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

Background: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs.

Methods: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs. Laboratory and clinical data from hospitalized patients with BSIs (excluding contaminants) were compared between 2 arms, 1 that underwent testing on AXDX (post-AXDX) and 1 that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) and 30-day mortality.

Results: A total of 854 patients with BSIs (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared with the pre-AXDX arm (40.9 hours; P<.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 vs 13.9 hours; P<.0001) and first antimicrobial deescalation (36.0 vs 27.2 hours; P=.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX vs 6.0% post-AXDX), length of stay (7.0 pre-AXDX vs 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 vs 6.4 days; P=.03) among patients with gram-negative bacteremia.

Conclusions: For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial deescalation.

Background: A better understanding of the risk for coronavirus disease 2019 (COVID-19) that people experiencing homelessness (PEH) face in congregate shelters versus unsheltered encampments is critical for an effective pandemic response.

Methods: We analyzed factors associated with current and past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among PEH in day and overnight shelters and encampments in Denver, Colorado, during June 2-July 28, 2020, and constructed multivariable logistic regression models to examine risk factors for SARS-CoV-2 RNA and seropositivity with age, race/ethnicity, testing location, testing month, and symptom status as predictor variables.

Results: A total of 823 participants were tested for SARS-CoV-2 RNA, and 276 individuals were tested for SARS-CoV-2 antibodies. A greater percentage of PEH at overnight shelters tested positive for SARS-CoV-2 RNA (8.6% vs 2.5%, P < .01) and antibodies (21.5% vs 8.7%, P = .03) compared with encampments. In regression models, testing at an overnight shelter compared with testing at encampments (odds ratio [OR] = 3.03, 95% confidence interval [CI]: 1.16-9.02) had increased odds of a positive SARS-CoV-2 RNA result. Age >60 years compared with age <40 years (OR = 5.92; 95% CI: 1.83-20.3), Hispanic ethnicity (OR = 3.43; 95% CI: 1.36-8.95), and non-Hispanic Black race compared with non-Hispanic White race (OR = 3.07; 95% CI: 1.16-8.26), and testing at an overnight shelter compared to testing at encampments (OR = 2.45; 95% CI: 1.04-6.17) had increased odds of a positive antibody result.

Conclusions: Our findings support the need for continuing assessment of mitigation strategies in shelters, increasing access to individual rooms and linkage to housing options for PEH, and supporting people to remain in encampments when these options are not available.

Meningococcal vaccination is recommended for patients with complement component deficiencies (CDs) in the United States. In this retrospective database study, only 4.6% and 2.2% of patients received MenACWY and MenB vaccination, respectively, within 3 years of CD diagnosis. Thus, meningococcal vaccination rates among patients with CDs need to be improved.

Background: In Spring 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 (Alpha) became the predominant variant in the United States. Research suggests that Alpha has increased transmissibility compared with non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections.

Methods: We followed households with SARS-CoV-2 infection for 2 weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, reverse transcription-polymerase chain reaction (RT-PCR), and whole-genome sequencing. We stratified SIR and symptoms by lineage and identified characteristics associated with transmission using generalized estimating equations.

Results: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval, 52.4-69.0%]) than non-Alpha (55.6% [44.7-65.9%], P = .49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = .01 and .03, respectively). Close contact (eg, kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs 76.8%, P = .05).

Conclusions: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households due to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members.

Background: Few robust longitudinal data on long-term coronavirus disease 2019 (COVID-19) symptoms are available. We evaluated symptom onset, severity and recovery across the full spectrum of disease severity, up to one year after illness onset.

Methods: The RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged ≥18 years were enrolled following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis via the local public health service and from hospitals. Standardized symptom questionnaires were completed at enrollment, 1 week and month later, and monthly thereafter. Clinical severity was defined according to World Health Organization (WHO) criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models.

Results: Between 11 May 2020 and 1 May 2021, 342 COVID-19 patients (192 [56%] male) were enrolled, of whom 99/342 (29%) had mild, 145/342 (42%) moderate, 56/342 (16%) severe, and 42/342 (12%) critical disease. The proportion of participants who reported at least 1 persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7% [95% confidence interval {CI} = 76.5-92.7%]) compared to those with mild or moderate disease (30.7% [95% CI = 21.1-40.9%] and 63.8% [95% CI = 54.8-71.5%], respectively). At 12 months after illness onset, two-fifths of participants (40.7% [95% CI = 34.2-7.1]) continued to report ≥1 symptom. Recovery was slower in female compared to male participants (adjusted hazard ratio [aHR] 0.65 [95% CI = .47-.92]) and those with a body mass index [BMI]  ≥30kg/m2 compared to BMI <25kg/m2 (hazard ratio [HR] 0.62 [95% CI = .39-.97]).

Conclusions: COVID-19 symptoms persisted for one year after illness onset, even in some individuals with mild disease. Female sex and obesity were the most important determinants of speed of recovery from symptoms.

Background: After the failure of antibody therapies in treating hospitalized patients with coronavirus disease 2019 (COVID-19), we investigated the impact of viral replication on the pharmacokinetics and efficacy of a hyperimmune severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (CoVIG) product in treating SARS-CoV-2 infection using an adult Syrian hamster model.

Methods: The CoVIG was manufactured from plasma donors who had recovered from COVID-19. The dose used (400 mg/kg) was based on the dose given in clinical trials to hospitalized patients with COVID-19. Hamsters were given a single dose of CoVIG 2 days after challenge with the SARS-CoV-2 virus (isolate NY/PV08410/2020), followed by sampling of blood, nasal, tracheal, and lung tissues at different time points. The blood samples were assayed for anti-SARS-CoV-2 spike binding and used to calculate pharmacokinetic (PK) parameters. Nasal wash, tracheal, and lung tissue samples were assayed for viral replication by polymerase chain reaction (subgenomic messenger RNA).

