The efficacy of mesenchymal stem cell treatment and colistin-fosfomycin combination on colistin-resistant Acinetobacter baumannii sepsis model.

INTRODUCTION: This study examines the role of mesenchymal stem cells (MSCs) in an experimental sepsis model developed with colistin-resistant Acinetobacter baumannii (CRAB). MATERIALS AND METHODS: BALB-c mice were divided into treatment groups (MSC, MSC + colistin (C)-fosfomycin (F), and C-F and control groups (positive and negative)). CRAB was administered to mice through intraperitoneal injection. Three hours later, C, F, and MSC were given intraperitoneally to the treatment groups. Colistin administration was repeated every 12 h, F administration was done every 4 h, and the second dose of MSC was administered after 48 h. Mice were sacrificed at 24 and 72 h. The bacterial load was determined as colony-forming units per gram (cfu/g). Histopathological examination was conducted on the left lung, liver, and both kidneys. IL-6 and C-reactive protein (CRP) levels in mouse sera were determined by enzyme-linked immunosorbent assay. RESULTS: Among the treatment groups, the C-F group had the lowest colony count in the lung (1.24 ± 1.66 cfu/g) and liver (1.03 ± 1.08 cfu/g). The highest bacterial clearance was observed at 72 h compared to 24 h in the MSC-treated groups (p = 0.008). The MSC + C-F group showed the lowest histopathological score in the liver and kidney (p = 0.009). In the negative control group, the IL-6 level at the 24th hour was the lowest (p < 0.001). Among the treatment groups, the CRP level was the lowest in the MSC + C-F group at 24 and 72 h. CONCLUSION: In a CRAB sepsis model, adding MSCs to a colistin-fosfomycin treatment may be beneficial in terms of reducing bacterial loads and preventing histopathological damage.

Severe and complicated soft tissue infections: a single-centre case series.

OBJECTIVE: To assess the demographic and clinical characteristics, laboratory findings, and economic burden of patients with a diagnosis of complicated skin and soft tissue infection (cSSTI). METHOD: The demographic and clinical characteristics, laboratory findings, surgical interventions, cost of treatment, and outcome of patients diagnosed with cSSTIs between January 2017 and December 2019 were retrospectively analysed. RESULTS: A total of 24 patients with cSSTIs were included in the study. The median age was 53 (22-85) years, and 14 (58%) were female. The most common comorbidity was diabetes (54%). On admission, 75% of patients presented with sepsis, and 70% had a high-grade Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score. The causative microorganism was isolated from 21 (87%) patients, and the multidrug resistance rate of Gram-negative bacteria was 50%. The median number of debridements was 3 (1-12). In all, 11 patients were followed up in the intensive care unit, and the mortality rate was 29%. The presence of confusion (p=0.025), causative Gram-negative microorganisms (p=0.009), hyponatraemia (p=0.034), the need for intensive care (p=0.001), anti-meticillin-resistant Staphylococcus aureus antibiotics (p=0.023) and the rate of antibiotic changes during treatment (p=0.019) were significantly higher in the non-survival patient group. Hyponatraemia was a significant independent risk factor for mortality (p=0.048). The median cost of per-patient treatment was $9453 USD in the non-surviving and $1536 in the surviving group. CONCLUSION: It is important to know possible factors and local resistance rates at the beginning of empirical antibacterial and surgical treatment. The presence of hyponatraemia, sepsis and a high LRINEC score can be considered to be the mortality predictors.

Investigation of pituitary functions after acute coronavirus disease 2019.

