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.

Can Serum ACE Level Be Used as a Prognostic Indicator in COVID-19?

BACKGROUND: SARS-COV-2 virus that causes COVID-19 binds to the host cell with angiotensin converting enzyme-2 causing acute respiratory distress syndrome (ARDS) and severe mortality and morbidity. There are studies in the literature conducted on the importance of serum angiotensin converting enzyme (ACE) and ACE-2 enzymes in ARDS pathogenesis. Serum ACE levels are higher in children and adolescents than in adults, and COVID-19 has a milder progression. All these reasons suggest that there may be a relationship between serum ACE levels and COVID-19 prognosis. METHODS: The serum ACE levels were determined at the time of hospitalization due to COVID-19 diagnosis in this single-centered, prospective study. According to discharge status, patients were divided into three groups as "Discharge with Healing", "Intensive Care Need" and "Mortality", and the effect of serum ACE levels on disease prognosis was investigated. RESULTS: The present study comprised a total of 103 patients, of whom 42.7% (n = 44) were female, and 57.3% (n = 59) were male. The mean age was 59.48 ± 16.47; 91.3% (n = 94) of them were discharged with healing, 5.8% (n = 6) needed intensive care, and 2.9% (n = 3) resulted in mortality. No differences were detected in terms of serum ACE levels between the groups. CONCLUSIONS: No relationships were detected between serum ACE levels at the time of hospitalization and COVID-19 prognosis.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

[Detection of intestinal parasites with conventional and molecular methods in follow-up HIV/AIDS cases]. / Izlemdeki hiv /aids olgularindaki intestinal parazitlerin konvansiyonel ve moleküler yöntemler ile saptanmasi.

In people living with human immunodeficiency virus (HIV), several complaints related to the gastrointestinal system, mainly diarrhea can be determined. In our study, we aimed to detect the existence of intestinal parasites with conventional methods based on microscopy and with molecular methods based on multiplex-PCR among 90 anti-retroviral treatment (ART) naive or ART adherent HIV/AIDS cases. The existence of Giardia spp., Blastocystis spp., Entamoeba histolytica, Dientamoeba spp. and Cryptosporidium spp. were searched in stool samples and the relation with the existence of these parasites and demographic/clinical data of the cases were determined. The demographic and clinical data of the participants included in the study were as follows; the average age was 34.02 ± 9.7 years, average time of diagnosis was 2.4 ± 1.7 years. Gender distribution was as follows; 85.6% male and 14.4% female. HIV transmission was related with heterosexual intercourse in 60%, homosexual intercourse in 33.3%, blood/blood products contact in 1.1% and with unknown routes in 5.6% of the cases. Fifty percent of the patients were in pre-ART and 50% was in on-ART state. The average CD4+ T lymphocyte count was detected as 400 cells/mm3 and the median of viral load was 114.527 copies/ml. An overall prevalence of at least one intestinal parasitic infection was recorded as 36.7% and the prevalence of this infection due to Blastocystis spp. was 22.2%, followed by Dientamoeba spp. (13.3%), E.histolytica (4.4%), Cryptosporidium spp. (3.3%), Giardia spp. (2.2%) and multiple parasitic infections (7.7%). The type of sexual behaviours related with the detection of intestinal parasites were statistically significant especially in homosexual intercourse (p< 0.001). The increase in CD4+ T lymphocyte counts were reversely associated (p= 0.062) and the increase in the levels of viral load were positively associated (p< 0.001) with detection rate of intestinal parasite. The detection of parasites by molecular methods was statistically significant in pre-ART participants (p= 0.002) and participants with diarrhea (p= 0.019). In the present study, the increase in the frequency of intestinal parasitic infections has shown that essential interventions are required. In all HIV/AIDS cases, routine parasitic screening should be performed by more sensitive methods to manage early and specific treatment.

Predictors of fatality in pandemic influenza A (H1N1) virus infection among adults.

BACKGROUND: The fatality attributed to pandemic influenza A H1N1 was not clear in the literature. We described the predictors for fatality related to pandemic influenza A H1N1 infection among hospitalized adult patients. METHODS: This is a multicenter study performed during the pandemic influenza A H1N1 [A(H1N1)pdm09] outbreak which occurred in 2009 and 2010. Analysis was performed among laboratory confirmed patients. Multivariate analysis was performed for the predictors of fatality. RESULTS: In the second wave of the pandemic, 848 adult patients were hospitalized because of suspected influenza, 45 out of 848 (5.3%) died, with 75% of fatalities occurring within the first 2 weeks of hospitalization. Among the 241 laboratory confirmed A(H1N1)pdm09 patients, the case fatality rate was 9%. In a multivariate logistic regression model that was performed for the fatalities within 14 days after admission, early use of neuraminidase inhibitors was found to be protective (Odds ratio: 0.17, confidence interval: 0.03-0.77, p=0.022), nosocomial infections (OR: 5.7, CI: 1.84-18, p=0.013), presence of malignant disease (OR: 3.8, CI: 0.66-22.01, p=0.133) significantly increased the likelihood of fatality. CONCLUSIONS: Early detection of the infection, allowing opportunity for the early use of neuraminidase inhibitors, was found to be important for prevention of fatality. Nosocomial bacterial infections and underlying malignant diseases increased the rate of fatality.

