bluuebunny/crossref_metadata_2025 huggingface dataset:
2601. A 14-year retrospective study of pulmonary nocardiosis in AIDS patients, Northeastern Thailand
Authors: thipmontree wilawan , Suputtamongkol Yupin
Published: November 2023

Background

Nocardiosis is an opportunistic infection in immunocompromised individuals, particularly patients with acquired immune deficiency syndrome (AIDS). Clinical manifestations of nocardiosis are wide-ranging but the most common is pneumonia.

Methods

This 14 year retrospective study included Nocardia species infected adult patients (≥15 years) with at least 28 days of treatment follow-up. This study aims to compare clinical manifestations and survival analysis of cultured confirmed pulmonary nocardiosis among AIDS and non-AIDS patients.

Results

From 2009 to 2022, 237 patients had culture confirmed Nocardia species infection, of which 22 were excluded from this study because 13 had cutaneous nocardiosis and nine had pulmonary nocardiosis with follow-up less than 28 days. A total of 215 confirmed pulmonary nocardiosis were recruited to the analysis, 97(45.1%) were HIV-infected and 118 (54.9%) were non-HIV. All HIV-infected patient has CD4 count below 200 cell/mm3 (range 1-198, 1-15%), known as AIDS. Most of them were male with a mean age of 37 (range 15-83) years. One hundred fifty of the 215 (69.7%) patients underwent brain imaging. Sixteen cases (10.7%) had brain abscess. Disseminated nocardiosis (brain abscess, bacteremia, cutaneous abscess) was found in equal proportions in AIDS (15/97, 15.5%) and non-AIDS patients (17/118, 14.4%), while pulmonary nocardiosis with local invasion (empyema thoracis, pericardial effusion) was more common in AIDS (11/97, 11.3%) than non-AIDS patients (9/118, 7.6%). Overall and 28 days mortality were 116 (53.9%) and 88 (40.9%), respectively. In Cox’s proportional hazard analysis, AIDS was the independent factor associated with 28 days mortality in pulmonary nocardiosis (adjusted HR 2.62; 95%CI, 1.38 to 4.98) and those who underwent brain imaging (adjusted HR 2.75; 95%CI, 1.23 to 6.15) after adjusted by sex, age, duration of illness, respiratory failure, shock, multi-lobar pneumonia, disseminated nocardiosis, and combination antibiotic therapy.

Conclusion

Pulmonary nocardiosis is a serious opportunistic infection in AIDS patient and has shown significantly higher mortality than non-AIDS. Therefore, nocardiosis should always be considered as a cause of pneumonia in AIDS patients in order to prompt aggressive treatment.

Disclosures

Yupin Suputtamongkol, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is partner in the Abbott Pandemic Defense Coalition
2606. Epidemiology of invasive pneumococcal disease in adults with and without underlying lung disease in Ontario, Canada
Authors: Zhong Zoe , Shigayeva Altynay , Plevneshi Agron , Martin Irene , Demczuk Walter , Kus Julianne , Baqi Mahin , Chen Danny , Gold Wayne , Lovinsky Reena , Rau Neil , Richardson David , McGeer Allison
Published: November 2023

Background

The advent of enhanced conjugate pneumococcal vaccines for adults has created a need to assess the burden of pneumococcal disease in different populations to support recommendations for vaccination. We assessed the epidemiology of invasive pneumococcal disease (IPD) in adults with underlying lung disease in Ontario, Canada.

Methods

Ontario introduced PCV7 and PCV13 for children in 2007 and 2010, and PCV13 for immunocompromised adults over 50 years in 2014. TIBDN performs population (pop’n)-based surveillance for IPD in a pop’n of ∼4.5 million. Microbiology laboratories serving area residents report sterile site isolates of Streptococcus pneumoniae; annual audits ensure completeness. Isolates are serotyped at the National Microbiology Laboratory. Population data are from Statistics Canada, with estimates of prevalence of underlying conditions from ICES.

Results

From 2014-2022, 2769 episodes of IPD occurred in adults; detailed clinical data are available for 2366 (85%), and serotyped isolates for 88%. Of these, 573 (24%) had no chronic underlying illness (undill); 1155 (49%) had an undill not affecting the lungs, 165 (7%) had asthma only, 409 (17%) had COPD (with/without asthma or other lung disease (OLD), 64 (2.7%) had OLD alone (most commonly ILD or bronchiectasis). Among those with asthma, 87 (53%) had another undill predisposing to IPD; compared to 290 (71%) of those with COPD and 45 (70%) of those with OLD. Persons with asthma were younger (median age 56y) than those with no or other undill (64y and 61y), and those with COPD or OLD (70 and 71y). Persons with lung disease were more likely to present with bacteremic pneumonia and less likely to have primary bacteremia or meningitis that those without or with other chrill. ICU admission and case fatality rates are in Table 1. The distribution of serotypes causing disease by conjugate vaccine types did not differ among those with lung disease and others (Figure 1). The incidence of disease in persons with asthma and COPD by age group is shown in Figure 2.

Conclusion

The epidemiology of IPD differs somewhat in persons with lung disease compared to others, but conditions other than lung disease have a greater impact on incidence and outcome of IPD in adults. Enhanced PCVs likely provide cost-effective protection for 50-64 year olds with asthma/COPD.

