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1.
Microbiol Spectr ; : e0172821, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35019772

RESUMO

Decreased susceptibility to carbapenems in Enterobacterales is an emerging concern. Conventional methods with short turnaround times are crucial for therapeutic decisions and infection control. In the current study, we used the Xpert CARBA-R (Cepheid, Sunnyvale, CA, USA) and the NG-Test CARBA 5 (NG Biotech, Guipry, France) assays for carbapenemase detection in 214 carbapenem-resistant Enterobacterales (CRE) blood isolates. We used the modified carbapenem inactivation method, conventional PCR, and sequencing to determine the production of five common carbapenemase families and their subtypes. We performed wzc-genotyping for all CR-Klebsiella pneumoniae (CRKP) and multilocus sequence typing for all carbapenemase-producing CRE isolates to reveal their genetic relatedness. The results showed a sensitivity of 99.8% and a specificity of 100% by the Xpert assay, and a sensitivity of 100% and a specificity of 99% by the NG-Test in detecting carbapenemases of 84 CRKP isolates with only one (VIM-1+IMP-8) failure in both tests. For CR-Escherichia coli, four carbapenemase-producing isolates were detected accurately for their subtypes. The two major clones of carbapenemase-producing CRKP isolates in Taiwan were ST11-K47 producing KPC-2 (n = 47) and ST11-K64 producing OXA-48-like (n = 9). Our results support the use of either test in routine laboratories for the rapid detection of common carbapenemases. Caution should be taken using the Xpert assay in areas with a high prevalence of CRE carrying blaIMP-8. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) are emerging worldwide, causing nosocomial outbreaks and even community-acquired infections since their appearance 2 decades ago. Our previous national surveillance of CPE isolates in Taiwan identified five carbapenemase families (KPC, OXA, NDM, VIM, and IMP) with the KPC-2 and OXA-48-like types predominant. Timely detection and classification of carbapenemases in CPE may be a useful test to guide optimal therapy and infection control. Genetic detection methods using the Xpert CARBA-R assay and the immunochromatographic assay using the NG-Test CARBA 5 have been validated with the advantage of short turnaround time. Our study demonstrated that the NG and Xpert assays are convenient methods to accurately identify carbapenemases in carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli blood isolates. Detecting IMP variants remains challenging, and the results of Xpert CARBA-R assay should be carefully interpreted.

2.
Expert Rev Anti Infect Ther ; : 1-13, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-34933656

RESUMO

OBJECTIVES: To determine the in vitro activities of novel and comparator antibiotics against Gram-negative bacteria (GNB) in Taiwan. METHODS: Isolates of Escherichia coli (n = 335), Klebsiella pneumoniae (n = 316; 144 isolates with hyperviscosity characteristics), Pseudomonas aeruginosa (n = 271), Acinetobacter baumannii complex (n = 187), and non-typhoidal Salmonella species (n = 226), Shigella species (n = 13) from miscellaneous culture sources were collected in 2020 in Taiwan. The MICs of the isolates to test antibiotics were determined using the broth microdilution method. GeneXpert was used to detect genes encoding carbapenemases among the carbapenem-non-susceptible (NS) Enterobacterales isolates. RESULTS: The MIC values of the cefepime-enmetazobactam combination against extended-spectrum ß-lactamase-producing E. coli and K. pneumoniae isolates (MIC90 ≤ 0.5 mg/L), blaKPC-harboring E. coli isolates (0.25 mg/L; n = 2), and 80% of blaOXA-48-like gene-harboring K. pneumoniae isolates (≤2 mg/L) were low. The MIC ranges of the cefepime-zidebactam against carbapenemase-producing Enterobacterales isolates (irrespective of the carbapenemase type [MIC90 ≤ 4 mg/L]) and carbapenem-NS or ceftolozane-tazobactam-NS P. aeruginosa isolates (MIC90 value, 8 mg/L) were significantly lower than those of the cefepime-enmetazobactam. CONCLUSIONS: The efficacy of novel antibiotics against important drug-resistant GNB must be monitored and validated during the clinical treatment of patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34958997

