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Article: Activity of Drug Combinations against Mycobacterium abscessus Grown in Aerobic and Hypoxic Conditions

Lanni, Alessio / Borroni, Emanuele / Iacobino, Angelo / Russo, Cristina / Gentile, Leonarda / Fattorini, Lanfranco / Giannoni, Federico

Microorganisms. 2022 July 14, v. 10, no. 7

2022

Abstract: Infections caused by Mycobacterium abscessus (Mab), an environmental non-tuberculous mycobacterium, are difficult to eradicate from patients with pulmonary diseases such as cystic fibrosis and bronchiectasis even after years of antibiotic treatments. In ... ...

Abstract	Infections caused by Mycobacterium abscessus (Mab), an environmental non-tuberculous mycobacterium, are difficult to eradicate from patients with pulmonary diseases such as cystic fibrosis and bronchiectasis even after years of antibiotic treatments. In these people, the low oxygen pressure in mucus and biofilm may restrict Mab growth from actively replicating aerobic (A) to non-replicating hypoxic (H) stages, which are known to be extremely drug-tolerant. After the exposure of Mab A and H cells to drugs, killing was monitored by measuring colony-forming units (CFU) and regrowth in liquid medium (MGIT 960) of 1-day-old A cells (A1) and 5-day-old H cells (H5). Mab killing was defined as a lack of regrowth of drug-exposed cells in MGIT tubes after >50 days of incubation. Out of 18 drugs tested, 14-day treatments with bedaquiline-amikacin (BDQ-AMK)-containing three-drug combinations were very active against A1 + H5 cells. However, drug-tolerant cells (persisters) were not killed, as shown by CFU curves with typical bimodal trends. Instead, 56-day treatments with the nitrocompounds containing combinations BDQ-AMK-rifabutin-clarithromycin-nimorazole and BDQ-AMK-rifabutin-clarithromycin-metronidazole-colistin killed all A1 + H5 Mab cells in 42 and 56 days, respectively, as shown by lack of regrowth in agar and MGIT medium. Overall, these data indicated that Mab persisters may be killed by appropriate drug combinations.
Keywords	Mycobacterium abscessus ; agar ; antibiotics ; biofilm ; cystic fibrosis ; liquids ; mucus ; oxygen ; people ; regrowth
Language	English
Dates of publication	2022-0714
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms10071421
Database	NAL-Catalogue (AGRICOLA)

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Article: Activity of Drug Combinations against

Lanni, Alessio / Borroni, Emanuele / Iacobino, Angelo / Russo, Cristina / Gentile, Leonarda / Fattorini, Lanfranco / Giannoni, Federico

Microorganisms

2022 Volume 10, Issue 7

Abstract	Infections caused by Mycobacterium abscessus (Mab), an environmental non-tuberculous mycobacterium, are difficult to eradicate from patients with pulmonary diseases such as cystic fibrosis and bronchiectasis even after years of antibiotic treatments. In these people, the low oxygen pressure in mucus and biofilm may restrict Mab growth from actively replicating aerobic (A) to non-replicating hypoxic (H) stages, which are known to be extremely drug-tolerant. After the exposure of Mab A and H cells to drugs, killing was monitored by measuring colony-forming units (CFU) and regrowth in liquid medium (MGIT 960) of 1-day-old A cells (A1) and 5-day-old H cells (H5). Mab killing was defined as a lack of regrowth of drug-exposed cells in MGIT tubes after >50 days of incubation. Out of 18 drugs tested, 14-day treatments with bedaquiline-amikacin (BDQ-AMK)-containing three-drug combinations were very active against A1 + H5 cells. However, drug-tolerant cells (persisters) were not killed, as shown by CFU curves with typical bimodal trends. Instead, 56-day treatments with the nitrocompounds containing combinations BDQ-AMK-rifabutin-clarithromycin-nimorazole and BDQ-AMK-rifabutin-clarithromycin-metronidazole-colistin killed all A1 + H5 Mab cells in 42 and 56 days, respectively, as shown by lack of regrowth in agar and MGIT medium. Overall, these data indicated that Mab persisters may be killed by appropriate drug combinations.
Language	English
Publishing date	2022-07-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms10071421
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Article ; Online: Monocyte-to-lymphocyte, neutrophil-to-lymphocyte and neutrophil-to-monocyte plus lymphocyte ratios in children with active tuberculosis: A multicentre study.

