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1.
J Antimicrob Chemother ; 79(3): 648-655, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38319833

RESUMO

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.


Assuntos
Bacteriemia , Infecções por Escherichia coli , Gammaproteobacteria , Humanos , Escherichia coli , Cefoperazona/uso terapêutico , Sulbactam/uso terapêutico , Klebsiella pneumoniae , Infecções por Escherichia coli/tratamento farmacológico , Bacteriemia/tratamento farmacológico
2.
BMC Microbiol ; 24(1): 109, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565985

RESUMO

BACKGROUND: The current understanding of acquired chromosomal colistin resistance mechanisms in Enterobacterales primarily involves the disruption of the upstream PmrAB and PhoPQ two-component system (TCS) control caused by mutations in the regulatory genes. Interestingly, previous studies have yielded conflicting results regarding the interaction of regulatory genes related to colistin resistance in Escherichia coli, specifically those surrounding PhoPQ and PmrAB TCS. RESULTS: In our study, we focused on two clinical non-mcr colistin-resistant strains of E. coli, TSAREC02 and TSAREC03, to gain a better understanding of their resistance mechanisms. Upon analysis, we discovered that TSAREC02 had a deletion (Δ27-45) in MgrB, as well as substitutions (G206R, Y222H) in PmrB. On the other hand, TSAREC03 exhibited a long deletion (Δ84-224) in PhoP, along with substitutions (M1I, L14P, P178S, T235N) in PmrB. We employed recombinant DNA techniques to explore the interaction between the PhoPQ and PmrAB two-component systems (TCSs) and examine the impact of the mutated phoPQ and pmrB genes on the minimum inhibitory concentrations (MICs) of colistin. We observed significant changes in the expression of the pmrD gene, which encodes a connector protein regulated by the PhoPQ TCS, in the TSAREC02 wild-type (WT)-mgrB replacement mutant and the TSAREC03 WT-phoP replacement mutant, compared to their respective parental strains. However, the expressions of pmrB/pmrA, which reflect PmrAB TCS activity, and the colistin MICs remained unchanged. In contrast, the colistin MICs and pmrB/pmrA expression levels were significantly reduced in the pmrB deletion mutants from both TSAREC02 and TSAREC03, compared to their parental strains. Moreover, we were able to restore colistin resistance and the expressions of pmrB/pmrA by transforming a plasmid containing the parental mutated pmrB back into the TSAREC02 and TSAREC03 mutants, respectively. CONCLUSION: While additional data from clinical E. coli isolates are necessary to validate whether our findings could be broadly applied to the E. coli population, our study illuminates distinct regulatory pathway interactions involving colistin resistance in E. coli compared to other species of Enterobacterales. The added information provided by our study contribute to a deeper understanding of the complex pathway interactions within Enterobacterales.


Assuntos
Antibacterianos , Colistina , Colistina/farmacologia , Antibacterianos/farmacologia , Escherichia coli/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana
3.
Eur J Clin Microbiol Infect Dis ; 43(9): 1777-1785, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38995342

RESUMO

BACKGROUND: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied. OBJECTIVES: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates. METHODS: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed. RESULTS: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes. CONCLUSION: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.


Assuntos
Antibacterianos , Bacteriemia , Cefoperazona , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Sulbactam , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Sulbactam/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Idoso , Cefoperazona/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Taiwan , Idoso de 80 Anos ou mais , Adulto
4.
Infection ; 52(3): 955-983, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38133713

RESUMO

PURPOSE: The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles. METHODS: Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay. RESULTS: The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-ß, SDF-1α, TNF-α, TNF-ß, VEGF, PDGF-BB, TRAIL, ß-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients. CONCLUSION: Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.


