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Background: This study aimed to investigate the molecular epidemiological characteristics of hypervirulent Klebsiella pneumoniae (hvKp) in Yakeshi City, Hulunbuir, China, analyze the resistance of hvKp to commonly used antibiotics, explore independent risk factors for hvKp infection, and provide a research basis for anti-infection treatment. Methods: In total, 519 strains of K. pneumoniae, identified by the Inner Mongolia Forestry General Hospital from January 2020 to December 2022, were collected, and high-viscosity (HMV-Kp) and non-HMV-Kp strains were differentiated using string test. PCR and agarose gel electrophoresis were used to detect the rmpA, rmpA2, and iutA genes to identify hvKp strains. Sixty strains of hvKp were randomly selected for capsular serotyping by PCR and agarose gel electrophoresis. Sanger sequencing was used to sequence the housekeeping genes of 60 hvKp strains and perform ST analysis. A minimum spanning tree was drawn using capsule serotyping and ST typing. Significant differences in resistance to commonly used antibiotics between classical K. pneumoniae (cKp) and hvKp were analyzed by using the chi-squared test. Finally, the risk factors for hvKp infection were analyzed through binary logistic regression. Results: The HMV-Kp detection rate was 39.69%, versus 37.19% for hvKp. HMV-Kp accounted for 84.97% of all hvKp isolates. The hvKp detection rate was highest in the general surgery department. In capsule serotyping, K1 was the main subtype, accounting for 63.33% of all isolates (38/60), followed by K2 (16.67%, 10/60). Through ST typing, 18 subtypes were detected, with ST23 being the most common (50.00%), followed by ST86 (8.33%), and the remaining subtypes were scattered throughout the distribution. Compared with cKp, hvKp strains exhibited higher sensitivity to commonly used antibiotics, excluding furantoin. Male gender (odds ratio (OR) = 1.977), liver abscess (OR = 15.019), and the use of macrolide antibiotics in the past 3 months (OR = 5.473) were independent risk factors for hvKp infection. Conclusions: The hvKp detection rate in the local area was 37.19%, and a strong correlation was noted between hvKp and HMV-Kp strains. K1-ST23 was the dominant subtype in this study. Compared with cKp, hvKp strains were more sensitive to commonly used antibiotics. Male gender, liver abscess, suppuration or infection of other tissues and organs, and recent macrolide antibiotic use were risk factors for hvKp infection. [ABSTRACT FROM AUTHOR]

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π–π stacking interaction and a water–magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance poses a significant threat to global public health, and excessive antimicrobial use (AMU) in animals is a major contributing factor. We used national AMU data for food animals to examine the current status and trends for AMU in food animals in China from 2018–2020. In 2020, China used 32,776.30 tons of antimicrobials in food animals, amounting to 165 g of antimicrobials per ton of animal products. AMU in China increased throughout the 2018–2020 study period; however, the data still showed a consistent and notable reduction from those of 2017, coinciding with the implementation of the China National Action Plan for Combating Animal Antimicrobial Resistance. Among the antimicrobials used, tetracyclines, macrolides and β-lactams (including β-lactam inhibitors) were the most commonly used in food animals. Analysis by antimicrobial class revealed shifts in usage patterns, such as decreased tetracycline use and increased macrolide and β-lactam use. Furthermore, the use of antimicrobial growth promoters decreased sharply, from 51.78% in 2018 to 28.7% in 2020. Compared with AMU data from other countries, China used more antimicrobials, but the values were relatively lower when adjusted for population correction units. These findings highlight China's remarkable efforts in combating antimicrobial resistance and promoting antimicrobial stewardship, thus contributing significantly to global initiatives. [ABSTRACT FROM AUTHOR]

With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as Streptococcus pneumoniae, Streptococcus (including Group A streptococcus, Group B streptococcus), Staphylococcus aureus, Bordetella pertussis, and Mycoplasma pneumoniae, have shown varying degrees of drug resistance. In order to provide such problem and related evidence for rational use of antibiotics in clinic, we reviewed the drug resistance of common bacteria to macrolides in children recent 20 years. [ABSTRACT FROM AUTHOR]

Despite limited biomonitoring studies suggesting extensive antibiotic exposure in general population, the body burden of antibiotics in young children and their potential health risks remain unclear. To assess the antibiotic exposure levels in young children, 508 preschoolers aged 3–6 years were recruited from eastern China in 2022, and a total of 50 representative antibiotics from 8 categories, including 17 human antibiotics (HAs), 4 antibiotics preferred as HAs (PHAs), 16 veterinary antibiotics (VAs), and 13 antibiotics preferred as VAs (PVAs), were analyzed by UPLC-MS/MS. Hazard quotient (HQ) and hazard index (HI) were calculated to evaluate the health risks, and multivariate logistic regression was applied to examine diet with antibiotic exposure. Our results showed that there were 41 antibiotics detected in children's urine, and the overall detection frequency was as high as 100%. Sulfonamides, macrolides, β-lactams, quinolones, and azoles were the predominant categories of antibiotic detected. Among the studied children, 6.5% had a sum of estimated daily intake (EDI) of all VAs and PVAs larger than 1 μg/kg/day. Notably, 10.0% of the children had a microbiological HI value exceeding 1, primarily contributed by ciprofloxacin. Children with higher consumption of seafood had a relatively increased exposure to multiple categories of antibiotics, including HAs, VAs, quinolones, azoles, and others. Principal component analysis suggested that "Aquatic products and viscera preferred dietary pattern" scores were positively correlated with the exposure levels of ciprofloxacin (OR: 1.23; 95% CI: 1.02–1.47) and carbadox (OR: 1.32; 95% CI: 1.10–1.59), and a relatively increased exposure of PHAs was realized in children with higher "Meat-egg preferred dietary pattern" scores (OR: 1.24; 95% CI: 1.03–1.50). In conclusion, there was a widespread exposure to antibiotics among preschool children from eastern China, and children who consumed more animal-derived foods may had an increased exposure to antibiotics. [ABSTRACT FROM AUTHOR]

Purpose: Ureaplasma urealyticum and Mycoplasma hominis began to show resistance to azithromycin, a macrolide antibiotic commonly used in pregnancy. Unfortunately, there are few effective and safe drugs in the clinic for genital mycoplasmas in pregnant women. In the present study, we investigated the prevalence of azithromycin-resistant U. urealyticum and M. hominis infections in pregnant women. The secondary research objects were possible influencing factors and consequences of insensitive Mycoplasma infection. Patients and methods: A retrospective analysis was carried out in pregnant women who underwent cervical Mycoplasma culture between October 2020 and October 2021 at a large general hospital in eastern China. The sociological characteristics and clinical information of these women were collected and analyzed. Results: A total of 375 pregnant women were enrolled, and 402 cultured mycoplasma specimens were collected. Overall, 186 (49.60%) patients tested positive cervical Mycoplasma infection, and 37 (9.87%) had infections caused by azithromycin-resistant Mycoplasma. In total, 39 mycoplasma samples were insensitive to azithromycin in vitro, also showing extremely high resistance to erythromycin, roxithromycin, and clarithromycin. Azithromycin was the only antibiotic used in women with Mycoplasma cervical infection, regardless of azithromycin resistance in vitro. Statistical results showed that azithromycin-resistant cervical Mycoplasma infection in pregnant women was unrelated to age, body mass index (BMI), gestational age, number of embryos, and assisted reproductive technology (ART) use, but led to a significantly increased incidence of adverse pregnancy outcomes (spontaneous abortion (SA), preterm birth (PTB), preterm prelabor rupture of membranes (PPROM), and stillbirth). Conclusion: Azithromycin-resistant U. urealyticum and M. hominis cervical infections are relatively common during pregnancy, and can increase the risk of adverse pregnancy outcomes; however, there is currently a lack of safe and effective drug treatments. Herein, we show that azithromycin-resistant mycoplasma infection requires timely intervention. [ABSTRACT FROM AUTHOR]