Cursi, Laura / Lancella, Laura / Mariani, Francesco / Martino, Laura / Leccese, Bianca / Di Giuseppe, Martina / Venuti, Francesco / Cristina, Russo / Gentile, Leonarda / Sali, Michela / Delogu, Giovanni / Valentini, Piero / Buonsenso, Danilo

Acta paediatrica (Oslo, Norway : 1992)

2023 Volume 112, Issue 11, Page(s) 2418–2425

Abstract: Aim: Higher number of monocytes and neutrophils may correlate with active tuberculosis (TB) in children. However, the few paediatric studies available are limited by the small numbers of children with TB disease or infection included.: Methods: We ... ...

Abstract	Aim: Higher number of monocytes and neutrophils may correlate with active tuberculosis (TB) in children. However, the few paediatric studies available are limited by the small numbers of children with TB disease or infection included. Methods: We calculated the monocyte-to-lymphocyte-ratio (MLR), neutrophil-to-lymphocyte-ratio (NLR) and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) in children with active TB, latent TB infection (LTBI), other infectious and non-infectious conditions and healthy children evaluated in two referral centres in Rome. Results: Overall, 649 children were included (41.8% females, mean age of 5.74 years). MLR, NLR and NMLR values were always significantly higher in patients with TB compared with the other groups (p < 0.001). Considering the entire population with the outcome of TB diagnosis, NMLR, with a cut-off of 1.2, had a sensitivity of 63% and a specificity of 76% (AUC: 0.71 [0.64-0.78]); NLR, with a cut-off of 1.5, had a sensitivity of 61% and a specificity of 79% (AUC: 0.72 [0.65-0.79]); MLR, considering a cut-off of 0.2, was less sensitive (56%) but more specific (82%) with a similar AUC (0.72 [0.65-0.79]). Conclusion: Our study provides further evidence that MLR, NLR and NMLR can serve as first level diagnostics to support the clinical suspicion of TB in children.
MeSH term(s)	Female ; Humans ; Child ; Child, Preschool ; Male ; Neutrophils ; Monocytes ; Lymphocytes ; Tuberculosis/diagnosis ; Latent Tuberculosis ; Retrospective Studies ; Prognosis
Language	English
Publishing date	2023-08-14
Publishing country	Norway
Document type	Multicenter Study ; Journal Article
ZDB-ID	203487-6
ISSN	1651-2227 ; 0365-1436 ; 0803-5253
ISSN (online)	1651-2227
ISSN	0365-1436 ; 0803-5253
DOI	10.1111/apa.16932
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Article ; Online: Influenza viruses circulation in a tertiary care children hospital in Rome: a comparison between 2022 and the previous 5 years.

Ranno, Stefania / Coltella, Luana / Linardos, Giulia / Di Maio, Velia Chiara / Colagrossi, Luna / Gentile, Leonarda / Galeno, Eugenia / Ciofi Degli Atti, Marta Luisa / Cristaldi, Sebastian / Villani, Alberto / Raponi, Massimiliano / Perno, Carlo Federico / Russo, Cristina

Italian journal of pediatrics

2023 Volume 49, Issue 1, Page(s) 121

Abstract: Background: Influenza surveillance aims to determine onset, duration and intensity of the seasonal Influence-like Illness (ILI); data collection begins in the week 42 of a year and ends in the week 17 of the following year. In this observational study, ... ...

