Immunogenicity after two doses of inactivated virus vaccine in healthcare workers with and without previous COVID-19 infection: Prospective observational study.

Vaccines have been seen as the most important solution for ending the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the antibody levels after inactivated virus vaccination. We included 148 healthcare workers (74 with prior COVID-19 infection and 74 with not). They received two doses of inactivated virus vaccine (CoronaVac). Serum samples were prospectively collected three times (Days 0, 28, 56). We measured SARS-CoV-2 IgGsp antibodies quantitatively and neutralizing antibodies. After the first dose, antibody responses did not develop in 64.8% of the participants without prior COVID-19 infection. All participants had developed antibody responses after the second dose. We observed that IgGsp antibody titers elicited by a single vaccine dose in participants with prior COVID-19 infection were higher than after two doses of vaccine in participants without prior infection (geometric mean titer: 898 and 607 AU/ml). IgGsp antibodies, participants with prior COVID-19 infection had higher antibody levels as geometric mean titers at all time points (p < 0.001). We also found a positive correlation between IgGsp antibody titers and neutralizing capacity (rs = 0.697, p < 0.001). Although people without prior COVID-19 infection should complete their vaccination protocol, the adequacy of a single dose of vaccine is still in question for individuals with prior COVID-19. New methods are needed to measure the duration of protection of vaccines and their effectiveness against variants as the world is vaccinated. We believe quantitative IgGsp values may reflect the neutralization capacity of some vaccines.

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.

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.

Evaluation of extensively drug-resistant gram-negative bacteremia among solid-organ transplant recipients: a multicenter study

Background/aim: The aim of this study is to evaluate the distribution, sources, clinical features, and mortality rates of bacteremia due to evaluation of extensively drug-resistant (XDR) gram negative among solid-organ transplant (SOT) recipients. Materials and methods: A retrospective study of SOT recipients with bacteremia due to XDR gram-negative pathogens in 11 centers between 2016 and 2018 was conducted. Patients' records were evaluated. Results: Of 171 bacteremia that occurred in 164 SOT recipients, 93 (56.7%) were liver, 46 (28%) kidney, 14 (8.5%) heart, and 11 (6.7%) lung recipients. Bacteremia episodes were recorded in the first year in 63.7% of the patients (n = 109), early-onset bacteremia was recorded in 45% (n = 77) of the episodes. In multivariate analysis, catheter-associated bacteremia was an independent risk factor for 7-day mortality (p = 0.037), and early-onset bacteremia was found as an independent risk factor for 30-day mortality (p = 0.017). Conclusion: Difficult-to-treat infections due to XDR bacteria in SOT recipients shadow the success of transplantation. Central venous catheters seem to be the main risk factor. Judicious use of medical devices is of pivotal importance.

Impact of the ST101 clone on fatality among patients with colistin-resistant Klebsiella pneumoniae infection.

Objectives: We describe the molecular characteristics of colistin resistance and its impact on patient mortality. Methods: A prospective cohort study was performed in seven different Turkish hospitals. The genotype of each isolate was determined by MLST and repetitive extragenic palindromic PCR (rep-PCR). Alterations in mgrB were detected by sequencing. Upregulation of pmrCAB, phoQ and pmrK was quantified by RT-PCR. mcr-1 and the genes encoding OXA-48, NDM-1 and KPC were amplified by PCR. Results: A total of 115 patients diagnosed with colistin-resistant K. pneumoniae (ColR-Kp) infection were included. Patients were predominantly males (55%) with a median age of 63 (IQR 46-74) and the 30 day mortality rate was 61%. ST101 was the most common ST and accounted for 68 (59%) of the ColR-Kp. The 30 day mortality rate in patients with these isolates was 72%. In ST101, 94% (64/68) of the isolates had an altered mgrB gene, whereas the alteration occurred in 40% (19/47) of non-ST101 isolates. The OXA-48 and NDM-1 carbapenemases were found in 93 (81%) and 22 (19%) of the total 115 isolates, respectively. In multivariate analysis for the prediction of 30 day mortality, ST101 (OR 3.4, CI 1.46-8.15, P = 0.005) and ICU stay (OR 7.4, CI 2.23-29.61, P = 0.002) were found to be significantly associated covariates. Conclusions: Besides ICU stay, ST101 was found to be a significant independent predictor of patient mortality among those infected with ColR-Kp. A significant association was detected between ST101 and OXA-48. ST101 may become a global threat in the dissemination of colistin resistance and the increased morbidity and mortality of K. pneumoniae infection.

