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1.

Objective

To investigate the efficacy and safety of sofosbuvir (SOF) plus daclatasvir (DCV) or simeprevir (SMV) in a randomized, open-label, noninferiority trial of patients infected with hepatitis C virus genotype 1, who were previously unresponsive to pegylated interferon and ribavirin or were treatment naive.

Methods

Patients were randomly assigned to receive SOF (400 mg once daily) plus DCV (60 mg once daily) or SMV (150 mg once daily) for 12 weeks. The analysis included all participants who received at least one dose of the study drugs. The primary endpoint was sustained virologic response 12 weeks after ending treatment (SVR12; hepatitis C virus RNA measured using COBAS TaqMan RT-PCR (lower limit of detection and quantification of 12 UI/mL)). This study was registered at ClinicalTrials.gov (NCT02624063).

Results

A total of 125 of 127 enrolled and randomized patients started treatment (n = 65 SOF + DCV; n = 60 SOF + SMV). SVR12 was attained in 121 patients (96.8%): 65 (100%) receiving SOF + DCV (95% confidence interval (CI), 94.5 to 100) and 56 (93.3%) receiving SOF + SMV (95% CI, 83.8 to 98.2; absolute difference, 6.6%; 95% CI, ?15.0 to 0). The most common adverse events were fatigue (n = 32, 25.6%), headache (n = 27, 21.6%), and mood swings (n = 24, 19.2%). No patients discontinued therapy.

Conclusions

The overall SVR rate was 96.9%; SOF + DCV (100%) was higher than that of SOF + SMV (93.3%). Despite no statistically significant intergroup difference in SVR12 rates, the noninferiority of SOF + SMV to SOF + DCV could not be established because the difference in efficacy was clinically relevant.  相似文献   

2.

Background

Intensive care unit (ICU) admission is a risk factor for fatal asthma. Little is known about risk factors for pediatric ICU admissions for asthma.

Objective

To examine characteristics of underserved minority children with prior ICU admissions for asthma.

Methods

Baseline survey data, salivary cotinine levels, and allergen specific IgE serologic test results were obtained from children with uncontrolled asthma enrolled in a randomized clinical trial of a behavioral education environmental control intervention. Characteristics of children with and without prior ICU admission were compared using χ2 and t tests. Logistic regression assessed significance of higher odds of prior ICU admission comparing factor-level categories.

Results

Patients included 222 primarily African American (93.7%), male (56%), Medicaid-insured (92.8%) children with a mean (SD) age of 6.4 (2.7) years with uncontrolled asthma. Most (57.9%) had detectable cotinine levels, 82.6% were sensitized to more than 1 environmental allergen, and 27.9% had prior ICU admissions. Prior ICU patients were more likely to be very poor (<$10,000 per year) and sensitized to more than 1 allergen tested (most importantly mouse) (P < .05). Allergen sensitization in the groups did not differ for cockroach, cat, dog, Alternaria, Aspergillus, dust mite, grass, or tree. Although more ICU patients received combination controller therapy, they also overused albuterol. Only 27.4% of ICU patients received specialty care in the previous 2 years, which was not significantly different from non-ICU patients.

Conclusion

Children with high mortality risk, including history of ICU admission, were twice as likely to live in extreme poverty, have atopy (particularly mouse allergen), use combination controller therapy, and overuse albuterol.

Trial Registration

ClinicalTrials.gov Identifier: NCT01981564.  相似文献   

3.

Background/purpose

It is controversial whether healthcare-associated pneumonia (HCAP) belongs to a unique clinical entity or it shares common characteristics with community-acquired pneumonia (CAP). The impact of prior pulmonary tuberculosis (PTB) in clinical presentation and treatment outcome of ICU-admitted CAP and HCAP patients also remains unknown.