Disclosures

All Authors: No reported disclosures
2620. Normalization of eosinophil count is predictive of reduced oxygen requirement during Covid-19 infection
Authors: Davido Benjamin , Jaffal Karim , Vaugier Isabelle , Bourlet Stephane , De Truchis Pierre , Annane Djillali
Published: November 2023

Background

The initial need for oxygen during Covid-19 has been correlated with the severity of lung involvement observed on CT-scan caused by the cytokine storm. A recent study showed that the normalization of eosinophil count (≥100/mm3) after 48 hours of appropriate regimen was related to a favorable outcome in sepsis. Our work intends to assess the kinetics of eosinophil count over time based on oxygen levels during the acute phase of this viral infection.

Methods

Retrospective study, conducted between March-April 2020 (first wave), among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and CRP were gathered daily during the first week of admission (day 0) according to oxygen level. In case of worsening requiring ICU, oxygen level was censored at 15 L/min. Aim of the study was to investigate whether normalization of eosinophil count could predict a decrease in oxygen requirements, and potentially patient’s outcome. Values were presented as median with 95% CI and statistical analysis utilized the Chi-2 square test.

Results

132 patients were admitted, mean age 59.0±16.3 years. Mean onset of symptoms was 7±4 days. Majority of patients had cardiovascular disease (43.1%), underlying respiratory disease (16.7%), diabetes (18.9%), immunosuppression (8.3%) and obesity (10.6%).

At admission, median (IQR) CRP=79(26-130) mg/L, lymphocyte count=1005(730-1380)/mm3 and eosinophil count=10(0-60)/mm3. 72% of patients required oxygen supply. Lung CT-scan (n=103) revealed: 53.5% had moderate (25-50%) to severe ( >50%) involvement.

Twenty-seven patients (20.5%) required ICU due to condition worsening.

Eosinophil count increased continuously until normalization from day0 to day3, while the oxygen level started to decrease on day 3 without any rebound observed thereafter (Figure 1). Similarly, CRP decreased to 43 mg/L on day2, but ultimately increased again. Patients requiring < 2L/min of oxygen were significantly associated with an eosinophil count≥100/mm3 on day 2 OR=0.2 [0.07-0.56] (p=0.002).

Conclusion

Normalization of eosinophil count over time seems predictive of a decrease of oxygen requirement during Covid-19. Those data should be confirmed on other type of respiratory tract infections.

Disclosures

All Authors: No reported disclosures
2628. Prevalence of respiratory symptoms in children and staff in Pre-K—12th grade schools and subsequent results from respiratory virus testing
Authors: Goldman Jennifer , Schuster Jennifer E , Selvarangan Rangaraj , Almendares Olivia , Sleweon Sadia , Kirking Hannah L , Lee Brian R
Published: November 2023

Background

Little is known about the prevalence of respiratory symptoms and associated respiratory virus detection in students/ staff in primary and secondary schools.

Methods

School KIDS is a prospective respiratory viral surveillance program in a large Missouri school district. Participating students/ staff complete a monthly electronic symptom survey that asks about respiratory symptoms (sx) in the preceding 7 days; participants are categorized based on the presence of any respiratory sx: ongoing (current), resolved, and no sx. Within 36 hours of survey completion, participants undergo surveillance respiratory viral testing at school. Self-administered nasal swabs are tested via multipathogen PCR assay (Table). Prevalence of respiratory viruses in participants with and without sx were calculated. A mixed-effect multivariable logistic regression model was used to compare odds of a sample testing positive based on surveillance sx and enrollee age.

Results

A total of 544 students (30 pre-kindergarten (preK), 320 elementary, 117 middle, and 77 high) and 224 staff enrolled. A total of 2,537 sx surveys with corresponding respiratory samples were collected from November 2, 2022–April 15, 2023 (Table). Of the samples provided, 1,138 were preK-elementary (45%), 368 middle (14%), 276 high (11%), and 755 staff (30%). Participants reported ongoing (20%), resolved (14%), and no sx (66%). Prevalence of commonly reported sx were congestion (21%), runny nose (17%), cough (16%), and fever (3%). Overall respiratory virus test positivity was 26%; 50% of positive samples came from participants without sx. Flu A, PIV, and RSV were more frequently detected in those with ongoing sx. AdV, HMPV, RV/EV, and SARS-CoV-2 were more frequently detected in those with no sx. Increased odds of a positive test were observed among enrollees who reported runny nose (adjusted OR 1.4 [CI 1.0, 1.8]), congestion (adjusted OR 2.2 [CI1.6, 2.8]), cough (adjusted OR 1.5 [CI 1.1, 1.9]), or sore throat (adjusted OR 1.5 [CI 1.1, 2.0]) but not fever (adjusted OR 1.1 [CI 0.7,1.8]).

Conclusion

More research is needed to understand if students with respiratory sx are more likely than asymptomatic students to shed transmissible respiratory viruses.

Disclosures

Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support
2633. Nasal Colonization Status of Respiratory Viruses in Patients During the COVID-19 Epidemic Period at a Tertiary Hospital in Japan
Authors: Katsuta Tomohiro , Niiya Ryo , Nakamura Yukitsugu , Shimizu Naoki
Published: November 2023

Background

Few reports have comprehensively investigated the frequency of respiratory virus nasal colonization in both children and adults. Since the coronavirus disease 2019 (COVID-19) pandemic in 2020, St. Marianna University Hospital has used the multiplex polymerase chain reaction (PCR) test (FirmArray® RP2.1 Panel) to diagnose symptomatic patients and admission screening of asymptomatic patients. Thus, we have obtained comprehensive multiplex PCR test results and analyzed the nasal colonization status of respiratory viruses in patients during the COVID-19 epidemic period.

