Viridans Group Streptococci Isolates Research Articles

Performance assessment of the Bruker Biotyper MALDI-TOF MS for the identification of difficult-to-identify viridans group streptococci.

Differentiating Streptococcus pneumoniae among nonpneumococcal viridans group streptococci (VGS) is challenging in conventional laboratories. Therefore, we aimed to evaluate the performance of the latest Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system in identifying VGS by comparing the results to those of the specific gene sequencing approach. Clinical isolates were initially identified using the BD Phoenix system to identify Streptococcus species. The optochin test was used to distinguish nonpneumococcal VGS from S. pneumoniae. The species of individual reference strains and clinical isolates were determined by comparing the sequences of the 16S rDNA, gyrB, sodA, groESL, or coaE genes with those in the GenBank sequence databases. We evaluated the performance of the Bruker Biotyper MALDI-TOF MS in VGS identification using two different machines with three databases. We collected a total of 103 nonpneumococcal VGS and 29 S. pneumoniae blood isolates at a medical center in northern Taiwan. Among these isolates, only seven could not be identified at the species level by the specific gene sequencing approach. We found that none of the nonpneumococcal VGS isolates were misidentified as pneumococci by the latest Biotyper system, and vice versa. However, certain strains, especially those in the mitis and bovis groups, could still not be correctly identified. The latest Bruker Biotyper 4.1 (DB_10833) showed significant improvement in identifying VGS strains. However, a specific gene sequencing test is still needed to precisely differentiate the species of strains in the mitis and bovis groups.

Oritavancin in vitro activity against Gram-positive organisms from European medical centers: a 10-year longitudinal overview from the SENTRY Antimicrobial Surveillance Program (2010–2019)

To assess oritavancin in vitro activity against clinically relevant Gram-positive pathogens in European (EU) hospitals, a total of 51,531 consecutive and unique clinical isolates collected in 2010–2019 were evaluated. All isolates were tested by CLSI broth microdilution methods. The key resistance phenotypes differed considerably between Eastern Europe (E-EU) and Western Europe (W-EU), respectively: methicillin-resistant (MR) Staphylococcus aureus 27.7%/22.9%; multidrug resistant (MDR) S. aureus, 19.7%/15.2%; MR coagulase-negative staphylococci, 77.3%/61.9%; vancomycin-resistant enterococci (E. faecium), 44.2%/20.9%; and MDR E. faecium, 63.8%/55.4%. There were no substantive differences in oritavancin minimum inhibitory concentration (MIC) values for the different species/organism groups over time or by EU region. Oritavancin inhibited 99.9% and 99.1% of all S. aureus and coagulase-negative staphylococci at 0.12 mg/L, respectively, and all isolates of E. faecalis and E. faecium at ≤0.5 mg/L. Oritavancin susceptibility rates against β-hemolytic and Viridans group streptococci isolates were 98.1% and 99.4%, respectively. Oritavancin had potent activity in vitro against this contemporary collection of European Gram-positive isolates from 2010 to 2019.

Emerging Resistance Trends in Viridans Group Streptococci Bloodstream Infections Among Immunocompromised Children Receiving Levofloxacin Prophylaxis.

Levofloxacin prophylaxis (LVXp) is often used for patients with underlying leukemia and severe neutropenia to reduce the risk of fever and bacteremia. This study evaluated trends in viridans group streptococci (VGS) antibiotic susceptibilities over time and clinical outcomes of children with VGS bloodstream infections (BSIs) during institutional adoption of LVXp. VGS blood culture isolates between 1/1/2010 and 12/31/2021 with susceptibility testing reported were included. Available isolates were re-identified to the species level and additional susceptibility testing was performed. Demographic and clinical data were abstracted from medical records. A total of 264 VGS BSI isolates were identified in immunocompromised (IC, n = 125) and non-immunocompromised subjects, (non-IC, n = 139). IC subjects had lower rates of VGS isolates susceptible (S) to LVX and higher minimum inhibitory concentration (MICs) to LVX (p = 0.004) and ciprofloxacin (p = 0.0005) compared with non-IC subjects. No other evaluated antibiotic had increased MICs in either group. Fifteen of 19 (74%) LVX not susceptible (NS) isolates occurred in IC subjects, 13 represented breakthrough infections. IC subjects had higher rates of VGS-related shock (p = 0.012), need for pressor support (p = 0.039), and longer duration of hospitalization than non-IC subjects (p < 0.001). Clinical outcomes were comparable between subjects with LVX S and NS VGS BSI isolates. VGS with reduced susceptibility to LVX emerged during institutional adoption of LVXp in high-risk children with immunocompromising conditions, but did not result in significant differences in clinical outcomes. Ongoing surveillance and susceptibility testing are critical in weighing the utility of LVXp against emerging antimicrobial resistance in this high-risk population.

