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Severe Infections (severe + infections)

Distribution by Scientific Domains

Medical Sciences	77%
Life Sciences	14%
2 Other Domains	9%

Distribution within Medical Sciences

Pediatrics	14%
Allergy & Clinical Immunology	9%

Selected Abstracts

Safety and efficacy of rituximab in systemic lupus erythematosus: Results from 136 patients from the French autoimmunity and rituximab registry

ARTHRITIS & RHEUMATISM, Issue 8 2010
Benjamin Terrier
Objective A number of open-label studies have suggested the potential benefit of rituximab (RTX) in systemic lupus erythematosus (SLE). However, in 2 recent randomized controlled trials (RCTs) of RTX, the primary end points were not met. We undertook this study to evaluate the safety and efficacy of RTX in off-trial patients with SLE seen in regular clinical practice. Methods We analyzed prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with RTX. Results One hundred thirty-six patients received treatment for SLE. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was 11.3 ± 8.9 at baseline. Severe infections were noted in 12 patients (9%), corresponding to a rate of 6.6/100 patient-years. Most severe infections occurred within the first 3 months after the last RTX infusion. Five patients died, due to severe infection (n = 3) or refractory autoimmune disease (n = 2). Overall response was observed in 80 of 113 patients (71%) by the SELENA,SLEDAI assessment. Efficacy did not differ significantly between patients receiving RTX monotherapy and those receiving concomitant immunosuppressive agents (who had higher baseline disease activity). Articular, cutaneous, renal, and hematologic improvements were noted in 72%, 70%, 74%, and 88% of patients, respectively. Among responders, 41% experienced a relapse of disease, with a response in 91% after retreatment with RTX. Conclusion Data from the AIR registry show a satisfactory tolerance profile and clinical efficacy of RTX in patients with SLE. The contrasting results with those from recent RCTs leave open the question of the therapeutic use of RTX in SLE. Additional controlled studies with new designs are needed to define the place of RTX in the therapeutic arsenal for SLE. [source]

Risk factors for severe infection in patients with hairy cell leukemia: a long-term study of 73 patients

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2009
Ghandi Damaj
Abstract Although the survival of patients with hairy cell leukemia (HCL) has been improved by the therapeutic introduction of interferon , and purine analogs, it is still worsened by complications such as severe infections. In this long-term study, we identified factors influencing patient outcomes in 73 patients with HCL. Median age at diagnosis was 53 yr and the gender ratio (M/F) was 2.3. At the time of HCL diagnosis, 60 patients (82%) were symptomatic and 22 of these had an infection. After a median follow-up of 13 yr, eight patients had died of secondary cancer (n = 2), HCL progression (n = 1) and age-related complications (n = 5). The 10-yr overall survival (OS), progression-free survival and relapse rates were 91 ± 3%, 14 ± 5% and 87 ± 5%, respectively. In multivariate analyses, age >53 yr was the only factor adversely influencing OS and secondary cancer incidence, with adjusted hazard ratio (HR) of 9.30 (95%CI, 1.15,76.6; P = 0.037) and 2.80 (95%CI, 1.05,7.71; P = 0.04), respectively. Eleven patients developed severe infections. Absolute lymphocyte count (<1 × 109/L) at diagnosis was the only factor influencing the occurrence of severe infections, with an adjusted HR of 4.01 (P = 0.007). Strikingly, we did not observe any significant correlation between neutrophil or monocyte counts and the incidence of infection. We confirmed long-term survival in HCL but found a high incidence of infection , even late in the course of the disease. The absolute lymphocyte count at diagnosis is a risk factor for the occurrence of severe infections. In addition to careful monitoring of infections, prompt initiation of anti-HCL treatment should be considered in patients with low lymphocyte counts. [source]

Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathway

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2002
D. A. LAMMAS
Summary Patients with genetic lesions in the Type-1 cytokine/cytokine receptor pathway exhibit a selective susceptibility to severe infections with poorly pathogenic mycobacteria and non-typhi salmonella spp. These experiments of nature demonstrate that IL-12-dependent IFN, production is critical for granuloma formation and therefore host immunity against such pathogens. The essential role of granuloma formation for protective immunity to these organisms is emphasized by the differing granuloma forming capabilities and resultant clinical sequelae observed in these patients which seems to reflect their ability to produce or respond to IFN, (Fig. 9). At one pole of this spectrum, represented by the complete IFN,R1/2 deficient patients, there is a complete absence of mature granuloma formation, whereas with the less severe mutations (i.e. partial IFN,R1/2, complete IL-12p40 and complete IL-12R,1 deficiency), granuloma formation is very heterogenous with wide variations in composition being observed. This suggests that in the latter individuals, who produce partial but suboptimal IFN, responses, other influences, including pathogen virulence and host genotype may also affect the type and scale of the cellular response elicited. Figure 9. ,Spectrum of genetic susceptibility to intracellular bacteria. At one pole of this spectrum complete IFN,R deficiencies are found; at the other pole are healthy resistant individuals. Partial IFN,R1 deficiencies, and complete IL-12R,1 and IL-12p40 deficiencies can be positioned in between, albeit closer to the former end of the spectrum, with clinical outcome also depending on pathogen virulence and host compensatory immune mechanism(s). Abbreviations: IFN,R , interferon gamma receptor, IL-12R,1 , interleukin 12 receptor-1 (modified from Ottenhoff et al. (1998)). [source]