Abstract	Background: Influenza surveillance aims to determine onset, duration and intensity of the seasonal Influence-like Illness (ILI); data collection begins in the week 42 of a year and ends in the week 17 of the following year. In this observational study, we report the experience of a tertiary care children hospital in Rome about Influenza viruses circulation during the calendar year 2022 (January-December) in comparison with the previous five years (2017-2021), with a special focus on the weeks 18-41, usually not under surveillance. Methods: This retrospective study involved 36782 respiratory samples referred to 21354 patients (pts), median age 2.63 years, admitted with respiratory symptoms at Bambino Gesù Children's Hospital in the years 2017-2022. Respiratory viruses were detected by molecular Allplex™ Respiratory Panel Assays (Seegene, Korea). Results: Regarding the pre pandemic years, 2017-2019, distribution of Flu positive patients focused in the first weeks of the year (weeks 1-17). During the pandemic period, Flu was not detected. In 2022, 239 Flu viruses were identified: 37 FluA (weeks 1-17), 29 FluA (weeks 18-41) and 168 FluA and 5 FluB (weeks 42-52). For the year 2022, during the non-epidemic period, the number of Flu viruses detected corresponded to 12.1% of total Flu detected, respect to 0-1.7% for the previous five years (p < 0.001). Conclusions: When compared with pre SARS-CoV-2 pandemic years, our data show a significant increase in Influenza cases during weeks 18-41/2022 and reveal an unexpected summer circulation of these viruses: just weeks 26-30 showed to be influenza virus free. A national year-round Flu surveillance could be useful to understand if changing in influenza epidemiology is transitional or likely to persist in the following years.
MeSH term(s)	Humans ; Child ; Child, Preschool ; Influenza, Human/epidemiology ; Retrospective Studies ; Rome/epidemiology ; Tertiary Healthcare ; COVID-19 ; SARS-CoV-2 ; Hospitals, Pediatric ; Orthomyxoviridae
Language	English
Publishing date	2023-09-13
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2088556-8
ISSN	1824-7288 ; 1720-8424
ISSN (online)	1824-7288
ISSN	1720-8424
DOI	10.1186/s13052-023-01519-3
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Article ; Online: QuantiFERON-TB Gold can help clinicians in the diagnosis of haemophagocytic lymphohistiocytosis.

Merli, Pietro / Gentile, Leonarda / Quagliarella, Francesco / Cefalo, Maria Giuseppina / Strocchio, Luisa / Locatelli, Franco / Russo, Cristina / Gaspari, Stefania

British journal of haematology

2020 Volume 191, Issue 2, Page(s) e64–e67

MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic/diagnostic imaging ; Lymphohistiocytosis, Hemophagocytic/immunology ; Male ; Reagent Kits, Diagnostic
Chemical Substances	Reagent Kits, Diagnostic
Language	English
Publishing date	2020-07-26
Publishing country	England
Document type	Letter
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.17001
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Article ; Online: Case Report: Successful Treatment With Monoclonal Antibodies in One APDS Patient With Prolonged SARS-CoV-2 Infection Not Responsive to Previous Lines of Treatment.

Rivalta, Beatrice / Amodio, Donato / Giancotta, Carmela / Santilli, Veronica / Pacillo, Lucia / Zangari, Paola / Cotugno, Nicola / Manno, Emma Concetta / Finocchi, Andrea / Bernardi, Stefania / Colagrossi, Luna / Gentile, Leonarda / Russo, Cristina / Perno, Carlo Federico / Rossi, Paolo / Cancrini, Caterina / Palma, Paolo

Frontiers in immunology

2022 Volume 13, Page(s) 891274

Abstract: We described the case of a patient affected by activated PI3K-kinase delta syndrome (APDS) and a long-lasting and pauci-symptomatic SARS-CoV-2 infection, treated with multiple therapeutic agents including remdesivir and SARS-CoV-2-neutralizing monoclonal ...

