Meningitis por Streptococcus pneumoniae resistente a ceftriaxona: reporte de un caso / Ceftriaxone-resistant Streptococcus pneumoniae meningitis: case report

RESUMEN La meningitis infecciosa es una emergencia médica. Dentro del espectro de agentes infecciosos, el más importante es el Streptococcus pneumoniae, agente etiológico más frecuente de la meningitis bacteriana. El inicio de tratamiento antimicrobiano empírico es de gran importancia y considera a las cefalosporinas de tercera generación como la primera alternativa. Sin embargo, casos de resistencia a ceftriaxona han sido reportados en diversas partes del mundo, siendo un problema emergente, por lo que necesita una reconsideración de los esquemas antibióticos empíricos actuales. Presentamos el caso de un varón de 56 años que presenta meningitis aguda infecciosa por Streptococcus pneumoniae resistente a ceftriaxona, que respondió favorablemente al tratamiento empírico combinado con ceftriaxona y vancomicina y que durante su estadía hospitalaria se detectó la presencia de hipotiroidismo y megacisterna magna.

ABSTRACT Infectious meningitis is a medical emergency. Within the spectrum of infectious agents, the most important is Streptococcus pneumoniae, the most frequent etiological agent of bacterial meningitis. The initiation of empirical antimicrobial treatment bears great importance and considers third-generation cephalosporins as the first alternative. However, cases of ceftriaxone resistance have been reported in several regions of the world. This has become an emerging problem in need of reconsideration of the current empirical antibiotic treatment schemes. We present the case of a 56-year old man with acute infectious meningitis caused by ceftriaxone-resistant Streptococcus pneumoniae, who responded favorably to combined empirical treatment with ceftriaxone and vancomycin and to whom, during his hospital stay, the presence of hypothyroidism and mega cisterna magna was diagnosed.

Comparison of PCR-based methods for the simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in clinical samples

Abstract Background Several in-house PCR-based assays have been described for the detection of bacterial meningitis caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from clinical samples. PCR-based methods targeting different bacterial genes are frequently used by different laboratories worldwide, but no standard method has ever been established. The aim of our study was to compare different in-house and a commercial PCR-based tests for the detection of bacterial pathogens causing meningitis and invasive disease in humans. Methods A total of 110 isolates and 134 clinical samples (99 cerebrospinal fluid and 35 blood samples) collected from suspected cases of invasive disease were analyzed. Specific sets of primers frequently used for PCR-diagnosis of the three pathogens were used and compared with the results achieved using the multiplex approach described here. Several different gene targets were used for each microorganism, namely ctrA, crgA and nspA for N. meningitidis, ply for S. pneumoniae, P6 and bexA for H. influenzae. Results All used methods were fast, specific and sensitive, while some of the targets used for the in-house PCR assay detected lower concentrations of genomic DNA than the commercial method. An additional PCR reaction is described for the differentiation of capsulated and non-capsulated H. influenzae strains, the while commercial method only detects capsulated strains. Conclusions The in-house PCR methods here compared showed to be rapid, sensitive, highly specific, and cheaper than commercial methods. The in-house PCR methods could be easily adopted by public laboratories of developing countries for diagnostic purposes. The best results were achieved using primers targeting the genes nspA, ply, and P6 which were able to detect the lowest DNA concentrations for each specific target.

Clinical and bacteriological characteristics of invasive pneumococcal disease after pneumococcal 10-valent conjugate vaccine implementation in Salvador, Brazil

Abstract Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during the post-implementation period. Eighty-two cases were eligible. Mean age was 31 years (interquartile range, 3–42); 17.1% and 30.5% were under 2 years and 5 years, respectively. Pneumococcal meningitis (n = 64, 78.1%), bacteraemic pneumococcal pneumonia (n = 12, 14.6%) and bacteraemia (n = 6, 7.3%) were the clinical syndromes identified. Thirty-three different serotypes were found. Of these, serotype 14 (n = 12, 14.6%) was the most common, followed by 23F (n = 10, 12.2%), 12F (n = 8, 9.8%), 18 C (n = 5, 6.1%) and 6B (n = 5, 6.1%). Investigations conducted in Salvador in the pre-vaccine period did not identify serotype 12F as one of the most prevalent serotypes. Increase of serotype 12F was observed in different regions of Brazil, in the post-vaccine period. Among children under two years of age, the target group for 10-valent pneumococcal conjugate vaccine, 11 (78.6%) of the 14 isolated strains of Streptococcus pneumoniae belonged to vaccine serotypes; at least 50% of these children were not vaccinated. The relatively recent implementation of 10-valent pneumococcal conjugate vaccine in Brazil reinforces the need to maintain an active surveillance of invasive pneumococcal disease cases, considering the possible increase of invasive pneumococcal disease cases related to non-vaccine serotypes and the changes on the clinical presentation of the disease.