Morganella morganii (M. morganii) is a member of the genera Morganella in the Enterobacteriaceae family. We tried to better understand the prevalence and characterization of M. morganii strains in cattle. A total of 191 nasal swab samples from beef cattle in Guang'an, Yibin, and Ziyang, Sichuan province, China were collected. The presence of M. morganii in the swabs was determined by PCR. Then positive swabs were processed using bacterial isolation and identification. The M. morganii isolates were assayed for antimicrobial susceptibility and pathogenicity using a mouse model. The prevalence of M. morganii in three cities was 10.5% (20/191). Three M. morganii strains (16GA7, 17GA61.2, and 17YB9) were isolated and identified from positive swab samples. Phylogenetic analysis demonstrated that the 16S rRNA gene of M. morganii isolates could be clustered with known Genbank M. morganii strains. All three M. morganii strains were sensitive to penicillin-type and quinolone antibiotics and were resistant to some cephalosporins, carbapenems, macrolide antibiotics and polymyxin B. Lesions in mice inoculated with M. morganii included pulmonary hemorrhage, thickened alveolar walls and pulmonary inflammatory cell infiltration, although lesions varied by strain. Through research on the M. morganii in beef cattle, it was found that mice were susceptible to M. morganii isolates. To the best of our knowledge, the present study is the first to report the prevalence of M. morganii in beef cattle. [ABSTRACT FROM AUTHOR]

Background: Over the past 20 years, excessive antibiotic use has led to serious antimicrobial resistance (AMR) worldwide, and the phenomenon is particularly serious in China. To this end, the Chinese health sector took a series of measures to promote rational antibiotic use. In this study, to reveal the impact of policies on antibiotic use, we explored the long-term trend and patterns of antibiotic use at public health care institutions from 2012 to 2020 in northwest China, taking Gansu Province as an example. Methods: Antibiotic procurement data were obtained from the provincial centralized bidding procurement (CBP) platform between 2012 and 2020. Antibiotic use was quantified using the Anatomical Therapeutic Chemical (ATC)/defined daily doses (DDD) methodology and standardized using the DDD per 1000 inhabitants per day (DID). Twelve relevant quality indicators were calculated for comparison with the European Surveillance of Antimicrobial Consumption (ESAC) project monitoring results. Results: Total antibiotic use increased from 18.75 DID to 57.07 DID and then decreased to 19.11 DID, a turning point in 2014. The top three antibiotics used were J01C (beta-lactam antibacterials, penicillins), J01F (macrolides, lincosamides and streptogramins), and J01D (other beta-lactam antibacterials, cephalosporins), accounting for 45.15%, 31.40%, and 11.99% respectively. The oral antibiotics used were approximately 2.5 times the parenteral antibiotics, accounting for 71.81% and 28.19%, respectively. Different use preferences were shown in public hospitals and primary health care centres (PHCs), and the latter accounted for more than half of total use. The absolute use of all classes of antibiotics in Gansu is almost higher than any of the 31 European countries included in the ESAC, but the relative use of some focused antibiotics is lower than theirs. Conclusions: The intervention policies of the health department reduced antibiotic use in Gansu Province, but the proportion of broad-spectrum and parenteral antibiotics was still high. It is necessary to further improve the quality of antibiotic prescriptions and pay more attention to the rationality of antibiotic use in PHCs. [ABSTRACT FROM AUTHOR]

The occurrence, spatial distribution, and source analysis of antibiotics in global coastal waters and estuaries are not well documented or understood. Therefore, the distribution of 14 antibiotics in inflowing river and bay water of Taizhou Bay, East China Sea, was studied. Thirteen antibiotics, excluding roxithromycin (ROM), were all detected in inflowing river and bay water. The total antibiotic concentrations in bay water ranged from 3126.62 to 26,531.48 ng/L, which were significantly higher than those in the inflowing river (17.20–25,090.25 ng/L). Macrolides (MAs) and sulfonamides (SAs) were dominant in inflowing river (accounting for 24.40% and 74.9% of the total antibiotic concentrations, respectively), while SAs in bay water (93.6% of the total concentrations). Among them, clindamycin (CLI) (concentration range: ND–8414 ng/L, mean 1437.59 ng/L) and sulfadimidine (SMX) (ND–25,184.00 ng/L, mean concentrations: 9107.88 ng/L) were the highest in those surface water samples. Source analysis showed that MAs and SAs in the inflowing river mainly came from the wastewater discharge of the surrounding residents and pharmaceutical companies, while SAs in the bay water mainly came from surrounding industrial activities and mariculture. However, the contribution of the inflowing river to the bay water cannot be ignored. The risk assessment showed that SMX and ofloxacin (OFX) have potential ecological risks. These data will support the various sectors of the environment in developing management strategies and to prevent antibiotic pollution. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile infection (CDI) caused by toxigenic strains leads to antibiotic-related diarrhea, colitis, or even fatal pseudomembranous enteritis. Previously, we conducted a cross-sectional study on prevalence of CDI in southwest China. However, the antibiotics resistance and characteristics of genomes of these isolates are still unknown. Methods: Antibiotic susceptibility testing with E-test strips and whole genome sequence analysis were used to characterize the features of these C. difficile isolates. Results: Forty-nine strains of C. difficile were used in this study. Five isolates were non-toxigenic and the rest carried toxigenic genes. We have previously reported that ST35/RT046, ST3/RT001 and ST3/RT009 were the mostly distributed genotypes of strains in the children group. In this study, all the C. difficile isolates were sensitive to metronidazole, meropenem, amoxicillin/clavulanic acid and vancomycin. Most of the strains were resistant to erythromycin, gentamicin and clindamycin. The annotated resistant genes, such as macB, vanRA, vanRG, vanRM, arlR, and efrB were mostly identified related to macrolide, glycopeptide, and fluoroquinolone resistance. Interestingly, 77.55% of the strains were considered as multi-drug resistant (MDR). Phylogenetic analysis based on core genome of bacteria revealed all the strains were divided into clade 1 and clade 4. The characteristics of genome diversity for clade 1 could be found. None of the isolates showed 18-bp deletion of tcdC as RT027 strain as described before, and polymorphism of tcdB showed a high degree of conservation than tcdA gene. Conclusions: Most of the C. difficile isolates in this study were resistant to macrolide and aminoglycoside antibiotics. Moreover, the MDR strains were commonly found. All the isolates belonged to clade 1 and clade 4 according to phylogenetic analysis of bacterial genome, and highly genomic diversity of clade 1 was identified for these strains. [ABSTRACT FROM AUTHOR]

Freshwater systems near highly urbanized areas are extremely susceptible to emerging contaminants (ECs), yet their stereoscopic persistence in aquatic ecosystems and related risks remain largely unknown. Herein, we characterized the multi-mediums distribution of 63 ECs in Baiyangdian Lake, the biggest urban lake in the North of China. We identified variations in the seasonal patterns of aquatic EC levels, which decreased in water and increased in sediment from wet to dry seasons. Surprisingly, higher concentrations and a greater variety of ECs were detected in reeds than in aquatic animals, indicating that plants may contribute to the transferring of ECs. Source analysis indicated that human activity considerably affected the distribution and risk of ECs. The dietary risk of ECs is most pronounced among children following the intake of aquatic products, especially with a relatively higher risk associated with fish consumption. Besides, a comprehensive scoring ranking method was proposed, and 9 ECs, including BPS and macrolide antibiotics, are identified as prioritized control pollutants. These findings highlight the risks associated with aquatic ECs and can facilitate the development of effective management strategies. [Display omitted] • Higher levels of ECs are detected in reeds than in aquatic animals. • Psychotropic drugs were the predominant contributors to ecological risk. • The dietary risk of ECs is most pronounced among children following aquatic products intake. • 9 ECs including BPS and macrolide antibiotics are identified as prioritized control pollutants. [ABSTRACT FROM AUTHOR]