Epidemiology, species distribution, clinical characteristics and mortality of candidaemia in a tertiary care university hospital in Turkey, 2007-2014.

Candidaemia still continues to be a serious medical concern and the epidemiology of candidaemia varies according to geographical areas. We aim to determine the incidence, local epidemiology, Candida species distribution and crude mortality rates of candidaemia. We retrospectively evaluated candidaemia episodes in between January 2007 and August 2014. We compared demographic, clinical, microbiological findings and mortality rates of episodes caused by Candida albicans and non-albicans Candida species. Overall the candidaemia incidences were 1.23 episodes/1000 admissions. A significant negative slope among candidaemia episodes and years was determined. Overall C. albicans (54.6%) was the most common species followed by Candida glabrata, Candida tropicalis and Candida parapsilosis respectively. Preinfection hospital stay and length of hospital stay were statistically longer in patients with non-albicans Candida candidaemia than in patients with C. albicans candidaemia. The source of candidaemia was unknown in 52.5% of all episodes. Central venous catheters among non-albicans Candida candidaemia episodes and urinary system among C. albicans candidaemia episodes were common source of candidaemia compared to each other. Previous antifungal therapy preceding candidaemia and concomitant bacteraemia were significantly associated with non-albicans Candida candidaemia. Continuous local surveillance will preserve its pivotal importance in formulating empirical antifungal therapy and improving management of candidaemia.

Emerging Escherichia coli O25b/ST131 clone predicts treatment failure in urinary tract infections.

BACKGROUND: We described the clinical predictive role of emerging Escherichia coli O25b/sequence type 131 (ST131) in treatment failure of urinary tract infection. METHODS: In this prospective observational cohort study, the outpatients with acute cystitis with isolation of E. coli in their urine cultures were assessed. All the patients were followed up for clinical cure after 10 days of treatment. Detection of the E. coli O25:H4/ST131 clone was performed by multiplex polymerase chain reaction (PCR) for phylogroup typing and using PCR with primers for O25b rfb and allele 3 of the pabB gene. RESULTS: In a cohort of patients with diagnosis of acute urinary cystitis, 294 patients whose urine cultures were positive with a growth of >10(4) colony-forming units/mL of E. coli were included in the study. In empiric therapy, ciprofloxacin was the first choice of drug (27%), followed by phosphomycin (23%), trimethoprim-sulfamethoxazole (TMP-SMX) (9%), and cefuroxime (7%). The resistance rate was 39% against ciprofloxacin, 44% against TMP-SMX, and 25% against cefuroxime. Thirty-five of 294 (12%) isolates were typed under the O25/ST131 clone. The clinical cure rate was 85% after the treatment. In multivariate analysis, detection of the O25/ST131 clone (odds ratio [OR], 4; 95% confidence interval [CI], 1.51-10.93; P = .005) and diabetes mellitus (OR, 2.1; 95% CI, .99-4.79; P = .05) were found to be significant risk factors for the treatment failure. In another multivariate analysis performed among quinolone-resistant isolates, treatment failure was 3 times more common among the patients who were infected with ST131 E. coli (OR, 3; 95% CI, 1.27-7.4; P = .012). CONCLUSIONS: In urinary tract infections, the E. coli ST131 clone seems to be a consistent predictor of treatment failure.

In vitro susceptibility of tigecycline against multidrug-resistant gram-negative strains: Etest versus agar dilution.

