New Treatment Options against Carbapenem-Resistant
            <i>Acinetobacter baumannii</i>
            Infections

Isler, Burcu; Doi, Yohei; Bonomo, Robert A.; Paterson, David L.

doi:10.1128/aac.01110-18

Cited by 252 publications

(199 citation statements)

References 97 publications

(102 reference statements)

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“…Recent studies suggest that kidney damage is more severe in patients treated with CMS than polymyxin B [27]. Further studies are needed to determine effective doses of available antibiotics that do not cause increased nephrotoxicity and prevent development of resistance until new agents active against MDR acinetobacter strains to be approved for clinical use [28].…”

Section: Discussionmentioning

confidence: 99%

Colistin nephrotoxicity in critically ill patients after implementation of a new dosing strategy

Özel

Ergönül

Korten

2019

J Infect Dev Ctries

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Introduction: Intravenous colistin is increasingly used to treat multidrug-resistant Gram-negative infections. Highly variable nephrotoxicity rates have been reported. Recent PK/PD studies propose a loading dose and a maintenance dose for better efficacy, but data on the renal toxicity of such regimens are rare. This study aimed to evaluate the incidence and risk factors for nephrotoxicity related to colistin after implementation of a new dosing regimen including a loading dose. Methodology: This was a prospective observational study that was made between adult patients who received a minimum of 48 hours of intravenous colistin from December 2012 to January 2014 at the medical and surgical intensive care units (ICU) of a university hospital. The severity of acute kidney injury (AKI) was defined by the RIFLE criteria. Results: Fifty-nine patients met the inclusion criteria, and 31 (52.5%) developed nephrotoxicity. The APACHE-II score was > 15 in 81% of patients. The median time to nephrotoxicity was 7 days. Patients with AKI were in risk (10.2%), injury (16.9%), failure (25.4%), and none of the patients developed permanent renal insufficiency. A logistic regression model identified three predictors of colistin-associated nephrotoxicity: age; the number of days that estimated target plasma concentrations of colistin were ≥ 3.5 mg/L in the first week of therapy; and baseline creatinine level. Conclusion: In this cohort of severely ill ICU patients, colistin led to a relatively high rate of nephrotoxicity. Further studies are needed to identify the optimal dose for both efficacy and safety.

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Section: Discussionmentioning

confidence: 99%

Colistin nephrotoxicity in critically ill patients after implementation of a new dosing strategy

Özel

Ergönül

Korten

2019

J Infect Dev Ctries

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“…117 However, the carbapenem-resistant A. baumannii complex can pose a significant treatment challenge; in recent years, this strain has been predominately treated with combinations of ampicillin-sulbactam, polymyxins, tigecycline, and aminoglycosides, but again these antibiotics have high toxicity and the associated efficacy is suboptimal. 118 Minocycline has also been considered to have efficacy in patients with carbapenem-resistant A. baumannii and is predominately used in combination with other reserve agents. 119 One study found that minocycline as monotherapy or combination therapy had a 73% clinical success rate in patients with a mean APACHE II score of 21.…”

Section: Mdr-acinetobacter Baumanniimentioning

confidence: 99%

“…121,122 While there are a few new potential therapeutic options for highly resistant A. baumannii in development, the majority are in preclinical phase or phase I studies. 118 A new tetracycline, eravacycline, that was FDA approved for complicated intraabdominal infections displays in vitro activity against carbapenem-resistant A. baumannii (►Table 1). 118,123 Eravacycline works by binding 30S bacterial ribosome inhibiting protein synthesis.…”

Section: Mdr-acinetobacter Baumanniimentioning

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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“…A. baumannii is the most common nosocomial pathogen that causes bloodstream infections (BSI) or ventilator-associated pneumonia (VAP) in many medical centers, particularly in Turkey (2, 5). Carbapenem resistance rates exceed 90% in some parts of the World (3). Carbapenem resistance among A. baumannii isolates in Turkey is ranged from 91% to 98% according to national health statistics (12).…”

Section: Discussionmentioning

confidence: 99%

“…Considering the prevalence of OXA-type carbapenemase activity in CRAB strains, eravacycline has been evaluated as a good treatment option (20–22). However, some type of carbapenemase activity, increased expression of the efflux pumps and the presence of tigecycline resistance are associated with increasing MIC values for eravacycline (1, 3).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Eravacycline in Combination with Colistin Against Carbapenem-Resistant A. baumannii Isolates

Özger

Çuhadar

Yıldız

et al. 2019

Preprint

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26The synergistic activity of eravacycline in combination with colistin on carbapenem-resistant 27 A.baumannii (CRAB) isolates was evaluated in this study. Minimum inhibitory 28 concentrations (MICs) of eravacycline and colistin were determined by the broth 29 microdilution method. MICs values ranged between 1 to 4 mg and 0,5 to 128 mg/L for 30 eravacycline and colistin, respectively. In-vitro synergy between eravacycline and colistin 31 was evaluated by using the chequerboard methodology. Synergistic activity was found in 10 32 % of the strains, and additive effect in 20 %. No antagonism was detected. Similar activity 33 was also observed in colistin resistant CRAB isolates. The result of this study indicates that 34 eravacycline and colistin combination may be a potential therapeutic option for the treatment 35 of CRAB related infections. (CRAB) is an important nosocomial 53 pathogen causing substantial morbidity and mortality (1, 2). Current treatment options 54 (polymyxins, tigecycline, aminoglycosides) for CRAB are limited and suffer from 55 pharmacokinetic limitations such as high toxicity and low plasma levels (3). Therefore, to 56 enhance clinical efficacy and to avoid toxicity, combination therapy is often used for CRAB 57 infections (4). 58Eravacycline is a novel fluorocycline that belongs to the tetracycline class of 59 antimicrobials may be a treatment option for CRAB (5). In vitro studies were shown that 60 eravacycline minimum inhibitory concentrations (MICs) were found to be 2-8 fold lower 61 than tigecycline MICs against CRAB (6-8). The drug is also active against colistin resistant 62 strains (9). Despite in vitro activity, treatment success of eravacycline in CRAB infections are 63 unknown due to lack of clinical trials (10, 11). Management of healthcare-associated 64 infections (HCAI) caused by CRAB should be required combination therapy. There is no in 65 vitro study related to the synergism of eravacycline with other antibiotics in the literature. 66The aim of this in vitro study is to evaluate the synergistic activity of eravacycline in 67 combination with colistin on CRAB isolates. 68 Results 69Ten carbapenem-resistant A. baumannii strains were used in this study. Three of these 70 strains were also resistant to colistin. All isolates were found to have bla OXA-51 and nine 71 harbored bla OXA-23. The characteristics of 10 CRAB isolates included in chequerboard 72 experiments were shown in Table 1. 73MIC values ranged between 1 to 4 mg and 0,5 to 128 mg/L for eravacycline and 74 colistin, respectively. Chequerboard analysis showed 10% synergy, 20% additive, 70% 132This research received no specific grant from any funding agency in the public, commercial, 133 or not-for-profit sectors.

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New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Cited by 252 publications

References 97 publications

Colistin nephrotoxicity in critically ill patients after implementation of a new dosing strategy

Colistin nephrotoxicity in critically ill patients after implementation of a new dosing strategy

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

In Vitro Activity of Eravacycline in Combination with Colistin Against Carbapenem-Resistant A. baumannii Isolates

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