Effectiveness of test-and-treat model with direct-acting antiviral for hepatitis C virus infection in migrants: a prospective interventional study in Italy.

BACKGROUND: Migrants, mainly undocumented and low-income refugees, are at high risk of hepatitis C virus (HCV) infection, but are a difficult-to-reach and to-treat population. The aim of the study was to evaluate the effectiveness of a test and treat model with direct-acting antiviral for HCV infection in these migrants coming from low-income and living in southern Italy. METHODS: A prospective, multicenter, collaborative study based on a four-phase-program (educational counseling, screening, linkage-to-care and treatment) was designed in southern Italy; the study started in June 2018, was stopped in February 2020 because of the outbreak of SARS-CoV2 infection in Italy and was resumed in February 2021 until November 2021. After educational counseling on infectious diseases that are transmitted through blood or sexually pseudonymized HCV screening was offered to all undocumented migrants and low-income refugees observed at one of the 1st level clinical centers. The HCV-RNA-positive subjects were referred to one of the 3rd level units of Infectious Diseases (ID) and treated with a 12-week course of sofosbuvir-velpatasvir and observed for 12 weeks after the end of direct antiviral agents (DAA) treatment. STATISTICAL ANALYSIS: For the descriptive analysis, the categorical variables were reported as absolute numbers and relative frequencies. Continuous variables were summarized as mean and standard deviation (SD) if normally distributed, or as a median and interquartile range (IQR) if not normally distributed. We used Pearson chi-square or Fisher's exact test for categorical variables and Student's t test or Mann-Whitney test for continuous variables. A P value < 0.05 was considered to be statistically significant. Analyses were performed with SPSS 21.0. RESULTS: Of the 3501migrants observed in the study period, 3417 (97.6%) agreed to be screened; 185 (4.7%) were anti-HCV-positive and, of these, 53 (28.6%) were HCV-RNA-positive. Of these 53 subjects, 48 (90.5%) were referred to an ID unit and started DAA treatment. The HCV-RNA-positive-subjects were older [median 36 years (IQR: 32-21) vs 27.19 (IQR: 30.5-19.25); P = 0.001], and less frequently males [35 (66.03 %) vs 119 (90.1%), P < 0 .0001] than seronegative participants. They more frequently came from Eastern Europe (70.8%) stayed longer in Italy [months of stay in Italy, mean ± SD: 51.02 ± 52.84 vs 25.7 ± 42.65, P = 0.001], and had more years of schooling [years of schooling, mean ± SD: 9.61±2.81 vs 7.10 ± 4, P = 0.0001]. HCV-RNA-positive-subjects less frequently reported piercing, tattoos and tribal scars as risk factors (23.6%). Of these 48 HCV RNA positive subjects who started DAA, 47 (97.9%) showed a sustained virological response and one dropped-out in follow-up after DAA treatment. No subject had any adverse event. CONCLUSIONS: This model of HCV screening and linkage to care seems effective to eliminate HCV infectionin a difficult-to-reach and to-treat population, such as undocumented migrants and low-income refugees. The participation of cultural mediators in the study made possible a better interaction between migrants and physicians, as is evident from the large number of subjects enrolled. Eliminating HCV among migrants will have a long-term positive impact from a public health and healthcare perspective by reducing the number of individuals who potentially develop HCV-related complications such as liver cirrhosis and hepatocellular carcinoma and reducing the circulation of HCV in the regions that host them which often, as in the case of Italy, are low endemic for HCV infection.

Burden of Antimicrobial Resistance Among Women with Post-Partum Infections in Low-Middle Income Countries: A Systematic Review.

BACKGROUND: Due to the rising incidence of multidrug-resistant (MDR) pathogens, especially in Low-Middle-Income Countries (LMIC), post-partum infections represent a significant treatment challenge. METHODS: We performed a systematic review of the literature from January 2005 to February 2023 to quantify the frequency of maternal post-partum infections due to MDR pathogens in LMICs, focusing on methicillin-resistant Staphylococcus aureus (MRSA) and/or extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales. SECONDARY OBJECTIVES: description of antimicrobials' prescriptions. FINDINGS: We included 22 studies with 14,804 total bacterial isolates from 12 countries, mostly from WHO African-Region. Twelve papers described wound- and 10 puerperal-infections. Seven were high-quality articles. Seventeen studies reported data on MRSA, and 18 on ESBL-producing Enterobacterales. Among high-quality studies, MRSA ranged from 9.8% in Ghana to 91.2% in Uganda; ESBL-producing Enterobacterales ranged from 22.8% in Ukraine to 95.2% in Uganda. Nine articles, mostly on C-sections, described different protocols for antibiotic prophylaxis and/or post-partum treatment. INTERPRETATION: We described a high burden of post-partum infections caused by MRSA and/or ESBL-producing Enterobacterales in LMICs, but only a few studies met quality standards. There is an urgent need for high-quality studies to better describe the real burden of antimicrobial resistance in low-resource settings and inform policies to contain the spread of multidrug-resistant organisms.