Methods

We conducted a retrospective analysis of the nasal colonization status of respiratory viruses in patients during the COVID-19 epidemic period at St. Marianna University Hospital in Japan, a tertiary hospital with 1,175 beds, including 90 beds for pediatric patients. The results of multiplex PCR tests from August 2020 to January 2023 were analyzed.

Results

A total of 15,107 patients were included in this survey. The patient age groups were < 20 years (1,788, 11.8%), 20–59 years (4,399, 29.1%), and ≥60 years (8,920, 59.1%). The positivity rates for severe acute respiratory syndrome coronavirus 2 were 14.8%, 10.2%, and 6.0%, respectively; rhinovirus or enterovirus 26.2%, 1.9%, and 0.7%, respectively; respiratory syncytial virus 7.1%, 0.4%, and 0.3%, respectively; parainfluenza virus type 3 3.6%, 0.3%, and 0.2%, respectively; and adenovirus 3.1%, 0.3%, and 0.1%, respectively, were detected significantly in children, and to some extent in adults.

Conclusion

Despite various restrictions during the COVID-19 pandemic period, children as well as adults had a certain degree of respiratory virus colonization in the nasal cavity. This result suggests that asymptomatic or mildly symptomatic adults may be spreaders of some viral infections to children.

Disclosures

All Authors: No reported disclosures
2636. Discovery of Spike Identification (SpiID) Nanobody Panel for SARS-CoV-2 Vaccine Development
Authors: Li Qi , Doering Jennifer , Ma Zepei , Mantis Nicholas , Cavacini Lisa , Wang Yang
Published: November 2023

Background

SARS-CoV-2 variants of concern (VoC), particularly the Omicron lineage, are spreading rapidly throughout the world even among vaccinated populations. Unfortunately, the first-generation vaccines and monoclonal antibody therapeutics have significantly reduced efficacy against new variants, creating a need for multivalent next-generation countermeasures, including spike protein-based subunit vaccines.

Methods

Although spike protein-based subunit vaccines are relatively easy and cost-effective to manufacture, the challenges present when it comes to Chemistry, Manufacturing, and Controls (CMC) from a clinical perspective. Specifically, multivalent and/or combination subunit vaccines of different variants require specific identity testing with analytical assay reagents which can distinguish closely related antigens. In order to overcome this difficulty, a panel of SARS-CoV-2 VoC-specific nanobodies was developed from a diverse synthetic yeast-display library.

Results

These nanobodies, when expressed with human IgG-Fc fragments as fusion antibodies, showed high specificity against individual variants with nanomolar range affinity (8.1- 68nM) against various VoCs, including Wuhan, Beta, Delta, and Omicron with no cross-reactivity with other variants. Additionally, a subset of nanobodies demonstrated potent virus-neutralizing activity in vitro in the sub-nanomolar range (0.1-0.8nM), and may be useful as biological standards in clinical settings.

Conclusion

These findings offer potential CMC solutions for developing multivalent and/or combination subunit vaccines against newly emerged SARS-CoV-2 variants, improving clinical outcomes for patients.

Disclosures

All Authors: No reported disclosures
2637. Activity of Respiratory Viruses in Georgia 2020-2022
Authors: machablishvili Ann , Tarkhan-Mouravi Olgha , Zakhashvili Khatuna , Kalandadze Irina , Karseladze Irakli , Gavashelidze Mari , Imnadze Paata
Published: November 2023

Background

The emergence of SARS-CoV-2 in early 2020 with subsequent implementation of public health and social measures influenced the epidemiology of respiratory viruses worldwide. This study describes circulation of respiratory viruses during two winter seasons and inter-seasonal periods in Georgia.

Methods

We aggregated data obtained from Influenza like illness (ILI) and Severe Acute Respiratory Infection (SARI) cases during 2020/21 and 2021/22 (weeks 40-20) and inter-seasonal (weeks 21-39) periods in Georgia. All specimens from patients were screened on 22 respiratory viruses by real time RT-PCR.

Results

During 2020/21 season 50% (868/1729) specimens tested positive on at least one virus. No influenza virus and few RSV detections were observed in Georgia. Mostly identified virus was Rhino (44.8%) circulating almost all season; followed by Coronavirus OC43 (23.7%), primarily seen in weeks 12-18 and SARS-Cov-2 (15%) with highest detection rates during weeks 48-52. In 2021 inter-season 54% (825/1513) of specimens were positive. A gradual increase in RSV detections was observed in summer. Most seen viruses were Rhino (30%), HMPV (22%) and Parainfluenza virus 3 (21%) circulating mainly in June and July. During 2021/22 season 44% (2012/4545) of specimens screened positive, out of which RSV (25.7%) with earlier circulation in weeks 40-2 and Rhino (25.7%) with most detections in the beginning and at the end of the season. Unusually influenza A/H3 (17%) peaked in late spring (weeks 12-18). SARS-Cov-2, Parainfluenza viruses 3 and 4, Adenoviruses, Human bocavirus, enteroviruses were actively co-circulating too. In 2022 inter-season 54% (1320/2456) of samples tested positive. Influenza A/H3 circulation continued until July. SARS-Cov-2 (27.7%), Rhino (22%), HMPV (14.5%), Parainfluenza virus 3 (12.7%), RSV (10.8%) were mostly seen viruses predominantly in June.

