Molecular characterisation of colistin and carbapenem-resistant clinical isolates of Acinetobacter baumannii from Southeast Europe.

OBJECTIVES: To characterise 11 colistin- and carbapenem-resistant Acinetobacter baumannii isolates recently emerging in hospital settings. METHODS: A. baumannii isolates were collected from hospitalised patients under colistin treatment in three countries of Southeast Europe: Turkey, Croatia, and Bosnia and Herzegovina. Isolates were identified using molecular methods. RESULTS: Isolates from Turkey and Croatia belong to the sequence types ST195 or ST281 of the clone lineage 2, while the single isolate from Bosnia and Herzegovina belongs to the ST231 of clone lineage 1. All isolates turned out to be highly resistant to colistin (MIC ≥ 16 mg/L) and have point mutations in pmrCAB operon genes. The colistin-resistant isolate from Bosnia and Herzegovina had a unique P170L point mutation in the pmrB gene and the R125H point mutation in the pmrC gene. The L20S mutation in the pmrA gene was detected only in isolates from Croatia and has never been reported before in isolates from this country. CONCLUSION: Colistin resistance in A. baumannii in hospitalised patients receiving colistin treatment is a result of chromosomal mutations. The pattern of point mutations in pmrCAB genes suggests a spread of specific colistin-resistant isolates within the hospital.

COVID-19 in cancer patients: patient characteristics and outcomes in the post-COVID-19 vaccination period.

Background/aim: It wasaimed herein to investigate coronavirus disease (COVID-19) in cancer patients and compare hematological and solid organ cancer patients in terms of the course and outcome of this disease. Materials and methods: Data from cancer patients with laboratory-confirmed COVID-19 infection were analyzed retrospectively. Risk factors for poor prognosis and the effect of vaccination on the clinical outcomes of the patients were evaluated. Results: A total of 403 cancer patients who were diagnosed with COVID-19 between March 1st, 2021, and November 30th, 2022, were included, of whom 329 (81.6%) had solid and 74 (18.4%) had hematological cancers. Hospitalization and intensive care unit (ICU) admission rates were significantly higher in the hematological cancer patients compared to the solid organ cancer patients (73.0% vs. 35.9%, p< 0.001 and 25.7% vs. 14.0%, p= 0.013, respectively). The COVID-19-related case fatality rate (CFR) was defined as 15.4%, and it was higher in the hematologicalcancer patientsthan inthe solid organ cancer patients (23.0% vs. 13.7%, p= 0.045) and was higher in patients with metastatic/advanced disease compared to the other cancer stages (p< 0.001). In the solid organ cancergroup, hospitalization, ICU admission, and the COVID-19 CFR were higher in patients with respiratory and genitourinary cancers (p< 0.001). A total of 288 (71.8%) patients had receivedCOVID-19 vaccination; 164 (56.94%) had≤2 doses and 124 (43.06%) had≥3 doses. The hospitalization rate was higher in patients with ≤2 doses of vaccine compared to those with ≥3 doses (48.2% vs. 29.8%,p= 0.002). Patients with COVID-19-related death had higher levels of leucocyte, neutrophil, D-dimer, troponin, C-reactive protein (CRP), procalcitonin, and ferritin and lower levels of lymphocyte than the survivors. In the logistic regression analysis,the risk of COVID-19-related mortality was higher in the hematological cancer patients(OR:1.726), those who were male (OR:1.757), and with the Pre-Delta/Delta variants (OR:1.817). Conclusion: This study revealed that there is an increased risk of COVID-19-related serious events (hospitalization, ICU admission, or death) in patients with hematological cancerscompared with those who have solid organ cancers. It wasalso shown that receiving ≥3 doses of COVID-19 vaccine is more protective against severe illness and the need for hospitalization than ≤2 doses.

Evaluation of the synergistic effect of a combination of colistin and tigecycline against multidrug-resistant Acinetobacterbaumannii.

OBJECTIVE: Acinetobacter baumannii species cause nosocomial infections and can subsequently develop multidrug resistance (MDR). The objective of this study was to evaluate the susceptibility of A. baumannii to a novel combination of colistin and tigecycline, which may provide a faster and more efficacious treatment via a synergistic effect. METHODS: We included 50 MDR A. baumannii samples that were isolated in our clinics between 2009 and 2014. We used broth microdilution (BMD) and the E-test to evaluate the effects of colistin and tigecycline, and the E-test to assess the interaction of the colistin-tigecycline combination. The interaction between the two antibiotics was evaluated using the fractional inhibition concentration (FIC) index and was classified as follows: FIC≤0.5, synergistic; 0.5

Two cases with HSS/DRESS syndrome developing after prosthetic joint surgery: does vancomycin-laden bone cement play a role in this syndrome?

We report two cases of hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (HSS/DRESS) syndrome following systemic and local (via antibiotic laden bone cement (ALBC)) exposures to vancomycin. Both cases developed symptoms 2-4 weeks after the initiation of treatment. They responded to systemic corticosteroid treatment and were cured completely. Various drug groups may cause HSS/DRESS syndrome, and vancomycin-related cases do not exceed 2-5% of the reported cases. Almost all of these cases developed the syndrome following systemic exposure to vancomycin. ALBC seems to be the safer antibiotic administration method, as systemic antibiotic levels did not reach a toxic threshold level. However, local administration may not always be sufficient for bone-related/joint-related infections; these infections may require systemic antibiotics as well. As HSS/DRESS syndrome can mimic infectious diseases, it must be considered during differential diagnosis before suspecting failure of treatment and initiation of a different antibiotic course.