Systematic application of SICA-PED protocol for central venous catheterization in neonates: A prospective clinical study on 104 cases.

BACKGROUND: Catheterization of central vessels can be associated with early and late, potentially fatal complications. A proactive approach is imperative to reduce the frequency and magnitude of adverse events. Recently, the GAVeCeLT has proposed a protocol called SICA-PED (i.e. Safe Insertion of Central Access in Pediatric patients) and includes seven evidence-based strategies. METHODS: Through a single-center prospective observational study, the authors wanted to consolidate the efficacy and safety of these protocol in newborns. In a series of 104 newborns, the seven steps of the protocol were applied (1) pre-procedural ultrasound study of the RaCeVA veins, (2) correct aseptic technique, (3) ultrasound-guided venipuncture, (4) intraprocedural localization of the tip of the catheter with TTE (ECHO TIP) and (iECG) intracavitary electrocardiogram, (5) reasoned choice of the implant exit site with the RAVESTO Tunneling technique, (6) anchoring without stitches, and (7) exit point protection with the use of glue and transparent semipermeable membrane. The authors have included a further precaution in point (6) the subcutaneous anchoring system has added the counter-fixation of the catheter wings that we will call 6Plus Point. RESULTS: All infants requiring implantation of elective us-guided central venous access were enrolled in the study. None of the 104 implanted central venous catheters experienced early complications (accidental arterial puncture, PNX, primary malposition); rare late complications such as ecchymosis, CRBSI, exit site infection or dislodgement were observed, No catheter-related thrombotic phenomena were observed. The CRBSI catheter-related infection rate was 2.47 × 1000 days catheter cases. CONCLUSION: The results of this prospective study strengthen the feasibility and efficacy of the SICA-Ped Protocol. Demonstrating that the systematic application of the evidence-based seven-step implantation strategy increases the success rate, minimizes early and late complications, which result in increased patient safety.

Efficacy of sotrovimab on omicron BA.2, BA.4 and BA.5 subvariants of sars-cov-2 vs. other early therapies: a systematic review and meta-analysis of literature data.

Background: The aim of this meta-analysis was to ascertain whether sotrovimab was effective in reducing COVID-19 related hospitalization and mortality also in Omicron BA.2, BA.4 and BA.5 subvariants compared to other antivirals effective in index period. Methods: A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) and observational studies comparing the efficacy of early treatment with sotrovimab compared to other early treatment effective in index period, antivirals or monoclonal antibodies (mAbs), in patients with COVID-19 during BA.2, BA.4, BA.5 waves, conducted in accordance with PRISMA guidelines. We searched MEDLINE, Google Scholar and the Cochrane Library. Mortality and hospitalization were defined as outcomes. Results: Four studies were included, allowing a meta-analysis of 8,041 patients. Meta-analysis showed no statistical difference between groups in hospitalization and mortality. Precisely, the RR of mortality showed no difference in the sotrovimab group compared to treatment with other drugs (OR 0.38, 95% CI 0.10-1.49, p<0.166). As regards the rate of hospitalization, no significant difference resulted between the patients treated with sotrovimab and those with other drugs (OR 1.66, 95% CI 0.41-6.66, p=0.477). Interpretation: In conclusion, this meta-analysis showed no significant difference between sotrovimab or other antivirals in reducing COVID-19 evolution in patients with a high risk of progression, considering both hospitalization and mortality.

Cefiderocol either in monotherapy or combination versus best available therapy in the treatment of carbapenem-resistant Acinetobacter baumannii infections: A systematic review and meta-analysis.

