Bread wheat milling behavior: effects of genetic and environmental factors, and modeling using grain mechanical resistance traits.

KEY MESSAGE: Genetic (Pinb-D1 alleles) and environment (through vitreousness) have important effects on bread wheat milling behavior. SKCS optimal values corresponding to soft vitreous or hard mealy grains were defined to obtain the highest total flour yield. Near-isogenic lines of bread wheat that differ in hardness, due to distinct puroindoline-b alleles (the wild type, Pinb-D1a, or the mutated forms, Pinb-D1b or Pinb-D1d), were grown in different environments and under two nitrogen fertilization levels, to study genetic and environmental effects on milling behavior. Milling tests used a prototype mill, equipped with two break steps, one sizing step, and two reduction steps, and this enabled 21 individual or aggregated milling fractions to be collected. Four current grain characters, thousand grain weight, test weight, grain diameter, and protein content, were measured, and three characters known to influence grain mechanical resistance, NIRS hardness, SKCS hardness index, and grain vitreousness (a character affecting the grain mechanical behavior but generally not studied). As expected, the wild type or mutated forms of Pinb-D1 alleles led to contrasted milling behavior: soft genotypes produced high quantities of break flour and low quantities of reduction flour, whereas reverse quantities were observed for hard genotypes. This different milling behavior had only a moderate influence on total flour production. NIRS hardness and vitreousness were, respectively, the most important and the second most important grain characters to explain milling behavior. However, contrary to NIRS hardness, vitreousness was only involved in endosperm reduction and not in the separation between the starchy endosperm and the outer layers. The highest flour yields were obtained for SKCS values comprised between 30 and 50, which corresponded either to soft vitreous or hard mealy grains. Prediction equations were defined and showed a good accuracy estimating break and reduction flours portions, but should be used more cautiously for total flour.

New in vitro and in vivo models to evaluate antibiotic efficacy in Staphylococcus aureus prosthetic vascular graft infection.

OBJECTIVE: Prosthetic vascular graft infection (PVGI) is an emerging disease, mostly caused by staphylococci, with limited data regarding efficacy of current antistaphylococcal agents. We aimed to assess the efficacy of different antibiotic regimens. METHODS: Six different strains of MSSA and MRSA were used. We compared results of minimal biofilm inhibitory and eradicating concentrations (MBICs and MBECs) obtained with a Calgary Biofilm Pin Lid Device (CBPD) with those yielded by an original Dacron(®)-related minimal inhibitory and eradicating concentration measure model. We then used a murine model of Staphylococcus aureus vascular prosthetic material infection to evaluate efficacy of different antibiotic regimens: vancomycin and daptomycin combined or not with rifampicin for MRSA and the same groups with cloxacillin and cloxacillin combined with rifampicin for MSSA. RESULTS: We demonstrated that classical measures of MBICs and MBECs obtained with a CPBD could overestimate the decrease in antibiotic susceptibility in material-related infections and that the nature of the support used might influence the measure of biofilm susceptibility, since results yielded by our Dacron(®)-related minimal eradicating assay were lower than those found with a plastic device. In our in vivo model, we showed that daptomycin was significantly more bactericidal than comparators for some strains of MRSA or MSSA but not for all. For the majority of strains, it was as efficient as comparators. The addition of rifampicin to daptomycin did not enhance daptomycin efficacy. CONCLUSIONS: Despite the heterogeneity of results according to bacterial strains, these innovative models represent an option to better evaluate the in vitro efficacy of antibiotics on Dacron(®)-related biofilm S. aureus infections, and to screen different antibiotic regimens in a mouse model of PVGIs.

Relationships between wheat grain physical characteristics studied through near-isogenic lines with distinct puroindoline-b allele.

