Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains, Media, and Growth Conditions
2.2. Determination of the MIC
2.3. Screen for Combinatorial Effects by Disc Diffusion
2.4. Checkerboard Assays
2.5. Interpretation of Data
2.6. Whole Genome Sequencing
2.7. Bioinformatics Analysis
3. Results
3.1. Determination of Susceptibilities of Clinical Isolates of A. baumannii to Standard-of-Care Drugs
3.2. Determination of Antibiotic Susceptibilities of New Antibiotics
3.3. Determination of Combinatorial Effects of Various Combinations of Antibiotics
3.4. Identification of Resistance Genes among A. baumannii Isolates
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antibiotic | Susceptible | Intermediate | Resistant |
---|---|---|---|
Gentamicin | 4.8% | 4.8% | 90.5% |
Amikacin | 33.3% | 4.8% | 61.9% |
Tobramycin | 9.5% | 9.5% | 81.0% |
Netilmicin | 4.8% | 9.5% | 85.7% |
Doxycycline | 33.3% | 9.5% | 57.1% |
Tetracycline | 23.8% | 4.8% | 71.4% |
Tigecycline | 0.0% | 0.0% | 100.0% |
Minocycline | 66.7% | 19.0% | 14.3% |
Ceftazidime | 0.0% | 4.8% | 95.2% |
Ceftriaxone | 0.0% | 9.5% | 90.5% |
Cefotaxime | 0.0% | 9.5% | 90.5% |
Cefepime | 9.5% | 9.5% | 81.0% |
Imipenem | 0.0% | 0.0% | 100.0% |
Meropenem | 4.8% | 4.8% | 90.5% |
Doripenem | 14.3% | 4.8% | 81.0% |
Ciprofloxacin | 0.0% | 0.0% | 100.0% |
Levofloxacin | 0.0% | 0.0% | 100.0% |
Ampicillin–Sulbactam | 14.3% | 0.0% | 85.7% |
Piperacillin–Tazobactam | 0.0% | 4.8% | 95.2% |
Ticarcillin–Clavulanic Acid | 0.0% | 0.0% | 100.0% |
Trimethoprim–Sulfamethoxazole | 0.0% | 0.0% | 100.0% |
Rifampin | 57.1% | 9.5% | 33.3% |
Strain | Eravacycline | Omadacycline | Plazomicin |
---|---|---|---|
M1 | 8 | 16 | >32 |
M2 | 2 | 12 | >32 |
M3 | 6 | 4 | 6 |
M4 | 8 | 4 | >32 |
M5 * | 12 | 2 | >32 |
M6 | 16 | 3 | >32 |
M7 | 16 | 8 | >32 |
M8 | 16 | 32 | >32 |
M9 * | 8 | 3 | >32 |
M10 | 3 | 6 | >32 |
M11 | 1 | 0.25 | >32 |
M12 | 4 | 1 | >32 |
M13 | 0.75 | 0.25 | 24 |
M14 | 4 | 5 | >32 |
M16 | 3 | 2 | >32 |
M17 * | 32 | 16 | >32 |
M18 | 8 | 4 | 32 |
M19 * | 4 | 2 | >32 |
M20 * | 4 | 2 | >32 |
M21 * | 4 | 2 | >32 |
M22 | 8 | 8 | >32 |
Combination | Synergistic | Additive | Indifferent |
---|---|---|---|
Cefepime × Ampicillin–Sulbactam | 76.2% | 19.0% | 4.8% |
Cefepime × Amikacin | 42.9% | 38.1% | 19.0% |
Cefepime × Rifampin | 0% | 57.1% | 42.9% |
Levofloxacin × Amikacin | 4.8% | 23.8% | 71.4% |
Levofloxacin × Cefepime | 9.5% | 76.2% | 14.3% |
Eravacycline × Ampicillin–Sulbactam | 38.1% | 57.1% | 4.8% |
Eravacycline × Amikacin | 19.0% | 42.9% | 38.1% |
Eravacycline × Rifampin | 9.5% | 85.7% | 4.8% |
Eravacycline × Levofloxacin | 0% | 38.1% | 61.9% |
Omadacycline × Ampicillin–Sulbactam | 23.8% | 19.0% | 57.1% |
Omadacycline × Amikacin | 0% | 33.3% | 66.7% |
Omadacycline × Rifampin | 0% | 57.1% | 42.8% |
Omadacycline × Levofloxacin | 9.5% | 47.6% | 42.9% |
Gene Symbol | Class | Description | M1 | M4 | M5 | M9 | M10 | M11 | M13 | M20 |
---|---|---|---|---|---|---|---|---|---|---|
aac(3)-Ia | Aminoglycoside | aminoglycoside N-acetyltransferase AAC(3)-Ia | X | X | X | |||||
aac(6′)-Ib′ | Aminoglycoside | aminoglycoside N-acetyltransferase AAC(6′)-Ib′ | X | |||||||
aadA1 | Aminoglycoside | ANT(3″)-Ia family aminoglycoside nucleotidyltransferase AadA1 | X | X | X | X | X | |||
aph(3′)-VIa | Aminoglycoside | aminoglycoside O-phosphotransferase APH(3′)-VIa | X | |||||||
