Timely diagnostic investigation to establish the microbial etiology of pneumonia is essential to ensure the administration of effective antibiotic therapy to individual patients.
We evaluated a ...multiplex PCR assay panel, the FilmArray® pneumonia panel (FilmArray PP, BioFire Diagnostics), for detection of 35 respiratory pathogens and resistance determinants and compared the performance of the standard-of-care test in intensive care unit patients with lower respiratory tract infections.
Among the 59 endotracheal aspirates and bronchoalveolar lavage specimens obtained from 51 adult patients, FilmArray PP was effective in detecting respiratory bacterial pathogens with an overall positive percent agreement of 90% (95% confidence interval CI, 73.5–97.9%) and negative percent agreement of 97.4% (95% CI, 96.0–98.4%). FilmArray PP semi-quantitative reporting demonstrated a concordance rate of 53.6% for the culture-positive specimens and 86.3% for the culture-negative specimens. FilmArray PP detected 16 viral targets, whereas the conventional viral isolation failed, except influenza A, which showed 100% concordance with PCR. Coinfections were detected in 42.3% of the specimens. Substantial discrepancies were observed in identifying antimicrobial resistance gene targets and in the susceptibility testing. However, FilmArray PP may still be useful at the early stage of pneumonia before culture and susceptibility test reports are available. Consequently, the results of FilmArray PP might alter the antibiotic prescription in 40.7% of the patients.
FilmArray PP offers a rapid and sensitive diagnostic method for lower respiratory tract infections. However, clinical correlation is advised to determine its significance in interpreting multiple pathogens and detection of genes involved in antimicrobial resistance.
We investigated the prevalence of latent tuberculosis infection (LTBI) among the residents in seven long-term care facilities (LTCFs) located in different regions of Taiwan and compared the ...performance of two interferon gamma release assays, i.e., QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) for screening LTBI. We also assessed the diagnostic performance against a composite reference standard (subjects with persistent-positive, transient-positive, and negative results from QFTs during reproducibility analysis were classified as definite, possible, and not LTBI, respectively). Two hundred forty-four residents were enrolled, and 229 subjects were included in the analysis. The median age was 80 years (range, 60 to 102 years old), and 117 (51.1%) were male. Among them, 66 (28.8%) and 74 (32.3%) subjects had positive results from QFT-GIT and QFT-Plus, respectively, and the results for 215 (93.9%) subjects showed agreement. Using the composite reference standard, 66 (28.8%), 11 (4.8%), and 152 (66.4%) were classified as definite, possible, and not LTBI, respectively. For definite LTBI, the sensitivity, specificity, positive predictive value, and negative predictive value of QFT-GIT were 89.4%, 95.7%, 89.4%, and 95.7%, respectively, and those for QFT-Plus were 100.0%, 95.1%, 89.2%, and 100.0%, respectively. The sensitivity of QFT-GIT decreased gradually with patient age. Compared to QFT-GIT, QFT-Plus displayed significantly higher sensitivity (100.0% versus 89.4%,
= 0.013) and similar specificity (95.1% versus 95.7%). In conclusion, a high prevalence of LTBI was found among elders in LTCFs in Taiwan. The new QFT-Plus test demonstrated a higher sensitivity than QFT-GIT in the older adults in LTCFs.
The performance of metagenomic next-generation sequencing (mNGS) was evaluated and compared with that of conventional culture testing in patients with sepsis. Prospective blood and bronchoalveolar ...lavage fluid (BALF) samples from 50 patients with sepsis were tested using cultures (bacterial, fungal, and viral) and mNGS of microbial DNA (blood and BALF) and RNA (BALF). mNGS had higher detection rates than blood culture (88.0% versus 26.0%, P < 0.001) and BALF culture (92.0% versus 76.0%, P = 0.054). RNA-based mNGS has increased the detection rate of several bacteria, fungi, and viruses, but not mycobacteria and Toxoplasma gondii. The number of multiple detections per specimen was higher in BALF (92.0%) than in blood (78.0%) samples, and the highest number of pathogens detected in a single specimen was 32. Among blood samples, compared to cultures, mNGS detected significantly more bacteria (P < 0.001), fungi (P = 0.012), and viruses (P < 0.001), whereas BALF mNGS had a higher detection rate for bacteria (P < 0.001) and viruses (P < 0.001). The percentage of mNGS-positive samples was significantly higher than that of culture-positive samples for several Gram-negative bacteria, some Gram-positive bacteria, and viruses, but not fungi. Mycobacteria had a higher detection rate by culture than by mNGS, but the difference was not significant due to the small sample size. The positive and negative agreements with 95% confidence intervals of mNGS and culture were 62.0% (50.4 to 72.7) and 96.8% (96.5 to 97.1), respectively. mNGS offers a sensitive diagnostic method for patients with sepsis and is promising for the detection of multipathogen infections. Clinical correlation is advised to interpret mNGS data due to the lack of unified diagnostic criteria. IMPORTANCE Delays in effective antimicrobial therapy have resulted in decreased survival rates among patients with sepsis. However, current culture-based diagnostic methods have low sensitivity because of concurrent antibiotic exposure and fastidious and atypical causative organisms. Among patients with sepsis, we showed that mNGS methods had higher positive rates than culture methods, especially for bacteria, viruses, and multipathogen infections, which are difficult to culture and detect in patients treated with antibiotics. RNA-based mNGS has increased the detection rate of several bacteria, fungi, and viruses, but not mycobacteria and Toxoplasma gondii. mNGS also showed a high negative percent agreement with cultures. However, the interpretation of mNGS data should be combined with clinical data and conventional methods considering the lack of unified diagnostic criteria.
