The efficacy of cefmetazole against pyelonephritis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae

SummaryObjectivesUrinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are on the increase. Although cefmetazole is stable in vitro against the hydrolyzing activity of ESBLs, no clinical study has ever evaluated its role in infections caused by these organisms. We therefore evaluated the efficacy of cefmetazole compared to carbapenems against pyelonephritis caused by ESBL-producing Enterobacteriaceae.MethodsA retrospective chart review was conducted at a tertiary care hospital from August 2008 to July 2010. Chart reviews were done for patients with ESBL-producing organisms in urine identified in the microbiology database. Patients who were treated with cefmetazole were compared to those treated with carbapenems. The clinical and bacteriological cure rates at 4 weeks after completion of therapy were evaluated.ResultsTwo hundred and fifty-six urine cultures growing ESBL-producing organisms were identified during the study period. Ten patients treated with cefmetazole and 12 patients treated with carbapenems were evaluated. There was no difference in clinical (9/10 vs. 12/12, p=0.46) or bacteriological cure rate (5/7 vs. 6/7, p=1.00) at 4 weeks after the completion of therapy. There was no difference in the incidence of adverse effects (2/10 vs. 2/12, p=1.00).ConclusionsCefmetazole may be a useful option for the treatment of UTIs caused by ESBL-producing organisms. Prospective and larger sized studies are needed to confirm our findings

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Radio-Protected Area Estimation Model Using Location-Dependent Gain for a Spectrum Sharing System in the VHF-Band

This paper proposes a radio-protected area (RPA) estimation model that achieves full protection and avoids overprotection by adding an appropriate margin to the extended-Hata (EH) model, for realizing efficient spectrum sharing in the V-High-band. This additional margin, called location gain, is a location-dependent value that accounts for knife-edge losses calculated from topographic information. This study experimentally obtains the location gain by conducting VHF-band-based propagation experiments in urban and suburban areas. Subsequently, we developed an estimation formula for the location gain using topographic data, which include correction terms based on the experimental data. As a result, RPA can be estimated using only the topographic data, excluding the need for propagation experiments. The proposed model resolved the problems of the EH model (incomplete protection) and free-space (FS) model (overprotection). In urban and suburban areas, the proposed model achieved full protection and over 99.7% reduction in the RPA size of the FS model when the threshold of the received power for determining the RPA was set to –80 dBm

Chromosomally Encoded blaCMY-2 Located on a Novel SXT/R391-Related Integrating Conjugative Element in a Proteus mirabilis Clinical Isolate ▿

Integrating conjugative elements (ICEs) are mobile genetic elements that can transfer from the chromosome of a host to the chromosome of a new host through the process of excision, conjugation, and integration. Although SXT/R391-related ICEs, originally demonstrated in Vibrio cholerae O139 isolates, have become prevalent among V. cholerae isolates in Asia, the prevalence of the ICEs among Gram-negative bacteria other than Vibrio spp. remains unknown. In addition, SXT/R391-related ICEs carrying genes conferring resistance to extended-spectrum cephalosporins have never been described. Here we carried out a genetic analysis of a cefoxitin-resistant Proteus mirabilis clinical isolate, TUM4660, which revealed the presence of a novel SXT/R391-related ICE, ICEPmiJpn1. ICEPmiJpn1 had a core genetic structure showing high similarity to that of R391 and carried xis and int genes completely identical to those of R391, while an IS10-mediated composite transposon carrying blaCMY-2 was integrated into the ICE. A nucleotide sequence identical to the 3′ part of ISEcp1 was located upstream of the blaCMY-2 gene, and other genes observed around blaCMY-2 in earlier studies were also present. Furthermore, the nucleotide sequences of hot spot 2 and hot spot 4 in ICEPmiJpn1 showed high similarity to that of hot spot 2 in SXTMO10 and with a part of the nucleotide sequence found in P. mirabilis ATCC 29906, respectively. ICEPmiJpn1 was successfully transferred to Escherichia coli, Klebsiella pneumoniae, Salmonella enterica serovar Typhimurium, and Citrobacter koseri in conjugation experiments. These observations suggest that ICEs may contribute to the dissemination of antimicrobial resistance genes among clinically relevant Enterobacteriaceae, which warrants careful observation of the prevalence of ICEs, including SXT/R391-related ICEs

Community-acquired liver abscess caused by capsular genotype K2-ST375 hypervirulent Klebsiella pneumoniae isolates

Hypervirulent Klebsiella pneumoniae has been associated with community-acquired liver abscesses in relatively healthy subjects since the 1990s, occasionally accompanied by disseminated disease. While isolates of capsular genotype K1 belonging to sequence type (ST) 23 have been the most prominent causative pathogen of this syndrome, other virulent clones have been implicated sporadically in recent years.A 68-year-old woman with diabetes in Okinawa, Japan suffered from a K. pneumoniae liver abscess, which recurred after a prolonged antibacterial treatment. The clinical course was further complicated with multiple sites of dissemination. Another 45-year-old woman living in Okinawa without underlying conditions was also diagnosed with a community-acquired K. pneumoniae liver abscess, which was cured with antibacterial treatment alone. Both of the causative isolates carried rmpA and aerobactin genes, and were confirmed as capsular genotype K2 and ST375.K. pneumoniae K2-ST375 is a hypervirulent clone of epidemiological significance causing severe community-acquired infections in relatively healthy subjects. More information about clinical characteristics and molecular epidemiology of hypervirulent K. pneumoniae clones other than K1-ST23 should be accumulated. Keywords: Community-acquired liver abscess, Hypervirulent Klebsiella pneumoniae, Capsular genotype K2, ST37