Hepatitis on High Dose Isoniazid: Reintroduction of the Drug in Severe Tuberculous Meningitis

Hepatitis developed in two patients treated with high doses (1000 mg/day) of isoniazid for severe tuberculous meningitis. Isoniazid was discontinued and later read-ministered in gradually increasing intrathecal and subsequently oral doses, up to the final dose of 400 mg/day. Transaminases remained normal, during 12 months on this dose, suggesting dose dependence of hepatotoxicity or a metabolic adaptation to the injury. Continued isoniazid treatment can be important in similar cases and it may become possible, if oral or intrathecal doses significantly lower than the initial hepatotoxic ones, are used.     

Survival improvement in coccidioidal meningitis by high-dose intrathecal amphotericin B

Eleven patients with coccidioidal meningitis were treated with high individual doses (1.0 to 1.5 mg) of intrathecal amphotericin B mixed with 25 to 50 mg of hydrocortisone in an attempt to reach a dose of 12 mg per month for at least two consecutive months. Patients received a mean intrathecal dose of amphotericin B of 82 mg (range, 40 to 157 mg) and 2.4 g intravenously (range, 1.0 to 3.5 g). No deaths related to disease or treatment occurred, and overall survival was 91% during an average follow-up period of 75 months (range, 30 to 137 months). Comparative analysis with eight well-known series in the literature reveals that our survival rate and follow-up time are significantly greater than the more recent series (1977-1981). Rank correlation and linear regression showed that the mean intrathecal dose of amphotericin B used in all series corresponds well with mean survival time. Our clinical results and analysis of the literature suggest that intrathecal amphotericin B administered at a high dose rate of 0.75 mg (or greater) three times per week promptly reaching 20 mg and a total surpassing 40 mg is associated with significantly enhanced survival rates.     

Convulsion following intrathecal cephaloridine

Following therapeutic intrathecal administration of cephaloridine to an 11-day-old premature infant with suspected meningitis, a generalized tonic convulsion was observed. Symptoms continued to subside over the next six hours, followed by postictal sleep. That convulsion and other symptoms were due to cephaloridine was confirmed when the second intrathecal administration produced the same symptom. Because of its possible damaging effect on CNS, it is strongly suggested that cephaloridine should not be administered directly into the cerebrospinal fluid space.     

Pediatric bacterial meningitis: is prior antibiotic therapy associated with an altered clinical presentation?

STUDY HYPOTHESIS: The clinical features of children treated with oral antibiotics before the diagnosis of bacterial meningitis differ from those who receive no antibiotics. DESIGN: Retrospective case series. SETTING: University medical center. PARTICIPANTS: Two hundred fifty-eight children 24 months old or younger with bacterial meningitis hospitalized during a 12-year period. Eighty-three children were treated with oral antibiotics before the diagnosis of meningitis, and 175 children were not. INTERVENTIONS: None. METHODS: The emergency department chart and hospital records were reviewed for presenting demographic, historical, physical examination, and laboratory features. Clinical features of pretreated and untreated patients were compared. RESULTS: Pretreated children demonstrated less frequent temperature of 38.3 C or higher, altered mental status and a longer duration of symptoms before diagnosis, with more frequent vomiting; ear, nose, and throat infections; and physician visits in the week before detection of meningitis (P less than .05 for all comparisons). There was no difference in incidence of upper respiratory symptoms, seizures, nuchal rigidity, Kernig's and Brudzinski's signs, focal neurologic signs, mortality, and length of hospitalization between groups. CONCLUSION: Clinical features of children who have taken antibiotics before the detection of meningitis differ significantly from those who have not undergone antibiotic therapy. Physicians should be aware of these differences when evaluating young children on antibiotics for the possibility of meningitis.     

Measurement of lactic acid in cerebrospinal fluid of patients with infections of the central nervous system

The concentration of lactic acid in cerebrospinal fluid (CSF) was determined by gas-liquid chromatography in 205 samples of CSF from 97 patients with or without infections of the central nervous system. Patients without infection or those with nonbacterial (presumably viral) meningitis consistently had low concentrations of lactic acid in CSF (i.e., less than or equal to 35 mg/100 ml), whereas patients with bacterial or tuberculosis meningitis consistently had concentrations of lactic acid in CSF of greater than 35 mg/100 ml. There was no overlap in concentrations of lactic acid between these two groups. Further, lactic acid concentrations in CSF from patients partially treated for meningitis were generally greater than 35 mg/100 ml through the third day of therapy and, thereafter, progressively declined to less than 20 mg/100 ml by the seventh to 10th day of therapy. Relapse of bacterial infection was consistently documented by a recurrence of an increased concentration of lactic acid in CSF. Preliminary experience with determination of the concentration of lactic acid in CSF suggests that it may be useful in distinguishing bacterial (with or without positive cultures) and tuberculous meningitis from meningitis due to nonbacterial causes.     