Optimal peak inspiratory flow rate (PIFR) is crucial for optimizing dry powder inhaler (DPI) effectiveness for chronic obstructive pulmonary disease (COPD). This study provide an insight that there ...was a substantial proportion of improper PIFRs (not only insufficient but also excessive) among COPD patients using DPIs. We enrolled 138 COPD patients from a medical center in Taiwan and measured PIFRs against different internal resistances of DPIs. Proportion of excessive, optimal, suboptimal, and insufficient PIFRs were 2%, 54%, 41%, 3%, respectively, against medium-high resistance; 2%, 77%, 20%, 1%, respectively, against medium resistance; 27%, 63%, 9%, 1%, respectively, against medium-low resistance; and 42%, 57%, 1%, 0%, respectively, against low resistance (p < 0.01). Although most PIFRs against medium-high (54%), medium (77%), medium-low (63%) and low (57%) resistance were optimal, a substantial proportion of PIFRs against low resistance were excessive (42%, p < 0.01), irrespective of age, body-mass index, dyspnea severity score, and COPD severity. Insufficient PIFRs were infrequent, but suboptimal/insufficient PIFRs were most prevalent in patients older than 75 years than in younger patients (36% vs. 56%, p = 0.036) against medium-high resistance. Regularly monitoring PIFRs against the specific resistance of the DPIs and instructing patients to employ a proper inspiration effort may help to optimize the effects of DPIs.
In order to correlate the mutations inside the entiregyrAandgyrBgenes with the level of resistance to ofloxacin (OFX) and moxifloxacin (MFX) in isolates of multidrug-resistantMycobacterium ...tuberculosis(MDR-TB), a total of 111 isolates were categorized into OFX-susceptible (MIC, ≤2 μg/ml) and low-level (MIC, 4 to 8 μg/ml) and high-level (MIC, ≥16 μg/ml) OFX-resistant isolates and MFX-susceptible (MIC, ≤0.5 μg/ml) and low-level (MIC, 1 to 2 μg/ml) and high-level (MIC, ≥4 μg/ml) MFX-resistant isolates. Resistance-associated mutations inside thegyrAgene were found in 30.2% of OFX-susceptible and 72.5% and 72.2% of low-level and high-level OFX-resistant isolates and in 28.6% of MFX-susceptible and 58.1% and 83.9% of low-level and high-level MFX-resistant isolates. Compared with OFX-susceptible isolates, low-level and high-level OFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (17.0%, 65.0%, and 72.2%, respectively;P< 0.001) and a higher prevalence of thegyrBG512R mutation (0.0%, 2.5%, and 16.7%, respectively;P= 0.006). Similarly, compared with MFX-susceptible isolates, low-level and high-level MFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (14.3%, 51.6%, and 80.6%, respectively;P< 0.001) as well as a higher prevalence of thegyrBG512R mutation (0.0%, 0.0%, and 12.9%, respectively;P= 0.011). D94G and D94N mutations ingyrAand the G512R mutation ingyrBwere correlated with high-level MFX resistance, while the D94A mutation was associated with low-level MFX resistance. The prevalence of mutations atgyrAcodons 88 to 94 and thegyrBG512R mutation were higher among fluoroquinolone (FQ)-susceptible East Asian (Beijing) and Indo-Oceanic strains than they were among Euro-American strains, implying that molecular techniques to detect FQ resistance may be less specific in areas with a high prevalence of East Asian (Beijing) and Indo-Oceanic strains.
We analyzed samples from 13,652 patients who had respiratory cultures positive for mycobacteria in Taiwan during 2000-2012 and found that 56.9% were positive for nontuberculous mycobacteria (NTM). ...Whereas annual prevalence of tuberculosis decreased during the study period, prevalence of NTM disease and colonization increased, particularly among older patients and male patients.
Although bisphosphonate-related osteonecrosis of the jaw (ONJ) develops mainly after tooth extractions (TEs), the strength of the association between them and how the existence of the disease among ...bisphosphonate (BP)-treated osteoporotic patients exposed to TE remain uncertain.
A nationwide retrospective cohort study investigated the influence of alendronate and TE on the development of ONJ.