Introduction: Moraxella catarrhalis, which is an opportunistic pathogen and is one of the three major pathogens of community-acquired pneumonia, causes a variety of infections in clinic. In recent years, the isolation rate of Moraxella catarrhalis has gradually increased. In China, due to the clinical empirical use of antibiotics, the resistance rate of Moraxella catarrhalis isolated from children to β-lactam antibiotics has reached 99%. The non-susceptible rate of Moraxella catarrhalis to macrolide antibiotics has also increased significantly. Methods: Two isolates of Moraxella catarrhalis (R17123922_R and R18013231_R) were isolated from in-patients and were confirmed to be resistant to macrolide antibiotics using the standard disk diffusion and broth microdilution method recommended by CLSI. Whole-genome sequencing (WGS) analysis was performed in these two resistant strains. Results: A total of 696 SNVs (single nucleotide variations), and 79 indels (Insertion and Deletion) were found in R17123922_R and R18013231_R. These SNVs and indels were distributed evenly in the genome, and no centralized distribution occurred. Moreover, two isolates did not harbor any previously reported mutations in the 23S rRNA and ribosomal proteins. Conclusion: A novel indel in the MCR_0492 gene encoding TonB-dependent receptor protein was identified, and we speculated that TonB-dependent protein receptor may play an important role in macrolide resistance of Moraxella catarrhalis. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is an important human pathogen that can cause severe invasive pneumococcal diseases (IPDs). The aim of this multicenter study was to investigate the serotype and sequence type (ST) distribution, antimicrobial susceptibility, and virulence of S. pneumoniae strains causing IPD in China. Methods: A total of 300 invasive S. pneumoniae isolates were included in this study. The serotype, ST, and antimicrobial susceptibility of the strains, were determined by the Quellung reaction, multi-locus sequence typing (MLST) and broth microdilution method, respectively. The virulence level of the strains in the most prevalent serotypes was evaluated by a mouse sepsis model, and the expression level of well-known virulence genes was measured by RT-PCR. Results: The most common serotypes in this study were 23F, 19A, 19F, 3, and 14. The serotype coverages of PCV7, PCV10, PCV13, and PPV23 vaccines on the strain collection were 42.3, 45.3, 73.3 and 79.3%, respectively. The most common STs were ST320, ST81, ST271, ST876, and ST3173. All strains were susceptible to ertapenem, levofloxacin, moxifloxacin, linezolid, and vancomycin, but a very high proportion (>95%) was resistant to macrolides and clindamycin. Based on the oral, meningitis and non-meningitis breakpoints, penicillin non-susceptible Streptococcus pneumoniae (PNSP) accounted for 67.7, 67.7 and 4.3% of the isolates, respectively. Serotype 3 strains were characterized by high virulence levels and low antimicrobial-resistance rates, while strains of serotypes 23F, 19F, 19A, and 14, exhibited low virulence and high resistance rates to antibiotics. Capsular polysaccharide and non-capsular virulence factors were collectively responsible for the virulence diversity of S. pneumoniae strains. Conclusion: Our study provides a comprehensive insight into the epidemiology and virulence diversity of S. pneumoniae strains causing IPD in China. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify the trends in antibiotics utilization and patients costs, evaluating the effect of the policy and exploring factors associated with the irrational use of antibiotics. Methods: Based on the Cooperation Project Database of Hospital Prescriptions, data were collected from 89 tertiary hospitals in nine cities in China during 2016–2019. The study sample consisted of prescription records with antibiotics for 3,422,710 outpatient and emergency visits and 26, 118, 436 inpatient hospitalizations. Results: For outpatients, the proportion of treated with antibiotics declined from 14.72 to 13.92% significantly (p < 0.01). The proportion of antibiotic costs for outpatients decreased from 5.79 to 4.45% significantly (p < 0.01). For emergency patients, the proportion of treated with antibiotics increased from 39.31 to 43.45% significantly (p < 0.01). The proportion of antibiotic costs for emergency patients decreased from 36.44 to 34.69%, with no significant change (p = 0.87). For inpatients, the proportion of treated with antibiotics increased from 23.82 to 27.25% significantly (p < 0.01). The proportion of antibiotic costs for outpatients decreased from 18.09 to 17.19% with no statistical significance (p = 0.89). Other β-lactam antibacterials (1,663.03 ten thousand DDD) far exceeded other antibiotics categories. Stablely ranked first, followed by Macrolides, lincosamide and streptogramins (965.74 ten thousand DDD), Quinolone antibacterials (710.42 ten thousand DDD), and β-lactam antibacterials, penicillins (497.01 ten thousand DDD). Conclusions: The proportion of treated with antibiotics for outpatients and inpatients meet the WHO standards. The antibiotics use varied by different survey areas, clinical departments, patient gender, patient age and antibiotics categories. More efforts should focus on improving the appropriateness of antibiotics use at the individual level. [ABSTRACT FROM AUTHOR]

Antibiotic residue stands as a significant ongoing environmental issue, with aquaculture being a major source of annual antibiotic discharge into the ocean. Nevertheless, there is still an incomplete evaluation of antibiotic residues in the Beibu Gulf, an area encompassed by two prominent aquaculture nations, China and Vietnam. The present systematic review and meta-analysis was conducted to examine the presence antibiotic residues in the Beibu Gulf based on published studies. Data were obtained through eight databases up to December 19th, 2023, and were updated on April 15th, 2024. The pooled concentration of antibiotic residues in seawater was 5.90 (ng/L), ranging from 5.73 to 6.06 (ng/L), and was 8.03 (ng/g), ranging from 7.77 to 8.28 (ng/g) in sediments. Fluoroquinolones, tetracyclines, and macrolides were identified as the main antibiotics found in both seawater and sediment samples. The Beibu Gulf showed higher antibiotic levels in its western and northeastern areas. Additionally, the nearshore mangrove areas displayed the highest prevalence of antibiotic residues. It is strongly advised to conduct regular long-term monitoring of antibiotic residues in the Beibu Gulf. Collaborative surveys covering the entire Beibu Gulf involving China and Vietnam are recommended. • Antibiotic residues data of the Beibu Gulf from 17 studies were analyzed using meta-analysis by Stata software. • Concentration of antibiotics in the Beibu Gulf was lower than most Asian bays both in seawater and sediments. • The highest concentration of the antibiotic residues was shown in nearshore mangrove samples. [ABSTRACT FROM AUTHOR]

• Food traceability system exerts a significant inhibitory effect on the overuse of antibiotics by farmers; • Inhibitory effects of food traceability system on over-the-counter and broad-spectrum antibiotics are more significant than those on prescription and narrow-spectrum antibiotics. • Inhibition effect of food traceability system on the overuse of antibiotics by different scale farmers exhibits an approximately inverse-U curvilinear relationship. • Intervention mechanism of the FTS on the overuse of antibiotics by farmers mainly consists of social reputation maintenance, liability traceability for antibiotic residues, and biosafety enhancement. The use of animal antibiotics is a double-edged sword. It can be used for disease treatment, health protection, and growth promoters. It also creates antibiotic residues and resistance, poses risks, and damages food safety, ecosystems, and public health. Under the pressure of disease risk and expected losses, farmers' overuse of animal antibiotics exacerbates this dual objective incompatibility. In this study, we employ the endogenous switching regression (ESR) model and the mediating effect method to empirically analyze the inhibitory effect and intervention mechanism of the food traceability system (FTS) on reducing farmers' overuse of antibiotics by using the survey data of hog farmers from China. This paper measures the "dose" unit of antibiotics farmers use regarding cost and the active ingredients of antibiotics per kilogram of treated infected hogs. The study finds evidence that the FTS exerts a significant inhibitory effect on the overuse of antibiotics by farmers. The counterfactual hypothesis unveils that non-participation in the FTS by the involved farmers will increase the cost of antibiotics overuse by 0.080 yuan/kg, while if the farmers currently not participating are to engage with the FTS, the price will decrease by 0.126 yuan/kg. This effect persists across control variables controlled in turn and the unit doses of active ingredients of tetracycline, sulfonamides, β -lactam, chloramphenicol, and macrolide antibiotics. Moreover, our results reveal that the inhibitory effects of the FTS on over-the-counter and broad-spectrum antibiotics are more significant than on prescription and narrow-spectrum antibiotics. The results show that the inhibition effect of the FTS on the overuse of antibiotics by free-range, professional, and large-scale farmers exhibits an approximately inverse-U curvilinear relationship. Besides, the intervention mechanism of the FTS on the overuse of antibiotics by farmers mainly consists of social reputation maintenance, liability traceability for antibiotic residues, and biosafety enhancement, and the proportion of their mediating effects in the total impact are 24.22%, 21.84%, and 10.87%, respectively. Our empirical study has yielded several implications, such as strengthening the FTS construction, improving farmers' antibiotic use skills, promoting standardized breeding levels, and increasing the market premium for food products that adhere to antibiotic residue standards. These outcomes not only contribute to the improvement of livestock production safety but also reduce the problem of antibiotic overuse. [ABSTRACT FROM AUTHOR]

