Penetration of meropenem into the cerebrospinal fluid of patients with inflamed meninges.
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Biomedical subjects
Publications and source records attributed to R Dagan.
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Because inactivated poliovirus vaccine (IPV) and Haemophilus influenzae b vaccine are advised in many programs and may be incorporated further in other programs, we undertook a study to determine whether the administration of a tetravalent preparation of diphtheria-tetanus-pertussis-IPV mixed in one syringe with tetanus-conjugate H. influenzae b vaccine (DTP-IPV-PRPT) is associated with increased reactogenicity or interference with immunogenicity of individual vaccine components. In a placebo-controlled, double blind study, a total of 161 infants were enrolled (80 DTP-IPV-PRPT and 81 DTP-IPV-placebo). Vaccine was administered at 2, 4 and 6 months of age. Oral poliovirus vaccine was added at 7 months of age and a booster of oral poliovirus vaccine and DTP-IPV was also administered at 12 months of age, according to the policy in Israel. Local and systemic side effects were similar in both groups except for irritability after the second dose and use of acetaminophen which we observed slightly but significantly more often in the DTP-IPV-PRPT recipients. After the third dose the geometric mean titers of anti-polyribosyl-ribitol phosphate antibodies were 3.7 and 0.05 micrograms/ml in the PRPT and placebo groups, respectively (P < 0.001). Higher tetanus antitoxin titers were observed among recipients of DPT-IPV-placebo (1.1 IU/ml vs. 0.7 IU/ml, P = 0.003). A similar trend was found for pertussis agglutinin titers (93.4 vs. 65.4, P = 0.054). No difference was observed for anti-diphtheria toxoid and poliovirus 1, 2, and 3.(ABSTRACT TRUNCATED AT 250 WORDS)
Palatability of oral antibiotic suspensions is important and may be a substantial factor in determining compliance in young pediatric patients. Because no comparative systematic data are available, we undertook the present study to assess the acceptance of and compliance with oral antibiotic suspensions commonly used in Israel. During a 4-month period lists of children receiving oral antibiotic suspensions were obtained from 3 major pediatric clinics, and parents were contacted by telephone 10 to 14 days after initiation of therapy, at which time information on age, sex, main disease, prescribed drugs and duration of treatment was obtained. Information regarding acceptance, side effects and compliance was obtained from 11 questions with graded scores. In the study 546 children received one of the following drugs: amoxicillin (n = 222); cefaclor (n - 142); cefuroxime axetil (n = 107); trimethoprim/sulfamethoxazole (n = 75). No major differences in background data were noted; more than 50% of each group had acute otitis media. Seventy-three percent of the cefaclor group reported acceptance of the drug with "pleasure" or "without problems" vs. 60, 55 and 20% for amoxicillin, trimethoprim/sulfamethoxazole and cefuroxime axetil, respectively, whereas "resentment" or "refusal" was reported in 11, 16, 26 and 56%, respectively (P < 0.0001). Mothers reported to be generally "satisfied" or "extremely satisfied" with the drug in 89, 81, 74 and 67% with cefaclor, amoxicillin, trimethoprim/sulfamethoxazole and cefuroxime axetil, respectively, and 85, 77, 73 and 67% of the children, respectively, received the drug for the entire prescribed course (P < 0.001). Our data demonstrate that marked variations exist in acceptance and compliance of oral antibiotic suspensions with children.(ABSTRACT TRUNCATED AT 250 WORDS)
Although penicillin-resistant pneumococci (PR-PnC) are recognized as an increasing problem worldwide, data on the prevalence of these strains among pediatric patients are incomplete. The present study was conducted in southern Israel (1) to investigate the frequency of PR-PnC in invasive and middle ear infections in pediatric patients and (2) to assess the impact of resistance on the potential role of the candidate conjugate vaccines in preventing childhood PR-PnC infections. A total of 120 blood or cerebrospinal fluid isolates from 1987 to 1993 and 78 ear isolates from 1992 to 1993 were serogrouped and tested for susceptibility to antibacterial agents. The prevalence of PR-PnC among invasive isolates increased from 16% in the years 1987 to 1991 to 36% in 1992 to 1993 (P = 0.019). This increase was noted mainly for intermediately resistant strains (minimal inhibitory concentration, 0.12 to 1.0 micrograms/ml) whereas the prevalence of highly resistant strains was 3 and 2% for the 2 periods, respectively. The prevalence of PR-PnC among ear isolates in 1992 to 1993 was 42%. Resistance to other antimicrobial agents (one or more of the following: tetracycline, erythromycin, clindamycin and chloramphenicol) was found in 16 (8%) isolates, and multiple resistance (resistance to > or = 3 antibacterial agents) was found in 9 (5%) isolates. Sixty-five (99%) of the 66 resistant isolates belong to Serogroups 6, 14, 19 and 23. The prevalence of these 4 serogroups rose from 37% in 1987 to 1991 to 66% in 1992 to 1993 (P = 0.043). This rise was mainly because of Serogroup 23, the prevalence of which rose from 3% in 1987 to 1991 to 23% in 1992 to 1993 (P < 0.001). Eighty-five percent of all isolates belonging to Serogroup 23 were resistant to penicillin. Because Serogroups 6, 14, 19 and 23 are among the commonest pediatric pneumococcal strains, the newly developed conjugate pneumococcal vaccines contain these 4 serogroups. The selection of antibiotic-resistant strains has thus led to a change in the spectrum of serotypes causing invasive disease and to a situation of potential increase in vaccine coverage for the proposed pneumococcal conjugate vaccines.
