Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization.

The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1-5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2-also termed the Delta variant-is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein.

Efficacy of single antibiotic therapy versus antibiotic combination in implant-free staphylococcal post-surgical spinal infections: a retrospective observational study.

BACKGROUND: Post-surgical spinal infections (pSSIs) are a serious complication of spinal surgeries, with Staphylococcus spp. being one of the most prominent bacteria identified. Optimal antimicrobial therapy for staphylococcal spinal infections without spinal implants is not well documented. METHODS: This single center retrospective 7-year observational study described and compared the outcome (treatment failure or mortality rate one year after diagnosis) of 20 patients with staphylococcal-implant-free pSSI treated with single or combination antibiotics. RESULTS: Median duration of treatment was 40 days (IQR 38-42), with 6 days (IQR 5-7) on intravenous antibiotics and 34 days (IQR 30-36) on oral therapy. Four patients (20%) underwent new surgical debridement, all due to surgical failure, and 1 patient died within the first year without significant differences between both treatment group. CONCLUSION: This study raises the possibility of single antibiotic therapy for patients with implant-free post-surgical spinal infections due to Staphylococcus spp.

TIVAP-related infection due to Gram-negative aerobic bacilli: should TIVAP stay or should it go?

We aimed to describe the outcome of totally implantable venous-access port (TIVAP)-related infections due to Gram-negative aerobic bacilli (Pseudomonas aeruginosa and other Pseudomonas spp., Acinetobacter spp., and Stenotrophomonas maltophilia), or GNAB, and assess the safety of conservative treatment. We conducted a retrospective study in a French teaching hospital, from January 2016 to December 2020, including adult patients treated for TIVAP-related infection due to GNAB. Success of conservative treatment was defined as a functional TIVAP 3 months after infection with no recurrence. We performed a bivariate analysis and analyzed causes for treatment failure. We included 68 patients (53 TIVAP-related bloodstream infections, 11 TIVAP-related infections, and 4 probable TIVAP-related infections) due to GNAB, mostly P. aeruginosa (50/68, 74%). TIVAP removal was initially decided for 49/68 patients (72%). Among the 19/68 (28%) patients with conservative treatment (all for infections caused by P. aeruginosa), 5/19 (26%) had successful treatment, 7/19 (37%) experienced failure (without sepsis or septic shock), 6/19 (32%) died within 3 months without TIVAP removal and no signs of infection recurrence, and 1 patient had TIVAP removal as it was no longer required. TIVAP-related infections caused by GNAB frequently require TIVAP removal. Conservative treatment can be performed in selected patients with a non-complicated infection caused by P. aeruginosa, who can benefit from the continuation of antineoplastic chemotherapy or palliative care. Treatment failures were not associated with sepsis or septic shock.

Incidence of and risk factors for local complications of peripheral venous catheters in patients older than 70 years: Empirical research quantitative.

AIMS: To assess the incidence density of local complications of peripheral venous catheters in patients aged 70 years and older, to identify risk factors for local complications of peripheral venous catheters, to describe microbiological epidemiology and to assess the impact of complications on patient outcomes. DESIGN: Prospective, observational, single-centre study. METHODS: Patients 70 years and older admitted to the geriatric department of a teaching hospital in France between December 2019 and May 2020 were considered for inclusion if they had a peripheral venous catheter during their stay. Nurses checked the catheter insertion site three times a day for local complications; physicians ensured the follow-up of complications. The STROBE checklist was used in this prospective observational study. RESULTS: A total of 322 patients were included, with 849 peripheral venous catheters; the median age was 88 years and 182 (56.5%) were women. The incidence density of local complications was 50.5/1000 peripheral venous catheter-days. Risk factors for local complications on multivariate analysis were dressing replacement (OR 1.18), furosemide (OR 1.11) and vancomycin (OR 1.60) infusion, urinary continence (OR 1.09) and hematoma at the catheter insertion site (OR 1.15). Thirteen cellulitis and three abscesses were diagnosed. Occurrence of a local complication was associated with a 3-day increased duration of hospital stay (17 vs. 14 days). CONCLUSION: Risk factors for peripheral venous catheter local complications include urinary continence, furosemide or vancomycin infusion, hematoma at the peripheral venous catheter insertion site or dressing replacement. IMPLICATION FOR THE PATIENT CARE: Closer clinical monitoring may help reduce the occurrence of local peripheral venous catheters complication in patients 70 years and older. RELEVANCE TO CLINICAL PRACTICE: Patients at greater risk of peripheral venous catheter local complications deserve closer clinical monitoring or improved preventive measures, which may be beneficial to reduce the length of hospital stay. NO PATIENT OR PUBLIC CONTRIBUTION: The study was designed to describe risk factors for local complications of peripheral venous catheters in order to reinforce surveillance in this specific population by nurses and medical staffs. Patients had their peripheral venous catheter insertion site checked thrice a day by the nurse in charge as part of usual care. They, as service users, caregivers or members of the public, were not solicited for data collection, analysis, interpretation or preparation of the manuscript.

