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2.
Emerg Infect Dis ; 26(4): 711-720, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32186492

RESUMO

Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013-2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32063458

RESUMO

BACKGROUND: A regional antibiotic susceptibility data of common pathogens is crucial to first-line physician for clinical judgment and appropriate selection of antimicrobial agents. The aim of this study is to update the epidemiology data of drug resistance of pneumococcus causing invasive pneumococcal disease (IPD) in adults. METHODS: From the logbooks of microbiology laboratories, we retrospectively retrieved Streptococcus pneumoniae isolates, collected from normally sterile sites in adult patients in three hospitals in Taiwan from July 2011 to June 2015. Antibiotic resistance and serotypes of the isolates and clinical manifestations were further analyzed. RESULTS: A total of 150 non-duplicated isolates were collected. According to CLSI meningitis breakpoint, the proportion of ceftriaxone non-susceptible pneumococcus (CNSP) showed an increasing trend from 4.5% in 2011 to > 40% in 2013-2015 (p = 0.007). Serotypes 19A and 23F were significantly associated with CNSP. Imipenem and meropenem had a relative low susceptible rate of 36.7% and 50.7%, respectively. Serotypes 6A, 14, 19A and 19F were significantly associated with the non-susceptibility to these carbepanems. CONCLUSION: The increase in the prevalence of CNSP using meningitis breakpoint was observed. For treating pneumococcal meningitis, empirical monotherapy with ceftriaxone might not be adequate. Imipenem and meropenem might not be a good choice for empirical treatment of adult IPDs. Antibiotic resistance of pneumococcus to ceftriaxone, cefepime, imipenem and meropenem were associated with 13-velent pneumococcal conjugate vaccine serotypes.

5.
J Surg Oncol ; 121(1): 25-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31264724

RESUMO

BACKGROUND: This high volume, single center study investigated the prevalence, bacterial epidemiology, and responsiveness to antibiotic therapy of cellulitis in extremity lymphedema. METHODS: From 2003 to 2018, cellulitis events from a cohort of 420 patients with extremity lymphedema were reviewed. Demographics, lymphedema grading, symptoms, inflammatory markers, cultures and antibiotic therapy regimens were compiled from cellulitis episodes data. Univariate and multivariate analyses were performed for detailed analysis. RESULTS: A total of 131 separate episodes of cellulitis were recorded from 43 (81.1%) lower limb and 10 (19.9%) upper limb lymphedema patients. The prevalence and recurrence rates for cellulitis in lymphedema patients were 12.6% (53 of 420) and 56.6% (30 of 53), respectively. The most common findings were increased limb circumference (127 of 131; 96.9%) and abnormal C-reactive protein (CRP) level (86 of 113; 76.1%). Blood cultures were obtained in 79 (60.3%) incidents, with 9 (11.4%) returning positive. Streptococcus agalactiae was the most isolated bacterium (5 of 9; 55.5%). CONCLUSIONS: The cellulitis prevalence and recurrence rate in extremity lymphedema were 12.6%, and 56.6%, respectively. Strongest indicators of cellulitis were increased affected limb circumference and elevated CRP level. Empiric antibiotic therapy began with coverage for Steptococcus species before broadening to anti-Methicillin-resistant Staphylococcus aureus and anti-Gram negatives if needed for effective treatment of extremity lymphedema cellulitis.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Celulite (Flegmão)/tratamento farmacológico , Celulite (Flegmão)/microbiologia , Linfedema/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/patologia , Celulite (Flegmão)/epidemiologia , Celulite (Flegmão)/patologia , Estudos de Coortes , Extremidades/microbiologia , Extremidades/patologia , Feminino , Humanos , Linfedema/epidemiologia , Linfedema/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
6.
Phytomedicine ; 64: 152904, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31454654

