Changes in the gut microbiota of pseudoxanthoma elasticum patients.

OBJECTIVE: Pseudoxanthoma elasticum (PXE) is a rare autosomal disorder with a variable phenotype that may be modulated by environmental factors. Plasma vitamin K (VK) levels may be involved in the ectopic calcification process observed in PXE. Since VK2 is predominantly produced by the gut microbiota, we hypothesized that changes in the gut microbiota of PXE patients might exacerbate the calcification process and disease symptoms. METHODS: Twenty PXE patients were included in the study and 60 gut microbiota profiles from the Biofortis laboratory database were used as controls. RESULTS: The Rhodospirillaceae family was more abundant in the PXE group while the Sphingomonadaceae family was more abundant in the control group. In a PXE severity subgroup analysis, microbiota dispersion was lower in "severe" than in "non-severe" patients, which was confirmed by permutation multivariate analysis of variance at the phylum, family and genus ranks. However, no significant association was found in a model incorporating relative abundance of bacterial families, severity score, and different blood and fecal VK species. CONCLUSION: These results suggest slight compositional changes in the gut microbiota of PXE patients. Further studies are needed to substantiate their impact on VK metabolism and the calcification process.

Invasive pneumococcal infections in France: Changes from 2009 to 2021 in antibiotic resistance and serotype distribution of Streptococcus pneumoniae based on data from the French Regional Pneumococcal Observatories network.

OBJECTIVE: The 23 French Regional Pneumococcal Observatories (ORPs) analyzed antibiotic resistance and serotypes of Streptococcus pneumoniae strains isolated from invasive infections in France over a 12-year period. METHODS: Between 2009 and 2021, the ORPs analyzed 19,319 strains, including 1,965 in children and 17,354 in adults. Strains were assessed for their resistance to penicillin G, amoxicillin and cefotaxime. Serotypes were identified in collaboration with the National Reference Centre. RESULTS: During this period, the number of strains collected yearly decreased significantly. The decrease was particularly pronounced up until 2013, especially in children (-61.0%). However, penicillin non-susceptible strains (PNSPs) increased in children (24.7% in 2009 vs 45.0% in 2021, p < 0.0001) and in adults (27.1% in 2009 vs 31.3% in 2021, p < 0.05), as well as resistance (I + R) to amoxicillin (children: 12.5% in 2009 vs 19.4% in 2021, p < 0.05; adults: 13.4% in 2009 vs 14.5% in 2021, NS) and resistance (I + R) to cefotaxime (children: 8.0% in 2009 vs 13.1% in 2021, p < 0.05; adults: 7.1% in 2009 vs 11.9% in 2021, p < 0.0001). All in all, the proportion of strains belonging to serotypes present in the PCV13 vaccine has fallen sharply, from 64.8% in 2009 to 23.6 % in 2021. At the same time, serotypes such as 8, 10A, 11A, 15B/C and 9N, not included in PCV13, were increasing. CONCLUSION: During the study period, data collected by the network highlighted an increase of invasive PNSPs in children and non-vaccine serotypes. Surveillance of resistance and serotypes remains instrumental, particularly to monitor the evolution of vaccine efficacy.

[In vitro activity of tigecycline on 760 bacterial strains isolated in the hospital university of Angers--2006-2009 TEST study]. / Activité in vitro de la tigécycline vis-à-vis de 760 souches bactériennes isolées au CHU d'Angers--le programme TEST 2006-2009.