BACKGROUND: The best treatment for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is still a matter of debate. OBJECTIVES: To describe the outcomes of patients treated with cefiderocol for CRAB infections, and to compare the efficacy of cefiderocol versus best available therapy (BAT). DATA SOURCES: We searched MEDLINE, the Cochrane Library and EMBASE to screen original reports published up to September 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies investigating 30-day mortality, clinical failure, microbiological failure or rate of adverse drug reactions of patients treated with cefiderocol or BAT. PARTICIPANTS: Patients with infections due to CRAB. INTERVENTIONS: Cefiderocol in monotherapy or in combination with other potentially active agents or BAT. ASSESSMENT OF RISK OF BIAS: We used the Cochrane Risk of Bias Tool for RCTs, and the Newcastle Ottawa scale for observational studies. METHODS OF DATA SYNTHESIS: We conducted a meta-analysis pooling risk ratios (RRs) through random effect models. RESULTS: We screened 801 original reports, and 18 studies (2 RCTs, 13 cohort studies and 3 case-series) were included in the analysis, for a total 733 patients treated with cefiderocol, and 473 receiving the BAT. Among patients receiving cefiderocol, the 30-day mortality rate was 42% (95% CI 38-47%), the rate of microbiological failure 48% (95% CI 31-65%), the clinical failure rate 43% (95% CI 32-55%), and the rate of ADRs was 3% (95% CI 1-6%). A lower mortality rate was observed among patients receiving cefiderocol monotherapy as compared to those treated with combination regimens (RR: 0.64; 95% CI: 0.43-0.94, p = 0.024). We found a significantly lower mortality rate (RR: 0.74; 95% CI: 0.57-0.95, p = 0.02) and a lower rate of ADRs (RR: 0.28; 95% CI: 0.09-0.91, p = 0.03) in the group treated with cefiderocol as compared to BAT. No difference was observed in microbiological and clinical failure rate. CONCLUSIONS: Our data strengthen the efficacy and safety profile of cefiderocol in CRAB infections.

Clinical and epidemiological factors causing longer SARS-CoV 2 viral shedding: the results from the CoviCamp cohort.

INTRODUCTION: The aim of this study was to investigate how long hospitalized patients stayed positive to the nasopharyngeal swab, and what demographic and clinical factors influence the time-to-negative swab. METHODS: We enrolled in a multicenter, observational, retrospective study involving 17 COVID-19 units in eight cities of the Campania, southern Italy all patients hospitalized from March 2020 to May 2021 diagnosed with Severe Acute Respiratory Distress Syndrome-Coronavirus-2 (SARS-CoV-2) infection for whom time-to-negative swab was available. RESULTS: 963 patients were enrolled. We defined three groups considering time-to-negative swab: the first including patients with time-to-negative swab before the 26th day, the second including patients with time-to-negative swab from day 26 to day 39, and the third including patients with time-to-negative swab > 39 days. 721 (74.9%) patients belonged to the first group, 194 (20.1%) to the second, and 52 (5.4%) belonged to the third group. Belonging to group 2 and 3 seemed to be influenced by age (p value < 0.001), Charlson comorbidity index (p = 0.009), arterial hypertension (p = 0.02), cardiovascular disease (p = 0.017), or chronic kidney disease (CKD) (p = 0.001). The multivariable analysis confers a leading role to CKD, with an odds ratio of 2.3 as factor influencing belonging to the groups showing a longer time-to-negative swab. Patients with CKD and diabetes were more frequently in the third group. DISCUSSION: Our analysis showed that CKD is a factor related to longer time-to-negative swab, probably because of immunosuppression related to this condition.

The impact of a non-restrictive Antimicrobial Stewardship Program in the emergency department of a secondary-level Italian hospital.

Evidence supporting the effectiveness of Antimicrobial Stewardship (AMS) Programs in the emergency department (ED) setting is limited. We conducted a prospective cohort study to assess the efficacy of an AMS program in an ED and a short-stay observation unit. The intervention included periodic prospective audits (twice a week), conducted by four infectious disease consultants. Primary outcomes included the difference in the hospital mortality rate, antibiotic consumption, and the incidence of bloodstream infections (BSI) caused by multidrug resistant (MDR) bacteria, before March 2020-February 2021 and after March 2021-February 2022 when the program was implemented. Interrupted time-series analysis was performed to assess the effect of our program. During the 12-month program, we performed 152 audits and evaluated 366 antibiotic therapies out of a total of 853 patients admitted. In the intervention period, we observed a non-statistically significant decrease in total antibiotic consumption, with a change in level of - 31.2 defined daily dose/100 patient-days (PD) (p = 0.71). Likewise, we found no significant variations in the rate of BSI due to MDR Gram-positive (CT - 0.02 events/PD, p = 0.84), MDR Gram-negative bacteria (CT 0.08, p = 0.71), or Candida spp. (CT 0.008, p = 0.86). Conversely, we found a significant decrease in the mortality rate between the pre- and post-intervention periods (- 1.98 deaths/100 PD, CI - 3.9 to - 0.007, p = 0.049). The Antibiotic Stewardship Program in the ED was associated with a significant decrease in the mortality rate. More high-quality studies are needed to determine the most effective ASP strategies in this unique setting.