Assuntos
COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus , Citocinas , Células Epiteliais , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , COVID-19/imunologia , COVID-19/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , SARS-CoV-2/imunologia , Citocinas/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Células Epiteliais/virologia , Células Epiteliais/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Idoso , Células A549 , Pulmão/patologia , Pulmão/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/sangue , Adulto , Anticorpos Antivirais/sangue , Fosfoproteínas
5.
J Med Virol ; 95(7): e28914, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37394776

RESUMO

The Omicron variant of concern (VOC) has surged in many countries and replaced the previously reported VOC. To identify different Omicron strains/sublineages on a rapid, convenient, and precise platform, we report a novel multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) method in one tube based on the Omicron lineage sequence variants' information. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subvariants were used in a PCR-based assay for rapid identification of Omicron sublineage genotyping in 1000 clinical samples. Several characteristic mutations were analyzed using specific primers and probes for the spike gene, del69-70, and F486V. To distinguish Omicron sublineages (BA.2, BA.4, and BA.5), the NSP1:141-143del in the ORF1a region and D3N mutation in membrane protein occurring outside the spike protein region were analyzed. Results from the real-time PCR assay for one-tube accuracy were compared to those of whole genome sequencing. The developed PCR assay was used to analyze 400 SARS-CoV-2 positive samples. Ten samples determined as BA.4 were positive for NSP1:141-143del, del69-70, and F486V mutations; 160 BA.5 samples were positive for D3N, del69-70, and F486V mutations, and 230 BA.2 samples were without del69-70. Screening these samples allowed the identification of epidemic trends at different time intervals. Our novel one-tube multiplex PCR assay was effective in identifying Omicron sublineages.


Assuntos
COVID-19 , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2/genética , Pandemias , Teste para COVID-19 , Reação em Cadeia da Polimerase Multiplex , Glicoproteína da Espícula de Coronavírus
6.
J Formos Med Assoc ; 122(3): 286-289, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36096862

RESUMO

Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by the bacterium Anaplasma phagocytophilum. In this study, we report an indigenous case of clinically diagnosed HGA. The patient was a 41-year-old man who experienced a tick bite and later developed fever, chills, myalgia, malaise, thrombocytopenia, leukocytosis with a left shift, elevated hepatic transaminase levels, and splenomegaly upon admission to the hospital. Immunofluorescence assays detected seroconversion against A. phagocytophilum, whereas tests for spotted fever group rickettsiae, murine typhus, scrub typhus, Q fever, and ehrlichiosis were negative. ELISA and Western blot analysis using recombinant MSP2 protein confirmed the exposure to A. phagocytophilum. Oral doxycycline and intravenous ceftriaxone were prescribed, and the patient made a full recovery. Our findings indicate the presence of HGA on the main island of Taiwan. Precautions against tick bites should be taken when engaging in outdoor activities, and HGA should be considered by physicians in the differential diagnosis.


Assuntos
Anaplasmose , Ehrlichiose , Tifo por Ácaros , Masculino , Animais , Camundongos , Humanos , Adulto , Anaplasmose/diagnóstico , Anaplasmose/microbiologia , Taiwan , Ehrlichiose/diagnóstico , Doxiciclina
7.
J Formos Med Assoc ; 120(1 Pt 3): 713-719, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32773262

RESUMO

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a worldwide pandemic. We present the clinical characteristics and outcomes of 28 COVID-19 patients treated in our hospital in Taiwan. METHODS: Patients with COVID-19, confirmed by positive real-time reverse-transcriptase polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral nucleic acids from oropharyngeal swab specimens between February 4, 2020 and July 6, 2020, were enrolled. Their clinical characteristics and outcomes were reviewed. RESULTS: Seventeen of the 28 patients (60.7%) had pneumonia. The most frequent symptoms were cough (n = 23, 82.1%) and fever (n = 17, 60.7%). The development of pneumonia was associated with age ≥40 years (p < 0.024), body mass index (BMI) ≥25 kg/m2 (p = 0.014), fever (p = 0.007), shortness of breath (p = 0.036), chills ((p = 0.047), and lower platelet counts (<200,000/µL) (p = 0.007). Increased quarantine duration was associated with age ≥40 years (p = 0.026), Charlson index ≥1 (p = 0.037), lower lymphocyte (<1500/uL; p = 0.028) or platelet counts (<200,000/µL) (p = 0.016), lower serum sodium (<140 mEq/L; p = 0.006), and higher C-reactive protein (CRP) level (≥1 mg/dl; p = 0.04). Treatment with hydroxychloroquine or in combination with other medicines did not reduce the quarantine duration. All 28 patients recovered with a median quarantine duration of 27.2 days. CONCLUSION: COVID-19 patients with older age, higher BMI, fever, chills or shortness of breath, lower serum sodium level, lower platelet or lymphocyte count, and higher CRP level may be associated with developing pneumonia or longer quarantine duration.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19 , Pneumonia Viral , SARS-CoV-2/isolamento & purificação , Adulto , Fatores Etários , Contagem de Células Sanguíneas/métodos , Índice de Massa Corporal , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/terapia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Quarentena , Fatores de Risco , Avaliação de Sintomas/métodos , Taiwan/epidemiologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-32284375