RESUMO

BACKGROUND: Millions of people are infected by the influenza virus worldwide every year. Current selections of anti-influenza agents are limited and their effectiveness and drug resistance are still of concern. PURPOSE: Investigation on in vitro and in vivo effect of aloin from Aloe vera leaves against influenza virus infection. METHODS: In vitro antiviral property of aloin was measured by plaque reduction assay in which MDCK cells were infected with oseltamivir-sensitive A(H1N1)pdm09, oseltamivir-resistant A(H1N1)pdm09, H1N1 or H3N2 influenza A or with influenza B viruses in the presence of aloin. In vivo activity was tested in H1N1 influenza virus infected mice. Aloin-mediated inhibition of influenza neuraminidase activity was tested by MUNANA assay. Aloin treatment-mediated modulation of anti-influenza immunity was tested by the study of hemagglutinin-specific T cells in vivo. RESULTS: Aloin significantly reduced in vitro infection by all the tested strains of influenza viruses, including oseltamivir-resistant A(H1N1)pdm09 influenza viruses, with an average IC50 value 91.83 ± 18.97 µM. In H1N1 influenza virus infected mice, aloin treatment (intraperitoneal, once daily for 5 days) reduced virus load in the lungs and attenuated body weight loss and mortality. Adjuvant aloin treatment also improved the outcome with delayed oseltamivir treatment. Aloin inhibited viral neuraminidase and impeded neuraminidase-mediated TGF-ß activation. Viral neuraminidase mediated immune suppression with TGF-ß was constrained and influenza hemagglutinin-specific T cell immunity was increased. There was more infiltration of hemagglutinin-specific CD4+ and CD8+ T cells in the lungs and their production of effector cytokines IFN-γ and TNF-α was boosted. CONCLUSION: Aloin from Aloe vera leaves is a potent anti-influenza compound that inhibits viral neuraminidase activity, even of the oseltamivir-resistant influenza virus. With suppression of this virus machinery, aloin boosts host immunity with augmented hemagglutinin-specific T cell response to the infection. In addition, in the context of compromised benefit with delayed oseltamivir treatment, adjuvant aloin treatment ameliorates the disease and improves survival. Taken together, aloin has the potential to be further evaluated for clinical applications in human influenza.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31138577

RESUMO

Cefoperazone, a third-generation cephamycin with broad-spectrum antibacterial activity and the ability to permeate bacterial cell membranes, is active against commonly encountered multidrug-resistant pathogens for hospital-acquired pneumonia (HAP) and health care-associated pneumonia (HCAP). To clarify the clinical effects of cefoperazone-sulbactam in the treatment of HAP and HCAP, we conducted an open-label, randomized, noninferiority trial that recruited patients aged ≥18 years suffering HAP/HCAP. Participants were randomly assigned to the cefoperazone-sulbactam (2 g of each per 12 h) or cefepime (2 g per 12 h) arm. Clinical and microbiological responses were evaluated at early posttherapy and test-of-cure visits. Recruited patients were allocated to subpopulations for intent-to-treat (n = 154), per-protocol (n = 147), and safety (n = 166) analyses. Intent-to-treat analysis demonstrated that (i) at the early posttherapy visit, 87.3% of patients receiving cefoperazone-sulbactam and 84.3% of patients receiving cefepime achieved clinical improvement or cure (risk difference of 3.0%; 95% confidence interval [CI], -9.0% to 15.0%), and (ii) at the test-of-cure visit, 73.1% of patients receiving cefoperazone-sulbactam and 56.8% of patients receiving cefepime were assessed as cured (risk difference of 16.3%; 95% CI, 0.0% to 33.0%). These results indicated the noninferiority of cefoperazone-sulbactam to cefepime, which was confirmed by per-protocol analysis. The chest radiographic consolidation/infiltration resolution rate, microbiological eradiation rate, and percentage of adverse events were comparable in both groups. Serious adverse events were rare, and none was judged to be related to the study drugs. Cefoperazone-sulbactam at 2 g every 12 h was noninferior to cefepime at 2 g every 2 h for patients with HCAP.

