In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy
Abstract
:1. Introduction
2. Results
2.1. Antimicrobial Susceptibility
2.2. Whole-Genome Sequencing of SUL–DUR Resistant A. baumannii: Resistome and Virulome Characterization
2.3. Molecular Analysis of PBP-3 Gene
3. Discussion
4. Materials and Methods
4.1. Antibiotics and Inhibitors
4.2. Bacterial Strains Selection
4.3. Bacterial Strains Identification
4.4. MIC Determination
4.5. Whole-Genome Sequencing
4.6. PBP-3 Amplification and Sequencing
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antimicrobial Agent | Number of Isolates at Each MIC (mg/L) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0.06 | 0.125 | 0,25 | 0.5 | 1 | 2 | 4 | >4 | 8 | 16 | 32 | 64 | 128 | >128 | MIC RANGE | MIC50 | MIC90 | |
SUL | / | / | / | / | / | 2 | 8 | _ | 27 | 45 | 33 | 8 | 13 | 5 | 0.06–>128 | 16 | 128 |
DUR | / | / | / | / | / | / | / | _ | 3 | 7 | 44 | 39 | 47 | 1 | 0.06–>128 | 64 | 128 |
SUL–DUR | / | 4 | 25 | 51 | 30 | 14 | 6 | _ | 4 | 2 | / | / | / | 5 | 0.06/4–>128/4 | 0.5 | 4 |
CST | / | 7 | 6 | 12 | 20 | 19 | 22 | 55 | _ | _ | _ | _ | _ | _ | 0.06–>4 | 4 | >4 |
City (No. Isolates) Antimicrobial Agents | Number of Isolates with MIC (mg/L) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0.06 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | >4 | 8 | 16 | 32 | 64 | 128 | >128 | |
Pavia (16) | ||||||||||||||
SUL | / | / | / | / | / | / | 1 | - | 1 | 5 | 7 | 2 | / | / |
DUR | / | / | / | / | / | / | / | - | / | / | / | 2 | 13 | 1 |
SUL–DUR | / | / | / | 6 | 6 | 4 | / | - | / | / | / | / | / | / |
CST | / | / | 1 | 6 | 9 | / | / | / | - | - | - | - | - | - |
Gemelli (26) | ||||||||||||||
SUL | / | / | / | / | / | 1 | 2 | - | 4 | 11 | 7 | 1 | / | / |
DUR | / | / | / | / | / | / | / | - | / | 2 | 6 | 11 | 7 | / |
SUL–DUR | / | / | 3 | 16 | 7 | / | / | - | / | / | / | / | / | / |
CST | / | / | / | / | / | / | 13 | 13 | - | - | - | - | - | - |
PE/AQ (9) | ||||||||||||||
SUL | / | / | / | / | / | / | / | - | / | 1 | 6 | 1 | 1 | / |
DUR | / | / | / | / | / | / | / | - | / | / | 3 | 2 | 4 | / |
SUL–DUR | / | / | 1 | 2 | 2 | 4 | / | - | / | / | / | / | / | / |
CST | / | / | / | / | / | / | / | 9 | - | - | - | - | - | - |
Roma Tre (20) | ||||||||||||||
SUL | / | / | / | / | / | 1 | 3 | - | 3 | 5 | 7 | 1 | / | / |
DUR | / | / | / | / | / | / | / | - | / | / | 6 | 6 | 8 | / |
SUL–DUR | / | / | 3 | 7 | 7 | 1 | 2 | - | / | / | / | / | / | / |
CST | / | / | / | / | / | 7 | 7 | 6 | - | - | - | - | - | - |
Catania (70) | ||||||||||||||
SUL | / | / | / | / | / | / | 2 | - | 19 | 23 | 6 | 3 | 12 | 5 |
DUR | / | / | / | / | / | / | / | - | 3 | 5 | 29 | 18 | 15 | / |
SUL–DUR | / | 4 | 18 | 20 | 8 | 5 | 4 | - | 4 | 2 | / | / | / | 5 |
CST | / | 7 | 5 | 6 | 11 | 12 | 2 | 27 | - | - | - | - | - | - |
Strain | Sequence Type | Ward | Sample | SUL–DUR MIC (mg/L) | SUL MIC (mg/L) | DUR MIC (mg/L) | CST MIC (mg/L) | Resistance Genes | Mobile Genetic Elements | |
---|---|---|---|---|---|---|---|---|---|---|
β-Lactamases | Other | |||||||||
A. baumannii CT20 | 2 | transplant | BAL | 8 | 128 | 128 | 0.125 | blaADC-25 blaOXA-20 blaOXA-58 | aac(6′)-Ib-cr aac(6′)-Ib3 tetA(41) | IS26, ISAba125 |
A. baumannii CT57 | 2 | ICU | BAL | 8 | 128 | 64 | 64 |
blaADC-25 blaOXA-20 blaOXA-58 | aac(6′)-Ib-cr aac(6′)-Ib3 tetA(41) | Tn6018, IS26, ISAba125 |
A. baumannii CT58 | 2 | ICU | wound | 8 | 128 | 32 | 32 |
blaADC-25 blaOXA-20 blaOXA-58 | aac(6′-)Ib-cr aac(6′)-Ib3 tetA(41) | Tn6018, IS26, ISAba125 |
