Pharmacokinetics of ceftriaxone in neonates and infants with meningitis

The pharmacokinetics of ceftriaxone was studied in the plasma, urine, and cerebrospinal fluid of seven neonates and seven infants with meningitis. In addition, plasma and urine data were obtained in five neonates and one infant receiving ceftriaxone for other serious infections. All neonates younger than 14 days received daily doses of 50 mg/kg ceftriaxone; all other patients but two received 100 mg/kg. The average weight-corrected values for total body clearance (ClT), volume of distribution (Vdss), and biologic half-life (t 1/2) were 0.37 ml/min/kg, 0.45 L/kg, and 16.2 hours in neonates younger than 1 week; 0.77 ml/min/kg, 0.48 L/kg, and 9.2 hours in neonates older than 1 week; and 1.03 ml/min/kg, 0.39 L/kg, and 7.1 hours in older infants, respectively. There was a significant difference in ClT and t 1/2 between the neonates younger and both neonates older than 1 week, and infants. The Vdss was not significantly different among the three age groups. The average renal clearance in neonates younger than 1 week (0.28 ml/min/kg was 70%, in neonates older than 1 week (0.54 ml/min/kg) was 77%, and in older infants (0.49 ml/min/kg) was 47% of ClT, indicating that nonrenal elimination was less developed in neonates. The quantitation of CSF diffusion of ceftriaxone was assessed by comparison of the areas under the CSF and plasma concentration-time curve. The mean ceftriaxone penetration into the CSF in neonates and infants with bacterial meningitis was 17%. On the other hand, penetration in patients with aseptic meningitis amounted to only 4%. Mean ceftriaxone concentrations in the CSF in patients with bacterial meningitis were 2.8 mg/L after 24 hours, exceeding by many times the minimum inhibitory concentration of the common meningitis pathogens at this time.     

Diagnostik und Therapie der bakteriellen Meningitis

The clinical picture and course of acute bacterial meningitis are determined by the patient’s age and immune status and the bacterial species that is the causative organism. While Group B streptococci and E. coli predominate in the neonatal period, in most patients older than this the disease is caused by Neisseria menigitidis, Streptococcus pneumoniae and, now a rarity in the western world, Haemophilus influenzae. In neonates the symptoms are typically nonspecific. With advancing age the classic triad of headache, meningism and fever is more typically observed. Morphological, chemical and microbiological analysis of the cerebrospinal fluid (CSF) is of decisive importance for the diagnosis. CSF cell count, glucose and protein levels provide crucial diagnostic information. Gram staining and a CSF culture should be performed in all cases. The appropriate choice of empirical antibiotic therapy is guided by the patient’s age and medical history. Neonates are usually best treated with ampicillin and a third-generation cephalosporin. In infants aged 3 months and over singe-agent therapy with a third-generation cephalosporin is considered most suitable. Glucocorticoids have been shown to reduce the incidence of neurological sequelae. Prophylaxis by way of exposure and vaccination is also discussed.     

Cerebrospinal fluid evaluation in neonates: comparison of high-risk infants with and without meningitis.

Results of CSF examinations from 117 high-risk neonates were reviewed. The mean CSF cell count was 8.4 cells/mm3 and the range was 0 to 32 cells/mm.3 Approximately 60% of the CSF WBC were polymorphonuclear leukocytes. Average CSF protein concentrations were 90 mg/dl (range, 20-170 mg/dl) in term and 115 mg/dl (range, 65-150 mg/dl) in preterm infants. The average CSF glucose was 81% of the blood glucose value in term and 74% in preterm infants. Comparison of these CSF findings with those from 119 infants with bacterial meningitis revealed that there was considerable overlapping of values, but only one of the 119 infants with meningitis had a completely normal initial CSF examination. The decision to initiate antimicrobial therapy in neonates with suspected meningitis must be based on total evaluation of the patient.     

