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Article ; Online: Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU-authors' response.

Pasquini, Zeno / Montalti, Roberto / Barchiesi, Francesco

The Journal of antimicrobial chemotherapy

2021 Volume 76, Issue 6, Page(s) 1651–1652

MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; COVID-19/drug therapy ; Humans ; Intensive Care Units ; Italy ; Respiration, Artificial ; SARS-CoV-2
Chemical Substances	remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2021-05-14
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkab092
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 124: Show issues

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Article: Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis.

Gatti, Milo / Fornaro, Giacomo / Pasquini, Zeno / Zanoni, Andrea / Bartoletti, Michele / Viale, Pierluigi / Pea, Federico

Antibiotics (Basel, Switzerland)

2023 Volume 12, Issue 4

Abstract: 1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole ... ...

Abstract	(1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA between January 2021 and December 2022 were included. The concentration/dose ratio (C/D) was used as a surrogate marker of voriconazole total clearance. A receiving operating characteristic (ROC) curve analysis was performed by using C-reactive protein (CRP) or procalcitonin (PCT) values as the test variable and voriconazole C/D ratio > 0.375 (equivalent to a trough concentration [C
Language	English
Publishing date	2023-04-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics12040764
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Article ; Online: A modular phage vector platform for targeted photodynamic therapy of Gram-negative bacterial pathogens.

Petrosino, Annapaola / Saporetti, Roberto / Starinieri, Francesco / Sarti, Edoardo / Ulfo, Luca / Boselli, Luca / Cantelli, Andrea / Morini, Andrea / Zadran, Suleman Khan / Zuccheri, Giampaolo / Pasquini, Zeno / Di Giosia, Matteo / Prodi, Luca / Pompa, Pier Paolo / Costantini, Paolo Emidio / Calvaresi, Matteo / Danielli, Alberto

iScience

2023 Volume 26, Issue 10, Page(s) 108032

Abstract: Growing antibiotic resistance has encouraged the revival of phage-inspired antimicrobial approaches. On the other hand, photodynamic therapy (PDT) is considered a very promising research domain for the protection against infectious diseases. Yet, very ... ...

Abstract	Growing antibiotic resistance has encouraged the revival of phage-inspired antimicrobial approaches. On the other hand, photodynamic therapy (PDT) is considered a very promising research domain for the protection against infectious diseases. Yet, very few efforts have been made to combine the advantages of both approaches in a modular, retargetable platform. Here, we foster the M13 bacteriophage as a multifunctional scaffold, enabling the selective photodynamic killing of bacteria. We took advantage of the well-defined molecular biology of M13 to functionalize its capsid with hundreds of photo-activable Rose Bengal sensitizers and contemporarily target this light-triggerable nanobot to specific bacterial species by phage display of peptide targeting moieties fused to the minor coat protein pIII of the phage. Upon light irradiation of the specimen, the targeted killing of diverse Gram(-) pathogens occurred at subnanomolar concentrations of the phage vector. Our findings contribute to the development of antimicrobials based on targeted and triggerable phage-based nanobiotherapeutics.
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108032
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Article ; Online: Clinical characteristics, management and health related quality of life in young to middle age adults with COVID-19.

Temperoni, Chiara / Grieco, Stefania / Pasquini, Zeno / Canovari, Benedetta / Polenta, Antonio / Gnudi, Umberto / Montalti, Roberto / Barchiesi, Francesco

BMC infectious diseases

2021 Volume 21, Issue 1, Page(s) 134

Abstract: Background: The outbreak of COVID-19 has rapidly spread to Italy, including Pesaro-Urbino province. Data on young to middle age adults with COVID-19 are lacking. We report the characteristics, management and health-related quality of life (HRQoL) in ... ...

