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1.

Background/purpose

This study investigated the distribution and persistence of multidrug resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and multidrug-resistant Acinetobacter baumannii (MDRAB) in six long-term care facilities (LTCFs).

Methods

We investigated the distribution of MDROs in residents of six LTCFs and their environments from January to December 2016 (intervention period). Active surveillance of colonization of MDROs was performed by culturing rectal and nasal swab samples from the residents every three months. Multilocus sequence typing (MLST) was conducted, and genes for panton-valentine leukocidin (PVL) from MRSA isolates were determined.

Results

A total of 521 samples were positive for MDROs, and MRSA was the most common organism (65.1%), followed by MDRAB (11.3%), carbapenem-resistant Klebsiella pneumoniae (11.1%), carbapenem-resistant Escherichia coli (4.6%), and carbapenem-resistant P. aeruginosa (2.1%, n = 11). By a linear regression model, positive MRSA isolates from the environment were found to be statistically significant and associated with the number of colonized LTCF residents (p = 0.01), while the timing of the surveillance culture was not (p = 0.227). The main MLST types associated with PVL-production were sequence type (ST) 59, (40.0%, 24/60), ST30 (21.4%, 3/14), ST8 (87.5%, 14/16), and ST45 (3.6%, 1/28). The susceptibility rates of tetracycline (96.7%), trimethoprim-sulfamethoxazole (96.7%), and ciprofloxacin (81.7%) were statistically significant and higher in MRSA ST59, compared to the rates in MRSA ST45 isolates.

Conclusions

MRSA was the most commonly colonized MDRO, both in the LTCF residents and in the environment, followed by MDRAB and carbapenem-resistant K. pneumoniae.  相似文献   

2.

Background

Rhodococcus equi is a recognized cause of disease in humans, especially in individuals who are immunocompromised. Because diphtheroids are regarded as part of normal respiratory flora, the importance of R. equi as a pulmonary pathogen may not be fully appreciated and its prevalence may be underestimated. Most treatment recommendations for R. equi infection were established before antiretroviral drugs became available for human immunodeficiency virus/AIDS therapy, and therapeutic strategies may need to be updated.

Objectives

To review the role of R. equi as a cause of pulmonary infection; to highlight its importance for clinicians and microbiologists; and to challenge current approaches to treatment, whether in immunodeficient or immunocompetent individuals.

Sources

A PubMed search using combinations of the following terms: ‘Rhodococcus (automatically including Corynebacterium) equi’ AND ‘pneumonia’ OR ‘pulmonary’ infection, then cross-checking references in the resulting cases, case series and reviews.

Content

We provide a review that details the challenges in the diagnosis, microbiology and pathogenesis of pulmonary infection caused by R. equi and the options for treatment.

Implications

Ten to 14 days of treatment may be effective for pneumonia due to R. equi. Our review suggests that longer courses of therapy are needed for cavitary lesions and lung masses. However, recommendations for excessively prolonged treatment of all pulmonary infections arose during a time when many cases occurred in individuals with AIDS and before effective antiretroviral therapy was available. We suggest that the rationale for prolonged therapy with multiple antibiotics needs to be re-evaluated.  相似文献   

3.

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   

4.

Background/Purpose

Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP.

Methods

A phase 3, multicenter, randomized (2:1) controlled trial was conducted in adult CAP patients receiving nemonoxacin 500 mg or levofloxacin 500 mg orally once daily for 7–10 days. Clinical, microbiological response and adverse events were assessed. Non-inferiority was determined in terms of clinical cure rate of nemonoxacin compared with that of levofloxacin in a modified intention-to-treat (mITT) population. NCT registration number: NCT01529476.

Results

A total of 527 patients were randomized and treated with nemonoxacin (n = 356) or levofloxacin (n = 171). The clinical cure rate at test-of-cure visit was 94.3% (300/318) for nemonoxacin and 93.5% (143/153) for levofloxacin in the mITT population [difference (95% CI), 0.9% (?3.8%, 5.5%)]. The microbiological success rate was 92.1% (105/114) for nemonoxacin and 91.7% (55/60) for levofloxacin in the bacteriological mITT population [difference (95% CI), 0.4% (?8.1%, 9.0%)]. The incidence of adverse events (AEs) was comparable between nemonoxacin (33.1%, 118/356) and levofloxacin (33.3%, 57/171) (P > 0.05).

Conclusion

Nemonoxacin 500 mg once daily for 7–10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile.ClinicalTrials.gov identifier: NCT01529476.  相似文献   

5.

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   

6.

