The Potentials of Melatonin in the Prevention and Treatment of Bacterial Meningitis Disease.

Bacterial meningitis (BM) is an acute infectious central nervous system (CNS) disease worldwide, occurring with 50% of the survivors left with a long-term serious sequela. Acute bacterial meningitis is more prevalent in resource-poor than resource-rich areas. The pathogenesis of BM involves complex mechanisms that are related to bacterial survival and multiplication in the bloodstream, increased permeability of blood-brain barrier (BBB), oxidative stress, and excessive inflammatory response in CNS. Considering drug-resistant bacteria increases the difficulty of meningitis treatment and the vaccine also has been limited to several serotypes, and the morbidity rate of BM still is very high. With recent development in neurology, there is promising progress for drug supplements of effectively preventing and treating BM. Several in vivo and in vitro studies have elaborated on understanding the significant mechanism of melatonin on BM. Melatonin is mainly secreted in the pineal gland and can cross the BBB. Melatonin and its metabolite have been reported as effective antioxidants and anti-inflammation, which are potentially useful as prevention and treatment therapy of BM. In bacterial meningitis, melatonin can play multiple protection effects in BM through various mechanisms, including immune response, antibacterial ability, the protection of BBB integrity, free radical scavenging, anti-inflammation, signaling pathways, and gut microbiome. This manuscript summarizes the major neuroprotective mechanisms of melatonin and explores the potential prevention and treatment approaches aimed at reducing morbidity and alleviating nerve injury of BM.

Intraventricular administration of tigecycline for the treatment of multidrug-resistant bacterial meningitis after craniotomy: a case report.

BACKGROUND: Intracranial infections, especially multidrug-resistant (MDR) bacterial meningitis, are one of the most severe complications after craniotomy and may greatly impact patient outcomes. CASE PRESENTATION: We report a case of severe MDR Klebsiella pneumonia meningitis after craniotomy that was treated with three different dosages of tigecycline (Pfizer, New York, NY, U.S.A.)via a combined intravenous (IV) and intracerebroventricular (ICV) administration. Here, we discuss the pharmacokinetics (PK) of a combined IV and ICV tigecycline administration for a patient with an intracranial infection after craniotomy. CONCLUSION: In the present case, three different dosages of tigecycline were administered: 49 mg IV plus 1 mg ICV q12 h, 45 mg IV plus 5 mg ICV q12 h, 40 mg IV plus 10 mg ICV q12 h. The combined IV and ICV administration might improve CSF tigecycline concentrations, and in this case, the methods of administration were safe and effective.

Nasopharyngeal glial heterotopia with delayed postoperative meningitis.

A male infant, who underwent radical resection of a large glial heterotopia at the nasopharynx at 8 days, developed delayed postoperative bacterial meningitis at 9 months. Neuroradiological examination clearly demonstrated that meningitis had occurred because of the intracranial and extracranial connections, which were scarcely seen in the perioperative period. A transsphenoidal extension of hypothalamic hamartoma is possible because the connection started from the right optic nerve, running through the transsphenoidal canal in the sphenoid bone and terminating at the recurrent mass in the nasopharyngeal region.

Clinical characteristics of Stenotrophomonas maltophilia meningitis in adults: a high incidence in patients with a postneurosurgical state, long hospital staying and antibiotic use.

