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1.
Intern Med J ; 54(1): 43-53, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37926861

RESUMO

BACKGROUND: Severe COVID-19 causes acute inflammation, which is complicated by venous thromboembolism events (VTE). However, it is unclear if VTE risk has evolved over time since the COVID-19 outbreak. AIMS: To determine markers of thrombo-inflammation and rates of symptomatic VTE in patients hospitalised for COVID-19 in a metropolitan hospital in Sydney, Australia. METHODS: A retrospective, single-centre, cohort study was performed by reviewing electronic medical records of consecutive patients admitted to Royal Prince Alfred Hospital between March 2020 and September 2021. This period included three waves of COVID-19 outbreaks in Australia with the ancestral, alpha and delta variants. Standard coagulation assays and inflammatory markers were recorded over 4 weeks. RESULTS: A total of 205 patients were consecutively admitted during the study period. Activated partial thromboplastin time, neutrophil count and C-reactive protein (CRP) were significantly increased in patients hospitalised in the intensive care unit (ICU) compared with non-ICU patients. The use of anti-inflammatory medication increased in 2021 compared with 2020. The mortality rate was 7.3% in our cohort. Ninety-four per cent of patients received anticoagulation with 6.3% of patients developing VTE. CONCLUSION: We observed lower rates of VTE compared to the internationally reported rate for the same period. We conclude that in the setting of controlled hospital admission rate and standard anticoagulation guidelines, COVID-19 resulted in similar thrombo-inflammatory response and VTE rates over the first 1.5 years of the pandemic.


Assuntos
COVID-19 , Tromboembolia Venosa , Humanos , COVID-19/complicações , Anticoagulantes/uso terapêutico , SARS-CoV-2 , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , Inflamação/epidemiologia
2.
Intern Med J ; 54(4): 613-619, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37929813

RESUMO

BACKGROUND: Nocardia is a ubiquitous saprophyte capable of causing human disease. Disease is primarily respiratory or cutaneous, usually acquired via inhalation or inoculation. Under the influence of environmental and host factors, Nocardia incidence and species distribution demonstrate geographical variation. AIMS: To examine for differences in Nocardia incidence within Western Australia (WA) and analyse species distribution in the context of prior published studies. To analyse antibiogram data from a nationwide passive antimicrobial resistance surveillance program. METHODS: Retrospective extraction of laboratory data for Western Australian Nocardia isolates over a 21-year period. Analysis of Nocardia antimicrobial susceptibility testing data submitted to the Australian Passive Antimicrobial Resistance Surveillance (APAS) program between 2005 and 2022. RESULTS: Nine hundred sixty WA isolates were identified, giving an annual incidence of 3.03 per 100 000 population with apparent latitudinal variation. The four most common species identified within WA and amongst APAS isolates were N. nova, N. cyriacigeorgica, N. brasiliensis and N. farcinica. APAS data demonstrated that all species exhibited high rates of susceptibility to linezolid (100%) and trimethoprim-sulfamethoxazole (98%). Amikacin (>90% susceptibility for all species except N. transvalensis) was the next most active parenteral agent, superior to both carbapenems and third-generation cephalosporins. Susceptibility to oral antimicrobials (other than linezolid) demonstrated significant interspecies variation. CONCLUSIONS: We demonstrate geographical variation in the distribution of Nocardia incidence. Four species predominate in the Australian setting, and nationwide data confirm a high in vitro susceptibility to trimethoprim-sulphamethoxazole and linezolid, justifying their ongoing role as part of first-line empiric therapy.

3.
J Antimicrob Chemother ; 72(4): 1103-1108, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28364558

RESUMO

Objectives: Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. Methods: These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™. Results: A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance. Conclusions: We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidemia/epidemiologia , Candidemia/microbiologia , Anidulafungina , Austrália/epidemiologia , Azóis/farmacologia , Candida/classificação , Candida/genética , Candida glabrata/efeitos dos fármacos , Candida glabrata/genética , Candida glabrata/isolamento & purificação , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/genética , Candida tropicalis/isolamento & purificação , Caspofungina , Farmacorresistência Fúngica/genética , Equinocandinas/farmacologia , Feminino , Fluconazol/farmacologia , Humanos , Incidência , Lipopeptídeos/farmacologia , Masculino , Micafungina , Testes de Sensibilidade Microbiana/métodos , Análise de Sequência de DNA/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Triazóis/farmacologia , Voriconazol/farmacologia
4.
Clin Infect Dis ; 62(2): 173-180, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26349552

RESUMO

BACKGROUND: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. METHODS: In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. RESULTS: We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. CONCLUSIONS: Combining an antistaphylococcal ß-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).


