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BACKGROUND: Genotyping isolates of a specific pathogen may demonstrate unique patterns of antimicrobial resistance, virulence or outcomes. However, evidence for genotype-outcome association in Candida glabrata is scarce. We aimed to characterize the mycological and clinical relevance of genotypes on C. glabrata bloodstream infections (BSIs). METHODS: Non-duplicated C. glabrata blood isolates from hospitalized adults were genotyped by MLST, and further clustered by the unweighted pair group method with arithmetic averages (UPGMA). A clonal complex (CC) was defined by UPGMA similarities of >90%. Antifungal susceptibility testing was performed by a colorimetric microdilution method and interpreted following CLSI criteria. RESULTS: Of 48 blood isolates evaluated, 13 STs were identified. CC7 was the leading CC (nâ=â14; 29.2%), including 13 ST7. The overall fluconazole and echinocandin resistance rates were 6.6% and 0%, respectively. No specific resistance patterns were associated with CC7 or other CCs. Charlson comorbidity index (adjusted OR, 1.49; 95% CI, 1.05-3.11) was the only predictor for CC7. By multivariable Cox regression analyses, CC7 was independently associated with 28â day mortality [adjusted HR (aHR), 3.28; 95% CI, 1.31-8.23], even after considering potential interaction with neutropenia (aHR, 3.41; 95% CI, 1.23-9.42; P for interaction, 0.24) or limited to 34 patients with monomicrobial BSIs (aHR, 2.85; 95% CI, 1.15-7.08). Also, the Kaplan-Meier estimate showed greater mortality with CC7 (Pâ=â0.003). Fluconazole resistance or echinocandin therapy had no significant impact on mortality. CONCLUSIONS: Our data suggested comorbid patients were at risk of developing CC7 BSIs. Further, CC7 was independently associated with worse outcomes.
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Antifúngicos , Candida glabrata , Candidemia , Farmacorresistência Fúngica , Genótipo , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Humanos , Candida glabrata/genética , Candida glabrata/efeitos dos fármacos , Candida glabrata/isolamento & purificação , Masculino , Feminino , Pessoa de Meia-Idade , Candidemia/microbiologia , Candidemia/tratamento farmacológico , Candidemia/mortalidade , Idoso , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Prognóstico , Farmacorresistência Fúngica/genética , Adulto , Idoso de 80 Anos ou mais , Fluconazol/farmacologia , Fluconazol/uso terapêuticoRESUMO
Longitudinal analysis of antibody responses following three-dose COVID-19 vaccination in patients with chronic liver disease (CLD) has been limited. From August 2021 to February 2023, sequential anti-SARS-CoV-2 spike IgG titers were determined in 45 patients with CLD who received two or three doses of COVID-19 vaccine. The geometric mean of anti-spike IgG at four weeks after the second and third doses were 1313.16 BAU/mL and 3042.29 BAU/mL, respectively, and it decreased significantly from four to 24 weeks after the second (1313.16 vs. 198.42 BAU/mL, p = 0.002) and the third (3042.29 vs. 636.71 BAU/mL, p < 0.001) dose. The anti-spike IgG titers in participants receiving prime-boost homologous mRNA vaccines (BNT162b2 or mRNA-1273) were comparable between participants with and those without significant liver fibrosis at each follow-up time point. This study demonstrated a notable decrease in anti-spike IgG after completion of the vaccination schedule in patients with CLD, highlighting the importance of additional booster doses.
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BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a substantial healthcare challenge. This study assessed the in vitro efficacy of selected antibiotic combinations against CRKP infections. METHODS: Our research involved the evaluation of 40 clinical isolates of CRKP, with half expressing Klebsiella pneumoniae carbapenemase (KPC) and half producing Metallo-ß-lactamase (MBL), two key enzymes contributing to carbapenem resistance. We determined the minimum inhibitory concentrations (MICs) of four antibiotics: eravacycline, tigecycline, polymyxin-B, and ceftazidime/avibactam. Synergistic interactions between these antibiotic combinations were examined using checkerboard and time-kill analyses. RESULTS: We noted significant differences in the MICs of ceftazidime/avibactam between KPC and MBL isolates. Checkerboard analysis revealed appreciable synergy between combinations of tigecycline (35%) or eravacycline (40%) with polymyxin-B. The synergy rates for the combination of tigecycline or eravacycline with polymyxin-B were similar among the KPC and MBL isolates. These combinations maintained a synergy rate of 70.6% even against polymyxin-B resistant isolates. In contrast, combinations of tigecycline (5%) or eravacycline (10%) with ceftazidime/avibactam showed significantly lower synergy than combinations with polymyxin-B (P < 0.001 and P = 0.002, respectively). Among the MBL CRKP isolates, only one exhibited synergy with eravacycline or tigecycline and ceftazidime/avibactam combinations, and no synergistic activity was identified in the time-kill analysis for these combinations. The combination of eravacycline and polymyxin-B demonstrated the most promising synergy in the time-kill analysis. CONCLUSION: This study provides substantial evidence of a significant synergy when combining tigecycline or eravacycline with polymyxin-B against CRKP strains, including those producing MBL. These results highlight potential therapeutic strategies against CRKP infections.
