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In this study, we evaluated the performance of the EUCAST RAST method on a collection of 154 clinical strains of P. aeruginosa, including strains resistant to ceftazidime and carbapenems. While the test is convenient for routine laboratories, we observed significant rates of VME (ranging from 0.0 to 15.0%) and ME (ranging from 1.3 to 16.3%) after 6 h, particularly for key antibiotics such as ceftazidime, piperacillin/tazobactam, and meropenem. Extending the incubation time to 8 h may improve results (CA ranging from 87.2 to 99%), but caution is required in interpretation due to persistence of VME (ranging from 0.0 to 15.6%) and ME (ranging from 0.0 to 11.7%).
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Carbapenem-resistant Acinetobacter baumannii (CRAB) are increasingly reported worldwide and a leading cause of mortality associated with antimicrobial resistance. Their early detection, particularly in the cases of bloodstream infections, is crucial in attempting to initiate effective antibiotic treatment. The immunochromatographic assay RESIST ACINETO (Coris BioConcept) is a new test developed for the detection of OXA-23, OXA-40/58, and New-Delhi Metallo-beta-lactamase (NDM) carbapenemases in Acinetobacter spp. We evaluated this test on a collection of 121 Acinetobacter spp. clinical isolates, including 104 carbapenemase producers (97 carbapenemases targeted by the test) and 17 non-carbapenemase producers. The performance of the RESIST ACINETO test was evaluated according to the manufacturer's recommendations from bacterial and blood cultures. The strains producing the carbapenemases OXA-23, -40, -58, or/and NDM were accurately detected from bacterial cultures and directly from blood cultures, with the exception of one OXA-23/NDM-1-positive Acinetobacter radioresistens isolate (only detected through standard culture). None of the non-carbapenemase producers tested positive. The RESIST ACINETO test demonstrated sensitivity/specificity of 100%/100% and 99%/100% on bacterial and blood cultures, respectively. IMPORTANCE: The incidence of bloodstream infections with carbapenem-resistant Acinetobacter baumannii (CRAB) could be very high in some countries such as the Balkans or Southeast Asia. In case of positive blood cultures with Gram-negative bacteria, the use of the RESIST ACINETO test could prove highly beneficial for the rapid identification of these imipenem-resistant bacteria and their antibiotic resistance mechanisms. In addition, it is now well established that New-Delhi Metallo-beta-lactamase (NDM) carbapenemase-producing isolates can have increased MICs of cefiderocol, which is an alternative treatment for these infections. This test may also allow the optimization of treatment based on the type of carbapenemase present. Finally, the RESIST ACINETO test is a rapid, easy-to-use, and cost-effective assay that demonstrates excellent performance in detecting the major acquired carbapenemases present in the Acinetobacter species.
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INTRODUCTION: In case of pneumonia, some biological findings are suggestive for Legionnaire's disease (LD) including C-reactive protein (CRP). A low level of CRP is predictive for negative Legionella Urinary-Antigen-Test (L-UAT). METHOD: Observational retrospective study in Nord-Franche-Comté Hospital with external validation in Besançon University Hospital, France which included all adults with L-UAT performed during January 2018 to December 2022. The objective was to determine CRP optimal threshold to predict a L-UAT negative result. RESULTS: URINELLA included 5051 patients (83 with positive L-UAT). CRP optimal threshold was 131.9 mg/L, with a negative predictive value (NPV) at 100%, sensitivity at 100% and specificity at 58.0%. The AUC of the ROC-Curve was at 88.7% (95% CI, 86.3-91.1). External validation in Besançon Hospital patients showed an AUC at 89.8% (95% CI, 85.5-94.1) and NPV, sensitivity and specificity was respectively 99.9%, 97.6% and 59.1% for a CRP threshold at 131.9 mg/L; after exclusion of immunosuppressed patients, index sensitivity and NPV reached also 100%. CONCLUSION: In case of pneumonia suspicion with a CRP level under 130 mg/L (independently of the severity) L-UAT is useless in immunocompetent patients with a NPV at 100%. We must remain cautious in patients with symptoms onset less than 48 h before CRP dosage.