Objectives

We aimed to detect Leishmania DNA carriage in nasal mucosa of individuals with cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis.

Methods

A cross-sectional study was performed in all individuals with CL without nasal lesions (n = 153) attended within 2 years in an endemic area of L. (Viannia) braziliensis in Bahia (Brazil). An otorhinolaryngologist assessed the clinical status of the nasal mucosa by anterior rhinoscopy and endoscopic examinations. Swab samples were collected for parasite DNA detection by PCR from all individuals before standard treatment for leishmaniasis. A second evaluation 3 months after treatment was performed to assess clinical outcomes.

Results

Parasite DNA was detected in 7.8% (12/153) of clinically healthy nasal mucosa of individuals with CL. Interestingly, DNA was more frequently identified in individuals with more skin lesions (median 1.5, interquartile range (IQR) 1–3.5 versus 1.0, IQR 1–1.5; p 0.044), or larger injuries (median 2.7, IQR 2–3.8 versus 1.6, IQR 1–2.5; p 0.013). Additionally, the disease of those individuals with positive PCR evolved more frequently to unusual forms of leishmaniasis (recidiva cutis and disseminated) (45.5% (5/11) versus 11.5% (14/122); p 0.009), and required more cycles of treatment to reach clinical cure (median 2, IQR 1–4 versus 1, IQR 1–2; p 0.05).

Conclusion

These findings suggest an early parasite tropism to nasal mucosa in L. (Viannia) braziliensis infection and a clinical phenotype of CL cases associated with parasite DNA in nasal mucosa. Future studies should evaluate whether PCR of nasal swab samples could serve as a prognostic tool for individuals at risk of mucocutaneous leishmaniasis.  相似文献   

7.

Background and objective

Screening and identification of methicillin-resistant Staphylococcus aureus (MRSA) carriage are helpful for controlling MRSA dissemination in hospitals. The aim of our study was to determine the prevalence of nasal carriages and diversity of MRSA among patients and healthcare workers (HCWs) at two regional hospitals in Taiwan.

Methods

Nasal swabs were obtained prospectively from 204 patients visiting the emergency department (ED) and 326 HCWs in two regional hospitals in Changhua, Taiwan, between February 2015 and June 2015. All the MRSA isolates were further molecularly characterized.

Results

Of the 204 participating patients, the nasal carriage rates of S. aureus and MRSA were 22.1% and 7.8%, respectively. For HCWs, the S. aureus and MRSA carriage rates were 26.1% and 6.1%, respectively. There was no statistically significant difference in MRSA carriage rate between patients and HCWs (P = 0.447). Patients receiving hemodialysis were significantly associated with MRSA colonization (P = 0.012). The leading three sequence types (ST) were ST59 (16, 44.4%), ST45 (11, 30.6%), and ST239 (3, 8.3%) for all 36 MRSA isolates. ST59/SCCmec IV/t437/PVL-negative and ST45/SCCmec V/t1081/PVL-negative were the predominant clones among HCWs (30%) and participating patients (19%), respectively.

Conclusion

Overall, a substantial proportion of patients visiting the ED and HCWs harbored CA-MRSA, mostly ST59 strains, in their nares. It is noteworthy that MRSA ST45 strains supplanted ST239 as the second leading nasal MRSA colonization strain in our study.  相似文献   

8.

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   

9.

Background

The aim of this study was to evaluate whether breastfeeding should be discontinued for exclusively breast-fed infants with atopic dermatitis (AD).

Methods

Eighty-seven exclusively breast-fed infants with AD were enrolled in a prospective observational study. The infants were divided into 3 groups: breastfeeding only (BM group), partial breastfeeding and partial partially hydrolyzed whey formula (pHF-W) (Partial group) and pHF-W only (DC group). The extent and severity of AD were evaluated with the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index at enrollment and 3 and 6 months later.

Results

There were no significant differences in parental atopy history, PO-SCORAD scores, and medication scores at baseline. At month 3 and 6, the PO-SCORAD scores were significantly decreased in all groups. PO-SCORAD scores at month 3 and 6 and at the last time point when topical corticosteroids were given were significantly different among the groups. Stepwise multiple linear regression analysis showed that baseline PO-SCORAD scores and stopping breastfeeding were significantly associated with month 3 PO-SCORAD scores (p < 0.001), after adjusting for sex, age, baseline medication scores, partial breastfeeding and parental atopy history. In addition to baseline PO-SCORAD scores and stopping breastfeeding, partial breastfeeding was significantly associated with month 6 PO-SCORAD scores. Long-term follow-up showed that only stopping breastfeeding was significantly associated with the last time point when topical corticosteroids were given (p = 0.014).

