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The NG-Test CARBA 5 and Carbapenem-resistant K.N.I.V.O. Detection K-Set are lateral flow assays (LFAs) that rapidly detect five carbapenemases (KPC, NDM, IMP, VIM and OXA-48-like). We evaluated the effect of inoculum size on the performance of these two assays using 27 Enterobacterales isolates. Whole-genome sequencing (WGS) was used as the reference method. Using the NG-Test CARBA 5, eight Serratia spp. and six M. morganii isolates showed false-positive NDM results with a high inoculum. Using the Carbapenem-resistant K.N.I.V.O. Detection K-Set, eight M. morganii, four Serratia spp. and one K. pneumoniae isolates showed false-positive NDM and/or OXA-48-like bands at large inoculum sizes, while the other two M. morganii isolates demonstrated false-positive NDM and OXA-48-like results at all inoculum sizes. The false-positive bands varied in intensity. WGS confirmed that no carbapenemase gene was present. No protein sequence with a ≥50% identity to NDM or OXA-48-like enzymes was found. This study emphasizes the importance of assessing inoculum size in the diagnostic evaluation of LFAs. [ABSTRACT FROM AUTHOR]

While molnupiravir (MOV) and nirmatrelvir–ritonavir (NMV-r) were developed for treatment of mild to moderate COVID-19 infection, there has been a lack of data on the efficacy among unvaccinated adult patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. A territory-wide retrospective cohort study was conducted in Hong Kong to investigate the efficacy of MOV and NMV-r against severe outcomes of COVID-19 in unvaccinated adult patients with chronic respiratory diseases. A total of 3267 patients were included. NMV-r was effective in preventing respiratory failure (66.6%; 95% CI, 25.6–85.0%, p = 0.007), severe respiratory failure (77.0%; 95% CI, 6.9–94.3%, p = 0.039) with statistical significance, and COVID-19 related hospitalization (43.9%; 95% CI, −1.7–69.0%, p = 0.057) and in-hospital mortality (62.7%; 95% CI, −0.6–86.2, p = 0.051) with borderline statistical significance. MOV was effective in preventing COVID-19 related severe respiratory failure (48.2%; 95% CI 0.5–73.0, p = 0.048) and in-hospital mortality (58.3%; 95% CI 22.9–77.4, p = 0.005) but not hospitalization (p = 0.16) and respiratory failure (p = 0.10). In summary, both NMV-r and MOV are effective for reducing severe outcomes in unvaccinated COVID-19 patients with chronic respiratory diseases. [ABSTRACT FROM AUTHOR]

The emergence and rapid spread of the mobile colistin resistance gene mcr-1 among bacterial species and hosts significantly challenge the efficacy of "last-line" antibiotic colistin. Previously, we reported silver nitrate and auranofin serve as colistin adjuvants for combating mcr-1-positive bacteria. Herein, we uncovered more gold-based drugs and nanoparticles, and found that they exhibited varying degree of synergisms with colistin on killing mcr-1-positive bacteria. However, pre-activation of the drugs by either glutathione or N-acetyl cysteine, thus releasing and accumulating gold ions, is perquisite for their abilities to substitute zinc cofactor from MCR-1 enzyme. X-ray crystallography and biophysical studies further supported the proposed mechanism. This study not only provides basis for combining gold-based drugs and colistin for combating mcr-1-positive bacterial infections, but also undoubtedly opens a new horizon for metabolism details of gold-based drugs in overcoming antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Objectives: Although the topic of antibiotic misuse is taught in medical schools, interns (fresh medical graduates) still encounter barriers to appropriate antibiotic prescription when they practice in hospitals under supervision. The impact of teaching in medical school, antibiotics stewardship program (ASP), and prescription guidelines was uncertain. This study explored the medical interns' views on antibiotic use and resistance, and their perceived enablers to appropriate antibiotic prescription. Methods: Two focus groups were conducted among medical interns with rotation experiences in different public hospitals of Hong Kong. The identified themes about attitudes to antibiotic resistance and enablers to appropriate antibiotic prescription were further examined by a questionnaire survey with 77 respondents. Results: The interns had lower preferences for tackling antibiotic resistance as they feared of delayed prescriptions. Guidelines provided by international evidence-based clinical resources and the interns' working hospitals were stronger enablers to appropriate antibiotic use than education materials from schools and the government. Qualitative findings revealed that the interns were aware of the existing ASP but doubted its effectiveness as it failed to get the prescribers' attention. They followed guidelines in their wards but perceived guidelines from local health authorities user-unfriendly. Knowledge from medical school was not very applicable. Varying prescribing practices between hospitals and the densely placed hospital beds made it difficult to prevent the spread of antimicrobial resistance. Conclusions: Minimizing delayed prescription is of a higher priority than tackling antibiotic resistance in medical interns' perspective. Interventions should target guidelines in hospitals and simplify the interface of local guidelines. [ABSTRACT FROM AUTHOR]

