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1.
Ann Hematol ; 101(7): 1421-1434, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35451619

RESUMO

Congenital asplenia is a rare disorder commonly associated with other visceral and cardiac congenital anomalies. Isolated congenital asplenia is even less common than syndromic forms. The risk of severe bacterial infections associated with asplenia is the most concerning clinical implication and carries a significant mortality risk. Prophylactic measures against the clinical syndrome known as overwhelming postsplenectomy infections (OPSI) include vaccination, prophylactic and emergency antibiotics and health education including fever management and travel advice. This case series describes fourteen adults with congenital asplenia and polysplenia syndrome, most of whom were diagnosed incidentally as adults, and outlines the nature of their diagnosis, clinical phenotype, family history and key pathology findings.


Assuntos
Esplenopatias , Antibacterianos/uso terapêutico , Humanos , Síndrome , Vacinação
2.
Clin Infect Dis ; 73(11): e3912-e3920, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-32663248

RESUMO

BACKGROUND: Multiresistant organisms (MROs) pose a critical threat to public health. Population-based programs for control of MROs such as carbapenemase-producing Enterobacterales (CPE) have emerged and evaluation is needed. We assessed the feasibility and impact of a statewide CPE surveillance and response program deployed across Victoria, Australia (population 6.5 million). METHODS: A prospective multimodal intervention including active screening, carrier isolation, centralized case investigation, and comparative pathogen genomics was implemented. We analyzed trends in CPE incidence and clinical presentation, risk factors, and local transmission over the program's first 3 years (2016-2018). RESULTS: CPE case ascertainment increased over the study period to 1.42 cases/100 000 population, linked to increased screening without a concomitant rise in active clinical infections (0.45-0.60 infections/100 000 population, P = .640). KPC-2 infection decreased from 0.29 infections/100 000 population prior to intervention to 0.03 infections/100 000 population in 2018 (P = .003). Comprehensive case investigation identified instances of overseas community acquisition. Median time between isolate referral and genomic and epidemiological assessment for local transmission was 11 days (IQR, 9-14). Prospective surveillance identified numerous small transmission networks (median, 2; range, 1-19 cases), predominantly IMP and KPC, with median pairwise distance of 8 (IQR, 4-13) single nucleotide polymorphisms; low diversity between clusters of the same sequence type suggested genomic cluster definitions alone are insufficient for targeted response. CONCLUSIONS: We demonstrate the value of centralized CPE control programs to increase case ascertainment, resolve risk factors, and identify local transmission through prospective genomic and epidemiological surveillance; methodologies are transferable to low-prevalence settings and MROs globally.


Assuntos
Infecções por Enterobacteriaceae , Proteínas de Bactérias/genética , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/prevenção & controle , Genômica , Humanos , Estudos Prospectivos , Vitória , beta-Lactamases/genética
3.
BMC Infect Dis ; 21(1): 683, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261450

RESUMO

BACKGROUND: Third-generation cephalosporin-resistant Gram-negatives (3GCR-GN) and vancomycin-resistant enterococci (VRE) are common causes of multi-drug resistant healthcare-associated infections, for which gut colonisation is considered a prerequisite. However, there remains a key knowledge gap about colonisation and infection dynamics in high-risk settings such as the intensive care unit (ICU), thus hampering infection prevention efforts. METHODS: We performed a three-month prospective genomic survey of infecting and gut-colonising 3GCR-GN and VRE among patients admitted to an Australian ICU. Bacteria were isolated from rectal swabs (n = 287 and n = 103 patients ≤2 and > 2 days from admission, respectively) and diagnostic clinical specimens between Dec 2013 and March 2014. Isolates were subjected to Illumina whole-genome sequencing (n = 127 3GCR-GN, n = 41 VRE). Multi-locus sequence types (STs) and antimicrobial resistance determinants were identified from de novo assemblies. Twenty-three isolates were selected for sequencing on the Oxford Nanopore MinION device to generate completed reference genomes (one for each ST isolated from ≥2 patients). Single nucleotide variants (SNVs) were identified by read mapping and variant calling against these references. RESULTS: Among 287 patients screened on admission, 17.4 and 8.4% were colonised by 3GCR-GN and VRE, respectively. Escherichia coli was the most common species (n = 36 episodes, 58.1%) and the most common cause of 3GCR-GN infection. Only two VRE infections were identified. The rate of infection among patients colonised with E. coli was low, but higher than those who were not colonised on admission (n = 2/33, 6% vs n = 4/254, 2%, respectively, p = 0.3). While few patients were colonised with 3GCR- Klebsiella pneumoniae or Pseudomonas aeruginosa on admission (n = 4), all such patients developed infections with the colonising strain. Genomic analyses revealed 10 putative nosocomial transmission clusters (≤20 SNVs for 3GCR-GN, ≤3 SNVs for VRE): four VRE, six 3GCR-GN, with epidemiologically linked clusters accounting for 21 and 6% of episodes, respectively (OR 4.3, p = 0.02). CONCLUSIONS: 3GCR-E. coli and VRE were the most common gut colonisers. E. coli was the most common cause of 3GCR-GN infection, but other 3GCR-GN species showed greater risk for infection in colonised patients. Larger studies are warranted to elucidate the relative risks of different colonisers and guide the use of screening in ICU infection control.


