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Biomedical subjects

R Dagan

Publications and source records attributed to R Dagan.

At least 55 records · Page 3Linked to original sources
PubMed2000

Antibiotic treatment for acute otitis media.

The major problems encountered in the antibiotic therapy of acute otitis media (AOM) are the tremendous increase in the resistance to antibiotics of its main pathogens and the lack of tight criteria (taking into consideration, as a major determinant, the eradication of the pathogens from the middle ear fluid) in the selection of the appropriate antibiotic drugs for the treatment of this disease. Future drugs for the treatment of AOM will have to be approved only after their in vivo microbiological efficacy for each major pathogen is documented. This documentation will be provided by more antibiotic studies with bacteriological outcome using the double-tympanocentesis method and stratifying the AOM patients by age and initial clinical severity. Judicious use of antibiotics for the treatment of AOM will have a major impact on society, leading to a less frequent but more skilled administration of the most effective drugs.

Acute Disease↗
PubMed2000

Mediterranean clone of penicillin-susceptible, multidrug-resistant serotype 6B Streptococcus pneumoniae in Greece, Italy and Israel.

In 1996, 19 isolates of serotype 6B Streptococcus pneumoniae with a unique resistance pattern were found in carriers attending daycare centres in Patras, Southwestern Greece. These isolates were penicillin susceptible but resistant to chloramphenicol, tetracycline, erythromycin, clindamycin and trimethoprim-sulphamethoxazole. Subsequently, isolates with the same characteristics were found in 23 additional carriers in central and southern Greece in 1997-98 as well as in 19 carriers in central Italy in 1997, and in seven carriers in southern Israel in 1998. Carriers were all children under 6 years of age, attending daycare centres or outpatient hospital visits. The relatedness of the isolates was determined on representative isolates from the three countries by pulsed-field gel electrophoresis of SmaI digests of chromosomal DNA. Most Greek isolates were identical to each other, while isolates from Italy and Israel showed one to three band differences, with all isolates being closely related to each other as well as to the isolates from Greece. We have therefore documented the presence of this unique clone of S. pneumoniae in these three countries and have named this the 'Mediterranean' clone. While isolates appear to have a common origin, their source and direction of spread are unknown. However, isolates from Italy showed the most diversity, suggesting that this clone had been present in that country for a longer period than it had been in Greece.

DNA, Bacterial↗
PubMed2000

Middle ear effusion IL-6 concentration in bacterial and non-bacterial acute otitis media.

BACKGROUND: The pathogenesis of acute otitis media is complex and multifactorial. It is characterized by inflammation of the middle ear with an infiltration of leukocytes, macrophages and mast cells. The resulting effusion contains a large amount of inflammatory mediators, among which are cytokines. OBJECTIVES: To test the role of IL-6 in the inflammatory process associated with acute otitis media. METHODS: We analyzed 20 middle ear fluid (MEF) sample pairs, obtained by aspiration before initiating antibiotic therapy (day 1) and during treatment (days 4-5), for the presence of IL-6. IL-6 concentrations were assayed with an ELISA kit (detection limit 5 pg/ml) and were correlated with bacterial etiology and bacterial eradication from the middle ear. RESULTS: IL-6 was detected in all middle ear effusions analyzed. We found decreased IL-6 concentrations in culture negative MEF compared to culture positive MEF on both days I and 4-5 (day 1, 1752.20+/-1001.31 pg/ml vs 1216.20+/-1015.44 pg/ml, p = 0.19; days 4-5, 1049.36+/-472.40 pg/ml vs 800.33+/-676.00 pg/ml, p = 0.23); however, differences did not achieve statistical significance. Overall, a marked and significant decrease in IL-6 concentration occurred following 72-96 h of antibiotic therapy (1618.15+/-1004.88 pg/ml vs 936.85+/-581.05 pg/ml, p = 0.04). While MEF IL-6 concentrations decreased in ears where bacteria persisted (1468.20+/-858.48 pg/ml vs 1044.80+/-514.16 pg/ml, p = 0.167) or were eradicated (2320.20+/-866.16 pg/ml vs 767.40+/-522.88 pg/ml, p = 0.029), a more prominent decline was demonstrated in the latter. CONCLUSIONS: These results strongly suggest the involvement of IL-6 in the ongoing inflammatory process in both bacterial and non-bacterial acute otitis media. Resolution of inflammation in the middle ear, especially where bacteria were eradicated, is reflected by low IL-6 levels.