KEY MESSAGE: Genetic (different forms of puroindoline-b) and environment (through variations in vitreousness), have important effects on wheat grain mechanical properties. The two methods of hardness measurements (NIRS, SKCS) do not give the same information. Bread wheat near-isogenic lines differing in hardness, due to distinct puroindoline-b alleles (the wild type, Pinb-D1a, or the mutated forms, Pinb-D1b or Pinb-D1d), were grown for three years in seven sites and under two nitrogen fertilization levels, to study genetic and environmental effects on grain mechanical properties. Two methods, Near-Infrared Reflectance Spectroscopy (NIRS) and Single Kernel Characterization System (SKCS), currently used for grain hardness characterization, were carried out. Grain vitreousness, which is known to affect the grain mechanical behavior but is generally not studied, was also measured, as well as three other characters (Thousand Grain Weight, Test Weight and protein content). The relationships between the different characters were studied. Results revealed a clear effect of the different Pinb-D1 alleles on NIRS hardness, and a marked impact of the environmental conditions on vitreousness. SKCS hardness was influenced by both Pinb-D1 alleles and environmental conditions. The relationship between SKCS and NIRS hardness was strong when considering together soft and hard genotypes, but moderate within a class of genetical hardness. Vitreousness had only a weak effect on NIRS hardness, whereas vitreousness and SKCS values were strongly correlated, with two distinct regressions for soft and hard genotypes. Vitreousness was positively related to protein content, especially in the case of hard genotypes, which were able to reach high vitreousness values never observed for soft genotypes.

Causes and consequences of anti-infective drug stock-outs.

Anti-infective drugs stock-outs are increasingly frequent, and this is unlikely to change. There are numerous causes for this, mostly related to parameters difficult to control: i) 60 to 80% of raw material or components are produced outside of Europe (compared to 20% 30 years ago), with subsequent loss of independence for their procurement; ii) the economic crisis drives the pharmaceutical companies to stop producing drugs of limited profitability (even among important drugs); iii) the enforcement of regulatory requirements and quality control procedures result in an increasing number of drugs being blocked during production. The therapeutic class most affected by drug stock-outs is that of anti-infective drugs, especially injectable ones, and many therapeutic dead ends have recently occurred. We provide an update on this issue, and suggest 2 major actions for improvement: i) to implement a group dedicated to anticipating drug stock-outs within the anti-infective committee in each health care center, with the objectives of organizing and coordinating the response whenever a drug stock-out is deemed at risk (i.e., contingency plans, substitution, communication to prescribers); ii) a national reflection lead by scientific societies, in collaboration with government agencies, upstream of the most problematic drug stock-outs, to elaborate and disseminate consensus guidelines for the management of these stock-outs.

Outpatient parenteral antimicrobial therapy for infective endocarditis: a cost-effective strategy.

OBJECTIVES: We evaluated the benefit/risk ratio of outpatient parenteral antimicrobial therapy (OPAT) in infective endocarditis (IE). METHOD: We performed an observational retrospective study of definite IE (Duke criteria) treated in an infectious diseases unit in 2012. We compared patients having completed the treatment in hospital (H), and those deemed sufficiently stable, and with adequate home environment, for OPAT. The costs were estimated through hospital bills, and, for OPAT, through the costs of drugs and their administration (material, staff), transportation, and outpatient visits. RESULTS: Eighteen out of 39 consecutive patients presenting with IE received OPAT, with a mean hospital stay of 23.5days (vs 34.7days for H group, P=0.014). No severe adverse event related to OPAT was reported. The global saving was estimated at 267,307euros, or 14,850euros per patient. CONCLUSIONS: OPAT in selected patients presenting with IE seems effective, safe, and reduces costs by approximately 15,000euros per patient.

Contribution of 18fluoro-deoxyglucose PET/CT for the diagnosis of infectious diseases.

The diagnosis of some infectious diseases is sometimes difficult to make and new diagnostic tools have been regularly assessed to that end. 18fluoro-deoxyglucose ((18)FDG) positron-emission tomography (PET) coupled with computed tomography (CT) is one of these new procedures. It has been evaluated for numerous infectious diseases with uneven results. A literature review allowed drawing some conclusions. First, (18)FDG-PET/CT is not currently a first-line procedure for infectious diseases. Second, it has proved useful for the evaluation of patients presenting with fever of unknown origin (FUO). Its negative predictive value is 100%: the symptoms of patients experiencing FUO with negative first-line investigations and a negative (18)FDG-PET/CT will almost always spontaneously disappear. Third, (18)FDG-PET/CT also seems to be contributive for the diagnosis of vascular prosthesis infections or osteomyelitis. Fourth, it has promising results for patients presenting with infective endocarditis, especially for secondary infectious foci, or for patients presenting with suspected infection of pacemakers or implanted defibrillator; but results are still preliminary and must be confirmed. Finally(18)FDG-PET/CT cannot be recommended yet for other infectious diseases due to lack of published data.

Fibrosis progression under maintenance interferon in hepatitis C is better detected by blood test than liver morphometry.