Assuntos
Infecção Hospitalar , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli , Trato Gastrointestinal/microbiologia , Controle de Infecções , Unidades de Terapia Intensiva , Enterococos Resistentes à Vancomicina , Antibacterianos/farmacologia , Austrália/epidemiologia , Resistência às Cefalosporinas/genética , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Humanos , Controle de Infecções/métodos , Controle de Infecções/normas , Unidades de Terapia Intensiva/normas , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos Prospectivos , Enterococos Resistentes à Vancomicina/genética , Enterococos Resistentes à Vancomicina/isolamento & purificação
4.
Intern Med J ; 51(4): 565-570, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32092233

RESUMO

BACKGROUND: Invasive group A streptococcal (iGAS) infections are increasing worldwide with at-risk groups being children, pregnant women and the elderly. In 2017, there was a rise in iGAS cases in Victoria, prompting a Chief Health Officer advisory. AIMS: To describe the characteristics of patients with GAS bacteraemia admitted to a tertiary hospital. To compare at-risk groups in our population with those identified in the Victorian Government health alert. METHODS: Retrospective review of patients with GAS bacteraemia admitted between June 2014 and December 2017 at a tertiary hospital in Melbourne, Victoria. RESULTS: Forty-three cases of GAS bacteraemia occurred. Average age was 52 years (range 15-88 years) with 63% male. Average length of stay was 14 days (range 0-72 days) and all-cause mortality occurred in two (5%) cases. Twelve (28%) patients presented with shock, 11 (26%) required intensive care unit admission and 13 (30%) surgical intervention. A history of intravenous drug use was documented in 18 (42%) cases and was commonly complicated by bone or joint involvement or thrombosis. Typing of GAS samples identified 22 different emm-types. CONCLUSION: GAS bacteraemia resulted in significant morbidity and prolonged hospitalisation. In contrast to the at-risk groups identified in the Victorian Government health advisory, the commonest risk group in this series were people who inject drugs and most commonly middle-aged men. Invasive GAS should be considered if a person who injects drugs presents with acute severe sepsis.


Assuntos
Bacteriemia , Infecções Estreptocócicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes , Centros de Atenção Terciária , Vitória/epidemiologia , Adulto Jovem
5.
Artigo em Inglês | MEDLINE | ID: mdl-30617095

RESUMO

Coagulase-negative staphylococci (CoNS) represent one of the major causes of health care- and medical device-associated infections. Emerging antimicrobial resistance has complicated the treatment of systemic infections caused by CoNS. Here, we describe the prevalence of antimicrobial resistance in clinical CoNS strains from a tertiary care hospital over a 4-year period, and we observed a significant increase in resistance to daptomycin. Notably, Staphylococcus capitis accounted for the majority of these daptomycin-resistant (DAP-R) CoNS. To further investigate the mechanisms of daptomycin resistance in CoNS, daptomycin-susceptible clinical strains of S. capitis and Staphylococcus epidermidis underwent in vitro daptomycin exposure to generate DAP-R CoNS mutants. Unlike that seen with Staphylococcus aureus, alteration of cell surface charge was not observed in the DAP-R CoNS strains, but biofilm formation was compromised. Whole-genome sequencing analysis of the DAP-R CoNS strains identified single nucleotide polymorphisms (SNPs) in walKR, the essential two-component regulatory system controlling cell wall biogenesis. PCR and sequencing of walK and walR from 17 DAP-R CoNS clinical isolates identified seven nonsynonymous mutations. The results were confirmed by the recreation of the walK SNP in S. epidermidis, which resulted in reduced susceptibility to daptomycin and vancomycin. This study highlights the significance of CoNS in evolving daptomycin resistance and showed that walKR is shared among the staphylococcal species and is involved in antibiotic resistance development. Notably, we did not observe mutations in genes responsible for phospholipid biosynthesis or an altered cell surface charge, suggesting that reduced daptomycin susceptibility in CoNS may emerge in a fashion distinct from that in S. aureus.


Assuntos
Antibacterianos/farmacologia , Daptomicina/farmacologia , Farmacorresistência Bacteriana/genética , Staphylococcus capitis/genética , Staphylococcus epidermidis/genética , Substituição de Aminoácidos/genética , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Infecção Hospitalar/microbiologia , Histidina Quinase/genética , Humanos , Testes de Sensibilidade Microbiana , Polimorfismo de Nucleotídeo Único/genética , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus capitis/efeitos dos fármacos , Staphylococcus capitis/isolamento & purificação , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/isolamento & purificação , Centros de Atenção Terciária , Vancomicina/farmacologia
6.
Intern Med J ; 49(3): 373-379, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30091232

RESUMO

BACKGROUND: Nocardiosis has historically been reported in immunocompromised patients, but Australian epidemiological and antimicrobial susceptibility data are limited. AIM: To describe the epidemiology, diagnosis and initial treatment of nocardiosis in an Australian tertiary hospital over 7 years. METHODS: In this retrospective study, all positive cultures for Nocardia species from any site isolated at the Alfred Hospital, Melbourne, between 1 January 2010 and 31 December 2016 were identified, and corresponding laboratory data and medical records reviewed. RESULTS: Sixty-eight non-duplicate isolates were identified from 67 patients. Common predisposing factors were chronic lung disease (38/67; 57%), organ, particularly lung, transplantation (13/67; 19%) and solid organ malignancy (6/67; 9%); 12% (8/67) of patients had no identifiable systemic risk factors. Seventy-nine percent (53/67) of patients had pulmonary nocardiosis only. Nocardia nova was the most commonly isolated species (20/68; 29%). In 48% (32/67) of patients, Nocardia species were isolated only on specific mycobacterial media. All tested species were susceptible to sulfamethoxazole-trimethoprim and amikacin, with the majority (58/63; 92%) susceptible to imipenem. All-cause mortality rates at 6 and 12 months where data were available were 15% (10/66 patients) and 22% (14/64 patients) respectively. CONCLUSION: In the largest Australian series in 25 years, nocardiosis predominantly affected patients with chronic lung disease or impaired cell-mediated immunity. A significant proportion of organisms from pulmonary sites were isolated on mycobacterial culture media only, suggesting that its use may improve yield. Isolates remain highly susceptible to sulfamethoxazole-trimethoprim, amikacin and imipenem, while other agents should be used only after confirmation of in vitro susceptibility.


Assuntos
Antibacterianos/uso terapêutico , Nocardiose/tratamento farmacológico , Nocardiose/epidemiologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Humanos , Pneumopatias/complicações , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/microbiologia , Nocardia , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Adulto Jovem
7.
Clin Infect Dis ; 67(4): 557-561, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29471470