During the summer of 1988, an outbreak of poliomyelitis caused by poliovirus 1 occurred in Israel, during which a national mass immunization campaign with oral poliovirus was undertaken. This prospective study was undertaken to assess the effect of maternal oral poliovirus immunization during the third trimester of pregnancy on neonatal immunity against poliovirus. Cord blood specimens of 88 neonates, born 2 to 7 weeks after maternal immunization, were examined for antipoliovirus antibodies and compared with 100 samples obtained from neonates 7 months before the outbreak. Blood samples were also obtained from the 62 mothers of neonates who had been immunized 2 to 5 weeks before delivery. Sera were tested for neutralizing antibodies to the 3 poliovirus types using a microneutralization technique. The geometric mean titer to poliovirus type 1 was significantly higher in neonates whose mothers were immunized during pregnancy (87.1) than in the offspring of the nonvaccinated group (53.0), P < 0.05. Two to 3 weeks after immunization, geometric mean titers against all 3 poliovirus types were higher in maternal blood than in cord blood whereas 4 to 5 weeks after vaccination a significant difference was found for type 3 only. Although oral poliovirus immunization during pregnancy resulted in higher neonatal antibody titers to poliovirus type 1, the proportion of newborns with titers of < 1:8 to the 3 poliovirus types did not change significantly.
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Three sibs born to consanguineous parents had congenital nephrotic syndrome, microcephaly, and psychomotor retardation. Pathology of the kidneys showed diffuse mesangial sclerosis with deposits of IgG and C3 in the mesangium and glomerular basement membranes. All three children died before the age of 3 years. Of 19 published cases of children with the association of congenital nephrotic syndrome and microcephaly, only four had histological evidence of diffuse mesangial sclerosis, and two of their sibs probably had the same disease. The association of nephrotic syndrome owing to congenital diffuse mesangial sclerosis, microcephaly, and mental retardation appears to be a distinct syndrome with an autosomal recessive mode of inheritance.
In phase I of a 2-phase study, 56 evaluable children (0.8 to 5 years) with lobar or segmental pneumonia received intravenous or intramuscular ceftriaxone 50 mg/kg/day for 2 days followed by oral cefetamet pivoxil 20 mg/kg/day in 2 divided doses to complete 7 days of treatment. All patients achieved a clinical cure. In phase II, a randomised open multicentre study, 62 children with pneumonia received an identical regimen to phase I (arm A), and 59 children received ceftriaxone 50 mg/kg/day for 1 day followed by 6 days' treatment with cefetamet pivoxil 20 mg/kg/day (arm B). Patients from phase I and arm A were combined giving a total of 118 evaluable patients in arm A. At the end of treatment, 100% of patients in arm A and 96% in arm B achieved a clinical cure; cure was maintained in 99 and 98% of patients, respectively. Two (4%) patients in arm B failed therapy; in both cases, factors other than treatment failure may have accounted for the poor response. 11 and 12% of patients in treatment arms A and B, respectively, experienced adverse events; gastrointestinal events (nausea and/or vomiting) were reported in 9 and 8% of patients, respectively. In conclusion, 1 or 2 days' treatment with parenteral ceftriaxone before switching to oral cefetamet pivoxil was safe and effective in the treatment of childhood pneumonia. Therefore, parenteral-oral switch is a feasible treatment option in the treatment of serious paediatric community-acquired pneumonia.
OBJECTIVE: Prospective studies were conducted to test the hypothesis that infants unlikely to have serious bacterial infections (SBI) can be accurately identified by low risk criteria. METHODS: Febrile infants (rectal T > or = 38 degrees C) < or = 60 days of age were considered at low risk for SBI if they met the following criteria: 1) appear well; 2) were previously healthy; 3) have no focal infection; 4) have WBC count 5.0-15.0 x 10(9) cells/L (5000-15,000/mm3), band form count < or = 1.5 x 10(9) cells/L (< or = 1500/mm3), < or = 10 WBC per high power field on microscopic examination of spun urine sediment, and < or = 5 WBC per high power field on microscopic examination of a stool smear (if diarrhea). The recommended evaluation included the culture of specimens of blood, cerebrospinal fluid, and urine for bacteria. Outcomes were determined. The negative predictive values of the low risk criteria for SBI and bacteremia were calculated. RESULTS: Of 1057 eligible infants, 931 were well appearing, and, of these, 437 met the remaining low risk criteria. Five low risk infants had SBI including two infants with bacteremia. The negative predictive value of the low risk criteria was 98.9% (95% confidence interval, 97.2% to 99.6%) for SBI, and 99.5% (95% confidence interval, 98.2% to 99.9%) for bacteremia. CONCLUSIONS: These data confirm the ability of the low risk criteria to identify infants unlikely to have SBI. Infants who meet the low risk criteria can be carefully observed without administering antimicrobial agents.
