Tsioutis, Constantinos

Limited data exist regarding prognostic factors and optimal antimicrobial treatment of infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). This retrospective cohort study included 93 adult patients who developed ventilator-associated pneumonia (VAP) due to XDR-AB in the ICU of the University Hospital of Heraklion, Greece, from October 2012 to April 2015. XDR-AB isolates were mainly susceptible to colistin (93.5%) and tigecycline (25.8%), whereas 6 (6.5%) were pandrug-resistant. Prior to infection, patients had long durations of mechanical ventilation and hospital stay and multiple exposures to antibiotics. Median Charlson co-morbidity and APACHE II scores were 2 and 17, respectively. Mortality at 28 days of infection onset was high (34.4%) despite high rates of in-vitro-active empirical (81.7%) and definitive (90.3%) treatment. Active colistin-based combination therapy (n = 55) and monotherapy (n = 29) groups had similar 28-day mortality (27.6% vs. 30.9%, respectively) and Kaplan–Meier survival estimates over time. In multivariable Cox regression, advanced age (aHR = 1.05 per year increase, 95% CI 1.02–1.09), rapidly fatal underlying disease (aHR = 2.64, 95% CI 0.98–9.17) and APACHE II score (aHR = 1.06 per unit increase, 95% CI 0.99–1.14) were identified as independent predictors of 28-day mortality, but no difference in mortality hazards between the active colistin-based combination therapy and monotherapy groups was produced (aHR = 0.88, 95% CI 0.35–2.38). These results support the use of colistin as a first-line agent against VAP in settings where XDR-AB is endemic, but oppose the introduction of colistin-based combination therapy as standard treatment.

Irritable bowel syndrome (IBS) is the most common reason to visit a gastroenterologist. IBS was believed to be a functional disease, but many possible pathophysiologic mechanisms can now explain the symptoms. IBS patients are classified into subtypes according to their predominant bowel habit, based on the Rome IV criteria. These include diarrhea-predominant and constipation-predominant IBS, as well as the mixed type, a combination of the two. Usually, IBS treatment is based on the predominant symptoms, with many options for each subtype. A new promising treatment option, fecal microbiota transplantation, seems to have beneficial effects on IBS. However, treating the pathophysiological causative agent responsible for the symptoms is an emerging approach. Therefore, before the appropriate therapeutic option is chosen for treating IBS, a clinical evaluation of its pathophysiology should be performed.

Data concerning clinical characteristics, microbiology, treatment and outcomes of external ventricular drainage-associated infections (EVDAI) are limited. All hospitalized patients with EVDAI in a University Hospital between January 2009 and December 2015 were retrospective recorded. Only the first episode per patient was included. An antibiotic was considered “active” when its pharmacokinetic properties were appropriate for EVDAI and the implicated microorganism was in vitro susceptible. During the 7-year study period, 36 EVDAI were identified. Median patient age was 53years and 23 (63.9%) were male. Catheter types were intraventricular (70.6%) and lumbar (29.4%). Median catheterization duration before infection was 14days. Gram-negative bacteria (GNB) predominated (57.9%), followed by gram-positives (36.8%) and fungi (5.3%). Administered antibiotics were considered “active” in 69.4% of empirical and in 86.1% of definitive treatment regimens. In 10 infections, intraventricular/intrathecal (IVT) antibiotics were administered. Eleven patients died (30.6%) during hospitalization. Patients who died had higher rates of EVDAI by GNB (p=0.011) and higher rates of treatment with intravenous colistin (p=0.019 for empirical and p=0.006 for definitive colistin). Compared to EVDAI by other pathogens, patients with EVDAI by GNB had longer catheter-days before infection (p<0.001) and higher mortality (p=0.011). In our study, GNB were a frequent cause of EVDAI, and were related with high rates of inactive treatment and mortality. Intravenous colistin alone is not effective and treatment should include IVT antibiotics and intravenous antibiotics that achieve adequate CSF levels.

Murine or endemic typhus, a febrile disease caused by Rickettsia typhi, is often misdiagnosed due to its non-specific presentation. We sought to evaluate all available evidence in the literature regarding the clinical and laboratory manifestations, epidemiological characteristics, and outcomes of murine typhus. Pubmed was searched for all articles providing available data. In an effort to incorporate contemporary data, only studies from 1980 were included. Thirty-three case series including 2074 patients were included in final analysis. Available evidence suggests that the classic triad of fever, headache and rash is encountered in only one-third of patients. Other frequent symptoms were chills, malaise, myalgia, and anorexia. A tetrad of reported laboratory abnormalities consisting of elevated liver enzymes, lactate dehydrogenase, erythrocyte sedimentation rate and hypoalbuminemia was detected. Complications were observed in one-fourth of patients, reported mortality was extremely low, but untreated patients had notably longer duration of fever. Among epidemiological characteristics, a seasonal distribution with most cases reported during warmer months, was the most prominent finding. Murine typhus in children exhibits several different characteristics, with abdominal pain, diarrhea, and sore throat reported more commonly, higher frequency of anemia, lower frequency of hypoalbuminemia, hematuria and proteinuria and a much lower rate of complications. This systematic review of published evidence provides a thorough description of the clinical and laboratory features of murine typhus and highlights important differences in children.

