Summaryobjective To investigate antibiotic use and antibiotic susceptibility of respiratory tract pathogens in children aged 1-5 years in Bavi, Vietnam.method Nasopharynx and throat specimens were collected from 200 children from randomly selected households in a demographically defined population. Respiratory isolates were tested for antibiotic susceptibility according to the standard disk diffusion method. A questionnaire survey of carers elicited information on type of antibiotic used, duration of treatment, where the antibiotics had been purchased, type of treatment information retained by carers and episodes of illness preceding the study.results 82% of the children had at least one symptom of acute respiratory tract infection (ARI) in the 4 weeks prior to the study, and of these 91% were treated with antibiotics. The most commonly used antibiotics were ampicillin (74%), penicillin (12%), amoxicillin (11%), erythromycin (5%), tetracycline (4%) and streptomycin (2%). Ampicillin was used for 3.3 days on average (SD:1.8) and penicillin for 2.6 days (SD:0.7). When deciding which antibiotic to use, 67% of the carers consulted the pharmacy seller, 11% decided themselves and 22% followed the doctor's prescription. The carrier rate of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis was 50%, 39% and 17%, respectively. Isolates from 145 children were susceptibility tested, and 74% were found to carry resistant pathogens. Of the tested isolates, 90% of S. pneumoniae, 68% of H. influenzae and 74% of M. catarrhalis were resistant to at least one antibiotic. The mean number of antibiotics (susceptible strains excluded) to which resistance was found was 2.0 (SD:1.2), 2.5 (SD:1.8) and 2.1 (SD:0.9), respectively. S. pneumoniae and H. influenzae showed high resistance to tetracycline (88% and 32%, respectively), trimethoprim/sulphonamide (32% and 44%), and chloramphenicol (25% and 24%). 23% of S. pneumoniae were erythromycin-resistant and 18% of H. influenzae isolates were resistant to ampicillin. There was a significant difference in ampicillin and penicillin resistance between the group of children previously treated with beta lactam antibiotics and the group of children who did not receive antibiotics.conclusion As reported by the carers, children in Bavi are treated with antibiotics frequently. Most antibiotics were obtained without consulting a doctor. High levels of antibiotic resistance and high prevalence of multidrug-resistant strains were found among respiratory pathogens. The existence of a large reservoir of resistance genes among children in low-income countries represents a threat to the success of antibiotic therapy throughout the world. Multi-faceted programmes to improve rational use of antibiotics in Vietnam are urgently needed.
Combinations of gentamicin with cefotaxime, moxalactam, and ceftazidime were tested against 43 bacterial strains, most of them blood isolates. With an interaction index of 0.5 as borderline, synergism was demonstrated against 30 to 40% of the strains by the fractional inhibitory concentration index and against 50 to 70% by the fractional bactericidal concentration index. The reproducibility of the index was within ±0.2 for two-thirds of 40 repetitive assays and within ±0.4 to 0.5 for all of these assays. Similar results were obtained when netilmicin was substituted for gentamicin. The killing curve system for studying antibiotic synergism was standardized to give results comparable to those obtained with the interaction index. This was achieved when one-half of a previously determined minimum bactericidal concentration was used for single drugs and the amount of antibiotic was at least halved again when drugs were used in combination. An initial bacterial concentration of 105 to 106 colony-forming units per ml is recommended. Given these conditions, synergism could be defined as a 2-log10 or more decrease in viable count given by both drugs together, as compared with the more active of the pair after 24 h. Prediction of killing curve results could then be obtained with the fractional bactericidal concentration index. When cephalosporins and gentamicin were combined from the start, the beta-lactam antibiotics were less susceptible to inactivation, as demonstrated in time-killing assays. If one of the antibiotics were added after 24 h, synergism was not demonstrable. The results indicate that the new cephalosporins may be advantageously combined with aminoglycosides.
A total of 188 strains representing 11 species of gram-negative bacteria were examined for the ability to interact with human plasminogen. Highly purified human plasminogen was labeled with 125I, and its uptake by different bacterial strains was measured. All 14 strains of Haemophilus influenzae and all 13 strains of Branhamella catarrhalis tested were positive with respect to plasminogen uptake. Also, eight species belonging to the family Enterobacteriaceae were tested, and of those, Proteus mirabilis demonstrated the most substantial uptake, with 28 of 39 strains taking up more than 10% of the plasminogen. Ten strains of Pseudomonas aeruginosa were also tested, of which seven showed uptake values higher than 10%. With H. influenzae and B. catarrhalis strains, Scatchard analysis indicated a two-phase receptor interaction, one more-avid receptor with a Kd of 6 to 8 nM and 2,000 to 2,500 sites per bacterium and a second receptor with a Kd of 50 to 80 nM and 9,000 sites per bacterium. With Pseudomonas aeruginosa strains, a single receptor interaction was detected with a Kd of 60 nM and the number of sites was estimated as 8,000 per bacterium. Scatchard analysis with strains of P. mirabilis indicated binding of a less-specific nature. However, plasminogen uptake by this species could be reduced by 50% by the addition of 2 mM unlabeled plasminogen. This estimate of Kd, as well as uptake studies with plasminogen fragments, suggests different properties of this receptor. With all receptor types, the addition of plasmin-aprotinin complex inhibited plasminogen uptake, which demonstrates that both forms of the molecule react with the same receptors. Plasminogen uptake could be eliminated by the addition of lysine or epsilon-aminocaproic acid, which suggests that the lysine-binding sites of the plasminogen molecule are involved in the receptor-ligand interaction.
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