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9. Growth in glucose-based medium and exposure to subinhibitory concentrations of imipenem induce biofilm formation in a multidrug-resistant clinical isolate of Acinetobacter baumannii

Author

Nucleo, E, Steffanoni, L, Fugazza, G, Migliavacca, R, Giacobone, E, Navarra, A, Pagani, L, Landini, P, Landini, P., FUGAZZA, GIULIA, Nucleo, E, Steffanoni, L, Fugazza, G, Migliavacca, R, Giacobone, E, Navarra, A, Pagani, L, Landini, P, Landini, P., and FUGAZZA, GIULIA

Abstract

BACKGROUND: Acinetobacter baumannii is emerging as an important nosocomial pathogen. Multidrug resistance, as well as ability to withstand environmental stresses, makes eradication of A. baumannii difficult, particularly from hospital settings. RESULTS: Over a six-year period, 73 isolates of A. baumannii were collected from infected patients in two hospitals in Italy. While 69 out of the 73 isolates displayed identical multidrug antibiotic resistance pattern, they were susceptible to carbapenems. Genetic profiles of these 69 isolates, determined by Pulsed Field Gel Electrophoresis (PFGE), indicated that they were genetically related and could be clustered in a specific clone, called SMAL. We tested the ability of the SMAL clone to form biofilm, an important determinant for bacterial colonization of the human host and for persistence in the hospital environment. Biofilm formation by A. baumannii SMAL, measured as surface adhesion to polystyrene, is strongly affected by growth conditions, being impaired in rich growth media such as LB, while being favoured in glucose-based medium. Surface adhesion in glucose-based media is inhibited by treatment with cellulase, suggesting that it depends on production of cellulose or of a chemically related extracellular polysaccharide. Exposure of A. baumannii SMAL to subinhibitory concentrations of imipenem resulted in biofilm stimulation and increased production of iron uptake proteins. Growth in iron-supplemented medium also stimulated surface adhesion, thus suggesting that increased intracellular iron concentrations might act as an environmental signal for biofilm formation in A. baumannii SMAL. CONCLUSIONS: Our results indicate that exposure to subinhibitory concentrations of imipenem can stimulate biofilm formation and induce iron uptake in a pathogenic strain of A. baumannii, with potential implications on antibiotic susceptibility and ability to persist in the human host.

Published
2009

17. Cloning the breakpoint cluster region of the inv(16) in acute nonlymphocytic leukemia M4 Eo

Author

Dauwerse, J.G., primary, Wessels, J.W., additional, Giles, R.H., additional, Wiegant, J., additional, van der Reijden, B.A., additional, Fugazza, G., additional, Jumelet, E.A., additional, Smit, E., additional, Baas, F., additional, Raap, A.K., additional, Hagemeijer, A., additional, Baverstock, G.C., additional, van Ommen, G.J.B., additional, and Breuning, M.H., additional

Published
1993
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26. Dissemination of an NDM-2-Producing Acinetobacter baumanniiClone in an Israeli Rehabilitation Center

Author

Espinal, P., Fugazza, G., López, Y., Kasma, M., Lerman, Y., Malhotra-Kumar, S., Goossens, H., Carmeli, Y., and Vila, J.

Abstract

ABSTRACTNew Delhi metallo-β-lactamase (NDM-1) was initially identified in various Enterobacteriaceaeand recently in Acinetobacter baumannii. This study described the clonal dissemination of an NDM-2-producing A. baumanniiisolate in an Israeli rehabilitation ward and the genetic surroundings of the gene. The blaNDM-2gene was surrounded by the bleand trpFgenes downstream and two copies of the ISAba125on both sides. These are the first NDM-producing A. baumanniistrains in Israel from patients with no previous travel or hospitalization on the Indian subcontinent.

Published
2011
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27. Rubinstein-Taybi syndrome caused by submicroscopic deletions within 16p13.3

Author

Mh, Breuning, Hg, Dauwerse, Fugazza G, Jj, Saris, Spruit L, Herman Wijnen, Tommerup N, Cb, Hagen, Imaizumi K, Kuroki Y, Mj, Den Boogaard, Jm, Pater, Ec, Mariman, Bc, Hamel, Himmelbauer H, Am, Frischauf, Stallings R, Gc, Beverstock, Gj, Ommen, and Rc, Hennekam

Subjects
Rubinstein-Taybi Syndrome, Humans, Original Articles, Chromosome Deletion, Cosmids, Chromosomes, Human, Pair 16, In Situ Hybridization, Fluorescence
Abstract

The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by facial abnormalities, broad thumbs and big toes, and mental retardation. The breakpoint of two distinct reciprocal translocations occurring in patients with a clinical diagnosis of RTS was located to the same interval on chromosome 16, between the cosmids N2 and RT1, in band 16p13.3. By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS. The parents of five of these patients did not show a deletion of RT1, indicating a de novo rearrangement. RTS is caused by submicroscopic interstitial deletions within 16pl3.3 in approximately 25% of the patients. The detection of microdeletions will allow the objective confirmation of the clinical diagnosis in new patients and provides an excellent tool for the isolation of the gene causally related to the syndrome.

