Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America最新文献

Background: Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal evidence supporting this recommendation. Our aim was to examine the association between beta-lactam plus doxycycline and mortality for patients hospitalized with community-acquired pneumonia.

Methods: We identified patients >65 years of age admitted to any US Department of Veterans Affairs hospital in fiscal years 2002-2012 with a discharge diagnosis of pneumonia. We excluded those patients who did not receive antibiotic therapy concordant with the 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) clinical practice guidelines. Using propensity score matching, we examined the association of doxycycline with 30- and 90-day mortality.

Results: Our overall cohort was comprised of 70533 patients and 5282 (7.49%) received doxycycline. Unadjusted 30-day mortality was 6.4% for those who received a beta-lactam plus doxycycline versus 9.1% in those who did not (P < .0001), and 90-day mortality was 13.8% for those who received a beta-lactam + doxycycline versus 16.8% for those who did not (P < .0001). In the propensity score matched models, both 30- (odds ratio 0.72, 95% confidence interval [CI], .63-.84) and 90-day (0.83, 95% CI, .74-.92) mortality were significantly lower for those who received doxycycline.

Conclusions: In this retrospective observational cohort study, we found that doxycycline use, as part of guideline-concordant antibiotic therapy, was associated with lower 30- and 90-day mortality than regimens without doxycycline. While this supports the safety and effectiveness of antibiotic regimes that include doxycycline, additional studies, especially randomized clinical trials, are needed to confirm this.

Background: The role of favipiravir in preventing disease progression in coronavirus disease 2019 (COVID-19) remains uncertain. We aimed to determine its effect in preventing disease progression from nonhypoxia to hypoxia among high-risk COVID-19 patients.

Methods: This was an open-label, randomized clinical trial conducted at 14 public hospitals across Malaysia (February-July 2021) among 500 symptomatic, RT-PCR-confirmed COVID-19 patients, aged ≥50 years with ≥1 comorbidity, and hospitalized within first 7 days of illness. Patients were randomized 1:1 to favipiravir plus standard care or standard care alone. Favipiravir was administered at 1800 mg 2×/day on day 1 followed by 800 mg 2×/day until day 5. The primary endpoint was rate of clinical progression from nonhypoxia to hypoxia. Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality.

Results: Of 500 patients randomized (mean [SD] age, 62.5 [8.0] years; 258 women [51.6%]; 251 [50.2%] had COVID-19 pneumonia), 487 (97.4%) patients completed the trial. Clinical progression to hypoxia occurred in 46 (18.4%) patients on favipiravir plus standard care and 37 (14.8%) on standard care alone (OR, 1.30; 95% CI: .81-2.09; P = .28). All 3 prespecified secondary endpoints were similar between both groups. Mechanical ventilation occurred in 6 (2.4%) vs 5 (2.0%) (OR, 1.20; 95% CI: .36-4.23; P = .76), ICU admission in 13 (5.2%) vs 12 (4.8%) (OR, 1.09; 95% CI: .48-2.47; P = .84), and in-hospital mortality in 5 (2.0%) vs 0 (OR, 12.54; 95% CI: .76-207.84; P = .08) patients.

Conclusions: Among COVID-19 patients at high risk of disease progression, early treatment with oral favipiravir did not prevent their disease progression from nonhypoxia to hypoxia.

Clinical trials registration: ClinicalTrials.gov (NCT04818320).

We assessed environmental contamination of inpatient rooms housing coronavirus disease 2019 (COVID-19) patients in a dedicated COVID-19 unit. Contamination with severe acute respiratory syndrome coronavirus 2 was found on 5.5% (19/347) of surfaces via reverse transcriptase polymerase chain reaction and 0.3% (1/347) of surfaces via cell culture. Environmental contamination is uncommon in hospitals rooms; RNA presence is not a specific indicator of infectious virus.

Background: Our objective was to determine if the addition of ultraviolet-C (UV-C) light to daily and discharge patient room cleaning reduces healthcare-associated infection rates of vancomycin-resistant enterococci (VRE) and Clostridioides difficile in immunocompromised adults.

Methods: We performed a cluster randomized crossover control trial in 4 cancer and 1 solid organ transplant in-patient units at the Johns Hopkins Hospital, Baltimore, Maryland. For study year 1, each unit was randomized to intervention of UV-C light plus standard environmental cleaning or control of standard environmental cleaning, followed by a 5-week washout period. In study year 2, units switched assignments. The outcomes were healthcare-associated rates of VRE or C. difficile. Statistical inference used a two-stage approach recommended for cluster-randomized trials with <15 clusters/arm.

