Impact of Low-Level-Viremia on HIV-1 Drug-Resistance Evolution among Antiretroviral Treated-Patients

to determine the emergence and evolution of DRAM during LLV in HIV-1-infected patients while receiving antiretroviral therapy (ART).Retrospective analysis of patients presenting a LLV episode defined as pVL between 40 and 500 c/mL on at least 3 occasions during a 6-month period or longer while on the same ART. Resistance genotypic testing was performed at the onset and at the end of LLV period. Emerging DRAM was defined during LLV if never detected on baseline genotype or before.48 patients including 4 naive and 44 pretreated (median 9 years) presented a LLV episode with a median duration of 11 months. Current ART included 2NRTI (94%), ritonavir-boosted PI (94%), NNRTI (23%), and/or raltegravir (19%). Median pVL during LLV was 134 c/mL. Successful resistance testing at both onset and end of the LLV episode were obtained for 37 patients (77%), among who 11 (30%) acquired at least 1 DRAM during the LLV period: for NRTI in 6, for NNRTI in 1, for PI in 4, and for raltegravir in 2. During the LLV period, number of drugs with genotypic resistance increased from a median of 4.5 to 6 drugs. Duration and pVL level of LLV episode, duration of previous ART, current and nadir CD4 count, number of baseline DRAM and GSS were not identified as predictive factors of resistance acquisition during LLV, probably due to limited number of patients.Persistent LLV episodes below 500 c/ml while receiving ART is associated with emerging DRAM for all drug classes and a decreasing in further therapeutic options, suggesting to earlier consider resistance monitoring and ART optimization in this setting

Evolution de la résistance du VIH-1 aux antirétroviraux chez des patients avec une virémie résiduelle persistante

PARIS-BIUP (751062107) / SudocSudocFranceF

Outbreak of NDM-1-producing Klebsiella pneumoniae in the intensive care unit during the COVID-19 pandemic: Another nightmare

International audienceAn outbreak of Klebsiella pneumoniae producing the carbapenemase NDM-1 occurred in our ICU during the last COVID-19 wave. Twelve patients were tested positive, seven remained asymptomatic whereas 5 developed an infection. Resistome and in silico multilocus sequence typing confirmed the clonal origin of the strains. The identification of a possible environmental reservoir suggested that difficulties in observing optimal bio-cleaning procedures due to workload and exhaustion contributed to the outbreak besides the inappropriate excessive glove use

Surging bloodstream infections and antimicrobial resistance during the first wave of COVID-19: a study in a large multihospital institution in the Paris region

International audienceObjectivesWe measured the impact of the first wave of COVID-19 (March-April 2020) on the incidence of bloodstream infections (BSIs) during at the Assistance Publique - Hôpitaux de Paris (APHP), the largest multisite public healthcare institution in France.MethodsThe number of patient admissions blood cultures (BCs) collected, positive BCs as well as antibiotic resistance and consumption was retrospectively analyzed for the first quarter of 2020, and of 2019 for comparison, in 25 APHP hospitals (ca. 14,000 beds).ResultsUp to a fourth on patients admitted in March-April 2020 in these hospitals had COVID-19. BSI rate per 100 admissions increased globally, by 24% in March and 115% in April 2020, and separately for the major pathogens (Escherichia coli, Klebsiella pneumoniae, enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, yeasts). A sharp increase in the rate of BSIs caused by microorganisms resistant to 3rd generation cephalosporins (3GC) was also observed in March-April 2020, particularly in K.pneumoniae, in enterobacterial species naturally producing inducible AmpC (Enterobacter cloacae...) and P.aeruginosa. A concomitant increase occurred in 3GC consumption.ConclusionsCOVID-19 pandemic had a strong impact on hospital management and also unfavorable effects on severe infections, antimicrobial resistance and laboratory work diagnostics

Characteristics of the 11 patients in whom new resistance-associated mutations (RAM) were detected during low-level viremia.

*<p>Baseline DRAM cumulated mutations detected in the genotype (G1) at the onset of LLV period and in all previous available genotypes.</p><p>DRAM: drug-resistance associated mutations, 3TC/FTC: lamivudine/emtricitabine, d4T: stavudine, ABC: abacavir, ddI: didanosine, TDF: tenofovir, EFV: efavirenz, ETV: etravirine, LPV: lopinavir, ATV: atazanavir, FPV: fosamprenavir, DRV: darunavir, RAL: raltegravir, T20: enfuvirtide, /r: ritonavir-boosted protease inhibitor, RT: reverse transcriptase, PR: protease, IN: integrase.</p

Resistance to antiretroviral drugs at the onset and the end of the low-level viremia period, assessed using the 2009 ANRS HIV-1 drug-resistance algorithm v18.

