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Chunjiang Zhao, Shuo Yang, Feifei Zhang, Zhanwei Wang, Yawei Zhang, Xiaojuan Wang, Henan Li, Hongbin Chen, Hui Wang Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Hui Wang, Department of Clinical Laboratory, Peking University People’s Hospital, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Email whuibj@163.comBackground: Emergence of antimicrobial resistance poses new challenges in the management of community acquired respiratory tract infections (CARTIs). Therefore, surveillance on the antimicrobial susceptibilities of common respiratory pathogens is valuable and guides empirical therapeutic choices in management of CARTIs.Objective: The objective of the current study is to summarize the antimicrobial resistance trends in common respiratory tract pathogens isolated from patients with CARTIs in China, over a 10-year period (2009– 2018).Methods: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis strains were collected from multicenter, and antimicrobial susceptibility testing was performed in the research central laboratory of each study period from 2009– 2018. The pathogens that accounted for CARTIs in the adult population was considered and summarized.Results: From 2009– 2018 a total of 3750 isolates were collected from 22 cities located across different regions of China. Among these the most common bacterial isolates include S. pneumoniae (53.7%) followed by H. influenza (32.4%), M. catarrhalis (13.9%). S. pneumoniae exhibited reduction in susceptibility and increase in resistance to penicillin, cephalosporins (cefaclor, cefuroxime, ceftriaxone) during the surveillance period. Invasive and noninvasive S. pneumoniae showed similar resistance. In the case of H. influenzae susceptibility to β-lactam and β-lactamase inhibitors (ampicillin, amoxicillin and AMC), SXT, clarithromycin and cephalosporins (cefuroxime, cefaclor, ceftazidime) was reduced over the past 10 years with an exception of ceftriaxone. Overall, moxifloxacin and levofloxacin have the highest susceptibility rates against S. pneumoniae (> 95%) and H. influenza (> 90%). M. catarrhalis exhibited susceptibility to almost all the tested antimicrobials.Conclusion: In China the 10-year trends showed a substantial increase in resistance to β-lactam drugs and reduction in sensitivity. However, certain antimicrobial agents namely fluoroquinolones including moxifloxacin and levofloxacin maintained low resistance rates with better susceptibility. Further, with few exceptions decline in susceptibility rates to macrolides and cephalosporins was observed among the tested pathogens.Keywords: Community-acquired respiratory tract infections, antimicrobial resistance, susceptibility, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis

Purpose The Chinese Meropenem Surveillance Study (CMSS) was conducted every 2 years from 2010 to 2018 to monitor the antimicrobial activity of commonly used antimicrobial agents against nosocomial gram-negative bacilli in China. Methods From 2010 to 2018, 6,537 gram-negative bacilli were collected from 14 teaching hospitals. The minimum inhibitory concentrations (MICs) of meropenem and other antimicrobial agents were determined using the agar dilution and broth microdilution methods. Results Continuous surveillance indicated that, except for Klebsiella pneumoniae, the susceptibility of Enterobacterales to carbapenems was relatively stable over time. Carbapenems had the highest activity against the tested isolates, with MIC90 values (MIC for 90% of organisms) ranging from 0.032 mg/L to 8 mg/L. More than 90% of bacteria were susceptible to either meropenem or imipenem; more than 80% were susceptible to ertapenem. The prevalence of extended-spectrum beta-lactamase (ESBL)-producing E. coli, K. pneumoniae, and P. mirabilis each year was 50.4-64.3%, 18-41.2%, and 1.9-33.8%, respectively. The prevalence of carbapenem-resistant K. pneumoniae (CRKP) and carbapenem-resistant Acinetobacter baumannii (CRAB) continued to increase significantly over time, from 7.6% to 21.2% and 64.6% to 69.3%, respectively. The prevalence of CRKP was higher from urinary tract infections (25.4%) than from bloodstream infections (14.2%), intra-abdominal infections (14.5%), and respiratory infections (14.4%). In total, 129 CRKP isolates were evaluated by PCR; of these, 92 (71.3%) carried the bla KPC-2 gene. Colistin maintained very high in vitro antimicrobial activity against P. aeruginosa and A. baumannii (more than 95% of isolates exhibited susceptibility at all timepoints). Conclusion The results indicate an increase in K. pneumoniae resistance to carbapenems over time, mainly owing to KPC-type carbapenemase production. A. baumannii was severely resistant to carbapenems in China. Ongoing MIC-based resistance surveillance, like CMSS, provides additional data for clinical anti-infective treatment.

