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127 results on '"Piccirilli, Alessandra"'

4. Synergistic Activity of Temocillin and Fosfomycin Combination against KPC-Producing Klebsiella pneumoniae Clinical Isolates

Author

Costantino, Venera, primary, Principe, Luigi, additional, Mehat, Jai, additional, Busetti, Marina, additional, Piccirilli, Alessandra, additional, Perilli, Mariagrazia, additional, Luzzati, Roberto, additional, Zerbato, Verena, additional, Meliadò, Antonietta, additional, La Ragione, Roberto, additional, and Di Bella, Stefano, additional

Published
2024
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5. Camel-Derived Nanobodies as Potent Inhibitors of New Delhi Metallo-β-Lactamase-1 Enzyme.

Author

Ben Abderrazek, Rahma, Hamdi, Emna, Piccirilli, Alessandra, Dhaouadi, Sayda, Muyldermans, Serge, Perilli, Mariagrazia, and Bouhaouala-Zahar, Balkiss

Subjects
RECOMBINANT antibodies, ENZYMES, BACTERIAL diseases, GRAM-negative bacteria, CAMELIDAE
Abstract

The injudicious usage of antibiotics during infections caused by Gram-negative bacteria leads to the emergence of β-lactamases. Among them, the NDM-1 enzyme poses a serious threat to human health. Developing new antibiotics or inhibiting β-lactamases might become essential to reduce and prevent bacterial infections. Nanobodies (Nbs), the smallest antigen-binding single-domain fragments derived from Camelidae heavy-chain-only antibodies, targeting enzymes, are innovative alternatives to develop effective inhibitors. The biopanning of an immune VHH library after phage display has helped to retrieve recombinant antibody fragments with high inhibitory activity against recombinant-NDM-1 enzyme. Nb02NDM-1, Nb12NDM-1, and Nb17NDM-1 behaved as uncompetitive inhibitors against NDM-1 with Ki values in the nM range. Remarkably, IC50 values of 25.0 nM and 8.5 nM were noted for Nb02NDM-1 and Nb17NDM-1, respectively. The promising inhibition of NDM-1 by Nbs highlights their potential application in combating particular Gram-negative infections. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Identification of IncA Plasmid, Harboring blaVIM-1 Gene, in S. enterica Goldcoast ST358 and C. freundii ST62 Isolated in a Hospitalized Patient

Author

Piccirilli, Alessandra, primary, Di Marcantonio, Sascia, additional, Costantino, Venera, additional, Simonetti, Omar, additional, Busetti, Marina, additional, Luzzati, Roberto, additional, Principe, Luigi, additional, Di Domenico, Marco, additional, Rinaldi, Antonio, additional, Cammà, Cesare, additional, and Perilli, Mariagrazia, additional

Published
2023
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7. Coexistence of blaNDM-5, blaCTX-M-15, blaOXA-232, blaSHV-182genes in multidrug-resistant K. pneumoniaeST437-carrying OmpK36 and OmpK37 porin mutations: First report in Italy

Author

Di Marcantonio, Sascia, Perilli, Mariagrazia, Alloggia, Giovanni, Segatore, Bernardetta, Miconi, Gianfranca, Bruno, Gianfranco, Frascaria, Patrizia, and Piccirilli, Alessandra

Abstract

•Whole-genome sequencing was used to characterise the genome of two K. pneumoniaeST437 strains.•Virulence factors in K. pneumoniaeST437 were analysed.•IncFIB(K), IncFII, IncFII(K), IncR, Col(BS512), ColKP3, and ColRNAI plasmids were identified.•Coexistence of blaNDM-5, blaCTX-M-15, blaOXA-232, blaSHV-182, and blaTEM-1Bβ-lactamase genes.

Published
2024
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8. New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians

Author

Carcione, Davide, primary, Intra, Jari, additional, Andriani, Lilia, additional, Campanile, Floriana, additional, Gona, Floriana, additional, Carletti, Silvia, additional, Mancini, Nicasio, additional, Brigante, Gioconda, additional, Cattaneo, Dario, additional, Baldelli, Sara, additional, Chisari, Mattia, additional, Piccirilli, Alessandra, additional, Di Bella, Stefano, additional, and Principe, Luigi, additional

Published
2023
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11. Identification of IncA Plasmid, Harboring bla VIM-1 Gene, in S. enterica Goldcoast ST358 and C. freundii ST62 Isolated in a Hospitalized Patient.

