bluuebunny/crossref_metadata_2025 huggingface dataset:
1145. The Role of the Plasmid-Mediated Fluoroquinolone-Resistance (PMFQR) Genes As Resistance Mechanisms in Pediatric Infections due to Enterobacterales (Ent)
Authors: Pitstick Claire E , Marshall Steven , Konda Sreenivas , Medernach Rachel L , Domitrovic T Nicholas , Hujer Andrea M , Qureshi Nadia K , Rudin Susan D , Zheng Xiaotian , Weinstein Robert A , Bonomo Robert A , Logan Latania K
Published: December 2021

Background

Fluoroquinolones (FQs) are not commonly prescribed in children, yet the increasing incidence of multidrug resistant (MDR) Ent infections in this population often reveals FQ resistance. We sought to define the role of FQ resistance in the epidemiology of MDR Ent in children, with an overall goal to devise treatment and prevention strategies.

Methods

A case-control study of children (0-18 years) at 3 Chicago hospitals was performed. Cases had infections by FQ susceptible, 3rd generation cephalosporin-resistant (3GCR) and/or carbapenem-resistant (CR) Ent harboring a non or low level expressed PMFQR gene (PMFQS Ent). Controls had FQR infections due to 3GCR and/or CR Ent with expressed PMFQR genes (PMFQR Ent). We sought bla genes by PCR or DNA (BD Max Check-Points assay®) and PMFQR genes by PCR. We performed Rep-PCR, MLST, and E. coli phylogenetic grouping. Demographics; comorbidities; and device, antibiotic, and healthcare exposures were evaluated. Predictors of infection were assessed.

Results

Of 170 G3CR and/or CR Ent isolates, 85 (50%) were FQS; 23 (27%) had PMFQR genes (PMFQS cases). 85 (50%) were FQR; 53 (62%) had PMFQR genes (PMFQR controls). The median age for children with PMFQS Ent and PMFQR Ent were 4.3 and 6.2 years, respectively (p=NS). Of 23 PMFQS Ent, 53% were Klebsiella and of 53 PMFQR Ent, 76% were E. coli. The most common bla and PMFQR genes in PMFQS Ent were blaSHV ESBL (44%); oqxB (57%) and aac-6’1b-cr (52%) and in PMFQR Ent were blaCTX-M-1 group (76%); aac-6’1b-cr (91%) and oqxA (17%).

Multivariable regression analysis showed children with PMFQS Ent infections were more likely to have hospital onset infection (OR 5.7, 95% CI 1.6-22) and isolates with multiple bla genes (OR 3.8, 95% CI 1.1-14.5). The presence of invasive devices mediated the effects of healthcare setting in the final model. Differences in demographics, comorbidities, or antibiotic use were not found.

Conclusion

Paradoxically, PMFQS Ent infections were often hospital onset and PMFQR Ent infections were community onset. PMFQS Ent commonly co-harbored multiple bla and PMFQR genes, affecting therapeutic options and suggesting need for contact precautions. Control of PMFQS Ent infections in children will require validating sources and risk factors.

Disclosures

Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)
1148. Duration of Antibiotic Therapy in the Treatment of Bacterial Meningitis in Young Infants: A Systematic Review and Narrative Synthesis
Authors: Van Hentenryck Maite , Schroeder Alan , McCulloh Russell , Stave Christopher D , Wang Marie E
Published: December 2021

Background

IDSA recommendations of 14-21 days of parenteral therapy for bacterial meningitis are based predominantly on expert consensus. Parenteral durations consistent with these recommendations are sometimes provided even when meningitis is suspected but not confirmed. We aimed to systematically review the literature on duration of parenteral antibiotic therapy and outcomes in bacterial meningitis in infants < 3 months of age.

Methods

We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for publications up until May 11, 2021. Eligible studies were published in English and included infants < 3 months of age with bacterial meningitis for which route and duration of antibiotic therapy and outcomes were reported. We excluded case reports and infants with birth weight < 1500g, major congenital malformations, or neurosurgical conditions. We assessed bias using published tools specific to study type. A meta-analysis was not conducted due to insufficient data on outcomes by duration of therapy. PROSPERO registration: CRD42020201667.

Results

A total of 2195 studies were identified; 280 were selected for full text review and 32 were included for narrative synthesis. There was 1 randomized-controlled trial (RCT), 25 cohort studies, and 6 case series. The RCT found no difference in treatment failure rates between 10 and 14 days of therapy, but only included 2 cerebrospinal fluid (CSF) culture-positive cases. A single cohort study including only CSF culture-negative cases presented outcomes by duration of therapy and concluded that courses >21 days had no impact on prognosis. Twenty-one studies had data on duration of therapy and outcomes by patient, most with small samples (median 4 patients). No conclusions on efficacy of shortened antibiotic courses could be drawn due to small sample sizes and lack of stratification of outcomes by short versus long courses.

Conclusion

Data on parenteral treatment duration in bacterial meningitis in infants < 3 months are primarily observational, and larger studies rarely report outcomes by duration of therapy. Given the associated risks and costs of prolonged parenteral therapy, there is a pressing need for comparative effectiveness research to determine the optimal parenteral treatment duration.

Disclosures

All Authors: No reported disclosures
1149. Application of a Multiplex Polymerase Chain Reaction Test for Diagnosing Bacterial Enteritis in Children in a Real-Life Clinical Setting
Authors: Lee Hyun Woo , Han Seung Beom , Rhim Jung-Woo
Published: December 2021

Background

Although a bacterial multiplex polymerase chain reaction (mPCR) test should be performed selectively in patients with gastrointestinal symptoms consistent with bacterial enteritis, its usefulness has been evaluated upon stool samples as requested by clinicians, without considering the patients’ gastrointestinal symptoms or clinical diagnoses. This study aimed to determine the subjects to bacterial mPCR testing and to interpret the mPCR test results with considering patients’ clinical symptoms and diagnoses.