Infected urachal cyst ruptured during medical palliation

INTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2003
Yasuyuki Kojima
Abstract Since most cases of urachal cyst are asymptomatic, they are frequently detected after complication by infection. Ruptured urachal cysts are frequently detected after complication by severe infections such as sepsis. We report on a 31-year-old man who was diagnosed preoperatively as having an infected urachal cyst and the decision was made to follow the patient because primary excision was scheduled to be performed a few days later. Symptoms were transiently relieved, but the cyst ruptured during medical palliation. We treated this case with a two-stage surgical procedure. [source]

Population pharmacokinetics of cefepime in neonates with severe nosocomial infections

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2008
V. Lima-Rogel MD
Summary Objective:, To define the pharmacokinetic behaviour of cefepime in neonates with severe nosocomial infections using a mixed effects model. Patients and methods:, Thirty-one newborn infants were included in the study; 10 additional infants participated in the validation of the pharmacokinetic model. Cefepime CL and V were determined using an open monocompartmental model with first-order elimination. The influence of demographic and clinical characteristics on the model was evaluated. The non-linear mixed effect model (nonmem) program was used to determine the pharmacokinetic population model. Results:, The mean corrected gestational age for infants participating in the construction and validation of the model were 35 and 33 weeks, respectively. Factors included in the final pharmacokinetic model were body surface area (BSA) and calculated CLCR. The final population model was CL (L/h) = 0·457 BSA (m2) + 0·243 CLCR (L/h) and V(L) = 4·12 BSA (m2). This model explains 33·3% of the interindividual variability for CL and 12·8% for V. This model was validated in ten neonates with nosocomial infections by assessing the predictive capacity of plasma cefepime concentrations using a priori and Bayesian strategies. Conclusions:, The predictive performance of this population model for cefepime plasma concentrations was adequate for clinical purposes and can be used for individualizing cefepime therapy in newborn infants with severe infections. Cefepime plasma concentrations can be predicted based on BSA and calculated CLCR. Cefepime therapy using a 250 mg/m2 dose administered every 12 h is adequate to achieve plasma concentrations greater than 8 ,g/mL during more than 60% of the dosing interval and is expected to be effective in the treatment of bloodstream infections caused by most gram negative organisms in newborn infants. A dose of 550 mg/m2 would be required for the treatment of infections caused by Pseudomonas sp. [source]

Prevalence of avian pox virus and effect on the fledging success of Laysan Albatross