A. baumannii CT68 | 2 | ICU | blood | 8 | 128 | 64 | 0.25 |
blaADC-25 blaOXA-20 blaOXA-58 | aac(6′)-Ib-cr aac(6′)-Ib3 sul1 | IS26, ISAba125 |
A. baumannii CT24 | 2 | ICU | blood | 16 | 64 | 128 | 0.5 |
blaADC-25 blaOXA-20 blaOXA-58 blaOXA-66 | aac(6′)-Ib-cr aac(6′)-Ib3 qacE sul1 gyrA (S81L) parC(V104I, D105E) | IS26, ISAba125 |
A. baumannii CT25 | 2 | ICU | catheter | 16 | 128 | 64 | 1 |
blaADC-25 blaOXA-20 blaOXA-58 blaOXA-66 | aac(6′)-Ib-cr aac(6′)-Ib3 sul1 | IS26, ISAba125 |
A. baumannii CT26 | 2 | surgery | bile | >128 | >128 | 64 | 0.5 |
blaADC-25 blaOXA-20 blaOXA-58 blaOXA-66 | aac(6′)-Ib-cr aac(6′)-Ib3 qacE sul1 gyrA (S81L) parC (V104I, D105E) | IS26, ISAba125 |
A. baumannii CT29 | 2 | ICU | exudate | >128 | >128 | 128 | 1 |
blaADC-25 blaOXA-20 blaOXA-58 blaOXA-66 | aac(6′)-Ib-cr aac(6′)-Ib3 qacE sul1 gyrA (S81L) parC (V104I, D105E) | IS26, ISAba125 |
A. baumannii CT30 | 20 | ICU | catheter | >128 | >128 | 32 | 1 |
blaADC-25 blaOXA-20 blaOXA-58 blaOXA-66 | aac(6′)-Ib-cr aac(6′)-Ib3 qacE sul1 gyrA (S81L) parC (V104I, D105E) | IS26, ISAba125 |
A. baumannii CT31 | 20 | ICU | pus | >128 | >128 | 128 | 0.125 |
blaADC-25 blaOXA-20 blaOXA-58 blaOXA-66 | aac(6′)-Ib-cr aac(6′)-Ib3 qacE sul1 gyrA (S81L) parC(V104I, D105E) | IS26, ISAba125 |
A. baumannii CT32 | 20 | ICU | BAL | >128 | >128 | 128 | 1 |
blaADC-25 blaOXA-20 blaOXA-58 blaOXA-66 | aac(6′)-Ib-cr aac(6′)-Ib3 qacE sul1 gyrA (S81L) parC (V104I, D105E) | IS26, ISAba125 |
SUL–DUR-Resistant A. baumannii (Strains No.: CT20, CT24, CT25, CT26, CT29, CT30, CT31, CT32, CT57, CT58, CT68) | |
---|---|
Virulence-Associated Genes | Virulence Factors |
adeA, adeC, adeF, adeG, adeH, adeI, adeK, adeL, adeN, adeJ, adeR | RND efflux pump AdeABC, AdeFGH and AdeIJK |
abeS | SMR family of transporter efflux pumps |
abaQ, abaF | MFS transporters |
plc, plcD | Phospholipase |
lpsB (only in CT57 and CT58) | Lipopolysaccharide synthesis (mutations are involved in CST resistance) |
lpxA, lpxB, lpxC, lpxD, lpxL, lpxM (only in CT57 and CT58) | Biosynthesis of lipid A (mutations are involved in CST resistance) |
barA, barB basA, basB, basC, basD, basF, basG, basH, basI, basJ bauA, bauB, bauC, bauD, bauE, bauF entE hemO | Iron uptake: acinetobactin and heme utilization |
bap, pgaA, pgaB, pgaC, pgaD, csuA, csuB, csuC, csuD, csuE, bfmR, bfmS | Biofilm formation system and cell–cell adhesion |
abaI, abaR | Quorum sensing |
pbpG (or PBP7) and PBP3Q488K and PBP3Y528H | Penicillin-binding protein |
katA | A secondary catalase/peroxidase |
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Segatore, B.; Piccirilli, A.; Cherubini, S.; Principe, L.; Alloggia, G.; Mezzatesta, M.L.; Salmeri, M.; Di Bella, S.; Migliavacca, R.; Piazza, A.; et al. In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy. Antibiotics 2022, 11, 1136. https://doi.org/10.3390/antibiotics11081136
Segatore B, Piccirilli A, Cherubini S, Principe L, Alloggia G, Mezzatesta ML, Salmeri M, Di Bella S, Migliavacca R, Piazza A, et al. In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy. Antibiotics. 2022; 11(8):1136. https://doi.org/10.3390/antibiotics11081136
Chicago/Turabian StyleSegatore, Bernardetta, Alessandra Piccirilli, Sabrina Cherubini, Luigi Principe, Giovanni Alloggia, Maria Lina Mezzatesta, Mario Salmeri, Stefano Di Bella, Roberta Migliavacca, Aurora Piazza, and et al. 2022. "In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy" Antibiotics 11, no. 8: 1136. https://doi.org/10.3390/antibiotics11081136