Methods

Medical records of 710 pediatric patients for whom a bacterial mPCR test was performed were retrospectively reviewed. Clinical characteristics and mPCR test results were compared between patients with positive mPCR test results (n = 199) and those with negative mPCR test results (n = 511) and between patients in whom inflammatory pathogens (Campylobacter spp. and Salmonella spp.) were identified (n = 95) and those in whom toxigenic pathogens (Clostridium spp.) were identified (n = 70).

Results

A positive mPCR test result was significantly associated with an older age (p < 0.001), diagnosis of acute gastroenteritis (p = 0.021), presence of hematochezia (p < 0.001), and absence of cough (p = 0.004). The diagnosis of acute gastroenteritis (p = 0.003), presence of fever (p = 0.027) and diarrhea (p = 0.043), and a higher C-reactive protein level (p = 0.025) were significantly associated with the identification of inflammatory pathogens rather than toxigenic pathogens in patients with positive mPCR test results.

Conclusion

Bacterial mPCR testing should be performed selectively based on patients’ clinical symptoms and diagnoses, and its results should be interpreted with considering identified pathogens.

Disclosures

All Authors: No reported disclosures
1150. Pediatric Osteoarticular Infections Caused by Mycobacteria Tuberculosis Complex: A Twenty-Six Year Review of Cases in San Diego, California
Authors: Drobish Ian , Ramchandar Nanda , Raabe Vanessa , Pong Alice , Bradley John S , Cannavino Christopher R
Published: December 2021

Background

Osteoarticular infections (OAI) account for 10-20% of extrapulmonary Mycobacteria tuberculosis (MTB) complex infections in children. Given the rarity of MTB OAI, the epidemiology, disease manifestations, and treatment are poorly characterized. We describe 21 children treated for MTB complex OAI over a 26-year period at a tertiary pediatric center in southern California.

Methods

We conducted a retrospective review of children diagnosed with MTB complex OAI and cared for between 31 Dec 1992 to 31 Dec 2018 at a single tertiary care pediatric hospital with close proximity to the United States-Mexico border.

Results

We identified 21 children with MTB complex OAI during the study period (Table 1). Concurrent pulmonary disease (4.8%), meningitis (9.5%), and intra-abdominal involvement (14.3%) were all observed. MTB complex was identified by culture from operative samples in 15/21 children (71.4%); 8/15 (51.3%) cultures were positive for Mycobacterium bovis. Of the eight cases of vertebral OAI (the most common site), one was culture-positive for M. bovis. Open bone biopsy was the most common procedure for procurement of a tissue sample and had the highest culture yield (Table 2). The median duration of antimicrobial therapy was 52 weeks (IQR 52-58). Successful completion of therapy was documented in 15 children (71.4%). Seven children (33.3%) experienced long term sequelae related to their infection.

Table 1. Twenty-one children with Mycobacteria tuberculosis complex osteoarticular infections.

Table 2. Surgical sample type and percent positivity.

Conclusion

Among the 21 children with MTB complex OAI assessed, 8 of 15 (53.3%) children with a positive tissue culture had M. bovis (intrinsically resistant to pyrazinamide), representing a higher percentage than in previous reports and potentially reflecting its presence in unpasteurized dairy products in the California-Baja region. Local epidemiological trends in endemic MTB complex species should be considered when evaluating and managing MTB complex OAI. Bone biopsy produced the highest culture yield in this study. Given the rarity of this disease, multicenter collaborative studies are needed to improve our understanding of the presentation and management of pediatric MTB complex OAI.

Disclosures

Vanessa Raabe, MD, MSc, Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, Editorial support)Sanofi (Scientific Research Study Investigator)
1151. Clinical Characteristics of Persistent Staph Aureus Bacteremia in Children
Authors: Venturelli Nicholas , Bhagat Palak , Nelson Allison , Kumar Madan
Published: December 2021

Background

Persistent Staphylococcus aureus bacteremia (pSAB) is a poorly defined entity, but associated with significant morbidity and mortality in children. We aim to better describe the epidemiological features of this clinical entity.

Methods

We performed a retrospective case series analysis of pediatric patients with pSAB at a single center children’s hospital using electronic medical data from 2016 – 2020. Bacterial persistence was defined as culture growth > 72 hours after first blood culture.

Results

Twenty-two patients with pSAB were included in the analysis. Sources of persistent infection were endovascular infection (n=11, 50%), osteoarticular infection (n=6, 27%,), isolated central line associated blood stream (n=4, 18%), isolated skin and soft tissue infection (n=2, 9%), and no known primary infectious site (n=1). Methicillin resistance occurred in 41% (n=9) of cases of pSAB. Total duration of therapy varied, with a median of 4 weeks from negative cultures (range of 2 – 8 weeks). Total days of positive cultures in pSAB were not significantly associated with methicillin susceptibility of the bacterial isolate, use of double gram-positive coverage, nor presence of a central venous catheter. Use of double gram-positive coverage occurred in 50% of cases with a mean duration of therapy of 11 days, most frequently in cases of septic thrombophlebitis (Table 1). Rifampin and gentamicin were the most commonly used agents.