JOURNAL OF FIELD ORNITHOLOGY, Issue 1 2008
Lindsay C. Young
ABSTRACT Avian pox virus (Poxvirus avium) is a mosquito-borne disease that occurs worldwide in a variety of bird species, but little is known about its prevalence or effect on seabirds. We monitored prevalence of pox virus and its effect on fledging success of Laysan Albatross (Phoebastria immutabilis) on Oahu, Hawaii, from 2003 to 2007. Pox prevalence in albatross chicks averaged 88% in years with high rainfall and 3% in years with low rainfall. Diagnosis of pox virus was clinically confirmed in two birds by Muscovy Duck (Cairina moschata) fibrolast cultures. Severity of infection ranged from small wart-like nodules and lesions on the bill, face, eyes, tarsus, and feet, to large tumorous growths that completely covered both eyes and caused deformation of the bill and skull. Most chicks recovered from infection, and the fledging rate in pox epizootic years (82%) did not differ from that in years with low pox prevalence (80%) or the average fledging rate on Midway Atoll (86%). Three chicks with severe infections were resighted as healthy adults on Kauai and Oahu in 2007, confirming postfledging survival of at least some birds. The high recovery rate, fledging success, and postfledging survival indicate that Laysan Albatross have strong immunity to avian pox virus. SINOPSIS La viruela aviar (Poxvirus avium) es una enfermedad que afecta muchas especies de aves a nivel mundial. La enfermedad es transmitida por mosquitos y se sabe poco de su prevalencia y efecto en aves acuáticas. Monitoreamos la prevalencia de este virus y su efecto en volantones de albatros (Phoebastria immutabilis) en Oahu, Hawaii, en trabajo que se llevo a cabo desde el 2003,2007. Encontramos una prevalencia de 88% en pichones de albatros en años lluviosos y de 3% en años de poca lluvia. Se diagnosticó el virus, clínicamente, en dos patos comunes (Cairina moschata) mediante la técnica de cultivo fibroblástico. La severidad de la infección varió desde leve con algunas lesiones en el pico, cara, ojos, tarso y patas, hasta casos severos con grandes tumores que cubrían los ojos y causaron malformación de pico y craneo. La mayoría de los pichones se recobraron de la infección. La tasa de pichones que dejaron el nido (82%) en años de alta incidencia (82%) fue similar (80%) a los años de pocas infecciones y al promedio de volantones (86%) en el Atolón de Midway. Tres individuos observados como pichones con infecciones severas fueron avistados posteriormente como adultos saludables en Kauai y Oahu en el 2007, lo que confirma la sobrevivencia post-volanton de al menos algunas aves. La tasa tan alta de recobro, éxito en dejar el nido y sobrevivencia post-volantón indican que en el Albatros de Laysan hay una alta inmunidad hacia la viruela aviar. [source]

A community-derived outbreak of adenovirus type 3 in children in Taiwan between 2004 and 2005

JOURNAL OF MEDICAL VIROLOGY, Issue 1 2008
Sui-Yuan Chang
Abstract An outbreak of respiratory adenovirus infection in children was observed in northern Taiwan between November 2004 and February 2005. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the serotype(s) of 172 adenovirus isolates in the outbreak period, we found that adenovirus type 3 (Ad3) was the predominant type (87.2%), followed by Ad2 (6.4%), Ad1 (4.1%), Ad7 (1.2%), Ad4 (0.6%), and Ad5 (0.6%). The genotype of Ad3 was analyzed for 15 isolates from the outbreak period by RFLP of the full-length genome. All these isolates belonged to genotype Ad3a2. Compared with the Ad3-infected patients in the baseline period, a significantly higher proportion of Ad3-infected patients in the outbreak period had severe infections (58.0% vs. 40.2%, P,=,0.01), which included bronchopneumonia (28.7%), exudative tonsillitis (24.1%), and tonsillitis (16.1%). Moreover, patients with severe infections were significantly younger than those without (4.10 vs. 8.15 years, P,<,0.001). In summary, our study demonstrated that Ad3 was the predominant serotype responsible for the respiratory adenovirus outbreak in northern Taiwan during 2004,2005 and was associated with severe infections in the outbreak period. J. Med. Virol. 80:102,112, 2008. © 2007 Wiley-Liss, Inc. [source]

Pathogenesis of simian varicella virus

JOURNAL OF MEDICAL VIROLOGY, Issue S1 2003
Wayne L. Gray
Abstract Simian varicella virus (SVV) is closely related to varicella-zoster virus (VZV) and induces a natural varicella-like disease in nonhuman primates. Therefore, simian varicella is a useful model to investigate varicella pathogenesis and to evaluate antiviral therapies. In this report, we review recent studies on SVV pathogenesis and latency. Experimental infection of African green monkeys is followed by a 7,10 day incubation period during which a viremia disseminates the virus throughout the body. Clinical disease is characterized by fever and vesicular skin rash. Pneumonia and hepatitis may occur during more severe infections. Examination of acutely infected tissues reveals histopathology including necrosis and hemorrhage in the skin, lung, liver, and spleen. In contrast, the neural ganglia exhibit minimal histopathology. SVV DNA, immediate early, early, and late gene transcripts, and viral antigens are detected in the tissues of acutely infected monkeys. Host immune responses are induced which resolve the acute infection within 21 days. During or after acute infection, SVV establishes latent infection in the ganglia of surviving monkeys. The virus may reactivate later in life to cause secondary disease and viral transmission to susceptible monkeys. J. Med. Virol. 70:S4,S8, 2003. © 2003 Wiley-Liss, Inc. [source]