A single daily injection of ceftriaxone for treating suppurated meningitis in infants and children. Apropos of 31 cases

Thirty-one infants and children aged 1 month to 15 years 3 months were treated with ceftriaxone once a day for the treatment of a meningitis related to Neisseria meningitidis (19 cases), haemophilus influenzae (7 cases), streptococcus pneumoniae (1 case), not identified bacteria (4 cases). All identified bacteria were sensitive to ceftriaxone. Twenty children were treated with 100 mg/kg/day, 11 with 50 mg/kg/day. CSF was sterile at the first control-generally performed 30 h after the onset of treatment-in all cases. Despite a great number of severe forms (fulminans purpura and septic shock; 11 cases; severe neurologic disturbances: 6 cases), all patients survived and recovered after a treatment of 9 to 22 days. Two infants exhibited neurologic sequelae: deafness, delayed development and hydrocephalus. Tolerance to ceftriaxone appeared to be good. With a 100 mg/kg/day dosage, mean CSF level at 6 h was 3.3 mg/l (0.8-7.7), on the first day of treatment. At the end of treatment, mean CSF level at 24h was 0.47 (0.15-2.5). With a 50 mg/kg/day dosage, mean CSF level at 6 h was 2,1 mg/l (1.1-3.9) in the first day of treatment. At the end of the treatment, mean CSF level at 24h was 0.22 mg/l (0.08-0.5). Once a day administration of ceftriaxone is adequate for the treatment of meningitis in infants and children. Though a 50 mg/kg/day dosage is probably sufficient in most cases, it seems to be more secure to use a 100 mg/kg/day dosage.     

Bacterial meningitis in India: An IJP survey

Conclusions It can be concluded that bacterial meningitis is an important cause of childhood morbidity and mortality. Isolation of causative pathogenes is poor in our country. A routine gram staining of CSF and use of rapid diagnostic kits with better culture facilities would be helpful in improving the outcome. In first 3 months of life, therapy should include one of the 3rd generation cephalosporins with an aminoglycoside. For meningitis in age groups between 3 months to 12 years, chloramphenicol and ampicillin should be the first line empirical therapy. If gram-ve organisms are suspected or isolated, one of the 3rd generation cephalosporins with or without an aminoglycoside is good alternative. The treatment can be stopped in uncomplicated case after 7–10 days (5 days of afebride period) in meningitis caused by meningococcus, pneumococcus andH. infuenzae. For BM caused by gram-ve bacilli treatment for 21 days is recommended. There is no need to perform CSF examination at the conclusion of therapy in cases of bacterial meningitis beyond neonatal period. There is a need to further evaluate therapeutic regimens like chloramphenicol alone, ceftriaxone home therapy, especially for rural areas etc. to decrease the cost of hospitalisation in referral hospitals.     

Pneumococcal meningitis in the newborn period in a prevaccination era: a 10-year experience at a tertiary intensive care unit

There are few data with respect to pneumococcal meningitis in neonates. Epidemiological aspects, clinical features and outcomes in newborn infants diagnosed with pneumococcal meningitis were evaluated in this study. Nineteen newborn infants in a neonatal intensive care unit diagnosed with culture-proven community-acquired bacterial meningitis between January 1999 and December 2008 were reviewed, and of them, eight patients were diagnosed as pneumococcal meningitis. Overall, among 10,186 hospitalized newborn infants, 132 community-acquired sepsis/meningitis cases (1.3%) were suspected, and blood cultures were performed in all, while cerebrospinal fluid (CSF) cultures could be performed in 124 cases. Rate of blood culture positivity was 45%. Nineteen (15.3%) of 124 were diagnosed as culture-proven community-acquired bacterial meningitis, which was confirmed by CSF growth. Eight (42.1%) of 19 had pneumococcal meningitis. In pneumococcal cases, abundant Gram-positive diplococci were seen on CSF smear and Streptococcus pneumoniae was isolated from CSF cultures. All isolates were susceptible to penicillin and third-generation cephalosporins. Irritability (n: 7), poor sucking (n: 7) and fever (n: 6) were the principal findings on the initial physical examination. Of all patients with pneumococcal meningitis, four were initially given cefotaxime plus amikacin treatment, and the remaining four were initially given cefotaxime plus ampicillin plus vancomycin. Antibiotic treatment in two patients was revised during their clinical course. Additionally, in three patients, vancomycin and ampicillin was discontinued on the third day when antibiogram of CSF cultures revealed penicillin sensitivity. Overall, mortality in pneumococcal meningitis was 50%. In the surviving patients, two had epilepsy, one sensorineural hearing loss, and two mental-motor retardation. Pneumococcal meningitis was the leading cause of community-acquired neonatal meningitis in our patients. Immunization against pneumococcal disease in developing countries would be beneficial for public health and for newborn infants.     

