Durability of doravirine with dolutegravir dual regimen compared with other dolutegravir-based dual combinations.

OBJECTIVES: The availability of doravirine (DOR) allowed clinicians to prescribe a dolutegravir (DTG)-based two-drug regimen (2DR) in individuals not eligible to receive lamivudine (3TC) or rilpivirine (RPV). The aims of this study were to describe the durability of DTG + DOR compared with DTG/3TC and DTG/RPV and the rate of virological failure and target not-detected maintenance over time. METHODS: This retrospective, monocentric analysis included all subjects who started a DTG-based 2DR from 2018 to 2022 as a simplification. Descriptive statistics and non-parametric tests to describe and compare the groups were applied. Kaplan-Meier probability curves and Cox regression models for regimens durability were used. RESULTS: The study enrolled 710 individuals: 499 treated with DTG/3TC, 140 with DTG/RPV, and 71 with DTG + DOR. A 2DR with DOR was prescribed to older subjects who had a longer infection, greater exposure to different antiretroviral regimens, a higher proportion of resistance-associated mutations, and a worse immune-virologic status. Over a cumulative follow-up of 68 152 weeks, 42 discontinuations were registered (5.9%). DTG + DOR had a risk of treatment interruption of 7.8% at 48 weeks and 9.8% at 96 weeks, significantly higher than the other 2DRs. In the multivariate Cox model, DTG + DOR and DTG/RPV were significantly associated with discontinuation. The maintenance of target not detected during follow-up was similar among groups. The rate of virological failure was higher for DTG + DOR through different event definitions. CONCLUSIONS: DTG + DOR durability was high over a long follow-up albeit lower than for other 2DRs. This combination might be an effective option in people with HIV that has proven difficult to treat.

Impact of treatment with direct-acting antivirals on inflammatory markers and autoantibodies in HIV/HCV co-infected individuals.

HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCV/HIV co-infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co-infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIV/HCV co-infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti-thyroglobulin Ab, anti-thyroid peroxidase Ab, ANCA, ASMA, anti-LKM, anti-DNA, AMA, ANA, T CD4+ and CD8+ cell count, and CD4/CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals: 51.9% with a F0-F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4; ferritin, anti-thyroglobulin Ab, and C4 fraction at EOT; total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p < .001). T CD4+ cell slightly increased at SVR12, but with an increase also in CD8+ resulting in stable CD4/CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p = .099): they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4/CD8 ratio over a follow up of 12 weeks.

Similar survival but higher and delayed hepatocellular carcinoma recurrence in HIV-positive compared to negative cirrhotics undergoing liver transplantation.

BACKGROUND: Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. AIMS: To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. METHODS: Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. RESULTS: Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p = 0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p = 0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p = 0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p < 0.001). CONCLUSIONS: Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population.

Contribution of integrase inhibitor use, body mass index, physical activity and caloric intake to weight gain in people living with HIV.

Background: Integrase inhibitor (INSTI) use has been associated with greater weight gain (WG) among people living with HIV (PLWH), but it is unclear how this effect compares in magnitude to traditional risk factors for WG. We assessed the population attributable fractions (PAFs) of modifiable lifestyle factors and INSTI regimens in PLWH who experienced a ≥5% WG over follow-up.Methods: In an observational cohort study from 2007 to 2019 at Modena HIV Metabolic Clinic, Italy, ART-experienced but INSTI-naive PLWH were grouped as INSTI-switchers vs non-INSTI. Groups were matched for sex, age, baseline BMI and follow-up duration. Significant WG was defined as an increase of ≥5% from 1st visit weight over follow-up. PAFs and 95% CIs were estimated to quantify the proportion of the outcome that could be avoided if the risk factors were not present.Results: 118 PLWH switched to INSTI and 163 remained on current ART. Of 281 PLWH (74.3% males), mean follow-up was 4.2 years, age 50.3 years, median time since HIV diagnosis 17.8 years, CD4 cell count 630 cells/µL at baseline. PAF for weight gain was the greatest for high BMI (45%, 95% CI: 27-59, p < 0.001), followed by high CD4/CD8 ratio (41%, 21-57, p < 0.001) and lower physical activity (32%, 95% CI 5-52, p = 0.03). PAF was not significant for daily caloric intake (-1%, -9-13, p = 0.45), smoking cessation during follow-up (5%, 0-12, p = 0.10), INSTI switch (11%, -19-36; p = 0.34).Conclusions: WG in PLWH on ART is mostly influenced by pre-existing weight and low physical activity, rather than switch to INSTI.