Although coronavirus disease 2019 (COVID-19) mainly involves the lungs, it also affects many systems. The hypothalamic/pituitary axis is vulnerable to hypoxia, hypercoagulation, endothelial dysfunction and autoimmune changes induced by COVID-19 infection. Given that there is no extensive investigation on this issue, we investigated the pituitary functions three to seven months after acute COVID-19 infection. Forty-three patients after diagnosis of COVID-19 infection and 11 healthy volunteers were included in the study. In addition to the basal pituitary hormone levels, growth hormone (GH) and hypothalamo-pituitary adrenal (HPA) axes were evaluated by glucagon stimulation test (GST) and low-dose adrenocorticotropic hormone (ACTH) stimulation test, respectively. The peak cortisol responses to low-dose ACTH test were insufficient in seven (16.2%) patients. Twenty (46.5%) and four (9.3%) patients had inadequate GH and cortisol responses to GST, respectively. Serum insulin-like growth factor-1 (IGF-1) values were also lower than age and sex-matched references in four (9.3%) patients. The peak GH responses to GST were lower in the patient group when compared to the control group. Other abnormalities were mild thyroid-stimulating hormone elevation in four (9.3%) patients, mild prolactin elevation in two (4.6%) patients and central hypogonadism in four (9.3%) patients. Mean total testosterone values were lower in male patients when compared to male controls; however, the difference was not significant. These findings suggest that COVID-19 infection may affect pituitary functions, particularly the HPA and GH axes. These insufficiencies should be kept in mind in post-COVID follow-up. Long-term data are needed to determine whether these deficiencies are permanent or not.

Determination of Risk Factors for Infectious Diarrhea in Patients with Hematological Malignancy.

BACKGROUND: This study aimed to determine the risk factors of infectious diarrhea in patients undergoing chemotherapy or hematopoietic stem cell transplantation for hematological malignancies. MATERIALS AND METHODS: This was a prospective, observational study. Patients in whom the infectious agent was determined by laboratory examination were considered to have infectious diarrhea. Patients with diarrhea were categorized as infectious or unidentified and compared in terms of demographic data, treatments, risk factors, laboratory findings, and prognosis. RESULTS: A total of 838 patients were hospitalized, among which 105 patients who met the inclusion criteria were included (12.5%). The patients were divided into two groups: 67 (63.8%) with unidentified diarrhea and 38 (36.2%) with infectious diarrhea. There were no differences between these groups in terms of age, sex, types of hematological malignancies, and presence of comorbidities. The most commonly isolated microorganism was Clostridioides difficile (12.4%). The rate of corticosteroid use was higher in the group with infectious diarrhea (39.5%) than in the group with unidentified diarrhea (7.5%) (P <0.001). The rate of granulocyte colony-stimulating factor (GCSF) use was higher in patients with unidentified diarrhea than in patients with infectious diarrhea (67.2% vs. 42.1%, P=0.022). The median duration of diarrhea was 9 (4-10) days in the group with infectious diarrhea and 5 (3-8) days in the group with unidentified diarrhea (P=0.012). According to the multivariate logistic regression model, corticosteroid treatment increased the risk of infectious diarrhea by a 4.75-fold (95% confidence interval [CI], 1.32-17.02) times. Moreover, the duration of diarrhea may result in a 1.15 (95% CI, 1.02-1.31) fold increase in the risk of infectious diarrhea, while GCSF treatment had a 2.84 (1/0.35) (95% CI, 0.12-0.96) fold risk-reducing effect against infectious diarrhea. CONCLUSION: Infectious diarrhea lasts longer than unidentified diarrhea in patients with hematological malignancies. Although corticosteroid use is a risk factor for developing infectious diarrhea, GCSF use has a protective effect.

Risk factors and mortality rates of carbapenem-resistant Gram-negative bacterial infections in intensive care units.