Performance of Two Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS) Systems for Identification of the Viridans Group Streptococci.

Due to similar colony morphology among viridans group streptococci (VGS), the differentiation of VGS species remains difficult in routine clinical microbiology. Recently, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) has been described as a fast method for identifying various bacteria at species level, and also for the VGS strains. A total of 277 VGS isolates were identified with the two MALDI-TOF MS systems (VITEK MS and Bruker Biotyper). The tuf and rpoB gene sequencing was used as the reference identification method for comparison. Based on tuf and rpoB gene sequencing, 84 isolates were S. pneumoniae and 193 strains were other VGS isolates including S. anginosus group (n=91, 47.2%), S. mitis group (n=80, 41.5%), S. bovis group (n=11, 5.7%), S. salivarius group (n=10, 5.2%), and S. mutans group (n=1, 0.5%). VITEK MS and Bruker Biotyper accurately identified 94.6% and 89.9% of all VGS isolates, respectively. VITEK MS showed better identification results than Bruker Biotyper for S. mitis group including S. pneumoniae and S. bovis group, but for other VGS isolates, two MALDI-TOF MS systems showed comparable identification performance. However, VITEK MS was able to identify S. gallolyticus to the subspecies level with high-confidence (S. gallolyticus ssp. pasteurianus), while the Bruker Biotyper system could not. While Bruker Biotyper system could be able to correctly differentiate the subspecies of S. salivarius from S. vestibularis, VITEK MS poorly identify. This study demonstrated that two MALDI-TOF MS systems allowed discrimination for most VGS isolates with different identification performance, but Bruker Biotyper could produce more misidentifications and VITEK MS system. It is crucial to be familiar with the performance of MALDI-TOF MS systems used in clinical microbiology.

Species designation of streptococci causing infective endocarditis in patients with mitral valve prolapse

Viridans group streptococci (VGS) have been previously linked to infective endocarditis (IE) in patients with mitral valve prolapse (MVP). The species identification of VGS is now available in clinical laboratories; however, it has not been examined in MVP IE. Therefore, we detailed the clinical profile, species designations, and antibiotic susceptibility of VGS isolates from patients with MVP IE. We retrospectively queried all adults with MVP and a definite or possible IE diagnosis seen at medical centers of the Mayo Clinic Enterprise from January 2009 to December 2021. Data, including clinical characteristics, comorbidities, microbiology, and outcomes, were extracted from electronic health records. VGS isolates from patients with MVP and IE were subclassified into mutans, salivarius, anginosus, sanguinis, and mitis groups. A total of 38 patients with MVP with IE due to streptococcal species were included. Overall, median age was 62.4 years and 32% of patients were females. The most prevalent comorbidities were diabetes mellitus (26%), hypertension (21%), heart failure (16%), and malignancy (16%). A total of (37%) patients presented with an embolic event at the time of their IE diagnosis, 27 (66%) required valve surgery, and no patient died within the hospital stay. The Streptococcus mitis group was the predominant (n=17, 45%) species designation; S. anginosus and S. sanguinis were identified in three (8%) each; S. mutans in two (5%); and S. salivarius in one (3%).Non-VGS streptococcal pathogens included S. agalactiae in three patients (8%), S. equi in two (5%), and S. dysgalactiae and S. bovis in one each (3%). VGS were identified in five (13%) patients, but species designation was not done. No penicillin resistance was identified among the isolates. The S. mitis group was the predominant species in our investigation. Continued evaluation of VGS species should be considered to profile the IE risk based on species identification.

1819. Characterizing Treatment Duration of Viridans Group Streptococci Bacteremia in Neutropenic Cancer Patients: Is 14 Days Necessary?

