SARS-CoV-2 variants with T135I nucleocapsid mutations may affect antigen test performance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic. Diagnostic testing for SARS-CoV-2 has continuously been challenged due to several variants with diverse spike (S) and nucleocapsid (N) protein mutations []. SARS-CoV-2 variant proliferation potentially affects N protein-targeted rapid antigen testing. In this study, rapid antigen and reverse transcription PCR (RT-PCR) tests were performed simultaneously in patients with suspected coronavirus disease 2019 (COVID-19). Direct whole genome sequencing was performed to determine the N protein variations, and the viral assemblies were uploaded to GISAID. The genomes were then compared with those of global virus strains from GISAID. These isolates belonged to the B.1.1.7 variant, exhibiting several amino acid substitutions, including D3L, R203K, G204R, and S235F N protein mutations. The T135I mutation was also identified in one variant case in which the rapid antigen test and RT-PCR test were discordantly negative and positive, respectively. These findings suggest that the variants undetected by the Panbio COVID-19 rapid antigen test may be due to the T135I mutation in the N protein, posing a potential diagnostic risk for commercially available antigen tests. Hence, we recommend concomitant paired rapid antigen tests and molecular diagnostic methods to detect SARS-CoV-2. False-negative results could be rapidly corrected using confirmatory RT-PCR results to prevent future COVID-19 outbreaks.

Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan.

OBJECTIVES: Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. METHODS: Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events. RESULTS: During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/µl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031-1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816-3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439-5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150-4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051-7.521) were independently associated with the development of hepatotoxicity. CONCLUSIONS: The baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naïve HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens.

Comparison of the effectiveness and antibiotic cost among ceftriaxone, ertapenem, and levofloxacin in treatment of community-acquired complicated urinary tract infections.

PURPOSE: To study characteristics of patients with community-acquired complicated urinary tract infections (cUTIs) and to compare effectiveness and antibiotic cost of treatment with ceftriaxone (CRO), levofloxacin (LVX), and ertapenem (ETP). METHODS: This retrospective study enrolled patients who had community-acquired cUTIs admitted to Division of Infectious Diseases in a single medical center from January 2011 to March 2013. Effectiveness, antibiotic cost, and clinical characteristics were compared among patients treated with CRO, LVX, and ETP. RESULTS: There were 358 eligible cases, including 139 who received CRO, 128 treated with ETP, and 91 with LVX. The most common pathogen was Escherichia coli. The susceptibilities of these three agents were higher and more superior than first-line antibiotics. Treatment with ETP was associated with a significantly shorter time to defervescence since admission (CRO: 39 hours, ETP: 30 hours, and LVX: 38 h; p = 0.031) and shorter hospitalization stay (CRO: 4 days, ETP: 3 days, and LVX: 4 days; p < 0.001). However, the average antibiotic costs in the CRO group were significantly lower than that in the other two groups [CRO: 62.4 United States dollars (USD), ETP: 185.33 USD, and LVX: 204.85 USD; p < 0.001]. CONCLUSION: The resistance of cUTIs isolates to first-line antibiotic is high. Using ETP, CRO, and LVX in the treatment of cUTIs for good clinical response should be suggested. Among the three agents, ETP had better susceptibility than CRO and LVX, reached defervescence sooner, and was associated with shorter hospital stays. However, using CRO in cUTIs was less expensive than the other two agents.