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Trichomonas vaginalis is a prevalent causative agent that causes trichomoniasis leading to uropathogenic inflammation in the host. The crucial role of the actin cytoskeleton in T. vaginalis cytoadherence has been established but the associated signaling has not been fully elucidated. The present study revealed that the T. vaginalis second messenger PIP2 is located in the recurrent flagellum of the less adherent isolate and is more abundant around the cell membrane of the adherent isolates. The T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) with conserved activity phosphorylating PI(4)P to PI(4, 5)P2 was highly expressed in the adherent isolate and partially colocalized with PIP2 on the plasma membrane but with discrete punctate signals in the cytoplasm. Plasma membrane PIP2 degradation by phospholipase C (PLC)-dependent pathway concomitant with increasing intracellular calcium during flagellate-amoeboid morphogenesis. This could be inhibited by Edelfosine or BAPTA simultaneously repressing parasite actin assembly, morphogenesis, and cytoadherence with inhibitory effects similar to the iron-depleted parasite, supporting the significance of PIP2 and iron in T. vaginalis colonization. Intriguingly, iron is required for the optimal expression and cell membrane trafficking of TvPI4P5K for in situ PIP2 production, which was diminished in the iron-depleted parasites. TvPI4P5K-mediated PIP2 signaling may coordinate with iron to modulate T. vaginalis contact-dependent cytolysis to influence host cell viability. These observations provide novel insights into T. vaginalis cytopathogenesis during the host-parasite interaction.
Assuntos
Parasitos , Trichomonas vaginalis , Animais , Cálcio/metabolismo , Citoesqueleto de Actina , Ferro/metabolismoRESUMO
BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (Pâ=â0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.
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Farmacorresistência Viral , Infecções por HIV , HIV-1 , Carga Viral , Humanos , Taiwan/epidemiologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Farmacorresistência Viral/genética , Feminino , Adulto , Pessoa de Meia-Idade , Mutação , Genótipo , Inibidores de Integrase de HIV/uso terapêutico , Inibidores de Integrase de HIV/farmacologia , Contagem de Linfócito CD4 , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Adulto Jovem , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/farmacologia , RNA Viral/genéticaRESUMO
BACKGROUND: Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor (InSTI)-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with HIV (PWH). METHODS: From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment, and the secondary outcomes included treatment completion rate and safety of LTBI regimens. RESULTS: During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200â copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. CONCLUSION: Combinations of short-course rifapentine-based regimens and InSTI-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.
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BACKGROUND: With initiation of antiretroviral therapy (ART) containing nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) with anti-hepatitis B virus (HBV) activity, the evolution of HBV serologic markers among people living with human immunodeficiency virus (PLWH) who were born in the era of nationwide neonatal HBV vaccination is rarely investigated. METHODS: This retrospective cohort study evaluated the changes of HBV serologic markers (hepatitis B surface antigen [HBsAg], antibody to hepatitis B surface antigen [anti-HBs], and antibody to hepatitis B core antigen [anti-HBc]) of PLWH who had undergone neonatal HBV vaccination. Clinical characteristics were analyzed and the incidences of evolution of HBV serologic markers were estimated. RESULTS: Between 2004 and 2020, 608 PLWH (mean age, 24 years) were included and 62.0% initiated tenofovir-containing ART: 13 (2.1%) were HBsAg-positive, 312 (51.3%) tested triple-negative, 209 (34.4%) had vaccine-induced seroprotection against HBV, and 74 (12.2%) tested positive for anti-HBc with or without anti-HBs. Among 492 PLWH who received a median follow-up of 2.8 years, 4 cases of incident HBV infection occurred (0.59 per 100 person-years of follow-up [PYFU]) in PLWH testing triple-negative at baseline despite ART containing NRTIs with anti-HBV activity. Of PLWH with seroprotection against HBV at baseline, 38 subsequently lost anti-HBs (4.46 per 100 PYFU) and 4 cases of incident HBV infection occurred (0.47 per 100 PYFU). PLWH with an anti-HBs antibody titer ≥100 mIU/mL at baseline (adjusted hazard ratio [aHR], 0.10 [95% confidence interval {CI}: .02-.42]) and CD4 ≥500 cells/µL during follow-up (aHR, 0.51 [95% CI: .30-1.00]) were less likely to lose HBV seroprotection. CONCLUSIONS: Among young PLWH who had undergone neonatal HBV vaccination, evolution of HBV serologic markers and incident infections occurred despite ART containing NRTIs with anti-HBV activity.