Abstract Background Neutropenic oncology patients often have mucosal barrier injury as a consequence of chemotherapy and are at risk of Viridans Group Streptococci (VGS) bacteremia. VGS is a commonly identified pathogen among oncology patients with neutropenic fever, however, limited data exists as to appropriate treatment duration. Methods The purpose of this study is to characterize the treatment duration and clinical course among neutropenic oncology patients with VGS bacteremia. A retrospective chart review of patients with VGS bacteremia from June 1, 2020 through January 31, 2022 at the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA). Eligible patients include adults ≥ 18 years with any cancer diagnosis, absolute neutrophil count ≤ 500 at time of blood culture collection, ≥ 1 positive blood culture for VGS, and treated with antibiotics for ≥ 48 hours. Polymicrobial infections were excluded. Results Among 86 patients identified with VGS bacteremia, 57 patients were included. Baseline characteristics are depicted in TABLE 1. Hematologic malignancy was present in a majority of patients. The mean duration of treatment was 12.4 (± 2.9) days. Mean time to defervescence was 3.7 days. The most common empiric regimen was cefepime + vancomycin (64.9%) with 78.9% of patients receiving ceftriaxone as definitive therapy. All VGS isolates were susceptible to at least one drug in their empiric regimen. Clinical outcomes are depicted in TABLE 2. There was 1 recurrence of VGS bacteremia and three deaths in the cohort. In TABLE 3, results are stratified by treatment duration. Conclusion There was significant heterogeneity in the duration of treatment of VGS bacteremia among neutropenic cancer patients utilizing levofloxacin prophylaxis, with &amp;gt; 50% treated in excess of 14 days. Fever persisted for several days despite active antimicrobials consistent with prior reports. The low rate of recurrence and death at any treatment duration suggests that a shorter duration of less than 14 days for VGS bacteremia may be feasible. A prospective evaluation is needed to confirm these findings. Disclosures All Authors: No reported disclosures.

Comparative Genomics of Streptococcus oralis Identifies Large Scale Homologous Recombination and a Genetic Variant Associated with Infection.

The viridans group streptococci (VGS) are a large consortium of commensal streptococci that colonize the human body. Many species within this group are opportunistic pathogens causing bacteremia and infective endocarditis (IE), yet little is known about why some strains cause invasive disease. Identification of virulence determinants is complicated by the difficulty of distinguishing between the closely related species of this group. Here, we analyzed genomic data from VGS that were isolated from blood cultures in patients with invasive infections and oral swabs of healthy volunteers and then determined the best-performing methods for species identification. Using whole-genome sequence data, we characterized the population structure of a diverse sample of Streptococcus oralis isolates and found evidence of frequent recombination. We used multiple genome-wide association study tools to identify candidate determinants of invasiveness. These tools gave consistent results, leading to the discovery of a single synonymous single nucleotide polymorphism (SNP) that was significantly associated with invasiveness. This SNP was within a previously undescribed gene that was conserved across the majority of VGS species. Using the growth in the presence of human serum and a simulated infective endocarditis vegetation model, we were unable to identify a phenotype for the enriched allele in laboratory assays, suggesting a phenotype may be specific to natural infection. These data highlighted the power of analyzing natural populations for gaining insight into pathogenicity, particularly for organisms with complex population structures like the VGS. IMPORTANCE The viridians group streptococci (VGS) are a large collection of closely related commensal streptococci, with many being opportunistic pathogens causing invasive diseases, such as bacteremia and infective endocarditis. Little is known about virulence determinants in these species, and there is a distinct lack of genomic information available for the VGS. In this study, we collected VGS isolates from invasive infections and healthy volunteers and performed whole-genome sequencing for a suite of downstream analyses. We focused on a diverse sample of Streptococcus oralis genomes and identified high rates of recombination in the population as well as a single genome variant highly enriched in invasive isolates. The variant lies within a previously uncharacterized gene, nrdM, which shared homology with the anaerobic ribonucleoside triphosphate reductase, nrdD, and was highly conserved among VGS. This work increased our knowledge of VGS genomics and indicated that differences in virulence potential among S. oralis isolates were, at least in part, genetically determined.