Conclusion

Wider range respiratory viruses with higher positivity rates were detected among ILI and SARI cases in 2021/22 season compared to 2020/21 presumably due to mitigation of public health and social measures. Low detection rates of SARS-CoV-2 at sentinel sites could be explained by referral of COVID-19 patients to dedicated clinics. RSV and Influenza circulations were unusual in summer months in Georgia.

Disclosures

All Authors: No reported disclosures
2638. Patterning of high-risk comorbidity associated with vaccination but not influenza status among hospitalized patients in an influenza test-negative design cohort
Authors: Leis Aleda M , Monto Arnold , Martin Emily T
Published: November 2023

Background

The test-negative design is common in studies of influenza vaccine effectiveness. However, estimates are biased when there is heterogeneity in healthcare seeking behavior by vaccination or case status, both influenced by presence of high risk comorbidities. This study sought to examine potential differences in case rate and vaccination status by patterning of these comorbidities among hospitalized patients enrolled during the 2018/19 influenza season.

Methods

Participants were hospitalized with acute respiratory illness during the 2018/2019 influenza season in three major hospital systems in southeast Michigan within the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). Influenza was confirmed by molecular testing of respiratory specimens. Latent class models with 4 classes were constructed from 17 ICD-10 diagnostic code defined high risk conditions to assess clustering among individuals; this analysis assumes latent similarities exist among those within a class defined using known conditions. Individuals were assigned the class with the highest membership posterior predicted probability. Chi-square tests were used to compare classes.

Results

Characteristics of latent classes are in Figure 1 (n=840). There were statistically significant differences between classes for all conditions; Class 2 had highest prevalence of comorbidity with high frequencies of cardiometabolic and lung disease, and Class 3 had lowest prevalence of comorbidity with only modest frequency of lung disease. Influenza cases represented 18.4%, 13.6%, 20.5%, and 18.3% of those in each class, respectively (p > 0.05 for all pairwise comparisons). Vaccination rates were 77.6%, 77.3%, 55.8%, and 67.6%, respectively, with statistically significant differences between all classes except Classes 1 and 2 (p < 0.05 for all other comparisons).Figure 1.Conditions included in the latent class construction and subsequent frequencies in the assigned class. Total n=840.

Conclusion

Latent class analysis identified significant variation in influenza vaccination rates by patterning of high risk comorbidity among adults hospitalized with acute respiratory illness. Care should be taken to examine such differences within test-negative studies of vaccine effectiveness in hospitalized populations, with particular concern during circulation of multiple vaccine-preventable respiratory viruses.

Disclosures

Arnold Monto, MD, Roche: Advisor/Consultant|Roche: Honoraria Emily T. Martin, PhD, MPH, Merck: Grant/Research Support
2641. Nirsevimab binding-site conservation in RSV F protein between 2015 and 2022: The US OUTSMART-RSV surveillance study
Authors: Morehouse Christopher A , Ahani Bahar , Aksyuk Anastasia A , Brady Tyler , Tuffy Kevin M , Ji Hong , Kelly Elizabeth J , Wilkins Deidre
Published: November 2023

Background

Nirsevimab is an extended half-life monoclonal antibody that binds the prefusion conformation of RSV fusion (F) protein and has been approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants in the EU, Great Britain, and Canada. Global surveillance studies found that the nirsevimab binding site was highly conserved across RSV variants between 1956–2021. While RSV B F protein binding site substitutions I206M and Q209R have dominated since the 2017/2018 RSV season, both remain fully susceptible to nirsevimab. OUTSMART-RSV is a multi-year (from 2015) prospective molecular surveillance study to monitor the prevalence and distribution of RSV variants in the USA and track the emergence and susceptibility of RSV F variants to nirsevimab.

Methods

Nasal swabs were collected from infants and adults seeking medical attention for respiratory infection (inpatient or outpatient); RSV-positive isolates underwent next generation sequencing. Subtyping comprised analysis of the hypervariable region of the G protein. F protein polymorphisms were identified by comparing with RSV A and B reference sequences; variants with increasing prevalence were phenotypically evaluated using reverse genetics rescue and in vitro microneutralization assays.

Results

RSV A and B subtypes circulated with alternate frequency during OUTSMART-RSV (Figure 1), with RSV B dominant in the 2021/2022 RSV season (sequence count 509 vs 46 for RSV A; Table 1). From 2020, several additional RSV B F protein substitutions have increased in prevalence, including the S211N binding site substitution. Importantly, S211N retains full susceptibility to nirsevimab (IC50 fold change = 1.24 vs reference). Also, no new nirsevimab binding site substitutions were seen in the 2021/2022 RSV season vs previous seasons.

Conclusion

While I206M and Q209R substitutions in RSV B F protein continue to dominate, the S211N nirsevimab binding site substitution has increased in prevalence since the 2020-2021 season. However, similar to I206M and Q209R, S211N variants remain fully susceptible to nirsevimab. Among recent circulating RSV strains, the frequency of emergent nirsevimab escape variants continue to be rare and not persistent.

Disclosures

Christopher A. Morehouse, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Bahar Ahani, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Anastasia A. Aksyuk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tyler Brady, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Kevin M. Tuffy, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Hong Ji, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Elizabeth J. Kelly, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Deidre Wilkins, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds
2657. Investigation of Respiratory Syncytial Virus (RSV) Stability in Nasal Aspirate Collected from RSV Infected Patients
Authors: Yamamoto Atsuko , Kajiwara Yoko , Baba Takamichi , Okaga Saori , Kakui Mayumi , Shishido Takao
Published: November 2023

Background

RSV is the leading cause of serious acute lower respiratory infection in infants and various therapeutic agents are under investigation. For reliable study of antiviral effect of the agent in clinical study/trial, appropriate specimen storage which keeps virus stability is needed. WHO recommends specimens to be stored in transport medium and placed at 4°C. In case the specimens cannot be processed within 48 hours, they are recommended to be frozen at or below -70 °C. However, there is no investigation of RSV stability of specimen stored under these conditions. In this study, we investigated the RSV stability of nasal aspirates stored in universal transport medium (UTM) at 4°C or frozen by evaluating infectious virus titer.