Abstract	Background: The outbreak of COVID-19 has rapidly spread to Italy, including Pesaro-Urbino province. Data on young to middle age adults with COVID-19 are lacking. We report the characteristics, management and health-related quality of life (HRQoL) in patients with COVID-19 aging ≤50 years. Methods: A retrospective analysis was performed in all patients ≤50 years with a confirmed diagnosis of COVID-19 admitted to Emergency department (ED) of San Salvatore Hospital in Pesaro from February 28th to April 8th, 2020. Data were collected from electronical medical records. HRQoL was investigated after 1 month from hospital discharge using the SF-36 questionnaire. Outcomes were evaluated between hospitalized and not hospitalized patients. Results: Among 673 patients admitted to the ED and diagnosed with COVID-19, 104 (15%) were ≤ 50 years old: 74% were discharged at home within 48 h, 26% were hospitalized. Fever occurred in 90% of the cases followed by cough (56%) and dyspnoea (34%). The most frequent coexisting conditions were hypertension (11%), thyroid dysfunction (8%) and neurological and/or mental disorders [NMDs] (6%). Mean BMI was 27. Hypokalaemia and NMDs were significantly more common in patients who underwent mechanical ventilation. Regardless of hospitalization, there was an impairment in both the physical and mental functioning. Conclusions: Overweight and hypertension are frequent conditions in young to middle age adults with COVID-19. Hypokalaemia and NMDs are commonly associated with progressive disease. A significant impact on HRQoL in the early stage of post-discharge is common in this population.
MeSH term(s)	Adult ; COVID-19/complications ; COVID-19/diagnosis ; COVID-19/virology ; Cough/etiology ; Dyspnea/etiology ; Female ; Health Surveys ; Hospitalization/statistics & numerical data ; Humans ; Hypertension/complications ; Hypokalemia/complications ; Italy ; Male ; Middle Aged ; Quality of Life ; Respiration, Artificial ; Retrospective Studies ; SARS-CoV-2/isolation & purification ; Young Adult
Language	English
Publishing date	2021-02-01
Publishing country	England
Document type	Journal Article
ISSN	1471-2334
ISSN (online)	1471-2334
DOI	10.1186/s12879-021-05841-1
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Article ; Online: Dual combined antiviral treatment with remdesivir and nirmatrelvir/ritonavir in patients with impaired humoral immunity and persistent SARS-CoV-2 infection.

Pasquini, Zeno / Toschi, Alice / Casadei, Beatrice / Pellegrini, Cinzia / D'Abramo, Alessandra / Vita, Serena / Beccacece, Alessia / Bussini, Linda / Chionsini, Maria Clara / Dentale, Nicola / Cantiani, Alessia / Lazzarotto, Tiziana / Bartoletti, Michele / Nicastri, Emanuele / Zinzani, Pierluigi / Giannella, Maddalena / Viale, Pierluigi

Hematological oncology

2023 Volume 41, Issue 5, Page(s) 904–911

Abstract: Despite global vaccination efforts, immunocompromized patients remain at high risk for COVID-19-associated morbidity. In particular, patients with impaired humoral immunity have shown a high risk of persistent infection. We report a case series of adult ... ...