BACKGROUND AND AIM: Tigecycline is a semi-synthetic tetracycline with activity against most multidrug-resistant (MDR) bacteria. METHODS: We studied in vitro activity of tigecycline by agar dilution (AD) and Etest methods to evaluate their correlation. The study included 206 isolates of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae and MDR Acinetobacter baumannii recovered from blood cultures of patients of Baskent University between 2008 and 2010. RESULTS: ESBL-producing E. coli had MIC50/MIC90 values of 0.5/0.5 µg/ml by AD and 0.25/0.5 µg/ml by Etest. ESBL-producing K. pneumoniae had MIC50/MIC90 values of 1/2 µg/ml by AD and 0.75/2 µg/ml by Etest, whereas MDR A. baumannii had MIC50/MIC90 values of 4/4 µg/ml by AD and 2/4 µg/ml by Etest. The correlation between AD and Etest was weak for ESBL-producing E. coli and strong for ESBL-producing K. pneumoniae and MDR A. baumannii. Tigecycline MIC values for ESBL-producing E. coli were lower than the tigecycline concentration, while they were higher than the concentrations attainable by treatment doses for A. baumannii. CONCLUSION: Tigecycline is an appropriate agent in the treatment of E. coli bacteremia, but it is not for treating A. baumannii bacteremia. Tigecycline could be used for K. pneumoniae bacteremia treatment after determining its MIC value. Determining the MIC value by gold-standard methods is more appropriate due to the correlation between Etest and AD at high MIC values.

An Emerging Issue: Carbapenem-Resistant Enterobacteriaceae in Solid-Organ Transplantation.

OBJECTIVES: Bloodstream infections caused by carbapenem-resistant bacteria have increased globally. Solid-organ transplant recipients are more prone to these infections. This study aimed to compare the clinical courses of carbapenem-susceptible and carbapenem-resistant Enterobacteriaceae bloodstream infections and to identify risk factors for carbapenem resistance in solid-organ transplant recipients. MATERIALS AND METHODS: For this retrospective descriptive study, data for solid-organ transplant recipients (age ≥18) treated from 2015 to 2022 were obtained from medical records. Enterobacteriaceaepositive blood culture was screened from laboratory data. RESULTS: Among 72 patients, there were 100 bacteremia episodes. Patients included 40 kidney (55.6%), 21 liver (29.2%), 7 heart (9.7%), and 4 combined liver and kidney (5.6%) transplant recipients. Fifty-seven bacteremia episodes were recorded between 2015 and 2020, and 43 bacteremia episodes were recorded between 2020 and 2022. Carbapenem resistance was reported in 15.8% of patients before 2020, whereas this rate increased to 39.5% after 2020 (P = .007). Pitt bacteremia score ≥4 (P < .001), Charlson comorbidity index ≥4 (P = .021), chronic liver disease (P = .015), septic shock at admission (P = .001), hypotension at admission (P = .006), bacteremia episodes 48 hours after hospitalization (P = .004), hospitalization in the past 3 months (P = .004), and prior invasive procedure (P = .043) were significant factors for carbapenem resistance. Logistic regression analysis showed that bacteremia 48 hours after hospitalization (P = .002) and hospitalization in the past 3 months (P = .006) were independent risk factors. CONCLUSIONS: Carbapenem resistance increased significantly over the years. Bacteremia 48 hours after hospitalization and hospitalization within the past 3 months were determined to be risk factors for carbapenem resistance. Carbapenem-resistant infections are still nosocomial infections. Patients should be hospitalized for as a short time as possible, and both patients and their physicians should follow infection control and prevention methods.

Antimicrobial dosing recommendations during continuous renal replacement therapy: different databases, different doses.

Meticulous antimicrobial management is essential among critically ill patients with acute kidney injury, particularly if renal replacement therapy is needed. Many factors affect drug removal in patients undergoing continuous renal replacement therapy CRRT. In this study, we aimed to compare current databases that are frequently used to adjust CRRT dosages of antimicrobial drugs with the gold standard. The dosage recommendations from various databases for antimicrobial drugs eliminated by CRRT were investigated. The book 'Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys' was chosen as the gold standard. There were variations in the databases. Micromedex, UpToDate, and Sanford had similar rates to the gold standard of 45%, 35%, and 30%, respectively. The Micromedex database shows the most similar results to the gold standard source. In addition, a consensus was reached as a result of the expert panel meetings established to discuss the different antimicrobial dose recommendations of the databases.

Evaluation of Candidemia in Solid-Organ Transplant Recipients.

