High Rate of Passenger Lymphocyte Syndrome after ABO Minor Incompatible Lung Transplantation.

Rationale: Passenger lymphocyte syndrome (PLS) may complicate minor ABO mismatched lung transplantation (LuTX) via donor-derived red cell antibody-induced hemolysis.Objectives: To ascertain the incidence and specificity of PLS-relevant antibodies among the study population as well as the dynamics of hemolysis parameters and the transfusion requirement of patients with or without PLS.Methods: In this cohort study, 1,011 patients who received LuTX between January 2010 and June 2019 were studied retrospectively. Prospectively, 87 LuTX (July 2019 to June 2021) were analyzed. Postoperative ABO antibody and hemolytic marker determinations, transfusion requirement, and duration of postoperative hospital care were analyzed. Retrospectively, blood group A recipients of O grafts with PLS were compared with those without.Measurements and Main Results: PLS affected 18.18% (retrospective) and 30.77% (prospective) of A recipients receiving O grafts, 5.13% of B recipients of O grafts, and 20% of AB patients receiving O transplants. Anti-A and anti-A1 were the predominant PLS-inducing antibodies, followed by anti-B and anti-A,B. Significantly lower hemoglobin values (median, 7.4 vs. 8.3 g/dl; P = 0.0063) and an approximately twice as high percentage of patients requiring blood transfusions were seen in PLS. No significant differences in other laboratory markers, duration of hospital stay, or other complications after LuTX were registered.Conclusions: Minor ABO incompatible LuTX recipients are at considerable risk of developing clinically significant PLS. Post-transplant monitoring combining red cell serology and hemolysis marker determination appears advisable so as not to overlook hemolytic episodes that necessitate antigen-negative transfusion therapy.

Panton-Valentine Leukocidin-Positive Staphylococcus aureus in Family and Pet Cat.

Continued detection of Panton-Valentine leukocidin-positive Staphylococcus aureus in samples from a family with severe repeated skin infections and their pet cat suggests transmission between the family and the cat. Decolonizing the pet led to successful elimination of the bacteria from the household. Clinicians should consider pet cats as possible reinfection sources.

Genetic basis of macrolide resistance in porcine Pasteurella multocida isolates from the German national resistance monitoring program GERM-Vet 2008-2021.

OBJECTIVES: To analyse porcine Pasteurella multocida isolates obtained from the national resistance monitoring program GERM-Vet 2008-2021 in Germany for phenotypic and genotypic macrolide resistance. METHODS: The antimicrobial susceptibility of the isolates was determined by broth microdilution according to CLSI standards. Closed genomes were obtained by WGS via Illumina MiSeq and MinION platforms followed by a hybrid assembly. RESULTS: Of 1114 porcine P. multocida isolates, only four isolates (0.36%), one each from 2008, 2010, 2019 and 2021, exhibited resistance to at least one macrolide tested. The isolate from 2010 was only resistant to erythromycin and WGS analysis neither revealed a macrolide resistance gene nor a macrolide resistance-mediating mutation. The isolates from 2008 and 2019 were resistant to erythromycin, tilmicosin, tildipirosin, tulathromycin and gamithromycin and showed either only the A2058G mutation in all six 23S rRNA operons or the chromosomally located macrolide resistance genes msr(E) and mph(E), respectively. The isolate from 2021 was resistant to erythromycin, tulathromycin, gamithromycin and tylosin and carried a novel integrative and conjugative element of 64 966 bp, designated Tn7730, in its chromosomal DNA. It harboured the macrolide resistance genes mef(C), mph(G) and estT, the lincosamide resistance gene lnu(H), and the tetracycline resistance gene tet(Y), the last two were detected for the first time in P. multocida. CONCLUSION: Macrolide resistance in German porcine P. multocida can be due to resistance-mediating mutations or resistance genes. The presence of the novel Tn7730 carrying three different macrolide resistance genes is alarming and should be monitored.

Tandem amplification of a plasmid-borne tet(A) variant gene confers tigecycline resistance in Escherichia coli.

