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1.

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   

2.

Objectives

This study was intended to investigate the clinical and microbiological characteristics of patients with bacteremia caused by Campylobacter species.

Methods

From April 1998 to May 2014, 56 adults with bacteremia caused by Campylobacter species were evaluated. These Campylobacter species isolates were confirmed to the species level using 16S rRNA gene sequencing (all isolates) and multiplex PCR analysis (for C. fetus only). The performance of identification for Campylobacter species by the Bruker Biotyper MALDI-TOF MS was evaluated. The genetic relatedness of C. fetus isolates was analyzed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE).

Results

The leading underlying medical conditions of these patients were malignancy (46.4%), hypertension (35.7%), and liver cirrhosis (23.2%). The overall 30-day mortality rate was 5.4%. Using 16S rRNA sequencing analysis, 26 isolates of C. coli, 11 of C. jejuni, and 19 of C. fetus, including 15 C. fetus subsp. fetus and five C. fetus subsp. venerealis, were identified. Among the five C. fetus subsp. venerealis isolates recognized by 16S rRNA gene sequencing, only two isolates were C. fetus subsp. venerealis by multiplex PCR method. The Bruker Biotyper MALDI-TOF MS failed to correctly identify C. fetus subsp. venerealis isolates. MLST analysis of C. fetus isolates revealed three STs: ST20 (n = 12), ST11 (n = 5), and ST57 (n = 2), which were compatible with three major PFGE clusters.

Conclusion

Database expansion of MALDI-TOF MS for the correct identification of C. fetus to subspecies levels is needed. A novel clone of ST57-PFGE Cluster C of C. fetus subsp. venerealis was noted.  相似文献   

3.

Background/purpose

In 2017, the World Health Organization categorized carbapenem-resistant Acinetobacter baumannii (CRAB) as a priority 1, critical antibiotic-resistant bacteria. This study analyzed the clinical outcomes and investigated the molecular epidemiology of CRAB bacteremia in a medical center in Northern Taiwan.

Methods

We collected 62 blood isolates from patients with CRAB bacteremia from January 2014 to December 2015 at MacKay Memorial Hospital and determined the clonal relationship using the PCR-based technique for molecular epidemiology. Medical charts were reviewed for clinical outcomes.

Results

Fifty-six isolates harbored the blaOXA-51-like and blaOXA-23-like carbapenemase genes, 4 isolates harbor the blaOXA-51-like and blaOXA-24-like carbapenemase genes and 2 isolates harbored only the blaOXA-51-like gene. After sequencing, all four isolates of blaOXA-24-like carbapenemase gene were confirmed to be isolates of blaOXA-72 carbapenemase genes. In multivariate analysis in the 60 patients, the independent mortality risk factors of CRAB bacteremia included ≥65 years (elderly) (Odds ratio, 4.04, 95% CI, 1.10–14.83, p = 0.035), chronic kidney disease (4.36, 1.14–16.72, p = 0.032). Isolates harboring the blaOXA-72 gene had the same sequence type (ST218) and PFGE pulsotype raising the possibility of intra-hospital transmission, and all infected patients died.

Conclusion

This study showed the clonal relationship of isolates harboring the carbapenemase gene in CRAB bacteremia. Patients with the ST218 strain harboring blaOXA-72 gene had high mortality. This warrants further research to determine the mechanism of virulence and risk factors in order to reduce mortality.  相似文献   

4.

Background/Purpose

: The increasing trend of ceftriaxone resistant non-typhoidal Salmonella (NTS) worldwide is of serious concern, however, data is lacked in southern Taiwan.

Methods

Salmonella isolates were collected at a regional hospital in Kaohsiung during 2004–2013. Ceftriaxone resistant NTS isolates were further characterized for beta-lactamases, typed by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and their plasmids were analyzed by PCR replicon typing and plasmid mutilocus sequence typing.

