Background. Persistent nasal carriers have an increased risk of Staphylococcus aureus infection, whereas intermittent carriers and noncarriers share the same low risk. This study was performed to ...provide additional insight into staphylococcal carriage types. Methods. Fifty‐one volunteers who had been decolonized with mupirocin treatment and whose carriage state was known were colonized artificially with a mixture of S. aureus strains, and intranasal survival of S. aureus was compared between carriage groups. Antistaphylococcal antibody levels were also compared among 83 carriage‐classified volunteers. Results. Persistent carriers preferentially reselected their autologous strain from the inoculum mixture (P=.02). They could be distinguished from intermittent carriers and noncarriers on the basis of the duration of postinoculation carriage (154 vs. 14 and 4 days, respectively; P=.017, by log‐rank test). Cultures of swab samples from persistent carriers contained significantly more colony‐forming units per sample than did cultures of swab samples from intermittent carriers and noncarriers (P=.004). Analysis of serum samples showed that levels of immunoglobulin G and immunoglobulin A to 17 S. aureus antigens were equal in intermittent carriers and noncarriers but not in persistent carriers. Conclusions. Along with the previously described low risk of infection, intermittent carriers and noncarriers share similar S. aureus nasal elimination kinetics and antistaphylococcal antibody profiles. This implies a paradigm shift; apparently, there are only 2 types of nasal carriers: persistent carriers and others. This knowledge may increase our understanding of susceptibility to S. aureus infection.
Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) ...or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).
Infective endocarditis, osteomyelitis, and osteosynthesis-associated infections are mostly caused by Gram-positive bacteria. They are often difficult to treat and are associated with a poor ...prognosis. In the past 20 years, nine antibiotic drugs with predominant activity against Gram-positive bacteria have been introduced and approved by the Food and Drug Administration or the European Medicines Agency: ceftaroline, daptomycin, telavancin, dalbavancin, oritavancin, linezolid, tedizolid, delafloxacin, and omadacycline. This narrative review aims to provide an overview on these antibiotics with a special focus on their use in infective endocarditis, osteomyelitis, and osteosynthesis-associated infections. Although some of these approved antibiotics are promising, they should not be used as first- or second-line therapy, awaiting more clinical data.
Attempts to develop an efficient anti-staphylococcal vaccine in humans have so far been unsuccessful. Therefore, more knowledge of the antigens that are expressed by Staphylococcus aureus in human ...blood and induce an immune response in patients is required. In this study we further characterize the serial levels of IgG and IgA antibodies against 56 staphylococcal antigens in multiple serum samples of 21 patients with a S. aureus bacteremia, compare peak IgG levels between patients and 30 non-infected controls, and analyze the expression of 3626 genes by two genetically distinct isolates in human blood. The serum antibody levels were measured using a bead-based flow cytometry technique (xMAP®, Luminex corporation). Gene expression levels were analyzed using a microarray (BµG@s microarray). The initial levels and time taken to reach peak IgG and IgA antibody levels were heterogeneous in bacteremia patients. The antigen SA0688 was associated with the highest median initial-to-peak antibody fold-increase for IgG (5.05-fold) and the second highest increase for IgA (2.07-fold). Peak IgG levels against 27 antigens, including the antigen SA0688, were significantly elevated in bacteremia patients versus controls (P≤0.05). Expression of diverse genes, including SA0688, was ubiquitously high in both isolates at all time points during incubation in blood. However, only a limited number of genes were specifically up- or downregulated in both isolates when cultured in blood, compared to the start of incubation in blood or during incubation in BHI broth. In conclusion, most staphylococcal antigens tested in this study, including many known virulence factors, do not induce uniform increases in the antibody levels in bacteremia patients. In addition, the expression of these antigens by S. aureus is not significantly altered by incubation in human blood over time. One immunogenic and ubiquitously expressed antigen is the putative iron-regulated ABC transporter SA0688.
