Search

Aim: This study aimed to establish the in vitro efficacy and susceptibility profiles of new β-lactam antibiotics against clinically isolated carbapenemase-producing Klebsiella pneumoniae (CPKP) strains. Materials and Methods: A total of 117 nonduplicated CPKP isolates were tested against cefiderocol, cefepime-zidebactam, ceftazidime-avibactam, tigecycline, and other 20 antibiotics by broth microdilution. The carbapenemase genes were identified using PCR and sequencing, while multilocus sequence typing established the bacterial strains. Results: Three significant sequence types (STs), including ST147, ST16, and ST11, were shown to be the dominant STs, which occupied ∼90% of the tested population. Three carbapenemase genes, blaNDM-1, blaOXA-181, and blaOXA-232, were detected. The blaNDM-1 was found in ST147 and ST16 but not in ST11, while the blaOXA-232 was not detected in ST147. The majority of ST16 isolates contained both blaNDM-1 and blaOXA-232, which was not seen in other strains. Cefiderocol, cefepime-zidebactam, and tigecycline were the most active agents against CPKP. Both MIC50 and MIC90 of these three antibiotics remained within the susceptible categories, while nearly all other antibiotics were in the resistant levels. However, in ST11, which carried only blaOXA genes without blaNDM-1, ceftazidime-avibactam was effective with the MIC90 at 2 μg/mL. In addition, amikacin was shown to have good activity in ST11. In contrast, gentamicin was active in only ST16 and ST147. Conclusions: This study is the first report that demonstrates the prevalence of CPKP, distribution of strains, resistant genes, and antimicrobial susceptibility profiles in northern Thailand. These data would contribute to appropriate individual treatment and the selection of infection control strategies. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Kentucky (S. Kentucky) has been regarded as a common serotype causing human nontyphoidal salmonellosis, frequently associated with the consumption of contaminated poultry products. Recently, multidrug-resistant (MDR) S. Kentucky ST198 with strong resistance to cefotaxime, ciprofloxacin, and tigecycline has emerged and been frequently detected in both poultry and humans in Europe and Asia. In this study, whole-genome sequencing (WGS) analysis divided 327 S. Kentucky ST198 isolates into two clades, of which ST198.2 is more prevalent than ST198.1 worldwide. We further compared the genomic characteristics of 70 ST198 isolates from animals and humans during 2019-2022 plus previously reported 38 isolates from 2013 to 2019 in China. One hundred five of the 108 isolates were ST198.2, which could be differentiated into two subclades. ST198.2-1 was prevalent in isolates during 2013-2019, while ST198.2-2 has increased to be the predominant subclade in isolates since 2019. CRISPR typing can differentiate the clade ST198.1 isolates from clade ST198.2 ones but cannot differentiate the two subclade isolates. The acquisition of a large multi-drug resistant region in ST198.2-2 enhanced bacterial resistance to β-lactam, aminoglycoside, amphenicol, and fosfomycin. In addition, compared with the extendedspectrum β-lactamase (ESBL)-encoding gene blaCTX-M-14b in ST198.2-1, co-existence of blaCTX-M-55 and blaTEM-1B was detected in most of the ST198.2-2 isolates. The emergence of ciprofloxacin- and tigecycline-resistant ESBL-producing S. Kentucky ST198.2-2 strains highlight the necessity for Salmonella surveillance. It is imperative to implement more effective measures to prevent and control transmission of these strains from poultry to humans. Salmonella enterica serovar Kentucky (S. Kentucky) can cause human infections through consumption of contaminated food of animal origin, and the emergence of multidrug-resistant (MDR) ST198-S. Kentucky strains are of concern for human and animal health. Based on whole-genome sequencing (WGS) analysis, this study revealed that the clade ST198.2-2 S. Kentucky has increased to the predominant group in both chickens and humans in China since 2019, which is different to previous studies of the prevalent ST198.2-1 S. Kentucky before 2019. Acquirement of a multidrug resistance region (MRR) makes the ST198.2-2 S. Kentucky to be extensively drug-resistant (XDR) isolate compared with ST198.2-1 S. Kentucky. Besides, the ST198.2-2 S. Kentucky was mainly detected in chickens (chicken meat, intestinal contents, and slaughterhouse) and humans, indicating chicken is the main reservoir for these XDR S. Kentucky isolates. Therefore, it is necessary to implement continuous Salmonella surveillance and effective measures, such as the development of phages and novel antibiotics/compounds, to prevent the transmission of XDR ST198.2-2 S. Kentucky from chickens to humans across China. [ABSTRACT FROM AUTHOR]

Tigecycline has been used to treat patients with febrile neutropenia (FN). This study aims to analyse the effectiveness of tigecycline as salvage treatment of FN. Patients records from 09/2004 to 04/2019 were reviewed. Cases were eligible if fever persisted/recurred (p/r-FN) after 3 days of second-line treatment with a carbapenem, and were divided into three groups: switch to tigecycline (TGC group), switch to other antibiotics (OAB group), and no switch (W&W group). The primary endpoint was response rate (defervescence for ≥ 7 days or at least until discharge); the key secondary endpoint was 30-day mortality rate. Two hundred cases from 176 patients (median 59 years; 53.5% men) treated were included, mostly acute myeloid leukaemias (61.0%). 45.5% of cases were in the TGC group (in combination with an anti-pseudomonal antibiotic, mostly ceftazidime [95.6%]); 35.5% were in the OAB and 19.0% in the W&W group. There was no significant difference in response rates (TGC, 73.6%; OAB, 62.0%; W&W, 78.9%; p = 0.12) or 30-day mortality rates (TGC, 7.7%; OAB, 7.0%; W&W, 5.3%; p = 0.94). Tigecycline plus an anti-pseudomonal antibiotic does not improve response or 30-day mortality rate compared to other antibiotics in patients with p/r-FN. Also, in some cases, no switch in antibiotics may be necessary at all. [ABSTRACT FROM AUTHOR]

Purpose: This research aims to profile ten novel strains of carbapenem-resistant Enterobacteriaceae (CRE) co-carrying blaKPC and blaNDM.Methods: Clinical CRE strains, along with corresponding medical records, were gathered. To ascertain the susceptibility of the strains to antibiotics, antimicrobial susceptibility tests were conducted. To validate the transferability and cost of fitness of plasmids, conjugation experiments and growth curves were employed. For determining the similarity between different strains, ERIC-PCR was utilised. Meanwhile, whole genome sequencing (WGS) was performed to characterise the features of plasmids and their evolutionary characteristics.Results: During the course of this research, ten clinical CRE strains co-carrying blaKPC and blaNDM were gathered. It was discovered that five out of these ten strains exhibited resistance to tigecycline. A closer examination of the mechanisms underlying tigecycline resistance revealed that tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 existed concurrently within a single Citrobacter freundii strain (CF10). This strain, with a minimum inhibitory concentration (MIC) of 32 mg/L to tigecycline, was obtained from a sepsis patient. Furthermore, an investigation of genome evolution implied that CF10 belonged to a novel ST type 696, which lacked analogous strains. Aligning plasmids exposed that similar plasmids all had less than 70% coverage when compared to pCF10-tmexCD1, pCF10-KPC, and pCF10-NDM. It was also found that tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 were transferred by Tn 5393, IS 5, and Tn 6296, respectively.Conclusion: This research presents the first report of coexistence of tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 in a carbapenem and tigecycline-resistant C. freundii strain, CF10.Importance: Tigecycline is considered a "last resort" antibiotic for treating CRE infections. The ongoing evolution of resistance mechanisms to both carbapenem and tigecycline presents an alarming situation. Moreover, the repeated reporting of both these resistance mechanisms within a single strain poses a significant risk to public health. The research revealed that the genes tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1, which cause carbapenem and tigecycline-resistance in the same strain, were located on mobile elements, suggesting a potential for horizontal transmission to other Gram-negative bacteria. The emergence of such a multi-resistant strain within hospitals should raise significant concern due to the scarcity of effective antimicrobial treatments for these "superbugs". [ABSTRACT FROM AUTHOR]

Youling Fang,1,2 Qiaoshi Zhong,1 Yanhui Chen,1 Yaping Hang,1 Xueyao Fang,1 Yanping Xiao,1 Xingwei Cao,1 Hongying Zhu,3 Hong Luo,1 Suqin Peng,1 Shumin Gu,1 Fuxing Li,1 Junqi Zhu,1 Jianqiu Xiong,4 Longhua Hu1 1Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2School of Public Health, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Clinical Laboratory of Ganzhou People’s Hospital, Ganzhou, Jiangxi, People’s Republic of China; 4Department of Nursing, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Longhua Hu; Jianqiu Xiong, Email longhuahu@163.com; 1773014059@qq.comObjective: To analyze the clinical characteristics, outcomes, and risk factors of patients treated with ceftazidime/avibactam, polymyxin, or tigecycline (CPT) compared with those receiving a conventional therapy (CT) (ie, imipenem, levofloxacin, or gentamicin).Methods: A single-center retrospective cohort study included patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) treated at one Chinese tertiary hospital between March 2012 and November 2022 was performed. Clinical characteristics, outcomes, and risk factors of patients treated with CPT or CT were compared. Predictors of 30-day mortality of patients with CRKP-BSI were also analysed in our study.Results: Among 184 recruited patients with CRKP-BSI, 39.7% (73/184) were treated with CPT, while 60.3% (111/184) were treated with CT. Compared to patients treated with CT, patients treated with CPT had worse conditions, as evidenced by a higher rate of underlying diseases and invasive procedures; however, they also had a better prognosis and lower rates of 14-day treatment failure (p = 0.024). In addition, univariate analysis and multivariate analysis showed that SOFA score [odds ratio (OR) = 1.310, 95% confidence interval (CI) 1.157– 1.483; p < 0.001] and cold weather (OR = 3.658, 95% CI 1.474– 9.081; p = 0.005) were independent risk factors for 30-day mortality.Conclusion: Compared to CRKP-BSI patients treated with CT, patients treated with CPT had worse conditions but better prognoses. CRKP-BSI occurred more frequently in hot weather; however, higher 30-day mortality was associated with cold weather. A randomized trial is needed to confirm these observational results.Keywords: carbapenem-resistantKlebsiella pneumoniae, polymyxin, tigecycline, ceftazidime/avibactam, bloodstream infection, hot weather, cold weather

Shumin Gu,1,* Jianqiu Xiong,2,* Suqin Peng,1 Longhua Hu,1 Hongying Zhu,3 Yanping Xiao,1 Hong Luo,1 Yaping Hang,1 Yanhui Chen,1 Xueyao Fang,1 Xingwei Cao,1 Youling Fang,1 Fuxing Li,1 Junqi Zhu,1 Qiaoshi Zhong1 1Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Departmentof Nursing, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Clinical Laboratory of Ganzhou People’s Hospital, Ganzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiaoshi Zhong, Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86151-8047-5673, Email zhong20000947@sina.comObjective: This study aimed to determine the clinical features, risk factors, and effective antimicrobial therapy for Carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI).Methods: This was a retrospective analysis of data from patients with CRAB bacteremia in a Chinese tertiary hospital between January 2012 and October 2021. Risk factors, predictors of 30-day mortality, and effective antimicrobial therapy for CRAB BSI were identified using logistic and cox regression analyses.Results: Data from 276 patients with Acinetobacter baumannii (AB) BSI were included, of whom 157 (56.9%) had CRAB BSI. The risk factors that were significantly associated with CRAB BSI included previous intensive care unit (ICU) stay (P < 0.001), immunocompromised status (P < 0.001), cephalosporin use (P = 0.014), and fluoroquinolone use (P = 0.007). The 30-day mortality of the CRAB BSI group was 49.7% (78/157). ICU stay after BSI (P = 0.047), sequential organ failure assessment (SOFA) score ≥ 10 (P < 0.001), and multiple organ failure (MOF) (P = 0.037) were independent predictors of 30-day mortality. Among antibiotic strategies for the treatment of patients with CRAB BSI, we found that definitive regimens containing cefoperazone/sulbactam were superior to those without cefoperazone/sulbactam in reducing the 30-day mortality rate (25.4% vs 53.4%, P = 0.005). After propensity score matching, we observed a significant increase in the 30-day mortality (77.8%vs 33.3%, P = 0.036) in patients receiving tigecycline monotherapy compared to those receiving cefoperazone/sulbactam monotherapy. The mortality rate of patients receiving tigecycline with cefoperazone/sulbactam was also higher than that of patients receiving cefoperazone-sulbactam monotherapy; however, the difference was not significant (28.6%vs 19.0%, P = 0.375).Conclusion: The severity of patient conditions was significantly associated with mortality in patients with CRAB BSI. Those Patients treated with cefoperazone/sulbactam had better clinical prognoses, and tigecycline should be used with caution.Keywords: carbapenem-resistant, Acinetobacter baumannii, bacteremia, tigecycline, cefoperazone/sulbactam

Xuehan Zou,1,&ast; Shaojun Jin,2,&ast; Lingxia Chen,1,&ast; Jie Li,1 Xiaofan Zhang,3 Hua Zhou,4 Xi Li,3 Haijun Huang1 1Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Emergency, Zhuji People’s Hospital of Zhejiang Province, Shaoxing, Zhejiang, People’s Republic of China; 3Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haijun Huang, Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel/Fax +86-0571-8589-3603, Email huanghaijun0826@163.com Xi Li, Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel/Fax +86-0571-8589-3267, Email lixi_0611@163.comObjective: Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, with a broad-spectrum antimicrobial activity, including against carbapenem-resistant gram-negative bacteria (CRGNB). However, the in vitro activity of eravacycline against CRGNB has not been well known in China. In this study, we analysed the antibacterial activity of eravacycline against CRGNB isolates in order to provide a theoretical basis for the clinical treatment.Methods: A total of 346 isolates of CRGNB were collected from two different tertiary care hospitals in Zhejiang, China. Carbapenem resistance genes of all isolates were detected by polymerase chain reaction. And we analysed the in vitro activity of eravacycline against CRGNB by antimicrobial susceptibility tests. In addition, the time-kill curves were generated to evaluate the antibacterial effect of tigecycline and eravacycline.Results: Four different types of carbapenem-resistant isolates were collected, including 50 Escherichia coli isolates, 160 Klebsiella pneumoniae isolates, 42 Enterobacter cloacae complex isolates, and 94 Acinetobacter baumannii isolates. The carbapenem resistance genes were identified in 346 isolates, including blaKPC-2 (48.0%), blaOXA-23 (27.2%), blaNDM-1 (23.1%), and blaNDM-16 (0.3%). The antimicrobial susceptibility testing results showed that the minimum inhibitory concentration (MIC) values of 346 isolates were within the sensitivity range (≤ 0.0625~16 mg/L) and that the MIC50 or MIC90 of eravacycline was generally approximately 2-fold lower than tigecycline. In addition, the time-kill curves showed that the bactericidal effect of eravacycline was stronger than that of tigecycline against four different types of isolates.Conclusion: Our research indicated that eravacycline had a good antibacterial effect on CRGNB, which could provide a theoretical basis for the clinical treatment of drug-resistant bacterial infections in the future.Keywords: eravacycline, tigecycline, carbapenem-resistant, gram-negative isolates, drug sensitivity, time-kill curves

Ling-Zhi Jiang, Ye Shen, Feng Liang, Xiang-Ming Ye, Jing Chen, Yan-Mei Yu Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiang-Ming Ye, Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-13750814756, Email yexmdr@hotmail.comAbstract: Intracranial infections are the most serious and common postoperative complications with significant mortality and morbidity. Myroides odoratimimus (M. odoratimimus), a Gram-negative environmental species and an opportunistic microorganism, predominantly infects immunocompromised individuals. Limited clinical experiences and documented multidrug resistance have resulted in a scarcity of data on the treatment of M. odoratimimus infections. As far as we know, this is the first reported case of an intracranial M. odoratimimus infection with external ventricular drains (EVD) that was effectively treated with a combination of intravenous and intraventricular tigecycline in an immunocompetent adult host.Keywords: Myroides odoratimimus, M. odoratimimus, intracranial infection, immunocompetent host, tigecycline

Abstract Background The development of tigecycline resistance in hypervirulent Klebsiella pneumoniae strains has resulted in decreased virulence that is associated with reduced production of capsular polysaccharides (CPS). In this study, we investigated the mechanisms that link tigecycline susceptibility to decreased virulence. Methods We compared transcriptomes from tigecycline-susceptible wild-type strains and tigecycline-resistant mutants using mRNA sequencing. ompR-overexpressed and ompR-deleted mutants were constructed from wild-type strains and tigecycline-resistant mutants, respectively. Antibiotic susceptibility tests were performed, and string tests and precipitation assays were conducted to identify phenotypic changes related to tigecycline susceptibility and ompR expression. Bacterial virulence was assessed by serum resistance and Galleria mellonella infection assays. Results Transcriptomic analyses demonstrated a significant decrease in the expression of ompK35 in the tigecycline-resistant mutants. We observed that tigecycline-resistant mutants overexpressed ompR, and that the expression of ompK35 was regulated negatively by ompR. While tigecycline-resistant mutants and ompR-overexpressed mutants exhibited reduced hypermucoviscosity and virulence, deletion of ompR from tigecycline-resistant mutants restored their hypermucoviscosity and virulence. Conclusions In hypervirulent K. pneumoniae strains, ompR expression, which is regulated by exposure to tigecycline, may affect the production of CPS, leading to bacterial virulence.

This study aimed to evaluate the potential of tamoxifen and N-desmethyltamoxifen metabolites as therapeutic agents against multidrug-resistant Escherichia coli and Acinetobacter baumannii, using a repurposing approach to shorten the time required to obtain a new effective treatment against multidrug-resistant bacterial infections. Characterisation and virulence studies were conducted on E. coli (colistin-susceptible C1-7-LE and colistin-resistant MCR-1+) and A. baumannii (tigecycline-susceptible Ab#9 and tigecycline-resistant Ab#186) strains. The efficacy of the metabolite mix (33.3% each) and N-desmethyltamoxifen in combination with colistimethate sodium (CMS) or tigecycline was evaluated in experimental models in mice. In the pneumonia model, N-desmethyltamoxifen exhibited significant efficacy against Ab#9 and both E. coli strains, especially E. coli MCR-1+ (−2.86 log10 CFU/g lungs, −5.88 log10 CFU/mL blood, and −50% mortality), and against the Ab#186 strain when combined with CMS (−2.27 log10 CFU/g lungs, −2.73 log10 CFU/mL blood, and −40% mortality) or tigecycline (−3.27 log10 CFU/g lungs, −4.95 log10 CFU/mL blood, and −50% mortality). Moreover, the metabolite mix in combination with both antibiotics decreased the bacterial concentrations in the lungs and blood for both A. baumannii strains. In the sepsis model, the significant efficacy of the metabolite mix was restricted to the colistin-susceptible E. coli C1-7-LE strain (−3.32 log10 CFU/g lung, −6.06 log10 CFU/mL blood, and −79% mortality). N-desmethyltamoxifen could be a new therapeutic option in combination with CMS or tigecycline for combating multidrug-resistant GNB, specifically A. baumannii.

Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.

The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial resources, remain dire. Furthermore, A. baumannii superinfections have also occurred during the COVID-19 pandemic. While prevention is important, the antibiotic armamentarium remains the most essential factor for the treatment of these infections. The main problem is the notorious resistance profile (including resistance to carbapenems and colistin) that this bacterium exhibits. While newer beta lactam/beta-lactamase inhibitors have entered clinical practice, with excellent results against various infections due to Enterobacteriaceae, their contribution against A. baumannii infections is almost absent. Hence, we have to resort to at least one of the following, sulbactam, polymyxins E or B, tigecycline or aminoglycosides, against multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Furthermore, the notable addition of cefiderocol in the fight against A. baumannii infections represents a useful addition. We present herein the existing information from the last decade regarding therapeutic advances against MDR/XDR A. baumannii infections.

Antimicrobial resistance (AMR) has been recognized as one of the most important crises affecting global human health in the 21st century. Tigecycline is one of the last resort antibiotics for treating severe infections caused by multi-drug resistant Enterobacteriaceae. However, the mobile resistance gene tet(X4), which could mediate high-level tigecycline resistance, was discovered in 2019. The outer membrane vesicle (OMV) has been recognized as a new route for horizontal gene transfer; antimicrobial resistant bacteria also have the ability to secret OMVs, while little is known about the impact of antibiotics on the secretion and characteristics of OMVs from tigecycline resistant bacteria till now. This study aimed to investigate the effects of antibiotics on the production and traits of a tigecycline resistant Escherichia coli strain of 47EC. The results showed that sub-inhibitory (1/2 MIC or 1/4 MIC) concentrations of gentamicin, meropenem, ceftazidime, chloramphenicol, tigecycline, ciprofloxacin, polymycin, rifaximin and mitomycin C could significantly increase the secretion of OMVs (0.713 ± 0.05~6.333 ± 0.15 mg/mL) from E. coli 47EC compared to the respective untreated control (0.709 ± 0.03 mg/mL). In addition, the particle sizes of OMVs were generally larger, and the zeta potential were lower in the antibiotics-treated groups than those of the antibiotic-free group. The copy numbers of the tigecycline resistance gene of tet(X4) in the OMVs of most antimicrobial-treated groups were higher than that of the control group. Moreover, transcriptome analysis on ciprofloxacin-treated E. coli 47EC indicated that the SOS response and prophage activation might participate in the ciprofloxacin-induced OMV formation. In conclusion, the clinical application of antibiotics in treating bacterial infections, especially multi-drug resistant bacteria, might lead to the increased secretion of bacterial OMVs and the enrichment of antimicrobial-resistant genes in the OMVs.

The emergence of the plasmid-mediated tigecycline resistance gene tetX family in pig farms has attracted worldwide attention. The use of tetracycline antibiotics in pig farms has a facilitating effect on the prevalence of the tetX family, but the relationship among its presence, expression, and resistance phenotype in resistant bacteria is unknown. In this study, the presence and expression characteristics of tetracycline resistance genes (TRGs) in 89 strains of doxycycline-resistant E. coli (DRE) isolated from pig manure samples from 20 pig farms under low concentrations of doxycycline stress (2 μg/mL) were analyzed. The detection rate of tetO was 96.63%, which is higher than those of other TRGs, such as tetA (94.38%), tetX (76.40%), tetB (73.03%), and tet(X4) (69.66%). At least three TRG types were present in DRE strains, which thus showed extensive resistance to tetracycline antibiotics, and 37% of these strains were resistant to tigecycline. In the presence of a low concentration of doxycycline, tetA played an important role, and the expression and existence ratio of TRGs indicated low expression of TRGs. Furthermore, the doxycycline resistance of DRE was jointly determined by the total absolute abundance of TRGs, and the absolute abundance of tetX and tet(X4) was significantly positively associated with tigecycline resistance in DRE (P < 0.05). Overall, DRE isolated from swine manure is an important reservoir of the tetX family, which suggests that DRE in swine manure has a high risk of tigecycline resistance, poses a potential threat to human health, and should be of public concern. [ABSTRACT FROM AUTHOR]

To investigate the effects of (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), tocopherol polyethylene glycol 1000 succinate (TPGS), sodium desoxycholate (SDOCH), trimethyl chitosan (TMC), and sodium caprate (C10) on the plasma concentration and the oral bioavailability of tigecycline in broiler chickens. To test the effects of the excipients on absorption of tigecycline, a tetracycline that is poorly absorbed from the gastrointestinal tract, broiler chickens were used as an animal model. Tigecycline (10 mg/kg body weight) was administered intravenously, orally, and orally with one of the excipients. Plasma samples were taken after administration. To measure tigecycline concentrations, high-performance liquid chromatography coupled with tandem mass spectrometry was used. Compartmental and non-compartmental analyses were used for pharmacokinetic analyses of mean plasma concentrations versus time. With the exception of sodium caprate, all the excipients significantly increased the area under the curve and bioavailability of tigecycline (p < 0.05). These parameters were approximately doubled by HP-β-CD, TPGS, and SDOCH, with 95% confidence intervals (95% CIs) for the difference that included only increases of 1.5-fold or higher (bioavailability: control, 1.67%; HP-β-CD, 3.24%; TPGS, 3.30%; and SDOCH, 3.24%). The increases in these parameters were smaller with DM-β-CD and TMC (DM-β-CD, 2.41%; TMC, 2.55%), and the 95% CIs ranged from close to no difference to nearly double the values in the control group. These results indicate that HP-β-CD, TPGS, and SDOCH substantially increase the area under the curve and oral bioavailability of tigecycline. They suggest that DM-β-CD and TMC may also substantially increase these parameters, but more research is needed for more precise estimates of their effects. [ABSTRACT FROM AUTHOR]

Introduction: The use of tigecycline (TG) for the treatment of Acinetobacter baumannii is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. Methods: We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR A. baumannii, published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. Results: There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2–66.6) and 40.2 (95% CI 31.1–50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8–47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1–48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7–62.5) and 43.1 (33.1–53.8), respectively. The pooled microbiological response rate was 42.9 (16.2–74.5), and the pooled all-cause mortality rate was 34.3 (26.1–43.5). Conclusions: According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR A. baumannii. However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the different efficacies between monotherapy and combination therapy with ceftazidime/avibactam (CAZ/AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection. Methods: We retrospectively analyzed observational multicenter data from 38 hospitals in China. Multivariate regression analysis was used to explore the association between combination therapy with CAZ/AVI and in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to validate our findings. Results: A total of 132 eligible patients were divided into CAZ/AVI combination therapy (n = 43) and monotherapy (n = 89) cohorts. Multivariate logistic regression showed that there was no statistically significant relationship between combination therapy and a lower risk of in-hospital mortality [odds ratio (OR) 0.907, 95% confidence interval (CI) 0.329–2.498, p = 0.850]. In the subgroup of critical patients who were in the intensive care unit (ICU) (OR 0.943, 95% CI 0.221–4.033, p = 0.937) or with sequential organ failure assessment (SOFA) ≥ 3 (OR 0.733, 95% CI 0.191–2.808, p = 0.650), CAZ/AVI combination therapy was not a lower risk factor for in-hospital mortality. Moreover, in the subgroup of patients using CAZ/AVI plus tigecycline (accounting for 46.5% in the combination therapy) compared with CAZ/AVI monotherapy, there was no statistical difference between the two groups in in-hospital mortality, nor in the subgroup of patients with CRKP-associated pneumonia. Conclusion: Combination therapy (or CAZ/AVI combined with tigecycline) and monotherapy with CAZ/AVI had similar prognoses in patients with only CRKP infection (or CRKP-associated pneumonia), as well as in critically ill patients. Larger randomized controlled trials are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Background and objective: Acinetobacter baumannii (A. baumannii) is an important nosocomial pathogen that not only possesses intrinsic resistance to many classes of antibiotics, but is also capable of rapidly developing antimicrobial resistance during treatment. The aim of this study was to determine the characteristics of resistance of A. baumannii strains to β-lactams and other tested antibiotics, to evaluate the associations between the phenotypes of resistance to β-lactams and other tested antibiotics, and to evaluate the changes in antibiotic resistance of A. baumannii strains over 5 years by comparing the periods of 2016–2017 and 2020–2021. Materials and methods: A total of 233 A. baumannii strains were isolated from different clinical specimens of patients treated at the Hospital of Lithuanian University of Health Sciences in 2016–2017 (n = 130) and 2021–2022 (n = 103). All clinical cultures positive for A. baumannii were analyzed. The type of β-lactamase was detected by phenotypic methods using ESBL plus AmpC screen disk tests and the combination meropenem disk test. Results: In both periods, all A. baumannii strains were resistant to ciprofloxacin; resistance to carbapenems, piperacillin/tazobactam, gentamicin, and tobramycin was noted in more than 80% of strains. A comparison of two periods showed that the percentages of A. baumannii strains producing two or three types of β-lactamases were significantly greater in 2021–2022 than in 2016–2017 (94.2% and 5.8% vs. 17.7% and 2.3%, respectively, p < 0.001). Isolates producing two or three types of β-lactamases were more often resistant to tigecycline, tetracycline, and doxycycline than strains producing one type of β-lactamase (p < 0.001). Conclusions: The frequency of isolation of A. baumannii strains producing two different types of β-lactamases (AmpC plus KPC, AmpC plus ESBL, or ESBL plus KPC) or three types of β-lactamases (AmpC, KPC, and ESBL) and the resistance rates to ampicillin/sulbactam, tigecycline, tetracycline, and doxycycline were significantly greater in 2020–2021 as compared with 2016–2017. The production of two or three types of β-lactamases by A. baumannii strains was associated with higher resistance rates to tetracyclines. [ABSTRACT FROM AUTHOR]

Background: Infection with extensive-drug-resistant (XDR) carbapenem-resistant (CR) Gram-negative bacteria (GNB) are viewed as a serious threat to human health because of the limited therapeutic options. This imposes the urgent need to find agents that could be used as adjuvants or combined with carbapenems to enhance or restore the susceptibility of XDR CR- GNB. Therefore, this study aimed to examine the effect of propranolol (PR) in combination with Meropenem (MEM) on the susceptibility profile of XDR CR-GNB recovered from severely infected patients as well as to evaluate combining MEM with either tigecycline (TGC) or amikacin (AK). Methods: A total of 59 non-duplicate CR- GNB were investigated for carbapenemase production by the major phenotypic methods. Molecular identification of five major carbapenemase-coding genes was carried out using polymerase chain reactions (PCR). Antimicrobial susceptibility tests were carried out using standard methods. Phenotypic and genotypic relatedness was carried out using the heatmap and ERIC PCR analysis. PR, 0.5 -1 mg/mL against the resulting non-clonal XDR CR-GNB pathogens were evaluated by calculating the MIC decrease factor (MDF). A combination of MEM with either AK or TGC was performed using the checkerboard assay. Results: A total of 21 (35.6%) and 38 (64.4%) CR-GNB isolates were identified as enterobacterial isolates (including 16 (27.1%) Klebsiella Pneumoniae and 5 (8.5%) Escherichia coli) and non-fermentative bacilli (including, 23 (39%), Acinetobacter baumannii, and 15 (25.4%) Pseudomonas aeruginosa). The heatmap and ERIC PCR analysis resulted in non-clonal 28 XDR CR isolates. PR, at a concentration of 0.5 mg /ml, decreased MICs values of the tested XDR CR isolates (28; 100%) and restored susceptibility of only 4 (14.3%) isolates. However, PR (1 mg/mL) when combined with MEM has completely (28; 100%) restored the susceptibility of the tested XDR CR- GNB to MEM. The MEM + AK and MEM + TGC combination showed mostly additive effects (92.8% and 71.4%, respectively). Conclusion: PR at a concentration of 1 mg/mL restored the susceptibility of XDR CR- GNB to MEM which is considered a promising result that should be clinically investigated to reveal its suitability for clinical use in patients suffering from these life-threatening pathogens. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the in vitro activity of antibiotic combinations against Stenotrophomonas maltophilia isolates and their associated biofilms. Methods: Thirty-two S. maltophilia clinical isolates with at least twenty-five different pulsotypes were tested. The antibacterial activity of various antibiotic combinations against seven randomly selected planktonic and biofilm-embedded S. maltophilia strains with strong biofilm formation was assessed using broth methods. Extraction of bacterial genomic DNA and PCR detection of antibiotic resistance and biofilm-related genes were also performed. Results: The susceptibility rates of levofloxacin (LVX), fosfomycin (FOS), tigecycline (TGC) and sulfamethoxazole-trimethoprim (SXT) against 32 S. maltophilia isolates were 56.3, 71.9, 71.9 and 90.6%, respectively. Twenty-eight isolates were detected with strong biofilm formation. Antibiotic combinations, including aztreonamclavulanic (ATM-CLA) with LVX, ceftazidime-avibactam (CZA) with LVX and SXT with TGC, exhibited potent inhibitory activity against these isolates with strong biofilm formation. The antibiotic resistance phenotype might not be fully caused by the common antibiotic-resistance or biofilm-formation gene. Conclusion: S. maltophilia remained resistant to most antibiotics, including LVX and ß-lactam/ß-lactamases; however, TGC, FOS and SXT still exhibited potent activity. Although all tested S. maltophilia isolates exhibited moderate-to-strong biofilm formation, combination therapies, especially ATM-CLA with LVX, CZA with LVX and SXT with TGC, exhibited a higher inhibitory activity for these isolates. [ABSTRACT FROM AUTHOR]

Introduction: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs. Methods: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without. Results: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline. Conclusion: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment. [ABSTRACT FROM AUTHOR]

Non‐tuberculous mycobacterial infections are gradually increasing worldwide, with slow‐growing mycobacteria such as Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium kansasii accounting for the majority of cases. The use of tetracyclines has received renewed attention in recent years, and this study was designed to investigate the antibacterial activity of omadacycline, eravacycline, tigecycline, sarecycline, minocycline and doxycycline against M. avium, M. intracellulare and M. kansasii. Susceptibility testing of six tetracyclines was conducted against M. avium, M. intracellulare and M. kansasii isolates, and all the clinical isolates were collected from January 2012 to December 2018. All six agents exhibited poor antibacterial activity against slowly growing mycobacteria (SGM) isolates of three subspecies with MIC50 and MIC90 ≥8 μg/mL. M. intracellulare and M. kansasii had lower resistance rates to omadacycline than the other five drugs. The severe resistance of SGM to tetracycline suggests that developing tetracycline‐class antibiotics needs to overcome existing resistance mechanisms. [ABSTRACT FROM AUTHOR]

tet(X4) is the critical resistance gene for tigecycline degradation that has been continually reported in recent years. In particular, pathogenic bacteria carrying tet(X4) are a severe threat to human health. However, information describing Escherichia coli coharboring tet(X4) with virulence genes is limited. Here, we isolated an E. coli strain coharboring tet(X4) and the heat-stable toxin gene astA from a dead piglet. The strain named 812A1-131 belongs to ST10. The genome was sequenced using the Nanopore and Illumina platforms. The virulence genes astA and tet(X4) are located on the chromosome and in the IncHI1-type plasmid p812A1-tetX4-193K, respectively. The plasmid could be conjugatively transferred to recipient E. coli J53 with high frequency. In vivo experiments showed that strain 812A1-131 is pathogenic to Galleria mellonella and could colonize the intestines of mice. In summary, pathogenic E. coli could receive a plasmid harboring the tet(X4) gene, which can increase the difficulty of treatment. The prevalence and transmission mechanisms of pathogenic bacteria coharboring the tet(X4) gene need more attention. [ABSTRACT FROM AUTHOR]

Background: Tigecycline and cefoperazone/sulbactam can cause coagulation disorders; tigecycline may also lead to hypofibrinogenemia, raising safety concerns. This study aimed to investigate whether tigecycline plus cefoperazone/sulbactam increases the risk of bleeding compared with other tigecycline-based combination therapies and identify risk factors for tigecycline-associated hypofibrinogenemia. Methods: In this multi-method, multicenter, retrospective study, coagulation and other baseline variables were compared using a cohort study, and risk factors for hypofibrinogenemia using a case-control study. Results: The 451 enrolled participants were divided into three group: tigecycline plus cefoperazone/sulbactam (Group A, 193 patients), tigecycline plus carbapenems (Group B, 200 patients) and tigecycline plus β-lactams without N-methylthio-tetrazole (NMTT) side chains (Group C, 58 patients). Activated partial thromboplastin time and prothrombin time were prolonged, and fibrinogen declined for all patients after tigecycline-based medication (all p < 0.05). Prothrombin time in Group B was significantly longer than in other groups (p < 0.05), but there were no significant differences in bleeding events between the three groups (p = 0.845). Age greater than 80 years (OR: 2.85, 95% CI: 1.07–7.60), treatment duration (OR: 1.29, 95% CI: 1.19–1.41), daily dose (OR: 2.6, 95% CI: 1.29–5.25), total bilirubin (OR: 1.01, 95% CI: 1.01–1.02) and basal fibrinogen (OR: 1.32, 95% CI: 1.14–1.63) were independent risk factors of hypofibrinogenemia. The optimal cut-off for treatment course was 6 days for high-dose and 11 days for lowdose. Conclusion: Tigecycline plus cefoperazone/sulbactam did not increase the risk of bleeding compared with tigecycline plus carbapenem, or tigecycline plus β-lactam antibiotics without NMTT-side-chains. Coagulation function should be closely monitored in patients receiving tigecycline treatment. [ABSTRACT FROM AUTHOR]

High mortality, aggressiveness, and the relatively low effectiveness of therapy make melanoma the most dangerous of skin cancers. Previously published studies presented the promising therapeutic potential of minocycline, doxycycline, and chlortetracycline on melanoma cells. This study aimed to assess the cytotoxicity of tigecycline, a third-generation tetracycline, on melanotic (COLO 829) and amelanotic (A375) melanoma cell lines. The obtained results showed that tigecycline, proportionally to the concentration and incubation time, efficiently inhibited proliferation of both types of melanoma cells. The effect was accompanied by the dysregulation of the cell cycle, the depolarization of the mitochondrial membrane, and a decrease in the reduced thiols and the levels of MITF and p44/42 MAPK. However, the ability to induce apoptosis was only found in COLO 829 melanoma cells. A375 cells appeared to be more resistant to the treatment with tigecycline. The drug did not induce apoptosis but caused an increase in LC3A/B protein levels—an autophagy marker. The observed differences in drug action on the tested cell lines also involved an increase in p21 and p16 protein levels in melanotic melanoma, which was related to cell cycle arrest in the G1/G0 phase. The greater sensitivity of melanotic melanoma cells to the action of tigecycline suggests the possibility of considering the use of the drug in targeted therapy. [ABSTRACT FROM AUTHOR]

Background: We investigated the presence of heteroresistance against both tigecycline and colistin in Acinetobacter baumannii and then evaluated the effectiveness of combined antibiotic treatment given the existence of discrete tigecycline- and colistin-resistant subpopulations. Methods: We performed population analysis profiling (PAP) to evaluate the degree of composite heteroresistance in A. baumannii isolates, with the extent of this resistance quantified using subsequent antibiotic susceptibility testing. We then evaluated the amino acid sequence of PmrBAC and the relative mRNA expression levels of pmrB. Finally, we investigated the combined antibiotic efficacy of tigecycline and colistin in multiple-heteroresistant isolates using dual PAP and in vitro time-killing assays. Results: All tigecycline-heteroresistant A. baumannii isolates, with the exception of one colistin-resistant isolate, were also heteroresistant to colistin. Evaluations of the colistin-resistant subpopulations revealed amino acid alterations in PmrA and PmrB and increased expression of pmrB. All tigecycline-resistant subpopulations were susceptible to colistin, and all colistin-resistant subpopulations were susceptible to tigecycline. Dual PAP analysis using tigecycline and colistin showed no heteroresistance, and in vitro time-killing assays revealed that a combination of these two antibiotics effectively eliminated the bacterial cells. Conclusion: Our results suggest that multiple heteroresistance to tigecycline and colistin is highly prevalent among A. baumannii clinical isolates and that these resistant subpopulations exist independently in single multiple heteroresistant isolates. Therefore, our findings may explain the success of combined antibiotic therapies in these infections. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the genetic factors promoting widespread Q6 dissemination of tet(X4) between Escherichia coli and to characterize the genetic contexts of tet(X4). Methods: We isolated E. coli from feces, water, soil and flies collected across a largescale chicken farm in China in 2020. Antimicrobial susceptibility testing and PFGE typing were used to identify tigecycline resistance and assess clonal relationships among isolates. Plasmids present and genome sequences were analyzed by conjugation, S1 pulsed-field gel electrophoresis (PFGE), plasmid stability testing and whole-genome sequencing. Results: A total of 204 tigecycline-resistant E. coli were isolated from 662 samples. Of these, we identified 165 tet(X4)-carrying E. coli and these strains exhibited a high degree of multidrug resistance. Based on the geographical location distribution of the sampled areas, number of samples in each area and isolation rate of tigecyclineresistant strains and tet(X4)-carrying isolates, 72 tet(X4)-positive isolates were selected for further investigation. Tigecycline resistance was shown to be mobile in 72 isolates and three types of tet(X4)-carrying plasmids were identified, they were IncHI1 (n= 67), IncX1 (n= 3) and pO111-like/IncFIA(HI1) (n= 2). The pO111-like/IncFIA(HI1) is a novel plasmid capable of transferring tet(X4). The transfer efficiency of IncHI1 plasmids was extremely high in most cases and IncHI1 plasmids were stable when transferred into common recipient strains. The genetic structures flanked by IS1, IS26 and ISCR2 containing tet(X4) were complex and varied in different plasmids. Discussion: The widespread dissemination of tigecycline-resistant E. coli is a major threat to public health. This data suggests careful use of tetracycline on farms is important to limit spread of resistance to tigecycline. Multiple mobile elements carrying tet(X4) are in circulation with IncHI1 plasmids the dominant vector in this setting. [ABSTRACT FROM AUTHOR]

Scrub typhus can be adequately treated with doxycycline or azithromycin unless it is treated too late. Such cases present as severe scrub typhus, and their treatment remains a challenging problem. In this article, we briefly review the literature on the treatment of scrub typhus and the limitations of the combination of doxycycline and azithromycin. Several options are suggested for further study in the treatment of severe scrub typhus (such as encephalitis, myocarditis, and pneumonia), including dose escalation of doxycycline, the adjuvant use of steroids, the selective use of beta-lactam antibiotics, and the use of tigecycline. [ABSTRACT FROM AUTHOR]

Objectives To characterize a novel transposon Tn 7533 carrying the tet (X2) gene in a tigecycline-resistant Acinetobacter pittii BM4623 of clinical origin. Methods Gene knockout and in vitro cloning were used to verify the function of tet (X2). WGS and comparative genomic analysis were used to explore the genetic characteristics and molecular evolution of tet (X2). Inverse PCR and electroporation experiments were used to evaluate the excision and integration capabilities of Tn 7533. Results A. pittii BM4623 belonged to a novel ST, ST2232 (Pasteur scheme). Knockout of tet (X2) in BM4623 restored its susceptibility to tigecycline. Cloning of the tet (X2) gene into Escherichia coli DH5α and Acinetobacter baumannii ATCC 17978 resulted in 16-fold or more increases in MICs of tigecycline. Sequence analysis showed that the region upstream of tet (X2) exhibited a high degree of diversity, while there was a 145 bp conserved region downstream of tet (X2). tet (X2) in BM4623 was located on a novel composite transposon Tn 7533 , which also contains multiple resistance genes including bla OXA-58. Tn 7533 could be excised from the chromosome to form a circular intermediate and transferred into A. baumannii ATCC 17978 by electroporation. Conclusions Our study demonstrates that tet (X2) is a determinant conferring clinical resistance to tigecycline in Acinetobacter species. The emergence of Tn 7533 may lead to the potential dissemination of tigecycline and carbapenem resistance in Acinetobacter , which requires continuous monitoring. [ABSTRACT FROM AUTHOR]

Drug-induced acute pancreatitis (AP) associated with tigecycline (TGC) is considered a rare complication (incidence between 1, and 1%). In this paper, we report five cases of AP occurring after the administration of TGC in septic patients hospitalized in intensive burn care in Tunisia over 9 years. The diagnosis of AP was based on clinical and/or biological signs. Among 303 cases treated with TGC, AP occurred with an incidence of 1.65%. The mean age was 28±6 years. Only one patient had a history of chronic alcoholism. The prescribed dose was 200 mg as a loading dose, followed by 100 mg twice a day. The time to onset of symptoms after initiation of TGC was 5.4 days [2-7]. PA was suspected due to abdominal pain associated with nausea and vomiting (n=2), occlusive syndrome (n=1) and fortuitously increased pancreatic enzymes in 2 patients under mechanical ventilation. The mean lipase level at diagnosis was 447 IU ± 135 IU (4.5 to 10 times the normal). All the aetiologies of AP were ruled out, including gallstones, hypercalcemia, hypertriglyceridemia, trauma and infections. The mean time to symptom resolution after stopping TGC was 4±2 days [5-7] and to the normalization of pancreatic enzymes it was 9 days [2-20 days]. In conclusion, clinical and biological monitoring was necessary in patients treated with TGC in order to avoid severe forms, especially in at-risk patients. [ABSTRACT FROM AUTHOR]

The emergence and spread of carbapenemase genes, colistin resistance genes mcr-1, and tigecycline resistance gene tet(X) represent a significant threat to clinical therapy and public health. In this study, we investigated the presence of carbapenemase genes, mcr-1, and tet(X) in 298 Escherichia coli strains obtained froma teaching hospital inChina. In total, eight (2.68%), six (2.01%), and one (0.34%) E. coli isolates carried blaNDM, mcr-1, and tet(X4), respectively. The blaNDM gene was located on IncX3 (n = 4), F2:A-:B- (n = 3), and F2:A1:B1 (n = 1) plasmids, with high similarity to multiple plasmids belonging to the same incompatibility type from Enterobacteriaceae. Six MCR-producing strains contained mcr-1-carrying IncI2 plasmids, organized similarly to other mcr-1-bearing IncI2 plasmids from animals in China. The blaCTX--M--55/64/132/199 gene located within a typical transposition unit (ISEcp1-blaCTX--M-orf477Δ) was inserted near dnaJ to generate 5-bp direct repeats in four mcr-1-positive plasmids. The tet(X) and another four resistance genes [aadA2, tet(A), floR, and Δlnu(F)] were co-located on an IncX1 plasmid, highly similar to other tet(X4)-carrying IncX1 plasmids from Escherichia and Klebsiella of animal or food origin, except that the conjugative transfer region of IncX1 plasmids was absent in our plasmid. Although a low prevalence of blaNDM, mcr-1, and tet(X) was observed in E. coli from patients in this study, their dissemination associated with some successful pandemic plasmids is of great concern. The continued surveillance of these crucial resistance genes in patients should be strengthened. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of the vulnerable neonatal population given the dearth of safe and effective therapeutic options. Evidence from studies mainly in adults is now available for several novel antimicrobial compounds, such as new β-lactam/β-lactamase inhibitors (e.g., ceftazidime–avibactam, meropenem–vaborbactam, imipenem/cilastatin–relebactam), although old antibiotics such as colistin, tigecycline, and fosfomycin are also encompassed in the fight against MDR-GN infections that remain challenging. Data in the neonatal population are scarce, with few clinical trials enrolling neonates for the evaluation of the efficacy, safety, and dosing of new antibiotics, while the majority of old antibiotics are used off-label. In this article we review data about some novel and old antibiotics that are active against MDR-GN bacteria causing sepsis and are of interest to be used in the neonatal population. [ABSTRACT FROM AUTHOR]

Diabetic foot infections (DFIs) are a common complication of diabetes; however, there is clinical uncertainty regarding the optimal antimicrobial selection. The aim of this review was to critically evaluate the recent systematic reviews on the efficacy and safety of systemic (parenteral or oral) antimicrobials for DFI. Medline, Embase, CENTRAL, and CINAHL databases and the PROSPERO register were searched from January 2015 to January 2023. Systematic reviews with or without meta-analyses on systemic antimicrobials for DFI, with outcomes of clinical infection resolution or complications, were included. Of the 413 records identified, 6 systematic reviews of 29 individual studies were included. Heterogeneity of individual studies precluded meta-analysis, except for ertapenem versus piperacillin–tazobactam (RR 1.07, 95% CI [0.96–1.19]) and fluoroquinolones versus piperacillin–tazobactam (RR 1.03, 95% CI [0.89–1.20]) in one review. The application of the AMSTAR-2 tool determined two reviews to be of high quality. There was no statistical difference in the clinical resolution of infections for 24 different antimicrobial regimens (penicillins, cephalosporins, carbapenems, fluoroquinolones, vancomycin, metronidazole, clindamycin, linezolid, daptomycin, and tigecycline). However, tigecycline did not meet non-inferiority against ertapenem ± vancomycin (absolute difference −5.5%, 95% CI [−11.0–0.1]) and was associated with a higher incidence of adverse drug events. There is minimal systematic review evidence to suggest one regimen is superior to another for DFI. [ABSTRACT FROM AUTHOR]

Study designA controlled, interventional animal study.ObjectiveSpinal implant infection (SII) is a devastating complication. The objective of this study was to evaluate the efficacy of a novel implant coating that has both a passive antibiotic elution and an active-release mechanism triggered in the presence of bacteria, using an in vivo mouse model of SII.Summary of background dataCurrent methods to minimize the frequency of SII include local antibiotic therapy (vancomycin powder), betadine irrigation, silver nanoparticles, and passive release from antibiotic-loaded poly(methyl methacrylate) cement beads, all of which have notable weaknesses. A novel implant coating has been developed to address some of these limitations but has not been tested in the environment of a SII.MethodsA biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics. The in vivo performance of this coating was tested in the delivery of either vancomycin or tigecycline in a previously established mouse model of SII. Noninvasive bioluminescence imaging was used to quantify the bacterial burden, and implant sonication was used to determine bacterial colony-forming units (CFUs) from the implant and surrounding bone and soft tissue.ResultsThe PEG-PPS-vancomycin coating significantly lowered the infection burden from postoperative day 3 onwards (P

Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next-generation tetracycline that is the final line of defense against severe infections by carbapenem-resistant Gram-negative bacteria. Unfortunately, this last-resort antibiotic has been challenged by the recent emergence of the mobile tet(X) orthologs that can confer high-level tigecycline resistance. This review will systematically introduce the latest progress in the type, distribution and dissemination, and genetic environment of this orthologs. At present, orthologs of tet(X) mainly include tet(X1), tet(X2), tet(X3), tet(X3.2), tet(X4), tet(X5), tet(X6) and tet(X7). The resistance gene has already been reported in a variety of bacterial hosts and spread to hospital-associated patients and environment in multiple countries/regions. The bacteria carrying tet(X3) and tet(X4) shows the highest resistance level. The insertion sequence ISCR2 is closely related to the horizontal spread of tet(X3), tet(X4) and tet(X5). In particular, the genetic environment of tet(X4) on plasmids is complex, that can be located on various mobile elements, which accelerates the spread of the drug resistance gene. The plasmid-mediated tigecycline resistance may further spread into a variety of ecological niches and into clinical high-risk pathogens and collective efforts are in urgent need to further strengthen the surveillance and research on tigecycline resistance.

Background & Aims: Chronic Suppurative Otitis Media (CSOM) is defined as chronic inflammation of middle ear and mastoid cavity that may present with recurrent ear discharges. Its importance lies in its refractoriness to treatment and chronicity, leading to complications. CSOM is almost always associated with mixed bacterial flora. Knowledge of the local microbial flora as well as continuous, periodic evaluation of microbiological pattern, and antibiogram of isolates are necessary to decrease the potential risk of complications by early institutions of appropriate treatment. Materials & Methods: In this prospective cross-sectional study, a total of 134 consecutive swab samples of the patients diagnosed with CSOM, referred to a tertiary care hospital in Kashmir Valley, India were included. The bacterial colonies were identified in line with standard procedures. Antimicrobial sensitivity testing (AST) was carried out according to the Clinical Laboratory Standards Institute (CLSI) guidelines by modified Kirby-Bauer disc diffusion method on Mueller Hinton agar (MHA) medium. The data was analysed using SPSS version 24 and the prevalence of the organisms was determined and expressed in percentages. Results: Out of total 134 ear swabs processed, microbial growth was seen in 111 (83%). The most common organism isolated was Methicillin Resistant Staphylococcus aureus (MRSA) in 43 (39%) of the patients, followed by Pseudomonas in 37 (27.6%). 9 (8%) of the cases had fungal etiology. Linezolid (LZ) showed 100% sensitivity in Gram-positive Cocci whereas, Tigecycline (TIG) showed 100% sensitivity in Gram-negative Bacilli. All MRSA were 100 % sensitive to tetracycline, linezolid, amikacin. All the isolates of Pseudomonas were 100 % sensitive to Tigecycline, Ofloxacin, Colistin, Imipenem, Aztreonam, Cefepime. Conclusion: Isolation of various aerobic, anaerobic, and fungal isolates shows that different conditions of CSOM could be differentiated on microbiological grounds. Thus, for better management of CSOM, microbial classification of infection as well as drug sensitivity test of organisms recovered are essential for making appropriate decision of antimicrobials that will effectively eradicate the pathogen.

Introduction: Multiple drug resistance (MDR) of the bacteria is an issue across any health-care setting worldwide. This leads to prolonged hospital stay and high cost of treatment. One must be cautious to use reserve drugs such as imipenem, meropenem, colistin, polymyxin, and tigecycline. Tigecycline is a mainstay to treat emerging single or MDR pathogens. The study was conducted to assess the in vitro sensitivity of tigecycline to MDR isolates and to compare the sensitivity of Kirby–Bauer (KB) disc-diffusion method with the Epsilometer (E-test) against various MDR clinical isolates. Materials and Methods: This prospective study was done from January 2019 to 2020 on MDR isolates from clinical specimens. The isolates were tested for their antibiotic sensitivity to tigecycline by KB and E-test method to know the minimum inhibitory concentration (MIC) of tigecycline. Statistical data were analyzed by the percentage method. Results: Tigecycline showed a higher in vitro sensitivity against multidrug-resistant isolates in our study. Among the 89 MDR isolates obtained, 38 (42.7) were found to be sensitive to tigecycline by the KB diffusion and 67 (75.3) were sensitive by the E-test method. Conclusions: Tigecycline is a reserve antibiotic against MDR organisms, especially useful to treat coinfections of Gram-positive and Gram-negative superbugs. The E-test was found to be far superior to the KB method to detect in vitro activity and the results of this test will guide the clinician to judiciously use this antibiotic in their day-to-day practice.

Zhaolin Li,1,&ast; Qiaojun Zeng,1,&ast; Shuwan Xu,2,&ast; Yuewei Li,1 Tiantian Tang,1 Jianting Shi,1 Xueming Song,1 Wenman He,1 Liang Chen,1 Guirong Liu,1 Boying Gao,3 Jianming Zheng,4 Linjie Huang,1 Ming Chen,1 Shanping Jiang1 1Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Cardiology, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Cardiovascular Medicine Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanping Jiang; Ming Chen, Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yan-jiang Xi Road 107, Guangzhou, 510120, People’s Republic of China, Tel +86-20-81332441, Email jiangshp@mail.sysu.edu.cn; chenm69@mail.sysu.edu.cnBackground: Although tigecycline is an effective drug against drug-resistant bacteria, it demonstrated a higher all-cause mortality than comparator antibiotics and a high incidence of coagulation disorders which can be accompanied by severe bleeding. At present, a predictive model for tigecycline-related coagulopathy is not readily available, and the prognostic value of coagulopathy in tigecycline-administered patients has not been elucidated. In this paper, we investigate the association between tigecycline-related coagulopathy and in-hospital mortality to develop a nomogram for the prediction of tigecycline-related coagulopathy.Methods: This retrospective cohort study includes 311 adults prescribed with tigecycline from 2018 to 2020. The primary cohort and validation cohort were constructed by dividing the participants in a ratio of 7:3. The endpoint is tigecycline-related coagulopathy, defined as a condition with no abnormality in coagulation prior to tigecycline application but developed the following symptoms upon prescription: activated partial thromboplastin time (APTT) extended by > 10 s than the upper limit of normal (ULN), prothrombin time (PT) prolonged for > 3 s than the ULN or reduced serum level of fibrinogen to < 2.0 g/L. A predictive nomogram based on logistic regression was subsequently constructed.Results: Tigecycline intake for over 7 days, combined other antibiotics, initial PT, initial fibrinogen and estimated glomerular filtration rate (eGFR), are independent prognostic factors of tigecycline-related coagulopathy. The primary and validation cohort each has an area under the receiver operating characteristic curve (AUC) of 0.792 (0.732– 0.851) and 0.730 (0.629– 0.832) for nomogram, respectively. Furthermore, the fitted calibration curve illustrated adequate fit of the model, while the decision curve analysis demonstrated good clinical value. Survival curves showed a high mortality rate among patients with tigecycline-related coagulopathy.Conclusion: This nomogram exhibited helpful clinical value in predicting tigecycline-related coagulopathy that could reduce the high mortality rate of patients prescribed with tigecycline.Keywords: tigecycline, drug-resistant bacteria, coagulopathy, nomogram

Abstract Background Tigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU). Methods This multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents. Results We analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p

IntroductionTreatment of open fractures routinely involves multiple surgeries and delayed definitive fracture fixation because of concern for infection. If implants were made less susceptible to infection, a one-stage procedure with intramedullary nailing would be more feasible, which would reduce morbidity and improve outcomes.MethodsIn this study, a novel open fracture mouse model was developed using Staphylococcus aureus (S. aureus) and single-stage intramedullary fixation. The model was used to evaluate whether implants coated with a novel "smart" polymer coating containing vancomycin or tigecycline would be colonized by bacteria in an open fracture model infected with S. aureus. In vivo bioluminescence, ex vivo CFUs, and X-ray images were evaluated over a 42-day postoperative period.ResultsWe found evidence of a markedly decreased bacterial burden with the local release of vancomycin and tigecycline from the PEG-PPS polymer compared to polymer alone. Vancomycin was released in a controlled fashion and maintained local drug concentrations above the minimum inhibition concentration for S. aureus for greater than 7 days postoperatively. Bacteria were reduced 139-fold from implants containing vancomycin and undetected from the bone and soft tissue. Tigecycline coatings led to a 5991-fold reduction in bacteria isolated from bone and soft tissue and 15-fold reduction on the implants compared to polymer alone. Antibiotic coatings also prevented osteomyelitis and implant loosening as observed on X-ray.ConclusionVancomycin and tigecycline can be encapsulated in a polymer coating and released over time to maintain therapeutic levels during the perioperative period. Our results suggest that antibiotic coatings can be used to prevent implant infection and osteomyelitis in the setting of open fracture. This novel open fracture mouse model can be used as a powerful in vivo preclinical tool to evaluate and optimize the treatment of open fractures before further studies in humans.

Ning Du,1 En-Qiang Mao,2 Zhi-Tao Yang,2 Hong-Ping Qu,3 Xian Qian,4 Ying Shi,5 Xiao-Lan Bian,6 Juan He,6,&ast; Er-Zhen Chen2,&ast; 1National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of China; 2Emergency Intensive Care Unit, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Critical Care Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 5Department of Clinical Pharmacy, Shaoxing Hospital of Traditional Chinese Medicine, Zhejiang, People’s Republic of China; 6Department of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Er-Zhen Chen, Emergency Intensive Care Unit, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email chenerzhen@hotmail.com Juan He, Department of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email hejuanwin@126.comPurpose: Infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great challenge. Central nervous system (CNS) infection caused by CRKP is rarely reported, and effective treatment is limited. Thus, this study aimed to assess intrathecal (IT) or intraventricular (IVT) injection of tigecycline for clearing infection with CRKP in CNS.Patients and Methods: Two patients who had intracranial infection with CRKP after craniotomy were treated in our institution and analyzed retrospectively, summarizing their therapeutic schedules.Results: They all had a fever with the positive results of cerebrospinal fluid (CSF) test, and CSF culture showed positive for CPKP, which was sensitive only to tigecycline. In addition, the MIC of polymyxin B was not tested due to the limited laboratory conditions. After IT or IVT injection of tigecycline treatment, the temperature of the patients became normal in 3 days, with normal levels of white blood cells, protein, glucose and chlorine concentrations in the CSF. Crucially, twice CSF cultures also became negative with no clinical symptoms of intracranial infection after IT or IVT injection of tigecycline treatment. Moreover, there were no adverse drug reactions observed.Conclusion: IT or IVT injection of tigecycline may be a bright choice to control intracranial infection with CRKP.Keywords: central nervous system infection, CNS, carbapenem-resistant Klebsiella pneumoniae, CRKP, tigecycline, treatment

Introduction Occurrence of colistin-resistant Enterobacteriaceae in response to the unregulated use of this antibiotic has been documented. This study reports an investigation of colistin resistance rates among carbapenem-resistant enterobacterial clinical isolates.Methods A total of 196 multidrug-resistant Enterobacteriaceae isolates (Klebsiella pneumoniae (n = 100), Escherichia coli (n = 89) and Enterobacter cloacae (n = 7) were selected from Gram-negative isolates over one year. Susceptibility to antimicrobials was determined using Vitek2. Broth microdilution method was used to detect colistin antimicrobial susceptibility. Identification of ESBL and carbapenemases were both done phenotypically and by PCR.Results All the studied isolates showed multidrug-resistant phenotypes with 51.5% resistance to carbapenems (meropenem, imipenem). Very low resistance rates towards tigecycline (n = 9) 4.6% were found. Thirty-nine isolates (19.9%) showed reduced susceptibility to colistin among the MDR isolates. Sixty-four isolates (32.7%) were ESBL producers. Hundred isolates (51%) were carbapenemase producers using Carba NP test. The PCR amplification results revealed that 40 isolates (20%) harboured NDM-1 and 40 isolates contained OXA-48-like gene. Coexistence of both (NDM-1 and OXA-48-like) was observed in nine (4.59%) isolates. A Statistically significant relationship was observed between carbapenem resistance and each of the followings; OXA-48 producers (p= .009), amikacin resistance (p = .000), gentamicin resistance (p = .032), tobramycin resistance (p = .000), and tigecycline resistance (p-value ≤ .001). A statistical significance was detected between ESBL-producing isolates and carbapenem susceptible isolates ESBL producers with p = 0.000.Conclusion An alarming sign is the increasing colistin resistance rates among carbapenem-resistant isolates. Aminoglycosides are still a therapeutic option to decrease the use of colistin and avoid further development of resistance.KEY MESSAGESHigh rates of colistin resistance among carbapenem-resistant Enterobacteriaceae.The choice of antibiotic is significantly associated with the clinical site of infection.Aminoglycosides are offered choices for treating multiple drug-resistant Enterobacteriaceae to preserve the colistin and carbapenems.

The progressive increase in antibiotic resistance in recent decades calls for urgent development of new antibiotics and antibiotic stewardship programs to help select appropriate treatments with the goal of minimising further emergence of resistance and to optimise clinical outcomes. Three new tetracycline-class antibiotics, eravacycline, omadacycline, and tigecycline, have been approved within the past 15 years, and represent a new era in the use of tetracyclines. These drugs overcome the two main mechanisms of acquired tetracycline-class resistance and exhibit a broad spectrum of in vitro activity against gram-positive, gram-negative, anaerobic, and atypical pathogens, including many drug-resistant strains. We provide an overview of the three generations of tetracycline-class drugs, focussing on the efficacy, safety, and clinical utility of these three new third-generation tetracycline-class drugs. We also consider various scenarios of unmet clinical needs where patients might benefit from re-engagement with tetracycline-class antibiotics including outpatient treatment options, patients with known β-lactam antibiotic allergy, reducing the risk of Clostridioides difficile infection, and their potential as monotherapy in polymicrobial infections while minimising the risk of any potential drug-drug interaction. KEY MESSAGESThe long-standing safety profile and broad spectrum of activity of tetracycline-class antibiotics made them a popular choice for treatment of various bacterial infections; unfortunately, antimicrobial resistance has limited the utility of the early-generation tetracycline agents.The latest generation of tetracycline-class antibiotics, including eravacycline, tigecycline, and omadacycline, overcomes the most common acquired tetracycline resistance mechanisms.Based on in vitro characteristics and clinical data, these newer tetracycline agents provide an effective antibiotic option in the treatment of approved indications in patients with unmet clinical needs – including patients with severe penicillin allergy, with renal or hepatic insufficiency, recent Clostridioides difficile infection, or polymicrobial infections, and those at risk of drug–drug interactions.

Objectives: This study presents 2016–2018 in vitro antimicrobial activity data and rates of resistant phenotypes for clinical isolates of Acinetobacter baumannii from Africa/Middle East, Asia/South Pacific, Europe, Latin America, and North America. Methods: A total of 4320 A. baumannii isolates were collected across all regions between 2016 and 2018. The in vitro antimicrobial activities of amikacin, colistin, levofloxacin, meropenem, and tigecycline were determined using the broth microdilution methodology of the Clinical and Laboratory Standards Institute. MICs were interpreted using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (version 11.0). Rates of subsets that were resistant to amikacin, colistin, levofloxacin, and meropenem, according to EUCAST breakpoints, are also presented. Results: In each region, tigecycline and colistin were active against isolates of A. baumannii (MIC90 values, 1 or 2 mg/L) and the lowest rate of resistance was to colistin (1.2%–7.3%). The rates of resistance to the panel of agents were generally lower among A. baumannii from North America (1.3%–42.7%), compared with the other regions. Fewer than 11% of meropenem-resistant A. baumannii were also resistant to colistin. The rates of amikacin-, levofloxacin- and meropenem-resistant A. baumannii were lowest in North America and mostly higher in Africa/Middle East and Latin America. Conclusion: In each geographical region, tigecycline and colistin maintained good in vitro antimicrobial activity against isolates of A. baumannii, including antimicrobial-resistant subsets. The higher rates of meropenem-resistant isolates, particularly in Africa/Middle East and Latin America, require continued monitoring because of the scarcity of effective treatment options.

ABSTRACT: Objectives: This work is aimed to investigate the prevalence of tet(X4) in healthy individuals and patients and assess risk factors associated with tet(X4)-positive populations. Methods: A total of 662 patients and 120 healthy individuals from three municipal hospitals during August 2021 to September 2021 were selected to investigate the prevalence of tet(X4) in gut microbiota. A further case-control study was conducted to identify the risk factors associated with tet(X4)-positive populations. The tet(X4)-positive isolates were characterised by antimicrobial susceptibility testing, multilocus sequence typing (MLST), whole genome sequencing, and bioinformatics analyses. Results: The prevalence of tet(X4)-positive Enterobacteriaceae in healthy individuals and patients (19.1%, 95% CI: 16.3%–21.8%) was substantially higher than previous studies in China (less than 1%). Patients ranging from 19 to 45 years of age had significantly higher odds of tet(X4)-positive bacterial colonization (OR = 2.545, 95% CI: 1.106–5.856). All tet(X4)-positive Enterobacteriaceae were resistant to tigecycline. In addition, tet(X4)-positive Escherichia coli were highly diverse, with CC10 belonging to the dominant clone. Genome analysis showed that tet(X4) was adjacent to ISVsa3 on the plasmids. Conclusion: Data from this study suggested that geographic region may partly explain the high prevalence of tet(X4)-positive Enterobacteriaceae in healthy individuals and patients. Young and middle-aged populations were associated with the colonization of tet(X4)-positive isolates.

Background: Tigecycline (TGC) is a recently developed antibiotic to battle resistant bacteria. The procedures outlined in the literature for analyzing TGC involve chemical solvents that could be hazardous. Therefore, this study aimed to create a sustainable and stable HPLC technique for quantifying Tigecycline in lyophilized powder. The powerful chemometric tool, experimental design (ED), will be applied to analyze the variables' interaction and impact on the selected analytical target profiles. Response surface methodology provides a tutorial on using the central composite design with three levels of variables and quadratic programming to optimize the design space of the developed method. Methods: The New HPLC method consisted of an aqueous buffer and ethanol as a green mobile phase run on a reversed-phase symmetry C18 column. A full resolution between the Tigecycline and its degradation product peaks was achieved in a short analytical runtime. Results: Further, the specificity, accuracy, precision, robustness and stability indicating power of the proposed approach were verified through stress degrading testing. Conclusions: Finally, the analytical eco-scale and the green Analytical Procedure Index (GAPI) were utilized to determine how environmentally friendly the recommended method was compared to other published approaches.