]
- Hasan, S.; Ali, S.Z.; Khan, A.U. Novel combinations of antibiotics to inhibit extended-spectrum β-lactamase and Metallo-β-lactamase producers in vitro: A synergistic approach. Future Microbiol. 2013, 8, 939–944. [Google Scholar] [CrossRef] [PubMed]
- Shakil, S.; Khan, R.; Zarrilli, R.; Khan, A.U. Aminoglycosides versus bacteria–a description of the action, resistance mechanism, and nosocomial battleground. J. Biomed. Sci. 2008, 15, 5–14. [Google Scholar] [CrossRef] [PubMed]
- Rawson, T.M.; Brzeska-Trafny, I.; Maxfield, R.; Almeida, M.; Gilchrist, M.; Gonzalo, X.; Moore, L.S.; Donaldson, H.; Davies, F. A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales infection. J. Glob. Antimicrob. Resist. 2022, 29, 558–562. [Google Scholar] [CrossRef] [PubMed]
- Lu, J.; Qing, Y.; Dong, N.; Liu, C.; Zeng, Y.; Sun, Q.; Shentu, Q.; Huang, L.; Wu, Y.; Zhou, H.; et al. Effectiveness of a double-carbapenem combinations against carbapenem-resistant Gram-negative bacteria. Saudi Pharm. J. 2022, 30, 849–855. [Google Scholar] [CrossRef] [PubMed]
- Bush, K. A resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens. Int. J. Antimicrob. Agents 2015, 46, 483–493. [Google Scholar] [CrossRef] [PubMed]
- Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; 28th Informational Supplement; CLSI document M100-S29; Clinical and Laboratory Standards Institute: Wayne, PA, USA, 2019. [Google Scholar]
- Doern, C.D. When does 2 plus 2 equal 5? A review of antimicrobial synergy testing. J. Clin. Microbiol. 2014, 52, 4124–4128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Strains | Resistance Markers | MIC µg/mL | MIC µg/mL FIC Index 5 | Ref. | |||||
---|---|---|---|---|---|---|---|---|---|
DRP 1 | FOX 2 | IMP 3 | STP 4 | DRP + FOX | DRP + STP | IMP + FOX | |||
AK-33 Escherichia coli | NDM-4, OXA-1, CTX-M, Amp C | 512 | 2048 | 1024 | 2048 | 128 + 512 0.5 | 128 + 256 0.375 | 128 + 256 0.25 | [13] |
AK-35 Escherichia coli | NDM-7, OXA-1 | 1024 | 2048 | 1024 | 2048 | 128 + 256 0.25 | 128 + 128 0.1875 | 256 + 512 0.5 | [13] |
AK-37 Escherichia coli | NDM-1, CMY-139, OXA-1, CTX-M | 1024 | 1024 | 512 | 512 | 128 + 128 0.375 | 256 + 128 0.5 | 256 + 128 0.5 | [13] |
AK-83 Escherichia coli | NDM-7, OXA-1, SHV-1 | 512 | 4096 | 1024 | 2048 | 64 + 512 0.25 | 128 + 512 0.5 | 128 + 512 0.25 | [8] |
AK-66 Klebsiella pneumoniae | NDM-1, OXA-1, OXA-9, CMY-1 | 256 | 1024 | 1024 | 2048 | 128 + 256 0.375 | 256 + 256 0.25 | 128 + 512 0.1875 | [8] |
AK-102 Klebsiella pneumoniae | NDM-5, OXA-1, OXA-9, CMY-4 | 1024 | 2048 | 1024 | 2048 | 128 + 512 0.375 | 64 + 512 0.3125 | 64 + 256 0.1875 | [8] |
AK-121 Klebsiella pneumoniae | NDM-1 | 512 | 1024 | 512 | 1024 | 128 + 256 0.5 | 64 + 256 0.375 | 128 + 256 0.5 | [10] |
AK-125 Klebsiella pneumoniae | NDM-1 | 512 | 1024 | 1024 | 2048 | 128 + 256 0.5 | 64 + 256 0.25 | 128 + 256 0.375 | [10] |
AK-130 Klebsiella pneumoniae | NDM-1 | 512 | 256 | 512 | 1024 | 64 + 64 0.375 | 128 + 128 0.375 | 128 + 64 0.5 | [10] |
AK-140 Klebsiella pneumoniae | NDM-1, OXA-48 | 1024 | 1024 | 2048 | 2048 | 128 + 256 0.375 | 256 + 512 0.5 | 512 + 128 0.375 | [10] |
AK-142 Klebsiella pneumoniae | NDM-1 | 512 | 1024 | 512 | 2048 | 128 + 526 0.5 | 64 + 512 0.375 | 128 + 128 0.25 | [10] |
AK-144 Klebsiella pneumoniae | NDM-1 | 512 | 2048 | 1024 | 1024 | 128 + 512 0.25 | 64 + 128 0.25 | 512 + 512 0.25 | [10] |
AK-147 Klebsiella pneumoniae | NDM-1, OXA-48 | 1024 | 2048 | 2048 | 1024 | 128 + 512 0.375 | 64 + 128 0.1875 | 512 + 512 0.5 | [10] |
AK-149 Klebsiella pneumoniae | NDM-1, OXA-48 | 1024 | 2048 | 2048 | 2048 | 128 + 512 0.375 | 512 + 128 0.375 | 256 + 512 0.375 | [10] |