RESUMO

OBJECTIVES: Cefiderocol, a siderophore cephalosporin, is active against Gram-negative bacteria including carbapenem-resistant Acinetobacter baumannii (CRAB). In this study, 100 isolates of CRAB from patients with bacteremia in Taiwan were characterized, of which 21 cefiderocol non-susceptible isolates were identified with an MIC of ≥8 mg/L. METHODS: The effect of avibactam on cefiderocol activity was evaluated using broth microdilution methods according to the CLSI guidelines. Whole genome sequencing was performed on all cefiderocol non-susceptible isolates (MIC of ≥8 mg/L) for multi-locus sequence typing analysis, possession of ß-lactamase genes and to identification of possible variations in the PiuA iron transporter. RESULTS: The addition of avibactam, a diazabicyclooctane inhibitor for serine-type ß-lactamase resulted in a ≥8-fold decrease in a cefiderocol MIC for 15 of 21 cefiderocol non-susceptible isolates, compared to only one out of 79 susceptible isolates with a cefiderocol MIC of ≤4 mg/L. Whole genome sequence analysis confirmed that all cefiderocol-non-susceptible isolates harboured multiple ß-lactamases including ADC-30 homologs, OXA-23 and OXA-66. One isolate with a high MIC (>32 mg/L) had a PER-type extended spectrum ß-lactamase (ESBL) gene. Twenty other isolates belonged to ST455, ST473 and ST787. Among these, 13 ST455 isolates were deficient in PiuA, a siderophore uptake receptor that may be required for optimal penetration of cefiderocol. CONCLUSIONS: The MICs of cefiderocol-non-susceptible CRAB isolates from Taiwan could be significantly decreased to susceptible levels by the addition of avibactam, suggesting the involvement of B-lactamases. Among the 21 cefiderocol non-susceptible isolates, one isolate had a PER-type ESBL gene and 13 isolates lacked a PiuA iron siderophore transporter.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34924338

RESUMO

BACKGROUND/PURPOSE: Streptococcus pneumoniae is an important human pathogen that causes invasive infections in adults and children. Accurate serotyping is important to study its epidemiological distribution and to assess vaccine efficacy. METHODS: Invasive S. pneumoniae isolates (n = 300) from 27 teaching hospitals in China were studied. The Quellung reaction was used as the gold standard to identify the S. pneumoniae serotypes. Subsequently, multiplex PCR and cpsB gene-based sequetyping methods were used to identify the serotypes. METHODS: Based on the Quellung reaction, 299 S. pneumoniae isolates were accurately identified to the serotype level and 40 different serotypes were detected. Only one strain was non-typeable, and five most common serotypes were identified: 23F (43, 14.3%), 19A (41, 13.7%), 19F (41, 13.7%), 3 (31, 10.3%), and 14 (27, 9.0%). Overall, the multiplex PCR method identified 73.3 and 20.7% of the isolates to the serotype and cluster levels, respectively, with 1.7% of the isolates misidentified. In contrast, the cpsB sequetyping method identified 59.0 and 30.3% of the isolates to the serotype and cluster levels, respectively, and 7% were misidentified. CONCLUSIONS: The cpsB gene sequetyping method combined with multiplex PCR, can greatly improve the accuracy and efficiency of serotyping, besides reducing the associated costs.

5.
Int J Antimicrob Agents ; : 106475, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34767917

RESUMO

Multidrug-resistant (MDR) bacterial infections in humans are increasing worldwide. The global spread of antimicrobial resistance poses a considerable threat to human health. Phage therapy is a promising approach to combat MDR bacteria. An increasing number of reports have been published on phage therapy and the successful application of antibacterials derived using this method. Additionally, the CRISPR-Cas system has been used to develop antimicrobials with bactericidal effects in vivo. The CRISPR-Cas system can be delivered into target bacteria in various ways, with phage-based vectors being reported as an effective method. In this review, we briefly summarise the results of randomised control trials on bacteriophage therapy. Moreover, we integrated mechanisms of the CRISPR-Cas system antimicrobials in a schematic diagram and consolidated the research on phage-delivered CRISPR-Cas system antimicrobials.