The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study.

BACKGROUND: The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. METHODS: In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. RESULTS: Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2-5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1-0.7) or in OT (HR = 0.1, 95% CI = 0.0-0.8) treated with tocilizumab. CONCLUSION: To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.

Adherence to Lipid-Lowering Medication in People Living with HIV: An Outpatient Clinic Drug Direct Distribution Experience.

OBJECTIVE: Adherence to lipid-lowering drugs could be challenging in our patients as it is in the general population, which is described as low as 25%. Our aim was to evaluate adherence to statins and to investigate clinical event impact on it. METHODS: This retrospective study on HIV+ patients attending to Clinic of Modena (Italy) was conducted in order to evaluate characteristics, clinical events, and adherence on lipid-lowering drugs. All drugs for comorbidities are distributed by the hospital pharmacy and recorded in an electronical database. Adherence was also evaluated in patients who were supplied with antilipemics in external pharmacies through phone calls. Patients were considered adherent if the percentage of correct time of drug refill was >80%. FINDINGS: Totally 1123 patients were evaluated. Lipid-lowering drugs (statins, fenofibrate, and omega-3 oil) were prescribed in 242 patients (21.5%). Prescription occurred mainly in those who were older, males, and Italians. Two hundred of them (82.6%) used statins alone, 23 (9.5%) only fenofibrate or omega-3 oil, and 19 (7.8%) a combination of both drugs. The median adherence was 90% while patients with adherence >80% resulted 153 (63.2%). Forty-six (19%) had a clinical history of cardiovascular events; 59% of them, placed in secondary prophylaxis, and 76%, already in treatment, continued to adhere. No differences in terms of adherence according to the type of drug distribution (hospital pharmacy or outside pharmacies) were found. CONCLUSION: Linking the supply of these drugs to that of antiretrovirals led to a good level of adherence higher than that described in the general population. The majority of the patients who experienced a cardiovascular event remain adherent to the prescribed therapy.

Neurological manifestations in patients hospitalized with COVID-19: A retrospective analysis from a large cohort in Northern Italy.

SARS-CoV2 infection is a systemic disease that may involve multiple organs, including the central nervous system (CNS). Aims of our study are to describe prevalence and clinical features of neurological manifestations, mortality and hospital discharge in subjects hospitalized with COVID-19. All individuals admitted for to our hospital COVID-19 were retrospectively included. Patients were classified according to the symptoms at hospital entry in (1) isolated respiratory, (2) combined respiratory and neurologic, (3) isolated neurologic and (4) stroke manifestations. Descriptive statistics and nonparametric tests to compare the groups were calculated. Kaplan Meier probability curves and multivariable Cox regression models for survival and hospital discharge were applied. The analysis included 901 patients: 42.6% showed a severe or critical disease with an overall mortality of 21.2%. At least one neurological symptom or disease was observed in 30.2% of subjects ranging from dysgeusia/anosmia (9.1%) to postinfective diseases (0.8%). Patients with respiratory symptoms experienced a more severe disease and a higher in-hospital mortality compared to those who showed only neurologic symptoms. Kaplan Meier estimates displayed a statistically significant different survival among groups (p = 0.003): subjects with stroke had the worst. After adjusting for risk factors such as age, sex and comorbidity, individuals with isolated neurologic manifestations exhibited a better survival (aHR 0.398, 95% CI [0.206, 0.769], p = 0.006). Neurologic manifestations in COVID-19 are common but heterogeneous and mortality in subjects with isolated neurologic manifestations seems lower than in those with respiratory symptoms.

Hypokalemia in Patients with COVID-19.

