Immunity to pneumococcal surface proteins in children with community-acquired pneumonia: a distinct pattern of responses to pneumococcal choline-binding protein A.

Clin Microbiol Infect ABSTRACT: The aetiological diagnosis of community-acquired pneumonia (CAP) is challenging in children, and serological markers would be useful surrogates for epidemiological studies of pneumococcal CAP. We compared the use of anti-pneumolysin (Ply) antibody alone or with four additional pneumococcal surface proteins (PSPs) (pneumococcal histidine triad D (PhtD), pneumococcal histidine triad E (PhtE), LytB, and pneumococcal choline-binding protein A (PcpA)) as serological probes in children hospitalized with CAP. Recent pneumococcal exposure (positive blood culture for Streptococcus pneumoniae, Ply(+) blood PCR finding, and PSP seroresponse) was predefined as supporting the diagnosis of presumed pneumococcal CAP (P-CAP). Twenty-three of 75 (31%) children with CAP (mean age 33.7 months) had a Ply(+) PCR finding and/or a ≥2-fold increase of antibodies. Adding seroresponses to four PSPs identified 12 additional patients (35/75, 45%), increasing the sensitivity of the diagnosis of P-CAP from 0.44 (Ply alone) to 0.94. Convalescent anti-Ply and anti-PhtD antibody titres were significantly higher in P-CAP than in non P-CAP patients (446 vs. 169 ELISA Units (EU)/mL, p 0.031, and 189 vs. 66 EU/mL, p 0.044), confirming recent exposure. Acute anti-PcpA titres were three-fold lower (71 vs. 286 EU/mL, p <0.001) in P-CAP children. Regression analyses confirmed a low level of acute PcpA antibodies as the only independent predictor (p 0.002) of P-CAP. Novel PSPs facilitate the demonstration of recent pneumococcal exposure in CAP children. Low anti-PcpA antibody titres at admission distinguished children with P-CAP from those with CAP with a non-pneumococcal origin.

Antimicrobial resistance of Staphylococcus aureus strains acquired by pig farmers from pigs

Carriage of animal-associated methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) is common among pig farmers. This study was conducted (i) to investigate whether pig farmers are colonized with pig-specific S. aureus genotypes other than CC398 and (ii) to survey antimicrobial resistance of S. aureus isolates from pigs and pig farmers. Forty-eight S. aureus isolates from pig farmers and veterinarians and 130 isolates from pigs collected in Western Switzerland were genotyped by spa typing and amplified fragment length polymorphism (AFLP). Antimicrobial resistance profiles were determined for representative sample of the isolates. The data obtained earlier on healthy S. aureus carriers without exposure to agriculture were used for comparison. The genotype composition of S. aureus isolates from pig farmers and veterinarians was similar to isolates from pigs with predominant AFLP clusters CC398, CC9, and CC49. The resistance to tetracycline and macrolides (clarithromycin) was common among the isolates from farmers and veterinarians (52 and 21%, respectively) and similar to resistance levels in isolates from pigs (39 and 23%, respectively). This was in contrast to isolates from persons without contact with agriculture, where no (0/128) isolates were resistant to tetracycline and 3% of the isolates were resistant to clarithromycin. MRSA CC398 was isolated from pigs (n = 11) and pig farmers (n = 5). These data imply that zoonotic transmission of multidrug-resistant S. aureus from pigs to farmers is frequent, and well-known MRSA transmission merely represents the tip of the iceberg for this phenomenon. We speculate that the relatively low frequency of MRSA isolation is related to lower antimicrobial use in Switzerland compared to, for example, the Netherlands.

Diagnosis of invasive candidiasis in the ICU.