1077. In Vitro Activity of Delafloxacin Agent Against Bacterial Isolates Recovered from Patients with Cancer

Abstract Background Fluoroquinolones have been used for infection prevention in patients with cancer (PWC). They are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms (GPO). Quinolone resistance is increasing and many institutions are using combination regimens for antimicrobial prophylaxis. We evaluated the in vitro activity of delafloxacin (DLX), a novel fluoroquinolone, and selected comparators against 560 bacterial isolates from PWC. Methods Isolates were from recent blood cultures. Susceptibility testing and time kill studies (TKS) were performed using CLSI approved methodology. Appropriate ATCC control strains were used. We calculated MIC50, MIC90, MIC ranges and percent susceptibility using FDA breakpoints when available. TKS were performed on 4 streptococcus mitis isolates at concentrations of MIC, 4x MIC, and 8x MIC. Results DLX was more active than ciprofloxacin (CIP) and levofloxacin (LEV) against methicillin-susceptible (MSSA), and resistant (MRSA) S. aureus, coagulase-negative staphylococci (CoNS), and viridans group streptococci (VGS), and had similar activity against beta-hemolytic streptococci. It also had low MICs for Bacillus species (SPP.), Listeria monocytogenes, Micrococcus spp., and Rothia spp. Overall GPO susceptibility was 73% to DLX, 42% to CIP, and 52% to LEV. The activity of DLX against Enterobacterales was similar to CIP and LEV. All 3 agents had moderate activity against Citrobacter spp., and non-MDR P. aeruginosa. Notably, all 3 quinolones had poor activity against E. coli, P. mirabilis, and MDR P. aeruginosa, all common pathogens in PWC. All 3 had low MICs for Acinetobacter spp. DLX and LEV achieved peak bactericidal activity at 6-8 h against all 4 VGS isolates (maximum activity at 8x MIC) but this was not always sustained at 24 h. Table 1. Percent Susceptibility of selected Gram-positive isolates to Delafloxacin, Ciprofloxacin and Levofloxacin Table 2. Percent Susceptibility of selected Gram-negative isolates to Delafloxacin, Ciprofloxacin and Levofloxacin Figure 1. Bactericidal Activity of DLX at 1x , 4x, and 8x MIC against VGS - Time Kill Study Conclusion DLX is more active than CIP and LEV against many GPO from PWC (including S. aureus and VGS), but like these agents there are significant gaps in its coverage against GNB. It is probably not suitable as a single agent for antimicrobial prophylaxis in high-risk PWC. The current practice of combining a quinolone with a beta-lactam probably still represents the best option in PWC who need prophylaxis. Disclosures Kenneth Rolston, MD, Tetraphase Pharmaceuticals (Grant/Research Support)

Isolation and Identification of Optochin-Resistant Viridans Group Streptococci from the Sputum Samples of Adult Patients in Jakarta, Indonesia.

Aim To investigate optochin-resistant viridans group streptococci (VGS) strains isolated from the sputum sample of adult patients with different clinical symptoms. Materials and Methods Optochin-resistant VGS isolates were identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). recA sequencing was used to confirm identified isolates at the genus level by MALDI-TOF MS. Finding. We identified 79% of tested isolates (148/187) at the species-level identification using the MALDI-TOF MS tool. We identified that the most common species isolated from sputum specimens were S. oralis (44.9%) followed by S. mitis (25.7%), S. infantis (9.1%), S. parasanguinis (7.5%), S. peroris (3.7%), S. anginosus (2.7%), and S. sanguinis (2.1%). Discussion. The S. oralis strains were majority of optochin-resistant VGS isolates obtained from sputum of adult patients in Jakarta, Indonesia. MALDI-TOF MS showed potential for the rapid identification tool to identify optochin-resistant VGS isolates. Although there were discrepancies in identifying isolates at the genus/species level, the performance could be improved by expanding its database.

Antibiotic Resistance of Viridans Group Streptococci Isolated from Dental Plaques.

Viridans group streptococci (VGS) are a common cause of infective endocarditis, and dental plaque is the major source of these bacteria. The present study examined the antibiotic resistance of 635 VGS isolates obtained from dental plaques. Isolates from supragingival plaques were identified using the rapid ID 32 Strep and mini API reader (bioMérieux, France), and minimal inhibitory concentrations (MICs) were determined by a broth microdilution method. High rates of resistance to ampicillin and tetracycline were detected among the isolates. The most resistant species were Streptococcus sanguinis and Streptococcus salivarius. Among the 635 isolates, 9.1% were resistant to erythromycin, and 20.6% to tetracycline. All isolates were sensitive to vancomycin. Resistance to amoxicillin was observed in 0.2% of all isolates. In this study, we showed the incidence of antimicrobial resistance and the susceptibility patterns among 635 VGS isolates from dental plaque.