Author

Piccirilli, Alessandra, Di Marcantonio, Sascia, Costantino, Venera, Simonetti, Omar, Busetti, Marina, Luzzati, Roberto, Principe, Luigi, Di Domenico, Marco, Rinaldi, Antonio, Cammà, Cesare, and Perilli, Mariagrazia

Subjects
INCAS, HOSPITAL patients, ACUTE myeloid leukemia, SALMONELLA enterica serovar Typhi, GENES
Abstract

In the present study, we analyzed the genome of two S. enterica strains TS1 and TS2 from stool and blood cultures, respectively, and one strain of C. freundii TS3, isolated from a single hospitalized patient with acute myeloid leukemia. The S. enterica Goldcoast ST358 (O:8 (C2-C3) serogroup), sequenced by the MiSeq Illumina system, showed the presence of β-lactamase genes (blaVIM-1, blaSHV-12 and blaOXA-10), aadA1, ant(2″)-Ia, aac(6′)-Iaa, aac(6′)-Ib3, aac(6′)-Ib-cr, qnrVC6, parC(T57S), and several incompatibility plasmids. A wide variety of insertion sequences (ISs) and transposon elements were identified. In C. freundii TS3, these were the blaVIM-1, blaCMY-150, and blaSHV-12, aadA1, aac(6′)-Ib3, aac(6′)-Ib-cr, mph(A), sul1, dfrA14, ARR-2, qnrVC6, and qnrB38. IncA plasmid isolated from E.coli/K12 transconjugant and C. freundii exhibited a sequence identity >99.9%. The transfer of IncA plasmid was evaluated by conjugation experiments. [ABSTRACT FROM AUTHOR]

Published
2023
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13. The crosstalk between gut barrier impairment, mitochondrial dysfunction, and microbiota alterations in people living with HIV

Author

Santinelli, Letizia, primary, Rossi, Giacomo, additional, Gioacchini, Giorgia, additional, Verin, Ranieri, additional, Maddaloni, Luca, additional, Cavallari, Eugenio N., additional, Lombardi, Francesca, additional, Piccirilli, Alessandra, additional, Fiorucci, Stefano, additional, Carino, Adriana, additional, Marchianò, Silvia, additional, Lofaro, Chiara M., additional, Caiazzo, Sara, additional, Ciccozzi, Massimo, additional, Scagnolari, Carolina, additional, Mastroianni, Claudio M., additional, Ceccarelli, Giancarlo, additional, and d'Ettorre, Gabriella, additional

Published
2023
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14. Evaluation of the Analytical Performances of the Biolabo SOLEA 100 Optical Coagulometer and Comparison with the Stago STA-R MAX Analyser in the Determination of PT, APTT, and Fibrinogen

Author

Bellio, Pierangelo, primary, De Angelis, Simonetta, additional, Piccirilli, Alessandra, additional, Di Michele, Giulio, additional, Barnabei, Remo, additional, Amicosante, Gianfranco, additional, Perilli, Mariagrazia, additional, and Celenza, Giuseppe, additional

Published
2022
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17. Molecular Characterization by Whole-Genome Sequencing of Clinical and Environmental Serratia marcescens Strains Isolated during an Outbreak in a Neonatal Intensive Care Unit (NICU)

Author

Piccirilli, Alessandra, primary, Cherubini, Sabrina, additional, Brisdelli, Fabrizia, additional, Fazii, Paolo, additional, Stanziale, Andrea, additional, Di Valerio, Susanna, additional, Chiavaroli, Valentina, additional, Principe, Luigi, additional, and Perilli, Mariagrazia, additional

Published
2022
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18. In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy

Author

Segatore, Bernardetta, primary, Piccirilli, Alessandra, additional, Cherubini, Sabrina, additional, Principe, Luigi, additional, Alloggia, Giovanni, additional, Mezzatesta, Maria Lina, additional, Salmeri, Mario, additional, Di Bella, Stefano, additional, Migliavacca, Roberta, additional, Piazza, Aurora, additional, Meroni, Elisa, additional, Fazii, Paolo, additional, Visaggio, Daniela, additional, Visca, Paolo, additional, Cortazzo, Venere, additional, De Angelis, Giulia, additional, Pompilio, Arianna, additional, and Perilli, Mariagrazia, additional