Background: In China, there were few studies to estimate antibiotic use for children with upper respiratory infections at the national level. The aim of this study was to describe the antibiotic prescribing practice for children aged < 5 years old with upper respiratory infections (URIs) using a nationwide claims database.Methods: This was a retrospective cross-sectional study using a sampled database from the China Health Insurance Research Association (CHIRA). Study subjects included children younger than 5 years with outpatient visits in 2015 that resulted in a diagnosis of a upper respiratory infection. We calculated the percentage of visits who received antibiotics, the proportion of injection formulations, the percentage of combined antibiotics and the proportion of each antibiotic class. The patterns of antibiotic prescription were also described by medical institution type, city level and geographical region.Results: Among the 92,821 visits, 27.1% were prescribed antibiotics, of which 27.0% received injection formulations. The rate of antibiotic prescribing varied by age group (P < 0.001), with the lowest (16.0%) in infants and the highest in patients at age 3 to < 4 years (29.9%) and age 4 to < 5 years (32.5%). The Midwestern region, underdeveloped cities and low-level hospitals represented relatively higher rates of prescribing antibiotics (P < 0.001) and higher proportions of injection dosage forms (P < 0.001). The most 3 common antibiotic classes prescribed of all visits with antibiotic prescriptions were the third-generation cephalosporins (34.9%), macrolides (24.3%), and the second-generation cephalosporins (23.3%).Conclusions: In mainland China, the overall rate of antibacterial prescribing and the proportion of injection formulations prescribed in children under 5 years with URIs were at a low level, but still higher in underdeveloped regions and cities. Moreover, the overuse of the second and third generation cephalosporins, macrolides, remains a serious issue. Further efforts should be focused on reducing those non-first-line antibiotic prescribing and narrowing the gaps among regions and cities. [ABSTRACT FROM AUTHOR]

Objective: To investigate the characteristics of hosts, antimicrobial susceptibility, and molecular epidemiology of mucoid serotype 3 Streptococcus pneumoniae (S. pneumoniae) isolated from children in China. Method: S. pneumoniae isolates collected between January 2016 and December 2019 were analyzed. S. pneumoniae isolates with mucoid phenotype were selected visually, and serotype 3 isolates were confirmed by Quellung reaction. The antimicrobial susceptibility was measured by E-test. Multilocus sequence typing was used for clonal analysis. Results: Twenty (3.04%) isolates of mucoid serotype 3 S. pneumoniae were identified from 657 clinical isolates, and all of them were noninvasive strains. The mean age of the hosts was 5.69 ± 3.28 years. The isolates included: 50.0% from the dissected tonsil or adenoid tissue in children with obstructive sleep apnea-hypopnea syndrome, 45.0% from sputum or bronchial lavages in children with pneumonia, and 5.0% from vaginal secretions of one patient with vulvovaginitis. All isolates were susceptible to penicillin, cefuroxime, ceftriaxone, meropenem, vancomycin, levofloxacin, trimethoprim/sulfamethoxazole, and rifampin but resistant to erythromycin. Sequence type (ST)505 and its clonal complex (CC) were the main genotypes (95%). Antimicrobial susceptibility of ST180 and ST505 were compared, and the minimum inhibitory concentration (MIC) of ST505 isolates was significantly higher than that of ST180 for tetracycline, trimethoprim/sulfamethoxazole, and meropenem. Conclusions: Mucoid serotype 3 Streptococcus pneumoniae can be isolated from various body parts, among which the respiratory system is the most common. It can cause noninvasive infection in children, and it has high susceptibility to a variety of antibiotics, especially β-lactams, but is resistant to macrolides. CC505 is the novel clonal complex found in China, which may be related to the worldwide mainstream clonal complex (CC180) but has its own biological characteristics. [ABSTRACT FROM AUTHOR]

Taklamakan desert is known as the largest dunefield in China and as the second largest shifting sand desert in the world. Although with long history and glorious culture, the Taklamakan desert remains largely unexplored and numerous microorganisms have not been harvested in culture or taxonomically identified yet. The main objective of this study is to explore the diversity, novelty, and pharmacological potential of the cultivable actinomycetes from soil samples at various sites along the Alar-Hotan desert highway in the Taklamakan desert. A total of 590 actinobacterial strains were recovered by the culture-dependent approach. Phylogenetic analysis based on 16S ribosomal RNA (rRNA) gene sequences unveiled a significant level of actinobacterial diversity with 55 genera distributed in 27 families of 12 orders. Thirty-six strains showed relatively low 16S rRNA similarities (<98.65%) with validly described species, among which four strains had already been characterized as novel taxa by our previous research. One hundred and forty-six actinobacterial isolates were selected as representatives to evaluate the antibacterial activities and mechanism of action by the paper-disk diffusion method and a double fluorescent protein reporter "pDualrep2" system, respectively. A total of 61 isolates exhibited antagonistic activity against the tested "ESKAPE" pathogens, among which seven strains could produce bioactive metabolites either to be able to block translation machinery or to induce SOS-response in the pDualrep2 system. Notably, Saccharothrix sp. 16Sb2-4, harboring a promising antibacterial potential with the mechanism of interfering with protein translation, was analyzed in detail to gain deeper insights into its bioactive metabolites. Through ultra-performance liquid chromatography (UPLC)-quadrupole time-of-flight (QToF)-MS/MS based molecular networking analysis and databases identification, four families of compounds (1 – 16) were putatively identified. Subsequent bioassay-guided separation resulted in purification of four 16-membered macrolide antibiotics, aldgamycin H (8), aldgamycin K (9), aldgamycin G (10), and swalpamycin B (11), and their structures were elucidated by HR-electrospray ionization source (ESI)-MS and NMR spectroscopy. All compounds 8 – 11 displayed antibacterial activities by inhibiting protein synthesis in the pDualrep2 system. In conclusion, this work demonstrates that Taklamakan desert is a potentially unique reservoir of versatile actinobacteria, which can be a promising source for discovery of novel species and diverse bioactive compounds. [ABSTRACT FROM AUTHOR]

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The concentrations and distributions of five sulfonamide, three tetracycline, and two macrolide antibiotics in leachates from three landfill sites in northern Zhejiang Province, China, were determined by solid-phase extraction and ultra-high performance liquid chromatography mass spectrometry. Most of the antibiotics were detected in the leachate samples. The concentrations and distributions of the antibiotics in leachates of different ages were very different. The total sulfonamide, tetracycline, and macrolide concentrations in the leachates ranged from not detected to 1.57 × 103, not detected to 5.19 × 103, and 7.30 to 5.42 × 102 ng/L, respectively. The total concentrations of detectable antibiotics were higher in fresh leachates than aged and middle-aged leachates. Higher TC-group concentrations were found in the leachates than have been found in previously published studies of landfill leachates in China. The results improve our understanding of and ability to manage antibiotic residues in landfills. [ABSTRACT FROM AUTHOR]

Strain HM190, a moderate halophile, was isolated from rhizosphere soil of the mangrove Kandelia obovata in Fugong village, China. The 16S ribosomal RNA (rRNA) gene sequence and the results of phylogenetic analysis revealed that strain HM190 belonged to the genus Streptomyces and had the highest sequence similarity of 99.79% to Streptomyces heilongjiangensis NEAU-W2T. The complete genome of strain HM190 comprised 7,762,826 bp in a linear chromosome with 71.97% G + C content. According to antiSMASH analysis, a total of 30 biosynthetic gene clusters (BGCs) were predicted to be involved in secondary metabolism, 12 of which were responsible for the production of polyketide- and non-ribosomal peptide-derived secondary metabolites. Gene cluster 5 was responsible for macrolide biosynthesis in a strain-specific 126,331-bp genomic island belonging to the left-arm region. Combined genomics–metabolomics analysis led to the discovery of three 22-membered macrolides (compounds 1 – 3). Their structures were elucidated by using spectroscopic techniques including high-resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR). The absolute configurations of compounds 1–3 were determined by the X-ray single crystal diffraction and NMR data analysis. All three compounds displayed moderate cytotoxic activities toward tumor cell lines HepG2, A549, and HCT116. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the usage of antibiotic utilisation rate (AUR) among Chinese hospitalised children over a 4‐year period to determine clinical characteristics. Design and Methods: AUR, antibiotic type and antibiotic use in combination were analysed among hospitalised children of the affiliated hospital of Beihua University in Northeast China from January 2015 to December 2018. The linear prediction was used to investigate the trends of antibiotics use in combination and AUR, and autoregressive integrated moving average model was used to predict AUR in 2019. Results: A total of 2,981 inpatients were admitted to the hospital during the study period. The AUR from 2015 to 2018 was 91.51%, 92.67%, 91.30%, and 93.00%, respectively. AUR was associated with season (p <.01), the peak period was found to be from November to January in 2019 (R2 = 0.802). The etiological delivery rate had increased (p <.01). Pneumonia was the main disease in children for which they received antibiotics. The combination of multidrug (≥3 agents used) had increased (p <.01) over the study period. Practice Implications: AUR was stable among hospitalised children in a hospital. Cephalosporin and macrolide antibiotics were the main antibiotic types, and the combination of multidrug had increased, more attention should be paid to the use of antibiotics in hospitalised children. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the clinical practice patterns in maximal medical therapy (MMT) before endoscopic sinus surgery for chronic rhinosinusitis (CRS) by Chinese otolaryngologists. An anonymous web-based survey of MMT was performed. This survey assessed types of therapies, the frequency of use, duration of use, and demographic data of respondents. A total of 134 (26.8%) questionnaires were completed and returned. The majority (62.69%) of respondents would consider surgery less than 3 months after commencing MMT, 33.58% would wait 3 to 6 months. Intranasal corticosteroid sprays, saline irrigation, oral antibiotics, oral mucolytics, and oral Chinese herbals were the most commonly used therapies and listed as "often (>70%)". Macrolides were most commonly antibiotics prescribed among the clinicians surveyed (51.49%). Intranasal corticosteroid sprays, oral antibiotics, oral mucolytics, nasal saline irrigations, and oral Chinese herbals are most commonly prescribed by the majority of Chinese otolaryngologists as MMT for CRS. Current practice patterns of MMT among Chinese otolaryngologists are not uniformly based on evidence-based guidelines. [ABSTRACT FROM AUTHOR]

