Genotypic and phenotypic characteristics of Candida parapsilosis bloodstream isolates: Health Care Associated Infections in a teaching Hospital in Italy.

BACKGROUND: Candidemia is the most common healthcare associated invasive fungal infection. Over the last few decades, candidemia caused by Candida species other than Candida albicans, particularly the Candida parapsilosis complex, has emerged worldwide. The aims of this study were: to analyze the genotypic and phenotypic characteristics of C. parapsilosis strains isolated from blood cultures and the environment in a hospital in southern Italy, to study the possible source of infection and to correlate the isolated strains. METHODS: From April to October 2022, cases of candidemia due to C. parapsilosis in patients admitted to a hospital in the Apulia region were investigated. However, 119 environmental samples from the intensive care unit were collected for identification of the likely environmental reservoir of infection. Routine antifungal (amphotericin B, anidulafungin, fluconazole) susceptibility was performed on all isolates. Whole genome sequencing was performed to study the genotypic correlation of the isolates. Biofilm biomass and metabolic activity were also quantified for all isolates. RESULTS: A total of 43 C. parapsilosis isolates were cultured from the bloodstream of each patient in different departments, and seven surface samples were positive for C. parapsilosis. Most of the isolated yeasts (41/50; 85 %) were resistant to fluconazole and were genetically related to each other, suggesting an ongoing clonal outbreak of this pathogen. The fluconazole-susceptible isolates produced significantly more biofilm than did the resistant isolates. Metabolic activity was also higher for fluconazole-susceptible than resistant isolates. CONCLUSION: Cross-transmission of the microorganisms is suggested by the phenotypic similarity and genetic correlation between clinical and environmental strains observed in our study.

Real life experience on the use of Remdesivir in patients admitted to COVID-19 in two referral Italian hospital: a propensity score matched analysis.

Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p < 0.0001). Moreover, the patients taking Remdesivir were less frequently vaccinated against COVID-19. All the other clinical, radiological, and pharmacological parameters were balanced between the two groups. The use of Remdesivir in our cohort was associated with a significantly lower risk of mortality during the follow-up period (HR 0.56; 95% CI 0.37-0.86; p = 0.007). Moreover, RDV was associated with a significantly lower incidence of non-invasive ventilation (OR 0.27; 95% CI 0.20-0.36). Furthermore, in the 365 patients taking Remdesivir, we observed two cases of mild renal failure requiring a reduction in the dosage of Remdesivir and two cases in which the physicians decided to interrupt Remdesivir for bradycardia and for QT elongation. Our study suggests that the use of Remdesivir in hospitalized COVID-19 patients is a safe therapy associated with improved clinical outcomes, including halving of mortality and with a reduction of around 75% of the risk of invasive ventilation. In a constantly changing COVID-19 scenario, ongoing research is necessary to tailor treatment decisions based on the latest scientific evidence and optimize patient outcomes.

Efficacy of Remdesivir and Neutralizing Monoclonal Antibodies in Monotherapy or Combination Therapy in Reducing the Risk of Disease Progression in Elderly or Immunocompromised Hosts Hospitalized for COVID-19: A Single Center Retrospective Study.

INTRODUCTION: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. METHODS: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate-multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed. RESULTS: Overall, 331 subjects were included; their median (q1-q3) age was 71 (51-80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3-11%) and 14% (95%CI = 3-25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02-0.77) when compared with monotherapy. CONCLUSIONS: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial.

Incidence and predictors of infections in patients with advanced non-small cell lung cancer treated with checkpoint inhibitor immunotherapies: A monocentric retrospective cohort study.