For children with acute respiratory infections in hospital, it is desirable to transfer from parenteral to oral therapy at the earliest opportunity. The introduction of a pediatric suspension of cefuroxime axetil provides a continuous course of one antibiotic with transition from injectable to oral therapy. This open study was designed to investigate the efficacy of cefuroxime in pediatric patients aged 3 months to 5 years with community-acquired pneumonia. Children had evidence of lobar pneumonia on chest X-ray, a white blood cell count of > 15,000/mm3 and a rectal temperature of > or = 38.5 degrees C on enrollment. Cefuroxime was given by i.v. injection at 75 mg/kg per day in three divided doses for 48-72 h followed by oral cefuroxime suspension at 30 mg/kg per day in two divided doses. Of 84 evaluable patients 82 (97.6%) were cured or improved post-treatment, and of 74 evaluable children who returned for follow-up assessment 73 (98.6%) remained well. Oral therapy with twice daily cefuroxime axetil suspension following 2-3 days of i.v. cefuroxime administration was confirmed as effective and safe treatment for lobar pneumonia in children under 5 years of age.
In 30 patients in whom osteomyelitis was suspected fine-needle bone biopsies (FNBB) were taken at the same time as bone was aspirated for bacteriological examination. The diagnosis of osteomyelitis was eventually confirmed in 15 patients; the other 15 had myositis (3), arthritis (3), trauma (2), microgeodic phalangeal syndrome (2), haematoma in a non-ossifying fibroma (1), and Ewing's sarcoma (1). In three patients no pathology was found. The temperature, WBC and ESR at presentation did not help to distinguish osteomyelitis from other conditions. FNBB, however, proved to be a useful additional investigation with a sensitivity for osteomyelitis of 87% and a specificity of 93%.
The serum antibody response induced by Haemophilus influenzae type b capsular polysaccharide (CPS)-tetanus protein conjugate vaccine combined to DTP vaccine was characterized in infants receiving three injections from 2 months of age. Sixty-five per cent and 94% of infants had anti-CPS antibody levels > or = 1 micrograms ml-1 after the second and third dose, respectively. The antibody response was mostly made up of IgG with a marked IgG1 predominance. Significant rises in bactericidal and in complement-mediated opsonic activities were observed after immunization. These data clearly show that this vaccine can be successfully administered in one syringe together with DTP vaccine during the regular infant immunization programme.
The results are reported of a nationwide prospective epidemiological study in Israel whose purpose was to provide a background for decisions regarding the need for Hib conjugate vaccinations. During the two study years, 344 patients < 13 years of age with a positive blood or cerebrospinal fluid culture for Hib were seen in 25 medical centres in which paediatric patients were hospitalized. The overall incidence of Hib disease was 34 per 100,000 persons < 5 years old, an incidence in the range of those reported for western Europe. Similarly, the incidence of meningitis was 18/100,000. During the first year of life, the incidence of Hib was 117/100,000 and 93% of all cases were < or = 24 months old. The age distribution of our patients resembles that of immunologically compromised populations or of persons living in less industrialized areas, but the incidence of disease is similar to that found in western Europe. The data presented justify the widespread use of conjugate Hib vaccines in Israel.
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To determine and compare the cost of Haemophilus influenzae type b (Hib) disease in Australia, Finland, Israel, Switzerland and the United Kingdom a collaborative study was undertaken. The incidence of Hib disease varies in these 5 countries from 34 to 58.5 cases per 100,000 children less than 5 years of age. Although the incidence of meningitis in this age group is similar (between 18 and 26/100,000) in these countries, the incidence of epiglottitis varies from 0 to 22.7/100,000. The cost of hospitalization and the frequency of sequelae are similar for 4 of the 5 countries; however, the break even cost of a vaccination program to prevent 90% of Hib disease is estimated to vary from $22 to $84 per child (US$). Because of a lower incidence of Hib disease and lower cost for hospitalization, these costs are considerably less than those for the United States ($301.64 using similar calculations).
We conducted a prospective study to determine the clinical picture and impact of respiratory syncytial virus (RSV) on hospitalization for acute bronchiolitis of pediatric patients less than 2 years of age belonging to two different ethnic groups in Southern Israel: Jews and Bedouins. All patients younger than 2 years of age hospitalized for bronchiolitis during a typical RSV season were enrolled. During the study period 120 patients with bronchiolitis were hospitalized, and 83 (69%) were RSV-positive. Their age ranged from 20 days to 9 months. Fifty-five percent of all patients with RSV bronchiolitis were < or = 3 months old and 92% were < or = 6 months old. Patients with RSV bronchiolitis represented 18% of all hospitalized infants < or = 9 months old and 35% of all hospitalizations for respiratory problems of infants < or = 9 months old. The yearly incidence of hospitalization for RSV bronchiolitis was 5.4/1000 live births for Jews and 18/1000 live births for Bedouins. The total number of hospitalization days calculated for 1000 births was 32.1 for the Jews and 86.7 for the Bedouins. RSV has a serious impact on infant morbidity in Southern Israel.