OBJECTIVE: Stenotrophomonas (S.) maltophilia is an uncommon pathogen of adult bacterial meningitis (ABM). METHODS: The clinical characteristics of six S. maltophilia ABM cases, collected during a study period of nine years (2001-2009) were included. In the related literature, 13 S. maltophilia ABM cases were reported, and their clinical data were also collected. RESULTS: The 19 S. maltophilia ABM cases included 11 men and 8 women, aged 28-70 years. Of these 19 cases, 89.5% (17/19) had underlying neurosurgical (NS) conditions as the preceding event. Before the development of S. maltophilia ABM, 52.6% (10/19) of them had long stays in hospital and 63.2% (12/19) had undergone antibiotic treatment. Among the implicated S. maltophilia cases, three strains were found to have a resistance to sulfamethoxazole-trimethoprim (SMZ-TMP). Two of our five cases had resistant strains to levofloxacin. Among the antibiotics chosen for treatment, SMZ-TMP was the most common followed by quinolone (ciprofloxacin, levofloxacin, moxifloxacin). The therapeutic results showed 2 cases expired while the other 17 cases survived. CONCLUSIONS: S. maltophilia ABM usually develops in patients with a preceding neurosurgical condition, a long hospital stay and antibiotic use. SMZ-TMP and quinolones, especially the ciprofloxacin, are the major antibiotic used. This study also shows the emergence of clinical S. maltophilia strains which are not susceptible to SMZ-TMP and quinolones and this development may pose a more serious threat in the near future because treatment options may become depleted and limited despite the mortality rate of this specific group of ABM not being high at this time.

Prevention and treatment of meningitis and acute otitis media in children with cochlear implants.

OBJECTIVE: To provide recommendations for 1) prevention of acute otitis media and meningitis via immunization and 2) antimicrobial therapy of acute otitis media and meningitis in children with cochlear implants. DATA SOURCES: Literature review and policy statement from the American Academy of Pediatrics. CONCLUSION: 1) Children who are candidates for cochlear implants or have received cochlear implants should receive all-age appropriate vaccinations, including indicated doses of 13-valent pneumococcal conjugate vaccine, Haemophilus influenzae type b conjugate vaccine, and influenza vaccine. A supplemental dose of 13-valent pneumococcal conjugate vaccine is indicated for children who have received indicated doses of 7-valent pneumococcal vaccine, but have not received 13-valent pneumococcal conjugate vaccine. In addition, children 24 months and older should receive a single dose of 23-valent pneumococcal polysaccharide vaccine. 2) Acute otitis media in children with cochlear implants should be treated with an antimicrobial. During the first 2 months after implant, initial treatment of acute otitis media with a parenteral antimicrobial, e.g., cetriaxone, is indicated. High-dose amoxicillin or amoxicillin-clavulanate is an appropriate antimicrobial choice for empiric treatment of acute otitis media occurring 2 or more months after implant. In cases of meningitis occurring during the first 2 months after implantation, broad spectrum empiric antimicrobial therapy, e.g., meropenem and vancomycin, should be initiated pending the results of CSF culture. Empiric antimicrobial therapy with ceftriaxone and vancomycin is appropriate for cases of meningitis occurring 2 or more months after implant.

Validación de una regla de predicción clínica para diferenciar meningitis bacteriana de meningitis aséptica / Validation of a clinical prediction rule to distinguish bacterial from aseptic meningitis

La mayoría de las meningitis en la infancia no son bacterianas, pero la dificultad en descartar tal etiología obliga con frecuencia a utilizar antibióticos inicialmente. El objetivo de este trabajo fue validar, en nuestro medio, una regla de predicción clínica para diferenciar la etiología de las meningitis en niños a su ingreso al hospital. Método. Estudio prospectivo que incluyó pacientes menores 19 años de edad con diagnósitco de meningitis. En todos se obtuvo líquido cefalorraquídeo (LCR) para análisis directo, citoquímico y cultivo, y hemograma. Se calculó el BMS (Bacterial Meningitis Score: puntaje de meningitis basteriana) descripto por Nigrovic (Pediatrics 2002; 110:712): tinción de Gram en LCR positiva = 2 puntos; proteinorraquia mayor o igual 80 mg/dl, neutrófilos en sangre periférica mayor o igual 10000/mn3, neutrofilos en LCR mayor o igual 1000/mm3, convulsiones, un punto cada uno. Se calculó sensibilidad (S), especificidad (E), valores predictivos positivo y negativo (VPP y VPN) y razones de verosimilitud positiva y negativa (RVP y RVN)del BMS para predecir meningitis bacteriana. Resultados. Se incluyeron 70 pacientes con meningitis (14 bacterianas) veinticinco pacientes presentaron BMS=0 puntos, 11 BMS=1 punto, y 34 BMS mayor o igual 2 puntos. Un BMS=0 evidenció S: 100 por ciento E: 44 por ciento, VPP; 31 por ciento, VPN: 100 por ciento, RVP: 1,81 RVN: 0 para predecir meningitis bacteriana. Un BMS mayor o igual 2 mostró S: 100 por ciento, E: 64 por ciento, VPP: 41 por ciento, VPN: 100 por ciento, RVP: 2,8 RVN: 0 para predecir meningitis bacteriana. Conclusión: La utilización del BMS fue simple y permitió identificar pacientes con bajo riesgo de meningitis bacteriana. Su empleo podría constituir una herramienta útil en la toma de decisiones clínicas.

