1634. Meningeal Tuberculosis: Experience of a Series of Cases from Cali, Colombia, 2008 - 2018

Background Meningeal tuberculosis (MTB) is the most lethal and disabling form of Mycobacterium Tuberculosis infection. In Colombia, it represents the second most frequent extrapulmonary location. Co-infection with the Human Immunodeficiency Virus (HIV) is one of the factors that most impacts their clinical results. Therefore, in this article we present the experience of 10 years of managing patients with MTB, with and without HIV coinfection. Methods A retrospective observational study was conducted between January 2008 and December 2018, with clinical information from patients diagnosed with MTB at Teaching Hospital Fundación Valle del Lili. Using absolute and relative frequency tables, sociodemographic, clinical characteristics and treatment outcomes were described, according to HIV infection status. P values < 0.05 were taken as significant and 95% confidence intervals were used for comparison of proportions. Results 61 patients with MTB diagnosed were enrolled. They represented 6.43% of all TB locations in the institutional registry. HIV coinfection was found in 26.2% of cases (n=16). Most of patients were men (65.6%), from urban areas (78.7%), and a median age of 39 years. Acute and subacute evolution of the infection was observed in half of the patients (50.8%). Also 85% presented some degree of neurological impairment. Bacteriological demonstration was achieved in 60.6% of all cases. 88% received drugs for sensitive TB, for a median of 9.5 months, and 52.5% received concomitant steroids drugs. Of the 36 subjects with information about their outcome, 42.6% were successful at treatment, 1 failed in the non-HIV group and 9 died (1 with HIV). 77% of all deaths were associated with TB. Conclusion MTB generates a significant burden disease. The characteristics of its insidious clinical presentation and the difficulty in achieving bacteriological demonstration in all patients make its timely diagnostic and therapeutic approach challenging. Disclosures All Authors: No reported disclosures

Effectiveness of the treatment of generalized tuberculosis in HIV-infected patients

The treatment of tuberculosis in HIV-infected persons is a complex task and often requires intensive therapy with intravenous administration of antituberculosis drugs, especially in generalized forms, malabsorption, presence of enteropathy, hepatitis B and C, severe condition. One of the dangerous forms of tuberculosis in HIV-infected people is meningeal tuberculosis. In these cases, the effectiveness of treatment for HIV-positive patients depends on timely detection, diagnosis of resistance to antituberculosis drugs, presence of other opportunistic diseases. Here is an example of treating a HIV-positive patient with miliary tuberculosis with lung damage, lymph nodes and meningeal tuberculosis caused by a multiresistant strain of tuberculosis. The treatment was performed taking into account drugs that cross the blood-brain barrier, drug sensitivity test, immunosuppression and the presence of malabsorption. Timely intensive therapy with intravenous administration of medications for medical sensitivity allowed to obtain positive dynamics and cure the patient in the short term.

Morbidity Trends and Risk of Tuberculosis: Mexico 2007–2017

Background. To know the current status of the epidemiological and geographic distribution of tuberculosis and its complication meningeal tuberculosis in Mexico, this work analyzes national surveillance data (ten years) issued by the General Directorate of Epidemiology (GDE). Methods. An observational and retrospective analysis of monthly and annual reports of pulmonary and meningeal tuberculosis cases from January 2007 to December 2017 was performed on the annual reports issued by the GDE in Mexico. The number of cases and incidence were classified by year, state, age group, gender, and seasons. Results. A national case distribution map of pulmonary and meningeal tuberculosis incidence was generated. During this period, a total of 184,003 and 3,388 cases were reported with a median of 16,727.5 and 308 cases per year for pulmonary and meningeal tuberculosis diseases, respectively. The number of cases and incidence of pulmonary and meningeal tuberculosis per year showed that male gender presented a continuous increase in both parameters. The geographic analysis of the distribution of cases of tuberculosis showed that states like Guerrero, Tabasco, and Veracruz presented higher means of tuberculosis cases during this period. Northern states had the highest number of cases in the country compared to other states. In Mexico, pulmonary tuberculosis and meningeal tuberculosis are seasonal. Interestingly, cases of meningeal tuberculosis show an increase during October and November (autumn). Conclusions. In Mexico, during the years 2007–2017, there has been an increase in the proportion of male TB patients. It remains necessary to implement strategies to detect TB in the adult population, especially among men, because tuberculosis could be difficult to recognize in an early stage in the population, and the appearance of resistant strains can cause an increase in the incidence of the disease.

Gatifloxacin Pharmacokinetics/Pharmacodynamics–based Optimal Dosing for Pulmonary and Meningeal Multidrug-resistant Tuberculosis

Background Gatifloxacin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB). The optimal dose is unknown. Methods We performed a 28-day gatifloxacin hollow-fiber system model of tuberculosis (HFS-TB) study in order to identify the target exposures associated with optimal kill rates and resistance suppression. Monte Carlo experiments (MCE) were used to identify the dose that would achieve the target exposure in 10000 adult patients with meningeal or pulmonary MDR-TB. The optimal doses identified were validated using probit analyses of clinical data from 2 prospective clinical trials of patients with pulmonary and meningeal tuberculosis. Classification and regression-tree (CART) analyses were used to identify the gatifloxacin minimum inhibitory concentration (MIC) below which patients failed or relapsed on combination therapy. Results The target exposure associated with optimal microbial kill rates and resistance suppression in the HFS-TB was a 0–24 hour area under the concentration-time curve-to-MIC of 184. MCE identified an optimal gatifloxacin dose of 800 mg/day for pulmonary and 1200 mg/day for meningeal MDR-TB, and a clinical susceptibility breakpoint of MIC ≤ 0.5 mg/L. In clinical trials, CART identified that 79% patients failed therapy if MIC was >2 mg/L, but 98% were cured if MIC was ≤0.5 mg/L. Probit analysis of clinical data demonstrated a >90% probability of a cure in patients if treated with 800 mg/day for pulmonary tuberculosis and 1200 mg/day for meningeal tuberculosis. Doses ≤400 mg/day were suboptimal. Conclusions Gatifloxacin doses of 800 mg/day and 1200 mg/day are recommended for pulmonary and meningeal MDR-TB treatment, respectively. Gatifloxacin has a susceptible dose-dependent zone at MICs 0.5–2 mg/L.