Comparison of piperacillin vs. ticarcillin plus tobramycin in the treatment of acute pulmonary exacerbations of cystic fibrosis.

During a 22-month period 35 children with cystic fibrosis received 52 courses of antibiotic therapy for acute pulmonary exacerbations, including 26 cases of therapy with piperacillin and 26 courses with ticarcillin plus tobramycin. Groups were similar in age (5 vs. 5.4 years), disease severity based on Schwachman scores and presenting symptoms. Pseudomonas aeruginosa was the most common organism isolated in 90% of sputum cultures. Mean minimal inhibitory concentrations for piperacillin, ticarcillin and tobramycin were 8, 64 and 1 microgram/ml, respectively. Piperacillin pharmacokinetic data revealed an average half-life in serum of 36 minutes. Peak serum concentrations averaged 144 micrograms/ml, and after 4 hours serum concentrations continued to exceed the P. aeruginosa 90% minimal inhibitory concentration in 50% of children. The dosage requirement for tobramycin was quite variable, necessitated monitoring of aminoglycoside serum concentrations and in most cases resulted in at least one dosage adjustment. Emergence of resistant bacteria was not seen in 26 courses of piperacillin therapy. Both regimens were effective and well-tolerated. Single agent therapy has the advantage of providing reliable serum concentrations and, in contrast to the standard therapy, does not necessitate monitoring of serum drug concentrations.

Effects of cystic fibrosis serum on calcium influx and secretion using isolated tracheal epithelial cells.

Hamster trachea epithelial (HTE) cells were shown to respond to 20% cystic fibrosis serum (CFS) by secreting twice as much protein as in the presence of 20% normal human serum (NHS). Serum from obligate heterozygotes (HHS) produced an intermediate effect. A peak of Ca2+ entry into the HTE cells occurred about 30 min after exposure to 20% CFS, followed by a slow decline to basal levels. In contrast, 20% NHS did not cause an influx of Ca2+ and HHS produced an influx to about half that of CFS. Increasing concentrations (5-30%) of pooled NHS had no effect on HTE cell Ca2+ uptake or secretion, but pooled CFS and HHS caused progressive increases in Ca2+ influx and protein secretion from 10 to 25% sera. The CFS-induced Ca2+ influx and secretion were about twice those of HHS throughout the range of serum concentrations tested, suggesting the presence of a modulatory influence in HHS. When EGTA was used to chelate extracellular Ca2+ in the presence of CFS, Ca2+ influx was prevented and there was no stimulation of secretion. Ionophore A23187 allowed Ca2+ entry into HTE cells in the presence or absence of serum and a heightened level of secretory activity followed. The time course of Ca2+ influx under the influence of CFS was shown to correspond to the efflux of Na+ from the cells. Also verapamil, a Ca2+ channel blocking agent, inhibited CFS-induced Ca2+ influx by 50% at 10(-5)M and prevented secretion. Thus, it appears that CFS, but not NHS, contains an agent which stimulates Ca2+ uptake into HTE cells by means of a Ca2+ channel and/or Na+-Ca2+ exchange mechanism, and that increased intracellular Ca2+ levels then trigger secretion. The intermediate HTE cell response to HHS suggests that half of the CFS stimulatory agent is present as would be expected in a gene dose effect, lending support for a genetic basis for CF.

Leakage of radioactive particle systems from a synovial joint studied with a gamma camera. Its application to radiation synovectomy.

UNLABELLED: We have determined rates of leakage of radioactivity from a rabbit synovial pouch in vivo for a number of particle systems of varying sizes and differing resistance to degradation. The estimates were made using a gamma scintillation camera and without killing the test animals. The lowest leakage at twenty-four hours was seen with inert carbonized microspheres and the highest rates were seen with surface-labeled particles of biodegradable denatured human serum albumin and with erythrocytes. The carbonized microspheres had no adverse long-term effects on the health of the animals' articular cartilage. CLINICAL RELEVANCE: Results obtained with inert particles indicate that reducing the biodegradability of the particle or increasing its diameter, or both, reduces radioactivity losses from the knee joint. Large (twenty-five-micrometer-diameter) microspheres of human serum albumin incorporating the radioactivity and carbonized microspheres are suggested as potential carriers of isotopes for human radiation synovectomy.

Acute pulmonary exacerbations in cystic fibrosis. A double-blind trial of tobramycin and placebo therapy.

To determine the effect of antimicrobial therapy on acute pulmonary exacerbations in cystic fibrosis, a randomized, double-blind trial of tobramycin and placebo was carried out. Clinical responses were satisfactory in all 11 children given tobramycin and in seven of 11 given placebo. Two patients in the placebo group died. No patient given placebo had improved results on pulmonary function studies, whereas improvement of 15% or more occurred in four of the six patients given tobramycin who could cooperate with the testing. Quantitative cultures of sputum showed a decrease of 1 logarithm or greater in Pseudomonas sp concentrations in six of seven patients in the tobramycin group and in two of eight in the placebo group. No difference in staphylococcal colonization was found. Several features indicate that children with severer disease were randomly assigned to the placebo group; nevertheless, the trend toward improved response in patients given tobramycin suggests that empirical therapy with antibiotics is beneficial for patients with acute pulmonary exacerbations in cystic fibrosis.