Prognostic Value of Creatinine Levels at Admission on Disease Progression and Mortality in Patients with COVID-19-An Observational Retrospective Study.

INTRODUCTION: Acute kidney disease and chronic kidney disease are considered conditions that can increase the mortality and severity of COVID-19. However, few studies have investigated the impact of creatinine levels on COVID-19 progression in patients without a history of chronic kidney disease. The aim of the study was to assess the impact of creatinine levels at hospital admission on COVID-19 progression and mortality. METHODS: We performed a multicenter, observational, retrospective study involving seventeen COVID-19 Units in the Campania region in southern Italy. All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction on a naso-oropharyngeal swab, from 28 February 2020 to 31 May 2021, were enrolled in the CoviCamp cohort. RESULTS: Evaluating inclusion/exclusion criteria, 1357 patients were included. Considering in-hospital mortality and creatinine value at admission, the best cut-off point to discriminate a death during hospitalization was 1.115 mg/dL. The logistic regression demonstrated that factors independently associated with mortality were age (OR 1.082, CI: 1.054-1.110), Charlson Comorbidity Index (CCI) (OR 1.341, CI: 1.178-1.526), and an abnormal creatinine value at admission, defined as equal to or above 1.12 mg/dL (OR 2.233, CI: 1.373-3.634). DISCUSSION: In conclusion, our study is in line with previous studies confirming that the creatinine serum level can predict mortality in COVID-19 patients and defining that the best cut-off of the creatinine serum level at admission to predict mortality was 1.12 mg/dL.

Prevalence and Epidemiological and Clinical Features of Bacterial Infections in a Large Cohort of Patients Hospitalized for COVID-19 in Southern Italy: A Multicenter Study.

BACKGROUND: The aim of this study was to evaluate the prevalence of bacterial infections and antimicrobial prescriptions in a large cohort of COVID-19 patients and to identify the independent predictors of infection and antibiotic prescription. METHODS: All consecutive patients hospitalized for COVID-19 from March 2020 to May 2021 at 1 of the 17 centers participating in the study were included. All subjects showing a clinical presentation consistent with a bacterial infection with microbiological confirmation (documented infection), and/or a procalcitonin value >1 ng/mL (suspected infection) were considered as having a coinfection (if present at admission) or a superinfection (if acquired after at least 48 h of hospital stay). RESULTS: During the study period, of the 1993 patients, 42 (2.1%) presented with a microbiologically documented infection, including 17 coinfections and 25 superinfections, and 267 (13.2%) a suspected infection. A total of 478 subjects (24.5%) received an antibacterial treatment other than macrolides. No independent predictors of confirmed or suspected bacterial infection were identified. On the contrary, being hospitalized during the second wave of the pandemic (OR 1.35, 95% CI 1.18-1.97, p = 0.001), having a SOFA score ≥3 (OR 2.05, 95% CI 1.53-2.75, p < 0.001), a severe or critical disease (OR 1.66, 95% CI 1.24-2.23, p < 0.001), and a high white blood cell count (OR 1.03, 95% CI 1.004-1.06, p = 0.023) were all independently related to having received an antimicrobial prescription. CONCLUSIONS: Our study reported a high rate of antimicrobial prescriptions despite a limited number of documented or suspected bacterial infections among the large cohort of hospitalized COVID-19 patients.

Obesity as a Risk Factor of Severe Outcome of COVID-19: A Pair-Matched 1:2 Case-Control Study.