RESUMO

We report the first clinical Escherichia coli strain EC3000 with concomitant chromosomal colistin and carbapenem resistance. A novel in-frame deletion, Δ6-11 (RPISLR), in pmrB that contributes to colistin resistance was verified using recombinant DNA techniques. Although being less fit than the wild-type (WT) strain or EC3000 revertant (chromosomal replacement of WT pmrB in EC3000), a portion of serially passaged EC3000 strains preserving colistin resistance without selective pressure raises the concern for further spread.


Assuntos
Colistina , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Deleção de Sequência/genética
9.
J Biomed Sci ; 27(1): 72, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32498686

RESUMO

On March 11, 2020, the World Health Organization declared the worldwide spread of the infectious disease COVID-19, caused by a new strain of coronavirus, SARS-CoV-2, as a pandemic. Like in all other infectious diseases, the host immune system plays a key role in our defense against SARS-CoV-2 infection. However, viruses are able to evade the immune attack and proliferate and, in susceptible individuals, cause severe inflammatory response known as cytokine storm, particularly in the lungs. The advancement in our understanding of the mechanisms underlying the host immune responses promises to facilitate the development of approaches for prevention or treatment of diseases. Components of immune system, such as antibodies, can also be used to develop sensitive and specific diagnostic methods as well as novel therapeutic agents. In this review, we summarize our knowledge about how the host mounts immune responses to infection by SARS-CoV-2. We also describe the diagnostic methods being used for COVID-19 identification and summarize the current status of various therapeutic strategies, including vaccination, being considered for treatment of the disease.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Técnicas e Procedimentos Diagnósticos/instrumentação , Pneumonia Viral/imunologia , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/virologia , SARS-CoV-2
10.
Artigo em Inglês | MEDLINE | ID: mdl-28533243

RESUMO

Tigecycline is regarded as a last-resort treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, but increasing numbers of tigecycline-resistant K. pneumoniae isolates have been reported. The tigecycline resistance mechanisms in CRKP are undetermined. This study aimed to elucidate the mechanisms underlying tigecycline resistance in 16 tigecycline- and carbapenem-resistant K. pneumoniae (TCRKP) isolates. Mutations in tigecycline resistance determinant genes [ramR, acrR, oqxR, tet(A), tet(L), tet(X), tet(M), rpsJ] were assessed by PCR amplicon sequencing, and mutations in ramR and tet(A) exhibited high prevalences individually (81%) and in combination (63%). Eight functional ramR mutation profiles reducing tigecycline sensitivity were verified by plasmid complementation of wild-type and mutant ramR Using a site-specific mutant, the most frequent RamR mutation, A19V (60%), had no significant effect on tigecycline susceptibility or the upregulation of ramA and acrA Two tet(A) variants with double frameshift mutations, type 1 and type 2, were identified; type 2 tet(A) is novel. A parent strain transformed with a plasmid carrying type 1 or type 2 tet(A) increased the tigecycline MIC by 8-fold or 4-fold, respectively. Synergistic effects were observed in strains harboring no ramR gene and a mutated tet(A), with an 8-fold increase in the tigecycline MIC compared with that in strains harboring only mutated tet(A) being seen. Overall, mutations in the ramR and tet(A) efflux genes constituted the major tigecycline resistance mechanisms among the studied TCRKP isolates. The identification of strains exhibiting the combination of a ramR deficiency and widespread mutated tet(A) is concerning due to the possible dissemination of increased tigecycline resistance in K. pneumoniae.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Proteínas de Membrana Transportadoras/genética , Minociclina/análogos & derivados , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Transativadores/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/farmacologia , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Minociclina/uso terapêutico , Mutação/genética , Plasmídeos/genética , Resistência a Tetraciclina/genética , Tigeciclina
11.
J Antimicrob Chemother ; 72(12): 3302-3316, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961715