Methods

We report a nationwide, multi-center, retrospective study. ICU-admitted CAP and HCAP patients from six medical centers in Taiwan were enrolled for analysis. Patients were defined as either CAP or HCAP cases, and with and without prior PTB, according to the database of Taiwan CDC. The disease severity, microbiologic characteristics, and treatment outcomes between CAP and HCAP patients with or without prior PTB were compared and analyzed.

Results

A total of 414 ICU-admitted patients, including 176 CAP cases and 238 HCAP cases were included for analysis during the study period. In both CAP and HCAP subgroups, the pneumonia severities, proportions of organ dysfunction, and microbiologic characteristics were similar between patients with and without prior PTB. In survival analysis, patients with prior PTB had higher 30-day mortality than those without prior PTB (38.9% vs. 16.5%, p = 0.021) in the CAP population. Multivariate analysis revealed that a history of prior PTB was an independent clinical factor associated with higher 30-day mortality rate in CAP patients (HR = 4.45, 95% CI: 1.81–10.98, P = 0.001).

Conclusion

History of prior PTB is an independent clinical factor for increased 30-day mortality rate in ICU-admitted CAP patients, but not in ICU-admitted HCAP patients.  相似文献   

4.

Background

Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed.

Methods

Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected.

Results

Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week.

Conclusions

BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.  相似文献   

5.

Background/purpose

Intestinal parasitic infections (IPIs) among school aged children (SAC) in Nigeria remains endemic, hence the need for regular surveillance to attract the attention of policy makers. This cross-sectional study investigated the current prevalence and factors associated with intestinal parasitic infections among school aged children in an urban slum of Lagos City, Nigeria.

Methods

Single stool samples from 384 school aged children (188 boys and 196 girls) were examined by employing Merthiolate-iodine-formaldehyde concentration (MIFC) and Kato-Katz methods. Demographic characteristics and risk factors were obtained by questionnaires investigation.

Results

The overall prevalence was 86.2% in school children, out of them 39.1% had polyparasitism. IPIs showed the highest to the lowest prevalence of 62% (238/384), 25% (97/384), 12.3% (47/384), 11.8% (45/384), 9.9% (38/384), 8.4% (32/384), 3.4% (13/384), and 0.5% (2/384) found in Ascaris lumbricoides, Entamoeba histolytica/dispar, Giardia duodenalis, Endolimax nana, Entamoeba coli, Trichuris trichiura, Blastocystis hominis, and hookworm infections, respectively. MIFC technique showed superiority to Kato-Katz technique in the detection of IPIs (p < 0.0001). Drinking untreated water was a significant risk factor for these school aged children in acquiring protozoan infections after multivariate adjustment (OR = 1.86, 95% CI = 1.08–3.20, p = 0.02).

Conclusion

Intestinal parasitic infections are very severe among school aged children in the urban slums, thus regular mass de-worming programs, health education, and the provision of safe drinking water is recommended to combat IPIs among the school aged children.  相似文献   

6.

Background/Purpose

In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens.

Methods

Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies.

Results

Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84–100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69–100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens.

Conclusion

Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application.  相似文献   

7.

Objectives

Pentraxin 3 (PTX3) contributes to resistance to Aspergillus infections. This study aimed to evaluate the presence of PTX3 in bronchoalveolar lavage fluid (BALF) and plasma in non-neutropenic patients with pulmonary aspergillosis.

Methods

BALF (n = 211) and plasma samples (n = 307) were collected from patients initially suspected of having pulmonary aspergillosis. Among these, 112 cases (51 BALF samples and 89 plasma samples) were proven to be pulmonary aspergillosis. These cases were classified as invasive pulmonary aspergillosis (IPA), subacute invasive aspergillosis (SAIA) and chronic pulmonary aspergillosis (CPA). The remaining cases were non-aspergillosis controls and were diagnosed with community-acquired pneumonia (CAP), lung cancer and pulmonary cryptococcosis. Plasma samples from healthy controls (n = 30) were also collected.

