Viridans Streptococci Bacteremia in Children with Malignancy

Husain, Entesar H.; Whitehead, Sue; Castell, Annette; Thomas, Eva; Speert, David P.

doi:10.1097/01.inf.0000164708.21464.03

Cited by 36 publications

(23 citation statements)

References 11 publications

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“…Accurate species identification is pertinent not only for epidemiological purposes but has potential implications for the clinical management of VGS infections. For example, recent studies show that Streptococcus mitis strains cause a higher incidence of severe clinical disease and have higher rates of resistance to penicillin and fluoroquinolones than do other VGS species (2,(4)(5)(6). Additionally, other VGS species have predilections to cause distinct types of infections, such as endocarditis by Streptococcus sanguinis and gastrointestinal infections by Streptococcus anginosus (2,6).…”

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confidence: 99%

“…iridans group streptococci (VGS) are a genetically heterogeneous group of commensal bacteria that cause a wide range of infections in humans, particularly in persons with hematologic disease or neutropenia as a result of chemotherapy (1,2). Although Ͼ25 VGS species have been described, rapid and reliable identification to the species level eludes this group of organisms (3,4).…”

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GyrB Polymorphisms Accurately Assign Invasive Viridans Group Streptococcal Species

et al. 2014

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Viridans group streptococci (VGS) are a heterogeneous group of medically important bacteria that cannot be accurately assigned to a particular species using conventional phenotypic methods. Although multilocus sequence analysis (MLSA) is considered the gold standard for VGS species-level identification, MLSA is not yet feasible in the clinical setting. Conversely, molecular methods, such as sodA and 16S rRNA gene sequencing, are clinically practical but not sufficiently accurate for VGS species-level identification. Here, we present data regarding the use of an ϳ400-nucleotide internal fragment of the gene encoding DNA gyrase subunit B (GyrB) for VGS species-level identification. MLSA, internal gyrB, sodA, full-length, and 5= 16S gene sequences were used to characterize 102 unique VGS blood isolates collected from 2011 to 2012. When using the MLSA species assignment as a reference, full-length and 5= partial 16S gene and sodA sequence analyses failed to correctly assign all strains to a species. Precise species determination was particularly problematic for Streptococcus mitis and Streptococcus oralis isolates. However, the internal gyrB fragment allowed for accurate species designations for all 102 strains. We validated these findings using 54 VGS strains for which MLSA, 16S gene, sodA, and gyrB data are available at the NCBI, showing that gyrB is superior to 16S gene and sodA sequence analyses for VGS species identification. We also observed that specific polymorphisms in the 133-amino acid sequence of the internal GyrB fragment can be used to identify invasive VGS species. Thus, the GyrB amino acid sequence may offer a more practical and accurate method for classifying invasive VGS strains to the species level.V iridans group streptococci (VGS) are a genetically heterogeneous group of commensal bacteria that cause a wide range of infections in humans, particularly in persons with hematologic disease or neutropenia as a result of chemotherapy (1, 2). Although Ͼ25 VGS species have been described, rapid and reliable identification to the species level eludes this group of organisms (3, 4). Accurate species identification is pertinent not only for epidemiological purposes but has potential implications for the clinical management of VGS infections. For example, recent studies show that Streptococcus mitis strains cause a higher incidence of severe clinical disease and have higher rates of resistance to penicillin and fluoroquinolones than do other VGS species (2, 4-6). Additionally, other VGS species have predilections to cause distinct types of infections, such as endocarditis by Streptococcus sanguinis and gastrointestinal infections by Streptococcus anginosus (2, 6).Routine tests and commercial kits used in clinical practice based on the phenotypic and biochemical traits of individual species, such as API Rapid ID32 Strep, Vitek 2, and Streptogram, have only a 30% to 80% accuracy rate for VGS, depending on the species (7-10). The inherent problems with these approaches lie in the variability of traits within V...