Table 1. Clinical Characteristics of Children Treated with Double Gram-Positive Coverage

Conclusion

Children presenting with persistent S. aureus bacteremia present with a heterogenous group of underlying conditions and epidemiological features. While pediatric recommendations for double gram-positive coverage for synergy have not been established, their use for pSAB is common, especially in endovascular infections where culture persistence is often an expected outcome. Further research should examine risk factors for pSAB and define optimal treatment modalities and duration.

Disclosures

All Authors: No reported disclosures
1152. Microbiology of Pediatric Neck Infections Based on Age and Anatomic Location
Authors: Dimo Joana , Zembles Tracy N , Bushee Glenn , Mitchell Michelle L
Published: December 2021

Background

Studies of pediatric neck infections demonstrate an increase in methicillin resistant Staphylococcus aureus (MRSA), and predominance of Staphylococcus aureus (S. aureus) in infants, and commonly polymicrobial infections. Thus, some providers treat acute neck infections with empiric broad spectrum antibiotics, often with two drugs. Our institution often uses clindamycin plus ampicillin-sulbactam as empiric therapy for hospitalized children with acute neck infection. We aimed to identify the microbiology of acute neck abscesses at our institution to determine if stratifying by age and abscess location would allow for single agent therapy.

Table 1. Causative organism based on anatomic location of neck infection.

Methods

Diagnosis codes identified patients hospitalized with acute neck infections. Cases with underlying malignancy, cervicofacial malformations, or lymphatic malformations were excluded. Patients with surgical cultures were categorized into two groups based on anatomic location of infection: medial (retropharyngeal, parapharyngeal, and peritonsillar), lateral (other locations), or both. Within each group, causative pathogen(s) were explored and further categorized by age (infants: < 1 year old; non-infants: ≥1 year old).

Results

412 patients were hospitalized for acute neck infection of which 132 had surgical cultures. 110 had growth of one or more pathogens (20 infants, 90 non-infants). 53 infections were located medially, 54 laterally, and 3 had both locations involved. S. aureus was most commonly identified, with lateral infections accounting for the majority (Table 1). 40/44 S. aureus isolates were susceptible to clindamycin. Among medial infections, Streptococcus Anginosus and Group A Streptococcus were most common followed by S. aureus (Table 1). 17/20 (85%) positive cultures in infants grew S. aureus with 8/17 (47%) MRSA. No polymicrobial infections were identified in infants. Among non-infants, 0/39 lateral infections had polymicrobial growth but 23/50 (46%) of medial infections did.

Conclusion

Local epidemiology based on anatomic location and patient age suggests a single agent (clindamycin for lateral and penicillin with beta-lactamase inhibitor for medial) may be reasonable for non-infants with uncomplicated neck infections. For infants, coverage of MRSA, regardless of anatomic location, is advisable.

Disclosures

All Authors: No reported disclosures
1153. ESBL Producing E. coli Urinary Tract Infections in Children: Is Carbapenem Always Necessary?
Authors: del Carmen Ruiz Cabrales Diva , Oviedo Gabriel Ivan Narvaez , Londono-Ruiz Juan Pablo , Tobar Ivan Felipe Gutiérrez
Published: December 2021

Background

Urinary tract infections (UTI) are common in children with a prevalence of 5% in infants. UTI are the main reason for beginning antibiotics in children’s hospitals and E. coli is approximate 80% of urinary pathogens. Extended-spectrum beta-lactamases (ESBL) producing E. coli are a common concern in daily practice. Carbapenems, especially ertapenem are the choice for the treatment in some hospitals, but aminoglycosides or trimethoprim and sulfamethoxazole are options for carbapenem saver. The aim of this study was comparing the clinical outputs in ESBL producing E. coli ITU in children treated with ertapenem or amikacin.

Methods

We designed a quasi-experimental study. In 2018 the antimicrobial stewardship program begins the use of amikacin for non-septic UTI for ESBL producing E. coli. Before this recommendation the use of ertapenem was common. We use WHONET 5.6 to identify ESBL producing E. coli UTI between 2016 and 2020. We analyzed the information using R 4.0.3.

Results

We analyzed 162 clinical records. 89 in ertapenem group, 45 in amikacin group, 23 in other treatments (TMP-SMX, meropenem) and 5 patients that received empirical treatment (Cefazolin) with clinical improvement and ambulatory management. The initial clinical and paraclinical variables was similar between two groups, only meropenem was more frequent in amikacin group as empiric treatment (table 1). Amikacin group received for media 7.4 days of antibiotic therapy (IQR 7-7.5) and ertapenem 8.2 days (IQR 7-10) (p value 0.049). The mortality, PICU requirement, mechanical ventilation and inotropic requirement was similar an both groups (Table 2). In amikacin group the median length of stay was 7.2 days (IQR 4-9) and in ertapenem group was 9 days (IQR 6-10). No significant adverse effects were documented in any group.

Table 1. Patient’s characteristics in both groups.

Table 2. Patient’s Clinical outcomes in both groups

Conclusion

The use of amikacin in ESBL producing E. coli UTI in children have similar clinical outputs that ertapenem. The use of amikacin could decrease de hospitalization time.