8.
Open Forum Infect Dis ; 6(2): ofy336, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30740468

RESUMO

Background: In a multicenter study from Taiwan, we aimed to investigate the outcome of patients who received different antimicrobial therapy in carbapenem-resistant Enterobacteriaceae bloodstream infections and proposed a new definition for tigecycline use. Methods: Patients from 16 hospitals in Taiwan who received appropriate therapy for bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae and Escherichia coli were enrolled in the study between January 2012 and June 2015. We used a cox proportional regression model for multivariate analysis to identify independent risk factors of 14-day mortality. Tigecycline was defined as appropriate when the isolates had a minimum inhibitory concentration (MIC) ≤0.5 mg/L, and we investigated whether tigecycline was associated with mortality among patients with monotherapy. Results: Sixty-four cases with carbapenem-resistant K pneumoniae (n = 50) and E coli (n = 14) bloodstream infections were analyzed. Of the 64 isolates, 17 (26.6%) had genes that encoded carbapenemases. The 14-day mortality of these cases was 31.3%. In the multivariate analysis, Charlson Comorbidity Index (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.42; P = .022) and colistin monotherapy (HR, 5.57; 95% CI, 2.13-14.61; P < .001) were independently associated with 14-day mortality. Among the 55 patients with monotherapy, the 14-day mortality was 30.9% (n = 17). Tigecycline use was not associated with mortality in the multivariate analysis. Conclusions: Tigecycline monotherapy was a choice if the strains exhibited MIC ≤0.5 mg/L, and colistin monotherapy was not suitable. Our findings can initiate additional clinical studies regarding the efficacy of tigecycline in carbapenem-resistant Enterobacteriaceae infections.

9.
Oncoimmunology ; 7(12): e1502129, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30524897

RESUMO

Toll-Like Receptor 9 (TLR9) stimulation selectively triggers the formation of a cell cluster termed intrahepatic myeloid aggregation for T cell expansion" (iMATE) in a mouse chronic viral hepatitis model. iMATE expands cytotoxic T cells and controls viral hepatitis infection. The liver-specific immune response prompted this investigation of whether the effect could control tumor growth in the murine hepatic tumor model. Murine hepatic BNL cells were used to establish an orthotropic liver tumor model. We found that intravenous infusion of TLR 9 agonist, CpG oligodeoxynucleotide (ODN) induced iMATE formation in non-tumor parts of liver and suppressed the murine BNL tumor growth. The ratio of intra-tumor CD8+ T cells have increased after CpG ODN. These cells expressed higher levels of effector and checkpoint molecules, and produce more Th1 cytokine upon ex vivo stimulation. The CD11b+Ly6ChiLy6G - subset of CD11b+ myeloid cells in the tumor microenvironment has increased. Both CD11b+Ly6ChiLy6G - and CD11b+Ly6CloLy6G+ subsets expressed higher level of interferon-gamma post CpG ODN treatment, although still presented a suppressive phenotype. Their suppressive ability was decreased, instead, the targeted CD8+ T cell proliferation was promoted at a higher dose of CD11b+Ly6ChiLy6G- cells. The phenomenon was further proven in DEN induced liver tumor model. In conclusion, systemic CpG ODN treatment induced iMATE formation that expanded effector CD8+ T cells to control tumor growth in the mouse hepatic tumor model. This novel strategy provides a new rationale for liver-specific tumor immunotherapy.

10.
Medicine (Baltimore) ; 97(50): e13607, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558035

RESUMO

The accuracy of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for identifying viridans group streptococcus (VGS) was improving. However, the clinical impact of identifying VGS had not been well recognized. Our study had comprehensively studied the clinical manifestations and outcome of VGS blood stream infection by using MALDI-TOF MS for identification.This retrospective study enrolled 312 adult patients with a monomicrobial blood culture positive for VGS. Blood culture was examined through MALDI-TOF MS.The most common VGS species were the Streptococcus anginosus group (38.8%) and Streptococcus mitis group (22.8%). Most species showed resistance to erythromycin (35.6%), followed by clindamycin (25.3%) and penicillin (12.5%). Skin and soft tissue infection and biliary tract infection were significantly related to S. anginosus group bacteremia (P = .001 and P = .005, respectively). S. mitis group bacteremia was related to infective endocarditis and bacteremia with febrile neutropenia (P = .005 and P < .001, respectively). Infective endocarditis was also more likely associated with S. sanguinis group bacteremia (P = .009). S. anginosus group had less resistance rate to ampicillin, erythromycin, clindamycin, and ceftriaxone (P = .019, <.001, .001, and .046, respectively). A more staying in intensive care unit, underlying solid organ malignancy, and a shorter treatment duration were independent risk factors for 30-day mortality. This study comprehensively evaluated different VGS group and their clinical manifestations, infection sources, concomitant diseases, treatments, and outcomes. Categorizing VGS into different groups by MALDI-TOF MS could help clinical physicians well understand their clinical presentations.


