Colistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae. As such, the recent plasmid-mediated spread of the colistin resistance gene mcr-1 poses a significant public health threat, requiring global monitoring and surveillance. Here, we characterize the global distribution of mcr-1 using a data set of 457 mcr-1-positive sequenced isolates. We find mcr-1 in various plasmid types but identify an immediate background common to all mcr-1 sequences. Our analyses establish that all mcr-1 elements in circulation descend from the same initial mobilization of mcr-1 by an ISApl1 transposon in the mid 2000s (2002–2008; 95% highest posterior density), followed by a marked demographic expansion, which led to its current global distribution. Our results provide the first systematic phylogenetic analysis of the origin and spread of mcr-1, and emphasize the importance of understanding the movement of antibiotic resistance genes across multiple levels of genomic organization.

Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of infection burden are lacking. We established incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem non-susceptible C. freundii, E. coli, E. cloacae, or K. pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase genes identification were performed. Among 664 CRE cases, most were caused by K. pneumoniae (73.9%), followed by E. coli (16.6%), and E. cloacae (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0, and differed significantly by region, with the highest in Jiangsu (14.97), and the lowest in Qinghai (0.34). 83.8% of patients had underlying co-morbidities; the median age was 62 years (range, 45–74) and 450 (67.8%) were male. Lower respiratory tract infections (65.4%) were most common, followed by urinary-tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed non-susceptibility to carbapenems and cephalosporins. Susceptibility rate of Polymyxin B was >90%. Tigecycline demonstrated higher susceptibility rate against E. coli, compared with K. pneumoniae (90.9% vs. 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases with a majority of isolates producing KPC (50%) and/or NDM (33.5%)-type beta-lactamases among K. pneumoniae and E. coli. Incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.

Hypervirulent Klebsiella pneumoniae (hvKP) is traditionally defined by hypermucoviscosity, but data based on genetic background are limited. Antimicrobial-resistant hvKP has been increasingly reported but has not yet been systematically studied. K. pneumoniae isolates from bloodstream infections, hospital-acquired pneumonia, and intra-abdominal infections were collected from 10 cities in China during February to July 2013. Clinical data were collected from medical records. All K. pneumoniae isolates were investigated by antimicrobial susceptibility testing, string test, extended-spectrum β-lactamase (ESBL) gene detection, capsular serotypes, virulence gene profiles, and multilocus sequence typing. hvKP was defined by aerobactin detection. Of 230 K. pneumoniae isolates, 37.8% were hvKP. The prevalence of hvKP varied among different cities, with the highest rate in Wuhan (73.9%) and the lowest in Zhejiang (8.3%). Hypermucoviscosity and the presence of K1, K2, K20, and rmpA genes were strongly associated with hvKP ( P < 0.001). A significantly higher incidence of liver abscess ( P = 0.026), sepsis ( P = 0.038), and invasive infections ( P = 0.043) was caused by hvKP. Cancer (odds ratio [OR], 2.285) and diabetes mellitus (OR, 2.256) appeared to be independent variables associated with hvKP infections by multivariate analysis. Importantly, 12.6% of hvKP isolates produced ESBLs, and most of them carried bla _CTX-M genes. Patients with neutropenia (37.5% versus 5.6%; P = 0.020), history of systemic steroid therapy (37.5% versus 5.6%; P = 0.020), and combination therapy (62.5% versus 16.7%; P = 0.009) were more likely to be infected with ESBL-producing hvKP. The prevalence of hvKP is high in China and has a varied geographic distribution. ESBL-producing hvKP is emerging, suggesting an urgent need to enhance clinical awareness, especially for immunocompromised patients receiving combination therapy.

Community‐acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline.

Metagenomic next-generation sequencing (mNGS) is a comprehensive approach for sequence-based identification of pathogenic microbes. However, reports on the use of mNGS in pulmonary infection applied to lung biopsy tissues remain scarce. In this study, we applied mNGS to detect the presence of pathogenic microbes in lung biopsy tissues from 20 patients with pulmonary disorders indicating possible infection. We applied a new data management for identifying pathogen species based on mNGS data. We determined the thresholds for the unique reads and relative abundance required to identify the infectious pathogens. Potential pathogens of pulmonary infections in 15 patients were identified by mNGS. The comparison between mNGS and culture method resulted that the sensitivity and specificity were 100.0% (95% CI: 31.0–100.0%) and 76.5% (95% CI: 49.8–92.2%) for bacteria, 57.1% (95% CI: 20.2–88.2%) and 61.5% (95% CI: 32.2–84.9%) for fungi. The positive predictive value (PPV) (42.9% for bacteria, 44.4% for fungi) was much lower than negative predictive value (NPV) (100% for bacteria, 72.7% for fungi) in mNGS vs. culture method. The mNGS showed the highest specificity (100.0 and 94.1%) and PPV (100.0 and 75.0%) in the evaluation of fungi and MTBC respectively, when compared with histopathology method. The study indicated that mNGS of lung biopsy tissues can be used to detect the presence (or absence) of pulmonary pathogens in patients, with potential benefits in speed and sensitivity. However, accurate data management and interpretation of mNGS are required, and should be combined with observations of clinical manifestations and conventional laboratory-based diagnostic methods.