•We reviewed the evidence on duration of antibiotic treatment for adults with uncomplicated Staphylococcus aureus bacteremia.•Antibiotic courses of less than 14 days could be considered on a ...case-by-case basis as this practice was not associated with higher mortality.
Staphylococcus aureus is an important cause of bloodstream infections. We aimed to summarize associations between different antibiotic durations (<14 days versus standard durations of ≥ 14 days) and patient outcomes in adult patients with uncomplicated Staphylococcus aureus bacteremia (SAB).
We searched the research literature up to 07/07/2022 for studies with direct comparison of shorter (<14 days) versus standard (≥14 days) antibiotic durations for treatment of SAB against short-term mortality and/or other patient outcomes. Crude odds ratios (ORs) were pooled through fixed and random effects analyses. Sub-group analyses were performed to evaluate differences between older versus more recent studies and between studies addressing selected versus comprehensive patient populations.
3,121 unique references were screened of which six met eligibility criteria. All were observational cohort studies from high-income countries published between 2001 and 2020. No consistent definition of “uncomplicated” SAB was found. In total, 2,150 patients with uncomplicated SAB from 21 hospitals were included; of these 758 (35 %) were treated with < 14 days of antibiotics. Using a fixed-effects meta-analysis, no association was found between treatment duration (<14 days versus ≥ 14 days) and 90-day mortality risk (pooled OR 1.12; 95 %CI 0.86–1.45, p = 0.40) or relapse (pooled OR 2.13; 95 %CI 0.11–42.73, p = 0.62). Sub-group analyses did not reveal any further differences and publication bias seemed unlikely (Egger test p = 0.6).
Based on evidence from six observational studies, treating uncomplicated SAB with less than 14 days of antibiotics was not associated with higher 90-day mortality or relapse risk, although the confidence interval for relapse risk was wide and bias and confounding cannot be excluded. Shorter treatment for uncomplicated SAB could therefore be considered as a treatment option. Randomized non-inferiority trials are needed to give a definitive answer to this question.
We aim to describe the epidemiological, clinical and microbiological characteristics of the linezolid- and vancomycin- resistant Enterococcus faecium (LVRE) in a tertiary care hospital in Germany.
We ...conducted a retrospective analysis of 196 LVRE cases observed from 1st January 2012 to 31th December 2018. Patients’ medical charts were reviewed and available LVRE (n = 102) were subjected to whole-genome-sequencing. Antibiotic consumption was measured in defined daily dose (DDD)/100 bed-days (BD).
The prevalence of LVRE isolates among VRE was 6.3 % in 2018. Most patients had an onco-hematological disease (134/196, 68.4 %). From 2012–2018 an increase of +356.7 % of linezolid defined daily dose/100 bed-days was observed. In 71.4 % (90/126, 70 missing values) of the patients, linezolid was prescribed in the previous 6 months. The median exposure to linezolid was 15 days (Interquartile, IQR 9–23). 42/196 (21.4 %) patients had an LVRE-related infection with an overall 30-day mortality rate of 33 %. In 121/196 (61.7 %) patients, linezolid-susceptible VREfm were isolated before LVRE, suggesting secondary acquisition of linezolid resistance. Genetic analysis revealed that most isolates belonged to ST117 (64/102 available isolates, 62.7 %). The G2576T 23S rDNA mutation was identified as the most common resistance mechanism (96/102, 94.1 %). poxtA was identified in two isolates, while cfr, and optrA were not detected.
Incidence of LVRE related to 23S rDNA mutations is rising and probably associated with antibiotic consumption. Restrictions in the use of linezolid may be needed in order to retain therapeutic options in VRE.
This study investigates preexisting and vaccine-induced vector immunity in 30 participants of a Phase-1 VSV-EBOV Ebola vaccine trial. No preexisting immunity was detected, however humoral and ...cell-mediated immunity against internal VSV proteins was observed in up to 36% of vaccines.
Abstract
In response to the Ebola virus (EBOV) crisis of 2013–2016, a recombinant vesicular stomatitis virus (VSV)–based EBOV vaccine was clinically tested (NCT02283099). A single-dose regimen of VSV-EBOV revealed a safe and immunogenic profile and demonstrated clinical efficacy. While EBOV-specific immune responses to this candidate vaccine have previously been investigated, limited human data on immunity to the VSV vector are available. Within the scope of a phase 1 study, we performed a comprehensive longitudinal analysis of adaptive immune responses to internal VSV proteins following VSV-EBOV immunization. While no preexisting immunity to the vector was observed, more than one-third of subjects developed VSV-specific cytotoxic T-lymphocyte responses and antibodies.