Assuntos
Bacteriemia/etiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Estreptococos Viridans/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Hemocultura/métodos , Hemocultura/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/estatística & dados numéricos , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/mortalidade , Taiwan/epidemiologia , Estreptococos Viridans/crescimento & desenvolvimento
11.
Sci Rep ; 8(1): 15636, 2018 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-30353096

RESUMO

A novel pandemic influenza A(H1N1)pdm09 virus emerged in 2009 globally, and it continues to circulate in humans. The National Influenza Surveillance Network in Taiwan identified five A(H1N1)pdm09-predominant seasons, representing the 2009/2010, 2010/2011, 2012/2013, 2013/2014, and 2015/2016 outbreaks from 2009 to 2016. Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. A phylogenetic analysis of hemagglutinin (HA) sequences showed that the circulating A(H1N1)pdm09 virus belonged to clades 1, 2, and 8 in 2009/2010; clades 3, 4, 5, and 7 in 2010/2011; clades 7 and 6C in 2012/2013; clades 6B in 2013/2014; and 6B/6B.1/6B.2 in 2015/2016. Compared to individuals infected in non-6B/6B.1/6B.2 seasons (2009/2010, 2010/2011, and 2012/2013), those infected in 6B/6B.1/6B.2 seasons (2013/2014 and 2015/2016) were at higher risk for influenza-related complications (adjusted odds ratio [aOR]: 1.6, 95% confidence interval [CI]: 1.0-2.8), pneumonia (aOR: 1.78, 95% CI: 1.04-3.04), mechanical ventilation (aOR: 2.6, 95% CI: 1.2-5.6), and acute respiratory distress syndrome (aOR: 5.5, 95% CI: 1.9-15.9). For the increased severity of infection during the influenza A(H1N1)pdm09 clade 6B/6B.1/6B.2 seasons, aspects related to the antigenic change of A(H1N1)pdm09 virus, immune response of the host, and environmental factors required further investigation.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Surtos de Doenças , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/diagnóstico , Masculino , Pessoa de Meia-Idade , Filogenia , Estudos Retrospectivos , Estações do Ano , Taiwan/epidemiologia , Adulto Jovem
12.
J Med Virol ; 90(6): 1010-1018, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29424435

RESUMO

To evaluate the diagnostic performance of the Sofia influenza A+B fluorescent immunoassay (Sofia FIA), we performed a prospective study at the Chang Gung Memorial Hospital in Taiwan from January 2012 to December 2013. Patients who presented at out-patient clinics or the emergency department with influenza-like illness were included. Upper respiratory tract specimens were collected from oropharynx or nasopharynx. Performance of the Sofia FIA was compared to that of the Formosa One Sure Flu A/B Rapid Test. A Real-time reverse transcriptase-polymerase chain reaction assay (RT-PCR) and/or virus culture were used as reference standards. Of the 109 enrolled patients, the sensitivity, specificity, positive, and negative predictive values of the Sofia FIA to detect influenza A virus were 82%, 89%, 77%, and 89%, respectively. These parameters were 100% when the samples were from nasopharynx. The positive predictive value for influenza B virus detection was 29%. The sensitivity of the Sofia FIA for detection of influenza A virus was 93% between days 2 and 4 after onset of symptoms. For specimens with low viral loads (RT-PCR cycle threshold between 30 and 34.9), the sensitivity of The Sofia FIA was 83% (10/12). The Sofia FIA performed effectively in detecting influenza A virus infection. With nasopharyngeal samples, the performance was comparable to RT-PCR. Although influenza viral load typically decreases with time, the Sofia FIA was sensitive enough to identify influenza infecting patients presenting after several days of illness. However, a high false positive rate limits the assay's usefulness to identify influenza B virus infection.


Assuntos
Testes Diagnósticos de Rotina/métodos , Fluorometria/métodos , Imunoensaio/métodos , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/diagnóstico , Adulto , Feminino , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Orofaringe/virologia , Pacientes Ambulatoriais , Valor Preditivo dos Testes , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Taiwan , Cultura de Vírus
13.
J Microbiol Immunol Infect ; 51(6): 705-716, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29046248