Infección invasiva por Streptococcus pneumoniae: reporte de caso de un paciente con síndrome de Austrian / Invasive Streptococcus pneumoniae infection (Austrian syndrome): a case report

Descrito inicialmente en 1957 por Robert Austrian, el síndrome que lleva su nombre se define como la tríada de neumonía, endocarditis y meningitis secundarias a una infección invasiva por Streptococcus pneumoniae . Desde entonces, y debido a su infrecuencia, se han reportado muy pocos casos en la literatura científica. A continuación se presenta el caso de un paciente de 61 años de edad con un cuadro inicial de meningitis bacteriana por S. pneumoniae , acompañado de neumonía bacteriana e insuficiencia mitral grave asociada a cuatro vegetaciones sobre la cara auricular de la valva posterior, con ruptura y prolapso de su festón central posterior. Se aisló S. pneumoniae , serotipo 18C, en líquido cefalorraquídeo y en dos hemocultivos. El paciente recibió antibióticos de amplio espectro y fue sometido a reemplazo valvular temprano con un resultado clínico satisfactorio. El principal factor pronóstico de esta condición lo determina el daño valvular subsecuente, sobre todo en pacientes con compromiso de la válvula aórtica, por lo que es necesario identificar tempranamente la extensión del compromiso valvular y definir oportunamente el tratamiento quirúrgico y antibiótico del paciente. En casos menos frecuentes, en los que solo hay compromiso de la válvula mitral, la evolución clínica es menos aguda y, por lo general, el tratamiento antibiótico dirigido y las medidas de soporte avanzado suelen ser suficientes para su control.

Austrian syndrome is defined as the triad consisting of pneumonia, endocarditis and meningitis due to invasive Streptococcus pneumoniae infection. Few case reports have been reported since its first description in 1975 by Robert Austrian, mainly because it is rarely observed. Below we report the case of a 61 year-old male patient who presented with bacterial meningitis due S. pneumoniae followed by bacterial pneumonia and severe mitral regurgitation, associated with four vegetations on the atrial surface of the posterior mitral leaflet; in addition, there was rupture and prolapse of its middle scallop. The S. pneumoniae bacterium was isolated from cerebrospinal fluid and blood cultures. In consequence, the patient was given broad-spectrum antibiotic therapy and had an early valve replacement performed, obtaining a good clinical outcome. The key prognostic factor of the Austrian syndrome is determined by the damage of cardiac valves, particularly in patients with a compromised aortic valve; hence, it is necessary to identify the degree of valve injury and define surgical and antibiotic treatment on a timely fashion. However, in subacute, less frequent clinical cases where the mitral valve is the main valve compromised, usually a directed antibiotic therapy associated with advanced support measures are sufficient to control this infection.

Meningitis neumocócica en niños menores de 15 años: Dieciséis años de vigilancia epidemiológica en Misiones, Argentina / Pneumococcal meningitis in children under 15 years of age in Misiones (Argentina): Sixteen year's epidemiological surveillance

Se presentan en este trabajo los resultados de 16 años de vigilancia epidemiológica de meningitis neumocócica llevada a cabo en el Hospital Provincial de Pediatría de Misiones (Argentina), antes de la introducción de la vacuna conjugada al calendario nacional. En el período que va de enero de 1994 a diciembre de 2009 se diagnosticaron 167 casos de meningitis por Streptococcus pneumoniae en niños (1 mes-15 años). La tasa de ataque cada 100 000 niños varió entre 19,2 (1997) y 4,3 (2009), con una media de 10,6 y una tendencia en disminución (y = ""0,689x + 16,52). Esto fue a expensas del grupo de niños entre 1 y 11 meses (94/167, 56 %), en el que disminuyó de 146,6 a 34,8 casos cada 100 000 niños. El 30,7 % de los aislamientos (46/150) fueron resistentes a penicilina y el 16,7 % (25/150) no sensibles a cefotaxima. La resistencia a β-lactámicos se incrementó a partir de 1997 y comenzó a disminuir en 2005. Se detectaron 19 serotipos, predominó el 14 (32 %; 40/125). El 84,8 % de los aislamientos quedaron circunscriptos a nueve serotipos: 14, 5, 1, 7F, 18C, 6B, 9N, 9V y 4. La cobertura teórica en los niños < 2 años y > 2 años fue de 84,1 % (74/88) y 83,8 % (31/37) con la vacuna 10-valente, y de 89,8 % (79/88) y 83,8 % (31/37) con la vacuna 13-valente, respectivamente. La resistencia a penicilina estuvo circunscripta a 8 serotipos (14, 6B, 6A, 9V, 4, 23B, 1 y 19A), y la no sensibilidad a cefotaxima a 3 serotipos (14, 9V y 1), el más importante fue en ambos casos el serotipo 14. Este estudio permitirá evaluar el impacto de la implementación de las vacunas conjugadas en nuestra zona.