Assuntos
Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Floxacilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/farmacologia , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Bacteriemia/microbiologia , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Estudos Prospectivos , Infecções Estafilocócicas/microbiologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
5.
Clin Microbiol Rev ; 25(2): 362-86, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22491776

RESUMO

Staphylococcus aureus bacteremia (SAB) is an important infection with an incidence rate ranging from 20 to 50 cases/100,000 population per year. Between 10% and 30% of these patients will die from SAB. Comparatively, this accounts for a greater number of deaths than for AIDS, tuberculosis, and viral hepatitis combined. Multiple factors influence outcomes for SAB patients. The most consistent predictor of mortality is age, with older patients being twice as likely to die. Except for the presence of comorbidities, the impacts of other host factors, including gender, ethnicity, socioeconomic status, and immune status, are unclear. Pathogen-host interactions, especially the presence of shock and the source of SAB, are strong predictors of outcomes. Although antibiotic resistance may be associated with increased mortality, questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin. Optimal management relies on starting appropriate antibiotics in a timely fashion, resulting in improved outcomes for certain patient subgroups. The roles of surgery and infectious disease consultations require further study. Although the rate of mortality from SAB is declining, it remains high. Future international collaborative studies are required to tease out the relative contributions of various factors to mortality, which would enable the optimization of SAB management and patient outcomes.


Assuntos
Bacteriemia/diagnóstico , Bacteriemia/mortalidade , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/patogenicidade , Humanos , Prognóstico , Fatores de Risco , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
6.
BMJ Open ; 14(5): e079144, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719318

RESUMO

INTRODUCTION: The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections. METHODS AND ANALYSES: This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison. ETHICS AND DISSEMINATION: The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.


Assuntos
Gonorreia , Vacinas Meningocócicas , Neisseria gonorrhoeae , Humanos , Gonorreia/prevenção & controle , Gonorreia/epidemiologia , Northern Territory/epidemiologia , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/uso terapêutico , Neisseria gonorrhoeae/imunologia , Austrália do Sul/epidemiologia , Estudos Observacionais como Assunto , Feminino
8.
BMC Infect Dis ; 12: 249, 2012 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-23043704

RESUMO

BACKGROUND: Investigations of the impact of ethnicity and socio-economic status on incidence and outcomes of Staphylococcus aureus bacteraemia are limited. METHODS: We prospectively identified all S. aureus bacteraemia episodes in the Australian New Zealand Cooperative on Outcomes in Staphylococcal Sepsis cohort study between 2007 and 2010. We calculated population level incidence rates using regional postcodes and stratified the analysis by ethnicity, age and socio-economic status indexes. RESULTS: There were 7539 episodes of S. aureus bacteraemia with an annual incidence of 11·2 episodes per 100,000 population. The age-adjusted incidence in the Indigenous population was 62·5 per 100,000 population with an age standardized incidence rate ratio of 5·9 compared to the non-Indigenous population and an incidence rate ratio of 29.2 for community-associated methicillin-resistant S. aureus (MRSA). Populations in the lowest socio-economic status quintile had an increased S. aureus bacteraemia incidence compared to higher quintiles. However, there was a disparity between Indigenous and non-Indigenous populations across all socio-economic status quintiles. The lower 30-day mortality for Indigenous patients (7%) compared to non-Indigenous patients (17%) was explained by differences in age. CONCLUSIONS: Indigenous Australians suffer from a higher rate of S. aureus bacteraemia than non-Indigenous Australians, particularly for community-associated MRSA. Ethnicity and socio-economic status had little impact on subsequent mortality, with other host factors contributing more significantly.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/patogenicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
J Clin Microbiol ; 49(4): 1489-94, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21270232