Faecal carriage of multidrug-resistant bacteria and associated risk factors: results from a point prevalence study.

OBJECTIVES: Since 2003, incidences of carbapenemase-producing Gram-negative bacilli (CP-GNB) and vancomycin-resistant Enterococcus faecium (VRE) have steadily increased in France. We therefore conducted a point prevalence study to estimate carriage rates of CP-GNB, VRE and ESBL-producing Enterobacterales (ESBL-PE) and associated risk factors. METHODS: Between September 2019 and January 2020, all inpatients hospitalized on a given day in 11 teaching hospitals in the Paris urban area were eligible. Patient interviews and rectal swab screening results were recorded by dedicated nurses. The swabs were plated onto selective chromogenic media and processed using the GeneXpert® system. RESULTS: Of 2396 patients, 364 (15.2%) yielded at least one multiresistant bacterial isolate, including 29 CP-GNB carriers (1.2%), 13 VRE carriers (0.5%) and 338 ESBL-PE carriers (14%). In 15 patients (4.4% of ESBL-PE carriers and 36.6% of CP-GNB/VRE carriers), concomitant CP-GNB/VRE and ESBL-PE carriage was observed. In 7/29 CP-GNB and 7/13 VRE carriers, carbapenemase production and vanA in the screening samples was only detected with Xpert® tests. The OXA-48 gene was predominant in 13/34 CP-GNB isolates from 29 carriers. From the 338 ESBL-PE carriers, 372 isolates were recovered, mainly Escherichia coli (61.2%). Among 379 children, 1.1% carried a CP-GNB/VRE strain, and 12.4% carried an ESBL strain. Previous hospitalization outside mainland France, previous antimicrobial treatment and previous ESBL-PE carriage were the main risk factors associated with CP-GNB and/or VRE carriage. CONCLUSIONS: The low CP-GNB and VRE prevalence likely reflects the French policy to limit intrahospital spread of CP-GNB and VRE strains.

Long-lasting successful dissemination of resistance to oxazolidinones in MDR Staphylococcus epidermidis clinical isolates in a tertiary care hospital in France.

OBJECTIVES: Patient- and procedure-related changes in modern medicine have turned CoNS into one of the major nosocomial pathogens. Treatments of CoNS infections are challenging owing to the large proportion of MDR strains and oxazolidinones often remain the last active antimicrobial molecules. Here, we have investigated a long-lasting outbreak (2010-13) due to methicillin- and linezolid-resistant (LR) CoNS (n = 168), involving 72 carriers and 49 infected patients. METHODS: Antimicrobial susceptibilities were tested by the disc diffusion method and MICs were determined by broth microdilution or Etest. The clonal relationship of LR Staphylococcus epidermidis (LRSE) was first determined using a semi-automated repetitive element palindromic PCR (rep-PCR) method. Then, WGS was performed on all cfr-positive LRSE (n = 30) and LRSE isolates representative of each rep-PCR-defined clone (n = 17). Self-transferability of cfr-carrying plasmids was analysed by filter-mating experiments. RESULTS: This outbreak was caused by the dissemination of three clones (ST2, ST5 and ST22) of LRSE. In these clones, linezolid resistance was caused by (i) mutations in the chromosome-located genes encoding the 23S RNA and L3 and L4 ribosomal proteins, but also by (ii) the dissemination of two different self-conjugative plasmids carrying the cfr gene encoding a 23S RNA methylase. By monitoring linezolid prescriptions in two neighbouring hospitals, we highlighted that the spread of LR-CoNS was strongly associated with linezolid use. CONCLUSIONS: Physicians should be aware that plasmid-encoded linezolid resistance has started to disseminate among CoNS and that rational use of oxazolidinones is critical to preserve these molecules as efficient treatment options for MDR Gram-positive pathogens.