Disclosures

Ivan Felipe Gutiérrez Tobar, n/a, Pfizer and MSD (Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau, Has received support from Pfizer and MSD for participation in congresses and has received conference payments from Pfizer)Pfizer and MSD (Speaker’s Bureau, Other Financial or Material Support, Has received support from Pfizer for participation in congresses)
1155. Covering Your Tracts? The Effect of Antibiotic Prophylaxis on Respiratory Tract Infections in Pediatric Acute Lymphoblastic Leukemia
Authors: Strength Rachel , Cross Shane , Pui Ching-Hon , Jeha Sima , Gowen Ashleigh , Wolf Joshua , Wolf Joshua
Published: December 2021

Background

Antibiotic prophylaxis decreases rates of febrile neutropenia and systemic infection in children with acute lymphoblastic leukemia (ALL). However, it is unknown whether prophylaxis prevents or ameliorates the severity of specific types of infections like upper respiratory tract infections (URTI) or lower respiratory tract infections (LRTI).

Methods

This is a retrospective, observational convenience cohort study of children with newly-diagnosed ALL, comparing respiratory tract infections (RTI) in participants receiving no antibiotic prophylaxis, levofloxacin prophylaxis, or non-levofloxacin prophylaxis. Information regarding the presence of URTI or LRTI, identified respiratory viruses, hospitalization, oxygen supplementation, and ICU admission was collected through medical record review. The proportion of participants in each group was estimated and compared between groups using Fisher’s exact test and the Kruskal-Wallis test.

Results

Of 262 evaluable participants, 126 received no antibiotic prophylaxis, 59 received levofloxacin prophylaxis, and 77 received non-levofloxacin prophylaxis, with a total of 136 children getting any antibiotic prophylaxis regimen. In the no-prophylaxis group, 22/126 (17.4%) had RTI, compared to 23/136 (16.9%) in the prophylaxis group. There was no significant difference in the numbers of LRTI and URTI, with or without an identified respiratory virus, regardless of the presence or type of antibiotic prophylaxis. Participants receiving prophylaxis did not have a significantly different risk of hospitalization, oxygen supplementation, or ICU admission.

Participant Characteristics

Comparisons of levofloxacin prophylaxis, other prophylaxis, any prophylaxis, and no prophylaxis

Conclusion

There was no observed difference in RTI, hospitalization, oxygen supplementation, or ICU admission for RTI between participants receiving or not receiving antibiotic prophylaxis in this cohort. Because of the relatively low number and severity of respiratory infections, and the high proportion that are viral in etiology, it would likely take a very large sample size to determine the impact of antibacterial prophylaxis on respiratory infections during induction therapy for pediatric ALL.

Disclosures

Joshua Wolf, MBBS, PhD, FRACP, Karius Inc. (Research Grant or Support) Joshua Wolf, MBBS, PhD, FRACP, Nothing to disclose
1161. Increasing incidence of Sinogenic Intracranial Infections in Utah Children 2004-2019
Authors: McNamara Isabella , Pershing Nicole L , Wilkes Jacob , Bonkowsky Anne
Published: December 2021

Background

Intracranial extension of sinusitis is a rare complication. Non-specific presentations are a diagnostic challenge, and complications include long-term neurologic sequelae. Early recognition is critical, although optimal management remains poorly characterized.

Methods

We conducted a retrospective chart review of 123 patients admitted to Primary Children’s Hospital between 2004-2019 with ICD9 and ICD10 codes for sinusitis and intracranial suppurative infection. Chart review confirmed cases in patients < 18 years with evidence of sinusitis and intracranial extension. Variables collected included: demographic data, clinical presentation, microbial profile, clinical management, and outcomes.

Results

We observed 84 pediatric sinogenic intracranial infections between 2004-2019. Incidence significantly increased over the interval. Median patient age was 12.8 years (IQR 10.5-14.7 years); most were male (n=52). The most common presenting symptoms were headache and fever. Most patients (n=80) required surgical management; 62 required neurosurgery. All but one patient survived. Most infections were polymicrobial (n=47). Streptococcus anginous group were most frequently identified (n=32). All patients were started on vancomycin empirically; only 10 required use for definitive management. Most patients were treated with a carbapenem (n=42) or ceftriaxone plus metronidazole (n=32). Average duration of antibiotics was 44 days (IQR 38-55 days). The most common complication was epilepsy (n=11). Patients with Streptococcus sp. infections were more likely to experience adverse outcomes (p= 0.04). We observed significantly decreased carbapenem use following introduction of an antimicrobial stewardship program in 2012, with no change in clinical outcomes.

Annual incidence of Sinogenic Intracranial Infections

Shown is the increasing incidence of sinogenic intracranial infections annually in the state of Utah/100,000 children.

Conclusion

Sinogenic intracranial infections are increasingly frequent severe pediatric infections with associated long term neurologic sequelae. Most patients require both surgical and long-term IV antibiotic treatment. Most infections are polymicrobial. Streptococcus sp. are commonly identified. Antibiotic resistant bacteria are rare. The combination ceftriaxone and metronidazole is appropriate for treatment of most infections.

Disclosures

Anne Bonkowsky, MD/PhD, BioFire Diagnostics (Consultant, Grant/Research Support, Other Financial or Material Support, I have intellectual property through the University of Utah in BioFire Diagnostics and the FilmArray and receive royalties through the University of Utah.)Merck (Advisor or Review Panel member)
1162. Antifungal Use in Immunocompromised Children in Europe: a 12-week Multicenter Modified Point prevalence Study (CALYPSO)
Authors: Chorafa Elisavet , Iosifidis Elias , Oletto Andrea , Warris Adilia , Castagnola Elio , Bruggemann Roger , Groll Andreas , Lehrnbecher Thomas , Ferreras-Antolin Laura , Mesini Alessio , Roilides Emmanuel
Published: December 2021

Background

While antifungal consumption in immunocompromised patients appears high, data on children are limited. We analyzed antifungal use in hospitalized immunocompromised children across Europe in order to better organize a European pediatric antifungal stewardship programs (pAFS).