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Proteína C-Reactiva , Legionella pneumophila , Enfermedad de los Legionarios , Humanos , Enfermedad de los Legionarios/diagnóstico , Enfermedad de los Legionarios/microbiología , Legionella pneumophila/aislamiento & purificación , Proteína C-Reactiva/análisis , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Sensibilidad y Especificidad , Serogrupo , Adulto , Francia , Curva ROC , Valor Predictivo de las PruebasRESUMEN
Cefiderocol is a siderophore-conjugated cephalosporin with potent activity against multidrug-resistant Gram-negative pathogens including Acinetobacter baumannii. The aim of this study was to evaluate cefiderocol testing methods on a relevant collection of 97 Acinetobacter spp. isolates. Commercialized broth microdilution methods (ComASP®, Liofilchem and UMIC®, Bruker), MIC test strips (Liofilchem) and disc diffusion using discs of three different brands (Mast Diagnostic, Liofilchem and Oxoid-Thermo Fisher Scientific) were compared with the broth microdilution reference method. None of the methods tested fulfilled acceptable criteria (essential agreement [EA] ≥ 90%; bias = ±30%) but both BMD methods achieved acceptable categorical agreement rates (CA = 95.9% [93/97, 95% CI 89.9-98.4] and CA = 93.8% [91/97, 95% CI 87.2-97.1] for ComASP® and UMIC®, respectively) and bias < 30% (-7.2% and -25.2% for ComASP® and UMIC®, respectively). The use of MIC gradient testing is strongly discouraged due to misclassification of 55% (n = 23/42) of resistant strains. Finally, the disc diffusion method could be used to rapidly screen for susceptible strains by setting a critical diameter of 22 mm.
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The incidence of campylobacteriosis has substantially increased over the past decade, notably in France. Secondary localizations complicating invasive infections are poorly described. We aimed to describe vascular infection or endocarditis caused by Campylobacter spp. We included 57 patients from a nationwide 5-year retrospective study on Campylobacter spp. bacteremia conducted in France; 44 patients had vascular infections, 12 had endocarditis, and 1 had both conditions. Campylobacter fetus was the most frequently involved species (83%). Antibiotic treatment involved a ß-lactam monotherapy (54%) or was combined with a fluoroquinolone or an aminoglycoside (44%). The mortality rate was 25%. Relapse occurred in 8% of cases and was associated with delayed initiation of an efficient antimicrobial therapy after the first symptoms, diabetes, and coexistence of an osteoarticular location. Cardiovascular Campylobacter spp. infections are associated with a high mortality rate. Systematically searching for those localizations in cases of C. fetus bacteremia may be warranted.
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Bacteriemia , Infecciones por Campylobacter , Campylobacter , Endocarditis , Humanos , Estudios Retrospectivos , Endocarditis/tratamiento farmacológico , Campylobacter fetus , Infecciones por Campylobacter/tratamiento farmacológico , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Francia , Estudios Multicéntricos como AsuntoRESUMEN
OBJECTIVES: To evaluate the performance of commercially available tests to determine the susceptibility of multidrug-resistant (MDR) clinical Pseudomonas aeruginosa strains to cefiderocol. METHODS: A collection of 150 clinical strains of P. aeruginosa resistant to ceftazidime, (MIC, Minimal Inhibitory Concentration, MIC > 8 mg/L) imipenem (MIC> 4 mg/L) and ceftolozane/tazobactam (MIC> 4/4 mg/L), isolated from 2015 to 2022 was selected. Cefiderocol susceptibility was determined in parallel (a) by disc diffusion using Mast, Oxoid and Liofilchem discs deposited on Mueller-Hinton agar batches from Bio-Rad, BioMérieux, Mast, Becton Dickinson, I2A and Oxoid; (b) by MIC gradient test strips (MTS) (Liofilchem); and (c) by EUMDROXF Sensititre microplates. MICs and inhibition zones were compared with the broth microdilution reference method (BMD) MICs. RESULTS: The MIC50 and MIC90 of cefiderocol were 1 mg/L and 8 mg/L by BMD, respectively, including 21.3% (32/150) resistant strains. None of the methods tested fulfilled acceptable criteria (essential agreement [EA] ≥ 90%; bias = ± 30%). Although the Sensititre EUMDROXF microplates overestimated MIC values (categorical agreement [CA] = 86.7% [130/150, 95% CI 80.3-91.2]; EA = 69.3% [104/150, 95% CI 61.6-76.2]; bias = 68.2%), MTS strips underestimated the MIC values for many strains (CA = 86.7%, 130/150, 95% CI 80.3-91.2; EA = 69.3%, 104/150, 95% CI 61.6-76.2; bias = -30.4%), classifying properly only 50% (16/32) of resistant strains. Finally, many cefiderocol-resistant strains were not identified by the disc method, although the CA ranged from 78.0% (117/150, 95% CI 70.7-83.0) to 89.3% (134/150, 95% IC 83.4-93.3) according to Mueller-Hinton agar batches. CONCLUSION: Determination of cefiderocol susceptibility in MDR P. aeruginosa clinical strains by Sensititre EUMDROXF microplates is an alternative to the reference BMD method. However, MIC values ± 1 dilution apart from the breakpoint (2 mg/L) should be controlled by BMD whereas the use of MTS gradient strips is discouraged. Disc diffusion might be useful for screening, unfortunately many cefiderocol-resistant strains are not detected.