RESUMO

OBJECTIVES: A strategic system for the screening and testing of new antibiotics was created to facilitate the development of antibiotics that are robustly effective against MDR bacteria. METHODS: In-frame deletion, site-directed mutagenesis and plasmid transformation were used to generate genetically engineered strains with various resistance mechanisms from a fully susceptible clinical isolate of Klebsiella pneumoniae. Antimicrobial susceptibility testing and a mouse infection model were used to test antibiotics against these strains in vitro and in vivo, respectively. RESULTS: A total of 193 strains, including 29 strains with chromosome-mediated resistance, 33 strains with plasmid-mediated resistance and 131 strains with a combination of both resistance mechanisms were constructed; these strains covered resistance to ß-lactams, quinolones, aminoglycosides, tetracyclines, folate pathway inhibitors and other antibiotics. MICs for all strains were tested, and the effects of genetic modifications on increasing the MICs were assessed. Ceftazidime and cefotaxime were used to assess the correlation between antibacterial activities in vitro and in vivo. Against a K. pneumoniae strain with blaOXA-48, ceftazidime had a lower MIC (0.5 mg/L) than cefotaxime (2 mg/L). Ceftazidime had an ED50 of 30 mg/kg, and no mice survived treatment with the same dose of cefotaxime. A positive correlation was observed between these in vitro and in vivo results. CONCLUSIONS: The system developed here could reduce the considerable time required to evaluate the effectiveness of new antibiotics against MDR bacteria, particularly in the early stages of drug development. This system could also be expanded as new resistance mechanisms emerge.


Assuntos
Antibacterianos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Farmacorresistência Bacteriana , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Animais , Antibacterianos/administração & dosagem , Modelos Animais de Doenças , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Masculino , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Análise de Sobrevida
12.
Antimicrob Agents Chemother ; 60(8): 4670-6, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27216052

RESUMO

Acinetobacter baumannii biofilms are difficult to eradicate. We investigated the effects of meropenem (2 mg/liter), imipenem (2 mg/liter), sulbactam (4 mg/liter), colistin (2 mg/liter), and tigecycline (2 mg/liter), alone or in combination, on biofilm-embedded carbapenem-resistant and carbapenem-susceptible A. baumannii (CRAb and CSAb, respectively) cells, as well as on the architecture of the biofilms. A. baumannii ATCC 15151 (Ab15151) and its OXA-82-overproducing transformant, along with two clinical CSAb and two clinical CRAb isolates of differing clonalities, were used. The minimal bactericidal concentrations for biofilm-embedded cells of the six tested isolates were >50-fold those of their planktonic cells. When used individually, meropenem exhibited a higher killing effect than the other four antimicrobials on biofilm-embedded CSAb cells in the colony biofilm assay. For two clinical CRAb isolates, meropenem plus sulbactam or sulbactam plus tigecycline showed >100-fold the bactericidal effect exhibited by these agents used alone after 48 h of treatment. The effect of antimicrobials on the architecture of Ab15151 biofilm emitting green fluorescence was determined by confocal laser scanning microscopy using COMSTAT software. Significant decreases in the maximum biofilm thickness were observed after exposure to meropenem and imipenem. Meropenem plus sulbactam significantly decreased the biomass and mean thickness and increased the roughness coefficient of biofilms, but sulbactam plus tigecycline only decreased the maximum and mean biofilm thickness compared to any of these agents used alone. Meropenem was active against biofilm-embedded CSAb, whereas meropenem plus sulbactam exhibited synergism against biofilm-embedded CRAb and caused significantly more damage to the biofilm architecture than did any of the agents used alone.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Colistina/farmacologia , Imipenem/farmacologia , Minociclina/análogos & derivados , Sulbactam/farmacologia , Tienamicinas/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Combinação de Medicamentos , Farmacorresistência Bacteriana , Sinergismo Farmacológico , Humanos , Meropeném , Testes de Sensibilidade Microbiana/métodos , Minociclina/farmacologia , Tigeciclina
14.
J Clin Microbiol ; 54(12): 3018-3021, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27707941