Methods

A multicenter 12-wk modified point-prevalence study was conducted. All patients hospitalized in hematology-oncology (HO) or bone marrow/solid organ transplant (BMT/SOT) units across Europe and receiving systemic antifungals were included. Data on ward demographics and policies were collected once at the beginning; weekly ward and patient data were prospectively collected during the 12-wk study period and entered in REDCap. Systemic antifungals administered were recorded (doses, duration, reason for administration or discontinuation).

Results

Twenty-one HO and 10 BMT/SOT units from 18 hospitals in 11 European countries participated in the study and 572 antifungal prescriptions were recorded. The most common underlying conditions were: 69% malignancy (81% hematologic, 19% solid tumors), 20% BMT, 6% hematologic diseases except malignancy and 4% primary immunodeficiency. Indication of antifungals was prophylaxis for 439 (77%) and treatment for 133 (23%) prescriptions (62 empirical, 43 pre-emptive, 28 targeted). Most common reasons for empirical, pre-emptive and targeted treatment were antibiotic-resistant febrile neutropenia (52%), abnormalities on chest-CT with/without positive galactomannan (72%) and candidiasis (82%), respectively. For targeted treatment, the most frequent pathogens were C. albicans (50%), C. parapsilosis (11%) and A. fumigatus (11%). Overall, fluconazole and liposomal amphotericin B were the most frequently prescribed agents both for prophylaxis (31% and 21%) and treatment (32% and 23%). However, in BMT patients the most frequently prescribed antifungal agents were fluconazole or micafungin for prophylaxis and caspofungin and voriconazole for treatment (Table).

Antifungal agents used per underlying condition

Antifungal agents used per underlying condition

Conclusion

Most systemic antifungal prescribing across European HO and BMT/SOT units is for prophylaxis, and fluconazole is the main antifungal prescribed. Results from this multicenter study can be a first step to guide a Europe-wide pAFS.

Disclosures

Emmanuel Roilides, MD, PhD, ECMM (Research Grant or Support, Other Financial or Material Support, ECMM grant for this study)
1163. HIV-1 NAAT Pitfalls in B-cell Lymphoblastic Leukemia Patients Following CAR-T Cell Therapy
Authors: Alali Muayad , Christenson John , skiles Jodi
Published: December 2021

Background

CAR-T Cell Therapy is approved for the treatment of pediatric patients with relapsed/refractory B-ALL. Lentiviral vector technology, highly modified from HIV-1, is used to induce stable, long-term transgene expression by integration into the host genome. This integration may interfere with HIV-1 NAAT producing false-positive results.

Methods

A retrospective chart review of Pre-B ALL patients who underwent to CAR T cell therapy with KYMRIAH(tisagenlecleucel) at a single institution between January 2019 and May 2021 to assess for patients whose CAR-T infusion interfered with post-infusion HIV-1 testing. All patients had HIV NAAT pre and post CAR T-cell therapy (using platform, Roche COBAS AmpliPrep/Quantitative TaqMan HIV-1 T). Reactive HIV NAAT by Roche test were subsequently tested using different HIV-1 assay platforms to rule out or confirm HIV infection.

Results

We report three cases in which interpretation of HIV-1 NAAT testing was complicated by CAR T cell therapy. Case 1: 1-year-old male with refractory infantile leukemia was found to have a reactive HIV NAAT post CAR-T in routine infectious screening prior to SCT. Case 2: 3-year-old refractory ALL planned for SCT who had a reactive HIV NAAT 9 months post CART. Fourth-generation HIV-1 testing (targeting the p24 antigen and anti-HIV-1 antibodies) was negative pre and post CART. Viral loads were also undetectable indicating false-positive post-CAR-T HIV-1 NAT test results. Case 3: 21-year-old sexually active female with relapsed B cell ALL. Post CAR-T HIV NAAT was reactive, and a quantitative viral load was positive at 176 copies/mm3 one day prior to start of stem cell transplant conditioning regimen. Aptima HIV testing is typically used as confirmatory test for CAR-T associated false positive HIV NAT cases, but surprisingly, the Aptima test was also reactive. Additional testing with Abbott m2000 Realtime HIV-1 assay and 4th generation p24 antigen-based testing were both negative.

Table 1 Summary of reported patients with false-positive HIV-1 NAAT test results following CAR T cell therapy and Table 2, HIV platforms used for screening and diagnosis with interpretations following CAR T cell therapy.

Conclusion

Clinicians need to be aware of potential false-positive HIV testing after CAR-T therapy. HIV testing platforms with targets not used in lentiviral vectors (4th generation test/P24, or Abbott test/integrase region) are highly recommended to avoid delays in subsequent therapy and unwanted stress for the patients, families, and clinicians

Disclosures

All Authors: No reported disclosures
1166. Reverse Syphilis Screening and Adherence to The Congenital Syphilis Guidelines: Institutional Experience
Authors: Chatani Brandon , Chaparro Aida , Alvarez Patricia , Arheart Kristopher , Gonzalez Ivan , Moraru Gabriela
Published: December 2021

Background

This study is analysis the consequences of the reverse syphilis screening on the management of newborns exposed to maternal syphilis, and pediatric physicians’ adherence to the existing guidelines.

Methods

We conducted a 5-year retrospective review of the maternal population and their newborns diagnosed with syphilis. Women with positive results (TT+/NTT+) and discordant (TT+/NTT-/TT+) and their newborns were included in the analysis.