Campylobacter jejuni and Campylobacter coli are major food-borne pathogens that cause bacterial gastroenteritis in humans, and poultry is considered as their most important reservoir. Macrolides, such as erythromycin, are the first-line choice for treatment of campylobacteriosis. In this study, of the 143 Campylobacter isolates recovered from poultry in central China during 2015–2017, 25.2% were erythromycin resistant. A2075G substitution in 23S ribosomal RNA (rRNA) and ribosomal methylase encoded by erm (B) were found in 4.2 and 4.9% isolates, respectively, and correlated with erythromycin resistance. The polymorphisms of CmeR-Box were also analyzed in our isolates. Among them, 9.1% isolates harbored a point deletion or insertion within the CmeR-Box, and we first showed that point deletion or insertion, but not substitution, in CmeR-Box led to high expression of cmeABC , which was significantly associated with erythromycin resistance (p < 0.05). These results suggest that point deletion or insertion in CmeR-Box, A2075G substitution in 23S rRNA, and presence of erm (B) are three main factors to erythromycin resistance in C. jejuni and C. coli. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma genitalium infection is significantly associated with an increased risk of male infertility. To date, few large M. genitalium studies have been conducted in China. Objective: This study aimed to estimate the M. genitalium incidence and treatment failure and to provide information regarding the resistance of M. genitalium to macrolide and tetracycline antibiotics among men of infertile couples in China. Materials and Methods: This study was performed as a retrospective survey of seminal and meatus urinarius secreta specimens of 30,094 men of infertile couples collected and used for microbiological tests for the evaluation of genital tract infections (Mycoplasma genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae) between October 2016 and December 2017. Mycoplasma genitalium RNA was detected using novel simultaneous amplification testing. Macrolide and tetracycline resistance screening was introduced using polymerase chain reaction (PCR) and Sanger sequencing. Results: The incidence of M. genitalium was 2.49% (749 of 30,094; 95% confidence interval (CI), 2.31–2.66%). After antibiotic treatment, the mean values of semen parameters increased from those measured before treatment. The overall incidence of treatment failure was 17.56% (82/467; 95% CI, 14.10%–21.02%) (112−26−4 = 82), irrespective of the drug used. Resistance to macrolide and tetracycline antibiotics was detected in 58 samples (58/60, 96.67%; 95% CI, 91.99–101.34%) and 27 samples (27/60, 45.00%; 95% CI, 32.04–57.96%), respectively. Conclusions: Although the M. genitalium incidence was relatively low, the detection of macrolide antibiotic resistance in >96.67% of the treatment failure samples most likely explained the high azithromycin treatment failure rate (73/195, 37.44%) in our study. These findings indicate the need to provide resistance testing and to reappraise the recommended antimicrobial options in China. [ABSTRACT FROM AUTHOR]

According to the government of China, reported cases of pertussis have increased remarkably and are still increasing. To determine the genetic relatedness of Bordetella pertussis strains, we compared multilocus variable-number tandem-repeat analysis (MLVA) results for isolates from China with those from Western countries. Among 335 isolates from China, the most common virulence-associated genotype was ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3A/tcfA2, which was more frequent among isolates from northern than southern China. Isolates of this genotype were highly resistant to erythromycin. We identified 36 ptxP3 strains mainly harboring ptxA1 and prn2 (35/36); ptxP3 strains were sensitive to erythromycin and were less frequently from northern China. For all isolates, the sulfamethoxazole/trimethoprim MIC was low, indicating that this drug should be recommended for patients infected with erythromycin-resistant B. pertussis. MLVA of 150 clinical isolates identified 13 MLVA types, including 3 predominant types. Our results show that isolates circulating in China differ from those in Western countries. [ABSTRACT FROM AUTHOR]

Background. Treatment response for the Mycobacterium abscessus (M. abscessus) lung disease remains far from satisfying. An effective regimen is needed to solve the problem. Methods. We retrospectively reviewed the medical records of all patients with M. abscessus lung disease who received antibiotics regimen at Beijing Chest Hospital Affiliated to Capital Medical University between July 1, 2010, and February 1, 2018. Patients were administered a conventional antibiotics regimen (including macrolide and moxifloxacin, along with an initial 12-week course of low-dose cefoxitin and amikacin) or intensified regimen (including a higher dosage of cefoxitin and linezolid besides conventional drugs), respectively. The time to sputum-culture conversion and proportion of sputum-culture conversion in liquid broth were investigated to evaluate the efficacy and evaluation of safety by performing the classification of adverse events according to the Division of AIDS, National Institute of Allergy and Infectious Disease. Patients were followed for 18 months from baseline. Results. In the conventional regimen group, the sputum conversion rate at 18 months was 29.4% (10/34), and the median time until sputum conversion was 2 months (IQR, 1-2 mo). Furthermore, in the intensified regimen group, the sputum conversion rate was 81.3% (13/16), and the median time until sputum conversion was 1 month (IQR, 1-1 mo). Leukopenia and drug-induced hepatotoxicity occurred more frequently in the intensified regimen group in contrast with the conventional regimen group patients. However, only 1 adverse event in the intensified regimen group was classified as severe adverse event. Conclusions. The intensified regimen could improve sputum conversion of M. abscessus lung disease compared with conventional regimen, but close safety surveillance is necessary to monitor adverse events. [ABSTRACT FROM AUTHOR]

A method was established for coupled solid phase extraction-ultra performance liquid chromatography and mass spectrometry, to simultaneously detect 12 common antibiotics belonging to 4 types (sulfonamides, macrolides, fluoroquinolones and cephalosporins) in the Harbin section of the Songhua River basin, Northeastern China. The results showed that the 12 antibiotics monitored were all detected to varying degrees, with 100% detection rates for sulfamethoxazole (SMX), cefazolin (CFZ), ofloxacin (OFL), flumequine (FLU), azithromycin (AZI) and roxithromycin (ROX), and the highest levels were in winter, the lowest in summer. The total concentrations of all 12 antibiotics in spring, summer, autumn and winter, were 39.7, 9.6, 27.5 and 136.2 ng L−1, respectively. Seasonality was also observed in antibiotic distribution along the riverbank, with winter concentrations of all antibiotics detected upstream of the Harbin section being lower than the downstream section; in summer, except for CFZ, the concentrations of all antibiotics detected were higher upstream, than downstream of the Harbin section. Finally, the health risks to people of different ages caused by residual antibiotic contamination in the Songhua River were evaluated, and the results showed that the risk of antibiotics was far lower than 1, with no direct threat to human health established. [ABSTRACT FROM AUTHOR]

Purpose: To describe trends and correlation between antibacterial exposure and bacterial resistance from hospitalized patients in a hospital in southern China. Patients and methods: This study used hospital-wide data regarding antimicrobial resistance and consumption between January 1, 2014 and December 31, 2018. Antibacterial consumption was expressed as antimicrobial use density (AUD). The changes in trends and associations between antibacterial utilization and resistance were analyzed using linear regression and time series analysis. Results: The total AUD of all antimicrobials decreased year by year (50.66 in 2014 vs 44.28 in 2018, P=0.03). The annual use of antimicrobials, such as penicillins, monobactams, aminoglycosides, macrolides, and lincosamides, significantly decreased (P<0.05), while the annual use of quinolones and tetracyclines significantly increased (P<0.05). Among the top ten isolated bacteria, antimicrobial resistance trends of Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Staphylococcus aureus, and Staphylococcus epidermidis significantly decreased (P<0.05). Significant positive correlation was found between AUD of carbapenems and resistance rate of Acinetobacter baumannii to imipenem (β=32.87, P<0.01), as well as the correlation between AUD of quinolones and resistance rate of Enterococcus faecium to levofloxacin (β=104.40, P<0.01). Conclusion: The consumption of antibiotics and antibiotic resistance has been significantly improved in this tertiary hospital. Additionally, the efforts of China's antibiotic management may be suggested by the relationship between indicated antibiotic resistance and consumption. However, overall AUD levels and poor control of the use of antibiotics, such as quinolones and tetracyclines, still require strengthened management. [ABSTRACT FROM AUTHOR]

