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Initial Antituberculous Regimen with Better Drug Penetration into Cerebrospinal Fluid Reduces Mortality in HIV Infected Patients with Tuberculous Meningitis: Data from an HIV Observational Cohort Study  [PDF]
Gerardo Alvarez-Uria,Manoranjan Midde,Raghavakalyan Pakam,Praveen Kumar Naik
Tuberculosis Research and Treatment , 2013, DOI: 10.1155/2013/242604
Abstract: Tuberculous meningitis (TM) is the deadliest form of tuberculosis. Nearly two-thirds of HIV infected patients with TM die, and most deaths occur within one month. Current treatment of TM involves the use of drugs with poor penetration into the cerebro-spinal fluid (CSF). In this study, we present the mortality before and after implementing a new antituberculous regimen (ATR) with a higher drug penetration in CSF than the standard ATR during the initial treatment of TM in an HIV cohort study. The new ATR included levofloxacin, ethionamide, pyrazinamide, and a double dose of rifampicin and isoniazid and was given for a median of 7 days (interquartile range 6–9). The new ATR was associated with an absolute 21.5% (95% confidence interval (CI), 7.3–35.7) reduction in mortality at 12 months. In multivariable analysis, independent factors associated with mortality were the use of the standard ATR versus the new ATR (hazard ratio 2.05; 95% CI, 1.2–3.5), not being on antiretroviral therapy, low CD4 lymphocyte counts, and low serum albumin levels. Our findings suggest that an intensified initial ATR, which likely results in higher concentrations of active drugs in CSF, has a beneficial effect on the survival of HIV-related TM. 1. Introduction In 2011, there were 8.7 million incident cases of tuberculosis (13% of them in HIV infected patients) and 1.4 million deaths from tuberculosis (30% of them in HIV infected patients) [1]. With 25% mortality in non-HIV infected patients and 67% in HIV infected patients, tuberculous meningitis has the highest mortality among all forms of tuberculosis [2]. Moreover, tuberculous meningitis is more common in HIV infected patients and can comprise up to 19% of all cases of HIV-related tuberculosis [3, 4]. Currently, treatment of tuberculous meningitis involves the same drugs and doses as other forms of tuberculosis [5–7]. While isoniazid and pyrazinamide have good cerebrospinal fluid (CSF) penetration, rifampicin concentration in CSF may not reach the minimal inhibitory concentration for tuberculosis, and ethambutol and streptomycin have poor CSF penetration [2, 8]. Among second line drugs, levofloxacin, ethionamide and cycloserine have good penetration in CSF [8–10]. In a phase 2 randomized controlled trial investigating the safety of moxifloxacin and a higher intravenous dose of rifampicin during the first two weeks of treatment of tuberculous meningitis, the use of a higher dose of rifampicin was associated with a survival benefit [11]. These data suggest that increasing the CSF penetration of the initial treatment of
Presentation and Outcome of Tuberculous Meningitis in a High HIV Prevalence Setting  [PDF]
Suzaan Marais,Dominique J. Pepper,Charlotte Schutz,Robert J. Wilkinson,Graeme Meintjes
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020077
Abstract: Mycobacterium tuberculosis is a common, devastating cause of meningitis in HIV-infected persons. Due to international rollout programs, access to antiretroviral therapy (ART) is increasing globally. Starting patients with HIV-associated tuberculous meningitis (TBM) on ART during tuberculosis (TB) treatment may increase survival in these patients. We undertook this study to describe causes of meningitis at a secondary-level hospital in a high HIV/TB co-infection setting and to determine predictors of mortality in patients with TBM.