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Infecções por HIV , Hepatite B , Herpesvirus Cercopitecino 1 , Adolescente , Adulto , Antirretrovirais/uso terapêutico , RNA Polimerases Dirigidas por DNA , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B , Vírus da Hepatite B , Humanos , Recém-Nascido , Estudos Retrospectivos , Tenofovir/uso terapêutico , Vacinação , Adulto JovemRESUMO
OBJECTIVES: Synergistic combinations of daptomycin and ß-lactam antibiotics are currently recommended for treatment of VRE bloodstream infection (BSI). The efficacy of these combinations is jeopardized by VRE inherently resistant to ß-lactam antibiotics. The combination of daptomycin and fosfomycin is recommended as an alternative therapy for VRE BSI; however, clinical data to support use of this combination are lacking. PATIENTS AND METHODS: We conducted a prospective observational multicentre study of patients treated with a combination of daptomycin and fosfomycin for VRE BSI during 2016-20. The primary outcome was 28â day mortality. Multivariable logistic regression was performed for outcome analysis. RESULTS: The study included 106 patients from 1112 VRE BSI episodes. The overall 28â day mortality was 40.6%. The median (IQR) daptomycin dose was 10.18â mg/kg (9.43-10.70). The fosfomycin dose was 16â g/day (8-22.5). Ninety-six isolates were available for MIC testing. The fosfomycin MIC was 32â mg/L in 6 (6.3%), 64â mg/L in 68 (70.8%) and ≥128â mg/L in 22 (22.9%) isolates. Independent of Charlson comorbidity index and Pitt bacteraemia score, fosfomycin MIC ≥128â mg/L [adjusted OR (aOR) = 3.05; 95% CI = 1.01-9.19; P = 0.047] and daptomycin dose (aOR = 0.64; 95% CI = 0.43-0.97; P = 0.04) predicted mortality. CONCLUSIONS: Higher daptomycin dose and susceptibility to fosfomycin were independently associated with lower mortality in patients with VRE BSI. Our results suggest that higher doses of daptomycin are indicated for VRE BSI, whether or not it is used in combination with fosfomycin. The combination was less effective for patients with fosfomycin-resistant isolates.
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Bacteriemia , Daptomicina , Enterococcus faecium , Fosfomicina , Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Antibacterianos , Bacteriemia/tratamento farmacológico , Daptomicina/farmacologia , Daptomicina/uso terapêutico , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Monobactamas/farmacologia , Estudos Prospectivos , Vancomicina/farmacologiaRESUMO
OBJECTIVES: The CLSI recommended high-dose daptomycin (8-12â mg/kg) for treating Enterococcus faecium bloodstream infections (BSI). The current study was designed to determine the safety and efficacy of increasing the daptomycin dose for VRE BSI patients receiving ≥8â mg/kg. METHODS: We conducted a multicentre prospective observational study of patients who received a ≥8â mg/kg dose of daptomycin for treatment of VRE BSI. The primary outcome was 28â day mortality. RESULTS: A total of 661 patients were included. The 28â day mortality rate was 45.1%. The survivors received higher doses of daptomycin than non-survivors (10.1 versus 9.8â mg/kg; Pâ<â0.001). An increase in the daptomycin dose independently predicted lower mortality [adjusted OR (aOR)â=â0.85; 95% CIâ=â0.73-0.99; Pâ=â0.03]. Eighty-six survivors (23.7%) and 43 non-survivors (14.4%) received a ≥11â mg/kg dose of daptomycin (Pâ=â0.003). The 8 to <11 and ≥11â mg/kg doses of daptomycin differed in the 28â day mortality in the higher MIC group (≥2â mg/L) (49.4% versus 33.3%; Pâ=â0.004), but not in the lower MIC group (≤1â mg/L) (29.3% versus 29.4%; Pâ=â0.99). A dose of ≥11â mg/kg was associated with a higher (3.9%) rate of highly elevated creatine kinase (>2000â U/L) compared with 1.1% with 8 to <11â mg/kg (Pâ=â0.04). CONCLUSIONS: The efficacy of daptomycin is dose dependent. A high daptomycin dose, especially at ≥11â mg/kg, improved survival in patients with VRE BSI, but was associated with highly elevated creatine kinase. We recommend a ≥11â mg/kg dose of daptomycin be considered for treatment of VRE BSI, particularly for isolates with higher MICs.