Methods

Infectious virus titer was measured by immunostaining HEp-2 cells infected with RSV. To assess the variability of virus titration assay data, aliquots of RSV propagated with HEp-2 cells (RSV stocks) were titrated in three independent experiments and standard deviation (SD) was calculated. When the variation of virus titer from baseline was within 3SD, RSV was considered to be stable. As a preliminary experiment, virus stability of RSV stock stored in UTM at 4°C was evaluated. The impact of freezing method on RSV stability was also assessed. Nasal aspirates from 16 patients with confirmed RSV infection by rapid diagnostic test were collected and stored in UTM at 4°C up to 9 days with titration at 2 or 3 timepoints. Duration of stable RSV was estimated by statistical analysis of virus titer with regression model. RSV stability of specimen stored at -80°C for 10-15 months was also assessed.

Results

SD of RSV stock titration data was 0.3 log10TCID50/mL. RSV was considered to be stable when the variation of virus titer from baseline was within 1.0 log10TCID50/mL. Virus of RSV stock stored in UTM at 4°C was stable up to 120 hours. Sample freezing in deep freezer affected RSV stability, whereas freezing in liquid nitrogen or dry ice-ethanol bath kept RSV stability. RSV in nasal aspirates collected and stored in UTM at 4°C was estimated to be stable for 2 days. RSV in the specimen stored at -80°C for 10-15 months was stable.

Conclusion

RSV in nasal aspirate collected and stored in UTM at 4°C was estimated to be stable for 2 days. RSV in specimen stored at -80°C suggested to be stable for 1 year and more.

Disclosures

All Authors: No reported disclosures
2662. Efficacy of Sitafloxacin and Doxycycline Combination Therapy as a Salvage Treatment for Refractory Mycoplasma genitalium Infection
Authors: Ando Naokatsu , Mizushima Daisuke , Takano Misao , Mitobe Morika , Kobayashi Kai , Miyake Hirofumi , Kubota Hiroaki , Suzuki Jun , Oka Shinichi , Gatanaga Hiroyuki
Published: November 2023

Background

The prevalence of resistant strains of Mycoplasma genitalium has increased over the past few decades, leading to limited treatment options. This study aimed to evaluate the efficacy of sitafloxacin and doxycycline combination therapy as a salvage treatment for refractory rectal and urogenital M. genitalium infections.

Methods

Men who have sex with men (MSM) diagnosed to have M. genitalium infection from urine samples or rectal swabs using a PCR assay were evaluated and administered sitafloxacin 200 mg and doxycycline 200 mg daily for 21 days. Each sample was tested for 23rRNA, parC, and gyrA mutations before and if a failure after the treatment.

Results

A total of 27 MSMs were included. The median age was 33 years (range 21-47), and 33.3% (9/27) were people with HIV(PWH) (Table). Among PWH, the median CD4 count was 642, and all were virally suppressed with antiretroviral therapy. Positive samples included 22 rectal and 5 urine specimens. The time to test of cure(TOC) was 14 days (range 0-227). In the two failure cases 9 and 20, the TOC was conducted too early, and it was rechecked after 21 days following treatment completion; both rechecked TOCs were positive. ParC mutations were detected in 100%(23/23) of the samples, gyrA mutations in 66.7%(16/24) and ,macrolide-resistance associated mutations in 100%(22/22). Among the parC mutations, 95.7%(22/23) was G248T(S83I), while 4.3%(1/23) was G259T(D87Y). The overall cure rate was 81.5%. The cure for rectal infection was 81.8%(18/22), while the cure rate for urogenital infection was 80%(4/5). No significant difference was observed between the anatomical sites (p=0.924). The cure rate for strains harboring parC mutation and wild-type in gyrA was 85.7% (6/7), whereas the cure rate for the strain harboring parC mutation and gyrA mutation was 73.3%(11/15). No significant difference was found regardless of gyrA mutations (p=0.519). Additionally, no significant difference was observed in the cure rate between TOC < 21 days and >= 21 days (p=0.964).

Cases of Mycoplasma genitalium treatment and antimicrobial-resistance profiles in participants before and after treatment with the combination therapy

Conclusion

The combination therapy showed high efficacy of 81.5% for highly resistant M. genitalium infection and can be considered as a salvage treatment option for refractory cases.

Disclosures

All Authors: No reported disclosures
2671. The Sexual Health Clinic Mpox Response in King County, Washington, May–October 2022
Authors: Karmarkar Ellora , Cannon Chase , Ramchandani Meena , Golden Matthew R , Dombrowski Julia C
Published: November 2023

Background

Sexual health clinics, vital to the 2022 mpox outbreak response, were challenged by high patient volumes and delayed access to vaccines and tecovirimat. We describe the Public Health - Seattle King County Sexual Health Clinic (SHC) response, including vaccine and tecovirimat distribution, from 5/23/22 (first case in King County) to 10/14/22.

