Mortality in hospitalized patients with tuberculous meningitis.

BACKGROUND: To evaluate the mortality in hospitalized patients with tuberculous meningitis and describe factors associated with an increased risk of mortality. METHODS: Retrospective study of hospitalized patients with tuberculous meningitis between 2006 and 2015 in Peru performing a generalized linear regression to identify factors predictive of in-hospital mortality. RESULTS: Of 263 patients, the median age was 35 years, 72.6% were men, 38% were positive for HIV upon admission, 24% had prior TB infections and 2.3% had prior MDR-TB infections. In-hospital mortality was 30.4% of all study patients with a final diagnosis of TBM. When multivariable analysis was applied, significant associations with in-hospital mortality were seen among patients with HIV (RR 2.06; Confidence Interval 95% (95% CI) 1.44-2.94), BMRC II (RR 1.78; 95% CI 1.07-2.97), BMRC III (RR 3.11; 95% CI 1.78-5.45) and positive CSF cultures (RR 1.95; 95% CI 1.39-2.74). CONCLUSIONS: In-hospital mortality is higher among patients with HIV infections, age over 40 years, positive CSF TB culture and BMRC stage II or III.

Evaluation of the GeneXpert MTB/RIF in patients with presumptive tuberculous meningitis.

BACKGROUND: Meningitis caused by Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide. We evaluated the performance of cerebrospinal fluid (CSF) testing with the GeneXpert MTB/RIF assay versus traditional approaches for diagnosing tuberculosis meningitis (TBM). METHODS: Patients were adults (n = 37) presenting with suspected TBM to the Hospital Nacional Dos de Mayo, Lima, Peru, during 12 months until 1st January 2015. Each participant had a single CSF specimen that was divided into aliquots that were concurrently tested for M. tuberculosis using GeneXpert, Ziehl-Neelsen smear and culture on solid and liquid media. Drug susceptibility testing used Mycobacteria Growth Indicator Tube (MGIT 960) and the proportions method. RESULTS: 81% (30/37) of patients received a final clinical diagnosis of TBM, of whom 63% (19/30, 95% confidence intervals, CI: 44-80%) were HIV-positive. 22% (8/37, 95%CI: 9.8-38%), of patients had definite TBM. Because definite TBM was defined by positivity in any laboratory test, all laboratory tests had 100% specificity. Considering the 30 patients who had a clinical diagnosis of TBM: diagnostic sensitivity was 23% (7/30, 95%CI: 9.9-42%) for GeneXpert and was the same for all culture results combined; considerably greater than 7% (2/30, 95%CI: 0.82-22%) for microscopy; whereas all laboratory tests had poor negative predictive values (20-23%). Considering only the 8 patients with definite TBM: diagnostic sensitivity was 88% (7/8, 95%CI: 47-100%) for GeneXpert; 75% (6/8, 95%CI: 35-97%) for MGIT culture or LJ culture; 50% (4/8, 95%CI 16-84) for Ogawa culture and 25% (2/8, 95%CI: 3.2-65%) for microscopy. GeneXpert and microscopy provided same-day results, whereas culture took 20-56 days. GeneXpert provided same-day rifampicin-susceptibility results, whereas culture-based testing took 32-71 days. 38% (3/8, 95%CI: 8.5-76%) of patients with definite TBM with data had evidence of drug-resistant TB, but 73% (22/30) of all clinically diagnosed TBM (definite, probable, and possible TBM) had no drug-susceptibility results available. CONCLUSIONS: Compared with traditional culture-based methods of CSF testing, GeneXpert had similar yield and faster results for both the detection of M. tuberculosis and drug-susceptibility testing. Including use of the GeneXpert has the capacity to improve the diagnosis of TBM cases.

A multi-centric Study of Candida bloodstream infection in Lima-Callao, Peru: Species distribution, antifungal resistance and clinical outcomes.

