High prevalence of HIV-1 transmitted drug resistance and factors associated with time to virological failure and viral suppression in Taiwan.

BACKGROUND: Integrase strand transfer inhibitor (InSTI)-based regimens have become the major first-line treatment for HIV-1-infected patients in Taiwan. Transmitted drug resistance (TDR) and several clinical characteristics are associated with time to virological failure or viral suppression; however, these have not been investigated in Taiwan. OBJECTIVES: To determine the impact of several factors on treatment outcomes in HIV-1-infected patients in Taiwan. METHODS: The cohort included 164 HIV-1 treatment-naive patients in Taiwan from 2018 to 2020. Blood specimens were collected to determine the genotypic drug resistance using the Stanford University HIV drug resistance database. Cox proportional hazards models were used to identify factors associated with time to virological failure or viral suppression. RESULTS: The prevalence of TDR in Taiwan was 27.4% and an increasing trend was seen from 2018 to 2020. TDR mutations related to NNRTIs were the most prevalent (21%) while TDR to InSTIs remained at a relatively low level (1.3%). A baseline HIV-1 viral load of ≥100 000 copies/mL was associated with a shorter time to virological failure [multivariate hazard ratio (mHR) 7.84; P = 0.018] and longer time to viral suppression (mHR 0.46; P < 0.001). Time to viral suppression was shorter in patients receiving InSTI-based regimens (mHR 2.18; P = 0.006). Different InSTI-based regimens as initial treatment did not affect the treatment outcomes. CONCLUSIONS: This study found an increasing trend of HIV-1 TDR prevalence from 2018 to 2020 in Taiwan. Baseline HIV-1 viral load and receiving InSTI-based regimens are important factors associated with time to virological failure or viral suppression.

Impact of Wearing Masks, Hand Hygiene, and Social Distancing on Influenza, Enterovirus, and All-Cause Pneumonia During the Coronavirus Pandemic: Retrospective National Epidemiological Surveillance Study.

BACKGROUND: The coronavirus disease (COVID-19) pandemic is an important health crisis worldwide. Several strategies were implemented to combat COVID-19, including wearing masks, hand hygiene, and social distancing. The impact of these strategies on COVID-19 and other viral infections remains largely unclear. OBJECTIVE: We aim to investigate the impact of implemented infectious control strategies on the incidences of influenza, enterovirus infection, and all-cause pneumonia during the COVID-19 pandemic. METHODS: We utilized the electronic database of the Taiwan National Infectious Disease Statistics System and extracted incidences of COVID-19, influenza virus, enterovirus, and all-cause pneumonia. We compared the incidences of these diseases from week 45 of 2016 to week 21 of 2020 and performed linear regression analyses. RESULTS: The first case of COVID-19 in Taiwan was reported in late January 2020 (week 4). Infectious control strategies have been promoted since late January. The influenza virus usually peaks in winter and decreases around week 14. However, a significant decrease in influenza was observed after week 6 of 2020. Regression analyses produced the following results: 2017, R2=0.037; 2018, R2=0.021; 2019, R2=0.046; and 2020, R2=0.599. A dramatic decrease in all-cause pneumonia was also reported (R2 values for 2017-2020 were 0.435, 0.098, 0.352, and 0.82, respectively). Enterovirus had increased by week 18 in 2017-2019, but this was not observed in 2020. CONCLUSIONS: Using this national epidemiological database, we found a significant decrease in cases of influenza, enterovirus, and all-cause pneumonia during the COVID-19 pandemic. Wearing masks, hand hygiene, and social distancing may contribute not only to the prevention of COVID-19 but also to the decline of other respiratory infectious diseases. Further studies are warranted to elucidate the causal relationship.

Effects of gallic acid on capsular polysaccharide biosynthesis in Klebsiella pneumoniae.

BACKGROUND: Klebsiella pneumoniae is a gram-negative opportunistic pathogen that causes diseases mostly in immunocompromised individuals. Recently, hypervirulent K. pneumoniae strains also cause severe disease in healthy individuals. Capsular polysaccharide (CPS) is the major virulence determinant in hypervirulent K. pneumoniae and protects the cell against the bactericidal activity of the immune system. Gallic acid (GA), a natural phenolic compound, is known to exhibit wide spectrum antibacterial activity; however, its effect on hypervirulent K. pneumoniae remains largely unresolved. We aimed to identify the effects of GA on CPS biosynthesis in hypervirulent K. pneumoniae. METHODS: Antibacterial activity of GA was evaluated by counting colonies. CPS amount was determined by glucuronic acid content. The transcriptions of cps gene cluster were measured by quantitative real time PCR (qRT-PCR) and the ß-galactosidase activity. The effect of GA on the resistance of K. pneumoniae to streptonigrin (SNG), an iron-activated antibiotic, was evaluated. The effect of GA on the resistance of K. pneumoniae to serum killing and phagocytosis by macrophages was observed. RESULTS: GA inhibited the growth and CPS biosynthesis in K. pneumoniae. GA may affect the iron availability in K. pneumoniae, thus possibly repressing the cps transcription. In addition, GA reduced the resistance of K. pneumoniae to serum killing and enhanced its susceptibility to phagocytosis. CONCLUSION: GA possesses bactericidal activity and inhibits the CPS biosynthesis in hypervirulent K. pneumoniae, thereby facilitating pathogen clearance by the host immune system. Therefore, GA may represent a promising strategy for the prevention or treatment of patients with hypervirulent K. pneumoniae infections.

