Background Tigecycline is regarded as one of the last-resort antimicrobials clinically. Emergence of plasmid-mediated tet(X) undermines such an important drug. However, the origins of tet(X) remain largely unexplored. Methods Riemerella anatipestifer strains were characterized by PCR, antimicrobial susceptibility testing, WGS and bioinformatics analysis. Functional analysis of tet(X) was verified by cloning experiments. Genomic structures of chromosome- and plasmid-mediated tet(X) were analysed. Results Thirty-eight R. anatipestifer strains were collected and found to be positive for tet(X). These strains were resistant to multiple antimicrobials; 55.3% (21/38) of the strains were resistant to tigecycline and all of the strains demonstrated resistance to tetracycline. The complete genome sequences of 18 representative strains were obtained. WGS analysis of 38 genomes identified 13 tet(X) variants located on chromosomes, which increased MICs of tigecycline (16–256-fold) for Escherichia coli, although most of them could not confer high-level resistance to tigecycline in the original R. anatipestifer hosts. Genomic environment analysis indicated that the occurrence of multiple tet(X) variants is common and other resistance genes, such as catB, tet(Q), floR, blaOXA, ereD and ermF, could be located in the same chromosomal regions. Two types of tet(X)-bearing segments were identified, one of which was floR-ISCR2-tet(X). This indicates that tet(X) variants were not conserved in chromosomal structures, but in regions with potential transferability. Furthermore, an MDR plasmid carrying tet(X18) was found in R. anatipestifer 20190305E2-2, different from the chromosomal tet(X21). Conclusions This study confirmed that tet(X) is highly prevalent in R. anatipestifer. The transfer risk of tet(X) across R. anatipestifer to other clinical pathogens warrants further investigations.

Acinetobacter baumannii (Ab) bacteraemia in patients with haematological malignancies is fatal but rarely reported. We explored the clinical characteristics, drug resistances and prognostic factors in these patients. This multicentre, retrospective study was conducted at the department of haematology wards of 18 tertiary hospitals in China from January 2014 to June 2015. The total clinical isolates from every source were collected from patients with haematological malignancy. Haematological malignancy patients diagnosed with Ab bacteraemia were analysed. During the study period, 40 patients with Ab bacteraemia were identified, accounting for 2.9% (40/1358) of bacteraemia cases, of which 25 (62.5%) had acute leukaemia (AL) and 27 (67.5%) had neutropaenia. Compared with non-neutropaenic patients, neutropaenic patients showed higher Acute Physiology and Chronic Health Evaluation (APACHE) scores and 30-day mortality rates (p < 0.05). The in vitro antibiotic susceptibility of Ab to colistin was highest, at 100%, followed by that of tigecycline (91.30%) and amikacin (75.86%). Compared with the patients who had carbapenem-susceptible Ab infections, patients infected with carbapenem-resistant Ab (CRAB) had significantly longer hospital stays and were more likely to have had exposure to carbapenem before bacteraemia (p < 0.05). The 30-day mortality rate was 32.5%. CRAB, neutropaenia, higher APACHE score, Pitt bacteraemia score and inappropriate initial antimicrobial therapy were significantly associated with 30-day mortality. Multivariable analysis showed that APACHE score and CRAB were independent predictors of 30-day mortality. Haematologic patients with AL and febrile neutropaenia were at high risk of Ab bacteraemia. More attention should be paid to CRAB, which is an independent risk factor for mortality in haematological malignancy patients with Ab bacteraemia.

