Fosfomycin targets the first step of peptidoglycan biosynthesis in Streptococcus pneumoniae catalyzed by UDP-N-acetylglucosamine enolpyruvyltransferase (MurA1). We investigated whether heteroresistance to fosfomycin occurs in S. pneumoniae. We found that of 11 strains tested, all but 1 (Hungary(19A)) displayed heteroresistance and that deletion of murA1 abolished heteroresistance. Hungary(19A) ...

"Heteroresistance" describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic. Unfortunately, a lack of standard methods to determine heteroresistance has led to inappropriate use of this term. Heteroresistance has been recognized since at least 1947 and occurs in Gram-positive and Gram-negative bacteria. Its clinica...

OBJECTIVES This study examined the phenomenon of heteroresistance in Mycobacterium tuberculosis clinical isolates obtained from retreated patients in Beijing, China between 2006 and 2011. METHODS The iPLEX Gold assay platform was used to determine the prevalence of heteroresistance to injectable second-line drugs (amikacin, kanamycin and capreomycin) in resistant isolates. RESULTS Heterores...

We describe an in vivo evolution of an antimicrobial profile from susceptibility to full-resistance to carbapenems, with heteroresistance as an intermediate stage, in an Acinetobacter baumannii strain. Heteroresistance was characterized by the growth of sub-populations within the susceptibility halo in both disk-diffusion and Etest. PCRs for the main A. baumannii carbapenemases were negative. T...

UNLABELLED Candida glabrata causes persistent infections in patients treated with fluconazole and often acquires resistance following exposure to the drug. Here we found that clinical strains of C. glabrata exhibit cell-to-cell variation in drug response (heteroresistance). We used population analysis profiling (PAP) to assess fluconazole heteroresistance (FLC(HR)) and to ask if it is a binary ...

Heteroresistance of Mycobacterium tuberculosis (MTB) is defined as the coexistence of susceptible and resistant organisms to anti-tuberculosis (TB) drugs in the same patient. Heteroresistance of MTB is considered a preliminary stage to full resistance. To date, no mechanism causing heteroresistance of MTB has been proven. Clinical specimens and cultures from 35 TB patients from Tashkent, Uzbeki...

Amplicon-based Next Generation Sequencing (NGS) is an emerging method for Mycobacterium tuberculosis drug susceptibility testing (DST) but has not been well described. We examined 158 clinical multidrug-resistant M. tuberculosis isolates via NGS of 11 resistance-associated gene regions covering 3519 nucleotides. Across these gene regions, complete resistance or heteroresistance (defined as 1%-9...

We compared the efficiencies of different drug susceptibility testing methods in detecting rifampin (RIF) heteroresistance in Mycobacterium tuberculosis. Our data revealed that the broth dilution method found more resistance than MGIT did (P=0.046) for the low-resistance group. Similarly, the broth dilution method was more sensitive in detecting RIF heteroresistance in subpopulations with low g...

23 We compared the efficiency of different drug susceptibility testing methods to detect 24 the rifampin (RIF) heteroresistance in Mycobacterium tuberculosis. Our data revealed 25 that broth dilution method found more resistance than MGIT (P=0.046) for low 26 resistance group. Similarly, broth dilution method was more sensitive to detect RIF 27 heteroresistance in subpopulation with slow grow r...

Colistin heteroresistance has been reported among Acinetobacter isolates; however, its association with prior colistin therapy has not been not described. A population analysis profile identified resistant Acinetobacter subpopulations from colistin-susceptible clinical isolates. The proportion of cells exhibiting heteroresistance was significantly higher among isolates recovered from patients t...