Severe chronic neutropenia in Chinese children in Hong Kong

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2001
TF Leung
Objective: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder in children. The epidemiology, clinical features and outcomes of SCN in Chinese children were reviewed. Methodology: A retrospective analysis of case records was undertaken for 18 children with SCN managed during a 12-year period in a university teaching hospital in Hong Kong. Results: The median (range) age of the patients at initial presentation was 6.5 months (4 days,19 months). The initial and lowest median absolute neutrophil counts (ANC) were 0.29 × 109 /L and 0.06 × 109 /L, respectively. Patients with congenital SCN had significantly fewer neutrophils in peripheral blood at diagnosis. Only five subjects received granulocyte colony-stimulating factor (G-CSF) treatment. All children were free from serious infection on follow up for 51 months. Only one child suffered from long-term infection-related morbidity. One patient with chronic neutropenia was subsequently shown to have common variable immunodeficiency. Conclusions: Most children with SCN in our series had favourable clinical outcomes. Our results support the recommendation that G-CSF should be used only in those with recurrent or severe infections. [source]

Oseltamivir Treatment Prevents the Increased Influenza Virus Disease Severity and Lethality Occurring in Chronic Ethanol Consuming Mice

ALCOHOLISM, Issue 8 2010
Ryan A. Langlois
Background:, Chronic consumption of ethanol (EtOH) is well recognized to lead to defective innate and adaptive immune responses and increase the severity of pulmonary infections. Our own studies have demonstrated that chronic EtOH consumption decreases CD8 T-cell immunity to influenza virus infections (IAV) leading to severe infections and mortality. Interestingly, antiviral treatment of IAVs has been shown to be compromised in mice and humans that are immuno-deficient. It is known that EtOH can alter the pharmacokinetics of antivirals. Therefore, the effectiveness of influenza antiviral therapy during chronic ethanol consumption remains in question. Methods:, BALB/c mice were placed on 18% (w/v) EtOH in their drinking water for 8 weeks. Chronic EtOH consuming and water controls were then treated with 10 mg/kg oseltamivir orally and infected intranasally with influenza virus 4 hours post-oseltamivir treatment. The mice were then treated with oseltamivir twice daily until day 7 postinfection. Influenza disease severity was measured by morbidity and mortality, pulmonary viral titers, and histology. Results:, Chronic EtOH consuming mice infected with IAV and treated with oseltamivir have decreased morbidity and mortality, pulmonary viral titers, and pulmonary pathology compared to untreated EtOH mice. Conclusions:, Despite the severe immune defect seen in chronic EtOH mice as well as the potential for EtOH to inhibit the conversion of oseltamivir into an active form, treatment with oseltamivir reduces viral shedding as well as disease severity. These data suggest that the combination of a limited adaptive immune response plus the anti-IAV drug oseltamivir is sufficient to curb high mortality and mediate resolution of IAVs in mice chronically consuming ethanol. [source]

Interactions between surface proteins of Streptococcus pyogenes and coagulation factors modulate clotting of human plasma

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2003
H. Herwald
Summary., Invasive and toxic infections caused by Streptococcus pyogenes are connected with high morbidity and mortality. Typical symptoms of these infections are hypotension, edema formation, tissue necrosis, and bleeding disorders. Here we report that components of the coagulation system including fibrinogen, factors V, XI, and XII, and H-kininogen, are assembled at the surface of S. pyogenes through specific interactions with bacterial surface proteins. In plasma environment, absorption of fibrinogen by S. pyogenes causes a hypocoagulatory state resulting in prolonged clotting times and impaired fibrin network formation. Moreover, the binding of coagulation factors and the subsequent activation of the coagulation system at the bacterial surface lead to the formation of a fibrin network covering S. pyogenes bacteria adhering to epithelial cells. The results suggest that interactions between S. pyogenes and components of the coagulation system contribute to some of the symptoms seen in severe infections caused by this important human pathogen. [source]

Increase in aspergillosis and severe mycotic infection in patients with leukemia and MDS: Comparison of the data from the Annual of the Pathological Autopsy Cases in Japan in 1989, 1993 and 1997

PATHOLOGY INTERNATIONAL, Issue 11 2003
Hikaru Kume
To study the relationship between the changes in visceral mycoses rates and recently advanced medical care in hematological settings, data on visceral mycosis cases with leukemia and myelodysplastic syndrome (MDS) that had been reported in the Annual of the Pathological Autopsy Cases in Japan in 1989, 1993 and 1997 were analyzed. The frequency rate of visceral mycoses with leukemia and MDS was 27.9% (435/1557) in 1989, 23.0% (319/1388) in 1993 and 22.3% (246/1105) in 1997. In comparing the rate of mycoses in recipients of organ or bone marrow transplantation with that of non-recipients, that of recipients was approximately 10% higher. The predominant causative agents were Candida and Aspergillus, at approximately the same rate as in 1989. The rate of candidosis decreased to one-half that of aspergillosis by 1993. Furthermore, severe mycotic infections clearly increased from 58.9% in 1989 to 75.6% in 1997. Among a total of 1000 cases with mycotic infection in those 3 years, acute lymphatic leukemia and acute myeloid leukemia were the major diseases (40.6% and 34.8%, respectively), followed by MDS (26.1%). The reasons for increased rates of aspergillosis and of severe mycotic infection can be surmised to be: (i) candidosis had become controllable by prophylaxis and by empiric therapy for mycoses with effective antifungal drugs; (ii) the marketed antifungal drugs were not sufficiently effective against severe infections or Aspergillus infections; and (iii) the number of patients surviving in an immunocompromised state had increased due to developments in chemotherapy and progress in medical care. [source]

