Treatment initiation rates of patients with positive anti-hepatitis C virus results in tertiary hospitals in Turkey.

INTRODUCTION: The aim of this national, multicenter, cross-sectional, retrospective chart review study was to determine the proportion of patients in Turkey who received hepatitis C virus (HCV) treatment after receiving positive anti-HCV results during HCV screening. METHODOLOGY: Data related to patients' demographics, laboratory results, time interval from obtaining a positive anti-HCV result to treatment initiation, specialty of the physician requesting anti-HCV screening, and type of hospital were analyzed. RESULTS: Among 1,000 patients who received a positive anti-HCV result, 50.3% were male and 78.5% were screened for HCV-RNA. Among HCV-RNA screened patients, 54.8% (n = 430) had a positive result. Among patients who tested positive for HCV-RNA, 72.8% received HCV treatment in line with their positive anti-HCV results. The median time from obtaining a positive anti-HCV result to initiation of HCV treatment was 91.0 days (interquartile range 42.0 to 178.5). Non-surgical branches requested HCV-RNA testing more frequently than surgical branches (p < 0.001). The rate of access to HCV treatment was higher among patients screened in university hospitals than among patients screened in training and research hospitals (p < 0.001). CONCLUSIONS: Our results indicate a higher rate of treatment initiation among patients with HCV infection than is described in the published literature. Furthermore, the time from screening to treatment initiation was considerably shorter compared with other international studies. However, since HCV-RNA testing was not requested in a significant portion of patients with a positive anti-HCV test result, there might be a large patient population with HCV who do not receive treatment.

Recovery from Respiratory Failure in Patients with Coronavirus Disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can cause hypoxic respiratory failure; long-term oxygen therapy (LTOT) duration is unknown. MATERIAL AND METHODS: The aim was to investigate which patients would need LTOT after COVID-19 pneumonia. This single-center, prospective study was conducted at the Ankara University Faculty of Medicine, Department of Chest Diseases, between May 2021 and December 2021. The 70 patients hospitalized for COVID-19 pneumonia and discharged with LTOT due to hypoxemic respiratory failure were included. Patients were divided into 2 groups as group I (LTOT requirement <3 months) and group II (LTOT requirement continued ≥3 months). RESULTS: The mean age was 64.4 ± 13.5 years, and 44 (62.9%) of them were male. The most frequently encountered comorbidities were cardiovascular disease (57.1%) and lung disease (22.9%). While PaO2 levels increased in both groups during the follow-up period, this increment was significantly higher in group I (PaO2: 66.6 ± 9.9 mm Hg, P < .001). The factors affecting the LTOT requirement were evaluated using binary logistic regression. On multivariate analyses of lymphocytes, ferritin, C-reactive protein, PaO2, SaO2, subpleural reticulation, and number of lobes affected (≥3 lobes), the SaO2 level and presence of subpleural reticulation were significantly different between the 2 groups [odds ratio (OR) (95% CI): 0.853 (0.749-0.971), P = .016] and [OR (95% CI): 0.171 (0.042-0.733), P = .017], respectively. CONCLUSION: A significant proportion of patients who develop respiratory failure due to COVID-19 recover within the first 3 months. Factors determining the LTOT requirement for more than 3 months were SaO2 and the presence of subpleural reticulation.

The Present and Future Aspects of Life-Long Pertussis Prevention: Narrative Review with Regional Perspectives for Türkiye.