We report the results of pneumococcal meningitis surveillance conducted at the Provincial Pediatric Hospital of Posadas, Misiones (Argentina), before the conjugate vaccine was introduced into the national vaccination schedule. Between January 1994 and December 2009, 167 cases of Streptococcus pneumoniae meningitis were diagnosed in children aged 1 month to 15 years. The attack rate/100,000 children ranged from 19.2 (1997) to 4.3 (2009), with a mean of 10.6 and a tendency to decrease (y=""0.689x+16.52). The number of cases per 100,000 children decreased from 146.6 to 34.8 and particularly involved the group of children aged 1 to 11 months (94/167, 56%). Thirty point seven percent (30.7%) (46/150) of the isolates were resistant to penicillin whereas 16.7% (25/150) were non-susceptible to cefotaxime. β-lactam resistance increased as from 1997 and began to decline in 2005. Nineteen serotypes were detected; type 14 was predominant and accounted for 32% (40/125). Eighty four point eight percent (84.8%) of the isolates were circumscribed to nine serotypes: 14, 5, 1, 7F, 18C, 6B, 9N, 9V and 4. Theoretical coverage for patients aged <2 years and >2 years was 84.1% (74/88) and 83.8% (31/37) for the 10-valent vaccine and 89.8 % (79/88) and 83.8% (31/37) for the 13-valent vaccine respectively. Penicillin resistance was restricted to 8 serotypes (14, 6B, 6A, 9V, 4, 23B, 19A1) and nonsusceptibility to cefotaxime was circumscribed to 3 serotypes (14, 9V and 1). This study will allow to evaluate the impact of the implementation of conjugate vaccines on our area.

Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines / Distribución de serotipos de neumococos aislados de pacientes pediátricos con otitis media aguda e infecciones invasivas y su cobertura potencial a través de vacunas conjugadas

A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AÜM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

Se realizó un estudio prospectivo descriptivo sobre la distribución de serotipos de neumococos aislados de niños con otitis media aguda (OMA) y con infecciones invasivas (INV) en un período de 16 meses. Se incluyeron 89 niños con INV neumocócicas y 324 con un primer episodio de OMA. Trescientos cuarenta y seis patógenos se aislaron de las secreciones de oído medio obtenidas de 250 pacientes. Se identificaron 30 serotipos y los más prevalentes fueron el 14, 19A, 9V, 3, 19F, 6A, 23F y 18C en OMA y el 14, 1, 19A, 5, 12F, 6B y 18C en INV. La cobertura potencial con la vacuna PCV10 sería de 46,5 % y 60,7 % para neumococos involucrados en OMA y en INV, respectivamente; con la PCV13, esta sería de 71,7 % y 73 %. La PCV10 conjugada con una proteína de Haemophilus tendría una cobertura inmunológica del 39,9 % para OMA, contra una cobertura del 18,5 % de la PCV13. Sin embargo, las diferencias en la prevención de INV fueron determinantes a la hora de considerar incorporarla al calendario nacional de vacunación para niños menores de 2 años en la Argentina.

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches / Fisiopatologia da meningite ocasionada pelo Streptococcus pneumoniae e novas possibilidades terapêuticas adjuvantes

Pneumococcal meningitis is a life-threatening disease characterized by an acute purulent infection affecting piamater, arachnoid and the subarachnoid space. The intense inflammatory host's response is potentially fatal and contributes to the neurological sequelae. Streptococcus pneumoniae colonizes the nasopharynx, followed by bacteremia, microbial invasion and blood-brain barrier traversal. S. pneumoniae is recognized by antigen-presenting cells through the binding of Toll-like receptors inducing the activation of factor nuclear kappa B or mitogen-activated protein kinase pathways and subsequent up-regulation of lymphocyte populations and expression of numerous proteins involved in inflammation and immune response. Many brain cells can produce cytokines, chemokines and others pro-inflammatory molecules in response to bacteria stimuli, as consequence, polymorphonuclear are attracted, activated and released in large amounts of superoxide anion and nitric oxide, leading to the peroxynitrite formation, generating oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage, blood-brain barrier breakdown contributing to cell injury during pneumococcal meningitis.

A meningite pneumocócica é doença potencialmente fatal caracterizada por infecção aguda purulenta que afeta a pia-máter, a aracnoide e o espaço subaracnoide. A resposta inflamatória do hospedeiro é potencialmente fatal e contribui para as sequelas neurológicas. O processo inicia-se com a colonização da nasofaringe pelo Streptococcus pneumoniae, seguida de invasão, bacteremia e passagem através da barreira hematoencefálica. O S. pneumoniae é reconhecido por células apresentadoras de antígenos através da ligação aos receptores Toll-like. Isto induz a ativação do fator nuclear kappa B ou proteína quinase ativada por mitógenos. Muitas células cerebrais também podem produzir citocinas, quimiocinas e outras moléculas pró-inflamatórias em resposta aos estímulos bacterianos. Como consequência, são atraídos polimorfonucleares, ocorrendo a liberação de grandes quantidades de ânion superóxido e óxido nítrico, o que leva à formação de peroxinitrito e ocasiona o estresse oxidativo. Esta cascata pró-inflamatória leva à peroxidação lipídica, a danos mitocondriais e à ruptura da barreira hematoencefálica, contribuindo para o dano celular em meningite pneumocócica.