RESUMO

In this study, a novel colloidal gold-based immunochromatographic strip (ICS) containing anti-Klebsiella pneumoniae capsular polysaccharide polyclonal antibodies was developed to specifically detect K. pneumoniae serotypes K1 and K2. Capsular polysaccharide K1 and K2 antigens were first used to produce polyclonal anti-K1 and anti-K2 antibodies. Reference strains with different serotypes, nontypeable K. pneumoniae strains, and other bacterial species were then used to assess the sensitivity and specificity of these test strips. The detection limit was found to be 105 CFU, and the ICSs were stable for 6 months when stored at room temperature. No false-positive or false-negative results were observed, and equivalent results were obtained compared to those of more conventional test methods, such as PCR or serum agglutination. In conclusion, the ICS developed here requires no technical expertise and allows for the specific, rapid, and simultaneous detection of K. pneumoniae serotypes K1 and K2.


Assuntos
Antígenos de Bactérias/imunologia , Cápsulas Bacterianas/imunologia , Cromatografia de Afinidade/métodos , Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae/imunologia , Polissacarídeos Bacterianos/imunologia , Anticorpos/imunologia , Coloide de Ouro/metabolismo , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/isolamento & purificação , Sensibilidade e Especificidade
16.
J Infect Dis ; 211(2): 249-57, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25124927

RESUMO

BACKGROUND: Patients contracting influenza A(H7N9) infection often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for influenza A(H7N9) is limited. METHODS: Four NA variants of A/Taiwan/1/2013(H7N9) virus containing a single substitution (NA-E119V, NA-I222K, NA-I222R, or NA-R292K) recovered from an oseltamivir-treated patient were tested for NAI susceptibility in vitro; their replicative fitness was evaluated in cell culture, mice, and ferrets. RESULTS: NA-R292K led to highly reduced inhibition by oseltamivir and peramivir, while NA-E119V, NA-I222K, and NA-I222R caused reduced inhibition by oseltamivir. Mice infected with any virus showed severe clinical signs with high mortality rates. NA-I222K virus was the most virulent in mice, whereas virus lacking NA change (NA-WT) and NA-R292K virus seemed the least virulent. Sequence analysis suggests that PB2-S714N increased virulence of NA-I222K virus in mice; NS1-K126R, alone or in combination with PB2-V227M, produced contrasting effects in NA-WT and NA-R292K viruses. In ferrets, all viruses replicated to high titers in the upper respiratory tract but produced only mild illness. NA-R292K virus, showed reduced replicative fitness in this animal model. CONCLUSIONS: Our data highlight challenges in assessment of the replicative fitness of H7N9 NA variants that emerged in NAI-treated patients.


Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral , Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Oseltamivir/uso terapêutico , Animais , Modelos Animais de Doenças , Furões , Humanos , Subtipo H7N9 do Vírus da Influenza A/enzimologia , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Proteínas Mutantes/genética , Mutação de Sentido Incorreto , Neuraminidase/genética , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Proteínas Virais/genética , Cultura de Vírus , Replicação Viral
17.
J Antimicrob Chemother ; 70(10): 2734-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26180132

