Multidrug-resistant Tuberculous Meningitis Research Articles

Clinical outcomes among patients with tuberculous meningitis receiving intensified treatment regimens.

SETTING: National Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.OBJECTIVE: To determine clinical outcomes of patients with tuberculous meningitis (TBM) treated with an intensified regimen including a fluoroquinolone (FQ) and an injectable agent.DESIGN: Prospective cohort of patients aged ≥16 years initiating treatment for TBM at the NCTLD from January 2018 to December 2019. Treatment outcomes and neurologic disability at 1, 6 and 12 months after treatment initiation were assessed.RESULTS: Among 77 patients with median follow-up time of 363 days (IQR 269-374), 97% received a FQ, 62% an injectable agent, 44% linezolid and 39% a carbapenem. Fifty-seven patients (74%) successfully completed treatment, 2 (2.6%) had treatment failure, 6 (7.8%) died, and the remainder (12%) were lost to follow up. Among 11 patients treated for multidrug-resistant TBM, the median follow-up time was 467 days and one patient (8%) died. Regarding neurologic outcomes, 14/76 (18%) patients had Modified Rankin Scores of 0 at baseline, improving to 85% (56/66) and 94% (47/50) at 6 and 12 months, respectively.CONCLUSION: Intensified multidrug treatment regimens including a FQ and an injectable agent in all patients and newly implemented drugs in patients with multidrug-resistant TBM resulted in low mortality and favorable neurologic outcomes.

Co-Infection of Cryptococcal and Multidrug Resistant Tuberculous Meningitis in Immunocompetent Patient

Co-Infection of Cryptococcal and Multidrug Resistant Tuberculous Meningitis in Immunocompetent Patient

Multi drug resistant (MDR) tuberculous meningitis with hydrocephalus treated with ventriculo-peritoneal shunting: a review

Introduction: Tubercular meningitis (TBM) is one of the severe manifestations of extra pulmonary tuberculosis. Prognosis of cases of multidrug resistance TBM is even worse. We present report of three cases of MDR tuberculous meningitis with hydrocephalus to highlight the challenges in the management of these patients.Materials and Methods: The present study was done was done at IHBAS, a tertiary care neuropsychiatry hospital in Delhi, India. Three patients of MDR CNS TB treated at neurosurgery department were included in this study. Study design was a descriptive case series.Results: All three cases were treated with second line ATT and ventrriculoperitoneal shunting. After a regular follow up with clinical and neuroimaging vigil and with laboratory testing, these patients showed improvement.Conclusion: The decision to start second line ATT to treat resistant cases of CNS TB is often delayed and increases the morbidity and mortality. Prompt and precise decision is possible with vigilant clinical observation, lab tests and neuroimaging. Close follow-up is mandatory for detecting any adverse drug effect and therapeutic response in patients of MDR-CNS TB.

Drug-resistant tuberculous meningitis

Drug-resistant tuberculosis, including drug-resistant tuberculous meningitis, is an emerging health problem in many countries. An association with Beijing strains and drug resistance-related mutations, such as mutations in katG and rpoB genes, has been found. The pathology, clinical features and neuroimaging characteristics of drug-resistant tuberculous meningitis are similar to drug-responsive tuberculous meningitis. Detection of mycobacteria in cerebrospinal fluid (CSF) by conventional methods (smear examination or culture) is often difficult. Nucleic acid amplification assays are better methods owing to their rapidity and high sensitivity. The Xpert® MTB/RIF assay (Cepheid, CA, USA) is a fully-automated test that has also been found to be effective for CSF samples. Treatment of multidrug-resistant tuberculous meningitis depends on the drug susceptibility pattern of the isolate and/or the previous treatment history of the patient. Second-line drugs with good penetration of the CSF should be preferred. Isoniazid monoresistant disease requires addition of another drug with better CSF penetration. Drug-resistant tuberculous meningitis is associated with a high mortality. HIV infected patients with drug-resistant tuberculous meningitis have severe clinical manifestations with exceptionally high mortality. Prevention of tuberculosis is the key to reduce drug-resistant tuberculous meningitis.

