Chemotherapy for Bacterial Infections of the Central Nervous System

Over the past six years, many new agents have become available for the treatment of bacterial central nervous system (CNS) infections. Certain principles guide the use of these agents for CNS infections: first, an antimicrobial agent must be able to penetrate the CNS to be effective; second, the CNS is a “relatively immunoincompetent site” so that an antimicrobial must achieve levels within the CNS capable of killing the offending bacterium. The lack of efficacy of chloramphenicol for meningitis due to gram-negative aerobes is probably due to its failure to achieve such killing levels, whereas the success of the newer cephalosporins, such as cefotaxime and ceftriaxone, is due to their very high killing activity against these organisms. Penicillin remains the first choice for pneumococcal and meningococcal meningitis. Ampicillin plus chloramphenicol is still recommended as initial therapy for meningitis due to Hemophilus influenzae. The newer cephalosporins are now the first choice for the treatment of meningitis due to many gram-negative bacilli. Trimethoprim-sulfamethoxazole may also be useful in some of these infections and those due to Listeria monocytogenes. In the treatment of severe CNS infections, a team approach is advised to ensure optimal therapy.     

Nosocomial meningitis caused by Enterobacteriaceae: risk factors and outcome in 18 cases in 1992-2007

Nosocomial neuroinfections due to Enterobacteriaceae represented 9.5% in our cohort of 171 cases of paediatric meningitis within last 15 years. Commonest etiologic agents was E. coli - 9 (50%) followed by Klebsiella pneumoniae - 3 (16,7%) and Enterobacter cloacae. Citrobacter freundii, Proteus mirabilis and Salmonella enteritidis (1 each). Commonest risk factors were neonatal age 13 - (72.2%), very low birth weight 5 (27.8%), craniocerebral trauma - 4 (22.2%) and neurosurgery - 5 (27.8%). All but 1 case were treated with antibiotics: 8 with III-rd and 3 with IV-th generation cephalosporins (ceftazidim, cefotaxim and cefepim) 2 with meropenem and 4 with ciprofloxacin: Nosocomial meningitis due to enterobacteriaceae was associated with significantly high mortality (29.9% vs. 15.1% in all cohort of pediatric meningitis - p<0.02).     

Bacterial meningitis after craniocerebral trauma in the community

Craniocerebral trauma is one of major risk factors for development of meningitis. We reviewed 30 cases of bacterial meningitis occurring in community after craniocerebral trauma. Alcohol abuse was significant risk factor occurring in trauma patients with meningitis present in 50% in our cohort (p=0.0001). The most common pathogen in posttraumatic meningitis was Str. pneumoniae (90% vs. 33.8%, p=0.0001). However mortality was very low, only 5% probably because of early diagnosis and treatment of patients at risk for bacterial meningitis but neurologic sequellea were significantly more common (p=0.00001) in patients after craniocerebral trauma.     

猪链球菌毒力因子和鉴定方法的研究进展

猪链球菌(Streptococcus suis)是一种重要的人畜共患病病原体,能够引起猪疫病,人类感染该菌可导致脑膜炎、败血症甚至死亡。鉴于其对养猪业的巨大经济影响和对公共卫生事业的威胁,关于猪链球菌的研究日益深入,即对其毒力相关蛋白和鉴定方法的研究进展做一综述。     

Complete genome sequence of the neonatal-meningitis-associated Escherichia coli strain CE10

Neonatal bacterial meningitis continues to be an important cause of mortality and morbidity worldwide. Escherichia coli possessing the K1 capsular polysaccharide is the most common Gram-negative pathogen causing neonatal meningitis. Here we present the complete genome sequence of neonatal meningitis-associated E. coli strain CE10, a unique K1 strain with a functional type III secretion system. Functional analysis of the genome should enhance our knowledge of the pathogenesis of neonatal E. coli K1 meningitis.     

