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Objectives We explored the epidemiological and molecular characteristics of Candida parapsilosis sensu stricto isolates in China, and their mechanisms of azole resistance. Methods Azole susceptibilities of 2318 non-duplicate isolates were determined using CLSI broth microdilution. Isolates were genotyped by a microsatellite typing method. Molecular resistance mechanisms were also studied and functionally validated by CRISPR/Cas9-based genetic alterations. Results Fluconazole resistance occurred in 2.4% (n = 56) of isolates, and these isolates showed a higher frequency of distribution in ICU inpatients compared with susceptible isolates (48.2%, n = 27/56 versus 27.8%, 613/2208; P = 0.019). Microsatellite-genotyping analysis yielded 29 genotypes among 56 fluconazole-resistant isolates, of which 10 genotypes, including 37 isolates, belonged to clusters, persisting and transmitting in Chinese hospitals for 1–29 months. Clusters harbouring Erg11Y132F (5/10; 50%) were predominant in China. Among these, the second most dominant cluster MT07, including seven isolates, characteristically harbouring Erg11Y132F and Mrr1Q625K, lent its carriage to being one of the strongest associations with cross-resistance and high MICs of fluconazole (>256 mg/L) and voriconazole (2–8 mg/L), causing transmission across two hospitals. Among mutations tested, Mrr1Q625K led to the highest-level increase of fluconazole MIC (32-fold), while mutations located within or near the predicted transcription factor domain of Tac1 (D440Y, T492M and L518F) conferred cross-resistance to azoles. Conclusions This study is the first Chinese report of persistence and transmissions of multiple fluconazole-resistant C. parapsilosis sensu stricto clones harbouring Erg11Y132F, and the first demonstration of the mutations Erg11G307A, Mrr1Q625K, Tac1L263S, Tac1D440Y and Tac1T492M as conferring resistance to azoles. [ABSTRACT FROM AUTHOR]

Background: There have been reports of increasing azole resistance in Candida tropicalis , especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study. Methods: From August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10–14, n = 1510) or Sensititre YeastOne (CHIF-NET15–18, n = 2192) methods. Results: Overall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P -value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P -value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole. Conclusion: The continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions. [ABSTRACT FROM AUTHOR]

Ergot alkaloids are toxins which are produced biotechnologically on an industrial scale. The chemical investigation of endophytic Aspergillus fumigatus resulted in the isolation of five new ergot alkaloids named fumigaclavines D-H (2-6), along with three known analogues, fumigaclavine C (1), festuclavine (7), and fumigaclavine A (8). Their structures were unequivocally elucidated by extensive spectroscopic analyses in association with X-ray single-crystal diffraction. Fumigaclavines D-H are interesting clavine-type ergot alkaloids featuring a reverse prenyl moiety at C-2, with 1-4, 6, and 8 bearing additional substituents, e.g., an OH or OAc group at C-9. Compounds 2, 4, and 6-8 showed a broad spectrum of antimicrobial activity against a panel of anaerobic microorganisms, of which compounds 4 and 6 were the most active against Veillonella parvula with an MIC=16 µg/mL compared to that (0.12 µg/mL) of tinidazole, co-assayed as a positive reference., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To explore the risk factors on prognosis of Acinetobacter baumannii bloodstream infection., Methods: Clinical data from 78 patients with Acinetobacter baumannii bloodstream infection hospitalized in First Affiliated Hospital of Nanjing Medical University from January 2010 to November 2012 were analyzed retrospectively. According to the 28-day prognosis after admission, the patients were divided into non-survivors (n=40) and survivors (n=38). Data on demographic and clinical characteristics, wards, underlying diseases, treatments, invasive medical procedures, bacterial resistance to antibiotics, and acute physiology and chronic health evaluation II (APACHEII) score in the beginning were collected. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. The predictor value was concluded by comparing area under the receiver operating characteristic curve (ROC curve) of each index., Results: Risk factors of mortality of Acinetobacter baumannii bloodstream infection goes as following, including intensive care unit admission[ICU, odds ratio (OR)=12.9,95% confidence interval (95%CI) 2.4-63.5, P=0.001], trachea intubation or tracheostomy (OR=6.2, 95%CI 1.5-30.4, P=0.023), invasive mechanical ventilation (OR=5.1, 95%CI 1.4-22.6, P=0.042), invasive medical procedure besides central venous catheter (including thoracentesis, bone marrow puncture, lumbar puncture, catheterization, bronchoalveolar lavage with bronchofibroscope, arteriovenous fistula plastic operation, OR=8.4, 95%CI 1.7-37.8, P=0.011), APACHEII score ≥19 in the beginning (OR=35.4, 95%CI 3.8-318.6, P=0.001). With respect to APACHE II score≥ 19 as mortality cut-off point, an area under the receiver operating curve of 0.938 was statistically significant (P<0.05), with sensitivity 76.2% and specificity 94.1%. The relationship between prognosis and antibiotic resistance did not have statistically significance., Conclusions: Invasive medical procedures and treatments were associated with increased mortality of patients with Acinetobacter baumannii bloodstream infection. A strong predictor of adverse outcome in such conditions was APACHEII score ≥19.