RESUMO

The best screening method for detecting heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) remains unclear. Using population analysis profiling utilizing the area under the concentration-time curve (PAP-AUC) as the gold standard, we screened 458 consecutive methicillin-resistant S. aureus (MRSA) bloodstream isolates to determine the most accurate and cost-effective testing strategy to detect the presence of heteroresistance. All isolates were also tested using the macromethod Etest (MET) and glycopeptide resistance detection (GRD) Etest. The MIC was determined by several methods, including standard vancomycin Etest, vancomycin broth microdilution (BMD), and Vitek2 testing. Fifty-five (12%) hVISA and 4 (1%) VISA isolates were detected by PAP-AUC. Compared to PAP-AUC, the sensitivities and specificities of MET, GRD Etest, BMD (using a MIC cutoff of ≥ 2 mg/liter), and standard vancomycin Etest (using a MIC cutoff of ≥ 2 mg/liter) were 89 and 55%, 71 and 94%, 82 and 97%, and 71 and 94%, respectively. Combination testing increased the overall testing accuracy by reducing the number of false-positive results. Cost was determined predominately by the number of PAP-AUC runs required following a screening assay. The most cost-effective strategy was BMD (using a MIC cutoff of ≥ 2 µg/ml) as a standalone assay or in combination with PAP-AUC, provided that BMD testing was batched. GRD Etest remained an alternative, with 71% of hVISA isolates detected. Prevalence influenced both cost and test accuracy, with results remaining unchanged for hVISA prevalences of up to 25%. Implementation of any testing strategy would therefore be dependent on balancing cost with accuracy in a given population and clinical context.


Assuntos
Bacteriemia/diagnóstico , Sangue/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/diagnóstico , Resistência a Vancomicina , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Análise Custo-Benefício , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana/economia , Testes de Sensibilidade Microbiana/métodos , Sensibilidade e Especificidade , Infecções Estafilocócicas/microbiologia , Vancomicina/farmacologia
10.
Access Microbiol ; 3(8): 000248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34888479

RESUMO

BACKGROUND: Infections due to metallo-beta-lactamase (MBL)-producing organisms are becoming a significant problem, and antibiotic treatment options are limited. Aztreonam inhibits MBLs, and its use in combination with ceftazidime-avibactam (CAZ-AVI-AZT) to inhibit other beta-lactamases shows promise. METHODS: A 45-year-old woman suffered from recurrent and sustained MBL (blaIMP-4)+ Enterobacter cloacae complex bacteraemia from an undrainable biliary source, and had failed nine alternative antibiotic regimens over a 5-month period. The 10th episode was successfully treated with CAZ-AVI-AZT, and she has had no further relapses. Three of the isolates underwent whole-genome sequencing (WGS) on the MiSeq platform and were analysed with the Nullarbor pipeline. RESULTS: A layered Etest method for synergy between CAZ-AVI and aztreonam demonstrated an MIC of 2 mg l-1 for the combination. Isolates were identified by WGS as Enterobacter hormaechei subsp. oharae . All three of the isolates had blaTEM-4 ESBL, blaOXA-1 and blaACT-25. Two of the carbapenem-resistant isolates contained blaIMP-4. CONCLUSION: While aztreonam inhibits MBLs, MBL-positive isolates often express other beta-lactamase enzymes. Avibactam inhibits ESBLs and other beta-lactamases, and its use in this case possibly contributed to therapeutic success due to inhibition of the concomitant blaTEM-4 in the isolates. This case demonstrates that phenotypic antimicrobial susceptibility testing (layered Etests for synergy), backed up by WGS, can produce results that allow tailored antimicrobial therapy in difficult infections. This case adds to the evidence for using CAZ-AVI-AZT in serious MBL infections.

11.
Emerg Infect Dis ; 14(7): 1141-3, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18598643

RESUMO

Entamoeba histolytica is a pathogenic ameba that has recently been recognized as an emerging pathogen in men who have sex with men (MSM) in Asia-Pacific countries where it is not endemic, i.e., Japan, Taiwan, and Republic of Korea. We report locally acquired invasive amebiasis in Sydney, Australia, exclusively in MSM.