BACKGROUND: The incidence of candidemia is increasing in developing countries. Very little is known about the epidemiology of candidemia in Peru. The aim of this study is to describe the incidence, microbiology, clinical presentation and outcomes of Candida bloodstream infections in three Lima-Callao hospitals. METHODS: Candida spp. isolates were identified prospectively at participant hospitals between November 2013 and January 2015. Susceptibility testing for amphotericin B, fluconazole, posaconazole, voriconazole and anidulafungin was performed using broth microdilution method. Clinical information was obtained from medical records and evaluated. RESULTS: We collected information on 158 isolates and 157 patients. Median age of patients was 55.0 yrs., and 64.1% were males. Thirty-eight (24.2%) episodes of candidemia occurred in those <18 yrs. The frequency of non-Candida albicans was 72.1%. The most frequently recovered species were C. albicans (n = 44, 27.8%), C. parapsilosis (n = 40, 25.3%), C. tropicalis (n = 39, 24.7%) and C. glabrata (n = 15, 9.5%). Only four isolates were resistant to fluconazole, 86.7% (n = 137) were susceptible and 17 were susceptible-dose dependent. Decreased susceptibility to posaconazole was also observed in three isolates, and one to voriconazole. All isolates were susceptible to anidulafungin and amphotericin B. The most commonly associated co-morbid conditions were recent surgery (n = 61, 38.9%), mechanical ventilation (n = 60, 38.2%) and total parenteral nutrition (n = 57, 36.3%). The incidence of candidemia by center ranged between 1.01 and 2.63 cases per 1,000 admissions, with a global incidence of 2.04. Only 28.1% of cases received treatment within 72 hrs. of diagnosis. Overall, the 30-day survival was 60.4% (treated subjects, 67.4%; not-treated patients, 50.9%). CONCLUSIONS: We found a very high proportion of non-albicans Candida species. Despite this, the decreased susceptibility/resistance to fluconazole was only 13.3% and not seen in the other antifungals. Overall, the incidence of candidemia mortality was high when compared to other international studies. It is possible, that the delay in initiating antifungal treatment contributed to the elevated mortality rate, in spite of low antifungal resistance.

Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection.

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58-92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures.

Impact of Infection Control Measures to Control an Outbreak of Multidrug-Resistant Tuberculosis in a Human Immunodeficiency Virus Ward, Peru.

Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000-56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug-susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB-coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective.

Factores asociados a mortalidad por neumonía nosocomial en un hospital público de Perú: 2006- 2010 / Factors associated with nosocomial pneumonia mortality in a public hospital in Peru: 2006-2010

Objetivos: determinar los factores asociados a mortalidad en pacientes con neumonía nosocomial en el Hospital Dos de Mayo, Lima - Perú entre el período enero 2006-diciembre 2010. Materiales y Métodos: estudio de cohorte retrospectivo de pacientes con diagnóstico de neumonía nosocomial. Los pacientes elegibles para el estudio fueron mayores de 18 años, tiempo de enfermedad, y condición de egreso conocido (alta o fallecido). Para el análisis de supervivencia se utilizó el método de Kaplan-Meier y regresión de Cox. Resultados: se identificaron 658 pacientes con diagnóstico de neumonía nosocomial, el agente causal fue identificado en 173 (26,75%) casos. La edad media fue 58,4 ± 19,6 años, fallecieron 238 (36,2%) pacientes, la mediana de supervivencia fue de 16 días. El sexo masculino presentó un Hazard Ratio (HR) de 1,15 (IC 95%: 0,89 a 1,49). A las 10 y 20 días la tasa de supervivencia fue de 70% y 40% en aquellos pacientes con Klebsiella, 85% y 75% en aquellos con Pseudomonas, y el 70% y 65% en aquellos con Staphylococcus aureus. En el análisis multivariado, se identificaron la exposición a ventilación mecánica (HR 1,98 (95% IC 1,35- 2,89), el uso de una sonda nasogástrica (HR 1,33 (95% IC 1,01- 1,76) y la edad mayor de 65 años (HR 1,96:95% IC 1,51-2,55). La resistencia a ceftazidima y amikacina (95% HR 1.45 (0.74- 2.84). Conclusiones: en la neumonía nosocomial, la exposición a ventilación mecánica, sonda nasogástrica y edad mayor de 65 años, se asoció con una menor supervivencia. Esto sugiere la instauración de medidas preventivas en este grupo de riesgo

Objectives: to determine factors associated with mortality in patients with nosocomial pneumonia in the Hospital Dos de Mayo, Lima - Peru during the period January 2006-December 2010. Materials and Methods: retrospective cohort study, patients eligible for the study were: age over 18 years of age, sick time record and known exit condition (discharge or deceased). For survival analysis we used the Kaplan- Meier and Cox regression. Results: we identified 658 patients diagnosed with nosocomial pneumonia, and the causative agent was identified in 173 (26,75%). The mean age was 58.4 ± 19.6 years, died 238 (36.2%); patients median survival time was 16 days. Male sex presented HR=1.15, IC95%: 0.89- 1.49. At 10 and 20 days the survival rate was 70% and 40% in those with Klebsiella, 85% and 75% in those with Pseudomonas, and 70% and 65% in those with Staphylococcus aureus. In the multivariate analysis, we identified exposure to mechanical ventilation (HR=1.98, IC95%:1.35-2.89, the use of a nasogastric tube (HR=1.33, IC95%:1.01-1,76) and age over 65 years (HR=1,96, IC95%:1.51-2.55). Resistance to ceftazidime and amikacin (HR=1.45, IC95%:0.74-2.84). Conclusions: in nosocomial pneumonia, the exposure to mechanical ventilation, nasogastric tube and age over 65 years, are associated with lower survival. This suggests the introduction of preventive measures in this risk group