Meningite bacteriana aguda na infância: fatores de risco para complicações agudas e sequelas / Childhood acute bacterial meningitis: risk factors for acute neurological complications and neurological sequelae

OBJETIVO: Estudo retrospectivo que visa avaliar as complicações neurológicas agudas e sequelas neurológicas das meningites bacterianas agudas na infância, a fim de determinar possíveis sinais de alerta. MÉTODOS: Foram avaliadas crianças (entre 1 mês e 14 anos) internadas entre 2003 e 2006, com meningite bacteriana aguda. RESULTADOS: Dos 44 pacientes incluídos, 17 (38,6%) apresentaram complicações neurológicas agudas, sendo crise convulsiva a mais frequente (31,8%). Os pacientes com complicações neurológicas agudas apresentaram com mais frequência: menor contagem de neutrófilos (p = 0,03), crise convulsiva na admissão (p < 0,01) e S. pneumoniae como agente etiológico (p = 0,01). Os fatores de risco para o desenvolvimento de complicações neurológicas agudas foram: S. pneumoniae [razão de chances (odds ratio, OR) = 6,4; intervalo de confiança (IC) 1,7-24,7] e contagem de neutrófilos < 60% (p < 0,01). De 35 pacientes seguidos ambulatorialmente, 14 apresentaram sequelas neurológicas (40%), sendo alteração comportamental a mais frequente. A ocorrência de crise convulsiva na internação (OR = 5,6; IC 1.2-25,9), proteinorraquia > 200 mg/dL (p < 0,01) e menor relação glicorraquia/glicemia (p < 0,01) foram identificadas como variáveis de risco para sequelas. CONCLUSÃO: Contagem de neutrófilos < 60%, crise convulsiva na admissão e S. pneumoniae como agente etiológico foram identificados como sinais de alerta para a ocorrência de complicação neurológica aguda, enquanto que proteinorraquia, menor relação glicorraquia/glicemia e crise convulsiva na internação foram observados como fatores de risco para a ocorrência de sequelas neurológicas.

OBJECTIVE: To assess acute neurological complications and neurological sequelae of childhood acute bacterial meningitis in order to determine possible warning signs. METHODS: This retrospective study evaluated children with acute bacterial meningitis (between 1 month and 14 years of age) admitted between 2003 and 2006. RESULTS: Of the 44 patients studied, 17 (38.6%) had acute neurological complications. Seizure was the most frequent (31.8%) complication. Patients with acute neurological complications showed a higher frequency of lower neutrophil count (p = 0.03), seizure at admission (p < 0.01), and S. pneumoniae as the etiologic agent (p = 0.01). Risk factors for the development of acute neurological complications were S. pneumoniae (odds ratio [OR] = 6.4, confidence interval [CI] 1.7-24.7) and neutrophil count < 60% (p < 0.01). Of the 35 patients who were followed up, 14 had neurological sequelae (40%). Behavioral change (22.9%) was the most frequent sequela. Seizures at admission (OR = 5.6, CI 1.2-25.9), cerebrospinal fluid protein concentration > 200 mg/dL (p < 0.01), and cerebrospinal fluid glucose concentration/glycemia ratio (p < 0.01) were identified as risk variables for sequelae. CONCLUSION: Neutrophil count < 60%, seizure at admission, and S. pneumoniae as the etiologic agent were identified as warning signs for acute neurological complications, while protein levels, cerebrospinal fluid glucose concentration/glycemia ratio, and seizure at admission were seen as risk factors for neurological sequelae.

Prevalence of pneumococcal serotypes and resistance to antimicrobial agents in patients with meningitis: ten-year analysis