Colistimethate sodium therapy for multidrug-resistant isolates in pediatric patients

PEDIATRICS INTERNATIONAL, Issue 3 2010
Solmaz Celebi
Abstract Aim:, The aim of the present study was to assess the efficacy and safety of colistimethate sodium therapy in multidrug-resistant nosocomial infections caused by Pseudomonas aeruginosa or Acinetobacter baumannii in neonates and children. Methods:, Pediatric patients hospitalized at the Uludag University Hospital who had nosocomial infections caused by multidrug-resistant P. aeruginosa or A. baumannii, were enrolled in the study. Colistimethate sodium at a dosage of 50,75 × 103 U/kg per day was given i.v. divided into three doses. Results:, Fifteen patients received 17 courses of colistimethate sodium for the following infections: ventilator-associated pneumonia (n= 14), catheter-related sepsis (n= 1) and skin and soft-tissue infection (n= 2). The mean age of patients was 53.2 + 74.7 months (range, 8 days,15 years) and 60% were male. Mortality was 26.6%. Conclusion:, Colistimethate sodium appears to be safe and effective for the treatment of severe infections caused by multidrug-resistant P. aeruginosa or A. baumannii in pediatric patients. [source]

Malaria during pregnancy in endemic areas: A lens for examining maternal,fetal conflict,

AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2009
Elizabeth T. Abrams
Most of our knowledge about maternal,fetal conflict derives from the battle over scarce nutritional resources. How do other stressors like infectious diseases alter the maternal,fetal relationship? In this article, we use the example of malaria infection during pregnancy to explore the altered maternal,fetal relationship in the presence of an infectious disease. While adults living in regions endemic to Plasmodium falciparum malaria are generally immune, pregnant women experience significantly more frequent and severe infections. These infections generally resolve within a few days of birth and rarely cross the placenta, but the infants often experience poor birth outcomes, particularly low birth weight. This article summarizes what is known about the proximate, or physiological, mechanisms by which malaria causes more severe or frequent infections for pregnant versus nonpregnant women in endemic regions and then utilizes an evolutionary approach to focus on the altered maternal,fetal relationship during malaria-infected pregnancy. Am. J. Hum. Biol. 2009. © 2009 Wiley-Liss, Inc. [source]

Structural features of a zinc binding site in the superantigen strepococcal pyrogenic exotoxin A (SpeA1): Implications for MHC class II recognition

PROTEIN SCIENCE, Issue 6 2001
Matthew Baker
Abstract Streptococcal pyrogenic exotoxin A (SpeA) is produced by Streptococcus pyogenes, and has been associated with severe infections such as scarlet fever and Streptococcal Toxic Shock Syndrome (STSS). In this study, the crystal structure of SpeA1 (the product of speA allele 1) in the presence of 2.5 mM zinc was determined at 2.8 Å resolution. The protein crystallizes in the orthorhombic space group P21212, with four molecules in the crystallographic asymmetric unit. The final structure has a crystallographic R -factor of 21.4% for 7,031 protein atoms, 143 water molecules, and 4 zinc atoms (one zinc atom per molecule). Four protein ligands,Glu 33, Asp 77, His 106, and His 110,form a zinc binding site that is similar to the one observed in a related superantigen, staphylococcoal enterotoxin C2. Mutant toxin forms substituting Ala for each of the zinc binding residues were generated. The affinity of these mutants for zinc ion confirms the composition of this metal binding site. The implications of zinc binding to SpeA1 for MHC class II recognition are explored using a molecular modeling approach. The results indicate that, despite their common overall architecture, superantigens appear to have multiple ways of complex formation with MHC class II molecules. [source]

Distribution of emm types and subtypes among noninvasive group A, C and G streptococcal isolates in western Norway,