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Bacteriemia , Daptomicina , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Sepse , Enterococos Resistentes à Vancomicina , Antibacterianos/efeitos adversos , Bacteriemia/tratamento farmacológico , Creatina Quinase/uso terapêutico , Daptomicina/efeitos adversos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Estudos Retrospectivos , Sepse/tratamento farmacológico , Resultado do TratamentoRESUMO
OBJECTIVES: Real-world experience regarding the effectiveness of co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/C/FTC/TAF) as a switch regimen is sparse among people living with HIV (PLWH) harbouring the M184V/I mutation with or without thymidine analogue-associated mutations (TAMs). METHODS: In this retrospective multicentre study, PLWH who were switched to EVG/C/FTC/TAF after having achieved viral suppression (plasma HIV RNA <200 copies/mL) for 6 months or longer were included. Patients with archived M184V/I mutation (case patients) were matched to controls without M184V/I mutation at a 1:4 ratio. Patients with a history of virological failure or resistance to elvitegravir were excluded. The primary endpoint was virological non-success (plasma HIV RNA ≥50 copies/mL) at Week 48 of switch using a modified FDA snapshot analysis. RESULTS: Overall, 100 case patients with the M184V/I mutation were identified, including 6 (6.0%) with K65R and 13 (13.0%) with at least one TAM, and were matched to 400 controls in terms of gender, age (mean = 40.3 versus 39.7 years) and cumulative exposure duration to tenofovir disoproxil fumarate (median = 146 versus 143 weeks). At Week 48, the rate of virological non-success for the case patients and controls was 5.0% (5/100) and 3.3% (13/400), respectively (difference = 1.7%; 95% CI = -2.9%-6.3%), while the rate of virological success was 88.0% and 89.5% for the case patients and controls, respectively. The presence of the K65R mutation or TAMs was not associated with virological non-response. CONCLUSIONS: Among virally suppressed PLWH, EVG/C/FTC/TAF is effective in maintaining viral suppression at Week 48 despite archived M184V/I mutation with or without TAMs.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adenina/análogos & derivados , Adulto , Alanina , Fármacos Anti-HIV/uso terapêutico , Cobicistat/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Mutação , Quinolonas , Estudos Retrospectivos , Tenofovir/análogos & derivadosRESUMO
Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)-positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV-positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV-positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case-control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow-up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow-up of 611 days. In a case-control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292-2.323, per 10-kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067-7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020-0.154) and 0.837 (95% CI, 0.704-0.979, per 100-cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two-dose HAV vaccination occurred in 3.9% of HIV-positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV-positive adults with predictors of early seroreversion.
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Soropositividade para HIV/sangue , Soropositividade para HIV/imunologia , Vacinas contra Hepatite A/administração & dosagem , Vacinas contra Hepatite A/imunologia , Hepatite A/prevenção & controle , Soroconversão , Adulto , Estudos de Casos e Controles , Surtos de Doenças , Feminino , Hepatite A/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Tenofovir disoproxil fumarate (TDF) is active against both HBV and HIV. Whether the introduction of TDF-containing combination antiretroviral therapy (cART) has improved the outcome of HIV/HBV-coinfected patients remains unclear in areas of higher HBV endemicity. METHODS: We retrospectively reviewed medical records of newly diagnosed antiretroviral-naïve HIV-infected patients between 2007 and 2015. Four groups of patients were defined, according to the HBV status and availability of TDF for HIV treatment in Taiwan in 2011. The primary outcome was all-cause mortality. RESULTS: During the 9-year study period, 1,723 HIV-infected patients were included, with a median age of 31 years and baseline CD4 count of 273 cells per µL. The HBV seroprevalence had declined from 18.1% (125/692) in the pre-TDF era to 10.1% (104/1031) in the post-TDF era. The respective mortality rate for HIV/HBV-coinfected and HIV-monoinfected patients in the pre-TDF era was 23.2 (95% CI, 12.5-43.1) and 9.6 (95% CI, 6.1-15.0) deaths per 1000 person-years of follow-up [PYFU], and the respective mortality rate in the post-TDF era was 15.7 (95% CI, 7.0-34.8) and 8.0 (95% CI, 5.5-11.6) deaths per 1000 PYFU. The adjusted hazard ratio for mortality in multivariate Cox proportional-hazards regression analysis among HIV/HBV-coinfected patients compared to HIV-monoinfected patients was 2.79 (95% CI, 1.25-6.22) in pre-TDF era and 1.11 (95% CI, 0.45-2.72) in post-TDF era. CONCLUSIONS: In this country of high HBV endemicity, the adverse impact of chronic HBV infection on the survival observed in the pre-TDF era has significantly diminished among HIV/HBV-coinfected patients compared to HIV-monoinfected patients in the era of TDF-containing cART.