Dexamethasone as an adjunctive treatment of bacterial meningitis

This study was conducted on 77 Libyan infants and children aged month to 10 years with acute bacterial meningitis. Upon admission, the patients were divided randomly in two groups. Group I (38 patients) received ceftriaxone plus dexamethasone I.V. Group II (39 patients) received ceftriaxone alone. Both groups were compared for mean changes in CSF sugar, CSF protein and CSF polymorph count at 4th day of treatment. There was a significant difference between the two groups in CSF sugar and protein changes (P < 0.05) but not in CSF polymorph (P > 0.05). Both groups showed prompt clinical response and similar occurrence of acute complications, fatality rate and permanent neurological sequelae. However, group I manifested shorter duration of fever (P < 0.05). Dexamethasone improved the inflammatory reaction in acute bacterial meningitis and shortened the duration of fever but it did not have any significant effect on the fatality and the occurrence of neurological sequelae of this disease.     

Concentrations of ceftazidime,tobramycin and ampicillin in the cerebrospinal fluid of newborn infants

Thirty-five neonates with suspected septicaemia were randomized to treatment with tobramycin or ceftazidime, both in combination with ampicillin. Concentrations of antibiotics in the CSF were measured 1 h after the third, fourth or fifth injection. In 13 of 17 neonates tobramycin CSF concentrations were below 0.5 mg/l. Ceftazidime CSF concentrations ranged from 2.5 to 17 mg/l, which should be sufficient for treatment of infections with group B streptococci and most aerobic gram-negative bacilli but not all strains of Staphylococcus aureus. Ampicillin CSF concentrations ranged from 1 to 80 mg/l, which should be sufficient for treatment of meningitis caused by enterococci and Listeria monocytogenes, the most important neonatal pathogens not covered by ceftazidime.     

Comparison of cerebrospinal fluid in newborns and in infants ≤2 months old with or without meningitis

Background: The aim of the present study was to evaluate the characteristics and accuracy of cerebrospinal fluid (CSF) parameters for neonatal meningitis, by comparing CSF data in newborns and in infants ≤2 months of age, with or without meningitis. Methods: This case–control study was performed on 120 newborns and infants ≤2 months old. 60 patients with meningitis were considered as the case group and 60 ill patients without meningitis were defined as the control group. Each of the two groups was divided into 0–1 months and 1–2 months old. CSF characteristics were compared in newborns in the case and control groups; in infants ≤2 months old in the case and control groups; and in healthy newborns and healthy infants ≤2 months old. Results: The mortality rate was 16.7% in the case group. The differences of CSF parameters in the case and control groups were mostly not significant, except for CSF glucose only in term newborns <7 days old (P= 0.04), and white cell count (WBC) only in 0–7‐day‐old term and preterm neonates (P= 0.04 and P= 0.01, respectively). Polymorphonuclear leukocyte (PMNL) level in the case group was significantly higher than in the control group (P= 0.02). CSF characteristics in healthy newborns were nearly the same as in healthy infants ≤2 months old. Prevalence of positive CSF culture was 31.7% in the case group. The most common pathogen was Neisseria meningitidis in the two age groups. The concomitant positive blood culture in the case group was 26.3%. Conclusion: In the case of meningitis with negative CSF culture and Gram stain, diagnosis can be made on CSF parameters, clinical and laboratory findings and suspicion of meningitis. Therefore, a clinical prediction rule to classify risk for bacterial meningitis on evaluation of CSF parameters in any region should be established. More regional trials are needed to enhance the probability of diagnosis according to CSF parameters.     

Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone.

STUDY OBJECTIVE: To determine the outcome of outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. DESIGN: Prospective consecutive cohort study. SETTING: Urban emergency department. PATIENTS: Five hundred three infants 28 to 89 days of age with temperatures greater than or equal to 38 degrees C who did not appear ill, had no source of fever detected on physical examination, had a peripheral leukocyte count less than 20 x 10(9) cells/L, had a cerebrospinal fluid leukocyte count less than 10 x 10(6)/L, did not have measurable urinary leukocyte esterase, and had a caretaker available by telephone. Follow-up was obtained for all but one patient (99.8%). INTERVENTION: After blood, urine, and cerebrospinal fluid cultures had been obtained, the infants received 50 mg/kg intramuscularly administered ceftriaxone and were discharged home. The infants returned for evaluation and further intramuscular administration of ceftriaxone 24 hours later; telephone follow-up was conducted 2 and 7 days later. RESULTS: Twenty-seven patients (5.4%) had a serious bacterial infection identified during follow-up; 476 (94.6%) did not. Of the 27 infants with serious bacterial infections, 9 (1.8%) had bacteremia (8 of these had occult bacteremia and 1 had bacteremia with a urinary tract infection), 8 (1.6%) had urinary tract infections without bacteremia, and 10 (2.0%) had bacterial gastroenteritis without bacteremia. Clinical screening criteria did not enable discrimination between infants with and those without serious bacterial infections. All infants with serious bacterial infections received an appropriate course of antimicrobial therapy and were well at follow-up. One infant had osteomyelitis diagnosed 1 week after entry into the study, received an appropriate course of intravenous antimicrobial therapy, and recovered fully. CONCLUSIONS: After a full evaluation for sepsis, outpatient treatment of febrile infants with intramuscular administration of ceftriaxone pending culture results and adherence to a strict follow-up protocol is a successful alternative to hospital admission.     

