Molnupiravir compared to nirmatrelvir/ritonavir for COVID-19 in high-risk patients with haematological malignancy in Europe. A matched-paired analysis from the EPICOVIDEHA registry.

INTRODUCTION: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. METHODS: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. RESULTS: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. CONCLUSIONS: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.

Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey.

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.

Efficacy and Safety of Direct-Acting Antivirals in Elderly Patients with Chronic Hepatitis C: A Nationwide Real-Life, Observational, Multicenter Study from Turkey.

BACKGROUND: The number and proportion of elderly patients living with chronic hepatitis C are expected to increase in the coming years. We aimed to compare the real-world efficacy and safety of direct-acting antiviral treatment in elderly and younger Turkish adults infected with chronic hepatitis C. METHODS: In this multicenter prospective study, 2629 eligible chronic hepatitis C patients treated with direct-acting antivirals between April 2017 and December 2019 from 37 Turkish referral centers were divided into 2 age groups: elderly (≥65 years) and younger adults (<65 years) and their safety was compared between 2 groups in evaluable population. Then, by matching the 2 age groups for demographics and pretreatment risk factors for a non-sustained virological response, a total of 1516 patients (758 in each group) and 1244 patients (622 in each group) from the modified evaluable population and per-protocol population were included in the efficacy analysis and the efficacy was compared between age groups. RESULTS: The sustained virological response in the chronic hepatitis C patients was not affected by the age and the presence of cirrhosis both in the modified evaluable population and per-protocol population (P = .879, P = .508 for modified evaluable population and P = .058, P = .788 for per-protocol population, respectively). The results of the per-protocol analysis revealed that male gender, patients who had a prior history of hepatocellular carcinoma, patients infected with non-genotype 1 hepatitis C virus, and patients treated with sofosbuvir+ribavirin had a significantly lower sustained virological response 12 rates (P < .001, P = .047, P = .013, and P = .025, respectively). CONCLUSION: Direct-acting antivirals can be safely used to treat Turkish elderly chronic hepatitis C patients with similar favorable efficacy and safety as that in younger adults.

Current status of HIV/AIDS-syphilis co-infections: a retrospective multicentre study.

OBJECTIVE: Treponema pallidum and HIV are transmitted frequently through sexual contact, these agents with epidemiological similarities co-infect the same host. The current number of HIV-infected cases in Turkey is increasing. For this reason, we aimed to reveal the characteristics of syphilis in HIV/AIDS cases. METHODS: A retrospective longitudinal cohort study was performed, patients were followed up at 24 clinics in 16 cities from all seven regions of Turkey between January 2010 to April 2018. We examined the socio-demographic characteristics, laboratory parameters and neurosyphilis association in HIV/AIDS-syphilis co-infected cases. RESULTS: Among 3,641 patients with HIV-1 infection, 291 (8%) patients were diagnosed with syphilis co-infection. Most patients were older than 25 years (92%), 96% were males, 74% were working, 23% unemployed, and 3% were students. The three highest prevalence of syphilis were in Black Sea (10.3%), Mediterranean (8.4%) and Marmara Regions (7.4%). As for sexual orientation, 46% were heterosexuals, 42% men who have sex with men (MSM), and no data available for 12%. Patients with the number of CD4+ ≤ 350 mm3 reached 46%, 17% of the patients received antiretroviral therapy and neurosyphilis association reached 9%. CONCLUSION: Although HIV/AIDS-syphilis co-infection status appeared high in heterosexuals, MSM had a moderate level increase in cases. Our results suggested syphilis co-infection in HIV/AIDS cases should be integral part of monitoring in a national sexual transmitted diseases surveillance system. However, our data may provide base for HIV/syphilis prevention and treatment efforts in the future.

Several Cytokines and Protein C Levels with the Apache II Scoring System for Evaluation of Patients with Sepsis.