Incidence of ONJ following long-term alendronate therapy was 262/100,000 person-years, while no event developed in the control group on raloxifene. Overall prevalence of ONJ in osteoporotic subjects receiving alendronate was estimated at 0.34% which rose to 2.16% after TE. Multiple logistic regression analysis, adjusted for the potential confounders, showed TE (adjusted odds ratio, 9.60 4.33-21.29), drug duration exceeding 3 years (3.00 1.33-6.76), and concomitant rheumatoid arthritis (4.94 1.64-14.90) were independent predictors of ONJ.
This article strengthens the relationship between ONJ and BPs. Among osteoporotic patients exposed to alendronate, TE confers a 9.6-fold increased risk for ONJ and it should be performed with caution irrespective of drug duration.
Background. Invasive trichosporonosis has raised attention as an opportunistic infection of immunocompromised patients in the past two decades. However, no recent case series has been reported. ...Methods. All patients with positive cultures for Trichosporon species from 2000 to 2008 at a medical center were evaluated. All Trichosporon species were further confirmed by analysis of intergenic spacer region of the fungal ribosomal RNA gene. In vitro susceptibility testing was performed using the broth microdilution method. Results. A positive culture for Trichosporon species was found in 43 patients. T. asahii was the most frequently species isolates (n=32, 74%), following by T. dermatis (n=5), T. montevideense (n=2), and one each of T. asteroids, T. cutaneum, T. faecale, and T. ovoides. Nineteen patients had invasive infections: 16 (84%) caused by T. asahii and one each caused be T. dermatis, T. montevideense, and T. asteroids. Among the 19 episodes of invasive trichosporonosis, 14 episodes (74%) were fungemia, three (16%) were pulmonary infection, and one (5%) each was soft tissue infection and meningitis. Most invasive infections were associated with prior antibiotics therapy (95%), use of central catheter (90%), malignancy (58%) and intensive care unit stay (50%). Azoles had good in vitro activities while amphotericin B and echinocandins were not active against Trichosporon isolates. The 30-day all-cause mortality rate was 42% and was higher among patients with malignancy (55%). Conclusions. Invasive trichosporonosis tended to develop in patients with malignancy and be associated with higher mortality. T. asahii and other unusual Trichosporon species might cause invasive trichosporonosis.
Early recognition of causative pathogens is critical for the appropriate management of central nervous system infection and improved outcomes. The BioFire® FilmArray® Meningitis/Encephalitis Panel ...(BioFire® ME Panel, BioFire Diagnostics) is the first U.S. Food and Drug Administration (FDA)-approved multiplex PCR assay that allows the rapid detection of 14 pathogens, including bacteria (n = 6), viruses (n = 7), and fungi (n = 1), from cerebrospinal fluid (CSF). The performance of the panel is expected to be dependent on the epidemiology of M/E in different geographical regions.
In this preliminary study, we used the BioFire® ME Panel in 42 subjects who presented to the emergency department with symptoms of M/E in our hospital. The results were compared to conventional culture, antigen detection, PCR, and various laboratory findings.
The panel detected six positive samples, of which five were viral and one bacterial. We observed an overall agreement rate of 88% between the BioFire® ME Panel results and the conventional methods. There were no false-positive findings, but five discordant results were observed for enterovirus, herpes simplex virus type 1, Escherichia coli, and Cryptococcus species.
The BioFire® ME Panel performed equivalently to the traditional PCR methods for virus detection, and better than bacterial cultures. This revolutionary system represents a paradigm shift in the diagnosis of M/E and may aid in the rapid identification of community-acquired M/E. However, the usefulness of this tool is limited in regions with a high prevalence of infectious M/E caused by microorganisms not included in the panel.
This study aimed to investigate the clinical characteristics and outcomes of bacteremia caused by Haemophilus and Aggregatibacter species in patients who were treated at a medical center between 2006 ...and 2018.
Haemophilus and Aggregatibacter isolates were identified up to the species level using Bruker Biotyper MALDI-TOF analysis and ancillary 16S rRNA gene sequencing analysis (in case of ambiguity). Clinical characteristics and outcomes of patients with bacteremia caused by these organisms were evaluated.
Sixty-five Haemophilus and Aggregatibacter species isolates causing bacteremia were identified from nonduplicated patients, including 51 (78.5%) Haemophilus influenzae, 6 (9.2%) Haemophilus parainfluenzae, 1 (1.5%) Haemophilus haemolyticus, 3 (4.6%) A. aphrophilus, and 4 (6.2%) A. segnis. Hospital mortality was observed in 18 (28.1%) of 64 patients with bacteremia caused by Haemophilus (n = 57) and Aggregatibacter species (n = 7). The majority of patients with bacteremia had community-acquired disease with low severity. The average Sequential Organ Failure Assessment (SOFA) score was low (4.4 ± 4.7). But, a higher SOFA score (adjusted odds ratio 2.5, 95% confidence interval 1.22–5.12; P = 0.01) was an independent factor predicting poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia (n = 39).
The overall hospital mortality of 28.1% was observed among patients with bacteremia due to Haemophilus and Aggregatibacter species. A higher SOFA score was and independent predictor of poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia.
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