Ceftazidime stability and pyridine toxicity during continuous i.v. infusion.

PURPOSE: This article reviews the literature concerning ceftazidime stability and potential for toxicity from pyridine (a degradation product) in the light of decades of apparent safe use of this antibiotic when given by continuous i.v. infusion but recent changes in regulatory body/manufacturer advise a need to change infusion devices more frequently. SUMMARY: In the outpatient setting, ceftazidime is ideally administered by continuous i.v. infusion because of its short half-life and lack of post-antibiotic effect. While continuous i.v. infusion provides the optimal pharmacokinetic/pharmacodynamic profile, the frequency with which infusion devices need to be changed is critical to the practicality in the outpatient setting, especially where trained staff are required to visit the patient in their home to change the device. The rate of ceftazidime degradation (and pyridine formation) is temperature, concentration, and solvent dependent. By using the lowest effective dose (guided by pathogen minimum inhibitory concentration [MIC] so as to achieve a blood concentration ≥ 4 × MIC over the whole dosage interval), keeping ceftazidime concentration ≤ 3%, using 0.9% sodium chloride injection as diluent and maintaining temperature between 15-25°C when connected to the patient, the amount of pyridine formed over a 24-hour period can be minimized and toxicity prevented. When pathogen MIC dictates that > 6 g ceftazidime/day is required, alternative antibiotics should be considered and/or greater attention paid to temperature and concentration of the infusion solution. CONCLUSION: Ceftazidime can be used safely and effectively via continuous i.v. infusion in the outpatient setting with once-daily changes of infusion device provided the concentration and temperature of the infusion solution is controlled. In this way, more frequent changes of infusion device (that increase the risk of blood-borne infection and reduce the practicality of continuous i.v. infusion in the home) can be avoided.

Gamma-ray-induced dominant mutations that cause skeletal abnormalities in mice. II. Description of proved mutations.

In a mutation-rate experiment described earlier, 31 dominant skeletal mutations were confirmed by breeding tests. Skeletal abnormalities were detected in the skeletons of some of the sons of irradiated males, and for 31 of these sons the study of skeletons in subsequent generations showed that they transmitted abnormalities. The detailed descriptions of these mutations, together with descriptions of 6 presumed mutations found in a later paper, provide the basis for determining which mutations cause effects that would, if they occurred in humans, cause a serious handicap. Such a determination is necessary before these data can be used to estimate genetic hazard to humans. Furthermore, these descriptions of syndromes caused by individual dominant mutations should be useful to clinicians interested in skeletal defects. The statistical analysis of the frequency of each abnormality in the mutant line versus an approximation of the frequency of the malformation in the absence of new mutations is essential to be sure that a mutation is indeed the cause of each abnormality. These analyses, together with analyses of the correlation of abnormalities caused by individual mutations, clearly demonstrate that dominant mutations exhibit low penetrance for many of their effects. A few of the mutations also cause the death of some heterozygotes. No externally visible effects have been detected in heterozygotes for most of these mutations. Externally visible effects found in some of the heterozygotes for a few of the mutations include hydrocephalus, circling behavior, increased nervous activity, gray coat color, webbing of digits, and small size. Two coat-color mutations were found that caused no detected skeletal abnormalities. The data suggest that a few of the mutations may be reciprocal translocations. In most of the mutant lines tested cytologically, however, there was no indication of chromosomal aberrations.