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.

[APOBEC3 hypermutations in HIV-1 infected cases in Turkey]. / Türkiye'de HIV-1 ile enfekte olgularda APOBEC3 hipermutasyonlari

Host genetic factors may play an effective role on the human immunodeficiency virus (HIV) pathogenesis. APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide like-3) proteins are cellular antiviral proteins which inhibits HIV replication in the absence of vif (virion infectivity factor). In this study, we aimed to determine the APOBEC 3G/F hypermutations in HIV-1 strains isolated in Turkey. A total of 515 HIV-1 infected patients between June 2009 - February 2012 were included in the study. Three hundred ninety four cases were newly diagnosed antiretroviral-naive patients [349 male, 45 female; median age (range): 37.1 (2-69) years; median CD4+ T-cell count (range): 340 (1-1660) mm3; median HIV-RNA load (range): 5.76 + E5 (8.7 + E2-9.4 + E6) IU/ml] and 121 were under HAART therapy [99 male, 22 female; median age (range): 40.7 (20-70) years; median CD4+ T-cell count (range): 195 (6-720) mm3; median HIV-RNA load (range): 5.4 + E5 (1.37 + E3-1.07 + E7) IU/ml]. APOBEC 3G/F hypermutations in HIV-1 pol sequences (reverse transcriptase; codons 41-238 and protease; codons 1-99) analysed by nested RT-PCR and direct sequencing techniques. APOBEC 3G/F hypermutations have been determined by using of HIVdb-Stanford algorithm. The prevalence of overall APOBEC 3G/F hypermutations was 2.5% (13/515) in HIV-1 pol gene sequences in study group, and the rates were 2% (8/394) and 4.1% (5/121) in antiretroviral naive and treatment groups, respectively. However, the location and marker hypermutations of determined APOBEC in the HIV-1 pol gene sequences were RT and 3G in the Turkish patients. The hypermutated HIV-1 strains identified in HIV-1 infected patients may facilitate our understanding the nature and the consequences of HIV-1 infections. Moreover, investigations of the motif and frequency of APOBEC 3G/F hypermutations in HIV-1 proviral DNA samples and understanding their relationships with HIV-1 subtypes in Turkish patients would be beneficial.

[First case of hepatitis B virus genotype H infection in Turkey]. / Türkiye'de ilk kez saptanan hepatit B virus genotip H enfeksiyonu olgusu.

Clinical studies reported from Turkey indicate that hepatitis B virus (HBV) genotype D is more prevalent than other genotypes. Epidemiological and clinical information on genotype H infection is currently limited. Genotype H infection is most likely due to its regional (Central and South America) prevalence throughout the world. The aim of this report is to present the first HBV genotype H infection in a chronic hepatitis B patient in Turkey. Laboratory findings of a 42 years old male patient admitted to our hospital revealed HBsAg (+), anti-HBs (-), HBeAg (-), anti-HBe (+), anti-HBc IgM (-), anti-HBc IgG (+), anti-HAV IgG (+), HBV-DNA: 5.689.776 IU/ml and high liver enzymes (ALT: 223 U/L, AST: 121 U/L). History of the patient indicated no risk factor (intravenous drug use, blood transfusion, suspicious sexual contact) related to HBV transmission. Since liver ultrasonography showed multiple hemangiomas, biopsy was performed and histologic activity index was found as 6/18 and fibrosis as 2/6, according to modified Knodell score system. HBV DNA isolated from the serum sample of the patient was amplified by polymerase chain reaction and polymerase gene segment of HBV was directly sequenced. UPGMA method was used for phylogenetic analysis, and the genotype of the virus was identified accordingly. The nucleotide sequence was compared to those from the international DNA data bank (GenBank). The genotyping of the patient revealed that the isolated HBV was genotype H. Treatment with tenofovir disoproxil fumarate was initiated and the patient responded to the treatment. This finding suggested that other HBV genotypes, except the predominant genotype D may also be in circulation in Turkey. In conclusion, detection of epidemiologic and molecular characteristics of HBV genotype H which is related to chronic hepatitis, seems to be necessary in order to better understand its circulation and progression around the world.

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.

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.