OBJECTIVE: We investigated whether determination IL-6, IL-8, IL-1beta and TNF-alpha at baseline, total protein C (PC) levels at time of admission and 48 hours after initiation could complement the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system to identify patients with sepsis, severe sepsis or septic shock for clinical outcome. MATERIAL AND METHODS: The study was carried out prospectively. 60 consecutive patients with sepsis, severe sepsis or septic shock were included. Blood samples were obtained at baseline and 48 hours after initiation. Cytokines and PC levels in plasma were measured with an enzyme-linked immunoabsorbent assay (ELISA). APACHE II score was calculated on admission. RESULTS: Baseline IL-6 levels and PC levels 48 hours after initiation were predictive of increased mortality (p=0.016, p=0.044 respectively). Baseline IL-6, IL-8 and TNF-alpha baseline levels correlate with the severity of physiologic insult, as determined by the APACHE II score. However, our multiple logistic regression analysis of these did not reveal any predictive value in combination with the APACHE II score. CONCLUSION: Determination of baseline IL-6 and PC 48 hours after initiation were of predictive value for prognostic evaluation of septic patients, but did not significantly increase predictive power of the APACHE scoring system to identify patients with sepsis for fatal clinical outcome.

[Analysis of the risk factors in nosocomial urinary tract infections and effect of urinary catheter use on distribution of the causative agents]. / Nozokomiyal üriner sistem enfeksiyonlarinda risk faktörlerinin analizi ve üriner kateter kullaniminin etkenlerin dagilimi üzerine etkisi.

Nosocomial urinary tract infections (NUTI) which are usually in the first rank in health care associated infections, significantly influence mortality, morbidity, hospitalization period and cost. In this retrospective study, it was aimed to analyze the risk factors in NUTI and also to investigate the effect of urinary catheter application on the distribution of pathogens in patients with NUTI. The study included 1236 NUTI episodes in 1103 patients (age range: 18-95 years; 641 female, 462 male) between January 2000-December 2006. Diagnosis of NUTI was agreed according to CDC criteria. Asymptomatic UTI (urinary tract infection) and other UTIs were excluded and only symptomatic UTI was evaluated. Of NUTIs, 87.9% (1086/1236) were found to be associated with urinary catheter use. No statistically significant difference by means of age, gender and mean interval between admission date and date of determination of infection was determined between the two patient groups, with and without urinary catheter (p>0.05). However, catheter associated NUTI development was statistically significantly higher in intensive care unit patients than patients in other wards (p<0.001). Respiratory failure, unconsciousness, multiple trauma, surgery, central vascular catheter, tracheostomy, mechanical ventilation and peritoneal dialysis were observed more frequently in patients who developed catheter-associated NUTIs (p<0.001). Escherichia coil was isolated in 23.6%, Candida albicans in 18% and non-albicans Candida spp. in 11% of the NUTI episodes. When all Candida species were taken into consideration, they were the most frequent causative agents of NUTI. C. albicans was the most frequent agent in catheter-associated NUTI and E. coli in non-catheter-associated NUTI, their isolation rates being statistically significant (p=0.007 and p=0.005, respectively). No statistically significant difference was detected in the distribution of the other organisms in the two study groups. These data revealed that in urinary tract infections Candida species have replaced the first rank which was occupied by E. coli previously.

The prevalence of extended-spectrum beta lactamase-producing Escherichia coli and Klebsiella pneumoniae in clinical isolates and risk factors.

OBJECTIVE: To determine the prevalence of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), risk factors of ESBL-producing strains and antimicrobial susceptibility pattern of ESBL-producing and non producing strains. METHODS: The study took place at the Faculty of Medicine, Osmangazi University, Eskisehir, Turkey from March to November 2002. We evaluated 100 K. pneumoniae and 100 E. coli strains isolated from various clinical specimens, as well as the patients from whom these strains were isolated. The double-disk synergy test was performed on the isolates for the detection of ESBL. We visited the patients with a growth of E. coli or K. pneumoniae or both from their clinical specimens in their wards if they were hospitalized, while the outpatients with a growth of these microorganisms were evaluated from their hospital records. RESULTS: The prevalence of ESBL-producing K. pneumoniae was 47% and E. coli was found as 12%. The ESBL-producing isolate rates were 50% (14/28) in intensive care units, 36.1% (35/97) in wards and 13.3% (10/75) in outpatients. Foley catheter (p<0.001), intravenous catheter (p<0.001), central venous catheter (p=0.002), intubation (p<0.001), surgery (p<0.001) and mechanical ventilation (p=0.002) were found as the risk factors for the acquisition of E. coli and K. pneumoniae with ESBLs. CONCLUSION: In our study, the prevalence of ESBL-producing isolates was high. The results of the study suggest that an antimicrobial policy and early removal of interventional apparatus be of importance for the control of ESBL-producing K. pneumoniae and E. coli.