RESUMO

Background: Overwhelming post-splenectomy infection (OPSI) is a serious complication of asplenia. Clinical guidelines recommend numerous measures to reduce the risk of OPSI, but awareness and adherence to preventative measures are generally poor. We aimed to determine whether a registry for asplenic/hyposplenic patients was associated with a reduction in the incidence of infection with encapsulated bacteria. Methods: We performed a retrospective cohort study of asplenic/hyposplenic patients in the state of Victoria, Australia, who registered with Spleen Australia from 2003 through 2014. Spleen Australia provides education, clinical guidance, and annual vaccination reminders to registrants and their healthcare providers. We compared the incidence of infection with Streptococcus pneumoniae, Haemophilus influenzae type B (Hib), and Neisseria meningitidis before and after registration. Registry data were linked with Victorian notifiable disease data on invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD), and Hib between 2000 and 2014. Results: Twenty-seven cases of IPD and 1 of IMD occurred among 3221 registrants. No cases of Hib were reported. The rate of IPD/IMD was 150 per 100000 patient-years prior to registration and 36 per 100000 patient-years after registration; registration was associated with a 69% reduction in the risk of infection (incidence rate ratio, 0.31; 95% confidence interval, 0.12 to 0.83; P = .019). Based on the absolute reduction in incidence, we estimate that Spleen Australia prevents 5-6 invasive infections with encapsulated organisms annually among registrants. Conclusions: Systematic, long-term approaches to post-splenectomy care can significantly reduce the risk of infection with encapsulated organisms among individuals with asplenia/hyposplenism.


Assuntos
Infecções Bacterianas/prevenção & controle , Sistema de Registros , Baço/anormalidades , Esplenectomia/efeitos adversos , Adulto , Feminino , Infecções por Haemophilus/prevenção & controle , Haemophilus influenzae tipo b , Humanos , Incidência , Masculino , Infecções Meningocócicas/prevenção & controle , Pessoa de Meia-Idade , Neisseria meningitidis , Infecções Pneumocócicas/prevenção & controle , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Baço/microbiologia , Streptococcus pneumoniae , Vitória , Adulto Jovem
8.
Clin Infect Dis ; 67(2): 161-170, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29340588

RESUMO

Background: Klebsiella pneumoniae is a leading cause of extended-spectrum ß-lactamase (ESBL)-producing hospital-associated infections, for which elderly patients are at increased risk. Methods: We conducted a 1-year prospective cohort study, in which a third of patients admitted to 2 geriatric wards in a specialized hospital were recruited and screened for carriage of K. pneumoniae by microbiological culture. Clinical isolates were monitored via the hospital laboratory. Colonizing and clinical isolates were subjected to whole-genome sequencing and antimicrobial susceptibility testing. Results: K. pneumoniae throat carriage prevalence was 4.1%, rectal carriage 10.8%, and ESBL carriage 1.7%, and the incidence of K. pneumoniae infection was 1.2%. The isolates were diverse, and most patients were colonized or infected with a unique phylogenetic lineage, with no evidence of transmission in the wards. ESBL strains carried blaCTX-M-15 and belonged to clones associated with hospital-acquired ESBL infections in other countries (sequence type [ST] 29, ST323, and ST340). One also carried the carbapenemase blaIMP-26. Genomic and epidemiological data provided evidence that ESBL strains were acquired in the referring hospital. Nanopore sequencing also identified strain-to-strain transmission of a blaCTX-M-15 FIBK/FIIK plasmid in the referring hospital. Conclusions: The data suggest the major source of K. pneumoniae was the patient's own gut microbiome, but ESBL strains were acquired in the referring hospital. This highlights the importance of the wider hospital network to understanding K. pneumoniae risk and infection prevention. Rectal screening for ESBL organisms on admission to geriatric wards could help inform patient management and infection control in such facilities.


Assuntos
Portador Sadio/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Klebsiella pneumoniae/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/diagnóstico , Feminino , Serviços de Saúde para Idosos , Unidades Hospitalares , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
BMC Infect Dis ; 18(1): 511, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309313