APMIS, Issue 6 2008
BÅRD REIAKVAM KITTANG
Characterization of the reservoir of beta-hemolytic streptococci in a community may shed light on the pathogenesis of severe infections caused by these bacteria. We used emm sequence typing to characterize group A streptococci (GAS), group C streptococci (GCS) and group G streptococci (GGS) in community isolates associated with noninvasive disease in western Norway. A total of 165 isolates during a 13-month period were examined. Skin and throat isolates accounted for 123 and 16, respectively, and the remaining 26 isolates were from other non-sterile sites. We identified 18 previously validated emm types and one novel subtype, emm11.7, among the 101 GAS isolates. The two predominant types, emm28 and 12, were found in 40.6% of the GAS isolates. Compared to other recent studies of noninvasive GAS infections from elsewhere in the world, we found a higher frequency of emm82 (5.9%) and emm87 (12.9%) and a lower frequency of emm1 (4.0%) and emm3 (4.0%). We found a different distribution of GAS emm types compared to a previous study from western Norway. Among the 64 isolates of GCS and GGS, 15 previously described emm types and four novel subtypes, stC1400.5, stCK401.3, stG6.3 and stG652.3, were found. stG6, stG643 and stG485 were the most prevalent types and accounted for 59.4% of the GCS and GGS isolates. The high proportion of skin isolates in the present study may indicate the existence of GAS, GCS and GGS strains with predominantly skin and soft tissue tropism in our community. [source]

Experimental white spot syndrome virus challenge of juvenile Litopenaeus vannamei (Boone) at different salinities

AQUACULTURE RESEARCH, Issue 15 2008
I S Carbajal-Sánchez
Abstract In recent years, the shrimp industry has turned to inland freshwater culture as one method to avoid problems such as the introduction of possible vectors of viral pathogens into seawater ponds. Our experiments evaluated susceptibility to white spot syndrome virus (WSSV) in Litopenaeus vannamei held under different salinity regimens. Juvenile L. vannamei that were conditioned at salinities of 35, 25, 15, 5 and 2 g L,1 were challenged with WSSV. In order to assess the severity of white spot disease, histological analysis and nested polymerase chain reaction (PCR) tests were carried out on the challenged shrimp every 4 h after 48 h post challenge. The results indicated that significantly more severe infections resulted at 15, than at other salinities. Mortality could not be compared due to the sampling design and because severe WSSV infections occurred in all test groups such that few shrimp remained alive in each challenged group at the end of the test. Despite this, the results suggest that salinity may affect the course and outcome of WSSV infections. [source]

Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry

ARTHRITIS & RHEUMATISM, Issue 9 2010
J.-E. Gottenberg
Objective The risk of severe infection is a crucial factor in the assessment of the short-term risk:benefit ratio of biologic drugs in rheumatoid arthritis (RA). There is no increase in severe infections in RA patients treated with rituximab (RTX) in controlled trials, but this has not yet been assessed in daily practice. We undertook this study to investigate the occurrence of and risk factors for severe infections in off-trial patients using data from the AutoImmunity and Rituximab (AIR) registry. Methods The AIR registry was set up by the French Society of Rheumatology. The charts of patients with severe infections were reviewed. Results Of the enrolled patients, 1,303 had at least 1 followup visit at 3 months or later, with a mean ± SD followup period of 1.2 ± 0.8 years (1,629 patient-years). Eighty-two severe infections occurred in 78 patients (5.0 severe infections per 100 patient-years), half of them in the 3 months following the last RTX infusion. Multivariate analysis showed that chronic lung disease and/or cardiac insufficiency (odds ratio 3.0 [95% confidence interval 1.3,7.3], P = 0.01), extraarticular involvement (odds ratio 2.9 [95% confidence interval 1.3,6.7], P = 0.009), and low IgG level (<6 gm/liter) before initiation of RTX treatment (odds ratio 4.9 [95% confidence interval 1.6,15.2], P = 0.005) were significantly associated with increased risk of a severe infection. Conclusion The rate of severe infections in current practice is similar to that reported in clinical trials. The risk factors for severe infections include chronic lung and/or cardiac disease, extraarticular involvement, and low IgG before RTX treatment. This suggests that serum IgG should be checked and the risk:benefit ratio of RTX discussed for patients found to have low levels of IgG. [source]

Safety and efficacy of rituximab in systemic lupus erythematosus: Results from 136 patients from the French autoimmunity and rituximab registry

Due to low infection rates no routine anti-infective prophylaxis is required in younger patients with chronic lymphocytic leukaemia during fludarabine-based first line therapy