OBJECTIVES: To elucidate the mechanism of tigecycline resistance in Escherichia coli that is mediated by the tet(A) variant gene. METHODS: E. coli strain 573 carried a plasmid-borne tet(A) variant gene, tentatively designated tet(A)TIG, that conferred decreased tigecycline susceptibility (MIC 0.5 mg/L). When exposed to increasing concentrations of tigecycline (0.25-8 mg/L), mutants growing at 2, 4 and 8 mg/L were obtained and sequenced. Copies of plasmid and tet(A)TIG relative to the chromosomal DNA in the mutants were determined by WGS and quantitative PCR (qPCR). Expression of tet(A)TIG in the mutants was evaluated by RT-qPCR. The tet(A)TIG-carrying plasmids were visualized by S1-PFGE and Southern blot hybridization. PCR served for the detection of a tet(A)TIG-carrying unconventional circularizable structure (UCS). RESULTS: Tigecycline resistance with maximum MICs of 16 mg/L was seen in E. coli mutants selected in the presence of tigecycline. Compared with the parental strain, the relative copy number and transcription level of tet(A)TIG in the mutants increased significantly in the presence of 2, 4 and 8 mg/L tigecycline, respectively. With increasing tigecycline selection pressure, the tet(A)TIG-carrying plasmids in the mutants increased in size, correlating with the number of tandem amplificates of a ΔTnAs1-flanked UCS harbouring tet(A)TIG. These tandem amplificates were not stable in the absence of tigecycline. CONCLUSIONS: Tigecycline resistance is due to the tandem amplification of a ΔTnAs1-flanked tet(A)TIG-carrying plasmid-borne segment in E. coli. The gain/loss of the tandem amplificates in the presence/absence of tigecycline represents an economic way for the bacteria to survive in the presence of tigecycline.

poxtA amplification and mutations in 23S rRNA confer enhanced linezolid resistance in Enterococcus faecalis.

OBJECTIVES: This study aimed to explore the evolutionary patterns and resistance mechanisms of an Enterococcus faecalis strain harbouring poxtA under linezolid exposure. METHODS: A poxtA-carrying E. faecalis electrotransformant DJH702 with a linezolid minimum inhibitory concentration of 4 mg/L was exposed to increasing concentrations of linezolid (8-64 mg/L). The derived strains growing at 8, 16, 32 and 64 mg/L, designed DJH702_8, DJH702_16, DJH702_32 and DJH702_64, were obtained. The amplification and overexpression of poxtA were measured using sequencing and RT-PCR, the fitness cost by competition assays and the stability of the repeat units by serial passage. RESULTS: In all derived strains, high-level linezolid resistance develops through poxtA amplification. The relative copy numbers and transcription levels of poxtA were significantly increased. However, in the presence of higher linezolid concentrations, DJH702_32 and DJH702_64 showed reduced poxtA copy numbers and transcription levels compared with DJH702_8 and DJH702_16, but additional mutations in the 23S rRNA (G2505A). IS1216E-mediated formation of translocatable units with subsequent tandem amplification of these translocatable units supported the gain of poxtA segments. However, these amplicons were not stable and were lost frequently in the absence of a linezolid selection pressure. The amplification of the poxtA region did not result in a fitness cost, but mutations in 23S rRNA did. CONCLUSIONS: poxtA-carrying E. faecalis electrotransformants used two distinct mechanisms to resist linezolid selection pressure: at lower concentrations, strains prioritized increasing poxtA expression levels, while at higher concentrations, a combination of increased poxtA expression and mutations in 23S rRNA was observed.

Global spread of the linezolid-resistant Enterococcus faecalis ST476 clonal lineage carrying optrA.