Results

The median (interquartile range, IQR) BALF PTX3 for aspergillosis cases was significantly higher than for non-aspergillosis cases: 6.97 (2.91–13.51) ng/mL versus 1.26 (0.76–1.76) ng/mL. When the PTX3 threshold was set at 1.9 ng/mL, sensitivity and specificity of BALF PTX3 for aspergillosis were 86.3% (95%CI 83.8–88.4%) and 82.5% (95%CI 79.7–85.0%), respectively. The median (IQR) plasma PTX3 for aspergillosis cases was significantly higher than for non-aspergillosis cases and healthy controls: 7.10 (3.36–9.53) ng/mL versus 1.57 (0.86–2.35) ng/mL versus 1.10 (0.49–1.51) ng/mL. With a PTX3 threshold of 2.3 ng/mL, sensitivity and specificity were 79.8% (95%CI 70.1–81.2%) and 72.1% (95%CI 69.5–74.5%) respectively.

Conclusions

BALF and plasma PTX3 may be biomarkers for differentiating aspergillosis from other conditions such as CAP, lung cancer, and pulmonary cryptococcosis in non-neutropenic patients.  相似文献   

8.

Objectives

Time to blood culture positivity (TTP), a routinely available parameter in automated blood culture systems, may be a proxy for infectious burden in patients with bloodstream infections. We aimed to study the association between TTP and infective endocarditis (IE), or death, in patients with Staphylococcus aureus bacteraemia.

Methods

VIRSTA is a multicentre prospective cohort study that included all adult patients with S. aureus bacteraemia in eight university hospitals in France (2009–2011). We analysed data from four centres which collected data on TTP. Regression models were used to study the association between TTP and definite IE (Duke-Li criteria), and 30 day-mortality.

Results

We included 587 patients with S. aureus bacteraemia: mean age was 65.3 ± 16.3 years, 420 out of 587 patients (71.6%) were male, 121 out of 587 (20.6%) died, and 42 out of 587 (7.2%) had definite IE. Median TTP of first positive blood culture was 13.7 h (interquartile range 9.9–18). On multivariate analysis, 30-day mortality was associated with TTP ≤13.7 h (74/295 (25.1%) vs. 47/292 (16.1%), p 0.02), as well as old age, McCabe score, methicillin resistance, stroke, pneumonia, and C-reactive protein. TTP was also independently associated with IE, but with a U-shape curve: IE was more common in the first (TTP <10 h, 17/148, 11.5%), and the last (TTP ≥18 h, 8/146, 5.5%) quartiles of TTP, p 0.002.

Conclusions

TTP provides reliable information in patients with S. aureus bacteraemia, on the risk of IE, and prognosis, with short TTP being an independent predictor of death. These data, readily available at no cost, may be used to identify patients who require specific attention.  相似文献   

9.

Objectives

 Nocardia, a Gram-positive bacterium, is responsible for rare and severe infections. Accurate microbiological data are essential to guide antibiotic treatment. Our primary objective was to describe species identification and results of antimicrobial susceptibility testing (AST) for Nocardia isolates analysed over a 6-year period. Secondary objectives were to study temporal trends in species distribution and AST results.

Methods

 We retrospectively analysed results from Nocardia isolates sent between January 2010 and December 2015 to a French laboratory dedicated to Nocardia (Observatoire Français des Nocardioses). Species identification was obtained by amplification and sequencing of a 600-bp fragment of the 16S rRNA gene (for all isolates) and of hsp65 (when required). AST was performed using disk diffusion.

Results

 We included 793 Nocardia isolates, mostly from the lungs (53.8%). The most frequent species were Nocardia farcinica (20.2%), Nocardia abscessus complex (19.9%) and Nocardia nova complex (19.5%). The proportion of N. farcinica increased significantly over time from 13% in 2010 to 27.6% in 2014. Linezolid, amikacin, trimethoprim-sulfamethoxazole, minocycline and imipenem were the most frequently identified active antibiotics with, respectively, 0% (0/734), 2.9% (21/730), 5.4% (40/734), 9.4% (69/734) and 19.5% (143/732) of isolates not susceptible. Nocardia farcinica was frequently not susceptible to cefotaxime (118/148, 79.7% of the isolates), but only about 5% of Nocardia cyriacigeorgica and N. abscessus complex isolates were not susceptible to cefotaxime.