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007
Barbara F. Eichhorst
Summary The impact of the combination therapy fludarabine plus cyclophosphamide (FC) in comparison with fludarabine alone regarding the incidence and severity of infections among previously untreated patients with chronic lymphocytic leukaemia (CLL) was evaluated within a multicentre phase III study. A total of 375 patients, up to 65 years old, were randomised between fludarabine or FC for first line therapy. No routine anti-infective prophylaxis was provided. A total of 196 infectious episodes, including 33 severe infections, were documented. In the fludarabine arm, 32·9% of the patients developed an infectious complication compared with 39·9% in the FC arm (P = 0·2). No difference was observed in the rate of severe infections (Common Toxicity Crtieria grades III and IV) between both treatment arms. Dose reductions were performed more frequently in FC-treated patients. Granulocyte colony-stimulating factor (G-CSF) was administered due to leucopenia in 5% of all patients. A multivariate regression model identified only elevated thymidine kinase, but not the treatment arm, as a statistically independent risk factor for infections. In summary, FC was not associated with a higher rate of infections compared with fludarabine alone. No routine antibiotic or virostatic prophylaxis, or pre-emptive treatment with G-CSF, is necessary in first line therapy with fludarabine-based regimens in younger patients with CLL, if adequate dose reduction is performed. The combination therapy FC is not associated with a higher rate of infections compared with fludarabine alone. No routine antibiotic or virostatic prophylaxis as well as pre-emptive treatment with G-CSF is necessary in first line therapy with fludarabine-based regimen in younger patients with CLL, if adequate dose reductions due to cytopenia or previous infections are performed. [source]

Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis

ACTA PAEDIATRICA, Issue 7 2010
Stephen D Marks
Abstract There is still a significant morbidity and mortality associated with childhood-onset systemic lupus erythematosus (SLE), despite an increasing armamentarium of immunosuppressive agents. The ideal therapeutic strategy for children and adolescents with SLE should provide the right amount of treatment to allow normal growth, development and fertility while reducing the disease activity and damage that can be accrued over the years. Each patient should have individualized treatments tailored to their organ involvement, disease severity and history of flares together with recent clinical, haematological and immunological parameters to avoid further flares of disease activity and side-effects of treatment, especially severe infections and future malignancies. The most commonly cited side-effects of medications include Cushingoid features of corticosteroids, infective complications of cyclophosphamide and gastrointestinal side-effects of mycophenolate mofetil. There is increasing evidence to support the use of oral mycophenolate mofetil as opposed to cyclophosphamide for both induction and maintenance therapies in many children with SLE with or without lupus nephritis (LN). Recently, case series utilizing B-lymphocyte depletion therapies with rituximab look promising for patients with severe or refractory disease activity. In this article, we explore current evidence to effectively treat children and adolescents with SLE with or without LN. Conclusion:, Modern therapeutic strategies include reduced doses and use of corticosteroids and intravenous cyclophosphamide respectively, with increased use of azathioprine, MMF and rituximab. [source]

Allergic sensitization is enhanced in early life through toll-like receptor 7 activation

CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2009
S. Phipps
Summary Background Prospective cohort studies suggest that children hospitalized in early life with severe infections are significantly more likely to develop recurrent wheezing and asthma. Objective Using an inhalational mouse model of allergic airways inflammation, we sought to determine the effect of viral and bacterial-associated molecular patterns on the magnitude of the allergic inflammatory response and whether this effect was age dependent. Methods BALB/c mice were sensitized by intranasal administration of endotoxinlow ovalbumin (OVA) in the absence or presence of viral single-stranded (ss)RNA, lipoteichoic acid or flagellin as neonates (within the first 24 h of life) or as weanlings (4 weeks of age). Mice were challenged four times with OVA at 6 weeks of age and end-points (bronchoalveolar lavage cytology, histology, antigen-specific T and B cell responses) determined at 7 weeks of age. Results Inhalational sensitization (<24 h or 4 weeks of age) and challenge with OVA induced a mild allergic inflammatory response in the airways as indicated by increased numbers of eosinophils and mucus cells, elevated serum OVA-specific IgG1, and production of T helper 2 (Th2) cytokines. Mice sensitized to endotoxinlow OVA at birth in the presence of ssRNA or lipoteichoic acid, but not flagellin, showed an increase in the numbers of airway and tissue eosinophils, mucus producing cells and antigen-specific production of IL-13 as compared with mice exposed only to endotoxinlow OVA. By contrast, all three TLR ligands failed to increase the magnitude of OVA-induced allergic inflammation in mice sensitized as weanlings. Conclusions Recognition of distinct microbial-associated patterns in early life may preferentially promote the de novo differentiation of bystander, antigen-specific CD4+ T cells toward a Th2 phenotype, and promote an asthma-like phenotype upon cognate antigen exposure in later life. [source]

