<i>In vitro</i> Activity of Colistin in Combination with Tigecycline against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains Isolated from Patients with Ventilator-Associated Pneumonia

Çıkman, Aytekin; Gülhan, Barış; Aydın, Merve; Ceylan, Mehmet Reşat; Parlak, Mehmet; Karakeçili, Faruk; Karagöz, Alper

doi:10.7150/ijms.11988

Cited by 19 publications

(11 citation statements)

References 37 publications

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“…This suggests that the addition of tigecycline to colistin may be harmful, considering the removal of susceptible-range wells and poor clinical outcomes seen in patients who received that combination. Our study correlates with a study by Cikman and colleagues that demonstrated a high rate of antagonism with tigecycline-colistin against XDR A. baumannii (12). Taken together, the results show that utilizing drug combinations that inhibit growth in SAC wells may be a more appropriate alternative than utilizing a combination that does not when treating XDR A. baumannii pneumonia.…”

supporting

confidence: 77%

Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections

Bremmer

Bauer

Pouch

et al. 2016

Antimicrob Agents Chemother

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We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P ‫؍‬ 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.A mong Gram-negative organisms, extensively drug-resistant (XDR) Acinetobacter baumannii is considered a serious threat to public health. As A. baumannii infections are associated with significant morbidity and mortality, the timely administration of effective broad-spectrum antibiotics is imperative (1). In recent years, increasing resistance among A. baumannii isolates has limited many therapy options, requiring the administration of empirical combination therapy for serious A. baumannii infections (2). In an attempt to select the most effective empirical antibiotic therapy, antimicrobial stewardship programs (ASPs) annually evaluate susceptibility based on institutional, unit-specific, or combination antibiograms. However, antibiograms are simply based on percent susceptibility and do not provide clinicians with additional aspects, including synergy or antagonism between agents. This presents significant limitations for ASPs in selecting optimal combination therapy for the treatment of A. baumannii infections.The comparison of specific antibiotic combinations identified in the literature provides ASPs with more definitive conclusions but does not address the heterogeneity of synergistic interactions of a specific combination against all isolates (3-6). Therefore, it may be more beneficial for ASPs to evaluate potential synergistic interactions in real time, particularly in critically ill patients infected with XDR A. baumannii. This study evaluated the use of a checkerboard platform to determine antibiotic combinations that are synergistic against XDR A. baumannii and compared the results to both time-kill assay results and clinical outcomes.We selected 76 unique XDR A. baumannii clinical isolates from our center between January 2009 and October 2013. Isolates were stored at Ϫ70°C and subcultured twice prior to testing. For the checkerboard assay, we identified the susceptibilities to amikacin (Crescent Chemical, Islandia, NY), colistin (MP Biomedical, Solon, OH), doripenem (TSZChem, Framingham, MA), minocycline (EMD Millipore, Darmstadt, Germany), and tigecycline (TSZChem, Framingham, MA) by microbroth dilution. Other susceptibilities were determined by the MicroScan system (Beckman Coulter, CA). The susceptibilities (percent) to the antibiotics tested were as follows: amikacin, 2/76 (3%); ampicillin-sulbactam, 2/76 (3%); cefepime, 0/76 (0%); ciprofloxacin, 0/76 (0%); do...

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supporting

confidence: 77%

Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections

Bremmer

Bauer

Pouch

et al. 2016

Antimicrob Agents Chemother

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“…Tigecycline and colistin combination therapy has been shown to be antagonistic in Ac. baumannii , specifically at low concentrations in some studies (Albur et al ., ; Cikman et al ., ) but synergistic in others (particularly in Enterobacteriaceae) (Ku et al . ; Betts et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods

et al. 2016

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SummaryA literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemaseproducing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, transcomplementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools.

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“…15,16 There were no antagonistic effects in our findings. In contrast, Cikman et al 17 reported 80% antagonistic effects from a colistin/tigecycline combination in CRAB strains. This different outcome might be a result of the method used for synergy testing.…”

Section: Discussionmentioning

confidence: 90%

“…8,9,15,16 However, antagonistic effects of such a combination might be detected. 17 Since the benefit of a combination of colistin and tigecycline is ambiguous, we conducted this particular study to determine in vitro antimicrobial susceptibility and the synergistic activity of colistin in combination with tigecycline against clinical strains of CRAB.…”

mentioning

confidence: 99%

Synergistic Activities of Colistin with Tigecycline Combination Against Clinical Isolates of Carbapenemresistant Acinetobacter baumannii

Sitaruno

Santimaleeworagun²,

Leelasupasri

2019

bkkmedj

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In vitro Activity of Colistin in Combination with Tigecycline against Carbapenem-Resistant Acinetobacter baumannii Strains Isolated from Patients with Ventilator-Associated Pneumonia

Cited by 19 publications

References 37 publications

Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections

Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections

Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods

Synergistic Activities of Colistin with Tigecycline Combination Against Clinical Isolates of Carbapenemresistant Acinetobacter baumannii

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