Published
2022
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19. Exploiting Bacteria for Improving Hypoxemia of COVID-19 Patients

Author

Trinchieri, Vito, primary, Marazzato, Massimiliano, additional, Ceccarelli, Giancarlo, additional, Lombardi, Francesca, additional, Piccirilli, Alessandra, additional, Santinelli, Letizia, additional, Maddaloni, Luca, additional, Vassalini, Paolo, additional, Mastroianni, Claudio Maria, additional, and d’Ettorre, Gabriella, additional

Published
2022
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21. A Two Amino Acid Duplication, L167E168, in the Ω-Loop Drastically Decreases Carbapenemase Activity of KPC-53, a Natural Class A β-Lactamase

Author

Piccirilli, Alessandra, primary, Cherubini, Sabrina, additional, Celenza, Giuseppe, additional, Rossolini, Gian Maria, additional, Brisdelli, Fabrizia, additional, Segatore, Bernardetta, additional, Principe, Luigi, additional, Luzzaro, Francesco, additional, Andriani, Lilia, additional, Amicosante, Gianfranco, additional, and Perilli, Mariagrazia, additional

Published
2022
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23. Exploring the Role of L10 Loop in New Delhi Metallo-��-lactamase (NDM-1): Kinetic and Dynamic Studies

Author

Piccirilli, Alessandra, Criscuolo, Emanuele, Brisdelli, Fabrizia, Mercuri, Paola Sandra, Cherubini, Sabrina, De Sciscio, Maria Laura, Maccarrone, Mauro, Galleni, Moreno, Amicosante, Gianfranco, and Perilli, Maria Grazia

Subjects
metallo-��-lactamases, NDM-1, kinetic studies, molecular dynamic
Abstract

Four NDM-1 mutants (L218T, L221T, L269H and L221T/Y229W) were generated in order to investigate the role of leucines positioned in L10 loop. A detailed kinetic analysis stated that these amino acid substitutions modified the hydrolytic profile of NDM-1 against some ��-lactams. Significant reduction of kcat values of L218T and L221T for carbapenems, cefazolin, cefoxitin and cefepime was observed. The stability of the NDM-1 and its mutants was explored by thermofluor assay in real-time PCR. The determination of TmB and TmD demonstrated that NDM-1 and L218T were the most stable enzymes. Molecular dynamic studies were performed to justify the differences observed in the kinetic behavior of the mutants. In particular, L218T fluctuated more than NDM-1 in L10, whereas L221T would seem to cause a drift between residues 75 and 125. L221T/Y229W double mutant exhibited a decrease in the flexibility with respect to L221T, explaining enzyme activity improvement towards some ��-lactams. Distances between Zn1-Zn2 and Zn1-OH- or Zn2- OH- remained unaffected in all systems analysed. Significant changes were found between Zn1/Zn2 and first sphere coordination residues.

Published
2021
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25. Oxygen Sparing Effect of Bacteriotherapy in COVID-19

Author

Ceccarelli, Giancarlo, primary, Marazzato, Massimiliano, additional, Celani, Luigi, additional, Lombardi, Francesca, additional, Piccirilli, Alessandra, additional, Mancone, Massimo, additional, Trinchieri, Vito, additional, Pugliese, Francesco, additional, Mastroianni, Claudio M., additional, and d’Ettorre, Gabriella, additional

Published
2021
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28. Molecular characterization of carbapenem-resistant Klebsiella pneumoniae ST14 and ST512 causing bloodstream infections in ICU and surgery wards of a tertiary university hospital of Verona (northern Italy): co-production of KPC-3, OXA-48, and CTX-M-15 β-lactamases

Author

Piccirilli, Alessandra, Perilli, Mariagrazia, Piccirilli, Valentina, Segatore, Bernardetta, Amicosante, Gianfranco, Maccacaro, Laura, Bazaj, Alda, Naso, Laura, Cascio, Giuliana Lo, and Cornaglia, Giuseppe

Published
2020
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29. A homozygous MED11 C-terminal variant causes a lethal neurodegenerative disease