Pertussis, caused by Bordetella pertussis, remains one of the most widespread, contagious, and vaccine-preventable diseases. It results in notable morbidity and mortality as well as severe medical, social, and economic burden. Despite high global vaccine coverage, pertussis continues to be a significant epidemiologic problem, with outbreak episodes every few years just as in the pre-vaccination era. In Türkiye, there is a lack of comprehensive data on the current burden of pertussis in different age and risk groups, leading to underdiagnosis and underreporting of the disease, especially in adults who are often not considered at risk. Available data from Türkiye also reveal inadequate levels of protective antibodies in preterm newborns, emphasizing the need for additional preventive measures. Authors stated that improving physician awareness of pertussis symptoms in patients with prolonged cough, increasing access to routine pertussis tests, and conducting surveillance studies would aid in accurate diagnosis and reporting in Türkiye. As the Turkish Ministry of Health Antenatal Care Management Guide suggests routine second and third pregnancy check-up visits at weeks 18-24 and 28-32 correspondingly, this period can be considered the ideal vaccination time for Türkiye. Introducing a booster dose of Tdap at around 10 years of age or during national military service would reduce transmission and protect susceptible individuals. Identifying individuals at high risk of severe pertussis and prioritizing them for a booster dose is also crucial in Türkiye. Enhancing surveillance systems, increasing healthcare professionals' awareness through training, and organizing catch-up visits for missed vaccinations during the COVID-19 pandemic are mentioned as additional strategies to improve pertussis prevention in Türkiye. This review focuses on the global and regional burden of pertussis and obstacles to effective prevention and evaluates existing strategies to achieve lifelong pertussis prevention. Literature and current strategies were also discussed from a Turkish national standpoint.

Herpes Zoster Burden of Disease and Clinical Management in Turkey: A Comprehensive Literature Review.

INTRODUCTION: Herpes zoster (HZ), or shingles, is caused by the reactivation of varicella zoster virus (VZV) and typically presents as an acute, painful dermatomal rash, but can lead to long-term, distressing complications such as postherpetic neuralgia (PHN). Increasing trends in HZ cases are evident globally among the aging population; however, reviews investigating the epidemiology and clinical management of HZ in Turkey are lacking. Therefore, a literature review of local studies in Turkey was conducted to identify the data available and identify gaps in the literature. METHODS: Literature searches were carried out in PubMed and local journals to retrieve published articles that reported surveillance data, seroepidemiology, patient outcomes, or clinical management related to HZ or VZV in Turkey until April 30, 2022. Studies included primary data reports, case studies, secondary data reviews, and epidemiological studies in healthy or at-risk populations; HZ was the primary focus of the review. RESULTS: No studies reported VZV or HZ epidemiological data at a national level. One large retrospective study in Istanbul reported that HZ incidence rates significantly increased in adults 18-44 years of age between 2011 and 2019. Four single-center studies reported the proportion of dermatological patients with HZ at 0.43-1.56%. PHN was the most common reported complication, occurring in 8-58.9% of patients with HZ. However, out of 39 identified case reports, HZ ophthalmicus was the most frequently reported complication. Two studies highlighted poor disease awareness and risk perception of HZ among Turkish citizens. CONCLUSION: Overall, there were limited comprehensive epidemiological data on HZ in Turkey. However, the abundance of case studies on HZ complications indicates a strong disease presence and diverse clinical management in Turkey. Further research will be important to understand the impact of HZ, increase disease awareness, and support the introduction of new preventative strategies.

Higher rates of cefiderocol resistance among NDM producing Klebsiella bloodstream isolates applying EUCAST over CLSI breakpoints.

BACKGROUND: Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria. METHODS: A unique collection (n = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes. RESULTS: Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24-26 mm) for all isolates and 18 mm (IQR 15-21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively. CONCLUSIONS: Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing.

BNT162b2 or CoronaVac as the Third Dose against Omicron: Neutralizing Antibody Responses among Transplant Recipients Who Had Received Two Doses of CoronaVac.

We evaluated neutralizing antibodies against the Omicron variant and Anti-Spike IgG response in solid organ (SOT) or hematopoietic stem cell (HSTC) recipients after a third dose of BNT162b2 (BNT) or CoronaVac (CV) following two doses of CV. In total, 95 participants underwent SOT (n = 62; 44 liver, 18 kidney) or HSCT (n = 27; 5 allogeneic, 22 autologous) were included from five centers in Turkey. The median time between third doses and serum sampling was 154 days (range between 15 to 381). The vaccine-induced antibody responses of both neutralizing antibodies and Anti-Spike IgGs were assessed by plaque neutralizing assay and immunoassay, respectively. Neutralizing antibody and Anti-Spike IgG levels were significantly higher in transplant patients receiving BNT compared to those receiving CV (Geometric mean (GMT):26.76 vs. 10.89; p = 0.03 and 2116 Au/mL vs. 172.1 Au/mL; p < 0.001). Solid organ transplantation recipients, particularly liver transplant recipients, showed lower antibody levels than HSCT recipients. Thus, among HSCT recipients, the GMT after BNT was 91.29 and it was 15.81 in the SOT group (p < 0.001). In SOT, antibody levels after BNT in kidney transplantation recipients were significantly higher than those in liver transplantation recipients (GMT: 48.32 vs. 11.72) (p < 0.001). Moreover, the neutralizing antibody levels after CV were very low (GMT: 10.81) in kidney transplantation recipients and below the detection limit (<10) in liver transplant recipients. This study highlights the superiority of BNT responses against Omicron as a third dose among transplant recipients after two doses of CV. The lack of neutralizing antibodies against Omicron after CV in liver transplant recipients should be taken into consideration, particularly in countries where inactivated vaccines are available in addition to mRNA vaccines.