Abstract	Despite global vaccination efforts, immunocompromized patients remain at high risk for COVID-19-associated morbidity. In particular, patients with impaired humoral immunity have shown a high risk of persistent infection. We report a case series of adult patients with B cell malignancies and/or undergoing B cell targeting therapies with persisting SARS-CoV-2 infection and treated with a combination antiviral therapy of remdesivir and nirmatrelvir/ritonavir, in three Italian tertiary academic hospitals. A total of 14 patients with impaired adaptive humoral immunity and prolonged SARS-CoV-2 infection were treated with the dual antiviral therapy. The median age was 60 (IQR 56-68) years, and 11 were male. Twelve patients had B cell lymphoma, one patient had chronic lymphocytic leukemia and one patient had multiple sclerosis. Thirteen out of 14 patients had received prior B cell-targeting therapies, consisting of anti-CD20 monoclonal antibodies in 11 patients, and chimeric antigen receptor T therapy in 2 patients. The median time between diagnosis and therapy start was 42.0 (IQR 35-46) days. Seven patients had mild, 6 moderate and one severe disease. Nine patients had signs of interstitial pneumonitis on chest computed tomography scans before treatment. The median duration of nirmatrelvir/ritonavir and remdesivir combination therapy was 10 days. All patients showed resolution of COVID-19-related symptoms after a median of 6 (IQR 4-11) days and viral clearance after 9 (IQR 5-11) days. Combination therapy with remdesivir and nirmatrelvir/ritonavir is a promising treatment option for persistent COVID-19 in immunocompromized patients with humoral immunity impairment, worthy of prospective comparative trials.
MeSH term(s)	Adult ; Humans ; Male ; Middle Aged ; Female ; Ritonavir/therapeutic use ; Immunity, Humoral ; Prospective Studies ; COVID-19 ; COVID-19 Drug Treatment ; SARS-CoV-2 ; Antiviral Agents/therapeutic use
Chemical Substances	nirmatrelvir (7R9A5P7H32) ; Ritonavir (O3J8G9O825) ; remdesivir (3QKI37EEHE) ; Antiviral Agents
Language	English
Publishing date	2023-07-15
Publishing country	England
Document type	Journal Article
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.3206
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Zs.A 1816: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Comparison between available early antiviral treatments in outpatients with SARS-CoV-2 infection: a real-life study.

Rinaldi, Matteo / Campoli, Caterina / Gallo, Mena / Marzolla, Domenico / Zuppiroli, Alberto / Riccardi, Riccardo / Casarini, Martina / Riccucci, Daniele / Malosso, Marta / Bonazzetti, Cecilia / Pascale, Renato / Tazza, Beatrice / Pasquini, Zeno / Marconi, Lorenzo / Curti, Stefania / Giannella, Maddalena / Viale, Pierluigi

BMC infectious diseases

2023 Volume 23, Issue 1, Page(s) 646

Abstract: Purpose: To investigate the clinical impact of three available antivirals for early COVID-19 treatment in a large real-life cohort.: Methods: Between January and October 2022 all outpatients tested positive for SARS-CoV-2 referring to IRCCS S. Orsola ...

Abstract	Purpose: To investigate the clinical impact of three available antivirals for early COVID-19 treatment in a large real-life cohort. Methods: Between January and October 2022 all outpatients tested positive for SARS-CoV-2 referring to IRCCS S. Orsola hospital treated with an early antiviral therapy were enrolled. A comparison between patients treated with nirmatrelvir/ritonavir (NTV/r), molnupiravir (MPV) and remdesivir (RDV) was conducted in term of indications and outcome. To account for differences between treatment groups a propensity score analysis was performed. After estimating the weights, we fitted a survey-weighted Cox regression model with inverse-probability weighting with hospital admission/death versus clinical recovery as the primary outcome. Results: Overall 1342 patients were enrolled, 775 (57.8%), 360 (26.8%) and 207 (15.4%) in MPV, NTV/r and RDV group, respectively. Median age was 73 (59-82) years, male sex was 53.4%. Primary indication was immunosuppression (438, 32.6%), the median time from symptom onset to drug administration was 3 [2-4] days. Overall, clinical recovery was reached in 96.9% of patients, with hospital admission rate of 2.6%. No significant differences were found in clinical recovery nor hospitalization. Cox regression showed a decreased probability of hospital admission/ death among prior vaccinated patients compared with unvaccinated (HR 0.31 [95%CI 0.14-0.70], p = 0.005]). No difference in hospitalization rates in early treatment compared to late treatment were found. Conclusions: No differences among MPV, NTV/r and RDV in terms of clinical recovery or hospitalization were found. Patients not vaccinated had a significant increased risk of hospitalization.
MeSH term(s)	Humans ; Male ; Aged ; Outpatients ; COVID-19 Drug Treatment ; COVID-19 ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; Ritonavir/therapeutic use
Chemical Substances	molnupiravir (YA84KI1VEW) ; Antiviral Agents ; Ritonavir (O3J8G9O825)
Language	English
Publishing date	2023-10-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-023-08538-9
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Article ; Online: Neutralizing monoclonal antibodies for early treatment of hospital-acquired SARS-CoV-2 infection in hematologic patients.