Author

Calì, Elisa, Lin, Sheng-Jia, Rocca, Clarissa, Sahin, Yavuz, Al Shamsi, Aisha, El Chehadeh, Salima, Chaabouni, Myriam, Mankad, Kshitij, Galanaki, Evangelia, Efthymiou, Stephanie, Sudhakar, Sniya, Athanasiou-Fragkouli, Alkyoni, Çelik, Tamer, Narlı, Nejat, Bianca, Sebastiano, Murphy, David, De Carvalho Moreira, Francisco Martins, Hannah, Michael G., Bugiardini, Enrico, Kriouile, Yamna, El Khorassani, Mohamed, Aguennouz, Mhammed, Groppa, Stanislav, Karashova, Blagovesta Marinova, Di Rosa, Gabriella, Goraya, Jatinder S., Sultan, Tipu, Avdjieva, Daniela, Kathom, Hadil, Tincheva, Radka, Banu, Selina, Veggiotti, Pierangelo, Verrotti, Alberto, Savasta, Salvatore, Ruiz, Alfons Macaya, Garavaglia, Barbara, Borgione, Eugenia, Papacostas, Savvas, Compagnoni, Chiara, Piccirilli, Alessandra, Vikelis, Michail, Chelban, Viorica, Kaiyrzhanov, Rauan, Cortese, Andrea, Sullivan, Roisin, Papanicolaou, Eleni Zamba, Dardiotis, Efthymios, Maqbool, Shazia, Ibrahim, Shahnaz, Kirmani, Salman, Rana, Nuzhat Noureen, Atawneh, Osama, Lim, Shen-Yang, Shaikh, Farooq, Scardamaglia, Annarita, Koutsis, George, Mangano, Salvatore, Scuderi, Carmela, Borgione, Eugenia, Morello, Giovanna, Zollo, Massimo, Heimer, Gali, Striano, Pasquale, Al-Khawaja, Issam, Al-Mutairi, Fuad, Alkuraya, Fowzan S., Rizig, Mie, Shashkin, Chingiz, Zharkynbekova, Nazira, Koneyev, Kairgali, Manizha, Ganieva, Isrofilov, Maksud, Guliyeva, Ulviyya, Salayev, Kamran, Khachatryan, Samson, Xiromerisiou, Georgia, Spanaki, Cleanthe, Tucci, Arianna, Fiorillo, Chiara, Rissotto, Federico, Munell, Francina, Gagliano, Antonella, Jan, Farida, Chimenz, Roberto, Gitto, Eloisa, Cuppari, Caterina, Romeo, Carmelo, Magrinelli, Francesca, Gupta, Neerja, Kabra, Madhulika, Benrhouma, Hanene, Tazir, Meriem, Zagaroli, Luca, Caloisi, Claudia, Fabiano, Cecilia, Bottone, Gabriella, Farello, Giovanni, Di Fabio, Sandra, Obeid, Makram, Bakhtadze, Sophia, Saadi, Nebal W., Zaki, Maha S., Triki, Chahnez C., Kara, Majdi, Belcastro, Vincenzo, Specchio, Nicola, Karimiani, Ehsan G., Salih, Ahmed M., Ramenghi, Luca A., David, Emanuele, Curró, Riccardo, Iezzi, Maria Laura, Iapadre, Giulia, Nanni, Giuliana, Scorrano, Giovanna, Fiorile, Maria F., Brancati, Francesco, Di Falco, Giovanna, Mandarà, Luana, Barrano, Giuseppe, Elia, Maurizio, Terrone, Gaetano, Operto, Francesca F., Valenzise, Mariella, Della Rocca, Ylenia, Zazzeroni, Francesca, Alesse, Edoardo, Manti, Filippo, Galosi, Serena, Nardecchia, Francesca, Leuzzi, Vincenzo, Pironti, Erica, Amore, Greta, Ceravolo, Giorgia, Zafar, Faisal, Ullah, Ehsan, Afzal, Erum, Javed, Iram, Rahman, Fatima, Ahmed, Muhammad Mehboob, Parisi, Pasquale, Borgia, Paola, Mangano, Giuseppe D., Chiarelli, Francesco, Genomics, Queen Square, Accogli, Andrea, Petree, Cassidy, Huang, Kevin, Monastiri, Kamel, Edizadeh, Masoud, Nardello, Rosaria, Ognibene, Marzia, De Marco, Patrizia, Ruggieri, Martino, Zara, Federico, Striano, Pasquale, Şahin, Yavuz, Al-Gazali, Lihadh, Abi Warde, Marie Therese, Gerard, Benedicte, Zifarelli, Giovanni, Beetz, Christian, Fortuna, Sara, Soler, Miguel, Valente, Enza Maria, Varshney, Gaurav, Maroofian, Reza, Salpietro, Vincenzo, and Houlden, Henry

Abstract

The mediator (MED) multisubunit-complex modulates the activity of the transcriptional machinery, and genetic defects in different MED subunits (17, 20, 27) have been implicated in neurologic diseases. In this study, we identified a recurrent homozygous variant in MED11(c.325C>T; p.Arg109Ter) in 7 affected individuals from 5 unrelated families.