2686. strong&gt;Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) with Fever and Neutropenia (FN): Viridans Group Streptococcus Emerges as an Important Pathogen

BackgroundIn this prospective nation-wide survey of bloodstream isolates associated with first episode of FN in high-risk cancer patients from 14 US cancer centers (December 2016 and June 2018), viridans group Streptococci (VGS) were the most common Gram-positive isolate. We sought to clinically and microbiologically characterize VGS bloodstream infections (BSI).MethodsAmong 343 patients,we compared 90 with VGS vs 253 with non-VGS BSI. Minimum inhibitory concentrations for blood culture isolates were determined by broth dilution for selected agents at our reference microbiology laboratory (UNMC). Clinical data were electronically captured in RedCap, including local site isolate identification and confirmatory reference lab identification via MALDI. Categorical and continuous variables were assessed via chi-square and Mann–Whitney U tests, respectively.ResultsNinety-two VGS isolates were identified among 90 FN patients, representing 27% of all BSI isolates. S. mitis or oralis comprised 64 (70%) of VGS. There were no differences between age, sex, and primary diagnosis (50% with AML) among the 2 groups; 1/3 were HSCT recipients. Fluoroquinolone prophylaxis was used in 64 (71%) vs. 139 (55%), P < 0.01, in VGS vs non-VGS groups. Critical illness composite (new need for pressor(s), mechanical ventilation or death within 30 days) was 6 (7%) vs. 44 (17%), P = 0.01, in the VGS vs non-VGS groups. Figure 1 displays an overview of antibiotic susceptibilities for 79 testable isolates. VGS susceptibilities to levofloxacin, penicillin, and ceftriaxone were 39%, 47%, and 94%, respectively.ConclusionVGS are common pathogens in FN patients. Prior fluoroquinolone prophylaxis use may be a risk factor. VGS BSI was not associated with increased critical illness compared with non-VGS. Finally, assuming ceftriaxone susceptibility confers that of cefepime, >90% of VGS are susceptible to empiric FN cefepime regimens. Disclosures All authors: No reported disclosures.

Variants of the bile: solubility test to differentiate Streptococcus pneumoniae from other viridans group streptococci.

Aim: Bile salts promote the specific autolysis of pneumococcal cells, allowing the differentiation between Streptococcus pneumoniae and other viridans group streptococci (VGS). Material & methods: One hundred clinical VGS isolates identified by amplification and sequencing of 16S rRNA, groEL and sodA genes were analyzed with different variants of bile-solubility tests: tube testing read by naked eye; tube testing where the lysis was measured as the decrease of turbidity with a densitometer; and direct testing on blood agar plate. Results: As expected, all S. pneumoniae isolates were fully lysed in the presence of bile salts except for one isolate that partially lysate in tube testing as well as on the blood agar plate. None of the VGS were lysed by bile salts. Conclusion: Bile-solubility testing is an accurate and technically nondemanding method to discriminate between S. pneumoniae and other VGS species.

Oropharyngeal Bacterial Colonization after Chlorhexidine Mouthwash in Mechanically Ventilated Critically Ill Patients.

WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Oropharyngeal care with chlorhexidine to prevent ventilator-associated pneumonia is currently questioned, and exhaustive microbiologic data assessing its efficacy are lacking. The authors therefore aimed to study the effect of chlorhexidine mouthwash on oropharyngeal bacterial growth, to determine chlorhexidine susceptibility of these bacteria, and to measure chlorhexidine salivary concentration after an oropharyngeal care. This observational, prospective, single-center study enrolled 30 critically ill patients under mechanical ventilation for over 48 h. Oropharyngeal contamination was assessed by swabbing the gingivobuccal sulcus immediately before applying 0.12% chlorhexidine with soaked swabs, and subsequently at 15, 60, 120, 240, and 360 min after. Bacterial growth and identification were performed, and chlorhexidine minimal inhibitory concentration of recovered pathogens was determined. Saliva was collected in 10 patients, at every timepoint, with an additional timepoint after 30 min, to measure chlorhexidine concentration. Two hundred fifty bacterial samples were analyzed and identified 48 pathogens including Streptococci (27.1%) and Enterobacteriaceae (20.8%). Oropharyngeal contamination before chlorhexidine mouthwash ranged from 10 to 10 colony-forming units (CFU)/ml in the 30 patients (median contamination level: 2.5·10 CFU/ml), and remained between 8·10 (lowest) and 3·10 CFU/ml (highest count) after chlorhexidine exposure. These bacterial counts did not decrease overtime after chlorhexidine mouthwash (each minute increase in time resulted in a multiplication of bacterial count by a coefficient of 1.001, P = 0.83). Viridans group streptococci isolates had the lowest chlorhexidine minimal inhibitory concentration (4 [4 to 8] mg/l); Enterobacteriaceae isolates had the highest ones (32 [16 to 32] mg/l). Chlorhexidine salivary concentration rapidly decreased, reaching 7.6 [1.8 to 31] mg/l as early as 60 min after mouthwash. Chlorhexidine oropharyngeal care does not seem to reduce bacterial oropharyngeal colonization in critically ill ventilated patients. Variable chlorhexidine minimal inhibitory concentrations along with low chlorhexidine salivary concentrations after mouthwash could explain this ineffectiveness, and thus question the use of chlorhexidine for ventilator-associated pneumonia prevention.