RESUMO

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE-fm) bacteremia causes significant mortality in hospitalized patients. We sought to investigate clinical characteristics, treatment outcomes, and microbiological eradication associated with VRE-fm bacteremia. METHODS: A retrospective cohort study was conducted and included 210 adult patients admitted between January 1, 2011 and December 31, 2015. RESULTS: The mean Pitt bacteremia score was 4.7. ICU stay (48.6%) and mechanical ventilation (46.2%) were common. Diabetes mellitus was the most common concomitant disease (43.3%), followed by malignancies, including hematologic malignancies (14.3%) and solid cancers (28.1%). The 14-day and 28-day mortality rates were 37.1% and 50.5%, respectively. Linezolid or daptomycin treatment for at least 10 days and higher Pitt bacteremia scores were independently associated with 14-day and 28-day mortality. Longer treatment duration of linezolid or daptomycin predicted microbiological eradication independently. Daptomycin-treated patients tended to have higher 14-day and 28-day mortality, and lower microbial eradication rates (20.8% versus 8.7%; 40.6% versus 26.1%; 14.1% versus 26.1%; respectively) than linezolid-treated patients, and cumulative survival rates at 14 and 28 days tended to be lower in patients who received low-dose daptomycin (<10 mg/kg/day) than that in those who received linezolid and high-dose daptomycin (≥10 mg/kg/day); however, the differences were not statistically significant. CONCLUSION: Higher disease severity and inappropriate treatment were associated with increased mortality and longer treatment duration of linezolid or daptomycin was associated with microbial eradication for the patient with VRE-fm bacteremia.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/mortalidade , Daptomicina/administração & dosagem , Daptomicina/farmacologia , Feminino , Humanos , Linezolida/administração & dosagem , Linezolida/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Taiwan , Centros de Atenção Terciária , Resultado do Tratamento , Enterococos Resistentes à Vancomicina/isolamento & purificação
14.
J Microbiol Immunol Infect ; 51(3): 332-336, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28082066

RESUMO

BACKGROUND: Invasive pneumococcal disease (IPD) causes significant morbidity and mortality, especially in children and older adults. Pneumococcal 7-valent and 13-valent conjugate vaccines (PCV7 and PCV13) were introduced in Taiwan in 2005 and 2011, respectively, for children. This study was conducted to evaluate the impact of PCV administered in children on adult IPD. METHODS: From the logbooks of microbiology laboratories, we retrospectively retrieved Streptococcus pneumoniae isolates, collected from normally sterile sites in adult patients. One hundred and fifty-seven consecutive, nonduplicated isolates were collected from one hospital during 2001 and 2003 (pre-PCV period) and 150 isolates from three hospitals from July 2011 to June 2015 (post-PCV period). Serotypes were determined by Quellung test. RESULTS: Among the 307 isolates, 31 serotypes/serogroups were identified. PCV7 serotypes, particularly types 14 (31.2%), 23F (19.7%) and 6B (12.7%) dominated in the pre-PCV period (78.3%) but significantly decreased in the post-PCV period (36%) (p < 0.01). PCV13 specific serotypes (PCV13-PCV7) significantly increased from 7% of the isolates in the pre-PCV period to 28.7% of the isolates in the post-PCV period (p < 0.001), particularly type 19A (from 0.6% to 10%) and 6A (from 0 to 6.7%). Serotype 15B also increased significantly from 0.6% to 6.7% (p < 0.01). Nonvaccine serotypes increased significantly in the post-PCV period (11.5% to 22.0%, p < 0.05), particularly type 15A (from 0 to 4.4%, p < 0.01). CONCLUSION: Serotype distribution of adult IPD in Taiwan has evolved after the introduction of PCV in children, indicating an indirect impact in adults. Continuous surveillance after the PCV13 vaccination program in children is needed.


Assuntos
Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Sorogrupo , Vacinas Conjugadas/administração & dosagem , Adolescente , Adulto , Idoso , Feminino , Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Estudos Retrospectivos , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Taiwan/epidemiologia , Adulto Jovem
15.
Diagn Microbiol Infect Dis ; 90(1): 44-49, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29132935