Published
2022
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32. Biofilm Formation among Stenotrophomonas maltophilia Isolates Has Clinical Relevance: The ANSELM Prospective Multicenter Study

Author

Pompilio, Arianna, primary, Ranalli, Marco, additional, Piccirilli, Alessandra, additional, Perilli, Mariagrazia, additional, Vukovic, Dragana, additional, Savic, Branislava, additional, Krutova, Marcela, additional, Drevinek, Pavel, additional, Jonas, Daniel, additional, Fiscarelli, Ersilia V., additional, Tuccio Guarna Assanti, Vanessa, additional, Tavío, María M., additional, Artiles, Fernando, additional, and Di Bonaventura, Giovanni, additional

Published
2020
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33. Amino Acid Replacement at Position 228 Induces Fluctuation in the Ω-Loop of KPC-3 and Reduces the Affinity against Oxyimino Cephalosporins: Kinetic and Molecular Dynamics Studies

Author

Piccirilli, Alessandra, primary, Brisdelli, Fabrizia, additional, Docquier, Jean Denis, additional, Aschi, Massimiliano, additional, Cherubini, Sabrina, additional, De Luca, Filomena, additional, Matagne, André, additional, Amicosante, Gianfranco, additional, and Perilli, Mariagrazia, additional

Published
2020
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35. Whole-Genome Sequencing (WGS) of Carbapenem-Resistant K. pneumoniae Isolated in Long-Term Care Facilities in the Northern Italian Region

Author

Piccirilli, Alessandra, Cherubini, Sabrina, Azzini, Anna, Tacconelli, Evelina, Cascio, Giuliana Lo, Maccacaro, Laura, Bazaj, Alda, Naso, Laura, Amicosante, Gianfranco, Group, LTCF-Veneto Working, and Perilli, Mariagrazia

Subjects
Microbiology (medical), Whole genome sequencing, Genetics, Carbapenem resistant, QH301-705.5, Klebsiella pneumoniae, β lactamases, K pneumoniae, β-lactamases, biochemical phenomena, metabolism, and nutrition, Biology, bacterial infections and mycoses, biology.organism_classification, Microbiology, Virology, polycyclic compounds, Biology (General), WGS, Illumina dye sequencing
Abstract

K. pneumoniae (KPN) is one of the widest spread bacteria in which combined resistance to several antimicrobial groups is frequent. The most common β-lactamases found in K. pneumoniae are class A carbapenemases, both chromosomal-encoded (i.e., NMCA, IMI-1) and plasmid-encoded (i.e., GES-enzymes, IMI-2), VIM, IMP, NDM, OXA-48, and extended-spectrum β-lactamases (ESBLs) such as CTX-M enzymes. In the present study, a total of 68 carbapenem-resistant KPN were collected from twelve long-term care facilities (LTCFs) in the Northern Italian region. The whole-genome sequencing (WGS) of each KPN strain was determined using a MiSeq Illumina sequencing platform and analysed by a bacterial analysis pipeline (BAP) tool. The WGS analysis showed the prevalence of ST307, ST512, and ST37 as major lineages diffused among the twelve LTCFs. The other lineages found were: ST11, ST16, ST35, ST253, ST273, ST321, ST416, ST1519, ST2623, and ST3227. The blaKPC-2, blaKPC-3, blaKPC-9, blaSHV-11, blaSHV-28, blaCTX-M-15, blaOXA-1, blaOXA-9, blaOXA-23, qnrS1, qnrB19, qnrB66, aac(6′)-Ib-cr, and fosA were the resistance genes widespread in most LTCFs. In this study, we demonstrated the spreading of thirteen KPN lineages among the LTCFs. Additionally, KPC carbapenemases are the most widespread β-lactamase.