Assuntos
Disenteria Amebiana/complicações , Infecções por HIV/complicações , Homossexualidade Masculina , Abscesso Hepático Amebiano/complicações , Adulto , Animais , Antiparasitários/uso terapêutico , Disenteria Amebiana/tratamento farmacológico , Humanos , Abscesso Hepático Amebiano/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , New South Wales
12.
Am J Trop Med Hyg ; 76(3): 549-52, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17360882

RESUMO

A prospective, comparative study of the prevalence of enteric protozoa was determined among human immunodeficiency virus (HIV)- positive and HIV-negative men who have sex with men (MSM) in Sydney, Australia. A total of 1,868 patients submitted stool specimens; 1,246 were from MSM (628 HIV positive and 618 HIV positive) and 622 from non-MSM were examined over a 36-month period. A total of 651 (52.2%) stool specimens from MSM were positive for protozoa compared with 85 (13%) from non-MSM. There was a significant difference in the prevalence of Blastocystis hominis, Endolimax nana, Entamoeba histolytica/dispar complex, Entamoeba hartmanni, Iodamoeba butschlii, and Enteromonas hominis detected between MSM and non-MSM (P<0.001). The only notable difference between HIV-negative and HIV-positive MSM was that HIV-infected MSM were found to more likely have a Cryptosporidium parvum infection. Entamoeba histolytica was found in 3 patients, E. dispar in 25, and E. moshkovskii in 17, all of whom were MSM. When compared with a control group, MSM were significantly more likely to harbor intestinal protozoa and have multiple parasites present. The results of this study show high rates of enteric parasites persist in MSM and highlight the importance of testing for intestinal parasites in MSM. This is the first report of E. moshkovskii from MSM.


Assuntos
Eucariotos/isolamento & purificação , Fezes/parasitologia , Soropositividade para HIV/parasitologia , Homossexualidade Masculina , Animais , Blastocystis hominis/isolamento & purificação , Cryptosporidium/isolamento & purificação , Entamoeba histolytica/isolamento & purificação , Humanos , Masculino , Prevalência , Estudos Prospectivos
13.
Intensive Care Med ; 43(10): 1464-1475, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28733718

RESUMO

PURPOSE: To describe the current standards of care and major recent advances with regard to antimicrobial resistance (AMR) and to give a prospective overview for the next 30 years in this field. METHODS: Review of medical literature and expert opinion were used in the development of this review. RESULTS: There is undoubtedly a large clinical and public health burden associated with AMR in ICU, but it is challenging to quantify the associated excess morbidity and mortality. In the last decade, antibiotic stewardship and infection prevention and control have been unable to prevent the rapid spread of resistant Gram-negative bacteria (GNB), in particular carbapenem-resistant Pseudomonas aeruginosa (and other non-fermenting GNB), extended-spectrum ß-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE). The situation appears more optimistic currently for Gram-positive, where Staphylococcus aureus, and particularly methicillin-resistant S. aureus (MRSA), remains a cardinal cause of healthcare-associated infections worldwide. Recent advancements in laboratory techniques allow for a rapid identification of the infecting pathogen and antibiotic susceptibility testing. Their impact can be particularly relevant in settings with prevalence of MDR, since they may guide fine-tuning of empirically selected regimen, facilitate de-escalation of unnecessary antimicrobials, and support infection control decisions. Currently, antibiotics are the primary anti-infective solution for patients with known or suspected MDR bacteria in intensive care. Numerous incentives have been provided to encourage researchers to work on alternative strategies to reverse this trend and to provide a means to treat these pathogens. Although some promising antibiotics currently in phase 2 and 3 of development will soon be licensed and utilized in ICU, the continuous development of an alternative generation of compounds is extremely important. There are currently several promising avenues available to fight antibiotic resistance, such as faecal microbiota, and phage therapy.