Tigecycline (TGC), an antibiotic belonging to glycylcyclines, is active against Gram-positive bacteria, including multi-resistant bacteria, and most of the Gram-negative bacteria, including extended spectrum ß-lactamase-producers (ESBL) and Acinetobacter sp. TGC is not active on Pseudomonas aeruginosa. The microbiological laboratory from the university hospital of Angers participates in the Tigecycline Evaluation and Surveillance Trial (TEST) since 2006. The objective of this study is to evaluate the effectiveness of TGC and of various comparators against nosocomial and community-acquired pathogens. We also evaluated the effectiveness of TGC on a panel of strains isolated between 2006 and 2009 in the university hospital of Angers. Minimum inhibitory concentrations (MIC) were determined using the microdilution method. A total of 760 clinical strains were tested. TGC had a very good activity against Gram-positive bacteria, with 100 % of susceptibility for all the strains tested, irrespective of their resistance profile. Concerning Gram-negative bacteria, TGC was active against 93 % of Enterobacteriaceae, with a MIC 90 not exceeding 2mg/L. Whole of the 20 strains ESBL-producers tested were susceptible to TGC. Acinetobacter sp. were also inhibited at low concentrations of TGC, with a MIC 90 of 1mg/L. These results suggest that TGC can be a useful therapeutic alternative, especially for infections involving multiresistant bacteria.

Cefoxitin-based combination for ESBL-producing Enterobacteriaceae endocarditis.

BACKGROUND: Endocarditis due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a rare but challenging condition. Its treatment relies on carbapenems alone or in combination, and no alternative has been described to date. The cephamycin cefoxitin has been used for treatment of mild ESBL-producing Enterobacteriaceae infections. CASE PRESENTATION: We report two patients with nosocomial endocarditis due to ESBL-producing Escherichia coli and Klebsiella pneumoniae who underwent clinical failure or adverse event, respectively, during treatment with imipenem-cilastatin. The first patient was subsequently treated with cefoxitin combined with ciprofloxacin with a favorable outcome. In the second patient, the endocarditis relapsed following a 6-week treatment with cefoxitin and fosfomycin. In time-kill assays, the cefoxitin/ciprofloxacin and cefoxitin/fosfomycin combinations showed synergistic effect. CONCLUSION: These cases illustrate that cefoxitin is an interesting alternative to carbapenems, even in severe infections such as endocarditis. Pharmacokinetic optimization and combination with another synergistic antibiotic should be considered whenever possible.

Accuracy of gradient diffusion method for susceptibility testing of dalbavancin and comparators.

OBJECTIVES: This multicenter study aimed to assess the performances of gradient diffusion (GD) method in comparison to broth microdilution (BMD) method for susceptibility testing of dalbavancin, daptomycin, vancomycin, and teicoplanin. METHODS: Minimum Inhibitory Concentrations (MICs) were retrospectively determined concomitantly by BMD and GD methods, for 93 staphylococci and enterococci isolated from clinical samples. BMD was considered as the gold standard. Essential (EA) and categorical agreements (CA) were calculated. Discordant categorical results were categorized as major (ME) and very major errors (VME). RESULTS: EA and CA were 95.7% and 96.8%, 82.8% and 100%, 97.8% and 96.8%, and 94.6% and 95.7% for dalbavancin, daptomycin, vancomycin, and teicoplanin respectively. Concerning dalbavancin, 3 ME without any VME were observed and discrepancies were low (≤ to 2 two-fold dilutions) between both methods. VME were noted in 1 and 3 cases for vancomycin and teicoplanin, respectively, and resulted from 1 two-fold dilution discrepancy in each case. EA was lower for daptomycin. When they were discrepant, BMD MICs were systematically higher than GD ones. Nevertheless, no categorical discrepancy was noted. CONCLUSIONS: GD appears as an acceptable and convenient alternative for dalbavancin, vancomycin, and teicoplanin MICs determination. Our study also emphasizes how achieving accurate daptomycin MICs remains challenging.

[Antibacterial activity against 224 clinical bacterial strains of JCA 250 and JCA 251 compounds containing essential oils provided from Aroma Technologies research]. / Étude de la sensibilité de 224 bactéries isolées d'infections hospitalières vis-à-vis des composés JCA 250 et JCA 251 à base d'huiles essentielles issus de la recherche Aroma Technologies.

