Combined therapy with ceftriaxone and doxycycline does not improve the outcome of meningococcal meningitis in mice compared to ceftriaxone monotherapy.

BACKGROUND: Meningococcal meningitis (MM) is a life-threatening disease associated with approximately 10% case fatality rates and neurological sequelae in 10-20% of the cases. Recently, we have shown that the matrix metalloproteinase (MMP) inhibitor BB-94 reduced brain injury in a mouse model of MM. The present study aimed to assess whether doxycycline (DOX), a tetracycline that showed a neuroprotective effect as adjuvant therapy in experimental pneumococcal meningitis (PM), would also exert a beneficial effect when given as adjunctive therapy to ceftriaxone (CRO) in experimental MM. METHODS: BALB/c mice were infected by the intracisternal route with a group C Neisseria meningitidis strain. Eighteen h post infection (hpi), animals were randomised for treatment with CRO [100 mg/kg subcutaneously (s.c.)], CRO plus DOX (30 mg/kg s.c.) or saline (control s.c.). Antibiotic treatment was repeated 24 and 40 hpi. Mouse survival and clinical signs, bacterial counts in cerebella, brain damage, MMP-9 and cyto/chemokine levels were assessed 48 hpi. RESULTS: Analysis of bacterial load in cerebella indicated that CRO and CRO + DOX were equally effective at controlling meningococcal replication. No differences in survival were observed between mice treated with CRO (94.4%) or CRO + DOX (95.5%), (p > 0.05). Treatment with CRO + DOX significantly diminished both the number of cerebral hemorrhages (p = 0.029) and the amount of MMP-9 in the brain (p = 0.046) compared to untreated controls, but not to CRO-treated animals (p > 0.05). Levels of inflammatory markers in the brain of mice that received CRO or CRO + DOX were not significantly different (p > 0.05). Overall, there were no significant differences in the parameters assessed between the groups treated with CRO alone or CRO + DOX. CONCLUSIONS: Treatment with CRO + DOX showed similar bactericidal activity to CRO in vivo, suggesting no antagonist effect of DOX on CRO. Combined therapy significantly improved mouse survival and disease severity compared to untreated animals, but addition of DOX to CRO did not offer significant benefits over CRO monotherapy. In contrast to experimental PM, DOX has no adjunctive activity in experimental MM.

El declive de la incidencia de enfermedad meningocócica en Barcelona entre 1988 y 2015: la influencia de la vacunación frente al serogrupo C / The decline of the incidence of meningococcal disease in Barcelona between 1988 and 2015: the influence of the vaccine against serogroup C

Introducción y objetivo: El objetivo es conocer la evolución de la enfermedad meningocócica en la ciudad de Barcelona entre 1988 y 2015 y evaluar el impacto de la vacuna contra el serogrupo C. Materiales y métodos: Se analizó la evolución de casos de enfermedad meningocócica y por serogrupo a partir del registro de enfermedades de declaración obligatoria. Se comparó la incidencia de todos los serogrupos antes y después de la introducción de la vacunación contra el serogrupo C en el año 2000. Se analizó la cobertura vacunal entre los casos, el serogrupo entre casos vacunados y la tasa de mortalidad y letalidad. Resultados: La enfermedad meningocócica ha pasado de una incidencia en menores de un año de 63,09 casos por 100.000 en 1997-2000 a 15,44 en 2001-2015. Todos los serogrupos han disminuido su incidencia tras la implementación vacunal, especialmente en niños de uno a 4 años para el C. A partir del 2000 la cobertura vacunal en los casos por este serogrupo era del 7,6% y en los afectos por el B era del 35,0% (p<0,01). De los vacunados, el 66,4% de los casos fue serogrupo B y un 5,2% fue C (p<0,01). La tasa global de letalidad y de mortalidad fue del 7,7% y del 0,19/100.000 respectivamente, sin cambios significativos en el tiempo en cuanto a la letalidad. Conclusiones: La incidencia por serogrupo C y también por B ha disminuido tras la vacunación sistemática contra el serogrupo C. La vacunación contra el serogrupo B podría reducir aún más esta grave enfermedad con una letalidad importante que no ha disminuido en todo el periodo