Bussini, Linda / Testi, Diletta / Tazza, Beatrice / Oltolini, Chiara / Mastaglio, Sara / Sepulcri, Chiara / Campoli, Caterina / Trapani, Filippo / Pasquini, Zeno / Zappulo, Emanuela / Bassetti, Matteo / Viale, Pierluigi / Mikulska, Malgorzata / Bartoletti, Michele

EJHaem

2022

Abstract: Efficacy of early treatment with anti-SARS-CoV-2 spike protein monoclonal antibodies (mAbs) for nosocomial SARS-CoV-2 infection in hematologic patients is unknown. Retrospective, cohort study conducted in four Italian teaching hospitals. We included ... ...

Abstract	Efficacy of early treatment with anti-SARS-CoV-2 spike protein monoclonal antibodies (mAbs) for nosocomial SARS-CoV-2 infection in hematologic patients is unknown. Retrospective, cohort study conducted in four Italian teaching hospitals. We included adult patients with hematologic malignancies and hospital-acquired SARS-CoV-2 infection diagnosed between November 2020 and December 2021. The principal exposure variable was administration of mAbs. The primary endpoint was clinical failure dea composite outcome of mortality and/or invasive and noninvasive ventilation within 90 days from infection onset. We included 52 patients with hospital-acquired SARS-CoV-2 infection. Males were 29 (60%), median age was 62 (interquartile range [IQR] 48-70). Forty-five (86%) patients were on chemotherapy or had received chemotherapy within 30 days. MAbs were administered in 19/52 (36%) patients. Clinical failure occurred in 22 (42%) patients; 21% (4/19) in mAbs group versus 54% (18/33) in non-mAbs group (
Language	English
Publishing date	2022-09-02
Publishing country	United States
Document type	Journal Article
ISSN	2688-6146
ISSN (online)	2688-6146
DOI	10.1002/jha2.554
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Article: Relationship between Pharmacokinetic/Pharmacodynamic Target Attainment and Microbiological Outcome in Critically Ill COVID-19 Patients with Documented Gram-Negative Superinfections Treated with TDM-Guided Continuous-Infusion Meropenem.

Sanz Codina, Maria / Gatti, Milo / Troisi, Carla / Fornaro, Giacomo / Pasquini, Zeno / Trapani, Filippo / Zanoni, Andrea / Caramelli, Fabio / Viale, Pierluigi / Pea, Federico

Pharmaceutics

2022 Volume 14, Issue 8

Abstract: Objectives: The objective of this study was to explore the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous-infusion (CI) meropenem and microbiological outcome in critical COVID-19 patients with documented Gram- ...

Abstract	Objectives: The objective of this study was to explore the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous-infusion (CI) meropenem and microbiological outcome in critical COVID-19 patients with documented Gram-negative superinfections. Methods: Patients receiving CI meropenem for documented Gram-negative infections at the COVID ICU of the IRCCS Azienda Ospedaliero-Universitaria di Bologna and undergoing therapeutic drug monitoring from January 2021 to February 2022 were retrospectively assessed. Average steady-state meropenem concentrations (Css) were calculated and the Css/MIC ratio was selected as a pharmacodynamic parameter of meropenem efficacy. The Css/MIC ratio was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The relationship between Css/MIC and microbiological outcome was assessed. Results: Overall, 43 critical COVID-19 patients with documented Gram-negative infections were retrieved. Combination therapy was implemented in 26 cases. Css/MIC ratios were optimal in 27 (62.8%), quasi-optimal in 7 (16.3%), and suboptimal in 9 cases (20.9%). Microbiological failure occurred in 21 patients (48.8%), with no difference between monotherapy and combination therapy (43.8% vs. 53.8%; p = 0.53). The microbiological failure rate was significantly lower in patients with an optimal Css/MIC ratio compared to those with a quasi-optimal or suboptimal Css/MIC ratio (33.3% vs. 75.0%; p = 0.01). Conclusion: Suboptimal attainment of meropenem PK/PD targets may be a major determinant impacting on microbiological failure in critical COVID-19 patients with Gram-negative superinfections.
Language	English
Publishing date	2022-07-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14081585
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Article ; Online: Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU.