The challenges in the monitoring of infectious diseases after the earthquake in Türkiye in 2023.

After the devastating earthquake in Türkiye and Syria in February, 2023, the long-term failure to meet the need for shelter, unfavourable living conditions in tent settlements, poor access to clean drinking water, water suitable for personal hygiene, and sanitary facilities, as well as interruptions in provision of primary health-care services, have emerged as the most important risk factors contributing to the spread of infectious diseases. 3 months after the earthquake, most of these problems persist in Türkiye. Data on the control of infectious diseases are scarce according to the reports prepared by medical specialist associations based on observations of health-care providers working in the region and statements made by the local health authorities. According to these unsystematised data, and considering the conditions in the region, faecal-oral transmissible gastrointestinal infections, as well as respiratory and vector-borne infections, are the main challenges. Vaccine-preventable diseases, such as measles, varicella, meningitis, and polio can be spread in temporary shelters due to interrupted vaccine services and crowded living conditions. In addition to controlling risk factors for infectious diseases, sharing data on the status and control of infectious diseases in the region with the community, health-care providers, and relevant expert groups should be a priority to improve the understanding of the effects of interventions and prepare for possible infectious disease outbreaks.

Clinical evaluation of DIAGNOVIR SARS-CoV-2 ultra-rapid antigen test performance compared to PCR-based testing.

Coronavirus Disease-19 (COVID-19) is a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The development of rapid antigen tests has contributed to easing the burden on healthcare and lifting restrictions by detecting infected individuals to help prevent further transmission of the virus. We developed a state-of-art rapid antigen testing system, named DIAGNOVIR, based on immune-fluorescence analysis, which can process and give the results in a minute. In our study, we assessed the performance of the DIAGNOVIR and compared the results with those of the qRT-PCR test. Our results demonstrated that the sensitivity and specificity of the DIAGNOVIR were 94% and 99.2%, respectively, with a 100% sensitivity and 96.97% specificity, among asymptomatic patients. In addition, DIAGNOVIR can detect SARS­CoV­2 with 100% sensitivity up to 5 days after symptom onset. We observed that the DIAGNOVIR Rapid Antigen Test's limit of detection (LoD) was not significantly affected by the SARS­CoV­2 variants including Wuhan, alpha (B1.1.7), beta (B.1.351), delta (B.1.617.2) and omicron (B.1.1.529) variants, and LoD was calculated as 8 × 102, 6.81 × 101.5, 3.2 × 101.5, 1 × 103, and 1 × 103.5 TCID50/mL, respectively. Our results indicated that DIAGNOVIR can detect all SARS-CoV-2 variants in just seconds with higher sensitivity and specificity lower testing costs and decreased turnover time.

The Impact of Vaccination Among Hospitalized Patients with the Diagnosis of COVID-19.

Objective: We aimed to investigate the vaccination status and the risk factors for the intensive care unit (ICU) support need of the laboratory-confirmed breakthrough COVID-19 infection inpatients. Materials and Methods: This multi-center point-prevalence study was conducted on inpatients, divided into two groups as 'fully' and 'partially' vaccinated according to COVID-19 vaccination status. Results: Totally 516 patients were included in the study. The median age was 65 (55-77), and 53.5% (n=276) of the patients were male. Hypertension (41.9%, n=216), diabetes mellitus (DM) (31.8%, n=164), and coronary artery disease (CAD) (16.3%, n=84) were the predominant comorbidities. Patients were divided into two groups ICU (n=196) and non-ICU (n=301). Hypertension (p=0.026), DM (p=0.048), and congestive heart failure (CHF) (p=0.005) were significantly higher in ICU patients and the median age was younger among non-ICU patients (p=0.033). Of patients, 16.9% (n=87) were fully vaccinated, and this group's need for ICU support was statistically significantly lower (p=0.021). Conclusion: We conclude that older age, hypertension, DM, CHF, and being partially vaccinated were associated with the need for ICU support. Therefore, all countries should continuously monitor post-vaccination breakthrough COVID-19 infections to determine the national booster vaccine administration approach that will provide vulnerable individuals the highest protection.

