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R Dagan

Publications and source records attributed to R Dagan.

At least 19 recordsLinked to original sources

Epidemiology of invasive childhood pneumococcal infections in Israel. The Israeli Pediatric Bacteremia and Meningitis Group.

OBJECTIVE: To study the epidemiology of childhood pneumococcal invasive infections in Israel as a background for immunization programs. DESIGN: A 2-year (October 1988 through September 1990) prospective, nationwide surveillance of all invasive pediatric pneumococcal infections. SETTING: All 25 medical centers hospitalizing children in Israel, including all laboratories performing blood cultures from pediatric patients. PATIENTS: Infants and children aged 0 to 12 years visiting the pediatric emergency department or hospitalized in pediatric departments were included if Streptococcus pneumoniae was isolated from blood or cerebrospinal fluid. RESULTS: Four hundred sixty-nine invasive infections were diagnosed. Pneumonia, bacteremia without apparent focus, meningitis, and cellulitis were found in 39%, 37%, 17%, and 3%, respectively. The annual incidence was 42 per 100,000 for children younger than 5 years of age (104 per 100,000 for those < 12 months old). The two most common serotypes were 1 and 5, which are rare in Western Europe and North America. Eight groups comprised 82% of all invasive infections. Extrapolated to a population in which 100,000 live births occur yearly, the total annual hospitalizations for pneumococci infections was calculated to be 1928 days. The overall case-fatality rate was 2.2%, but it was 30% during the first month of life. CONCLUSIONS: Pneumococcal invasive infections are common in children in Israel and carry considerable morbidity.

Acute Disease

A comparison of ceftazidime and aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn. European Society for Paediatric Infectious Diseases--Neonatal Sepsis Study Group.

We report a prospective, non-blind, randomised, multicentre, parallel group, multinational investigation to compare ceftazidime to aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn. In each of the 15 study centres either ceftazidime alone (CAZ) or ceftazidime + ampicillin (CAZ + AMP) was compared to an amino-glycoside/ampicillin combination (AG + AMP). In all cases treatment was based on "an intention to treat". Bacteria considered to be pathogenic were isolated from 176/1316 (13.4%) patients. The incidence of proven infection varied from 39% in a Yugoslav centre to 6% in a British centre; a further 489/1316 (37.1%) patients fulfilled the criteria for clinically suspected sepsis. A total of 210 bacterial isolates from 197 infection sites in 176 patients were considered to be clinically significant. The cure rate for evaluable patients with proven infection who were treated with CAZ + AMP (97%, 30/31) was significantly higher than that for the corresponding patients treated with AG + AMP (66%, 26/39), (P < 0.002). The difference in cure rate between CAZ monotherapy (79%, 34/43) and AG + AMP (86%, 32/37) was not significant. Treatment failed in 28/150 (18.7%) evaluable patients. There were significantly fewer failures (P < 0.001) with CAZ + AMP than with AG + AMP therapy. There were 55 staphylococcal infections. Treatment was successful in 16/19 evaluable patients treated with CAZ or CAZ + AMP and in 16/29 evaluable patients treated with AG + AMP. None of the study centres encountered problems with ceftazidime resistant bacteria. The cure rate for patients with only clinical and radiological evidence of sepsis was greater than 94% in all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides

Otolaryngology and infectious disease team approach for outpatient management of serious pediatric infections requiring parenteral antibiotic therapy.

Children with community-acquired serious otolaryngologic infections are conventionally hospitalized for parenteral antibiotic therapy. However, effective and safe outpatient therapy is desirable since it is less traumatic and less costly. During a 24-month period outpatient parenteral antibiotic therapy, usually once daily i.m. ceftriaxone, was evaluated in 41 children with serious otolaryngologic infections (acute mastoiditis, complicated otitis media, severe external otitis and severe sinusitis with orbital or periorbital involvement). Daily visits and compliant capable parents were considered essential for outpatient management. Diagnosis, plan for management and daily follow-up evaluations were carried out in cooperation by otolaryngology and infectious disease specialists. Nineteen children (45%) were treated initially in the hospital and 22 children (55%) were treated entirely as outpatients. The mean duration of outpatient treatment, using once daily i.m. ceftriaxone was 5.7 days (range 1-13). The overall clinical cure rate was 98% and no serious side effects were observed. One case of sinusitis-orbital cellulitis relapsed during therapy. Most patients and parents returned to normal life activities within 72 h from starting outpatient therapy. Our data suggest that many children with serious otolaryngologic infections can be managed successfully and safely as outpatients by a combined team of otolaryngology and infectious disease specialists.