Background: Bronchiectasis is a rare complication in patients with thymic neoplasm. The aim of this study was to investigate the clinical and radiological manifestations, laboratory tests, pathologic features, and outcome of treatment of bronchiectasis in patients with thymic neoplasm. Methods: From January 2000 to January 2018, 20 patients with a diagnosis of thymic neoplasm and bronchiectasis were hospitalized at the Peking Union Medical College Hospital. Clinical data was retrospectively analyzed. Results: The prevalence of bronchiectasis in thymic neoplasms in our cohort was 1.56% (20/1279). Eighteen patients were diagnosed with thymoma, while two patients were diagnosed with thymic carcinoid. The duration from diagnosis of thymic neoplasm to bronchiectasis varied. Distributions of bronchiectasis were bilateral in 17 patients and unilateral in three patients. Four patients were previously diagnosed with diffuse panbronchiolitis and another two were suspected with diffuse panbronchiolitis. Twelve patients had various parathymic syndromes, including Good syndrome, myasthenia gravis, and aplastic anemia. Thymectomy was performed in all of these patients. Macrolide antibiotics were administered to 10 patients, and the symptoms improved in 8. Conclusion: Bronchiectasis is a complication in thymic neoplasms, although prevalence is low. There may be multifactorial etiologies for bronchiectasis in patients with thymic neoplasms. Comprehensive treatment should be carried out to ensure optimal outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Community-acquired pneumonia (CAP) is a global disease responsible for a large number of deaths, with significant economic impact. As diagnostic tools have increased in sensitivity, understanding of the etiology of CAP has begun to change. Mycoplasma pneumoniae is one of the major pathogens causing CAP. Macrolides and related antibiotics are first-line treatments for M. pneumoniae. Macrolide resistance has been spreading for 15 years and now occurs in worldwide. We undertook the first study on macrolide resistance of M. pneumoniae in Yantai. This may be helpful to determine the appropriate therapy for CAP in this population. Objective: To investigate the rate and mechanism of macrolide resistance in Yantai. Methods: Pharyngeal swab samples were collected from adult CAP patients. Samples were assayed by polymerase chain reaction (PCR) and cultivated to test for M. pneumoniae. Nested PCR was used to specifically amplify M. pneumoniae 23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations. Results were confirmed by sequencing. Twenty-seven strains of M. pneumoniae were isolated and the activities of nine antibiotics against M. pneumoniae were tested in vitro. Results: Out of 128 samples tested, 27 were positive for M. pneumoniae. Mycoplasma 100% macrolides resistance to Mycoplasma pneumoniae. The mechanism of macrolides resistance was A2063G point mutation in the sequence directly binding to macrolides in the 23S rRNA V domain in vitro. The mean pyretolytic time for the fluoroquinolone group was 4.7 ±2.9 d, which was significantly shorter than 8.2 ±4.1 d for the azithromycin group. Conclusions: Macrolides are not the first-line treatment for M. pneumoniae respiratory tract infections in Yantai. [ABSTRACT FROM AUTHOR]

Objective Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria (NTM) isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. Methods Four macrolides, including clarithromycin (CLAR), azithromycin (AZM), roxithromycin (ROX), and erythromycin (ERY), were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23S rRNA and erm , were analyzed with nucleotide sequence analysis. Results Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191A and T2221C on rrl were specific for the M. abscessus complex (MABC). Seven sites, G2140A, G2210C, C2217G, T2238C, T2322C, T2404C, and A2406G, were specifically carried by M. avium and M. intracellulare . Three sites, A2192G, T2358G, and A2636G, were observed only in M. fortuitum and one site G2152A was specific for M. gordonae . The genes erm (39) and erm (41) were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar. Conclusion The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23S rRNA and erm , failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species. [ABSTRACT FROM AUTHOR]

The occurrence and seasonal variation of 24 dissolved emerging organic contaminants in the Yangtze Estuary were studied, including 12 non-antibiotic pharmaceuticals, seven sulfonamides, two macrolides and three chloramphenicols. Sulfadiazine, erythromycin, thiamphenicol and paracetamol were the primary contaminants in sulfonamides, macrolides, chloramphenicols and non-antibiotic pharmaceutical groups, respectively. Compared to the concentrations at Datong, chloramphenicols at Xuliujing were significantly higher in autumn and winter, while macrolides were lower in spring. Based on the flux estimation, approximately 37.1 tons of sulfonamides, 17.4 tons of macrolides, 79.2 tons of chloramphenicols and 14.1 tons of non-antibiotic pharmaceuticals were discharged into the Yangtze Estuary from June 2013 to May 2014. However, the total flux from the Huangpu River only represented 5% of the total. The pharmaceutical sources were speculated on by analyzing the seasonal variations in pharmaceutical concentrations and fluxes at various sites. Both environmental and social factors might affect the fluxes. [ABSTRACT FROM AUTHOR]

• Antibiotics have been found in tap water and well water in rural Eastern China. • The dominant contaminations in drinking-water samples were macrolides and sulfonamides. • Drinking-water may be an important exposure source to antibiotics, inducing potential health risks. • Ingestion route, compared with dermal contact, may be the primary mode of exposure to antibiotic residues in drinking-water. Trace levels of antibiotics were frequently found in drinking-water, leading a growing concern that drinking-water is an important exposure source to antibiotics in humans. In this study, we investigated antibiotics in tap water and well water in two rural residential areas in Eastern China to assess the related human health exposure risks in drinking-water. Twenty-seven antibiotics were analyzed using ultra performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-MS/MS). The average daily dose (ADD) and the health risk quotient (HRQ) for exposure to antibiotics in humans were evaluated using 10000 times of Monte Carlo simulations. Ten antibiotics were detected in drinking-water samples, with the maximum concentrations of antibiotic mixture of 8.29 ng/L in tap water and 2.95 ng/L in well water, respectively. Macrolides and sulfonamides were the predominant contaminants and showed the seasonality. Azithromycin had the highest detection frequencies (79.71-100%), followed by roxithromycin (25.71-100%) and erythromycin (21.43-86.96%). The estimated ADD and HRQ for human exposure to antibiotic mixture through drinking-water was less than 0.01 μg/kg/day and 0.01, respectively, which varied over sites, water types, seasons and sex. Ingestion route was more important than dermal contact route (10−6 to 10−4 μg/kg/day magnitude vs. 10−11 to 10−8 μg/kg/day magnitude). Macrolides also contributed mainly to health exposure risks to antibiotics through drinking-water, whose HRQ accounted for 46% to 67% of the total HRQs. Although the individual antibiotic and their combined effects contributed to acceptable health risks for human, the long-term exposure patterns to low-dose antibiotics in drinking-water should not be ignored. [ABSTRACT FROM AUTHOR]

• Most antibiotics pose insignificant risks in the Yellow River. • Different classes of antibiotics vary significantly in upstream and downstream.DOM can be used to indicate antibiotic pollution levels of the river. • Differential contribution of antibiotics to rivers from point and nonpoint sources. • SMX, SDX and ERY are mainly discharged from wastewater treatment plants. Understanding the sources of antibiotics is important for managing antibiotic contamination and preventing environmental risks in the aquatic environment. In this study, the distribution of dissolved organic matter (DOM) and 24 antibiotics from four typical classes (quinolones, macrolides, sulfonamides and tetracyclines) in the Yellow River basin containing distinct sources of pollution was investigated. In particular, relationships between the antibiotic concentrations and fluorescent properties of DOM were to be established to identify antibiotic sources. A total of 22 antibiotics were detected, with maximum concentrations ranging from 0.27 to 30.14 ng/L in the mainstream of the Yellow River. Of these antibiotics, only erythromycin (ERY) and sulfamethoxazole (SMX) posed potential risks to aquatic organisms. Spatially, tetracyclines were mainly distributed in the upstream reaches of the river, and quinolones were largely distributed in the midstream. High levels of sulfonamides were present downstream of the investigated river. Only EYR belonging to the macrolide group was detected and had a high downstream concentration. EEM-PARAFAC analysis showed that DOM was composed of visible fulvic acid-like fluorescence fraction (C1), ultraviolet fulvic acid-like fluorescence fraction (C2) and protein-like fraction (C3). Using Pearson correlation analysis, this study demonstrated a close relationship between DOM spectral parameters and antibiotic concentrations in the Yellow River basin. Specifically, r (C3, C2) was significantly and positively correlated with the concentrations of SMX, sulfadoxine (SDX), and ERY, while humification index (HIX) had an opposite relationship with these antibiotics. These results suggested that SMX, SDX and ERY were mainly discharged from wastewater treatment plants into the mainstream of the Yellow River. This work provides a powerful demonstration that DOM plays an important role in indicating the occurrence and sources of antibiotics in the aquatic environment. [Display omitted] [ABSTRACT FROM AUTHOR]