Results

Per American Academy of Pediatrics (AAP), the 202 newborns were divided in two groups: proved or highly probable and possible congenital syphilis (Group A, n=102) and less likely and unlikely congenital syphilis (Group B, n=100). Except for the RPR, none of the other laboratory tests showed higher odds for predicting congenital syphilis. The RPR titers above 1:16 were only identified among newborns belonging to the Group A (5%); 32 patients (31%) in the Group A and 19 (9%) in the Group B had an RPR titer equal to or below 1:8. An RPR titer equal to or above 1:4 was almost three times more likely to be identified in patients from Group A (OR 2.91; CI 1.51- 5.59, p< 0.05). The newborns with non-reactive RPRs represented 64% of the patients in the Group A and 47% of them were born to mother with non-reactive RPR also (mothers with discordant results). Among the Group B, 82% of the neonates had a non-reactive RPR and 54% were delivered to mother with non-reactive RPRs. Babies in Group B had additional work-up performed 69% (n=37) of the time; 15% of these babies were treated with intramuscular penicillin which does not follow established AAP guidelines.

Statistical analysis of the laboratory tests used for the congenital syphilis work-up

Result table comparing the two groups of newborns

Conclusion

The reverse syphilis screening and non-adherence to the guidelines led to additional screening to half of the newborns in both groups. This study highlights the need for a comprehensive maternal history at the time of delivery that is effectively communicated between the providers. This might lead to greater congruence with the established AAP guidelines.

Disclosures

All Authors: No reported disclosures
136. Impact of an OPAT Pharmacist on Guideline Adherence and Clinical Outcomes
Authors: Lin Alice , Nakasone Trisha S , Nguyen Nancy N , Yang Catherine
Published: December 2021

Background

Outpatient parenteral antibiotic therapy (OPAT) provides select patients a cost-effective alternative to completing intravenous (IV) antibiotic therapy outside the hospital. The Infectious Diseases Society of America (IDSA) OPAT practice guidelines and handbook recommend weekly laboratory monitoring and timely follow-up for OPAT patients. An analysis at VA Palo Alto Healthcare System (VAPAHCS) conducted prior to pharmacist involvement demonstrated that IDSA recommendations were not routinely followed, leading to a clinical cure rate of 62.7%. This led to the implementation of an OPAT pharmacist in 2019. This analysis aims to determine the impact of a pharmacist-managed OPAT program at VAPAHCS.

Methods

This comparative, retrospective analysis included patients who received OPAT at VAPAHCS between October 1, 2019 and September 30, 2020 and those who received OPAT in a prior analysis. Primary outcomes included rates of adherence to IDSA recommendations on follow-up visits and weekly lab monitoring during OPAT. Secondary outcomes included rates of clinical cure, 90-day readmission, and adverse events or complications. Data was analyzed using Fisher’s exact test and independent t-test.

Results

This analysis included 74 patients and 76 total OPAT episodes. Bacteremia was the most common diagnosis (n=35, 38.0%), and the most common organism was methicillin-susceptible Staphylococcus aureus (MSSA) (n=23, 29.9%). With respect to guideline adherence pre- and post- pharmacist-managed OPAT, 31.3% versus 93.4% of patients had follow-up within 7 to 14 days of discharge (p< 0.001). Rates of weekly lab monitoring of CBC, BMP, and LFTs pre-pharmacist were 63.2%, 63.3%, and 49.5%, respectively, compared to post-pharmacist rates of 93.0%, 92.1%, and 83.6%, respectively. Clinical cure rates were 62.7% pre-pharmacist and 89.6% post-pharmacist (p< 0.001). More adverse drug reactions were identified in the post-pharmacist period, of which 30% required pharmacist intervention.

Figure 1. Weekly Laboratory Monitoring of Antimicrobials (%)

Figure 2. Adherence to IDSA Guideline Follow-up Recommendation

Figure 3. Rates of Clinical Cure

Conclusion

Pharmacist involvement in OPAT significantly increased IDSA guideline adherence to lab monitoring and follow-up visits, and clinical cure rates. Identification of adverse drug reactions prompting pharmacist intervention further highlights the importance of follow-up in OPAT patients.

Disclosures

All Authors: No reported disclosures
1167. Hospital Readmissions among Infants Diagnosed with Early-Onset Neonatal Sepsis in Connecticut
Authors: Hudon Rebecca , Leung Vivian , Leung Vivian , Petit Susan , Banach David
Published: December 2021

Background

Early-onset neonatal sepsis, defined as sepsis within 72 hours of birth, results in significant infant morbidity and mortality. Readmissions associated with neonatal sepsis have not previously been well-described. Early-onset neonatal sepsis is a mandatory reportable condition in Connecticut, allowing for expanded data collection through public health surveillance to evaluate readmissions.

Methods

Infants with early-onset neonatal sepsis born in Connecticut during 2007–2016 were identified from statewide surveillance data and matched with a statewide hospital discharge database. We describe readmission rates, causes and timing of readmissions, and demographic and clinical factors associated with readmission among this group.

Results

Among 250 infants with early-onset neonatal sepsis matched to discharge data, 208 (82%) infants survived their initial hospitalization at birth. During the first year of life, 49 (23.6%) infants were readmitted. The most frequent reasons for readmissions were pulmonary complications (19%), systemic symptoms (17%), and gastrointestinal illness (13%). Infants with initial hospitalizations lasting longer than 30 days after birth were associated with higher rates of readmission compared to those discharged within 30 days after birth (35% vs. 19%, p=0.02). Higher readmission rates were observed among non-white infants (29% vs. 18%, p=0.06).

