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1.
Eur J Orthop Surg Traumatol ; 34(2): 815-821, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37713001

RESUMO

PURPOSE: Empiric antibiotic strategies in the treatment of fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis should be based on local microbiological antibiograms. This study aims to describe the microbiology and review the antibiogram profiles of bacterial isolates from patients undergoing surgical treatment for non-spinal orthopaedic infections, to identify the most appropriate empiric antibiotic strategy. METHODS: A retrospective review was performed of all cases of non-spinal orthopaedic infections treated surgically from 1 January 2018 to 31 December 2018. The National Health Laboratory Service microbiology database was used to identify all intra-operative microbiological specimens obtained from orthopaedic patients, and data were correlated with the orthopaedic surgical database. Cases were divided into fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis. Antibiotic susceptibility data were used to predict the efficacy of different empiric antibiotic regimens. RESULTS: A total of 107 cases were included in the study; 184 organisms were cultured. Overall, the most common organism cultured was Staphylococcus aureus (25%) followed by Acinetobacter baumannii (9%), Enterococcus faecalis (7%) and Enterobacter cloacae (5%). Across all categories the oral antibiotic combination with the highest effectiveness (81%) would have been a combination of co-trimoxazole, ciprofloxacin and amoxicillin. The most effective intravenous antibiotic combination would have been either piperacillin-tazobactam, amikacin and vancomycin or meropenem and vancomycin; 90% of tested isolates were susceptible to either of these combinations. CONCLUSION: Antibiogram profiles can serve to guide to empiric antibiotic choice in the management of different categories of non-spinal orthopaedic infections.


Assuntos
Artrite Infecciosa , Ortopedia , Osteomielite , Adulto , Humanos , Antibacterianos/uso terapêutico , Vancomicina , Osteomielite/tratamento farmacológico , Artrite Infecciosa/tratamento farmacológico , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
2.
Semin Respir Crit Care Med ; 43(1): 75-96, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35172360

RESUMO

The prevalence of suspected or proven infections in critically ill patients is high, with a substantial attributable risk to in-hospital mortality. Coordinated guidance and interventions to improve the appropriate microbiological assessment for diagnostic and therapeutic decisions are therefore pivotal. Conventional microbiology follows the paradigm of "best practice" of specimen selection and collection, governed by laboratory processing and standard operating procedures, and informed by the latest developments and trends. In this regard, the preanalytical phase of a microbiological diagnosis is crucial since inadequate sampling may result in the incorrect diagnosis and inappropriate management. In addition, the isolation and detection of contaminants interfere with multiple intensive care unit (ICU) processes, which confound the therapeutic approach to critically ill patients. To facilitate bedside enablement, the microbiology laboratory should provide expedited feedback, reporting, and interpretation of results. Compared with conventional microbiology, novel rapid and panel-based diagnostic strategies have the clear advantages of a rapid turnaround time, the detection of many microorganisms including antimicrobial resistant determinants and thus promise substantial improvements in health care. However, robust data on the clinical evaluation of rapid diagnostic tests in presumed sepsis, sepsis and shock are extremely limited and more rigorous intervention studies, focusing on direct benefits for critically ill patients, are pivotal before widespread adoption of their use through the continuum of ICU stay. Advocating the use of these diagnostics without firmly establishing which patients would benefit most, how to interpret the results, and how to treat according to the results obtained, could in fact be counterproductive with regards to diagnostic "best practice" and antimicrobial stewardship. Thus, for the present, they may supplement but not yet supplant conventional microbiological assessments.


