Antonios Papadopoulos

Effect of the Novel Influenza A (H1N1) Virus in the Human Immune System

Background The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. Methodology/Principal Findings Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-18, interferon (FN)-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs). Conclusions/Significance Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

HIV-positive patients treated with protease inhibitors have vascular changes resembling those observed in atherosclerotic cardiovascular disease.

A metabolic syndrome associated with atherosclerosis and cardiovascular disease has been described in HIV-positive individuals. In the present study we investigated whether HIV-positive individuals and CAD (coronary artery disease) patients have similarities in their vascular function and structure. In a case-control study, we compared measurements of carotid artery IMT (intima-media thickness) and brachial artery FMD (flow-mediated vasodilation) in HIV-positive individuals with age- and sex-matched controls with similar risk factors and patients with established CAD. Seventy-one HIV patients, age 42+/-13.9 years (91% male), were compared with 29 CAD patients and 25 controls. HIV patients had higher IMT than controls and similar IMT to CAD patients (0.64+/-0.2 compared with 0.55+/-0.05 and 0.66+/-0.08 mm respectively; F=4.2, P=0.01). Patients taking protease inhibitors had higher IMT (0.69+/-0.2 compared with 0.57+/-0.15 mm; P=0.01), blood pressure, cholesterol and triacylglycerols than those not taking protease inhibtors (P<0.05). In multiple regression analyses, increasing blood pressure (beta: 0.37, P=0.001), glucose (beta: 0.26, P=0.016), cholesterol (beta: 0.24, P=0.033), duration of HIV disease (beta: 0.33, P=0.008) and use of protease inhibitors (beta: 0.27, P=0.04) were the most important determinants of IMT respectively. FMD was associated only with triacylglycerol measurements. Patients with HIV present arterial changes resembling those found in patients with atherosclerotic cardiovascular disease. These vascular changes are closely related to protease-inhibitor-induced changes of metabolic parameters. Thus intensive treatment of these metabolic parameters might retard atherosclerosis in HIV patients.

Procalcitonin as an early indicator of outcome in sepsis: a prospective observational study

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT >0.12 ng/mL [P<0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT >0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission.

Bloodstream infections and sepsis in Greece: over-time change of epidemiology and impact of de-escalation on final outcome

BackgroundChoice of empirically prescribed antimicrobials for sepsis management depends on epidemiological factors. The epidemiology of sepsis in Greece was studied in two large-periods.MethodsSepsis due to bloodstream infections (BSI) from July 2006 until March 2013 was recorded in a multicenter study in 46 departments. Patients were divided into sepsis admitted in the emergencies and hospitalized in the general ward (GW) and sepsis developing after admission in the Intensive Care Unit (ICU). The primary endpoints were the changes of epidemiology and the factors related with BSIs by multidrug-resistant (MDR) pathogens; the secondary endpoint was the impact of de-escalation on antimicrobial therapy.Results754 patients were studied; 378 from 2006–2009 and 376 from 2010–2013. Major differences were recorded between periods in the GW. They involved increase of: sepsis severity; the incidence of underlying diseases; the incidence of polymicrobial infections; the emergence of Klebsiella pneumoniae as a pathogen; and mortality. Factors independently related with BSI by MDR pathogens were chronic hemofiltration, intake of antibiotics the last three months and residence into long-term care facilities. De-escalation in BSIs by fully susceptible Gram-negatives did not affect final outcome. Similar epidemiological differences were not found in the ICU; MDR Gram-negatives predominated in both periods.ConclusionsThe epidemiology of sepsis in Greece differs in the GW and in the ICU. De-escalation in the GW is a safe strategy.

No Effect of Pyridoxine on the Incidence of Myelosuppression during Prolonged Linezolid Treatment

Complications of long-term linezolid administration include anemia and thrombocytopenia. A recent report has suggested that pyridoxine may prevent myelosuppression. Pyridoxine was administered to 24 patients with bone infections who were being treated with linezolid. Thrombocytopenia occurred in 11 patients (45.8%), and anemia occurred in 6 (25%). We concluded that treatment wtih pyridoxine is unlikely to benefit patients who have been receiving linezolid for >2 weeks.

Association of Toll-Like Receptor 4 Asp299Gly and Thr399Ile Polymorphisms with Increased Infection Risk in Patients with Advanced HIV-1 Infection

BACKGROUND. The Toll-like receptor 4 (TLR4) is an essential component of the innate immune response to various microorganisms. We investigated the association between TLR4 polymorphism and the risk of acquiring severe infections, in patients with human immunodeficiency virus (HIV)-1 infection. METHODS. The presence of TLR4 Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs) was determined in a cohort of 199 HIV-1 infected patients and evaluated in relation to the occurrence of various infections. RESULTS. One hundred seventy-two patients were homozygous for the wild-type genotype; 22 patients (11%) were heterozygous for both SNPs; 4 were heterozygous for 1 polymorphism; 1 patient was heterozygous for the Asp299Gly SNP and homozygous for the Thr399Ile SNP. Of individuals with a nadir CD4 cell count of <100 cells/mm(3), those who carried both SNPs, compared with those who carried the wild-type genotype, demonstrated a >3-fold increase in the odds ratio (OR) of any serious infection (OR, 6.33 vs OR, 1.83, P = .043). CONCLUSIONS. This study suggests an association between the presence of TLR4 Asp299Gly and Thr399Ile polymorphisms and the occurrence of serious infections in HIV-1 infected patients with a history of nadir CD4 cell count of <100 cells/mm(3).

