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Aims Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may lead to the development of severe respiratory failure. In hospitalized-patients, prompt interruption of the virus-driven inflammatory process by using combination treatments seems theoretically of outmost importance. Our aim was to investigate the hypothesis of multifaceted management of these patients. Methods A treatment algorithm based on ferritin was applied in 311 patients (67.2% males; median age 63-years; moderate disease, n=101; severe, n=210). Patients with ferritin

Background Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. Objectives To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). Methods A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. Results One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. Conclusions Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

Risk stratification of coronavirus disease-19 (COVID-19) patients by simple markers is critical to guide treatment. We studied the predictive value of soluble interleukin-2 receptor (sIL-2R) for the early identification of patients at risk of developing severe clinical outcomes. sIL-2R levels were measured in 197 patients (60.9% males; median age 61 years; moderate disease, n = 65; severe, n = 132, intubated and/or died, n = 42). All patients received combined immunotherapies (anakinra ± corticosteroids ± intravenous immunoglobulin ± tocilizumab) according to our local treatment algorithm. The endpoint was the composite event of intubation due to severe respiratory failure (SRF) or mortality. Median (interquartile range) sIL-2R levels were significantly higher in patients with severe disease, compared with those with moderate disease (6 (6.2) vs. 5.2 (3.4) ng/mL, p = 0.017). sIL-2R was the strongest laboratory predictive factor for intubation/death (hazard ratio 1.749, 95%CI 1.041–2.939, p = 0.035) after adjustment for other known risk factors. Youden’s index revealed optimal sIL-2R cut-off for predicting intubation/death at 9 ng/mL (sensitivity: 67%; specificity: 86%; positive and negative predictive value: 57% and 91%, respectively). Delta sIL-2R between the day of event or discharge minus admission date was higher in patients that intubated/died than in those who did not experience an event (2.91 (10.42) vs. 0.44 (2.88) ng/mL; p = 0.08)). sIL-2R on admission and its dynamic changes during follow-up may reflect disease severity and predict the development of SRF and mortality.

Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19. Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied. Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20–0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25–0.97). Anakinra was associated with decrease in circulating interleukin (IL)−6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata. Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance. Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme. Clinical trial number: NCT04357366., eLife digest People infected with the SARS-CoV-2 virus, which causes COVID-19, can develop severe respiratory failure and require a ventilator to keep breathing, but this does not happen to every infected individual. Measuring a blood protein called suPAR (soluble urokinase plasminogen activator receptor) may help identify patients at the greatest risk of developing severe respiratory failure and requiring a ventilator. Previous investigations have suggested that measuring suPAR can identify pneumonia patients at highest risk for developing respiratory failure. The protein can be measured by taking a blood sample, and its levels provide a snapshot of how the body’s immune system is reacting to infection, and of how it may respond to treatment. Anakinra is a drug that forms part of a class of medications called interleukin antagonists. It is commonly prescribed alone or in combination with other medications to reduce pain and swelling associated with rheumatoid arthritis. Kyriazopoulou et al. investigated whether treating COVID-19 patients who had developed pneumonia with anakinra could prevent the use of a ventilator and lower the risk of death. The findings show that treating COVID-19 patients with an injection of 100 milligrams of anakinra for ten days may be an effective approach because the drug combats inflammation. Kyriazopoulou et al. examined various markers of the immune response and discovered that anakinra was able to improve immune function, protecting a significant number of patients from going on a ventilator. The drug was also found to be safe and cause no significant adverse side effects. Administering anakinra decreased of the risk of progression into severe respiratory failure by 70%, and reduced death rates significantly. These results suggest that it may be beneficial to use suPAR as an early biomarker for identifying those individuals at highest risk for severe respiratory failure, and then treat them with anakinra. While the findings are promising, they must be validated in larger studies.