Molecular Epidemiology of Echovirus 18 Circulating in Mainland China from 2015 to 2016

Echovirus 18(E18), a serotype of Enterovirus B(EV-B) species, is an important pathogen in aseptic meningitis. E18 had rarely been detected in mainland China, but became the predominant pathogen associated with viral encephalitis(VE) and meningitis in Hebei province for the first time in 2015. To investigate the molecular epidemiology and genetic characteristics of E18 in mainland China, sixteen E18 strains from patient throat swabs with hand, foot, and mouth disease(HFMD) in six provinces in China collected between 2015 and 2016, and four E18 strains isolated from 18 patient cerebrospinal fluid specimens with VE in Hebei Province in 2015 were obtained and sequenced. Combined with the sequences from the GenBank database, we performed an extensive genetic analysis. Phylogenetic analysis of VP1 gene sequences revealed that all E18 strains from mainland China after 2015 belonged to subgenotype C2. There were no obvious specific differences in phylogenetic and variation analyses of E18 genome sequences between HFMD and VE/meningitis strains. Potential multiple recombination may have occurred in the 50-untranslated region and in the P2 and P3 nonstructural protein-encoding regions of E18 strains from China. The current E18 strains were potential multiplerecombinant viruses. Overall, these findings supported that E18 caused HFMD, VE, and meningitis, although there were no significant associations between clinical features and viral genomic characteristics.     

Nosocomial meningitis caused by Staphylococcus other than S. aureus in children: multicentre study

Analysing 101 cases of nosocomial meningitis due to staphylococci other than S. aureus within last 15 years, coagulase negative staphylococci represented the commonest pathogen. Major risk factor for staphylococcal meningitis was prior neurosurgery, mainly ventriculoperitoneal shunt insertion. Ten of 101 cases were caused by glycopeptide intermediate resistant strains in patients pretreated with multiple combination of antibiotics including vancomycin and shunt exchanges: 76% of strains were also oxacillin resistant.     

Subtractive Proteomics and Reverse Vaccinology Strategies for Designing a Multiepitope Vaccine Targeting Membrane Proteins of Klebsiella pneumoniae

International Journal of Peptide Research and Therapeutics - Klebsiella pneumoniae is a Gram-negative opportunistic pathogen that causes bacteremia, meningitis, endocarditis, cellulitis, urinary...     

Phenotypic Plasticity in the Productions of Virulence Factors Within and Among Serotypes in the Cryptococcus neoformans Species Complex

Mycopathologia - The Cryptococcus neoformans species complex (CNSC) is a common opportunistic human fungal pathogen and the most frequent cause of fungal meningitis. There are three major serotypes...     

Achievements and problems from the view of a physician

Penicillin made possible the cure of many common, and also the most serious, infections, such as meningococcal meningitis and bacterial endocarditis, often with few or no sequelae. Endocarditis had been invariably fatal. Semisynthetic penicillins added new dimensions of convenience of administration and a broader spectrum in the presence of many beta-lactamases. A quantum step forward was permitted by the derivatives of cephalosporin C. Specific clinical advances were (1) the opportunity to use these in some penicillin-allergic patients, (2) activity against wider range of Gram-negative bacilli, (3) activity against Bacteroides fragilis (cefoxitin), (4) more complete renal excretion after oral cephalosporins than with oral penicillins, and (5) delayed renal excretion. Major remaining problems limiting beta-lactam use are (1) allergy, (2) resistant organisms, (3) relatively poor entry into the cerebrospinal fluid (especially of cephalosporins, (4) some nephrotoxicity, (5) local irritation of veins and tissues during administration, and (6) poor results in patients with agranulocytosis.     

Genome sequence of a porcine extraintestinal pathogenic Escherichia coli strain

Extraintestinal pathogenic Escherichia coli (ExPEC) is an important pathogen which can infect humans and animals and cause many diseases outside the intestine. Here, we report the first draft genome sequence of a porcine ExPEC strain, PCN033, isolated from a pig with meningitis.     

Increasing antimicrobial resistance in STDs and the need for surveillance: Neisseria gonorrhoeae as a model.

Neisseria gonorrhoeae has a rising trend of resistance against antimicrobials. Today, third generation cephalosporins are the only antibiotics for treatment of gonorrhea against which there is no resistance in gonococci. On the other hand, decreased susceptibility against this group, including ceftriaxone, has already been observed. This historically famous pathogen deserves current attention and is reviewed here with respect to its resistance mechanisms and patterns, and the problems concerning standardization of its susceptibility testing are discussed.     

Antibiotics and Clostridium difficile

Clostridium difficile is now established as a major nosocomial pathogen. C. difficile infection is seen almost exclusively as a complication of antibiotic therapy, and is particularly associated with clindamycin and third-generation cephalosporins. Depletion of the indigenous gut microflora by antibiotic therapy has long been established as a major factor in the disease. However, the direct influence of antimicrobials upon virulence mechanisms such as toxin production and adhesion in the bowel, and the exact mechanisms by which the organism causes disease remain to be elucidated.     