Sterile cerebrospinal fluid pleocytosis in young infants with urinary tract infection

BACKGROUND: During the first 3 months of life febrile infants are subjected to sepsis workup, which includes evaluation for urinary tract infection (UTI) and meningitis. We investigated the existence of concomitant meningeal inflammation in infants younger than 90 days old affected with UTI. METHODS: We reviewed the medical records of all infants younger than 90 days old, who were hospitalized for UTI from January, 1990, to January, 2001. For the diagnosis of sterile cerebrospinal fluid (CSF) pleocytosis, the child's age, the CSF total white blood cell (WBC) count and the CSF absolute neutrophil count were taken into consideration. CSF pleocytosis was defined as the presence of > or = 35, > or = 21 and > or = 15 WBC/mm3 of CSF during the first, second and third month of life, respectively. The CSF Gram-stained smear, latex agglutination test and bacterial culture were negative. RESULTS: Sterile CSF pleocytosis was found in 15 (12.8%) of 117 infants with UTI who had had a lumbar puncture included in their initial laboratory evaluation. The 15 infants had a median age +/- semiinterquartile range of 40 +/- 25 days (range, 4 to 75 days). In these infants the median CSF WBC count +/- semiinterquartile range was 55 +/- 125/mm3 (range, 21 to 1,270/mm3). CONCLUSIONS: Sterile CSF pleocytosis was found in 12.8% of infants younger than 90 days old with UTI. The pathogenesis of this meningeal inflammation is not fully understood. Although bacterial infection of the subarachnoid space, with low bacterial seeding, cannot be excluded, at least in some cases, it is possible that CSF pleocytosis in some of the infants with UTI is mainly caused by the endotoxin of Gram-negative or other inflammation-inducing molecules of Gram-positive urine pathogens.     

Bacterial meningitis--an update.

This report emphasizes new clinical information about bacterial meningitis in infants and children. Important elements of diagnosis include examination for the presence of shock and increased intracranial pressure. In such cases, initial treatment should focus on appropriate fluid therapy, administration of oxygen, reduction of intracranial pressure and use of corticosteroids. Currently, antibiotics of choice include ampicillin plus either cefotaxime or ceftriaxone in young infants, and one of these cephalosporins in older patients (beyond 3 months of age). Shorter durations of therapy (5 to 7 days for meningococcus, 7 days for haemophilus and 7-10 days for pneumococcus) are now commonly employed. In many centers, dexamethasone is started before the first dose of antibiotic and continued for 4 days to reduce neurologic and audiologic sequelae. Future trends will include studies of endotoxin neutralizers and non-steroidal anti-inflammatory drugs to reduce further tissue injury in meningitis. Prevention of meningitis is the ultimate goal. Since Haemophilus influenzae vaccination can now begin at 2 months, this approach may bring important results soon.     

Cerebrospinal fluid C-reactive protein in meningitis: diagnostic value and pathophysiology

We examined the diagnostic value of C-reactive protein (CRP) in cerebrospinal fluid (CSF) on initial lumbar puncture in a prospective study including 126 patients (30 neonates, 96 infants and children) suspected of having meningitis. Twenty patients were considered to have bacterial and 25 were considered to have viral meningitis. In infants and children, a retrospectively chosen cut-off CRP titre of 4 (i.e. 0.4 mg/l CRP) had a sensitivity of 100% and a specificity of 94% for differentiating bacterial meningitis from both viral meningitis and normal. It was a more sensitive and selective test for differentiating bacterial from viral meningitis on initial CSF examination than was the CSF leucocyte count, glucose concentration or protein concentration. In neonates, no such cut-off CRP titre could be found, presumably due to the immaturity of the blood-CSF-barrier (Bl-CSF-B) during the first weeks of life. In a parallel study including a non-selected group of 13 infants and children (4 without, 9 with bacterial meningitis), the serum/CSF CRP concentration ratios were determined and inserted in the individual Bl-CSF-B diagrams according to Felgenhauer. The results were fully consistent with the hypothesis that the CRP concentration in CSF reflects the normal permeability characteristics of the Bl-CSF-B, or the degree of its impairment. Based on our results, we recommend the CSF CRP estimation in the routine evaluation of infants and children suspected of having meningitis.Abbreviations CRP C-reactive protein - CSF cerebrospinal fluid - Bl-CSF-B blood-cerebrospinal fluid-barrier - Qp Concentration ratio in serum/CSF of a given protein P - IgG immunoglobulin G - R (Å) hydrodynamic radius in ångström     