Results: In total, 302 new VRE infections were observed during 45787 at risk patient-days. The incidence in control and intervention groups was 6.68 and 6.52 per 1000 patient-days respectively; the unadjusted incidence rate ratio (IRR) was 0.98 (95% confidence interval [CI], .78 - 1.22; P = .54). There were 84 new C. difficile infections observed during 26118 at risk patient-days. The incidence in control and intervention periods was 2.64 and 3.78 per 1000 patient-days respectively; the unadjusted IRR was 1.43 (95% CI, .93 - 2.21; P = .98).

Conclusions: When used daily and at post discharge in addition to standard environmental cleaning, UV-C disinfection did not reduce VRE or C. difficile infection rates in cancer and solid organ transplant units.

Background: Individuals with high microfilarial densities (MFDs) of Loa loa are at risk of developing serious adverse events (SAEs) after ivermectin treatment. Pretreatment with drugs progressively reducing Loa MFDs below the risk threshold might help prevent these SAEs. We assessed the safety and efficacy of levamisole for this purpose.

Methods: A double-blind, randomized, placebo-controlled, MFD-ascending trial was conducted in the Republic of the Congo. Participants were treated in 3 cohorts defined by pretreatment MFD and levamisole dose (cohort 1: 1.0kg and 1.5mg/kg; cohorts 2 and 3: 2.5mg/kg). Safety outcomes were occurrence of SAE and adverse event frequency during the first week. The efficacy outcomes were MFD reduction from baseline and proportions of individuals with at least 40% and 80% MFD reduction at day 2 (D2), D7, and D30.

Results: The 2 lowest doses (1.0mg/kg and 1.5mg/kg) caused no SAEs but were ineffective. Compared with placebo, 2.5mg/kg levamisole caused more mild adverse events (10/85 vs. 3/85, P=.018), a higher median reduction from baseline to D2 (-12.9% vs. +15.5%, P<.001), D7 (-4.9% vs. +18.7%, P<.001), and D30 (-0.5% vs. +13.5%, P=.036) and a higher percentage of participants with >40% MFD reduction at D2 (17.5% vs. 1.2%, P<.001), D7 (11.8% vs. 6.3%, P=.269), and D30 (18.5% vs. 9.6%, P=.107).

Conclusions: A single 2.5mg/kg levamisole dose induces a promising transient reduction in Loa loa MFDs and should encourage testing different regimens.

Background: Approximately 15-30% of hospitalized coronavirus disease 2019 (COVID-19) patients develop acute respiratory distress syndrome, systemic tissue injury, and/or multi-organ failure leading to death in around 45% of cases. There is a clear need for biomarkers that quantify tissue injury, predict clinical outcomes, and guide the clinical management of hospitalized COVID-19 patients.

Methods: We herein report the quantification by droplet-based digital polymerase chain reaction (ddPCR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia and the plasmatic release of a ubiquitous human intracellular marker, the ribonuclease P (RNase P) in order to evaluate tissue injury and cell lysis in the plasma of 139 COVID-19 hospitalized patients at admission.

Results: We confirmed that SARS-CoV-2 RNAemia was associated with clinical severity of COVID-19 patients. In addition, we showed that plasmatic RNase P RNAemia at admission was also highly correlated with disease severity (P < .001) and invasive mechanical ventilation status (P < .001) but not with pulmonary severity. Altogether, these results indicate a consequent cell lysis process in severe and critical patients but not systematically due to lung cell death. Finally, the plasmatic RNase P RNA value was also significantly associated with overall survival.

Conclusions: Viral and ubiquitous blood biomarkers monitored by ddPCR could be useful for the clinical monitoring and the management of hospitalized COVID-19 patients. Moreover, these results could pave the way for new and more personalized circulating biomarkers in COVID-19, and more generally in infectious diseases, specific from each patient organ injury profile.

Background: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected more socioeconomically disadvantaged persons and areas. We sought to determine how certain sociodemographic factors were correlated to adolescents' COVID-19 vaccination rates in towns and cities ("communities") in the Commonwealth of Massachusetts.

Methods: Data on COVID-19 vaccination rates were obtained over a 20-week period from 30 March 2021 to 10 August 2021. Communities' adolescent (ages 12-19) vaccination rates were compared across quintiles of community-level income, COVID-19 case rate, and proportion of non-Hispanic Black or Hispanic individuals. Other variables included population density and earlier COVID-19 vaccination rates of adolescents and adults, averaged from 30 March to 11 May to determine their effects on vaccination rates on 10 August. Linear and logistic regression was used to estimate individual effects of variables on adolescent vaccination rates.