Background Development of sepsis is a process with significant variation among individuals. The precise elements of this variation need to be defined. This study was designed to define the way in which comorbidities contribute to sepsis development. Methods Three thousand five hundred nine patients with acute pyelonephritis (AP), community-acquired pneumonia (CAP), intraabdominal infections (IAI) or primary bacteremia (BSI) and at least two signs of the systemic inflammatory response syndrome were analyzed. The study primary endpoint was to define how comorbidities as expressed in the Charlson’s comorbidity index (CCI) and the underlying type of infection contribute to development of organ dysfunction. The precise comorbidities that mediate sepsis development and risk for death among 18 comorbidities recorded were the secondary study endpoints. Results CCI more than 2 had an odds ratio of 5.67 for sepsis progression in patients with IAI between significantly higher than AP and BSI. Forward logistic regression analysis indicated seven comorbidities that determine transition into sepsis in patients with AP, four comorbidities in CAP, six comorbidities in IAI and one in BSI. The odds ratio both for progression to sepsis and death with one comorbidity or with two and more comorbidities was greater than in the absence of comorbidities. Conclusions The study described how different kinds of infection vary in the degree to which they lead to sepsis. The number of comorbidities that enhances the risk of sepsis and death varies depending on the underlying infections. Electronic supplementary material The online version of this article (10.1186/s12879-018-3156-z) contains supplementary material, which is available to authorized users.

The COVID-19 pandemic represents one of the greatest challenges in modern medicine. The disease is characterized by a variable clinical phenotype, ranging from asymptomatic carriage to severe and/or critical disease, which bears poor prognosis and outcome because of the development of severe acute respiratory distress syndrome (SARS) requiring ICU hospitalization, multi-organ failure and death. Therefore, the determination of risk factors predisposing to disease phenotype is of outmost importance. The aim of our study was to evaluate which predisposing factors, including MBL2 genotyping, affected clinical phenotype in 264 COVID-19 patients. We demonstrated that older age along with underlying comorbidities, primarily obesity, chronic inflammatory disorders and diabetes mellitus, represent the most important risk factors related to hospitalization, the development of pneumonia and SARS. Moreover, we found that the presence of the MBL deficiency-causing B allele (rs1800450) was significantly associated with almost 2-fold increased risk for developing pneumonia and requiring hospitalization, suggesting its usage as a molecular predictor of severe disease in SARS-CoV-2 infected individuals.

Although analysis of retrospective studies has documented survival benefit from the addition of a macrolide to the treatment regimen for community-acquired pneumonia (CAP), no data are available to determine if there is differential efficacy between members of the macrolide family. In order to investigate this, an analysis was undertaken of data from 1174 patients with CAP who met the new Sepsis-3 definitions and were enrolled prospectively in the data registry of the Hellenic Sepsis Study Group. Four well-matched treatment groups were identified with 130 patients per group: clarithromycin and β-lactam; azithromycin and β-lactam; respiratory fluoroquinolone and β-lactam monotherapy. The primary endpoint was comparison of the effects of clarithromycin with β-lactam monotherapy on 28-day mortality. The secondary endpoint was resolution of CAP. Mortality rates for the clarithromycin, azithromycin, respiratory fluoroquinolone and β-lactam groups were 20.8%, 33.8% (P=0.026 vs clarithromycin), 32.3% (P=0.049 vs clarithromycin) and 36.2% (P=0.009 vs clarithromycin), respectively. After stepwise Cox regression analysis among all groups, clarithromycin was the only treatment modality associated with a favourable outcome (hazard ratio 0.61; P=0.021). CAP resolved in 73.1%, 65.9% (P=0.226 vs clarithromycin), 58.5% (P=0.009 vs clarithromycin) and 61.5% (P=0.046 vs clarithromycin) of patients, respectively. It is concluded that the addition of clarithromycin to the treatment regimen of patients with severe CAP leads to better survival rates.

Aims We sought to determine whether primary outcomes differ between non-ICU septic patients with and without type 2 diabetes (T2D). Methods This study utilized the Hellenic Sepsis Study Group Registry, collecting nationwide data for sepsis patients since 2006, and classified patients upon presence or absence of T2D. Patients were perfectly matched for a) Sepsis 3 definition criteria (including septic shock) b) gender, c) age, d) APACHE II score and e) Charlson's comorbidity index (CCI). Independent sample t-test and chi-square t-test was used to compare prognostic indices and primary outcomes. Results Of 4320 initially included non-ICU sepsis patients, 812 were finally analysed, following match on criteria. Baseline characteristics were age 76 [±10.3] years, 46% male, APACHE II 15.5 [±6], CCI 5.1 [±1.8], 24% infection, 63.8% sepsis and 12.2% septic shock. No significant difference was noted between two groups in qSOFA, SOFA, or suPAR1 levels (p = 0.7, 0.1 & 0.3) respectively. Primary sepsis syndrome resolved in 70.9% of cases (p = 0.9), while mortality was 24% in 28-days time. Cause of death was similar between patients with and without T2D (sepsis 17.8% vs 15.8%, heart event 3.7% vs 3.2%, CNS event 0.5% vs 0.5%, malignancy 0.7% vs 2% respectively, p = 0.6). Conclusions DM does not appear to negatively affect outcomes in septic patients not requiring ICU.