Creatine kinase in the serum of patients with acute infections of the central nervous system

Serum creatine kinase was assessed in 94 consecutive patients without convulsions admitted to hospital due to suspicion of infection of the central nervous system. No reliable discrimination between patients with aseptic and those with bacterial meningitis was obtained. Patients with bacterial meningitis and brain oedema, as well as patients with encephalitis, had significantly higher values (P less than 0.01) than patients with meningism, aseptic meningitis and bacterial meningitis without cerebral oedema. Very high values, above 2500 U/1, were encountered in only the most severe cases of bacterial meningitis. The highest serum CK value found in patients with encephalitis was 725 U/l. Reference values for control patients with meningism were 16-269 U/1. In a subset of 9 patients creatine kinase isoenzyme analysis was performed. In all cases only muscle type (MM) isoenzyme was found.     

地塞米松鞘内注射与静脉注射在显微血管减压术后无菌性脑膜炎中的疗效比较

目的比较腰椎穿刺鞘内注射地塞米松与静脉推注地塞米松治疗显微血管减压术（MVD）术后无菌性脑膜炎（AM）的临床疗效。 方法选择自2015年1月至2020年1月于胜利油田中心医院神经外科就诊行MVD并诊断为AM的138例患者为研究对象,将患者分为对照组（68例）和观察组（70例）。对照组患者采用静脉推注地塞米松（10 mg/次）治疗,频率为按需给药;观察组患者采用腰穿放液联合鞘内注射地塞米松[60 μg/（kg·次）]治疗,频率为每日或隔日1次。比较2组患者治疗后的头痛及发热缓解情况、术后住院时间、治疗次数及激素不良反应情况。 结果治疗后8、72 h后,2组患者头痛、发热症状均明显好转,且观察组明显优于对照组,差异均有统计学意义（P<0.05）;观察组患者的术后住院时间[（7.68±2.23）d]短于对照组[（12.76±2.37）d],治疗次数[（3.5±0.6）次]明显低于对照组[（6.8±0.9）次],差异具有统计学意义（P<0.05）,2组患者均未见明显的激素不良反应。 结论腰穿放液联合鞘内注射地塞米松在治疗MVD术后AM患者中疗效确切,可有效改善患者头痛、发热等临床症状,减轻激素用量,缩短术后住院时间,具有重要的临床推广价值。     

Dexamethasone in the treatment of experimental Haemophilus influenzae type b meningitis

A model of experimental lapin meningitis was used to assess the effect of meningeal inflammation caused by Haemophilus influenzae type b on development of brain edema, increase in intracranial pressure, and production of brain lactate. Four treatments were assessed: dexamethasone alone, dexamethasone plus ceftriaxone, ceftriaxone alone, and no treatment. The brain water content in untreated rabbits with meningitis was 419 +/- 10 g of H2O/100g of dry weight after 29 hr of infection (vs. 405 +/- 14 in uninfected rabbits; P less than .05). In rabbits treated with dexamethasone, dexamethasone plus ceftriaxone, or ceftriaxone alone, these values were 404 +/- 12, 406 +/- 12, and 411 +/- 14 g, respectively (P greater than .05). The cerebrospinal fluid (CSF) pressure and lactate levels were significantly increased in all animals during the 24 hr of meningeal inflammation (P less than .005), and these levels were comparably reduced after 9 hr of treatment. Although the values for brain water content, CSF pressure, and lactate concentrations in infected animals treated with ceftriaxone plus dexamethasone were not significantly different from those in animals treated with ceftriaxone alone, the values were consistently lower in the former group.     

Granulocytopenia in hospitalized patients: II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients

The results of empiric antibiotic therapy in 126 hospitalized patients with fever during 192 episodes of granulocytopenia were studied. Febrile granulocytopenic patients were randomly allocated to receive either carbenicillin, methicillin and gentamicin, or carbenicillin and cephalothin. The response rate for the two antibiotic regimens was similar, 49 (60 per cent) of 81 responded to the former and 42 (54 per cent) of 78 to the latter. The response rate in patients receiving other antibiotics because of specific indications or counterindications was 19 (58 per cent) of 33. Thirty-nine (35 per cent) of 110 patients who responded to initial antibiotic therapy had an increase in circulating granulocytes of one log₁₀ or more compared to only 10 (12 per cent) of 79 nonresponders with such an increase. The mortality rate in adult patients receiving carbenicillin, methicillin and gentamicin was eight (16 per cent) of 51, compared to 18 (37 per cent) of 49 in those receiving cephalothin and carbenicillin (P < 0.05). The significance of this difference in mortality rate is uncertain, as there was no difference in the initial response rate or mortality rate between patients treated with the two antibiotic regimens when only patients with documented bacterial infection were considered. Patients who responded to their initial antibiotic regimen, and patients for whose fever no explanation was found, had the best prognosis.     

