Acinetobacter baumannii: Evolution of Antimicrobial Resistance—Treatment Options

Doi, Yohei; Murray, Gerald L; Peleg, Anton Y.

doi:10.1055/s-0034-1398388

Cited by 226 publications

(122 citation statements)

References 163 publications

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“…For example, we observed that majority of isolates were less susceptible to tigecycline and doxycycline compared to A. baumannii ATCC17978 (Table 3). Tigecycline is the drug of choice for pandrug resistant A. baumannii infections (Doi et al, 2015). On the other hand, reduced susceptibility to doxycycline is not uncommon in clinical isolates of A. baumannii (Castanheira et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of Acinetobacter baumannii Recovered from Campylobacter Selective Medium

et al. 2016

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Acinetobacter baumannii, a Gram-negative opportunistic pathogen, is known to cause multidrug resistant infections. This organism has primarily been isolated from clinical environments and its environmental reservoirs remain largely unknown. In the present study, we recovered seven isolates of A. baumannii growing under conditions selective for Campylobacter spp. (microaerophilic at 42°C and in the presence of antibiotics) from dairy cattle manure storage tank or surface water impacted by livestock effluents. Antibiotic susceptibility tests revealed that all of these isolates were less susceptible to at least two different clinically relevant antibiotics, compared to the type strain A. baumannii ATCC17978. Expression of resistance-nodulation-division efflux pumps, an important mechanism of intrinsic resistance in these organisms, was analyzed, and adeB was found to be overexpressed in one and adeJ was overexpressed in three isolates. Comparison of these isolates using genomic DNA Macro-Restriction Fragment Pattern Analysis (MRFPA) revealed relatively low relatedness among themselves or with some of the clinical isolates from previous studies. This study suggests that A. baumannii isolates are capable of growing under selective conditions for Campylobacter spp. and that this organism can be present in manure and water.

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Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of Acinetobacter baumannii Recovered from Campylobacter Selective Medium

et al. 2016

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“…cinetobacter baumannii has become a major health care-associated pathogen over the past 2 decades, due to its intrinsic resistance to several classes of antimicrobial agents, its propensity to acquire resistance to other drug classes, and its ability to resist desiccation in environments typically found in hospitals (1). A. baumannii causes a variety of infections, with respiratory tract infections being the most common (1).…”

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“…Treatment options for carbapenem-resistant A. baumannii infections have not been well defined but generally include polymyxins (colistin and polymyxin B), tigecycline, or sulbactam, alone or in combination with a second agent, such as rifampin or a carbapenem, with the expectation of synergistic activities (4). However, toxicity (polymyxins), suboptimal pharmacokinetics (tigecycline), and the propensity for development of resistance (sulbactam) limit these options (1).…”

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Comparison of Minocycline Susceptibility Testing Methods for Carbapenem-Resistant Acinetobacter baumannii

et al. 2016

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cTreatment options for infections due to carbapenem-resistant Acinetobacter baumannii are extremely limited. Minocycline is a semisynthetic tetracycline derivative with activity against this pathogen. This study compared susceptibility testing methods that are used in clinical microbiology laboratories (Etest, disk diffusion, and Sensititre broth microdilution methods) for testing of minocycline, tigecycline, and doxycycline against 107 carbapenem-resistant A. baumannii clinical isolates. Susceptibility rates determined with the standard broth microdilution method using cation-adjusted Mueller-Hinton (MH) broth were 77.6% for minocycline and 29% for doxycycline, and 92.5% of isolates had tigecycline MICs of <2 g/ml. Using MH agar from BD and Oxoid, susceptibility rates determined with the Etest method were 67.3% and 52.3% for minocycline, 21.5% and 18.7% for doxycycline, and 71% and 29.9% for tigecycline, respectively. With the disk diffusion method using MH agar from BD and Oxoid, susceptibility rates were 82.2% and 72.9% for minocycline and 34.6% and 34.6% for doxycycline, respectively, and rates of MICs of <2 g/ml were 46.7% and 23.4% for tigecycline. In comparison with the standard broth microdilution results, very major rates were low (ϳ2.8%) for all three drugs across the methods, but major error rates were higher (ϳ5.6%), especially with the Etest method. For minocycline, minor error rates ranged from 14% to 37.4%. For tigecycline, minor error rates ranged from 6.5% to 69.2%. The majority of minor errors were due to susceptible results being reported as intermediate. A cinetobacter baumannii has become a major health care-associated pathogen over the past 2 decades, due to its intrinsic resistance to several classes of antimicrobial agents, its propensity to acquire resistance to other drug classes, and its ability to resist desiccation in environments typically found in hospitals (1). A. baumannii causes a variety of infections, with respiratory tract infections being the most common (1). Significant clinical challenges are posed by carbapenem-resistant A. baumannii, which accounted for over 75% of A. baumannii clinical isolates tested in a recent global survey (2). Mortality rates for carbapenem-resistant A. baumannii infections may be as high as 76% (3). Treatment options for carbapenem-resistant A. baumannii infections have not been well defined but generally include polymyxins (colistin and polymyxin B), tigecycline, or sulbactam, alone or in combination with a second agent, such as rifampin or a carbapenem, with the expectation of synergistic activities (4). However, toxicity (polymyxins), suboptimal pharmacokinetics (tigecycline), and the propensity for development of resistance (sulbactam) limit these options (1).Minocycline is a semisynthetic tetracycline derivative that was introduced into clinical practice in the 1960s (5). With the recent reintroduction of an intravenous formulation of minocycline, there is increasing interest in this agent as an additional treatment option for carbapenem-resi...