Dark Side of the COVID-19 Pandemic; 'Long COVID'.

Objective: Besides its morbidity and mortality all over the world, SARS-CoV-2 infection maintains its importance with prolonged symptoms after acute disease. The post-infectious period including a heterogeneous group of symptoms is named 'long COVID'. This study aimed to describe persisting symptoms three months after COVID-19 and risk factors associated with 'long COVID'. Materials and Methods: This cross-sectional retrospective study included COVID-19 patients diagnosed with SARS-CoV-2 PCR positivity in the first 18 months of the COVID-19 pandemic, between March 2020 and September 2021. We conducted a survey in 2022 to inquire about the participants' symptoms that lasted three months or more after their own COVID-19 period. All patients were employees of one of the biggest national banks in Turkey. Participants answered a total of 31 questions over the phone. The presence of one or more symptoms persisting ≥3 months was defined as 'long COVID'. The risk factors associated with 'long COVID' were determined. Results: A total of 1301 patients were included in our study. The median age of patients was 40 (22-57), and 558 (42.9%) were women. 257 (19.8%) patients had 'long COVID' symptoms. The most prevalent symptoms were myalgia (14.3%), arthralgia (14.1%), and back pain (13.8%). Female gender ( p=0.000, OR=2.19 [95% CI=1.655-2.904]) and diabetes mellitus ( p=0.016, OR=2.43 [95% CI=1.177-5.017]) were found as independent risk factors for 'long COVID' by multivariant logistic regression analysis. Conclusion: Female gender and diabetes mellitus are risk factors for 'long COVID'. Detecting patients with a high risk for developing 'long COVID' is crucial for their management during the COVID and post-COVID periods.

Anaphylaxis is rare due to CoronaVac in a population of healthcare workers.

Background: CoronaVac, the first coronavirus disease 2019 vaccine administered in our country, was found safe in clinical trials. Objective: We aimed to reveal the rate and features of CoronaVac vaccine-associated allergic reactions among vaccinated healthcare workers (HCWs) in real-life. Methods: This study was planned as a questionnaire-based study. Participants who reported a postvaccination allergic reaction were interviewed on phone and their medical records were also checked for confirmation. Results: A total of 2,488 HCWs took part in the study and 4,054 postvaccination complete questionnaire-responses were obtained. Twenty-one HCWs (female: male, 17:4) with a mean age of 40.95 ± 10.09 stated that they had an allergic reaction after a total of 23 vaccine injections. Accordingly, the reaction rate was 0.56% among all vaccine doses. The most common reactions were systemic skin reactions (2.7%) consisting of generalized pruritus, diffuse pruritic erythema, urticaria, and maculopapular rash. That was followed by local injection site reaction (0.12%). Anaphylaxis was reported in 4 cases (0.09%) with a mean onset time of 12 ± 6 minutes. One of them had a history of anaphylaxis with 2 drugs, another had venom and food allergy. Three of the subjects had level 2 diagnostic certainty according to the Brighton Collaboration criteria and one had level 3. All anaphylaxis cases were discharged within 24 hours and none of them required intensive care. Conclusion: Our study demonstrated that allergic reactions to CoronaVac were rare and mostly mild. Although anaphylaxis was also rare, the importance of early intervention with close follow-up was once again emphasized.

Comparison of ceftazidime-avibactam susceptibility testing methods against OXA-48-like carrying Klebsiella blood stream isolates.

