Key Points Question How is natural variation in cytochrome P450 2D6 activity associated with therapeutic efficacy of primaquine phosphate against latent Plasmodium vivax malaria? Findings In this nested case-control study of 57 patients who had participated in a clinical trial of primaquine for radical cure of acute P vivax malaria, exposure to low levels of cytochrome P450 2D6 activity determined by genotype or measured by dextromethorphan metabolism phenotype was associated with a significantly increased likelihood of relapse of malaria in the year after directly observed high-dose primaquine therapy. Meaning Impaired cytochrome P450 2D6 activity was significantly associated with high risk of therapeutic failure of primaquine, and this finding suggests cytochrome P450 2D6 involvement in producing a therapeutically active metabolite.

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in China, has become a pandemic in March 2020. Repurposing old and relatively safe drugs becomes an advantageous option to obtain the urgently needed effective treatment. Repurposing chloroquine, hydroxychloroquine, oseltamivir, lopinavir/ritonavir, andfavipiravir, and the use of investigational drug remdesivir for treatment of COVID-19, are reviewed from the clinical pharmacology perspective, particularly its efficacy and safety. Limited clinical studies of chloroquine, hydroxychloroquine, favipiravir, and remdesivir showed some efficacy in COVID-19 treatment with tolerable adverse effects. Potential serious adverse effect of chloroquine and hydroxychloroquine is cardiac arrhythmia. Oseltamivir has no documented activity against SARS-CoV-2, while lopinavir/ritonavir showed limited efficacy in COVID-19. Currently, there is no sufficient evidence to recommend any specific anti-COVID-19 treatment. The decision to use these drugs during the COVID-19 pandemic must be based on careful consideration of the potential benefits and risks to the patient.

Xanthine oxidase (XO) is an enzyme that catalyzes the production of uric acid and superoxide radicals from purine bases: hypoxanthine and xanthine and is also expressed in respiratory epithelial cells. Uric acid, which is also considered a danger associated molecule pattern (DAMP), could trigger a series of inflammatory responses by activating the inflammasome complex path and NF-κB within the endothelial cells and by inducing proinflammatory cytokine release. Concurrently, XO also converts the superoxide radicals into hydroxyl radicals that further induce inflammatory responses. These conditions will ultimately sum up a hyperinflammation condition commonly dubbed as cytokine storm syndrome (CSS). The expression of proinflammatory cytokines and neutrophil chemokines may be reduced by XO inhibitor, as observed in human respiratory syncytial virus (HRSV)-infected A549 cells. Our review emphasizes that XO may have an essential role as an anti-inflammation therapy for respiratory viral infection, including coronavirus disease 2019 (COVID-19).

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Background: Frequency of tropical infection in Indonesia are still high nowadays. This condition can cause high frequency of antibiotic usage and antibiotic resistance in the future. Aim of this study was to quantify the antibiotic usage in tropical infection patients in Cipto Mangunkusumo Hospital on June 2014-June 2015 using defined daily dose (DDD) method. The advantage of this method is easy to apply, used to compare between different medicine with same therapeutic group, have similar efficacy but different dose requirement, and also compare between institution or area. Methods: It was a descriptive, cross-sectional study, used medical record as data sources. All tropical infection patients in Internal Medicine Ward, on June 2014-June 2015 period, were included in our study. DDD formula is DDD/100 bed-days= (total amount of antibiotic in gram/DDD value from WHO) x (100 / length of stay of all patients with tropical infection diseases). One DDD mean average maintenance dose per day for a drug used for its main indication for adults. Results: We found 34 patients with tropical infection diagnosis and only 22 patients used antibiotic. The total length of stay for tropical infection patients was 314 days. Three antibiotics with highest DDD were ceftriaxone (54.46), levofloxacin (24.20) and meropenem (21.66). The highest DDD in typhoid fever subjects was ceftriaxone and in leptospirosis subjects were levofloxacin and meropenem. The antibiotic usage pattern could be difference between institutions or area, depends on the etiology and microbial resistance pattern. There were six patients with malaria and DHF treated with antibiotics, even though these diagnosis are not indication for antibiotic treatment. It might be due to bacterial infection as comorbid condition. Conclusions: Ceftriaxone, levofloxacin, and meropenem were antibiotics with the highest DDD unit. The usage of antibiotics for viral and parasite infection might be due to secondary infection.