Empiric therapy for infections in granulocytopenic cancer patients: continuous infusion of amikacin plus cephalothin.

A combination of amikacin sulfate given by continuous infusion (800 mg/sq m/24 hr) plus cephalothin sodium (2 g every four hours) was used as initial empiric therapy for the treatment of 65 evaluable febrile (greater than 38.5 degrees C) episodes in 54 granulcoytopenic (neutrophils, less than 1,000/microliter) adult cancer patients. Carbenicillin disodium (5 g every four hours) was substituted for cephalothin in patients with Pseudomonas infections and in patients in whom the initial regimen was unsuccessful. Thirty-two of the 38(84%) identifiable infections responded to therapy, including all of the eight septicemias and eight of 11 pneumonias. Three additional infections responded to the substitution of carbenicillin for cephalothin, for a total response rate of 92% (35/38). Nephrotoxicity occurred in five patients (7.1%), most commonly in patients over 60 years of age. Ototoxicity, highly correlated with a duration of greater than 19 days and a total dosage of greater than 25 g of amikacin sulfate, occurred in four patients (5.6%). Amikacin given by continuous infusion plus cephalothin is a safe and efficacious empiric therapy for infections in granulocytopenic cancer patients.     

Group Y meningococcal disease in United States Air Force recruits.

Between 1971 and 1974, group Y meningococcal disease developed in 88 Air Force recruits; 68 had primary bacterial pneumonia. None of the patients with primary pneumonia had the stigmata of meningococcemia or meningitis. Patients with pneumonia responded well to small doses of parenteral penicillin. Ten patients had meningococcemia, and six had meningitis. Pneumonia, therefore, predominated over meningococcemia and meningitis 4:1. Skin lesions were rare in patients with meningococcemia but frequent in those with meningitis; otherwise, these clinical syndromes were similar to group B and C meningococcal disease. There was only one death, a patient with known preexisting leukopenia.     

Clinical pharmacology of intrathecal methotrexate. II. An improved dosage regimen derived from age-related pharmacokinetics

Cerebrospinal fluid (CSF)-antifolate concentration was analyzed in 100 specimens from 47 patients treated with intrathecal methotrexate (MTX) (12 mg/m2 of body surface area [BSA]). The drug concentrations varied 100-fold, with high levels associated with neurotoxicity and low levels with a poor response to therapy. CSF-MTX concentration was correlated directly with patient age, suggesting that a constant dose, regardless of age or BSA, should provide more consistent CSF-drug concentrations. In a subsequent study 25 patients treated with a conventional-dose schedule of 12 mg/m2 of BSA were compared with a matched group of 24 patients administered a constant dose of 12 mg. There was significantly less variability of drug levels in the CSF with the constant-dose method than with the dosage derived from BSA. It is recommended that patients between 3 and 40 years of age receive the same intrathecal dose rather than varying doses adjusted for patient BSA.     

Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimental Escherichia coli meningitis in rabbits

We investigated the effect of cefotaxime and chloramphenicol on endotoxin concentrations in cerebrospinal fluid (CSF) and on the development of brain edema in rabbits with Escherichia coli meningitis. Both antibiotics were similarly effective in reducing bacterial titers. Cefotaxime, but not chloramphenicol, induced a marked increase of endotoxin in CSF, from log10 1.5 +/- 0.8 to log10 2.8 +/- 0.7 ng/ml (P less than .01). This result was associated with an increase in brain water content (405 +/- 12 g of water/100 g of dry weight compared with 389 +/- 8 g in untreated controls; P less than .01), whereas in animals treated with chloramphenicol, brain water content was identical to controls. The cefotaxime-induced increase in endotoxin concentration and brain edema were both neutralized by polymyxin B, which binds to the lipid A moiety of endotoxin, or by a monoclonal antibody to lipid A. These results indicate that treating gram-negative bacillary meningitis with selected antibiotics induces increased endotoxin concentrations in CSF that are associated with brain edema.     