Detection of vancomycin-resistant
Enterococcus faecium
(VRE) is hampered by low sensitivity of rectal swab cultures. This study aimed to define the number of screening cultures needed to increase ...sensitivity to detect VRE transmission, and to determine time from presumed exposure to detectable colonization. In a tertiary care setting, we retrospectively analyzed data from 9 VRE outbreaks. As a proxy or estimation for time to detectable colonization, the time between first positive culture of the presumed index patient and that of their contacts was determined. Only 64% of secondary cases were positive in the first out of five cultures. By using the first three out of five rectal swabs, 89% (95%CI: 78–95%) of all secondary cases would have been identified. The median number of days between the positive culture of the index patient and the first positive culture of secondary cases was 9 days. Eleven percent of secondary cases would have been missed if only three rectal samples would have been obtained. Furthermore, our results show that one or more rectal swabs taken around day 9 after presumed exposure should at least be included in the screening approach. In our setting, obtaining a fourth and a fifth rectal swab showed a relevant additional value compared to only one to three swabs. Our findings are useful for determining the most effective VRE contact tracing approach to prevent transmission.
can colonize the human vestibulum nasi for many years. It is unknown whether and, how
adapts to this ecological niche during colonization. We determined the short (1 and 3 months) and mid-term (36 ...months) genomic evolution of
in natural carriers and artificially colonized volunteers. Eighty-five
strains were collected from 6 natural carriers during 3 years and 6 artificially colonized volunteers during 1 month. Multi-locus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis based on whole-genome sequencing (WGS) were carried out. Mutation frequencies within resident bacterial populations over time were quantified using core genome SNP counts (comparing groups of genomes) and pairwise SNP divergence assessment (comparing two genomes from strains originating from one host and sharing identical MLST). SNP counts (within 1-3 months) in all naturally colonizing strains varied from 0 to 757 (median 4). These strains showed random and independent patterns of pairwise SNP divergence (0 to 44 SNPs, median 7). When the different core genome SNP counts over a period of 3 years were considered, the median SNP count was 4 (range 0-26). Host-specific pairwise SNP divergence for the same period ranged from 9 to 57 SNPs (median 20). During short term artificial colonization the mutation frequency was even lower (0-7 SNPs, median 2) and the pairwise SNP distances were 0 to 5 SNPs (median 2). Quantifying mutation frequencies is important for the longitudinal follow-up of epidemics of infections and outbreak management. Random pattern of pairwise SNP divergence between the strains isolated from single carriers suggested that the WGS of multiple colonies is necessary in this context. Over periods up to 3 years, maximum median core genome SNP counts and SNP divergence for the strains studied were 4 and 20 SNPs or lower. During artificial colonization, where median core genome SNP and pairwise SNP distance scores were 2, there is no early stage selection of different genotypes. Therefore, we suggest an epidemiological cut off value of 20 SNPs as a marker of
strain identity during studies on nasal colonization and also outbreaks of infection.
This study investigated the frequency of change of the antimicrobial susceptibility pattern when the same isolate was found in the same patient in various situations. We used laboratory data ...collected over a period of 8 years (January 2014 to December 2021) at the clinical microbiology laboratory of a tertiary hospital for Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Staphylococcus aureus. Antimicrobial susceptibility tests (AST) were performed using Vitek 2 automated system. We determined essential agreement and categorical agreement, and introduced the new terms essential MIC increase and change from nonresistant to resistant to present changes in antimicrobial susceptibility over time. During the study period, 18,501 successive AST were included. The risk for S. aureus to be resistant to any antibiotic upon repeated culture was <10% during a follow-up of 30 days. For Enterobacterales, this risk was approximately 10% during a follow-up of 7 days. For P. aeruginosa, this risk was higher. The longer the follow-up period, the higher the risk that the bacteria would show phenotypic resistance. We also found that some drug-bug combinations were more likely to develop phenotypical resistance (i.e., E. coli/amoxicillin-clavulanic acid and E. coli/cefuroxime). A potential consequence of our finding is that if we regard a risk of resistance below 10% as acceptable, it may be feasible to omit follow-up AST within 7 days for the microorganisms investigated in this study. This approach saves money, time, and will reduce laboratory waste. Further studies are needed to determine whether these savings are in balance with the small possibility of treating patients with inadequate antibiotics.