Efficacy and tolerability of linezolid in chronic osteomyelitis and prosthetic joint infections: a case-control study.

Abstract Clinical experience of prolonged use of linezolid in patients with bone infections is accumulating. However more efficacy and safety data are required. This is a case-control study of patients who received linezolid for difficult-to-treat, intolerant or resist-ant-to-other-antibiotics bone infections. Linezolid was administered i.v. or orally in 34 patients. Results concerning efficacy and safety were compared to a group of well-matched controls. The clinical arrest rate was 74% in the linezolid group and 68% in the control group (p=NS). Treatment was discontinued in 14 (44%) patients of the linezolid group and in 2 (6%) patients of the control group due to adverse events. In the linezolid group 11 (33%) patients developed anemia and 3 (9%) developed thrombocytopenia that led to discontinuation of treatment. Linezolid is effective in a substantial proportion of patients, but the incidence of hematologic adverse events makes close follow-up and laboratory monitoring mandatory.

Efficacy of teicoplanin for the prevention of surgical site infections after total hip or knee arthroplasty: a prospective, open-label study

A prospective randomised study was conducted in three centres to evaluate the efficacy of teicoplanin as antimicrobial prophylaxis for arthroplasties. From a total of 616 patients undergoing total hip or knee arthroplasty, 278 patients operated on in one centre were administered a single dose of 10mg/kg teicoplanin upon introduction of anaesthesia and the remaining 338 patients operated on in the other two centres were administered multiple doses of comparators for 4-6 days as decided by the attending physicians. Follow-up was done for 24 months. No differences were found between the two groups regarding gender, underlying diseases and duration of the operation. Surgical site infections (SSIs) were present in two patients in the teicoplanin arm (0.78%) and in 11 patients in the comparator arm (3.53%) (P=0.025 between groups). These were deep SSIs in four patients (two in each arm). Two cases of severe allergic reaction occurred, one in the teicoplanin arm and another in the comparator arm. It is concluded that single-dose teicoplanin was more effective as prophylaxis for total hip or knee arthroplasty compared with multiple doses of broad-spectrum antimicrobials.

In vitro elution of moxifloxacin and fusidic acid by a synthetic crystallic semihydrate form of calcium sulphate (Stimulan).

Stimulan was evaluated in vitro as a biodegradable carrier for local delivery of moxifloxacin and fusidic acid. Moxifloxacin or fusidic acid was mixed with calcium sulphate at a ratio of 95:5 to prepare five replicas per antibiotic. In vitro elution was estimated daily using a high-performance liquid chromatography (HPLC) system. Elution of moxifloxacin lasted for 31 days. Eluted concentrations reached their peak on Day 13 (mean level 745 microg/mL); the lowest eluted concentration was detected on Day 30 (mean level 367 microg/mL). Elution of fusidic acid lasted for 14 days. Eluted concentrations reached their peak on Day 6 (mean value 249.5 microg/mL); the lowest eluted concentration was detected on Day 13 (mean value 10.9 microg/mL). The presented results revealed that Stimulan may allow adequate in vitro elution of moxifloxacin and fusidic acid. The latter results support the application of this system in experimental models of osteomyelitis.

The impact on community acquired pneumonia empirical therapy of diagnostic bronchoscopic techniques

The aim of the present study was to examine the modification of initial empirical treatment based on the microbiological results of bronchoscopic techniques after comparing the diagnostic yield of protected specimen brush (PSB) and bronchoalveolar lavage (BAL) in the immunocompetent patient with community acquired pneumonia (CAP) with results obtained from conventional sputum cultures. 88 patients with presumptive diagnosis of CAP necessitating hospitalization were prospectively studied. Fibreoptic bronchoscopy with quantitative PSB and BAL cultures for common pathogens, mycobacteria and fungi was performed. Conventional sputum cultures were also obtained. PSB and BAL quantitative cultures added 26.1% and 36.4%, respectively, more microbiological documentation for CAP compared to conventional sputum cultures (p<0.0001). Gram staining was indicative of the pathogen mostly in cases where Streptococcus pneumoniae was isolated, which was also the most frequently isolated pathogen (19.3%), followed by Haemophilus influenzae (9%). M. tuberculosis was isolated in 6.8% of patients. Modification of treatment ensued in 27.3% of patients because of the application of the cultures of sputum and invasive technique. PSB and BAL added significant information to the aetiological diagnosis of hospitalized immunocompetent patients with CAP.