Comparison of effects of high and low dosage regimens of antithyroid drugs in the management of Graves' hyperthyroidism

We compared the effects of high and low dosages of antithyroid drugs in 113 patients with Graves' hyperthyroidism. The patients were randomly divided into 2 groups. In group A, 65 patients received either methimazole (MMI): 60 +/- 14.5 mg/day (mean +/- SD); range 40-100 mg/day, or propylthiouracil (PTU): 693 +/- 173 mg/day; range 500-1200 mg/day. These high doses were maintained throughout treatment with later addition of 50-75 micrograms T3 daily. Forty eight patients (group B) were treated with lower doses of MMI or PTU without thyroid hormone addition. The maintenance dose of MMI was 13.6 +/- 7 mg/day (range 5-25 mg/day) and that of PTU was 180 +/- 58 mg/day (range 100-300 mg/day). The treatment period was 15.1 +/- 4.2 (range 10-30) months for group A and 13.5 +/- 2.2 (range 12-20) months for group B. Remission occurred in 75.4% patients from group A and in 41.6% patients from group B (P less than 0.001). The mean follow-up was 42 +/- 14 months (17-81 months). The free T4 index (FT4I) in group A remained below the normal range during treatment. The mean FT4I, obtained during the course of treatment, of patients who went into remission from group A was significantly (P less than 0.001) lower than in relapsed patients (4.8 vs. 6.5). Moreover, there was an inverse correlation between mean FT4I and maintenance daily dose of either MMI (r = -0.567; P less than 0.001), or PTU (r = -0.379; P less than 0.01). A fall in microsomal antibody (MCHA) titer occurred mainly in remission patients, and was more significant (P less than 0.05) in group A patients. In contrast, 11 (7 from group B) of the 16 patients with an increase of microsomal antibody levels relapsed. The frequency of negative tests of thyroid-stimulating antibody was higher in group A patients (71%) than in group B (29%) at the end of therapy (P less than 0.01). No correlation was found between thyroid T3 suppressibility and either mean FT4I or thyroid-stimulatory antibody activity during treatment. Our findings show that patients treated with high doses of PTU or MMI throughout treatment have a higher remission rate when compared to those treated with a more conventional regimen. These results support the hypothesis that large antithyroid drug doses may have greater immunosuppressive effects than low dosage regimens. Furthermore, a high dosage regimen could permit the restoration of the immune surveillance mechanisms and, thus, lasting remission of Graves' disease.     

Treatment of central nervous system fungal infection with ketoconazole

Two patients with fungal infection of the central nervous system (coccidioidal meningitis and cerebral histoplasmomas) were treated with ketoconazole for 30 months. Both responded to dosages substantially less than those described previously for similar infections. Neither patient experienced any significant adverse effects from the prolonged therapy.     

Promptness of antibiotic therapy in acute bacterial meningitis

We reviewed 135 cases of acute community-acquired bacterial meningitis at a municipal teaching hospital during a six-year period, with special emphasis on promptness of initial antimicrobial therapy. Overall mortality was 5% for the 121 childhood cases, compared to 43% for the 14 adult cases (P less than .001). The mean duration between arrival in the emergency department and the administration of appropriate antibiotics was 2.1 hours for the pediatric cases, compared to 4.9 hours for the adult cases (P less than .02). Factors that may contribute to delays in institution of appropriate antimicrobial therapy for adult patients with meningitis include the relative infrequency of this condition, the presence of concomitant disease processes, and the frequent practice of obtaining a computed tomography scan prior to performing lumbar puncture. Prompt institution of antimicrobial therapy for acute meningitis, especially for adult pneumococcal meningitis, remains a major challenge for emergency physicians.     

α-2b干扰素联合利巴韦林治疗丙型肝炎疗效分析

目的探讨α-2b干扰素治疗丙型肝炎的近期与远期疗效。方法给予急、慢性丙型肝炎患者α-2b干扰素5M。肌肉注射，开始一个月每日1次，以后隔日1次，12个月为一个疗程；给予丙型肝炎肝硬化患者3Mu肌肉注射，隔日1次，治疗12个月。所有患者均联合应用利巴韦林，每日0．8～1．2g口服。随访2—5年。结果急性丙型肝炎患者在治疗结束时的应答率（ETR）为84．6％，稳定应答率（SR）为76．9％，慢性丙型肝炎ETR为61．4％，SR为52．3％（P〈0．05）；在5例丙型肝炎肝硬化患者，ETR为3例，SR2例；急慢性肝炎患者在治疗的最初1个月内应答者，其复发率低于1个月后才应答者（P〈0．01）。结论α-2b干扰素治疗丙型肝炎的近期与远期疗效均较好，干扰素治疗的安全性较好，代偿期肝硬化患者也可抗病毒治疗。     