<p>LLV: low level viremia, 3TC/FTC: lamivudine/emtricitabine, ZDV: zidovudine, d4T: stavudine, ABC: abacavir, ddI: didanosine, TDF: tenofovir, EFV: efavirenz, NVP: nevirapine, ETV: etravirine, IDV: indinavir, NFV: nelfinavir, TPV: tipranavir, SQV: saquinavir, LPV: lopinavir, ATV: atazanavir, FPV: fosamprenavir, DRV: darunavir, RAL: raltegravir.</p

Empirical antibiotic therapy modalities for Enterobacteriaceae bloodstream infections in older patients and their impact on mortality: a multicentre retrospective study

International audiencePurpose: Enterobacteriaceae (EB) bloodstream infections (BSI) are frequent and serious in older patients. Physicians are faced with the dilemma of prescribing early appropriate empirical antibiotics to limit the risk of death, and sparing broad-spectrum antibiotic prescription. The aim of the study was to assess the rate of appropriate empirical antibiotics prescription to treat EB BSI in older patients and its impact on survival.Methods: This study conducted in 49 centres enrolled retrospectively up to the 10 last consecutive patients aged 75 years and over and treated for EB BSI. Factors related to in-hospital death were investigated using logistic regression.Results: Among the 487 enrolled patients (mean age 86 ± 5.9 years), 70% had at least one risk factor of being infected by third-generation cephalosporins (3GC)-resistant strain; however, only 13.8% of EB strains were resistant to 3GC. An empirical antimicrobial treatment was initiated for 418 patients (85.8%), and for 86% (n = 360/418) of them, it was considered appropriate. In-hospital mortality was 12.7% (n = 62) and was related to the severity of infection (OR 3.17, CI 95% 1.75-5.75), while a urinary portal of entry was protective (OR 0.34, CI 95% 0.19-0.60). Neither the absence of nor inappropriate empirical antibiotics prescription was associated with increased mortality.Conclusion: While patients enrolled in this study were at risk of being infected by multidrug-resistant bacteria, yet mainly treated with 3GC, empirical antibiotics prescription was appropriate in most cases and did not influence mortality

Decrease of hospital- and community-acquired bloodstream infections due to Streptococcus pneumoniae and Streptococcus pyogenes during the first year of the COVID-19 pandemic: A time-series analysis in Paris region

Members of the Collégiale de Bactériologue – Virologie – Hygiène (CBVH)Guillaume Arlet, Laurence Armand Lefevre, Alexandra Aubry, Laurent Belec, Béatrice Bercot, Stéphane Bonacorsi, Vincent Calvez, Emmanuelle Cambau, Etienne Carbonnelle, Stéphane Chevaliez, Jean-Winoc Decousser, Constance Delaugerre, Diane Descamps, Florence Doucet-Populaire, Jean-Louis Gaillard, Antoine Garbarg-Chenon, Elyanne Gault, Jean-Louis Herrmann, Vincent Jarlier, Jérôme Le Goff, Jean-Christophe Lucet, Jean-Luc Mainardi, Anne-Geneviève Marcellin, Laurence Morand-Joubert, Xavier Nassif, Jean-Michel Pawlotsky, Jérôme Robert, Anne-Marie Roque Afonso, Martin Rottman, Christine Rouzioux, Flore Rozenberg, François Simon, Nicolas Veziris, David Skurnik, Jean-Ralph Zahar, Guilene Barnaud, Typhaine Billard Pomares, Gaëlle Cuzon, Dominique Decré, Alexandra Doloy, Jean-Luc Donay, Laurence Drieux-Rouzet, Isabelle Durand, Agnès Ferroni, Vincent Fihman, Nicolas Fortineau, Camille Gomart, Nathalie Grall, Christelle Guillet Caruba, Françoise Jaureguy, Valérie Lalande, Luce Landraud, Véronique Leflon, Patricia Mariani, Liliana Mihaila, Didier Moissenet, Latifa Noussair, Isabelle Podglajen, Isabelle Poilane, Hélène Poupet, Emilie Rondinaud, Valérie Sivadon Tardy, David Trystram, Charlotte Verdet, Emmanuelle Vigier, Sophie Vimont BillarantInternational audienceThe impact of the COVID-19 pandemic on bloodstream infections (BSIs) due to Streptococcus pneumoniae and Streptococcus pyogenes was assessed in 25 university hospitals of Paris. Monthly BSIs incidence rates that appeared stable in 2018 and 2019, decreased for the 2 pathogens during the 2 COVID-19 lockdown periods of 2020. Containment policies, including social distancing, masking and hand hygiene strengthening in both community and hospital settings are likely to reduce BSIs due to these pathogens