RESUMO

BACKGROUND: Clinical studies and mathematical simulation suggest that active surveillance with contact isolation is associated with reduced vancomycin-resistant enterococci (VRE) prevalence compared to passive surveillance. Models using pre- and post-intervention data that account for the imperfect observation and serial dependence of VRE transmission events can better estimate the effectiveness of active surveillance and subsequent contact isolation; however, such analyses have not been performed. METHODS: A mathematical model was fitted to surveillance data collected pre- and post-implementation of active surveillance with contact isolation in the haematology-oncology ward. We developed a Hidden Markov Model to describe undetected and observed VRE colonisation/infection status based on the detection activities in the ward. Bayesian inference was used to estimate transmission rates. The effectiveness of active surveillance was assumed to be via increased detection and subsequent contact isolation of VRE positive patients. RESULTS: We estimated that 31% (95% credible interval: 0.33-85%) of the VRE transmissions were due to cross-transmission between patients. The ratio of transmission rates from patients with contact isolation versus those without contact isolation was 0.33 (95% credible interval: 0.050-1.22). CONCLUSIONS: The majority of the VRE acquisitions in the haematology-oncology ward was estimated to be due to background rates of VRE, rather than within ward patient to patient acquisition. The credible interval for cross-transmission was wide which results in a large degree of uncertainty in the estimates. Factors that could account for background VRE acquisition include endogenous acquisition from antibiotic selection pressure and VRE in the environment. Contact isolation was not significantly associated with reduced VRE transmission in settings where the majority of VRE acquisition was due to background acquisition, emphasising the need to identify and address the source of acquisition. As the credible interval for the ratio of VRE transmission in contact isolated versus non-contact isolated patients crossed 1, there is a probability that the transmission rate in contact isolation was not lower. Our finding highlights the need to optimise infection control measures other than active surveillance for VRE and subsequent contact isolation to reduce VRE transmission. Such measures could include antimicrobial stewardship, environmental cleaning, and hand hygiene.


Assuntos
Infecções por Bactérias Gram-Positivas/transmissão , Modelos Teóricos , Enterococos Resistentes à Vancomicina/isolamento & purificação , Teorema de Bayes , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Cadeias de Markov , Enterococos Resistentes à Vancomicina/patogenicidade
10.
Intern Med J ; 48(2): 204-206, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29415349

RESUMO

Given the long term sequelae of untreated neurosyphilis and insensitive tests to detect treponemes in the cerebrospinal fluid, questions regarding the utility of a lumbar puncture and cerebrospinal fluid analysis either to confirm or exclude neurosyphilis are raised.


Assuntos
Gerenciamento Clínico , Neurossífilis/diagnóstico , Neurossífilis/terapia , Treponema pallidum/isolamento & purificação , Australásia/epidemiologia , Testes Diagnósticos de Rotina/métodos , Humanos , Neurossífilis/epidemiologia , Sorodiagnóstico da Sífilis/métodos , Fatores de Tempo
11.
Clin Infect Dis ; 65(2): 208-215, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28369261

RESUMO

BACKGROUND: Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. Intensive care unit (ICU) patients are particularly at risk. Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of gut colonization and its contribution to infections are not well characterized. METHODS: We conducted a 1-year prospective cohort study in which 498 ICU patients were screened for rectal and throat carriage of K. pneumoniae shortly after admission. Klebsiella pneumoniae isolated from screening swabs and clinical diagnostic samples were characterized using whole genome sequencing and combined with epidemiological data to identify likely transmission events. RESULTS: Klebsiella pneumoniae carriage frequencies were estimated at 6% (95% confidence interval [CI], 3%-8%) among ICU patients admitted direct from the community, and 19% (95% CI, 14%-51%) among those with recent healthcare contact. Gut colonization on admission was significantly associated with subsequent infection (infection risk 16% vs 3%, odds ratio [OR] = 6.9, P < .001), and genome data indicated matching carriage and infection isolates in 80% of isolate pairs. Five likely transmission chains were identified, responsible for 12% of K. pneumoniae infections in ICU. In sum, 49% of K. pneumoniae infections were caused by the patients' own unique strain, and 48% of screened patients with infections were positive for prior colonization. CONCLUSIONS: These data confirm K. pneumoniae colonization is a significant risk factor for infection in ICU, and indicate ~50% of K. pneumoniae infections result from patients' own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.