Conclusion

For exclusively breast-fed infants with AD, discontinuing breastfeeding and shifting to pHF-W might help to improve symptoms and shorten the duration of AD regardless of sex, age and parental atopy history.  相似文献   

10.

Objectives

To determine MIC distributions for Mycobacterium chimaera, Mycobacterium intracellulare, Mycobacterium colombiense and Mycobacterium avium, and to derive tentative epidemiological cut-off (ECOFF) values.

Methods

A total of 683 bacterial isolates (M. chimaera, n = 203; M. intracellulare, n = 77; M. colombiense, n = 68; M. avium, n = 335) from 627 patients were tested by broth microdilution according to CLSI protocol M24-A2 on Sensititre RAPMYCOI plates. MICs were interpreted based on CLSI breakpoints for clarithromycin, and tentative breakpoints for amikacin, moxifloxacin and linezolid. Tentative ECOFFs were determined by visual approximation and the ECOFFinder algorithm.

Results

Modal MIC, MIC50 and MIC90 values were within ± one dilution step from the respective aggregated data set for 47/48 (97.9%), 48/48 (100%) and 48/48 (100%) species–drug combinations. Clarithromycin wild-type populations were mostly classified as susceptible (MIC90 4–8 mg/L; S ≤8 mg/L). Rifabutin MICs were lower than those of rifampicin. Tentative moxifloxacin, linezolid and amikacin breakpoints split wild-type populations. No ECOFFs could be set for rifampicin, ethambutol, ciprofloxacin, isoniazid, trimethoprim/sulfamethoxazole and doxycycline because of truncation of MIC distributions. Agreement between the visually determined and the modelled 97.5% ECOFFs was 90.9%. All 99.0% ECOFFs were one titre step higher than by visual approximation.

Conclusions

Drug susceptibility patterns of M. chimaera are comparable to those of closely related species. Except for clarithromycin, breakpoints for Mycobacterium avium-intracellulare complex should be re-evaluated. Statistical determination of the 99.0% ECOFF may be superior to visual approximation.  相似文献   

11.

Background

The clinical features and outcomes of cytomegalovirus (CMV) diseases in patients with systemic lupus erythematosus (SLE) are unknown. We analyzed such data from a medical center in Taiwan.

Methods

We retrospectively reviewed the medical records of patients with SLE who were diagnosed with CMV diseases between 2006 and 2016 in Taipei Veterans General Hospital Taiwan. Clinical and laboratory parameters and treatment outcomes were analyzed.

Results

The study enrolled 56 eligible patients with CMV diseases and separated them into survival (n = 24) and mortality (n = 32) groups. All cases showed a significantly high incidence of pneumonitis (71.43%). The patients in the mortality group had a higher SLE disease activity index (SLEDAI)-2000 (p = 0.009), more cases of recent methylprednisolone pulse therapy (p = 0.013) and pancytopenia (p = 0.001), stronger evidence of CMV infection demonstrated by polymerase chain reaction (PCR) in blood (p < 0.001) and bronchoalveolar lavage (p = 0.021), and more concurrent infections (bacteremia p = 0.026; fungemia p < 0.001).

Conclusions

Recent pulse therapy, pancytopenia, and concurrent infections constituted risk factors for mortality in patients with SLE and CMV infection. Among mortality patients, PCR rather than serological tests (IgM antibodies) helped to arrive at an earlier diagnosis.  相似文献   

12.

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   

13.

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   

14.

Objectives

Acinetobacter baumannii can cause severe nosocomial and community-acquired pneumonia. To study the pathogenesis of A. baumannii and to develop new treatments, appropriate mouse models are needed. Most reported mouse models of pulmonary A. baumannii infection are non-lethal or require mouse immunosuppression to enhance infection. These models are not suitable for studying host immune responses or evaluating immunotherapies.

Methods

The virulence of 30 clinical isolates was assessed in mice. The most virulent isolate, SJZ24, was selected to develop a pneumonia model in immunocompetent mice. The cytokine mRNA expression in the lung was assessed with real-time PCR. The cell infiltration in bronchoalveolar lavage fluid (BALF) after SJZ24 infection was determined by flow cytometry. Vaccine efficacy was assessed using this model.

