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  • 1
    Online Resource
    Online Resource
    Multicenter Observational Retrospective Study on Febrile Events in Patients with Acute Myeloid Leukemia Treated with Cpx-351 in “Real-Life”: The SEIFEM Experience
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 13 ( 2023-07-01), p. 3457-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 13 ( 2023-07-01), p. 3457-
    Abstract: In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included. Overall, 336 CPX-351 courses were counted: all 200 patients received the first induction cycle, 18 patients (5%) received a second CPX-351 induction, while 86 patients (26%) proceeded with the first CPX-351 consolidation cycle, and 32 patients (10%) received a second CPX-351 consolidation. A total of 249 febrile events were recorded: 193 during the first or second induction, and 56 after the first or second consolidation. After the diagnostic work-up, 92 events (37%) were classified as febrile neutropenia of unknown origin (FUO), 118 (47%) were classifiable as microbiologically documented infections, and 39 (17%) were classifiable as clinically documented infections. The overall 30-day mortality rate was 14% (28/200). The attributable mortality–infection rate was 6% (15/249). A lack of response to the CPX-351 treatment was the only factor significantly associated with mortality in the multivariate analysis [p-value: 0.004, OR 0.05, 95% CI 0.01–0.39]. Our study confirms the good safety profile of CPX-351 in a real-life setting, with an incidence of infectious complications comparable to that of the pivotal studies; despite prolonged neutropenia, the incidence of fungal infections was low, as was infection-related mortality.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15133457
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Online Resource
    XDR-Pseudomonas aeruginosa Outside the ICU: Is There Still Place for Colistin?
    MDPI AG ; 2022
    In:  Antibiotics Vol. 11, No. 2 ( 2022-02-01), p. 193-
    Details
    In: Antibiotics, MDPI AG, Vol. 11, No. 2 ( 2022-02-01), p. 193-
    Abstract: Background: Pseudomonas aeruginosa represents, among the nosocomial pathogens, one of the most serious threats, both for the severity of its clinical manifestations and its ability to develop complex profiles of resistance; Methods: we retrospectively collected the data of 21 patients admitted to a tertiary-care University Hospital of Rome with infections due to XDR-P. aeruginosa isolates during the second half of 2020; Results: in our institution, the percentage of XDR-P. aeruginosa isolates is 3.1%. None of the patients was admitted to the intensive care unit at the moment of the infection’s onset. Susceptibility to colistin was preserved in all the tested isolates. Rates of resistance to ceftolozane/tazobactam and ceftazidime/avibactam in these XDR strains were consistent; Conclusions: XDR-P. aeruginosa can be a threatening problem even outside the ICUs, especially in frail patients in wards with features of long-term acute care hospitals. In such a setting, ceftolozane/tazobactam and ceftazidime/avibactam should be administered with caution taking into account the microbiological susceptibility results. Colistin, even with its known safety and efficacy limits, could represent the only available therapeutic option due to its highly preserved susceptibility against XDR isolates of P. aeruginosa.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    URL: Article
    DOI: 10.3390/antibiotics11020193
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2681345-2
    SSG: 15,3
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  • 3
    Online Resource
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    Efficacy and Durability of Dolutegravir- or Darunavir-Based Regimens in ART-Naïve AIDS- or Late-Presenting HIV-Infected Patients
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 5 ( 2023-05-08), p. 1123-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 5 ( 2023-05-08), p. 1123-
    Abstract: Background: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. Methods: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up. Results: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA 〉 1000 cp/mL or two consecutive HIV-RNA 〉 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p 〉 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046). Conclusions: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15051123
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 4
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    Invasive Respiratory Fungal Infections in COVID-19 Critically Ill Patients
    MDPI AG ; 2022
    In:  Journal of Fungi Vol. 8, No. 4 ( 2022-04-17), p. 415-
    Details
    In: Journal of Fungi, MDPI AG, Vol. 8, No. 4 ( 2022-04-17), p. 415-
