PubMed · 9625642
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J R Johnson. 1998-06-11. A computer-assisted management program for antiinfective agents.. https://pubmed.ncbi.nlm.nih.gov/9625642/
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BACKGROUND: Dapsone is commonly used for pneumocystis carinii pneumonia (PCP) prophylaxis in immunocompromised patients. Methemoglobinemia is a known complication of dapsone, but its true frequency and pathogenesis in childhood cancer patients are unknown. Additionally, practice guidelines for evaluation and management of dapsone-induced methemoglobinemia are not available. PROCEDURE: We studied 15 children with acute lymphoblastic leukemia (ALL) receiving dapsone for PCP prophylaxis to determine the frequency of methemoglobinemia, and correlate its occurrence with cytochrome b5 reductase (Cb5R) enzyme levels. Ten children with ALL receiving trimethoprim-sulfamethaxazole (TMP-SMX) were studied as controls. All patients underwent physical examination, pulse oximetry, and methemoglobin (metHb) estimation. Commercially available assay was used to measure Cb5R levels. RESULTS: Three (20%) patients receiving dapsone developed symptomatic methemoglobinemia. Average duration of dapsone prophylaxis prior to diagnosis was 6.6 weeks (range 3.5-10 weeks). Mean metHb level in symptomatic patients was 11.67%; 95% confidence interval (CI) 0-25.79 (range 7-18%), and 1.37%; 95% CI 0.6-2.14 (range 0.02-3%) in asymptomatic patients (P = 0.09), whereas the mean metHb level in the control group was 0.54%; 95% CI 0.35-0.73 (range 0.1-0.8%) (asymptomatic vs control P < 0.0001). Mean Cb5R level in symptomatic patients was 8.6 IU/g Hb; 95% CI 3.4-13.7 (range 6.9-10.9) compared to 12.5 IU/g Hb; 95% CI 11.1-13.9 (range 10.8-14.6) in asymptomatic patients (P = 0.06). Two symptomatic patients had Cb5R levels at or below 50% of normal, consistent with heterozygosity. Parental studies for Cb5R levels were suggestive of a carrier state in one of each patient's parents. CONCLUSIONS: Heterozygosity for Cb5R deficiency may pre-dispose to methemoglobinemia even on a thrice-weekly regimen of dapsone. Such individuals should avoid subsequent exposure to oxidant agents, if possible. Children with ALL tend to be symptomatic at low levels of metHb and may have delayed detection of methemoglobinemia. Hence, frequent monitoring of patients receiving dapsone is recommended. Monitoring guidelines for dapsone prophylaxis are proposed.
Tylosin is a macrolide antibiotic commonly used for therapeutic treatment and prophylaxis in livestock. As part of a larger ecotoxicological study, the potential phytotoxic effects of tylosin on the rooted macrophyte Myriophyllum spicatum and the floating macrophyte Lemna gibba were assessed under semi-field conditions using 15 12 000-L microcosms. Concentrations of 0, 10, 30, 300 microg/L (n = 3), and 600, 1000, and 3000 microg/L (n = 1) were evaluated as part of separate ANOVA and regression analyses over an exposure period of 35 days. Fate of tylosin was monitored over time in the highest three treatments, where dissipation followed pseudo-first order kinetics with associated half-lives ranging from 9 to 10 days. For both M. spicatum and L. gibba, tylosin was found to cause no biologically significant changes to any endpoint assessed compared to controls at a Type I error rate of 0.1. However, subsequent power analyses revealed that there was generally insufficient power to declare that there were no significant differences at a Type II error rate of 0.2. Conclusions concerning biologically significant impacts were therefore further assessed based on other statistical criteria including comparisons of percent differences between replicated treatments and controls, minimum significant and minimum detectable differences, and coefficients of variation. Based on these criteria, at an ecological effect size of >20% change, tylosin was concluded to elicit no biologically or ecologically significant toxicity to M. spicatum or L. gibba. A hazard quotient assessment indicated that tylosin poses little risk to either species of macrophyte, with an HQ value calculated to be nearly three orders of magnitude below 1 (0.002).
Cefdinir is an oral cephalosporin approved by the US Food and Drug Administration in 1997 for the treatment of community-acquired (CA) respiratory tract and uncomplicated skin and soft tissue infections. The objective of the present study was to evaluate the in vitro activity of cefdinir against recent clinical isolates collected from CA-urinary tract infections (UTIs), a possible expanded indication. A total of 456 isolates from CA-UTI were collected from medical centres in North America (NA; United States and Canada) in 2003 and susceptibility tested by NCCLS reference broth microdilution methods. Cefdinir and cefpodoxime were the most active compounds tested against Escherichia coli (98.7% susceptibility), followed by nitrofurantoin (97.0%) and ciprofloxacin (95.0%). Cefdinir was 8- to 16-fold more potent than cefuroxime axetil and cefprozil against E. coli, Klebsiella spp. and Staphylococcus saprophyticus. The activity of cefdinir was most similar to that of cefpodoxime against E. coli and Klebsiella spp., but cefpodoxime showed inferior activity against S. saprophyticus. The cefdinir spectrum was significant superior (+3.8 to 16.5%) to that of trimethoprim/sulphamethoxazole against all pathogens evaluated. The cefdinir spectrum and potency were comparable or superior to other orally administered beta-lactams tested against recent (2003) clinical isolates from CA-UTI.