Assuntos
Gestão de Antimicrobianos , Sepse , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Sepse/diagnóstico , Sepse/tratamento farmacológico
3.
Muscle Nerve ; 57(3): 371-379, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28561925

RESUMO

INTRODUCTION: We studied the evolution of sensory neuropathy after antiretroviral therapy (ART) in human immunodeficiency virus-infected South Africans. METHODS: Enrolment commenced before ART with 6-monthly follow-ups for 24 months. Symptomatic distal sensory polyneuropathy (SDSP) was defined as one symptom and sign. Symptom/sign scores were compared between visits. RESULTS: We enrolled 184 participants. Pre-ART, 16% had SDSP. After 18 months of ART, pain prevalence decreased in those with pre-ART SDSP (odds ratio [OR], 0.09; 95% confidence interval [95%CI], 0.03-0.29). Symptoms improved in 50% ever experiencing pain (mean improvement = 4.5 on 11-point scale). Participants SDSP-free pre-ART developed SDSP at a rate of 18 per 100 person-years. After 24 months (n = 102), 18% had SDSP. Stavudine (60% of cohort) did not predict incident SDSP, but associated with increased prevalence of reduced/absent reflexes at 18 months (OR, 2.24; 95% CI, 1.08-4.65). DISCUSSION: Painful symptoms improved during ART. Evolving sensory neuropathy was due to increasing small and large fiber dysfunction. Muscle Nerve 57: 371-379, 2018.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Polineuropatias/tratamento farmacológico , Adulto , Fatores Etários , Progressão da Doença , Feminino , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/etiologia , Polineuropatias/fisiopatologia
4.
Int J Infect Dis ; 142: 106907, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38141961

RESUMO

OBJECTIVES: Sub-Saharan African (SSA) countries are severely impacted by antimicrobial resistance (AMR). Due to gaps in access to diagnostics in SSA, the true extent of AMR remains unknown. This diagnostic gap affects patient management and leads to significant antimicrobial overuse. This review explores how point-of-care (POC) testing for pathogen identification and AMR may be used to close the diagnostic gap in SSA countries. METHODS: A narrative review exploring current clinical practice and novel developments in the field of POC testing for infectious diseases and AMR. RESULTS: POC assays for identification of various pathogens have been successfully rolled out in SSA countries. While implementation studies have mostly highlighted impressive test performance of POC assays, there is limited data on the impact of implementation on clinical outcomes and cost-effectiveness. We did not encounter local studies of host-directed POC assays relevant to AMR. Novel POC assays using real-time polymerase chain reaction, isothermal amplification, microfluidics, and other technologies are in various stages of development. CONCLUSIONS: Available literature shows that POC testing for AMR applications is implementable in SSA and holds the potential to reduce the diagnostic gap. Implementation will require effective regulatory pathways, incorporation of POC testing in clinical and laboratory guidelines, and adequate value capture in existing health financing models.


Assuntos
Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Testes Imediatos , África Subsaariana , Sistemas Automatizados de Assistência Junto ao Leito
5.
Lancet Microbe ; : 100902, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39146948

RESUMO

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR.

6.
PLoS One ; 19(5): e0303846, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820372

RESUMO

There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18%) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52% were female. Overall FujiLAM sensitivity was 54·4% (95% CI: 48·7-60·0), overall specificity was 85·2% (83·2-87·0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26·5% (95% CI: 17·4%-38·0%) to 73·2% (60·4%-83·0%), and 75·0 (65·0%-82·9%) to 96·5 (92·1%-98·5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423).


Assuntos
Infecções por HIV , Tuberculose , Humanos , Feminino , Masculino , Adulto , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Estudos Prospectivos , Tuberculose/diagnóstico , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Mycobacterium tuberculosis/isolamento & purificação , Lipopolissacarídeos/urina , Escarro/microbiologia
7.
PLOS Glob Public Health ; 4(8): e0003554, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39106267

RESUMO

In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe and characterise the extent of the pandemic, as well as elucidate protection conferred by prior exposure. We conducted repeated cross-sectional serosurveys (July 2020 -November 2021) using residual samples from patients from Cape Town, South Africa, sent for routine laboratory studies for non-COVID-19 conditions. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses. Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.19% (95% confidence interval [CI] 37.23-41.19) in July 2020 to 67.8% (95%CI 66.31-69.25) in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Using COVID-19 hospital admission and death data at the Provincial Health Data Centre, antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19 disease. In low-income communities, where diagnostic testing capacity is often limited, surveillance systems dependent on them will underestimate the true extent of an outbreak. Rapidly conducted seroprevalence studies can play an important role in addressing this.