Factores asociados a mortalidad por neumonía nosocomial en un hospital público de Perú / Factors associated with nosocomial pneumonia mortalityin a public hospital in Peru

Objetivo: Determinar los factores asociados a mortalidad en pacientes con neumon¡a nosocomial en el Hospital Dos de Mayo, Lima-Perú entre el per¡odo enero 2006-diciembre 2010. Métodos: Se realizó un estudio de cohorte única, retrospectivo, de pacientes con diagnóstico de neumon¡a nosocomial. Los pacientes elegibles para el estudio fueron mayores de 18 años, tiempo de enfermedad y condicón de egreso conocido (alta o fallecido). Para el análisis de supervivencia se utilizó el método de Kaplan-Meier y regresión de Cox. Resultados: Se identificaron 658 pacientes con diagnóstico de neumon¡a nosocomial, el agente causal fue identificado en 173 (26,75%) casos. La edad media fue 58,4ñ19,6 años, fallecieron 238 (36,2%) pacientes, la mediana de supervivencia fue de 16 d¡as. El sexo masculino presentó un hazard ratio (HR) de 1,15 (IC 95%: 0,89 a 1,49). A los 10 y 20 d¡as la tasa de supervivencia fue de 70% y 40% en aquellos pacientes con Klebsiella, 85% y 75% en aquellos con Pseudomonas, y el 70% y 65% en aquellos con Staphylococcus aureus. En el análisis multivariado, se identificaron a la exposición a ventilación mecánica (HR 1,98; IC95% 1,35-2,89), el uso de una sonda nasogástrica (HR 1,33; IC95% 1,01-1,76) y la edad mayor de 65 años (HR 1,96; IC95% 1,51-2,55) como factores asociados a mortalidad, mientras que la resistencia a ceftazidima y amikacina presentó HR 1,45 (IC95% 0,74-2,84). Conclusiones: En la neumon¡a nosocomial, la exposición a ventilación mecánica, sonda nasogástrica y edad mayor de 65 años, se asoció con una menor supervivencia. Esto sugiere la instauración de medidas preventivas en este grupo de riesgo.

Objective: To determine factors associated with mortality in patients with nosocomial pneumonia at the Hospital Dos de Mayo, Lima-Peru between January 2006 to December 2010. Methods: Retrospective cohort study, patients eligible for the study were over 18 years of age, sick time record and known exit condition (discharge or deceased). For survival analysis we used the Kaplan-Meier and Cox regression. Results: We identified 658 patients diagnosed with nosocomial pneumonia, and the causative agent was identified in 173 (26,75%). The mean age was 58,4ñ19,6 years, 238 patientes died (36,2%); median survival time was 16 days. Male sex presented HR=1,15, 95%CI 0.89-1.49. At 10 and 20 days the survival rate was 70% and 40% in those with Klebsiella, 85% and 75% in those with Pseudomonas, and 70% and 65% in those with Staphylococcus aureus. In the multivariate analysis, we identified exposure to mechanical ventilation (HR 1,98; 95%CI 1,35 to 2,89), use of a nasogastric tube (HR 1,33; 95%CI 1,01 to 1,76) and age over 65 years (HR 1,96; (95%CI 1,51 to 2,55) as factors associated with mortality, while resistance to ceftazidime and amikacin present HR 1,45 (95%CI 0,74 -2,84). Conclusions: In nosocomial pneumonia, the exposure to mechanical ventilation, nasogastric tube and age over 65 years, are associated with lower survival. This suggests the introduction of preventive measures in this risk group.

The pathophysiology of the acute phase of human bartonellosis resembles AIDS.

Human bartonellosis is a South American anthroponosis caused by Bartonella bacilliformis. The disease has an acute phase characterized by invasion of red blood cells by parasites, and consequent severe anemia; and a chronic phase presenting with benign vascular tumors. During the acute phase, affected individuals are prone to developing opportunistic infections with a variety of organisms similar to the ones seen in AIDS. After antibiotic treatment is instituted, a subgroup of patients may develop atypical symptoms which potentially represent clinical manifestations of the restoration of macrophage function. We speculate that the pathophysiology of the acute phase of human bartonellosis resembles AIDS, with a period of immunosuppression following the infection and later, clinical manifestations of immune reconstitution subsequent to treatment.

Recomendaciones para el control de la transmisión de la tuberculosis en los hospitales / Recommendations for the control of tuberculosis transmission in hospitals

La transmisión nosocomial de la tuberculosis (TB) es un problema vigente en el Perú, tanto por el riesgo de enfermar que corre el personal de salud y pacientes, como por la presencia cada vez más frecuente de cepas resistentes: TB MDR (multidrogo resistente), TB XDR (extensivamente resistente a drogas). Se describen los factores condicionantes de la transmisión de TB en los hospitales, así como las medidas de control recomendadas, incluyendo: 1) control administrativo, 2) control ambiental y 3) protección respiratoria personal. Además, se señala la importancia de los Planes de Control deInfecciones de Tuberculosis en los hospitales y la experiencia en su implementación en 19 centros hospitalarios del país.