Assuntos
Portador Sadio/epidemiologia , Infecção Hospitalar/microbiologia , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Unidades de Terapia Intensiva , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Adulto , Idoso , Antibacterianos/farmacologia , Portador Sadio/tratamento farmacológico , Portador Sadio/microbiologia , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Feminino , Variação Genética , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/transmissão , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Faringe/microbiologia , Estudos Prospectivos , Reto/microbiologia , Fatores de Risco
12.
Intern Med J ; 47(8): 848-855, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27925427

RESUMO

People with asplenia/hyposplenism are at increased risk of fulminant sepsis, which carries a high mortality rate. A range of preventive measures is recommended although there is ongoing evidence that knowledge of and adherence to these strategies is poor. There have been significant changes in recommended vaccinations since the previously published recommendations in 2008. We provide current recommendations to help Australian and New Zealand clinicians in the prevention of sepsis in patients with asplenia and hyposplenia. The guideline includes Australian epidemiological data, preferred diagnostic techniques and recommendations for optimal antimicrobial prophylaxis and vaccination protocols.


Assuntos
Antibacterianos/uso terapêutico , Guias de Prática Clínica como Assunto , Sepse/prevenção & controle , Baço/anormalidades , Esplenectomia/efeitos adversos , Esplenopatias/complicações , Vacinação/normas , Austrália/epidemiologia , Humanos , Incidência , Nova Zelândia/epidemiologia , Sepse/epidemiologia , Sepse/etiologia , Esplenectomia/estatística & dados numéricos , Esplenopatias/tratamento farmacológico , Esplenopatias/epidemiologia , Esplenopatias/cirurgia
13.
Antimicrob Agents Chemother ; 59(4): 2365-73, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25645855

RESUMO

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Endocardite/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Candidíase/microbiologia , Candidíase/mortalidade , Estudos de Coortes , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/mortalidade , Equinocandinas/uso terapêutico , Endocardite/microbiologia , Endocardite/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
14.
Semin Respir Crit Care Med ; 36(5): 756-66, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26398541

RESUMO

In recent decades, sporotrichosis, caused by thermally dimorphic fungi Sporothrix schenckii complex, has become an emerging infection in many parts of the world. Pulmonary infection with S. schenckii still remains relatively uncommon, possibly due to underrecognition. Pulmonary sporotrichosis presents with distinct clinical and radiological patterns in both immunocompetent and immunocompromised hosts and can often result in significant morbidity and mortality despite treatment. Current understanding regarding S. schenckii biology, epidemiology, immunopathology, clinical diagnostics, and treatment options has been evolving in the recent years with increased availability of molecular sequencing techniques. However, this changing knowledge has not yet been fully translated into a better understanding of the clinical aspects of pulmonary sporotrichosis, as such current management guidelines remain unsupported by high-level clinical evidence. This article examines recent advances in the knowledge of sporotrichosis and its application to the difficult challenges of managing pulmonary sporotrichosis.


Assuntos
Antifúngicos/uso terapêutico , Pneumopatias Fúngicas/microbiologia , Sporothrix , Esporotricose/diagnóstico , Esporotricose/epidemiologia , Gerenciamento Clínico , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/diagnóstico por imagem , Radiografia , Fatores de Risco
16.
Antimicrob Agents Chemother ; 58(4): 2334-43, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24514086

RESUMO

Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10- to 28-day therapy for platelet nadirs of <100 ×10(9)/liter. The risk for toxicity did not differ noticeably between 14 and 28 days of therapy and was significantly higher for patients with lower baseline platelet counts. Due to the increased risk of toxicity after longer durations of linezolid therapy and large between-patient variability, close monitoring of patients for development of toxicity is important. Dose individualization based on plasma linezolid concentration profiles and platelet counts should be considered to minimize linezolid-associated thrombocytopenia. Overall, oxazolidinone therapy over 5 to 7 days even at relatively high doses was predicted to be as safe as 10-day therapy of 600 mg linezolid every 12 h.