Invasive candidiasis ranges from 5 to 10 cases per 1,000 ICU admissions and represents 5% to 10% of all ICU-acquired infections, with an overall mortality comparable to that of severe sepsis/septic shock. A large majority of them are due to Candida albicans, but the proportion of strains with decreased sensitivity or resistance to fluconazole is increasingly reported. A high proportion of ICU patients become colonized, but only 5% to 30% of them develop an invasive infection. Progressive colonization and major abdominal surgery are common risk factors, but invasive candidiasis is difficult to predict and early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New nonculture-based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Both serologic (mannan, antimannan, and betaglucan) and molecular (Candida-specific PCR in blood and serum) have been applied as serial screening procedures in high-risk patients. However, although reasonably sensitive and specific, these techniques are largely investigational and their clinical usefulness remains to be established. Identification of patients susceptible to benefit from empirical antifungal treatment remains challenging, but it is mandatory to avoid antifungal overuse in critically ill patients. Growing evidence suggests that monitoring the dynamic of Candida colonization in surgical patients and prediction rules based on combined risk factors may be used to identify ICU patients at high risk of invasive candidiasis susceptible to benefit from prophylaxis or preemptive antifungal treatment.

Panobacumab adjunctive immuno-therapy for Pseudomonas aeruginosa hospital-acquired pneumonia versus a cohort group

Objectives: To assess the efficacy of Panobacumab, a fully human IgM monoclonal antibody against P. aeruginosa serotype O11, by comparing a phase IIa trial with a standard care cohort trial both in hospital acquired pneumonia (HAP) caused by P. aeruginosa O11. Methods: Demographics, outcome and survival of HAP including Ventilator Associated Pneumonia (VAP) in patients either treated with standard antimicrobial therapy in a retrospective cohort trial (CT) or with adjunctive Panobacumab therapy during an open phase IIa trial were compared. Both trials applied the same inclusion exclusion criteria and the same trial period of 30 days. Results: 17 patients with VAP/HAP (14 / 3) caused by P. aeruginosa O11 were enrolled in a phase IIa trial (ITT population) and treated with Panobacumab, 13 of them received the full treatment course of 3 infusions (PP population, 12 VAP, 1 HAP) and 4 patients received only one infusion. In the cohort trial 14 patients (VAP/HAP: 12 / 2) treated with standard antibiotic therapy were included. The mean age and weight were 65.8 y (years) (SD 17.2) and 78.0 kg (SD 22.1) in the PP, 67.8 y (SD 15.4) and 77.1 kg (SD 20.2) in the ITT population and 51.8 y (SD 22.3) and 67.1 kg (SD 13.0) in the CT. At the time of suspicion of pneumonia a mean APACHE II and CPIS of 19.4 (13 - 33) and 8.7 (7 - 11) in the PP, 18.9 (13-33) and 8.5 (7 -11) in the ITT and 14.5 (2 - 24) and 7.5 (3 -12) in the CT population were observed. Tracheostomy was present in 53.8% and 52.9% in the PP and ITT populations and 38.4% in the CT. The pneumonia was polymicrobial in 69.2%, 70.6% and 85.7% in the PP, ITT and CT respectively. Stay at ICU and hospital before diagnosis of pneumonia were similar in the 3 groups. All 13 patients that received 3 doses of Panobacumab achieved resolution of pneumonia with only two relapsing during the study. Hence 85% achieved resolution and 15% recurrence at day 30. In the ITT group 64.7% of the pneumonia resolved 11.8% recurred and 23.5% continued while in the CT 57% resolved, 7% recurred and 34% continued. Resolution of pneumonia occurred markedly earlier in the Panobacumab trial (8.9 days, SD: 3.3) than in the cohort trial (15.3 days, SD: 9.5). The expected mortality derived from APACHE II score was 31% and 32% in the PP and ITT population and 22% in the cohort group. All patients who received 3 doses of Panobacumab survived, 18% died in the ITT group while in the CT 21% mortality matched the predicted mortality. Conclusions: Treatment of VAP/HAP caused by P. aeruginosa O11 with 3 doses of Panobacumab resulted in 100% survival, with highest pneumonia resolution (85%), and in a shorter time when compared with patients under standard therapy. The results indicate that Panobacumab may be effective in such life-threatening indication and warrants larger controlled trials.