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Antibacterianos , Pseudomonas aeruginosa , Humanos , Antibacterianos/farmacología , Agar , Cefalosporinas/farmacología , Ceftazidima/farmacología , Pruebas de Sensibilidad Microbiana , CefiderocolRESUMEN
In the context of increasing antimicrobial resistance in Enterobacterales, the management of these UTIs has become challenging. We retrospectively assess the prevalence of antimicrobial resistance in Enterobacterales isolates recovered from urinary tract samples in France, between 1 September 2017, to 31 August 2018. Twenty-six French clinical laboratories provided the susceptibility of 134,162 Enterobacterales isolates to 17 antimicrobials. The most frequent species were E. coli (72.0%), Klebsiella pneumoniae (9.7%), Proteus mirabilis (5.8%), and Enterobacter cloacae complex (2.9%). The overall rate of ESBL-producing Enterobacterales was 6.7%, and ranged from 1.0% in P. mirabilis to 19.5% in K. pneumoniae, and from 3.1% in outpatients to 13.6% in long-term care facilities. Overall, 4.1%, 9.3% and 10.5% of the isolates were resistant to cefoxitin, temocillin and pivmecillinam. Cotrimoxazole was the less active compound with 23.4% resistance. Conversely, 4.4%, 12.9%, and 14.3% of the strains were resistant to fosfomycin, nitrofurantoin, and ciprofloxacin. However, less than 1% of E. coli was resistant to fosfomycin and nitrofurantoin. We identified several trends in antibiotics resistances among Enterobacterales isolates recovered from the urinary tract samples in France. Carbapenem-sparing drugs, such as temocillin, mecillinam, fosfomycin, cefoxitin, and nitrofurantoin, remained highly active, including towards ESBL-E.
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Although being a potential major source of infection in extracorporeal membrane oxygenation (ECMO) patients, data regarding cannula-related infections (CRI) remain scarce. We therefore aimed at describing the epidemiology of CRI among critically ill patients supported by ECMO. Between October 2017 and November 2019, adult patients supported by either venoarterial (VA), venopulmonary arterial, or venovenous (VV) ECMO for more than 24 hours were prospectively enrolled. When CRI was suspected, cannula swab and subcutaneous needle aspirate samples were obtained for microbiological culture. Cannula tips were systematically sent for culture at the time of ECMO removal. Primary end-point was CRI, which was defined by sepsis or local sign of cannula infection and at least one positive culture among swab, subcutaneous needle aspirate or tip. Multivariate analysis was performed to identify risk factors of CRI. Hundred patients were included, including 77 VA, 12 venopulmonary arterial, and 11 VV ECMO. Cannula-related infections were diagnosed after a median duration of ECMO of 10 [7-13] days. Rate of CRI was 24%, including 10% with bacteremia. Most frequent involved pathogens were Enterobacteriaceae (n = 14), Enterococci (n = 8), and coagulase-negative Staphylococci (n = 7). By multivariate analysis, diabetes and ECMO duration were independently associated with CRI.