Results

Intratracheal inoculation of SJZ24 (5 × 107 CFU) resulted in death in 100% of the mice (5/5). SJZ24-infected mice showed high bacterial burdens in blood and organs as well as severe lung-tissue damage. Infection with SJZ24 induced increased inflammatory cytokine expression in the lung and increased neutrophil infiltration in BALF. Immunization with inactivated whole cells of SJZ24 showed 100% protection (5/5) against A. baumanni infection in this model.

Conclusions

We established a lethal pneumonia model in immunocompetent mice with hypervirulent A. baumannii isolate SJZ24. This model can be used to study the immune response to A. baumannii infection and to evaluate vaccine efficacy.  相似文献   

15.

Background/Purpose

To determine serum semaphorin 3A (Sema 3A) levels in ankylosing spondylitis (AS).

Methods

Serum Sema 3A was measured in 46 AS patients and 30 healthy controls (HCs). For the patients, we recorded demographic data, disease activity, functional index & global assessment, detected human leukocyte antigen-B27 (HLA-B27), and measured erythrocyte sedimentation rate (ESR) & C-reactive protein (CRP).

Results

Sema 3A was higher in AS patients than in HCs (3.98 ± 2.57 vs. 1.34 ± 0.48 ng/ml, p = 0.013). Area under the curve (AUC) of standard receiver operating characteristic (ROC) has suggested that Sema 3A > 2 ng/ml is better to predict the higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, > 4) than ESR or CRP. There were good correlations between higher Sema 3A and uveitis, Schöber's test, as well as interstitial lung disease. AS patients undergoing anti-tumor necrosis factor therapies for 3 months exhibited a positive correlation of change in Sema 3A (ΔSema 3A) with disease activity fluctuation [ΔBASDAI, ΔBath Ankylosing Spondylitis Functional Index (BASFI) and ΔBath Ankylosing Spondylitis - Global score (BAS-G)].

Conclusion

Serum Sema 3A level was increased in AS patients and was inversely correlated to Schöber's test. Serum Sema 3A is better as a bio-marker than ESR or CRP to correlate with high disease activity in AS patients, and it is also a good indicator for monitoring disease activity and functional status during anti-TNF treatment. Also, Sema 3A may be taken as a predictor for extra-articular presentations in AS, but this needs further study to elucidate.  相似文献   

16.

Background

Disease activity may correlate with environmental aeroallergen exposure in eosinophilic esophagitis. The association between seasons and flares of eosinophilic esophagitis (EoE) histologic activity has not been extensively studied.

Objective

We aimed to assess the frequency of seasonal exacerbations of eosinophilic esophagitis, as well as changes in symptom reporting, endoscopic findings, and histologic findings attributed to aeroallergens in an EoE cohort.

Methods

In this retrospective cohort study, we analyzed EoE patients in histologic remission (<15 eosinophil/high-power field) but who doubled the esophageal eosinophil count between seasons without change in eosinophilic esophagitis–specific therapy. Outcomes were: symptomatic global worsening (yes/no); change in endoscopic severity (EREFS scoring system); and histologic change (peak eosinophil count).

Results

Of 782 patients, 13 (4%) met inclusion criteria (mean age: 36.2; 85% male; 86% white; 85% atopic disease diagnosis), and 14 exacerbations were recorded. Of these, 71% occurred in fall and summer months. Peak eosinophil counts increased from 6.8 to 86.8 eosinophil per high-power field (P < .001). Four patients (31%) reported worsening of seasonal allergies and 5 (38%) a global worsening of symptoms. Endoscopic severity was also significantly worse during seasonal exacerbations (total EREFS 3.7 vs 1.7; P = .01). Baseline features differed by atopic diagnoses and endoscopic findings between patients with and without seasonal exacerbations.

Conclusion

Seasonal exacerbations of eosinophilic esophagitis were uncommon in this cohort and most commonly recorded over the summer and fall months. These data support a role of aeroallergens in the pathogenesis of eosinophilic esophagitis in some patients, and clinicians should consider aeroallergens as a potential cause of disease exacerbation.  相似文献   

17.

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   

18.

Objectives

The high microbiologic diversity encountered in prosthetic joint infection (PJI) makes the choice of empirical antimicrobial therapies challenging, especially in cases of implant retention or one-stage exchange. Despite the risk of dysbiosis and toxicity, the combination of vancomycin with a broad-spectrum β-lactam is currently recommended in all cases, even if Gram-negative bacilli (GNB) might be less represented in late PJI. In this context, this study aimed to describe the microbiologic epidemiology of PJI according to the chronology of infection.

Methods

This prospective cohort study (2011–2016) evaluated the microbiologic aetiology of 567 PJI according to time of occurrence from prosthesis implantation—early (<3 months), delayed (3–12 months) and late (>12 months)—as well as mechanism of acquisition.