Published
2021

37. First Identification of β-Lactamases in Antibiotic-Resistant Escherichia coli, Citrobacter freundii, and Aeromonas spp. Isolated in Stream Macroinvertebrates in a Central Italian Region

Author

Segatore, Bernardetta, primary, Piccirilli, Alessandra, additional, Setacci, Domenico, additional, Cicolani, Bruno, additional, Di Sabatino, Antonio, additional, Miccoli, Francesco Paolo, additional, Perilli, Mariagrazia, additional, and Amicosante, Gianfranco, additional

Published
2020
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38. Transient disappearance of CD19+/CD5+ B-lymphocyte clone in peripheral blood in a patient with CLL during SARS-CoV-2-related mild disease.

Author

Barnabei, Remo, Di Michele, Giulio, Cellini, Antonio, Amicosante, Gianfranco, Perilli, Mariagrazia, Bellio, Pierangelo, Piccirilli, Alessandra, and Celenza, Giuseppe

Subjects
CHRONIC lymphocytic leukemia, COVID-19, BIOMARKERS, PROGNOSIS, LYMPHOCYTIC leukemia, LYMPHOPENIA
Abstract

Although lymphopenia is currently considered a good predictor for the prognosis of COVID-19, it must be critically evaluated in patients with CLL, where other clinical markers should be considered to define the prognosis and treatment. [ABSTRACT FROM AUTHOR]

Published
2021
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43. Laboratory Variants GESG170L, GESG170K, and GESG170HIncrease Carbapenem Hydrolysis and Confer Resistance to Clavulanic Acid

Author

Piccirilli, Alessandra, Mercuri, Paola Sandra, Segatore, Bernardetta, Galleni, Moreno, Brisdelli, Fabrizia, Kerff, Frédéric, Amicosante, Gianfranco, and Perilli, Mariagrazia

Abstract

The Guiana extended-spectrum (GES) β-lactamase GESG170H, GESG170L, and GESG170Kmutants showed kcat, Km, and kcat/Kmvalues very dissimilar to those of GES-1 and GES-5. The enhancement of the hydrolytic activity against carbapenems is potentially due to a shift of the substrate in the active site that provides better positioning of the deacylating water molecule caused by the presence of the imidazole ring of H170 and of the long side chain of K170 and L170.

Published
2021
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45. Kinetic Studies on CphA Mutants Reveal the Role of the P158-P172 Loop in Activity versus Carbapenems

Author

Bottoni, Carlo, primary, Perilli, Mariagrazia, additional, Marcoccia, Francesca, additional, Piccirilli, Alessandra, additional, Pellegrini, Cristina, additional, Colapietro, Martina, additional, Sabatini, Alessia, additional, Celenza, Giuseppe, additional, Kerff, Frédéric, additional, Amicosante, Gianfranco, additional, Galleni, Moreno, additional, and Mercuri, Paola Sandra, additional

Published
2016
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46. Resistome and Virulome of Multi-Drug Resistant E. coli ST131 Isolated from Residents of Long-Term Care Facilities in the Northern Italian Region.

Author

Cherubini, Sabrina, Perilli, Mariagrazia, Azzini, Anna Maria, Tacconelli, Evelina, Maccacaro, Laura, Bazaj, Alda, Naso, Laura, Amicosante, Gianfranco, Lo Cascio, Giuliana, and Piccirilli, Alessandra

Subjects
LONG-term care facilities, KLEBSIELLA pneumoniae, DRUG resistance in bacteria, GENETIC transformation, GENETIC mutation, CARBAPENEMASE
Abstract

Long-term care facilities (LTCFs) are important reservoirs of antimicrobial-resistant (AMR) bacteria which colonize patients transferred from the hospital, or they may emerge in the facility as a result of mutation or gene transfer. In the present study, we characterized, from a molecular point of view, 43 E. coli strains collected from residents of LTCFs in Northern Italy. The most common lineage found was ST131, followed by sporadic presence of ST12, ST69, ST48, ST95, ST410 and ST1193. All strains were incubators of several virulence factors, with iss, sat, iha and senB being found in 84%, 72%, 63% and 51% of E. coli, respectively. Thirty of the ST131 analyzed were of the O25b:H4 serotype and H30 subclone. The ST131 isolates were found to be mainly associated with IncF plasmids, CTX-M-1, CTX-M-3, CTX-M-15, CTX-M-27 and gyrA/parC/parE mutations. Metallo-β-lactamases were not found in ST131, whereas KPC-3 carbapenemase was found only in two ST131 and one ST1193. In conclusion, we confirmed the spread of extended-spectrum β-lactamase genes in E. coli ST131 isolated from colonized residents living inside LTCFs. The ST131 represents an incubator of fluoroquinolones, aminoglycosides and other antibiotic resistance genes in addition to different virulence factors. [ABSTRACT FROM AUTHOR]

Published
2022
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47. Biofilm Formation among Stenotrophomonas maltophilia Isolates Has Clinical Relevance: The ANSELM Prospective Multicenter Study.