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Compostos Azabicíclicos , Proteínas de Bactérias , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Tetraciclinas , Humanos , Ceftazidima/uso terapêutico , Tigeciclina/farmacologia , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Klebsiella pneumoniae , Infecções por Klebsiella/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases/farmacologia , Polimixinas/farmacologia , Polimixinas/uso terapêutico , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Patients with hematological malignancies (HM) were at a high risk of developing severe disease from coronavirus disease 2019 (COVID-19). We aimed to assess the clinical outcome of COVID-19 in hospitalized patients with HM. METHODS: Adult patients with HM who were hospitalized with a laboratory-confirmed COVID-19 between May, 2021 and November, 2022 were retrospectively identified. Primary outcome was respiratory failure requiring mechanical ventilation or mortality within 60 days after hospitalization. We also analyzed associated factors for de-isolation (defined as defervescence with a consecutive serial cycle threshold value > 30) within 28 days. RESULTS: Of 152 eligible patients, 22 (14.5%) developed respiratory failure or mortality in 60 days. Factors associated with developing respiratory failure that required mechanical ventilation or mortality included receipt of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) (adjusted hazards ratio [aHR], 5.10; 95% confidence interval [CI], 1.64-15.85), type 2 diabetes mellitus (aHR, 2.47; 95% CI, 1.04-5.90), lymphopenia at admission (aHR, 6.85; 95% CI, 2.45-19.15), and receiving <2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines (aHR, 3.00; 95% CI, 1.19-7.60). Ninety-nine (65.1%) patients were de-isolated in 28 days, against which two hazardous factors were identified: receipt of B-cell depletion therapies within one year prior to COVID-19 (aHR, 0.55, 95% CI, 0.35-0.87) and lymphopenia upon admission (aHR, 0.65; 95% CI, 0.43-1.00). CONCLUSION: We found a high rate of respiratory failure and mortality among patients with HM who contracted the SARS-CoV-2. Factors associated with developing respiratory failure or mortality in 60 days included receipt of allo-HSCT, type 2 diabetes mellitus and lymphopenia upon admission. Having received ≥2 doses of vaccination conferred protection against clinical progression.
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COVID-19 , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/mortalidade , COVID-19/epidemiologia , Neoplasias Hematológicas/complicações , Masculino , Pessoa de Meia-Idade , Feminino , Fatores de Risco , Estudos Retrospectivos , Idoso , Adulto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Índice de Gravidade de Doença , Insuficiência Respiratória/epidemiologia , Respiração Artificial , Hospitalização/estatística & dados numéricos , Linfopenia , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.