Pasquini, Zeno / Montalti, Roberto / Temperoni, Chiara / Canovari, Benedetta / Mancini, Mauro / Tempesta, Michele / Pimpini, Daniela / Zallocco, Nicoletta / Barchiesi, Francesco

The Journal of antimicrobial chemotherapy

2020 Volume 75, Issue 11, Page(s) 3359–3365

Abstract: Background: Remdesivir is a prodrug with in vitro activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Its clinical efficacy in patients with COVID-19 under mechanical ventilation remains to be evaluated.: Methods: This ... ...

Abstract	Background: Remdesivir is a prodrug with in vitro activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Its clinical efficacy in patients with COVID-19 under mechanical ventilation remains to be evaluated. Methods: This study includes patients under mechanical ventilation with confirmed SARS-CoV-2 infection admitted to the ICU of Pesaro hospital between 29 February and 20 March 2020. During this period, remdesivir was provided on a compassionate use basis. Clinical characteristics and outcome of patients treated with remdesivir were collected retrospectively and compared with those of patients hospitalized in the same time period. Results: A total of 51 patients were considered, of which 25 were treated with remdesivir. The median (IQR) age was 67 (59-75.5) years, 92% were men and symptom onset was 10 (8-12) days before admission to ICU. At baseline, there was no significant difference in demographic characteristics, comorbidities and laboratory values between patients treated and not treated with remdesivir. Median follow-up was 52 (46-57) days. Kaplan-Meier curves showed significantly lower mortality among patients who had been treated with remdesivir (56% versus 92%, P < 0.001). Cox regression analysis showed that the Charlson Comorbidity Index was the only factor that had a significant association with higher mortality (OR 1.184; 95% CI 1.027-1.365; P = 0.020), while the use of remdesivir was associated with better survival (OR 3.506; 95% CI 1.768-6.954; P < 0.001). Conclusions: In this study the mortality rate of patients with COVID-19 under mechanical ventilation is confirmed to be high. The use of remdesivir was associated with a significant beneficial effect on survival.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/therapeutic use ; Aged ; Alanine/analogs & derivatives ; Alanine/therapeutic use ; Antiviral Agents/therapeutic use ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/diagnosis ; Coronavirus Infections/mortality ; Coronavirus Infections/therapy ; Female ; Follow-Up Studies ; Humans ; Intensive Care Units/trends ; Italy/epidemiology ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/mortality ; Pneumonia, Viral/therapy ; Respiration, Artificial/mortality ; Respiration, Artificial/trends ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome
Chemical Substances	Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
Keywords	covid19
Language	English
Publishing date	2020-08-12
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkaa321
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 124: Show issues

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Article ; Online: Corrigendum to: "Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study)" Clinical Microbiology and Infection 26 (2020) 1545-1553.

Bartoletti, Michele / Giannella, Maddalena / Scudeller, Luigia / Tedeschi, Sara / Rinaldi, Matteo / Bussini, Linda / Fornaro, Giacomo / Pascale, Renato / Pancaldi, Livia / Pasquini, Zeno / Trapani, Filippo / Badia, Lorenzo / Campoli, Caterina / Tadolini, Marina / Attard, Luciano / Puoti, Massimo / Merli, Marco / Mussini, Cristina / Menozzi, Marianna /

Meschiari, Marianna / Codeluppi, Mauro / Barchiesi, Francesco / Cristini, Francesco / Saracino, Annalisa / Licci, Alberto / Rapuano, Silvia / Tonetti, Tommaso / Gaibani, Paolo / Ranieri, Vito M / Viale, Pierluigi

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2023 Volume 29, Issue 6, Page(s) 817

Language	English
Publishing date	2023-03-01
Publishing country	England
Document type	Published Erratum
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2023.02.017
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Zs.A 4541: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 284: Show issues

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