Thiamphenicol in treatment of Haemophilus influenzae meningitis.

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.     

Cost analysis of enteroviral polymerase chain reaction in infants with fever and cerebrospinal fluid pleocytosis

BACKGROUND: Infants with fever and cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital for parenteral antibiotic therapy for potential bacterial meningitis pending results of CSF culture. Published estimates suggest that 90% of all episodes of meningitis are caused by enterovirus. Enteroviral polymerase chain reaction (ePCR) has a sensitivity of 92% to 100% and a specificity of 97% to 100% in CSF. OBJECTIVE: To compare a management strategy using ePCR with current practice to determine potential savings by allowing earlier discharge. METHODS: Decision analysis comparing 2 strategies for the care of a retrospective cohort of infants with fever and CSF pleocytosis: standard practice vs ePCR testing of all CSF samples. Model assumptions include the following: (1) standard practice patients continue parenteral antibiotic therapy until CSF cultures are negative at 48 hours, (2) patients with positive ePCR results would be discharged after 24 hours, (3) patients with positive ePCR results have a negative CSF culture, and (4) costs are calculated from actual patient charges with a cost-to-charge ratio of 0.65. SUBJECTS: All infants aged 28 days to 12 months admitted to an urban teaching hospital with fever, CSF pleocytosis, and a negative CSF Gram stain from January 1996 through December 1997. OUTCOME MEASURE: Total cost of hospitalization. RESULTS: A total of 126 infants were identified. One hundred twelve (89%) were discharged with a diagnosis of aseptic meningitis; 72% of these cases occurred during the peak enterovirus season (June to October). Three of 3 patients with positive CSF cultures had bacterial growth within 24 hours of admission. Mean length of stay for patients with aseptic meningitis was 2.3 days (SD, +/-1.4 days). Total cost of hospital care for all 126 infants was $381,145. In our patient population, total patient costs would be reduced by the ePCR strategy if enterovirus accounts for more than 5. 9% of all meningitis cases. Varying the sensitivity of the ePCR assay from 100% to 90% changes the "break-even" prevalence from 5.8% to 6.5%. Total cost savings of 10%, 20%, and 30% would occur at an enteroviral meningitis prevalence of 36.3%, 66.7%, and 97.1%, respectively. CONCLUSIONS: Enteroviral PCR analysis of CSF for infants admitted to the hospital with meningitis can result in cost savings when the prevalence of enteroviral meningitis exceeds 5.9%. Limiting use of ePCR to the enterovirus season would increase cost savings. A prospective study is needed to validate these results. Arch Pediatr Adolesc Med. 2000;154:817-821     

Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial

In a multicenter randomized trial, 107 children with bacterial meningitis were initially given either cefuroxime or ampicillin plus chloramphenicol. Patients were alternately assigned to 7- or 10-day courses of the designated antimicrobial regimen. CSF isolates included Haemophilus influenzae type b (89, of which 25% were beta-lactamase positive), Streptococcus pneumoniae, and Neisseria meningitidis. Although mean CSF bactericidal titers against Haemophilus isolates were 1:6 in each treatment group, H. influenzae was cultured from CSF in four of 39 patients receiving cefuroxime, 24 to 48 hours after initiation of therapy, compared with none of 40 patients given ampicillin plus chloramphenicol (P = 0.11). Clinical cure rates were similar (95%); one death occurred in each group. One child given cefuroxime had persistent meningitis after 5 days of therapy, and mastoiditis with secondary bacteremia developed in one on day 10. Three patients had relapse or reinfection. One patient who received cefuroxime for 10 days had a relapse of epiglottitis 17 days later, and of the patients given ampicillin plus chloramphenicol, one had a relapse of meningitis 1 week after 7 days of therapy, and bacteremia developed in one 42 days after completion of 10 days of therapy. No increase in either in-hospital complications or relapses occurred with a 7-day treatment course. Proof of the equivalence of the antibiotic regimens and the efficacy of 7-day courses of treatment, as well as the consequences of delayed CSF sterilization, will require additional investigation.     