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Bacteriemia , Oxigenación por Membrana Extracorpórea , Adulto , Arterias , Bacteriemia/etiología , Cánula/efectos adversos , Oxigenación por Membrana Extracorpórea/efectos adversos , Humanos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Campylobacter spp. bacteremia is a severe infection. A nationwide 5-year retrospective study was conducted to characterize its clinical features and prognostic factors. METHODS: The study included patients with Campylobacter spp. bacteremia diagnosed in 37 French hospitals participating in the surveillance network of the National Reference Center for Campylobacters and Helicobacters, from 1 January 2015 to 31 December 2019. The goal was to analyze the effects of a delay of appropriate antibiotic therapy and other risk factors on 30-day mortality rates, antibiotic resistance, patient characteristics, and prognosis according to the Campylobacter species. RESULTS: Among the 592 patients, Campylobacter jejuni and Campylobacter fetus were the most commonly identified species (in 42.9% and 42.6%, respectively). The patients were elderly (median age 68 years), and most had underlying conditions, mainly immunodepression (43.4%), hematologic cancers (25.9%), solid neoplasms (23%), and diabetes (22.3%). C. jejuni and Campylobacter coli were associated with gastrointestinal signs, and C. fetus was associated with secondary localizations. Among the 80 patients (13.5%) with secondary localizations, 12 had endocarditis, 38 vascular, 24 osteoarticular, and 9 ascitic fluid infections. The 30-day mortality rate was 11.7%, and an appropriate antibiotic treatment was independently associated with 30-day survival (odds ratio, 0.47 [95% confidence interval, .24-.93]; Pâ =â .03). The median efficient therapy initiation delay was quite short (2 days [interquartile range, 0-4 days]) but it had no significant impact on the 30-day mortality rate (Pâ =â .78). CONCLUSIONS: Campylobacter spp. bacteremia mainly occurred in elderly immunocompromised individuals with variable clinical presentations according to the species involved. Appropriate antimicrobial therapy was associated with improved 30-day survival.
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Bacteriemia , Infecciones por Campylobacter , Campylobacter jejuni , Campylobacter , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Infecciones por Campylobacter/tratamiento farmacológico , Infecciones por Campylobacter/epidemiología , Humanos , Estudios RetrospectivosRESUMEN
OBJECTIVES: To assess performance of disc diffusion, gradient tests and Vitek 2 system to determine the susceptibility of clinical Pseudomonas aeruginosa strains to ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA). METHODS: Two-hundred non-duplicate P. aeruginosa strains isolated by 47 French medical laboratories were selected to cover a wide range of C/T and CZA MICs. Performance of C/T disc (30/10 µg, Bio-Rad), CZA discs (10/4 µg) (Thermo Fisher and Bio-Rad), C/T and CZA gradient tests (Etest, BioMérieux; MIC Test Strip, Liofilchem), and AST-XN12 card of Vitek 2 system (BioMérieux) were compared with a broth microdilution (BMD) method (Thermo Fisher). MIC and disc results were interpreted using current EUCAST breakpoints. RESULTS: Twenty percent and 17% of strains were resistant to C/T and CZA, respectively. All the methods tested satisfactorily determined the susceptibility of P. aeruginosa to C/T [Category Agreement (CA) ≥95%] except the disc diffusion method. Because of the high rates of Major Errors (MEs) (12.5%), this latter method tends to overestimate the resistance. For CZA, only the gradient tests yielded more than 90% of CA. The Vitek 2 system and disc diffusion misclassified 18.1%, 10.1% (disc Bio-Rad) and 11.9% (disc Thermo Fisher) of susceptible strains, respectively. CONCLUSIONS: The gradient tests (MIC Test Strip and Etest) and Vitek 2 card XN12 performed the best to determine the susceptibility of P. aeruginosa to C/T, whereas gradient tests were an acceptable alternative to BMD to assess CZA susceptibility.