Acute Disease↗
PubMed2000

An outbreak of Streptococcus pneumoniae serotype 1 in a closed community in southern Israel.

An outbreak of Streptococcus pneumoniae serotype 1 occurred in a closed community that was characterized by poverty and crowding. Vaccine was administered to individuals aged >2 years; no new cases occurred among vaccine recipients. Six weeks after vaccination, carriage of serotype 1, but not of other serotypes, decreased 8.8-fold. This suggests that the reduction in serotype 1 carriage reflects the natural course of the outbreak rather than a vaccine effect. Polysaccharide vaccine may be helpful in terminating pneumococcal outbreaks but may not affect pneumococcal carriage.

Adolescent↗
PubMed2000

Giardia lamblia carriage in Israeli Bedouin infants: risk factors and consequences.

Giardiasis is a common protozoan infection, with varying clinical manifestations. We investigated the associations between Giardia lamblia carriage and environmental, family, illness, and growth characteristics. Bedouin infants (n=234) were followed from birth to age 18-23 months. At monthly home visits, stool samples were obtained, history of illness was determined, and an environmental assessment was done. The comparisons presented are between 4 groups defined by length of carriage of G. lamblia. Study children had a mean+/-SD of 4.1+/-2.9 diarrhea episodes. No illness, environmental, or family characteristics were associated with length of carriage. Significant differences were found in weight-for-age and weight-for-height z scores between the never-positive-for-G. lamblia group and all other carriage groups combined. Faltering growth was shown to be subsequent to G. lamblia infection rather than preceding it. Our findings confirm that G. lamblia carriage is not associated with diarrhea. However, the effect on growth deserves further investigation.

Adolescent↗
PubMed2000

Molecular typing of Streptococcus pneumoniae in northeastern Romania: unique clones of S. pneumoniae isolated from children hospitalized for infections and from healthy and human immunodeficiency virus-infected children in the community.

Microbiologic, serologic, and molecular typing techniques were used to characterize 272 isolates of Streptococcus pneumoniae colonizing or infecting children in Iasi, Romania, during a surveillance study conducted in 1996-1998. The 574 children in the study were from the following groups: healthy children attending 2 institutions, healthy children hospitalized for elective surgery, hospitalized children with pneumococcal infections, and human immunodeficiency virus (HIV)-infected children in an orphanage. Pneumococci colonizing healthy children from closed communities showed close similarities to pneumococci from children with pneumococcal infections; they expressed a limited number of similar serotypes, showed high frequency of penicillin and multidrug resistance, and shared several common clonal types. In contrast, isolates recovered from healthy children hospitalized for elective surgery expressed a large variety of serotypes, were less frequently resistant to antimicrobial agents, and showed great genetic diversity. Pneumococcal flora colonizing HIV-infected children showed a more complex epidemiology. These observations suggest a possible epidemiologic connection between the flora of S. pneumoniae colonizing healthy children in closed communities and the flora found in children hospitalized for infection.

Child↗
PubMed2000

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Journal Article↗
PubMed2000

Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media.

