Investigation of Colistin Heteroresistance and Some Factors Affecting Heteroresistance in Carbapenem-Resistant A. baumannii Strains

Gazel, Deniz; Otkun, Metin

doi:10.4274/mjima.2017.1

Cited by 12 publications

(19 citation statements)

References 30 publications

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“…It is known that in low concentrations colistin is not effective, that is because in 2012, optimal dosage regimens for colistin were updated and increased up to three times [1]. Heteroresistance to colistin among MDR acinetobacter strains was known for more than a decade [19,20,21,22]. While lower doses could cause treatment failure and selection of heteroresistant clones, increased dose could become nephrotoxic.…”

Section: Discussionmentioning

confidence: 99%

“…Combined therapies have synergistic effects and they could be less toxic due to administration of decreased doses of two antimicrobials. The most frequently studied in-vitro combinations were colistin with rifampicin [21,23], colistin with carbapenems [24] and colistin with tigecycline [21,25]. All these three combinations have synergistic activity against heteroresistant A.baumanni isolates.…”

Section: Discussionmentioning

confidence: 99%

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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%

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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“…Moreover, endolysins have been recognized in the US "National Action Plan for Combating Antibiotic-resistant Bacteria" 24 , which identified the use of "phage-derived lysins to kill specific bacteria while preserving the microbiota" as a key strategy to reduce the development of antimicrobial resistance due to www.nature.com/scientificreports www.nature.com/scientificreports/ the absence of toxicity in human cells 25,26 . Moreover, some endolysins have been found to display activity against sub-populations of microbes 27,28 extracted from biofilm [29][30][31] and to be useful in other innovative treatments.…”

Section: Discussionmentioning

confidence: 99%

“…baumannii 25 clinical isolates (22 STs) from the II Spanish Multicentre Study (GEIH-REIPI Acinetobacter baumannii 2000-2010) (Accession number Genbank PRJNA422585) 27 Pseudomonas aeruginosa 25 clinical isolates (ST274 [n = 15]; ST1089 [n = 3]; ST not known [n = 7])28 Description of the bacterial strains, plasmids and primers used in this study. Abbreviations: ST; multilocus sequence type.…”

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confidence: 99%

In vitro and in vivo efficacy of combinations of colistin and different endolysins against clinical strains of multi-drug resistant pathogens

Blasco

Ambroa

Trastoy

et al. 2020

Sci Rep

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The emergence of multidrug resistant (MDR) pathogenic bacteria is jeopardizing the value of antimicrobials, which had previously changed the course of medical science. In this study, we identified endolysins ElyA1 and ElyA2 (GH108-PG3 family), present in the genome of bacteriophages Ab1051Φ and Ab1052Φ, respectively. The muralytic activity of these endolysins against MDR clinical isolates (Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae) was tested using the turbidity reduction assay. Minimal inhibitory concentrations (MICs) of endolysin, colistin and a combination of endolysin and colistin were determined, and the antimicrobial activity of each treatment was confirmed by time kill curves. Endolysin ElyA1 displayed activity against all 25 strains of A. baumannii and P. aeruginosa tested and against 13 out of 17 strains of K. pneumoniae. Endolysin ElyA2 did not display any such activity. The combined antimicrobial activity of colistin and ElyA1 yielded a reduction in the colistin MIC for all strains studied, except K. pneumoniae. These results were confirmed in vivo in G. mellonella survival assays and in murine skin and lung infection models. In conclusion, combining colistin (1/4 MIC) with the new endolysin ElyA1 (350 µg) enhanced the bactericidal activity of colistin in both in vitro and in vivo studies. This will potentially enable reduction of the dose of colistin used in clinical practice.

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“…Various studies from clinical settings throughout the world have indicated the emergence of colistin-resistant AB as an important healthcare problem [10,14]. Colistin-susceptible AB strains can easily transform into colistin-resistant or heteroresistant clones, or colistin heteroresistant strains can transform into colistin-resistant clones via exposure to colistin [15][16][17][18]. In 2016, the emergence of plasmid-mediated colistin resistance in an E. coli strain by the MCR-1 mechanism was reported from China, which made scientists focus on the urgent need for global action in the fight against pan-drug-resistant Gram-negative bacteria [19].…”

Section: Introductionmentioning

confidence: 99%

In vitro activity of methylene blue and EMB agar on colistin-resistant A.baumannii: An experimental study

Gazel

Otkun

Akçalı

2019

Preprint

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Background Colistin is one of the last resort antibiotics used against carbapenem-resistant Acinetobacter baumannii (AB); however, colistin resistance has been reported recently. Methylene blue (MB) is used in microbiology for staining, and in medicine as an antidote drug. Here, we investigated antimicrobial effects of MB and Eosin Methylene blue (EMB) agar against colistin-resistant AB strains. Methods The AB ATCC 19606 strain and 31 AB clinical isolates were included in the study. In the first round, ATCC strain and a clinical isolate were transformed into colistin-resistant forms, using Li's method, with increasing colistin concentrations. At each step, new MICs were determined and subcultures were inoculated to EMB and sheep blood agar (SBA). The colistin MIC values of the subcultures were also determined using Mueller Hinton Agar (MHA) containing 14 µg/mL MB. In the second round, colistin resistant clones of all collected clinical isolates (n=31) were obtained and screened to investigate their susceptibility to EMB agar by inoculating on SBA and EMB agar. Results At the beginning, the MICs of two strains were 0.5 µg/mL. At the last stage, both MICs had risen to 64 µg/mL. Subpopulations with high colistin resistance (>=32 µg/mL) were inhibited by MB and EMB agar, but could grow well on SBA. In MHA plates containing MB, the MICs decreased to the 0.5 µg/mL level for colistin-susceptible or moderately resistant clones. Additionally, clones with high colistin resistance showed atypical colony morphology on SBA. In the second round, MICs of the colistin resistant clones of all clinical isolates rose to 8 µg/mL after colistin exposure and 35% of those clinical isolates were inhibited by EMB agar while they could grow on SBA. Conclusion Highly resistant strains were totally inhibited by the effect of MB and EMB agar, while the MICs of the susceptible and moderate resistant clones decreased. EMB agar and MB may have inhibitory effects against colistin-resistant AB strains and MB may have a potential to be used as an antimicrobial drug. Secondly, using only EMB agar for subculturing may cause missing of colistin-resistant strains and giving incorrect identification or antibiogram reports in clinical microbiology laboratories.

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Investigation of Colistin Heteroresistance and Some Factors Affecting Heteroresistance in Carbapenem-Resistant A. baumannii Strains

Cited by 12 publications

References 30 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

In vitro and in vivo efficacy of combinations of colistin and different endolysins against clinical strains of multi-drug resistant pathogens

In vitro activity of methylene blue and EMB agar on colistin-resistant A.baumannii: An experimental study

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