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Vacina de mRNA-1273 contra 2019-nCoV , Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Infecções por HIV , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Masculino , Feminino , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Antivirais/sangue , Pessoa de Meia-Idade , Infecções por HIV/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacina BNT162/administração & dosagem , Vacina BNT162/imunologia , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Adulto , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/administração & dosagem , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinação/métodos , Eficácia de Vacinas , SoroconversãoAssuntos
Monofosfato de Adenosina , Monofosfato de Adenosina/análogos & derivados , Adenosina/análogos & derivados , Alanina , Alanina/análogos & derivados , Antivirais , Tratamento Farmacológico da COVID-19 , Quimioterapia Combinada , Hospedeiro Imunocomprometido , SARS-CoV-2 , Humanos , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/administração & dosagem , Alanina/uso terapêutico , Alanina/administração & dosagem , Antivirais/uso terapêutico , Antivirais/administração & dosagem , SARS-CoV-2/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Resultado do Tratamento , COVID-19 , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagemRESUMO
Background: This study evaluated the in vitro activity of cefiderocol, ceftazidime/avibactam, and aztreonam/avibactam against clinically important multidrug-resistant non-fermenting Gram-negative bacilli. Methods: Bacteraemic isolates of 126 multidrug-resistant Acinetobacter baumannii (MDRAB), 110 imipenem-resistant Pseudamoas aeruginosa [including 14 difficult-to-treat resistant P. aeruginosa (DTRPA)], 45 beta-lactam-non-susceptible Burkholderia cepacia complex (BCC), 47 levofloxacin or trimethoprim/sulfamethoxazole-non-susceptible Stenotrophomonas maltophilia and 22 ciprofloxacin-non-susceptible Elizabethkingia spp. collected between 2019 and 2021 were subjected to MIC determination for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam. Results: The MIC50/90s of ceï¬derocol for drug-resistant A. baumannii, P. aeruginosa, BCC, S. maltophilia and Elizabethkingia spp. were 0.25/2, 0.25/1, ≤0.06/≤0.06, ≤0.06/0.25 and >32/>32â mg/L, respectively. Cefiderocol inhibited 94.4% (119/126) of MDRAB, 100% of imipenem-resistant P. aeruginosa, 100% of DTRPA and 100% of BCC at an MIC ≤4â mg/L, and 97.9% (46/47) of S. maltophilia at ≤1â mg/L. Ceftazidime/avibactam inhibited 76.4% (84/110) of imipenem-resistant P. aeruginosa, 21.4% (3/14) of DTRPA and 68.9% (31/45) of BCC at an MIC ≤8â mg/L. Aztreonam/avibactam had MIC50/90s of 16/>32, 8/16 and 4/8â mg/L for imipenem-resistant P. aeruginosa, BCC and S. maltophilia, respectively. At ≤8â mg/L, aztreonam/avibactam inhibited 7.1% (1/14) of DTRPA and 93.6% (44/47) of S. maltophilia isolates. Elizabethkingia spp. demonstrated high MICs for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam, with all MIC50s and MIC90sâ>â32â mg/L. Conclusion: Cefiderocol may serve as an alternative treatment for multidrug-resistant A. baumannii, P. aeruginosa, BCC and S. maltophilia when other antibiotics have been ineffective or intolerable. The role of ceftazidime/avibactam and aztreonam/avibactam in the management of BCC or S. maltophilia infections warrants further investigation.
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BACKGROUND: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain. METHODS: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days. RESULTS: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98). CONCLUSION: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Dexametasona , Pontuação de Propensão , SARS-CoV-2 , Humanos , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Masculino , Feminino , COVID-19/mortalidade , Pessoa de Meia-Idade , Taiwan/epidemiologia , Idoso , SARS-CoV-2/efeitos dos fármacos , Resultado do Tratamento , Respiração Artificial/estatística & dados numéricos , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricos , AdultoRESUMO
Actinomycosis is an uncommon infection caused by Actinomyces species, and the diagnosis is often challenging owing to low prevalence and diverse clinical manifestations. Pericardial involvement of actinomycosis is particularly rare. Here, we present a case of a 79-year-old man who initially complained of exertional dyspnea, orthopnea, and decreased urine amount. There was no fever, chest pain, or productive cough. Physical examination was remarkable for decreased breath sounds at the left lower lung field. Poor dental hygiene and a firm, well-defined mass without discharge over the hard palate were noted. Echocardiography revealed reduced ejection fraction of the left ventricle, global hypokinesia, and thickened pericardium (> 5 mm) with a small amount of pericardial effusion. On admission, the patient underwent diagnostic thoracentesis, and the results suggested an exudate. However, bacterial and fungal cultures were all negative. There was no malignant cell by cytology. Computed tomography revealed contrast-enhanced pericardial nodular masses. Video-assisted thoracoscopic pericardial biopsy was performed. Histopathology confirmed actinomycosis with chronic abscess formation, and a tissue culture yielded Aggregatibacter actinomycetemcomitans. The symptoms resolved with administration of clindamycin for 6 months. This case highlights the challenge in the diagnosis of cardiac actinomycosis, the potential role of concomitant microorganisms as diagnostic clues, and the favorable clinical response achieved with appropriate antibiotic treatment.