Assuntos
Acetamidas/farmacocinética , Antibacterianos/farmacocinética , Oxazolidinonas/farmacocinética , Acetamidas/efeitos adversos , Acetamidas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/sangue , Feminino , Humanos , Linezolida , Masculino , Pessoa de Meia-Idade , Oxazolidinonas/efeitos adversos , Oxazolidinonas/sangue , Estudos Prospectivos , Adulto Jovem
17.
J Antimicrob Chemother ; 69(7): 1972-80, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24710025

RESUMO

BACKGROUND: Long-term care facilities (LTCFs) are a potentially important reservoir of multidrug-resistant (MDR) organisms; however, limited data exist. METHODS: A point-prevalence study was conducted in four co-located LTCFs in Australia. Nasal and rectal swabs were cultured for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and MDR Gram-negative bacilli (GNB). Molecular typing and resistance detection were performed. Risk factors for colonization with an MDR organism were determined using a nested case-control study. RESULTS: Consent was obtained from 115 (85%) of 136 eligible participants. Forty-one (36%) residents carried at least one type of MDR organism. The prevalence was 16% MRSA (n = 18), 6% VRE (n = 7) and 21% MDR GNB [n = 24; including extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 12) and Acinetobacter baumannii (n = 6)]. The majority of ESBL-producing E. coli and A. baumannii were clonal. Current wound management [adjusted OR (AOR) 8.81 (95% CI 2.78-27.94), P < 0.001], medical device in situ [AOR 5.58 (95% CI 1.34-23.32), P = 0.018] and pressure ulcer [AOR 3.69 (95% CI 1.06-12.86), P = 0.04] were independent risk factors for MDR organism colonization. Advanced dementia [AOR 3.54 (95% CI 1.23-10.23), P = 0.02] and prolonged antibiotic use [AOR 2.95 (95% CI 1.01-8.60), P = 0.047] were independently associated with MRSA colonization, whilst current wound management [AOR 15.59 (95% CI 4.85-50.10), P < 0.001] and fluoroquinolone use [AOR 4.27 (95% CI 1.20-15.25), P = 0.025] were risk factors for MDR GNB colonization. CONCLUSIONS: LTCFs are an important reservoir of MDR organisms, with person-to-person transmissions being a potential issue. We have identified several predictors of colonization with MDR organisms, allowing a more targeted management of high-risk residents.


Assuntos
Infecções Bacterianas/epidemiologia , Portador Sadio/epidemiologia , Farmacorresistência Bacteriana Múltipla , Assistência de Longa Duração , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Infecções Bacterianas/microbiologia , Portador Sadio/microbiologia , Estudos de Casos e Controles , Feminino , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Mucosa Nasal/microbiologia , Prevalência , Reto/microbiologia , Medição de Risco
18.
BMC Infect Dis ; 14: 353, 2014 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-24973797

RESUMO

BACKGROUND: Enterococci are a major cause of healthcare-associated infection. In Australia, vanB vancomycin-resistant enterococci (VRE) is the predominant genotype. There are limited data on the factors linked to vanB VRE bacteraemia. This study aimed to identify factors associated with vanB VRE bacteraemia, and compare them with those for vancomycin-susceptible enterococci (VSE) bacteraemia. METHODS: A case-case-control study was performed in two tertiary public hospitals in Victoria, Australia. VRE and VSE bacteraemia cases were compared with controls without evidence of enterococcal bacteraemia, but may have had infections due to other pathogens. RESULTS: All VRE isolates had vanB genotype. Factors associated with vanB VRE bacteraemia were urinary catheter use within the last 30 days (OR 2.86, 95% CI 1.09-7.53), an increase in duration of metronidazole therapy (OR 1.65, 95% CI 1.17-2.33), and a higher Chronic Disease Score specific for VRE (OR 1.70, 95% CI 1.05-2.77). Factors linked to VSE bacteraemia were a history of gastrointestinal disease (OR 2.29, 95% CI 1.05-4.99) and an increase in duration of metronidazole therapy (OR 1.23, 95% CI 1.02-1.48). Admission into the haematology/oncology unit was associated with lower odds of VSE bacteraemia (OR 0.08, 95% CI 0.01-0.74). CONCLUSIONS: This is the largest case-case-control study involving vanB VRE bacteraemia. Factors associated with the development of vanB VRE bacteraemia were different to those of VSE bacteraemia.