Microbiology and clinical characteristics of viridans group streptococci in patients with cancer

This study assessed the microbiology, clinical syndromes, and outcomes of oncologic patients with viridans group streptococci isolated from blood cultures between January 1st, 2013 and December 31st, 2016 in a referral hospital in Mexico using the Bruker MALDI Biotyper. Antimicrobial sensitivity was determined using BD Phoenix 100 according to CLSI M100 standards. Clinical information was obtained from medical records and descriptive analysis was performed.Forty-three patients were included, 22 females and 21 males, aged 42 ± 17 years. Twenty (46.5%) patients had hematological cancer and 23 (53.5%) a solid malignancy. The viridans group streptococci isolated were Streptococcus mitis, 20 (46.5%); Streptococcus anginosus, 14 (32.6%); Streptococcus sanguinis, 7 (16.3%); and Streptococcus salivarius, 2 (4.7%). The main risk factors were pyrimidine antagonist chemotherapy in 22 (51.2%) and neutropenia in 19 (44.2%) cases, respectively. Central line associated bloodstream infection was diagnosed in 18 (41.9%) cases. Septic shock occurred in 20.9% of patients, with an overall mortality of 18.6%. Only four S. mitis revealed penicillin-resistance.Our results are similar to those of other series, identifying these bacteria as emerging pathogens with significant morbidity and mortality in oncologic patients. The MALDI-TOF system increased the rate of viridans group streptococci isolation in this population.

Identificación y sensibilidad a los antimicrobianos de aislados de estreptococos del grupo viridans provenientes de pacientes internados en un hospital universitario de la ciudad de Buenos Aires

Members of the viridans group streptococci (VGS) are the cause of local and invasive infections. Due to the severity of these infections and taking into account that reports regarding epidemiological aspects are scarce, the aims of this work were the identification and the study of the antibiotic susceptibility profiles of the isolates recovered from patients that were hospitalized in order to find out about the resistance level and the epidemiology of infections in which VGS are involved. A hundred and thirty two isolates identified as VGS were isolated at Hospital de Clínicas «José de San Martín» during the period 2011-2015. The identification was performed by biochemical test and mass spectrometry by Matrix Assisted Laser Desorption Ionization -Time of Flight Mass Spectrometry. Streptococcus anginosus group was prevalent (42%) followed by Streptococcus mitis group (33%). In the latter, isolates of Streptococcus pneumoniae were excluded. All the VGS isolates were susceptible to ertapenem, meropenem, linezolid and vancomycin; 25.8% were resistant (I+R) to penicillin, being prevalent in the S. mitis group. Regarding ceftriaxone and cefepime 96.9% of the isolates were susceptible. Only two isolates were resistant to levofloxacin, 27.2% to tetracycline and it was not found high level resistance to gentamycin (MIC range 0.5-32μg/ml). Resistance to erythromycin was 17.4% with no significant difference between M and MLS phenotypes. The most active antibiotics were in addition to ceftriaxone and cefepime, vancomycin, ertapenem, meropenem and linezolid. These results highlight the importance of the continuous surveillance of the infections caused by VGS in order to predict a correct antibiotic therapy.