Immune checkpoint inhibitors (ICIs) represent the cornerstone of the current treatment of non-small cell lung cancer (NSCLC). However, the occurrence of concomitant infections might hamper success. All consecutive patients with advanced NSCLC who started ICIs as a first- or second-line therapy from January 1, 2017 to June 30, 2020 were retrospectively evaluated. The occurrence of infectious events during ICIs was correlated with clinical characteristics, including previous Cytotoxic Chemotherapy (CC), occurrence of immune-related-adverse-events (irAEs). A total of 211 patients were included, 46 (22%) females, with a median (q1-q3) age of 69 (62-76) years. Overall, 85 patients (40%) received ICIs as a first treatment line and 126 (60%) as a second line; 40 patients (19%) had at least one infection during ICIs, and 17 (8%) more than one. Notably, autoimmune diseases (P < .005), neutropenia (P = .001) or infections during previous CC (P = .001), irAEs (P = .006), or steroid therapy for irAEs (P < .001) were associated with infection development. By multivariate Cox-regression, autoimmune diseases (aHR = 6.27; 95%CI = 2.38-16.48; P < .001) and steroid therapy for irAEs (aHR = 2.65; 95%CI = 1.27-5.52; P < .009) were associated with a higher risk of infection during ICIs. Interestingly, autoimmune diseases were confirmed as risk factors in patients treated with ICIs as a first line, while previous infections were the only independent predictor of infections in patients treated with ICIs as a second line. Patients with NSCLC treated with ICIs with concurrent autoimmune disease, receiving steroid therapy for management of irAEs, or having a history of previous infections during CC should be actively monitored for the risk of developing infectious complications.

Multidisciplinary Approach in the Treatment of Descending Necrotizing Mediastinitis: Twenty-Year Single-Center Experience.

Descending necrotizing mediastinitis (DNM) is an acute, rare, severe condition with high mortality, but the optimal management protocol is still controversial. We retrospectively analyzed the results of multidisciplinary management in patients treated for DNM at our center over the last twenty years. Fifteen male patients, mean age 49.07 ± 14.92 years, were treated: 9 with cervico-pharyngeal etiopathogenesis, 3 peri-tonsillar/tonsillar, 2 odontogenic, 1 post-surgical; 6 with DNM type I, 6 with type IIA, and 3 with type IIB (Endo's classification). Mean time between diagnosis and treatment was 2.24 ± 1.61 days. In all cases, mediastinum drainage via thoracotomy was performed after neck drainage via cervicotomy, associated with tooth treatment in two; one required re-operation; tracheostomy was necessary in 9, temporary intensive care unit stay in 4; 6 developed complications, without post-operative mortality. Main isolated germs were Staphylococci and Candida; 7 had polymicrobial infection. The most used antibiotics were meropenem, metronidazole, teicoplanin, third-generation cephalosporins and clyndamicin; anti-fungal drugs were fluconazole, caspofungin and anidulafungin. On multivariate analysis, presence of cardiovascular disease was statistically significantly associated with longer chest tube duration and hospital stay. DNM requires early diagnosis and treatment to reduce mortality and morbidity. The most effective treatment should provide a multidisciplinary approach, combining cervicotomy and thoracotomy to drain all infectious collections with administration and monitoring of the proper antimicrobial therapy.

Emerging issue of fluconazole-resistant candidemia in a tertiary care hospital of southern italy: time for antifungal stewardship program.

An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%. This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.

Incidence of Infections and Predictors of Mortality During Checkpoint Inhibitor Immunotherapy in Patients With Advanced Lung Cancer: A Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized nonsmall cell lung cancer (NSCLC) treatment and significantly increased overall survival of patients. However, the incidence of concurrent infections and their management is still debated. METHODS: From August 2015 to October 2019, all consecutive patients with NSCLC who received nivolumab or pembrolizumab as first- or second-line therapy were retrospectively evaluated. At the time of analysis all patients had died. Clinical characteristics of patients, type of infections, and predictors of mortality were analyzed. RESULTS: A total of 118 patients were identified: 74 in the nivolumab group and 44 in the pembrolizumab group. At least 1 infection was recorded in 22% of the nivolumab-group versus 27% of the pembrolizumab-group (P = .178). In both groups, the main infection was pneumonia, followed by skin and soft tissue infections, urinary tract infections, and gastroenteritis. Crude mortality for first infection was 10.7%, followed by 25% and 40% for the second and third recurrence, respectively (p for trend = .146). No opportunistic infections were recorded. It is notable that, by Cox-regression model, the independent predictor of mortality was a higher Eastern Cooperative Oncology Group performance status at baseline (P < .001), whereas the multidisciplinary diagnosis and treatment of concurrent infections was associated with a reduced probability of mortality (adjusted hazard ratio = 0.50; 95% confidence interval = 0.30-0.83; P < .001). CONCLUSIONS: In patients with NSCLC treated with ICIs, multidisciplinary management of concurrent infections may reduce the risk of mortality. Further studies to investigate risk factors for infections, as well as appropriate management strategies and preventive measures in this setting, are warranted.