OBJECTIVES: To determine the prevalence of pneumococcal serotypes and antimicrobial susceptibility in patients with meningitis, and to evaluate the implications for vaccine coverage. METHODS: Pneumococcal strains obtained from normally sterile fluids from patients admitted with meningitis were isolated at the Hospital de Clínicas of the Universidade Federal de Uberlândia, Minas Gerais State, and sent to the Instituto Adolfo Lutz, city of São Paulo, São Paulo State, for further identification, serotyping, and antimicrobial susceptibility determination. RESULTS: From April 1999 to April 2009, 338 pneumococcal strains were isolated, and 72 obtained from patients with meningitis, were analyzed. Patients' ages varied from one month to 82.2 years (mean of 18.4 ± 22.9 years; median of 5.2 years) and 46 (63.9 percent) patients were male. Strains were isolated from cerebrospinal fluid [66 occasions (91.7 percent)] and blood [6 occasions (8.3 percent)]. The most commonly identified serotypes were 14, 19F, 3, 7F, 6A, 6B, 10A, 18C, 23F, 5, and 34. Of the 20 [27.8 percent] oxacillin-resistant strains, 17 [23.6 percent] were resistant to penicillin and nine [12.5 percent] to ceftriaxone, both resistance patterns being more common in children aged two years or less and during the 2005-2009 period. CONCLUSIONS: Resistance to penicillin and ceftriaxone was detected in 23.6 percent and 12.5 percent of the strains, respectively, and predominated in children aged two years or less and during the 2005-2009 period. There were 24 different serotypes of pneumococcus and 79.8 percent of the serotypes were represented in the 7-valent conjugated vaccine [PVC7].

Invasive pneumococcal diseases among hospitalized children in Lima, Peru / Enfermedades neumocócicas invasoras en niños hospitalizados en Lima, Perú

OBJECTIVE: To determine the epidemiology of invasive pneumococcal disease (IPD) and the antibiotic susceptibility and serotype distribution of S. pneumoniae in pediatric patients in Lima, Peru. METHODS: A 2-year, multicenter, passive surveillance study conducted from May 2006- April 2008 in 11 public hospitals and five private laboratories in Lima, Peru, in patients less than 16 years of age with sterile site cultures yielding S. pneumoniae. Antibiotic susceptibility was performed by Etest® (AB Biodisk, Solna, Switzerland). Strains were serotyped by the Quellung reaction. RESULTS: In all, 101 IPD episodes were studied, 68.3 percent of which were among children less than 24 months of age. Diagnoses were: pneumonia (47.5 percent), meningitis (38.6 percent), and sepsis (7.9 percent). The overall case fatality rate was 22.0 percent; case fatality rate in meningitis was 32.4 percent. While 80.0 percent of fatal cases were in those less than 24 months of age, only 50.7 percent of non-fatal cases (P < 0.05) were in this age group. Resistance rates were high for trimethoprim/ sulfamethoxazole (76.2 percent), erythromycin (24.8 percent), and penicillin (22.8 percent). The most common serotypes were 14, 6B, 19F, 23F, and 5, which accounted for 69.7 percent of all strains and 87.0 percent of penicillin non-susceptible strains. CONCLUSIONS: IPD in hospitalized children in Lima is associated with high antimicrobial resistance levels and elevated case fatality rate, especially in young children. This baseline data will be useful for evaluating the effects of vaccine introduction.

OBJETIVO: Determinar la epidemiología de la enfermedad neumocócica invasora y la sensibilidad a los antibióticos y la distribución de los serotipos de S. pneumoniae en pacientes pediátricos en Lima, Perú. MÉTODOS: Estudio multicéntrico de vigilancia pasiva durante dos años, entre mayo del 2006 y abril del 2008, en 11 hospitales públicos y 5 consultorios privados de Lima, en pacientes menores de 16 años con cultivos de sitios estériles positivos para S. pneumoniae. Se determinó la sensibilidad a los antibióticos mediante Etest® (AB Biodisk, Solna, Suiza). Se serotipificaron las cepas mediante la reacción de Quellung. RESULTADOS: En total, se estudiaron 101 episodios de enfermedad neumocócica invasora, 68,3 por ciento de ellos en niños menores de 24 meses, con los siguientes diagnósticos: neumonía (47,5 por ciento), meningitis (38,6 por ciento) y septicemia (7,9 por ciento). La tasa de letalidad general fue de 22,0 por ciento y la tasa de letalidad por meningitis de 32,4 por ciento. Si bien 80,0 por ciento de los casos mortales ocurrió en menores de 24 meses, solo 50,7 por ciento de los casos no mortales (P < 0,05) ocurrió en este grupo de edad. Las tasas de resistencia fueron elevadas para trimetoprima-sulfametoxazol (76,2 por ciento), eritromicina (24,8 por ciento) y penicilina (22,8 por ciento). Los serotipos más comunes, 14, 6B, 19F, 23F y 5, representaron 69,7 por ciento de todas las cepas, y 87,0 por ciento de las cepas no sensibles a la penicilina. CONCLUSIONES: La enfermedad neumocócica invasora en niños hospitalizados en Lima se asocia con altos niveles de resistencia a los antimicrobianos y una tasa de letalidad elevada, especialmente en niños pequeños. Estos datos iniciales serán útiles para evaluar los efectos de la introducción de las vacunas.