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Ceftazidima , Infecciones por Pseudomonas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/farmacología , Ceftazidima/farmacología , Cefalosporinas/farmacología , Combinación de Medicamentos , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Tazobactam/farmacologíaRESUMEN
Temocillin is used for several years in some European countries but, only since 2015 in France. We assessed the susceptibility of Enterobacterales strains isolated from blood culture 1 year before (2014) and 2 years after (2017) its use in France. 1,387 strains were included by 17 clinical laboratories located throughout France: 363 in 2014 and 1,024 in 2017. The rate of resistance to temocillin was 4.6% and 26.7% in 3rd generation cephalosporin (3GC) susceptible and resistant strains respectively. Cephalosporinase-overproducer (COPE) strains were significantly more resistant to temocillin (37.7%) than ESBL-producer (ESBL-PE) (23.5%) (P < 0.01). The rate of temocillin resistance was correlated to the number of inactive beta-lactams. The rate of resistance to temocillin trend to increase from 13.9% in 2014 to 23.9% in 2017 (P < 0.01). Temocillin remains highly active against Enterobacterales but the trend in resistance should be assessed over time.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Infecciones por Enterobacteriaceae/microbiología , Enterobacteriaceae/efectos de los fármacos , Penicilinas/farmacología , Relación Dosis-Respuesta a Droga , Infecciones por Enterobacteriaceae/epidemiología , Francia/epidemiología , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Resistance mechanisms of Pseudomonas aeruginosa to ceftolozane/tazobactam (C/T) were assessed on a collection of 420 nonredundant strains nonsusceptible to ceftazidime (MIC > 8 µg/ml) and/or imipenem (>4 µg/ml), collected by 36 French hospital laboratories over a one-month period (the GERPA study). Rates of C/T resistance (MIC > 4/4 µg/ml) were equal to 10% in this population (42/420 strains), and 23.2% (26/112) among the isolates resistant to both ceftazidime and imipenem. A first group of 21 strains (50%) was found to harbor various extended-spectrum ß-lactamases (1 OXA-14; 2 OXA-19; 1 OXA-35; 1 GES-9; and 3 PER-1), carbapenemases (2 GES-5; 1 IMP-8; and 8 VIM-2), or both (1 VIM-2/OXA-35 and 1 VIM-4/SHV-2a). All the strains of this group belonged to widely distributed epidemic clones (ST111, ST175, CC235, ST244, ST348, and ST654), and were highly resistant to almost all the antibiotics tested except colistin. A second group was composed of 16 (38%) isolates moderately resistant to C/T (MICs from 8/4 to 16/4 µg/ml), of which 7 were related to international clones (ST111, ST253, CC274, ST352, and ST386). As demonstrated by targeted mass spectrometry, cloxacillin-based inhibition tests, and gene blaPDC deletion experiments, this resistance phenotype was correlated with an extremely high production of cephalosporinase PDC. In part accounting for this strong PDC upregulation, genomic analyses revealed the presence of mutations in the regulator AmpR (D135N/G in 6 strains) and enzymes of the peptidoglycan recycling pathway, such as AmpD, PBP4, and Mpl (9 strains). Finally, all of the 5 (12%) remaining C/T-resistant strains (group 3) appeared to encode PDC variants with mutations known to improve the hydrolytic activity of the ß-lactamase toward ceftazidime and C/T (F147L, ΔL223-Y226, E247K, and N373I). Collectively, our results highlight the importance of both intrinsic and transferable mechanisms in C/T-resistant P. aeruginosa Which mutational events lead some clinical strains to massively produce the natural cephalosporinase PDC remains incompletely understood.
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Infecciones por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ceftazidima/farmacología , Cefalosporinas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/genética , Tazobactam/farmacología , beta-LactamasasRESUMEN
The Sun's magnetic field is generated by subsurface motions of the convecting plasma. The latitude at which the magnetic field emerges through the solar surface (as sunspots) drifts toward the equator over the course of the 11-year solar cycle. We use helioseismology to infer the meridional flow (in the latitudinal and radial directions) over two solar cycles covering 1996-2019. Two data sources are used, which agree during their overlap period of 2001-2011. The time-averaged meridional flow is shown to be a single cell in each hemisphere, carrying plasma toward the equator at the base of the convection zone with a speed of ~4 meters per second at 45° latitude. Our results support the flux-transport dynamo model, which explains the drift of sunspot-emergence latitudes through the meridional flow.
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Four ST664 (serotype O:5) strains of Pseudomonas aeruginosa highly resistant to antibiotics including ceftolozane/tazobactam and ceftazidime/avibactam but susceptible to colistin, were found to harbor the rare class C ß-lactamase PAC-1 encoding gene on a chromosomally-located Tn1721-like transposon. Gene bla PAC-1 was associated with the 16S rRNA methylase determinant rmtF2, that confers pan-aminoglycoside resistance. These genotypically-related strains were isolated in repatriated patients from Mauricius and Afghanistan and close to a lineage reported in Nepal, Pakistan and India.
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The immunochromatographic assay NG-Test Carba 5 (NG-Biotech) was evaluated with a collection of 107 carbapenemase-producing nonfermenters (CP-NF) (55 Pseudomonas spp., 51 Acinetobacter spp., and 1 Achromobacter xylosoxidans isolate) and 61 carbapenemase-negative isolates. All KPC, VIM, and NDM carbapenemase producers tested were accurately detected. Of the 16 IMP variants tested, 6 (37.5%) variants were not detected. Considering the epidemiology of CP-NFs in France, the NG-Test Carba 5 would detect 89.4% of CP Pseudomonas spp. but only 12.9% of CP Acinetobacter spp.