BACKGROUND AND AIM: The nature of the association between obesity and poor prognosis of COVID-19 without the evaluation of other co-pathologies associated has not yet been clearly evaluated. The aim of the present pair-matched case-control study was to investigate the outcome of patients with SARS-CoV-2 infection in obese and non-obese patients matched considering gender, age, number of comorbidities, and Charlson Comorbidity Index. METHODS: All the adults hospitalized for SARS-CoV-2 infection and with BMI ≥ 30 kg/m2 were included (Cases). For each Case, two patients with BMI < 30 kg/m2 pair matched for gender, age (±5 years), number of comorbidities (excluding obesity), and Charlson Comorbidity Index (±1) were enrolled (Controls). RESULTS: Of the 1282 patients with SARS-CoV-2 infection followed during the study period, 141 patients with obesity and 282 patients without were enrolled in the case and control groups, respectively. Considering matching variables, there was no statistical difference between the two groups. Patients in the Control group developed more frequently a mild-moderate disease (67% vs. 46.1%, respectively), whereas obese patients were more prone to need intensive care treatment (41.8% vs. 26.6%, respectively; p = 0.001). Moreover, the prevalence of death during hospitalization was higher in the Case group than in the Control group (12.1% vs. 6.4%, p = 0.046). DISCUSSION: We confirmed an association between obesity and severe outcome of patients with COVID-19, also considering other factors associated with a severe outcome of COVID-19. Thus, in the case of SARS-CoV-2 infection, the subjects with BMI ≥ 30 kg/m2 should be evaluated for early antiviral treatment to avoid the development of a severe course.

Outcome of patients with carbapenem-resistant Acinetobacter baumannii infections treated with cefiderocol: A multicenter observational study.

BACKGROUND: No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections. METHODS: We conducted an observational retrospective/prospective multicenter study including all patients> 18 years with carbapenem-resistant A. baumannii (CRAB) infections treated with cefiderocol, from June 12021 to October 30 2022. Primary endpoint was 30-day mortality, secondary end-points the clinical and microbiological response at 7 days and at the end of treatment. Furthermore, we compared the clinical and microbiological outcomes among patients who received cefiderocol in monotherapy or in combination. RESULTS: Thirty-eight patients with forty episodes of infection were included [mean age 65 years (SD+16.3), 75% males, 90% with hospital-acquired infections and 70% showing sepsis or septic shock]. The most common infections included unknown source or catheter-related bacteremia (45%) and pneumonia (40%). We observed at 7 days and at the end of therapy a rate of microbiological failure of 20% and 10%, respectively, and of clinical failure of 47.5% and 32.5%, respectively; the 30-day mortality rate was 47.5%. At multivariate analysis clinical failure at 7 days of treatment was the only independent predictor of 30-day mortality. Comparing monotherapy (used in 72.5%) vs. combination therapy (used in 27.5%), no differences were observed in mortality (51.7 vs 45.5%) and clinical (41.4 vs 63.7%) or microbiological failure (24.1 vs 9.1%). CONCLUSIONS: The findings of this study reinforce the effectiveness of cefiderocol in CRAB infections, also as monotherapy. However, prospective multicenter studies with larger sample sizes and a control group treated with standard of care are needed to identify the best treatment for CRAB infections.

Characterization of hepatitis virus co-infections in a cohort of immigrants living in southern Italy.

To characterize viral hepatitis co-infections in a cohort of immigrants living in southern Italy. In a prospective multicenter study, all undocumented immigrants and low-income refugees consecutively evaluated for a clinical consultation at one of the five first-level clinical centers in southern Italy from January 2012 to February 2020 were enrolled. All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) and anti-HIV; the HBsAg-positive were screened also for anti-delta. Of the 2923 subjects enrolled, 257 (8%) were HBsAg-positive alone (Control group B), 85 (2.9%) only anti-HCV-positive (Control group C), 16 (0.5%) HBsAg/anti-HCV-positive (Case group BC), and 8 (0.2%) HBsAg/anti-HDV-positive (Case group BD). Moreover, 57 (1.9%) subjects were anti-HIV-positive. HBV-DNA positivity was found less frequently in the 16 subjects in Case group BC (43%) and in the 8 in Case group BD (12.5%) than in the 257 in Control group B (76%; p = 0.03 and 0.0000, respectively). Similarly, HCV-RNA positivity was more frequent in Case group BC than in Control group C (75% vs. 44.7% p = 0.02). The subjects in Group BC had a lower prevalence of asymptomatic liver disease (12.5%) than Control group B (62.2%, p = 0.0001) and Control group C (62.3%, p = 0.0002). Conversely, liver cirrhosis was more frequently identified in Case group BC (25%) than in Control groups B and C (3.11% and 2.35%, p = 0.0000 and 0.0004, respectively). The present study contributes to the characterization of hepatitis virus co-infections in the immigrant population.