Oritavancin in vitro activity against gram-positive organisms from European and United States medical centers: results from the SENTRY Antimicrobial Surveillance Program for 2010–2014

The in vitro activity of oritavancin was assessed against 44,715 gram-positive pathogens causing infections in European and United States (US) hospitals (2010–2014). There were no substantive differences (>±2-fold dilution) in oritavancin MIC50 or MIC90 values for different species/organism groups over time or by region. Oritavancin (99.9% susceptible) showed modal MIC, MIC50, and MIC90 results of 0.03, 0.03, and 0.06–0.12 mg/L when tested against Staphylococcus aureus, regardless of methicillin susceptibility, year, or region. Coagulase-negative staphylococci from the US and Europe demonstrated equal MIC50 values for oritavancin (MIC50, 0.03 mg/L). Oritavancin inhibited 99.9% of Enterococcus faecalis and all E. faecium at ≤0.5 mg/L, including vancomycin-resistant isolates. Oritavancin exhibited MIC50 results of 0.03 and ≤0.008 mg/L when tested against β-hemolytic and viridans group streptococci isolates, respectively, regardless of geographical region. Oritavancin maintained potent activity in vitro against this contemporary collection of European and US gram-positive isolates over 5 years (2010–2014).

In Vitro Activity of Tedizolid against Gram-Positive Cocci Isolates from Patients Hospitalized with Pneumonia in the United States and Europe, 2014-2016

Objectives: Tedizolid and comparator agent in vitro activities were assessed against clinically relevant gram-positive pathogens causing pneumonia in patients in European and US hospitals. Tedizolid was approved in the United States, Europe, and other regions to treat adults with acute bacterial skin and skin structure infections (ABSSSIs) and is being evaluated for treating nosocomial pneumonia. Methods: A total of 6,019 unique clinical isolates deemed to be responsible for community-acquired (CAP) and healthcare-associated pneumonia (HCAP), including hospital-acquired (HAP) in hospitalized patients, were included. A separate analysis included the HAP subset. Isolates originated from 33 and 30 institutions in Europe and the United States, respectively, between 2014 and 2016. Results: No substantive differences in tedizolid MIC values were found for the different species/organism groups over time or by geographic region. Isolates causing HAP showed slightly decreased activity to comparator agents compared to CAP/HCAP isolates. Tedizolid (100.0% susceptible) showed MIC50/90 results of 0.12/0.12 mg/L (US) and 0.12/0.25 mg/L (Europe) when tested against S. aureus HAP isolates, regardless of methicillin susceptibility or year of isolation. Coagulase-negative staphylococci from the United States and Europe (MIC50, 0.12 mg/L) demonstrated identical MIC50 values for tedizolid. Tedizolid exhibited MIC50 results of 0.25 mg/L and 0.12 mg/L when tested against β-hemolytic streptococci and viridans group streptococci isolates, respectively, regardless of geographic region. Conclusions: Tedizolid had potent activity in vitro against this contemporary collection of European and US gram-positive pneumonia isolates that was sustained over a period of 3 years (2014–2016).

Activity of dalbavancin tested against Gram-positive clinical isolates causing skin and skin-structure infections in paediatric patients from US hospitals (2014-2015).

This study provides an in vitro analysis of dalbavancin activity against isolates causing skin and skin-structure infections (SSSIs) in children. A total of 770 Staphylococcus aureus, 167 β-haemolytic streptococci (BHS), 42 coagulase-negative staphylococci (CoNS), 25 Enterococcus faecalis and 13 viridans group streptococci (VGS) were collected from children (<18years old) in the USA (2014-2015). Dalbavancin had MIC50/90 values of 0.03/0.06μg/mL against S. aureus and CoNS, including methicillin-resistant (MRSA) and -susceptible (MSSA) isolates. Dalbavancin MICs were 8-32-fold lower than those of daptomycin (MIC50/90, 0.25/0.5μg/mL), vancomycin (MIC50/90, 0.5/1μg/mL) and linezolid (MIC50/90, 1/1μg/mL) against MRSA. These agents showed 100.0% susceptibility against MRSA, and clindamycin also had a high (92.7%) susceptibility rate. Dalbavancin (MIC50/90, 0.03/0.06μg/mL) and daptomycin (MIC50/90, 0.25/0.5μg/mL) were the most active agents against CoNS. When tested against E. faecalis, dalbavancin was up to 32-fold more active than ampicillin (MIC50/90, ≤0.5/1μg/mL), daptomycin (MIC50/90, 1/1μg/mL), linezolid (MIC50/90, 1/2μg/mL) and vancomycin (MIC50/90, 1/2μg/mL). Dalbavancin (MIC50/90, 0.008/0.03μg/mL), ceftriaxone (MIC50/90, ≤0.06/≤0.06μg/mL) and penicillin (MIC50/90, ≤0.06/≤0.06μg/mL) were the most active against BHS. VGS isolates were susceptible to dalbavancin (MIC100, 0.03μg/mL), with MICs 32-64-fold lower than daptomycin (MIC50/90, 0.5/0.5μg/mL), linezolid (MIC50/90, 0.5/1μg/mL) and vancomycin (MIC50/90, 0.5/0.5μg/mL). Approved agents available for the treatment of SSSI in children are limited. Dalbavancin demonstrated potent in vitro activity against isolates causing SSSI in children. Developing dalbavancin for SSSI treatment in children is warranted, provided safety and tolerability are satisfactory.