Results

Initial microbiologic documentation (n = 511; 90.1%) disclosed 164 (28.9%) Staphylococcus aureus (including 26 (16.1%) methicillin-resistant S. aureus), 162 (28.6%) coagulase-negative staphylococci (including 81 (59.1%) methicillin-resistant coagulase-negative staphylococci), 80 (14.1%) Enterobacteriaceae, 74 (13.1%) streptococci and 60 (10.6%) Cutibacterium acnes. Considering nonhaematogenous late PJI (n = 182), Enterobacteriaceae (n = 7; 3.8%) were less represented than in the first year after implantation (n = 56; 17.2%; p <0.001), without difference regarding nonfermenting GNB (4.6% and 2.7%, respectively). The prevalence of anaerobes (n = 40; 21.9%; including 32 (80.0%) C. acnes) was higher in late PJI (p <0.001). Consequently, a broad-spectrum β-lactam might be useful in 12 patients (6.6%) with late PJI only compared to 66 patients (20.3%) with early/delayed PJI (p <0.001).

Conclusions

Considering the minority amount of GNB in late postoperative PJI, the empirical use of a broad-spectrum β-lactam should be reconsidered, especially when a two-stage exchange is planned.  相似文献   

19.

Background

Data on the prevalence of allergic disorders over time are limited. Recent studies have noted marked increase in the prevalence of allergic conditions in different parts of the world.

Objective

To examine time trends in the prevalence of anaphylaxis, angioedema, and urticaria in the United States.

Methods

Using the largest inpatient National Inpatient Sample data in the United States from 2001 to 2014, adults admitted with a primary diagnosis of anaphylaxis, angioedema, or urticaria were identified based on International Classification of Diseases, Ninth Revision codes. Yearly distribution of hospital admissions was stratified per different age groups, and yearly trends of hospitalizations related to anaphylaxis, angioedema, and urticaria were calculated.

Results

Although an increasing trend in the rate of hospitalizations was seen for angioedema (annual percentage change [APC], 4.48), a decreasing trend (APC, ?2.19) was observed for urticaria-related hospitalizations. Overall anaphylaxis-related hospitalizations were noted to be stable, but a significant increasing trend was observed among those aged 5 to 14 years (APC, 4.19), mostly because of the subgroup of food-related hospitalizations (APC, 5.86). Angioedema-related hospitalizations were highest among the 35- to 64-year age group (APC, 5.38).

Conclusion

An increasing trend of hospitalizations has been observed for allergic conditions, with varying age distribution according to the nature of eliciting agent and susceptibility of different age groups. Although angioedema has been observed as an increasing problem in older populations, food-induced anaphylaxis is an increasing concern in the younger population.  相似文献   

20.

Objectives

To compare the performance of self-collected vaginal (V) specimens with clinician-collected cervical (C) specimens for detection of high-risk human papillomavirus (hrHPV) and cervical disease using the Cepheid Xpert HPV, Roche Cobas 4800 HPV and Hologic Aptima HPV assays.

Methods

Women aged 30–59 years (n = 1005) were recruited at two clinics in Papua New Guinea, and they provided specimens for testing at point-of-care using the Xpert HPV Test, and for subsequent testing using the Cobas HPV (n = 981) and Aptima HPV (n = 983) assays. Liquid-based cytology was performed on C specimens to predict underlying high-grade squamous intraepithelial lesions (HSIL). V specimen results of each assay were evaluated against a constructed reference standard and for detection of HSIL or worse.

Results

There was substantial (κ >0.6) agreement in hrHPV detection between V and C specimens across all three assays. The sensitivity, specificity, and positive and negative predictive values of Xpert HPV using self-collected V specimens for the detection of HPV type 16 according to the constructed reference standard were 92.1%, 93.1%, 63.6% and 98.9%, respectively; compared with 90.4%, 94.3%, 67.8% and 98.7% for Cobas 4800 HPV; and 63.2%, 97.2%, 75.0% and 95.3% for Aptima HPV. Similar results were observed for all hrHPV types (combined) and for HPV types 18/45, on all three assays. The detection of any hrHPV using self-collected specimens had high sensitivity (86%–92%), specificity (87%–94%) and negative predictive value (>98%) on all assays for HSIL positivity.

Conclusions

Xpert HPV, using self-collected vaginal specimens, has sufficient accuracy for use in point-of-care ‘test-and-treat’ cervical screening strategies in high-burden, low-resource settings.  相似文献   

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