Ceftazidime-avibactam exhibits good in vitro activity against carbapenem resistant Klebsiella carrying OXA-48-like enzymes. We tested two hundred unique carbapenem resistant Klebsiella blood stream isolates (71% with single OXA-48-like carbapenemases, including OXA-48, n = 62; OXA-232, n = 57; OXA-244, n = 17; OXA-181, n = 5) that were collected as part of a multicentre study against ceftazidime-avibactam using Etest (bioMérieux, Marcyl'Étoile, France), 10/4 µg disc (Thermo Fisher) and Sensititre Gram Negative EURGNCOL Plates (Lyophilized panels, Sensititre, Thermo Fisher) with the aim of comparing the performances of the Etest and disc to that of Sensititre. Ceftazidime-avibactam MIC50/90 was 2/>16 mg/L for the entire collection and was 2/4 mg/L for single OXA-48-like producers. Categorical and essential agreements between the Etest and Sensititre were 100% and 97%, respectively. Categorical agreement between the disc and Sensititre was 100%. Etest and 10/4 µg discs are suitable alternatives to Sensititre for ceftazidime-avibactam sensitivity testing for OXA-48-like producers.

Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting.

A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam.

High prevalence of ArmA-16S rRNA methyltransferase among aminoglycoside-resistant Klebsiella pneumoniae bloodstream isolates.

Introduction. Aminoglycosides are used for the treatment of carbapenemase-producing Klebsiella pneumoniae (CPK) infections. 16S rRNA methyltransferases (RMTs) confer resistance to all aminoglycosides and are often cocarried with NDM.Hypothesis/Gap Statement. There is a dart of studies looking at the aminoglycoside resistance mechanisms for invasive CPK isolates, particularly in OXA-48 endemic settings.Aim. We aimed to determine the prevalence of RMTs and their association with beta lactamases and MLSTs amongst aminoglycoside-resistant CPK bloodstream isolates in an OXA-48 endemic setting.Methodology. CPK isolates (n=181), collected as part of a multicentre cohort study, were tested for amikacin, gentamicin and tobramycin susceptibility using custom-made sensititre plates (GN2XF, Thermo Fisher Scientific). All isolates were previously subjected to whole-genome sequencing. Carbapenemases, RMTs, MLSTs and plasmid incompatibility groups were detected on the assembled genomes.Results. Of the 181 isolates, 109(60 %) were resistant to all three aminoglycosides, and 96 of 109(88 %) aminoglycoside-resistant isolates carried an RMT (85 ArmA, 10 RmtC, 4 RmtF1; three isolates cocarried ArmA and RmtC). Main clonal types associated with ArmA were ST2096 (49/85, 58 %) and ST14 (24/85, 28 %), harbouring mainly OXA-232 and OXA-48 +NDM, respectively. RmtC was cocarried with NDM (5/10) on ST395, and NDM +OXA-48 or NDM +KPC (4/10) on ST14, ST15 and ST16. All RMT producers also carried CTX-M-15, and the majority cocarried SHV-106, TEM-150 and multiple other antibiotic resistance genes. The majority of the isolates harboured a combination of IncFIB, IncH and IncL/M type plasmids. Non-NDM producing isolates remained susceptible to ceftazidime-avibactam.Conclusion. Aminoglycoside resistance amongst CPK bloodstream isolates is extremely common and mainly driven by clonal spread of ArmA carried on ST2096 and ST14, associated with OXA-232 and OXA48 +NDM carriage, respectively.

SARS-CoV-2 Infection may be Prevented with Cytochrome Inhibitors: Cobicistat and Ritonavir.

Objective: Highly contagious character of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of specific drugs have led many scientists worldwide to re-evaluate the molecules currently in use for other diseases/viruses. Thus, high-throughput screening with docking studies has the rationale to identify potential therapeutics from existing drug molecules. Conflicting results of the studies, including SARS-CoV-2 and human immunodeficiency virus (HIV) coinfected population, suggested a possible preventive effect of antiretroviral regimens they have been receiving. Materials and Methods: Interactions between the widely used antiretroviral molecules, in particular; abacavir, cobicistat, dolutegravir, elvitegravir, emtricitabine, lamivudine, raltegravir, and tenofovir, and the main proteins on SARS-CoV-2 that may be targeted for SARS-CoV-2 infection were analyzed using molecular docking studies. Results: Analysis of the compounds strikingly revealed that not the antiretroviral drugs but cobicistat and ritonavir, the inhibitors of cytochrome P450, had strong interactions with the main protease active site and RNA polymerase on SARS-CoV-2, as well as the active site of angiotensin-converting-enzyme 2, the protein that enables the entry of the virus into human cells. Conclusion: Our results suggest cobicistat and ritonavir may be used to prevent SARS-CoV-2 infection.