6.
Antimicrob Agents Chemother ; : AAC0200021, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807753

RESUMO

Pseudomonas aeruginosa is a common pathogen that is associated with multidrug-resistant (MDR) and carbapenem-resistant (CR) phenotypes; therefore, we investigated its resistance patterns and mechanisms by using data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program in the Asia-Pacific region during 2015-2019. MICs were determined using the broth microdilution method. Genes encoding major extended-spectrum ß-lactamases and carbapenemases were investigated by multiplex PCR assays. Susceptibility was interpreted using the Clinical and Laboratory Standards Institute (CLSI) breakpoints. A total of 6,349 P. aeruginosa isolates were collected in the ATLAS program between 2015 and 2019 from 14 countries. According to the CLSI definitions, the numbers (and rates) of CR and MDR P. aeruginosa were 1,198 (18.9%) and 1,303 (20.5%), respectively. For 747 of the CR P. aeruginosa strains that were available for gene screening, 253 ß-lactamases genes were detected in 245 (32.8%) isolates. The most common gene was blaVIM (29.0, 71/245), followed by blaNDM (24.9%, 61/245) and blaVEB (20.8%, 51/245). The resistance patterns and associated genes varied significantly between the countries in the Asia-Pacific region. India had the highest rates of carbapenem resistance (29.3%, 154/525) and gene detection (17.7%, 93/525). Compared to those harboring either class A or B ß-lactamase genes, the CR P. aeruginosa without detected ß-lactamase genes had lower MICs for most of the antimicrobial agents, including ceftazidime/avibactam and ceftolozane/tazobactam. In conclusion, MDR and CR P. aeruginosa infections pose a major threat, particularly those with detected carbapenemase genes. Continuous surveillance is important for improving antimicrobial stewardship and antibiotic prescriptions.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34635425

RESUMO

BACKGROUND: Patients with invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially those with an elevated minimal inhibitory concentration (MIC) of vancomycin (VA), are likely to have treatment failure and poor outcomes. The aim of this study was to delineate and correlate the genotypes and phenotypes of clinical VA-intermediate S. aureus (VISA) from invasive infections in Taiwan. METHODS: Between 2006 and 2010, a total of 670 non-duplicate MRSA isolates were collected from patients with invasive infections, mostly from blood, as part of a nationwide antimicrobial surveillance program named Tigecycline in vitro Surveillance in Taiwan. Among them, 10 (1.5%) VISA (VA MIC = 4 mg/L) isolates were identified. Molecular typing with staphylococcal cassette chromosome mec (SCCmec), multilocus sequence typing, staphylococcal protein A (spa), mec-associated hypervariable region (dru), accessory gene regulator (agr), and pulse-field gel electrophoresis, and phenotypic analysis including antibiotic susceptibility testing, gene encoding Panton-Valentine leukocidin (pvl), and superantigenic toxin profiles, were analyzed. RESULTS: All but one isolate was defined as molecular health-care-associated MRSA: 6 as SCCmecIII-ST239-spa t037-agrI-dru7 (1 isolate) and dru14 (5 isolates), 2 as SCCmecII-ST5-spa t586-agrII-dru4, and one as SCCmecII-ST89-spa t3520-agrIII-dru7. One isolate was defined as SCCmecIV-ST59-spa t437-agrI-dru8, which was categorized as molecular community-associated MRSA. Five pulsotypes were identified; only one had a positive D-test and 3 were insusceptible to daptomycin (MIC ≧1 mg/L). Five isolates possessed sea-selk-selq, among them 4 belonged to SCCmecIII-ST239-spa t037-agrI. CONCLUSION: In this study, VISA was rarely isolated from invasive MRSA infections, and most cases harbored limited genotypes and corresponding phenotypes.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34503920