33. Rubinstein-Taybi syndrome caused by submicroscopic deletions within 16p13.3

Author

Breuning, M. H., Dauwerse, H. G., Fugazza, G., Saris, J. J., Spruit, L., Wijnen, H., Tommerup, N., Hagen, C. B., Imaizumi, K., Kuroki, Y., Den Boogaard -, M. J., Pater, J. M., Mariman, E. C. M., Hamel, B. C. J., Heinz Himmelbauer, Frischauf -, A. M., Stallings, R. L., Beverstock, G. C., Ommen, G. -J B., Hennekam, R. C. M., and Other departments

Abstract

The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by facial abnormalities, broad thumbs and big toes, and mental retardation. The breakpoint of two distinct reciprocal translocations occurring in patients with a clinical diagnosis of RTS was located to the same interval on chromosome 16, between the cosmids N2 and RT1, in band 16p13.3. By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS. The parents of five of these patients did not show a deletion of RT1, indicating a de novo rearrangement. RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximately 25% of the patients. The detection of microdeletions will allow the objective conformation of the clinical diagnosis in new patients and provides an excellent tool for the isolation of the gene causally related to the syndrome

43. Growth in glucose-based medium and exposure to subinhibitory concentrations of imipenem induce biofilm formation in a multidrug-resistant clinical isolate of Acinetobacter baumannii

Author

Giacobone Ernesto, Migliavacca Roberta, Fugazza Giulia, Steffanoni Laura, Nucleo Elisabetta, Navarra Antonella, Pagani Laura, and Landini Paolo

Subjects
Microbiology, QR1-502
Abstract

Abstract Background Acinetobacter baumannii is emerging as an important nosocomial pathogen. Multidrug resistance, as well as ability to withstand environmental stresses, makes eradication of A. baumannii difficult, particularly from hospital settings. Results Over a six-year period, 73 isolates of A. baumannii were collected from infected patients in two hospitals in Italy. While 69 out of the 73 isolates displayed identical multidrug antibiotic resistance pattern, they were susceptible to carbapenems. Genetic profiles of these 69 isolates, determined by Pulsed Field Gel Electrophoresis (PFGE), indicated that they were genetically related and could be clustered in a specific clone, called SMAL. We tested the ability of the SMAL clone to form biofilm, an important determinant for bacterial colonization of the human host and for persistence in the hospital environment. Biofilm formation by A. baumannii SMAL, measured as surface adhesion to polystyrene, is strongly affected by growth conditions, being impaired in rich growth media such as LB, while being favoured in glucose-based medium. Surface adhesion in glucose-based media is inhibited by treatment with cellulase, suggesting that it depends on production of cellulose or of a chemically related extracellular polysaccharide. Exposure of A. baumannii SMAL to subinhibitory concentrations of imipenem resulted in biofilm stimulation and increased production of iron uptake proteins. Growth in iron-supplemented medium also stimulated surface adhesion, thus suggesting that increased intracellular iron concentrations might act as an environmental signal for biofilm formation in A. baumannii SMAL. Conclusions Our results indicate that exposure to subinhibitory concentrations of imipenem can stimulate biofilm formation and induce iron uptake in a pathogenic strain of A. baumannii, with potential implications on antibiotic susceptibility and ability to persist in the human host.

Published
2009
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49. Chronic myeloid leukemia: a prospective comparison of interphase fluorescence in situ hybridization and chromosome banding analysis for the definition of complete cytogenetic response: a study of the GIMEMA CML WP

Author

Emilia Giugliano, Nicoletta Testoni, Marilina Amabile, Simonetta Kerim, Alessandro Gozzetti, Mauro Nanni, Elisabetta Abruzzese, Fabrizio Pane, Simona Luatti, Francesco Albano, Monica Stacchini, Giuseppina Fugazza, Michele Baccarani, Barbara Crescenzi, Carmen Baldazzi, Carlo Carcassi, Gianantonio Rosti, Paolo Bernasconi, M.G. Grimoldi, Giovanna Rege-Cambrin, Ursula Giussani, Giovanni Martinelli, Antonio Cuneo, Alfonso Zaccaria, Giulia Marzocchi, Testoni, N, Marzocchi, G, Luatti, S, Amabile, M, Baldazzi, C, Stacchini, M, Nanni, M, Rege Cambrin, G, Giugliano, E, Giussani, U, Abruzzese, E, Kerim, S, Grimoldi, Mg, Gozzetti, A, Crescenzi, B, Carcassi, C, Bernasconi, P, Cuneo, A, Albano, F, Fugazza, G, Zaccaria, A, Martinelli, G, Pane, Fabrizio, Rosti, G, Baccarani, M., Testoni N, Marzocchi G, Luatti S, Amabile M, Baldazzi C, Stacchini M, Nanni M, Rege-Cambrin G, Giugliano E, Giussani U, Abruzzese E, Kerim S, Grimoldi MG, Gozzetti A, Crescenzi B, Carcassi C, Bernasconi P, Cuneo A, Albano F, Fugazza G, Zaccaria A, Martinelli G, Pane F, Rosti G, and Baccarani M.