Results

Among 528 NTS isolates, the most common serogroup is serogroup B (44.9%), followed by serogroup D, and serogroup C. Eleven (2.1%) isolates were resistant to ceftriaxone and were distributed in three peak periods (2010, 2011, and 2013). PFGE and MLST revealed the ten serogroup B isolates were of two clones. Beta-lactamase genes were detected in 10 of the 11 isolates, including CMY-2 (5 isolates), TEM-1 (2), CTX-M-14 (1), and 2 isolates carried both TEM-1 and CMY-2. Plasmid incompatibility types were identified in 9 (81.8%) isolates; three were IncI1, three was IncHI2, one was IncFIB and two had both replicons of IncI1 and IncHI2. The only ESBL gene blaCTM-X-14 was found in an isolate with plasmid belonged to IncHI2, which has not been reported in NTS in Taiwan before. Most MLST types and plasmid MLST types of NTS isolates in this study are different from those in northern Taiwan.

Conclusion

Though clonal spread of ceftriaxone resistant NTS was suggested by PFGE and MLST, plasmid characterization and beta-lactamase detection revealed their plasmid types and beta-lactamase types were different.  相似文献   

5.

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   

6.

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   

7.

Background

Encephalitis and meningoencephalitis are severe, sometime life-threatening infections of the central nervous system. Travellers may be exposed to a variety of neurotropic pathogens.

Aims

We propose to review known infectious causes of encephalitis in adults acquired outside Europe, and how to identify them.

Sources

We used Pubmed and Embase, to search the most relevant publications over the last years.

Content

Microbiologic tests and radiological tools to best identify the causative pathogen in travellers presenting with encephalitis and ME are presented in this narrative review, as well as a diagnostic approach tailored to the visited area and types of exposures.

Implications

This review highlights the diagnostic difficulties inherent to exotic causes of central nervous system infections, and attempts to guide clinicians with respect to which microbiological tests to consider, in addition to brain MRI, when approaching a returning traveller presenting with encephalitis.  相似文献   

8.

Objectives

A comprehensive overview of the ways control measures directed at carriers of multidrug-resistant organisms (MDRO) affect daily life of carriers is lacking. In this systematic literature review, we sought to explore how carriers experience being a carrier and how they experience being subjected to control measures by looking at the impact on basic capabilities.

Methods

We searched Medline, Embase and PsychINFO until 26 May 2016 for studies addressing experiences of MDRO carriers. Twenty-seven studies were included, addressing experiences with methicillin-resistant Staphylococcus aureus (n = 21), ESBL (n = 1), multiple MDRO (n = 4) and other (n = 1, not specified). We categorized reported experiences according to Nussbaum's capability approach.

Results

Carriage and control measures were found to interfere with quality of care, cause negative emotions, limit interactions with loved ones, cause stigmatization, limit recreational activities and create financial and professional insecurity. Further, carriers have difficulties with full comprehension of the problem of antimicrobial resistance, thus affecting six out of ten basic capabilities.

Conclusions

Applying Nussbaum's capability approach visualizes an array of unintended consequences of control measures. Carriers experience stigmatization, especially in healthcare settings, and have limited understanding of their situation and the complexities of antimicrobial resistance.  相似文献   

9.

Background

Encephalitis and meningoencephalitis imply inflammation of the brain parenchyma, and comprise many diagnostic entities, such as various infections and causes of dysimmunity. The cause remains unknown in around 50% of cases.

Objectives

To summarize the main infectious causes of encephalitis and meningoencephalitis acquired in Europe, and the diagnostic means to identify them.

Sources

PubMed, ECDC and WHO websites, personal experience.

Content

The principal infectious causes of encephalitis and meningoencephalitis acquired in Europe in adults are discussed in this review, with special emphasis on the microbiological and imaging diagnostic approaches. The role of electroencephalography in diagnosing encephalitis is also mentioned. Among infections, viruses are more frequent than other pathogen types, and their epidemiology varies according to geographic area. A few bacteria, such as Listeria monocytogenes and Mycobacterium tuberculosis, are also to be considered. In contrast, parasites and fungi are rare encephalitis causes in Europe.