OBJECTIVES: To investigate the global distribution of an optrA-harbouring linezolid-resistant Enterococcus faecalis ST476 clonal lineage. METHODS: Comprehensive searches of the NCBI database were performed to identify published peer-reviewed articles and genomes of E. faecalis ST476. Each genome was analysed for resistome, virulome, OptrA variant and optrA genetic contexts. A phylogenetic comparison of ST476 genomes with publicly available genomes of other STs was also performed. RESULTS: Sixty-six E. faecalis ST476 isolates from 15 countries (China, Japan, South Korea, Austria, Denmark, Spain, Czech Republic, Colombia, Tunisia, Italy, Malaysia, Belgium, Germany, United Arab Emirates and Switzerland) mainly of human and animal origin were identified. Thirty available ST476 genomes compared with genomes of 591 STs indicated a progressive radiation of E. faecalis STs starting from ST21. The closest ancestral node for ST476 was ST1238. Thirty E. faecalis ST476 genomes exhibited 3-916 SNP differences. Several antimicrobial resistance and virulence genes were conserved among the ST476 genomes. The optrA genetic context exhibited a high degree of or complete identity to the chromosomal transposon Tn6674. Only three isolates displayed an optrA-carrying plasmid with complete or partial Tn6674. The WT OptrA protein was most widespread in the ST476 lineage. CONCLUSIONS: Linezolid-resistant optrA-carrying E. faecalis of the clonal lineage ST476 is globally distributed in human, animal and environmental settings. The presence of such an emerging clone can be of great concern for public health. Thus, a One Health approach is needed to counteract the spread and the evolution of this enterococcal clonal lineage.

Bidirectional transfer of human cytomegalovirus strains in donor and recipient seropositive lung transplant patients.

Donor and recipient human cytomegalovirus (HCMV) seropositive (D+R+) lung transplant recipients (LTRs) often harbor multiple strains of HCMV, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post-transplantation (post-Tx) strain population is unknown. Here, we deciphered the D and R origin of the post-Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin-fixed paraffin-embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained before transplantation. HCMV strains were characterized by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first 6 months after transplantation, likely by infiltrating CD14+ CD163+/- alveolar macrophages. In three LTRs, we demonstrate both rapid D-strain dissemination and persistence in the transplanted lung for >1 year post-Tx. Broad inter-host diversity contrasts with intra-host genotype sequence stability upon transmission, during follow-up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long-term in subsequent episodes of infection, indicating replication of both sources despite pre-existing immunity.

Diversity of Staphylococcus aureus isolated from nares of ruminants.

AIMS: To examine the diversity of Staphylococcus aureus isolated from nasal swabs of ruminants in Rwanda. METHODS AND RESULTS: A total of 454 nasal swabs from 203 cows, 170 goats, and 81 sheep were examined for the presence of S. aureus, and 30 S. aureus isolates were detected and characterized pheno- and genotypically. Resistance to penicillin and/or tetracycline was observed. The isolates were assigned to eight different spa types (t21057 (novel), t10103, t18853, t20842, t318, t355, t458, and t9432) belonging to six clonal complexes (CCs) (CC152, CC30, CC3591, CC3666, CC522, and CC97). Panton-Valentine leukocidin (PVL) genes (lukF-PV/lukS-PV), the bovine leukocidin genes (lukM/lukF-P83), and the human and bovine variants of the toxic shock syndrome toxin gene tst-1 variants were detected. CONCLUSION: These findings demonstrate that the nares of ruminants in Rwanda are colonized with mastitis-associated S. aureus, including lineages that are also carried by humans, underscoring the zoonotic risk, especially for livestock keepers. These results highlight the crucial importance of hygiene measures when handling livestock.

Computed Tomography-Based Body Composition is Related to Perioperative Morbidity in Older Lung Transplant Recipients.

BACKGROUND: In older patients, a limited physical reserve is considered a contraindication for lung transplantation (LTx). Herein, we aimed to establish a computed tomography (CT)-based quantification of physical reserve in older patients scheduled for transplantation. METHODS: This retrospective study included patients older than 60 years who received LTx. Semiautomatic measurements of the mediastinal fat area and the dorsal muscle group area in pretransplantation CT scans were performed, and normalized data were correlated with clinical parameters. RESULTS: Patients (n = 108) were assigned into three groups (Musclehighfatlow [n = 25], Musclelowfathigh [n = 24], and other combinations [n = 59]). The Musclelowfathigh group had a significantly increased risk of wound infections (p = 0.002) and tracheostomy (p = 0.001) compared with Musclehighfatlow patients. The median length of intensive care unit stay (25 vs. 3.5 days; p = 0.002) and the median length of hospital stay (44 vs. 22.5 days; p = 0.013) post-LTx were significantly prolonged in the Musclelowfathigh group. Significantly more patients in this group had a prolonged ventilation time (11 vs. 0; p < 0.001). CONCLUSION: Body composition parameters determined in pretransplant chest CT scans in older LTx candidates might aid in identifying high-risk patients with a worse perioperative outcome after LTx.

