1243. Eravacycline in Bacteremia: A Case Series

Background Eravacycline (ERV) is FDA-approved for the treatment of complicated intra-abdominal infections, but there is limited experience for non-FDA approved indications. Methods We present five cases that utilized ERV for treatment of bacteremia. Results Patient 1 in septic shock (SS) started on vancomycin (VAN) and ceftazidime-avibactam (CZA). Blood culture (BC) finalized to E. coli and regimen narrowed to CZA. On day 9, gram-positive cocci in chains in BC grew and VAN was added. BC finalized to VRE faecium and regimen was modified to ERV on day 12. Repeat BC on day 15 finalized to no growth with no recurrence of bacteremia until discharged (day 78). Patient 2 treated for MSSA bacteremia with cefazolin and subsequent K. pneumoniae VAP treated with ceftriaxone (CRO) (day 18-26). On day 27, meropenem (MEM) was initiated for gram-negative bacteremia and started on IV trimethoprim/sulfamethoxazole (TMP/SMX) the following day for pneumonia caused by TMP/SMX-susceptible S. maltophila. BC finalized on day 29 to S. maltophila resistant to TMP/SMX, regimen modified to ERV. Repeat BC on day 30 finalized to no growth and ERV was continued until day 42 with no recurrence of bacteremia; however, patient died on day 45. Patient 3 with renal failure and on day 11, CRO started for SBP prophylaxis. On day 13, switched to daptomycin and cefepime (FEP) as patient was febrile and BC repeated. BC finalized to VRE faecium and was started on ERV on day 17 and completed a 7-day course with no recurrence of bacteremia; however, patient died on day 34. Patient 4 initially treated for bacterial superinfection with CRO and azithromycin, and subsequent worsening pneumonia treated with VAN and MEM (day 10-17). On day 19, patient was febrile and treated with VAN and FEP until day 27. Repeat BC on day 29 finalized to VRE species and modified to ERV on day 32. ERV continued for a 7-day course and was discharged with no repeat BC obtained to confirm clearance. Patient 5 in SS started on VAN and MEM. On day 3, BC on admission finalized to VRE faecium and therapy switched to ERV. Repeat BC taken on day 3 after ERV initiation were negative. Discharged to complete two-week course of ERV. Conclusion ERV may be an option for bacteremia as demonstrated by clearance in four of five cases. More studies must be conducted as these reports show variable clinical outcomes. Disclosures Joshua R. Rosenberg, MD, Allergan/Abbvie (Consultant)La Jolla/Tetraphase (Consultant)Melinta (Consultant)Merck (Consultant)Paratek (Consultant)Sanofi (Consultant)Shionogi (Consultant)

1288. Evaluation of Predictors for Clinical Success in Patients Treated with Eravacycline for Various Infections

Background Eravacycline (ERV) is approved in the United States (US) for the treatment of complicated intra-abdominal infections in adults. We aimed to evaluate the independent predictors of clinical success in patients treated with ERV for various infections. Methods Multicenter, retrospective, observational study conducted from September, 2018 to April, 2021. We included adults treated with ERV for ≥ 72hours. Clinical success was defined as 30-day survival, lack of 30-day infection-recurrence, and resolution of infection signs/symptoms. All outcomes were measured from ERV initiation. Multivariable logistic regression (MLR) was performed to identify independent predictors of clinical success. Clinically relevant variables were selected for model entry based on bivariate comparisons (P< 0.2) in a backward fashion. Results We included 223 patients from 16 medical centers in 13 geographically unique states. The median (IQR) age was 61 (50-69) years, 57% were male and 62% were Caucasian. Median (IQR) APACHE II, and Charlson Comorbidity scores were 15 (10-21), and 3 (1-5), respectively. Sources of infection were primarily intra-abdominal (27%) and respiratory (27%). Common pathogens included Acinetobacter baumannii (21%) and those of the Enterobacterales order (36%). Infectious diseases consultation and surgical interventions were obtained in 93.7% and 52% respectively. Clinical success occurred in 64%, specifically 30-day survival in 78%, absence of 30-day infection-recurrence in 93%, and 74% experienced resolution of infection signs/symptoms. Since characteristics and outcomes were similar among various pathogens, MLR was conducted using the overall cohort. Skin as a source and combination therapy with ERV were independently associated with higher clinical success: odds ratio 3.3 [CI 1.1-10.2] and 2.9 [1.4-5.9], respectively. Whereas, ICU admission at culture time and undergoing surgery within 30 days of culture were independently associated with reduced odds of clinical success: 0.4 [0.17-0.80] and 0.3 [0.11-0.63] respectively. Conclusion Although most ERV treated patients experienced clinical success, factors independently associated with higher clinical success are crucial to consider for optimum antibiotic selection. Disclosures Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau) Madeline King, PharmD, tetraphase (Speaker’s Bureau) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Bruce M. Jones, PharmD, BCPS, Abbvie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)La Jolla (Speaker’s Bureau)Melinta (Consultant)Merck (Consultant)Paratek (Consultant, Speaker’s Bureau) Susan L. Davis, PharmD, Nothing to disclose Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

