Search

Background: We examined the effectiveness of molnupiravir and nirmatrelvir/ritonavir in reducing hospitalization and deaths in a real-world cohort of nonhospitalized patients with coronavirus disease 2019 (COVID-19)., Methods: This was a territory-wide retrospective cohort study in Hong Kong. Nonhospitalized COVID-19 patients who attended designated outpatient clinics between 16 February and 31 March 2022 were identified. Patients hospitalized on the day of the first clinic appointment or used both oral antivirals were excluded. The primary endpoint was hospitalization. The secondary endpoint was a composite of intensive care unit admission, invasive mechanical ventilation use, and/or death., Results: Of 93 883 patients, 83 154 (88.6%), 5808 (6.2%), and 4921 (5.2%) were oral antiviral nonusers, molnupiravir users, and nirmatrelvir/ritonavir users, respectively. Compared with nonusers, oral antiviral users were older and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year. Molnupiravir users were older and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year than nirmatrelvir/ritonavir users. At a median follow-up of 30 days, 1931 (2.1%) patients were hospitalized and 225 (0.2%) patients developed the secondary endpoint. After propensity score weighting, nirmatrelvir/ritonavir use (weighted hazard ratio 0.79; 95% confidence interval [CI], 0.65-0.95; P = .011) but not molnupiravir use (weighted hazard ratio 1.17; 95% CI, 0.99-1.39; P = .062) was associated with a reduced risk of hospitalization than nonusers. The use of molnupiravir or nirmatrelvir/ritonavir was not associated with a lower risk of the secondary endpoint as compared with nonusers., Conclusion: Use of nirmatrelvir/ritonavir but not molnupiravir was associated with a reduced risk of hospitalization in real-world nonhospitalized patients with COVID-19., Competing Interests: Potential conflicts of interest. T. Y. has served as an advisory committee member and a speaker for Gilead Sciences. G. L. has served as an advisory committee member for Gilead, Merck, and GSK; speaker for Merck, Pfizer, and Gilead; and received research grant from Gilead, Merck, and GSK. V. W. has served as a consultant or advisory committee member for 3V-BIO, AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Merck, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences, and TARGET PharmaSolutions; and a speaker for Bristol-Myers Squibb, Abbott, AbbVie, Echosens, Gilead Sciences, Merck, and Novo Nordisk. He has received a research grant from Gilead Sciences and is a cofounder of Illuminatio Medical Technology Limited. H. C. has served as an Independent Non-Executive Director for Shanghai Henlius Biotech Inc; as an advisory board member for Aligos, Aptorum, Arbutus, Hepion, Janssen, Gilead, Glaxo-Smith-Kline, Roche, Vaccitech, Virion Therapeutics, and Vir Biotechnology; and as a speaker for Gilead, Roche, and Viatris. G. W. has served as an advisory committee member for Gilead Sciences and Janssen, and as a speaker for Abbott, Abbvie, Ascletis, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen, and Roche. She has also received a research grant from Gilead Sciences. D. H. is an advisory committee member for Roche (personal fees). E. H. reports grants from Merck and GSK; is an advisory committee member for Merk, Gilead, Sanofi Pasteur, and GSK; and speaker for Merck and Gilead sciences. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Previous studies have demonstrated increased cardiovascular mortality related to azithromycin and levofloxacin. Risks associated with alternative drugs in the same class, including clarithromycin and moxifloxacin, were unknown. We used the Taiwan National Health Insurance Database to perform a nationwide, population-based study comparing the risks of ventricular arrhythmia and cardiovascular death among patients using these antibiotics., Methods: Between January 2001 and November 2011, a total of 10 684 100 patients were prescribed oral azithromycin, clarithromycin, moxifloxacin, levofloxacin, ciprofloxacin, or amoxicillin-clavulanate at outpatient visits. A logistic regression model adjusted for propensity score was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for adverse cardiac outcomes occurring within 7 days after the initiation of antibiotic treatment., Results: Compared with amoxicillin-clavulanate treatment, the use of azithromycin and moxifloxacin was associated with significant increases in the risks of ventricular arrhythmia and cardiovascular death. The adjusted ORs for ventricular arrhythmia were 4.32 (95% CI, 2.95-6.33) for azithromycin, 3.30 (95% CI, 2.07-5.25) for moxifloxacin, and 1.41 (95% CI, .91-2.18) for levofloxacin. For cardiovascular death, the adjusted ORs for azithromycin, moxifloxacin, and levofloxacin were 2.62 (95% CI, 1.69-4.06), 2.31 (95% CI, 1.39-3.84), and 1.77 (95% CI, 1.22-2.59), respectively. No association was noted between clarithromycin or ciprofloxacin and adverse cardiac outcomes., Conclusions: Healthcare professionals should consider the small but significant increased risk of ventricular arrhythmia and cardiovascular death when prescribing azithromycin and moxifloxacin. Additional research is needed to determine whether the increased risk of mortality is caused by the drugs or related to the severity of infection or the pathogens themselves., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Observational studies and fatal case reports raise concern about the safety of severe dysglycemia associated with fluoroquinolone use. The objective of this study was to assess the risk of severe dysglycemia among diabetic patients who received different fluoroquinolones., Methods: In a population-based inception cohort study of diabetic patients covering the period from January 2006 to November 2007, outpatient new users of levofloxacin, ciprofloxacin, moxifloxacin, cephalosporins, and macrolides orally were identified. Study events were defined as emergency department visits or hospitalization for dysglycemia within 30 days following the initiation of antibiotic therapy. Results were analyzed with adjusted multinomial propensity score., Results: A total of 78 433 diabetic patients receiving the antibiotics of interest were included in the study. The absolute risk of hyperglycemia per 1000 persons was 6.9 for moxifloxacin and 1.6 for macrolides. In contrast, the risk of hypoglycemia was 10.0 for moxifloxacin and 3.7 for macrolides. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) of levofloxacin, ciprofloxacin, and moxifloxacin compared with macrolides were 1.75 (1.12-2.73), 1.87 (1.20-2.93), and 2.48 (1.50-4.12), respectively, for hyperglycemia and 1.79 (1.33-2.42), 1.46 (1.07-2.00), and 2.13 (1.44-3.14), respectively, for hypoglycemia. Patients taking moxifloxacin faced a significantly higher risk of hypoglycemia than those receiving ciprofloxacin. A significant increase in the risk of hypoglycemia was also observed among patients receiving moxifloxacin concomitantly with insulin (AOR, 2.28; 95% CI, 1.22-4.24)., Conclusions: Diabetics using oral fluoroquinolones faced greater risk of severe dysglycemia. The risk of hypoglycemia varied according to the type of fluoroquinolone administered, and was most commonly associated with moxifloxacin.