Background: The prevalence of hospital-acquired infections caused by carbapenem-resistant gram-negative bacteria (CRGNB) is increasing worldwide. Several risk factors have been associated with such infections. The present study aimed to identify risk factors and determine the mortality rates associated with CRGNB infections in intensive care units. Methods: This retrospective case-control study was conducted at Erciyes University Hospital (Kayseri, Turkey) between January 2017 and December 2021. Demographic and laboratory data were obtained from the Infection Control Committee data and record system. Patients who had CRGNB infection 48-72 h after hospitalization were assigned to the case group, while those who were not infected with CRGNB during hospitalization formed the control group. Risk factors, comorbidity, demographic data, and mortality rates were compared between the two groups. Results: Approximately 1449 patients (8.97%) were monitored during the active follow-up period; of those, 1171 patients were included in this analysis. CRGNB infection developed in 14 patients (70.00%) who had CRGNB colonization at admission; in 162 (78.26%) were colonized during hospitalization, whereas 515 (54.56%) were not colonized. There was no significant difference in age, sex (male/female) or comorbidities. The total length of hospital stay was statistically significantly longer (P=0.001) in the case group (median: 24 [interquartile range: 3-378] days) than the control group (median: 16 [interquartile range: 3-135] days). The rates of colonization at admission (25.5%; vs. 10.6%, P=0.001) and mortality (64.4% vs. 45.8%, P=0.001) were also significantly higher in the cases than in the control group, respectively. In the univariate analysis, prolonged hospitalization, the time from intensive care unit admission to the development of infection, presence of CRGNB colonization at admission, transfer from other hospitals, previous antibiotic use, enteral nutrition, transfusion, hemodialysis, mechanical ventilation, tracheostomy, reintubation, central venous catheter, arterial catheterization, chest tube, total parenteral nutrition, nasogastric tube use, and bronchoscopy procedures were significantly associated with CRGNB infections (P <0.05). Multivariate analysis identified the total length of stay in the hospital (odds ratio [OR]=1.02; 95% confidence interval [CI]: 1.01 to 1.03; P=0.001), colonization (OR=2.19; 95% CI: 1.53 to 3.13; P=0.001), previous antibiotic use (OR=2.36; 95% CI: 1.53 to 3.62; P=0.001), intubation (OR=1.59; 95% CI: 1.14 to 2.20; P=0.006), tracheostomy (OR=1.42; 95% CI: 1.01 to 1.99; P=0.047), and central venous catheter use (OR=1.62; 95% CI: 1.20 to 2.19; P=0.002) as the most important risk factors for CRGNB infection. Conclusions: Colonization, previous use of antibiotics, and invasive interventions were recognized as the most important risk factors for infections. Future research should focus on measures for the control of these parameters.

Identification, molecular characterization, and antifungal susceptibility of Cyberlindnera fabianii strains isolated from urinary tract.

OBJECTIVES: Cyberlindnera fabianii is an opportunistic pathogen isolated from clinical specimens. It can be incorrectly identified as Candida utulis by phenotypic methods. This study aimed to accurately identify Cy.fabianii strains isolated from the urinary tract, and to determine their molecular characterization and antifungal susceptibilities as well. METHODS: Twenty-nine yeast strains isolated from urinary tract samples were studied. Strains were identified by phenotypically, sequence analysis and MALDI-TOF MS. Sequence analysis using different gene regions (ITS1-2,D1/D2,EF-1-alpha) in ribosomal DNA was performed for the molecular analysis. Phylogenetic analysis was done by the neighbor-joining method. Antifungal susceptibilities of strains were determined for nine antifungals by reference broth microdilution and the Sensititre YeastOne broth microdilution method (SensititreTMYeastOneTMAST Plate, Thermo Fisher Scientific™,USA) according to CLSI M60-Ed2 recommendations. RESULTS: All strains were identified as C.utulis phenotypically by conventional methods, however all strains were identified as Cy.fabianii by sequence analysis and MALDI-TOF MS. It was observed that the gene regions examined in terms of determining evolutionary relatedness did not show intraspecies nucleotide variations. In all strains, the MIC50/MIC90 values for fluconazole were higher than the other antifungals tested. CONCLUSION: Cy.fabianii should be considered in fluconazole-resistant urinary tract yeast infections. Although conventional phenotypical methods were insufficient to identify Cy.fabianii, it could be correctly identified with sequence analysis using different gene regions (ITS1-2,D1/D2,EF-1-alpha) in ribosomal DNA and MALDI-TOF MS.