The transmission risk of multidrug-resistant organisms between hospital patients and their pets - a case-control study, Germany, 2019 to 2022.

BackgroundCarriage of multidrug-resistant organisms (MDROs) in humans constitutes an important public health concern. Cross-transmission of bacteria between animals and humans has been demonstrated before.AimOur aim was to quantify the risk factor 'pet ownership' for MDRO colonisation in hospital patients.MethodsWe performed a matched case-control study from 2019 to 2022 in Berlin, Germany and compared MDRO-positive and MDRO-negative patients in terms of contact with pets and other risk factors for MDRO acquisition. Patients completed a questionnaire-based interview and provided nasal and rectal swabs. Pet owners provided swab samples from the throat and stool of their pets (dogs and cats). Phenotypically matching samples of owners and pets were analysed via whole genome sequencing.ResultsThe analyses included 2,891 patients. Reported pet ownership was 17.7% in MDRO-positives (154/871) and 23.4% in MDRO-negatives (472/2,020). Among 397 owner-pet pairs, we identified one pair sharing genotypically indistinguishable pathogens (0.3%). A risk factor analysis of pet ownership was performed for carriers of meticillin-resistant Staphylococcus aureus (MRSA) (OR = 0.662; 95% CI: 0.343-1.277), vancomycin-resistant enterococci (VRE) (OR = 0.764; 95% CI: 0.522-1.118) and multidrug-resistant Gram-negative bacteria (MDR-GNB) (OR = 0.819; 95% CI: 0.620-1.082). Colonisation with MDRO was rare in pets, and dogs were more often colonised than cats (MRSA: 0% vs 0%, VRE: 1.5% vs 1.0%, MDR-GNB: 17.2% vs 3.6%).ConclusionTransmission of MDROs between humans and pets is possible though rare. In an urban living space, neither cat nor dog ownership appears as a relevant risk factor for MDRO carriage in hospital patients.

Genome-wide association reveals host-specific genomic traits in Escherichia coli.

BACKGROUND: Escherichia coli is an opportunistic pathogen which colonizes various host species. However, to what extent genetic lineages of E. coli are adapted or restricted to specific hosts and the genomic determinants of such adaptation or restriction is poorly understood. RESULTS: We randomly sampled E. coli isolates from four countries (Germany, UK, Spain, and Vietnam), obtained from five host species (human, pig, cattle, chicken, and wild boar) over 16 years, from both healthy and diseased hosts, to construct a collection of 1198 whole-genome sequenced E. coli isolates. We identified associations between specific E. coli lineages and the host from which they were isolated. A genome-wide association study (GWAS) identified several E. coli genes that were associated with human, cattle, or chicken hosts, whereas no genes associated with the pig host could be found. In silico characterization of nine contiguous genes (collectively designated as nan-9) associated with the human host indicated that these genes are involved in the metabolism of sialic acids (Sia). In contrast, the previously described sialic acid regulon known as sialoregulon (i.e. nanRATEK-yhcH, nanXY, and nanCMS) was not associated with any host species. In vitro growth experiments with a Δnan-9 E. coli mutant strain, using the sialic acids 5-N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) as sole carbon source, showed impaired growth behaviour compared to the wild-type. CONCLUSIONS: This study provides an extensive analysis of genetic determinants which may contribute to host specificity in E. coli. Our findings should inform risk analysis and epidemiological monitoring of (antimicrobial resistant) E. coli.

Characterization of an optrA-harbouring unconventional circularizable structure located on a novel ICESa2603 family-like integrative and conjugative element ICESsuHN38 in Streptococcus suis.