Background: Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease.Objective: To apply a metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration to investigate the effect of border restriction as a public health measure to limit outbreak of coronavirus disease 2019.Methods: We apply a modified metapopulation SEIR model with inspected migration with simulating population migration, and incorporating parameters such as efficiency of custom inspection in blocking infected travelers in the model. The population sizes were retrieved from government reports, while the number of COVID-19 patients were retrieved from Hong Kong Department of Health and China Centre for Disease Control (CDC) data. The R0 was obtained from previous clinical studies.Results: Complete border closure can help to reduce the cumulative COVID-19 case number and mortality in Hong Kong by 13.99% and 13.98% respectively. To prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary, apart from having complete border closure.Conclusions: Early complete travel restriction is effective in reducing cumulative cases and mortality. However, additional anti-COVID-19 measures to reduce local R0 to below 1.6 are necessary to prevent COVID-19 cases from overwhelming hospital isolation facilities. [ABSTRACT FROM AUTHOR]

This retrospective study analyzed the susceptibility levels of Bacteroides fragilis group (BFG) in a hospital-based laboratory where disk diffusion test (DDT) was routinely performed. Isolates non-susceptible to imipenem and metronidazole by DDT were further investigated using a gradient method. The DDT and MIC susceptibility data of clindamycin, metronidazole, moxifloxacin and imipenem obtained on Brucella blood agar for 1264 non-duplicated isolates during 2020–2021 were analyzed. Species identification was obtained by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and 16S rRNA sequencing. Interpretative agreement of DDT results using the 2015 EUCAST tentative and 2021 CA-SFM breakpoints was compared against MIC as the reference. The dataset included 604 B. fragilis (483 division I, 121 division II isolates), 415 non- fragilis Bacteroides , 177 Phocaeicola and 68 Parabacteroides. Susceptibility rates for clindamycin (22.1–62.1%) and moxifloxacin (59.9–80.9%) were low and many had no inhibition zones. At the EUCAST and CA-SFM breakpoints, 83.0 and 89.4% were imipenem-susceptible, and 89.6% and 97.4 were metronidazole-susceptible. MIC testing confirmed 11.4% and 2.8% isolates as imipenem-non-susceptible and metronidazole-resistant, respectively. Significant numbers of false-susceptibility and/or false-resistance results were observed at the CA-SFM breakpoint but not the EUCAST breakpoint. Higher rates of imipenem and/or metronidazole resistance were detected in B. fragilis division II, B. caccae, B. ovatus, B. salyersiae, B. stercoris and Parabacteroides. Co-resistance to imipenem and metronidazole was detected in 3 B. fragilis division II isolates. The data demonstrated emerging BFG resistance to several important anti-anaerobic antibiotics and highlights the importance of anaerobic susceptibility testing in clinical laboratories to guide therapy. • Antimicrobial resistance in Bacteroides fragilis group is emerging. • Antimicrobial susceptibilities of 1264 B. fragilis group were analyzed. • Clindamycin and moxifloxacin resistance rates were high. • Imipenem resistance rate was 11.4%. • Metronidazole resistance rate was 2.8%. [ABSTRACT FROM AUTHOR]

To compare the phylogeny of cfiA -positive Bacteroides fragilis isolates from diverse human and animal sources. Complete genome sequences were obtained from 42 cfiA -positive B. fragilis isolates (Hong Kong, 2015–2017) and additional 24 genomes deposited in the GenBank (multiple countries, 1985–2019) were included. The genomic clusters were constructed using PopPUNK. The CfiA alleles and polymorphism in the cfiA locus were analyzed in silico. The 66 isolates were grouped into 12 genomic clusters (BFSC-1 to 12). Human infection isolates were distributed in diverse clusters, being many of them common to fecal isolates from both human and animals. Thirteen CfiA alleles including 2 novel ones were identified. CfiA-1 (n = 28) is the predominating allele, following by CfiA-13 (n = 8), CfiA-4 (n = 7) and CfiA-14 (n = 6). The other CfiA alleles were identified in 1–3 isolates. Six patterns of gene context were identified in the regions flanking cfiA locus. No consistent association between genomic clusters and CfiA alleles could be detected. Similarly, markedly elevated imipenem MIC was linked to the integration, immediately upstram of cfiA of an IS element but not the CfiA allele or gene context. The phylogeny of cfiA -positive B. fragilis isolates causing human diseases was diverse and overlaped with those from human and animal carriage. • The genomic phylogeny of 66 cfiA -positive Bacteroides fragilis isolates was analyzed. • The isolates were grouped into 12 PopPUNK-based genomic clusters. • Clinical isolates shared the same genome clusters as carriage isolates from human and animals. • No correlation between CfiA allele and genome cluster was identifed. • The phylogeny of emerging cfiA -positive B. fragilis is diverse. [ABSTRACT FROM AUTHOR]