Role of Coptis chinensis in antibiotic susceptibility of carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: The incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has rapidly increased. This study aimed to assess the effect of Coptis chinensis and its compounds on the minimal inhibitory concentrations (MICs) of eight antibiotics against CRKP. METHODS: Cell cultures were used to investigate the effects of C. chinensis and its compounds on the MICs of eight antibiotics against CRKP. The MICs for antibiotics alone and antibiotics with C. chinensis or compounds were measured and compared. Furthermore, the effects of C. chinensis on cell membrane injury and intracellular adenosine triphosphate (ATP) CRKP concentration were also measured. The Mann-Whitney rank-sum test was used to analyze the differences between means. RESULTS: C. chinensis exhibits a notable MIC bacteriostatic effect at 5 mg/mL on CRKP. A significant MIC reduction against CRKP exists when C. chinensis was added to colistin and colistin-containing two-antibiotic combinations. Moreover, C. chinensis could damage cell membrane integrity and decrease intracellular ATP concentration in CRKP. Thus, C. chinensis exhibits antimicrobial activity superiority with colistin against CRKP. Furthermore, the effects of identified compounds in C. chinensis on the MICs of colistin, four-to eight-, two-to four-, and one-to two-fold reductions were found in ferulic acid, magnoflorine, and jatrorrhizine hydrochloride, respectively. Among these compounds, ferulic acid destroys membrane integrity and decreases intracellular ATP concentration. CONCLUSION: C. chinensis and ferulic acid can potentiate the antimicrobial activity of colistin and may represent a promising component of combination therapy against CRKP infections in a clinical setting.

The Effect of a Name-Based Mask Rationing Plan in Taiwan on Public Anxiety Regarding a Mask Shortage During the COVID-19 Pandemic: Observational Study.

BACKGROUND: The COVID-19 pandemic is a severe global health crisis. Wearing a mask is a straightforward action that can be taken, but shortage of stock and equity of allocation were important issues in Taiwan. Furthermore, increased anxiety leading to the stockpiling of masks has been common during the pandemic. OBJECTIVE: We aim to summarize the name-based mask rationing plan implemented in Taiwan and explore the public's perceived anxiety about mask shortages. METHODS: The government of Taiwan took action to control the supply and allocation of face masks. We summarize the timeline and important components of the mask rationing plan. A survey that aimed to investigate the overall response to the mask rationing plan was answered by 44 participants. RESULTS: The mask rationing plan was implemented in late January 2020. Daily production capacity was increased from 2 million masks to 16 million masks in April 2020. People could buy 9 masks in 14 days by verification via their National Health Insurance card. Digital face mask availability maps were created. Moreover, the mask plan safeguarded the purchase of masks and resulted in decreased anxiety about a mask shortage (4.05 [SD 1.15] points; 72.7% [n=32] of participants answered "agree" or "strongly agree"). The majority of people felt that the mask plan was satisfactory (4.2 [SD 0.92] points; 79.5% [n=35] of participants answered "agree" or "strongly agree"). CONCLUSIONS: We found that the unique name-based mask rationing plan allowed for control of the production and supply of masks, and contributed to the appropriate allocation of masks. The mask rationing plan not only provided the public with physical protection, but also resulted in reduced anxiety about mask shortages during the pandemic.

Clinical features of neonates born to mothers with coronavirus disease-2019: A systematic review of 105 neonates.

BACKGROUND: Despite the increasingly recognized impact of novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), on many aspects of health in adults and children, its effects on neonates born to infected mothers remain unclear. We conducted this study to investigate the outcomes of neonates born to mothers with COVID-19. METHODS: We searched the medical databases from inception to March 31, 2020 to perform a systematic review of outcomes in neonates born to mothers with COVID-19. Data were pooled using a random effects regression model. Primary and secondary outcomes were neonatal clinical outcomes and infectious status, respectively. RESULTS: Fourteen studies involving 105 neonates fulfilling the study criteria were identified. The rates of preterm neonates and those small for gestational age (SGA) were 25 (23.8%) and 10 (11.2%), respectively. Among 91 neonates who were tested, 8 (8.8%) were positive for nucleic acids or antibodies for SARS-CoV-2. Additionally, 28 (26.7%) of the neonates were symptomatic and two test-negative neonates died, including one stillbirth. Between test-positive and test-negative groups, the rates of SGA, preterm delivery, duration between maternal symptom onset and delivery, and perinatal complication were not significantly different; but the rate of symptomatic after birth reached significant difference (62.5% vs 20.5%, p = 0.008). CONCLUSIONS: Most neonates born to infected mothers had favorable outcomes. Although direct evidences of intrauterine infection were scarce, the risk of intrauterine infection should be considered based on a positive test in 8.8% of the neonates. Symptomatic neonates born to infected mothers should receive tests for SARS-CoV-2 to initiate appropriate treatment and quarantine. Further studies are warranted to assess the outcomes of COVID-19 in neonates.