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Adenina/análogos & derivados , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Ácidos Fosforosos/uso terapêutico , Adenina/uso terapêutico , Adulto , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Hepatite B/complicações , Hepatite B/mortalidade , Humanos , Masculino , Estudos Retrospectivos , Taiwan/epidemiologiaRESUMO
OBJECTIVES: To investigate the prevalence of polypharmacy and potential drug-drug interactions (DDIs), and the factors associated with DDIs among people living with human immunodeficiency virus (HIV; PLWH) in the modern era of antiretroviral therapy (ART). METHODS: This cross-sectional study included PLWH who had been on ART for ≥3 months at two designated HIV hospitals in Taiwan. All ART and non-ART prescriptions were collected from the NHI-MediCloud System and screened for DDIs using the University of Liverpool HIV drug interactions database. A case-control analysis was conducted to investigate the factors associated with DDIs. RESULTS: In total, 1007 PLWH were included in this study from June 2021 to August 2022. The median age was 40 (interquartile range 33-49) years, and 96.2% were taking integrase strand transfer inhibitor (INSTI)-based ART. The proportions of PLWH with at least one non-communicable disease and polypharmacy were 50.0% and 18.7%, respectively. Seven (0.7%) PLWH had red-flagged DDIs, and 159 (15.8%) had amber-flagged DDIs. In multi-variable models, the prevalence of DDIs was associated with older age [adjusted odds ratio (aOR) per 1-year increase 1.022), number of co-medications (aOR 1.097), use of boosted INSTI-based ART (vs unboosted INSTI, aOR 8.653), and concomitant medications in the alimentary tract and metabolism category (aOR 11.058) and anti-neoplastic and immunomodulating agents (aOR 14.733). CONCLUSIONS: In the INSTI era, the prevalence of potential DDIs is lower than noted previously, but remains substantial. Clinicians should monitor DDIs routinely, especially in older PLWH, those taking a higher number of co-medications, and those who are taking booster-containing ART or medications from specific categories.
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Infecções por HIV , HIV , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Polimedicação , Estudos Transversais , Infecções por HIV/complicações , Interações Medicamentosas , IntegrasesRESUMO
OBJECTIVES: We described a case of Strongyloides hyperinfection syndrome, reported a case series, and reviewed published cases of strongyloidiasis in Taiwan. METHODS: Confirmed cases of strongyloidiasis at the National Taiwan University Hospital (NTUH) and NTUH Hsin-Chu Branch from 1988 to 2020 were identified in the medical record database. Literature search was carried out through Pubmed, Google Scholar, and Index to Taiwan Periodical Literature System to identify published cases of strongyloidiasis in Taiwan from 1979 to 2020. Data pertaining to the demographics, underlying medical conditions, clinical manifestations, laboratory findings, and outcomes were extracted. RESULTS: A total of 117 cases of strongyloidiasis were identified, including 20 previously unpublished cases from the two hospitals and 97 published cases in the literature. Overall, 85 (73%) were male and the mean age was 64 years (range, 6-95 years). Classical symptoms such as diarrhea, cough, and skin rash were only observed in 43%, 37%, and 18% of the patients, respectively, whereas eosinophilia at presentation was only found in 48%. Strongyloides hyperinfection syndrome and disseminated strongyloidiasis were identified in 41 (35%) and 4 (3%) patients, respectively. Four (3%) patients had concurrent meningitis. In univariable analysis, being older and having pre-existing chronic obstructive pulmonary disease or asthma were associated with hyperinfection or dissemination (p = 0.024 and 0.003, respectively). The mortality rate was 43% among those with hyperinfection or disseminated infection. CONCLUSIONS: Strongyloidiasis can cause serious complications and mortality. Efforts to diagnose strongyloidiasis early are urgently needed to improve the outcome of patients with strongyloidiasis in Taiwan.