Safety and immunogenicity of an inactivated whole virion SARS-CoV-2 vaccine, TURKOVAC, in healthy adults: Interim results from randomised, double-blind, placebo-controlled phase 1 and 2 trials.

BACKGROUND: Development of safe and effective vaccine options is crucial to the success of fight against COVID-19 pandemic. Herein, we report interim safety and immunogenicity findings of the phase 1&2 trials of ERUCoV-VAC, an inactivated whole virion SARS-CoV-2 vaccine. METHODS: Double-blind, randomised, single centre, phase 1 and 2 trials included SARS-CoV-2 seronegative healthy adults aged 18-55 years (18-64 in phase 2). All participants, except the first 4 in phase 1 who received ERUCoV-VAC 3 µg or 6 µg unblinded and monitored for 7 days for safety purposes, were assigned to receive two intramuscular doses of ERUCoV-VAC 3 µg or 6 µg (an inactivated vaccine containing alhydrogel as adjuvant) or placebo 21 days apart (28 days in phase 2) according to computer-generated randomisation schemes. Both trials are registered at ClinicalTrials.gov (phase 1, NCT04691947 and phase 2, NCT04824391). RESULTS: Forty-four participants (3 µg [n:17], 6 µg [n:17], placebo [n:10]) in phase 1 and 250 (3 µg [n:100], 6 µg [n:100], placebo [n:50]) in phase 2 received ≥1 dose. In phase 1 trial, 25 adverse events AEs (80 % mild) occured in 15 participants (34.1 %) until day 43. There was no dose-response relationship noted in safety events in ERUCoV-VAC recipients (p = 0.4905). Pain at injection site was the most common AE (9/44;20.5 %). Both doses of ERUCoV-VAC 3 µg and 6 µg groups were comparable in inducing SARS-CoV-2 wild-type neutralising antibody (MNT50): GMTs (95 %CI) were 8.3 (6.4-10.3) vs. 8.6 (7.0-10.2) at day 43 (p = 0.7357) and 9.7 (6.0-13.4) vs. 10.8 (8.8-12.8) at day 60 (p = 0.8644), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wild-type neutralising antibody GMTs (95 %CI) were 8.4 (6.3-10.5) vs. 9.0 (7.2-10.8) at day 43 (p = 0.5393) and 11.0 (7.0-14.9) vs. 12.3 (10.3-14.5) at day 60 (p = 0.8578). Neutralising antibody seroconversion rates (95 %CI) were 86.7 % (59.5-98.3) vs 94.1 % (71.3-99.8) at day 43 (p = 0.8727) and 92.8 % (66.1-99.8) vs. 100 % (79.4-100.0) at day 60 (p = 0.8873), in ERUCoV-VAC 3 µg and 6 µg groups, respectively. In phase 2 trial, 268 AEs, (67.2 % moderate in severity) occured in 153 (61.2 %) participants. The most common local and systemic AEs were pain at injection site (23 events in 21 [8.4 %] subjects) and headache (56 events in 47 [18.8 %] subjects), respectively. Pain at injection site was the only AE with a significantly higher frequency in the ERUCoV-VAC groups than in the placebo arm in the phase 2 study (p = 0.0322). ERUCoV-VAC groups were comparable in frequency of AEs (p = 0.4587). ERUCoV-VAC 3 µg and 6 µg groups were comparable neutralising antibody (MNT50): GMTs (95 %CI) were 30.0 (37.9-22.0) vs. 34.9 (47.6-22.1) at day 43 (p = 0.0666) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60, (p = 0.2166), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wildtype neutralising antibody GMTs were 28.9 (20.0-37.7) and 30.1 (18.5-41.6) at day 43 (p = 0.3366) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60 (p = 0.8777). Neutralising antibody seroconversion rates (95 %CI) were 95.7 % (91.4-99.8) vs. 98.9 % (96.9-100.0) at day 43 (p = 0.8710) and 96.6 % (92.8-100.0) vs 98.9 % (96.7-100.0) at day 60 (p = 0.9129) in ERUCoV-VAC 3 µg and 6 µg groups, respectively. CONCLUSIONS: Two-dose regimens of ERUCoV-VAC 3 µg and 6 µg 28 days both had an acceptable safety and tolerability profile and elicited comparable neutralising antibody responses and seroconversion rates exceeding 95 % at day 43 and 60 after the first vaccination. Data availability Data will be made available on request.