Acute Disease

Medical treatment of chronic suppurative otitis media without cholesteatoma in children--a two-year follow-up.

A prospective long-term study was carried out in 48 infants and children with chronic suppurative otitis media without cholesteatoma treated initially with wide spectrum intravenous antibiotics and suction and debridement. Patients were followed for a period of two years. All children were cured after completion of therapy. At 3 and 6 months follow-up 75% of the children were still free of discharge and at 12, 18 and 24 months the proportion of dry ears dropped to 71%, 66% and 52%, respectively. Eighty percent of all recurrences developed already during the first 6 months of follow-up. Pseudomonas aeruginosa was the most common pathogen isolated, both in the initial and recurrent bouts of the disease, and was commonly associated with other pathogens. Children with early reappearance of ear discharge were less likely to benefit from further antimicrobial or surgical treatment. The recurrence rate was not affected by the antibiotic regimen, age, duration of drainage before treatment or the presence of granulation tissue. No intracranial or intratemporal complications were observed during the follow-up period.

Ceftazidime

A two-year prospective, nationwide study to determine the epidemiology and impact of invasive childhood Haemophilus influenzae type b infection in Israel. The Israeli Pediatric Bacteremia and Meningitis Group.

Accurate data on invasive Haemophilus influenzae type b (Hib) disease from countries other than the United States and western Europe are limited, and none are available from the Middle East. We report the results 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 2 study years, 344 patients less than 13 years of age with a positive blood or CSF culture for Hib were seen in 25 medical centers in which pediatric patients were hospitalized. The overall incidence of Hib disease was 34 per 100,000 persons less than 5 years old, an incidence in the range of those reported for western Europe. Twenty-two percent of patients were less than or equal to 6 months old, 69% were less than or equal to 12 months, 87% were less than or equal to 18 months, and 93% were less than or equal to 24 months. Thus, our findings represent a unique epidemiological pattern: 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. In view of these data, the Israeli Ministry of Health decided to license conjugate vaccines for immunization of infants beginning at 2 months of age.

Bacteremia

Failure of ceftriaxone in the treatment of acute brucellosis.

In an open, multicenter study conducted in Israel in 1989, 18 patients with acute brucellosis were randomized to receive either less than or equal to 2 g of intramuscularly administered ceftriaxone daily for at least 2 weeks or doxycycline for 4 weeks plus streptomycin for 2 weeks. All 10 patients treated with the combination of doxycycline plus streptomycin responded promptly, and their infections did not relapse during 6 months of follow-up. Of eight patients treated with ceftriaxone, six did not respond initially; when ceftriaxone was replaced by the combination of doxycycline and streptomycin, patients responded immediately. No relapses of infection were observed in these patients during follow-up. One patient who received ceftriaxone responded and remained well at the end of 6 months of follow-up, and one patient who initially responded to therapy with this drug experienced relapse of infection within 3 weeks but recovered when the doxycycline/streptomycin regimen was initiated. We conclude that despite encouraging data from in vitro studies and promising clinical studies, 2 g of ceftriaxone administered im daily should not be considered appropriate therapy for brucellosis.

Acute Disease

Once daily cefixime compared with twice daily trimethoprim/sulfamethoxazole for treatment of urinary tract infection in infants and children.

We conducted a randomized prospective multicenter study to compare the safety and efficacy of once daily oral cefixime (8 mg/kg) to twice daily oral trimethoprim/sulfamethoxazole (TMP/SMX) (8/40 mg/kg/day) for the treatment of acute urinary tract infection in children ages 6 months to 13 years. Seventy-six patients (38 in each group) were studied. Thirty-seven percent were younger than 3 years of age. Escherichia coli was the most common isolate in both groups (85%). Eighty-five percent of all Gram-negative organisms were susceptible to TMP/SMX and all were susceptible to cefixime. Seventy-two percent of all patients were febrile at the time of diagnosis. Both groups were treated for 7 to 10 days. Peripheral white blood cell counts, erythrocyte sedimentation rate, body temperature and urinalysis returned to normal at the same rate in both groups. No failures were observed and relapse occurred in 3 cases within the 4 weeks after treatment (2 in the cefixime group and one in the TMP/SMX group). Side effects were observed in 14% of the cefixime group and 16% of the TMP/SMX group and were all mild enough not to necessitate discontinuation of therapy. We conclude that the efficacy and safety of cefixime administered once daily compared favorably with TMP/SMX administered twice daily for acute uncomplicated urinary tract infection.