RESUMO

To investigate the risk factors and outcomes associated with Candida parapsilosis candidemia, a retrospective study was conducted at a tertiary medical center in northern Taiwan. Patients with C. parapsilosis candidemia and corresponding controls with C. albicans candidemia were chosen and their demographics, comorbidities, risk factors, and clinical outcomes were reviewed. Antifungal susceptibility tests were performed using the Sensititre YeastOne colorimetric system. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was used to classify the genomic species. Of the 270 candidemias found in 253 patients, C. albicans was the most common Candida species isolated (43.0%), followed by C. parapsilosis (22.6%), C. tropicalis (17.4%), and C. glabrata (10.0%). The 30-day mortality of C. parapsilosis candidemia was significantly lower than that of C. albicans candidemia (21.7% vs. 53.9%, P<0.001). C. parapsilosis was positively associated with antifungal agent exposure [OR 7.261 (95% CI, 1.603-32.879), P=0.010], but negatively associated with Candida colonization [OR 0.303 (95% CI, 0.123-0.745), P=0.009], and immunosuppressant use [OR 0.264 (95% CI, 0.099-0.705), P=0.008]. In-hospital mortality was associated with the Sequential Organ Failure Assessment Score [OR 1.255 (95% CI, 1.002-1.573), P=0.048]. The clinical outcomes did not differ across genomic species and in the minimum inhibitory concentrations of fluconazole.


Assuntos
Antifúngicos/uso terapêutico , Azóis/uso terapêutico , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Candidemia/tratamento farmacológico , Candida albicans/isolamento & purificação , Candida glabrata/isolamento & purificação , Candida parapsilosis/classificação , Candida parapsilosis/isolamento & purificação , Candida tropicalis/isolamento & purificação , Candidemia/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Taiwan , Centros de Atenção Terciária , Resultado do Tratamento
16.
Eur J Clin Microbiol Infect Dis ; 37(4): 651-659, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29238934

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality, and experiences with its treatment are usually based on carbapenemase-producing strains. Non-carbapenemase-producing CRKP is of clinical significance, but relevant studies are lacking. This nationwide study aimed to evaluate the outcome of antimicrobial therapy in patients with non-carbapenemase-producing CRKP infections. Patients with non-carbapenemase-producing CRKP infections were enrolled from 16 hospitals during January 2013 to December 2014 in Taiwan. Carbapenem resistance was defined as reduced susceptibility with a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. The resistance mechanisms of CRKP isolates were analyzed, and the clinical data of these patients were collected retrospectively. Independent risk factors of 14-day morality were determined by Cox regression analysis. A total of 99 patients with non-carbapenemase-producing CRKP infections were enrolled, and 14-day mortality was 27.3%. Among 67 patients treated with appropriate antimicrobial therapy, most (n = 61) patients received monotherapy. The 14-day mortality was lower in patients treated with appropriate monotherapy (21.3%) than in those with inappropriate therapy (37.5%). The multivariate regression model identified monotherapy (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.13-0.71; P = 0.005) as protective factor, and APACHE II scores (HR, 1.09; 95% CI, 1.01-1.18; P = 0.022) as risk factor associated with 14-day mortality. Tigecycline, colistin, and carbapenem were the most commonly used drugs in monotherapy. This study provides evidence supporting the efficacy of monotherapy in the treatment of non-carbapenemase-producing CRKP infections, and provides a future target for antibiotics stewardship for CRKP infection.


Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecções por Klebsiella , Klebsiella pneumoniae , Resistência beta-Lactâmica , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Feminino , Hospitalização , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Resultado do Tratamento
17.
BMC Infect Dis ; 17(1): 598, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28854887

RESUMO

BACKGROUND: Information is limited about the effect of restricted carbapenem use on clearance of multi-drug resistant Acinetobacter baumannii (MDRAB). We sought to determine the time effect of antibiotic exposure on multi-drug resistant Acinetobacter baumannii (MDRAB) acquisition and clearance. METHODS: We conducted a retrospective observational study at the intensive care units of a tertiary medical center. Forty-two of a cohort of previously healthy young adults who were concurrently burned by a dust explosion was included. Cases consisted of those from whom MDRAB was isolated during hospitalization. Controls consisted of patients from whom MDRAB was not isolated in the same period. Use of antimicrobial agents was compared based on days of therapy per 1,000 patient-days (DOT/1,000PD). A 2-state Markov multi-state model was used to estimate the risk of acquisition and clearance of MDRAB. RESULTS: MDRAB was discovered in 9/42 (21.4%) individuals. The cases had significantly higher use of carbapenem (652 DOT/1,000PD vs. 385 DOT/1,000PD, P < 0.001) before MDRAB isolation. For the cases, clearance of MDRAB was associated with lower use of carbapenem (469 DOT/1,000PD vs. 708 DOT/1,000PD, P = 0.003) and higher use of non-carbapenem beta-lactam (612 DOT/1,000PD vs. 246 DOT/1,000PD, P <0.001). In multi-state model, each additional DOT of carbapenem increased the hazard of acquiring MDRAB (hazard ratio (HR), 1.08; 95% confidence interval (CI) 1.01-1.16) and each additional DOT of non-carbapenem beta-lactam increased the protection of clearing MDRAB (HR, 1.25; 95% CI 1.07-1.46). CONCLUSIONS: Both acquisition and clearance of MDRAB were related to antibiotic exposure in a homogeneous population. Our findings suggest that early discontinuation of carbapenem could be an effective measure in antibiotic stewardship for the control of MDRAB spreading.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/patogenicidade , Adolescente , Queimaduras/microbiologia , Queimaduras/terapia , Carbapenêmicos/uso terapêutico , Estudos de Casos e Controles , Poeira , Explosões , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Estudos Retrospectivos , Taiwan , Adulto Jovem
18.
Ann Clin Microbiol Antimicrob ; 16(1): 52, 2017 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-28738848