aph(3″)-Ib | Aminoglycoside | aminoglycoside O-phosphotransferase APH(3″)-Ib | X | X | X | X | X | X | X | |
aph(3′)-Ia | Aminoglycoside | aminoglycoside O-phosphotransferase APH(3′)-Ia | X | |||||||
aph(6)-Id | Aminoglycoside | aminoglycoside O-phosphotransferase APH(6)-Id | X | X | X | X | X | X | X | X |
ant(3″)-IIa | Aminoglycoside | aminoglycoside nucleotidyltransferase ANT(3″)-IIa | X | X | X | X | X | X | X | X |
armA | Aminoglycoside | 16S rRNA (guanine(1405)-N(7))-methyltransferase ArmA | X | X | X | X | X | |||
tet(B) | Tetracycline | tetracycline efflux MFS transporter Tet(B) | X | X | X | X | X | X | X | X |
blaADC-30 | Beta-lactam | extended-spectrum class C beta-lactamase ADC-30 | X | |||||||
blaADC-33 | Beta-lactam | cefepime-hydrolyzing class C beta-lactamase ADC-33 | X | |||||||
blaADC-73 | Beta-lactam | extended-spectrum class C beta-lactamase ADC-73 | X | X | X | X | ||||
blaADC-80 | Beta-lactam | extended-spectrum class C beta-lactamase ADC-80 | X | |||||||
blaADC-150 | Beta-lactam | extended-spectrum class C beta-lactamase ADC-150 | X | |||||||
blaOXA-23 | Beta-lactam | OXA-23 family carbapenem-hydrolyzing class D beta-lactamase OXA-23 | X | X | X | X | ||||
blaOXA-66 | Beta-lactam | OXA-51 family carbapenem-hydrolyzing class D beta-lactamase OXA-66 | X | X | X | X | X | X | ||
blaOXA-82 | Beta-lactam | OXA-51 family carbapenem-hydrolyzing class D beta-lactamase OXA-82 | X | |||||||
blaOXA-94 | Beta-lactam | OXA-51 family carbapenem-hydrolyzing class D beta-lactamase OXA-94 | X | |||||||
blaOXA-421 | Beta-lactam | OXA-213 family carbapenem-hydrolyzing class D beta-lactamase OXA-421 | X | |||||||
ftsI_A515V | Beta-lactam | penicillin-binding protein PBP3 FtsI | X | X | X | X | ||||
gyrA_S81L | Flouroquinolone | DNA gyrase subunit A GyrA | X | X | X | X | X | X | X | |
parC_S84L | Flouroquinolone | DNA topoisomerase IV subunit A ParC | X | X | X | X | X | X | X | |
parC_E88K | Flouroquinolone | DNA topoisomerase IV subunit A ParC | X | |||||||
mph(E) | Macrolide | Mph(E) family macrolide 2′-phosphotransferase | X | X | X | X | X | X | ||
msr(E) | Macrolide | ABC-F type ribosomal protection protein Msr(E) | X | X | X | X | X | |||
catB8 | Phenicol | type B-3 chloramphenicol O-acetyltransferase CatB8 | X | |||||||
floR | Phenicol | chloramphenicol/florfenicol efflux MFS transporter FloR | X | |||||||
sul1 | Sulfonamide | sulfonamide-resistant dihydropteroate synthase Sul1 | X | X | X | X | X | |||
sul2 | Sulfonamide | sulfonamide-resistant dihydropteroate synthase Sul2 | X | X | X | X | X | X | X | X |
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Halim, J.; Carr, R.A.; Fliorent, R.; Jonnalagadda, K.; Kurbonnazarova, M.; Kaur, M.; Millstein, I.; Carabetta, V.J. Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates. Microorganisms 2024, 12, 1353. https://doi.org/10.3390/microorganisms12071353
Halim J, Carr RA, Fliorent R, Jonnalagadda K, Kurbonnazarova M, Kaur M, Millstein I, Carabetta VJ. Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates. Microorganisms. 2024; 12(7):1353. https://doi.org/10.3390/microorganisms12071353
Chicago/Turabian StyleHalim, Justin, Rachel A. Carr, Rebecca Fliorent, Keertana Jonnalagadda, Maftuna Kurbonnazarova, Muskanjot Kaur, Ian Millstein, and Valerie J. Carabetta. 2024. "Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates" Microorganisms 12, no. 7: 1353. https://doi.org/10.3390/microorganisms12071353