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Acinetobacter baumannii
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
Secondly, the presence of colistin heteroresistance may be missed by standard phenotypic antimicrobial susceptibility testing. Heteroresistance is the presence of a subpopulations of resistant organisms in an isolate.
Drug-Resistant Tuberculosis
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Keertan Dheda, Aliasgar Esmail, Anzaan Dippenaar, Robin Warren, Jennifer Furin, Christoph Lange
Sequencing has the potential to provide a comprehensive genotypic DST. It facilitates the crafting of individualized treatment regimens, which are more likely to result in cure.152 However, the clinical impact of this strategy in different settings remains to be established. Targeted next-generation sequencing (NGS) (sequencing of specific genes amplified by polymerase chain reaction [PCR]) is more sensitive and allows for the detection of resistance conferring mutations in sputum samples (see Figure 16.3). It also has the additional advantage of detecting, otherwise undetectable, micro-heteroresistance (emerging low-level drug-specific resistant populations) at diagnosis and during the course of treatment.
Antifungal drug resistance: Significance and mechanisms
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Sharvari Dharmaiah, Rania A. Sherif, Pranab K. Mukherjee
Development of cross-resistance to itraconazole following fluconazole treatment is an under-reported problem [71,73,74]. Mondon et al. [75] reported isolation of C. neoformans isolates that exhibited unusual patterns of resistance (“heteroresistance”) to fluconazole and voriconazole from seven isolates from two different geographical regions (Israel and Italy), where most of the cells of each isolate were susceptible, but cells highly resistant to fluconazole (MICs ≥ 64 µg/mL) were recovered at a variable frequency. In a subsequent study, Yamazumi et al. [76] evaluated fluconazole susceptibility among 107 clinical isolates of C. neoformans (MIC between 0.25 and 32 µg/mL) and showed that exposure to fluconazole can induce heteroresistance. Other investigators have also reported the development of resistance in C. neoformans [77–79]. Taken together, these studies clearly demonstrate that C. neoformans isolates can acquire resistance against azoles.
Antimicrobial resistance in enteric bacteria: current state and next-generation solutions
Published in Gut Microbes, 2020
M. J. Wallace, S. R. S. Fishbein, G. Dantas
More recently, a non-canonical form of altered drug susceptibility called heteroresistance has been characterized, wherein a subpopulation of a monoisolate culture survives and replicates in the presence of certain antibiotics while the remaining population is killed off. The resistance phenotype observed in heteroresistant cells is characteristically transient and reversible after removal of the antibiotic stressor, underlining an intimate link between heteroresistance and cellular physiology.117 In the case of E. cloacae, heteroresistance appears dependent on the presence of phoQ, a broad regulator of a number of cellular processes, including colistin resistance genes.118,119C. difficile has also been described to have heteroresistance to metronidazole through an unknown mechanism.120 This phenomenon has been studied in other organisms and is not driven by one regulatory mechanism but rather, a number of diverse, stochastic cellular processes that are organism- and antibiotic-specific. Future efforts in continuing to understand, diagnose, and treat heteroresistance are greatly warranted. Furthermore, understanding the effect of the complex environment of the human gut on both innate drug susceptibility and phenotypic tolerance of enteric pathogens will be key to the development of novel therapeutic strategies.
Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam – epidemiology, laboratory detection and treatment implications
Published in Expert Review of Anti-infective Therapy, 2018
Norelle Sherry, Benjamin Howden
Heteroresistance, or the presence of an antimicrobial-resistant subpopulation of organisms within an overall susceptible population, has been demonstrated for fosfomycin against E. coli, K. pneumoniae, and particularly Pseudomonas aeruginosa. This usually manifests as the presence of small colonies (‘squatter colonies’) within zones of inhibition on either disk diffusion or E-tests, and has been confirmed by population analysis profile testing [5,38]. One of these studies has postulated that the inconsistency of fosfomycin BMD results may be due to the higher inoculum usually employed by BMD testing compared to AD, favoring growth of resistant subpopulations in BMD, which was partially ameliorated by decreasing the initial bacterial inoculum [38]. Time–kill curves in heteroresistant populations also demonstrated rapid regrowth of the resistant subpopulation in single-dose models [39]. Although emergence of resistance during treatment has been observed clinically [40], formal studies to demonstrate the clinical impact of this in vitro phenomenon have not been performed and are clearly warranted [38]. While the use of fosfomycin in combination with other antimicrobials has been suggested to decrease the risk of resistance emerging during treatment, in vitro data suggest that this may not completely mitigate the risk, particularly in Pseudomonas aeruginosa [41,42].
Emergence of coagulase-negative staphylococci
Published in Expert Review of Anti-infective Therapy, 2020
Karsten Becker, Anna Both, Samira Weißelberg, Christine Heilmann, Holger Rohde
A complicating factor is the ‘heteroresistance’ phenomenon, which describes that subpopulations of a given isogenic bacterial strain exhibit different susceptibilities to a particular antibiotic agent [139]. Classically, in the case of CoNS, a majority of the staphylococcal population is susceptible to β-lactams and glycopeptides, respectively, with a highly resistant minority, which is very difficult to detect by standard tests for susceptibility testing [140–144]. Antibiotic treatment guided according to the traditional susceptibility testing breakpoints could lead to therapeutic failure due to selection for the resistant subpopulation [139].