OBJECTIVES: To identify the novel genetic elements involved in the horizontal transfer of the oxazolidinone/phenicol resistance gene optrA in Streptococcus suis. METHODS: Whole-genome DNA of the optrA-positive isolate S. suis HN38 was subjected to WGS via both Illumina HiSeq and Oxford Nanopore platforms. MICs of several antimicrobial agents (erythromycin, linezolid, chloramphenicol, florfenicol, rifampicin and tetracycline) were determined by broth microdilution. PCR assays were performed to identify the circular forms of the novel integrative and conjugative element (ICE) ICESsuHN38, but also the unconventional circularizable structure (UCS) excised from this ICE. The transferability of ICESsuHN38 was evaluated by conjugation assays. RESULTS: S. suis isolate HN38 harboured the oxazolidinone/phenicol resistance gene optrA. The optrA gene was flanked by two copies of erm(B) genes in the same orientation, located on a novel ICESa2603 family-like ICE, designated ICESsuHN38. PCR assays revealed that a novel UCS carrying the optrA and one copy of erm(B) could be excised from ICESsuHN38. Conjugation assays confirmed that ICESsuHN38 was able to successfully transfer into the recipient strain S. suis BAA. CONCLUSIONS: In this work, a novel optrA-carrying mobile genetic element, a UCS, was identified in S. suis. The optrA gene was flanked by copies of erm(B) and its location on the novel ICESsuHN38 will aid its horizontal dissemination.

Various mobile genetic elements carrying optrA in Enterococcus faecium and Enterococcus faecalis isolates from swine within the same farm.

OBJECTIVES: In this study, the distribution of the oxazolidinone/phenicol resistance gene optrA and the mobile genetic elements involved in its dissemination were analysed among enterococcal isolates from a farrow-to-finish swine farm. METHODS: Enterococcus faecium and Enterococcus faecalis isolates were obtained from all pig production stages in the farm. The optrA-carrying E. faecium and E. faecalis isolates were subjected to PFGE and antimicrobial susceptibility testing. Complete sequences of the genetically unrelated optrA-carrying E. faecium and E. faecalis isolates were determined using Illumina HiSeq and MinION platforms. RESULTS: The optrA gene was present in 12.2% (23/188) of the E. faecium and E. faecalis isolates, most of which originated from nursery and finishing stages. The 23 optrA-positive Enterococcus isolates represented 15 PFGE types. WGS of representative isolates of the 15 PFGE types showed that optrA was carried by diverse genetic elements either located in the chromosomal DNA or on plasmids. A novel optrA-bearing genetic element was identified on two distinct multi-resistance plasmids from E. faecium. Two new hybrid plasmids carrying several resistance genes were found in two E. faecalis isolates. pC25-1-like plasmids and chromosomally integrated Tn6674 and Tn6823-like transposons were prevalent in the remaining Enterococcus isolates. CONCLUSIONS: The gene optrA was found in genetically unrelated E. faecium and E. faecalis isolates from the same farm. Analysis of the genetic contexts of optrA suggested that horizontal transfer including different plasmids and transposons played a key role in the dissemination of optrA in this farm.

Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria.

Seven mobile oxazolidinone resistance genes, including cfr, cfr(B), cfr(C), cfr(D), cfr(E), optrA, and poxtA, have been identified to date. The cfr genes code for 23S rRNA methylases, which confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The optrA and poxtA genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. The optrA gene confers resistance to oxazolidinones and phenicols, while the poxtA gene confers elevated MICs or resistance to oxazolidinones, phenicols, and tetracycline. These oxazolidinone resistance genes are most frequently found on plasmids, but they are also located on transposons, integrative and conjugative elements (ICEs), genomic islands, and prophages. In these mobile genetic elements (MGEs), insertion sequences (IS) most often flanked the cfr, optrA, and poxtA genes and were able to generate translocatable units (TUs) that comprise the oxazolidinone resistance genes and occasionally also other genes. MGEs and TUs play an important role in the dissemination of oxazolidinone resistance genes across strain, species, and genus boundaries. Most frequently, these MGEs also harbor genes that mediate resistance not only to antimicrobial agents of other classes, but also to metals and biocides. Direct selection pressure by the use of antimicrobial agents to which the oxazolidinone resistance genes confer resistance, but also indirect selection pressure by the use of antimicrobial agents, metals, or biocides (the respective resistance genes against which are colocated on cfr-, optrA-, or poxtA-carrying MGEs) may play a role in the coselection and persistence of oxazolidinone resistance genes.