We evaluated whether quantitative measurements of liver fibrosis with recently developed diagnostics outperform histological staging in detecting natural or interferon-induced changes. We compared Metavir staging, morphometry (area and fractal dimension) and six blood tests in 157 patients with chronic hepatitis C from two trials testing maintenance interferon for 96 weeks. Paired liver biopsies and blood tests were available for 101 patients, and there was a significant improvement in Metavir activity and a significant increase in blood tests reflecting fibrosis quantity in patients treated with interferon when compared with controls - all per cent changes in histological fibrosis measures were significantly increased in F1 vs F2-4 stages only in the interferon group. For the whole population studied between weeks 0 and 96, there was significant progression only in the area of fibrosis (AOF) (P = 0.026), FibroMeter (P = 0.020) and CirrhoMeter (P = 0.003). With regards to dynamic reproducibility, agreement was good (r(ic) ≥ 0.72) only for Metavir fibrosis score, FibroMeter and CirrhoMeter. The per cent change in AOF was significantly higher than that of fractal dimension (P = 0.003) or Metavir fibrosis score (P = 0.015). CirrhoMeter was the only blood test with a change significantly higher than that of AOF (P = 0.039). AOF and two blood tests, reflecting fibrosis quantity, have high sensitivity and/or reproducibility permitting the detection of a small progression in liver fibrosis over two years. A blood test reflecting fibrosis quantity is more sensitive and reproducible than morphometry. The study also shows that maintenance interferon does not improve fibrosis, whatever its stage.

Assessment of interindividual variability of plasma concentrations after administrazion of high doses of intravenous amoxicillin or cloxacillin in critically ill patients.

The aim of the present retrospective observational clinical study was to assess the interindividual pharmacokinetic variability of plasma concentrations of amoxicillin or cloxacillin administered in high doses intravenously in critically ill patients, related to renal function or administration method.Four hundred and two plasma concentrations were measured at steady-state with a high performance liquid chromatography technique in 162 patients treated with 100 - 300 mg/kg/day of intravenous amoxicillin or cloxacillin.For both drugs and administration methods, plasma concentrations were significantly higher for patients with creatinine clearance below 60 ml/min, even though doses were adapted for renal impairment. the correlations calculated between plasma concentrations and creatinine level, creatinine clearance or doses were all low. There were fewer outlying drug concentrations in patients receiving continuous rather than intermittent regimens.Our results are in favor of adapting dosages of these beta-lactam antibiotics based on plasma concentrations, especially in cases of renal impairment.

Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.

BACKGROUND: Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). OBJECTIVE: To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. METHODS: A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease. RESULTS: 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002). CONCLUSION: Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.

Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults.

Referral bias occurs because of the clustering of patients at tertiary care centers. This may result in the distortion of observed clinical manifestations of rare diseases. This analysis evaluates the effect of referral bias on the epidemiology of infective endocarditis (IE) in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). This is a prospective multicenter cohort study comparing transferred and non-transferred patients with IE. Factors independently associated with transfer status were evaluated using multivariable logistic regression. A total of 2,760 patients were included in the analysis, of which 1,164 (42.2%) were transferred from other medical centers. Transferred patients more often underwent surgery for IE (odds ratio [OR] = 2.5; 95% confidence interval [CI] 1.9-3.2). They were also more likely to have complications such as stroke (OR = 1.5; 95% CI 1.3-1.9), heart failure (OR = 1.4; 95% CI 1.1-1.6), and new valvular regurgitation (OR = 1.3; 95% CI 1.1-1.6). The in-hospital mortality rates were similar in both groups. Patients with IE who require surgery and suffer complications are referred to tertiary hospitals more frequently than patients with an uncomplicated course. Hospital transfer has no obvious effect on the in-hospital mortality. Referral bias should be taken into consideration when describing the clinical spectrum of IE.

Influence of job seniority, hand hygiene education, and patient-to-nurse ratio on hand disinfection compliance.