Multiplex PCR for detection of seven virulence factors and K1/K2 capsular serotypes of Klebsiella pneumoniae.

A single multiplex PCR assay targeting seven virulence factors and the wzi gene specific for the K1 and K2 capsular serotypes of Klebsiella pneumoniae was developed and tested on 65 clinical isolates, which included 45 isolates responsible for community-acquired severe human infections. The assay is useful for the surveillance of emerging highly virulent strains.

Complete nucleotide sequence of the first KPC-2- and SHV-12-encoding IncX plasmid, pKpS90, from Klebsiella pneumoniae.

We report the complete nucleotide sequence of the pKpS90 plasmid, carrying the bla(KPC-2) and bla(SHV-12) genes. This plasmid was isolated from a sequence type 258 (ST258) Klebsiella pneumoniae strain responsible for an outbreak in a French university hospital in 2009. pKpS90 is a 53,286-bp plasmid that belongs to the IncX incompatibility group. pKpS90 consists of a backbone from IncX plasmids, in which the KPC-2-encoding Tn4401 transposon and a bla(SHV-12)-encoding region have been inserted.

wzi Gene sequencing, a rapid method for determination of capsular type for Klebsiella strains.

Pathogens of the genus Klebsiella have been classified into distinct capsular (K) types for nearly a century. K typing of Klebsiella species still has important applications in epidemiology and clinical microbiology, but the serological method has strong practical limitations. Our objective was to evaluate the sequencing of wzi, a gene conserved in all capsular types of Klebsiella pneumoniae that codes for an outer membrane protein involved in capsule attachment to the cell surface, as a simple and rapid method for the prediction of K type. The sequencing of a 447-nucleotide region of wzi distinguished the K-type reference strains with only nine exceptions. A reference wzi sequence database was created by the inclusion of multiple strains representing K types associated with high virulence and multidrug resistance. A collection of 119 prospective clinical isolates of K. pneumoniae were then analyzed in parallel by wzi sequencing and classical K typing. Whereas K typing achieved typeability for 81% and discrimination for 94.4% of the isolates, these figures were 98.1% and 98.3%, respectively, for wzi sequencing. The prediction of K type once the wzi allele was known was 94%. wzi sequencing is a rapid and simple method for the determination of the K types of most K. pneumoniae clinical isolates.

Prevalence and risk factors of toxigenic Clostridioides difficile asymptomatic carriage in 11 French hospitals.

Clostridioides difficile infection (CDI) incidence has increased over the last 20 years. Studies suggest that asymptomatic carriers may be an important reservoir of C. difficile in healthcare settings. We conducted a point prevalence study to estimate the toxigenic C. difficile asymptomatic carriage rate and the associated risk factors in patients >3 years old. Between September 16, 2019 and January 15, 2020, all patients hospitalized in 11 healthcare facilities in the Paris urban area were included in the study. They were screened on the day of the survey for toxigenic C. difficile carriage by rectal swab and interviewed. Isolates were characterized by PCR ribotyping and multiplex PCR targeting toxin genes. A logistic regression model was used to determine the risk factors associated with toxigenic C. difficile asymptomatic carriage using uni- and multivariate analysis in the subpopulation of patients >3 years old. During the study period, 2,389 patients were included and screened. The median age was 62 years (interquartile range 35-78 years) and 1,153 were male (48.3%). Nineteen patients had a previous CDI (0.9%). Overall, 185/2389 patients were positive for C. difficile (7.7%), including 93 toxigenic strains (3.9%): 77 (82.8%) were asymptomatic (prevalence 3.2%) whereas 12 (12.9%) were diarrheic. Prevalences of toxigenic C. difficile were 3.5% in patients >3 years old and 7.0% in ≤3 years old subjects, respectively. Toxigenic strains mainly belonged to PCR ribotypes 106 (n = 14, 15.0%), 014 (n = 12, 12.9%), and 020 (n = 10, 10.8%). Among toxigenic strains, 6 (6.4%) produced the binary toxin. In multivariate analysis, two factors were positively associated with toxigenic C. difficile asymptomatic carriage in patients >3 years old: multidrug-resistant organisms co-carriage [adjusted Odd Ratio (aOR) 2.3, CI 95% 1.2-4.7, p = 0.02] and previous CDI (aOR 5.8, CI 95% 1.2-28.6, p = 0.03). Conversely, consumption of raw milk products were associated with reduced risk of toxigenic C. difficile colonization (aOR 0.5, CI 95% 0.2-0.9, p = 0.01). We showed that there was a low prevalence of asymptomatic toxigenic C. difficile carriage in hospitalized patients. Consumption of raw milk prevents toxigenic C. difficile colonization, probably due to the barrier effect of milk-associated bacteria.