[Therapy-relevant antibiotic resistances in a One Health context]. / Therapierelevante Antibiotikaresistenzen im One-Health-Kontext.

One Health refers to a concept that links human, animal, and environmental health. In Germany, there is extensive data on antibiotic resistance (AMR) and multidrug-resistant (micro)organisms (MDRO) in human and veterinary medicine, as well as from studies in various environmental compartments (soil, water, wastewater). All these activities are conducted according to different specifications and standards, which makes it difficult to compare data. A focus on AMR and MDRO of human therapeutic importance is helpful to provide some guidance. Most data are available across sectors on methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Enterobacterales such as Escherichia coli and Klebsiella pneumoniae. Here, the trends of resistance are heterogeneous. Antibiotic use leads to MRE selection, which is well documented. Success in minimizing antibiotic use has also been demonstrated in recent years in several sectors and could be correlated with success in containing AMR and MDRO (e.g., decrease in MRSA in human medicine). Sector-specific measures to reduce the burden of MDRO and AMR are also necessary, as not all resistance problems are linked to other sectors. Carbapenem resistance is still rare, but most apparent in human pathogens. Colistin resistance occurs in different sectors but shows different mechanisms in each. Resistance to antibiotics of last resort such as linezolid is rare in Germany, but shows a specific One Health correlation. Efforts to harmonize methods, for example in the field of antimicrobial susceptibility testing and genome-based pathogen and AMR surveillance, are an important first step towards a better comparability of the different data collections.

Characterization of qnrB-carrying plasmids from ESBL- and non-ESBL-producing Escherichia coli.

BACKGROUND: Escherichia coli carrying clinically important antimicrobial resistances [i.e., against extended-spectrum-beta-lactamases (ESBL)] are of high concern for human health and are increasingly detected worldwide. Worryingly, they are often identified as multidrug-resistant (MDR) isolates, frequently including resistances against quinolones/fluoroquinolones. RESULTS: Here, the occurrence and genetic basis of the fluoroquinolone resistance enhancing determinant qnrB in ESBL-/non-ESBL-producing E. coli was investigated. Overall, 33 qnrB-carrying isolates out of the annual German antimicrobial resistance (AMR) monitoring on commensal E. coli (incl. ESBL-/AmpC-producing E. coli) recovered from food and livestock between 2013 and 2018 were analysed in detail. Whole-genome sequencing, bioinformatics analyses and transferability evaluation was conducted to characterise the prevailing qnrB-associated plasmids. Furthermore, predominant qnrB-carrying plasmid-types were subjected to in silico genome reconstruction analysis. In general, the qnrB-carrying E. coli were found to be highly heterogenic in their multilocus sequence types (STs) and their phenotypic resistance profiles. Most of them appeared to be MDR and exhibited resistances against up to ten antimicrobials of different classes. With respect to qnrB-carrying plasmids, we found qnrB19 located on small Col440I plasmids to be most widespread among ESBL-producing E. coli from German livestock and food. This Col440I plasmid-type was found to be highly conserved by exhibiting qnrB19, a pspF operon and different genes of unassigned function. Furthermore, we detected plasmids of the incompatibility groups IncN and IncH as carriers of qnrB. All qnrB-carrying plasmids also exhibited virulence factors and various insertion sequences (IS). The majority of the qnrB-carrying plasmids were determined to be self-transmissible, indicating their possible contribution to the spread of resistances against (fluoro)quinolones and other antimicrobials. CONCLUSION: In this study, a diversity of different plasmid types carrying qnrB alone or in combination with other resistance determinants (i.e., beta-lactamase genes) were found. The spread of these plasmids, especially those carrying antimicrobial resistance genes against highest priority critically important antimicrobial agents, is highly unfavourable and can pose a threat for public health. Therefore, the dissemination pathways and evolution of these plasmids need to be further monitored.

Lung transplantation for acute respiratory distress syndrome: A multicenter experience.

