Daily Respiratory Research Analysis

BACKGROUND: Based on high population immunity to SARS-CoV-2 from prior infection, vaccination, or both, in fall 2023, regulatory agencies globally authorized/approved a single mRNA XBB.1.5-adapted vaccine dose for individuals aged ≥5 years regardless of prior vaccination. METHODS: We conducted a systematic review on vaccine effectiveness (VE) of a single COVID-19 mRNA dose in individuals with a history of prior infection compared to individuals who were (i) SARS-CoV-2 naïve, (ii) unvaccinated with prior infection, and (iii) vaccinated with >1 dose with or without prior infection. We searched MEDLINE and Embase for studies published January 2021-October 2023. Data were synthesized following Synthesis Without Meta-Analysis guidelines; bias was assessed using the Newcastle-Ottawa Scale. This study was registered with PROSPERO (CRD42023453257). RESULTS: Eighteen studies were eligible. None of these studies reported bivalent or XBB.1.5-adapted VE, and none reported VE for immunocompromised populations or children aged <5 years. Among those with prior infection, a single mRNA dose increased protection by 8-71% against infection (during Omicron BA.1, BA.4/5, or XBB predominance), 39-67% against symptomatic infection (BA.1, BA.2, or BA.4/5), and 25-60% against hospitalization or hospitalization or death (BA.1). VE of one dose was comparable to two doses among those with prior infection, and higher than following two doses without prior infection. CONCLUSIONS: A single dose of original mRNA COVID-19 vaccine provides similar protection to two doses for immunocompetent individuals aged ≥5 years in the current setting of high pre-existing immunity. This supports current recommendations for one dose to be given in advance of the respiratory season, regardless of history of infection or vaccination, with considerations for additional doses for certain populations including young children, older adults, and the immunocompromised.

BACKGROUND: Infections are the second leading cause of death in patients with cancer and are often caused by resistant bacteria. However, the frequency of antimicrobial resistance (AMR) in outpatients with cancer is not well understood. We aimed to compare the frequency of AMR bacterial pathogens in outpatients with and without cancer. METHODS: This retrospective cohort study evaluated antimicrobial susceptibility of bacteria isolated from adults (aged ≥18 years) with and without cancer seeking care in 198 outpatient health-care settings in the USA. Data were collected using the BD Insights Research Database. Patients who were not prescribed cancer medications or not admitted to an inpatient cancer unit in the predefined period were categorised as patients without cancer. Patients were included in the cancer cohort if they received medication solely or sometimes indicated for cancer. Data on gender and race or ethnicity were not collected. Non-duplicate and non-contaminant pathogens collected from various samples (ie, blood, intra-abdominal, respiratory, urine, skin or wound, and other) in outpatients were used to assess the coprimary outcomes: overall and source-specific proportions of non-susceptible pathogen isolates with corresponding AMR odds ratios (ORs); and rates of AMR pathogens per 1000 isolates with corresponding AMR incidence rate ratio (IRR) in patients with and without cancer. FINDINGS: Data were collected between April 1, 2018, and Dec 31, 2022. 53 006 (3·2%) of 1 655 594 pathogens identified were from 27 421 patients with cancer and 1 602 588 (96·8%) were from 928 128 patients without cancer. For Pseudomonas aeruginosa, carbapenem non-susceptibility was higher in pathogen isolates from patients with cancer (816 [14·4%] of 5683) than patients without cancer (10 709 [11·3%] 94 419; OR 1·22 [95% CI 1·13-1·32]). For Enterobacterales, fluoroquinolone non-susceptibility was higher in pathogen isolates from patients with cancer (8662 [28·0%] of 30 867) than patients without cancer (238 479 [21·8%] of 1 095 996; OR 1·44 [1·40-1·47]), as was carbapenem non-susceptibility (472 [1·5%] of 30 867 vs 9165 [0·8%] of 1 095 996; OR 1·89 [1·72-2·07]), multidrug-resistant pathogens (2672 [8·7%] of 30 867 vs 48 962 [4·5%] of 1 095 996; OR 2·03 [1·95-2·11]), and extended-spectrum β-lactamase producers (4343 [16·5%] of 26 327 vs 93 977 [9·4%] of 996 853; OR 1·96 [1·90-2·03]). For Staphylococcus aureus, meticillin resistance was higher in pathogen isolates from patients with cancer (4747 [53·0%] of 8959) than patients without cancer (129 291 [48·3%] of 267 520; OR 1·20 [1·15-1·25]). For Enterococcus spp, vancomycin resistance was higher in pathogen isolates from patients with cancer (1329 [18·6%] of 7145) than patients without cancer (12 333 [9·1%] of 135 772]; ORR 2·20 [2·06-2·34). The rates and corresponding IRRs of AMR pathogens per 1000 isolates was also higher in patients with cancer compared with patients without cancer, particularly for carbapenem non-susceptible P aeruginosa (IRR 2·06 [1·91-2·21]) and vancomycin-resistant enterococci (IRR 3·06 [2·89-3·24]). For all comparisons, p<0·0001. INTERPRETATION: AMR proportions and IRRs for most key pathogens were up to three-times higher in isolates from outpatients with cancer than those without cancer, highlighting the need for enhanced surveillance, infection prevention, and timely diagnostic stewardship to improve antibiotic prescribing in this population. FUNDING: AMR Action Fund.

OBJECTIVES: Viral respiratory infections can be complicated by bacterial superinfections. SARS-CoV-2 patients may suffer from superinfections, and negative effects of additional infections have been identified. When analysing hospital data, patients typically leave the facility of observation, due to discharge or death, which leads to changes in the study cohort over time. This may distort the estimate of the impact of superinfection. Therefore, it is essential for the statistical analysis of hospital data to acknowledge this change of the risk set over time. We analysed superinfections in a retrospective cohort study with 268 critically ill patients, taking into account discharge and death as competing risks in the statistical analysis. METHODS: We evaluated bacterial respiratory infections and bloodstream infections and used multi-state statistical modelling to account for the different patient states. We calculated risks of superinfection, probability of discharge or death over time and analysed subgroups according to age and sex. RESULTS: The observed pathogen spectrum was mainly composed of Enterobacterales, Nonfermenters but also Staphylococcus aureus. We identified an elevated mortality due to bacterial infection of the respiratory tract or bloodstream infection (adj. cause-specific HR 1.7, CI 1.15-2.52) as well as a reduced discharge rate (adj. cause-specific HR 0.51, CI 0.36-0.73). Female patients showed a tendency to have a reduced risk of acquiring a superinfection (adj. subdistribution HR 0.71, CI 0.48-1.04), and in case of infection a higher mortality compared to male patients (interaction effect HR 1.49, CI 0.67-3.30). CONCLUSIONS: The study accounts for competing risks and quantifies the risk of death associated with bacterial superinfection in critically ill COVID-19 patients. We observed an increased risk of death for patients who developed a superinfection, with Enterobacterales being the predominant agent. The results emphasize the need for microbiological sampling in SARS-CoV-2-infected patients. CLINICAL TRIAL NUMBER: German Clinical Trials Register number: DRKS00031367, registration date: 01.03.2023 ( https://drks.de/search/de/trial/DRKS00031367 ).