8.
Infect Drug Resist ; 16: 5427-5432, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37638062

RESUMO

Purpose: Carbapenem-resistant bacteria (CRB) pose a major health risk to patients in intensive care units (ICU) across African hospitals. There are hardly any data about the role of hospital sinks as reservoirs of CRB in resource-poor African settings. Furthermore, the specific within-sink location of the highest concentration of pathogens and the role of splash back as a transmission mechanism remains poorly clarified. Methods: We swabbed ICU sluice room sinks in a tertiary hospital in Cape Town, South Africa. Swabs were taken from four different parts of the sluice room sinks (tap-opening, trap, below the trap, and u-bend). Dilutions were prepared and plated on carbapenem-infused agar. Colonies were identified and drug resistance profiles were determined using a biochemical analyser. To evaluate the potential transmission from the sink, similar plates were placed at fixed distances from the sink when the tap was turned on and off. Results: CRB were isolated from the trap, water interface below the trap, and the u-bend (the latter harboured the highest density of CRB species). Five CRB, resistant to at least 7 antibiotic classes, were isolated including Pseudomonas, Klebsiella, Citrobacter, Serratia, and Providencia. CRB could be cultured from droplets that fell on agar-containing plates placed at a varying distance from the trap. Conclusion: There is a higher density of CRB in the u-bend of ICU sluice room sinks which can act as a potential source of transmission. The data inform targeted CRB transmission-interruption strategies in resource-poor settings.

9.
Lancet Microbe ; 4(10): e822-e829, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37739001

RESUMO

BACKGROUND: Xpert MTB/RIF Ultra (Ultra) is a widely used rapid front-line tuberculosis and rifampicin-susceptibility testing. Mycobacterium Growth Indicator Tube (MGIT) 960 liquid culture is used as an adjunct but is vulnerable to contamination. We aimed to assess whether Ultra can be used on to-be-discarded contaminated cultures. METHODS: We stored contaminated MGIT960 tubes (growth-positive, acid-fast bacilli [AFB]-negative) originally inoculated at a high-volume laboratory in Cape Town, South Africa, to diagnose patients with presumptive pulmonary tuberculosis. Patients who had no positive tuberculosis results (smear, Ultra, or culture) at contamination detection and had another, later specimen submitted within 3 months of the contaminated specimen were selected. We evaluated the sensitivity and specificity of Ultra on contaminated growth from the first culture for tuberculosis (next-available non-contaminated culture result reference standard) and rifampicin resistance (vs MTBDRplus on a later isolate). We calculated potential time-to-diagnosis improvements and also evaluated the immunochromatographic MPT64 TBc assay. FINDINGS: Between June 1 and Aug 31, 2019, 36 684 specimens from 26 929 patients were processed for diagnostic culture. 2402 (7%) cultures from 2186 patients were contaminated. 1068 (49%) of 2186 patients had no other specimen submitted. After 319 exclusions, there were 799 people with at least one repeat specimen submitted; of these, we included in our study 246 patients (31%) with a culture-positive repeat specimen and 429 patients (54%) with a culture-negative repeat specimen. 124 patients (16%) with a culture-contaminated repeat specimen were excluded. When Ultra was done on the initial contaminated growth, sensitivity was 89% (95% CI 84-94) for tuberculosis and 95% (75-100) for rifampicin-resistance detection, and specificity was 95% (90-98) for tuberculosis and 98% (93-100) for rifampicin-resistance detection. If our approach were used the day after contamination detection, the time to tuberculosis detection would improve by a median of 23 days (IQR 13-45) and provide a result in many patients who had none. MPT64 TBc had a sensitivity of 5% (95% CI 0-25). INTERPRETATION: Ultra on AFB-negative growth from contaminated MGIT960 tubes had high sensitivity and specificity, approximating WHO criteria for sputum test target product performance and exceeding drug susceptibility testing. Our approach could mitigate negative effects of culture contamination, especially when repeat specimens are not submitted. FUNDING: The European & Developing Countries Clinical Trials Partnership, National Institutes of Health.