Assuntos
Bacteriemia/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Resistência a Vancomicina , Adulto , Idoso , Austrália/epidemiologia , Bacteriemia/microbiologia , Estudos de Casos e Controles , Enterococcus/patogenicidade , Feminino , Genótipo , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Enterococos Resistentes à Vancomicina/patogenicidade , Vitória
19.
Heart Lung Circ ; 23(3): 234-41, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24268488

RESUMO

BACKGROUND: Ventricular assist device (VAD) implantation has become an effective option for patients with severe heart failure. However, device-related infections remain a significant problem. The aim of this study was to describe the incidence and microbiological aetiology of bacteraemia in patients with VADs, and to assess the impact of bacteraemia on clinical outcomes. METHODS: A retrospective study was conducted of patients having VAD implantation at the Alfred Hospital (Melbourne, Australia) from October 1990 to July 2009. Medical records and microbiology databases were reviewed. Patients who were supported with a VAD for 72h or more were evaluated for demographic data, VAD type, the occurrence of bacteraemia and clinical outcomes. RESULTS: During the 19-year period, 135 VAD patients (89 Thoratec PVAD, 10 Novacor, and 36 Ventrassist) supported for a total duration of 17,304 (median 74) support days were included. Sixty-one patients (45%) developed VAD-associated bacteraemia, an incidence of 5.6 episodes per 1000 support days. The incidence of bacteraemia per 1000 days of support was similar for the three devices used: Thoratec PVAD, Novacor and Ventrassist VADs (7.8±0.8, 5.2±1.5 and 3.4±0.5, respectively, p=0.74). Staphylococcus aureus was the most common pathogen (25%). The rates of death on device, survival to transplant, recovery with explant and outcomes after transplantation, including 30-day mortality, median survival time and incidence of cerebrovascular accidents were not significantly impacted upon by bacteraemia. CONCLUSIONS: Bacteraemia is common in VAD patients. However, the incidence of VAD-associated bacteraemia is independent of device type and with aggressive antimicrobial therapy; clinical outcomes need not be affected by the bacteraemia.


Assuntos
Antibacterianos/administração & dosagem , Bacteriemia , Coração Auxiliar/efeitos adversos , Prontuários Médicos , Infecções Estafilocócicas , Staphylococcus aureus , Adolescente , Adulto , Idoso , Bacteriemia/tratamento farmacológico , Bacteriemia/etiologia , Bacteriemia/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/mortalidade , Taxa de Sobrevida
20.
J Infect Public Health ; 17(4): 657-662, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430719

RESUMO

BACKGROUND: COVID-19 has had enormous impact on health and social systems, with stringent public health measures enacted across Australia. The virus itself disproportionately affects immunocompromised individuals including people without functioning spleens. We thus sought to characterise the psychological and physical impact of COVID-19 and such measures upon this oft-neglected patient group. METHODS: Adults ≥ 18 years old identified from the Spleen Australia (SA) database were invited to participate in an online survey in November to December 2021 to assess the impact of the COVID-19 pandemic. Stata (v17, StataCorps, Texas, USA) was used to conduct descriptive and frequency analyses. RESULTS: 2864 respondents were surveyed. The majority were female (1473/2838, 51.9%), Australian-born (2257/2835, 79.6%), and living in Victoria (1755/2822, 62.2%). The largest age group was 61-70 years-old (841/2858, 29.4%). Trauma was the commonest reason for asplenia (826/2724, 30.3%). Respondents reported the pandemic reduced their ability to visit a GP (753/2864, 26.3%), access food (153/2864, 5.3%), medications (179/2864, 6.3%) or spleen-specific vaccines (120/2864, 4.2%), maintain relationships (503/2864, 17.6%), or care for children (127/2864, 4.4%). 84.8% of participants reported at least one impact of COVID, including negative physical health (1463/2864, 51.1%), mental health (733/2864, 25.6%) and financial repercussions (509/2864, 17.8%). 96.9% (2743/2831) had received at least one dose of COVID-19 vaccines. CONCLUSIONS: Overall, we found detailed evidence of the negative psychological and physical impacts of the pandemic upon this cohort. We recommend that providers consider people without functioning spleens as requiring extra social and psychological support in circumstances such as the COVID-19 pandemic.


Assuntos
COVID-19 , Baço , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Adolescente , Austrália/epidemiologia , COVID-19/epidemiologia , Vacinas contra COVID-19 , Pandemias
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