RESUMO

OBJECTIVES: To explore the in vitro antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan. METHODS: From 2016 through 2018, a total of 5458 GNB isolates, including Escherichia coli (n = 1545), Klebsiella pneumoniae (n = 1255), Enterobacter species (n = 259), Pseudomonas aeruginosa (n = 1127), Acinetobacter baumannii complex (n = 368), and Stenotrophomonas maltophilia (n = 179), were collected. The susceptibility results were summarized by the breakpoints of minimum inhibitory concentration (MIC) of CLSI 2020, EUCAST 2020 (for colistin), or published articles (for ceftolozane/tazobactam). The resistance genes among multidrug-resistant (MDR) or extensively drug-resistant (XDR)-GNB were investigated by multiplex PCR. RESULTS: Significantly higher rates of non-susceptibility (NS) to ertapenem and carbapenemase production, predominantly KPC and OXA-48-like beta-lactamase, were observed in Enterobacterales isolates causing respiratory tract infection than those causing complicated urinary tract or intra-abdominal infection (12.7%/3.44% vs. 5.7%/0.76% or 7.7%/0.97%, respectively). Isolates of Enterobacter species showed higher rates of phenotypic extended-spectrum ß-lactamase and NS to ertapenem than E. coli or K. pneumoniae isolates. Although moderate activity (54-83%) was observed against most potential AmpC-producing Enterobacterales isolates, ceftolozane/tazobactam exhibited poor in vitro (44.7-47.4%) activity against phenotypic AmpC Enterobacter cloacae isolates. Additionally, 251 (22.3%) P. aeruginosa isolates exhibited the carbapenem-NS phenotype, and their MDR and XDR rate was 63.3% and 33.5%, respectively. Fifteen (75%) of twenty Burkholderia cenocepacia complex isolates were inhibited by ceftolozane/tazobactam at MICs of ≤4 µg/mL. CONCLUSIONS: With the increase in antibiotic resistance in Taiwan, it is imperative to periodically monitor the susceptibility profiles of clinically important GNB.

9.
Antibiotics (Basel) ; 10(9)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34572668

RESUMO

Probiotic supplements have been used to decrease the gut carriage of antimicrobial-resistant Enterobacterales through changes in the microbiota and metabolomes, nutrition competition, and the secretion of antimicrobial proteins. Many probiotics have shown Enterobacterales-inhibiting effects ex vivo and in vivo. In livestock, probiotics have been widely used to eradicate colon or environmental antimicrobial-resistant Enterobacterales colonization with promising efficacy for many years by oral supplementation, in ovo use, or as environmental disinfectants. In humans, probiotics have been used as oral supplements for infants to decease potential gut pathogenic Enterobacterales, and probiotic mixtures, especially, have exhibited positive results. In contrast to the beneficial effects in infants, for adults, probiotic supplements might decrease potentially pathogenic Enterobacterales, but they fail to completely eradicate them in the gut. However, there are several ways to improve the effects of probiotics, including the discovery of probiotics with gut-protection ability and antimicrobial effects, the modification of delivery methods, and the discovery of engineered probiotics. The search for multifunctional probiotics and synbiotics could render the eradication of "bad" Enterobacterales in the human gut via probiotic administration achievable in the future.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34521591

RESUMO

BACKGROUND/PURPOSE: This study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel ß-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics. METHODS: In total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data. RESULTS: Among the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC50/90, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC50/90, 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC50/90, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC50/90, 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC50/90, 4/8 mg/L). CONCLUSIONS: The spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance.