In vivo characterization of streptococcus pneumoniae genes involved in the pathogenesis of meningitis by differential fluorescence induction

To further understand the pathogenesis of pneumococcal meningitis, and provide some target candidates for the development of drugs. This study was performed at the Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine [Ministry of Education], Chongqing Medical University, Chongqing, China from March 2006 to December 2007. A promoter-trap library of Streptococcus pneumoniae TIGR4, reported by green fluorescent protein was constructed, and used to infect BALB/c mice [n=15] intranasally, to set up a meningitis model. The control group [n=5] were inoculated with sterile phosphate buffered saline. The bacteria containing the promoter fusions induced only in meningitis brain tissue, not in vitro were screened by differential fluorescence induction. The obtained bacteria were prepared to re-infect the mice and re-screened, as above. The sorted bacteria were spread on trypticase soy agar with 5% sheep blood agar plates containing chloramphenicol [2.5 micro g/ml], and were used for DNA cloning, sequencing, and bioinformatics analysis. A total of 52 genes were obtained. Bioinformatics analysis revealed that these in vivo induced genes were involved in functions such as, adherence, energy metabolism, nutrient substance transport, transcription regulation, DNA metabolism, as well as, cell wall synthesis. In addition, there were some genes encoding for some hypothetical proteins with unknown, or putative functions. Pneumococcal genes involved in meningitis identified in this study are potential targets to understand the pathogenesis of pneumococcal meningitis

Establishment of population-based surveillance for invasive pneumococcal disease in Bangalore, India.

Background :Invasive pneumococcal disease (IPD) is vaccine-preventable but few data on the incidence of PD exist for Indian children. Aims: To assess the feasibility of implementing prospective, population-based surveillance for PD among children less than five years of age. Settings and Design :Hospitals and health agencies, Bangalore, India. Retrospective review and analysis of hospitalization records as well as public health and demographic data. Material and Methods : Records for 2006 hospitalizations for pneumococcal disease-associated syndromes (meningitis, pneumonia and sepsis) were identified at three pediatric referral hospitals (Indira Gandhi Institute of Child Health, Kempegowda Institute of Child Health and Vani Vilas Hospital) in Bangalore using International Classification of Diseases, 9th revision codes. Hospital microbiology laboratory records were assessed to ensure capacity for identifying S. pneumoniae. Population data were identified from national census and polio surveillance data. Results : The Bangalore city southern zone includes 33 wards occupying 51 Km 2 with 150,945 children between 0-5 years of age served by three referral pediatric hospitals. From January--December 2006, records of these three hospitals showed 2,219 hospitalizations of children less than five years of age (967 pneumonia, 768 sepsis, and 484 meningitis) with PD-associated diagnoses (southern zone area incidence: 0.15/100,000 PD-associated hospitalizations, less than five years of age). There were 178 deaths in children less than five years of age, of which 87 were attributable to sepsis, 56 to pneumonia and 35 to meningitis. Conclusion : Our analysis suggests that the PD-associated disease burden in Bangalore is high and local institutions have capacity for population-based surveillance. In a prospective study, systematic attention to potential barriers in identifying children with pneumococcal infections will improve estimation of IPD incidence in India.

Doença pneumocócica invasiva em crianças e adolescentes soropositivos para HIV / Invasive pneumococcal disease in HIV seropositive children and adolescents

OBJETIVO: Doença Invasiva Pneumocócica (DPI) afeta crianças principalmente menores de 5 anos, idosos e grupos de risco, especialmente pessoas infectadas pelo vírus da Imunodeficiência Humana (HIV). O objetivo deste trabalho foi analisar as doenças pneumocócicas invasivas (DPI) em crianças e adolescentes infectados pelo vírus da imunodeficiência humana (HIV), de acordo com morbiletalidade, sorotipos, sensibilidade à penicilina e ceftriaxona e distribuição de Streptococcus pneumoniae (Sp) sensíveis e resistentes presentes na vacina antipneumocócica conjugada 7-valente, já licenciada. MÉTODOS: Foram identificados 19 casos de DPI entre pacientes HIV soropositivos com idade entre 1 mês e 20 anos hospitalizados de 1993 a 2000. Os dados foram registrados em fichas padronizadas, contendo informações sobre idade, diagnóstico clínico e evolução, sorotipos e perfil de sensibilidade para penicilina e ceftriaxona das cepas de Sp isoladas em cultura. Sp com concentração inibitória mínima < 0,1 mcg/mL foi considerado sensível à penicilina (SpSPn), e as demais cepas como não sensíveis (SpNSPn). RESULTADOS: Dos 19 casos de DPI em HIV soropositivos, 16 (84 por cento) tinham pneumonia e três (16 por cento), meningite; 13 (68 por cento) ocorreram em crianças menores de 2 anos e 16 (84 por cento) em menores de 5 anos. A letalidade foi de 10 por cento. Dos 13 casos em menores de 2 anos, sete (54 por cento) foram SpNSPn e 10 (77 por cento) foram causados por sorotipos contemplados na vacina antipneumocócica conjugada 7-valente. Foram isolados 10 sorotipos, sendo mais freqüentes o 14, 6B e 23F, todos sensíveis à ceftriaxona. Dos três casos de meningite, dois foram causados por SpNSPn. CONCLUSÃO: A maioria das DPI ocorreu em menores de 2 anos de idade; 77 por cento das cepas e 86 por cento dos sorotipos de SpNSPn estão contemplados pela vacina antipneumocócica conjugada 7-valente.