Impact of Drug Resistance on Clinical Outcome in Children With Tuberculous Meningitis

Tuberculous meningitis (TBM) is associated with delayed diagnosis and poor outcome in children. This study investigated the impact of drug resistance on clinical outcome in children with TBM. All children (0-13 years) were included if admitted to Tygerberg Children's Hospital, Cape Town, South Africa, from January 2003 to April 2009 with a diagnosis of either confirmed TBM, or probable TBM with mycobacterial isolation from a site other than cerebrospinal fluid. Mycobacterial samples underwent drug susceptibility testing to rifampin and isoniazid. Children were treated with isoniazid, rifampin, pyrazinamide and ethionamide according to local guidelines. One hundred twenty-three children were included; 13% (16 of 123) had any form of drug resistance, and 4% (5 of 123) had multidrug-resistant tuberculosis. Time from start of symptoms to appropriate treatment was longer in children with any drug resistance (median: 31 days versus 9 days; P=0.001). In multivariable analysis, young age (P=0.013) and multidrug-resistant tuberculosis (adjusted odds ratio: 12.4 [95% confidence interval: 1.17-132.3]; P=0.037) remained risk factors for unfavorable outcome, and multidrug-resistant tuberculosis remained a risk for death (adjusted odds ratio: 63.9 [95% confidence interval: 4.84-843.2]; P=0.002). We did not detect any difference in outcome between those with isolates resistant to only isoniazid and those with fully susceptible strains (adjusted odds ratio: 0.22 [confidence interval: 0.03-1.87]; P=0.17). Multidrug-resistant TBM in children has poor clinical outcome and is associated with death. We did not find any difference in the outcomes between children with isoniazid monoresistant TBM and those with drug-susceptible TBM. One explanation could be the local treatment regimen. Further investigation of this regimen is indicated.

O2-1.1 Multidrug resistant tuberculous meningitis in the United States, 1993-2005

<h3>Background</h3> Little is known about the epidemiology of multidrug resistant tuberculous meningitis (TBM), defined as resistance to at least isoniazid and rifampin. We sought to describe cases of multidrug resistant TBM reported in the United States with respect to clinical characteristics and treatment outcomes. <h3>Methods</h3> We conducted a retrospective cohort study using data collected by the National Tuberculosis Surveillance System at the Centers for Disease Control and Prevention in the United States. We included patients diagnosed with TBM between 1 January 1993 and 31 December 2005, with a positive culture from cerebrospinal fluid and drug susceptibility testing performed. We compared clinical and demographic characteristics of TBM patients with and without multidrug resistance, as well as the proportion of patients in each group that died while still receiving anti-tuberculosis therapy. <h3>Results</h3> 26 of 1683 patients (1.5%) with cerebrospinal fluid culture-positive TBM were found to have multidrug resistance on initial susceptibility testing. Anti-tuberculosis therapy was stopped due to death in 19 of 26 patients (73%), after a median of 42 days of treatment (IQR 15–225). Of the 19 patients with known HIV status, 17 were HIV-positive (89%). <h3>Discussion</h3> Most cases of multidrug resistant TBM in the United States occurred in HIV-infected patients, and the associated mortality was high. Due to the time period required to obtain drug susceptibility results based on conventional methods, rapid molecular diagnosis of drug resistance is of great potential benefit in this setting and needs to be evaluated further.

Description of Primary Multidrug-Resistant Tuberculous Meningitis in an Italian Child

Tuberculous meningitis is the most severe form of tuberculosis and causes substantial morbidity and mortality in adults and children. The prevalence of multidrug-resistant (rifampin-isoniazid) strains requires the use of more toxic second-line drugs. We report a case of tuberculous meningitis in a 3-year-old Italian child.

885 Tuberculous Meningitis: A Rare and Severe Form of An Emerging Disease?

Background and aims: Tuberculous meningitis (TBM) accounts for 0.7% of all cases of tuberculosis (TB). The incidence is related to the prevalence of TB in the community. In Portugal BCG vaccine is routinely administered and has been proven to reduce the incidence of severe disseminated disease in children. Methods: Retrospective study, between January 2000 and December 2010, of children with TBM. Diagnosis confirmed by culture and/or polymerase chain reaction of the CSF or cerebral tissue. Results: 5 patients, mean 4.2 years old (9 months-10 years); one of african origin. All children were immunized against Mycobacterium tuberculosis. Fever was the first clinical manifestation in four children, accompanied by vomiting (5), malaise (3), lethargy (5), headache (2), cough (2), with more than two weeks in duration in three. One had concomitant miliary disease. Tuberculin skin test was positive only in one and all had contact with patients with TB. There was one multidrug-resistant TBM. First line agents were replaced in two patients because of oral intolerance and antimicrobial resistance. 4/5 required intensive care. Complications occurred in all cases: seizures (3), coma (3), cranial nerve paralysis (2), cerebral stroke (1), motor disabilities (3), hydrocephalus (5) and venous thrombosis (1). One child died, whose diagnosis was made postmortem. Conclusion: TB remains among the great public health challenges. It should be considered when diagnosing children with nonpecific/subacute symptoms of neurologic infection, even in absence of respiratory symptoms or an epidemiologic context. Death may occur as a result of missed diagnosis and delayed treatment.

