Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990–2017 / Mortalidad y secuelas de la meningitis tuberculosa en Barcelona (España): Estudio de cohortes, 1990-2017

Introduction: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. Methods: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. Results: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990–1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71–9.25), 0.70 (0.13–3.85), and 1.29 (0.28–5.91) for the 1997–2003, 2004–2010, and 2011–2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990–1996 period, the odds ratios and 95% CIs were 0.80 (0.09–7.22); 1.94 (0.21–17.96), and 2.42 (0.25–23.07) for the 1997–2003, 2004–2010, and 2011–2017 periods respectively. Conclusion: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.(AU)

Introducción: La meningitis tuberculosa (TBM), la forma más grave de tuberculosis, provoca una alta mortalidad y discapacidad a largo plazo en países con bajos recursos. Nuestro objetivo es investigar la tendencia temporal de la mortalidad y las secuelas en un país con recursos elevados y baja incidencia. Métodos: Hemos realizado un estudio de cohortes retrospectivo de los pacientes adultos con TBM en dos hospitales universitarios de tercer nivel en Barcelona (España), entre 1990 y 2017, evaluando las tendencias temporales de mortalidad y secuelas a los 12 meses, comparando cuatro periodos consecutivos de siete años. Las tasas observadas en los cuatro periodos se han ajustado por covariables. Resultados: De los 135 casos incluidos, todos menos uno inició tratamiento antituberculoso y 120 (89,6%) recibieron rifampicina, isoniazida y pirazinamida, con o sin etambutol. La probabilidad de estar vivo a los 12 meses fue de 81,8%, sin diferencias entre los cuatro periodos: en comparación con el periodo 1990-1996, los coeficientes de riesgo ajustados y los intervalos de confianza (IC) del 95% fueron 2,55 (0,71-9,25), 0,70 (0,13-3,85) y 1,29 (0,28-5,91) para los periodos 1997-2003, 2004-2010 y 2011-2017, respectivamente. Las secuelas estaban presentes en 28,3% en el mes 12, sin diferencias entre los cuatro periodos en el análisis ajustado: en comparación con el periodo 1990-1996, los coeficientes de probabilidad y los IC 95% fueron 0,80 (0,09-7,22); 1,94 (0,21-17,96) y 2,42 (0,25-23,07) para los periodos 1997-2003, 2004-2010 y 2011-2017, respectivamente. Conclusión: Este estudio muestra que la TBM todavía causa una alta mortalidad y discapacidad sin mejoría con el tiempo, incluso en un entorno con baja incidencia de tuberculosis y con elevados recursos.(AU)

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990-2017.

INTRODUCTION: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. METHODS: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. RESULTS: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990-1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71-9.25), 0.70 (0.13-3.85), and 1.29 (0.28-5.91) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990-1996 period, the odds ratios and 95% CIs were 0.80 (0.09-7.22); 1.94 (0.21-17.96), and 2.42 (0.25-23.07) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. CONCLUSION: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.

Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis: Treatment in the Real World and in Guidelines.

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L. We treated 363 episodes of pneumococcal meningitis during the study period. Of these, 24 had no viable strain, leaving 339 episodes with a known MIC for inclusion. Penicillin-susceptible strains accounted for 246 episodes (73%), penicillin-resistant strains for 93 (27%), CTX susceptible for 58, and CTX resistant for 35. Nine patients failed or relapsed and 69 died (20%), of whom 22% were among susceptible cases and 17% were among resistant cases. During the dexamethasone period, mortality was equal (12%) in both susceptible and resistant cases. High-dose CTX (300 mg/Kg/day) helped to treat failed or relapsed cases and protected against failure when used as empirical therapy (P = 0.02), even in CTX-resistant cases. High-dose CTX is a good empirical therapy option for pneumococcal meningitis in the presence of a high prevalence of penicillin and cephalosporin resistance, effectively treating pneumococcal strains with MICs up to 2 mg/L for either penicillin or CTX.

Immunomodulatory therapy, risk factors and outcomes of hospital-acquired bloodstream infection in patients with severe COVID-19 pneumonia: a Spanish case-control matched multicentre study (BACTCOVID).

OBJECTIVES: The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia. METHODS: We performed a severity matched case-control study (1:1 ratio) nested in a large multicentre prospective cohort of hospitalized adults with COVID-19. Cases with BSI were identified from the cohort database. Controls were matched for age, sex and acute respiratory distress syndrome. A Cox proportional hazard ratio model was performed. RESULTS: Of 2005 patients, 100 (4.98%) presented 142 episodes of BSI, mainly caused by coagulase-negative staphylococci, Enterococcus faecalis and Pseudomonas aeruginosa. Polymicrobial infection accounted for 23 episodes. The median time from admission to the first episode of BSI was 15 days (IQR 9-20), and the most frequent source was catheter-related infection. The characteristics of patients with and without BSI were similar, including the use of tocilizumab, corticosteroids, and combinations. In the multivariate analysis, the use of these immunomodulatory drugs was not associated with an increased risk of BSI. A Cox proportional hazard ratio (HR) model showed that after adjusting for the time factor, BSI was associated with a higher in-hospital mortality risk (HR 2.59; 1.65-4.07; p < 0.001). DISCUSSION: Hospital-acquired BSI in patients with severe COVID-19 pneumonia was uncommon and the use of immunomodulatory drugs was not associated with its development. When adjusting for the time factor, BSI was associated with a higher mortality risk.