Prevalence and analysis of microbiological factors associated with phenotypic heterogeneous resistance to carbapenems in Acinetobacter baumannii

Cuenca, Felipe Fernández; Sánchez, M.; Caballero-Moyano, Francisco Javier; Vila, Jordi; Martínez-Martínez, Luis; Bou, Germán; Rodríguez-Baño, Jesús; Pascual, Álvaro

doi:10.1016/j.ijantimicag.2012.01.015

Cited by 25 publications

(15 citation statements)

References 29 publications

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“…1a). The behavior of these strains is in accordance with a previous report that a bla OXA-58-like gene-encoded hydrolase was demonstrated to always lead to phenotypic heterogeneous resistance (PHR) (heteroresistance) to carbapenems in Acinetobacter baumannii (1). …”

Section: Resultssupporting

confidence: 90%

“…The exploration of possible mechanisms of such resistance has led to intensive investigations of heteroresistance: phenotypic heterogeneous resistance to an antibiotic treatment within a clonal population (1–3). In laboratory practice, such resistant subpopulations emerge as resistant colonies grown inside the inhibitory halos in Etest and lead to a gradual decrease in the colony count on agar plates as the antibiotic concentration increases in a population analysis profile (PAP) assay (4).…”

Section: Introductionmentioning

confidence: 99%

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Heteroresistance at the Single-Cell Level: Adapting to Antibiotic Stress through a Population-Based Strategy and Growth-Controlled Interphenotypic Coordination

Wang

Luo

et al. 2014

mBio

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Heteroresistance refers to phenotypic heterogeneity of microbial clonal populations under antibiotic stress, and it has been thought to be an allocation of a subset of “resistant” cells for surviving in higher concentrations of antibiotic. The assumption fits the so-called bet-hedging strategy, where a bacterial population “hedges” its “bet” on different phenotypes to be selected by unpredicted environment stresses. To test this hypothesis, we constructed a heteroresistance model by introducing a blaCTX-M-14 gene (coding for a cephalosporin hydrolase) into a sensitive Escherichia coli strain. We confirmed heteroresistance in this clone and that a subset of the cells expressed more hydrolase and formed more colonies in the presence of ceftriaxone (exhibited stronger “resistance”). However, subsequent single-cell-level investigation by using a microfluidic device showed that a subset of cells with a distinguishable phenotype of slowed growth and intensified hydrolase expression emerged, and they were not positively selected but increased their proportion in the population with ascending antibiotic concentrations. Therefore, heteroresistance—the gradually decreased colony-forming capability in the presence of antibiotic—was a result of a decreased growth rate rather than of selection for resistant cells. Using a mock strain without the resistance gene, we further demonstrated the existence of two nested growth-centric feedback loops that control the expression of the hydrolase and maximize population growth in various antibiotic concentrations. In conclusion, phenotypic heterogeneity is a population-based strategy beneficial for bacterial survival and propagation through task allocation and interphenotypic collaboration, and the growth rate provides a critical control for the expression of stress-related genes and an essential mechanism in responding to environmental stresses.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Heteroresistance at the Single-Cell Level: Adapting to Antibiotic Stress through a Population-Based Strategy and Growth-Controlled Interphenotypic Coordination

Wang

Luo

et al. 2014

mBio

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“…In current study, emergence of heterogeneous resistance was confirmed in three strains through E-test and disk diffusion methods for Colistin, isolates presenting colonies inside the inhibition zone were considered to have phenotypic heterogeneous resistance to Colistin (14). Isolated strains are increasingly becoming pan resistant and even those strains that are especially resistant are difficult to treat due to the nephrotoxicity and increasing intermediate sensitivity to Colistin.…”

Section: Discussionmentioning

confidence: 86%

Nosocomial Outbreak of Extensively and Pan Drug-Resistant Acinetobacter baumannii in Tertiary Hospital in Central Part of Iran