Tuberculous meningitis in patients infected with human immunodeficiency virus

Tuberculosis is the most common opportunistic infection in human immunodeficiency virus (HIV) infected persons. HIV-infected patients have a high incidence of tuberculous meningitis as well. The exact incidence and prevalence of tuberculous meningitis in HIV-infected patients are not known. HIV infection does not significantly alter the clinical manifestations, laboratory, radiographic findings, or the response to therapy. Still, some differences have been noted. For example, the histopathological examination of exudates in HIV-infected patients shows fewer lymphocytes, epithelioid cells, and Langhan's type of giant cells. Larger numbers of acid-fast bacilli may be seen in the cerebral parenchyma and meninges. The chest radiograph is abnormal in up to 46% of patients with tuberculous meningitis. Tuberculous meningitis is likely to present with cerebral infarcts and mass lesions. Cryptococcal meningitis is important in differential diagnosis. The recommended duration of treatment in HIV-infected patients is 9-12months. The benefit of adjunctive corticosteroids is uncertain. Antiretroviral therapy and antituberculosis treatment should be initiated at the same time, regardless of CD4 cell counts. Tuberculous meningitis may be a manifestation of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Some studies have demonstrated a significant impact of HIV co-infection on mortality from tuberculous meningitis. HIV-infected patients with multidrug-resistant tuberculous meningitis have significantly higher mortality. The best way to prevent HIV-associated tuberculous meningitis is to diagnose and isolate infectious cases of tuberculosis promptly and administer appropriate treatment.

Multidrug-resistant tuberculous meningitis

Multidrug-resistant tuberculous meningitis is now appearing worldwide, including in the United States, and is difficult to diagnose and treat. We discuss methods to diagnose tuberculous meningitis, review current and experimental assays for determining drug resistance, and consider approaches to management of the patient. We review the epidemiology of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis in both pulmonary and meningeal infections, discuss promising molecular methods for determining drug resistance, and review current approaches toward treatment of patients. The incidence of multidrug-resistant tuberculous meningitis is increasing, and diagnosing and treating these patients will be a major challenge. There is a need to improve rapid methods of isolating the organism from cerebrospinal fluid, to advance molecular methods to rapidly test the isolate for antibiotic sensitivity, and to develop new antituberculosis drugs, especially ones that cross the blood-cerebrospinal fluid barrier.

Multidrug-Resistant Tuberculous Meningitis in Children in Durban, South Africa

Tuberculous meningitis (TBM) is the most frequent manifestation of central nervous system tuberculosis (TB) and is more common in children than in adults. The diagnosis of TBM in children is difficult because signs and symptoms are vague. Information about drug resistant TB in children is scarce, and there is no published information on drug resistant TBM in children. This is a retrospective review of medical records of children with culture-confirmed multidrug-resistant tuberculous meningitis (MDR-TBM) at King George V Hospital in Durban, South Africa. Between 1992 and 2003, there were 8 children with MDR-TBM; 6 were HIV infected and 2 were HIV negative. Only one child survived. The diagnosis was made posthumously in almost all the children. The changes in the cerebrospinal fluid (CSF) in early TBM can be nonspecific and can change rapidly; therefore, CSF studies should always include culture and susceptibility testing. Factors that contributed to the high mortality were disseminated TB, HIV infection, delay in diagnosis and treatment, the absence of a standardized approach to the management of MDR-TBM and the poor CSF penetration of most MDR-TB drugs. MDR-TB therapy should be considered if there is a history of TB: a MDR-TB contact or a poor clinical response to TB therapy despite adequate adherence to treatment. Early diagnosis is important because TBM in children is often associated with a grave outcome.