Activity of TP-6076 against carbapenem-resistant Acinetobacter baumannii isolates collected from inpatients in Greek hospitals

Falagas, Matthew E.; Skalidis, Tilemachos; Vardakas, Konstantinos Z.; Voulgaris, Georgios L; Παπανικολάου, Γεώργιος; Legakis, Nicholas J.

doi:10.1016/j.ijantimicag.2018.03.009

Cited by 13 publications

(9 citation statements)

References 8 publications

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“…Eravacycline and tigecycline MIC 50/90 values were 0.5/1 and 1/2 g/ml, respectively, for the same isolates (67). The TP-6076 MIC 50/90 values were 0.03/0.06 g/ml when tested against 121 clinical isolates from Greek hospitals between 2015 and 2017 (68). TP-6076 activity was minimally affected by recombinant overexpression of several tetracycline efflux pumps, and it was also potent against clinical CRAB isolates expressing tetA (3 isolates) and tetB (18 isolates) efflux pump genes, showing a maximum MIC 90 of 1 g/ml (69).…”

Section: New Therapeutic Optionsmentioning

confidence: 88%

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Isler¹,

Doi

Bonomo

et al. 2019

Antimicrob Agents Chemother

266

179

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Carbapenem-resistantAcinetobacter baumannii(CRAB) is a perilous nosocomial pathogen causing substantial morbidity and mortality. Current treatment options for CRAB are limited and suffer from pharmacokinetic limitations, such as high toxicity and low plasma levels. As a result, CRAB is declared as the top priority pathogen by the World Health Organization for the investment in new drugs. This urgent need for new therapies, in combination with faster FDA approval process, accelerated new drug development and placed several drug candidates in the pipeline. This article reviews available information about the new drugs and other therapeutic options focusing on agents in clinical or late-stage preclinical studies for the treatment of CRAB, and it evaluates their expected benefits and potential shortcomings.

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Section: New Therapeutic Optionsmentioning

confidence: 88%

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Isler¹,

Doi

Bonomo

et al. 2019

Antimicrob Agents Chemother

266

179

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“…The impact of these in vitro findings is not known yet, pending phar macokinetic-pharmacodynamic studies and break point decisions. In tigecycline non susceptible and minocycline non susceptible Acinetobacter isolates, the MICs of TP6076 were slightly increased 86 . In K. pneumoniae, tigecycline resistant strains are mostly also resistant to TP6076 (ref.…”

Section: Tetracycline Derivativesmentioning

confidence: 93%

Critical analysis of antibacterial agents in clinical development

Theuretzbacher¹,

et al. 2020

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| The antibacterial agents currently in clinical development are predominantly derivatives of well-established antibiotic classes and were selected to address the class-specific resistance mechanisms and determinants that were known at the time of their discovery. Many of these agents aim to target the antibiotic-resistant priority pathogens listed by the WHO, including Gram-negative bacteria in the critical priority category, such as carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacterales. Although some current compounds in the pipeline have exhibited increased susceptibility rates in surveillance studies that depend on geography, pre-existing cross-resistance both within and across antibacterial classes limits the activity of many of the new agents against the most extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negative pathogens. In particular, cross-resistance to unrelated classes may occur by co-selection of resistant strains, thus leading to the rapid emergence and subsequent spread of resistance. There is a continued need for innovation and new-class antibacterial agents in order to provide effective therapeutic options against infections specifically caused by XDR and PDR Gram-negative bacteria. ✉

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“…TP-6076 did not demonstrate higher MIC values when comparing colistin-susceptible and non-susceptible isolates. However, the MIC 90 was one dilution lower for tigecycline-and minocycline-susceptible and nonsusceptible isolates [117]. In isolates overexpressing genes encoding the AdeABC multidrug efflux pump, the major contributor to tigecycline resistance, TP-6076 had an MIC range of 0.008 to 0.13 μg/mL [118].…”

Section: Tp-6076mentioning

confidence: 99%

“…It has a similar mechanism of action to tetracyclines in which it disrupts bacterial synthesis by binding to the 30S ribosomal subunit. In vitro data have shown potent activity against CRAB isolates with many containing OXA and OXA-like β-lactamases [117][118][119][120]. In the largest of these studies with 326 global isolates from the years 2005-2016, TP-6076 had MIC 50 and MIC 90 values of 0.06 μg/mL and 0.125 μg/ mL while eravacycline had values of 0.5 μg/mL and 1 μg/mL, respectively ( Table 1) [119].…”

Section: Tp-6076mentioning

confidence: 99%

Developments for the Treatment of Invasive Infections Due to Multidrug-resistant Acinetobacter baumannii

David¹,

Drew²,

Wilson³

2019

JRI

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Acinetobacter baumannii is a significant pathogen in healthcare settings (specifically prominent in healthcare-and ventilator-associated pneumonia) due primarily to its virulence and resistance to a wide variety of antimicrobial drug classes, including carbapenems (CRAB). Existing therapies (notably polymyxins, minocycline, tigecycline, amikacin, and sulbactam) often result in suboptimal tissue concentrations, high rates of toxicity, and increasing rates of resistance. Although utilizing combinations of antibiotics (specifically those containing colistin) have been employed, results have been mixed, and control trials are lacking. Eravacycline is a novel tetracycline with an improved pharmacokinetic profile and more potent activity against A. baumannii relative to tigecycline. Cefiderocol has a unique mechanism of action that has performed well in vitro against multidrugresistant (MDR) and CRAB isolates. Limited clinical data exists with each of these agents. Other novel antimicrobials are still in early phase clinical trials (ETX2514/sulbactam, TP-271, TP-6076, VNRX-5133/cefepime, cefepime/zidebactam, AIC-499, GSK3342830, and SPR741) while further research is underway for non-antibiotic approaches, specifically monoclonal antibodies and bacteriophage therapies.

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Activity of TP-6076 against carbapenem-resistant Acinetobacter baumannii isolates collected from inpatients in Greek hospitals

Cited by 13 publications

References 8 publications

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Critical analysis of antibacterial agents in clinical development

Developments for the Treatment of Invasive Infections Due to Multidrug-resistant Acinetobacter baumannii

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