185. Trends in Clinical Presentation and Antibiotic Resistance of Viridans Group Streptococci Bloodstream Infections in Immunocompromised Children

Background Levofloxacin prophylaxis (LVXp) is recommended in children with severe neutropenia from underlying malignancy or hematopoietic cell transplantation (HCT). The impact of LVXp on the epidemiology of viridans group streptococcus bloodstream infections (VGS-BSI) is unknown. At our center, LVXp was prescribed to high-risk children with expected prolonged neutropenia (ANC < 100, > 7 days) as part of a clinical trial (2013-17) and routinely since November 2018. We aim to describe our local epidemiology, antibiotic susceptibilities, and clinical outcomes of VGS-BSI over time. Methods VGS-BSI from 1/1/10-1/31/21 were identified via the laboratory database. Clinical data of patients followed at NCH with underlying malignancy, severe neutropenia, or HCT were extracted from the electronic health record. Available VGS isolates were subcultured, species identification confirmed by MALDI-ToF or 16s rDNA sequencing and susceptibility to penicillin (PCN), cefepime (CEF), vancomycin (VAN), and LVX performed via Etest per CLSI M100 guidelines. Non-parametric descriptive statistics were applied. Results Over a 10-yr period, 111 VGS-BSI occurred in 93 patients (Table 1); 15 (16%) patients had ≥ 2 VGS-BSI. 80 (86%) patients had fever and neutropenia (F&N); 26 (28%) required ICU care for vasopressors (N=17, 18%) or mechanical ventilation (N=10, 11%). Most VGS isolates were S. mitis/oralis group. In total, 15 (16%) patients received LVXp ≤ 6 months before VGS-BSI; 9 (10%) had breakthrough VGS-BSI while receiving LVXp and all isolates were LVX resistant. Figure 1 shows susceptibilities: overall, 24% of isolates had frank resistance to PCN, 19% CEF, 13% LVX; all were VAN susceptible. When evaluating for changes in susceptibilities over time, there was a significant difference in the proportion of LVX-resistant isolates (p=0.009, Cochran-Armitage χ 2), but not CEF (p=0.08) or PCN (p=0.86). Table 1. Demographic and Clinical Characteristics of Immunocompromised Children with Viridans Group Streptococci Bloodstream Infections (VGS-BSI) Figure 1. Antimicrobial Susceptibility Profile of Viridans Group Streptococci Bloodstream Isolates from Immunocompromised children, 2010-2021. Of 111 VGS-BSI reported during the study period from immunocompromised children, 83 (75%) were available for further testing. Antimicrobial susceptibility testing was performed by Etest and interpreted per CLSI M100. Susceptibility profiles to penicillin (PCN), cefepime (CEP) and, levofloxacin (LVX) are shown. Abbreviations: S—susceptible, I—intermediate, R—resistant. Conclusion Breakthrough, LVX-resistant VGS-BSI occurred in 10% of patients, most frequently in children with AML or HCT. Over time, there was a trend towards increased LVX resistance in the cohort. Routine antimicrobial testing and ongoing monitoring for emergence of resistance are warranted to inform local prophylaxis and empirical antibiotic strategies for high-risk children with F&N. Disclosures Monica I. Ardura, DO, MSCS, Shire (Grant/Research Support)

Activity of KBP-7072 (a novel aminomethylcycline) and comparators against 1,057 geographically diverse recent clinical isolates from the SENTRY Surveillace Program (2019)

KBP-7072 is a novel third generation tetracycline (aminomethylcycline) antibacterial in clinical development (oral and intravenous formulations) for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and complicated intra-abdominal infections. KBP-7072 is active against many of the World Health Organization-priority pathogens. In this study, KBP-7072 and tetracycline class comparators were susceptibility tested against 1,057 geographically diverse surveillance isolates from 2019 according to Clinical and Laboratory Standards Institute (CLSI) guidelines. KBP-7072 demonstrated potent in vitro activity against gram-positive and gram-negative bacterial pathogens. KBP-7072 was active against Staphylococcus aureus (MIC 50/90 , 0.06/0.12 mg/L), methicillin-resistant S. aureus (MIC 50/90 , 0.06/0.12 mg/L), S. lugdunensis (MIC 50/90 , 0.03/0.03 mg/L), and other coagulase-negative staphylococci (MIC 50/90 , 0.06/0.25 mg/L). KBP-7072 was active against Enterococcus faecalis (MIC 50/90 , 0.03/0.06 mg/L) and vancomycin-susceptible and -nonsusceptible E. faecium (MIC 50/90 , 0.03/0.03 mg/L); Streptococcus pneumoniae (MIC 50/90 , ≤0.015/0.03 mg/L), including penicillin- and tetracycline-resistant strains; S. agalactiae (MIC 50/90 , 0.03/0.06 mg/L), including macrolide-resistant strains; S. pyogenes (MIC 50/90 , 0.03/0.03 mg/L); and viridans group streptococci, including S. anginosus group (MIC 50/90 , ≤0.015/0.03 mg/L) isolates. KBP-7072 inhibited 90.2% (MIC 50/90 , 0.25/2 mg/L) of all Enterobacterales isolates, including ESBL-phenotype strains, at ≤2 mg/L. KBP-7072 demonstrated potent activity against Acinetobacter baumannii -calcoaceticus species complex and Stenotrophomonas maltophilia isolates (MIC 50/90 values, 0.5/1 mg/L), Haemophilus influenzae (MIC 50/90 , 0.12/0.25 mg/L; 100.0% inhibited at ≤0.25 mg/L), and Moraxella catarrhalis (MIC 50/90 , 0.06/0.06 mg/L). Based on MIC 90 values, KBP-7072 in vitro activity was generally superior to the other tetracycline class comparators tested. The potent activity of KBP-7072, including resistant organism groups, merits further clinical investigation in infections where these organisms are likely to occur.

A New Species-Specific Typing Method for Salivarius Group Streptococci Based on the Dephospho-Coenzyme A Kinase (coaE) Gene Sequencing

Viridans streptococci are a group of α-hemolytic streptococcal species. They are mainly commensals, most abundant in the mouth supporting oral health. But they also include important human pathogens such as Streptococcus pneumoniae. Identification and molecular typing of viridans group streptococci are challenging, especially for members of the salivarius group. In this study, we developed a single-locus molecular typing method that is able to differentiate among the highly phylogenetically related members of the salivarius group (S. salivarius, S. vestibularis and S. thermophilus) and might support differentiation in other groups as well. This typing approach is based on the amplification and sequence analysis of the housekeeping gene dephospho-coenzyme A kinase (coaE), a gene with unrecognized taxonomic potential to date. Here, we analysed coaE gene sequences of 154 publicly available genomes and of 30 salivarius group isolates of our own collection that together belong to 20 different gram-positive bacterial (sub) species. Our results revealed that the coaE phylogeny distinguished between streptococcal and non-streptococcal genomes and that coaE gene sequences were species-specific. In contrast to MALDI-TOF MS performance, the coaE typing was able to precisely identify the phylogenetically very closely related members of the salivarius group.

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.

Streptococcus gordonii septic arthritis of the glenohumeral joint following deltoid intramuscular vaccination

A 68-year-old woman presented for left shoulder pain, decreased range of motion (ROM) and fever 7 days following COVID-19 vaccination. Investigations showed a tender left deltoid mass, decreased shoulder ROM and elevated inflammatory markers. MRI demonstrated a large glenohumeral effusion with synovitis, and arthrocentesis confirmed septic arthritis (SA). She required subtotal bursectomy. Intraoperative joint cultures grew Streptococcus gordonii. She completed 6 weeks of antibiotics and is undergoing physical therapy for post-infectious adhesive capsulitis. SA is most commonly due to Staphylococcus aureus and β-haemolytic streptococci, and rarely due to viridans group streptococci including S. gordonii. To avoid inadvertent injection into the glenohumeral joint, vaccination should be performed posteriorly and inferiorly into the deltoid musculature. Progressive pain, fever or decreased passive ROM following vaccination should raise concern for SA. Given its rarity, however, concern for secondary SA should not affect the general population’s consideration for vaccination.

