Jiayuan Qin

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is classified by the World Health Organization as a top-priority pathogen due to its extensive prevalence and dissemination, antimicrobial resistance, and high mortality rates. ST11 CRKP is the most prevalent type in parts of Asia and South America. The success and dissemination of ST11 CRKP can be partly attributed to several key evolutionary events, including the acquisition of the KPC-2 plasmid plus altered outer membrane proteins OmpK35 and OmpK36 that confer carbapenem resistance, the subsequent capsule switching that led to the emergence of the KL64 capsule type, and the further acquisition of virulence plasmids commonly associated with the hypervirulent ST23 lineage. In this review, we summarize the current research advances of these key events, discuss existing knowledge gaps, and propose future directions to understand why ST11 CRKP has emerged as such a dominant and clinically significant clone.

Background: Factors contributing to the success of carbapenem-resistant Klebsiella pneumoniae (CRKP) of sequence type 11 (ST11) remain poorly understood. Methods: All GenBank-available K. pneumoniae genome sequences were retrieved. Isolates from mainland China carrying blaKPC and exhibiting high-quality assembly were selected for determining ST, virulence factors, antimicrobial resistance genes, plasmid types, and outer membrane porins (OmpK35 and OmpK36). Cloning experiments were performed for complementing porin deficiencies. In vitro growth assays under carbapenem selection pressure and carbon utilization assays were conducted. The structure alteration of OmpK36 with a two-amino-acid Gly-Asp insertion (OmpK36GD) was modeled. Results: ST11 accounted for 87.22% (8930/10 238) of all blaKPC-carrying CRKP Chinese strains. The majority (96.13%, 8584/8930) of ST11 CRKP strains had a truncated OmpK35 (OmpK35-del), with a 17%-amino-acid remnant, and OmpK36GD. Only 6.42% (84/1308) of non-ST11 CRKP possessed such alterations. The GD insertion obstructs the outermost channel and compromises OmpK36 function. ST11 CRKP with OmpK35-del and OmpK36GD exhibited higher minimum inhibitory concentrations to carbapenems, which was reduced by complementing wild-type of OmpK35 and/or OmpK36. Strains possessing OmpK35-del and OmpK36GD had better growth under low concentration (2 or 4 mg/L) meropenem. Unlike truncations of OmpK36, OmpK36GD does not interfere with utilizing carbon sources. Conclusions: OmpK35 deficiency and OmpK36 structure alteration, combined with KPC-2 carbapenemase production, contribute to the high-level carbapenem resistance observed in ST11 CRKP strains. OmpK36GD represents an optimal model for OmpK36 deficiencies due to its minimal fitness cost. With the porin deficiencies, ST11 CRKP strains demonstrate enhanced growth and proliferation under carbapenem selection pressure, likely promoting their prevalence.

We describe the genome of a lytic phage isolated from sewage, which is capable of lysing ST2 KL104-type carbapenem-resistant Acinetobacter baumannii strains. The genome is 167,208 bp in length, has a guanine-cytosine (GC) content of 37%, and includes 266 protein-coding sequences and five tRNAs.

We report the genome of a phage phi1_092033, isolated from sewage, which effectively lyses carbapenem-resistant Acinetobacter baumannii strains of various capsule types. phi1_092033 represents a species of genus Saclayvirus . Its genome consists of 104,070 bp, with a GC content of 38%, containing 188 protein-coding sequences and 13 tRNAs.

Background: Invasive mucormycosis (IM) poses a substantial morbidity and mortality burden among immunocompromised patients. Objectives: We aim to compare the real-world effectiveness and safety of isavuconazole with those of amphotericin B in patients with IM. Patients and methods: In this observational cohort study, we enrolled patients who were diagnosed with IM and treated with either isavuconazole or amphotericin B. Results: A total of 106 patients met the study criteria. Of these, 47 received isavuconazole, and 59 received amphotericin B as the primary treatment. The two cohorts had similar baseline characteristics, including a history of malignancy, use of immunosuppressants, infection sites, and pathogens. The amphotericin B group demonstrated a significantly greater incidence of renal disorders (p < 0.001) and hypokalemia (p < 0.001) than the isavuconazole group. The proportion of patients who received salvage therapy was greater in the amphotericin B group than in the isavuconazole group (42% vs. 6%, p < 0.001). Eighteen patients in the amphotericin B group discontinued treatment because of adverse events, whereas no patients in the isavuconazole group discontinued treatment because of adverse events. A significant difference in the primary therapeutic response between the isavuconazole and amphotericin B groups was noted (p = 0.013), with a higher treatment failure rate in the amphotericin B group (68% vs. 36%, p = 0.001). However, there were no significant differences in all-cause mortality or mucormycosis-attributable mortality rates between the two groups. Conclusions: Isavuconazole outperformed amphotericin B as a first-line treatment option for IM in terms of its clinical effectiveness and safety.