Abstract	We described the case of a patient affected by activated PI3K-kinase delta syndrome (APDS) and a long-lasting and pauci-symptomatic SARS-CoV-2 infection, treated with multiple therapeutic agents including remdesivir and SARS-CoV-2-neutralizing monoclonal antibodies. We detected the clearance of the virus 105 days from the first positive swab and 7 days after monoclonal antibody administration. At genotyping, the SARS-CoV-2 virus resulted as wild type on all samples tested. This case shows the monoclonal antibodies' good tolerability and efficacy in reducing viral shedding in long-lasting infections refractory to other treatments.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Antibodies, Viral ; COVID-19/drug therapy ; Humans ; SARS-CoV-2 ; Virus Shedding
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Viral
Language	English
Publishing date	2022-06-21
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.891274
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Article ; Online: Erratum to: High Resolution Melting Analysis is Very Useful to Identify BRCA1 c.4964_4982del19 (rs80359876) Founder Calabrian Pathogenic Variant on Peripheral Blood and Buccal Swab DNA.

Minucci, Angelo / De Bonis, Maria / De Paolis, Elisa / Gentile, Leonarda / Santonocito, Concetta / Concolino, Paola / Mignone, Flavio / Capoluongo, Ettore

Molecular diagnosis & therapy

2017 Volume 21, Issue 2, Page(s) 233

Language	English
Publishing date	2017-04
Publishing country	New Zealand
Document type	Published Erratum
ZDB-ID	2232796-4
ISSN	1179-2000 ; 1177-1062
ISSN (online)	1179-2000
ISSN	1177-1062
DOI	10.1007/s40291-017-0273-0
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Article ; Online: High Resolution Melting Analysis is Very Useful to Identify Breast Cancer Type 1 Susceptibility Protein (BRCA1) c.4964_4982del19 (rs80359876) Founder Calabrian Pathogenic Variant on Peripheral Blood and Buccal Swab DNA.

Minucci, Angelo / De Bonis, Maria / De Paolis, Elisa / Gentile, Leonarda / Santonocito, Concetta / Concolino, Paola / Mignone, Flavio / Capoluongo, Ettore

Molecular diagnosis & therapy

2017 Volume 21, Issue 2, Page(s) 217–223

Abstract: Introduction: Detection of pathogenic variants in hereditary breast and ovarian cancer-related breast cancer type 1 and type 2 susceptibility proteins (BRCA1/2) genes is an effective strategy in cancer prevention and treatment. Some ethnic and ... ...

Abstract	Introduction: Detection of pathogenic variants in hereditary breast and ovarian cancer-related breast cancer type 1 and type 2 susceptibility proteins (BRCA1/2) genes is an effective strategy in cancer prevention and treatment. Some ethnic and geographical regions show different BRCA1/2 mutation spectrum and prevalence. In Italy, elucidation of founder effect in BRCA1/2 genes can have an impact on the management of hereditary cancer families on a healthcare system level, making genetic testing more affordable and cost effective in certain regions. Methods: The purpose of this paper is to develop a rapid, low-cost, high-throughput single-tube technology for genotyping the Italian founder mutation c.4964_4982del19 (rs80359876) in the BRCA1 gene, starting from peripheral blood and/or buccal swab DNA. Results: Heterozygote samples for c.4964_4982del19 variant were easily and unambiguously identified by the altered shape of the melting curves and were clearly distinguished by a change in melting temperature that differed by approximately 5 °C. The same results were obtained both with DNA from peripheral blood than buccal swab. Conclusions: We provide evidence about application of high-resolution melting analysis (HRMA) in unambiguously genotyping of the founder BRCA1 c.4964_4982del19 variant (rs80359876) in individuals from the Calabria region of Italy. In fact, HRMA was confirmed to be particularly suitable for the identification of BRCA1 c.4964_4982del19 variant, making this approach useful in clinical molecular diagnostics.
MeSH term(s)	Alleles ; BRCA1 Protein/genetics ; Female ; Founder Effect ; Genetic Testing/methods ; Germ-Line Mutation ; Hereditary Breast and Ovarian Cancer Syndrome/diagnosis ; Hereditary Breast and Ovarian Cancer Syndrome/genetics ; Heterozygote ; Humans ; Italy ; Nucleic Acid Amplification Techniques ; Reproducibility of Results ; Sensitivity and Specificity ; Sequence Deletion
Chemical Substances	BRCA1 Protein
Language	English
Publishing date	2017-04
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2232796-4
ISSN	1179-2000 ; 1177-1062
ISSN (online)	1179-2000
ISSN	1177-1062
DOI	10.1007/s40291-017-0262-3
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Article ; Online: Rapid and simple identification of the commonest glucose-6-phosphate dehydrogenase (G6PD) Italian mutations: from DNA extraction to genotyping.