Previous studies indicate that macrolide resistance in Moraxella catarrhalis isolates is less common in adults than in children. However, few studies have investigated M. catarrhalis macrolide resistance mechanisms in adult patients. In this study, 124 M. catarrhalis isolates were collected from adult patients in a Chinese tertiary hospital, between 2010 and 2013, and investigated for antimicrobial resistance. We found that only seven isolates were macrolide resistant and all exhibited high-level macrolide resistance (minimum inhibitory concentrations >256 μg/ml). Multilocus sequence typing (MLST) suggested that M. catarrhalis has a diverse population; in particular, both pulsed-field gel electrophoresis and MLST revealed that all the seven high-level macrolide-resistant M. catarrhalis belonged to different clones. A 934-bp 23S rRNA gene sequencing showed that only nine isolates (including all the seven macrolide-resistant isolates) had mutations within the studied region, and only the seven macrolide-resistant isolates had mutation of A2330T. No other known macrolide-resistance determinant genes ( ermA, ermB, mefA, or mefE) were detected. These findings support previous studies in children on M. catarrhalis macrolide-resistant isolates and suggest that the 23S rRNA gene A2330T mutation is responsible for the high M. catarrhalis macrolide resistance. The findings prompted us to successfully develop a simple allele-specific polymerase chain reaction assay for high-level macrolide-resistant 23S rRNA gene A2330T mutation for future clinical and further surveillance use. [ABSTRACT FROM AUTHOR]

To explore the antibiotic body burden of Chinese school children, total urinary concentrations (free and conjugated) of 18 representative antibiotics (5 macrolides, 2 β-lactams, 3 tetracyclines, 4 quinolones, and 4 sulfonamides) were measured by ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry among 1064 school students recruited from 3 economically and geographically distinct areas in east China in 2013. All 18 antibiotics were detected in urine samples with the detection frequencies ranging from 0.4 to 19.6%. The antibiotics were detected in 58.3% of urine samples overall, and this detection frequency reached at 74.4% in one study site. Of them, 47.8% of the urine samples had a sum of mass concentration of all antibiotics between 0.1 (minimum) and 20.0 ng/mL, and 8 antibiotics had their concentrations of above 1000 ng/mL in some urine samples. Three veterinary antibiotics, 4 human antibiotics, and 11 human/veterinary antibiotics were found overall in 6.3, 19.9, and 49.4% of urine samples, respectively. The detection frequencies and concentration levels of antibiotics in urine samples differed by study areas. Concerning mixed exposures, a total of 137 combinations of antibiotics and 20 combinations of antibiotic categories were found overall. Two or more antibiotics or categories were concurrently detected in more than 20% of urine samples. On the basis of a usage analysis, contaminated food or environment might be relevant exposure sources for tetracyclines, quinolones, and sulfonamides. [ABSTRACT FROM AUTHOR]

Streptococcus suis is one of the major etiologic agents of contagious infection in swine and is also emerged as a zoonotic agent. A recent large scale outbreak has also affected human in China. So far, the accurate information about the macrolide resistant mechanism in S. suis clinical isolates of swine as well as human was not enough. Here we investigated the macrolide resistance in S. suis. MIC, followed by PCR and sequencing, to detect the genetic determinants involved in macrolide resistance. MIC results showed a high level resistant rate to macrolides. Likewise, methylation in the 23S rRNA genes by ErmB and efflux mediated by the MefA and MsrD were both found responsible for macrolide resistance in these studied clinical strains of S. suis. Furthermore, the mutants produced from clinical susceptible strains by stepwise induction of resistance were also checked for any other possible mechanism involved in macrolide resistance. Mutations on 23S rRNA, L4 and L22 ribosomal proteins were found responsible for macrolide resistance in passage mutants, these findings were different as compared with studied clinical strains. To our knowledge, this is first to report that the correlation between efflux pump and modifications in L22 ribosomal protein contributed to develop the macrolide resistance in S. suis isolates. [ABSTRACT FROM AUTHOR]

Abstract: Ten antibiotics belonging to three groups (macrolides, fluoroquinolones and sulfonamides) were investigated in riverine runoff of the Pearl River Delta (PRD) and Pearl River Estuary (PRE), South China for assessing the importance of riverine runoff in the transportation of contaminants from terrestrial sources to the open ocean. All antibiotics were detected in the eight outlets with concentrations ranging from 0.7 to 127 ng L−1. The annual mass loadings of antibiotics from the PRD to the PRE and coast were 193 tons with 102 tons from the fluoroquinolone group. It showed that antibiotics decreased from the riverine outlets to the PRE and open ocean. Risk assessment showed that most of these antibiotics showed various ecological risks to the relevant aquatic organisms, in which ofloxacin (OFL), erythromycin (ETM) and ciprofloxacin (CIP) posed high ecological risks to the studied aquatic environments. [Copyright &y& Elsevier]

Abstract: The occurrence and distribution of ten selected antibiotics from three groups (sulfonamides, macrolides, and trimethoprim) were investigated in the Yongjiang River, which flows through Nanning City, a typical developing city in China. The study also assessed the ecological risks and the potential effects caused by discharge from tributaries and anthropogenic activities. Concentrations of most of the antibiotics were elevated along the section of the river in the urban area, highlighting the significant impact of high population density and human activities on the presence of antibiotics in the environment. The concentrations in the tributaries (ranged from not detected to 1336ngL−1) were generally higher than those in the main stream (ranged from not detected to 78.8ngL−1), but both areas contained the same predominant antibiotics, revealing the importance of tributary discharge as a source of antibiotic pollution. A risk assessment for the surface water contamination revealed that sulfamethoxazole and erythromycin posed high ecological risks to the most sensitive aquatic organisms (Synechococcus leopoliensis and Pseudokirchneriella subcapitata, respectively) in the midstream and some tributaries. Most of the selected antibiotics presented high ecological risks (risk quotients up to 95) in the sediments. [Copyright &y& Elsevier]

Abstract: The occurrence and distribution of eight quinolones, nine sulfonamides, and five macrolides were investigated in sewage sludge from 45 wastewater treatment plants in 23 cities in China. Among all the antibiotics considered, quinolones were the dominant antibiotics detected in all samples [total concentrations up to 8905μg/kg, dry weight (dw)], followed by macrolides (85.1μg/kg, dw), and sulfonamides (22.7μg/kg, dw). High concentrations of quinolones in sewage sludge indicated that antibiotics are widely used and extensive pollutants in China. Significant differences were observed for the total concentrations of antibiotics in sludge samples among the 45 WWTPs. To evaluate the potential factors affecting the antibiotic levels in sewage sludge, wastewater and sludge characteristics, as well as the operational conditions and treatment techniques in WWTPs were investigated. The results indicated that the antibiotic levels in sewage sludge depend to a great extent on wastewater characteristics. Significant correlation between total organic carbon (TOC) and total concentrations of antibiotics was also found in studied WWTPs, indicating that TOC could affect the sludge adsorption capability to the antibiotics to some extent. Moreover, the relation between treatment techniques and the total concentrations of antibiotics in sludge showed that antibiotic levels in sludge increased with longer solid retention time. [Copyright &y& Elsevier]

