Plazomicin for Infections Caused by Carbapenem-Resistant Enterobacteriaceae

McKinnell, James A.; Dwyer, Jamie P.; Talbot, George H.; Connolly, Lynn; Friedland, Ian R.; Smith, A. Hayes; Jubb, Adrian M.; Serio, Alisa W.; Krause, Kevin M.; Daikos, George L.

doi:10.1056/nejmc1807634

Cited by 154 publications

(104 citation statements)

References 3 publications

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“…All of these isolates had MICs >128 µg/mL and were confirmed to express 16S rRNA methyltransferases. 45,46 Treatment emergent resistance to plazomicin was also noted in phase III clinical trials, though this too was a rare occurrence. In total, seven isolates cultured from six patients met the criteria for resistance emergence (an isolate having a ⩾4-fold increase in MIC and whose baseline MIC changed from ⩽4 µg/mL to > 4 µg/mL after treatment).…”

Section: Clinical Resistancementioning

confidence: 99%

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Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Clark

Burgess

2020

Therapeutic Advances in Infection

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Objective: To review the mechanism of action, mechanisms of resistance, in vitro activity, pharmacokinetics, pharmacodynamics, and clinical data for a novel aminoglycoside. Data sources: A PubMed search was performed from January 2006 to August 2019 using the following search terms: plazomicin and ACHN-490. Another search was conducted on clinicaltrials.gov for published clinical data. References from selected studies were also used to find additional literature. Study selection and data extraction: All English-language studies presenting original research ( in vitro, in vivo, pharmacokinetic, and clinical) were evaluated. Data synthesis: Plazomicin has in vitro activity against several multi-drug-resistant organisms, including carbapenem-resistant Enterobacteriaceae. It was Food and Drug Administration (FDA) approved to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis, following phase II and III trials compared with levofloxacin and meropenem, respectively. Despite the FDA Black Box Warning for aminoglycoside class effects (nephrotoxicity, ototoxicity, neuromuscular blockade, and pregnancy risk), it exhibited a favorable safety profile with the most common adverse effects being decreased renal function (3.7%), diarrhea (2.3%), hypertension (2.3%), headache (1.3%), nausea (1.3%), vomiting (1.3%), and hypotension (1.0%) in the largest in-human trial. Relevance to patient care and clinical practice: Plazomicin will likely be used in the treatment of multi-drug-resistant cUTIs or in combination to treat serious carbapenem-resistant Enterobacteriaceae infections. Conclusions: Plazomicin appears poised to help fill the need for new agents to treat infections caused by multi-drug-resistant Enterobacteriaceae.

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Section: Clinical Resistancementioning

confidence: 99%

“…Summary table of phase II and III clinicaltrials of plazomicin. ClinicalTrials.gov identifier: NCT01096849], Connolly et al,43 EPIC 44 , CARE 45. a Included blood stream infection, hospital-acquired pneumonia, and ventilator-associated pneumonia.…”

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confidence: 99%

Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Clark

Burgess

2020

Therapeutic Advances in Infection

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“…103,104 In addition to the complicated urinary tract infection indication, FDA approval for bloodstream infections caused by documented or presumed CRE was also sought but was denied because the RCT did not meet its predefined enrollment. 105,106 In this study 39 patients underwent randomization with 18 receiving plazomicin and 21 receiving a colistin-based regimen with an overall microbiological modified intention to treat population of 37 patients with confirmed CRE. The primary endpoint (composite of death from any cause at 28 days or clinically significant disease-related complications) occurred in 4 of 17 (24%) patients in the plazomicin arm and 10 of 20 (50%) in the colistin arm.…”

Section: Enterobacteriaceae (Carbapenem Resistant)mentioning

confidence: 99%

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

Strich

Kadri

2019

Semin Respir Crit Care Med

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Antibiotic resistance among gram-negative pathogens is a world-wide problem that poses a constant threat to patients in the intensive care unit and a therapeutic challenge for the intensivist. Furthermore, the substantial economic burden and increased mortality associated with infections due to highly resistant gram-negative pathogens exacerbate these challenges. Understanding the mechanisms, epidemiology, and risk factors for these infections is paramount to the successful control of outbreaks and for guiding therapy which often entails use of antibiotics with suboptimal efficacy and/or toxicity profiles. In this review we will discuss the global epidemiology, burden, risk factors, and treatment of highly resistant gram-negative infections as they apply to the intensive care population.

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“…The recently published phase III, open-label CARE trial evaluated 28-day mortality among patients with CRE bacteremia or nosocomial pneumonia receiving plazomicin or colistin, each combined with meropenem or tigecycline. Both clinically significant disease-related complications and 28-day mortality were lower in the plazomicin arm (24% vs. 50%), and rates of Higher MICs reported in the presence of the New Delhi metallo-β-lactamase nephrotoxicity were lower among patients treated with plazomicin than colistin (16.7% vs. 50%) [106]. Additional studies addressing the role of plazomicin in solid organ and hematopoietic stem cell transplant recipients with invasive CRE infections are warranted.…”

Section: Carbapenem-resistant Enterobacteralesmentioning

confidence: 92%

Multidrug-Resistant Organisms: Posttransplant Management for Extended-Spectrum Beta-Lactamase Producers and Carbapenem-Resistant Enterobacterales

Howard‐Anderson¹,

Pouch²

2020

Emerging Transplant Infections

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The incidence of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-EB) and carbapenem-resistant Enterobacterales (CRE) infections has been increasing worldwide, although the prevalence and mechanism of resistance vary by geographic region and institutional patterns of resistance. These multidrug-resistant infections are challenging to diagnose and treat and can cause significant morbidity and mortality in transplant patients. In this chapter we highlight recent trends in epidemiology, including risk factors for acquiring ESBL-EB and CRE, clinical outcomes, and new strategies for

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Plazomicin for Infections Caused by Carbapenem-Resistant Enterobacteriaceae

Cited by 154 publications

References 3 publications

Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

Multidrug-Resistant Organisms: Posttransplant Management for Extended-Spectrum Beta-Lactamase Producers and Carbapenem-Resistant Enterobacterales

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