BACKGROUND: Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19. METHODS: A retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020. RESULTS: Hypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3-3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassium-to-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%). Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36-4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08-3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228-1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170-1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222-1.047; P = 0.065) in our cohort of patients. CONCLUSIONS: Hypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.

The Burden of Clostridioides Difficile Infection during the COVID-19 Pandemic: A Retrospective Case-Control Study in Italian Hospitals (CloVid).

Data on the burden of Clostridioides difficile infection (CDI) in Coronavirus Disease 2019 (COVID-19) patients are scant. We conducted an observational, retrospective, multicenter, 1:3 case (COVID-19 patients with CDI)-control (COVID-19 patients without CDI) study in Italy to assess incidence and outcomes, and to identify risk factors for CDI in COVID-19 patients. From February through July 2020, 8402 COVID-19 patients were admitted to eight Italian hospitals; 38 CDI cases were identified, including 32 hospital-onset-CDI (HO-CDI) and 6 community-onset, healthcare-associated-CDI (CO-HCA-CDI). HO-CDI incidence was 4.4 × 10,000 patient-days. The percentage of cases recovering without complications at discharge (i.e., pressure ulcers, chronic heart decompensation) was lower than among controls (p = 0.01); in-hospital stays was longer among cases, 35.0 versus 19.4 days (p = 0.0007). The presence of a previous hospitalisation (p = 0.001), previous steroid administration (p = 0.008) and the administration of antibiotics during the stay (p = 0.004) were risk factors associated with CDI. In conclusions, CDI complicates COVID-19, mainly in patients with co-morbidities and previous healthcare exposures. Its association with antibiotic usage and hospital acquired bacterial infections should lead to strengthen antimicrobial stewardship programmes and infection prevention and control activities.

Effectiveness of infection-containment measures on SARS-CoV-2 seroprevalence and circulation from May to July 2020, in Milan, Italy.

OBJECTIVE: Through a hospital-based SARS-CoV-2 molecular and serological screening, we evaluated the effectiveness of two months of lockdown and two of surveillance, in Milan, Lombardy, the first to be overwhelmed by COVID-19 pandemics during March-April 2020. METHODS: All subjects presenting at the major hospital of Milan from May-11 to July-5, 2020, underwent a serological screening by chemiluminescent assays. Those admitted were further tested by RT-PCR. RESULTS: The cumulative anti-N IgG seroprevalence in the 2753 subjects analyzed was of 5.1% (95%CI = 4.3%-6.0%), with a peak of 8.4% (6.1%-11.4%) 60-63 days since the peak of diagnoses (March-20). 31/106 (29.2%) anti-N reactive subjects had anti-S1/S2 titers >80 AU/mL. Being tested from May-18 to June-5, or residing in the provinces with higher SARS-CoV-2 circulation, were positively and independently associated with anti-N IgG reactivity (OR [95%CI]: 2.179[1.455-3.264] and 3.127[1.18-8.29], respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%). CONCLUSION: SARS-CoV-2 seroprevalence in Milan is low, and in a downward trend after only 60-63 days since the peak of diagnoses. Italian confinement measures were effective, but the risk of contagion remains concrete. In hospital-settings, the performance of molecular and serological screenings upon admission remains highly advisable.

Machine learning in predicting respiratory failure in patients with COVID-19 pneumonia-Challenges, strengths, and opportunities in a global health emergency.

AIMS: The aim of this study was to estimate a 48 hour prediction of moderate to severe respiratory failure, requiring mechanical ventilation, in hospitalized patients with COVID-19 pneumonia. METHODS: This was an observational prospective study that comprised consecutive patients with COVID-19 pneumonia admitted to hospital from 21 February to 6 April 2020. The patients' medical history, demographic, epidemiologic and clinical data were collected in an electronic patient chart. The dataset was used to train predictive models using an established machine learning framework leveraging a hybrid approach where clinical expertise is applied alongside a data-driven analysis. The study outcome was the onset of moderate to severe respiratory failure defined as PaO2/FiO2 ratio <150 mmHg in at least one of two consecutive arterial blood gas analyses in the following 48 hours. Shapley Additive exPlanations values were used to quantify the positive or negative impact of each variable included in each model on the predicted outcome. RESULTS: A total of 198 patients contributed to generate 1068 usable observations which allowed to build 3 predictive models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth "boosted mixed model" included 20 variables was selected from the model 3, achieved the best predictive performance (AUC = 0.84) without worsening the FN rate. Its clinical performance was applied in a narrative case report as an example. CONCLUSION: This study developed a machine model with 84% prediction accuracy, which is able to assist clinicians in decision making process and contribute to develop new analytics to improve care at high technology readiness levels.

