Periklis Panagopoulos

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.

Septic arthritis due to Salmonella enteritidis associated with infliximab use.

A unique case of septic arthritis caused by Salmonella enteritidis in a patient receiving infliximab for rheumatoid arthritis is presented. Antimicrobial chemotherapy with surgical intervention was necessary for eradication of the infection. Physicians should be aware of rare manifestations of Salmonella infections associated with infliximab use, especially in endemic areas.

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.

Acute uncomplicated cystitis: from surveillance data to a rationale for empirical treatment.

The objectives of this study were to explore the epidemiological features and resistance rates in uropathogens isolated from cases of acute uncomplicated cystitis (AUC) in Greece, and subsequently to guide empirical treatment. Urine samples from outpatients aged >16 years were cultured and for each uropathogen isolated non-susceptibility to orally administered antimicrobial agents was defined. Demographic and clinical data were provided in questionnaire form. From January 2005 to March 2006 a total of 1936 non-duplicate positive urinary cultures were collected and 889 AUC cases were evaluated. Escherichia coli was the main aetiological agent (83%). In the AUC group, non-susceptibility rates for E. coli isolates were as follows: amoxicillin 25.8%; co-trimoxazole 19.2%; cefalothin 14.9%; nitrofurantoin 10.7%; amoxicillin/clavulanic acid 5.2%; nalidixic acid 6%; mecillinam 3.4%; ciprofloxacin 2.2%; cefuroxime 1.7%, and fosfomycin 1.6%. Amoxicillin and/or co-trimoxazole use in the previous 3 months was significantly associated with isolation of a co-trimoxazole-resistant E. coli isolate. The same applied for previous use of a fluoroquinolone agent and isolation of a ciprofloxacin-resistant E. coli isolate. In conclusion, increased co-trimoxazole non-susceptibility rates undermine its use as a first-line agent in empirical treatment, especially in cases of recent use of co-trimoxazole and/or amoxicillin. Fluoroquinolones display potent in vitro activity against community uropathogens, but prudent use is warranted for uncomplicated infections. Mecillinam and nitrofurantoin could serve as effective front-line agents in an effort to design fluoroquinolones-sparing regimens.

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).

In Vitro Elution of Daptomycin by a Synthetic Crystallic Semihydrate Form of Calcium Sulfate, Stimulan

ABSTRACT A synthetic crystallic semihydrate form of calcium sulfate, Stimulan, was evaluated as a biodegradable carrier for the daily in vitro elution of daptomycin. Daptomycin and Stimulan were admixed at a ratio of 95:5. Elution lasted for 28 days. Eluted concentrations peaked on days 1 and 11, when the mean values were 1,320.1 and 949.2 μg/ml, respectively. The lowest eluted concentration was detected on day 28. These results support the application of the system described in experimental models of osteomyelitis.

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.

Comparing classic and newer phenotypes in Greek PCOS women: the prevalence of metabolic syndrome and their association with insulin resistance.

Objective: Recently, it has been debated whether the new polycystic ovary syndrome (PCOS) phenotypes, according to the Rotterdam criteria, share the same metabolic risk with the classic ones (National Institutes of Health 1990). Our study sought to compare the prevalence of metabolic syndrome (MS) and glucose homeostasis disorders in Greek women with classic and new PCOS phenotypes. Materials and methods: Two hundred and sixty-six Greek PCOS women were recruited and divided into groups according to two of the three Rotterdam criteria that they fulfilled. Two subgroups were formed; the first represented the classic phenotypes and the second the new phenotypes. The clinical, biochemical, and ultrasound characteristics of both groups were explored. All subjects were evaluated for MS and underwent a 2-h glucose tolerance test to assess insulin resistance (IR) as measured by the homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUIC-KI), and MATSUDA indices. Results: 62.4% of PCOS women were classified as classic NIH phenotypes of which 32 women had MS (prevalence 19.6%). Only 4 patients categorized in the newer phenotypic groups had MS (prevalence 4.1%). Among the subjects with classic phenotypes, 11.7% exhibited impaired glucose tolerance (3-fold higher percentage compared to patients with newer phenotypes). Regarding IR indices, HOMA-IR was significantly higher and QUICKI significantly lower for classic phenotypes. Conclusions: Greek PCOS women with classic phenotypes are at increased risk for MS and impaired glucose homeostasis compared to women with newer phenotypes. A subclassification of PCOS permits the earlier recognition and closer surveillance of women whose metabolic profile indicates potential risks for adverse health outcomes.

Promoting prudent use of antibiotics: the experience from a multifaceted regional campaign in Greece

BackgroundAntibiotic resistance, a major public health problem, has been linked to antibiotic consumption. In Greece both consumption and resistance rates are among the highest in Europe. A multifaceted campaign targeting both physicians and parents of school children was implemented for the first time in order to educate the public and update doctors, aiming to promote judicious use of antibiotics and hopefully decrease its consumption.MethodsThe programme consisted of a public education campaign and academic detailing of primary care physicians in the district of Corinth in Peloponnese. The experience and perceptions of parents were recorded in the meetings in the form of course evaluation and assessment, anonymous questionnaires. The use of Rapid Antigen Detection Test (RADT) for streptococcal pharyngitis by primary care physicians was also assessed by use of anonymous questionnaires. Antibiotic consumption was compared before and after the programme between the district of Corinth and the other districts of Peloponnese, as well as at a national level.ResultsAntibiotic consumption remained unaltered at 26 Defined daily doses per 1000 Inhabitants per Day (DID) in accordance with the trend in other regions and at a national level. However, the utilization of Amoxycillin and Penicillin was increased by 34.3%, while the use of other antimicrobial classes including macrolides, cephalosporins and fluoroquinolones decreased by 6.4-21.9%. The use of RADT did not lead to a significantly decreased antimicrobial consumption.ConclusionsA multifaceted educational programme targeting both the general public and primary care physicians was associated with rationalization in the choice of antimicrobial. A reduction in the total antimicrobial consumption was not achieved.