Conclusions

 In this first epidemiological study of Nocardia isolated from human samples in France, N. farcinica was the species most frequently identified and its prevalence increased over time.  相似文献   

10.

Objectives

We aimed to describe the current time-to-positivity (TTP) of blood cultures in individuals with onco-haematological diseases with febrile neutropenia. We assessed the probability of having a multidrug-resistant Gram-negative bacilli (MDR-GNB) bloodstream infection (BSI) 24 h after cultures were taken, to use this information for antibiotic de-escalation strategies.

Methods

BSI episodes were prospectively collected (2003–2017). When a patient experienced more than one BSI, only one episode was randomly chosen. Time elapsed from the beginning of incubation to a positive reading was observed; TTP was recorded when the first bottle had a positive result.

Results

Of the 850 patient-unique episodes, 323 (38%) occurred in acute leukaemia, 185 (21.8%) in non-Hodgkin's lymphoma and 144 (16.9%) in solid neoplasms. Coagulase-negative staphylococci (225; 26.5%), Escherichia coli (207; 26.1%), Pseudomonas aeruginosa (136; 16%), Enterococcus spp. (81; 9.5%) and Klebsiella pneumoniae (67; 7.9%), were the most frequent microorganisms isolated. MDR-GNB were documented in 126 (14.8%) episodes. Median TTP was 12 h (interquartile range 9–16.5 h). Within the first 24 h, 92.1% of blood cultures were positive (783/850). No MDR-GNB was positive over 24 h. Of the 67 (7.9%) episodes with a TTP ≥24 h, 25 (37.3%) occurred in patients who were already receiving active antibiotics against the isolated pathogen. Most common isolations with TTP ≥24 h were coagulase-negative staphylococci, candidaemia and a group of anaerobic GNB.

Conclusions

Currently, the vast majority of BSI in individuals with onco-haematological diseases with febrile neutropenia have a TTP <24 h, including all episodes caused by MDR-GNB. Our results support reassessing empiric antibiotic treatment in neutropenic patients at 24 h, to apply antibiotic stewardship de-escalation strategies.  相似文献   

11.

Background

Genitourinary tuberculosis (GUTB) is rare but fatal if not diagnosed early. The purpose of this study was to investigate the outcomes of GUTB in Taiwan.

Methods

We retrospectively reviewed medical records of 57 patients who were diagnosed as GUTB from January 2002 to December 2016, over a 15-year period. Demographic data and clinical manifestations were recorded for analysis.

Results

There were 37 males and 20 females with a median age of 71 years. Kidney (24.6%) was the most involved organ. Fever (56.1%) was the major presentation. Sixteen (28.1%) patients presented unfavorable outcome. Compared with the favorable outcome group, the unfavorable outcome group had more malignancy (p = 0.013), fever (p = 0.020), anemia (p = 0007), thrombocytopenia (p = 0.003), and hypoalbuminemia (p = 0.015). In a multivariate analysis, fever (odds ratio: 42.716, 95% confidence interval: 1.032–1767.569; p = 0.048) was identified as prognostic factors for unfavorable outcome.

Conclusion

GUTB is often in advanced stages with a high mortality in Taiwan. Establishing a diagnosis is difficult and requires thorough investigation. Fever is associated with unfavorable outcome.  相似文献   

12.

Objectives

Rapid detection of macrolide resistance–associated mutations in Mycoplasma pneumoniae is crucial for effective antimicrobial treatment. We evaluated the Lightmix Mycoplasma macrolide assay for the detection of point mutations at nucleotide positions 2063 and 2064 in the 23S ribosomal RNA (rRNA) gene of M. pneumoniae that confer macrolide resistance.

