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This study identified and characterized extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) from farmed freshwater fish and pig offal procured from the wet markets across Hong Kong. During March 2018 to January 2019, 730 food animal samples, namely, 213 snakehead fish, 198 black carp, and 339 pig organs, were examined. ESBL-E and CPE were isolated from the homogenized samples plated on selective media and identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF-MS). All ESBL-E and CPE strains were tested for antimicrobial susceptibilities. ESBL-E and CPE gene groups were detected by multiplex PCR and blaCTX-M-1/-2/-9 group strains were Sanger sequenced for CTX-M types. All CPE isolates were whole-genome sequenced. Isolation of ESBL-E from pig small (52.4%) and large (50%) intestines and tongues (25.1%) was significantly (P < 0.05) more frequent than from snakehead (0.94%) and black carp (0.5%) fish. ESBL-E isolates (n = 171) revealed resistance rates of 16.3%, 29.8%, 35.6%, 53.2%, 55.0%, and 100% to piperacillin-tazobactam, amoxicillin-clavulanate, cefepime, gentamicin, ciprofloxacin, and ampicillin, respectively, whereas CPE (n = 28) were resistant to almost all the antibiotics tested except gentamicin, ciprofloxacin, and fosfomycin. The predominant ESBL gene groups in fishes and pig offals were blaCTX, where blaCTX-M-55 was the major subtype in the blaCTX-M-1 group (64.4% of isolates in the group). blaCTX-M-14/-17 was the major genotype in the blaCTX-M-9 group (32.2%). All CPE strains possessed blaNDM genes. High rates of ESBL-E and CPE were identified in food animals from wet markets of Hong Kong, which may serve as a potential reservoir of antimicrobial-resistant genes and increase the challenges in tackling antimicrobial resistance beyond health care settings. IMPORTANCE Extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are of global health importance, yet there is a paucity of surveillance studies on food animals in Hong Kong. Here, we report a high prevalence of ESBL-E (ranging from 0.5% to 52.4%) and CPE (0% to 9.9%) from various food animal samples procured from wet markets across Hong Kong. All CPE strains were characterized by whole-genome sequencing and possessed NDM-1 and -5 genes and other resistance determinants. Given the increased resistance profile of these strains, this study highlights the emerging threat of ESBL-E and CPE disseminated in farmed animals. Furthermore, our data enriched our understanding of antibiotic resistance reservoirs from a One Health perspective that can widely spread across various niches, beyond health care settings.

Objectives The aim of current systematic review and meta-analysis is to provide insight into the therapeutic efficacy of fecal microbiota transplantation (FMT) for the decolonization of antimicrobial-resistant (AMR) bacteria from the gut. Methods The protocol for this Systematic Review was prospectively registered with PROSPERO (CRD42020203634). Four databases (EMBASE, MEDLINE, SCOPUS, and WEB of SCIENCE) were consulted up until September 2020. A total of fourteen studies [ in vivo ( n = 2), case reports ( n = 7), case series without control arm ( n = 3), randomized clinical trials (RCT, n = 2)], were reviewed. Data were synthesized narratively for the case reports, along with a proportion meta-analysis for the case series studies ( n = 102 subjects) without a control arm followed by another meta-analysis for case series studies with a defined control arm ( n = 111 subjects) for their primary outcomes. Results Overall, seven non-duplicate case reports ( n = 9 participants) were narratively reviewed and found to have broad AMR remission events at the 1-month time point. Proportion meta-analysis of case series studies showed an overall 0.58 (95% CI: 0.42-0.74) AMR remission. Additionally, a significant difference in AMR remission was observed in FMT vs treatment naïve (RR = 0.44; 95% CI: 0.20-0.99) and moderate heterogeneity ( I 2 =65%). A subgroup analysis of RCTs ( n = 2) revealed FMT with further benefits of AMR remission with low statistical heterogeneity (RR = 0.37; 95% CI: 0.18-0.79; I 2 =23%). Conclusion More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted. KEY MESSAGE Existing studies in this subject are limited and of low quality with moderate heterogeneity, and do not allow definitive conclusions to be drawn. More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.

A series of cationic boron dipyrromethene (BODIPY) derivatives were synthesized and characterized with various spectroscopic methods. Having the ability to generate singlet oxygen upon irradiation, these compounds could potentially serve as photosensitizers for antimicrobial photodynamic therapy. Of the five BODIPYs being examined, the dicationic aza-BODIPY analogue (compound 5) demonstrated the highest potency against a broad spectrum of clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), including four ATCC-type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two strains carrying specific antibiotic resistance mechanisms [-AAC(6’)-APH(2”) and RN4220/pUL5054], and ten non-duplicate clinical strains from hospital- and community-associated MRSAs of the important clonal types ST239, ST30, and ST59, which have previously been documented to be prevalent in Hong Kong and its neighboring countries. The in vitro anti-MRSA activity of compound 5 was achieved upon irradiation with near-infrared light (>610 nm) with minimal bactericidal concentrations (MBCs) ranging from 12.5 to 25 µM against the whole panel of MRSAs, except the hospital-associated MRSAs for which the MBCs were in the range of 50–100 µM. Compound 5 was significantly (p < 0.05) more potent than methylene blue, which is a clinically approved photosensitizer, indicating that it is a promising antimicrobial agent that is worthy of further investigation.

Antimicrobial photodynamic therapy (aPDT) is an innovative approach to combat multi-drug resistant bacteria. It is known that cationic Zn(II) phthalocyanines (ZnPc) are effective in mediating aPDT against methicillin-resistant Staphylococcus aureus (MRSA). Here we used ZnPc-based photosensitizer named ZnPcE previously reported by our research group to evaluate its aPDT efficacy against broad spectrum of clinically relevant MRSAs. Remarkably, in vitro anti-MRSA activity was achieved using near-infrared (NIR, >610 nm) light with minimal bactericidal concentrations ranging <0.019-0.156 µM against the panel of MRSAs. ZnPcE was not only significantly (p < .05) more potent than methylene blue, which is a clinically approved photosensitizer but also demonstrated low cytotoxicity against human fibroblasts cell line (Hs-27) and human immortalized keratinocytes cell line (HaCaT). The toxicity was further evaluated on human 3-D skin constructs and found ZnPcE did not manifest in vivo skin irritation at ≤7.8 µM concentration. In the murine MRSA wound model, ZnPcE with PDT group demonstrated > 4 log 10 CFU reduction and the value is significantly higher (p < .05) than all test groups except positive control. To conclude, results of present study provide a scientific basis for future clinical evaluation of ZnPcE-PDT on MRSA wound infection.

Background: We report herein the synthesis of a novel dicationic boron dipyrromethene derivative (compound 3) which is symmetrically substituted with two trimethylammonium styryl groups. Methods: The antibacterial photodynamic activity of compound 3 was determined against sixteen methicillin-resistant Staphylococcus aureus (MRSA) strains, including four ATCC type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two mutant strains [AAC(6’)-APH(2”) and RN4220/pUL5054], and ten non-duplicate clinical strains of hospital- and communityassociated MRSA. Upon light irradiation, the minimum bactericidal concentrations of compound 3 were in the range of 1.56-50 µM against all the sixteen MRSA strains. Interestingly, compound 3 was not only more active than an analogue in which the ammonium groups are not directly connected to the pconjugated system (compound 4), but also showed significantly higher (p < 0.05) antibacterial potency than the clinically approved photosensitizer methylene blue. The skin irritation of compound 3 during topical application was tested on human 3-D skin constructs and proven to be non-irritant in vivo at concentrations below 1.250 mM. In the murine MRSA infected wound study, the colony forming unit reduction of compound 3 + PDT group showed significantly (p < 0.05) higher value (>2.5 log10) compared to other test groups except for the positive control. Conclusion: In conclusion, the present study provides a scientific basis for future development of compound 3 as a potent photosensitizer for photodynamic therapy for MRSA wound infection.

High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625–10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log10 CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower (p < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.