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Objectives: To characterize a novel plasmid-mediated tigecycline resistance-related gene, tet(Y), in a clinical Acinetobacter baumannii isolate from China.Methods: The tet(Y)-encoded tigecycline-resistant A. baumannii 2016GDAB1 was screened through antimicrobial susceptibility testing and WGS. The function of tet(Y) was verified by complementation of tet(Y). The plasmid transferability and stability were detected via plasmid conjugation and in vitro bacterial passaging. The 3D structure of Tet(Y) was predicted and docked using tFold and AutoDock Vina.Results: The tigecycline-resistant A. baumannii 2016GDAB1 was isolated from bronchoalveolar lavage fluid of a patient with hospital-acquired pneumonia. However, this strain did not harbour any common tigecycline resistance genes, determinants or mutations. 2016GDAB1 belongs to the non-epidemic clone ST355 (Oxford scheme), which has been mainly reported in animals. The tet(Y) gene was located on a 72 156 bp plasmid and genomic environment analysis revealed that Tn5393 may play a role in tet(Y) transmission, whereas phylogenetic analysis indicated the origin of tet(Y) as from Aeromonas. Overexpression of tet(Y) resulted in a 2- to 4-fold increase in tigecycline MIC. Introduction of the tet(Y)-harbouring plasmid p2016GDAB1 via electroporation resulted in a 16-fold increase in tigecycline MIC but failed to transfer into the tigecycline-susceptible A. baumannii recipient via conjugation. Isolates carrying the tet(Y) gene were vulnerable to tigecycline pressure and exhibited decreased susceptibility to tigecycline. A tet(Y)-carrying plasmid was stably maintained in the host strains.Conclusions: This study identified the tigecycline resistance-related gene tet(Y) in A. baumannii. This gene conferred an increased tigecycline MIC and the transposable element Tn5393 may play a role in its transmission across isolates. [ABSTRACT FROM AUTHOR]

Background: SPR206 is a novel polymyxin analogue. Activity against clinical isolates is little documented.Methods: A collection of 200 MDR, carbapenem-resistant, tigecycline-resistant, colistin-resistant and non-MDR clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Stenotrophomonas maltophilia was obtained from 50 centres across China (2016-17). All isolates were derived from respiratory tract, urine and blood samples. Strains were purposely selected on the basis of phenotypes, genotypes and specimen origins. MICs of SPR206 and other antimicrobials were determined.Results: SPR206 was active against all bacteria tested except colistin-resistant isolates. The MIC50/90 values of SPR206 for colistin-resistant strains were comparable to known polymyxins (16/128 versus 8/128 mg/L). SPR206 exhibited potent activity against colistin-susceptible OXA-producing A. baumannii (MIC50/90 = 0.064/0.125 mg/L), NDM-producing Enterobacteriaceae (MIC50/90 = 0.125/0.25 mg/L) and KPC-2-producing Enterobacteriaceae (MIC50/90 = 0.125/0.5 mg/L). In fact, SPR206 was the most potent agent tested, with 2- to 4-fold lower MICs than colistin and polymyxin B for A. baumannii, P. aeruginosa and Enterobacteriaceae. Additionally, MIC values of SPR206 (MIC50/90 = 0.064/0.125 mg/L) were 16- to 32-fold lower than those of tigecycline (MIC50/90 = 2/2 mg/L) for tigecycline-susceptible carbapenem-resistant A. baumannii.Conclusions: SPR206 showed good in vitro activity against MDR, tigecycline-resistant and non-MDR clinical isolates of Gram-negative pathogens. SPR206 also exhibited superior potency to colistin and polymyxin B, with 2- to 4-fold lower MIC50/90 values. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate in vitro activity of the novel β-lactamase boronate inhibitor taniborbactam (VNRX-5133) combined with cefepime or meropenem against 500 urinary Gram-negative bacilli.Methods: Cefepime/taniborbactam and 14 comparators were tested by broth microdilution or agar dilution methods. A total of 450 Enterobacteriaceae and 50 Pseudomonas aeruginosa were selected from 2017 to 2019 based on different β-lactamase-producing or resistance phenotypes. For carbapenem-non-susceptible isolates, the modified carbapenem inactivation method (mCIM), EDTA-CIM (eCIM) and amplification of carbapenemase genes were performed. For NDM-producing isolates and those with cefepime/taniborbactam MICs >8 mg/L, the MICs of meropenem/taniborbactam and/or mutations in PBP3 were investigated.Results: Taniborbactam improved cefepime activity with the same efficiency as avibactam improved ceftazidime activity against 66 KPC-2 producers, 30 non-carbapenemase-producing carbapenem-non-susceptible Enterobacteriaceae and 28 meropenem-susceptible P. aeruginosa. However, cefepime/taniborbactam exhibited more potent activity than ceftazidime/avibactam against 56 ESBL-producing, 61 AmpC-producing, 32 ESBL and AmpC co-producing, 87 NDM-producing and 21 MBL-producing Enterobacteriaceae predicted by phenotypic mCIM and eCIM, 82 Enterobacteriaceae that were susceptible to all tested β-lactams and 22 carbapenem-non-susceptible P. aeruginosa. A four-amino acid 'INYR' or 'YRIN' insertion, with or without a one/two-amino acid mutation in PBP3, may have caused cefepime/taniborbactam MICs >8 mg/L among 96.6% (28/29) of the NDM-5-producing Escherichia coli, which accounted for the majority of isolates with cefepime/taniborbactam MICs >8 mg/L (76.1%, 35/46).Conclusions: Taniborbactam's superior breadth of activity, when paired with cefepime or meropenem, suggests these β-lactam/β-lactamase inhibitor combinations could be promising candidates for treating urinary tract infections caused by ESBL and/or AmpC, KPC or NDM-producing Enterobacteriaceae or P. aeruginosa. [ABSTRACT FROM AUTHOR]

Sequence type (ST) 398 is the most prevalent clone of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). To evaluate the molecular characteristics and phylogeny of Chinese ST398 isolates, 4 MRSA ST398 strains and 4 methicillin-susceptible S. aureus (MSSA) ST398 strains were collected from patients with bacteremia at 6 teaching hospitals in China between 1999 and 2016. Moreover, 689 ST398 genome sequences were downloaded from the GenBank database for comparison. The 4 MRSA ST398 strains were resistant to β-lactam antibiotics, and 2 strains were also resistant to erythromycin. Among the 4 MSSA ST398 strains, 2 strains displayed multidrug resistance (MDR) and were resistant to penicillin, erythromycin, tetracycline, and gentamicin. The accessory genome of MSSA ST398 was more diverse than that of MRSA ST398. All 4 MRSA ST398 strains carried type V staphylococcal cassette chromosome mec elements; however, MSSA ST398 carried more resistance genes than MRSA ST398. These 4 MRSA ST398 strains carried hemolysin, along with virulence genes associated with immune invasion and protease. Phylogenic analysis showed that the 4 MRSA ST398 strains clustered in 1 clade. The global ST398 phylogeny showed that ST398 was divided into an animal clade and a human clade, and the ST398 strains of this study clustered in the human clade. A small number of human strains were also present in the animal clade and vice versa, suggesting transmission of ST398 between animals and humans. In conclusion, livestock-associated MRSA ST398 has caused severe infections in Chinese hospitals, and it should therefore be paid more attention to and monitored. [ABSTRACT FROM AUTHOR]