Methods

Samples from 3438 patients with a respiratory tract infection were analysed by M. pneumoniae real-time PCR, and 208 (6%) of them were tested positive. In this retrospective study, 163 M. pneumoniae real-time PCR–positive samples were analysed by the Lightmix assay, and results were compared to targeted 23S rRNA sequencing.

Results

Macrolide-resistant M. pneumoniae were found in 15 (9%) of 163 retrospectively analysed samples. The Lightmix assay showed a sensitivity of 100% (95% confidence interval, 78.2–100) and a specificity of 100% (95% confidence interval, 97.5–100) as the detected M. pneumoniae genotype (148 wild type and 15 non–wild type) was confirmed by 23S rRNA sequencing in all samples.

Conclusions

The Lightmix assay is an easy-to-use and accurate molecular test that allows rapid determination of macrolide resistance in M. pneumoniae.  相似文献   

13.

Background/purpose

The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear.

Methods

We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18–64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002–2011.

Results

Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01–0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33–9.99).

Conclusion

The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications.  相似文献   

14.

Background

Concerns about non-typeable Haemophilus influenzae (NTHi) in otitis media (OM) have grown after the introduction of pneumococcal conjugate vaccine (PCV). We aim to better understand the clinical role of NTHi in pediatric OM.

Methods

Middle ear fluid samples from children <18 years with OM were obtained from 2010 to 2015. For culture-positive episodes (Streptococcus pneumoniae, H. influenzae, Moraxella catarrhalis, and Streptococcus pyogenes), patients' demographic and clinical information were reviewed and analyzed.

Results

A total of 783 episodes were included with 31.8% of isolates as positive. S. pneumoniae was recovered in 69.4%, NTHi in 24.6%, M. catarrhalis in 5.6%, and S. pyogenes in 4.0% of culture-positive episodes. The proportion of pneumococcal OM has declined since 2012 (P for trend <0.005), but NTHi OM rose simultaneously (P for trend = 0.009). Factors associated with increased risk of NTHi infection included less spontaneous otorrhea (OR 0.15, 95% CI 0.06–0.39, P < 0.001), absence of fever (OR 0.30, 95% CI 0.14–0.66, P = 0.003), concurrent sinusitis (OR 2.91, 95% CI 1.36–6.20, P = 0.006), previous ventilation tube insertion (OR 12.02, 95% CI 3.15–45.92, P < 0.001) and recurrent OM (OR 3.43, 95% CI 1.01–11.71, P = 0.049). The susceptibility of NTHi to amoxicillin/clavulanate was 82.0%.

Conclusions

NTHi OM has trended upward in the post-PCV era. Concurrent sinusitis, previous ventilation tube insertion, and recurrent OM were associated with NTHi OM implicated a correlation between NTHi and complex OM. In consideration of NTHi infection, we suggest amoxicillin/clavulanate as the first-line therapy for OM among Taiwanese children.  相似文献   

15.

Background/purposes

Human adenovirus (HAdV) infection is prevalent and has an important clinical impact on children. We aim to investigate the molecular epidemiology of HAdV infection and discover the correlations between clinical features and HAdV species in an HAdV outbreak of 2014.

Methods

This is a retrospective study, enrolling patients under 19 years of age with HAdV infection at the National Taiwan University Hospital in 2014. We gathered the demographic and clinical data, carried out molecular typing and constructed a phylogenetic tree. Statistical analyses were performed in terms of HAdV species and hospitalization.

Results

A total of 531 patients with HAdV infection were identified. HAdV-B accounted for the largest proportion (n = 387, 73%). On average, patients infected with HAdV-E were oldest, whereas those with HAdV-C infection were youngest (p < 0.001). Patients with HAdV-B (HAdV-3) infection were associated with a lower incidence of co-infection with other viruses (p < 0.001). Complications occurred in 203 (38%) patients. There were 149 (28%) patients requiring hospitalization. The risk factors for hospitalization included underlying neurological abnormalities, prematurity and the diagnosis of pneumonia. Five patients (1%) had severe HAdV infection requiring intensive care; all of them fully recovered. The phylogenetic study showed that the partial hexon genes of HAdV-1, HAdV-3, HAdV-4 and HAdV-5 remain stable over time.