Background: Recent evidence has shown that community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is less virulent than traditional hospital-associated MRSA. We explored whether the antimicrobial susceptibilities of the different strains account for their disparity in clinical virulence., Methods: This 10-year retrospective cohort study enrolled 291 patients with community-onset, healthcare-associated MRSA bacteremia. The vancomycin minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type were determined for all isolates. CA-MRSA was defined as an isolate possessing the SCCmec type IV or V genes, and hospital-associated MRSA (HA-MRSA) was defined as an isolate possessing SCCmec type I, II, or III genes. Low and high vancomycin MICs were defined as MICs of ≤1 and ≥2 μg/mL, respectively. Patients with bacteremia due to CA-MRSA with a low vancomycin MIC (n = 111), due to HA-MRSA with a low vancomycin MIC (n = 127), or due to HA-MRSA with a high vancomycin MIC (n = 47) entered the outcome analysis. The outcomes of the 2 HA-MRSA bacteremia groups were compared to those of the CA-MRSA bacteremia group., Results: Treatment failure was observed in 35 (31.5%), 59 (46.5%), and 27 (57.4%) of patients with low-vancomycin-MIC CA-MRSA, low-vancomycin-MIC HA-MRSA, and high-vancomycin-MIC HA-MRSA bacteremia, respectively. After adjustment for potential confounding factors, the risk of treatment failure was significantly higher among patients with low-vancomycin-MIC HA-MRSA (adjusted odds ratio [aOR], 1.853; 95% confidence interval [CI], 1.006-3.413) and high-vancomycin-MIC HA-MRSA (aOR, 2.393; 95% CI, 1.079-5.309), compared with patients with low-vancomycin-MIC CA-MRSA., Conclusions: The higher risk for treatment failure among patients with traditional hospital-associated MRSA infections, compared with patients with CA-MRSA infections, is independent of the vancomycin MIC, suggesting a potential intrinsic strain-specific virulence effect.

Background: We sought to elaborate the epidemiology and outcomes of adult patients with occult Staphylococcus aureus bacteremia who were inadvertently discharged from the emergency department (ED) before positive blood culture results were obtained., Methods: Between 2001 and 2010, 759 true occult bacteremia cases were identified, including 65 patients with S. aureus bacteremia. Sixty-two patients were enrolled (case group) and analyzed using two 1:2 case-control strategies. Control group I patients were selected from among 997 S. aureus bacteremia patients directly admitted from the ED. Control group II patients were selected from 694 ED patients with occult bacteremia other than S. aureus. Cox regression analyses were used to assess the independent effect of occult S. aureus bacteremia on patient mortality., Results: There was no significant difference between the case group and control group I with respect to organ failure, septic shock, intensive care unit (ICU) admission proportion, length of ICU stay, and 30-day mortality. However, compared with control group II, the case group had significantly higher rates of hospital admission, organ failure, septic shock, ICU admission, and 30-day mortality. Age, endocarditis, and S. aureus infection were independent predictors of mortality among adult occult bacteremia patients., Conclusions: Among patients with occult bacteremia, S. aureus infections had significantly greater adverse impacts on a variety of outcome variables than other bacterial infections. Because S. aureus bacteremia is frequently associated with endovascular or deep-seated infection, it is imperative that first-line clinicians perform prudent evaluations of cases with nonapparent infection foci before discharging febrile patients from EDs.