Implications

Identifying the causative pathogen of infectious encephalitis and meningoencephalitis is complex because of the variety of pathogens, the epidemiology of which is determined by geography and environmental factors. Furthermore, despite extensive microbiological testing, many cases of encephalitis remain of unknown origin. Brain magnetic resonance imaging and electroencephalography are useful complementary diagnostic tools, and newer unbiased sequencing technologies might help to fill in the diagnostic gap.  相似文献   

10.

Objectives

Rapid identification of Elizabethkingia species is essential because these species show variations in antibiotic susceptibility and clinical outcomes. Many recent inaccuracies in Elizabethkingia identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) have been noted. Accordingly, in this study, we evaluated the use of MALDI-TOF MS with an amended database to identify isolates of Elizabethkingia anophelis, E. miricola and E. meningoseptica. We then investigated the antimicrobial susceptibility of Elizabethkingia.

Methods

MALDI-TOF MS spectra were acquired from formic acid extracts overlaid with α-cyano-4-hydroxycinnamic acid matrix on target slides in linear positive ion mode for m/z 2000 to 20?000 Da. Spectra were analysed and SuperSpectra were created with SARAMIS premium software. 16S rRNA gene sequencing was used as the reference standard for species identification. Antibiotic susceptibility was assessed by broth microdilution.

Results

A total of 103 E. anophelis, 21 E. miricola and 11 E. meningoseptica isolates were used to calculate the average spectra and exclude common peaks. SuperSpectra were added to the SARAMIS taxonomy database; all validation results were correct, even for isolates not included in SuperSpectra. Confirmation by direct colony formation was also performed. Overall, the positive predictive value of SuperSpectra was 100% for all isolates. E. miricola (77%, 17/22) was more susceptible to levofloxacin than E. anophelis (16%, 17/105). Doxycycline and minocycline were effective against all Elizabethkingia species.

Conclusions

Spectral analysis software identified significant species-specific peaks to create reference masses for efficient and accurate identification of Elizabethkingia species, providing accurate information for clinical treatment of Elizabethkingia infections.  相似文献   

11.

Objective

To review the current state of the literature regarding the socioeconomics of atopic dermatitis (AD)—more specifically how socioeconomic status (SES) affects AD risk and how the presence of AD may affect one’s SES—as well as discuss the cost of the disease to society.

Data Sources

A PubMed search was performed to include English-language articles with the keywords atopic dermatitis, cost, finances, economic, income, career, socioeconomic, with preference to those written in the last 5 years.

Study Selections

Studies were included if they provided information pertaining to socioeconomics in relation to disease severity, disease incidence, direct costs, indirect costs, and effects on work, education, and career choice.

Results

Many studies have reported that higher SES is associated with increased AD prevalence, whereas lower SES is associated with increased AD severity. Regardless of patient SES, AD creates substantial direct costs that affect the patient, patient’s family, and the payer. Additionally, the effects of the disease create indirect costs from absenteeism and presenteeism, as well as opportunity costs from hinderances in learning, affecting patient SES and the economy.

Conclusion

Given the substantial and growing burden on the patient and the economy when access to appropriate treatment is limited, the socioeconomic burden of AD represents a tangible public health concern that must be addressed.  相似文献   

12.

Background

Carriage of methicillin-resistant Staphylococcus aureus (MRSA) is associated with its transmission. International travels and massive gatherings may accelerate such transmission. MRSA carriage was surveyed among the attendees of two international medical conferences held in Taipei in 2010.