Nosocomial transmission of tuberculosis (TB) is a current problem in Peru, on the one hand because of the risk for healthpersonal and for inpatients to acquire the infection, and on the other because of the increasing frequency of resistant strains: MDR (multidrug resistant) TB, XDR (extensively drug resistant) TB. Factors conditioning transmission of tuberculosis in hospitals are described, as well as recommended control measures, including: 1) administrative control, 2) environmental control, and 3) personal respiratory protection. Furthermore, the importance of the Plans of Tuberculosis Infection Control inhospitals is stressed and experience in its implementation in 19 hospital centers in the country is addressed.

Tuberculosis mortality, drug resistance, and infectiousness in patients with and without HIV infection in Peru.

The effects of HIV co-infection and multi-drug resistant tuberculosis (MDRTB) on tuberculosis prognosis are poorly defined. Therefore, we studied infectiousness and mortality of 287 tuberculosis patients treated with standard, directly observed, short-course therapy in the Peruvian community. During 6-17 months of treatment, 49 (18%) of patients died, of whom 48 (98%) had AIDS and 28 (57%) had MDRTB; 17/31 (55%) of MDRTB-patients with AIDS died within 2 months of diagnosis, before traditional susceptibility testing would have identified their MDRTB. Most non-MDRTB became smear- and culture-negative within 6 weeks of therapy, whereas most MDRTB remained sputum-culture-positive until death or treatment completion. HIV-negative patients with non-MDRTB had good outcomes. However, MDRTB was associated with prolonged infectiousness and HIV co-infection with early mortality, indicating a need for greater access to anti-retroviral therapy. Furthermore, early and rapid tuberculosis drug-susceptibility testing and infection control are required so that MDRTB can be appropriately treated early enough to reduce mortality and transmission.

Niveles de magnesio en pacientes VIH estadio SIDA, que cursan con tuberculosis, criptococosis, y su relación con la respuesta al tratamiento / Magnesium levels in AIDS-associated tuberculosis or cryptococcosis patients, and relationship with treatment response

Objetivos: Demostrar que los pacientes con virus de inmunodeficiencia humana (VIH) estadio síndrome de inmunodeficiencia adquirida (SIDA), asociada a tuberculosis (TBC) o criptococosis, tienen hipomagnesemia, que produce una inadecuada respuesta al tratamiento. Diseño: Estudio prospectivo, longitudinal. Material y Métodos: Se estudió 300 personas, divididos en seis grupos de 50 personas cada uno: pacientes VIH positivo, pacientes con tuberculosis, pacientes en estadio SIDA con TBC, pacientes en estadio SIDA con criptococosis, pacientes con enfermedades infecciosas agudas y una población normal (donadores de sangre). Resultados: Los valores promedio de magnesio estuvieron significativamente por debajo de los valores normales en los grupos SIDA+TBC, SIDA+criptococosis y TBC. Se aprecia que existe diferencia estadísticamente significativa en los niveles de magnesio en los grupos VIH, SIDA+TBC, SIDA+criptococosis y TBC. Con respecto a la hipomagnesemia y respuesta al tratamiento, el grupo que menos respondió al tratamiento fue el grupo de pacientes con SIDA+TBC (27 por ciento). Conclusiones: La hipomagnesemia es prevalente en los pacientes con infecciones crónicas, con diferencia significativa de los niveles de magnesio entre los grupos estudiados. El grupo VIH estadio SIDA+TBC es el que cursa con mayor anormalidad en las diferentes variables estudiadas.Palabras clave: Magnesio; síndrome de inmunodeficiencia adquirida; tuberculosis; criptococosis; deficiencia de magnesio.

Resistencia in vitro del Vibrio cholerae O1 a seis antimicrobianos / In vitro resistance of Vibrio cholerae O1 to six anticrobials

Se estudio la resistencia in vitro por el método de disco-difusión a 332 cepas de V. cholerae aislados en 151 adultos del Hospital Dos de Mayo de Lima, 146 de niños y 35 adultos del Hospital Carrión del Callao. Se obtuvo una resistencia promedio total del 8.4 por ciento a la ampicilina, 5.4 por ciento a la doxiciclina, 3.3 por ciento a la tetraciclina, 3 por ciento al cotrimoxazol, 0.6 por ciento a la furazolidona y ninguna a norfloxacina. No se justifica por el momento en cambio en el tratamiento antimicrobiano del cólera, que se realiza con tetraciclina o cotrimoxazol, y se tiene como alternativa en casos particulares de resistencia a la furazolidona y la fluoquinolonas