Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call.

OBJECTIVES: KPC-2-producing Klebsiella pneumoniae (KPC-KP) ST258 has been rapidly expanding and is often associated with serious nosocomial infections. Last-line antibiotics such as colistin and tigecycline often remain the only treatment option. We describe here the evolving genetic background of KPC-KP isolates in Crete, Greece. METHODS: We tested the antibiotic susceptibility of 34 clinical isolates from patients hospitalized in 2010 and 2013-14. Whole-genome sequences of these isolates were analysed for acquired resistance genes and gene mutations. RESULTS: All KPC-KP isolates belonged to ST258 with the exception of one ST147 isolate. From 2014, 26% of isolates were non-susceptible to all antibiotics, compared with 0 of 11 isolates from 2010. Colistin resistance was associated with mutations in mgrB, which was present in 61% of isolates from 2014. Core-genome MLST analysis showed that pan-resistant isolates were closely related and appeared in two separate clusters. CONCLUSIONS: KPC-KP is rapidly evolving to pan-resistance in Crete. We identified molecular resistance markers for pan-resistant isolates and showed that core-genome MLST is a promising tool for molecular fingerprinting of KPC-KP ST258.

Infections by pandrug-resistant gram-negative bacteria: clinical profile, therapeutic management, and outcome in a series of 21 patients.

Clinical reports on infections by pandrug-resistant (PDR) bacteria are scarce. This observational case series study was conducted during a 2-year period at a university hospital. Patients infected by PDR gram-negative bacteria comprised the study cohort. An isolate was defined as PDR if it was resistant to all antibiotic classes available for empirical treatment. A total of 21 patients infected by PDR gram-negative bacteria were recorded. The mean APACHE II score on admission was 18.8, the mean Charlson comorbidity index was 2.9, and 20 (95.2%) patients had a history of intensive care unit hospitalization. All patients had recent exposure to multiple antibiotics (median, 6 antibiotic groups). Infections occurred at a mean of 41.5 days after admission. The mean length of stay after infection was 54.6 days and 5 (23.8%) patients died due to the infection. Treatment was mainly based on a colistin-containing regimen (47.6%) or tigecycline (33.3%). All patients treated with tigecycline had total resolution of the infection and a notably shorter length of hospital stay after infection. In conclusion, PDR gram-negative bacterial infections are associated with considerable prolongation of hospitalization and mortality, although the mortality is not as high as that expected. Tigecycline appears to be effective for the successful treatment of PDR infections

Gram-negative bacteria as emerging pathogens affecting mortality in skin and soft tissue infections.

INTRODUCTION: Skin and soft tissue infections (SSTIs) are commonly encountered in clinical practice and mainly caused by gram-positive cocci such as S.aureus and ß-hemolytic streptococci. Complicated SSTIs involving deeper tissues often necessitate surgical intervention and occur in patients with significant comorbidities such as diabetes or immunocompromising conditions. METHODS: In this study, we retrospectively reviewed the epidemiology, clinical characteristics, microbiology, and treatment of patients admitted with SSTI during a five-year period in the Internal Medicine Department of a tertiary hospital. RESULTS: During the study period, 317 patients were recorded, with a mean age of 72.1 years. The most common underlying medical conditions were diabetes mellitus, chronic kidney disease, and heart failure. Cultures were positive in 23.3 % of cases, 62.2 % of which were polymicrobial. The most frequently isolated microorganisms were Enterococci, Escherichia coli, and Pseudomonas aeruginosa. Significant antimicrobial resistance rates were noted, in particular for gram-negative microorganisms. Mortality was higher than described in the literature and associated with age, comorbidities, and infection by gram-negative microorganisms. CONCLUSION: This study denotes the role of gram-negative bacteria in SSTI epidemiology. Therapeutic protocols regarding the empiric treatment of SSTIs should necessarily take into account the local epidemiology of isolated pathogens and antimicrobial resistance. HIPPOKRATIA 2018, 22(1): 23-28.

Serum BAFF levels are related to angiogenesis and prognosis in patients with multiple myeloma.

B-cell activating factor (BAFF) is a B-cell growth factor. We measured its serum levels and correlated them with parameters of disease activity, as serum levels of tumor necrosis factor-α and lactate dehydrogenase, bone marrow microvascular density and proliferating cell nuclear antigen expression, in 50 myeloma patients, in 22 of them in plateau phase and in 20 controls. All of them were higher in patients and in advanced disease while reduced in plateau phase. BAFF correlated with all the above markers. Higher BAFF levels predicted a shorter survival, suggesting an important prognostic marker and a possible therapeutic target in myeloma.

Serum concentrations and clinical significance of soluble CD40 ligand in patients with multiple myeloma.

Multiple myeloma (MM) is a disease of plasma cells that express the CD40 receptor. Binding of the CD40 by its natural ligand, CD40 ligand (CD40L), produces growth arrest and/or apoptosis in MM. To evaluate serum levels of soluble CD40L (sCD40L) in MM patients and to correlate them with markers of disease activity and angiogenesis, such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), interleukin-6 (IL-6), proliferation marker Ki-67 proliferation index (Ki-67 PI) and bone marrow plasma cell infiltration, fifty-eight MM patients were studied in diagnosis and 43 of them after completion of treatment. Serum levels of sCD40L, VEGF, HGF and IL-6 were measured by ELISA, whereas Ki-67 PI and bone marrow plasma cell infiltration were measured by immunohistochemistry. Pre-treatment levels of sCD40L in MM patients were higher compared to controls and to their levels after effective treatment. Treatment regimen did not affect the degree of reduction of sCD40L levels, whereas patient in partial remission had increased levels compared to those with better response. Significant differences were found among disease stages. There were also positive correlations between CD40L with HGF, VEGF, IL-6 and Ki-67 PI. Elevated serum sCD40L is found in patients with advanced MM stage and can be reduced after effective treatment. Increased levels of this mediator are correlated with angiogenic cytokines, providing evidences that CD40L/CD40 interactions play a significant role in the mechanisms of angiogenesis in MM patients.