Methods

A total of 209 attendees from 23 countries were recruited. Nasal specimens were collected from each volunteer and subjected to polymerase chain reaction (PCR) detection for MRSA. Molecular analysis, including pulsed-field gel electrophoresis, multilocus sequence typing (MLST), typing of staphylococcal cassette chromosome mec (SCCmec) and staphylococcal protein A (spa) genes, and detection of Panton-Valentine leukocidin (PVL) and sasX genes, was performed.

Results

MRSA carriage was detected in 10 (4.8%) attendees from Vietnam (3/8, 37.5%), Korea (2/6, 33.3%), Japan (2/41, 4.9%), Philippines (2/52, 3.8%), and Bangladesh (1/4, 25.0%). The proportion of MRSA colonizers was significantly higher in the local hospital group compared to those from the other groups (3/17 vs. 7/192, p < 0.05). Six MRSA isolates were available for molecular analysis. They all carried a type IV SCCmec gene. Five pulsotypes were identified; four genotypes, respectively, were identified by MLST and spa typing. None of the isolates carried either PVL or sasX genes. None of common molecular characteristics was shared by isolates from different countries. Most of these isolates were local endemic community clone in each country.

Conclusions

As healthcare workers, a certain proportion of international medical conference attendees harbored MRSA in their nares, mostly local endemic community clones in each country, which has the potential of spread among attendees.  相似文献   

13.

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   

14.

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   

15.

Objective

To evaluate relevant studies and documents that address the cost-effectiveness and comparative effectiveness of biologics current approved by the US Food and Drug Administration for the treatment of asthma.

Data Sources

Publications currently available on biologics, the Global Initiative for Asthma pocket book on difficult-to-treat asthma in adolescents and adults, and the recent Institute for Clinical and Economic Review on biologic therapies for the treatment of asthma.

Study Selections

Priority was placed on studies that speak to the cost-effectiveness and comparative effectiveness of biologic therapies published from 2016 to 2019.

Results

Current pricing for all biologics exceeds measures of cost-effectiveness. To meet available measures indicating cost-effectiveness, prices would have to be reduced by a minimum of approximately 60%. The effect of biologics on exacerbations is similar but should be interpreted in the context of comparable patient phenotypes. The effect on quality of life is deemed modest based on the available study designs.

Conclusion

To maximize cost-effectiveness of the biologics, emphasis should be placed on identifying predictors of response, focusing on those patients receiving oral corticosteroid therapy, and assessing the effect of treatment for decisions that relate to continuation. Multidisciplinary stakeholder efforts are needed to ensure responsible application of biologic therapy.  相似文献   

16.

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   

17.

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   

18.

Background/purpose

Staphylococcus aureus (S. aureus) causes diseases ranging from mild skin infections to invasive diseases. Carriage of S. aureus, including methicillin-resistant S. aureus (MRSA), is a significant risk factor for subsequent staphylococcal infection. Several studies discussed MRSA colonization in Taiwan, but mostly in northern Taiwan. This is the first study that estimates the prevalence of MRSA nasal colonization in healthy children and identifies the potential risk factors in central Taiwan.

Methods

A total of 3144 healthy children aged 2–60 months who visited Taichung Veterans General Hospital (TCVGH) were screened for nasal S. aureus carriage from July 2005 to December 2010. Questionnaires included demographic information and potential risk factors for carriage of S. aureus were completed by parents/guardians.

Results

Prevalence of MSSA and MRSA were 12.09% and 5.25%, respectively. The youngest group aged 2–6 months had the highest S. aureus carriage rate, and the carriage rate revealed a peak in summer. The nasal colonization of Streptococcus pneumoniae (S. pneumoniae) was a protective factor against S. aureus colonization. 85% of the MRSA colonizing isolates belonged to clonal complex 59/staphylococcal cassette chromosome type IV or VT, the local community clone in Taiwan.

Conclusion

An increasing trend of MRSA nasal carriage rate in Taiwan had been brought forward, however, it was not observed in central Taiwan during the period of 2005–2010. We found a summer peak on both MRSA and MSSA carriages.  相似文献   

19.

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   

20.

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   

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