Hand hygiene compliance was evaluated by direct observation in 2006 and 2007. In 2007, data on characteristics such as job seniority, hand hygiene education, and patient-to-nurse ratio during direct observations were collected. A hand hygiene promotional programme was performed between the two evaluations. Univariate and multivariate analysis identified factors associated with improved hand hygiene compliance. Between 2006 and 2007, from 761 hand hygiene opportunities, overall and partial compliance improved from 44.9% to 58% (P<0.001) and from 73.5% to 88.4% (P<0.001), respectively. In 2007, improvements in hand hygiene overall or partial compliance were seen when senior healthcare workers (HCWs) were present in the clinical area under investigation (P=0.04 or P=0.08, respectively). Partial hand hygiene compliance was significantly better in 2007 after a hand hygiene educational programme had been presented (P<0.015). Similar rates of compliance were observed whatever the patient-to-nurse ratio during the observation. Multivariate analysis identified job seniority as an independent predictor of hand hygiene compliance. Our results suggest that hand hygiene compliance is influenced by education on hand hygiene and that a senior HCW could act as a role model for other HCWs. These data should be considered when developing future hygiene interventions.

[Predisposing factors of community acquired bacterial meningitis (excluding neonates)]. / Recherche de facteurs favorisants la survenue de méningites bactériennes communautaires (nouveau-né exclu).

Meningeal defects and primitive ENT infections are known to promote pneumococcal meningitis. Other risk factors can be identified in the occurrence of community acquired bacterial meningitis (CABM) and play a key role either in the frequency of this kind of infection, the type of bacteria concerned, the prognosis or the risk of recurrence. Thus, epidural infiltrations are rarely responsible for staphylococcal or streptococcal meningitis. Cochlear implants are also known to increase the risk of pneumococcal meningitis. The occurrence in children of aseptic meningitis or meningitis due to Staphylococcus aureus or Enterobacteriaceae is strongly suggestive of congenital spinal or cerebral anomalies (dermal sinus or spina bifida). MRI must be rapidly performed. In cases of splenectomy or asplenism, pneumococcal meningitis is common and must be prevented. According to the larger series available on this topic, age over 60, diabetes mellitus, alcoholism and immune deficiency are found to promote CABM in about 25% of cases. Streptococcus pneumoniae is the most frequent causative bacteria in elderly patients, in case of alcoholism, as well as Listeria monocytogenes and some Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae). L. monocytogenes is frequently isolated in immunodepressed patients and patients treated by anti-TNF molecules (infliximab notably). Finally, some genetic polyphormisms promote CABM: complement and properdin deficiencies (meningococcal meningitis), mannose-binding lectin deficiency, Fcgamma receptors alteration or interleukin-1 and IL-1R polymorphisms. Screening for such genetic disorders may be discussed in case of CABM but is mandatory in case of recurrent meningococcal infections.

[Recurrent tick-borne fever: a possible diagnosis in patients returning from Senegal]. / Fièvre recurrente à tiques: un diagnostic non rare au décours d'un séjour touristique au Sénégal.

In Senegal, tick-borne relapsing fever caused by the spirochetes Borrelia crucidurae is the most common cause of fever after malaria in rural areas. However, this is only rarely diagnosed in France, probably because: i) the diagnosis relies on investigations that are not routinely done; ii) even undiagnosed, borreliosis may be cured with empirical antibiotic treatment. We report four observations of tick-borne relapsing fever in patients returning from Senegal: In two patients, the diagnosis relied on the observation of spirochetes in blood smears; in the other two, the diagnosis relied on typical clinico-biological signs, borreliosis serology and exposure. These four cases diagnosed over a four year period in one institution suggest that relapsing fever is not rare in patients returning from West Africa. Patients who return form Senegal with unexplained fever should be investigated with careful examination of blood smears and PCR on blood samples.

A retrospective study of 230 consecutive patients hospitalized for presumed travel-related illness (2000-2006).

A good knowledge of morbidity profiles among ill-returned travelers is necessary in order to guide their management. We reviewed the medical charts of 230 patients hospitalized in one infectious diseases department in France for presumed travel-related illnesses. The male-to-female ratio was 1.6 and the median age was 33 years (interquartile range [IQR], 25-50). Most patients (70.9%) were returning from sub-Saharan Africa. The median duration of travel was 28 days (IQR, 15-60) and the median time from return of travel to hospitalization was 13 days (IQR, 7-21). Malaria was the most frequent diagnosis (49.1%), which was especially encountered in patients returning from sub-Saharan Africa (95.6%), without adequate chemoprophylaxis (78.2%). Imported diseases at risk of secondary transmission were also diagnosed, including pulmonary tuberculosis (n = 8), viral hepatitis (n = 8), typhoid fever (n = 6), human immunodeficiency virus (HIV) (six new diagnosis), non-typhoid salmonellosis (n = 5), severe acute respiratory syndrome, and Crimean-Congo hemorrhagic fever. This study underlines the need to maintain tropical expertise for infectious diseases physicians, even in Europe.