Methods

SHC began vaccinations in clinic on 7/4/22 and implemented a mass vaccination clinic on 7/25/22. Tecovirimat prescriptions initially required positive test results; by 7/29/22 SHC offered same-day presumptive treatment based on clinical suspicion. We calculated vaccines administered per week, proportion of visits related to mpox evaluation, and collected and summarized demographic and clinical data for diagnosed mpox cases. We assessed temporal trends in treatment type (presumptive vs results-based) using Kruskal-Wallis testing and differences in treatment receipt by race/ethnicity using chi-square testing (p< 0.05).

Results

From 5/23/22 to 10/14/22, SHC provided ≥1 vaccine dose to 9,753 people; the highest number within a week (n=1,537) were provided the week of 8/1/22 (Figure 1). Of 4,845 clinic visits, 486 (10%) patients were evaluated and tested for mpox; 174 (36%) were positive, comprising 36% of cases in King County at the time. 94% were cisgender men; 57% were White. 74 (43%) had severe symptoms including proctitis, hematochezia, or need for adjunctive pain control. Of 172 patients with complete clinical data, 154 (90%) received tecovirimat, including 83 (54%) treated presumptively. Provision of presumptive treatment increased significantly over time (P< 0.001) (Figure 2). Treatment receipt did not differ significantly by race/ethnicity (P=0.4).

Conclusion

The SHC substantially expanded vaccine access, served over 1/3 of patients with mpox in King County, and expedited mpox treatment through presumptive therapy, while continuing general sexual health services for patients within the county.

Disclosures

Chase Cannon, MD MPH, Roche Diagnostics: Advisor/Consultant Julia C. Dombrowski, MD, MPH, Hologic: Grant/Research Support|Mayne Pharmaceuticals: Grant/Research Support
2677. Evaluation of Expedited Partner Therapy Prescribing in an Urban Emergency Department
Authors: Perkins Nicholson B , Terrazas William Campillo , Boyer Casey , Kenney Rachel M , MacDonald Nancy
Published: November 2023

Background

Expedited Partner Therapy (EPT) is a useful tool that facilitates prompt treatment of sex partners in patients diagnosed with sexually transmitted infections (STIs). This study describes EPT utilization and documentation practices in an urban Emergency Department (ED) after implementing electronic EPT orders into a medical record system.

Methods

This retrospective, cross-sectional study evaluated EPT prescribing and documentation practices in an urban ED from 1/1/22 – 9/30/22. The study included patients older than 18 years of age with suspected chlamydia, gonorrhea, and/or trichomoniasis who received either a physical EPT prescription or an EPT kit. Collected data included patient characteristics, diagnostic and treatment data, and documentation measures. Descriptive statistics were used to assess the number of STI cases and those who received EPT.

Results

Data was collected on 37 patients who received EPT during their ED visit. The majority were uninsured (43%), and each patient had an average of 1.27 sex partners. HIV and syphilis screening were performed only in 8 (22%) and 7 (19%) of patients seen for a suspected STI. The number of cases for chlamydia (n=228), gonorrhea (n=149), and trichomoniasis (n=282) were disproportional to the total number of EPT orders throughout the 9-month study period. The number of EPT prescriptions was highest after the implementation of electronic sentences (n=27). At discharge, 76% of patients received a medication kit to provide direct treatment access for sex partners of index patients. Electronic dot phrases were used by 81% of providers to meet state documentation requirements. The results of this study demonstrate a significant STI burden with low EPT utilization from providers.

Conclusion

There was an increase of EPT utilization after the implementation of electronic order sentences in the electronic medical record. Screenings for HIV and syphilis are an area for improvement among patients at risk for an STI who are seen in the ED. The integration of electronic EPT methods can help address the growing rates of STIs in the U.S.

Disclosures

All Authors: No reported disclosures
2680. A Dangerous Comeback: Delivery Hospitalizations and Sexually Transmitted Diseases in Mississippi, 2016-2021
Authors: Staneva Manuela , Dobbs Thomas
Published: November 2023

Background

The United States is facing a new public health crisis: a surge in sexually transmitted diseases (STDs). The increase in STDs among pregnant patients is of special concern because these infections could lead to delivery complications and poor neonatal outcomes. To respond to this public health emergency, we examined trends and prevalence of STDs among pregnant patients admitted for deliveries in Mississippi.

Methods

This was a retrospective cross-sectional study of Mississippi’s hospital discharge data for the 2016-2021 period. This population-level data set contains demographic, clinical, and financial information from all non-federal hospitals in the state. The study included pregnant Mississippi residents (12-49 years) with a delivery admission. The unit of analysis was individual patients. We used the International Classification of Diseases-10-Clinical Modification to identify STDs among delivery admissions. We described patients' characteristics and performed trend analyses.

Results

Of the 4,466 (2.2%) delivery admissions with at least one coexisting STD diagnosis, the majority involved African Americans (62.2%), Medicaid-insured (64.6%), and non-urban residents (56.9%). Herpes simplex was the most prevalent infection, accounting for 57.0% of all STD-associated delivery admissions, followed by trichomoniasis (16.0%), other/unspecified STDs (11.0%), syphilis (8.5%), chlamydia (7.9%), and gonorrhea (4.8%).

Between 2016 and 2021, STD-associated delivery admissions rose 90.9%, beginning this increase in 2017 but soaring in 2019 right before COVID-19 (Figure). Alarmingly, syphilis-associated delivery admissions demonstrated the highest increase (545.0%). Herpes simplex (134.9%) and chlamydia (69.1%) also rose significantly. Over the course of the study period, only trichomoniasis-associated and gonorrhea-associated delivery admissions remained stable.