AK-158 Klebsiella pneumoniae | NDM-5 | 1024 | 2048 | 2048 | 2048 | 128 + 256 0.25 | 64 + 512 0.3125 | 512 + 512 0.5 | [10] |
AK-100 Klebsiella oxytoca | NDM-4, OXA-1, OXA-9 | 1024 | 4096 | 1024 | 2048 | 256 + 256 0.3125 | 256 + 512 0.5 | 128 + 512 0.25 | [8] |
AK-67 Enterobacter aerogenes | NDM-1, OXA-1, SHV-2 | 1024 | 2048 | 1024 | 2048 | 64 + 128 0.1875 | 128 + 64 0.1562 | 32 + 64 0.3125 | [8] |
AK-93 Enterobacter aerogenes | NDM-4, OXA-1, OXA-9, SHV-1 | 512 | 1024 | 256 | 1024 | 64 + 64 0.185 | 128 + 128 0.375 | 32 + 64 0.25 | [11] |
AK-95 Enterobacter aerogenes | NDM-5, OXA-1, OXA-9, CMY-149 | 256 | 1024 | 256 | 1024 | 64 + 128 0.375 | 64 + 256 0.5 | 32 + 256 0.375 | [11] |
AK-96 Enterobacter aerogenes | NDM-7, OXA-1, OXA-9, CMY-145 | 256 | 1024 | 256 | 2048 | 64 + 128 0.375 | 32 + 256 0.375 | 64 + 256 0.5 | [11] |
AK-108 Enterobacter cloacae | NDM-4, OXA-1, OXA-9, CMY-149 | 512 | 2048 | 512 | 1024 | 128 + 256 0.375 | 128 + 256 0.5 | 64 + 256 0.25 | [8] |
AK-154 Acinetobacter baumannii | NDM-5 | 1024 | 2048 | 1024 | 2048 | 128 + 256 0.25 | 128 + 256 0.25 | 64 + 256 0.1875 | [9] |
AK-42 Citrobacter freundii | NDM-1, CMY-42, OXA-1, CTX-M, AmpC | 1024 | 4096 | 1024 | 4096 | 256 + 1024 0.5 | 256 + 512 0.375 | 128 + 1024 0.375 | [13] |
AK-58 Citrobacter freudii | NDM-7, CMY-2, OXA-1, CTX-M | 256 | 1024 | 128 | 2048 | 32 + 256 0.375 | 64 + 512 0.5 | 32 + 128 0.375 | [13] |
AK-82 Citrobacter freundii | NDM-4, OXA-9, SHV-1, CMY-149 | 512 | 4096 | 2048 | 2048 | 128 + 1024 0.5 | 64 + 256 0.25 | 128 + 512 0.1875 | [8] |
AK-48 Citrobacter braakii | NDM-4, CMY-4, OXA-48 | 512 | 1024 | 1024 | 4096 | 128 + 256 0.5 | 128 + 512 0.375 | 128 + 128 0.25 | [13] |
AK-49 Citrobacter farmer | NDM-4, CMY-4, OXA-48 | 256 | 1024 | 1024 | 2048 | 64 + 256 0.5 | 128 + 1024 0.5 | 128 + 128 0.25 | [13] |
AK-68 Cedecea lapagei | NDM-1, CTX-M, SHV, TEM | 512 | 1024 | 512 | 1024 | 128 + 256 0.5 | 128 + 256 0.5 | 128 + 128 0.375 | [12] |
AK-152 Cedecea davisae | NDM-1 | 1024 | 2048 | 1024 | 1024 | 128 + 256 0.25 | 128 + 256 0.375 | 64 + 256 0.1875 | [9] |
AK-65 Shigella boydii | NDM-5, CMY-42, OXA-1, CTX-M | 1024 | 2048 | 128 | 2048 | 64 + 64 0.125 | 128 + 128 0.1875 | 32 + 128 0.3125 | [13] |
AK-92 Moellerella wisconsensis | NDM-1 | 512 | 1024 | 256 | 2048 | 128 + 256 0.5 | 64 + 256 0.25 | 64 + 128 0.375 | [7] |
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Khalid, S.; Migliaccio, A.; Zarrilli, R.; Khan, A.U. Efficacy of Novel Combinations of Antibiotics against Multidrug-Resistant—New Delhi Metallo-Beta-Lactamase-Producing Strains of Enterobacterales. Antibiotics 2023, 12, 1134. https://doi.org/10.3390/antibiotics12071134
Khalid S, Migliaccio A, Zarrilli R, Khan AU. Efficacy of Novel Combinations of Antibiotics against Multidrug-Resistant—New Delhi Metallo-Beta-Lactamase-Producing Strains of Enterobacterales. Antibiotics. 2023; 12(7):1134. https://doi.org/10.3390/antibiotics12071134
Chicago/Turabian StyleKhalid, Shamsi, Antonella Migliaccio, Raffaele Zarrilli, and Asad U. Khan. 2023. "Efficacy of Novel Combinations of Antibiotics against Multidrug-Resistant—New Delhi Metallo-Beta-Lactamase-Producing Strains of Enterobacterales" Antibiotics 12, no. 7: 1134. https://doi.org/10.3390/antibiotics12071134
APA StyleKhalid, S., Migliaccio, A., Zarrilli, R., & Khan, A. U. (2023). Efficacy of Novel Combinations of Antibiotics against Multidrug-Resistant—New Delhi Metallo-Beta-Lactamase-Producing Strains of Enterobacterales. Antibiotics, 12(7), 1134. https://doi.org/10.3390/antibiotics12071134