OBJECTIVE: Invasive pneumococcal disease (IPD) primarily affects children less than 5 years old, the elderly and certain at-risk groups; especially people infected by the human immunodeficiency virus (HIV). The objective of this study was to analyze invasive pneumococcal diseases (IPD) in children and adolescents infected by the human immunodeficiency virus (HIV), with relation to morbidity, the case fatality ratio, pneumococcus serotypes, susceptibility to penicillin and ceftriaxone and to the proportion of susceptible and resistant Streptococcus pneumoniae (Sp) included in the 7-valent pneumococcal conjugate vaccine that has already been licensed. METHODS: A total of 19 cases of IPD were identified among HIV seropositive patients aged from 1 month to 20 years and hospitalized between 1993 and 2000. Data were recorded on standardized charts containing information on age, clinical diagnosis and progression, serotypes and the susceptibility to penicillin and ceftriaxone of the Sp strains identified in cultures. When the minimum inhibitory concentration was < 0.1 mcg/mL, Sp were defined as susceptible to penicillin (SpSPn), and all other strains were defined as not susceptible (SpNSPn). RESULTS: Of the 19 HIV seropositive cases with IPD, 16 (84 percent) had pneumonia and three (16 percent), had meningitis; 13 (68 percent) cases were children less than 2 years old and 16 (84 percent) were less than 5 years old. The case fatality ratio was 10 percent. Seven (54 percent) of the 13 cases less than 2 years old were SpNSPn and 10 (77 percent) were caused by serotypes covered by the 7-valent pneumococcal conjugate vaccine. From the 10 isolated serotypes the most frequent were 14, 6B and 23F, all them susceptible to ceftriaxone. From the three patients with meningitis, two were caused by SpNSPn. CONCLUSION: In this study most of the IPD occurred in children less than 2 years old; 77 percent of the strains and 86 percent of the serotypes of SpNSPn...

Meningitis neonatal por Streptococcus pneumoniae atípico: Reporte de un caso y revisión / Neonatal meningitis caused by atypical Streptococcus pneumoniae: Case report and review

Streptococcus pneumoniae is a rarely recognized cause of neonatal sepsis and/or meningitis, but it is associated with substantial morbidity and mortality. Traditionally, S. pneumoniae is identified in the laboratory by demonstrating susceptibility to optochin. However, the emergence of optochin-resistant organisms makes definite identification difficult when only phenotypic tests are taken as markers. We present the case of a severe early-onset neonatal meningitis due to an atypical strain of S. pneumoniae. Laboratory methods utilized to certify this species diagnosis are discussed.

Streptococcus pneumoniae es una causa infrecuente de infección en el recién nacido y se caracteriza por gran capacidad invasora (sepsis, meningitis) y alta mortalidad. Tradicionalmente, esta bacteria se diagnostica en base a su susceptibilidad a optoquina. Sin embargo, la emergencia de cepas de S. pneumoniae resistentes a optoquina (atípicas) dificulta el diagnóstico sin utilizar varias pruebas diagnósticas, incluyendo las de biología molecular. Se describe el caso de una neonata con infección invasora causada por una cepa de S. pneumoniae atípico y se discuten los métodos empleados para certificar el diagnóstico de esta especie.

Pneumococcal subdural empyema in young infants.

We report three young infants including a neonate with fulminant pneumococcal subdural effusion.

Características clínico-microbiológicas de la meningitis por Streptococcus pneumoniae resistente a la penicilina / Streptococcus pneumoniae meningitis resistant to penicillin clinical and microbiological characteristics

Objetivo. Evaluar la susceptibilidad antimicrobiana de Streptococcus pneumoniae aislado del líquido cefalorraquídeo de niños con meningitis, así como describir y comparar las características clínicas y microbiológicas, el tratamiento y la evolución del padecimiento entre niños infectados con cepas sensibles y resistentes a la penicilina y la cefalosporina. Material y métodos. Treinta y ocho niños con meningitis neumocóica, durante el lapso 1994-1998. Los datos clínicos y de laboratorio se colectaron de cada expediente. Resultados. Del total de niños, 63 por ciento era menor de dos años de edad, 28.9 por ciento mostró cepas insensible a la penicilina, 18.4 por ciento tenía resistencia intermedia, y 10.5 por ciento tenía resistencia elevada. El 2.6 por ciento mostró también resistencia a la cefotaxima. La única característica (por la prueba exacta de Fisher) asociada con la resistencia fue: enfermedad de base previa al procesos (p< 0.001), y condiciones de gravedad al ingreso como convulsiones, choque tóxico y coma (p< 0.07). El curso de la enfermedad y la evolución clínica fue similar para los niños infectados con cepas sensibles a la penicilina o a la cefotaxima vs. las cepas no susceptibles. Conclusiones. El perfil actual de resistencia del S. pneumoniae a la penicilina y la cefalosporina no se encontró asociado con un aumento en la mortalidad de niños con meningitis neumocóica