Effect of Coptis chinensis on Biofilm Formation and Antibiotic Susceptibility in Mycobacterium abscessus.

Mycobacterium abscessus infections are notoriously difficult to be treated and newer treatment options are required. Coptis chinensis (C. chinensis) and its main compound berberine are frequently used to treat bacterial and viral infections. In this study, the susceptibility of M. abscessus to C. chinensis extract and berberine was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) evaluation. The effects of C. chinensis and berberine on biofilm formation and antibiotic susceptibility in M. abscessus were observed. C. chinensis at concentrations of MIC (1.5 mg/mL) and 2 × MIC (3.0 mg/mL) and berberine at ½ × MIC (0.125 mg/mL) demonstrated a strong inhibition of biofilm formation. Concentration of C. chinensis at ½ × MIC resulted in a significant reduction in MICs of trimethoprim/sulfamethoxazole (TMP/SXT), clarithromycin (CLA), and linezolid (LZD). Similarly, ½ × MIC berberine had a significant effect on the MIC reductions of nine antibiotics including TMP/SXT, CLA, and LZD. Notably, the resistance level MIC of LZD against M. abscessus was reversed to a susceptible level by treatment with either C. chinensis or berberine. Therefore, C. chinensis and berberine have the potential to produce a synergistic antimycobacterial effect, reduce biofilm formation, and decrease antibacterial resistance to LZD in M. abscessus.

Taiwan Government-Guided Strategies Contributed to Combating and Controlling COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is highly contagious, and thus has become an emerging health crisis worldwide. The optimal strategies to prevent the spread of this disease are inconclusive, and therefore, the adopted measurements to combat COVID-19 varies in different countries. In mid-March and late-August 2020, we performed internet searches to collect relevant information, from sources such as the website of the World Health Organization. The epidemiological data of COVID-19 from several countries were collected and we found that Taiwan had a comparably successful story for combating the pandemic. As of mid-March, Taiwan had high rates of diagnostic testing (688.5 tests per million citizens) with a lower infection rate (49 cases, 2.1 cases per million people). As of late-August, there were 488 cases (20 cases per million people). Furthermore, Taiwanese government-guided strategies and hospital data were also reviewed. We summarized some important strategies to combat COVID-19, which include: (1) border control; (2) official media channel and press conferences; (3) name-based rationing system for medical masks; (4) TOCC-based rapid triage, outdoor clinics, and protective sampling devices; and (5) social distancing, delaying the start of new semesters, and religious assembly restriction. In conclusion, Taiwan had lower rates of COVID-19 compared with other countries, and Taiwan government-guided strategies contributed to the control of the disease's spread.

IscR Regulation of Type 3 Fimbriae Expression in Klebsiella pneumoniae CG43.

In Klebsiella pneumoniae, we have previously shown that IscR, an Fe-S cluster-containing transcriptional factor, plays a dual role in controlling capsular polysaccharide biosynthesis and iron-acquisition systems by switching between its holo and apo forms. In this study, the effect of IscR on type 3 fimbriae expression and biofilm formation was investigated. We found that production of the major subunit of type 3 fimbriae, MrkA, was increased in the ΔiscR and iscR3CA strains, a strain expressing a mutant IscR that mimics apo-IscR, at both the translational and transcriptional levels. Based on the fact that type 3 fimbriae expression is the major factor affecting biofilm formation, increased biofilm formation was also found in ΔiscR or iscR3CA, suggesting that holo-IscR represses biofilm formation. However, the repression of type 3 fimbriae expression by IscR is indirect. To further understand the regulatory mechanism of IscR, the effect of IscR on the expression of mrkHIJ, which encodes cyclic di-GMP (c-di-GMP)-related regulatory proteins that control type 3 fimbriae expression, was studied. We found that holo-IscR could directly repress mrkHI transcription, indicating that MrkHI is required for IscR regulation of type 3 fimbriae expression. Finally, deletion of iscR attenuated K. pneumoniae virulence in a peritonitis model of mouse infection, while the absence of the [2Fe-2S] cluster of IscR had no effect on K. pneumoniae virulence during infection. Taken together, our results demonstrate the underlying mechanism of the [2Fe-2S] cluster of IscR in controlling type 3 fimbriae expression and its effect on K. pneumoniae pathogenesis.