11.
Viruses ; 13(8)2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34452372

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus in humans, has expanded globally over the past year. COVID-19 remains an important subject of intensive research owing to its huge impact on economic and public health globally. Based on historical archives, the first coronavirus-related disease recorded was possibly animal-related, a case of feline infectious peritonitis described as early as 1912. Despite over a century of documented coronaviruses in animals, the global animal industry still suffers from outbreaks. Knowledge and experience handling animal coronaviruses provide a valuable tool to complement our understanding of the ongoing COVID-19 pandemic. In this review, we present an overview of coronaviruses, clinical signs, COVID-19 in animals, genome organization and recombination, immunopathogenesis, transmission, viral shedding, diagnosis, treatment, and prevention. By drawing parallels between COVID-19 in animals and humans, we provide perspectives on the pathophysiological mechanisms by which coronaviruses cause diseases in both animals and humans, providing a critical basis for the development of effective vaccines and therapeutics against these deadly viruses.


Assuntos
Doenças dos Animais/virologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Coronavirus/fisiologia , Doenças dos Animais/epidemiologia , Animais , COVID-19/epidemiologia , COVID-19/virologia , Coronavirus/genética , Infecções por Coronavirus/epidemiologia , Humanos , Saúde Pública , SARS-CoV-2/genética , SARS-CoV-2/fisiologia
12.
Microorganisms ; 9(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34361971

RESUMO

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used in the field of clinical microbiology since 2010. Compared with the traditional technique of biochemical identification, MALDI-TOF MS has many advantages, including convenience, speed, accuracy, and low cost. The accuracy and speed of identification using MALDI-TOF MS have been increasing with the development of sample preparation, database enrichment, and algorithm optimization. MALDI-TOF MS has shown promising results in identifying cultured colonies and rapidly detecting samples. MALDI-TOF MS has critical research applications for the rapid detection of highly virulent and drug-resistant pathogens. Here we present a scientific review that evaluates the performance of MALDI-TOF MS in identifying clinical pathogenic microorganisms. MALDI-TOF MS is a promising tool in identifying clinical microorganisms, although some aspects still require improvement.

13.
Expert Rev Anti Infect Ther ; : 1-10, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34383624

RESUMO

INTRODUCTION: Clostridioides difficile (C. difficile) infection (CDI) is the most common cause of antibiotic-associated diarrhea and one of the common infections in healthcare facilities. In recent decades, there has been an emerging threat of community-acquired CDI (CA-CDI). Environmental transmission of C. difficile in the community setting has become a major concern, and animals are an important reservoir for C. difficile causing human diseases. AREAS COVERED: In this article, the molecular epidemiology of C. difficile in animals and recent evidences of zoonotic transfer to humans are reviewed based on an electronic search in the databases of PubMed and Google Scholar. EXPERT OPINION: C. difficile can be found in stool from diarrheal dogs and cats; therefore, household pets could be a potential source. C. difficile will threaten human health because hypervirulent C. difficile ribotype 078 strains have been found in retail chickens, pig farms, and slaughterhouses. Risk factors for fecal C. difficile carriage in animals include young age, dietary changes, and antibiotic abuse in domestic animals. With the advent of whole genome sequencing techniques, there will be more solid evidence indicating zoonotic transfer of C. difficile from animals to humans.

14.
Lancet Infect Dis ; 21(12): e375-e386, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34419208

RESUMO

Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections.