OBJECTIVES: To compare the bacteriologic and clinical efficacy of amoxicillin/clavulanate and azithromycin in patients with acute otitis media (AOM), particularly the ability to eradicate the predominant AOM pathogens from middle ear fluid as assessed by mandatory second tympanocentesis. METHODS: In this single blind study 238 infants and children with AOM were randomized to receive amoxicillin/clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or azithromycin (10 mg/kg on Day 1, then 5 mg/kg daily on Days 2 through 5). Tympanocentesis was performed before the first dose and repeated on Day 4, 5 or 6. Clinical response was assessed at end of therapy between Days 12 and 14 and at follow-up between Days 22 and 28. RESULTS: Amoxicillin/clavulanate was significantly more likely to eradicate all bacterial pathogens [83% (54 of 65) vs. 49% (35 of 71), P = 0.001] and Haemophilus influenzae [87% (26 of 30) vs. 39% (13 of 33), P = 0.0001] from middle ear fluid than was azithromycin. Amoxicillin/clavulanate was also more likely to eradicate Streptococcus pneumoniae, but the difference was not statistically significant [90% (18 of 20) vs. 68% (13 of 19) [corrected], P = 0.095]. On Days 12 to 14, signs and symptoms were more likely to resolve completely or improve in all culture-positive patients [86% (60 of 70) vs. 70% (51 of 73), P = 0.023] and in those with H. influenzae infections [91% (30 of 33) vs. 65% (22 of 34), P = 0.010] who received amoxicillin/clavulanate compared with those who received azithromycin. Otherwise there were no significant differences between groups in clinical outcomes on Days 12 to 14 or at follow-up. CONCLUSIONS: Our findings indicate that amoxicillin/clavulanate has superior bacteriologic and clinical efficacy compared with azithromycin in children with AOM.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2000

Predictive value of pneumococcal nasopharyngeal cultures for the assessment of nonresponsive acute otitis media in children.

BACKGROUND: Nonresponsive acute otitis media (NR-AOM) is reported in > 10% of children with AOM treated with antibiotics. Drug-resistant Streptococcus pneumoniae is currently considered the leading cause of antibiotic failures in AOM. Nasopharyngeal colonization with S. pneumoniae was found to increase significantly during episodes of AOM. OBJECTIVES: To investigate the nasopharyngeal colonization with S. pneumoniae during NR-AOM and compare it with that found in AOM not recently treated with antibiotics (NT-AOM); to assess the predictive value of nasopharyngeal pneumococcal cultures results for the bacteriologic assessment of NR-AOM. MATERIALS AND METHODS: Patients age 3 to 48 months with NT-AOM and NR-AOM were prospectively studied. Simultaneous nasopharyngeal cultures for S. pneumoniae and middle ear fluid cultures were obtained at enrollment. Antibiotic susceptibility testing was performed in all S. pneumoniae isolates. Penicillin and ceftriaxone MICs for S. pneumoniae were determined by E-test. The sensitivity, specificity and positive and negative predictive values of positive or negative nasopharyngeal cultures for the presence of S. pneumoniae in middle ear fluid were calculated. RESULTS: We studied 362 and 217 children with NT-AOM and NR-AOM, respectively. Of the children with NT-AOM and NR-AOM, 95 and 97%, respectively, were younger than 2 years of age. S. pneumoniae was isolated in the nasopharynx of 66 and 58% of children with NT-AOM and NR-AOM, respectively. Penicillin-nonsusceptible S. pneumoniae was isolated more frequently from the nasopharynx of patients with NR-AOM than from those with NT-AOM (84% vs. 47%; P < 0.01). Antibiotic susceptibility patterns were similar for S. pneumoniae isolates recovered from the nasopharynx and those from the middle ear fluid in both NT-AOM and NR-AOM. A positive nasopharyngeal culture had only little predictive value for the presence of S. pneumoniae in middle ear fluid (41 and 51% for NT-AOM and NR-AOM, respectively). However, the negative predictive value of nasopharyngeal cultures for recovery of S. pneumoniae in NR-AOM was high and significantly higher in NR-AOM than in NT-AOM (91% vs. 78%, respectively; P = 0.009). The negative predictive value of nasopharyngeal cultures for recovery of antibiotic-resistant S. pneumoniae was 95 and 93% in NT-AOM and NR-AOM, respectively. Conclusions. A significantly higher nasopharyngeal colonization rate with antibiotic-resistant S. pneumoniae was found in patients with NR-AOM than in those with NT-AOM. Negative nasopharyngeal culture for antibiotic-resistant S. pneumoniae practically rules out its presence in middle ear fluid.

Acute Disease↗
PubMed2000

Clinical significance of resistant organisms in otitis media.