Validación de una regla de predicción clínica para diferenciar meningitis bacteriana de meningitis aséptica / Validation of a clinical prediction rule to distinguish bacterial from aseptic meningitis

La mayoría de las meningitis en la infancia no son bacterianas, pero la dificultad en descartar tal etiología obliga con frecuencia a utilizar antibióticos inicialmente. El objetivo de este trabajo fue validar, en nuestro medio, una regla de predicción clínica para diferenciar la etiología de las meningitis en niños a su ingreso al hospital. Método. Estudio prospectivo que incluyó pacientes menores 19 años de edad con diagnósitco de meningitis. En todos se obtuvo líquido cefalorraquídeo (LCR) para análisis directo, citoquímico y cultivo, y hemograma. Se calculó el BMS (Bacterial Meningitis Score: puntaje de meningitis basteriana) descripto por Nigrovic (Pediatrics 2002; 110:712): tinción de Gram en LCR positiva = 2 puntos; proteinorraquia mayor o igual 80 mg/dl, neutrófilos en sangre periférica mayor o igual 10000/mn3, neutrofilos en LCR mayor o igual 1000/mm3, convulsiones, un punto cada uno. Se calculó sensibilidad (S), especificidad (E), valores predictivos positivo y negativo (VPP y VPN) y razones de verosimilitud positiva y negativa (RVP y RVN)del BMS para predecir meningitis bacteriana. Resultados. Se incluyeron 70 pacientes con meningitis (14 bacterianas) veinticinco pacientes presentaron BMS=0 puntos, 11 BMS=1 punto, y 34 BMS mayor o igual 2 puntos. Un BMS=0 evidenció S: 100 por ciento E: 44 por ciento, VPP; 31 por ciento, VPN: 100 por ciento, RVP: 1,81 RVN: 0 para predecir meningitis bacteriana. Un BMS mayor o igual 2 mostró S: 100 por ciento, E: 64 por ciento, VPP: 41 por ciento, VPN: 100 por ciento, RVP: 2,8 RVN: 0 para predecir meningitis bacteriana. Conclusión: La utilización del BMS fue simple y permitió identificar pacientes con bajo riesgo de meningitis bacteriana. Su empleo podría constituir una herramienta útil en la toma de decisiones clínicas.(AU)

[Fulminant strongyloidiasis successfully treated by subcutaneous ivermectin: an autopsy case].

We report a 49-year-old man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier, born in Okinawa prefecture where both strongyloidiasis and HTLV-1 are endemic. He presented with fever, headache and urinary retention. On the basis of CSF examination and MRI findings, his condition was diagnosed as myelitis. He received methylprednisolone pulse therapy. He was transferred to our hospital due to severe paralytic ileus. Strongyloides stercoralis (S. stercoralis) was found in the duodenal stained tissue of a biopsy specimen. Ivermectin applied both orally and through enema were ineffective because of severe ileus and intestinal bleeding. Nine mg (200 microg/kg) of ivermectin solution was administered subcutaneously every other day for five days (total amount 45 mg). The S. stercoralis burden in the stool decreased and paralytic ileus gradually resolved. Three weeks after the resolution of S. stercoralis infection, purulent meningitis developed and acute obstructive hydrocephalus appeared. The hydrocephalus improved by ventricular drainage. Approximately three months after drainage, he died of incidental aspiratory pneumonia. Autopsy showed neither eggs nor larvae of S. stercoralis in the organs. In this case, the fourth reported case in the world, subcutaneous ivermectin injection was dramatically effective. We should consider a diagnosis of strongyloidiasis for any patient from Okinawa prefecture who was an HTLV-1 carrier presenting with unknown origin ileus after treatment of steroid therapy.