Assuntos
Antibióticos Antituberculose , Mycobacterium tuberculosis , Tuberculose , Estados Unidos , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Mycobacterium tuberculosis/genética , Antibióticos Antituberculose/farmacologia , Antibióticos Antituberculose/uso terapêutico , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética , África do Sul , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico
10.
S Afr J Infect Dis ; 37(1): 398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35815226

RESUMO

Background: Microbiological confirmation of pulmonary tuberculosis (PTB) in children is a well-documented challenge. This study evaluated Xpert Mycobacterium Tuberculosis (MTB)/Rifampicin (RIF) Ultra (Ultra) and mycobacterial cultures in routine clinical care at a tertiary paediatric hospital. Methods: Children treated for PTB and who had at least one respiratory specimen investigated by Ultra and mycobacterial culture before tuberculosis (TB) treatment was commenced were included. The findings of this retrospective study were summarised using descriptive and inferential statistics. Results: A total of 174 children were included. The median age was 2.5 years. Microcytic anaemia, airway compression, cavitary disease and miliary TB were significantly observed in children with microbiologically confirmed TB (cTB). Tuberculosis was microbiologically confirmed in 93 (53.4%) children. The positive yield from testing the first respiratory specimens was 68/174 (39.1%) on Ultra and 82/174 (47.1%) on combined Ultra and mycobacterial culture. In the subset of children (n = 70) tested with Ultra on two sequential respiratory specimens, the incremental yield from the second specimen was 30.3%. In the subset of children (n = 16) tested with Ultra on three sequential respiratory specimens, the incremental yield from the second and third specimens was 16.7% and 0.0%, respectively. When Ultra and mycobacterial culture results were combined, the incremental yield in children who had two sequential respiratory specimens tested was 24.4% and 3.1% on Ultra and mycobacterial culture, respectively. Conclusion: Ultra and mycobacterial culture on a single respiratory specimen resulted in a high microbiological yield. Ultra-testing on a second respiratory specimen increased the yield of microbiologically cTB. Additional diagnostic testing may require further study.

11.
Int J Infect Dis ; 117: 74-86, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35077877

RESUMO

BACKGROUND: Outbreaks of community-acquired Pseudomonas aeruginosa are typically small and localized. We investigated an increase in community-acquired infections with P. aeruginosa in Cape Town, South Africa. METHODS: Cases were defined as P. aeruginosa isolated from any clinical sample, and "wild-type" as those susceptible to all antibiotics tested. The residential addresses of community-acquired wild-type cases were mapped. Whole-genome sequencing and multilocus sequence typing were used to determine clonality and identify virulence genes. A clinical study in a subset of patients with bloodstream infection compared demographic and clinical characteristics between sequence types (STs). RESULTS: The outbreak lasted 10 months from December 2016 to September 2017 with 3,321 documented cases. At the peak, cases reached 2.3-fold baseline rates. Cases were distributed widely across the city. Multilocus ST 303 was predominant during the outbreak. A total of 51 virulence genes were differentially present in ST303 compared with other STs, including genes involved in biofilm formation, iron uptake, and gut penetration. CONCLUSION: The investigation confirmed a citywide outbreak of P. aeruginosa. We identified a predominant outbreak-associated clone, ST303, which harbored genes that could contribute to virulence and survival in adverse environmental conditions such as those associated with drought.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Surtos de Doenças , Humanos , Tipagem de Sequências Multilocus , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/genética , África do Sul/epidemiologia
12.
medRxiv ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36523408

RESUMO

Background: In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure. Methods: We conducted repeated cross-sectional serosurveys (July 2020 - November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity. Findings: Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). Interpretation: The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19. Funding: Wellcome Trust, National Health Laboratory Service, the Division of Intramural Research, NIAID, NIH (ADR) and Western Cape Government Health.