    Abstract: Patients with coronavirus disease 19 (COVID-19) admitted to the intensive care unit (ICU) often develop respiratory fungal infections. The most frequent diseases are the COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated pulmonary mucormycosis (CAPM) and the Pneumocystis jirovecii pneumonia (PCP), the latter mostly found in patients with both COVID-19 and underlying HIV infection. Furthermore, co-infections due to less common mold pathogens have been also described. Respiratory fungal infections in critically ill patients are promoted by multiple risk factors, including epithelial damage caused by COVID-19 infection, mechanical ventilation and immunosuppression, mainly induced by corticosteroids and immunomodulators. In COVID-19 patients, a correct discrimination between fungal colonization and infection is challenging, further hampered by sampling difficulties and by the low reliability of diagnostic approaches, frequently needing an integration of clinical, radiological and microbiological features. Several antifungal drugs are currently available, but the development of new molecules with reduced toxicity, less drug-interactions and potentially active on difficult to treat strains, is highly warranted. Finally, the role of prophylaxis in certain COVID-19 populations is still controversial and must be further investigated.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    URL: Article
    DOI: 10.3390/jof8040415
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2784229-0
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  • 5
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    Online Resource
    Primary Cutaneous Cryptococcosis in an Immunocompetent Patient: Diagnostic Workflow and Choice of Treatment
    MDPI AG ; 2023
    In:  Diagnostics Vol. 13, No. 19 ( 2023-10-07), p. 3149-
    Details
    In: Diagnostics, MDPI AG, Vol. 13, No. 19 ( 2023-10-07), p. 3149-
    Abstract: Cryptococcosis is an opportunistic infection in immunocompromised patients, involving mainly the lungs and central nervous system; however, the skin, eyes and genitourinary tract could also be involved as secondary sites of infection. Primary cutaneous cryptococcosis (PCC) is a distinct clinical entity that can occur in both immunocompetent and -compromised patients, usually trough skin injury. In immunocompetent patients, it is a very rare infection, presenting with non-specific clinical pictures and being challenging to diagnose. Herein, we present the case of an immunocompetent man with PCC due to Cryptococcus neoformans on his right forearm. PCC was diagnosed by a histological and cultural examination. Causes of concomitant immunosuppression were ruled out. A secondary cutaneous cryptococcosis was excluded with careful investigations. Therapy with oral fluconazole for three months was successfully performed, without evidence of recurrence in the following six months. Complete clinical recovery was achieved after three months of oral antifungal therapy, suggesting that longer courses of treatment could be avoided when faced with PCC in immunocompetent patients.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics13193149
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662336-5
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  • 6
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    New Drugs for the Treatment of Pseudomonas aeruginosa Infections with Limited Treatment Options: A Narrative Review
    MDPI AG ; 2022
    In:  Antibiotics Vol. 11, No. 5 ( 2022-04-26), p. 579-
    Details
    In: Antibiotics, MDPI AG, Vol. 11, No. 5 ( 2022-04-26), p. 579-
    Abstract: P. aeruginosa is still one of the most threatening pathogens responsible for serious hospital-acquired infections. It is intrinsically resistant to many antimicrobial agents and additional acquired resistance further complicates the management of such infections. High rates of combined antimicrobial resistance persist in many countries, especially in the eastern and south-eastern parts of Europe. The aim of this narrative review is to provide a comprehensive assessment of the epidemiology, latest data, and clinical evidence on the current and new available drugs active against P. aeruginosa isolates with limited treatment options. The latest evidence and recommendations supporting the use of ceftolozane-tazobactam and ceftazidime-avibactam, characterized by targeted clinical activity against a significant proportion of P. aeruginosa strains with limited treatment options, are described based on a review of the latest microbiological and clinical studies. Cefiderocol, with excellent in vitro activity against P. aeruginosa isolates, good stability to all β-lactamases and against porin and efflux pumps mutations, is also examined. New carbapenem combinations are explored, reviewing the latest experimental and initial clinical evidence. One section is devoted to a review of new anti-pseudomonal antibiotics in the pipeline, such as cefepime-taniborbactam and cefepime-zidebactam. Finally, other “old” antimicrobials, mainly fosfomycin, that can be used as combination strategies, are described.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    URL: Article
    DOI: 10.3390/antibiotics11050579
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2681345-2
    SSG: 15,3
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  • 7
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    Factors Associated with Inadequate Intravenous Colistin Dosages: Post Hoc Analysis of a Multicenter, Cross-Sectional Study
    MDPI AG ; 2021
    In:  Antibiotics Vol. 10, No. 12 ( 2021-12-19), p. 1554-
    Details
    In: Antibiotics, MDPI AG, Vol. 10, No. 12 ( 2021-12-19), p. 1554-