Antimicrobial susceptibility of cerebrospinal isolates from patients with meningitis.

Str. pneumoniae isolates were susceptible to penicillin, all to also ofloxacin and chloramphenicol and cefotaxim and 39 (100%) to cotrimoxazol. Concerning S. aureus, all isolates 22 were susceptible to oxacillin and chloramphenicol, and 21 also to cotrimoxazol. All N. meningitidis isolates but one-10 of all were susceptible to penicillin, all to cefotaxim, chloramphenicol and cotrimoxazol. All H.influenzae isolates were susceptible to ampicillin and chloramphenicol, as well as to ofloxacin and cotrimoxazol. Those surprisingly high susceptibilities to rather "old" antibiotics may be explained by low antibiotic consumption, accessibility and therefore low usage which is a key promoter of resistance both in community and hospital.

Primary pseudomonas meningitis in an adult, splenectomized, multitransfused thalassaemia major patient.

A 19-year-old splenectomized, multitransfused female patient with beta-thalassaemia major developed primary meningitis due to P. putida. Her blood cultures were negative. P. putida is an unusual nosocomial organism to cause primary meningitis. Infection due to this organism carries high mortality. However, owing to early diagnosis and energetic treatment this patient survived without any sequelae. A review of serious infections over the last 7 years in patients in our thalassaemia care centre revealed 11 serious infections among our splenectomized patients (n = 46) and none in the non-splenectomized group (n = 106). Surprisingly, all overwhelming infections (23.8% in the splenectomized group) were caused by Gram-negative bacilli like Klebsiella, Pseudomonas, Aeromonas and Campylobacter species. As all our splenectomized patients had prior pneumococcal vaccination and oral penicillin prophylaxis, overwhelming septicaemia due to S. Pneumoniae was successfully prevented, but an increasing incidence of overwhelming sepsis due to Gram-negative bacilli, against which no vaccination or suitable prophylactic antibiotics are available, is now posing a new threat to this vulnerable group of patients.

Nocardia asteroides pneumonia, subcutaneous abscess and meningitis in a patient with advanced malignant lymphoma: successful treatment based on in vitro antimicrobial susceptibility.

Nocardia asteroides pneumonia, subcutaneous abscess and meningitis without brain abscesses developed in a patient with advanced non-Hodgkin's lymphoma, who had received corticosteroid therapy and cancer chemotherapy for a long time. At the time of nocardial pneumonia, profound lymphocytopenia and hypogammaglobulinemia was seen. The severely immunosuppressed condition most likely accounted for the uncommon infection, nocardiosis. The organism isolated from the sputum, subcutaneous abscess and cerebrospinal fluid was strongly resistant to cotrimoxazole, which is the recommended standard treatment, but it was susceptible to imipenem (IPM) and erythromycin (EM) in an in vitro antimicrobial susceptibility study. The patient's nocardiosis responded well to chemotherapy including IPM and EM.

Environmental growth conditions influence the ability of Escherichia coli K1 to invade brain microvascular endothelial cells and confer serum resistance.

A major limitation to advances in prevention and therapy of neonatal meningitis is our incomplete understanding of the pathogenesis of this disease. In an effort to understand the pathogenesis of meningitis due to Escherichia coli K1, we examined whether environmental growth conditions similar to those that the bacteria might be exposed to in the blood could influence the ability of E. coli K1 to invade brain microvascular endothelial cells (BMEC) in vitro and to cross the blood-brain barrier in vivo. We found that the following bacterial growth conditions enhanced E. coli K1 invasion of BMEC 3- to 10-fold: microaerophilic growth, media buffered at pH 6.5, and media supplemented with 50% newborn bovine serum (NBS), magnesium, or iron. Growth conditions that significantly repressed invasion (i.e., 2- to 250-fold) included iron chelation, a pH of 8.5, and high osmolarity. More importantly, E. coli K1 traversal of the blood-brain barrier was significantly greater for the growth condition enhancing BMEC invasion (50% NBS) than for the condition repressing invasion (osmolarity) in newborn rats with experimental hematogenous meningitis. Of interest, bacterial growth conditions that enhanced or repressed invasion also elicited similar serum resistance phenotype patterns. This is the first demonstration that bacterial ability to enter the central nervous system can be affected by environmental growth conditions.