Pasteurella multocida (P. multocida) infection causes substantial economic loss in the duck industry. Danofloxacin, a fluoroquinolone solely used in animals, shows good antibacterial activity against P. multocida. In this study, the in vitro pharmacodynamics of danofloxacin against P. multocida was studied. The serum and lung tissue pharmacokinetics of danofloxacin were studied in healthy and P. multocida infected ducks following oral administration of a single dose of 5 mg/kg body weight (b.w.). The MIC, MBC and MPC of danofloxacin against P. multocida (C ) were 0.25, 1 and 3.2 μg/ml, respectively. The Cmax was 0.34 μg/ml, attained at 2.03 hr in healthy ducks, and was 0.35 μg/ml, attained at 2.87 hr in diseased ducks. Compared to the serum pharmacokinetics of danofloxacin in healthy ducks, the absorption rate and extent were similar in healthy and diseased animals. In contrast, the elimination rate was slower, with an elimination half-life (T ) of 13.17 and 16.18 hr for healthy and infected animals, respectively; the AUCs in the two groups were 5.70 and 7.68 μg hr/ml, respectively, which means the total amount of drug in the circulation was increased in the infected ducks. The maximum concentration in lung tissues between healthy and infected animals was not significantly different (8.96 vs. 8.93 μg/g). However, the T in healthy ducks was longer than that in infected ducks (4 hr vs. 1.75 hr), which means that the distribution rate of danofloxacin was slower in healthy ducks. The concentration of danofloxacin in lung tissues was approximately 24-fold higher than that in the serum. In the serum pharmacokinetic profiles, the ƒAUC /MIC was 18.19 in healthy ducks and was 25.04 in P. multocida infected ducks at the clinical recommended dose, which is far from the PK/PD target (125 hr) of fluoroquinolones. Danofloxacin, at a dose of 5 mg/kg b.w., seems to be insufficient for ducks infected with P. multocida, with an MIC equal to 0.25 μg/ml.

BackgroundSystemic Escherichia coli infections cause early mortality of commercial broiler chickens. Although enrofloxacin has long been used in poultry, the in vivo pharmacokinetic/pharmacodynamic (PK/PD) relationship of enrofloxacin against E. coli is unclear. The present study aimed to establish an in vivo PK/PD model of enrofloxacin against E. coli in seven-day-old chicks and to ascertain whether the selection of target organ for PD determination is critical for parameter magnitude calculation in enrofloxacin PK/PD modeling.ResultsThe in vivo effectiveness of enrofloxacin against E. coli in different organs varied, with the Emax ranging from − 4.4 to − 5.8 Log10 colony forming units (cfu)/mL or cfu/g. Both the surrogate AUC0–24/MIC of enrofloxacin or AUC0–24/MIC of the combination of enrofloxacin and ciprofloxacin correlated well with effectiveness in each organ. The AUC0–24/MIC ratio of the combination of enrofloxacin and ciprofloxacin producing bactericidal and elimination effects were 21.29 and 32.13 in blood; 41.68, and 58.52 in the liver; and 27.65 and 46.22 in the lung, respectively.ConclusionsThe in vivo effectiveness of enrofloxacin against E. coli in different organs was not identical after administration of the same dosage. To describe the magnitude of PK/PD parameter exactly, bacterial loading reduction in different organs as PD endpoints should be evaluated and compared in PK/PD modeling. The selection of a target organ to evaluate PDs is critical for rational dosage recommendation.

Pasteurella multocida is the causative agent of fowl cholera, and florfenicol (FF) has potent antibacterial activity against P. multocida and is widely used in the poultry industry. In this study, we established a P. multocida infection model in ducks and studied the pharmacokinetics of FF in serum and lung tissues after oral administration of 30 mg/kg bodyweight. The maximum concentrations reached (Cmax) were lower in infected ducks (13.88 ± 2.70 μg/ml) vs. healthy control animals (17.86 ± 1.57 μg/ml). In contrast, the mean residence time (MRT: 2.35 ± 0.13 vs. 2.27 ± 0.18 hr) and elimination half‐life (T½β: 1.63 ± 0.08 vs. 1.57 ± 0.12 hr) were similar for healthy and diseased animals, respectively. As a result, the area under the concentration curve for 0–12 hr (AUC0–12 hr) for FF in healthy ducks was significantly greater than that in infected ducks (49.47 ± 5.31 vs. 34.52 ± 8.29 μg hr/ml). The pharmacokinetic differences of FF in lung tissues between the two groups correlated with the serum pharmacokinetic differences. The Cmax and AUC0–12 hr values of lung tissue in healthy ducks were higher than those in diseased ducks. The concentration of FF in lung tissues was approximately 1.2‐fold higher than that in serum both in infected and healthy ducks indicating that FF is effective in treating respiratory tract infections in ducks.