Editorial: Horizontal Gene Transfer Mediated Bacterial Antibiotic Resistance

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013–2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47–like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like–positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

In order to investigate the epidemiology, molecular characteristics, and distribution of extended-spectrum β-lactamase (ESBL)- and AmpC-producing Escherichia coli from community-onset infections in Chinese county hospitals. E. coli isolates were collected from patients with community-onset infections in 30 county hospitals. ESBL activity was confirmed by double-disc diffusion. Genetic confirmation and molecular typing of ESBL- and AmpC-producing isolates was determined by PCR and DNA sequencing. ESBL-positive isolates were further characterised by multi-locus sequence typing. Of 550 E. coli isolates, 256 (46.5%) carried ESBL genes and all were of the CTX-M type. The prevalence of ESBL-producing strains varied from 30.2% to 57.0% across different regions of China. Overall, 12 bla CTX-M subtypes were detected; the most abundant were bla CTX-M-14 (163/256 isolates, 64.5%), bla CTX-M-55(47/256, 18.4%), and bla CTX-M-15 (31/256, 12.1%). CMY-2-like AmpC β-lactamases were detected in 11 strains, three of which co-existed with bla CTX-M. A total of 64 sequence types (STs) were detected in 256 ESBL-producing strains, including nine that were new. ST131 was the most abundant type (27 isolates, 12.7%), followed by ST69 (14 isolates, 6.6%), ST405 (14 isolates, 6.6%), and ST38 (12 isolates, 5.6%). This study revealed that the widespread prevalence of ESBLs among outpatient infections has reached a high level in county hospitals. The CTX-M genotype was most dominant, comprising a variety of subtypes. This is the first time the incidence of CTX-M-55 has exceeded that of CTX-M-15 in China. No predominant ST was detected, suggesting that ESBL-producing E. coli strains originate in different clones.

Xonghong Xiao and colleagues analyze the challenge of antimicrobial resistance in China. A government strategy to promote rational use of antimicrobials in health care reduced antibiotic sales and percentage of prescriptions for antimicrobials for both hospitalized patients and outpatients, and offers insights to shape future initiatives. Please see later in the article for the Editors' Summary