Summary of early-onset neonatal sepsis cases and return hospital visits in Connecticut, 2007-2016

Demographic and clinical factors for Connecticut neonatal sepsis cases, 2007-2016

Reason for one-year readmissions of Connecticut neonatal sepsis cases, 2007-2016

The top three reasons for readmission include pulmonary (19%), systemic (17%), and GI problems (13%).

Conclusion

Given the high proportion of infants diagnosed with early-onset neonatal sepsis who are readmitted within the first year of life, further efforts are needed to prevent readmissions among this vulnerable patient population. Non-white infants and infants with prolonged initial hospitalizations after birth might be at higher risk for readmission. These groups warrant intensified strategies to prevent readmission.

Disclosures

Vivian Leung, MD, Nothing to disclose
1169. Revenge of the Syph(ilis): Investigating Congenital Syphilis at a Tertiary Care Center Amidst a Rising Epidemic
Authors: Ness Tara , Rochat Ryan H , Bocchini Claire , Mary Healy C
Published: December 2021

Background

Congenital syphilis is a chronic infection acquired by the fetus in utero from a mother infected with Treponema palladium. It has a large spectrum of disease manifestations from asymptomatic infection to blindness, abnormal bone and teeth formation, deafness, or even death. Despite antenatal screening and the availability of effective treatment the incidence of congenital syphilis has risen since 2012, with 23.3 cases per 100,000 live births in 2017 according to the Centers for Disease Control. We sought to investigate the epidemiology, clinical manifestations, and treatment outcomes of congenital syphilis.

Methods

We undertook a retrospective review of individuals born at Texas Children’s Hospital from January 1, 2010 to May 15, 2021 to evaluate compliance with current diagnostic and treatment recommendations. Diagnostic and billing codes for congenital syphilis were used to generate a list of subjects. Patient demographics and clinical details were abstracted from the electronic medical record (EMR). Statistics were performed using Microsoft Excel.

Results

107 children (52% male, 48% female) were identified from diagnostic and billing codes in the EMR under the SNOMED-CT diagnosis of “congenital syphilis” and were less than two years of age at the time of diagnosis. All received penicillin within one month of diagnosis. 94 of these had a skeletal x-ray performed, with 11 (12%) having an abnormal skeletal x-ray consistent with congenital syphilis. 88 (82%) had a lumbar puncture done with a quantitative CSF VDRL obtained. 88 received aqueous penicillin G for proven/highly probable or possible syphilis. Four patients were deceased at the time of data inquiry. Of those with abnormal skeletal x-rays, “metaphyseal lucency” was the most common finding.

Conclusion

Congenital syphilis remains a significant concern in the United States and carries the risk of significant long-term morbidity for infants and children. Antenatal screening with appropriate treatment in pregnancy and adequate follow-up would decrease the need for neonatal evaluation and treatment.

Disclosures

C. Mary Healy, MD, Dexcom (Shareholder)Intuitive (Shareholder)Quidel Corporation (Shareholder)Up to Date (Other Financial or Material Support, Honorarium)Vapotherm (Shareholder)
1170. Do Rotavirus Strains Affect Vaccine Effectiveness? A Systematic Review And Meta-analysis
Authors: Cates Jordan , Amin Avnika , Tate Jacqueline , Lopman Ben , Parashar Umesh D
Published: December 2021

Background

Rotavirus causes 215,000 deaths from severe childhood diarrhea annually. Two rotavirus vaccines – a monovalent vaccine containing a single rotavirus strain (RV1) and a pentavalent vaccine containing 5 rotavirus strains (RV5) – are used in routine immunization programs of nearly 100 countries. Concerns exist that rotavirus vaccines may be less effective against rotavirus strains not contained in the vaccines which could subsequently cause selective pressure and strain replacement. We estimated the vaccine effectiveness (VE) of RV1 and RV5 against vaccine (homotypic) and non-vaccine (partially and fully heterotypic) strains.

Methods

After conducting a systematic review, we meta-analyzed 31 case-control studies (N=27,293) conducted between 2006 and 2020 using a random-effect regression model.

Results

In high-income countries, RV1 VE was 10% lower against partially heterotypic (p-value=0.04) and fully heterotypic (p-value=0.10) compared to homotypic strains (homotypic VE: 90% [95% CI: 82, 94]; partially heterotypic VE: 79% [95% CI: 71, 85]; fully heterotypic VE: 80% [95% CI: 65, 88]; Figure 1). In middle-income countries, RV1 VE was 14 to 16% lower against partially heterotypic (p-value=0.06) and fully heterotypic (p-value=0.04) compared to homotypic strains (homotypic VE: 81% [95% CI: 69, 88]; partially heterotypic VE: 67% [95% CI: 54, 76]; fully heterotypic VE: 65% [95% CI: 52, 75]; Figure 1). Strain-specific RV5 VE differences were less pronounced (Figure 2). Limited data were available from low-income countries.

Figure 1. Vaccine effectiveness by country income level and strain type, for RV1.

Figure 2. Vaccine effectiveness by country income level and strain type, for RV5.

Conclusion

Vaccine effectiveness of RV1 and RV5 was somewhat lower VE against non-vaccine than vaccine strains. Ongoing surveillance is crucial to continue long-term monitoring for strain replacement, particularly in low-income settings where data are limited.

Disclosures

All Authors: No reported disclosures
1172. SARS-CoV-2 Vaccine Hesitancy in Caregivers of Hospitalized Children
Authors: Orbea Marisa , Cunningham Rachel , Mary Healy C , Boom Julie A , Bocchini Claire
Published: December 2021

Background

SARS-CoV-2 vaccine hesitancy (VH) is hindering nationwide vaccination efforts; little is known about caregiver SARS-CoV-2 vaccine acceptance for children. We aimed to identify associations with SARS-CoV-2 VH in caregivers of hospitalized children.