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Achromobacter denitrificans/genética , Acinetobacter/genética , Proteínas Bacterianas/genética , Cromatografía de Afinidad/métodos , Pseudomonas/genética , Resistencia betalactámica/genética , beta-Lactamasas/genética , Achromobacter denitrificans/efectos de los fármacos , Achromobacter denitrificans/enzimología , Achromobacter denitrificans/aislamiento & purificación , Acinetobacter/efectos de los fármacos , Acinetobacter/enzimología , Acinetobacter/aislamiento & purificación , Antibacterianos/farmacología , Carbapenémicos/farmacología , Cromatografía de Afinidad/normas , Francia/epidemiología , Expresión Génica , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana/normas , Pseudomonas/efectos de los fármacos , Pseudomonas/enzimología , Pseudomonas/aislamiento & purificación , Sensibilidad y Especificidad , Especificidad de la EspecieRESUMEN
In this study, the activity of 18 non-carbapenem antibiotics was evaluated against 100 extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) and 50 ESBL-producing Klebsiella pneumoniae (ESBL-Kp) isolated from urinary tract infections and bacteraemia in 2016. Minimum inhibitory concentrations (MICs) were determined using reference methods and the susceptibility profiles were defined according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2017 recommendations. All of the ESBL-Ec isolates were susceptible to ceftazidime/avibactam and a great majority of them were susceptible to fosfomycin (98%), piperacillin/tazobactam (97%), amikacin (97%) and nitrofurantoin (96%). Mecillinam, cefoxitin and ceftolozane/tazobactam remained active against 92%, 83% and 78% of the ESBL-Ec isolates, respectively. Moreover, 100%, 94% and 90% of the ESBL-Kp tested were susceptible to ceftazidime/avibactam, amikacin and mecillinam, respectively. This study showed that there are non-carbapenem options (including orally administrable drugs) for the treatment of all of the situations of ESBL-Ec or ESBL-Kp infections, with ceftazidime/avibactam being the most efficient alternative.
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Antibacterianos/farmacología , Enterobacteriaceae/efectos de los fármacos , beta-Lactamasas/metabolismo , Compuestos de Azabiciclo/farmacología , Carbapenémicos/farmacología , Ceftazidima/farmacología , Cefalosporinas/farmacología , Combinación de Medicamentos , Enterobacteriaceae/aislamiento & purificación , Enterobacteriaceae/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Escherichia coli/efectos de los fármacos , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/farmacología , Tazobactam , Infecciones Urinarias/microbiologíaRESUMEN
A 5 years-old girl, seriously burnt with fire, was first hospitalized during four days in an hospital at Alger, and then transferred to our hospital at Paris. Admitted in our intensive care burns unit, she was third degree burnt on 78% of total body surface area, already treated with imipenem and vancomycin at her arrival. Clinical aggravation was rapidly observed and death occurred within 24 hours. Cultures of blood and multiple wound swabs yielded 3 multi-drug resistant bacterial strains: Acinetobacter baumannii with carbapenemase OXA-23, Pseudomonas aeruginosa serotype O11 with metallo-ß-lactamase VIM-4 and Klebsiella pneumoniae with CTX-M-15 extended-spectrum ß-lactamase. Culture of a rectal swab showed colonization by Enterococcus faecium with vanA glycopeptides resistance. Patients colonized with one or two multi-drug-resistant strains were not rare in our burns unit, especially those transferred from Algeria, but this case of a single patient harboring four multi-drug-resistant strains is exceptional.
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The aim of this work was to investigate the impact of single amino acid substitutions occurring in specific porin OprD on carbapenem resistance of cystic fibrosis (CF) strains of Pseudomonas aeruginosa. A PAO1ΔoprD mutant was complemented with the oprD genes from five carbapenem-resistant CF strains exhibiting very low amounts of mutated OprD porins in their outer membrane despite wild-type levels of oprD transcripts. Compared with wild-type porin from strain PAO1, single amino acid substitutions S403P (in periplasmic loop 8), Y242H, S278P and L345P (in ß-sheets 10, 12 and 14, respectively) were found to result in reduced amounts of OprD in the outer membrane, increased carbapenem resistance, and slower growth in minimal medium containing gluconate, an OprD substrate, as the sole source of carbon and energy. This indicates that in CF strains of P. aeruginosa, loss of porin OprD may not only result from mutations downregulating the expression of or disrupting the oprD gene, but also from mutations generating deleterious amino acid substitutions in the porin structure.