Administration, Oral

Outpatient management of chronic suppurative otitis media without cholesteatoma in children.

Prolonged antipseudomonal parenteral antibiotic therapy combined with daily aural toilet has been effective in resolving long standing ear discharge in children with chronic suppurative otitis media. However, such treatment suffered from the disadvantages of prolonged hospitalization. We conducted a prospective study to investigate the feasibility and efficacy of exclusive outpatient treatment of children with chronic suppurative otitis media without cholesteatoma who had failed ototopical/oral antimicrobial therapy. The treatment consisted of daily aural toilet (suction and debridement) and twice daily parenteral ceftazidime (50 mg/kg/dose). Thirty-seven children were included. The duration of discharge from the ear before treatment was 6 to 121 months (median, 30 months). Aerobic cultures yielded Pseudomonas aeruginosa in 97%, often with other organisms. The management and follow-up were performed jointly by otolaryngology and infectious diseases physicians using the hospital ambulatory services. The route of ceftazidime administration (intravenous or intramuscular) was chosen according to the parents' and patients' convenience. Discharge stopped within 3 to 20 days (median, 8 days) in all children but one. Seventy-six percent of the 29 children available for follow-up 12 months after treatment were still free of discharge. Our results demonstrate that a regiment combining daily aural toilet and twice daily parenteral ceftazidime is highly efficacious in resolving ear discharge in children with chronic suppurative otitis media without cholesteatoma and that such a regimen does not require hospitalization.

Adolescent

Respiratory tract colonization with Ureaplasma urealyticum and bronchopulmonary dysplasia in neonates in southern Israel.

Ureaplasma urealyticum has been recognized as an important potential pathogen in premature neonates. Reported rates of colonization of the respiratory tract vary. Data on neonatal ureaplasma colonization outside the United States and Western Europe are rare. Therefore we prospectively studied nasopharyngeal and endotracheal colonization in a cohort of 114 preterm and 100 full term infants within 48 hours of birth. The colonization rate was 24% in the premature infants and zero in the full term infants. Bronchopulmonary dysplasia developed in 19% of infants with nasopharyngeal Ureaplasma colonization and in 4.6% of noncolonized infants (P < 0.03). Bronchopulmonary dysplasia developed in 40% of intubated infants with positive endotracheal Ureaplasma cultures and only in 9.8% of infants with negative endotracheal cultures (P < 0.04). Thus Ureaplasma colonization of either the nasopharynx or the trachea was associated with an increased risk for the development of bronchopulmonary dysplasia (relative risk, 4.0 and 4.1, respectively).

Bronchopulmonary Dysplasia

Safety and immunogenicity of oral tetravalent human-rhesus reassortant rotavirus vaccine in neonates.

We conducted a prospective randomized double blind study to determine: (1) the safety and immunogenicity of live oral tetravalent human-rhesus rotavirus reassortant vaccine in neonates; and (2) whether a second dose at the age of 6 to 8 weeks enhances the immunogenicity. Two hundred forty healthy neonates were enrolled and received vaccine (183) or placebo (57) on the second day of life. At the age of 6 to 8 weeks 133 received placebo and 88 received a second dose of vaccine. Medical events were noted within 10 days from vaccine administration in 6 of 183 (3.3%) vaccine recipients vs. 0 of 57 placebo recipients (P = 0.34) after the first dose and in 8 of 88 (9%) vs. 4 of 133 (3%) after the second dose (P = 0.069); none was severe and all were of short duration. Seroresponse of any type (detectable IgA or 4-fold increase of titer to rhesus rotavirus was 9% for the placebo, vs. 52 and 46% for those who received one and two doses of vaccine, respectively. However, neutralizing antibodies against human serotypes 1, 2 and 3 were not raised successfully in vaccinated infants when compared with placebo recipients. The same pattern was found when geometric mean titers were compared. Vaccine take was better when cord blood titers were low. At the age of 1 year the vaccinees had more often high titers for antirhesus rotavirus antibodies (> 640) than the placebo recipients (49% vs. 0%; P < 0.001). NO difference was found between the groups in neutralizing antibodies to human serotypes 1, 2 and 3 rotavirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Double-blind study comparing erythromycin and mupirocin for treatment of impetigo in children: implications of a high prevalence of erythromycin-resistant Staphylococcus aureus strains.