Bacterial meningitis and lumbar epidural hematoma due to lumbar acupunctures: a case report.

A 48-year-old female expressed signs of meningeal irritation after having received several lumbar acupunctures within one week for back pain. Bacterial meningitis was diagnosed from cerebrospinal fluid examinations. Magnetic resonance image (MRI) of spine at admission demonstrated a fusiform lesion with characters of subacute hematoma in the epidural space of the first and second lumbar level. She received antibiotics treatment only and recovered from her central nervous system infection completely. The epidural lesion disappeared spontaneously in the MRI follow up three weeks later. We report the diagnosis and follow-up of epidural hematoma of the lumbar spine by MRI which aided the medical physician to treat meningitis attentively.

Duración de la evolución pre-terapia y pronóstico en meningitis bacteriana aguda en el niño menor / Duration of the pre-therapy and prognostic evolution in acute bacterial meningitis in little child

Se ha informado sobre retraso en el diagnóstico de meningitis bacteriana (MB) y el consiguiente impedimento para el tratamiento oportuno en nuestra población infantil. La duración de la enfermedad previa al tratamiento (DEPT), definida como las horas de fiebre (HF) o número de consultas (NC) por el mismo síndrome febril previos al diagnóstico clínico de MB, podría influir en la evlución de la enfermedad en niños. Para examinar si ha habido cambios de la DEPT en los últimos años, revisamos los casos MB del primer estudio, egresados del Hospital Roberto del Río durante 1978-90 (G1)(N=186) y los comparamos con 105 casos egresados del mismo hospital durante 1978-90 (G2). También utilizamos en segundo grupo para probar la hipótesis que el diagnóstico de MB hecho después de las primeras 24 hrs está asociado a mal pronóstico medido como muerte o secuelas al alta de los pacientes. La letalidad fue 25,8 por ciento y 8,6 por ciento en G1 y G2. respectivamente (OR= 3.7; 95 por ciento CI= 1,5, 9,2; p= 0,002). El riesgo de DEPT más larga fue mayor en G1, con punto de corte en las primeras 12 hrs del síndrome febril (OR= 3,34; 95 por ciento CI= 1,29, 8,87; p= 0,01) y también cuando el número de consultas necesarias fue de 3 o más (OR= 2,77; 95 por ciento CI= 0,96, 8,29; p= 0,06). El riesgo de muerte o secuelas graves al alta, apareció con punto de corte de la DEPT en 24 hrs sólo en G2 (OR= 3,5; 95 por ciento CI= 1,0, 15,6; p= 0,025). Igualmente, el NC >1 se asoció a mayor riesgo en (OR= 5,56; 95 por ciento CI= 1,1, 37,7; p= 0,01). En este segundo grupo, la combinación de DEPT >24 hrs y NC= 1, mostró la razón de riesgos más alta de las observadas (OR= 8,92; 95 por ciento CI= 1,1, 193; p= 0,01). Estos resultados sugieren que el diagnóstico precoz (< 24 hrs) puede influenciar la evolución de la MB en niños

Biotypes and serotypes of Haemophilus influenzae from patients with meningitis in the city of São Paulo, Brazil.

A total of 1,094 Haemophilus influenzae isolates from cerebrospinal fluid were examined by biochemical and serological means. Most of them belonged to biotype I (70.9%) and to serotype b (99.4%). The relationship of biotypes I and II to the ages of the patients was shown to be significant (P < 0.001).