bluuebunny/crossref_metadata_2025_split huggingface dataset:
1452. A Clinico-Epidemiological Study of Childhood Herpes Zoster
Authors: Mitra Barnali , Mitra Debdeep 
Published: December 2022

Abstract

Background
Herpes Zoster (HZ) is a viral infection believed to be due to re-activation of Varicella zoster virus (VZV) or human herpesvirus type 3 (HHV-3) that persists in the posterior nerve root ganglion. HZ is rarely reported in the pediatric age group with an intact immunity. Past infection with VZV and immunization with chicken pox vaccine are key markers in the onset of varicella zoster in children.

Methods
A prospective observational study over a total duration of two years was conducted in a tertiary hospital and all children less than 12 years of age with diagnosed HZ were included in the study.
Herpes zoster in a 2 years old child
Herpes zoster in a 11 years old child

Results
A total of 39 children were diagnosed to have pediatric HZ infection during the study period of two years. The children were followed up over 4 weeks post diagnosis and treated with oral Acyclovir therapy along with symptomatic management. All the children had an uneventful benign course and their siblings and close pediatric contacts were also screened for the development of HZ or chicken pox during the incubation period. All children were screened for an underlying immunodeficiency, and two cases of HIV co-infection was detected.
Tzank smear
Skin biopsy

Conclusion
HZ is a rare disease in childhood. Varicella in early childhood is a risk factor of HZ in immunocompromised and immunocompetent children. Childhood zoster occurs in either healthy or underlying immunodeficient children. The appearance of HZ in a young child does not always imply an underlying immunodeficiency or malignancy but the children should be screened for immunodeficiency. The prognosis is generally good in healthy children.

Disclosures
All Authors: No reported disclosures.
1469. Drug-resistance associated mutations of Human Cytomegalovirus (CMV) UL97 and UL54 genes in immunocompromised patients. Experience in Colombia, South America.
Authors: Rosso Fernando , Tafur Eric , Zapata-Vasquez Isabel L , Piedrahita Daniela , Valencia Alvaro Martinez , Agudelo Olga , Pachajoa Harry , Pérez-Castellano Paola , Ríos-Serna Lady , Diaz-Ordonez Lorena 
Published: December 2022

Abstract

Background
Cytomegalovirus (CMV) infection is a significant disease in immunocompromised patients, particularly transplant patients. The wide use of antivirals for prophylaxis and treatment has decreased the incidence and impact of this disease. Although, this exposure can lead to mutations in CMV UL54 and UL97 genes, which are associated with antiviral resistance. Little is known of the frequency of these mutations in Latin America, despite an increase in the transplant population.

Methods
We performed a prospective observational study. Patients with suspected CMV resistance based on the persistence of CMV DNAemia despite treatment were included from April to December 2019 in Fundación Valle del Lili. The blood samples were processed for DNA extraction, amplification, and sequencing for molecular characterization of (UL97) and (UL54) genes. Laboratory and clinical data were recollected from the clinical laboratory database and clinical charts.

Results
We enrolled 50 patients with CMV DNAemia, 32 amplified for gene sequencing. The median age was 31.7 years old, and 46.8% were males. 65.6% had a stem cell transplant, and 28.1% had a solid organ transplant. Only 65.2% had previous antiviral exposure. 93.7% manifested with CMV DNAemia alone, and 6.2% had CMV disease, hepatitis, and colitis. According to our findings, 56.2% had only UL54 mutations, 6.25% had only UL97 mutations, and 37.5% had both. The mutations associated with antiviral resistance were D605E and A594V for UL97 and A692S for UL54. The most common UL97 polymorphisms were V355A and F396L, while for UL54 were N898D, N685S, and S655L. On day 14 of treatment, 21.8% (7/32) had treatment failure. No canonic resistance mutations were found. 15.6% (5/32) of patients died; none had UL97 mutations, two had UL54 mutations associated with antiviral resistance, and three had polymorphisms of this gene.

Conclusion
Our study is the first one performed in Colombia. Although resistance was low, it was present in a few patients and related to mortality. It is important to study this evolving resistance as the use of antivirals increases in the transplant population in Latin America.

Disclosures
Olga Agudelo, n/a, Fundación valle del lili: Board Member.
1670. Activity of Ceftolozane/Tazobactam and Comparators Against Clinical MDR and DTR Pseudomonas aeruginosa isolates – SMART United States 2018-2020
Authors: Lob Sibylle , Hackel Meredith , Siddiqui Fakhar , Bauer Karri A , DeRyke Charles A , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: December 2022

Abstract

Background
Antimicrobial resistance of P. aeruginosa to commonly used β-lactams is typically higher in isolates collected from ICU patients and those with hospital-acquired infections. P. aeruginosa with multidrug-resistance (MDR) or difficult-to-treat resistance (DTR) is especially challenging as clinicians have limited treatment options. Ceftolozane/tazobactam was specifically developed to provide enhanced antibacterial activity against P. aeruginosa. We evaluated the activity of ceftolozane/tazobactam (C/T) and comparators against clinical P. aeruginosa isolates by ward type and length of hospital stay at time of specimen collection, including against MDR and DTR isolates.

Methods
In 2018-2020, 24 clinical labs participated in the global SMART surveillance program in the United States (US) and each collected up to 250 consecutive gram-negative pathogens per year from patients with bloodstream, intraabdominal, lower respiratory tract, and urinary tract infections. MICs were determined using CLSI broth microdilution and interpreted with CLSI breakpoints.

Results
C/T and amikacin were the only studied agents with activity &gt;95% against all isolates in all strata, with only small differences between the strata (Table). Susceptibility to commonly used β-lactams was 4-8 percentage points lower among isolates collected ≥48 hours post-admission than &lt; 48h and from patients in ICUs compared to non-ICU wards. Correspondingly, the prevalence of MDR and DTR isolates was higher among isolates collected ≥48 hours post-admission (14.6% and 7.3%, respectively) than &lt; 48h (10.5%/6.1%) and those collected from ICU patients (16.1%/7.2%) than non-ICU (10.0%/5.8%). The pattern of lower susceptibility among isolates collected ≥48h post-admission or in ICUs was less clear when the MDR and DTR subsets were analyzed. C/T remained active against ≥72% of MDR and ≥68% of DTR isolates, 7-31 percentage points higher than ceftazidime/avibactam.

Conclusion
Based on these in vitro data, C/T represents a treatment option for patients with infections caused by MDR and DTR P. aeruginosa, regardless of time to infection or treatment in the ICU.

Disclosures
Fakhar Siddiqui, MD, MBA, Merck & