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1.
J Clin Microbiol ; : e0052424, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934589

RESUMO

This study compared the performance of two commercial molecular assays, the STANDARD M10 Clostridioides difficile assay (M10) and the Xpert C. difficile assay (Xpert), for detecting toxigenic C. difficile in stool specimens. A total of 487 consecutive stool specimens submitted for routine C. difficile testing between June and November 2023 were included. Following routine testing using C. DIFF QUIK CHEK COMPLETE (QCC), M10 and Xpert were tested in parallel, alongside toxigenic culture (reference standard). Additionally, two-step algorithms, using QCC on the first step and either M10 or Xpert on the second step, were assessed. Both M10 and Xpert demonstrated a sensitivity and negative predictive value (NPV) of 100%. M10 exhibited significantly higher specificity and positive predictive value (PPV; 91.9% and 64.2%, respectively) than Xpert (90.3% and 59.8%, respectively). Both two-step algorithms showed a sensitivity and NPV of 98.4% and 99.8%, respectively. The specificity and PPV of the two-step algorithm using M10 (95.2% and 75.0%, respectively) were slightly higher than those of the one using Xpert (94.8% and 73.2%, respectively), without statistical significance. Receiver operating characteristic curve analysis, assessing the predictive ability of cycle threshold (Ct) values for the detection of free toxin, exhibited an area under the curve of 0.825 for M10 and 0.843 for Xpert. This indicates the utility of Ct values as predictors for the detection of free toxin in both assays. In conclusion, M10 proves to be an effective diagnostic tool with performance comparable to Xpert, whether utilized independently or as part of a two-step algorithm.

2.
J Clin Lab Anal ; 38(9): e25043, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38804639

RESUMO

BACKGROUND: Rapid antimicrobial susceptibility testing (AST) for bloodstream infections (BSIs) facilitates the optimization of antimicrobial therapy, preventing antimicrobial resistance and improving patient outcomes. QMAC-dRAST (QuantaMatrix Inc., Korea) is a rapid AST platform based on microfluidic chip technology that performs AST directly using positive blood culture broth (PBCB). This study evaluated the performance of QMAC-dRAST for Gram-negative bacteria using PBCB and subcultured colony isolates, comparing it with that of VITEK 2 (bioMérieux, France) using broth microdilution (BMD) as the reference method. METHODS: We included 141 Gram-negative blood culture isolates from patients with BSI and 12 carbapenemase-producing clinical isolates of Enterobacterales spiked into blood culture bottles. QMAC-dRAST performance was evaluated using PBCB and colony isolates, whereas VITEK 2 and BMD were tested only on colony isolates. RESULTS: For PBCB, QMAC-dRAST achieved 92.1% categorical agreement (CA), 95.3% essential agreement (EA), with 1.8% very major errors (VMEs), 3.5% major errors (MEs), and 5.2% minor errors (mEs). With colony isolates, it exhibited 92.5% CA and 95.1% EA, with 2.0% VMEs, 3.2% MEs, and 4.8% mEs. VITEK 2 showed 94.1% CA and 96.0% EA, with 4.3% VMEs, 0.4% MEs, and 4.3% mEs. QMAC-dRAST yielded elevated error rates for specific antimicrobial agents, with high VMEs for carbapenems and aminoglycosides. The median time to result for QMAC-dRAST was 5.9 h for PBCB samples and 6.1 h for subcultured colony isolates. CONCLUSIONS: The QMAC-dRAST system demonstrated considerable strengths and comparable performance to the VITEK 2 system; however, challenges were discerned with specific antimicrobial agents, underlining a necessity for improvement.


Assuntos
Antibacterianos , Hemocultura , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Testes de Sensibilidade Microbiana/métodos , Humanos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Hemocultura/métodos , Antibacterianos/farmacologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-33685889

RESUMO

We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.

4.
J Clin Microbiol ; 61(1): e0108622, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36602360

RESUMO

The World Health Organization recently lowered the rifampin (RIF) critical concentration (CC) for drug-susceptibility testing (DST) of Mycobacterium tuberculosis complex (MTBC) using the mycobacterial growth indicator tube (MGIT) 960 system. Here, we evaluated the diagnostic performance of the MGIT system with the revised CC for determining MTBC RIF resistance with 303 clinical MTBC isolates, including 122 isolates with rpoB mutations, of which 32 had single borderline-resistance mutations, and 181 wild-type rpoB isolates. The phenotypic RIF resistance was determined via the absolute concentration method (AC) and via MGIT using both previous (1 mg/L) and revised (0.5 mg/L) CCs for the latter method. The diagnostic accuracy of each phenotypic DST (pDST) was assessed based on rpoB genotyping as the reference standard. The overall sensitivity of the AC was 95.1% (95% confidence interval [CI], 89.6 to 98.2%), while the MGIT results with previous and revised CCs were 82.0% (95% CI 74.0 to 88.3%) and 83.6% (95% CI 75.8 to 89.7%), respectively. The 32 MTBC isolates with single borderline-resistance mutations showed a wide range of MICs, and sensitivity was not significantly increased by reducing the MGIT CC. All 181 wild-type rpoB isolates were RIF-susceptible in the AC and with MGIT using the previous CC, whereas 1 isolate was misclassified as RIF-resistant with the revised CC. Our results demonstrate that the overall diagnostic performances of the MGIT DST with the revised RIF CC and previous CC were comparable. A further large-scale study is required to demonstrate the optimal RIF CC for MGIT.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , RNA Polimerases Dirigidas por DNA/genética , Testes de Sensibilidade Microbiana , Mutação , Rifampina/farmacologia , Avaliação Pré-Clínica de Medicamentos
5.
Clin Lab ; 69(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37436396

RESUMO

BACKGROUND: Rapid and accurate identification of nontuberculous mycobacteria (NTM) species is essential for the diagnosis and treatment of NTM disease. MolecuTech REBA Myco-ID (YD Diagnostics, Yongin, Korea) is a line probe assay for identification of NTM species and can be performed using HybREAD480, an instrument for automating the post-PCR steps. In this study, we assessed the performance of MolecuTech REBA Myco-ID using HybREAD480. METHODS: Seventy-four reference strains, including 65 Mycobacterium strains and nine non-Mycobacterium strains within the order Mycobacteriales, were used to determine the analytical specificity of MolecuTech REBA Myco-ID. The clinical performance of this assay was evaluated with 192 clinical Mycobacterium strains, and the assay results were compared to those of multigene sequencing-based typing. RESULTS: The accuracy of MolecuTech REBA Myco-ID for the 74 reference strains and 192 clinical strains was 77.0% (57/74; 95% confidence interval [CI], 65.8 - 86.0%) and 94.3% (181/192; 95% CI, 90.0 - 97.1%), respectively. Although some rarely isolated NTM species are misidentified, the most commonly isolated NTM species, including M. avium complex, M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. fortuitum com-plex, were all correctly identified. Of note, all M. lentiflavum strains tested (reference strain, n = 1; clinical strain, n = 10) were misidentified as M. gordonae. CONCLUSIONS: MolecuTech REBA Myco-ID using HybREAD480 was accurate for identifying commonly isolated NTM species and for discriminating between M. abscessus subsp. abscessus and M. abscessus subsp. massiliense. However, the main limitations of this assay, including misidentification of some rarely isolated NTM species and cross-reactivity between M. lentiflavum and M. gordonae, should be considered.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , Humanos , Micobactérias não Tuberculosas/genética , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA , Escarro/microbiologia
6.
Antimicrob Agents Chemother ; 66(4): e0202721, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35266825

RESUMO

We evaluated the associations between the in vitro activities of ethambutol and rifampin and clinical outcomes of Mycobacterium avium complex (MAC) pulmonary disease (PD). Among 158 patients with MAC-PD, there was no relationship between high MICs for ethambutol and/or rifampin and treatment failure for MAC-PD. Ethambutol and rifampin resistance was common among MAC isolates (rates of 87% and 59%, respectively), but mutations in embB, rpoB, and rpoC were rare, with detection in only 4% of the drug-resistant MAC isolates.


Assuntos
Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Etambutol/farmacologia , Etambutol/uso terapêutico , Humanos , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Complexo Mycobacterium avium/genética , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Rifampina/farmacologia , Rifampina/uso terapêutico
7.
Antimicrob Agents Chemother ; 66(11): e0088922, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36226945

RESUMO

We investigated the evolution of fluconazole resistance mechanisms and clonal types of Candida parapsilosis isolates from a tertiary care hospital in South Korea. A total of 45 clinical isolates, including 42 collected between 2017 and 2021 and 3 collected between 2012 and 2013, were subjected to antifungal susceptibility testing, sequencing of fluconazole resistance genes (ERG11, CDR1, TAC1, and MRR1), and microsatellite typing. Twenty-two isolates carried Y132F (n = 21; fluconazole MIC = 2 to >256 mg/L) or Y132F+R398I (n = 1; fluconazole MIC = 64 mg/L) in ERG11 and four isolates harbored N1132D in CDR1 (fluconazole MIC = 16 to 64 mg/L). All 21 Y132F isolates exhibited similar microsatellite profiles and formed a distinct group in the dendrogram. All four N1132D isolates displayed identical microsatellite profiles. Fluconazole MIC values of the Y132F isolates varied depending on their MRR1 mutation status (number of isolates, year of isolation, and MIC): K177N (n = 8, 2012 to 2020, 2 to 8 mg/L); K177N + heterozygous G982R (n = 1, 2017, 64 mg/L); K177N + heterozygous S614P (n = 2, 2019 to 2020, 16 mg/L); and K177N + homozygous S614P (n = 10, 2020 to 2021, 64 to > 256 mg/L). Our study revealed that Y132F in ERG11 and N1132D in CDR1 were the major mechanisms of fluconazole resistance in C. parapsilosis isolates. Furthermore, our results suggested that the clonal evolution of Y132F isolates persisting and spreading in hospital settings for several years occurred with the acquisition of heterozygous or homozygous MRR1 mutations associated with a gradual increase in fluconazole resistance.


Assuntos
Candida parapsilosis , Fluconazol , Fluconazol/farmacologia , Candida parapsilosis/genética , Farmacorresistência Fúngica/genética , Centros de Atenção Terciária , Antifúngicos/farmacologia , Proteínas Fúngicas/genética , Testes de Sensibilidade Microbiana
8.
BMC Infect Dis ; 22(1): 686, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948963

RESUMO

PURPOSE: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. METHODS: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC24/MIC) and trough concentration (Ctrough) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. RESULTS: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for Ctrough, 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 µg/mL, but not AUC24/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010). CONCLUSION: Mean Ctrough ≥ 13.94 µg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.


Assuntos
Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Área Sob a Curva , Bacteriemia/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/farmacologia
9.
Clin Lab ; 68(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443595

RESUMO

BACKGROUND: Prototheca algaemia is a rare but life-threatening disease that occurs primarily in immunocompromised patients. We report a fatal case of Prototheca zopfii bloodstream infection in a 54-year-old woman receiving chemotherapy for relapsed acute lymphoblastic leukemia. METHODS: The isolate was identified using an automated biochemical identification system (VITEK 2; bioMerieux) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (VITEK MS; bioMerieux). Partial 18S and 28S rDNA sequencing was performed for definitive identification and genotyping. RESULTS: The patient had persistent neutropenic fever, and isolates from blood culture were identified as P. zopfii. Sequencing was performed and the isolate was confirmed to be P. zopfii genotype 2, which was newly named as P. bovis. The patient was treated with liposomal amphotericin B but died of septic shock. CONCLUSIONS: Prototheca spp. should be considered an emerging pathogen, especially in immunocompromised patients, due to its ubiquitous nature.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Prototheca , DNA Ribossômico/genética , Feminino , Genótipo , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prototheca/química , Prototheca/genética
10.
J Korean Med Sci ; 37(24): e196, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35726147

RESUMO

BACKGROUND: Acinetobacter baumannii infections cause high morbidity and mortality in intensive care unit (ICU) patients. However, there are limited data on the changes of long-term epidemiology of imipenem resistance in A. baumannii bacteremia among pediatric ICU (PICU) patients. METHODS: A retrospective review was performed on patients with A. baumannii bacteremia in PICU of a tertiary teaching hospital from 2000 to 2016. Antimicrobial susceptibility tests, multilocus sequence typing (MLST), and polymerase chain reaction for antimicrobial resistance genes were performed for available isolates. RESULTS: A. baumannii bacteremia occurred in 27 patients; imipenem-sensitive A. baumannii (ISAB, n = 10, 37%) and imipenem-resistant A. baumannii (IRAB, n = 17, 63%). There was a clear shift in the antibiogram of A. baumannii during the study period. From 2000 to 2003, all isolates were ISAB (n = 6). From 2005 to 2008, both IRAB (n = 5) and ISAB (n = 4) were isolated. However, from 2009, all isolates were IRAB (n = 12). Ten isolates were available for additional test and confirmed as IRAB. MLST analysis showed that among 10 isolates, sequence type 138 was predominant (n = 7). All 10 isolates were positive for OXA-23-like and OXA-51-like carbapenemase. Of 27 bacteremia patients, 11 were male (41%), the median age at bacteremia onset was 5.2 years (range, 0-18.6 years). In 33% (9/27) of patients, A. baumannii was isolated from tracheal aspirate prior to development of bacteremia (median, 8 days; range, 5-124 days). The overall case-fatality rate was 63% (17/27) within 28 days. There was no statistical difference in the case fatality rate between ISAB and IRAB groups (50% vs. 71%; P = 0.422). CONCLUSION: IRAB bacteremia causes serious threat in patients in PICU. Proactive infection control measures and antimicrobial stewardship are crucial for managing IRAB infection in PICU.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriemia , Infecção Hospitalar , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Criança , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Imipenem/farmacologia , Imipenem/uso terapêutico , Unidades de Terapia Intensiva Pediátrica , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , beta-Lactamases
11.
J Clin Lab Anal ; 35(1): e23585, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32969071

RESUMO

BACKGROUND: The Automated Fluorescent Immunoassay System ROTA (AFIAS-Rota) and NORO (AFIAS-Noro) assays (Boditech Med Inc.) are newly developed diagnostic tests for rotavirus and norovirus infections. METHODS: Performance of AFIAS-Rota/Noro assays was evaluated in comparison with RIDASCREEN® Rotavirus and Norovirus ELISA kits (R-Biopharm) using clinical stool samples submitted from November 2018 to January 2019. Multiplex real-time reverse transcription-polymerase chain reaction was used as reference method. RESULTS: A total of 256 clinical specimens were analyzed. AFIAS-Rota and RIDASCREEN Rotavirus had almost perfect agreement (Kappa value = 0.95), and substantial agreement was observed between AFIAS-Noro and RIDASCREEN Norovirus (Kappa value = 0.80). For detection of rotavirus, AFIAS and RIDASCREEN assays showed satisfactory diagnostic sensitivity (100% and 97.8%, respectively) and specificity (99.5% and 99.1%). For detection of norovirus, the RIDASCREEN assay showed significantly higher sensitivity than the AFIAS-Noro (86.0% and 66.0%, respectively; P = .002). Analytic specificity of AFIAS-Rota/Noro assays showed no cross-reactivity against any other bacteria (14 strains) or viruses (2 strains). Hands-on time (6 minutes) and turnaround time (26 minutes) required to perform AFIAS assays were much shorter than those required for RIDASCREEN assays (20 and 150 minutes, respectively). CONCLUSION: The AFIAS-Rota/Noro assays showed overall excellent agreement with the RIDASCREEN assays. Although the AFIAS-Noro assay exhibited lower sensitivity than the RIDASCREEN Norovirus assay for detection of norovirus, the AFIAS-Rota/Noro assays could be useful as a rapid initial screening test in clinical laboratories due to its convenience and rapid turnaround time.


Assuntos
Infecções por Caliciviridae/diagnóstico , Imunofluorescência , Norovirus/isolamento & purificação , Infecções por Rotavirus/diagnóstico , Rotavirus/isolamento & purificação , Fezes/virologia , Imunofluorescência/métodos , Imunofluorescência/normas , Imunofluorescência/estatística & dados numéricos , Humanos , Norovirus/genética , Norovirus/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Rotavirus/genética , Rotavirus/imunologia , Sensibilidade e Especificidade , Virologia
12.
Mycopathologia ; 186(1): 15-26, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33180204

RESUMO

With the increasing number of fungal infections and immunocompromised patients, rapid and accurate fungal identification is required in clinical microbiology laboratories. We evaluated the applicability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, MicroIDSys Elite (ASTA Corp., South Korea) for the identification of medically important filamentous fungi. A total of 505 strains comprising 37 genera and 90 species collected from 11 Korean hospitals were sent to the microbiology laboratory of International St. Mary's Hospital. All isolates were tested using MicroIDSys Elite, and data were analyzed using the MoldDB v.1.22 database (ASTA). Correct identification rates were compared with the multigene sequencing results. MicroIDSys Elite correctly identified 86.5% (437/505) and 88.9% (449/505) of all tested isolates at the species and genus level, respectively. About 98.2% of Aspergillus isolates were identified at the species level, including cryptic and rare species of A. calidoustus, A. tamarii, A. lentulus, A. versicolor and A. aculeatus. MicroIDSys Elite identified 75.0% of basidiomycetes, including Schizophyllum commune, and 84.3% of the dermatophytes. It also distinguished Sprothrix globosa at the species level. The mean scores of total isolates corresponding to correct species identification were significantly higher than those obtained for genus-level identification (253.5 ± 50.7 vs. 168.6 ± 30.3, P < 0.001). MicroIDSys Elite showed high accuracy for the identification of filamentous fungi, including cryptic and rare Aspergillus species. It is suitable for use in clinical laboratories as a rapid and efficient tool for clinical mold identification. Further evaluations are recommended for MicroIDSys Elite as a rapid and efficient tool for the identification of medically important filamentous fungi.


Assuntos
Fungos , Micoses , Aspergillus , Humanos , República da Coreia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
13.
Clin Infect Dis ; 71(9): e487-e496, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31994704

RESUMO

BACKGROUND: Clinically relevant categorization of antimicrobial resistance is critical to mitigating the threat it poses. Difficult-to-treat resistance (DTR) is a recently proposed category defined as nonsusceptibility to all first-line antibiotic agents. METHODS: A retrospective study was conducted with nonduplicate cases of gram-negative bloodstream infection (GNBSI) caused by 4 major taxa (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter species) identified from a nationwide surveillance database. DTR was defined as nonsusceptibility to all the ß-lactams and fluoroquinolones tested. Patient characteristics and mortality were compared between DTR GNBSI and GNBSI caused by carbapenem-resistant but not DTR and extended-spectrum cephalosporin-resistant but not DTR isolates using Centers for Disease Control and Prevention definitions. Adjusted odds ratios (aORs) for 30-day in-hospital mortality were examined for DTR in overall and in propensity score-matched cohorts. RESULTS: A total of 1167 episodes of monomicrobial GNBSI were identified, and 147 (12.6%) of the isolates were DTR. The majority of DTR isolates were Acinetobacter species (79.6%) and P. aeruginosa (17.7%). DTR infections were associated with previous antibiotic use, healthcare contact, ventilator use, and lower respiratory tract infection. Crude mortality for GNBSI caused by DTR was 50.3%. A multivariable model showed that only DTR, but not other categories, was significantly associated with mortality (adjusted odds ratio [aOR], 3.58 [95% confidence interval {CI}, 1.27-10.19]). DTR was also a significant predictor for mortality in the analysis of propensity score-matched cohorts (aOR, 3.48 [95% CI, 1.82-6.79]). CONCLUSIONS: In patients with GNBSI, DTR was associated with higher mortality than those in other resistance categories. Our findings suggest that DTR could be useful for surveillance and prognostication.


Assuntos
Bacteriemia , Infecções por Bactérias Gram-Negativas , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Carbapenêmicos , Farmacorresistência Bacteriana , Fluoroquinolonas , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
14.
Eur Respir J ; 55(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31619468

RESUMO

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus (n=129) and M. massiliense (n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality: M. intracellulare had an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03-1.91; M. abscessus had an aHR of 2.19, 95% CI 1.36-3.51; and M. massiliense had an aHR of 0.99, 95% CI 0.61-1.64, compared to M. avium Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12-2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57-3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Seguimentos , Humanos , Masculino , Complexo Mycobacterium avium , Micobactérias não Tuberculosas , Prognóstico , Estudos Retrospectivos
15.
Clin Genet ; 98(1): 64-68, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32185794

RESUMO

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by defects in the function or structure of motitle cilia. In most cases, causative variants result in axonemal dynein arm anomalies, however, PCD due to radial spoke (RS) and central pair (CP) of microtubules has been rarely reported. To identify the molecular basis of PCD characterized by RS/CP defects, we performed whole exome sequencing in PCD patients with RS/CP defects. We identified a homozygous nonsense variant (c.572G>A; p.Trp191*) in NME5, which encodes a protein component of the RS neck, in one PCD patient with situs solitus. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy. This is the first study to show NME5 as a PCD-causative gene in humans. Our findings indicate that NME5 screening should be considered for PCD patients with RS/CP defects.


Assuntos
Cílios/genética , Transtornos da Motilidade Ciliar/genética , Códon sem Sentido/genética , Mutação/genética , Nucleosídeo NM23 Difosfato Quinases/genética , Adulto , Sequência de Aminoácidos , Animais , Dineínas do Axonema/genética , Axonema/genética , Feminino , Homozigoto , Humanos , Microtúbulos/genética , Fenótipo , Peixe-Zebra/genética
16.
Eur J Clin Microbiol Infect Dis ; 39(6): 1193-1199, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32219584

RESUMO

The etiologic diagnostic yield of community-onset pneumonia (COP) using conventional methods is low. Bacterial multiplex polymerase chain reaction (mPCR) has been shown to be more sensitive than conventional methods. This study assessed the clinical factors influencing bacterial mPCR results in patients with COP. Patients with COP admitted to a tertiary care hospital between November 2015 and April 2016 were retrospectively assessed. Conventional methods included culture-based methods and serology for Mycoplasma pneumoniae. Bacterial mPCR that could identify Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Legionella pneumophilia was performed. Bacterial mPCR was performed in a total of 342 patients with COP in the study. Bacterial mPCR alone provided etiology in 99 patients. The total etiologic diagnosis rates improved from 22.2 to 51.1% when bacterial mPCR was added to conventional methods. Additional diagnostic benefits of bacterial mPCR were more prominent in the prior antibiotic non-exposure group (77.8% vs 63.5%, P = 0.015) and in the low-risk group with low CURB 65 score (62.6% vs 44.9%, P = 0.005). Patients who required ICU care, those with healthcare-associated pneumonia (HCAP), and patients with any underlying diseases were not associated with the additional pathogen detection rates using bacterial mPCR. By supplementing conventional diagnostic methods with bacterial mPCR-based methods, the overall pathogen detection rates improved in patients with COP. Moreover, the additional diagnostic usefulness of bacterial mPCR was significantly higher in patients without prior antibiotic exposure and in the mild-to-moderate-risk group with lower CURB 65 score.


Assuntos
Bactérias/isolamento & purificação , Técnicas Bacteriológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Multiplex , Pneumonia Bacteriana/microbiologia , Idoso , Antibacterianos/uso terapêutico , Bactérias/classificação , Bactérias/genética , Técnicas Bacteriológicas/normas , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , República da Coreia , Estudos Retrospectivos
17.
J Infect Chemother ; 26(9): 995-998, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32402736

RESUMO

A 37-year-old healthy man was admitted with fever, skin rash, migratory arthralgia, and headache without preceding urogenital symptoms. Sexual contact history and positive CSF culture for Neisseria gonorrhoeae using BacT/Alert blood culture bottles were diagnostic for gonococcal meningitis. Multilocus sequence typing of this isolate showed sequence type (ST) 7363, the most predominant ST among ceftriaxone-resistant strains. The isolate from this case remained susceptible to ceftriaxone although it was resistant to penicillin, tetracycline, and ciprofloxacin. With the high selective pressure of ceftriaxone for treatment of plasmid-mediated ß-lactamase producing N. gonorrhoeae, resistance to ceftriaxone and molecular characteristics should be monitored.


Assuntos
Gonorreia , Meningites Bacterianas , Adulto , Antibacterianos/uso terapêutico , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Humanos , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/genética , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-31611366

RESUMO

We evaluated the efficacy of intermittent azithromycin and ethambutol therapy for noncavitary Mycobacterium avium complex pulmonary disease (MAC-PD). Twenty-nine (76%) of 38 patients achieved sputum culture conversion after 12 months of treatment, and sputum smear positivity was an independent factor for failure to achieve culture conversion (adjusted odds ratio, 26.7; 95% confidence interval, 2.1 to 339.9; P = 0.011). Intermittent azithromycin and ethambutol may be an optional treatment regimen for noncavitary MAC-PD.


Assuntos
Antituberculosos/uso terapêutico , Azitromicina/uso terapêutico , Etambutol/uso terapêutico , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/patogenicidade , Índice de Massa Corporal , Quimioterapia Combinada/métodos , Feminino , Humanos , Pneumopatias/microbiologia , Masculino , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Razão de Chances , Resultado do Tratamento
19.
Artigo em Inglês | MEDLINE | ID: mdl-30885902

RESUMO

The understanding of species distribution and inducible macrolide resistance in the Mycobacterium fortuitum complex (MFC) is limited. Of 90 mostly respiratory MFC clinical isolates, half were M. fortuitum, followed by M. peregrinum, M. porcinum, M. septicum, and M. conceptionense Most M. fortuitum, M. porcinum, and M. septicum isolates were inducibly resistant to clarithromycin, whereas two-thirds of the M. peregrinum isolates were clarithromycin susceptible. Clarithromycin-resistant M. fortuitum isolates exhibited common mutations of erm(39), potentially involved in clarithromycin resistance.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Mycobacterium fortuitum/efeitos dos fármacos , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana
20.
Artigo em Inglês | MEDLINE | ID: mdl-31182533

RESUMO

We evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii However, bedaquiline showed low MIC values for the major pathogenic NTM, including Mycobacterium avium complex, Mycobacterium abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. kansasii Bedaquiline also had low MIC values with macrolide-resistant NTM strains and warrants further investigation as a potential antibiotic for NTM treatment.


Assuntos
Antibacterianos/farmacologia , Antituberculosos/farmacologia , Diarilquinolinas/farmacologia , Macrolídeos/farmacologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Nitroimidazóis/farmacologia , Micobactérias não Tuberculosas/efeitos dos fármacos , Oxazóis/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/efeitos dos fármacos , Complexo Mycobacterium avium/efeitos dos fármacos , Mycobacterium kansasii/efeitos dos fármacos
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