Objective: To explore the antimicrobial resistance of nosocomial Gram-negative bacilli across China., Methods: A total of 1247 consecutive and non-repetitive Gram-negative bacilli were isolated from 13 Chinese teaching hospitals from March to August 2012. All isolates were sent to a central laboratory for reidentification and susceptibility testing. The minimal inhibitory concentration (MICs) of meropenem and other antibacterial agents were determined by agar dilution method. And the data were analyzed with WHONET-5.6 software., Results: The activity of antimicrobial agents against Enterobacteriaceae was in the following descending order of susceptibility rate: meropenem (97.5%, 849/871) , amikacin (94.5%, 823/871) , imipenem (93.6%, 815/871) , ertapenem (92.9%, 809/871) , piperacillin/tazobactam (89.9%, 783/871) , cefoperazone/sulbactam (83.5%, 727/871) , cefepime (78.1%, 680/871) , polymyxin B (77.0%, 670/871) , cefiazidime (69.6%, 606/871) , levofloxacin (69.2%, 603/871) , ciprofloxacin (63.6%, 554/871) , minocyline (63.1%, 550/871) , ceftriaxone (55.7%, 485/871) , cefotaxime (54.2%, 472/871) and cefoxitin (51.4%, 448/871) . The prevalence of extended-spectrum beta-lactamase (ESBL) was 64.3% (117/182) in Escherichia coli (E. coli) and 32.1% (60/187) in Klebsiella pneumonia (K. pneumoniae) . The sensitivities of E. coli to meropenem and imipenem were 100%. And over 90% of E. coli was sensitive to ertapenem, amikacin, piperacillin/tazobactam and polymyxin B. However, over 60% of E. coli was resistant to ciprofloxacin, levofloxacin, ceftriaxone and cefotaxime. The susceptibility of K. pneumoniae to meropenem, imipenem, amikacin and polymyxin B maintained at over 90%. The activities of antimicrobial agents against E. cloacae, E. aerogenes and Citrobacter freundii were in the following descending order of susceptibility rate: meropenem (96.0%-100%) , imipenem (96.0%-100%) , polymyxin B (95.8%-100%) , amikacin (92.2%-100%) , ertapenem (85.6%-93.3%) , cefepime (77.8%-93.3%) , cefoperazone/sulbactam (78.4%-90.0%) and piperacillin/tazobactam (65.0%-89.8%) . The most susceptible agent against Acinetobacter baumannii (A. baumannii) was polymyxin B (100%) . The susceptibilities of A.baumannii to imipenem, meropenem and minocyline were 37.8% (65/172) , 36.0% (62/172) and 62.8% (108/172) respectively. The most active agents against Pseudomonas aeruginosa (P. aeruginosa) were polymyxin B (97.2%, 173/178) , followed by amikacin (89.3%, 159/178) and cefiazidime (83.7%, 149/178) . Clinical and Laboratory Standards Institute revised P.aeruginosa susceptibility standard in 2012. The sensitivity of piperacillin/tazobactam changed from 83.7% (149/178) to 77.5% (138/178) . The sensitivity of meropenem decreased from 78.1% ( 139/178 ) to 71.3% ( 127/178 ) while that of imipenem declined from 69.7% (124/178) to 59.6% (106/178) . The prevalence of multi-drug resistant A. baumannii and P. aeruginosa were 65.7% (113/172) and 9.0% (16/178) respectively., Conclusions: Carbapenems remain highly active against Enterobacteriaceae. Increasing resistance of A. baumannii to all antimicrobial agents is noted. New breakpoint to P.aeruginosa has obvious effects on antimicrobial sensitivity.

Objective: To investigate the antimicrobial resistance among the nosocomial gram-negative pathogens from 15 teaching hospitals located in different areas in China in 2005., Methods: A total of 1927 non-repetitive nosocomial gram-negative pathogens were collected from 15 teaching hospitals in different areas in China and sent to the central lab for reidentification and susceptibility testing. The levels of minimal inhibitory concentration (MIC) of 18 antimicrobial agents were determined by agar dilution method. WHONET 5.4 software was used to analyze the data., Results: The strains of Escherichia coli, Klebsiella pneumoniae, and Proteous mirabilis isolates that did not produce extended spectrum beta lactamases (ESBLs) showed high sensitivity to beta-lactams. The antibiotics with a susceptibility rates over 80% against the strains of Entorobacter cloacae, Enterobacter aerogene, Citrobacter spp, Serratia spp, and Proteous vulgaris producing AmpC enzyme included meropenem, imipenem, and piperacillin-tazobactam, and these 3 drugs showed a susceptibility rate of more than 80% against the ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Other antimicrobial agents showing a relatively high activity against Enterobacter spp, Citrobacter spp, Serratia spp and Proteous vulgaris included cefepime (67.3% - 100%), amikacin (67.3% - 95.2%), ceftazidime (52.9% - 100%) and cefoperazone-sulbactam (51.9% - 100%). The susceptibility rate of fluoroquinolones was 34.8% - 36.1% against non-ESBL-producing Escherichia coli and was 13.4% - 17.1% against ESBL-producing isolates. The most active agent against Pseudomonas aeruginosa was polymyxin B (95.6%). The agents with the activity rates of 70% - 80% included meropenem, imipenem, amikacin, and piperacillin-tazobactam. The antibiotic with a high susceptible rate against Acinetobacter baumannii was polymyxin B (98.3%), followed by imipenem (80.8%), meropenem (76.2%), and minocycline (67.4%). The susceptible rates of other agents were all below 60%. The agents with relatively high activity against Stenotrophomonas maltophilia included minocycline (85%), levofloxacin (82.5%), and trimethoprim-sulfamethoxazole (77.5%). The agents with a relatively high activity against Burkholderia cepacia included minocycline (77.2%) and meropenem (61.4%)., Conclusion: Carbapenem, piperacillin-tazobactam, amikacin and cefepime remained relatively high activity against nosocomial Enterobacteriaceae, Non-fermenting pathogens have lower susceptibility to the antimicrobial agents than before.