Meningitis por streptococcus pneumoniae con sensibilidad disminuída a cefotaxima / Streptococcus pneumoniae meningitis with cefotaxime decreased activity

Se reporta un lactante de 15 meses de edad, el primer caso de meningitis neumocóccica documentado en el Hospital Exequiel González Cortés, cuyo tratamiento con cefotaxima, en dosis de 200 mg/kg/día, no logró esterilizar el LCR tras 24 horas de aplicación debiendo adicionarse vancomicina según las recomendaciones internacionales vigentes. Las CIM, efectuadas por epsilometría, fueron de 1 µg/ml tanto para penicilina como cefotaxima. El paciente egresó del hospital sin secuelas neurológicas inmediatas aparentes

Aspectos dos líquidos cefalorraquidianos nas meningites bacterianas / The cerebrospinal fluid in bacterial meningitis

Samples of 1815 cerebrospinal fluid (CSF) were studied in a meningitis outbreak during 1989 in S ao Paulo, Brazil. Neisseria meningitis 56 per cent with 44 per cent type B, Haemophilus influenzae 17 per cent , from which 72 per cent in children (days to 3-year-old) and Streptococcus pneumoniae 14 per cent from which 60 per cent in children (day to 1-year-old) of 443 (24 per cent ) of all strains. Cytochemistry study showed: purulent or turbidity aspects in 70 to 79 per cent positive bacterioscopy or culture of CSF; white cells count > 500/mm3; glucose < 45 mg/dl; protein > 90 mg/dl in 90 per cent of all patients. We concluded that: CSF prognostic factors: (aspect and cytochemistry) were correlated with bacterial meningitis. Bacterioscopy and positive cultures were correlated to NM, SP and HI isolation from these patients (Goodman Test)

Inmunización contra neumococos / Immunization against pneumococcus

Streptococus pneumoniae o neumococo, es una bacteria Gram-positiva considerada como uno de los principales agentes patógenos del aparato respiratorio en personas de todas las edades, particularmente aquellas de edad avanzada. En este último grupo de edad, la neumonía neumocócica sigue siendo una de las causas más importantes de morbilidad y mortalidad. Vacunas disponibles: el primer programa de vacunación antineumocócica se efectuó en 1911 en Africa del Sur en los trabajadores mineros, pues en ellos la incidencia de la enfermedad era muy alta y producía muchas defunciones. Al principio de la década de los 70 se usó la primera vacuna polisacarídica antineumocócica; en 1977 en los Estados Unidos se autorizó y en 1978 se inició la comercialización de la vacuna neumocócica de 14 serotipos, con 50 g. de polisacárido capsular. Hasta 1983 fue que se volvieron a autorizar cambios en la vacuna, ahora con 25 g. de cada polisacárido de 23 serotipos. Por lo que respecta a las vacunas en desarrollo se anota: desde su aparición, muchos se ha dicho sobre la antigenicidad y seguridad de la vacuna neumocócica. Aunque quedan por despejarse muchas dudas, lo que si está claro es que se necesita una vacuna más inmunogénica, especialmente para los niños menores de 2 años. Hasta el momento, lo más promisorio son las vacunas conjugadas a proteínas. Existen otras posibilidades de nuevas vacunas, las cuales se encuentran aún en estudio experimental e incluyen utilización de conjugados hexasacáridos y de anticuerpos monoclonales

A profile of pyogenic meningitis in children.

Clinical profile of pyogenic meningitis was studied in 256 cases over a period of 8 years. The male to female ratio was 1.46: 1 and 83.6% of the patients were less than 3 years of age. Fever, altered sensorium, refusal to feed, convulsions and vomiting were the common presenting symptoms. Six (2.3%) of them had subnormal temperature and the sensorium was normal in 12.5% of cases. Cerebrospinal fluid was clear in 9.4%, cell count was less than 100/cmm in 8.2%, sugar was more than 40 mg% in 24.2% and protein was less than 50 mg% in 12.5% of cases. Diplococcus pneumoniae was the commonest causative agent. The overall mortality was 30.5%. It is concluded that young children suffering from this disease may not have the typical features and one should have the highest suspicion to make an early diagnosis so that the morbidity and mortality from this condition can be reduced.