Results: Higher median household income, lower proportion of Black or Hispanic individuals, higher early adolescent COVID-19 vaccination rates, and higher early adult COVID-19 vaccination rates were associated with higher later adolescent COVID-19 vaccination rates. Income per $10 000 (adjusted odds ratio [aOR] = 1.01 [95% confidence interval [CI] = 1.01-1.02]), proportion of Hispanic individuals (aOR = 1.33 [95% CI: 1.13-1.56]), early adolescent COVID-19 vaccination rates (aOR = 5.28 [95% CI: 4.67-5.96]), and early adult COVID-19 vaccination rates (aOR = 2.31 [95% CI: 2.02-2.64]) were associated with higher adolescent COVID-19 vaccination on 10 August, whereas proportion of Black individuals approached significance (aOR = 1.26 [95% CI: .98-1.61]).

Conclusions: Vaccination efforts for adolescents in Massachusetts should focus on boosting vaccination rates early in communities with the lowest incomes and greatest proportion of Hispanic individuals and consider targeting communities with a greater proportion of Black individuals.

Background: There is a lack of data regarding how the Delta variant of coronavirus disease 2019 (COVID-19) has impacted the effectiveness of the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines at preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 hospitalization.

Methods: We compared the effectiveness of the three vaccines during the pre- and post-Delta variant period (before and after 1 July 2021) in a large cohort of vaccinated and unvaccinated patients in the Michigan Medicine healthcare system. We assessed vaccine effectiveness (VE) using 2 analyses: an inverse propensity weighted (IPW) Kaplan-Meier (KM) analysis based on time from vaccination, and a Cox model based on calendar time with vaccination as a time-varying covariate.

Results: Compared to Ad26.COV2.S recipients, the risk of hospitalization for COVID-19 in the post-Delta variant period was lower for BNT162b2 recipients (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: [.14-.98]; P = .05) and mRNA-1273 recipients (HR = 0.21; 95% CI: [.07-.64]; P = .006). Recipients of the mRNA-1273 vaccine had a lower risk of SARS-CoV-2 infection than Ad26.COV2.S recipients (HR = 0.6; 95% CI: [.43-.83]; P = .003) and BNT162b2 recipients (HR = 0.64; 95% CI: [.54-.76]; P < .001). After 1 July, efficacy against SARS-CoV-2 infection declined for Ad26.COV2.S recipients (VE = 76% before; VE = 49% after; P = .02), BNT162b2 recipients (VE = 87% before; VE = 52% after; P < .001), and mRNA-1273 recipients (VE = 92% before; VE = 70% after; P < .001). Waning immunity and the Delta variant contributed independently and significantly to this decline.

Conclusions: Although there is a substantial decline in effectiveness, the approved COVID-19 vaccines remain effective against infection and hospitalization due to the Delta variant. The mRNA-based vaccines are more effective than the Ad26.COV2.S vaccine.

Background: Risk of invasive meningococcal disease (IMD) is increased in patients with complement deficiency and human immunodeficiency virus (HIV) infection. Risk associated with comorbidity is not well described.

Methods: This was a nationwide adult case-control study. Cases for the period 1977-2018 were identified by the national meningococcus reference laboratory. Matched controls were identified by registry linkage. Comorbidities diagnosed prior to IMD were based on the International Classification of Diseases, Eighth or Tenth Revision. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression after adjustment for sex, age, and other comorbidities.

Results: We identified 1221 cases (45% male), with a median age of 45 years (interquartile range, 22-64 years). The dominant meningococcal serogroups were B (n = 738) and C (n = 337). Increased risk of IMD was associated with solid organ transplantation (SOT) (OR 40.47 [95% CI: 4.84-337.23]), hemolytic anemia (OR 7.56 [95% CI: 2.63-21.79]), renal disease (OR 2.95 [95% CI: 1.77-4.92]), liver disease (OR 2.54 [95% CI: 1.58-4.08]), cancer (OR 2.31 [95% CI: 1.85-2.89]), diabetes (OR 1.74 [95% CI: 1.27-2.39]), neurological disease (OR 1.72 [95% CI: 1.20-2.46]), and autoimmune disease (OR 1.70 [95% CI: 1.63-2.11]). Having 1, 2, and ≥3 comorbidities was associated with increased risk of IMD (ORs 1.6-3.5). Increased risk was not associated with specific serogroups.

Conclusions: This study of adults with IMD over 4 decades showed increased risk of IMD associated with renal disease, immunological disorders, liver disease, cancer, and SOT ranging from a 2- to 40-fold increased risk. Vaccination may be warranted in these populations.