Japoni-Nejad

Sofian

Belkum

et al. 2013

Jundishapur J Microbiol

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Background:Acinetobacter baumannii has emerged as a cause of nosocomial infections in hospitalized patients, particularly in intensive care units. Carbapenems are a common choice for treating nosocomial infections caused by A. baumannii strains. Increasing antimicrobial resistance among Acinetobacter isolates has been documented and multidrug-resistant A. baumannii is recognized to be among the most difficult antimicrobial-resistant bacilli to control and treat. Objectives: This study describes carbapenem resistance in A. baumannii isolates obtained during an outbreak from intensive care units of a peripheral hospital in central part of Iran. Patients and Methods: Sixty-three non-repetitive A. baumannii isolates were collected over a six months period. Susceptibility of the isolated bacteria to a panel of 23 different antimicrobial agents was defined by using the standard disk diffusion method. Production of Metallo-β-lactamases (MBL) and AmpC β-lactamase were determined by using the E-test MBL strip and AmpC disk tests, respectively. Results: The present study indicates that carbapenems and new cephalosporin antibiotics were practically ineffective against the extensive drug resistance (XDR) strains. Colistin was observed to be more effective, although in seven cases resistance to colistin observed. AmpC β-lactamase and MBL could be an important contributory factor for imipenem resistance among the isolates in our hospital. The elevated prevalence of XDR and pan drug resistance (PDR) strains indicates that local antibiotic prescription policies should be revised and infection control should be improved. Conclusions:The elevated prevalence of XDR and PDR strains indicates that local antibiotic prescription policies should be revised and infection control should be improved.

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“…The overproduction of intrinsic chromosomal OXA-51-like enzymes and the production of acquired OXA23, OXA-24/40, and OXA-58 enzymes has been associated with carbapenem-resistant A. baumannii isolates. The use of carbapenems may also be diminished via heteroresistance to these antibiotics, which is a phenomenon that can occur in both carbapenem-susceptible and -resistant isolates (3). As a consequence of limited therapeutic options, drug treatment with newer antimicrobials or antimicrobial combinations has become increasingly important for treating infections caused by these isolates.…”

mentioning

confidence: 99%

Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?

García-Salguero

Rodríguez-Avial

Picazo

et al. 2015

Antimicrob Agents Chemother

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Nosocomial pathogens can be associated with a variety of infections, particularly in intensive care units (ICUs) and in immunocompromised patients. Usually these pathogens are resistant to multiple drugs and pose therapeutic challenges. Among these organisms, Acinetobacter baumannii is one of the most frequent being encountered in the clinical setting. Carbapenems are very useful to treat infections caused by these drug-resistant Gram-negative bacilli, but carbapenem resistance is increasing globally. Combination therapy is frequently given empirically for hospital-acquired infections in critically ill patients and is usually composed of an adequate beta-lactam and an aminoglycoside. The purpose of this study was to evaluate the in vitro activity of plazomicin against carbapenem-resistant Acinetobacter baumannii. Amikacin was used as a comparator. The activity of plazomicin in combination with several different antibiotics was tested by disk diffusion, the checkerboard method, and time-kill studies. Synergy was consistently observed with carbapenems (meropenem and/or imipenem) along with plazomicin or amikacin. When the aminoglycosides were combined with other classes of antibiotics, synergy was observed in some cases, depending on the strain and the antibiotic combination; importantly, there was no antagonism observed in any case. These findings indicate the potential utility of plazomicin in combination with other antibiotics (mainly carbapenems) for the treatment of A. baumannii infections, including those caused by carbapenem-resistant isolates.

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Prevalence and analysis of microbiological factors associated with phenotypic heterogeneous resistance to carbapenems in Acinetobacter baumannii

Cited by 25 publications

References 29 publications

Heteroresistance at the Single-Cell Level: Adapting to Antibiotic Stress through a Population-Based Strategy and Growth-Controlled Interphenotypic Coordination

Heteroresistance at the Single-Cell Level: Adapting to Antibiotic Stress through a Population-Based Strategy and Growth-Controlled Interphenotypic Coordination

Nosocomial Outbreak of Extensively and Pan Drug-Resistant Acinetobacter baumannii in Tertiary Hospital in Central Part of Iran

Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?

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