Author

Pompilio, Arianna, Ranalli, Marco, Piccirilli, Alessandra, Perilli, Mariagrazia, Vukovic, Dragana, Savic, Branislava, Krutova, Marcela, Drevinek, Pavel, Jonas, Daniel, Fiscarelli, Ersilia V., Tuccio Guarna Assanti, Vanessa, Tavío, María M., Artiles, Fernando, and Di Bonaventura, Giovanni

Subjects
STENOTROPHOMONAS maltophilia, BIOFILMS, DISC diffusion tests (Microbiology), MICROBIOLOGICAL assay, LONGITUDINAL method, TREATMENT effectiveness, PSEUDOMONAS aeruginosa infections
Abstract

The ability to form biofilms is a recognized trait of Stenotrophomonas maltophilia, but the extent of its clinical relevance is still unclear. The present multicenter prospective study (ANSELM) aims at investigating the association between biofilm formation and clinical outcomes of S. maltophilia infections. One hundred and nine isolates were collected from various geographical origins and stratified according to their clinical relevance. Biofilm formation was evaluated by the microtiter plate assay and correlated with microbiological and clinical data from the associated strains. Antibiotic susceptibility of the planktonic cells was tested by the disk diffusion technique, while antibiotic activity against mature biofilms was spectrophotometrically assessed. Most strains (91.7%) were able to form biofilm, although bloodborne strains produced biofilm amounts significantly higher than strains causing hospital- rather than community-acquired infections, and those recognized as "definite" pathogens. Biofilm formation efficiency was positively correlated with mechanical ventilation (p = 0.032), whereas a negative relationship was found with antibiotic resistance (r2 = 0.107; p < 0.001), specifically in the case of the pathogenic strains. Mature S. maltophilia biofilms were markedly more resistant (up to 128 times) to cotrimoxazole and levofloxacin compared with their planktonic counterparts, especially in the case of bloodborne strains. Our findings indicate that biofilm formation by S. maltophilia is obviously a contributing factor in the pathogenesis of infections, especially in deep ones, thus warranting additional studies with larger cohort of patients and isolates. [ABSTRACT FROM AUTHOR]

Published
2021
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48. Deciphering the Role of V88L Substitution in NDM-24 Metallo-β-Lactamase.

Author

Liu, Zhihai, Piccirilli, Alessandra, Liu, Dejun, Li, Wan, Wang, Yang, and Shen, Jianzhong

Subjects
*BETA lactam antibiotics, *IMIPENEM, *BACTERIAL diseases, *CARBAPENEMASE, *MEROPENEM, *CEPHALOSPORINS, *DATA analysis, *PROTEIN stability
Abstract

The New Delhi metallo-β-lactamase-1 (NDM-1) is a typical carbapenemase and plays a crucial role in antibiotic-resistance bacterial infection. Phylogenetic analysis, performed on known NDM-variants, classified NDM enzymes in seven clusters. Three of them include a major number of NDM-variants. In this study, we evaluated the role of the V88L substitution in NDM-24 by kinetical and structural analysis. Functional results showed that V88L did not significantly increase the resistance level in the NDM-24 transformant toward penicillins, cephalosporins, meropenem, and imipenem. Concerning ertapenem, E. coli DH5α/NDM-24 showed a MIC value 4-fold higher than that of E. coli DH5α/NDM-1. The determination of the kcat, Km, and kcat/Km values for NDM-24, compared with NDM-1 and NDM-5, demonstrated an increase of the substrate hydrolysis compared to all the β-lactams tested, except penicillins. The thermostability testing revealed that V88L generated a destabilized effect on NDM-24. The V88L substitution occurred in the β-strand and low β-sheet content in the secondary structure, as evidenced by the CD analysis data. In conclusion, the V88L substitution increases the enzyme activity and decreases the protein stability. This study characterizes the role of the V88L substitution in NDM-24 and provides insight about the NDM variants evolution. [ABSTRACT FROM AUTHOR]