Staphylococcus aureus has been consistently isolated from a high proportion of impetiginous lesions, and in several recent studies, it was present in the majority of the cases. Since recently a large proportion of S. aureus strains in our community showed erythromycin resistance, we undertook a prospective double-blind controlled study comparing topical mupirocin with oral erythromycin to determine (i) the prevalence of erythromycin-resistant S. aureus strains in impetigo and (ii) whether an increased rate of failure of erythromycin treatment was associated with such resistance. A total of 102 patients 3 to 185 months old (median = 49 months) were enrolled. Culture was positive for 97 of 102 (95%) patients, and S. aureus was present in 93% of the patients for whom cultures were positive. S. aureus was the single pathogen in 64% of these patients. Erythromycin-resistant S. aureus strains were present in 27 of 91 (28%) patients for whom cultures were positive. In all cases but one, S. aureus was resistant to penicillin, and in all cases it was sensitive to mupirocin. A marked difference was observed in favor of mupirocin in the clinical courses of the disease. However, only patients with erythromycin-resistant S. aureus strains had unfavorable courses compared with those treated with mupirocin (failure rate, 47 versus 2%, respectively). Patients with erythromycin-susceptible S. aureus strains who received erythromycin had a failure rate of 8%. In four patients, S. aureus strains initially susceptible to erythromycin became resistant during treatment. We conclude that erythromycin-resistant S. aureus strains are commonly isolated from impetigo in our region.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria

High prevalence of Kingella kingae in joint fluid from children with septic arthritis revealed by the BACTEC blood culture system.

In an effort to improve detection of fastidious organisms, joint fluid aspirates of pediatric patients were inoculated into BACTEC 460 aerobic blood culture bottles, in addition to cultures on solid media. Culture records for the 1988 to 1991 period were reviewed to compare the performance of both methods for the recovery of pathogens. Overall, 216 children underwent a diagnostic joint tap, and 63 specimens grew significant organisms, including Kingella kingae in 14. While both methods were comparable for recovery of usual pathogens, with a single exception, K. kingae isolates were detected by the BACTEC system only. K. kingae appears to be a more common cause of septic arthritis in children than has been previously recognized. The BACTEC blood culture system enhances the recovery of K. kingae from joint fluid and improves bacteriologic diagnosis of pediatric septic arthritis.

Adolescent

Clinical studies in pediatric respiratory-tract infections: what is desirable, feasible, or simply misleading.

In recent years, attempts have been made to make the regulatory requirements for clinical studies more uniform, and much has been discussed on the issue of good clinical practice. There is no doubt that clinical trials involving new drugs have to be conducted according to the highest standards. However, ideal design is not always feasible or ethical. The ideal design for efficacy studies demands randomization, double-blind comparisons, adequate group size, specification of the type of patients and isolated organisms. The present paper points out some difficulties regarding these points when studying cephalosporins in pediatric respiratory-tract infections, and proposes some solutions.

Anti-Bacterial Agents

Aerobic bacteriology of chronic suppurative otitis media without cholesteatoma in children.

Medical management of chronic suppurative otitis media without cholesteatoma in children was shown recently to be efficacious. We undertook a prospective study in order to determine 1) the organisms associated with the disease and their sensitivity to various antibiotics and 2) their association with clinical variables. Pseudomonas was isolated from 84% of the patients, enteric gram-negative bacilli from 32%, Staphylococcus aureus from 20%, streptococci from 14%, and Hemophilus influenzae from 15%. Pseudomonas aeruginosa was the sole isolate in 48 of the 128 patients (38%). The sensitivity of P aeruginosa (78 isolates) was 100% (of isolates) to mezlocillin and ciprofloxacin, 99% to tobramycin and ceftazidime, 97% to piperacillin, 94% to gentamicin, and 78% to ceftriaxone. The isolated organisms and their sensitivity to antibiotics were not associated with age, sex, duration of otorrhea, or the presence of granulation tissue or polyps. We believe that our data may contribute to the appropriate choice of antibiotics when nonsurgical management of chronic suppurative otitis media without cholesteatoma is considered.

Adolescent