BACKGROUND: Otitis media is an important health care problem of childhood. The bacteriology of otitis media comprises three main pathogens: Streptococcus pneumoniae, nontypable Haemophilus influenzae and Moraxella catarrhalis. Although the prevalence of resistant strains varies geographically and temporally, antimicrobial resistance is widespread and increasing. RESISTANCE TO ANTIBIOTIC DRUGS: Among the risk factors for development of resistance in otitis media are antimicrobial use, young age, day-care attendance and prior hospitalization. The increasing rate of resistance to antibiotic drugs is associated with a decreased rate of successful eradication of pathogens from middle ear fluid, which is associated with clinical failure. A bacteriologic cure rate of 80 to 85% is observed for S. pneumoniae and nontypable H. influenzae when serum concentrations exceed the MIC for 40 to 50% of dosing interval. Comparative trials indicate that some of the beta-lactams can achieve bacteriologic eradication in acute otitis media, although major differences in outcome exist among agents based on pathogen, beta-lactamase status and MIC values. ANTIBIOTIC CHOICE: Overall the choice of antibiotics for treatment of otitis media should take into consideration their in vitro activity against the locally prevalent organisms, especially resistant organisms, and results obtained from studies in which bacteriologic outcome was used as the endpoint.

Anti-Bacterial Agents↗
PubMed2000

Bacteriologic and clinical efficacy of one day vs. three day intramuscular ceftriaxone for treatment of nonresponsive acute otitis media in children.

BACKGROUND: One dose of intramuscular ceftriaxone has been recently licensed in the United States for the treatment of acute otitis media. However, data regarding the bacteriologic and clinical efficacy of this regimen in the treatment of nonresponsive acute otitis media are incomplete. OBJECTIVES: To determine the bacteriologic and clinical efficacy of a 1-day 50-mg/kg vs. a 3-day 50-mg/kg/day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media in children. PATIENTS AND METHODS: In an open, prospective study 109 patients ages 3 to 36 months with culture-proved, nonresponsive acute otitis media were randomized to receive 1 (n = 49) or 3 (n = 60) 50-mg/kg/day intramuscular ceftriaxone doses, respectively. Middle ear fluid was aspirated for culture by tympanocentesis on the day of enrollment (Day 1); a second tympanocentesis with middle ear fluid culture was performed on Days 4 to 5. Additional middle ear fluid cultures were obtained if clinical relapse occurred after completion of therapy. Bacteriologic failure was defined by positive cultures on Days 4 to 5. Patients were followed until Day 28 after completion of therapy. Susceptibility of the middle ear pathogens was measured by E-test. RESULTS: Organisms recovered (n = 133) were Streptococcus pneumoniae (30 and 35 isolates for the 1-day and 3-day treatment group, respectively), Haemophilus influenzae (26 and 38, respectively) and Moraxella catarrhalis (n = 4). Of the 30 S. pneumoniae isolated from the 1-day group, 27 (90%) and 6 (20%) were nonsusceptible to penicillin and ceftriaxone, respectively; 9 of 27 (33%) were fully resistant to penicillin. Thirty-four (97%) and 6 (17%) of the 35 S. pneumoniae isolated from the 3-day group were nonsusceptible to penicillin and ceftriaxone, respectively; 16 of 34 (47%) were fully resistant to penicillin. Bacterial eradication of all H. influenzae and penicillin-susceptible S. pneumoniae was achieved in both treatment groups. Bacterial eradication of 14 of 27 (52%) and 33 of 34 (97%) penicillin-nonsusceptible S. pneumoniae was achieved in the 1-day and 3-day group, respectively. Seven (50%) of the 14 patients from the 2 groups who did not achieve bacterial eradication did not improve clinically on Days 4 to 5 and required additional ceftriaxone treatment. CONCLUSION: The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media caused by penicillin-resistant S. pneumoniae.

Acute Disease↗
PubMed2000

Immunization against hepatitis A in the first year of life: priming despite the presence of maternal antibody.