Results: CoVIG-treated hamsters showed a reduction in viral replication in the lower respiratory tract, but minimal reduction in the upper respiratory tract, after challenge with SARS-CoV-2. Challenge resulted in altered PK parameters proportionate to viral replication, resulting in decreased area under the curve, accelerated clearance, and shorter half-life of CoVIG.

Conclusions: These data indicate that in the presence of actively replicating SARS-CoV-2 virus, PK parameters are altered and should trigger an adjustment in CoVIG dosing.

Background: Prompt initiation of antibiotic therapy improves the survival of patients with bloodstream infections (BSIs). We sought to determine if the sequence of administration of the first dose of antibiotic therapy (ie, β-lactam or vancomycin, if both are deemed necessary and cannot be administered simultaneously) impacts early mortality for patients with BSI.

Methods: We conducted a multicenter, observational study of patients ≥13 years with BSIs to evaluate the association of the sequence of antibiotic administration with 7-day mortality using inverse probability of treatment weighting (IPTW) incorporating propensity scores. Propensity scores were generated based on demographics, Pitt bacteremia score, intensive care unit status, highest lactate, highest white blood cell count, Charlson comorbidity index, severe immunocompromise, administration of active empiric therapy, combination therapy, and time from emergency department arrival to first antibiotic dose.

Results: Of 3376 eligible patients, 2685 (79.5%) received a β-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. In the IPTW cohort, exposed and unexposed patients were similar on all baseline variables. Administration of a β-lactam agent prior to vancomycin protected against 7-day mortality (adjusted odds ratio [aOR], 0.48 [95% confidence interval {CI}, .33-.69]). Similar results were observed when evaluating 48-hour mortality (aOR, 0.45 [95% CI, .24-.83]). Administration of vancomycin prior to a β-lactam was not associated with improved survival in the subgroup of 524 patients with methicillin-resistant Staphylococcus aureus BSI (aOR, 0.93 [95% CI, .33-2.63]).

Conclusions: For ill-appearing patients likely to be experiencing a BSI, prioritizing administration of a β-lactam over vancomycin may reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival.

Background: Testing of an entire community has been used as an approach to control coronavirus disease 2019 (COVID-19). In Hong Kong, a universal community testing program (UCTP) was implemented at the fadeout phase of a community epidemic in July to September 2020. We described the utility of the UCTP in finding unrecognized infections and analyzed data from the UCTP and other sources to characterize transmission dynamics.

Methods: We described the characteristics of people participating in the UCTP and compared the clinical and epidemiological characteristics of COVID-19 cases detected by the UCTP versus those detected by clinical diagnosis and public health surveillance (CDPHS). We developed a Bayesian model to estimate the age-specific incidence of infection and the proportion of cases detected by CDPHS.

Results: In total, 1.77 million people, 24% of the Hong Kong population, participated in the UCTP from 1 to 14 September 2020. The UCTP identified 32 new infections (1.8 per 100000 samples tested), consisting of 29% of all local cases reported during the two-week UCTP period. Compared with the CDPHS, the UCTP detected a higher proportion of sporadic cases (62% vs 27%, P<.01) and identified 6 (out of 18) additional clusters during that period. We estimated that 27% (95% credible interval: 22%, 34%) of all infections were detected by the CDPHS in the third wave.

Conclusions: We reported empirical evidence of the utility of population-wide COVID-19 testing in detecting unrecognized infections and clusters. Around three quarters of infections have not been identified through existing surveillance approaches including contact tracing.

Background: Remdesivir is an antiviral used to treat coronavirus disease 2019 (COVID-19), which improves some clinical outcomes. Dexamethasone has been shown to be effective in reducing mortality. It has been hypothesized that combination of these two drugs can improve mortality. We evaluated the effect of combination on mortality of COVID-19 patients requiring O2 therapy.

Methods: A prospective quasi-experimental study, including two independent, sequential controlled cohorts, one received remdesivir-dexamethasone and the other dexamethasone alone, was designed. All COVID-19 patients requiring supplemental O2 therapy were enrolled consecutively. The sample size to power mortality was a priori calculated. The primary endpoints were 30-day mortality and viral clearance differences. Secondary endpoints were differences in hospitalization times, improvement in respiratory failure (PO2/FiO2) and inflammatory indices (fibrinogen, CRP, neutrophil/lymphocyte ratio, D-Dimer). Kaplan-Meier curves and the log-rank test were used to evaluate significant differences in mortality between groups.

Results: In total, 151 COVID-19 patients were enrolled (remdesivir/dexamethasone group, 76, and dexamethasone alone, 75). No differences in demographic, clinical, and laboratory characteristics were observed between the 2 groups at baseline. Faster viral clearance occurred in the remdesivir/dexamethasone group compared to dexamethasone alone (median 6 vs 16 days; P < .001). The 30-day mortality in the remdesivir/dexamethasone group was 1.3%, whereas in dexamethasone alone was 16% (P < .005). In the remdesivir/dexamethasone group compared to dexamethasone alone there was a reduction in hospitalization days (P < .0001) and a faster improvement in both respiratory function and inflammatory markers.

Conclusions: Remdesivir/dexamethasone treatment is associated with significant reduction in mortality, length of hospitalization, and faster SARS-CoV-2 clearance, compared to dexamethasone alone.