Distinguishing cerebrospinal fluid abnormalities in children with bacterial meningitis and traumatic lumbar puncture

The characteristics of cerebrospinal fluid (CSF) associated with traumatic lumbar puncture, defined as CSF red blood cell (RBC) count greater than 1000/mm3, were reviewed in 92 previously healthy children greater than 1 month of age; 30 had bacterial meningitis and 62 had negative CSF cultures. The purpose was to distinguish CSF profiles of the two groups despite contamination with peripheral blood elements. In each case, white blood cell (WBC) counts were observed (O) and compared with those predicted (P), calculated as P = CSF RBC X (blood WBC/blood RBC). Comparison of O:P ratios revealed that all 30 patients with bacterial meningitis had ratios greater than or equal to 1, 28 (93%) had ratios greater than 10, and 24 (80%) had ratios greater than 100; by contrast, only 2 patients (3%) with culture-negative CSF had ratios greater than 10, 21 (34%) had ratios of 1-10, and 39 (63%) had ratios less than 1. Significant differences were observed in the rate of O:P ratio greater than or equal to 1 (100% vs. 32%), CSF differential cell count predominance of polymorphonuclear leukocytes (97% vs. 11%), hypoglycorrhachia (73% vs. 3%), and positive Gram's-stained smear for pathologic organisms (80% vs. 0) in those with and without bacterial meningitis, respectively (P less than .0001). Thus, in children greater than 1 month of age, CSF abnormalities associated with bacterial meningitis are rarely obscured by blood contamination from traumatic lumbar puncture.     

Staphylococcus aureus meningitis: experience with cefuroxime treatment during a 16 year period in a Danish region

Staphylococcus aureus is a rare cause of bacterial meningitis and there is no consensus on antibiotic treatment. Nafcillin is a common choice in countries where it is approved and marketed. High-dose cefuroxime has been the systemic treatment used in the study region, and a retrospective record review was conducted to determine its clinical efficacy. Cases of bacterial meningitis during 1984-1999 in the County of North Jutland, Denmark (approx. 490000 inhabitants), were identified in a regional bacteriology register. Inclusion of a case required either growth of S. aureus from > or = 2 specimens of cerebrospinal fluid (CSF), 1 positive CSF specimen with a CSF leucocyte count > 10(8)/l or 1 positive CSF specimen with a concurrent positive blood culture. A diagnosis of brain abscess required growth of S. aureus from aspirated pus. Staphylococcus aureus meningitis was confirmed in 45 patients, and 5 additional patients had a brain abscess. 44 cases were nosocomial (mortality 16%) and 6 were community acquired (mortality 83%). None of the isolates was methicillin resistant and 6 were penicillin susceptible. Intraventricular antibiotic treatment was given to 28 patients, systemic therapy included cefuroxime in 32 patients (64%) as either a primary or secondary choice, 6 (12%) were treated with penicillin G, 10 (20%) with penicillinase-resistant penicillin and 2 (4%) with cephalothin. Among 31 nosocomial cases treated systemically with cefuroxime the mortality was 10% (95% exact confidence limits 2-26%). In conclusion, cefuroxime seems to be a valid choice for S. aureus meningitis in the nosocomial setting.     

Clinical predictors of bacterial versus aseptic meningitis in childhood.

STUDY OBJECTIVE: To assess the reliability of meningeal signs and other physical findings in predicting bacterial and aseptic meningitis at various ages. DESIGN: Children requiring lumbar puncture were evaluated prospectively for meningeal signs and other physical parameters before lumbar puncture. SETTING: Emergency department of Children's Hospital of Wisconsin. PARTICIPANTS: One hundred seventy-two children, aged 1 week to 17 years, with meningitis (53 bacterial and 119 aseptic). MEASUREMENTS AND MAIN RESULTS: Nuchal rigidity was present in 27% of infants aged 0 to 6 months with bacterial meningitis versus 95% of patients 19 months or older (P = .0001). Three percent of infants 0 to 6 months old with aseptic meningitis had nuchal rigidity versus 79% of patients 19 months or older (P = .0005). Seventy-two percent of infants 12 months of age or younger with bacterial meningitis has at least one positive meningeal sign versus 17% of infants with aseptic meningitis (P = .0001). Eighty-five percent of children older than 12 months with meningitis had at least one positive meningeal sign, 93% with bacterial meningitis, and 82% with aseptic meningitis. CONCLUSION: Despite a lack of meningeal signs, a high index of suspicion for meningitis is essential when evaluating the febrile infant 12 months of age or younger.