Rifampicin has been widely used due to its broad antibacterial spectrum. Acute haemolysis is a rarely encountered complication of rifampicin. A 58-year-old woman was admitted to our department because of high-grade fever with rigors, accompanied by abdominal and lumbar pain and laboratory evidence of acute haemolysis. She had been treated for brucellosis initially with doxycycline and streptomycin. Due to subsequent appearance of myositis, ciprofloxacin and rifampicin were added for treatment of localised brucellosis. After intravenous administration of rifampicin, the patient deteriorated significantly. After exclusion of other causes of haemolysis, autoimmune haemolytic anaemia related to rifampicin was established by strongly positive direct Coombs test. Drug withdrawal in conjunction with intravenous immune globulin and prednisolone resulted in resolution of haemolysis and no relapse in the ensuing 1-year period. Our case highlights the importance of recognising commonly administrative drugs as cause of haemolytic anaemia, that can often be life threatening.

The efficiency of Rapid Polymyxin NP test for detection of colistin-resistant isolates was tested against a collection of 131 non-repetitive Klebsiella pneumoniae , including 98 colistin-resistant and 33 colistin-susceptible isolates. In addition, the performance of this test was compared with those of the automated systems, BD Phoenix™ and VITEK®2, and the Etest . Determination of imipenem and meropenem MICs showed that 95 of colistin-resistant (Col-R) isolates were also resistant to at least one carbapenem. Characterization of colistin resistance mechanisms showed that 75 out of 98 Col-R isolates were associated with the presence of alterations in the mgrB gene, while no mcr genes were detected among our isolates. Rapid Polymyxin NP correctly detected 97 out of 98 colistin-resistant isolates (Geometric mean MIC value 9.89 mg/L), except one ST147 K. pneumoniae harboring a wild-type mgrB gene (MIC: 8 mg/L), yielding a sensitivity 99%. The other methods gave more false-negative results with colistin-resistant strains; BD Phoenix™,VITEK®2, and the gradient Etest missed five, two and three colistin-resistant, respectively (95%, 98% and 97%). The Rapid Polymyxin NP test gave false positive results with six isolates, for which colistin MICs were 1–2 mg/L (specificity 82%). Despite the fact that Rapid Polymyxin exhibited lower specificity than other methods (82% versus 94%, 88% and 85%), it is easy-to-perform and rapid. Thus, these findings indicate that the Rapid Polymyxin NP test can be an initial tool for the detection of colistin-resistant isolates.

Summary Background Spontaneous spondylodiscitis is an uncommon disease, which may result in serious complications with potentially high morbidity and mortality. We conducted a prospective case study over a 2-year period in order to analyze the clinical features, approaches to management, and outcome of spondylodiscitis. Methods Eight consecutive patients (four men, four women; age range 53–82 years) suffering from spondylodiscitis were identified during the study period. Parameters recorded included: demographics, past medical history, predisposing factors, presenting signs and symptoms, spinal level and extension of the infection, laboratory indices of inflammation, microbiological testing, radiological assessment, kind and duration of treatment, follow-up magnetic resonance imaging (MRI) studies, and outcome. Results Duration of symptoms varied from 14 to 90 days. All patients had back pain; fever ≥38°C was present in 5/8 (62.5%) and neurological findings in 6/8 (75%). Diabetes mellitus was identified in six (75%). Most of the patients had elevated laboratory markers of inflammation. At the initial MRI, 12 anatomical levels were found. The microorganism was identified in 7/8 by blood or bone marrow cultures (50% Staphylococcus aureus ). None of the patients underwent surgical intervention. Seven patients (87.5%) recovered to full activity; follow-up MRI study results were not always in parallel with the clinical improvement of patients. Conclusions Spontaneous spondylodiscitis should be considered in every patient with back pain accompanied by fever and laboratory markers of inflammation. The major predisposing risk factor seems to be uncontrolled diabetes. MRI appears to be the method of choice for confirming diagnosis. Timely and accurate diagnosis along with prompt administration of antibiotics appears mandatory for a favorable outcome and avoidance of surgical intervention.