Cryptococcal meningitis among HIV infected patients  [cached]
Manoharan G,Padmavathy B,Vasanthi S,Gopalte R
Indian Journal of Medical Microbiology , 2001,
Abstract: Cryptococcal meningitis is an emerging opportunistic infection among HIV infected patients and an important cause of mortality among these patients. The incidence of cryptococcal meningitis varies from place to place. A total of 31 specimens of CSF out of 89 samples processed from known HIV positive cases yielded Cryptococcus neoformans during the period of 3 years. C.neoformans was the most common opportunistic pathogen isolated from CSF samples of these patients with an incidence of 34.8%
Factors associated to the positive cerebrospinal fuid culture in the tuberculous meningitis
Puccioni-Sohler, Marzia;Brand?o, Carlos Otávio;
Arquivos de Neuro-Psiquiatria , 2007, DOI: 10.1590/S0004-282X2007000100011
Abstract: central nervous system involvement is the most common neurological complication in the course of tuberculosis. the lack of rapid and sensitive tests delays the early diagnosis. here, we retrospectively reviewed the cerebrospinal fluid (csf) examination of 30 patients with tuberculous meningitis confirmed by bacteriological tests (culture and/or polymerase chain reaction). the purpose of the present study was to determine the csf parameters associated to the positive csf culture for mycobacterium tuberculosis in tuberculous meningitis. we found higher frequency of positive csf culture in patients infected with hiv as well in patients with high number of neutrophils and high protein content (characteristic in the early or acute-stage patients), which suggests that the positive culture found in these patients may be associated with the presence of high bacillary load in csf occurring in these stages.
Clinical and Microbiological Features of HIV-Associated Tuberculous Meningitis in Vietnamese Adults  [PDF]
M. Estee Torok, Tran Thi Hong Chau, Pham Phuong Mai, Nguyen Duy Phong, Nguyen Thi Dung, Ly Van Chuong, Sue J. Lee, M. Caws, Menno D. de Jong, Tran Tinh Hien, Jeremy J. Farrar
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001772
Abstract: Methods The aim of this prospective, observational cohort study was to determine the clinical and microbiological features, outcome, and baseline variables predictive of death, in Vietnamese adults with HIV-associated tuberculous meningitis (TBM). 58 patients were admitted to the Hospital for Tropical Diseases in Ho Chi Minh City and underwent routine clinical and laboratory assessments. Treatment was with standard antituberculous therapy and adjunctive dexamethasone; antiretroviral therapy was not routinely available. Patients were followed up until the end of TB treatment or death. Results The median symptom duration was 11 days (range 2–90 days), 21.8% had a past history of TB, and 41.4% had severe (grade 3) TBM. The median CD4 count was 32 cells/mm3. CSF findings were as follows: median leucocyte count 438×109cells/l (63% neutrophils), 69% smear positive and 87.9% culture positive. TB drug resistance rates were high (13% mono-resistance 32.6% poly-resistance 8.7% multidrug resistance). 17% patients developed further AIDS-defining illnesses. 67.2% died (median time to death 20 days). Three baseline variables were predictive of death by multivariate analysis: increased TBM grade [adjusted hazard ratio (AHR) 1.73, 95% CI 1.08–2.76, p = 0.02], lower serum sodium (AHR 0.93, 95% CI 0.89 to 0.98, p = 0.002) and decreased CSF lymphocyte percentage (AHR 0.98, 95% CI 0.97 to 0.99, p = 0.003). Conclusions HIV-associated TBM is devastating disease with a dismal prognosis. CSF findings included CSF neutrophil predominance, high rates of smear and culture positivity, and high rates of antituberculous drug resistance. Three baseline variables were independently associated with death: increased TBM grade; low serum sodium and decreased CSF lymphocyte percentage.