Identification of muscle-specific calpain and beta-sarcoglycan genes in progressive autosomal recessive muscular dystrophies.

The autosomal recessive forms of limb-girdle muscular dystrophies are encoded by at least five distinct genes. The work performed towards the identification of two of these is summarized in this report. This success illustrates the growing importance of genetics in modern nosology.

Lésions cutanées et infiltrats pulmonaires d'évolution défavorable sans cause infectieuse [Progressive cutaneous and pulmonary lesions without infectious etiology: two cases reports of sweet syndrome with pulmonary involvement].

Sweet syndrome is a non infectious febrile disease with a neutrophilic infiltrate of dermis. Extracutaneous involvement can occur. We report two cases of Sweet syndrome with cutaneous and pulmonary involvement and give a short review of the literature of pulmonary involvement in Sweet syndrome.

Progressive Taxes and Firm Births

Tax reform proposals in the spirit of the "flat tax" model typically aim to reduce three parameters: the average tax burden, the progressivity of the tax schedule, and the complexity of the tax code. We explore the implications of changes in these three parameters for entrepreneurial activity, measured by counts of firm births. The Swiss fiscal system offers sufficient intra-national variation in tax codes to allow us to estimate such effects with considerable precision. We find that high average taxes and complicated tax codes depress firm birth rates, while tax progressivity per se promotes firm births. The latter result supports the existence of an insurance effect from progressive corporate income taxes for risk averse entrepreneurs. However, implied elasticities with respect to the level and complexity of corporate taxes are an order of magnitude larger than elasticities with respect to the progressivity of tax schedules.

Le QT long acquis [Acquired long QT syndrome].

The long QT syndrome may be acquired or genetically determined. The syndrome is characterized by a prolonged QT interval and is associated with an increased risk of cardiac arrhythmia such as a torsade de pointe and death. Electrolytes disorders such as hypomagnesemia and hypokaliemia and several drugs may increase the risk to develop a long QT syndrome. The epidemiology, the aetiology, the diagnostic approach as well as the management options of an acquired QT prolongation is discussed and reviewed herein.

Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines.

Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.

Clinical predictors for Legionella in patients presenting with community-acquired pneumonia to the emergency department.

BACKGROUND: Legionella species cause severe forms of pneumonia with high mortality and complication rates. Accurate clinical predictors to assess the likelihood of Legionella community-acquired pneumonia (CAP) in patients presenting to the emergency department are lacking. METHODS: We retrospectively compared clinical and laboratory data of 82 consecutive patients with Legionella CAP with 368 consecutive patients with non-Legionella CAP included in two studies at the same institution. RESULTS: In multivariate logistic regression analysis we identified six parameters, namely high body temperature (OR 1.67, p < 0.0001), absence of sputum production (OR 3.67, p < 0.0001), low serum sodium concentrations (OR 0.89, p = 0.011), high levels of lactate dehydrogenase (OR 1.003, p = 0.007) and C-reactive protein (OR 1.006, p < 0.0001) and low platelet counts (OR 0.991, p < 0.0001), as independent predictors of Legionella CAP. Using optimal cut off values of these six parameters, we calculated a diagnostic score for Legionella CAP. The median score was significantly higher in Legionella CAP as compared to patients without Legionella (4 (IQR 3-4) vs 2 (IQR 1-2), p < 0.0001) with a respective odds ratio of 3.34 (95%CI 2.57-4.33, p < 0.0001). Receiver operating characteristics showed a high diagnostic accuracy of this diagnostic score (AUC 0.86 (95%CI 0.81-0.90), which was better as compared to each parameter alone. Of the 191 patients (42%) with a score of 0 or 1 point, only 3% had Legionella pneumonia. Conversely, of the 73 patients (16%) with > or =4 points, 66% of patients had Legionella CAP. CONCLUSION: Six clinical and laboratory parameters embedded in a simple diagnostic score accurately identified patients with Legionella CAP. If validated in future studies, this score might aid in the management of suspected Legionella CAP.