OBJECTIVE: It was to determine the antibacterial spectrum of JCA 250 and JCA 251, two naturally occurring compounds from Aroma Technologies research, on a bacterial population isolated from clinical infections. METHOD: Two hundred and twenty-four bacterial strains were tested. The minimum inhibitory concentrations (MIC) of JCA 250 and JCA 251 were determined by agar dilution method. Tests were performed in triplicate. RESULTS: The mean MIC was 0.20% for JCA 250 and 0.15% for JCA 251. JCA 251 regularly exhibited greater activity. All Enterobacteriaceae were inhibited at concentrations less or equal to 0.15% for JCA 250 or JCA 251. For strict aerobes, the MIC values were more spread out. Two Pseudomonas aeruginosa strains differed from the population with JCA 251 MIC of 0.25 and 0.40%. Concerning Gram-positive cocci, all the strains were inhibited with less or equal to 0.25% of compound. The most resistant population were the Enterococci and the Lactobacilli, with MIC more or equal to 0.2% for JCA 250 or JCA 251. Anaerobes showed MIC closely grouped for a heterogeneous bacterial group. One Propionibacterium sp. strain came apart from the group and was inhibited with a MIC of 0.5%. CONCLUSION: The overall results showed an interesting antibacterial activity on bacteria isolated from clinical samples. Most of the bacterial strains were inhibited at a concentration of 0.2%. The highest mean values were obtained for commensal bacteria from the flora, which is of particular interest in this study.

Two-color Kerr microscopy of two-dimensional materials with sub-picosecond time resolution.

We present a two-color Kerr microscopy system based on two electronically synchronized erbium-fiber laser oscillators with independently tunable emission energies spanning most of the visible spectrum. Combining a spatial resolution below 2 µm and sub-ps time resolution with high sensitivity and cryogenic sample temperatures, it is ideally suited for studying spin and valley dynamics in a wide range of two-dimensional materials. We illustrate its capabilities by studying a monolayer of the common semiconducting transition metal disulfide MoS2.

[Pays de la Loire Pneumococcus Observatory: antimicrobial resistance of Streptococcus pneumoniae in 2007]. / Observatoire régional du pneumocoque en région Pays de la Loire: résistance de Streptococcus pneumoniae aux antibiotiques en 2007.

OBJECTIVES: Between 1st January and 31st December 2007, 331 Streptococcus pneumoniae strains were collected from 20 participating laboratories in the Pneumococcus Network Pays de la Loire county to assess their susceptibility to antibiotics and to evaluate serogroups of strains. METHOD: The coordinating centre performed MICs of penicillin G, amoxicillin and cefotaxime by the reference agar dilution method. Results were interpreted according to CA-SFM breakpoints. Sensitivity to other antibiotics were studied and serotyping of each strain performed. RESULTS: Three hundred and thirty one strains were isolated in 2007. They were collected from 30 cerebrospinal fluids, 239 blood samples, 53 middle ear fluids and nine pleural fluids. The percentage of pneumococci with decreased susceptibility to penicillin G (PDSP) was 39% and was higher in children (51%) than in adults (35%). The PDSP were often multidrug resistants especially with a high percentage of resistance to erythromycin (87.6% versus 8.4% for pneumococci sensitive to penicillin G). Finally, the most prevalent serogroup was the serogroup 19 (29.6% of isolates). CONCLUSION: A decrease of PDSP was observed since 2001 and high-level resistant strains to beta-lactams remain low. The rate of PDSP in Pays de la Loire is in the national average.

The prevalence, clinical features, risk factors and outcome associated with cryptococcal meningitis in HIV positive patients in Kenya.

OBJECTIVES: To determine the prevalence, clinical features, risk factors and outcomes associated with cryptococcal meningitis (CM) in human immunodeficiency virus (HIV) positive patients at two referral hospitals in Nairobi, Kenya. DESIGN: Prospective, observational study. SETTING: Kenyatta National Hospital (KNH) and Mbagathi District Hospital (MDH), Nairobi, Kenya. SUBJECTS: Three hundred and forty HIV patients presenting with suspected CM. RESULTS: Of three hundred and forty suspected CM patients, 111 (33%) were diagnosed with CM by CrAg. Among CM patients, in-hospital mortality was 36% (38/106), median age was 35 years (range, 19-60 years) and median CD4 count was 41 cells/microL (n = 89, range 2-720 cells/microL). Common clinical manifestations among CM patients included headache 103 (93%), neck stiffness 76 (69%) and weight loss 53 (48%). Factors independently associated with CM were male sex, headache, blurred vision and previous antifungal drug use. Night sweats and current use of anti-retroviral therapy were associated with reduced risk for CM. CONCLUSIONS: There is a high prevalence of CM and CM-associated mortality in HIV patients at KNH and MDH despite treatment with antifungal and anti-retroviral drugs. This study demonstrates the need to address the existing inadequacies of CM patient outcomes in Kenya.

Stenotrophomonas maltophilia susceptibility to ceftazidime-avibactam combination versus ceftazidime alone.

OBJECTIVE: To compare the minimum inhibitory concentrations (MIC) of the ceftazidime-avibactam (CZA) combination versus ceftazidime alone (TZ) for Stenotrophomonas maltophilia. PATIENTS AND METHODS: MIC comparison was performed by E-tests. We assumed that CZA was more effective in vitro than TZ alone when CZA led to a category change from "Resistant" with TZ alone to "Susceptible" or "Intermediate" with CZA, or if the MIC of CZA was at least 4-fold lower than the MIC of TZ for TZ-susceptible isolates. RESULTS: For the 54 clinical isolates included in the study, CZA showed better results in terms of the proportion of susceptible isolates (66.7% vs. 38.9%, P<0.01), MIC50 (2µg/mL vs. 12µg/mL, P<0.05), and MIC distribution. According to our definition, CZA was also more effective in vitro than TZ alone for 50% of the isolates. CONCLUSION: Using CZA for empirical treatments in severe or polymicrobial infections with S. maltophilia seems appropriate.

Extended-spectrum ß-lactamase Enterobacteriaceae (ESBLE) in intensive care units: strong correlation with the ESBLE colonization pressure in patients but not same species.

Sink drains of six intensive care units (ICUs) were sampled for screening contamination with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBLE). A high prevalence (59.4%) of sink drain contamination was observed. Analysing the data by ICU, the ratio 'number of ESBLE species isolated in sink drains/total number of sink drains sampled' was highly correlated (Spearman coefficient: 0.87; P = 0.02) with the ratio 'number of hospitalization days for patients with ESBLE carriage identified within the preceding year/total number of hospitalization days within the preceding year'. Concurrently, the distribution of ESBLE species differed significantly between patients and sink drains.

Effect of chemical composition on superconductivity and magnetism in layered ruthenocuprates.

The ruthenium-based layered cuprates RuSr(2)GdCu(2)O(8) (RuGd1212) can be considered naturally occurring magnetic and superconducting multilayer systems. We have concentrated on the preparation of RuGd1212-type compounds with nominally stoichiometric composition under ambient pressure conditions. For small rare earth ions R  = Gd, Eu (and Sm), single phase compounds are obtained with the typical ordered layered structure and no significant changes of physical properties. With large rare earth ions (R  = Nd, Pr), multiphase samples are obtained. In these cases, no ordered layered structure was observed. The effect of substituting Sr(2+) with the smaller Ca(2+) and larger Ba(2+) is examined. A different number and different types of phases in equilibrium are found with different alkaline earths (A  = Ca, Sr, Ba) at the nominal RuA(2)NdCu(2)O(8) composition. The variation in the mismatch of the A/Nd size does not lead to the formation of an ordered layered RuA(2)NdCu(2)O(8) compound. Chemical transport in an open system was used to vary the Ru content in the RuGd1212 samples during the annealing step. With an increase of the Ru mass transport to the sample, the composition can be driven beyond the limit of the homogeneity range. Systematic changes in the phase composition of the resulting sample were observed. The magnetic and superconducting transition temperatures vary in a systematic way and are attributed to a variation of the Ru content in the RuR1212 phase.