Relationship between cytokine gene polymorphisms and chronic hepatitis B virus infection.

Hepatitis B virus (HBV) infection is still a public health problem worldwide, being endemic in some parts of the world. It can lead to serious liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular cancer. The differences in host immune response can be one of the reasons for the various clinical presentations of HBV infection. Polymorphisms of genes encoding the proinflammatory and antiinflammatory cytokines, which are responsible for regulation of the immune response, can affect the clinical presentation of the infection. Particularly, the polymorphisms of the genes encoding cytokines such as interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, IL-28B, interferon-γ, tumor necrosis factor-α, tumor growth factor-ß1, and regulatory molecules like vitamin D receptor and chemokine receptor 5 can be responsible for different clinical presentations of HBV infections. The genomic information about cytokines and other mediators can be important for determining high-risk people for developing chronic hepatitis or hepatocellular cancer and may be used to plan treatment and preventive approaches for these people. In this review, the current knowledge in the literature on the association between cytokine/regulatory molecule gene polymorphisms and clinical course of chronic HBV infection is summarized, and the clinical implementations and future prospects regarding this knowledge are discussed.

Vitamin D and Tumor Necrosis Factor-Alpha Receptor Gene Polymorphisms in Various Hepatitis B Clinical Conditions in Turkey.

BACKGROUND: The aim is to define the role of single nucleotide polymorphism on the progress of hepatitis B virus (HBV) infection. We evaluated polymorphisms of TNF-α-308, Vitamin D receptor Apa I and Taq I gene in patients with HBV infection. METHODS: All subjects included were older than 18 years old. Sixty three patients had chronic HBV infection, 61 were HBsAg positive carriers and 59 were positive for anti-HBs and anti-HBc. Gene polymorphisms were evaluated by Amplification Refractory Mutation System PCR. For patients with chronic hepatitis, viral load, ALT levels, and histopathological evaluation of the liver were also compared. RESULTS: Gender distribution was not different among groups; however, anti-HBs positive patients were significantly older than the other patients. ALT levels and viral load were significantly higher in chronic hepatitis group than the asymptomatic carriers group. Vitamin D receptor Apa I gene and Taq I gene and TNF-α -308 gene variant alleles were not different in all three groups. Variant alleles of three genes were not different in subgroups of chronic hepatitis patients formed according to ALT levels, viral load, histological activity index, and fibrosis score. CONCLUSIONS: Role of single nucleotide polymorphism in clinical status of various HBV infection states was not shown in this study. Considering the other studies performed with this aim, which strengthens the notion that ethnicity is an important factor, future studies with more patients from different ethnic groups may help to clear the role of polymorphisms in the clinical progress of HBV infection.

Lamivudine resistance in untreated chronic hepatitis B patients in Turkey.

BACKGROUND/AIMS: Hepatitis B virus infection is an epidemiological problem throughout the world, including in Turkey. Lamivudine is one of the hepatitis B virus reverse-transcriptase inhibitors used for the treatment of chronic hepatitis B virus infection. Lamivudine resistance can develop not only following treatment; it can also be seen in untreated patients. This resistance is related with structural changes in the tyrosine-methionine- aspartate-aspartate motif of the polymerase enzyme gene. Our objective was to evaluate the prevalence of lamivudine resistance in Turkish chronic hepatitis B virus-infected patients with D genotype before antiviral treatment. METHODS: Seventyseven patients with chronic hepatitis B virus infection were evaluated for viral loads, HBeAg, anti-HBe antibody, ALT levels, histological activity index, and tyrosine-methionine-aspartateaspartate mutations. RESULTS: Tyrosine-methionine-aspartateaspartate motif mutations were determined in 3 of 24 HBeAg positive and 3 of 53 anti-HBe positive patients with a rate of 7.8%. Two of the mutations were YIDD and 4 were YVDD. Median ALT value in patients with mutations was 88 IU/L (range 55-276) and histological activity index was 9 (range 6-10); these values in patients without mutations were 58 (range 19- 176) and 10 (range 2-18), respectively. Knodell fibrosis scores of patients were as follows: 0: 13.2%, 1: 28.9%, 2: 21.1%, 3: 34.2%, and 4: 2.6%. There were no significant differences between the patients regarding Knodell fibrosis scores. One patient was diagnosed as cirrhosis. CONCLUSIONS: Evaluation of chronic hepatitis B virus patients for lamivudine resistance and planning the treatment accordingly may prevent complications and can increase the effectiveness of the treatment.

Evaluation of serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha in patients with Crimean-Congo hemorrhagic fever.

We investigated the role played by cytokines in the mortality of patients with Crimean-Congo hemorrhagic fever (CCHF). Serum levels of several cytokines were measured in 3 patients with fatal CCHF and in 27 patients with nonfatal CCHF. Levels of interleukin (IL)-6 (P< or = .001) and tumor necrosis factor (TNF)-alpha (P = .004) were significantly higher in patients with fatal CCHF than in patients with nonfatal CCHF, whereas levels of IL-10 were not significantly different between the 2 groups (P = .937). Disseminated intravascular coagulation (DIC) scores were also higher in the patients with fatal CCHF (P = .023). Levels of IL-6 and TNF-alpha were positively correlated with DIC scores, whereas levels of IL-10 were negatively correlated with DIC scores. In conclusion, these findings demonstrate that proinflammatory cytokines play a major role in the mortality of patients with CCHF.