RESUMO

BACKGROUND: We assessed the influence of current cefepime minimal inhibitory concentration (MIC) breakpoints and the maximal cefepime dose on treatment outcomes in patients with bacteremia caused by cefepime-susceptible Pseudomonas aeruginosa. METHODS: Adult patients hospitalized between July 2010 and June 2014 with a positive blood culture for cefepime-susceptible P. aeruginosa and receipt of cefepime as the primary therapy throughout the course were reviewed. Cefepime Etest® MICs and clinical outcomes for P. aeruginosa bacteremia were reviewed to identify the MIC breakpoint influencing treatment outcomes. RESULTS: Of the 90 patients enrolled, 49 (54.4%) were male (mean age = 66.8 years). The mean Acute Physiology and Chronic Health Evaluation II score was 22.01. Sixty patients (66.7%) received a maximal cefepime dose, and the 30-day crude mortality rate was 36.7%. MIC90 of cefepime for P. aeruginosa was 8 mg/L. The cumulative survival rate at 30 days revealed that a lower cefepime MIC (<4 mg/L) for P. aeruginosa was associated with a higher survival rate than a higher MIC (≥4 mg/L) (72.6% vs. 23.5%, p < 0.0001). A cefepime MIC of ≥4 mg/L and age were independent risk factors for mortality, whereas the maximal cefepime dose was the independent protective factor. The use of a maximal cefepime dose did not improve the outcomes of patients with P. aeruginosa bacteremia at a MIC of ≥4 mg/L. CONCLUSIONS: A cefepime MIC of 4 mg/L may predict an unfavorable outcome among patients with serious infections caused by P. aeruginosa, even the MICs still within the CLSI susceptibility breakpoint.


Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Cefalosporinas/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Cefepima , Relação Dose-Resposta a Droga , Feminino , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , Estudos Retrospectivos , Resultado do Tratamento
19.
Sci Rep ; 7(1): 4136, 2017 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-28646236

RESUMO

Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice. We found that Rapamycin had no antiviral effect against H1N1, H3N2 and novel-H1N1 influenza viruses in vitro. Rapamycin alone aggravated the severe disease of PR8 H1N1 influenza virus infection in mice. Timely Oseltamivir anti-viral therapy abolished the disease. Delayed Oseltamivir treatment could not prevent severe illness and Rapamycin adjuvant was associated with exacerbated disease. Rapamycin adjuvant suppressed influenza hemagglutinin antigen-specific T cell immunity and impaired virus clearance from the lungs. It also resulted in intensified lung pathology with increased intra-alveolar edema and hyaline deposition. Rapamycin may work as the salvage therapy for severe influenza but it is very difficult to define the appropriate window for such treatment to take effect.


Assuntos
Vírus da Influenza A/efeitos dos fármacos , Infecções por Orthomyxoviridae/diagnóstico , Infecções por Orthomyxoviridae/virologia , Sirolimo/farmacologia , Animais , Antivirais/farmacologia , Modelos Animais de Doenças , Progressão da Doença , Imunidade Celular/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Transgênicos , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/mortalidade , Oseltamivir/farmacologia , Índice de Gravidade de Doença , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo
20.
Sci Rep ; 6: 32973, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27596047

RESUMO

Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity.


Assuntos
Anticorpos Antivirais/imunologia , Antígenos/imunologia , Linfócitos T CD8-Positivos/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Pulmão/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/virologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Infecções por Orthomyxoviridae/virologia
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