Dynamics of Lipid Profile in Antiretroviral-Naïve HIV-Infected Patients, Treated with TAF-Based Regimens: A Multicenter Observational Study.

Background: The introduction of tenofovir alafenamide (TAF) in antiretroviral therapy has deeply modified the choice of the backbone for different treatment regimens, allowing the prevention of the bone and renal toxicity that was related to the previous formulation of tenofovir disoproxil fumarate (TDF). At the same time, literature data show an onset of dyslipidemia after a switch from TDF to TAF. To better understand the possible role of TAF in dyslipidemia, antiretroviral-naïve HIV-infected patients were evaluated, comparing those treated with TAF/emtricitabine with those with abacavir/lamivudine. Methods: We enrolled 270 antiretroviral-naïve HIV-infected patients in an observational, retrospective, longitudinal, multicenter study; they started treatment from 2017 to 2019 and were followed up for at least 72 weeks. We divided patients into two groups, one treated with a TAF-based backbone in their antiretroviral regimens (TAF group) and one without TAF (NO TAF group), to evaluate possible differences in the dynamics of lipid profiles from baseline(T0) to week 24 (T24), 48 (T48) and 72 (T72). Results: No significant differences were observed at baseline between the 2 groups. In the TAF group we observed a significant development of hypercholesterolemia throughout the follow-up (p < 0.0001), not evident in the NO TAF group, that instead showed a significant increase in high-density lipoprotein (HDL). There were no significant differences between the two groups regarding triglycerides, low-density lipoprotein (LDL) and cardiovascular risk index (CRI). A cholesterol-lowering treatment with statin, finally, was prescribed in 6 patients in both groups during the study. At binary logistic regression analysis, no factor was independently associated with hypercholesterolemia, except for higher age at T0. Conclusions: This real-life study shows that in HIV-naïve patients, TAF was associated with hypercholesterolemia throughout the follow-up. The clinical significance of this hypercholesterolemia will have to be clarified in further studies.

Hepatitis D virus infection in a large cohort of immigrants in southern Italy: a multicenter, prospective study.

BACKGROUND: Since few data are available in the literature on the prevalence of anti-Delta-positive subjects in immigrant populations, the aim of the present study was to evaluate the demographic and virological characteristics of HDV infection in a large cohort of immigrants living in southern Italy. METHODS: Between January 2012 and February 2020 all immigrants attending one of the 5 first- level centers were enrolled and screened for HBsAg, the HBsAg-positive for anti-Delta and if positive, for HDV-RNA and HDV genotype. RESULTS: Of the 3521 immigrants observed in the study period, 3417 (97.0%) agreed to be screened; they were mainly males (61%), with a median age of 27 years (IQR 8-74) and came prevalently (58%) from sub-Saharan Africa. Of the 3417 patients enrolled, 319 (9%) subjects were HBsAg-positive, and of those, 8 (2.5%) were anti-Delta-positive. No difference in the demographic and epidemiological characteristics was observed between the anti-Delta-negative vs -positive. Of the 8 anti-Delta-positive subjects, only one was HDV-RNA-positive (viral load: 7050 IU/mL), genotype 1, with clinical signs of cirrhosis. CONCLUSIONS: the present study showed a prevalence of HDV of 2.5% in a large cohort of asymptomatic immigrants, suggesting the need for screening campaigns for viral infections including delta hepatitis in this population.

Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion.

Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are urgently needed. Fortunately, several drugs and combinations have been introduced in recent years to treat multi-drug-resistant (MDR) bacteria. However, a correct use of these molecules is needed to preserve their efficacy. In the present paper, we will provide an overview on the epidemiology and mechanisms of resistance of the most common MDR Gram-negative bacteria, proposing a treatment algorithm for the management of infections due to carbapenem-resistant bacteria based on the most recent clinical evidence.

Fatal Outcome of COVID-19 Relapse in a Fully Vaccinated Patient with Non-Hodgkin Lymphoma Receiving Maintenance Therapy with the Anti-CD20 Monoclonal Antibody Obinutuzumab: A Case Report.