Control of Toxoplasma gondii infection by athymic LEW-Whn rnu rats.

In immunocompetent rats and humans infection with Toxoplasma gondii remains mostly without overt clinical symptoms, but can be fatal, if the T-cell response is impaired. For a better understanding of the lack of control of T. gondii infection under immunosuppressed conditions, congenitally athymic rats were used as the experimental model. Whereas athymic F344-Whn(rnu) (F344 nude) rats die from a generalized infection during the first 3 weeks after peritoneal inoculation with 10(6) tachyzoites of T. gondii strain NTE, LEW-Whn(rnu) (LEW nude) rats and euthymic LEW rats infected with a 10-fold higher number of parasites developed chronic infection. To identify underlying mechanisms of LEW rats resistance to T. gondii infection and to investigate a possible contribution of residual T-cells to LEW-Whn(rnu) rat resistance, we characterized the immune response of LEW rats by determination of cellularity and composition of lymphocyte population, antigen-specific IgG2b response as well as assays of antigen-specific proliferation and production of IL-2, IFN-gamma and TNF-alpha. As only euthymic LEW rats developed production of antigen-specific IgG and cellular in vitro responses, these results strongly suggest that the genetic background of LEW rats permits a control of the infection independent of an adaptive immune response.

Acinetobacter pittii isolated more frequently than Acinetobacter baumannii in blood cultures: the experience of a French hospital.

This study assessed the characteristics of hospital-acquired Acinetobacter calcoaceticus-Acinetobacter baumannii complex bloodstream infections (BSI). From 2010 to 2017, A. calcoaceticus-A. baumannii complex BSI were investigated. Of 73 cases, 54.8% were associated with Acinetobacter pittii, 39.7% with Acinetobacter baumannii and 5.5% with Acinetobacter nosocomialis. Multi-drug-resistant isolates were significantly higher in A. baumannii BSI. Thirty-day mortality was no different between A. baumannii or non-baumannii A. calcoaceticus-A. baumannii complex BSI. In contrast with other studies, this study found that most hospital-acquired A. calcoaceticus-A. baumannii complex BSI were associated with non-baumannii A. calcoaceticus-A. baumannii complex species. This study found that these species were important hospital-acquired pathogens, and emphasizes the importance of A. calcoaceticus-A. baumannii complex species identification.

Assessment of the automated multiplex-PCR Unyvero i60 ITI® cartridge system to diagnose prosthetic joint infection: a multicentre study.

OBJECTIVES: Prosthetic joint infections (PJI) are responsible for significant morbidity and mortality and their number continues to rise. Their management remains complex, especially the microbiological diagnosis. Besides 'homemade' tests developed by several teams, new molecular biology methods are now available with different analytical performance and usability. METHODS: We studied the performances of one of these tests: ITI® multiplex PCR (mPCR) by the Curetis® company and compared it to either 'optimized' culture or 16S rRNA PCR. We performed a retrospective multicentre study to assess the contributions of mPCR in the diagnosis of PJI. We randomly selected 484 intraoperative specimens among 1252 of various types (biopsy, bone, tissue around the prosthesis, synovial fluid) from 251 patients in seven different hospitals. Each sample was treated according to the recommendations of the manufacturer. RESULTS: In all, 154 out of 164 (93.9%) samples negative in culture were negative with the mPCR. Among the 276 positive samples in culture, 251 (90.9%) were monomicrobial, of which 119 (47.4%) were positive with the mPCR, and 25 (9.1%) were polymicrobial, of which 12 (48%) were positive with the mPCR. The concordance rate of mPCR with culture was 58.1% (53.6%-62.7%) and the concordance rate with 16S rRNA PCR was 70.1% (65.5%-74.6%). CONCLUSION: This new standardized molecular test showed a lack of detection when the bacterial inoculum was low (number of positive media per sample and number of colonies per media) but can be useful when patients have received antibiotic therapy previously.

