Successful Treatment of PulmonaryInvasive Aspergillosis with Voriconazole in Patients who FailedConventional Therapy

Abstract.: Background: The incidence of fungal infections, including those due to Aspergillosis species has continued to increase in recent years. Invasive aspergillosis remains an important cause of morbidity and mortality, despite therapeutics interventions. Patients and Methods: We reported five cases of invasive pulmonary aspergillosis treated with voriconazole failing to respond to conventional treatments. Results: The clinical and radiological resolution of pulmonary aspergillosis reported in these cases following therapy with voriconazole is remarkable, considering the infections had proved refractory to standard antifungal therapies. Long-term therapy (in two cases ≥ 1 year, in one case 6 months) was very well tolerated by patients who were unable to tolerate other antifungal agents. Conclusion: Therapy with voriconazole offers a new therapeutic option for otherwise difficult-to-treat infections and the potential to significantly improve the management of Aspergillosis infection

Reconsidering mammal extinctions in the Pernambuco Endemism Center of the Brazilian Atlantic Forest

Reconsiderando la extinción de mamíferos en el Centro de Endemismo Pernambuco perteneciente al bosque atlántico brasileño Se ha calculado que, en los últimos 500 años, se han extinguido 21 mamíferos en el Centro de Endemismo Pernambuco. En el presente estudio, realizamos un examen crítico de los datos aportados en las publicaciones científicas históricas y recientes, y concluimos que el número real de mamíferos extintos es de siete, lo que indica que la cifra anterior de 21 especies extintas es una sobrestimación de aproximadamente 30 %. Nuestra lista difiere de las publicaciones previas en que incluye especies aún existentes (n = 5) y excluye otras que nunca habían sido registradas en el Centro de Endemismo Pernambuco (n = 8). Asimismo, señalamos que, al elaborar listas de fauna extinta a escala regional, es necesario adoptar un planteamiento más riguroso en relación con los registros históricos y recientes, dado que las identificaciones erróneas y las suposiciones falsas podrían conducir a la pérdida de credibilidad ante las partes interesadas y, en última instancia, ser negativas para la conservación de especies.In the last 500 years, there have been an estimated 21 mammal extinctions in the Pernambuco Endemism Center. We critically reviewed the published historical and recent literature records and concluded that the actual number of mammal species extinction was seven, indicating that the previous figure of 21 species lost is an overestimation of approximately 30 %. Our checklist differs from previous publications by including species that are still extant (n = 5), and removing species that have never been recorded in the Pernambuco Endemism Center (n = 8). We point out that a more rigorous approach towards historical and recent records is needed when producing lists of regionally extinct fauna, given that the implications of misidentifications and false assumptions can potentially lead to loss of credibility by stakeholders and ultimately have a negative effect on species conservation.Reconsiderando la extinción de mamíferos en el Centro de Endemismo Pernambuco perteneciente al bosque atlántico brasileño Se ha calculado que, en los últimos 500 años, se han extinguido 21 mamíferos en el Centro de Endemismo Pernambuco. En el presente estudio, realizamos un examen crítico de los datos aportados en las publicaciones científicas históricas y recientes, y concluimos que el número real de mamíferos extintos es de siete, lo que indica que la cifra anterior de 21 especies extintas es una sobrestimación de aproximadamente 30 %. Nuestra lista difiere de las publicaciones previas en que incluye especies aún existentes (n = 5) y excluye otras que nunca habían sido registradas en el Centro de Endemismo Pernambuco (n = 8). Asimismo, señalamos que, al elaborar listas de fauna extinta a escala regional, es necesario adoptar un planteamiento más riguroso en relación con los registros históricos y recientes, dado que las identificaciones erróneas y las suposiciones falsas podrían conducir a la pérdida de credibilidad ante las partes interesadas y, en última instancia, ser negativas para la conservación de especies

A Randomized Prospective Study of Cefepime Plus Metronidazole with Imipenem-Cilastatin in the Treatment of Intra-abdominal Infections