Conclusion

We identified an explosive upward trend in escalating STDs among delivery admissions in Mississippi. Especially troubling is the spike in syphilis among such patients. This study can provide public health structures with urgently needed information on the distribution and trends of STDs among Mississippi’s most vulnerable populations.

Disclosures

All Authors: No reported disclosures
2690. Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia Treated with Bruton Tyrosine Kinase Inhibitors - A Case-Control Propensity Score Match Analysis
Authors: Higuita Nelson I Agudelo , Chastain Daniel B , Scott Brian M , Sahra Syeda , Barahona Lilian Vargas , Cordero José Henao , Lee Alfred L H , Martínez Andrés F Henao
Published: November 2023

Background

Invasive fungal infections (IFIs) have been reported with increasing frequency in patients with chronic lymphocytic leukemia (CLL) treated with Bruton tyrosine kinase inhibitors (BTKi). High-quality real world data examining the frequency of IFIs and identifying risk factors to guide preventive measures in this patient population is lacking. We characterized the risk of IFIs among patient with CLL on BTKi one year after diagnosis using a global health research network.

Methods

We used TrinetX to identify patients with CLL based on diagnosis codes and stratified based on treatment with BTKi. Patients from each group were matched based on demographics, comorbidities, and medications to analyze the frequency of IFIs and outcomes at one year after CLL diagnosis.

Results

A total of 17,624 patients with CLL underwent propensity score matching. Approximately 82% of patients were white, 64% were male with a mean age of 69.5 years. Use of systemic corticosteroids, anti-CD20 antibodies, voriconazole, and fluconazole was higher in patients treated with BTKi (p < 0.001 for each drug). TMP/SMX administration was slightly higher in the BTKi group (18% vs. 17%, p = 0.01). At one year after CLL diagnosis, hospitalization was similar among groups (12.2% vs. 11.15%, p = 0.07), while mortality was lower in patients with CLL on a BTKi (9.9% vs. 12.3%, p < 0.001). Invasive candidiasis was less common (1.6% vs. 2.1%, p = 0.01) while pneumocystis was more common (0.3% vs. 0.1%, p = 0.007; risk ratio: 2.6, 95% CI: 1.3-5.4) in patients taking BTKi one year following diagnosis. The proportion of patients with invasive aspergillosis (0.1% vs. 0.2%, p = 0.143) or cryptococcosis (0.2% vs. 0.1%, p = 0.238) was similar between groups.

Conclusion

The overall frequency of IFIs was very low in patients with CLL on BTKi despite a higher frequency of steroid administration and only significant for PJP, albeit at a low annual risk of 0.3%. We calculated 500 patients needed prophylaxis to prevent one episode of PJP in patients with CLL on BTKi. This finding does not support routine PJP primary prophylaxis, considering the historical PJP risk of greater than 6.2% per person-year as the recommended threshold for primary prophylaxis in non-HIV immunocompromised patients.

Disclosures

All Authors: No reported disclosures
2698. Trends of Antibiotic Resistance in E. coli, Klebsiella Spp., Pseudomonas aeruginosa and Enterococcus spp. Urinary Tract Infection in Renal Transplant Recipients from Pakistan over a Decade
Authors: Dodani Sunil Kumar , Nasim Asma
Published: November 2023

Background

Antimicrobial resistance is a major public threat worldwide. In Pakistan many studies reported a rising trend of resistance to antimicrobials in clinical isolates of Klebsiella species (spp.), E-coli, Pseudomonas aeruginosa and Enterococcus spp. Solid organ transplant (SOT) recipients are more prone to infections, particularly with MDR organisms due to immunocompromised status, multiple hospital visits and increase exposure to antibiotics. There is paucity of data on antibiotic susceptibility pattern among renal transplant recipients from Pakistan. This study is conducted to find the trends in antimicrobial resistance pattern among common organisms isolated in urinary tract over a 10-year period in renal transplant recipients. The aim is to guide the physicians regarding decision over empirical antimicrobial choices.

Methods

A retrospective computerized data review of urine cultures from renal transplant recipients in 2010 and 2020 was conducted. The trend and sensitivity patterns of E.coli, Klebsiella spp. Pseudomonas aeruginosa and Enterococcus spp was collected. The resistance pattern of diffferent antibiotics were compared over the 10 years period.

Results

A total of 2,088 out of 6,249 (33%) and 2902 out of 8,115 (36%) urine cultures were positive in 2010 and 2020 respectively. The most common organisms isolated and their trend in the last decade is shown in figure 1. Over the decade, E-coli strains become 100% resistant to ciprofloxacin, ceftriaxone resistance has increased to 85% and imipenem to 10%. In Klebsiella spp. imipenem resistance has increased to 14%. There is no significant change in resistance pattern among Pseudomonas aeruginosa. Regarding Enterococcus spp. there is a rise in vancomycin resistance over the decade from 13% to 17%. (fig. 2)

Trends of organism over decade

Conclusion

Resistance to broad spectrum antimicrobials has been increased with >10% increase in carbapenems resistance over the last 10 years. E-coli have particularly become more resistant over the decade. We are also seeing more vancomycin resistant enterococcus. The alarming increase in resistance may lead to increased morbidity in renal transplant recipients because we left with only injectable options. We need a robust stewardship program for judicious use of antimicrobials to contain increasing resistance.