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Actinomicose , Higiene Bucal , Masculino , Humanos , Idoso , Actinomicose/diagnóstico , Actinomicose/tratamento farmacológico , Actinomyces , Antibacterianos/uso terapêutico , Pericárdio/patologiaRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has reached a turning point. The non-pharmaceutical interventions for preventing COVID-19 are lifting. Vaccination uptake is increasing in general, but this strategy is continuously challenged by the rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of note, the Omicron subvariants spread globally for at least one year, and the most recently developed subvariants show strong immune evasion to preexisting immunity, either from previous infection, vaccination or both. Therefore, early and appropriate antiviral agents to treat patients at risk for severe COVID-19 or death is crucial to decrease morbidities and mortalities, to restore the healthcare capacities and to facilitate a return to the new normal. Current antiviral therapy for COVID-19 consist of neutralizing monoclonal antibodies (mAbs) and direct antiviral agents. Each agent has been proved for early ambulatory treatment of COIVD-19, but suffer from variable effectiveness and limitations due to patients' comorbidities, drug properties, or antiviral resistance. Besides, some specific mAbs are indicated for prophylaxis of COVID-19 before or after close contact with confirmed COVID-19 patients. This review article summarizes the evidence and unmet needs of the currently available antiviral agents for management of COVID-19 in the context of the Omicron subvariants.
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COVID-19 , Humanos , SARS-CoV-2 , Anticorpos Monoclonais , Farmacorresistência Viral , Antivirais/uso terapêuticoRESUMO
COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan.
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COVID-19 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , SARS-CoV-2 , Taiwan/epidemiologia , Quarentena , Busca de Comunicante/métodos , HospitaisRESUMO
BACKGROUND: B cells are essential for providing humoral protection against acute influenza A virus (IAV) infection. FcγRIIB, a regulator of antibody (Ab) production, influences immune responses during pathogen infections, but its specific impact on humoral protection and B cell-mediated responses against IAV remains unclear. METHODS: To investigate FcγRIIB's role in host defense and B cell function during acute IAV infection, we generated mice with systemic FcγRIIB deficiency, functional impairment, and B cell-specific FcγRIIB deletion. We infected these mice with PR8 (H1N1) or Hkx31 (H3N2) IAVs and evaluated body weight preservation, survival rates, Ab production, viral neutralization, Ab affinity maturation, and germinal center B cell development. RESULTS: Mice lacking FcγRIIB or with impaired function showed improved protection, preserved body weight, and increased survival rates during IAV infection. Notably, mice with haploinsufficient FcγRIIB function displayed protective effects. Selective deficiency of FcγRIIB in B cells led to enhanced Ab production, resulting in elevated IAV-specific Abs in the serum with superior viral neutralizing potency. However, the impact on the affinity maturation index of virus-specific Abs was modest. Accordingly, FcγRIIB-deficient B cells maintained normal germinal center B cell development during IAV infection, whereas wild-type mice exhibited delayed differentiation. CONCLUSION: Our research underscores the pivotal role of FcγRIIB in host defense and B cell-mediated immunity during acute IAV infection. Additionally, our discoveries hold implications for antiviral treatments, particularly during the initial stages of IAV infection, aimed at enhancing the host's humoral immune response.
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Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Humanos , Camundongos , Peso Corporal , Centro Germinativo , Vírus da Influenza A Subtipo H3N2RESUMO
BACKGROUND: The clinical burden of Clostridioides difficile infections (CDIs) remains substantial globally. This study aimed to investigate the ribotypes (RTs) and antimicrobial susceptibility of C. difficile isolates collected in Taiwan. METHODS: C. difficile isolates were prospectively collected from four medical centers in Taiwan from 2019 to 2021. In a reference laboratory, in vitro susceptibility to clindamycin, moxifloxacin, metronidazole, vancomycin, fidaxomicin, and rifaximin were tested, and ribotyping was conducted to determine their genetic diversity. RESULTS: A total of 568 C. difficile isolates were included. Metronidazole resistance was not observed, and the susceptibility rate of vancomycin was 99.5 %. Clindamycin showed poor activity against these isolates, with a resistance rate of 74.8 %. Fidaxomicin exhibited potent activity and 97.4 % of isolates were inhibited at 0.25 µg/mL. Rifaximin MIC90 increased from 0.015 µg/mL in 2019 to 0.03 µg/mL in 2020 and 2021. Of 40 RTs identified, two predominant RTs were RT 078/126 (78, 14 %) and 014/020 (76, 13 %). RT 017, traditional harboring truncated tcdA, accounted for 3 % (20 isolates) and there was no isolate belonging to RT 027. The proportions of RT 078 increased from 11.2 % in 2019 to 17.1 % in 2021, and the predominance of RT 078/126 was more evident in central Taiwan. CONCLUSIONS: Vancomycin, fidaxomicin, and metronidazole remain in vitro effective against clinical C. difficile isolates in Taiwan. The reservoirs and genetic relatedness of two major RTs with zoonotic potentials, RT 078/126 and 014/020, warrant further investigations.