Published
2019
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49. In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy

Author

Bernardetta Segatore, Alessandra Piccirilli, Sabrina Cherubini, Luigi Principe, Giovanni Alloggia, Maria Lina Mezzatesta, Mario Salmeri, Stefano Di Bella, Roberta Migliavacca, Aurora Piazza, Elisa Meroni, Paolo Fazii, Daniela Visaggio, Paolo Visca, Venere Cortazzo, Giulia De Angelis, Arianna Pompilio, Mariagrazia Perilli, Segatore, Bernardetta, Piccirilli, Alessandra, Cherubini, Sabrina, Principe, Luigi, Alloggia, Giovanni, Mezzatesta, Maria Lina, Salmeri, Mario, Di Bella, Stefano, Migliavacca, Roberta, Piazza, Aurora, Meroni, Elisa, Fazii, Paolo, Visaggio, Daniela, Visca, Paolo, Cortazzo, Venere, De Angelis, Giulia, Pompilio, Arianna, and Perilli, Mariagrazia

Subjects
Microbiology (medical), Acinetobacter baumannii, durlobactam, A. baumannii, WGS, Biochemistry, Microbiology, Infectious Diseases, Pharmacology (medical), antimicrobial resistance, General Pharmacology, Toxicology and Pharmaceutics
Abstract

In the present study, the in vitro activity of the sulbactam–durlobactam (SUL–DUR) combination was evaluated against 141 carbapenem-resistant A. baumannii (CRAb) clinical strains collected from six Italian laboratories. Over half (54.6%) of these isolates were resistant to colistin. The SUL–DUR combination was active against these CRAb isolates with MIC50 and MIC90 values of 0.5 mg/L and 4 mg/L, respectively. Only eleven isolates were resistant to SUL–DUR with MIC values ranging from 8 to 128 mg/L. The SUL–DUR resistant A. baumannii exhibited several antimicrobial resistance genes (ARGs) such as blaOXA-20, blaOXA-58, blaOXA-66, blaADC-25, aac(6′)-Ib3 and aac(6′)-Ib-cr and mutations in gyrA (S81L) and parC (V104I, D105E). However, in these isolates, mutations Q488K and Y528H were found in PBP3. Different determinants were also identified in these CRAb isolates, including adeABC, adeFGH, adeIJK, abeS, abaQ and abaR, which encode multidrug efflux pumps associated with resistance to multiple antibacterial agents. This is the first report on the antimicrobial activity of SUL–DUR against carbapenem-resistant A. baumannii isolates selected from multiple regions in Italy.

Published
2022

50. Acinetobacter baumannii Resistance to Sulbactam/Durlobactam: A Systematic Review

Author

Luigi Principe, Stefano Di Bella, Jacopo Conti, Mariagrazia Perilli, Alessandra Piccirilli, Cristina Mussini, Giuliana Decorti, Principe, Luigi, Di Bella, Stefano, Conti, Jacopo, Perilli, Mariagrazia, Piccirilli, Alessandra, Mussini, Cristina, and Decorti, Giuliana

Subjects
Microbiology (medical), Acinetobacter, efficacy, sulbactam/durlobactam, Biochemistry, Microbiology, susceptibility, sulbactam-durlobactam, resistance, Infectious Diseases, resistances, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics
Abstract

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have limited therapeutic options. Sulbactam-durlobactam is a combination of two βlactamase inhibitors with activity against CRAB under phase 3 clinical investigation. We performed a systematic review on in vitro studies reporting A. baumannii resistances against sulbactam/durlobactam. We considered “resistant” species to be those with MIC ≥ 8 mg/L. Ten studies were included in the review (9754 tested isolates). Overall, 2.3% of A. baumannii were resistant to sulbactam/durlobactam, and this percentage rose to 3.4% among CRAB subgroups and to 3.7% among colistin-resistant strains. Resistance was 100% among metallo β-lactamase-producing strains. Overall, in 12.5% of cases, sulbactam/durlobactam resistance was associated with the production of NDM-1, in 31.7% of cases with the substitutions in the PBP3 determinants, and in the remaining cases the resistance mechanism was unknown. In conclusion, A. baumannii resistance towards sulbactam/durlobactam is limited, except for MBL-producing strains.

Published
2022

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