Efficacy of Sulbactam and Its Combination with Imipenem, Colistin and Tigecycline in an Experimental Model of Carbapenem-Resistant &lt;b&gt;&lt;i&gt;Acinetobacter baumannii&lt;/i&gt;&lt;/b&gt;  Sepsis

Dinç, Gökçen; Demiraslan, Hayati; Elmalı, Ferhan; Ahmed, Salman; Metan, Gökhan; Alp, Emine; Doğanay, Mehmet

doi:10.1159/000356755

Cited by 33 publications

(33 citation statements)

References 30 publications

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“…Among all the combination regimens, the one that may be most rational is colistincarbapenem, which has been found to be synergistic in multiple in vitro studies (275)(276)(277)(278)(279). This synergy may be observed in particular for isolates with intermediate resistance to the carbapenems (e.g., if the carbapenem MIC is 4 to 16 g/ml).…”

Section: Combination Antimicrobial Therapymentioning

confidence: 99%

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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SUMMARY Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

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Section: Combination Antimicrobial Therapymentioning

confidence: 99%

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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“…Tigecycline with doripenem (Hong et al . ; Dinc et al ., ) or amikacin (Dinc et al ., ) has been very promising.…”

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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“…isolates are a source of deep concern due to their multidrug resistance pattern and ability to persist in the environment [16]. Early detection of these genes will help in prevention and adequate infection control by limiting the spread of these organisms [20]. Therapeutic options are often very limited particularly since colistin-resistant isolates of Acinetobacter spp.…”

Section: Resultsmentioning

confidence: 99%

First Report of NDM-1-Producing Acinetobacter guillouiae

et al. 2014

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Background: Acinetobacter spp. is an opportunistic pathogen that has demonstrated increasing relevance in nosocomial infections. Carbapenem-resistant strains have been reported worldwide. Methods: Since 2014, screening for metallo-β-lactamases (MBLs) in all Acinetobacter spp. isolates using phenotypic methods and PCR has been implemented at the University Hospital Center Zagreb. Results: The bacterial strain was isolated from the drain of a child hospitalized in a paediatric intensive care unit and identified as Acinetobacter guillouiae using a MALDI TOF automated system. The strain was resistant to meropenem, ceftazidime, cefotaxime, ceftriaxone, cefepime, sulbactam/ampicillin, gentamicin and ciprofloxacin, intermediately susceptible to piperacillin/tazobactam and imipenem, and susceptible to amikacin and colistin. The Hodge test and combined disk test with EDTA were positive. The MICs of meropenem and imipenem were not reduced by cloxacillin, but a small reduction of two dilutions was observed following the addition of sodium chloride, which indicated that OXA-58 was produced. PCR and sequencing of chromosomal DNA from boiled colonies revealed bla_OXA-58 and bla_NDM-1 genes. Conclusion: This is the first report of NDM-1 in Acinetobacter spp. in Croatia. The early detection of these genes will aid in the prevention and in the achievement of adequate infection control by limiting the spread of these organisms.

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Efficacy of Sulbactam and Its Combination with Imipenem, Colistin and Tigecycline in an Experimental Model of Carbapenem-Resistant <b><i>Acinetobacter baumannii</i></b> Sepsis

Cited by 33 publications

References 30 publications

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

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

First Report of NDM-1-Producing <b><i>Acinetobacter</i></b> <b><i>guillouiae</i></b>

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