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Clostridioides difficile , Infecções por Clostridium , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fidaxomicina , Vancomicina/farmacologia , Metronidazol/farmacologia , Ribotipagem , Clindamicina , Rifaximina/farmacologia , Taiwan/epidemiologia , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Testes de Sensibilidade MicrobianaRESUMO
The diagnosis of adult-onset immunodeficiency syndrome associated with neutralizing anti-interferon γ autoantibodies (AIGA) presents substantial challenges to clinicians and pathologists due to its nonspecific clinical presentation, absence of routine laboratory tests, and resemblance to certain lymphoma types, notably nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI). Some patients undergo lymphadenectomy for histopathological examination to rule out lymphoma, even in the absence of a preceding clinical suspicion of AIGA. This study aimed to identify reliable methods to prevent misdiagnosis of AIGA in this scenario through a retrospective case-control analysis of clinical and pathological data, along with immune gene transcriptomes using the NanoString nCounter platform, to compare AIGA and nTFHL-AI. The investigation revealed a downregulation of the C-X-C motif chemokine ligand 9 (CXCL9) gene in AIGA, prompting an exploration of its diagnostic utility. Immunohistochemistry (IHC) targeting CXCL9 was performed on lymph node specimens to assess its potential as a diagnostic biomarker. The findings exhibited a significantly lower density of CXCL9-positive cells in AIGA compared to nTFHL-AI, displaying a high diagnostic accuracy of 92.3% sensitivity and 100% specificity. Furthermore, CXCL9 IHC demonstrated its ability to differentiate AIGA from various lymphomas sharing similar characteristics. In conclusion, CXCL9 IHC emerges as a robust biomarker for differentiating AIGA from nTFHL-AI and other similar conditions. This reliable diagnostic approach holds the potential to avert misdiagnosis of AIGA as lymphoma, providing timely and accurate diagnosis.
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Linfadenopatia , Linfoma , Adulto , Humanos , Estudos Retrospectivos , Linfoma/diagnóstico , Autoanticorpos , Biomarcadores , Quimiocina CXCL9RESUMO
PURPOSE: We compared hypermetabolic lymphadenopathy (HLN) on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after virus-vector and mRNA vaccines for coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 573 participants who underwent FDG PET/CT after receiving a virus-vector vaccine (ChAdOx1, AstraZeneca [AZ] group) or an mRNA vaccine (mRNA-1273, Moderna [M] group) from July 2021 to October 2021. The incidence and avidity of HLN were evaluated and correlated with clinical features and vaccine type. The final analysis was conducted with 263 participants in the AZ group and 310 participants in the M group. RESULTS: The HLN incidence was significantly lower in the AZ group than in the M group (38/263 [14%] vs. 74/310 [24%], p = 0.006). The FDG avidity of HLN was comparable between the two groups. The HLN incidence in both groups was significantly higher within 4 weeks after the vaccination compared with more than 4 weeks. The HLN incidence within 4 weeks of the vaccination was significantly higher in the M group than in the AZ group (p = 0.008), whereas a difference in HLN incidence between the two groups was not observed after the same duration (p = 0.11). CONCLUSIONS: The mRNA mRNA-1273 COVID-19 vaccine was found to be associated with higher glucose hypermetabolism in regional lymph nodes within the first 4 weeks compared with the virus-vector vaccine, as indicated by the presence of HLN on FDG PET/CT. The degree of glucose hypermetabolism was comparable between the two vaccines.