Subcutaneous Human Dirofilariosis By D. Repens In South Italy: A Case Report.

Human dirofilariosis is a zoonosis caused by different Dirofilaria species: D. repens, D. immitis, D. tenuis and D. ursi, thin nematodes belonging to the Onchocercidae family, whose larval stages are generally found in the natural (felines and canids) or accidental (human) definitive host. In Europe, human infection is rare, even in areas considered endemic such as Spain or Italy. In this paper we describe the case of an 82-year-old woman living in Modugno (Bari municipality), who came to our observation for a subcutaneous nodule on her right thigh that had appeared in the previous two weeks and gradually became necrotic. The woman lived in an apartment with a dog. An adult worm, white, thin, about 140 mm long, came out of the necrotic area spontaneously. After microscopic examination, the worm was identified as D. repens. In Apulia, a South-Italy region, human dirofilariosis is a rare disease and since 1885 only 11 cases have been reported. In recent years we have witnessed an increase in the number of diseases transmitted by vectors at all latitudes, and in our region an increase in the Aedes albopticus population has been reported, so it is reasonable to expect an increase in dirofilariosis cases in humans.

Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study.

Coinfection of blood-borne hepatitis B and hepatitis C viruses (HBV and HCV, respectively) in human immunodeficiency virus type 1 (HIV-1)-positive individuals frequently occurs in inmate population and peculiar viral strains and patterns of virological markers may be observed.Plasma from 69 HIV-1-positive inmates was obtained from 7 clinical centers connected with correctional centers in different towns in Italy. HIV, HBV, and HCV markers were tested by commercial assays. Virus genotyping was carried out by sequencing the protease and reverse transcriptase-encoding region (PR-RT region) for HIV and a region encompassing the NS5B gene for HCV and subsequent phylogenetic analysis.Twelve over 14 HIV-subtyped inmates were infected with HIV-1 subtype B strains. The 2 non-B strains belonged to subtype G and CRF02_AG, in an Italian and a Gambian patient, respectively. Variants carrying the K103N and Y181C resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were found in 2 out of 9 patients naive for combined antiretroviral therapy (cART) (22.2%). Most HIV-positive patients (92.8%) showed evidence of past or present HBV and/or HCV infection. Prevalence of HBV and HCV was 81.2% for both viruses, whereas prevalence of HBV/HCV coinfection was 69.6%. A significantly higher presence of HCV infection was found in Italians [odds ratio (OR) 11.0; interval 1.7-80.9] and in drug users (OR 27.8; interval 4.9-186.0). HCV subtypes were determined in 42 HCV or HBV/HCV-coinfected individuals. HCV subtypes 1a, 3a, 4d, and 1b were found in 42.9%, 40.5%, 14.3%, and 2.4% of inmates, respectively. Low titers of HBV DNA in HBV DNA positive subjects precluded HBV subtyping.The high prevalence of HBV and HCV coinfections in HIV-infected inmates, as well as the heterogeneity of HIV and HCV subtypes suggest the need to adopt systematic controls in prisons to monitor both the burden and the genetic forms of blood-borne viral infections, in order to apply targeted therapeutic interventions.