RNA virome diversity and Wolbachia infection in individual Drosophila simulans flies

The endosymbiont bacteria of the genus Wolbachia are associated with multiple mutualistic effects on insect biology, including nutritional and antiviral properties. Members of the genus Wolbachia naturally occur in fly species of the genus Drosophila, providing an operational model host for studying how virome composition may be affected by its presence. Drosophila simulans populations can carry a variety of strains of members of the genus Wolbachia , with the wAu strain associated with strong antiviral protection under experimental conditions. We used D. simulans sampled from the Perth Hills, Western Australia, to investigate the potential virus protective effect of the wAu strain of Wolbachia on individual wild-caught flies. Our data revealed no appreciable variation in virus composition and abundance between individuals infected or uninfected with Wolbachia associated with the presence or absence of wAu. However, it remains unclear whether wAu might affect viral infection and host survival by increasing tolerance rather than inducing complete resistance. These data also provide new insights into the natural virome diversity of D. simulans. Despite the small number of individuals sampled, we identified a repertoire of RNA viruses, including nora virus, galbut virus, thika virus and La Jolla virus, that have been identified in other species of the genus Drosophila. Chaq virus-like sequences associated with galbut virus were also detected. In addition, we identified five novel viruses from the families Reoviridae, Tombusviridae, Mitoviridae and Bunyaviridae. Overall, this study highlights the complex interaction between Wolbachia and RNA virus infections and provides a baseline description of the natural virome of D. simulans.

Epidermal Microbiomes of Triakis Semifasciata Are Consistent Across Captive and Wild Environments

Background: Characterizations of sharks-microbe systems in wild environments have outlined patterns of species-specific microbiomes; however, whether captivity affects these trends has yet to be determined. We used high-throughput shotgun sequencing to assess the epidermal microbiome belonging to leopard sharks (Triakis semifasciata) in captive (Birch Aquarium, La Jolla California), semi-captive (<1 year in captivity; Scripps Institute of Oceanography, California) and wild environments (Moss Landing and La Jolla, California). Results: Here we report captive environments do not drive microbiome composition of T. semifasciata to significantly diverge from wild counterparts as life-long captive sharks maintain a species-specific epidermal microbiome resembling those associated with semi-captive and wild populations. Major taxonomic composition shifts observed were inverse changes of top taxonomic contributors across captive duration, specifically an increase of Pseudoalteromonadaceae and consequent decrease of Pseudomonadaceae relative abundance as T. semifasciata increased duration in captive conditions. Moreover, we show captivity did not lead to significant losses in microbial α-diversity of shark epidermal communities. Finally, we present a novel association between T. semifasciata and the Muricauda genus as MAGs revealed a consistent relationship across captive, semi-captive, and wild populations. Conclusions: Our report illustrates the importance of conservation programs for coastal fishes as epidermally-associated microbes of near-shore shark species do not suffer detrimental impacts from long or short-term captivity. Our findings also expand on current understanding of shark epidermal microbiomes, explore the effects of ecologically different scenarios on benthic shark microbe associations, and highlight novel microbial associations that are consistent across captive gradients.

Orthodontic treatment consent forms: A readability analysis

Objective: To evaluate the readability of orthodontic treatment informed consent forms (ICFs). Design: A cross-sectional observational investigation. Methods: An online search strategy was adopted to identify ICFs for orthodontic treatment. The text of each form that satisfied inclusion criteria was modified to a standardised protocol. The readability was evaluated using three validated instruments. GraphPad Software (GraphPad Software Inc., La Jolla, CA, USA) was used for statistical analyses. Results: A total of 59 ICFs were evaluated. The majority were available on the websites of orthodontists (66.1%) and general dentists (27.1%). The scores recorded from the three instruments indicated that the content of 93.2%–98.3% of ICFs was difficult to read. A strong correlation was observed between the Simple Measure of Gobbledegook (SMOG) and the Flesch Kincaid Grade level (FKGL) instruments (r = 0.9782; P < 0.0001). The mean SMOG score for all assessed forms was 11.19 (95% confidence interval [CI] 10.85−11.54). The ICFs authored by the manufacturers of orthodontic appliances provided by clinicians recorded a mean Flesch Reading (FRE) score of 40.14 (95% CI 33.91−46.37) out of a maximum 100. An analysis of the SMOG scores indicated that the content of ICFs authored by national orthodontic societies was more difficult to read than those written by all other authors ( P=0.01; 95% CI −1.6 to −0.2) Conclusion: The readability of the ICFs was too difficult for a significant number of the population. Many patients will be unable to validly consent to treatment based solely on reading of the content of the evaluated ICFs. A greater effort is required to improve the readability of ICFs to help ensure patient autonomy regarding orthodontic treatment decision-making and management.