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Vacinas contra COVID-19 , COVID-19 , Linfadenopatia , Humanos , Vacina de mRNA-1273 contra 2019-nCoV , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Fluordesoxiglucose F18 , Glucose , Linfonodos/diagnóstico por imagem , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/etiologia , Vacinas de mRNA , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Vacinação , VacinasRESUMO
Purpose: Early studies showed that the risks of mRNA vaccine-associated myocarditis and pericarditis are low but with substantial variation across studies. Study characteristics, ethnicity, vaccine types, dose intervals, and SARS-CoV-2 infection prevalence may influence the rates of myocarditis and pericarditis after mRNA vaccination in population-based studies. Methods: We comprehensively searched MEDLINE for relevant articles published before November 30, 2022. We also searched the websites of health authorities in several countries for unpublished surveillance data on myocarditis and pericarditis after mRNA vaccination. The outcome of interest was the incidence of myocarditis and pericarditis developed after mRNA vaccination for COVID-19. Results: A total of 17 studies form 10 countries were included for review. We noted that considerable heterogeneity in study characteristics, including surveillance method, case definition, and observation period, may partially be responsible for the widely varied reported rates. Studies from countries that adopted active surveillance reported higher rates than those using passive surveillance. Compared to BNT162b2 vaccine, mRNA-1273 may have a higher risk of myocarditis only in young men after the second dose. Our comparison of sex-, age-, vaccine type-, and dose-specific rates of myocarditis across countries did not support the hypothesis that individuals with recent SARS-CoV-2 infection and young Asian males were at higher risk. We also could not find sufficient evidence to conclude whether extending the between-dose interval could reduce myocarditis incidence following mRNA vaccination. Conclusion: Differences in the study characteristics must be fully considered when comparing the risks of mRNA vaccine-related myocarditis and pericarditis in different countries.
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Repeated annual influenza vaccinations have been associated with reduced vaccine-induced antibody responses. This prospective study aimed to explore the role of vaccine antigen-specific regulatory T (Treg) cells in antibody response to repeated annual influenza vaccination. We analyzed pre- and postvaccination hemagglutination inhibition (HI) titers, seroconversion rates, seroprotection rates, vaccine antigen hemagglutinin (HA)-specific Treg cells, and conventional T (Tconv) cells. We compared these parameters between vaccinees with or without vaccine-induced seroconversion. Our multivariate logistic regression revealed that prior vaccination was significantly associated with a decreased likelihood of achieving seroconversion for both H1N1(adjusted OR, 0.03; 95% CI, 0.01-0.13) and H3N2 (adjusted OR, 0.09; 95% CI, 0.03-0.30). Furthermore, individuals who received repeated vaccinations had significantly higher levels of pre-existing HA-specific Treg cells than those who did not. We also found that vaccine-induced fold-increases in HI titers and seroconversion were negatively correlated with pre-existing HA-specific Treg cells and positively correlated with the ratio of Tconv to Treg cells. Overall, our findings suggest that repeated annual influenza vaccination is associated with a lower vaccine-induced antibody response and a higher frequency of vaccine-specific Treg cells. However, a lower frequency of pre-existing Treg cells correlates with a higher postvaccination antibody response.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Humanos , Influenza Humana/prevenção & controle , Linfócitos T Reguladores , Formação de Anticorpos , Vírus da Influenza A Subtipo H3N2 , Estudos Prospectivos , Anticorpos Antivirais , Vacinação , Testes de Inibição da HemaglutinaçãoRESUMO
Bloodstream infections are a growing public health concern due to emerging pathogens and increasing antimicrobial resistance. Rapid antibiotic susceptibility testing (AST) is urgently needed for timely and optimized choice of antibiotics, but current methods require days to obtain results. Here, we present a general AST protocol based on surface-enhanced Raman scattering (SERS-AST) for bacteremia caused by eight clinically relevant Gram-positive and Gram-negative pathogens treated with seven commonly administered antibiotics. Our results show that the SERS-AST protocol achieves a high level of agreement (96% for Gram-positive and 97% for Gram-negative bacteria) with the widely deployed VITEK 2 diagnostic system. The protocol requires only five hours to complete per blood-culture sample, making it a rapid and effective alternative to conventional methods. Our findings provide a solid foundation for the SERS-AST protocol as a promising approach to optimize the choice of antibiotics for specific bacteremia patients. This novel protocol has the potential to improve patient outcomes and reduce the spread of antibiotic resistance.