Recurrent pneumococcal meningitis in a splenectomised HIV-infected patient
Philippe C Morand, Veronique Veuillez, Claire Poyart, Eric Abachin, Gilles Quesne, Bertrand Dupont, Patrick Berche, Jean-Paul Viard
Annals of Clinical Microbiology and Antimicrobials , 2003, DOI: 10.1186/1476-0711-2-9
Abstract: We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination.Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case.Streptococcus pneumoniae is a Gram-positive, encapsulated bacterium that is a major human pathogen, predominantly in young children and elderly people, as well as in patients presenting with asplenia, sickle cell disease, and inherited or acquired immunodeficiencies [1]. In industrialized countries, where vaccination against Haemophilus influenzae type b is widespread, S. pneumoniae has become a major cause of bacterial meningitis, together with Neisseria meningitidis, and bacterial meningitis is now a disease predominantly of adults rather than of infants and children [2,3]. In the developing world, bacterial meningitis remains a major problem, with increased incidence and mortality compared to more developed countries [4,5]. With the onset of the HIV pandemic and the worldwide emergence of drug-resistant pneumococci, the incidence of invasive pneumococcal infection has increased in adults as well as children [6-9], and pneumococcal vaccine was recommended in the USPHS/IDSA guidelines for the management of HIV-infected patients. We report the case of an HIV-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite anti-pneumococcal vaccination and chemoprophylaxis.A 29 year-old patient was found to be HIV-1-infected through investigations for an idiopathic thrombocytopenic purpura in 1989. After unsuccessful medical treatments, splenectomy was performed and anti-pneumococcal chemoprophylaxis (phenoxymethylpenicillin, 2 MU/day) was carried out until 1996. Meanwhile, a series of HIV-related infections occurred: Pneumocystis carinii pneumonia in 1993, herpetic esophagitis, herpetic anorectal
Meningitis due to Rhodotorula glutinis in an HIV infected patient  [cached]
Shinde R,Mantur B,Patil G,Parande M
Indian Journal of Medical Microbiology , 2008,
Abstract: Rhodotorula spp, though considered a common saprophyte, recently has been reported as causative agent of opportunistic mycoses. We present a case of meningitis in an immunocompromised human immunodeficiency virus infected patient who presented with longstanding fever. He was diagnosed as a case of chronic meningitis. Diagnosis was confirmed by cell cytology, India ink preparation, Gram staining and culture of cerebrospinal fluid (CSF) sample. CSF culture grew Rhodotorula glutinis . Therapy with amphotericin B was successful in eliminating the yeast from CSF and the patient was discharged after recovery.
Frequency of tuberculous and non-tuberculous mycobacteria in HIV infected patients from Bogota, Colombia
Martha I Murcia-Aranguren, Jorge E Gómez-Marin, Fernando S Alvarado, José G Bustillo, Ellen de Mendivelson, Bertha Gómez, Clara I León, William A Triana, Erwing A Vargas, Edgar Rodríguez
BMC Infectious Diseases , 2001, DOI: 10.1186/1471-2334-1-21
Abstract: Patients who attended the three major HIV/AIDS healthcare centres in Bogota were prospectively studied over a six month period. A total of 286 patients were enrolled, 20% of them were hospitalized at some point during the study. Sixty four percent (64%) were classified as stage C, 25% as stage B, and 11% as stage A (CDC staging system, 1993). A total of 1,622 clinical samples (mostly paired samples of blood, sputum, stool, and urine) were processed for acid-fast bacilli (AFB) stain and culture.Overall 43 of 1,622 cultures (2.6%) were positive for mycobacteria. Twenty-two sputum samples were positive. Four patients were diagnosed with M. tuberculosis (1.4%). All isolates of M. tuberculosis were sensitive to common anti-tuberculous drugs. M. avium was isolated in thirteen patients (4.5%), but only in three of them the cultures originated from blood. The other isolates were obtained from stool, urine or sputum samples. In three cases, direct AFB smears of blood were positive. Two patients presented simultaneously with M. tuberculosis and M. avium.Non-tuberculous Mycobacterium infections are frequent in HIV infected patients in Bogota. The diagnostic sensitivity for infection with tuberculous and non-tuberculous mycobacteria can be increased when diverse body fluids are processed from each patient.Mycobacterium