Modelling the influence of activation-induced apoptosis of CD4+ and CD8+ T-cells on the immune system response of a HIV-infected patient.

On the basis of the human immunodeficiency virus (HIV) infection dynamics model proposed by Adams, the authors propose an extended model that aims at incorporating the influence of activation-induced apoptosis of CD4+ and CD8+ T-cells on the immune system response of HIV-infected patients. Through this model, the authors study the influence of this phenomenon on the time evolution of specific cell populations such as plasma concentrations of HIV copies, or blood concentrations of CD4+ and CD8+ T-cells. In particular, this study shows that depending on its intensity, the apoptosis phenomenon can either favour or mitigate the long-term evolution of the HIV infection.

Liver-related mortality in human-immunodeficiency-virus-infected patients between 1995 and 2003 in the French GERMIVIC Joint Study Group Network (MORTAVIC 2003 Study).

The objective of the present study was to determine mortality because of end-stage liver disease (ESLD) in a nationwide population of HIV-infected patients, 7 years following the introduction of highly active antiretroviral therapy (HAART). All departments of internal medicine and infectious diseases from the GERMIVIC Study Group prospectively recorded all deaths in HIV-infected patients during 2003. Fifty-nine departments, following a total of 20 940 HIV-infected patients, participated in the study. Results were compared with those of previous surveys conducted using similar methodology in 1995, 1997 and 2001. Among 215 deaths observed during 2003, 101 (46.9%) were related to AIDS, 27 (12.6%) to ESLD and 87 (40.5%) to other causes. Mortality because of ESLD represented 23.7% of non-AIDS-related deaths. Patients dying from ESLD had chronic hepatitis because of hepatitis C virus (HCV) in 92.6% of cases and moderate (30-60 g) or high (>60 g) alcohol consumption (43.5% and 26.0%, respectively). In this population, deaths because of ESLD were 1.5% in 1995, 6.6% in 1997, 14.3% in 2001 and 12.6% in 2003. The prevalence of hepatocellular carcinoma as a cause of death remained high in 2003 but stable when compared with 2001 (25%vs 14.8%). Treatment of hepatitis C in patients who died from ESLD was more frequent in 2003 (44.4%) than in 2001 (26.3%). Seven years after the introduction of HAART, ESLD associated with HCV infections is a leading cause of mortality in HIV-infected patients, which did not increase between the years 2001 and 2003.

Respiratory manifestations of leptospirosis: a retrospective study.

We retrospectively reviewed 34 consecutive patients with serologically confirmed leptospirosis admitted during years 1992-2002. Nine patients (26.5%) had respiratory symptoms on admission including cough (n = 4), shortness of breath (n = 4), cyanosis (n = 2), and hemoptysis (n = 1). Six patients had pulmonary radiographic findings including (1) diffuse, ill-defined, ground-glass density (n = 3); (2) diffuse alveolar opacities (n = 2); and (3) small nodular density (n = 1). Male/female ratio was 8/1 and mean age was 47 years. Seven patients reported their exposure source including hunting (n = 2), fishing (n = 2), fresh water swimming (n = 2), and canoeing (n = 1). All patients had fever (mean = 40.1 degrees C). Other common symptoms were headache (n = 4), vomiting (n = 3), and myalgia (n = 3). Biological abnormalities included elevated liver enzymes (n = 8), proteinuria (n = 7), lymphopenia (n = 6), hematuria (n = 5), renal failure (n = 4), anemia (n = 4), and elevated neutrophil count (n = 4). PaO(2 )was measured for 3 patients while they were breathing room air (32, 55, and 66 mmHg). Suspected diagnosis on admission included leptospirosis (n = 2), bacterial pneumonia (n = 2), intoxication, influenza, viral hepatitis, biliary tract lithiasis, and rapidly progressive glomerulonephritis (one patient each). The first serologic testing for leptospirosis was positive for 5 patients (55%). Serovar was presumptively identified for 7 patients: Australis (n = 3), Grippotyphosa (n = 2), and Icterohaemorrhagiae (n = 2). Seven patients were treated with penicillin; two patients received no antibiotics. All patients were cured. In conclusion, patients with leptospirosis may present predominantly with nonspecific pulmonary symptoms. In these patients, leptospirosis must be suspected when there is a potential exposure to rats, especially in case of high-grade fever, myalgia, hepatitis, and renal abnormalities.