Background In Greece, there are few data on the epidemiological characteristics of HBV. Our aim was to study the epidemiological patterns of HBV in Central Greece and identify the possible differences in HBV prevalence (clusters) among areas inside this region using data from the hepatitis registry. Methods The study was performed in Thessaly, one out of the thirteen regions of Greece and covers most of the part of Central Greece. A total of 921 HBV patients were registered in the hepatitis registry during the period 1999–2004 while 303 were randomly selected to be studied further using a detailed questionnaire on several epidemiological factors. Results 187/303 patients (61.7%) classified as chronic inactive HBV carriers, 78/303 (25.7%) had chronic hepatitis B, 29/303 (9.6%) had HBV-related cirrhosis and 9/303 (3%) HBV-related hepatocellular carcinoma (HCC). The route of HBV transmission was vertical in 103 (34%), sexual in 46 (15.1%) and intrafamilial in 98 (32.4%). Folk remedies were identified as the predisposing risk factor for contracting HBV infection in 38 (12.5%), previous transfusion in 9 (3%) and unknown mode of transmission in 9 patients (3%). Alcohol abuse was the only independent factor (OR: 2.5; p = 0.01) associated with the progression to cirrhosis–HCC. There were specific areas (clusters) inside Thessaly region with increased ratio of HBV infection; Vertical and sexual modes of transmission were more prominent in some of these areas. Conclusions Vertical, intrafamilial and sexual modes of HBV transmission identified as the major routes of HBV infection in our study. We also identified cluster areas of HBV infection in Central Greece. Alcohol abuse is frequent among HBV patients and is acting as an effect modificator risk factor for the development of HBV-related cirrhosis and HCC. Extended population studies in Greece are needed to assess in detail the epidemiological patterns of HBV and evaluate control programmes.

Summary Objectives Visceral leishmaniasis (VL) is re-emerging in endemic areas. The epidemiological, clinical, laboratory, and treatment outcome characteristics in a large cohort of VL patients is described herein. Methods The cases of 67 VL patients (57% male, mean age 56 years) treated in two Greek hospitals over the last 7 years were identified and evaluated retrospectively. Results Forty-six percent of patients reported contact with animals. Seventeen patients (25%) were immunocompromised, and 22% were co-infected with another pathogen. Sixty-four percent of patients had fever, 57% had weakness, 37% had sweats, 21% had weight loss, and 13% had a dry cough, while 6% developed haemophagocytic syndrome. The median duration of symptoms was 28 days. Fifty-eight percent of patients had splenomegaly, 49% had hepatomegaly, and 36% had lymphadenopathy. The diagnosis was established by positive PCR in peripheral blood (73%) and/or bone marrow specimens (34%). Sixty-one patients (91%) received liposomal amphotericin (L-AMB). Six patients (10%) did not respond or relapsed but were eventually cured after a second cycle of L-AMB. During a 6-month follow-up, the overall mortality was 9%, although none of these deaths was attributed to VL. Conclusions VL is still a common disease in endemic areas, affecting immunocompetent and immunocompromised patients. Its diagnosis is challenging, and molecular techniques are valuable and helpful tools to achieve this. Treatment with L-AMB is safe and very effective.

Hepatopulmonary syndrome (HPS) is defined as a clinical triad including liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations. We report a 61-year-old male presented with fatigue, long-lasting fever, loss of weight, signs of portal hypertension, hepatosplenomegaly, cholestasis and progressive dyspnoea over the last year. Clinical, laboratory and histological findings confirmed the diagnosis of granulomatous hepatitis. HPS due to hepatic granuloma-induced portal hypertension was proved to be the cause of severe hypoxemia of the patient as confirmed by contrast-enhanced echocardiography. Reversion of HPS after corticosteroid therapy was confirmed by a new contrast-enhanced echocardiography along with the normalization of cholestatic enzymes and improvement of the patient's conditions. This is the first case of complete reversion of HPS in a non-cirrhotic patient with hepatic granuloma, indicating that intrapulmonary shunt in liver diseases is a functional phenomenon and HPS can be developed even in miscellaneous liver involvement as in this case.

Besides the classical manifestations, leptospirosis may rarely occur with erythroid hypoplasia and/or pancytopenia. In this study, we reported two cases of leptospirosis presented with pancytopenia as the prevailing manifestation. In addition, the presence of pancytopenia in leptospirosis is reviewed. In both patients, the outcome was favourable as the bone marrow aplasia reversed completely after treatment with intravenous penicillin. In conclusion, this case study suggests that Leptospira infection should be included in the differential diagnosis of febrile pancytopenia, even in the absence of classical signs of severe disease as jaundice, meningitis, renal failure and pulmonary infiltrates.