OBJECTIVES: Solid-organ transplant recipients have high rates of invasive fungal infections. Candida species are the most commonly isolated fungi. Our aim was to identify risk factors, clinical presentations, and outcomes of candidemia in solid-organ transplant recipients. MATERIALS AND METHODS: We evaluated adult (≥18 years old) transplant recipients seen from May 2011 to December 2022 at Baskent University Ankara Hospital. From medical records, we retrospectively reviewed age, sex, transplant type, candidemia agent, risk factors, concomitant infections, and mortality of patients with Candida detected in blood culture. We used SPSS statistics software (version 25) to analyze data. RESULTS: There were 1080 organ transplants performed during the study period (717 kidney, 279 liver, 84 heart). There were 855 who were ≥18 years (655 kidney, 127 liver, 73 heart), of whom candidemia was detected in 26 (16 male; 11 kidney, 11 liver, 4 heart) with a median age of 47.5 years. The most common agents were Candida albicans and Candida glabrata. The most common chronic diseases were hypertension, cirrhosis, and cardiomyopathy. Eighteen patients had a concomitant focus of infection. Ten patients had pneumonia accompanying candidemia. The 30-day mortality rate was as high as 53.8%. The mean duration of candidemia after transplant was 23 months. Catheter-related candidemia was observed in 65% of patients. The 30-day mortality was found to be significantly higher in patients followed in the intensive care unit (P = .014), receiving total parenteral nutrition (P = .001), using broad-spectrum antibiotics (P = .001), and having pneumonia (P = .042) accompanying candidemia. CONCLUSIONS: For adult solid-organ transplant recipients with candidemia, careful monitoring is essential for successful management of total parenteral nutrition, central catheter, use of broadspectrum antibiotics, and invasive interventions.

Enterobacterales carrying chromosomal AmpC ß-lactamases in Europe (EuESCPM): Epidemiology and antimicrobial resistance burden from a cohort of 27 hospitals, 2020-2022.

INTRODUCTION: The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs. METHODS: We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a 3-year period (2020-2022). Diagnostic approach, epidemiology, and antimicrobial susceptibility were investigated. RESULTS: Our study comprised 6,774 ESCPM isolates. MALDI-TOF coupled to mass spectrometry was the predominant technique for bacterial identification. Susceptibility to new ß-lactam/ß-lactamase inhibitor combinations and confirmation of AmpC overproduction were routinely tested in 33.3% and 29.6% of the centres, respectively. The most prevalent species were E. cloacae complex (44.8%) and S. marcescens (22.7%). Overall, third-generation cephalosporins (3GC), combined third- and fourth-generation cephalosporins (3GC + 4GC) and carbapenems resistance phenotypes were observed in 15.7%, 4.6%, and 9.5% of the isolates, respectively. AmpC overproduction was the most prevalent resistance mechanism detected (15.8%). Among carbapenemase-producers, carbapenemase type was provided in 44.4% of the isolates, VIM- (22.9%) and OXA-48-enzyme (16%) being the most frequently detected. E. cloacae complex, K. aerogenes and Providencia species exhibited the most notable cumulative antimicrobial resistance profiles, with the former displaying 3GC, combined 3GC + 4GC and carbapenems resistance phenotypes in 15.2%, 7.4%, and 12.8% of the isolates, respectively. K. aerogenes showed the highest rate of both 3GC resistant phenotype (29.8%) and AmpC overproduction (32.1%), while Providencia species those of both carbapenems resistance phenotype (42.7%) and carbapenemase production (29.4%). ESCPM isolates exhibiting both 3GC and combined 3GC + 4GC resistance phenotypes displayed high susceptibility to ceftazidime/avibactam (98.2% and 95.7%, respectively) and colistin (90.3% and 90.7%, respectively). Colistin emerged as the most active drug against ESCPM species (except those intrinsically resistant) displaying both carbapenems resistance phenotype (85.8%) and carbapenemase production (97.8%). CONCLUSIONS: This study presented a current analysis of ESCPM species epidemiology in Europe, providing insights to inform current antibiotic treatments and guide strategies for antimicrobial stewardship and diagnostics.

