Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00035 (CSF)
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Purulent meningitis in patients admitted to the pediatric department of Kyoto University Hospital and affiliated institutions from 1951 through 1973 were studied with emphasis on the kinds of the causative organisms and the susceptibility of these organisms to antibiotics. The findings in this study have served to help select antibiotics most likely to be effective against this disease. The overall incidence of purulent meningitis was 0.68%. This figure decreased little throughout the period. As for the frequency of causative organisms, Neisseria meningitidis led the list, and Diplococcus pneumoniae ranked just behind. Haemophilus influenzae was rare. The frequency of N. meningitidis, however, decreased sharply in spite of the essentially unchanged overall incidence of this disease. The probable reason for the poor prognosis of this disease in spite of the remarkable strides in chemotherapy is the decreased frequency of N. meningitidis and the inversely increased organisms that are resistant to usual chemotherapy. The therapeutic effectiveness of cefazolin against this disease was studied in 15 children including eight newborns and four infants. The daily per kg bodyweight dose was 50 mg or less in four, 50 approximately 100 mg in five, and more than 100 mg in the remaining six. The route of administration was either intramuscular or intravenous. No deaths occurred. The rate of effectiveness was as high as 80%. Residual symptoms were recorded in six and, in as many as five of them, the cause was a-tributable to the delayed detection of the disease. Neither side effects nor aberrent laboratory findings attributable to large doses of cefazolin were recorded. Diffusibility of cefazolin into the CSF was studied in nine subjects. The CSF concentration of this antibiotic was shown to be somewhat lower than that of ampicillin or cephaloridine and to account on an average for 13% of the mean peak serum level. This relatively low diffusibility will be offset by its high serum concentration and safe large-dose therapy. These findings have clearly shown that the therapeutic effectiveness of cefazolin is as high as that of ampicillin, and that this excellent effectiveness holds true even when the causative organism happens to be Escherichia coli, Klebsiella, etc. that are resistant to ampicillin. The authors have furthermore scrutinized much literature on the frequency of the causative organisms, emergence of resistant strains, and the diffusibility of antibiotics into the CSF, and arrived at the conclusion that cefazolin is a promising antibiotic of choice for the treatment of purulent meningitis in newborn. The daily dose is preferably 150 mg/kg or more given in three divided intravenous doses. Meanwhile ampicillin proved to be useful as the antibiotic of choice for the treatment of purulent meningitis in infants and children.
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PMID:[Chemotherapy of purulent meningitis in children (author's transl)]. 24 48

Successful therapy of bacterial meningitis is dependent upon achieving adequate antibacterial activity in the CSF. The percent penetration (CSF concentration/serum concentration X 100) of various antimicrobial agents was determined in a rabbit model of bacterial meningitis. The percent penetration of the penicillin and cephalosporin derivatives was found to vary inversely with the protein binding of the respective drugs. Esterification of ampicillin increased its lipid solubility and likewise increased the penetration into the CSF. Probenecid competitively inhibits the active transport efflux of various organic acids from the CSF and increased the CSF concentrations of penicillin and cephalosporin derivatives. The percent penetration of all drugs was increased in the presence of the inflamed meninges.
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PMID:Factors influencing the penetration of antimicrobial agents into the cerebrospinal fluid of experimental animals. 27 68

The incidence of ampicillin resistance in Hemophilus influenzae and its medical significance have not been extensively determined. During 1975-1977, we tested for ampicillin resistance 489 consecutive middle-ear isolates of HI obtained from children in Huntsville, Alabama, and 719 consecutive laboratory isolates of HI from Children's Hospital, Boston. The annual incidence of Amp resistance rose progressively in each survey, from initial values of 1.4 to 5.3% in 1975, to 14 to 16% in 1977 (P less than 0.05), a mean annual rate of increase approximately twofold. Resistance was equally prevalent among type b and non-b isolates and among nasally carried and disease-associated isolates (from blood, CSF, middle ears). Patients harboring AmpR isolates were much more likely to have had recent exposure to beta-lactam antibiotics (P less than 0.01).
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PMID:Increasing incidence of ampicillin resistance in Hemophilus influenzae. 30 55

17 infants and children with pyogenic meningitis (14 Haemophilus influenzae, 2 Diplococcus pneumoniae, 1 Neisseria meningitidis) were treated with thiamphenicol, 100 mg/kg body weight/day in 4 doses i.v., as single drug. In the H. influenzae group 10 patients were cured, 4 had relapses of meningitis, 3 with documented subdural effusions. This group is compared with 14 children matched for age, initial leucocyte and CSF cell count treated with ampicillin: all of these were cured, 1 had a subdural effusion. Thiamphenicol concentrations were determined in the serum and CSF 2 h after administration. The mean serum levels were between 10-12 mcg/ml, the mean CSF levels varied from 5.4 mcg/ml at the beginning to 1-1.9 mcg/ml at the end of meningitis. The MIC of H. influenzae was 0.6-12 mcg/ml. A significant, acute, and dose related bone marrow toxicity of thiamphenicol could be documented, but was always rapidly fully reversible. We conclude that thiamphenicol cannot replace chloramphenicol in the treatment of pyogenic meningitis as single systemic antibiotic. Special indications for thiamphenicol in this disease are discussed.
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PMID:Thiamphenicol in treatment of Haemophilus influenzae meningitis. 31 71