Once daily ceftriaxone for meningococcemia and meningococcal meningitis

Twenty children with meningococcal disease (15 with meningococcal meningitis and 5 with meningococcemia without meningitis) were treated with ceftriaxone, 80 to 100 mg/kg/day for 4 days. An additional 22 patients with meningococcal disease (13 with meningitis, 9 with meningococcemia without meningitis) were treated with penicillin G. On the basis of the Damrosch-Stiehm scoring system, 19 patients were classified in the poor prognostic group and were treated with antishock therapy. Clinical recovery time and normalization of CSF were compared in two groups. When the complications were compared, necrotic skin lesions were more frequently seen in the penicillin G group than in those who received ceftriaxone. Ceftriaxone is an effective and safe drug and offers the advantage of once daily administration for treatment of meningococcal disease in pediatric patients.     

Initial Chemotherapy for Purulent Meningitis in Children

The combination of ampicillin with either gentamicin or chloramphenicol, which is currently the initial chemotherapy for purulent meningitis, has lost its effectiveness in recent years because of an increase in the incidence of ampicillin-resistant strains. This has made it necessary to search for a suitable substitute therapy. Twenty-two new β-lactam agents were compared with penicillin G and ampicillin in terms of their antibacterial activity in relation to the principal causative microbes of meningitis and their ability to transfer into the cerebrospinal fluid (CSF) of rabbits with experimental staphylococcal meningitis. In addition, a survey was conducted of the therapeutic efficacy achieved by these drugs in cases seen by the authors and in other domestic and overseas cases. Finally, an investigation was made as to whether or not the transfer of the drug into the CSF was suppressed when it was administered simultaneously with ampicillin. From the results, it was surmised that in future the most appropriate initial chemotherapy for purulent meningitis will be a combination of cefotaxime, or perhaps ceftriaxone, plus ampicillin.     

Interleukin-6 and tumor necrosis factor-alpha levels in plasma and cerebrospinal fluid of term newborn infants with hypoxic-ischemic encephalopathy

OBJECTIVES: To determine plasma and cerebrospinal fluid (CSF) levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: A controlled, prospective study of 20 control neonates, 19 term newborn infants presenting with sepsis and no meningitis, and 19 asphyxiated term newborn infants. Blood and CSF samples were collected within 48 hours of birth for IL-6 and TNF-alpha determinations. RESULTS: Median plasma IL-6 was similar in sepsis and asphyxia but significantly higher than in control neonates. Median plasma TNF-alpha was similar in asphyxia and control neonates but significantly lower than in sepsis. In asphyxiated newborn infants, median CSF IL-6 and TNF-alpha were significantly higher than in sepsis and control neonates. Median CSF IL-6 was significantly higher in sepsis than in control neonates. Median CSF TNF-alpha was similar in newborn infants with sepsis and control neonates. IL-6 and TNF-alpha CSF/plasma ratios were similar in newborn infants with sepsis and control neonates but lower than in asphyxiated newborn infants. CONCLUSIONS: Term newborn infants with HIE have elevated CSF IL-6 and TNF-alpha levels. Plasma IL-6 is increased in asphyxia and sepsis. Plasma TNF-alpha is increased only in sepsis. High IL-6 and TNF-alpha CSF/plasma ratios in asphyxia suggest that these cytokines are produced in the brain of term newborn infants with HIE.     

Early diagnosis of neonatal infection

In 93 preterm and term infants with proven neonatal septicemia and/or meningitis different leukocyte indexes were evaluated at onset of septicemia [absolute neutrophil count, immature neutrophil count, immature to total neutrophil ratio (I/T-ratio)]. 75% of the patients who developed septicemia within the first three days of life and 60% of all neonates with septicemia or meningitis could be identified by an elevated I/T-ratio, the most sensitive leukocyte count. Thrombocytopenia was observed in only 33% of the patients. Additional analysis of IgM and fibrinogen was neither helpful in identifying neonatal infections nor a valuable follow-up parameter of successful treatment. In contrast C-reactive protein (CRP) was increased in 88% of all infants with neonatal septicemia and/or meningitis at time of diagnosis; when used in combination neutrophil indexes and CRP even improved the sensitivity of a single laboratory screening test.