13.
S Afr J Infect Dis ; 36(1): 244, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485501

RESUMO

BACKGROUND: Culture remains the diagnostic standard for Streptococcus pneumoniae bacteraemia but is limited by time to identification, prior antibiotics and bacterial autolysis. Culture-independent methods for detecting S. pneumoniae include PCR and antigen tests. We evaluated an antigen test on blood culture broth for the rapid detection of S. pneumoniae bacteraemia. METHOD: We collected 212 signal-positive blood cultures, with gram-positive cocci in pairs, chains or with uncertain morphology. The BinaxNOW S. pneumoniae urinary antigen test, Gram stain, culture and lytA PCR were performed on all samples. Diagnostic accuracy of the antigen test and Gram stain with gram-positive cocci in pairs were compared with culture, polymerase chain reaction (PCR) and the composite of culture and PCR. RESULTS: Streptococcus pneumoniae was isolated in 26% of samples, 66% cultured other gram-positive organisms and 8% of samples had no growth. Sensitivity and negative predictive values of the antigen test were 100%, specificity and positive predictive values were 87% - 88% and 76% - 81%, but increased to 93% - 96% and 96% - 98% when applied to subsets with gram-positive cocci in pairs, or history compatible with respiratory illness or meningitis. Sensitivity (69% - 75%) and specificity (81%) of Gram stain (gram-positive cocci in pairs) were lower than the antigen test even when applied to the same subsets. CONCLUSION: Accurate and rapid diagnosis of S. pneumoniae bacteraemia is challenging. Specificity of this antigen test is limited by cross-reactivity with other gram-positive organisms, but could be improved if Gram stain morphology and clinical history are available. The antigen test is a useful adjunct for rapid diagnosis of S. pneumoniae bacteraemia.

14.
Int J Infect Dis ; 105: 688-694, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33684562

RESUMO

BACKGROUND: Cycloserine, or its structural analogue terizidone, has been associated with neuropsychiatric toxicity (psychosis, depression, and neuropathy). Prospective clinical data on the incidence of and risk factors for neuropsychiatric toxicity in TB patients treated with cycloserine are limited. METHODS: A prospective evaluation of neuropsychiatric toxicity was performed using validated screening tools in patients with multidrug-resistant tuberculosis treated with terizidone. Cox proportional hazard modelling was performed to explore the effects of clinical variables and measures of cycloserine pharmacokinetics in plasma. RESULTS: A total 144 participants were recruited: 86 were male and 58 were female; their median age was 35.7 years and 91 (63%) were HIV-infected. Fifty-five (38%) participants developed at least one neuropsychiatric event (30 cases per 100 person-months): 50 (35%) neuropathy, 14 (10%) depression, and 11 (8%) psychosis. Neuropathy was independently associated with cycloserine clearance ((adjusted hazard ratio 0.34 (aHR), P = 0.03)) and high-dose pyridoxine (200 mg vs 150 mg daily, aHR: 2.79, P = 0.01). CONCLUSIONS: A high incidence of early neuropsychiatric toxicity was observed in this cohort of patients treated with terizidone. Cycloserine clearance and higher doses of pyridoxine are associated with incident or worsening peripheral neuropathy.


Assuntos
Antibióticos Antituberculose/efeitos adversos , Antibióticos Antituberculose/farmacocinética , Ciclosserina/efeitos adversos , Ciclosserina/farmacocinética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Antibióticos Antituberculose/administração & dosagem , Ciclosserina/administração & dosagem , Depressão/induzido quimicamente , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Isoxazóis/efeitos adversos , Isoxazóis/farmacocinética , Masculino , Pessoa de Meia-Idade , Oxazolidinonas/efeitos adversos , Oxazolidinonas/farmacocinética , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos , Psicoses Induzidas por Substâncias/epidemiologia , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
15.
Afr J Lab Med ; 9(1): 988, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33392048

