Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC). This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10–14 days with PTZ, cefepime, or ertapenem. A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC. Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC. The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895)
OBJECTIVES: Since the report of the first confirmed case in Daegu on February 18, 2020, local transmission of coronavirus disease 2019 (COVID-19) in Korea has continued. In this study, we aimed to identify the pattern of local transmission of COVID-19 using mathematical modeling and predict the epidemic size and the timing of the end of the spread. METHODS: We modeled the COVID-19 outbreak in Korea by applying a mathematical model of transmission that factors in behavioral changes. We used the Korea Centers for Disease Control and Prevention data of daily confirmed cases in the country to estimate the nationwide and Daegu/Gyeongbuk area-specific transmission rates as well as behavioral change parameters using a least-squares method. RESULTS: The number of transmissions per infected patient was estimated to be about 10 times higher in the Daegu/Gyeongbuk area than the average of nationwide. Using these estimated parameters, our models predicts that about 13,800 cases will occur nationwide and 11,400 cases in the Daegu/Gyeongbuk area until mid-June. CONCLUSIONS: We mathematically demonstrate that the relatively high per-capita rate of transmission and the low rate of changes in behavior have caused a large-scale transmission of COVID-19 in the Daegu/Gyeongbuk area in Korea. Since the outbreak is expected to continue until May, non-pharmaceutical interventions that can be sustained over the long term are required.
Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409–0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697–0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.
Although some intravenous drugs have been used to treat coronavirus disease 2019 (COVID-19), no effective antiviral agents are currently available in the outpatient setting. We aimed to evaluate the efficacy and adverse events of 14-day ciclesonide treatment vs. standard care for patients with mild-to-moderate COVID-19. A randomized, open-label, multicenter clinical trial of ciclesonide inhalers was conducted in patients with mild-to-moderate COVID-19. Patients were enrolled within 3 days of diagnosis or within 7 days from symptom onset and randomly assigned to receive either ciclesonide (320 µg inhalation twice per day for 14 days) or standard care. The primary endpoint was the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eradication rate on day 14 from study enrollment. Clinical status was assessed once daily, and serial nasopharyngeal viral load was evaluated by quantitative reverse transcription polymerase chain reaction. There were 35 and 26 patients in the ciclesonide and standard care groups, respectively. The SARS-CoV-2 eradication rate at day 14 was significantly higher in the ciclesonide group (p = 0.021). In multivariate analysis, SARS-CoV-2 negative conversion within 14 days was 12 times more likely in the ciclesonide group (95% confidence interval, 1.187–125.240). Additionally, the clinical failure rate (high-flow nasal oxygen therapy or mechanical ventilation) was significantly lower in the ciclesonide group (p = 0.034). In conclusion, ciclesonide inhalation shortened SARS-CoV-2 viral shedding duration, and it may inhibit the progression to acute respiratory failure in patients with mild-to-moderate COVID-19. Clinical Trial Registration NCT04330586.