Surrogate analysis of vancomycin to predict susceptible categorization of dalbavancin

Dalbavancin (DAL) represents a recently approved addition for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Newly released antimicrobial agents are rarely found on commercial susceptibility testing devices, and surrogate testing may be an option for clinical microbiology laboratories. A total of 33,688 Staphylococcus aureus, 2800 viridans group streptococci (VGS), and 5722 β-hemolytic streptococci (BHS) were included in this cross-susceptibility (DAL versus vancomycin [VAN]) analysis as well as 4576 coagulase-negative staphylococci and 6515 enterococci (nonindicated species groups). Isolates were collected as part of the SENTRY Antimicrobial Surveillance Program for the United States (USA) and Europe (2011–2013). Susceptibility testing followed CLSI (M07-A9 and M100-S24) methods. USA Food and Drug Administration (DAL) and CLSI (VAN) breakpoint criteria were used for correlations between DAL and VAN susceptibility results. A categorical agreement (CA; susceptible) rate of 99.9% was observed between DAL and VAN when testing S. aureus. Only 48 (0.14%) very major (false-susceptible) errors were noted against VAN-susceptible isolates that displayed a DAL-nonsusceptible (MIC, 0.25 or 0.5μg/mL) phenotype. When susceptible MIC correlations were analyzed against indicated BHS species (Streptococcus agalactiae and Streptococcus pyogenes), an overall CA rate of 97.7–100.0% was obtained. Complete (100.0%) CA was documented for S. pyogenes, as well as against all VGS isolates, including the indicated Streptococcus anginosus group (758 strains). In conclusion, high susceptible CA rates between DAL and VAN were observed when testing a contemporary collection of indicated clinical isolates found in ABSSSI. VAN-susceptible isolates can be inferred to be inhibited by DAL (97.7–100.0%) at the regulatory agency–approved susceptible interpretive breakpoint of ≤0.12μg/mL.

Development and validation of a clinical model to predict the presence of β-lactam resistance in viridans group streptococci causing bacteremia in neutropenic cancer patients.

Concern for serious infection due to β-lactam-resistant viridans group streptococci (VGS) is a major factor driving empiric use of an anti-gram-positive antimicrobial in patients with febrile neutropenia. We sought to develop and validate a prediction model for the presence of β-lactam resistance in VGS causing bloodstream infection (BSI) in neutropenic patients. Data from 569 unique cases of VGS BSI in neutropenic patients from 2000 to 2010 at the MD Anderson Cancer Center were used to develop the clinical prediction model. Validation was done using 163 cases from 2011 to 2013. In vitro activity of β-lactam agents was determined for 2011-2013 VGS bloodstream isolates. In vitro resistance to β-lactam agents commonly used in the empiric treatment of febrile neutropenia was observed only for VGS isolates with a penicillin minimum inhibitory concentration (MIC) of ≥ 2 µg/mL. One hundred twenty-nine of 732 patients (17%) were infected with VGS strains with a penicillin MIC ≥ 2 µg/mL. For the derivation and validation cohorts, 98% of patients infected by VGS with a penicillin MIC of ≥ 2 µg/mL had at least 1 of the following risk factors: current use of a β-lactam as antimicrobial prophylaxis, receipt of a β-lactam antimicrobial in the previous 30 days, or nosocomial VGS BSI onset. Limiting empiric anti-gram-positive therapy to neutropenic patients having at least 1 of these 3 risk factors would have reduced such use by 42%. Simple clinical criteria can assist with targeting of anti-gram-positive therapy to febrile neutropenic patients at risk of serious β-lactam-resistant VGS infection.