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Asma , Doença Pulmonar Obstrutiva Crônica , Strongyloides stercoralis , Estrongiloidíase , Animais , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estrongiloidíase/diagnóstico , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/epidemiologia , Taiwan/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Asma/complicaçõesRESUMO
INTRODUCTION: High-dose daptomycin-based combinations are recommended for vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). Preclinical data have shown a synergistic effect of daptomycin/fosfomycin combinations against VRE. However, clinical studies comparing daptomycin monotherapy with daptomycin/fosfomycin combinations are unavailable. METHODS: An observational study of VRE-BSI was performed between 2010-2021 on patients receiving daptomycin monotherapy (≥ 8 mg/kg) or daptomycin combined with intravenous fosfomycin. Patients treated with concomitant ß-lactam combinations were excluded. The primary outcome was in-hospital mortality. Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW) analyses. RESULTS: Among 224 patients, 176 received daptomycin monotherapy, and 48 received fosfomycin combinations. The median daptomycin and fosfomycin doses were 9.8 mg/kg and 12 g/day, respectively. In-hospital mortality was 77.3% and 47.9% in the daptomycin monotherapy and fosfomycin combination groups (P < 0.001), respectively. Multivariable logistic regression analysis predicted lower mortality with fosfomycin combination treatment (adjusted odds ratio, 0.35; 95% confidence interval (CI), 0.17-0.73; P = 0.005). AIPW demonstrated a 17.8% reduced mortality with fosfomycin combinations (95% CI, - 30.6- - 4.9%; P = 0.007). The survival benefit was significant, especially among patients with a lower Pitt bacteremia score or fosfomycin minimum inhibitory concentration (MIC) ≤ 64 mg/l. Fosfomycin combination resulted in higher hypernatremia (10.4% vs. 2.8%, P = 0.04) and hypokalemia (33.3% vs. 15.3%, P = 0.009) compared to daptomycin monotherapy. CONCLUSION: The combination of high-dose daptomycin with fosfomycin improved the survival rate of patients with VRE-BSI compared to daptomycin alone. The benefit of the combination was most pronounced for VRE with fosfomycin MIC ≤ 64 mg/l and for patients with a low Pitt bacteremia score.
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OBJECTIVES: We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). METHODS: We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. RESULTS: A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. CONCLUSION: The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.
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Bacteriemia , Daptomicina , Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Humanos , Linezolida/uso terapêutico , Antibacterianos/efeitos adversos , Vancomicina/uso terapêutico , Daptomicina/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Fatores de Risco , Testes de Sensibilidade MicrobianaRESUMO
Serologic responses to hepatitis A virus (HAV) vaccination may wane among immunocompromised populations. To evaluate the long-term seroresponses to 2-dose HAV vaccination, we retrospectively included people living with HIV (PLWH) who had achieved seroconversion within 12 months after vaccination at a university hospital during an outbreak of acute hepatitis A between 2015 and 2017. PLWH included in the study received either Havrix or Vaqta. The seroresponses were evaluated 60 months after the second dose of vaccination and estimated by the intention-to-treat (ITT) with last-observation-carried-forward (LOCF) and per-protocol (PP) analyses. Overall, 986 PLWH (median age, 34 years and CD4 count, 587 cells/µL) were included. The rates of PLWH with persistent seroprotection at month 60 of vaccination were 90.7% (894/986) and 97.4% (748/768) in the ITT with LOCF and PP analyses, respectively. PLWH with persistent seroprotection had achieved higher peak anti-HAV IgG titers after vaccination and had a slower decline in antibody levels compared with those with seroreversion. In the multivariable analysis, seroreversion at month 60 was associated with a higher body-mass index (per 1-kg/m2 increase, AOR, 1.10; 95% CI, 1.04-1.17), lowest-ever CD4 count (per 10-cell/µL increase, AOR 0.98; 95% CI, 0.97-1.00), plasma HIV RNA <200 copies/ml at vaccination (AOR, 0.28; 95% CI, 0.14-0.59), and having received Vaqta as the first dose of HAV vaccination (AOR, 0.44; 95% CI, 0.27-0.70). The seroprotection against HAV remained high in the long-term follow-up among PLWH on antiretroviral therapy after 2-dose HAV vaccination. Regular monitoring of seroresponses and timely administration of HAV vaccines are warranted to maintain seroprotection.