So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a ...genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant. The infectious virus was shed from the patient during the second infection episode despite the presence of neutralizing antibodies in her blood. Our data indicate that a moderate immune response after the first infection, but not a viral escape, did allow for reinfection and live virus shedding.
The global epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is heterogeneous. The objective of this study was to evaluate MRSA epidemiology in Switzerland over an 11-year period.
We ...conducted a retrospective study with time series analysis on S. aureus including MRSA and non-multidrug resistant MRSA (NmMRSA). We used NmMRSA as a marker for community-acquired MRSA. NmMRSA was defined as MRSA susceptible to at least three of the following agents: ciprofloxacin, clindamycin, tetracycline and trimethoprim-sulfamethoxazole.
A total of 14 648 MRSA and 115 917 methicillin-susceptible S. aureus (MSSA) isolates were included. Despite an overall decrease of the proportion of MRSA among S. aureus clinical isolates (from 14% in 2004 to 8% in 2014), an increasing trend in NmMRSA was observed. Variations in geographical distribution were noted, with a decrease in the proportion of MRSA in the Italian- and French-speaking regions (from 20-26% in 2004 to 12% in 2014) and low prevalence (3-5%) in the German-speaking region. We noticed an increase in the proportion of MRSA in outpatients (+0.03% per quarter per year) and in the younger population (+0.05% per quarter per year) compared with a decreasing trend in inpatients and the elderly.
The proportion of MRSA among S. aureus isolates in Switzerland decreased overall from 2004 to 2014. Worrisome increases of NmMRSA were found in younger persons and outpatients.
The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I ...clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date.
Methods: We recruited 30 healthy subjects aged 18–55 into an open-label, dose-escalation phase I trial testing three doses of rVSV-ZEBOV (3×105 plaque-forming units (PFU), 3×106 PFU, 2×107 PFU) (ClinicalTrials.gov; NCT02283099). Main study objectives were safety and immunogenicity, while exploratory objectives included lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were assessed using flow cytometry, ELISpot and LUMINEX assay.
Findings: Immunization with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse events. Ebola virus-specific neutralizing antibodies were induced in nearly all individuals. Additionally, vaccinees, particularly within the highest dose cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a cascade of signaling molecules following stimulation of peripheral blood mononuclear cells with Ebola GP peptides.
Interpretation: In addition to a benign safety and robust humoral immunogenicity profile, subjects immunized with 2×107 PFU elicited higher cellular immune responses and stronger interlocked cytokine networks compared to lower dose groups. To our knowledge these data represent the first detailed cell-mediated immuneprofile of a clinical trial testing rVSV-ZEBOV, which is of particular interest in light of its potential upcoming licensure as the first Ebola vaccine.
VEBCON trial Hamburg, Germany (NCT02283099).
•A phase I clinical trial was conducted to investigate the live-attenuated Ebola vaccine rVSV-ZEBOV.•Ebola-specific humoral and cell-mediated immune responses show a favorable profile for subjects immunized with 2×107 PFU of rVSV-ZEBOV.•The highest dose cohort induced stronger antigen-specific CTL-responses and interlocked cytokine networks compared to lower dose groups.
rVSV-ZEBOV is the first Ebola vaccine with human efficacy data, currently undergoing an accelerated licensing process. Nevertheless, to date no human immunological correlate of protection has been identified and mechanisms of immune responses elicited by rVSV-ZEBOV remain incompletely understood.
We conducted a phase I trial to test rVSV-ZEBOV in 30 healthy subjects using three dosage levels. We here present a comprehensive evaluation of humoral and cell-mediated responses with an in-depth analysis of signaling molecules following ex vivo stimulation with Ebola GP peptides. Our data suggest a favorable immune response profile for subjects immunized with 2×107 PFU.
These data address critical knowledge gaps with respect to mechanisms of immuneprotection in the context of Ebola vaccines and may provide additional evidence to support the current dosage used in later stage clinical trials.