Molecular typing of methicillin-susceptible Staphylococcus aureus isolates collected in the Yogyakarta area in Indonesia, 2006

CLINICAL MICROBIOLOGY AND INFECTION, Issue 1 2010
R. H. Deurenberg
Abstract The characterization of 62 community-associated methicillin-sensitive Staphylococcus aureus (MSSA) isolates from 440 individuals in the Yogyakarta area of Indonesia in 2006 showed that: (i) almost half of the isolates were associated with methicillin-resistant S. aureus lineages [clonal complex (CC)1, CC8 and CC45] and (ii) ten Panton,Valentine leukocidin-positive isolates were associated with CC1 (n = 7), CC30 (n = 1) and CC51 (n = 2). The high Panton,Valentine leukocidin prevalence (16%) among S. aureus is of concern because these strains can cause severe infections and the introduction of staphylococcal cassette chromosome mec into virulent and epidemic MSSA could pose a serious public health threat. [source]

New developments in carbapenems

CLINICAL MICROBIOLOGY AND INFECTION, Issue 12 2008
J. N. Kattan
Abstract Antibiotic resistance among Gram-negative pathogens in hospitals is a growing threat to patients and is driving the increased use of carbapenems. Carbapenems are potent members of the ,-lactam family of antibiotics, with a history of safety and efficacy for serious infections that exceeds 20 years. Original and review articles were identified from a Medline search (1979,2008). Reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and package inserts were also used. Carbapenems are effective in treating severe infections at diverse sites, with relatively low resistance rates and a favourable safety profile. Carbapenems are the ,-lactams of choice for the treatment of infections caused by multidrug-resistant organisms. Optimized dosing of carbapenems should limit the emergence of resistance and prolong the utility of these agents. The newly approved doripenem should prove to be a valuable addition to the currently available carbapenems: imipenem, meropenem and ertapenem. [source]

Clusters of imipenem-resistant Acinetobacter baumannii clones producing different carbapenemases in an intensive care unit

CLINICAL MICROBIOLOGY AND INFECTION, Issue 6 2008
A. Tsakris
Abstract During a 2-year period (April 2005,March 2007), 31 intensive care unit (ICU) patients in a Greek hospital were infected or colonised with imipenem-resistant isolates of Acinetobacter baumannii. Twelve patients died, with imipenem-resistant A. baumannii infection contributing to the death of seven patients. The 31 representative A. baumannii isolates were multidrug-resistant and clustered in four distinct clones, each of which contained different carbapenemase genes: clone I was predominant and contained blaVIM-1, blaOXA-58 and the intrinsic blaOXA-66 gene; clone II contained blaVIM-4, blaOXA-58 and the intrinsic blaOXA-69 gene; clone III contained blaOXA-58 and the intrinsic blaOXA-69 gene; and clone IV contained only the intrinsic blaOXA-66 gene. ISAba1 was not associated with the intrinsic blaOXA-51-like alleles, whereas ISAba3 was found upstream and downstream of blaOXA-58 in isolates of clone I, and upstream of blaOXA-58 in isolates of clone III, but was not detected in isolates of clone II. PCR, curing and hybridisation experiments indicated that the blaVIM alleles were chromosomally located, whereas the blaOXA-58 alleles were plasmid-located. This study provides the first description of the clonal spread of multidrug-resistant A. baumannii isolates carrying blaVIM-1 and blaVIM-4 metallo-,-lactamase genes, and revealed that distinct carbapenem-resistant A. baumannii clusters bearing different carbapenemase genes may emerge and cause severe infections, even in a well-defined regional hospital setting. [source]

Empirical therapy for diabetic foot infections: are there clinical clues to guide antibiotic selection?

CLINICAL MICROBIOLOGY AND INFECTION, Issue 4 2007
B. A. Lipsky
Abstract Initial antibiotic therapy for diabetic foot infections is usually empirical. Several principles may help to avoid selecting either an unnecessarily broad or inappropriately narrow regimen. First, clinically severe infections require broad-spectrum therapy, while less severe infections may not. Second, aerobic Gram-positive cocci, particularly Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA) for patients at high-risk) should always be covered. Third, therapy should also be targeted at aerobic Gram-negative pathogens if the infection is chronic or has failed to respond to previous antibiotic therapy. Fourth, anti-anaerobe agents should be considered for necrotic or gangrenous infections on an ischaemic limb. Parenteral therapy is needed for severe infections, but oral therapy is adequate for most mild or moderate infections. [source]