Infection with Listeria monocytogenes is demonstrated over a 141/2 year period in 24 newborns, three infants 1 to 2 months of age, and two children. Comparison of the 22 cases of Listeria meningitis in newborns with 118 cases of neonatal meningitis due to other bacteria indicates a later onset of symptoms in cases of Listeria meningitis with a more favorable outcome than with most other agents. Treatment with ampicillin sodium appears effective. Monocytic cell increases in peripheral blood or CSF may be helpful in suspecting this diagnosis. The cases of Listeria meningitis in the older children were unusual. In one child it occurred as a concomitant infection with Staphylococcus epidermidis of a ventricular shunt. In the second case in an otherwise healthy child the acquisition of the bacteria from gerbils was suggested, but could not be confirmed.
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PMID:Infection in infants and children. 32 73

Nowadays, in severe infections during the neonatal period new bacteria--group B streptococci--have to be taken into account, since in some clinics they already predominate over gramnegative rods. Septicemia and meningitis may be caused by group B streptococci. The septicemia which especially threatents prematures starts with apnoeic spells in the very first hours after birth and may be easily misdiagnosed as an idiopathic respiratory distress syndrome. The mortality is very high (about 60%). Meningitis starts later, normally during the 3rd to 4th week. Seizures are typical at the onset. Group B streptococci may be identified in the CSF by counterimmunoelectrophoresis within one hour. The prognosis is more favourable in meningitis than in septicemia (mortality about 20%). Survivors have little neurological sequelae. Penicillin G or ampicillin combination with an aminoglycoside is recommended as chemotherapy. Exchange transfusion should be considered early. Group B streptococci causing the septic form may be transfered during labour since up to 25% of pregnant women are colonized. Nosocomial transmission of group B streptococci may be the reason for meningitis. Prophylactic penicillin does not seem to help in preventing the disease, but it is possible, that meningitis of the newborn may be prevented by immunizing the mother during pregnancy.
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PMID:[Group B streptococcus infections during the neonatal period (author's transl)]. 35 54

Two patients with purulent meningitis, of which causative organism was presumed to be E. coli, were treated with intravenous administration of cefmetazole, 300 approximately 400 mg/kg/day in 4 approximately 6 divided doses, and the following conclusions were obtained. 1) Clinical response was favorable and a complete cure was obtained without sequelae in both patients. There were no adverse reactions noted except for a mild and transient eosinophilia (12%) in one case. 2) Of two strains of E. coli recovered from CSF, one was sensitive to ampicillin, cefazolin and cefmetazole, among which cefmetazole had the highest bacterial activity. Although another strain was sensitive to cefmetazole, it showed resistance to cefazolin (greater than 12.5 microgram/ml) and to ampicillin (greater than 100 microgram/ml). 3) Concentrations of cefmetazole in CSF following 1 approximately 2 hours of its intravenous administration were either equal to or higher than those of ampicillin, which was given to the same patient for a short period of time. The concentrations in CSF were higher than 3.1 microgram/ml on each occasion except for in some specimens during the convalescent phase and exceeded well the MIC of the causative organism. 4) Based on the above results, cefmetazole is considered to be a potent antibiotic in the treatment of E. coli meningitis. Although further studies are needed as to the dosage, an intravenous administration at 4-hour interval appears to be warranted based on the studies that the half-life of the drug is short in CSF in animal experiments.
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PMID:[Treatment of E. coli meningitis with cefmetazole. Report of two cases with favorable response and determination of the concentrations in CSF (author's transl)]. 37 88

A case of brainstem infection by Listeria monocytogenes is described. The patient was a 63 year old man previously in good health and his illness did not follow the usual bi-phasic pattern. There was no prodromal phase, and the progressive brainstem signs with a lymphocytosis and a normal sugar level in the CSF led to a tentative diagnosis of viral brainstem encephalitis. Ampicillin was begun only when signs of pulmonary infection developed. Clinical diagnosis is difficult but ampicillin should probably be used in any doubtful case in which a "viral" brainstem encephalitis is being considered.
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PMID:Infection of the brainstem by Listeria monocytogenes. 51 67

The passage of 6-[(R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido)-penicillanic acid sodium salt (mezlocillin, Baypen), into the CSF was studied in 9 patients with symptoms of acute meningitis, presumed to be of viral origin. The antibiotic was given as a single 5 g dose i.v. over 30 min. The CSF/serum concentration ratio of mezlocillin showed a variation from 0 to 10.7%. The antibiotic could be effective in the treatment of bacterial meningitis caused by ampicillin-resistant strains of Haemophilus influenzae and by most Enterobacteriaceae, provided these results will be confirmed by a study now in progress. In one patient suffering from meningococcal meningitis this concentration ratio varied between 72% (day 3) and 54% (day 12).
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PMID:Cerebrospinal fluid penetration of mezlocillin. 54 3

For the specific and unspecific treatment of purulent meningitis, penicillin, ampicillin and chloramphenicol are usually sufficient. Only resistant pathogens (Klebsiella, Pseudomonas among others) and meningitis in infants require other treatment. Cephalosporins and aminoglycosides only come into consideration for the treatment of very rare exceptional cases. The still relatively poor prognosis of purulent meningitis is largely independent of the efficacy of the treatment. Delay in beginning therapy, lack of intensive care, primary diseases and complications are principally responsible for this. Medicamentous prophylaxis is only possible for meningococcal meningitis. The distribution of antibiotics in the CSF is irregular. Also the antibacterial activity in the CSF is different from culture media.
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PMID:[Therapy of meningitis (author's transl)]. 82 9


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