Few data are available regarding the effectiveness of anti-SARS-CoV-2 vaccine in immunocompromised patients. Vaccination may have a suboptimal efficacy in this population, in particular if patients are exposed to anti-B-cell therapy. We report the virological and clinical characteristics of a patient with follicle center lymphoma under bimonthly maintenance therapy with obinutuzumab, an anti-CD20 monoclonal antibody. Despite three doses of BNT162b2 vaccine, the patient was infected by the SARS-CoV-2 Omicron variant. After an initial period of clinical and molecular remission due to early therapy with sotrovimab, the patient experienced a fatal relapse sustained by the same viral strain.

Long-Term Impact of the COVID-19 Pandemic on In-Hospital Antibiotic Consumption and Antibiotic Resistance: A Time Series Analysis (2015-2021).

The coronavirus disease 2019 (COVID-19)-pandemic-related overload of health systems has compromised the application of antimicrobial stewardship (AS) models and infection prevention and control (IPC) programs. We aimed to evaluate the impact of COVID-19 on antimicrobial consumption (AC) and antimicrobial resistance (AMR) in the University Hospital of Modena. A time series analysis with an autoregressive integrated moving average model was conducted from January 2015 to October 2021 to evaluate the AC in the whole hospital and the intensive care unit (ICU), the incidence density (ID) of bloodstream infections (BSIs) due to the main multidrug-resistant organisms, and of C. difficile infections (CDIs). After an initial peak during the COVID-19 period, a decrease in the trend of AC was observed, both at the hospital (CT: -1.104, p = 0.025) and ICU levels (CT: -4.47, p = 0.047), with no significant difference in the single classes. Among the Gram-negative isolates, we observed a significant increase only in the level of BSIs due to carbapenem-susceptible Pseudomonas aeruginosa (CL: 1.477, 95% CI 0.130 to 2.824, p = 0.032). Considering Gram-positive bacteria, an increase in the level of BSIs due to methicillin-resistant Staphylococcus aureus and in the trend of CDIs were observed, though they did not reach statistical significance (CL: 0.72, 95% CI -0.039 to 1.48, p = 0.062; CT: 1.43, 95% CI -0.002 to 2.863, p = 0.051; respectively). Our findings demonstrated that the increases in AMR and AC that appeared in the first COVID-19 wave may be later controlled by restoring IPC and AS programs to pre-epidemic levels. A coordinated healthcare effort is necessary to address the longer-term impact of COVID-19 on AC to avoid irreversible consequences on AMR.

Epidemiological, Clinical and Microbiological Characteristics of Patients with Bloodstream Infections Due to Carbapenem-Resistant K. Pneumoniae in Southern Italy: A Multicentre Study.

BACKGROUND: In the present study, our aim was to evaluate the clinical and microbiological characteristics of a cohort of patients with bloodstream infections (BSI) due to Carbapenem-Resistant Enterobacteriaceae (CRE) and investigate the independent predictors of mortality. METHODS: All episodes of carbapenem-resistant E. coli (CREc) or K. pneumoniae (CRKp) BSI that were subject to a mandatory notification from January to December 2020 in all acute care hospitals and long-term care facilities of the Campania region in southern Italy were enrolled. All carbapenem-resistant strains were assessed through molecular tests for the presence of five carbapenemase gene families, i.e., K. pneumoniae Carbapenemase (KPC), oxacillinase-48 (OXA-48), New Delhi Metallo-ß-lactamase (NDM), Verona integron encoded metallo-ß-lactamase (VIM) and Imipenemase (IMP). RESULTS: During the study period, a total of 154 consecutive non-repeated CRE BSI, all due to CRKp, were reported. The most frequently identified genes were KPC in 108 cases (70.1%), followed by metallo-betalactamases (MBL) (16.2%), and OXA-48 (2.6%); in 17 isolates (11%) no carbapenemase was detected. The overall mortality at 90 days was 41.9%. Using a log-rank test, patients without risk factors for CRE infections showed a significantly lower cumulative mortality (p = 0.001). After multivariate logistic regression analysis, the presence of at least one risk factor was the only predictor of mortality (OR: 1.7, 95% CI 1.2-6.1, p = 0.015). CONCLUSIONS: The study reported a non-negligible prevalence of MBL-producing organisms among CRKp isolated from blood cultures in our region. This data highlights the importance of molecular characterization of all clinical isolates of carbapenem-resistant organisms.