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“…These strains are usually multidrug-resistant (MDR) due to the coexpression of mechanisms involving other classes of antibiotics, thus drastically limiting our therapeutic armamentarium (2)(3)(4). In particular, extensively drug-resistant (XDR) isolates are commonly detected worldwide (5), whereas the prevalence of pandrug-resistant (PDR) isolates is increasing worryingly in several countries (6)(7)(8).…”

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In Vitro Activity of the Novel Antimicrobial Peptide Dendrimer G3KL against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa

Pires

Siriwardena

Stach

et al. 2015

Antimicrob Agents Chemother

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eThe in vitro activity of the novel antimicrobial peptide dendrimer G3KL was evaluated against 32 Acinetobacter baumannii (including 10 OXA-23, 7 OXA-24, and 11 OXA-58 carbapenemase producers) and 35 Pseudomonas aeruginosa (including 18 VIM and 3 IMP carbapenemase producers) strains and compared to the activities of standard antibiotics. Overall, both species collections showed MIC 50/90 values of 8/8 g/ml and minimum bactericidal concentrations at which 50% or 90% of strains tested are killed (MBC 50/90 ) of 8/8 g/ml. G3KL is a promising molecule with antibacterial activity against multidrug-resistant and extensively drug-resistant A. baumannii and P. aeruginosa isolates. The spread of Acinetobacter baumannii and Pseudomonas aeruginosa isolates that are resistant to carbapenem antibiotics due to the production of carbapenemases represents a serious threat (1). These strains are usually multidrug-resistant (MDR) due to the coexpression of mechanisms involving other classes of antibiotics, thus drastically limiting our therapeutic armamentarium (2-4). In particular, extensively drug-resistant (XDR) isolates are commonly detected worldwide (5), whereas the prevalence of pandrug-resistant (PDR) isolates is increasing worryingly in several countries (6-8). Therefore, novel antimicrobial strategies need to be rapidly developed.Recently, there has been a rising interest in evaluating naturally occurring or synthetic antimicrobial peptides (AMPs) with activity against prokaryotic membranes. This attention is due to their wide spectrum of activity against both Gram-positive and Gramnegative species, potent bactericidal activity, and ability to bypass common mechanisms of resistance that affect standard antibiotics (9, 10). However, several reasons have so far limited the clinical implementation of AMPs: (i) high susceptibility to degradation by endogenous and microbial proteases; (ii) toxicity due to the high concentration necessary to inhibit bacteria; and (iii) short half-life because of high protein binding (11). Several authors have modified AMPs to obtain proteolytically resistant versions, mostly by sequence variations and the use of D-amino acids (12-15). However, redesigning the peptide chain topology, in particular by introducing multiple branching points to obtain synthetic AMP dendrimers (AMPDs), seems a promising solution to overcome all of the the aforementioned problems (16-18).G3KL is a novel AMP dendrimer (AMPD) developed at the Department of Chemistry and Biochemistry of the University of Bern (Switzerland) by sequence optimization of an initial hit compound identified by screening a combinatorial library of dendrimers using a tailored high-throughput screening assay and presumed to act as a membrane-disrupting agent (19)(20)(21)(22). Its activity requires a dendritic topology and only natural lysine and leucine residues alternating in the branches (Fig. 1). This novel AMPD has demonstrated in vitro activity against several Gram-negative strains, low toxicity to human red blood cells (minimal hemolytic ...

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Acinetobacter baumannii: Evolution of Antimicrobial Resistance—Treatment Options

Cited by 226 publications

References 163 publications

Isolation and Characterization of Acinetobacter baumannii Recovered from Campylobacter Selective Medium

Isolation and Characterization of Acinetobacter baumannii Recovered from Campylobacter Selective Medium

Comparison of Minocycline Susceptibility Testing Methods for Carbapenem-Resistant Acinetobacter baumannii

In Vitro Activity of the Novel Antimicrobial Peptide Dendrimer G3KL against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa

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