Emergence of NDM-1 and OXA-72 producing Acinetobacter pittii clinical isolates in Lebanon.

Acinetobacter spp. have emerged as global opportunistic pathogen causing a wide range of infections. Emergence of carbapenem resistance in these organisms is a matter of great concern. We report here the first detection of Acinetobacter pittii clinical isolates in Lebanon carrying either the bla NDM-1 or the bla OXA-72 gene.

First report of Oxa-72-producing Acinetobacter calcoaceticus in Lebanon.

Emergence of carbapenem-resistant Acinetobacter spp. has been increasingly reported worldwide. We report here the first detection of an Acinetobacter calcoaceticus isolate from vegetables in Lebanon carrying the bla Oxa-72 gene. These findings show that the Lebanese environment may constitute a potential reservoir for this antibiotic resistance gene.

A comparison of cold storage solutions for pancreas preservation prior to islet isolation.

BACKGROUND: Several solutions are used to preserve the pancreas prior to islet isolation. This study sought to assess whether the type of solution had an impact on the isolation outcome. METHODS: We reviewed data from 125 islet isolation procedures performed from January 2002 to January 2005. Pancreata were preserved in University of Wisconsin (UW) (n = 101), Celsior (CS) (n = 19), or IGL-1 (n = 5) solutions. Islet isolation results and transplantation rates were compared between groups. RESULTS: UW, CS, and IGL-1 groups were similar according to donor's age, weight, and body mass index. Weight of undigested pancreas was 20 +/- 13.1, 21.4 +/- 15.7, and 17.4 +/- 8.7 g for UW, CS, and IGL-1, respectively (P > .2). Final total number of IEQ was 267,000 +/- 132,000, 277,000 +/- 155,000, and 311,000 +/- 163,000, respectively (P > .4). Success rate (defined as >250,000 IEQ) was 55.5%, 52.9%, and 60% for UW, Celsior, and IGL-1 (P > .9); the transplantation rate was 42.2% for UW, 36.8% for Celsior, and 80% for IGL-1 preservation (P > .2). CONCLUSIONS: In this preliminary study, UW, Celsior, and IGL-1 solutions demonstrated similar islet isolation results. The new IGL-1 solution appears promising.

Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

The effects of roxatidine acetate on 24-hour intragastric acidity. Investigations in healthy volunteers and comparison with ranitidine and placebo.

In a series of double-blind randomised studies in normal volunteers with continuous intragastric pH monitoring, the effects of different dosage regimens of roxatidine acetate, a new H2-receptor antagonist, were compared with placebo and ranitidine. Roxatidine acetate 75 mg twice daily decreased median 24-hour gastric acidity from pH 1.6 to 3.2 and median nocturnal acidity from 1.5 to 3.0. Roxatidine acetate 150 mg at bedtime raised median 24-hour pH in the same 17 subjects to 2.4 and nocturnal pH to 5.9. In the second experiment, in 14 volunteers, roxatidine acetate 150 mg at bedtime was as effective as ranitidine 300 mg at night, raising median nocturnal pH from 1.4 to 6.65 compared to 6.7 for ranitidine. However, when drugs were taken after the evening meal (post cenam nocte; PCN) roxatidine acetate 150 mg was less potent than ranitidine 300 mg, with median night-time pH rising from 1.3 to 3.2 and 4.0, respectively, in 28 volunteers. Roxatidine acetate 300 mg PCN produced the greatest rise of pH, to 4.9, suggesting that the true potency ratio of the 2 drugs is between 1 and 2.