infections are frequent opportunistic pathogens associated with the acquired immunodeficiency syndrome (AIDS). Its relative virulence and potential for person-to-person transmission distinguishes Mycobacterium tuberculosis. Persons infected with the human immunodeficiency virus (HIV) are particularly susceptible to tuberculosis, either by the reactivation of latent infection or by a primary infection with rapid progression to active disease [1-4]. The annual incidence rate of tuberculosis in Colombia during 1998 was 19.6 per 100,000 persons [5], but rates 1,000-fold higher have been reported in some HIV-seropositive populations [6-14]. In addition, disseminated i
Acute bacterial meningitis in HIV, pacients in southern Brazil: Curitiba, Paraná, Brazil
Almeida, Sérgio M. de;Savalla, George;Gabardo, Betina Mendez A.;Ribeiro, Clea Elisa;Rossoni, Andrea M.;Araújo, Josiane M.R.;
Arquivos de Neuro-Psiquiatria , 2007, DOI: 10.1590/S0004-282X2007000200016
Abstract: acute communitarian bacterial meningitis and aids are prevalent infectious disease in brazil. the objective of this study was to evaluate the frequency of acute communitarian bacterial meningitis in aids patients, the clinical and cerebrospinal fluid (csf) characteristics. it was reviewed the health department data from city of curitiba, southern brazil, from 1996 to 2002. during this period, 32 patients with aids fulfilled criteria for acute bacterial meningitis, representing 0.84% of the aids cases and 1.85% of the cases of bacterial meningitis. s. pneumoniae was the most frequent bacteria isolated. the number of white blood cells and the percentage of neutrophils were higher and csf glucose was lower in the group with no hiv co-infection (p 0.12; 0.008; 0.04 respectively). bacteria not so common causing meningitis can occur among hiv infected patients. the high mortality rate among pneumococcus meningitis patients makes pneumococcus vaccination important.
Aetiology, Clinical Presentation, and Outcome of Meningitis in Patients Coinfected with Human Immunodeficiency Virus and Tuberculosis  [PDF]
Smita Bhagwan,Kogieleum Naidoo
AIDS Research and Treatment , 2011, DOI: 10.1155/2011/180352
Abstract: We conducted a retrospective review of confirmed HIV-TB coinfected patients previously enrolled as part of the SAPiT study in Durban, South Africa. Patients with suspected meningitis were included in this case series. From 642 individuals, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients. Mortality was 70% (7/10), with 4 deaths directly due to meningitis. In an HIV TB endemic region we identified cryptococcus followed by tuberculosis as the leading causes of meningitis. We highlight the occurrence of tuberculous meningitis in patients already receiving antituberculous therapy. The development of meningitis heralded poor outcomes, high mortality, and relapsing meningitis despite ART. 1. Introduction Tuberculosis (TB) is the most common opportunistic infection in patients with Human Immunodeficiency Virus (HIV). The estimated relative risk of HIV-infected individuals developing TB is 20.6 compared to HIV uninfected, in populations with a generalized HIV epidemic [1]. HIV contributes significantly to the overall incidence, prevalence and poorer outcomes of meningitis. There is a predominance of chronic opportunistic meningitides in HIV-infected individuals with a higher risk of mortality and impaired cognition [2–6]. It is assumed that positive TB status would account for a greater proportion of tuberculous meningitis among HIV-TB coinfected patients as opposed to cryptococcal meningitis. However, in patients with advanced HIV infection, cryptococcus is the most common aetiology [2]. With increasing numbers of HIV-TB coinfected patients presenting to health facilities and high mortality related to meningitis, we aim to describe the aetiology, clinical presentation, and outcomes of meningitis in HIV-TB coinfected individuals. 2. Methods We retrospectively reviewed HIV-TB coinfected patients with suspected meningitis. Patients 18 years and older, with confirmed pulmonary TB and HIV, enrolled into the SAPiT study, presenting with suspected meningitis were included in this study. The SAPiT study was a prospective randomized control trial conducted in Durban, South Africa (June 2005–July 2008), investigating the optimal timing of antiretroviral therapy (ART) initiation in patients on antituberculous therapy. All patients
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