No SARS-CoV-2 reinfection among staff health-care workers: Prospective hospital-wide screening during the first and second waves in Paris.

OBJECTIVES: Risk of reinfection with SARS-CoV-2 among health-care workers (HCWs) is unknown. We assessed the incidence rate of SARS-CoV-2 reinfection in the real-life setting of a longitudinal observational cohort of HCWs from the Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, France, during the first and second waves of COVID-19 epidemic. METHODS: From March to December 2020, HCWs were subjected to molecular and serology testing of SARS-CoV-2. Reinfection was defined as a positive test result during the first wave, either by serology or PCR, followed by a positive PCR during the second wave. Evolution of COVID-19 status of HWCs was assessed by a Sankey diagram. RESULTS: A total of 7765 tests (4579 PCR and 3186 serology) were carried out and 4168 HCWs had at least one test result during the follow-up period with a positivity rate of 15.9%. No case of reinfection during the second wave could be observed among 102 positive HCWs of the first wave, nor among 175 HCWs found positive by PCR during the second wave who were negative during the first wave. CONCLUSIONS: SARS-CoV-2 reinfection was not observed among HCWs, suggesting a protective immunity against reinfection that lasts at least 8 months post infection.

Link between carbapenemase-producing Enterobacteria carriage and cross-border exchanges: eight-year surveillance in a large French multihospitals institution.

Assistance Publique-Hôpitaux de Paris launched a specific strategy to survey and control the spread of emerging multidrug-resistant bacteria such as carbapenemase-producing Enterobacteria (CPE). Among the 63 CPE events that occurred between 2004 and 2011, 87% involved patients with a link with cross-border exchanges, justifying the recommendation to screen and isolate such patients.

First outbreak of multidrug-resistant Klebsiella pneumoniae carrying blaVIM-1 and blaSHV-5 in a French university hospital.

OBJECTIVES: We studied eight imipenem-resistant isolates of Klebsiella pneumoniae involved in an outbreak in a French teaching hospital. METHODS: The eight isolates were recovered from clinical specimens or rectal swabs. Antibiotic susceptibilities were determined using standard agar diffusion and dilution methods including synergy tests. PFGE was used to study the relatedness of isolates. Genes encoding beta-lactamases were characterized by transfer assays, specific amplification and cloning. RESULTS: The eight isolates were closely related by PFGE analysis and highly related to a K. pneumoniae strain from Greece. They were highly resistant to beta-lactams, including aztreonam and imipenem (MIC > or =32 mg/L), and were positive by the imipenem-EDTA disc synergy test. Isolates were also resistant to aminoglycosides, newer quinolones and sulfamethoxazole, and showed an intermediate level of resistance to tetracycline. VIM-1 and SHV-5 beta-lactamases were revealed in all isolates by PCR. The analysis of plasmid contents of Escherichia coli DH10B electroporants expressing the VIM-1 beta-lactamase or the SHV-5 beta-lactamase confirmed that the two enzymes were coded by two different plasmids. The bla(VIM-1) gene was part of a class 1 integron that also included aac6, dhfrI and aadA genes and was similar to those reported from strains isolated in Greece. CONCLUSIONS: This study confirms the potential risk of spread of multiresistant bacteria with international transfer of patients.