Methods

We conducted a prospective cross-sectional survey in English and Spanish of caregiver COVID-19 knowledge, attitudes, behaviors, and associated VH among hospitalized children 6 months - 18 years at a large pediatric medical institution. Parents were approached daily, averaging 4-5 days/week, from 12/8/2020--4/5/2021. VH was assessed using the Parent Attitudes about Childhood Vaccines (PACV) survey; PACV score ≥50 denoted VH. Descriptive statistics and multivariable logistic regression were used. Responses were categorized.

Results

295/307 (96%) of approached caregivers enrolled; 79% were ≥ 30 years, 68% were married/ living with a partner, and 57% had at least some college. 36% identified as white, 19% Black, and 46% Hispanic/ Latino. 53% of caregiver children had public insurance. 91% of caregivers self-reported their children were up to date with routine vaccines. 17% of caregivers were vaccine-hesitant overall. 50% of caregivers were willing to receive COVID-19 vaccine themselves. Figure 1 shows intention to vaccinate their child by PACV score.

65% knew someone who was hospitalized for COVID-19. 67% were scared of their child getting COVID-19. However, 49% were scared of their child getting the vaccine, 28% did not want to vaccinate their child and 27% were neutral in the intention to vaccinate their child. Caregivers who did not intend to vaccinate their child were more likely to be Black (27% vs. 16%, p=0.04) and less likely to be Hispanic/ Latino (33% vs. 49%, p=0.02). Table 1 shows attitudes, beliefs, and behaviors surrounding the COVID-19 pandemic and vaccine in caregivers who did or did not intend to vaccinate their child.

Figure 1

COVID-19 vaccine uptake by PACV score

Table 1

Caregiver attitudes, beliefs, and behaviors surrounding the COVID-19 pandemic and the COVID-19 vaccine

Conclusion

The majority of caregivers believe that SARS-CoV-2 vaccine will help control the pandemic, but less than half plan to vaccinate their children. A quarter of caregivers expressed uncertainty regarding the vaccine and therefore may be amenable to education and discussion. COVID-19 VH is different from VH towards routine vaccinations. More research is needed to address COVID-19 specific VH.

Disclosures

C. Mary Healy, MD, Dexcom (Shareholder)Intuitive (Shareholder)Quidel Corporation (Shareholder)Up to Date (Other Financial or Material Support, Honorarium)Vapotherm (Shareholder)
1175. Influenza Vaccine Hesitancy in Hospitalized Children, Before and During the COVID-19 Pandemic
Authors: Orbea Marisa , Dominguez Jose , Cunningham Rachel , Mary Healy C , Boom Julie A , Bocchini Claire
Published: December 2021

Background

Influenza vaccine is recommended for all children ≥6 months, yet uptake is suboptimal. We aimed to quantify child influenza vaccine coverage and identify factors associated with influenza vaccine hesitancy (VH) before and during the COVID-19 pandemic.

Methods

We conducted a prospective, repeated cross-sectional assessment in English and Spanish of caregiver influenza knowledge, attitudes, behaviors, and associated VH among hospitalized children 6 months through 18 years at a large pediatric medical institution. Caregivers were enrolled 4-5 days per week, between 12/11/2019--1/31/2020 and 12/8/2020--4/5/2021. VH was assessed using the Parent Attitudes about Childhood Vaccines (PACV) survey; PACV score ≥50 denoted VH. Descriptive statistics and multivariable logistic regression were used.

Results

During 2019-2020 and 2020-2021 influenza seasons, 269/282 (95%) and 295/307 (96%) of approached caregivers enrolled, respectively. By caregiver report, 94% of children in 2019-2020 and 91% in 2020-2021 were up-to-date with routine childhood vaccines (p=0.13). Specific to influenza vaccine, 73% and 68% of children received or planned to receive influenza vaccine in 2019-2020 and 2020-2021, respectively (p=0.13). Based on PACV score, 13% of parents were VH in 2019-2020 compared with 17% in 2020-2021 (p=0.24; Figure 1).

Caregivers who had not/did not intend to vaccinate their children had a higher family income (71% vs. 57% >&30,000, p< 0.01) and were less likely to be Hispanic/Latino (35% vs. 47%, p=0.02). 77% of caregivers were satisfied with information about influenza vaccine received from healthcare providers. Overall, 36% believed “you can get the flu from the flu shot.” In 2020-2021, caregivers were less likely to believe that “flu can be a dangerous infection in children,” to be “scared of my child getting the flu” and to agree that “all children over 6 months of age should receive the flu shot every year” (Table 1).

Table 1. Caregiver knowledge and attitudes about seasonal influenza vaccine, 2019-20 versus 2020-21

Figure 1. Influenza vaccine uptake by PACV score during 2019-2020 (a) and 2020-2021 (b) seasons

Conclusion

During the COVID-19 pandemic, caregivers of hospitalized children were less concerned about influenza than pre-pandemic and misinformation about influenza and influenza vaccine persisted. Increased efforts may be needed to educate caregivers about the importance of influenza immunization during the 2021-22 season.

Disclosures

C. Mary Healy, MD, Dexcom (Shareholder)Intuitive (Shareholder)Quidel Corporation (Shareholder)Up to Date (Other Financial or Material Support, Honorarium)Vapotherm (Shareholder)