PubMed · 6252176
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H Knothe. 1980. Sensitivity testing and synergy.. https://doi.org/10.1093/jac%2F6.suppl_a.31
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A combination of esterase electrophoretic typing and analysis of the restriction fragment length polymorphism of ribosomal DNA regions (ribotyping) was used to compare 27 Pseudomonas aeruginosa strains isolated before and after two-week courses of anti-pseudomonal treatment in seven cystic fibrosis patients. A total of 12 courses of therapy were studied in which ciprofloxacin, ceftazidime, azlocillin or imipenem were used alone or in combination with tobramycin. Isolates at a count of greater than or equal to 10(6) cfu/ml of sputum were collected when there was evidence of therapeutic failure on the basis of persistence of isolates whether or not they were resistant to the antibiotic used for therapy. Emergence of resistance was observed in ten cases and failure to eradicate sensitive strains in five cases. Among the 27 isolates, eight zymotypes and five ribotypes were identified. With this typing approach, resistant post-therapy isolates were found to be identical to pre-therapy isolates in all cases but one. However, in one case an additional resistant strain was isolated after therapy besides that initially present. In all five cases in which susceptibility was still observed after treatment, pre-therapy and post-therapy isolates were indistinguishable. Using this molecular typing approach, all the strains were typable. Thus combination of esterase typing and ribotyping should improve the analysis of therapeutic failure in cystic fibrosis patients.
BACKGROUND: In-vitro and clinical efficacy of a combination therapy consisting of 3 antibiotic agents was to be assessed in neonatal septicemia. METHODS: From 1980 to 1987, 152 newborns with septicemia as proven by blood culture were treated with an initial antibiotic regimen consisting of azlocillin (150 mg/kg bw), cefotaxime (100 mg/kg bw), and tobramycin (5 mg/kg bw). RESULTS: According to the microbiologic testing, antimicrobic therapy was effective in each of the 152 organisms: 101/152 bacteria were susceptible to all 3 agents; resistance to 1 or 2 of the antibiotics was evident in 33/152 and in 18/152 organisms, respectively. Mortality due to septicemia was 7.2%. CONCLUSION: As no difference was observed in the frequency in which one of the three antibiotic substances was the only effective drug, each of the 3 agents seemed to be necessary for clinical effectiveness of this antibiotic combination.
The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa.