-
European Journal of Clinical... Jul 2022Tigecycline is unique glycylcycline class of semisynthetic antimicrobial agents developed for the treatment of polymicrobial infections caused by multidrug-resistant... (Review)
Review
Tigecycline is unique glycylcycline class of semisynthetic antimicrobial agents developed for the treatment of polymicrobial infections caused by multidrug-resistant Gram-positive and Gram-negative pathogens. Tigecycline evades the main tetracycline resistance genetic mechanisms, such as tetracycline-specific efflux pump acquisition and ribosomal protection, via the addition of a glycyclamide moiety to the 9-position of minocycline. The use of the parenteral form of tigecycline is approved for complicated skin and skin structure infections (excluding diabetes foot infection), complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults. New evidence also suggests the effectiveness of tigecycline for the treatment of severe Clostridioides difficile infections. Tigecycline showed in vitro susceptibility to Coxiella spp., Rickettsia spp., and multidrug-resistant Neisseria gonnorrhoeae strains which indicate the possible use of tigecycline in the treatment of infections caused by these pathogens. Except for intrinsic, or often reported resistance in some Gram-negatives, tigecycline is effective against a wide range of multidrug-resistant nosocomial pathogens. Herein, we summarize the currently available data on tigecycline pharmacokinetics and pharmacodynamics, its mechanism of action, the epidemiology of tigecycline resistance, and its clinical effectiveness.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; Treatment Outcome
PubMed: 33403565
DOI: 10.1007/s10096-020-04121-1 -
International Journal of Clinical... Dec 2019Background Several adverse reactions to tigecycline, which is widely used in patients with severe infections, have been documented. Coagulopathy is a lesser known side... (Review)
Review
Background Several adverse reactions to tigecycline, which is widely used in patients with severe infections, have been documented. Coagulopathy is a lesser known side effect of tigecycline. Aim of the review We summarize the characteristics, possible mechanisms, and treatment of tigecycline-induced coagulopathy. Method PubMed, Ovid, Embase, ISI Web of Knowledge, CNKI, and Wanfang were searched up to March 5, 2019. All articles concerning coagulopathy induced by tigecycline were included. The article types and languages were not limited. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts. Results Ultimately, 17 articles were targeted, including 13 case reports and 4 retrospective observational studies. Tigecycline-induced coagulopathy usually manifests as the dose-dependent prolongation of prothrombin time and activated partial thromboplastin time and a reduction in the fibrinogen level. Tigecycline and its metabolites may have multiple effects on coagulation, influencing the extrinsic or intrinsic pathway and even the common pathway. There is no specific treatment for tigecycline-induced coagulopathy, but it can be reversed by withdrawing tigecycline. Conclusion Tigecycline acts on the coagulation system in a dose-dependent manner, and the most severe adverse event is bleeding. Overdose and prolonged use should be avoided, suspected coagulopathy must be recognized in time, and tigecycline should be withdrawn to prevent severe adverse events. Also, drug clearance disorders can develop in patients with liver and/or renal dysfunction. For patients with severe hepatic or renal impairment, the maintenance dose should be reduced, and indicators of coagulation function should be closely monitored.
Topics: Anti-Bacterial Agents; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Dose-Response Relationship, Drug; Hemorrhage; Humans; Tigecycline
PubMed: 31713108
DOI: 10.1007/s11096-019-00912-5 -
Nature Microbiology Sep 2019Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria. tet(X) has been shown to encode a...
Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria. tet(X) has been shown to encode a flavin-dependent monooxygenase that modifies tigecycline. Here, we report two unique mobile tigecycline-resistance genes, tet(X3) and tet(X4), in numerous Enterobacteriaceae and Acinetobacter that were isolated from animals, meat for consumption and humans. Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline. Both tet(X3) and tet(X4) increase (by 64-128-fold) the tigecycline minimal inhibitory concentration values for Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii. In addition, both Tet(X3) (A. baumannii) and Tet(X4) (E. coli) significantly compromise tigecycline in in vivo infection models. Both tet(X3) and tet(X4) are adjacent to insertion sequence ISVsa3 on their respective conjugative plasmids and confer a mild fitness cost (relative fitness of >0.704). Database mining and retrospective screening analyses confirm that tet(X3) and tet(X4) are globally present in clinical bacteria-even in the same bacteria as bla, resulting in resistance to both tigecycline and carbapenems. Our findings suggest that both the surveillance of tet(X) variants in clinical and animal sectors and the use of tetracyclines in food production require urgent global attention.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Proteins; DNA Transposable Elements; Humans; Meat; Microbial Sensitivity Tests; Mixed Function Oxygenases; Plasmids; Tetracycline Resistance; Tigecycline
PubMed: 31133751
DOI: 10.1038/s41564-019-0445-2 -
Emerging Microbes & Infections Dec 2021Hypervirulent carbapenem-resistant (hv-CRKP) has recently aroused increasing attention, especially ST11, the predominant CRKP clone in China. Here, we report a case of...
Hypervirulent carbapenem-resistant (hv-CRKP) has recently aroused increasing attention, especially ST11, the predominant CRKP clone in China. Here, we report a case of hv-CRKP-associated infection and reveal the in-host evolution of its mechanism of resistance to tigecycline and polymyxin under clinical therapy. A total of 11 carbapenemase (KPC)-producing CRKP strains were consecutively isolated from a male patient who suffered from continuous and multisite infections. String and antimicrobial susceptibility tests identified seven hypermucoviscous strains and three tigecycline-resistant and four colistin-resistant strains. larvae infection model confirmed the hypervirulence. Pulsed-field gel electrophoresis (PFGE) separated three PFGE clusters among all strains, and further Southern blotting detected that was located on the same-sized plasmid. Whole-genome sequencing showed that all strains belonged to the hv-CRKP ST11-KL64 clone. Diverse hypervirulence factors and resistance genes were identified. Further sequencing with the Nanopore platform was performed on the CRKP-Urine1 strain, which contained one virulence plasmid (pVi-CRKP-Urine1) and two resistance plasmids (pKPC-CRKP-Urine1 and pqnrS1-CRKP-Urine1). The gene mutations responsible for tigecycline or colistin resistance were then amplified with PCR followed by sequencing, which indicated that mutations of and were the potential loci for tigecycline resistance and that the , and genes for colistin resistance. A novel frameshift mutation of was identified in the high-level tigecycline-resistant strain (MIC, 128 mg/L). The results indicate that the hypervirulent ST11-KL64 clone is a potential threat to antiinfection treatment and is capable of rapid and diverse evolution of resistance during tigecycline and polymyxin treatment.
Topics: Aged; Carbapenems; Drug Resistance, Bacterial; Evolution, Molecular; Frameshift Mutation; High-Throughput Nucleotide Sequencing; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Polymyxins; Tigecycline; Whole Genome Sequencing
PubMed: 34074225
DOI: 10.1080/22221751.2021.1937327 -
Frontiers in Cellular and Infection... 2023is widely distributed in nature and in hospital settings and is a common pathogen causing various infectious diseases. Currently, the drug resistance rate of has been... (Review)
Review
is widely distributed in nature and in hospital settings and is a common pathogen causing various infectious diseases. Currently, the drug resistance rate of has been persistently high, showing a worryingly high resistance rate to various antibiotics commonly used in clinical practice, which greatly limits antibiotic treatment options. Tigecycline and polymyxins show rapid and effective bactericidal activity against CRAB, and they are both widely considered to be the last clinical line of defense against multidrug resistant . This review focuses with interest on the mechanisms of tigecycline resistance in . With the explosive increase in the incidence of tigecycline-resistant , controlling and treating such resistance events has been considered a global challenge. Accordingly, there is a need to systematically investigate the mechanisms of tigecycline resistance in . Currently, the resistance mechanism of to tigecycline is complex and not completely clear. This article reviews the proposed resistance mechanisms of to tigecycline, with a view to providing references for the rational clinical application of tigecycline and the development of new candidate antibiotics.
Topics: Humans; Tigecycline; Acinetobacter baumannii; Minocycline; Acinetobacter Infections; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37228666
DOI: 10.3389/fcimb.2023.1141490 -
Drug Resistance Updates : Reviews and... Sep 2018Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens. Invasive VRE infections are difficult to treat since common therapeutic options including... (Review)
Review
Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens. Invasive VRE infections are difficult to treat since common therapeutic options including ampicillin and glycopeptides often fail. In vitro, most VRE remain susceptible to last-resort antibiotics such as linezolid, tigecycline and daptomycin. However, neither tigecycline nor linezolid act in a bactericidal manner, and daptomycin has proven activity only at high dosages licensed for treating enterococcal endocarditis. Despite these pharmacological and therapeutic limitations, reports on resistance to these last-resort drugs in VRE, and enterococci in general, have increased in recent years. In this review, we briefly recapitulate the current knowledge on the mode of action as well as the known and novel mechanisms of resistance and describe surveillance data on resistance to linezolid, tigecycline and daptomycin in enterococci. In addition, we also suggest a common nomenclature for designating enterococci and VRE with resistances to these important last-resort antibiotics.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbon-Oxygen Ligases; Daptomycin; Genotype; Gram-Positive Bacterial Infections; Humans; Linezolid; Microbial Sensitivity Tests; Mutation; Tigecycline; Vancomycin Resistance; Vancomycin-Resistant Enterococci
PubMed: 30447411
DOI: 10.1016/j.drup.2018.10.002 -
Nature Microbiology Sep 2019Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria....
Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria. Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection. Here, we report the emergence of the plasmid-mediated mobile tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including tigecycline and the US FDA newly approved eravacycline. The tet(X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet(X4)-positive E. coli strains, including isolates co-harbouring mcr-1, have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics.
Topics: Animals; Chickens; China; Drug Resistance, Bacterial; Environmental Microbiology; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Genes, Bacterial; Humans; Mice; Microbial Sensitivity Tests; Plasmids; Swine; Tetracyclines; Tigecycline
PubMed: 31235960
DOI: 10.1038/s41564-019-0496-4 -
Drug Design, Development and Therapy 2022Although tigecycline is widely used in clinical practice, its efficiency and optimal dosage regimens remain controversial. The purpose of this article was to help guide... (Review)
Review
Although tigecycline is widely used in clinical practice, its efficiency and optimal dosage regimens remain controversial. The purpose of this article was to help guide tigecycline dosing in different patient subpopulations through comparing the published population pharmacokinetic models of tigecycline, as well as summarizing and determining the potential covariates that markedly influence tigecycline pharmacokinetics. In this review, literature was systematically searched from the PubMed database from inception to March 2022. The articles focusing on population pharmacokinetics for tigecycline in healthy volunteers or patients were included; finally, a total of eight studies were included in this review. NONMEM methods were used in five studies to generate the population pharmacokinetic models. Tigecycline pharmacokinetics were mostly described by a two-compartment model in these included studies. Estimated clearance and volumes of distribution of tigecycline at steady state () varied widely in different target patient populations, with a range of 7.5-23.1 L/h and 212.7-1087.7 L, respectively. Body-weight and creatinine clearance were the most important predictors of clearance in these studies, while other predictors include age, gender, bilirubin and aspartate aminotransferase. In conclusion, this review showed the large variability of tigecycline population pharmacokinetics, which can provide guide dosing in different target populations. For clinicians, the individual dosing adjustment should be based not only on the indication and pathogen susceptibility but also on the potential important predictors. However, more studies were needed to confirm the necessity of modified dosage regimens in different patient subpopulations.
Topics: Anti-Bacterial Agents; Body Weight; Databases, Factual; Humans; Models, Biological; Tigecycline
PubMed: 35747442
DOI: 10.2147/DDDT.S365512 -
Advances in Therapy Mar 2020Studies assessing the effect of high dose tigecycline on severe infections are limited and remain controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies assessing the effect of high dose tigecycline on severe infections are limited and remain controversial.
OBJECTIVES
To assess systematically the effectiveness and safety of high dose tigecycline in the treatment of severe infections.
METHODS
Pubmed, Web of Science, Embase, MEDLINE, Cochrane Library and ClinicalTrials were searched up to February 20, 2019 for studies that compared the effectiveness and safety of high dose tigecycline with standard dose tigecycline or other non-tigecycline-containing regimens in the treatment of severe infections. Rates for all-cause mortality, clinical cure, microbiological eradication and adverse events were analysed.
RESULTS
Ten studies with 593 patients were included. The results indicated that using high dose tigecycline resulted in better outcomes compared with controls with lower all-cause mortality (OR 0.44, 95% CI 0.30-0.66, p < 0.0001), higher clinical cure (OR 3.43, 95% CI 2.09-5.63, p < 0.00001), higher microbiological eradication (OR 2.25, 95% CI 1.44-3.50, p = 0.0003), and without increasing adverse events rates. Subgroup analysis showed that high dose tigecycline reduced all-cause mortality in nosocomial acquired pneumonia (OR 0.39, 95% CI 0.22-0.70, p = 0.002), bloodstream infections (OR 0.19, 95% CI 0.06-0.58, p = 0.004) and mixed infections (OR 0.20, 95% CI 0.07-0.59, p = 0.003), with no statistical differences in complicated intra-abdominal infections (OR 2.04, 95% CI 0.80-5.23, p = 0.14). In carbapenem-resistant pathogens, the microbiological eradication rate in those given high dose tigecycline did not differ from controls (OR 1.07, 95% CI 0.44-2.60, p = 0.87), although mortality was reduced (OR 0.20, 95% CI 0.09-0.45, p = 0.0001). The main limitation of the review is that most of the included studies are observational studies with small sample sizes and high risks of bias.
CONCLUSIONS
High dose tigecycline treatment is effective and safe for severe infections owing to its lower all-cause mortality, higher clinical cure, microbiological eradication and comparable adverse events. However, as a result of the high risks of bias of the included studies, well-designed randomised clinical trials are warranted to establish the effectiveness and safety of high dose tigecycline compared with standard dose tigecycline and other commonly used antibiotics.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Infections; Observational Studies as Topic; Severity of Illness Index; Tigecycline
PubMed: 32006240
DOI: 10.1007/s12325-020-01235-y -
Journal of Clinical Pharmacy and... Nov 2022Acinetobacter baumannii is one of the most important nosocomial pathogens with the ability to cause infections such as meningitis, pneumonia, urinary tract, septicaemia... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Acinetobacter baumannii is one of the most important nosocomial pathogens with the ability to cause infections such as meningitis, pneumonia, urinary tract, septicaemia and wound infections. A wide range of virulence factors are responsible for pathogenesis and high mortality of A. baumannii including outer membrane proteins, lipopolysaccharide, capsule, phospholipase, nutrient- acquisition systems, efflux pumps, protein secretion systems, quarom sensing and biofilm production. These virulence factors contribute in pathogen survival in stressful conditions and antimicrobial resistance.
COMMENT
According to the World Health Organization (WHO), A. baumannii is one of the most resistant pathogens of ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.). In recent years, resistance to a wide range of antibiotics in A. baumannii has significantly increased and the high emergence of extensively drug resistant (XDR) isolates is challenging. Among therapeutic antibiotics, resistance to tigecycline as a last resort antibiotic has become a global concern. Several mechanisms are involved in tigecycline resistance, the most important of which is RND (Resistance-Nodulation-Division) family efflux pumps overexpression. The development of new therapeutic strategies to confront A. baumannii infections has been very promising in recent years.
WHAT IS NEW AND CONCLUSION
In the present review we highlight microbiological and virulence traits in A. baumannii and peruse the tigecycline resistance mechanisms and novel therapeutic options. Among the novel therapeutic strategies we focus on combination therapy, drug repurposing, novel antibiotics, bacteriophage therapy, antimicrobial peptides (AMPs), human monoclonal antibodies (Hu-mAbs), nanoparticles and gene editing.
Topics: Humans; Acinetobacter baumannii; Tigecycline; Virulence Factors; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 36200470
DOI: 10.1111/jcpt.13787