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GyrB Polymorphisms Accurately Assign Invasive Viridans Group Streptococcal Species

et al. 2014

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“…Antibiotic resistance has been reported primarily for penicillin, macrolides, and fluoroquinolones (4,6,7,9,12). The resistance related to the mef and erm genes, which confer resistance to macrolides, lincosamides, and streptogramin B, has been well characterized in VGS (3,4,7,12). More recently, reports of daptomycin and linezolid resistance have also been published; these reports include both in vitro studies and in vivo studies with 2 clinical cases for each agent (20)(21)(22)(23)(24)(25).…”

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confidence: 99%

“…iridans group streptococci (VGS) include a number of species and are commensal Gram-positive bacteria often responsible for human disease, particularly infective endocarditis and bacteremia in neutropenic patients (1)(2)(3)(4)(5). Historically, these organisms have been relatively susceptible to most antibiotics.…”

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Characterization of High-Level Daptomycin Resistance in Viridans Group Streptococci Developed upon In Vitro Exposure to Daptomycin

Akins

Katz

Monahan

et al. 2015

Antimicrob Agents Chemother

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cViridans group streptococci (VGS) are part of the normal flora that may cause bacteremia, often leading to endocarditis. We evaluated daptomycin against four clinical strains of VGS (MICs ‫؍‬ 1 or 2 g/ml) using an in vitro-simulated endocardial vegetation model, a simulated bacteremia model, and kill curves. Daptomycin exposure was simulated at 6 mg/kg of body weight and 8 mg/kg every 24 h for endocardial and bacteremia models. Total drug concentrations were used for analyses containing protein (albumin and pooled human serum), and free (unbound) drug concentrations (93% protein bound) were used for analyses not containing protein. Daptomycin MICs in the presence of protein were significantly higher than those in the absence of protein. Despite MICs below or at the susceptible breakpoint, all daptomycin regimens demonstrated limited kill in both pharmacodynamic models. A reduction of approximately 1 to 2 log 10 CFU was seen for all isolates and dosages except daptomycin at 6 mg/kg, which achieved a reduction of 2.7 log 10 CFU/g against one strain (Streptococcus gordonii 1649) in the endocardial model. Activity was similar in both pharmacodynamic models in the presence or absence of protein. Similar activity was noted in the kill curves over all multiples of the MIC. Regrowth by 24 h was seen even at 8؋ MIC. Postexposure daptomycin MICs for both pharmacodynamic models increased to >256 g/ml for all isolates by 24 and 72 h. Despite susceptibility to daptomycin by standard MIC methods, these VGS developed high-level daptomycin resistance (HLDR) after a short duration following drug exposure not attributed to modification or inactivation of daptomycin. Further evaluation is warranted to determine the mechanism of resistance and clinical implications.

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“…A mong the viridans group streptococci, the members of the Streptococcus mitis group are the most frequent cause of human infective endocarditis (IE) and the most common cause of the toxic streptococcal bacteremia syndrome seen in immunocompromised hosts (1)(2)(3)(4)(5)(6)(7)(8). This organism is often resistant in vitro to ␤-lactam antibiotics, including penicillin and ceftriaxone (9)(10)(11)(12)(13)(14)(15)(16).…”

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Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis

García-de-la-Mària

Xiong

Pericàs

et al. 2017

Antimicrob Agents Chemother

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Among the viridans group streptococci, the Streptococcus mitis group is the most common cause of infective endocarditis. These bacteria have a propensity to be ␤-lactam resistant, as well as to rapidly develop high-level and durable resistance to daptomycin (DAP). We compared a parental, daptomycin-susceptible (DAP s ) S. mitis/S. oralis strain and its daptomycin-resistant (DAP r ) variant in a model of experimental endocarditis in terms of (i) their relative fitness in multiple target organs in this model (vegetations, kidneys, spleen) when animals were challenged individually and in a coinfection strategy and (ii) their survivability during therapy with daptomycin-gentamicin (an in vitro combination synergistic against the parental strain). The DAP r variant was initially isolated from the cardiac vegetations of animals with experimental endocarditis caused by the parental DAP s strain following treatment with daptomycin. The parental strain and the DAP r variant were comparably virulent when animals were individually challenged. In contrast, in the coinfection model without daptomycin therapy, at both the 10 6 -and 10 7 -CFU/ml challenge inocula, the parental strain outcompeted the DAP r variant in all target organs, especially the kidneys and spleen. When the animals in the coinfection model of endocarditis were treated with DAP-gentamicin, the DAP s strain was completely eliminated, while the DAP r variant persisted in all target tissues. These data underscore that the acquisition of DAP r in S. mitis/S. oralis does come at an intrinsic fitness cost, although this resistance phenotype is completely protective against therapy with a potentially synergistic DAP regimen.

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Viridans Streptococci Bacteremia in Children with Malignancy

Cited by 36 publications

References 11 publications

GyrB Polymorphisms Accurately Assign Invasive Viridans Group Streptococcal Species

GyrB Polymorphisms Accurately Assign Invasive Viridans Group Streptococcal Species

Characterization of High-Level Daptomycin Resistance in Viridans Group Streptococci Developed upon In Vitro Exposure to Daptomycin

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis

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