PubMed · 66493
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H Pratt. 1977-03-26. Research on infants.. https://doi.org/10.1016/s0140-6736(77)92134-1
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OBJECTIVE: To investigate the impact of the introduction of a consultative service on the use, efficiency of dosing and clinical toxicology of the aminoglycoside antibiotics, gentamicin and tobramycin, in a general hospital. METHODS: Two audits were conducted six months and 18 months after the introduction of the consultative service. The audits reviewed the use of drug assay services, the adequacy of drug administration (as measured by serum antibiotic concentrations), indications for prescription, adverse outcomes (by noting markers of nephrotoxicity) and the antibiotic sensitivity of Gram-negative pathogens. The results were compared with the results of an audit conducted before the consultative service was instituted. RESULTS: There was a significant (P < 0.001 by chi 2 test) increase in the use of assays, with drug assays performed in 67% (first audit) and 77% (second audit) of aminoglycoside courses compared with 48.2% in the pre-intervention audit. Sample timing was greatly improved, with more than 70% of the samples collected at the appropriate times. Assay wastage in terms of uninterpretable assay results decreased significantly (P < 0.001) from 42.9% of total assays to 6.3% at the first audit and 3.8% at the second audit. The percentage of assay results in the desirable range increased significantly (P < 0.001) from 39.1% to 71.9% (first audit) and 75.4% (second audit). Pharmacokinetic recommendations were made in 39.1% and 64% of all aminoglycoside courses during the first and second audits respectively, with clinician acceptance of dosage recommendations at 83.1% and 82.8% respectively. For aminoglycoside courses prescribed for therapeutic reasons, 97.9% (first audit, n = 325) and 98.6% (second audit, n = 280) of indications for use were judged as clinically appropriate. The incidence of suspected aminoglycoside-induced nephrotoxicity was reduced from 8.9% of patients to 1.6% (first audit, P < 0.001) and 2.4% (second audit). Bacterial sensitivity audits showed that the great majority of clinical isolates of target organisms (n = 3523, Year 1 and n = 3385, Year 2) were sensitive to gentamicin (92.2% and 91.5% respectively) and tobramycin (98.1% and 98.8% respectively); these aminoglycosides exceeded all alternative agents in effectiveness, including first and third generation cephalosporins. CONCLUSIONS: The overall results indicate that introduction of the consultative service had a positive impact on the effective use of aminoglycosides, with a marked decrease in clinical toxicity. These influences were shown to persist for at least 18 months. The availability of reliable predictive techniques to reduce toxicity allows active promotion of aminoglycosides as the agents of choice on grounds of efficacy and economy.
Blood sampling on filter paper has many advantages for the detection of perinatal human immunodeficiency virus (HIV) infection by the polymerase chain reaction (PCR). However, if the method is to be widely used, an assessment of its performance under field conditions is required. To simulate conditions in the field, 50-microliters aliquots of whole blood containing low levels of HIV proviral DNA (4 to 1,024 copies per 100,000 nucleated cells) were spotted onto filter paper; dried; and subjected to heat, humidity, and prolonged storage at room temperature. After exposure, the DNA was recovered and amplified with primers to human leukocyte antigen DQ alpha- and HIV-specific sequences. Treatment at 37 degrees C and 60% humidity for 7 days, storage for 12 weeks at 22 degrees C, and freeze-thawing twice had no adverse effect on PCR reactivity when compared with the results obtained with reference spots stored at -20 degrees C. The lower limits of HIV detection in all tests ranged from 4 to 16 HIV copies per 100,000 cells. Fixation in 70% ethanol improved the amplification of low levels of HIV DNA and reduced biohazard risks. These findings suggest that dried blood spots will provide a powerful new resource for testing for HIV by PCR, especially in remote areas where refrigeration and immediate sample processing are unavailable.