Clinical Features And Outcomes Of Streptococcus Anginosus Group Infective Endocarditis: A Multicenter Matched Cohort Study

Background Although Streptococcus anginosus group (SAG) endocarditis is considered a severe disease associated with abscess formation and embolic events, there is limited evidence to support this assumption. Methods We performed a retrospective analysis of prospectively collected data from consecutive patients with definite SAG endocarditis in 28 centers in Spain and Italy. A comparison between cases due to SAG endocarditis and viridans group streptococci (VGS) or Streptococcus gallolyticus group (SGG) was performed in a 1:2 matched analysis. Results Of 5,336 consecutive cases of definite endocarditis, 72 (1.4%) were due to SAG and matched with 144 cases due to VGS/SGG. SAG endocarditis was community acquired in 64 (88.9%) cases and affected aortic native valve in 29 (40.3%). When comparing SAG and VGS/SGG endocarditis, no significant differences were found in septic shock (8.3% vs. 3.5%, P = 0.116); valve disorder, including perforation (22.2% vs. 18.1%, P = 0.584), pseudoaneurysm (16.7% vs. 8.3%, P = 0.108), or prosthesis dehiscence (1.4% vs. 6.3%, P = 0.170); paravalvular complications, including abscess (25% vs. 18.8%, P = 0.264) and intracardiac fistula (5.6% vs. 3.5%, P = 0.485); heart failure (34.7% vs. 38.9%, P = 0.655); and embolic events (41.7% vs. 32.6%, P = 0.248). Indications for surgery (70.8% vs. 70.8%; P =1) and mortality (13.9% vs. 16.7%; P = 0.741) were similar between groups. Conclusions SAG endocarditis is an infrequent but serious condition that presents a prognosis similar to that of VGS/SGG

Post-traumatic endophthalmitis caused by streptococcus species in preschool children: clinical features, antibiotic susceptibilities and outcomes

Background/Objectives Streptococcus is a common cause of post-traumatic endophthalmitis in children. This study aimed to analyse the clinical features, antibiotic susceptibilities and outcomes of traumatic endophthalmitis caused by streptococcus in preschool children. Subjects/Methods Patients aged ≤6 years with traumatic streptococcal endophthalmitis seen at Zhongshan Ophthalmic Center between January 2013 and December 2018 were included in this retrospective study. Results In total, 21 patients (21 eyes) were included. The mean age of the patients was 3.3 ± 1.7 years, where 57.1% were males. Scissors (28.6%, n = 6) were the most common cause of injury; 86.7% of patients were injured at home. Zone I (80.9%) was the most common wound site; 90.5% of patients presented with a traumatic cataract. In general, Streptococcus pneumoniae (47.6%) was the most common isolate. Viridans group streptococci accounted for 58.3% of cases in children aged 0–3 years, while S. pneumoniae accounted for 66.7% of cases in children aged 4–6 years. The susceptibility rates of streptococcus to cefuroxime, levofloxacin and ofloxacin were 100%, 95.0% and 90.5%, respectively. Although all the patients underwent vitrectomy combined with silicone oil tamponade, the final visual outcomes were no better than counting fingers. Conclusions Although S. pneumoniae was the most prevalent organism in general, the dominant species varied between different age groups. The commonly used antibiotics, cefuroxime and fluoroquinolone, showed higher antibiotic susceptibility. Despite prompt treatment, the visual outcomes of paediatric post-traumatic endophthalmitis in preschool children were poor.