99mTc‐Ceftizoxime in diagnosis of diabetic foot osteomyelitis: More evidences are needed

Abstract

Dear Editor, With interest, we read the article ‘Tc-Ceftizoxime: Synthesis, characterization and its use in diagnosis of diabetic foot osteomyelitis’ by Ahmed et al. The authors evaluated the results of Tc-Ceftizoxime (Tc-CFT) scans of five patients of known type II diabetes mellitus suspected of diabetic foot osteomyelitis. The use of Tc-CFT in diagnosis was excellently described and the article is an eye-opener for the readers. However, there are still some topics we would like to debate. To start with, the authors only included five patients and the limited number could influence the accuracy of diagnosis. When designing diagnostic test studies, sample size calculations should be performed in order to guarantee the design accuracy and are needed for estimation of adequate sensitivity/specificity. Ahmed et al. demonstrated that the radiolabelled leucocytes were considered as a gold standard for the identification of infective foci in the intestine, bone tissue and for peripheral bone osteomyelitis including diabetic foot patients. However, the radiolabelled leucocytes was not applied to diagnosis in the study and Tc-CFT scans were interpreted as true or false positive and true or false negative based on bone histopathology/culture or/ and clinical follow-up. In addition, we found no explicit details of bone histopathology/culture or/and clinical follow-up in the study. To further evaluate the test characteristics of TcCFT, we provided an estimate of diagnostic sensitivity, specificity and 95% confidence interval (CI) by Stata 12.1 (StataCorp LP, College Station, TX, USA). The results of diagnosis are shown in a fourfold table (Table 1). Infectious bone histology and microbiological examination was used as the gold standard according to 2012 infectious diseases society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. We calculated the sensitivity of the Tc-CFT was estimated to be 1.00 (95% CI, 0.29–1.00) and the specificity was 1.00 (95% CI, 0.16–1.00). The wide CIs showed the diagnosis was lack of precision which may be limited by the small sample size. We also have questions about the clinical application of Tc-CFT. Firstly, the authors reported that no sign of toxicity was observed in the animal model and radiopharmaceutical was considered safe for use in humans. However, 17.40% of Tc-ceftizoxime was localized in foci of infection, 2.64% in lungs, 7.06% in liver and 4.30% was excreted through kidney when Tc-CFT was injected to animal model (infected) after 60 minutes. In this case, we think the safety of Tc-CFT application and its influence on organs needs further studies. Secondly, Tc-CFT was time-consuming in practical use. All patients underwent three and two phase Tc-MDP bone scan and Tc-CFT scan. Time interval between two scan was 4 days. In addition, injected dose was still with mild retention in liver and excreted through kidney at 3 hours. Thirdly, preparation of Tc-CFT is laborious and requires specialized equipment and skills. This antibiotic is sensitive to light, soluble in water, stable at high temperatures and with a stability of only 6 hours after the labelling process, which means rigorous preparation requirement.