Background Streptococcus pneumoniae infections are the major cause of global morbidity and mortality among children and patients aged more than 65 years. This study aimed to investigate the antimicrobial resistance, bacterial serotype distribution, and genetic characteristics of invasive S. pneumoniae from different cities in North China. Materials and methods A total of 164 invasive S. pneumoniae strains were collected from 8 hospitals in 5 regions of North China between April 2016 and October 2017. Minimum inhibitory concentrations (MICs) were determined using the agar dilution method. Capsular serotypes were identified using the Quellung reaction test. Molecular epidemiology was investigated using multilocus sequence typing. Results S. pneumoniae isolates were highly resistant to macrolides, clindamycin, and tetracycline in all age groups. The overall rate of resistance to penicillin was 56.7%. However, fluoroquinolones and vancomycin maintained excellent antimicrobial activities. The rate of resistance to β-lactam in strains isolated from children aged less than 18 years was significantly higher than that in strains from other age groups. The most prevalent serotypes were 14 (22.6%), 19F (16.5%), non-vaccine types (14.0%), 19A (9.8%), and 23F (9.1%). The coverage for PCV10 and PCV13 was 59.8% and 75.6%, respectively. The vaccine coverage rate was the highest among children aged less than 5 years. The proportion of penicillin-resistant isolates was higher among vaccine-covered strains compared with non-covered strains. S. pneumoniae showed considerable clonal dissemination, and ST876 (28, 17.1%), ST271 (22, 13.4%), ST81 (17, 10.4%) and ST320 (14, 8.5%) were the major STs. Conclusion All the 164 invasive S. pneumoniae isolates demonstrated high resistance to antibiotics. The coverage of S. pneumoniae vaccine was higher in children than in adults.

Henan Li, Jiangang Zhang, Zhiren Wang, Yuyao Yin, Hua Gao, Ruobing Wang, Longyang Jin, Qi Wang, Chunjiang Zhao, Zhanwei Wang, Hui Wang Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Hui WangDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaTel +86-10-88326300Email whuibj@163.comIntroduction: Colonization of the respiratory tract by Acinetobacter baumannii has been established as an independent risk factor for bacteremia. However, within-host evolution of A. baumannii in bacteremia has not been extensively investigated.Methods: We performed whole-genome sequencing to discover the evolutionary characteristics that accompany the transition from respiratory tract carriage to bloodstream infection in three patients with A. baumannii bacteremia.Results: Within-host genetic diversity was identified. A total of 21 single nucleotide variants (SNVs) were detected. Genic and intergenic evolution occurred particularly in secretion system, DNA recombination, and cell motility genes. Intergenic SNVs occurred more frequently compared to synonymous and non-synonymous SNVs, which indicated potential transcription or translation regulation. Non-synonymous mutations mostly occurred during the transition from respiratory tract carriage to bloodstream infection. Isolates of clonal complex 208 (CC208) had lower substitution rate with approximately 10− 6 nucleotide substitutions per site year− 1, compared with non-CC208 isolates (approximately 10− 5). We found evidence for the occurrence of recombination in one patient. A total of 259 genes were found to be gained or lost during the within-host evolution, and 231 genes were only detected in one patient. Gene function annotation results suggested that most genes (71/259) were related to replication, recombination, and repair. Universal bloodstream specific genes were not found in all three patients, and only one putative membrane protein related gene was lost in two patients.Conclusion: Our results indicated that within-host evolution of A. baumannii bacteremia was driven by mutations, gene content changes, and limited effect of recombination. Gene content diversity between different patients was identified, which suggested interplay of both host and pathogen factors in within-host genetic diversity. Secretion system-related genes showed higher frequency of genomic variations during the within-host evolution. Our findings enhanced our understanding of within-host evolution of A. baumannii bacteremia and provided a framework for discovering novel genomic changes and pathogenicity genes important for bacteremia, which will be validated in future studies.Keywords: Acinetobacter baumannii, within-host evolution, mutation, secretion system, bacteremia

Purpose The Chinese Meropenem Surveillance Study (CMSS) was conducted every 2 years from 2010 to 2018 to monitor the antimicrobial activity of commonly used antimicrobial agents against nosocomial gram-negative bacilli in China. Methods From 2010 to 2018, 6,537 gram-negative bacilli were collected from 14 teaching hospitals. The minimum inhibitory concentrations (MICs) of meropenem and other antimicrobial agents were determined using the agar dilution and broth microdilution methods. Results Continuous surveillance indicated that, except for Klebsiella pneumoniae, the susceptibility of Enterobacterales to carbapenems was relatively stable over time. Carbapenems had the highest activity against the tested isolates, with MIC90 values (MIC for 90% of organisms) ranging from 0.032 mg/L to 8 mg/L. More than 90% of bacteria were susceptible to either meropenem or imipenem; more than 80% were susceptible to ertapenem. The prevalence of extended-spectrum beta-lactamase (ESBL)-producing E. coli, K. pneumoniae, and P. mirabilis each year was 50.4–64.3%, 18–41.2%, and 1.9–33.8%, respectively. The prevalence of carbapenem-resistant K. pneumoniae (CRKP) and carbapenem-resistant Acinetobacter baumannii (CRAB) continued to increase significantly over time, from 7.6% to 21.2% and 64.6% to 69.3%, respectively. The prevalence of CRKP was higher from urinary tract infections (25.4%) than from bloodstream infections (14.2%), intra-abdominal infections (14.5%), and respiratory infections (14.4%). In total, 129 CRKP isolates were evaluated by PCR; of these, 92 (71.3%) carried the blaKPC-2 gene. Colistin maintained very high in vitro antimicrobial activity against P. aeruginosa and A. baumannii (more than 95% of isolates exhibited susceptibility at all timepoints). Conclusion The results indicate an increase in K. pneumoniae resistance to carbapenems over time, mainly owing to KPC-type carbapenemase production. A. baumannii was severely resistant to carbapenems in China. Ongoing MIC-based resistance surveillance, like CMSS, provides additional data for clinical anti-infective treatment.