Conclusion

We established the molecular epidemiology of HAdV infection and demonstrated the relationship between clinical features and HAdV species.  相似文献   

16.

Background

Inhaled corticosteroid (ICS) titration in asthma is primarily based on symptoms and pulmonary function. ICSs may not be increased on this basis despite residual airway inflammation.

Objective

To compare the dose-response relationships of ICSs on measures of pulmonary function, symptoms, and inflammation in patients with persistent asthma.

Methods

We performed a pooled post hoc analysis of 121 patients with mild to moderate asthma from 4 randomized clinical trials that incorporated an ICS dose ramp. Dose ramps were 0 to 200, 0 to 800, and 200 to 800 μg/d (beclomethasone equivalents). Outcome measures included spirometry, fractional exhaled nitric oxide, airway hyperresponsiveness (AHR), symptoms, serum eosinophilic cationic protein, and blood eosinophils.

Results

We found a plateau beyond a small improvement at 0 to 200 μg for forced expiratory volume in 1 second: 3.3% (95% confidence interval [CI], 2.0%–4.7%) at 0 to 200 μg vs 0.3% (95% CI, ?0.8% to 1.4%) 200 to 800 μg (P = .001). A similar plateau was seen for symptom improvement beyond 0 to 200 μg. Inflammatory and AHR outcomes revealed further room for improvement beyond low-dose ICSs. There was dose-related suppression (P < .001) for fractional exhaled nitric oxide: 40.4 ppb (95% CI, 34.7–46.9 ppb) for ICS free, 26.8 ppb (95% CI, 23.4–30.2 ppb) for 200 μg, and 20.8 ppb (95% CI, 18.8–23.1 ppb) for 800 μg. Eosinophilic cationic protein concentration was significantly reduced with both higher dose ramps. Eosinophil counts also improved across all 3 dose ramps, with dose separation of 370/μL (95% CI, 280–450/μL) for ICS free vs 250/μL (95% CI, 200–300/μL) 800 μg (P = .03). AHR improved with all 3 dose ramps, with greater improvement at lower doses for indirect vs direct challenges.

Conclusion

ICS dose response may extend beyond low dose for inflammation and AHR but not symptoms or spirometry. Further study is required to identify whether this correlates with suboptimal longitudinal asthma control.

17.

Objectives

Genomic characterization of the internationally spread sequence type (ST) 16 carbapenem-resistant Klebsiella pneumoniae.

Methods

The complete genomes of three carbapenem producing ST16 K. pneumoniae from Italian patients were analysed by single-nucleotide polymorphism-based phylogeny, core genome multilocus sequence typing, resistance, plasmid, and virulence content and compared with ten genomes of ST16 strains isolated in other countries. Plasmids carrying blaNDM-1 or blaOXA-232 carbapenemase genes were assembled and sequences were analysed.

Results

The internationally spread ST16 K. pneumoniae clone showed variability in terms of distribution of NDM-1 and OXA-232 type carbapenemases. In some ST16 strains, up to six plasmids can be simultaneously present in the same cell, including ColE-like plasmids carrying blaOXA-232 and IncF plasmids carrying blaNDM-1. The differences observed in plasmid, resistance, and virulence content and core genome suggested that there is not a unique, highly conserved ST16 clone, but instead different variants of this lineage circulate worldwide.

Conclusions

The ST16 K. pneumoniae clone has spread worldwide and may become a high-risk clone.  相似文献   

18.

Objectives

To evaluate the relationship between individual bacterial and viral pathogens and disease severity.