Assuntos
Infecções por HIV , Vírus da Hepatite A , Hepatite A , Humanos , Adulto , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , Vacinas contra Hepatite A/uso terapêutico , Seguimentos , Estudos Retrospectivos , Infecções por HIV/tratamento farmacológico , Vacinação , Surtos de DoençasRESUMO
Trichomoniasis (TV), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) are the most common causes of vaginitis. This study investigated the prevalence of these diagnoses, their associated factors, and the appropriateness of the empirical treatment. From March 25, 2019, to June 17, 2022, 429 women with symptoms or signs of vaginitis were enrolled in a hospital in northern Taiwan with 438 episodes of vaginitis. Vaginal swabs were collected for Gram's staining, in vitro cultures for Trichomonas vaginalis, bacteria, and yeasts, and multiplex PCR assay for TV, BV, and VVC. Their empirical treatments were recorded. Factors associated with different etiologies of vaginitis were sought in multivariable logistic regression models. The prevalence of TV, BV, and VVC were 2.1%, 22.8%, and 21.7%, respectively, while coinfections of BV and VVC, TV and BV, TV and VVC, and triple infection occurred in 5.0%, 0.2%, 0.2%, and 0.7%, respectively. Multivariable analyses revealed that having multiple sexual partners was associated with TV and BV (adjusted odds ratio [aOR] 9.756 and 3.246, respectively), while menopausal women were less likely to have VVC (aOR 0.184). Moreover, dysuria was associated with TV (aOR 4.981), vaginal itch and pelvic pain with VVC (aOR 3.223 and 0.425, respectively), and discharge pH > 4.5 with BV (aOR 1.767). Other clinical symptoms and pelvic examination features had limited value for differential diagnosis. Among the 78 empirical antifungal and metronidazole prescriptions, 55.2% were ineffective or unnecessary. Our study highlights the importance to integrate appropriate diagnostic tools into the clinical care of women with vaginitis. IMPORTANCE Vaginal complaints are widespread among women and are associated with emotional, physical, and economic burdens with challenges in their diagnosis and management. In this survey, we identified that 40% of vaginitis in Taiwan was caused by either trichomoniasis, bacterial vaginosis, vulvovaginal candidiasis, or a combination of these infections. Our data suggested that typical physical findings appeared infrequently among women with these infections and their empirical treatments were frequently inappropriate. Our findings highlighted the importance of integrating proper diagnostic tools into clinical practice to improve the diagnosis and management of vaginitis, as recommended by national and international guidelines.
Assuntos
Candidíase Vulvovaginal , Tricomoníase , Vaginite por Trichomonas , Vaginose Bacteriana , Feminino , Humanos , Vaginose Bacteriana/diagnóstico , Vaginose Bacteriana/tratamento farmacológico , Vaginose Bacteriana/epidemiologia , Candidíase Vulvovaginal/diagnóstico , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/epidemiologia , Prevalência , Vaginite por Trichomonas/diagnóstico , Vaginite por Trichomonas/tratamento farmacológico , Vaginite por Trichomonas/epidemiologia , Tricomoníase/complicaçõesRESUMO
BACKGROUND: The prevalence of rectal chlamydia among men who have sex with men (MSM) without human deficiency virus infection (non-HIV) remains uncertain in Taiwan, and rectal lymphogranuloma venereum (LGV) among MSM has never been reported in the Far East. MATERIAL AND METHODS: From January 2020 to April 2022, MSM coming for anonymous voluntary counseling and testing, for pre-exposure prophylaxis, and for antiretroviral therapy were enrolled. All participants submitted his fecal samples and completed a QR-code questionnaire. Medical records of those who took regular medical visits for HIV were recorded. Multiplex polymerase chain reaction (PCR) was performed for all fecal samples, and ompA gene sequencing was therefore performed for each Chlamydia-positive fecal sample. RESULTS: Among 341 MSM during 2020-2022 in southern Taiwan, 21 (6.2%) had rectal chlamydia infection. Risk factors of rectal chlamydia included co-infection with rectal gonorrhea (adjusted odds ratio [AOR] 6.78, 95% confidence interval [CI] 1.44-31.91, P = 0.015) and multiple sexual partners (AOR 1.373, 95% CI 1.002-1.882, P = 0.048). Further ompA gene sequencing from 19 Chlamydia-positive fecal samples revealed that the prevalent genotypes or genovariants were Da (26.3%) and L2b (26.3%), followed by B (21.1%), J (14.3%), and G (9.5%). All cases of rectal LGV genovariant L2b presented as acute proctitis with diarrhea, anal pain, or discharge and were treated successfully with prolonged treatment of doxycycline. CONCLUSIONS: Rectal gonorrhea and multiple sexual partners are risk factors for rectal chlamydia. Clinicians in Taiwan should be aware of the emerging threat of rectal LGV among MSM with acute proctitis.