Introduction and objective: The purpose of this study was to describe the evolution of meningococcal disease (MD) in the city of Barcelona between 1988 and 2015 and to assess the impact of the vaccine against serogroup C. Materials and methodology: The evolution of MD and by serogroup was analysed using the information included in the mandatory notification diseases registry. Incidences of all serogroups between the periods of before and after the implementation of the serogroup C vaccine in 2000 were compared. Vaccination coverage among cases, serogroup among vaccinated cases and mortality and case fatality rates were analysed. Results: MD has evolved from an incidence rate in children aged under 1 of 63.09 cases per 100,000 in 1997-2000 to 15.44 per 100,000 in 2001-2015. All MD serogroups incidences decreased after the implementation of the vaccine, especially for serogroup C among children aged between 1 and 4. Since 2000 vaccine coverage in MD cases by this serogroup was 7.6% while in those affected by serogroup B it was 35.0% (p<.01). Among those vaccinated, 66.4% of cases were serogroup B and 5.2% were C (p<.01). Mortality and case fatality rates were 7.7% and 0.19/100,000 respectively, without significant changes in time regarding case fatality. Conclusions: Incidence caused by serogroups B and C has decreased after the systematic vaccination against serogroup C. Vaccination against serogroup B could further reduce the impact of this lethal disease which has not decreased during this period

Neisseria meningitidis: evolution of penicillin resistance and phenotype in a children's hospital in Barcelona, Spain.

UNLABELLED: Neisseria meningitidis is the most prevalent micro-organism involved in paediatric bacterial meningitis in the Barcelona area in children over 3 mo of age and it is an important cause of morbidity and mortality in Spain. A total of 498 strains of N. meningitidis, obtained between the years 1986 and 1997 from children with sepsis and/or meningitis, were characterized according to their serogroup and penicillin resistance; their distribution in serotypes and subtypes was studied from 1990. A decreasing tendency in the number of annual isolates was observed in this period. Most isolates belonged to serogroups B (403 strains) and C (77 strains). Serogroup C accounted for 1.8% of the strains in 1986 and 57.1% in 1997. The most prevalent phenotype between 1990 and 1996 was B:4:P1.15. but C:2b:P1.2,5 was the most prevalent in 1997. Overall penicillin-resistance rates ranged from 9.1% in 1986 (when a non-susceptible strain was isolated for the first time in the Hospital Sant Joan de Déu, Barcelona, Spain) to 71.4% in 1997, and it was more common among strains belonging to serogroup C (52% of resistant strains) than to serogroup B (22.1 % of resistant strains). The penicillin-resistance level was low, MIC always < or = 0.5 microg/ml. The present increase in N. meningitidis group C isolates, mainly C:2b:P1.2,5, and the availability of preventive measures for this highly pathological and resistant phenotype, argues strongly for the establishment of an epidemiological monitoring system. Detection of penicillin resistance should be standardized worldwide in order to unify data from all laboratories. CONCLUSION: A shift between serogroups B and C is observed in Barcelona from 1986 to 1997, as well as a rapid distribution of decreased penicillin susceptibility.

[Analysis of 59 cases of non-traumatic sudden death in various neurological diseases].

Sudden death is a common complication of myocardial infarction, necrotic pancreatitis and other diseases. Physicians usually neglect the possibility of neurological disorders. 59 cases of sudden death among 314 autopsied cases with neurological diseases were analyzed. The most frequent cause of neurological sudden death was cerebrovascular disease (CVD). It was present in 53 (89.9%) cases. 48 of them had hemorrhagic CVD. 37 of these 48 cases were due to hypothalamic lesions. In 37 cases general autopsy was performed; pathological abnormalities of heart, lungs, stomach etc, were found in 28 of them. In conclusion, the size and location of the lesion correlated with the prognosis of the disease. Concomitant multiple organ damage may deteriorate the lesion. Awareness of sudden death resulting from CVD may elevate the rate of correct diagnosis.