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Background: The recent emergence of distinct and highly successful SARS-CoV-2 lineages has substantial implications for individual patients and public health measures. While ...next-generation-sequencing is routinely performed for surveillance purposes, RT-qPCR can be used to rapidly rule-in or rule-out relevant variants, e.g., in outbreak scenarios. The objective of this study was to create an adaptable and comprehensive toolset for multiplexed Spike-gene SNP detection, which was applied to screen for SARS-CoV-2 B.1.617 lineage variants. Methods: We created a broad set of single nucleotide polymorphism (SNP)-assays including del-Y144/145, E484K, E484Q, P681H, P681R, L452R, and V1176F based on a highly specific multi-LNA (locked nucleic acid)-probe design to maximize mismatch discrimination. As proof-of-concept, a multiplex-test was compiled and validated (SCOV2-617VOC-UCT) including SNP-detection for L452R, P681R, E484K, and E484Q to provide rapid screening capabilities for the novel B.1.617 lineages. Results: For the multiplex-test (SCOV2-617VOC-UCT), the analytic lower limit of detection was determined as 182 IU/mL for L452R, 144 IU/mL for P681R, and 79 IU/mL for E484Q. A total of 233 clinical samples were tested with the assay, including various on-target and off-target sequences. All SNPs (179/179 positive) were correctly identified as determined by SARS-CoV-2 whole genome sequencing. Conclusion: The recurrence of SNP locations and flexibility of methodology presented in this study allows for rapid adaptation to current and future variants. Furthermore, the ability to multiplex various SNP-assays into screening panels improves speed and efficiency for variant testing. We show 100% concordance with whole genome sequencing for a B.1.617.2 screening assay on the cobas6800 high-throughput system.
We have recently shown a high prevalence of diabetes and obesity in rural Cameroon, despite an improved lifestyle. Diabetes in rural Africa remains underdiagnosed and its role in increasing risk of ...atherosclerosis in these populations is unknown. We investigated the prevalence of carotid atherosclerosis and cardiovascular risk factors in a population of subjects with recently-diagnosed diabetes from rural Cameroon.
In a case-control study, carotid intima-media thickness (IMT) was measured in 74 subjects with diabetes (diagnosed <2 years), aged 47-85 and 109 controls comparable for age and sex. Subjects were recruited during a health campaign conducted in April 2009. Blood glucose control (HbA1c, fasting blood glucose) and major cardiovascular risk factors (complete lipid panel, blood pressure) were also measured. Mean carotid IMT was higher in subjects with diabetes than healthy controls at each scanned segment (common, internal carotid and bulb) (P<0.05), except the near wall of the left bulb. Vascular stiffness tended to be higher and pressure-strain elastic modulus of the left carotid was increased in subjects with diabetes than controls (P<0.05), but distensibility was similar between the two groups. At least one plaque >0.9 mm was found in 4%, 45.9% and 20% of diabetic subjects at the common, bulb or internal carotid, respectively. Only 25% of patients had an HbA1c<7%, while over 41.6% presented with marked hyperglycemia (HbA1c>9%). The prevalence of diabetic subjects with abnormal levels of LDL-cholesterol, triglycerides, HDL-cholesterol or blood pressure was 45%, 16.6%, 15% and 65.7%, respectively.
Carotid thickness is increased in subjects with diabetes from a rural area of Cameroon, despite the relatively recent diagnosis. These findings and the high rate of uncontrolled diabetes in this population support the increasing concern of diabetes and cardiovascular diseases in African countries and indicate the need for multifaceted health interventions in urban and rural settings.
Abstract
Background
The emergence of antibiotic-resistant species calls for fast and reliable phenotypic susceptibility testing to adapt clinical management as fast as possible.
Objectives
We ...assessed the real-life performance of EUCAST rapid antimicrobial susceptibility testing (RAST) and analysed its impact on patient management.
Methods
RAST was performed on clinical blood cultures containing Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii complex. Categorical agreement with VITEK2 was analysed. A pre-post quasi-experimental observational study was designed to compare antibiotic treatment in sepsis patients in the RAST patient group (n = 51) and a historical control cohort (n = 54).
Results
In total, 436 isolates, corresponding to 2314 disc diameters, were measured; 18.4% of these measurements were in the area of technical uncertainty. For the 81.6% categorical results, which could be compared, 94.7% were in agreement, whereas 5.3% of the results were not. In the RAST group, optimal therapy was initiated on the same day as blood culture positivity, while this was the case in the historical group after 24 h. In six cases, RAST allowed for rapid antibiotic escalation. The 30 day mortality rate was lower in the RAST group, although this was not statistically significant.
Conclusions
RAST provides a reliable tool to improve clinical management of sepsis patients by providing rapid phenotypic susceptibility data. While not necessarily being an instrument for de-escalation, especially in areas of low prevalence, early detection allows for timely coverage of resistant isolates. Thus, RAST significantly adds to successful antibiotic stewardship programmes.
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