RESUMO

OBJECTIVES: To investigate the link between two NDM-1-positive Acinetobacter isolates from the same hospital, the plasmid profiles of the isolates were examined. These two isolates were found from a surveillance programme within 3 months from two patients without obvious physical contact or hospitalization time overlap. METHODS: Antimicrobial susceptibility tests, genome sequencing of both isolates and plasmid transfer experiments were performed. A comparative study of similar plasmids was performed using BLAST analysis. RESULTS: The antimicrobial susceptibility of the isolates (Acinetobacter soli M131 and Acinetobacter pittii MS32) and their Escherichia coli transconjugants revealed a conjugative plasmid that carried the carbapenem resistance determinant. Eleven plasmids were observed in M131 and three in MS32. Each isolate shared an identical plasmid that carried the blaNDM-1 gene. This 47 271 bp plasmid harbours a conserved blaNDM-1-containing region that is flanked by ISAba125 and ISAba11 elements, and also contains a Ti-type conjugative operon. The plasmid is nearly identical in sequence to those of Acinetobacter isolates from China. In contrast to the mobilization of the blaNDM-1 sequence in Enterobacteriaceae, which is mainly by transposition, this plasmid moves as a whole among Acinetobacter species. Consistently, this plasmid was found to transfer effectively by in vitro conjugation to several Acinetobacter species. CONCLUSIONS: The clinical and laboratory findings suggest that Acinetobacter species may serve as a reservoir of this blaNDM-1 plasmid. Our study demonstrates the potential of applying genome sequencing to the surveillance of antimicrobial-resistant bacteria.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter/genética , Conjugação Genética , Transferência Genética Horizontal , Plasmídeos/genética , beta-Lactamases/genética , Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Infecção Hospitalar , Elementos de DNA Transponíveis , Ordem dos Genes , Genoma Bacteriano , Humanos , Testes de Sensibilidade Microbiana , Resistência beta-Lactâmica
18.
J Heart Valve Dis ; 24(2): 236-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26204692

RESUMO

Libman-Sacks endocarditis is the most widely encountered aseptic endocarditis among patients with systemic lupus erythematosus. Due to the deformed cardiac valves, secondary infective endocarditis should be considered in lupus patients with acute refractory heart failure and fever of unknown origin. The case is reported of a woman with lupus and Libman-Sacks endocarditis who had concurrent coagulase-negative Staphylococcus infective endocarditis that resulted in cerebral septic emboli and acute pulmonary edema. She underwent valve replacement surgery for acute heart failure, and gradually recovered with antibiotic treatment.


Assuntos
Endocardite Bacteriana/complicações , Lúpus Eritematoso Sistêmico/complicações , Infecções Estafilocócicas/complicações , Staphylococcus epidermidis , Idoso , Coagulase/metabolismo , Endocardite Bacteriana/diagnóstico por imagem , Endocardite Bacteriana/metabolismo , Endocardite Bacteriana/microbiologia , Feminino , Humanos , Embolia Intracraniana/etiologia , Valva Mitral/diagnóstico por imagem , Valva Mitral/microbiologia , Infecções Estafilocócicas/metabolismo , Staphylococcus epidermidis/metabolismo , Ultrassonografia
19.
Emerg Infect Dis ; 20(5): 857-60, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24750594

RESUMO

Six persons in Taiwan who had contact with poultry infected with influenza A(H5N2) showed seroconversion for the virus by hemagglutinin inhibition or microneutralization testing. We developed an ELISA based on nonstructural protein 1 of the virus to differentiate natural infection from cross-reactivity after vaccination; 2 persons also showed seroconversion by this test.


Assuntos
Anticorpos Antivirais/imunologia , Vírus da Influenza A Subtipo H5N2/imunologia , Influenza Humana/imunologia , Animais , Anticorpos Antivirais/sangue , Galinhas , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Humanos , Influenza Aviária/virologia , Influenza Humana/transmissão , Aves Domésticas , Doenças das Aves Domésticas/virologia , Taiwan , Proteínas não Estruturais Virais/imunologia
20.
PLoS Med ; 11(4): e1001625, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24714449

RESUMO

BACKGROUND: Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID. METHODS AND FINDINGS: The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6-12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06-0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates. CONCLUSIONS: Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID. Please see later in the article for the Editors' Summary.


Assuntos
Epidemias/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Soroprevalência de HIV/tendências , HIV-1/isolamento & purificação , Redução do Dano , Abuso de Substâncias por Via Intravenosa , Adulto , Estudos de Coortes , Feminino , Infecções por HIV/virologia , Humanos , Incidência , Masculino , Avaliação de Programas e Projetos de Saúde , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/prevenção & controle , Taiwan/epidemiologia , Adulto Jovem
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