Objective: Resistant strains of Mycoplasma pneumoniae lead to antibiotic inefficacy. The relationship between M pneumoniae 23S rRNA (GenBank: X68422.1) gene mutations and macrolide resistance phenotype has not been fully established, to our knowledge. In this study, we isolated and cultured macrolide-resistant strains of M pneumoniae and tested them for 23S rRNA gene mutations. Methods: Throat swab samples from patients (n = 800) with community-acquired respiratory tract infections were isolated by nested PCR for the molecular identification of clinical isolates. An in vitro drug sensitivity test was performed on clinical isolates for macrolide antibiotic efficacy. The minimum inhibitory concentration (MIC) was used to select resistant strains. Resistant strains of 23S rRNA were sequenced and compared with the sequences of standard macrolidesensitive M129 strains by comparative sequence analysis, focusing the analysis on mutations linked to the drug-resistance phenotype. Results: One hundred M pneumoniae strains were isolated, of which 82 strains were macrolide sensitive and 18 strains were resistant. Mutations were identified in 16 of the 18 macrolide-resistant strains. The following mutations were detected: A2063G, A2064G, C2617G, and A2067G. Of these mutations, A2063G exhibited 14-ring macrolide resistance, A2064G exhibited 14- and 16-ring macrolide resistance, C2617G demonstrated 14- and 15-ring macrolide resistance, and A2067G demonstrated josamycin resistance. Conclusion: M pneumoniae resistance to macrolide antibiotics is a serious clinical issue: our results indicate that 23S rRNA mutations are associated with drug resistance. By analysis of the 23S rRNA mutation and resistance phenotype, our understanding of the clinical drug resistance of M pneumoniae can aid in the rational selection and application of antibiotics for optimal therapeutic treatments. [ABSTRACT FROM AUTHOR]

Fluoroquinolones, sulfonamides and macrolides were analyzed in soil samples collected from suburban areas in Tianjin, China. Fluoroquinolones were the predominant class of antibiotics. The mean total concentration of fluoroquinolones (33.56 μg/kg) was 30-fold higher than one of macrolides, which were the second dominant class antibiotics. Sulfonamides showed the lowest level in soil. The spatial distribution of fluoroquinolones showed wastewater irrigation was a potential source of antibiotics. The individual antibiotics levels were all below the trigger value (100 μg/kg) set by the Steering Committee of Veterinary International Committee, indicating the low risk for organisms in the agricultural soils of Tianjin. [ABSTRACT FROM AUTHOR]

This study focused on the presence and distribution of 22 antibiotics, including eight quinolones, nine sulfonamides and five macrolides in mollusks from the Bohai Sea of China. 190 samples of eleven species were collected in 2006, 2007 and 2009. Laboratory analyses revealed that antibiotics were widely distributed in the mollusks with quinolones as the major compounds with concentrations of 0.71∼1575.10 μg/kg, which were up to two orders of magnitude higher than those of sulfonamides (0∼76.75 μg/kg) and macrolides (0∼36.21 μg/kg). The contents of quinolones and macrolides did not show significant changes from 2006, 2007 to 2009, while sulfonamides decreased significantly from 2006 to 2009. Compared with other sites, the city of Dalian was more polluted with quinolones, while Beidaihe was more contaminated with erythromycin and sulfapyridine. In addition, Mactra veneriformis and Meretrix merehjgntrix Linnaeus contained higher concentrations of quinolones and sulfamonomethoxine, while Mytilus edulis had higher levels of erythromycin and sulfapyridine. [Copyright &y& Elsevier]

Abstract: The occurrence, removal efficiency and seasonal variation of 22 antibiotics, including eight fluoroquinolones, nine sulfonamides and five macrolides, were investigated in eight sewage treatment plants (STPs) in Beijing, China. A total of 14 antibiotics were detected in wastewater samples, with the maximum concentration being 3.1μgL−1 in the influent samples and 1.2μgL−1 in the effluent samples. The most frequently detected antibiotics were ofloxacin, norfloxacin, sulfadiazine, sulfamethoxazole, erythromycin and roxithromycin; of these, the concentration of ofloxacin was the highest in most of the influent and effluent samples. Eighteen antibiotics were detected in the sludge samples, with concentrations ranging from 1.0×10−1 to 2.1×104 μgkg−1. The dominant antibiotics found in the sludge samples were the fluoroquinolones, with ofloxacin having the highest concentration in all the sludge samples. The antibiotics could not be removed completely by the STPs, and the mean removal efficiency ranged from −34 to 72%. Of all the antibiotics, the fluoroquinolones were removed comparatively more efficiently, probably due to their adsorption to sludge. Seasonal variation of the antibiotics in the sludge samples was also studied. The concentrations of antibiotics in winter were higher than in spring and autumn. Since the total levels of the fluoroquinolones detected in the influent samples were lower than the predicted no-effect concentration (PNEC) of 8.0μgL−1, the residues of these antibiotics would be unlikely to have adverse effects on microorganisms involved in sewage treatment processes. [Copyright &y& Elsevier]

Strain JAU4234, identified as Streptomyces padanus, was isolated from soil collected in Jiangxi Province, China. It introduced actinomycin X2, fungichromin, and a new polyene macrolide compound with antifungal activity, antifungalmycin 7O2 Antifungalmycin 702 had good general antifungal activity and may have potential future agricultural and/or clinical applications. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is the main pathogen that causes respiratory infections in children younger than five years. The increasing incidence of macrolide- and tetracycline-resistant pneumococci among children has been a serious problem in China for many years. The molecular characteristics of erythromycin-resistant pneumococcal isolates that were collected from pediatric patients younger than five years in Beijing in 2010 were analyzed in this study. Results: A total of 140 pneumococcal isolates were collected. The resistance rates of all isolates to erythromycin and tetracycline were 96.4% and 79.3%, respectively. Of the 135 erythromycin-resistant pneumococci, 91.1% were non-susceptible to tetracycline. In addition, 30.4% of the erythromycin-resistant isolates expressed both the ermB and mef genes, whereas 69.6% expressed the ermB gene but not the mef gene. Up to 98.5% of the resistant isolates exhibited the cMLSB phenotype, and Tn6002 was the most common transposon present in approximately 56.3% of the resistant isolates, followed by Tn2010, with a proportion of 28.9%. The dominant sequence types (STs) in all erythromycin-resistant S. pneumoniae were ST271 (11.9%), ST81 (8.9%), ST876 (8.9%), and ST320 (6.7%), whereas the prevailing serotypes were 19F (19.3%), 23F (9.6%), 14 (9.6%), 15 (8.9%), and 6A (7.4%). The 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) coverage of the erythromycin-resistant pneumococci among the children younger than five years were 45.2% and 62.2%, respectively. ST320 and serotype 19A pneumococci were common in children aged 0 to 2 years. CC271 was the most frequent clonal complex (CC), which accounts for 24.4% of all erythromycin-resistant isolates. Conclusions: The non-invasive S. pneumoniae in children younger than five years in Beijing presented high and significant resistance rates to erythromycin and tetracycline. The expressions of ermB and tetM genes were the main factors that influence pneumococcal resistance to erythromycin and tetracycline, respectively. Majority of the erythromycin-resistant non-invasive isolates exhibited the cMLSB phenotype and carried the ermB, tetM, xis, and int genes, suggesting the spread of the transposons of the Tn916 family. PCV13 provided higher serotype coverage in the childhood pneumococcal diseases caused by the erythromycin-resistant isolates better than PCV7. Further long-term surveys are required to monitor the molecular characteristics of the erythromycin-resistant S. pneumoniae in children. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, the serotype distribution and antibiotic resistance of S. pneumoniae from pediatric patients with upper respiratory infections in Beijing, 2010 were described. 140 pneumococcal isolates were obtained, and the prevailing five serotypes were 19F (18.6%), 23F (9.3%), 14 (9.3%), 15 (9.3%), and 6A (7.1%). The vaccine coverage of PCV7, PCV10, and PCV13 were 43.6%, 43.6%, and 60.0%, respectively. According to the CLSI 2010 criteria, 99.3% of the S. pneumoniae isolates were susceptible to penicillin. The resistance rates to erythromycin and azithromycin were 96.4% and 97.1%, respectively. Meanwhile, 64.3% (90/140) of all pneumococcal isolates were multidrug-resistant S. pneumoniae (MDRSP). PCV13 covered 68.9% (62/90) of MDRSP strains, whereas it was 47.8% (43/90) for PCV7. ErmB was the dominant macrolide-resistance gene, whereas 30.4% pneumococcal isolates expressed both ermB and mefA. No isolate expressed ermTR. The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 6A and 19A, and the conjugate vaccines could prevent the spread of MDRSP. S. pneumoniae is still sensitive to penicillin. The resistance rate of S. pneumoniae to macrolides is high and ermB is the dominant macrolide-resistance gene in China, so continued surveillance of the antimicrobial susceptibility of S. pneumoniae may be necessary. [Copyright &y& Elsevier]