Acute respiratory distress syndrome (ARDS) is a rapidly progressive lung disease with a high mortality rate. Although lung transplantation (LTx) is a well-established treatment for a variety of chronic pulmonary diseases, LTx for acute lung failure (due to ARDS) remains controversial. We reviewed posttransplant outcome of ARDS patients from three high-volume European transplant centers. Demographics and clinical data were collected and analyzed. Viral infection was the main reason for ARDS (n = 7/13, 53.8%). All patients were admitted to ICU and required mechanical ventilation, 11/13 were supported with ECMO at the time of listing. They were granted a median LAS of 76 (IQR 50-85) and waited for a median of 3 days (IQR 1.5-14). Postoperatively, median length of mechanical ventilation was 33 days (IQR 17-52.5), median length of ICU and hospital stay were 39 days (IQR 19.5-58.5) and 54 days (IQR 43.5-127). Prolongation of peripheral postoperative ECMO was required in 7/13 (53.8%) patients with a median duration of 2 days (IQR 2-7). 30-day mortality was 7.7%, 1 and 5-year survival rates were calculated as 71.6% and 54.2%, respectively. Given the lack of alternative treatment options, the herein presented results support the concept of offering live-saving LTx to carefully selected ARDS patients.

Mobilization of tet(X4) by IS1 Family Elements in Porcine Escherichia coli Isolates.

The dissemination mechanism of the high-level tigecycline resistance gene tet(X4) in porcine Escherichia coli was investigated. tet(X4) and other antimicrobial resistance genes were located on the plasmids p1919D3-1 and p1919D62-1 and flanked by two or three copies of IS1 family elements, which can form one to three translocatable units (TUs). Using a reduced transposition model, IS1A was experimentally demonstrated to mediate the transposition of tet(X4) from a suicide plasmid into the E. coli chromosome.

Multi-omics profiling predicts allograft function after lung transplantation.

RATIONALE: Lung transplantation is the ultimate treatment option for patients with end-stage respiratory diseases but bears the highest mortality rate among all solid organ transplantations due to chronic lung allograft dysfunction (CLAD). The mechanisms leading to CLAD remain elusive due to an insufficient understanding of the complex post-transplant adaptation processes. OBJECTIVES: To better understand these lung adaptation processes after transplantation and to investigate their association with future changes in allograft function. METHODS: We performed an exploratory cohort study of bronchoalveolar lavage samples from 78 lung recipients and donors. We analysed the alveolar microbiome using 16S rRNA sequencing, the cellular composition using flow cytometry, as well as metabolome and lipidome profiling. MEASUREMENTS AND MAIN RESULTS: We established distinct temporal dynamics for each of the analysed data sets. Comparing matched donor and recipient samples, we revealed that recipient-specific as well as environmental factors, rather than the donor microbiome, shape the long-term lung microbiome. We further discovered that the abundance of certain bacterial strains correlated with underlying lung diseases even after transplantation. A decline in forced expiratory volume during the first second (FEV1) is a major characteristic of lung allograft dysfunction in transplant recipients. By using a machine learning approach, we could accurately predict future changes in FEV1 from our multi-omics data, whereby microbial profiles showed a particularly high predictive power. CONCLUSION: Bronchoalveolar microbiome, cellular composition, metabolome and lipidome show specific temporal dynamics after lung transplantation. The lung microbiome can predict future changes in lung function with high precision.

Oxazolidinones: mechanisms of resistance and mobile genetic elements involved.

The oxazolidinones (linezolid and tedizolid) are last-resort antimicrobial agents used for the treatment of severe infections in humans caused by MDR Gram-positive bacteria. They bind to the peptidyl transferase centre of the bacterial ribosome inhibiting protein synthesis. Even if the majority of Gram-positive bacteria remain susceptible to oxazolidinones, resistant isolates have been reported worldwide. Apart from mutations, affecting mostly the 23S rDNA genes and selected ribosomal proteins, acquisition of resistance genes (cfr and cfr-like, optrA and poxtA), often associated with mobile genetic elements [such as non-conjugative and conjugative plasmids, transposons, integrative and conjugative elements (ICEs), prophages and translocatable units], plays a critical role in oxazolidinone resistance. In this review, we briefly summarize the current knowledge on oxazolidinone resistance mechanisms and provide an overview on the diversity of the mobile genetic elements carrying oxazolidinone resistance genes in Gram-positive and Gram-negative bacteria.