Herpes Zoster Infections in Solid-Organ Transplant Recipients.

OBJECTIVES: Herpes zoster infections can be complicated and mortal in solid-organ transplant recipients. In our study, we investigated herpes zoster infections in solid-organ transplant recipients. MATERIALS AND METHODS: UntilJune 2022, our center has performed 3342 kidney, 708 liver, and 148 heart transplants.Herpes zosterinfections were investigated in 1050 adult solid-organ transplant recipients from January 1, 2011, to June 31, 2022. We studied 44 patients diagnosed with herpes zoster infections. RESULTS: Of the 44 patients with herpes zoster, 32 had kidney, 7 had heart, and 5 had liver transplant procedures. Crude incidence rate was 5.2%.,with 9.7% being heart, 5.1% being kidney, and 3.9% being liver transplant recipients; 72.7% were male patients. The median age was 47.5 years, and 61% of patients were aged >45 years. Postherpetic neuralgia was significantly higher in patients older than 45 years (P = .006). The median duration to infection posttransplant was 16.5 months. The dermatomes of patients were 43.2% thoracic. Sacral dermatome involvement was significantly higher in heart transplant patients than in other transplant recipients (P = .015). We reviewed specific findings of the Tzanck test in 36.4% of the patients. There was concomitant infection in 15.9% of the patients, and 6.8% had pneumonia. Acute neuritis was more common in kidney transplant recipients (65.6%). The mean duration of acute neuritis/neuralgia was longest in liver transplant recipients (13.5 months; P = .047). Postherpetic neuralgia was detected as high as 24%. CONCLUSIONS: Early specific and supportive treatmentis important for transplant recipients with herpes zoster infections. Appropriate antiviral prophylaxis regimens and vaccination strategies for varicella zoster (chickenpox) and herpes zoster infections should be implemented in the vaccination schedule of solidorgan transplant candidates to prevent herpes zoster infections and complications.

Evaluation of Clinical Approach and Outcomes Staphylococcus aureus Bacteremia.

Objective: Despite appropriate treatment and early diagnosis methods, Staphylococcus aureus bacteremia (SAB) is still associated with a high mortality rate. This study aims to evaluate the clinical features and approaches to SAB and to analyze the parameters that may affect 7-day and 30-day mortality. Materials and Methods: Adult patients with SAB data between 2011 and 2018 were evaluated retrospectively. Clinical data, patient demographics, and 7-day and 30-day mortality rates were obtained from their medical records. Results: In total, 144 patients were included in the study; 57.6% (83/144) of patients were men, and the mean age was 65.2±16.5 years. The most common source of infection was the central-line catheter (38.9%), followed by intra-abdominal (21%), respiratory (16.7), infective endocarditis (5.6%), and osteoarticular foci (2.1%). Fifteen percent (15%) of the strains were methicillin resistant. Transthoracic echocardiography (TTE) was performed for 80.6% (116/144) patients. Infectious diseases specialist consultation within 96 hours from blood culture signal was requested in 79.9%. Overall, 7-day mortality was 11.8%, and 30-day mortality was 21.5%. Staying in intensive care units (ICU) increased the risk of 30-day mortality by 1.1 times, and respiratory-focused SAB increased the risk by 4.3 times. Conclusion: SAB is still a big threat. Staphylococcal pneumonia remains a severe infection. Several prognostic factors influence mortality. Identifying the source, ensuring source control, and appropriate initial therapy as soon as possible are critical for reducing mortality and morbidity in SAB.

Ophthalmologic Examination and Echocardiography Should be the Essential Components of Candidemia Bundle.