Gerald Edelman’s Steps Toward a Conscious Artifact

In 2006, during a meeting of a working group of scientists in La Jolla, California at The Neurosciences Institute (NSI), Gerald Edelman described a roadmap towards the creation of a Conscious Artifact. As far as I know, this roadmap was not published. However, it did shape my thinking and that of many others in the years since that meeting. This short paper, which is based on my notes taken during the meeting, describes the key steps in this roadmap. I believe it is as groundbreaking today as it was more than 15 years ago.

Citizen-Sourced Sightings and Underwater Photography Reveal Novel Insights About Green Sea Turtle Distribution and Ecology in Southern California

East Pacific (EP) green turtles (Chelonia mydas) have undergone substantial population recovery over the last two decades owing to holistic protection at nesting beaches and foraging areas. At the northern end of their range in southern California United States, green turtles have been seen in more areas and in greater numbers since 2014 than before as a result. A resident population of green turtles has established near La Jolla Shores (LJS), a protected site with daily marine tourism (e.g., kayakers, snorkelers, divers). To study this local aggregation, innovative and non-invasive methods were required because the traditional capture-recapture methods were infeasible due to public relations sensitivities. Green turtle habituation to humans at this site has created a unique opportunity for citizen-based science using underwater photography to document turtles and their surroundings. We obtained 309 usable photographs of local green turtles from members of the dive/snorkel community in LJS. Photos were taken from April 2016 to June 2019. Images were processed in Hotspotter—a patterned species instance recognition software—to identify seven individuals, five of which were consistently photographed throughout that period. These images helped infer minimum residency duration (MRD), seasonal differences in algal coverage on the carapace, habitat association, behavioral patterns, and diet. Mean MRD was 424 days (SE = 131 days, calculated from entire population, n = 7), during which turtles were active in 82.8% of the photographs; the remainder of the photographs depicted foraging (14.9%) or resting behavior (2.3%). Green turtles were seen foraging in water temperatures as low as 15.8°C, the lowest recorded temperature for foraging green turtles documented in literature. Additional opportunistic observational platforms were used to look at trends of increasing green turtle abundance in southern California since 2015 that supported the arrival of a new aggregation of green turtles in LJS. Our use of citizen-sourced photographs confirms the presence of a resident aggregation of green turtles in LJS. Existence of green turtles and other protected species in highly populated areas provide excellent opportunities to educate beachgoers and seafarers about conservation of these species. This study also highlights the value of citizen-based science in areas where traditional research techniques are ill-suited.

RNA virome diversity and Wolbachia infection in individual Drosophila simulans flies

The endosymbiont bacterium Wolbachia is associated with multiple mutualistic effects on insect biology, including nutritional and antiviral properties. Wolbachia naturally occurs in Drosophila fly species, providing an operational model host to study how virome composition may be impacted by its presence. Drosophila simulans populations can carry a variety of Wolbachia strains. In particular, the wAu strain of Wolbachia has been associated with strong antiviral protection under experimental conditions. We used D. simulans sampled from the Perth Hills, Western Australia, to investigate the potential virus protective effect of the wAu strain on individual wild-caught flies. Our data revealed no appreciable variation in virus composition and abundance between Wolbachia infected/uninfected individuals associated with the presence/absence of wAu. However, it remains unclear whether wAu might impact viral infection and host survival by increasing tolerance rather than inducing complete resistance. These data also provide new insights into the natural virome diversity of D. simulans. Despite the small number of individuals sampled, we identified a repertoire of RNA viruses, including Nora virus, Galbut virus, Chaq virus, Thika virus and La Jolla virus, that have been identified in other Drosophila species. In addition, we identified five novel viruses from the families Reoviridae, Tombusviridae, Mitoviridae and Bunyaviridae. Overall, this study highlights the complex interaction between Wolbachia and RNA virus infections and provides a baseline description of the natural virome of D. simulans.

Organization of the Structural Protein Region of La Jolla Virus Isolated from the Invasive Pest Insect Drosophila suzukii

Drosophila suzukii (Ds) is an invasive pest insect that infests ripening fruit, causing severe economic losses. Control measures based on chemical pesticides are inefficient and undesirable, so biological alternatives have been considered, including native Ds viruses. We previously isolated a strain of La Jolla virus (LJV-Ds-OS20) from Ds in Germany as a candidate biopesticide. Here we characterized the new strain in detail, focusing on the processing of its capsid proteins. We tested LJV growth during Ds development to optimize virus production, and established a laboratory production system using adult flies. This system was suitable for the preparation of virions for detailed analysis. The LJV-Ds-OS20 isolate was cloned by limiting dilution and the complete nucleotide sequence was determined as a basis for protein analysis. The terminal segments of the virus genome were completed by RACE-PCR. LJV virions were also purified by CsCl gradient centrifugation and analyzed by SDS-PAGE and electron microscopy. The capsid proteins of purified LJV virions were resolved by two-dimensional SDS-PAGE for N-terminal sequencing and peptide mass fingerprinting. The N-terminal sequences of VP1 and VP2, together with MS data representing several capsid proteins, allowed us to develop a model for the organization of the LJV structural protein region. This may facilitate the development of new viral strains as biopesticides.