Liver steatosis and nonalcoholic fatty liver disease with fibrosis are predictors of frailty in people living with HIV.

OBJECTIVE: The aim was to investigate the contribution of liver steatosis and significant fibrosis alone and in association [nonalcoholic fatty liver disease (NAFLD) with fibrosis] to frailty as a measure of biological age in people living with HIV (PLWH). DESIGN: This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018-2019. METHODS: Patients with hazardous alcohol intake and viral hepatitis coinfection were excluded. Liver steatosis was diagnosed by controlled attenuation parameter (CAP), while liver fibrosis was diagnosed by liver stiffness measurement (LSM). NAFLD was defined as presence of liver steatosis (CAP ≥248 dB/m), while significant liver fibrosis or cirrhosis (stage ≥F2) as LSM at least 7.1 kPa. Frailty was assessed using a 36-Item frailty index. Logistic regression was used to explore predictors of frailty using steatosis and fibrosis as covariates. RESULTS: We analysed 707 PLWH (mean age 53.5 years, 76.2% men, median CD4 cell count 700 cells/µl, 98.7% with undetectable HIV RNA). NAFLD with fibrosis was present in 10.2%; 18.9 and 3.9% of patients were classified as frail and most-frail, respectively. Univariate analysis demonstrated that neurocognitive impairment [odds ratio (OR) = 5.1, 1.6-15], vitamin D insufficiency (OR = 1.94, 1.2-3.2), obesity (OR = 8.1, 4.4-14.6), diabetes (OR = 3.2, 1.9-5.6), metabolic syndrome (OR = 2.41, 1.47-3.95) and osteoporosis (OR = 0.37, 0.16-0.76) were significantly associated with NAFLD with fibrosis. Predictors of frailty index included steatosis (OR = 2.1, 1.3-3.5), fibrosis (OR = 2, 1-3.7), NAFLD with fibrosis (OR = 9.2, 5.2-16.8), diabetes (OR = 1.7, 1-2.7) and multimorbidity (OR = 2.5, 1.5-4). CONCLUSION: Liver steatosis and NAFLD with fibrosis were associated with frailty. NAFLD with fibrosis exceeded multimorbidity in the prediction of frailty, suggesting the former as an indicator of metabolic age in PLWH.

Acute myocarditis as the main clinical manifestation of SARS-CoV 2 infection.

We describe a case of acute myocarditis, which was reported as the main COVID-19 clinical manifestation, with a favorabile outcome. In addition to symptoms, laboratory tests (BNP and troponin), echocardiogram and cardiac MRI contributed to diagnosis. Regardless heart biopsy was not obtained, it is likely an immunological pathogenesis of this condition which pave the way to further therapeutic implications, since there are currently no standardized treatments.

Sex Differences in People Aging With HIV.