Assuntos
Gestão de Antimicrobianos/tendências , Infecção Hospitalar/mortalidade , Farmacorresistência Bacteriana/efeitos dos fármacos , Previsões , Controle de Infecções/tendências , Antibacterianos/efeitos adversos , Saúde Global/tendências , Política de Saúde/tendências , Humanos , Unidades de Terapia Intensiva , Microbiota , Terapia por Fagos , Padrões de Prática Médica
14.
J Neurol Sci ; 378: 55-58, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28566179

RESUMO

INTRODUCTION: Neurosyphilis producing basal meningitis presenting as sequential transient cranial nerve palsies was well recognized before the antibiotic era. OBJECTIVE: To report two patients presenting with acute unilateral peripheral vestibulopathy due to syphilitic basal meningitis. RESULTS: In Case 1 basal meningitis occurred early in the secondary phase of the infection, in Case 2 in the late latent phase. The diagnosis was not made immediately in either case; in Case 1 after previous presentation with increasing hearing loss and then with facial palsy and then a subsequent presentation with optic neuritis; in Case 2 after investigation for possible lymphoma. CONCLUSION: Syphilitic basal meningitis in either the secondary or in the latent phase can present as acute unilateral peripheral vestibulopathy with transient involvement of the facial or auditory nerve.


Assuntos
Neurossífilis/complicações , Neurossífilis/diagnóstico , Neuronite Vestibular/diagnóstico , Neuronite Vestibular/etiologia , Idoso , Diagnóstico Tardio , Nervo Facial/diagnóstico por imagem , Humanos , Masculino , Testes de Função Vestibular
15.
Int J Rheum Dis ; 20(9): 1277-1285, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28480561

RESUMO

AIM: Sarcoidosis is a multisystem granulomatous disease. This condition has a documented association with the diagnosis of melanoma and can be induced in melanoma patients receiving anti-neoplastic therapy. We evaluated a case series of melanoma patients who developed immunotherapy-induced sarcoidosis. METHODS: Three patients with melanoma (n = 1 resected Stage III, n = 2 metastatic) treated with anti-programmed cell death (PD)-1 antibody therapy at two institutions developed biopsy-proven sarcoidosis. We used mass cytometry to determine expression of the relevant chemokine receptors (CR) by peripheral blood mononuclear cells for two of the three patients who developed sarcoidosis and 13 melanoma patients who did not. Blood samples were collected before receiving PD-1 checkpoint inhibitor therapy. RESULTS: Immunophenotypic analysis demonstrated abnormally high numbers of circulating Th17.1 (CCR6+ CCR4- CXCR3+ CCR10- ) cells prior to commencing PD-1 checkpoint inhibitor therapy in five of 15 melanoma patients, including both the patients who developed sarcoidosis during the course of therapy. CONCLUSION: Our findings support prior literature implicating Th17.1 cells in the pathogenesis of sarcoidosis. However, we demonstrate these findings in patients with melanoma prior to administration of checkpoint therapy and before the onset of clinically symptomatic sarcoidosis. The identification of elevated Th17.1 cells in melanoma patients who have not developed sarcoidosis may reflect the established association between melanoma and sarcoidosis. With some patients receiving these agents over a prolonged period, the clinical course of immunotherapy-induced sarcoidosis is uncertain.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Imunofenotipagem , Imunoterapia/efeitos adversos , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Sarcoidose Pulmonar/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Células Th17/efeitos dos fármacos , Corticosteroides/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Feminino , Humanos , Masculino , Melanoma/sangue , Melanoma/imunologia , Melanoma/secundário , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Receptor de Morte Celular Programada 1/imunologia , Sarcoidose Pulmonar/sangue , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Células Th17/imunologia , Células Th17/metabolismo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
Trials ; 17: 170, 2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-27029920

RESUMO

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20-50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal ß-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia. METHODS/DESIGN: We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal ß-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint. DISCUSSION: Key potential advantages of adding anti-staphylococcal ß-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02365493 . Registered 24 February 2015.


Assuntos
Antibacterianos/uso terapêutico , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , beta-Lactamas/uso terapêutico , Antibacterianos/efeitos adversos , Austrália , Cefazolina/uso terapêutico , Protocolos Clínicos , Cloxacilina/uso terapêutico , Daptomicina/uso terapêutico , Quimioterapia Combinada , Floxacilina/uso terapêutico , Humanos , Israel , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Nova Zelândia , Projetos de Pesquisa , Singapura , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Fatores de Tempo , Resultado do Tratamento , Vancomicina/uso terapêutico , beta-Lactamas/efeitos adversos
17.
Int J Antimicrob Agents ; 48(4): 453-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27562696

RESUMO

Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre(®) YeastOne(®) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and amphotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of ≤0.25 mg/L, followed by posaconazole and itraconazole at ≤1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of ≤0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing individual patient isolates to guide therapy. The Sensititre(®) YeastOne(®) offers a practical alternative to the reference methodology for susceptibility testing of moulds.