BACKGROUND: Maternal antibodies interfere with hepatitis A vaccination in young infants. We examined the response to a high dose hepatitis A vaccine administered concomitantly with a combination of diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus vaccine/Haemophilus influenzae type b vaccine to initially seropositive vs. initially seronegative infants. METHODS: Three hundred subjects were originally planned to be enrolled at age 6 to 10 weeks and received hepatitis A vaccine (formalin-inactivated vaccine, SB-Bio, 720 enzyme-linked immunosorbent assay units) at 2, 4 and 6 months concomitantly with a diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus vaccine/H. influenzae type b vaccine. Children initially seropositive received a booster dose at 12 months of age. An additional 100 twelve-month-old infants previously not vaccinated with hepatitis A vaccine were given 1 dose, to observe the primary response at that age. Reactogenicity was recorded on diary cards for the 3 subsequent days. Immunogenicity was measured at Months 2, 4, 5, 10 and 11 after administration of the first vaccine dose. For the subjects enrolled at 12 months, blood was drawn before and 1 month after the first vaccination. RESULTS: Of 297 initially enrolled infants 36% were seronegative before vaccination (Group A). The geometric mean concentration (GMC) (milli-International Units/ml) of the seropositive infants (Group B) before immunization was 2587. The GMCs of Group A infants 1 month after each dose and at 12 months of age were 93, 518, 1656 and 786, respectively. For Group B infants, the respective GMCs were 1165, 460, 508 and 167. One hundred subjects of Group B received a booster dose at age 12 months; at Month 13 all were seropositive with a GMC of 1902. For comparison, a third group of 100 not previously immunized 12-month-old infants (Group C) were enrolled and received 1 dose of hepatitis A vaccine with pre- and postimmunization GMCs of 52 and 120, respectively. CONCLUSIONS: Our results suggest that the initially seropositive infants were primed despite maternal antibody interference. The hepatitis A vaccine was well-tolerated in this population of young infants.

Female↗
PubMed2000

Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children.

BACKGROUND: Acute invasive diarrhea is a potentially serious condition in children. Because of the increasing resistance of enteric pathogens to commonly used oral antibiotics, intramuscular ceftriaxone has become the routine drug in the treatment of acute invasive diarrhea requiring an emergency visit in southern Israel. The inconvenience of this parenteral regimen created an increased need for oral pediatric formulations for the treatment of invasive diarrhea. OBJECTIVES: To evaluate the efficacy and safety of a suspension formulation of ciprofloxacin in the treatment of acute invasive diarrhea in infants and children. PATIENTS AND METHODS: From July 1996 through December 1997, 201 evaluable children ages 6 months to 10 years (35% <1 year; 70% <3 years) presenting with acute invasive diarrhea at the Pediatric Emergency Room were randomized to receive either ciprofloxacin suspension (10 mg/kg twice a day + im placebo; n = 95) or im ceftriaxone (50 mg/kg/day + placebo suspension; n = 106) for 3 days in a double blind manner. Stool cultures for Shigella, Salmonella, Campylobacter spp. and diarrheagenic Escherichia coli were obtained on Days 1, 3, 4 to 5 and 21 +/- 5. Clinical response and safety were assessed on Days 1, 2, 3, 4 to 5 and 21 +/- 5. RESULTS: We isolated 127 pathogens from 121 (60%) patients: 73 (57%) Shigella; 23 (18%) Salmonella; 18 (14%) E. coli; and 13 (10%) Campylobacter. Overall bacteriologic eradication on Day 4 to 5 was 99% for Shigella, 77% for Salmonella and 77% for Campylobacter, with no difference between the 2 groups. Clinical cure or improvement was observed in 100 and 99% of the ciprofloxacin and ceftriaxone groups, respectively. Serum ciprofloxacin values determined on Day 3 of the treatment were higher in the majority of patients than were the MIC50 and MIC90 values for the Shigella and Salmonella spp. isolated. Possible drug-related adverse events occurred in 13 patients [ciprofloxacin, 8 (8%); ceftriaxone, 5 (4.7%)] and were mild and transient. Joint examination was normal during and after completion of therapy in all patients. CONCLUSION: Oral ciprofloxacin was as safe and effective as intramuscular ceftriaxone for the empiric treatment of acute invasive diarrhea in ambulatory pediatric patients requiring an emergency room visit.

Acute Disease↗
PubMed2000

Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children.

A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for H. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae.

Acute Disease↗