BACKGROUND: To evaluate differences between older women and men with HIV regarding HIV variables, comorbidity, physical function, and quality of life (QOL). SETTING: The Modena HIV clinic. METHODS: Prospective cohort study. Cross-sectional analysis. Patients >50 years were included, stratified by sex. We recorded sociodemographic data, comorbidities, variables related to HIV infection, frailty, data on body composition, physical function, physical activity, and QOL. RESULTS: We evaluated 1126 older adults with HIV, of which 284 (25.2%) were women. Median age was 55 (IQR 6) years. There were significant differences between women and men in the median current CD4 T-cell and the mean CD4/CD8 ratio. There were differences regarding alcohol consumption, cardiovascular (CV) disease, hypertension, diabetes mellitus, and renal failure. Sarcopenia and slower gait speed were found more prevalent among men, but without significant differences. Significant differences were found regarding lower extremity strength measured by the chair stand test and in the short physical performance battery score. Short physical performance battery <9 was detected for 11.1% women vs. 5.6% men (P = 0.002). EQ5D5L score was 0.87 in women vs. 0.89 in men (P = 0.002). CONCLUSIONS: In our cohort, older women represented one in 4 of the total patients. Despite the fact that women have better immunological recovery measured by CD4 T-cell count and CD4/CD8 ratio, and fewer CV disease and CV risk factors than men, their physical function and their QOL are worse. Therefore, older HIV-infected women have special characteristics, and the assessment of physical function in this group seems to be crucial.

Thymus Imaging Detection and Size Is Inversely Associated With Metabolic Syndrome and Frailty in People With HIV.

BACKGROUND: People with HIV (PWH) may experience accentuating aging in relation to immuno-activation. Little is known regarding thymus (THY) involution in this process. We sought to investigate the relationship between THY imaging detection/size and clinically relevant aging outcomes such as metabolic syndrome (MetS), multimorbidity (MM), and frailty in PWH. METHODS: This was a cross-sectional observational study including 665 HIV patients (81% males; median age, 53 years) attending Modena HIV Metabolic Clinic from 2014 to 2017. They underwent thoracic computed tomography scan as part of the medical assessment for cardiovascular disease, in which THY detection and size were reported using a semiquantitative score. Outcome measures were MetS, MM, and frailty. RESULTS: THY was detected in 27.0% of subjects; 71.1% showed THY size of grade 1-2, and 28.9% exhibited grade ≥3. Covariates that inversely correlated with THY detection were age, male gender, body mass index (BMI), and HIV duration. Covariates that inversely correlated with MetS were age, HIV duration, BMI, and THY grade 1-2. Covariates that inversely correlated with MM were age, HIV duration, and CD4 nadir. Covariates that inversely correlated with frailty were age, HIV duration, CD4 nadir, BMI, and THY detection. CONCLUSIONS: THY is inversely associated with MetS and frailty in PWH.

Genotype-based differentiation of the Cryptococcus neoformans serotypes by combined PCR-RFLP analysis of the capsule-associated genes CAP10 and CAP59.

This report describes an indirect identification method for Cryptococcus neoformans serotypes developed using combined restriction enzyme pattern analysis of two PCR-amplified portions of the capsule-associated genes CAP10 and CAP59. The method relies on the recognition of the sequence conformation of nine serotype-related polymorphic sites by the analysis of four restriction profiles. A 610 nucleotides long trait of the CAP10 gene was digested with the enzymes Sty I or Sal I and a 597 nucleotides long trait of the CAP59 gene was digested with the enzymes Sal I or EcoRV+PstI. The resulting profiles, reported as a string of four numbers, defined for each strain an intrinsically coherent allelic profile closely correlated to the serotype. We analyzed by this method 172 C. neoformans strains obtained from different sources. All the serotype A strains examined and all the strains of the B-C serotypes group were recognized by specific allelic profiles, but serotypes B and C could not be distinguished from each other. Of the serotype D strains, 84% were characterized by a unique allelic pattern, while the remaining 16% were genotypically indistinguishable from the AD serotype organisms among which differences in the ploidy number and evidence of recombination could be recognized.

4-Alkyl- and 4-phenylcoumarins from Mesua ferrea as promising multidrug resistant antibacterials.

Supercritical CO2 selectively extracted a series of 4-alkyl and 4-phenyl 5,7-dihydroxycoumarins from Mesua ferrea blossoms. Chemical modifications of the isolated compounds allowed us to confirm the structures elucidated by spectroscopic means and to prepare new derivatives amenable to SAR studies and potential pharmaceutical development. Biological investigations towards the screening on a number of bacteria strains and Plasmodium falciparum, identified compounds 1-9 as weak antiprotozoal agents and potent antibacterials on resistant Gram-positive strains.