15.
J Glob Antimicrob Resist ; 26: 301-307, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34303027

RESUMO

OBJECTIVES: Decreased susceptibility to ceftazidime/avibactam (CZA) and ceftaroline (CPT) has been reported during antimicrobial resistance surveillance and therapy. Conventional laboratories are unable to provide timely susceptibility testing for CZA and CPT because these antimicrobial agents are not incorporated in automated susceptibility testing systems. METHODS: We evaluated Etest and the Sensititre broth microdilution (BMD) method for testing CZA against carbapenem-resistant Gram-negative bacilli and CPT against important Gram-positive cocci bloodstream isolates. Genotypes of carbapenemases in Enterobacterales were also determined using the Xpert® Carba-R assay. RESULTS: Etest showed ≥90% agreement with Sensititre BMD for carbapenem-resistant Klebsiella pneumoniae (CRKP) (n = 187), carbapenem-resistant Escherichia coli (CREC) (n = 28) and Streptococcus pneumoniae (n = 35); however, the very major error rate exceeded 3%. Agreement between Etest and Sensititre BMD was <90% for carbapenem-resistant Pseudomonas aeruginosa (CRPA) (n = 81), methicillin-susceptible Staphylococcus aureus (MSSA) (n = 92) and methicillin-resistant S. aureus (MRSA) (n = 170). Both agents remained potent with a high susceptibility rate by Sensititre BMD as follows: CZA against CRKP (95.0%), CREC (89.3%) and CRPA (84.5%); and CPT against MSSA (100.0%), MRSA (95.3%) and S. pneumoniae (94.3%). CZA was active against blaKPC-carrying CRKP (98.5% susceptible), and resistance in the majority of CZA-resistant Enterobacterales isolates (6 of 10 CRKP and 2 of 3 CREC) was due to the presence of a metallo-ß-lactamase gene. CONCLUSION: Our results suggest that interpretation of susceptibility results obtained by Etest for both agents should be undertaken cautiously and remains challenging.


Assuntos
Ceftazidima , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos , Carbapenêmicos , Ceftazidima/farmacologia , Cefalosporinas , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , Staphylococcus aureus , Streptococcus pneumoniae
16.
J Microbiol Immunol Infect ; 54(5): 767-775, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34253490

RESUMO

Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Carbamatos/uso terapêutico , Cobicistat/uso terapêutico , Darunavir/uso terapêutico , Dibenzotiepinas/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Humanos , Imidazóis/uso terapêutico , Indóis/uso terapêutico , Irã (Geográfico) , Lopinavir/uso terapêutico , Morfolinas/uso terapêutico , Pirazinas/uso terapêutico , Piridonas/uso terapêutico , Pirrolidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/uso terapêutico , SARS-CoV-2 , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Triazinas/uso terapêutico , Valina/análogos & derivados , Valina/uso terapêutico
17.
J Glob Antimicrob Resist ; 26: 308-316, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34289409

RESUMO

OBJECTIVES: The aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017-2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic. METHODS: During the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes. RESULTS: Susceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23. CONCLUSION: The incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD.


Assuntos
COVID-19 , Streptococcus pneumoniae , Adulto , Aminoglicosídeos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Humanos , Lipoglicopeptídeos , Oxazolidinonas , Pandemias , SARS-CoV-2 , Sorogrupo , Taiwan/epidemiologia , Teicoplanina/análogos & derivados , Teicoplanina/farmacologia , Tetraciclinas , Tetrazóis
18.
Artigo em Inglês | MEDLINE | ID: mdl-34219043

RESUMO

BACKGROUND/PURPOSE: Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. METHODS: A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. RESULTS: Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. CONCLUSION: Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