Abstract : Background: : Presumptive antimicrobial therapy is an important aspect of the management of intra-abdominal infections. Together with surgery, antimicrobial combinations are still widely used to achieve the required spectrum of activity. The aim of this study was to evaluate the efficacy of parenteral cefepime + metronidazole vs imipenemcilastatin for the treatment of intra-abdominal infections in adult patients. Methods: : Patients with a clinically confirmed diagnosis of intra-abdominal infection were randomized to one of two treatment regimens: cefepime 2 g iv/12 h plus metronidazole 500 mg/8 h or imipenem-cilastatin 500 mg iv/6 h. The primary measure of clinical response was the decline of pre-treatment signs and symptoms of infection. The duration of follow-up was 30 days. Treatment failure was defined as either a lack of improvement or a worsening of pre-treatment signs and symptoms of infection. Surgical management of the infection was determined by the surgeon-in-charge. Results: : Of the 122 intended-to-treat patients included in the study, 60 patients (33 men) were randomized to cefepime + metronidazole and 61 (27 men) to imipenemcilastatin. Cefepime + metronidazole treatment was successful in 52 (87%) patients and imipenem-cilastatin in 44 (72%) patients (p = 0.004). Microbiological eradication was established in similar proportions in both groups (cefepime + metronidazole, 43; imipenem-cilastatin, 38). Conclusion: : Further studies are warranted to confirm the better results with the cefepime + metronidazole regimen for the treatment of intra-abdominal infection

Children's environmental health: an under-recognised area in paediatric health care

The knowledge that the environment in which we live, grow and play, can have negative or positive impacts on our health and development is not new. However the recognition that adverse environments can significantly and specifically affect the growth and development of a child from early intrauterine life through to adolescence, as well as impact their health later in adulthood, is relatively recent and has not fully reached health care providers involved in paediatric care

Treatment options of invasive fungal infections in adults.

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events

Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Human Rhinovirus Infections in Rural Thailand: Epidemiological Evidence for Rhinovirus as Both Pathogen and Bystander

BACKGROUND: We describe human rhinovirus (HRV) detections in SaKaeo province, Thailand. METHODS: From September 1, 2003-August 31, 2005, we tested hospitalized patients with acute lower respiratory illness and outpatient controls without fever or respiratory symptoms for HRVs with polymerase chain reaction and molecularly-typed select HRVs. We compared HRV detection among hospitalized patients and controls and estimated enrollment adjusted incidence. RESULTS: HRVs were detected in 315 (16%) of 1919 hospitalized patients and 27 (9.6%) of 280 controls. Children had the highest frequency of HRV detections (hospitalized: <1 year: 29%, 1-4 year: 29%, ≥ 65 years: 9%; controls: <1 year: 24%, 1-4 year: 14%, ≥ 65 years: 2.8%). Enrollment adjusted hospitalized HRV detection rates were highest among persons aged <1 year (1038/100,000 persons/year), 1-4 years (457), and ≥ 65 years (71). All three HRV species were identified, HRV-A was the most common species in most age groups including children aged <1 year (61%) and all adult age groups. HRV-C was the most common species in the 1-4 year (51%) and 5-19 year age groups (54%). Compared to controls, hospitalized adults (≥ 19 years) and children were more likely to have HRV detections (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5, 15.8; OR: 2.0, CI: 1.2, 3.3, respectively) and hospitalized children were more likely to have HRV-A (OR 1.7, CI: 0.8, 3.5) or HVR-C (OR 2.7, CI: 1.2, 5.9) detection. CONCLUSIONS: HRV rates were high among hospitalized children and the elderly but asymptomatic children also had substantial HRV detection. HRV (all species), and HRV-A and HRV-C detections were epidemiologically-associated with hospitalized illness. Treatment or prevention modalities effective against HRV could reduce hospitalizations due to HRV in Thailand