Methods

Children <18 years with three or more episodes of vomiting and/or diarrhoea were enrolled in two Canadian paediatric emergency departments between December 2014 and August 2016. Specimens were analysed employing molecular panels, and outcome data were collected 14 days after enrolment. The primary outcome was severe disease over the entire illness (symptom onset until 14-day follow-up), quantified employing the Modified Vesikari Scale (MVS) score. The score was additionally analysed in two other time periods: index (symptom onset until enrolment) and follow-up (enrolment until 14-day follow-up).

Results

Median participant age was 20.7 (IQR: 11.3, 44.2) months; 47.4% (518/1093) and 73.4% (802/1093) of participants had index and total MVS scores ≥11, respectively. The most commonly identified pathogens were rotavirus (289/1093; 26.4%) and norovirus (258/1093; 23.6%). In multivariable analysis, severe disease over the entire illness was associated with rotavirus (OR = 9.60; 95%CI: 5.69, 16.19), Salmonella (OR = 6.61; 95%CI: 1.50, 29.17), adenovirus (OR = 2.53; 95%CI: 1.62, 3.97), and norovirus (OR = 1.43; 95%CI: 1.01, 2.01). Pathogens associated with severe disease at the index visit were: rotavirus only (OR = 6.13; 95%CI: 4.29, 8.75), Salmonella (OR = 4.59; 95%CI: 1.71, 12.29), adenovirus only (OR = 2.06; 95%CI: 1.41, 3.00), rotavirus plus adenovirus (OR = 3.15; 95%CI: 1.35, 7.37), and norovirus (OR = 0.68; 95%CI: 0.49, 0.94). During the follow-up period, rotavirus (OR = 2.21; 95%CI: 1.50, 3.25) and adenovirus (OR = 2.10; 95%CI: 1.39, 3.18) were associated with severe disease.

Conclusions

In children presenting for emergency department care with acute gastroenteritis, pathogens identified were predominantly viruses, and several of which were associated with severe disease. Salmonella was the sole bacterium independently associated with severe disease.  相似文献   

19.

Objectives

To examine the effect of a combination of probiotics on the antibody response to pneumococcal and pertussis vaccination in healthy Danish children, aged 8–14 months, at the time of starting day care. Moreover, the cytokine response to lipopolysaccharide of whole blood was assessed.

Methods

A total of 290 children were randomly allocated to receive a combination of Bifidobacterium animalis ssp. lactis and Lactobacillus rhamnosus GG daily for a 6-month intervention period, and blood samples were drawn at the start and end of the study. Specific antibody response towards Streptococcus pneumoniae serotypes and Bordetella pertussis toxin, as well as endotoxin-induced interleukin-6 (IL-6) and interferon-γ (IFN-γ) production in blood were analysed by Luminex and ELISA.

Results

There was no significant difference between the average individual changes from baseline to end of study in antibody concentrations for S. pneumoniae for both the probiotics (340.4% ± 11.2%) and the placebo group (382.9% ± 10.4%) (p 0.525), nor for B. pertussis toxin in the two groups (probiotics 190.1% ± 12.6% versus placebo 238.8% ± 1.1%, p 0.340). The average individual change in IL-6 concentration was significantly lower in the probiotics versus the placebo group (2.9% ± 10.3% versus 33.7% ± 9.0%, p 0.024), whereas there was no difference in IFN-γ concentration (0.0% ± 0.2% versus –0.2% ± 0.1%, p 0.279).

Conclusions

The probiotic intervention did not affect the antibody response against S. pneumoniae and B. pertussis toxin in healthy Danish children.  相似文献   

20.

Objectives

Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027– Clostridium difficile infection (CDI).

Methods

Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027– CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated.

Results

Overall, 238 patients with 027+ CDI and 267 with 027– CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549–3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906–5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051–3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281–4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437–9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155–125.000, p 0.007) were associated with recurrence in 027– CDI.

Conclusions

Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity.  相似文献   

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