Assuntos
Gonorreia , Linfogranuloma Venéreo , Proctite , Doenças Retais , Minorias Sexuais e de Gênero , Masculino , Humanos , Linfogranuloma Venéreo/epidemiologia , Homossexualidade Masculina , Chlamydia trachomatis/genética , Taiwan/epidemiologia , Doenças Retais/epidemiologia , Proctite/epidemiologiaRESUMO
BACKGROUND: Understanding the risk behaviors associated with sexually-transmitted hepatitis C virus (HCV) infection among men who have sex with men (MSM) may inform the public health policies and interventions aiming to achieve HCV microelimination. METHODS: HIV-positive MSM who had one of the following conditions were enrolled to undergo face-to-face questionnaire interviews to collect information on their sexual practices in the past 12 months: (1) elevation of aminotransferases in the past 6 months; (2) acquisition of sexually transmitted infections in the past 6 months; and (3) previous HCV infections. Plasma HCV RNA were tested at enrolment and every 3 months during follow-up. Baseline characteristics and risky behaviors were compared to identify factors associated with HCV viremia between HCV-viremic MSM and HCV-aviremic MSM in multivariate analysis. RESULTS: Among 781 MSM with a median age of 36 years, 57 (7.3%) had HCV viremia and 724 (92.7%) no HCV viremia during follow-up. A high proportion (38.9%) of the participants reported having used recreational drugs in the past 12 months, with 34.4% of them having slamming, but only 4.8% reported having shared their injection equipment. In multivariate analysis, use of recreational drugs (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.96), having participated in group sex (aOR, 2.35; 95% CI 1.24-4.40) and having had condomless receptive anal intercourse (aOR, 1.97; 95% CI 1.07-3.62) were significantly associated with HCV viremia. CONCLUSION: Among high-risk HIV-positive MSM, use of recreational drugs and risky sexual contacts were associated with HCV viremia, suggesting the mucosal contacts as the major route of HCV transmission.
Assuntos
Infecções por HIV , Hepatite C , Drogas Ilícitas , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Masculino , Humanos , Adulto , Homossexualidade Masculina , Hepacivirus/genética , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Taiwan/epidemiologia , Viremia , Fatores de Risco , Comportamento Sexual , Hepatite C/epidemiologiaRESUMO
BACKGROUND: The short-term impact of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) combined with antiretroviral therapy (ART) on renal function in patients with HIV/HCV-coinfection remains controversial. METHODS: This multicenter, retrospective study aimed to sequentially record the estimated glomerular filtration rate (eGFR) at baseline, end of therapy (EOT), 12 weeks off-treatment (SVR12), and at time points after SVR12 (post-SVR12) and to identify the factors associated with an eGFR decline to <60 ml/min/1.73 m2 in HIV/HCV-coinfected patients receiving DAAs. The evolution of mean eGFRs between different ART and DAAs combinations among patients of different HIV transmission routes were compared using a generalized linear mixed effects model. The periods between baseline and EOT, between EOT and post-SVR12, and between baseline and post-SVR12 were defined as the on-treatment, post-treatment, and all-course periods, respectively. Acute kidney disease (AKD) was defined as a decline of eGFR to <60 ml/min/1.73 m2. RESULT: A total of 445 patients with baseline eGFRs >60 ml/min/1.73 m2 were included. We found that eGFRs declined during the on-treatment period in the tenofovir-containing ART and SOF-based DAA groups. There were no differences in the slope coefficient during the on-treatment and post-treatment periods among all risk groups except for people who inject drug. Increasing age and plasma HIV RNA >20 copies/ml before DAA treatment were factors independently associated with AKD during the on-treatment period while increasing age was independently associated with AKD during the all-course period. CONCLUSION: Only increasing age was an independent factor associated with AKD among HIV/HCV-coinfected patients during and after DAA treatments.