19.
Expert Rev Vaccines ; 20(8): 1013-1025, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34180347

RESUMO

INTRODUCTION: Several vaccine candidates have been developed using different platforms, including nucleic acids (DNA and RNA), viral vectors (replicating and non-replicating), virus-like particles, peptide-based, recombinant proteins, live attenuated, and inactivated virus modalities. Although many of these vaccines are undergoing pre-clinical trials, several large clinical trials investigating the clinical efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines have produced promising findings. AREAS COVERED: In this review, we provide a status update on COVID-19 vaccines currently undergoing clinical trials and discuss issues of concern beyond vaccine efficacy and safety, including dosing regimens, the mixed vaccine strategy, prior severe acute respiratory syndrome coronavirus-2 infection, antibody levels, cellular immunity and protection, variants of concern, COVID-19 vaccine distribution, vaccination willingness, herd immunity, immunity passports, and vaccine indications. EXPERT OPINION: Four vaccines have obtained emergency use authorization, 87 are at the clinical development stage, and 186 are in pre-clinical development. While the knowledge and development of COVID-19 vaccines is rapidly expanding, the benefits of COVID-19 vaccines must outweigh the potential risks of adverse events. To combat the COVID-19 pandemic, clinicians should consistently update COVID-19-associated information, and healthcare authorities and manufacturers should work together to provide adequate and appropriate vaccinations for the prevention of COVID-19. PLAIN LANGUAGE SUMMARY: What is the context?Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic: the coronavirus disease 2019 (COVID-19) outbreak. The development and implementation of the COVID-19 vaccine could be an important measure to control the COVID-19 pandemic.What is new?Several phase 3 clinical trials have demonstrated the effectiveness and safety of COVID-19 vaccines for the prevention of SARS-CoV-2 infections. Several COVID-19 vaccines have obtained emergency use authorization and been implemented in many countries. Although concerns regarding unusual blood clots and low platelet counts have been raised, the benefits of COVID-19 vaccines outweigh the potential risks of adverse events.What is the impact?Except for children, the COVID-19 vaccine is recommended for all people, including those pregnant or immunocompromised. Healthcare authorities should advise people receiving the vaccine that they must seek medical attention if they have associated thromboembolism and thrombocytopenia symptoms. More studies are necessary to determine the appropriate vaccine dose and regimen strategy, as well as the effectiveness of COVID-19 vaccines against variants of concerns. A global effort must be made to achieve widespread vaccination and herd immunity.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Segurança do Paciente , Animais , COVID-19/epidemiologia , Ensaios Clínicos Fase III como Assunto/métodos , Fadiga/induzido quimicamente , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/fisiologia , Masculino , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento
20.
Front Immunol ; 12: 626609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084161

RESUMO

Accurate detection of anti-SARS-CoV-2 antibodies provides a more accurate estimation of incident cases, epidemic dynamics, and risk of community transmission. We conducted a cross-sectional seroprevalence study specifically targeting different populations to examine the performance of pandemic control in Taiwan: symptomatic patients with epidemiological risk and negative qRT-PCR test (Group P), frontline healthcare workers (Group H), healthy adult citizens (Group C), and participants with prior virologically-confirmed severe acute respiratory syndrome (SARS) infection in 2003 (Group S). The presence of anti-SARS-CoV-2 total and IgG antibodies in all participants were determined by Roche Elecsys® Anti-SARS-CoV-2 test and Abbott SARS-CoV-2 IgG assay, respectively. Sera that showed positive results by the two chemiluminescent immunoassays were further tested by three anti-SARS-CoV-2 lateral flow immunoassays and line immunoassay (MIKROGEN recomLine SARS-CoV-2 IgG). Between June 29 and July 25, 2020, sera of 2,115 participates, including 499 Group P participants, 464 Group H participants, 1,142 Group C participants, and 10 Group S participants, were tested. After excluding six false-positive samples, SARS-CoV-2 seroprevalence were 0.4, 0, and 0% in Groups P, H, and C, respectively. Cross-reactivity with SARS-CoV-2 antibodies was observed in 80.0% of recovered SARS participants. Our study showed that rigorous exclusion of false-positive testing results is imperative for an accurate estimate of seroprevalence in countries with previous SARS outbreak and low COVID-19 prevalence. The overall SARS-CoV-2 seroprevalence was extremely low among populations of different exposure risk of contracting SARS-CoV-2 in Taiwan, supporting the importance of integrated countermeasures in containing the spread of SARS-CoV-2 before effective COVID-19 vaccines available.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/epidemiologia , Adulto , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Reações Cruzadas , Estudos Transversais , Surtos de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Síndrome Respiratória Aguda Grave/imunologia , Taiwan/epidemiologia
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