Infective endocarditis (IE) is a life-threatening microbial infection of native and prosthetic heart valves, endocardial surface, and/or indwelling cardiac device. Prevalence of IE is increasing and ...mortality has not significantly improved despite technological advances. This review provides an updated overview using recent literature on the clinical presentation, diagnosis, imaging, causative pathogens, treatment, and outcomes in native valve, prosthetic valve, and cardiac device-related IE. In addition, the experimental approaches used in IE research to improve the understanding of disease mechanisms and the current diagnostic pipelines are discussed, as well as potential innovative diagnostic and therapeutic strategies. This will ultimately help towards deriving better diagnostic tools and treatments to improve IE patient outcomes.
Abstract
OBJECTIVES
Driveline infections continue to be a significant complication following left ventricular assist device (LVAD) implantation. Driveline exit-site care is crucial for the ...prevention of infections; however, there are no uniform guidelines. The goal of this study was to provide an overview of the currently published driveline exit-site care protocols in patients with LVAD.
METHODS
A systematic literature review was performed. Studies before 15 December 2020 were included if the number of driveline infections was a primary outcome and the driveline exit-site care protocol was explained.
RESULTS
Eleven articles were included in the systematic review, including 1602 patients with LVADs. The median of the frequency of driveline infections in the articles was 13.8% with a range of 0–52.6%. There was a marked variability in the methods of care of driveline exit sites, without a standardized driveline dressing technique in patients with LVADs. The frequency of driveline infections was 6–7.5% in studies using a dressing kit that included chlorhexidine, a silver-based dressing and an anchoring device. Furthermore, there was variability in the anchoring devices and the frequency of dressing changes, which varied from daily to weekly. No specific anchoring device or change frequency was found to be superior.
CONCLUSIONS
Based on this systematic review, driveline exit care protocols that included chlorhexidine, a silver-based dressing, the use of an anchoring device and dressing kits might be best in reducing driveline infection rates. However, prospective studies with larger cohorts are needed to establish the optimal protocol for driveline exit-site care.
The aim of this study was to describe the frequency of positive
tests in COVID-19 patients and investigate the association between COVID-19 and a positive
test result. We compared the proportion of ...positive
tests in COVID-19 patients admitted to the intensive care unit (ICU) for >24 h with two control groups: patients with community-acquired pneumonia with (i) a PCR-confirmed influenza infection (considered a positive control since the link between influenza and invasive aspergillosis has been established) and (ii)
pneumonia (in whom positive
tests are mostly considered as colonization). During the study period, 92 COVID-19 patients (mean standard deviation age, 62 14 years; 76.1% males), 48 influenza patients (55 14; 56.2% males), and 65 pneumococcal pneumonia patients (58 15, 63,1% males) were identified. Any positive
test from any respiratory sample was found in 10.9% of the COVID-19 patients, 6.2% of the patients with pneumococcal pneumonia, and 22.9% of those infected with influenza. A positive culture or PCR or galactomannan test on bronchoalveolar lavage (BAL) fluid only was found in 5.4% of COVID-19 patients, which was lower than in patients with influenza (18.8%) and comparable to that in the pneumococcal pneumonia group (4.6%). Using logistic regression analysis, the odds ratio (OR) (95% confidence interval) for a positive
test on BAL fluid for COVID-19 patients was 1.2 (0.3 to 5.1;
= 0.8) compared to the pneumococcal pneumonia group, while it was 0.2 (0.1 to 0.8;
= 0.02) compared to the influenza group. This difference remained significant when corrected for age and sex. In conclusion, in COVID-19 patients, the prevalence of a positive
test was comparable to that in patients admitted for pneumococcal pneumonia but substantially lower than what we observed in patients with influenza.
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