Objective: Candidemia is the most common form of invasive candidiasis, and it is associated with end-organ involvement, prolonged hospitalization, increased mortality, and higher healthcare costs. Candidemia can lead to metastatic heart and ocular infections. This study aimed to define the incidence, characteristics, and mortality of candidemia episodes and compare the data with our center's previous results. Materials and Methods: In this single-center retrospective observational study, we enrolled 250 patients over 18 years diagnosed with candidemia between January 2015 and December 2020. We obtained patients' demographic, clinical, laboratory, and therapeutic data from medical records. An ophthalmologic examination and screening with echocardiography were carried out within the first week after candidemia diagnosis. Results: There were 275 candidemia episodes from 250 patients. The incidence of candidemia was 2.8/1000 admissions and 5.68/ 10,000 inpatient days, higher than our previous results (1.23/1000 and 3.29/10,000). The median age was 65 (interquartile range [IQR]=52-75) years. Malignancies were the most frequent comorbidity (50%). The most common type was Candida albicans (n=115, 41.8%). Candida glabrata (n=61, 22.2%) was common, particularly in surgical patients, patients with malignancy, and critically ill patients. There was Infectious disease consultation in 93.3% (257) episodes.The ophthalmoscopic examination was made in 145 episodes (52.7%), and ophthalmitis was detected in 16 (11.0%). Echocardiography was performed in 139 (50.5%) episodes; one case had an endocarditis diagnosis. The 30-day mortality was 44.7% (n=123). Mortality rates in C. glabrata and Candida krusei infections were higher (54.1% and 66.7). The factors related to mortality were intensive care unit requirement (p=0.0001), chronic liver disease (p=0.005), corticosteroid usage (p=0.0001), previous antibiotic usage (p=0.013), multiple antibiotic usage ( p=0.020), and CVC related candidemia (p=0.010). Conclusion: Because of the life-threatening complications such as endocarditis, increased mortality rates, and higher healthcare costs, systematic and comprehensive candidemia bundle applications would be effective strategies for providing an effective antifungal stewardship program.

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.

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.

[A fatal case of West Nile virus encephalitis]. / Ölümcül Seyreden Bati Nil Virusu Ensefaliti Olgusu.

Although West Nile virus (WNV) serologic evidence has been well demonstrated throghout Turkey in the last 40 years; the first symptomatic WNV infection was reported in 2009 and increased number of cases were reported during August 2010. In that period WNV encephalitis was diagnosed serologically (WNV IgM positivity in serum sample detected by ELISA and IFA) and confirmed by plaque reduction neutralization test in a 76-year-old man who was admitted to Baskent University Faculty of Medicine with complaints of fever, impaired consciousness and generalized tremors. Despite all supportive treatment, he died on the 9th day of hospitalization. In this report, detailed clinical course, laboratory features and diagnosis of this mortal case of WNV encephalitis were described. WNV encephalitis should be considered in the differential diagnosis of patients with fever of unknown origin and loss of consciousness especially in summer and early fall in Turkey.

ESCMID COVID-19 living guidelines: drug treatment and clinical management.

SCOPE: In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon ß-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon ß-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19. SCOPE: The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.

European society of clinical microbiology and infectious diseases guidelines for coronavirus disease 2019: an update on treatment of patients with mild/moderate disease.

SCOPE: Despite the large availability of vaccines, coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2, continues to be a major threat for health-care providers and fragile people. A number of options are now available for outpatients with mild-to-moderate COVID-19 at the risk of disease progression for the prevention of deaths or hospitalization. METHODS: A European Society of Clinical Microbiology and Infectious Diseases COVID-19 guidelines task force was established by the European Society of Clinical Microbiology and Infectious Diseases Executive Committee. A small group was established, half appointed by the chair and the remaining selected based on an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the population, intervention, comparison, outcome format was developed at the beginning of the process. For each population, intervention, comparison, outcome, two panel members performed a literature search, with a third panelist involved in case of inconsistent results. Voting was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RECOMMENDATIONS: In this update, we focus on anti-viral agents, monoclonal antibodies (mAbs) and other treatment options proposed for patients with mild or moderate COVID-19 who are at the risk of hospitalization or death. Although the use of anti-virals is recommended, especially nirmatrelvir/ritonavir and remdesivir or, alternatively, molnupirarvir, the administration of mAbs against the spike protein strictly depends on circulating variants or the ability to test timely for variants and sub-variants. At the time of writing (April-June 2022), the only active mAb was tixagevimab/cilgavimab given the predominance of the Omicron BA.2, BA.3, BA.4 and BA.5 sub-lineages in Europe. However, considering that the epidemiological scenario is extremely dynamic, constant monitoring of variants of concern is mandatory.