Background Streptococcus pneumoniae infections are the major cause of global morbidity and mortality among children and patients aged more than 65 years. This study aimed to investigate the antimicrobial resistance, bacterial serotype distribution, and genetic characteristics of invasive S. pneumoniae from different cities in North China. Materials and Methods A total of 164 invasive S. pneumoniae strains were collected from 8 hospitals in 5 regions of North China between April 2016 and October 2017. Minimum inhibitory concentrations (MICs) were determined using the agar dilution method. Capsular serotypes were identified using the Quellung reaction test. Molecular epidemiology was investigated using multilocus sequence typing. Results S. pneumoniae isolates were highly resistant to macrolides, clindamycin, and tetracycline in all age groups. The overall rate of resistance to penicillin was 56.7%. However, fluoroquinolones and vancomycin maintained excellent antimicrobial activities. The rate of resistance to β-lactam in strains isolated from children aged less than 18 years was significantly higher than that in strains from other age groups. The most prevalent serotypes were 14 (22.6%), 19F (16.5%), non-vaccine types (14.0%), 19A (9.8%), and 23F (9.1%). The coverage for PCV10 and PCV13 was 59.8% and 75.6%, respectively. The vaccine coverage rate was the highest among children aged less than 5 years. The proportion of penicillin-resistant isolates was higher among vaccine-covered strains compared with non-covered strains. S. pneumoniae showed considerable clonal dissemination, and ST876 (28, 17.1%), ST271 (22, 13.4%), ST81 (17, 10.4%) and ST320 (14, 8.5%) were the major STs. Conclusion All the 164 invasive S. pneumoniae isolates demonstrated high resistance to antibiotics. The coverage of S. pneumoniae vaccine was higher in children than in adults.

Jiangang Zhang, Chunjiang Zhao, Hongbin Chen, Henan Li, Qi Wang, Zhanwei Wang, Feifei Zhang, Hui Wang On behalf of the CARES Network Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, China Objective: This study aimed to determine the risk factors for intra-abdominal infections (IAIs), assess the clinical outcomes of IAIs, and investigate the spectrum and antimicrobial resistance of major pathogens causing IAIs. Patients and methods: This prospective observational study enrolled patients from the Chinese Antimicrobial Resistance Surveillance of Nosocomial Infections (CARES) program between 2007 and 2016. Data on the clinicopathological factors and causative pathogens were collected. The results of antimicrobial susceptibility tests were interpreted according to the minimum inhibitory concentration (MIC) interpretive breakpoints recommended by the Clinical and Laboratory Standards Institute in 2017. Results: A total of 2,756 patients were included. The 30-day all-cause mortality was 9.5% (262/2,756). Multivariable analysis showed that the following independent risk factors were associated with the 30-day mortality: age >60 years, pulmonary disease, tracheal cannula, infection occurring in intensive care unit (ICU), prior admission within 3 months, antibiotic use before infection, recent use of immunosuppressants, and multidrug-resistant organisms. In addition, 2,913 clinical isolates were collected. The Gram-negative and Gram-positive bacteria accounted for 70.8% and 29.2% of all isolates, respectively. The most common pathogens were Escherichia coli (33.4%), Klebsiella pneumoniae (10.8%), and Enterococcus faecium (10.7%). Pseudomonas aeruginosa and Acinetobacter baumannii were the most common non-Enterobacteriaceae Gram-negative pathogens. E. faecium, Enterococcus faecalis, and Staphylococcus aureus were the most common Gram-positive pathogens. E. coli, A. baumannii, and Enterobacter cloacae were more commonly found in ICU patients than in non-ICU patients. Overall, the antibiotics tested in the CARES exhibited diminished susceptibility to pathogens over the study period, especially extended spectrum β-lactamase producing isolates. Conclusion: Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of IAIs and their susceptibility to antibiotics through the CARES is warranted. Keywords: intra-abdominal infections, risk factors, clinical outcomes, antimicrobial susceptibility, epidemiology