Minucci, Angelo / Gentile, Leonarda / Zuppi, Cecilia / Giardina, Bruno / Capoluongo, Ettore

Clinica chimica acta; international journal of clinical chemistry

2012 Volume 413, Issue 11-12, Page(s) 1018–1019

MeSH term(s)	DNA/isolation & purification ; DNA Mutational Analysis/methods ; Genotype ; Glucosephosphate Dehydrogenase/genetics ; Glucosephosphate Dehydrogenase Deficiency/genetics ; Humans ; Italy ; Mutation ; Polymerase Chain Reaction/instrumentation ; Polymerase Chain Reaction/methods ; Polymorphism, Restriction Fragment Length
Chemical Substances	DNA (9007-49-2) ; Glucosephosphate Dehydrogenase (EC 1.1.1.49)
Language	English
Publishing date	2012-06-14
Publishing country	Netherlands
Document type	Letter
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2012.01.032
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Article ; Online: Surfactant inadvertent loss using feeding catheters or endotracheal tubes.

De Luca, Daniele / Luca, Daniele De / Minucci, Angelo / Gentile, Leonarda / Capoluongo, Ettore D

American journal of perinatology

2014 Volume 31, Issue 3, Page(s) 209–212

Abstract: Objective: Surfactant has been administered through endotracheal tubes and also under spontaneous breathing using feeding catheters. We asked if different tube diameters and temperature may affect the amount of surfactant effectively delivered to the ... ...

Abstract	Objective: Surfactant has been administered through endotracheal tubes and also under spontaneous breathing using feeding catheters. We asked if different tube diameters and temperature may affect the amount of surfactant effectively delivered to the lungs. Design: Bench study using high-accuracy, legal balance and tube/catheters of different diameters. We injected 200 mg of poractant alfa into the tubes followed by air boluses. Experiments were performed in triplicate, both at room temperature and at 37°C. Surfactant and phospholipid remaining in the tube were calculated. Results: Surfactant lost into thin catheters (11 ± 0.4%) was more than that in endotracheal tubes (2-mm diameter: 3.6 ± 1.4%; 2.5-mm diameter: 3.7 ± 0.2%; 3-mm diameter: 5.2 ± 0.4%; p < 0.001 at post hoc test in each comparison against the thin catheter). Similar findings were found at 37°C (2-mm tube: 3.4 ± 0.4%; 2.5-mm tube: 3.8 ± 0.2%; 3-mm tube: 3.6 ± 0.4%; feeding tube: 11.5 ± 0.6%; p < 0.001 as above). In terms of lost phospholipids, 23 ± 0.8 mg were lost in the feeding tubes; 7.2 ± 2.9 mg (2-mm diameter), 7.4 ± 0.4 mg (2.5-mm diameter), and 10.3 ± 0.9 mg (3-mm diameter) of phospholipids remained in endotracheal tubes (p < 0.001 in each comparison against the feeding tube). Conclusions: Surfactant loss using thin catheters is around two to three times higher than using common endotracheal tubes; on average, 20 mg of phospholipids (11% of the administered dose) are lost. These data may be useful to refine surfactant dosing.
MeSH term(s)	Enteral Nutrition/instrumentation ; Equipment Design ; Intubation, Intratracheal ; Surface-Active Agents
Chemical Substances	Surface-Active Agents
Language	English
Publishing date	2014-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	605671-4
ISSN	1098-8785 ; 0735-1631
ISSN (online)	1098-8785
ISSN	0735-1631
DOI	10.1055/s-0033-1345262
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