Is pulse oximeter a reliable tool for non-critically ill patients with COVID-19?

INTRODUCTION: Guidelines recommend using a pulse oximeter rather than arterial blood gas (ABG) for COVID-19 patients. However, significant differences can be observed between oxygen saturation measured by pulse oximetry (SpO2 ) and arterial oxygen saturation (SaO2 ) in some clinical conditions. We aimed to assess the reliability of the pulse oximeter in patients with COVID-19. METHODS: We retrospectively reviewed ABG analyses and SpO2 levels measured simultaneously with ABG in patients hospitalised in COVID-19 wards. RESULTS: We categorised total 117 patients into two groups, in whom the difference between SpO2 and SaO2 was ≤4% (acceptable difference) and >4% (large difference). A large difference group exhibited higher neutrophil count, C-reactive protein, ferritin, fibrinogen, D-dimer and lower lymphocyte count. Multivariate analyses revealed that increased fibrinogen, increased ferritin and decreased lymphocyte count were independent risk factors for a large difference between SpO2 and SaO2 . The total study group demonstrated the negative bias of 4.02% with the limits of agreement of -9.22% to 1.17%. The bias became significantly higher in patients with higher ferritin, fibrinogen levels and lower lymphocyte count. CONCLUSION: Pulse oximeters may not be sufficient to assess actual oxygen saturation, especially in COVID-19 patients with high ferritin and fibrinogen levels and low lymphocyte count with low SpO2 measurements.

Ceftazidime - Avibactam susceptibility among carbapenem-resistant Enterobacterales in a pilot study in Turkey.

This study aimed to detect carbapenemase genes and to determine the in vitro susceptibility of Ceftazidime-Avibactam (CZA) in Enterobacterales isolates. Carbapenemase genes were detected by polymerase chain reaction. CZA sensitivity of isolates was evaluated with broth microdilution (BMD) and disk diffusion methods. A total of 318 carbapenem-resistant Enterobacterales isolates were included. Most of the isolates (n = 290, 91.2%) were identified as Klebsiella pneumoniae. The most common carbapenemase type was OXA-48 (n = 82, 27.6%). CZA susceptibility was evaluated in 84 isolates with OXA-48 and KPC carbapenemase activity. Both BMD and disk diffusion methods revealed that 95.2% of the isolates were sensitive to CZA; whereas, 4 (4.76%) isolates were resistant to CZA. Among colistin resistant isolates, 96.5% (n = 80) of them were susceptible to CZA. Our study demonstrated high in vitro efficacy of CZA in Enterobacterales isolates producing OXA-48 carbapenemase. High susceptibility rates against colistin resistant isolates which generally are also pan drug resistant, makes CZA a promising therapeutic choice for difficult-to-treat infections. Due to its high correlation with the BMD, disk diffusion method is a suitable and more practical method in detecting CZA in vitro activity.

Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.

Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 in vitro.

Ribavirin is a guanosine analog with broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico, and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection, whereas the drug itself did not show any toxic effect over the concentration range tested. In silico analysis suggested that ribavirin has a broad-spectrum impact on SARS-CoV-2, acting at different viral proteins. According to the detailed molecular techniques, ribavirin was shown to decrease the expression of TMPRSS2 at both mRNA and protein levels 48 h after treatment. The suppressive effect of ribavirin in ACE2 protein expression was shown to be dependent on cell types. Finally, proteolytic activity assays showed that ribavirin also showed an inhibitory effect on the TMPRSS2 enzyme. Based on these results, we hypothesized that ribavirin may inhibit the expression of TMPRSS2 by modulating the formation of inhibitory G-quadruplex structures at the TMPRSS2 promoter. As a conclusion, ribavirin is a potential antiviral drug for the treatment against SARS-CoV-2, and it interferes with the effects of TMPRSS2 and ACE2 expression.