Subjects
Oncology, medicine.medical_specialty, Pathology, Immunology, Antineoplastic Agents, Biology, Biochemistry, Fluorescence, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, INTERPHASE FLUORESCENCE IN SITU HYBRIDIZATION (I-FISH), COMPLETE CYTOGENETIC RESPONSE, Chronic, Prospective cohort study, In Situ Hybridization, Fluorescence, In Situ Hybridization, CHRONIC MYELOID LEUKEMIA, Clinical Trials as Topic, Hematology, Leukemia, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, Remission Induction, Cytogenetics, Myeloid leukemia, Karyotype, Treatment Outcome, Chromosome Banding, Cell Biology, medicine.disease, Real-time polymerase chain reaction, BCR-ABL Positive, Chronic myelogenous leukemia, Fluorescence in situ hybridization, Myelogenous
Abstract

In chronic myeloid leukemia, different methods are available to monitor the response to therapy: chromosome banding analysis (CBA), interphase fluorescence in situ hybridization (I-FISH), and real-time quantitative polymerase chain reaction (RT-Q-PCR). The GIMEMA CML WP (Gruppo Italiano Malattie Ematologiche Adulto Chronic Myeloid Leukemia Working Party) has performed a prospective study to compare CBA and I-FISH for the definition of complete cytogenetic response (CCgR). Samples (n = 664) were evaluated simultaneously by CBA and I-FISH. Of 537 cases in CCgR, the number of positive nuclei by I-FISH was less than 1% in 444 cases (82.7%). Of 451 cases with less than 1% positive nuclei by I-FISH, 444 (98.4%) were classified as CCgR by CBA. The major molecular response rate was significantly greater in cases with I-FISH less than 1% than in those with I-FISH 1% to 5% (66.8% vs 51.6%, P < .001) and in cases with CCgR and I-FISH less than 1% than in cases with CCgR and I-FISH 1% to 5% (66.1% vs 49.4%, P = .004). I-FISH is more sensitive than CBA and can be used to monitor CCgR. With appropriate probes, the cutoff value of I-FISH may be established at 1%. These trials are registered at http://www.clinicaltrials.gov as NCT00514488 and NCT00510926.

Published
2009

50. Comparing Outcomes Between CPX-351 and Fludarabine-Based Induction in Secondary Acute Myeloid Leukemia in the Real-World Setting: The Prognostic Role of Measurable Residual Disease.

Author

Riva C, Minetto P, Chies M, Vernarecci C, Colombo N, Rosellini S, Parodi A, Tedone E, Carminati E, Nurra C, Puglisi F, Frello M, Maio E, Ferro B, Zecchetti G, Fugazza G, Nozza P, Cea M, Lemoli RM, and Guolo F

Subjects
Aged, Female, Humans, Male, Middle Aged, Cytarabine administration & dosage, Cytarabine therapeutic use, Prognosis, Remission Induction, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute pathology, Neoplasm, Residual, Vidarabine analogs & derivatives, Vidarabine administration & dosage, Vidarabine therapeutic use
Abstract

Secondary acute myeloid leukemia (s-AML) is associated with inferior outcomes with conventional chemotherapy, and fludarabine combinations (FLAG-Ida) have been tested to improve results. More recently, CPX-351 resulted superior to conventional 3 + 7 in s-AML patients. In the UK NCRI AML19 trial, AML patients were randomized to receive either FLAG-Ida or CPX-351. Subgroup analysis revealed better overall survival (OS) with CPX-351 in patients with MDS-related gene mutations. Unfortunately, minimal residual disease (MRD) was evaluated only in a minority of patients. The aim of this study was to further disclose the mechanisms of higher efficacy of CPX-351 in s-AML, with a focus on MRD. We analyzed 183 consecutive s-AML elderly patients (median age 69, range 60-77) treated with CPX-351 (n = 82) or receiving FLAG-Ida (n = 101). Complete remission (CR) rate and MRD negativity probability were higher among patients receiving CPX-351 (MRD negative CR rate of 40/64, 62.5%, compared to 25/55, 45% in patients who received FLAG-Ida, p < 0.05). Extra-hematological toxicity was lower in CPX-351 arm, and 30 days mortality was 3.6% and 8% in patients receiving CPX-351 or FLAG-Ida, respectively. Notably, 21/64 (32.8%) CR patients treated with CPX 351 underwent allogeneic stem cell transplantation (HSCT), compared to 5/55 with FLAG-Ida (9%, p < 0.05). Overall, CPX-351 treatment resulted in higher OS (median OS 17.7 vs. 11.2 months with FLAG-Ida, p < 0.05). The better outcome of CPX-351 compared to FLAG-Ida in our cohort may be explained by a greater probability of MRD negativity, alongside with an improved tolerance, enabling more s-AML patients to undergo HSCT., (© 2024 John Wiley & Sons Ltd.)

Published
2025
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