RESUMO

BACKGROUND: There is a shortage of data on the accuracy of statistical methods for the prediction of N-acetyltransferase 2 (NAT2) haplotypes in the mixed ancestry population of the Western Cape. OBJECTIVE: This study aimed to identify the NAT2 haplotypes and assess the accuracy of PHASE version 2.1.1 in assigning NAT2 haplotypes to a mixed ancestry population from the Western Cape. METHODS: This study was conducted between 2013 and 2016. The NAT2 gene was amplified and sequenced from the DNA of 100 self-identified mixed ancestry participants. Haplotyping was performed by molecular and computational techniques. Agreement was assessed between the two techniques. RESULTS: Haplotypes were assigned to 93 samples, of which 67 (72%) were ambiguous. Haplotype prediction by PHASE demonstrated 94.6% agreement (kappa 0.94, p < 0.001) with those assigned using molecular techniques. Five haplotype combinations (from 10 chromosomes) were incorrectly predicted, four of which were flagged as uncertain by the PHASE software. Only one resulted in the assignment of an incorrect acetylation phenotype (intermediate to slow), although the software flagged this for further analysis. The most common haplotypes were NAT2*4 (28%) followed by NAT2*5B (27.4%), NAT2*6A (21.5%) and NAT2*12A (7.5%). Four rare single nucleotide variants (c.589C>T, c.622T>C, c.809T>C and c.387C>T) were detected. CONCLUSION: PHASE accurately predicted the phenotype in 92 of 93 samples (99%) from genotypic data in our mixed ancestry sample population, and is therefore a suitable alternative to molecular methods to individualise isoniazid therapy in this high burden tuberculosis setting.

16.
J Infect ; 77(6): 509-515, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30217659

RESUMO

OBJECTIVES: Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests are insensitive. Recent reports suggest simple modifications to conventional cerebrospinal fluid (CSF) Ziehl-Neelsen (ZN) staining may greatly improve sensitivity. We sought to define the performance of modified and conventional ZN stain for TBM diagnosis. METHODS: In hospitals in Vietnam, South Africa and Indonesia we conducted a prospective study of modified ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF in adults with suspected TBM. RESULTS: A total of 618 individuals were enrolled across 3 sites. Compared with the TBM clinical diagnostic gold standard for research (definite probable or possible TBM), sensitivity of conventional ZN and modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the difference between tests), compared with culture 31.8% and Xpert 25.1%. Using culture as a reference, sensitivities of conventional ZN, modified ZN with cytospin, and Xpert were 66.4%, 67.5%, and 72.3%, respectively. Higher CSF volume and lactate, and lower CSF:blood glucose ratio were independently associated with microbiologically confirmed TBM. CONCLUSIONS: Modified ZN stain does not improve diagnosis of TBM. Currently available tests are insensitive, but testing large CSF volumes improves performance. New diagnostic tests for TBM are urgently required.


Assuntos
Técnicas Bacteriológicas , Testes Diagnósticos de Rotina/métodos , Técnicas de Diagnóstico Molecular , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/diagnóstico , Adulto , Líquido Cefalorraquidiano/microbiologia , Corantes , Feminino , Humanos , Indonésia , Internacionalidade , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , Sensibilidade e Especificidade , África do Sul , Coloração e Rotulagem , Tuberculose Meníngea/microbiologia , Vietnã
17.
Lancet Neurol ; 12(3): 295-309, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23415569

RESUMO

Peripheral nerve disorders are associated with all stages of HIV infection. Distal sensory polyneuropathy is characterised by often-disabling pain that is difficult to treat. It is prevalent in both high-income and low-income settings. In low-income settings, use of potentially neurotoxic antiretrovirals, which are inexpensive and widely available, contributes substantially to incidence. Research has focused on identification of factors that predict risk of distal sensory polyneuropathy and elucidation of the multifactorial mechanisms behind pathogenesis. Sensorimotor polyneuropathies and polyradiculopathies are less frequent than distal sensory polyneuropathy, but still occur in low-income settings and have potentially devastating consequences. However, many of these diseases can be treated successfully with a combination of antiretroviral and immune-modulating therapies. To distinguish between peripheral nerve disorders that have diverse, overlapping, and frequently atypical presentations can be challenging; a framework based on a clinicoanatomical approach might assist in the diagnosis and management of such disorders.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Terapia Antirretroviral de Alta Atividade/métodos , Quimioterapia Combinada/métodos , Infecções por HIV/tratamento farmacológico , Humanos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico
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