Infections by Gram-positive pathogens pose a public health risk, especially due to increasing antibiotic resistance. Daptomycin has efficacy against most clinically important Gram-positive bacteria. Although experience regarding use of daptomycin in adults is increasing, studies on pediatric populations are limited.We aimed to evaluate the efficacy, safety, and pharmacokinetics of daptomycin in pediatric settings. We searched MEDLINE and Clinicaltrials.gov (through April 2016) and included 29 original studies in the final analysis. Available evidence suggests that daptomycin in pediatric patients has a favorable safety and tolerability profile and is an efficacious alternative for treatment of Gram-positive bacteremia, endocarditis, and infections of the skin, soft tissues, joints, and bones, especially when resistant strains are involved. However, future studies need to address several issues to determine the optimal dose and various pharmacokinetic parameters in different pediatric age groups.

mcr-1 has been reported as the first plasmid-encoded gene conferring colistin resistance. In KPC-producing Klebsiella pneumoniae (KPC-KP), however, colistin resistance is rapidly emerging through other mechanisms. Resistance is frequently due to disruption of the mgrB gene by insertion sequences, e.g. ISL3. The aim of this study was to investigate the expansion of mgrB-mutated KPC-KP isolates. In addition, the localisation and targets of ISL3 sequences within the core and accessory genome of common KPC-KP lineages were identified. A total of 29 clinical K. pneumoniae isolates collected from Italian patients were randomly selected. Whole genome sequences were analysed for resistance genes, plasmids and insertion sequences. In addition, 27 colistin-resistant KPC-KP isolates from a previous study from Crete (Greece) were assessed. Clonal expansion of KPC-KP isolates with various mutations in mgrB among all lineages was observed. In two Italian MLST ST512 isolates and eight Greek ST258 isolates, an identical copy of ISL3 was inserted in mgrB nucleotide position 133. ISL3, a transposable restriction–modification system of 8154 nucleotides, was located on pKpQIL-like plasmids and may transpose into the chromosome. In four isolates, chromosomal integration of ISL3 in diverse inner membrane proteins other than mgrB was identified. Colistin resistance is most often explained by clonal expansion of isolates with mutated mgrB. pKpQIL-like plasmids, which are omnipresent in KPC-KP, carry insertion sequences such as ISL3 that have mgrB as a target hotspot for transposition. Transposition of insertion sequences from plasmids and subsequent clonal expansion may contribute to the emerging colistin resistance in KPC-KP.

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.

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.

A 54-year-old otherwise healthy male, who was being evaluated for prolonged fever, developed clinical and ultrasonographic signs compatible with acute acalculous cholecystitis. Diagnosis of murine typhus was confirmed by serology and the patient was treated with doxycycline. He improved rapidly and all clinical and laboratory abnormalities returned to normal. The present case dictates that knowledge of the local epidemiology and keeping a high index of clinical suspicion can help recognize uncommon manifestations of murine typhus, in order to treat appropriately and avoid unnecessary investigations and interventions.

Background: The characteristics of Rickettsia typhi infection in elderly patients have not been extensively described in the literature. Methods: We conducted a prospective study on murine typhus in patients > 65 years old in two endemic areas of Greece. Results: Forty-nine elderly patients were analyzed, including 30 (61.2%) males. The clinical triad of fever (100% of patients), headache (83.7%), and rash (73.5%), occurred in 63% of patients, whereas malaise (85.7%), anorexia (65.3%), and myalgia (59.2%) were also common. Frequent laboratory findings were transaminasemia (89.8%), lactate dehydrogenase elevation (65.3%), hematuria (55.1%), thrombocytopenia (53.1%), anemia (51%), leucopenia (40.8%), and mild hyponatremia (23.5%). Complications developed in 16 patients (32.7%); no deaths were recorded. Conclusions: The main clinical and laboratory characteristics of murine typhus are similar in elderly and younger adults. However, elderly patients have a more severe clinical picture, evidenced by a higher complication rate and longer duration of fever, even with appropriate treatment. To our knowledge, this is the first study to focus on murine typhus in a geriatric population.