Disclosures

All Authors: No reported disclosures
158. Diagnostic Yield and Clinical Utility of Broad Range PCR Testing at a Tertiary Children’s Hospital
Authors: Schneider Jack , Prabhudas-Strycker Kirsten , Samaro Matthew , Student Medical , Goings Michael , Mellencamp Kagan A , Khan Haseeba , Boyd LaKeisha
Published: November 2023

Background

Broad range PCR testing (BR-PCR) targets highly conserved DNA sequences of bacteria, fungi, or mycobacteria to detect a broad range of organisms in various clinical samples. Given its potential impact in providing timely diagnoses that cannot always be made through conventional testing (CT), we evaluated the diagnostic yield and clinical impact of BR-PCR at our institution.

Methods

We retrospectively evaluated all clinical specimen types obtained for BR-PCR at Riley Hospital for Children from October 2019 to May 2022. Percent positivity (PP) was determined by specific PCR test type (Bacterial/Fungal/NTM/TB), along with median turn-around times (in days) from sample collection. Medical charts were reviewed, and clinical impact of results was determined.

Results

We identified 956 BR-PCR tests sent from 271 specimens collected from 178 patients. Only 14.5% yielded a positive result with a median days-to-result being the longest for fungal PCR at 8.1 days (7.0, 10.1) and TB PCR being the fastest at 7.8 days (6.8, 9.9). Bacterial BR-PCR yielded an overall PP of 42.6% while Fungal BR-PCR was 10.7%. Positivity rates for NTM and TB were 0% and 0.5%, respectively. Bronchial lavage was the most common specimen type (35.5%) with an overall PP of 19.9%. Of the 271 specimens, 245 returned conclusive results from both BR-PCR and clinical testing (CT) for comparison. A clinically significant organism based on CT was identified in 68 specimens (27.8%), 45 of which were confirmed by BR-PCR. 23 (33.8%) were detected by CT but not BR-PCR. 21 clinically significant organisms not detected by CT were identified by BR-PCR, which led to a change in clinical management in 12 instances: new diagnosis (91.7%); or appropriate initiation (91.7%), escalation (25.0%), or de-escalation (25.0%) of antimicrobial therapy.

Conclusion

BR-PCR overall had low diagnostic yield at our institution but was influenced by specimen type. The clinical utility was predominantly seen in immunocompromised patients in which conventional testing was negative. Further data is needed to determine which specimen types and diagnoses will increase the yield and clinical value of BR-PCR and thus, aid in enhancing diagnostic stewardship.

Disclosures

All Authors: No reported disclosures
2701. Mycobacterial Immune Reconstitution Inflammatory Syndrome Following Hematopoietic Cell Transplantation for GATA2 Deficiency
Authors: Epling Brian P , Cuellar-Rodriguez Jennifer , Arnold Danielle , Avila Daniele , Bauer Thomas , Cole Kristen , Daub Janine , Duncan Lisa , Gea-Banacloche Juan , Ma Stella , Merkel Roxanne , Palmer Cindy , Zerbe Christa , Holland Steven M , Sereti Irini , Hickstein Dennis , Manion Maura
Published: November 2023

Background

Immune reconstitution inflammatory syndrome (IRIS) was first described in patients with HIV and opportunistic infections starting antiretroviral therapy, but may be seen following hematopoietic cell transplantation (HCT) in patients with pre-existing infections. GATA2 deficiency is a genetic disorder with a marked susceptibility to mycobacterial infections, and is treated definitively with HCT. The clinical factors and pathogenesis of IRIS in HCT require further investigation.

Methods

We conducted a retrospective review of 32 patients with GATA2 deficiency and mycobacterial infections who completed > 6 months of follow-up after HCT. Uniform criteria were used to define cases of IRIS (Image 1). IRIS cases were classified as either early (post-HCT day < 60), intermediate (days 61-120), or late (day > 120).

Image 1. Post-Hematopoietic Cell Transplant IRIS Criteria

Criteria were adapted to hematopoietic cell transplantation from the AIDS Clinical Trial Group IRIS criteria.

Results

Clinical characteristics are shown in Image 2. IRIS was identified in 12 (35%) patients (Images 2-3). These patients were more likely to have disseminated infection (P=0.03), an elevated pre-HCT ferritin (P=0.03), and a lower day 30 post-HCT CD4 count (P=0.04).

Median time to IRIS was 100 days (Image 4). Pre-transplant duration of mycobacterial therapy correlated with time to IRIS (Pearson’s r=0.58, P=0.05). Conditioning regimens using total body irradiation with or without cyclophosphamide were associated with longer time to IRIS (hazard ratio=0.04, P=0.02). A rise in CD3 chimerism was seen during early cases of IRIS, but not intermediate to late (P=0.002). IRIS emerged during tapering of systemic immunosuppressive therapy in 33% of cases. IRIS was managed conservatively (50%), by intensification of anti-mycobacterial treatment (8%) or by intensification of immunosuppression (42%).

Conclusion

Development of mycobacterial IRIS after HCT for GATA2 deficiency was associated with disseminated infection, a high pre-transplant ferritin, and low day 30 CD4 count. These findings suggest that antigen burden, a hyperinflammatory state leading into transplantation, and CD4 nadir after HCT have a role in its pathogenesis. Early cases of IRIS may emerge during lymphoid engraftment and CD4 recovery, whereas late cases may emerge with decreases in immunosuppressive therapy and more intensive conditioning regimens. Clinical outcomes were similar to non-IRIS patients.

Disclosures

All Authors: No reported disclosures