    Abstract: Colistin is a last-resort agent for the treatment of infections due to Gram-negative bacteria with difficult-to-treat resistance. The primary objective of this post hoc analysis of a cross-sectional study conducted in 22 Italian hospitals was to assess factors associated with inadequate intravenous colistin dosage. Overall, 187 patients receiving intravenous colistin were included in the analyses. Inadequate colistin dosages were administered in 27% of cases (50/187). In multivariable analysis, AKI (dummy variable with KDIGO stage 0 as a reference, odds ratio (OR) 3.98 with 95% confidence interval (CI) 1.48–10.74 for stage 1, OR 4.44 with 95% CI 1.17–16.93 for stage 2, OR 9.41 with 95% CI 1.59–55.70 for stage 3; overall p = 0.001) retained an independent association with inadequate colistin dosage, whereas the presence of a central venous catheter was associated with adequate colistin dosage (OR: 0.34 for inadequate dosage, 95% CI: 0.16–0.72, p = 0.004). These results were confirmed in an additional multivariable model with the center as a random effect. The association between AKI and inadequate dosage may reflect the perception of an increased risk of nephrotoxicity in patients with impaired renal function, which nonetheless should not be accompanied by dosage reductions beyond those recommended and could represent the target of dedicated antimicrobial stewardship efforts.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    URL: Article
    DOI: 10.3390/antibiotics10121554
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2681345-2
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  • 8
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    Online Resource
    Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort)
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 2 ( 2023-02-05), p. 438-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 2 ( 2023-02-05), p. 438-
    Abstract: Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration 〉 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15020438
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 9
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    Molecular Mechanisms, Epidemiology, and Clinical Importance of β-Lactam Resistance in Enterobacteriaceae
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 14 ( 2020-07-18), p. 5090-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 14 ( 2020-07-18), p. 5090-
    Abstract: Despite being members of gut microbiota, Enterobacteriaceae are associated with many severe infections such as bloodstream infections. The β-lactam drugs have been the cornerstone of antibiotic therapy for such infections. However, the overuse of these antibiotics has contributed to select β-lactam-resistant Enterobacteriaceae isolates, so that β-lactam resistance is nowadays a major concern worldwide. The production of enzymes that inactivate β-lactams, mainly extended-spectrum β-lactamases and carbapenemases, can confer multidrug resistance patterns that seriously compromise therapeutic options. Further, β-lactam resistance may result in increases in the drug toxicity, mortality, and healthcare costs associated with Enterobacteriaceae infections. Here, we summarize the updated evidence about the molecular mechanisms and epidemiology of β-lactamase-mediated β-lactam resistance in Enterobacteriaceae, and their potential impact on clinical outcomes of β-lactam-resistant Enterobacteriaceae infections.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21145090
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
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    Rapid Decrease in Fluoroquinolones Consumption following Implementation of a Simple Antimicrobial Stewardship Bundled Intervention in a University Hospital during the COVID-19 Pandemic
    MDPI AG ; 2023
    In:  Antibiotics Vol. 12, No. 4 ( 2023-04-02), p. 694-
    Details
    In: Antibiotics, MDPI AG, Vol. 12, No. 4 ( 2023-04-02), p. 694-
    Abstract: Fluoroquinolones (FQs) represent an class of antibiotics of medical importance, but their use has been restricted due to their ecologic impact and associated side effects. The reduction of FQs use is an important goal of antimicrobial stewardship programs (ASP). This work describes an ASP focused on overall antibiotics and FQs consumption reduction. From January 2021, an ASP was implemented in a 700-bed teaching hospital. The ASP was based on: (i) antibiotics consumption monitoring system (DDD/100 bed days); (ii) mandatory antibiotic prescription-motivation (using a dedicated informatic format) with the goal of 〉 75% of motivated prescriptions; and (iii) data feedback and training on FQs use indications. We evaluated the impact of the intervention on overall systemic antibiotics and FQs consumption according to the objectives posed by Italian PNCAR (National Action Plan on Antimicrobial Resistance). A decrease of 6.6% in antibiotic use was observed (2019 vs. 2021). Notably, the FQs consumption fell by 48.3% from 7.1 DDD/100 bd in 2019 to 3.7 DDD/100 bd in 2021 (p 〈 0.001). After six months of mandatory antibiotic prescription-indication, all units achieved the target set. The study suggests that a simple, bundled ASP intervention can be rapidly effective obtaining the objectives of PNCAR on the reduction of overall antibiotics and FQs consumption.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    URL: Article
    DOI: 10.3390/antibiotics12040694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2681345-2
    SSG: 15,3
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