Assuntos
Bacteriemia , Técnicas Bacteriológicas , Farmacorresistência Bacteriana , Análise Espectral Raman , Bacteriemia/microbiologia , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Humanos , Técnicas Bacteriológicas/métodos , HemoculturaRESUMO
Burkholderia cepacia is an emerging nosocomial pathogen frequently associated with outbreaks, but the exact transmission route of this pathogen can at times be elusive in spite of extensive environmental investigative cultures. Active surveillance for sputum cultures was performed for all patients from September 2008 to September 2009 in an intensive care unit (ICU) with B. cepacia outbreak. With evidence of persistent positive conversion of sputum cultures (colonization) and infections among patients, discontinuing re-usable ventilator circuits was introduced. A total of 689 patients were admitted to this unit for a mean duration of 8.7 ± 7.5 days. There were 489 patients (71.0%) with a stay for one to ten days; 161 (23.4%) patients for 11 to 20 days; and 39 (5.7%) with over 20 days. In the first group, 13.5% of patients had cultures converting from negative to positive, in contrast to 66.7% in the last group (p < 0.01). With intervention of using disposable ventilator circuits since June 2009, the incidence of isolated B. cepacia decreased gradually. The estimated 30-day isolation-free probabilities of the groups before, during, one month (August 2009) after, and two months (September 2009) after this intervention were 38.5%, 47.3%, 66.5%, and 96.0%, respectively (p < 0.01). Furthermore, the effect of discontinuing reusable ventilator circuit persisted in the following 6 years; both total isolates of B. cepacia and the infection caused by it were much lower compared to the outbreak period. In summary, this six-year outbreak in a medical ICU persisted until reusable ventilator circuits were discontinued in 2009. The effect of disposable circuits on the decreased incidence of B. cepacia infection maintained in the following years.
RESUMO
Cefiderocol and aztreonam-avibactam (ATM-AVI) both had activity against carbapenem-resistant Gram-negative bacilli, including those that produce metallo-ß-lactamases (MBLs). We compared the in vitro activities and inoculum effects of these antibiotics against carbapenemase-producing Enterobacteriaceae (CPE), especially MBL-producing isolates. The MICs of cefiderocol and ATM-AVI were determined using broth microdilution method for a 2016 to 2021 collection of Enterobacteriaceae isolates which produced MBL, KPC, or OXA-48-like carbapenemases. MICs with high bacteria inoculum were also evaluated for susceptible isolates. A total of 195 CPE were tested, including 143 MBL- (74 NDM, 42 IMP, and 27 VIM), 38 KPC-, and 14 OXA-48-like-producing isolates. The susceptible rates of MBL-, KPC-, and OXA-48-like producers to cefiderocol were 86.0%, 92.1%, and 92.9%, respectively, and that to ATM-AVI were 95.8%, 100%, and 100%, respectively. NDM producers displayed lower susceptibility and higher MIC50s/MIC90s of cefiderocol (78.4%, 2/16 mg/L) than IMP (92.9%, 0.375/4 mg/L) and VIM (96.3%, 1/4 mg/L) producers. NDM- and VIM-producing Escherichia coli showed lower susceptibility to ATM-AVI (77.3% and 75.0%, respectively) compared to MBL-CPE of other species (100% susceptible). Inoculum effects for cefiderocol and ATM-AVI were observed among 95.9% and 95.2% of susceptible CPE, respectively. A switch from susceptible to resistant category was observed in 83.6% (143/171) of isolates for cefiderocol and 94.7% (179/189) for ATM-AVI. Our results revealed that NDM-producing Enterobacteriaceae had lower susceptibility to cefiderocol and ATM-AVI. Prominent inoculum effects on both antibiotics were observed for CPE, which suggested a risk of microbiological failure when they were used for CPE infections with high bacteria burden. IMPORTANCE The prevalence of infections caused by carbapenem-resistant Enterobacteriaceae is increasing worldwide. Currently, therapeutic options for metallo-ß-lactamase (MBL)-producing Enterobacteriaceae remain limited. We demonstrated that clinical metallo-ß-lactamase (MBL)-producing Enterobacteriaceae isolates were highly susceptible to cefiderocol (86.0%) and aztreonam-avibactam (ATM-AVI) (95.8%). However, inoculum effects on cefiderocol and ATM-AVI were observed for over 90% of susceptible carbapenemase-producing Enterobacteriaceae (CPE) isolates. Our findings highlight a potential risk of microbiological failure when using monotherapy with cefiderocol or ATM-AVI to treat severe CPE infection.