Trimethoprim-sulfamethoxazole Versus Azithromycin for the Treatment of Undifferentiated Febrile Illness in Nepal: A Double-blind, Randomized, Placebo-controlled Trial.

BACKGROUND: Azithromycin and trimethoprim-sulfamethoxazole (SXT) are widely used to treat undifferentiated febrile illness (UFI). We hypothesized that azithromycin is superior to SXT for UFI treatment, but the drugs are noninferior to each other for culture-confirmed enteric fever treatment. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of azithromycin (20 mg/kg/day) or SXT (trimethoprim 10 mg/kg/day plus sulfamethoxazole 50 mg/kg/day) orally for 7 days for UFI treatment in Nepal. We enrolled patients >2 years and <65 years of age presenting to 2 Kathmandu hospitals with temperature ≥38.0°C for ≥4 days without localizing signs. The primary endpoint was fever clearance time (FCT); secondary endpoints were treatment failure and adverse events. RESULTS: From June 2016 to May 2019, we randomized 326 participants (163 in each arm); 87 (26.7%) had blood culture-confirmed enteric fever. In all participants, the median FCT was 2.7 days (95% confidence interval [CI], 2.6-3.3 days) in the SXT arm and 2.1 days (95% CI, 1.6-3.2 days) in the azithromycin arm (hazard ratio [HR], 1.25 [95% CI, .99-1.58]; P = .059). The HR of treatment failures by 28 days between azithromycin and SXT was 0.62 (95% CI, .37-1.05; P = .073). Planned subgroup analysis showed that azithromycin resulted in faster FCT in those with sterile blood cultures and fewer relapses in culture-confirmed enteric fever. Nausea, vomiting, constipation, and headache were more common in the SXT arm. CONCLUSIONS: Despite similar FCT and treatment failure in the 2 arms, significantly fewer complications and relapses make azithromycin a better choice for empirical treatment of UFI in Nepal. CLINICAL TRIALS REGISTRATION: NCT02773407.

A Comparative Study of Raja Isteri Pengiran Anak Saleha and Alvarado Scores to Diagnose Acute Appendicitis.

BACKGROUND: Acute Appendicitis is a clinical diagnosis with atypical presentation in young, elderly, females, genitourinary and gynecological conditions. Delayed appendectomy increases the risk of appendicular perforation, sepsis morbidity and mortality. Literature reports as high as 20-40% negative appendectomy. Raja Isteri Pengiran Anak Saleha score has come with higher sensitivity and diagnostic accuracy than Alvarado score in Asian population. This study aims to compare RIPASA and Alvarado score for diagnostic accuracy. METHODS: Appendectomy patients at Patan Hospital from April to September 2014 were compared on raja isteri pengiran anak saleha (cut-off value 7.5 out of 15) and Alvarado score (cut-off value 7 out of 10). Final diagnosis was histopathology based. Microsoft Excel and SPSS 17 were used for analysing sensitivity, specificity and diagnostic accuracy of both scores. The study included patients who underwent appendectomy with histopathology report and excluded those with conservative management, generalized peritonitis, appendicular lump and abscess. RESULTS: There were 88 appendectomy patients with median age 26 (18.25, 35) years, and male 52 (59.1%). Negative appendectomy was 10 (11.36%). Sensitivity and specificity of Raja Isteri Pengiran Anak Saleha 98.71% and 80.00% respectively, and for Alvarado 52.56% and 70%.The Raja Isteri Pengiran Anak Saleha score had statistically significant sensitivity (p=0.000). Positive Predictive value, Negative Predictive Value and diagnostic accuracy were 97.46%, 88.89% and 96.6% for RIPASA and 93.18%, 15.19% and 54.4% for Alvarado respectively. CONCLUSIONS: The Raja Isteri Pengiran Anak Saleha score had better diagnostic accuracy compared to Alvarado score for diagnosis of Acute Appendicitis.