Emerging therapies for multidrug resistant Acinetobacter baumannii

García-Quintanilla, Meritxell; Pulido, Marta; López-Rojas, Rafael; Pachón, Jerónimo; McConnell, Michael J.

doi:10.1016/j.tim.2012.12.002

Cited by 109 publications

(86 citation statements)

References 62 publications

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“…and particularly those belonging to the A. baumannii-A. calcoaceticus complex have emerged globally as common nosocomial and community pathogens with high levels of MDR or pandrug resistance (494,495). The modest genome size of A. baumannii of ca.…”

Section: Acinetobacter Sppmentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

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Section: Acinetobacter Sppmentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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“…Nevertheless, such peptides can have broad-spectrum activity against highly resistant Gram-negative bacteria, including Acinetobacter. For example, cecropin A-melittin hybrid proteins have shown in vitro bactericidal activity against resistant A. baumannii, but a short half-life has limited their utility thus far (288). Peptides derived from frog and toad skin have been shown to have strong bactericidal activity.…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

“…Peptides derived from frog and toad skin have been shown to have strong bactericidal activity. Highlighting this potential, in preclinical models of blood and wound infections treatment with A3-APO (a proline-rich antibacterial peptide) improved survival and decreased bacterial density more than either imipenem or colistin (288). Before peptide therapies can be reliably used systemically, they must overcome problematic pharmacology, toxicity, and inactivation in the context of biological matrices such as serum, surfactant, and other biological fluids and tissues.…”

Section: Antimicrobial Peptidesmentioning

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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“…Nonetheless, a kidney function test is necessary before the combined application of these two drugs, given that polymyxin may induce ototoxicity and renal toxicity. It has also been suggested that antibacterial peptides and vaccination may also be potential choices for therapeutic strategies (15).…”

Section: Sensivity Medium Sensivity Resistance ----------------------mentioning

confidence: 99%

Detection of AmpC β-lactamases in Acinetobacter baumannii in the Xuzhou region and analysis of drug resistance

Liu

2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to determine the prevalence and related drug resistance of AmpC β-lactamases in Acinetobacter baumannii in tertiary-level hospitals in the Xuzhou region in China. A total of 134 clinical isolates of non-repetitive Acinetobacter baumannii were collected from different hospitals in the Xuzhou region, and multiplex polymerase chain reaction (PCR) was employed to determine the genotype of AmpC. The PCR products were purified and sequenced. The susceptibility to antibiotics was tested using the biometrics automated microbiological-assay system, VITEK-2. Amongst the 134 isolated strains, 96 strains were found to produce AmpC β-lactamases, and the positive rate was 72%, all of which carried acinetobacter-derived cephalosporinase (ADC) type AmpC resistance genes. The drug sensitivity tests indicated that the positive Acinetobacter baumannii strains were resistant to the majority of extended-spectrum β-lactam antibiotics, but were only sensitive to polymyxin. In conclusion, the incidence of AmpC enzymes in Acinetobacter baumannii strains in tertiary-level hospitals in the Xuzhou area is relatively high, and resistance to the majority of extendedspectrum β-lactam antibiotics may be related to the ADC type of AmpC.

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Emerging therapies for multidrug resistant Acinetobacter baumannii

Cited by 109 publications

References 62 publications

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

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

Detection of AmpC β-lactamases in Acinetobacter baumannii in the Xuzhou region and analysis of drug resistance

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