Assuntos
Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Fungos/isolamento & purificação , Micoses/microbiologia , Austrália , Humanos , Testes de Sensibilidade Microbiana
18.
Pediatr Dev Pathol ; 18(1): 30-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25361230

RESUMO

Parvovirus B19 infection causes 5% to 15% of cases of nonimmune hydrops fetalis. The aim of our study was to evaluate the use of immunohistochemistry in diagnosing parvovirus infection in fetal and placental tissue during routine fetal and perinatal autopsies. Histology slides of 20 cases of confirmed parvovirus infection were reviewed, and immunohistochemistry was applied to selected blocks of fetal and placental tissue. Immunohistochemistry was positive in all 20 cases, and histologic viral inclusions were seen in 19 cases. Immunohistochemical staining was closely correlated with histology and was more sensitive than histology in detecting virally infected cells, especially in autolyzed tissue. All cases also had confirmatory evidence of parvovirus infection by polymerase chain reaction of fetal liver and positive maternal serology, where it was available. We conclude that parvovirus immunohistochemistry is a reliable method for diagnosing parvovirus infection, especially in autolyzed tissue where histologic assessment may be suboptimal.


Assuntos
Feto/patologia , Hidropisia Fetal/virologia , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/patologia , Placenta/patologia , DNA Viral/metabolismo , Bases de Dados Factuais , Edema/patologia , Feminino , Morte Fetal , Humanos , Hidropisia Fetal/patologia , Imuno-Histoquímica , Recém-Nascido , Masculino , Prontuários Médicos , Parvovirus , Reação em Cadeia da Polimerase , Gravidez
19.
Artigo em Inglês | MEDLINE | ID: mdl-26798556

RESUMO

OBJECTIVE: There is a lack of information about the prevalence of gastrointestinal illnesses in Australia. Current disease surveillance systems capture only a few pathogens. The aim of this study is to describe the epidemiology of infectious gastrointestinal illnesses in Sydney, Australia. METHODS: A retrospective cross-sectional study of patients with gastrointestinal symptoms who visited tertiary public hospitals in Sydney was conducted between 2007 and 2010. Patients with diarrhoea or loose stools with an enteric pathogen detected were identified. Demographic, clinical and potential risk factor data were collected from their medical records. Measures of association, descriptive and inferential statistics were analysed. RESULTS: In total, 1722 patients were included in this study. Campylobacter (22.0%) and Clostridium difficile (19.2%) were the most frequently detected pathogens. Stratified analysis showed that rotavirus (22.4%), norovirus (20.7%) and adenovirus (18.1%) mainly affected children under 5 years; older children (5-12 years) were frequently infected with Campylobacter spp. (29.8%) and non-typhoid Salmonella spp. (24.4%); infections with C. difficile increased with age.Campylobacter and non-typhoid Salmonella spp. showed increased incidence in summer months (December to February), while rotavirus infections peaked in the cooler months (June to November). DISCUSSION: This study revealed that gastrointestinal illness remains a major public health issue in Sydney. Improvement of current disease surveillance and prevention and control measures are required. This study emphasizes the importance of laboratory diagnosis of enteric infections and the need for better clinical data collection to improve management of disease risk factors in the community.


Assuntos
Infecções Bacterianas/epidemiologia , Gastroenterite/epidemiologia , Viroses/epidemiologia , Adolescente , Adulto , Idoso , Infecções Bacterianas/microbiologia , Criança , Pré-Escolar , Estudos Transversais , Diarreia/epidemiologia , Feminino , Gastroenterite/microbiologia , Gastroenterite/virologia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , New South Wales/epidemiologia , Estudos Retrospectivos , Viroses/virologia , Adulto Jovem
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