Toxoplasmic encephalitis after allogeneic hematopoietic stem cell transplantation.

Cerebral toxoplasmosis is a rare but often life-threatening infection after hematopoietic stem cell transplantation (HSCT). In such cases, early diagnosis and initiation of treatment are vital. We describe a case of cerebral toxoplasmosis in a patient who underwent HSCT for acute myeloid leukemia. Infection was diagnosed with polymerase chain reaction (PCR) test of cerebrospinal fluid and cranial magnetic resonance imaging scan. The patient treated with trimethoprim-sulfamethoxazole and clindamycin combination. However, she died from nosocomial infection after 15 days of treatment. This life-threatening infection should be considered in a patient who is post-HSCT present with neurologic symptoms and brain lesions. PCR is an important and rapid diagnostic tool for toxoplasmosis. Cranial imaging scan and PCR should be used together to diagnosed.

Current therapeutic strategy in osteoarticular brucellosis.

Brucellosis is a common zoonotic disease with high morbidity. In the majority of human cases, the causative agent is B. melitensis. Infection is transmitted to humans by direct/indirect contact with the contaminated animal products (e.g., consumption of unpasteurized milk), infectious aerosols and aborted fetus. Brucellosis often affects middle-aged adults and young people. Patients with brucellosis tend to have non-specific symptoms, including fever, chills, night sweats, joint pain and myalgia. Brucellosis affects various organs and tissues. The osteoarticular system is one of the most commonly described affected systems in humans. In several clinical studies, the prevalence of Osteoarticular Brucellosis (OB) is reported as 2-77%. Most important osteoarticular clinical forms osteomyelitis, spondylitis, sacroiliitis, arthritis and bursitis. Spondylitis and spondylodiscitis are the most frequent complications. Spondylodiscitis often affects the lumbar (especially at the L4- L5 levels) and low thoracic vertebrae than the cervical spine. Back pain and sciatica radiculopathy are the most common complaints about patients. Sacroiliitis is associated with severe pain, especially back pain in affected individuals. Spinal destructive brucellar lesions are also reported in adults in previous studies. Brucellosis is diagnosed with clinical inflammatory signs (eg. tenderness, pain) of the affected joints together with positive serological tests and positive blood/synovial fluids cultures. Serological test measures the total amount of IgM/IgG antibodies. Standard agglutination test (SAT) titer ≥1:160 is in favor of brucellosis diagnosis. Enzyme-Linked Immunosorbent Assay (ELISA) and Polymerase chain reaction (PCR) are other types of diagnostic tests. Radiological assessments, such as joint sonography, computed tomography, magnetic resonance imaging, are the most helpful radiological methods to diagnose spinal brucellosis. The agents commonly used in the treatment of brucella spondylitis are doxycycline, streptomycin, gentamicin, ciprofloxacin, trimethoprim/sulfamethoxazole and rifampicin. The recommended regimens for treatment of brucella involve two or three antibiotics combinations. No standard treatment, physicians prescribe drugs based on conditions of the disease. Patients need a long-term (usually at three months) antibiotic therapy for mainly aiming to prevent relapses. Surgery may be required for patients with spinal abscess. This review focused on physicians' awareness for osteoarticular involvement, clinical presentation, diagnosis and current treatment of OB.