Amoeba host model for evaluation of Streptococcus suis virulence

The Gram-positive bacterium Streptococcus suis is a major swine pathogen worldwide that causes meningitis, septicemia, and endocarditis. In this study, we demonstrate that the amoeba Dictyostelium discoideum can be a relevant alternative system to study the virulence of S. suis.     

Genome sequence of Neisseria meningitidis serogroup B strain H44/76

Neisseria meningitidis is an obligate human pathogen. While it is a frequent commensal of the upper respiratory tract, in some individuals the bacterium spreads to the bloodstream, causing meningitis and/or sepsis, which are serious conditions with high morbidity and mortality. Here we report the availability of the genome sequence of the widely used serogroup B laboratory strain H44/76.     

Reconciling West Nile virus with the autophagic pathway

West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus responsible for recurrent outbreaks of meningitis and encephalitis. Several studies analyzing the interactions of this pathogen with the autophagic pathway have reported opposite results with evidence for and against the upregulation of autophagy in infected cells. In this regard, we have recently reported that minimal genetic changes (single amino acid substitutions) in nonstructural proteins of WNV can modify the ability of the virus to induce autophagic features such as LC3 modification and aggregation in infected cells. We think that these results could help explain some of the previously reported discrepancies. These findings could also aid in deciphering the interactions of this pathogen with the autophagic pathway at the molecular level aimed to develop feasible antiviral strategies to combat this pathogen, and other related flaviviruses.     

Isolation of Propionibacterium acnes from central nervous system infections

Propionibacterium acnes is a common skin colonizer and its involvement in central nervous system (CNS) infections may be related with previous neurosurgical procedures. P. acnes was isolated in pure or mixed cultures from ten patients with CNS infections during a 5-year period. The clinical presentation, treatment and outcome were retrospectively reviewed. Nine out of 11 patients had CNS infections after a neurosurgical procedure. The clinical presentation was: brain abscess (five patients), subdural or epidural empyema (four patients) and shunt meningitis (one patient). Three patients had also secondary meningitis. All patients received antibiotic therapy and all abscesses and empyemas were drained. The patient with shunt meningitis cured without catheter removal. Only one patient with a brain abscess by P. acnes died, but several months thereafter and as a consequence of a Gram-negative superinfection. P. acnes is a pathogen for the CNS and infections must be surgically managed under adequate antibiotic treatment.     

普通裂褶菌真菌学及实验室研究进展

普通裂褶菌是一种条件致病菌,可侵犯人体多个器官多种组织,导致各种表现形式的疾病,如脑脓肿、脑膜炎、鼻窦炎、肺部真菌球、蜂窝肺、肺结节、甲真菌病等.由于普通裂褶菌感染引起的真菌病病例少见报道,临床医生对其认识不足,再加上某些实验室不具备鉴定条件,所以感染该菌的病例常被漏诊、误诊.现将近年来临床分离的普通裂褶菌株真菌学及实...     

Conquering the meningococcus

Since the first outbreaks of meningococcal meningitis were first described in Geneva in 1804 and in New England in 1806, and since the discovery of the causative agent by Weichselbaum in 1887 and the beginning of epidemics of meningococcal meningitis in the sub-Saharan Africa approximately 100 years ago, Neisseria meningitidis has been recognized as the cause worldwide of epidemic meningitis and meningococcemia. The massive epidemic outbreaks in sub-Saharan Africa in the 1990's, the emergence since 1995 of serogroups Y, W-135 and X and the prolonged outbreak of serogroup B meningococcal disease in New Zealand over the last decade serve to remind us of the continued potential of the meningococcus to cause global morbidity and mortality. This report reviews new discoveries impacting prevention and future prospects for conquering the meningococcus as a human pathogen.     

Genetic characterization of thermal tolerance in Enterobacter sakazakii

Enterobacter sakazakii is an opportunistic pathogen that causes meningitis and necrotizing enterocolitis in neonates. Here we characterized the thermal tolerance of E. sakazakii isolates obtained from powdered infant formula and other food products in Japan. Isolates were categorized into three classes according to their thermal tolerance, and differential gene expression analysis showed that the heat-resistant clones expressed a higher level of infB (which encodes a translation initiation factor), than did the heat-sensitive isolates. Gene expression and DNA polymorphism analyses suggested that this gene target might be useful to unequivocally detect and identify heat-resistant clones, permitting epidemiological surveillance for this pathogen.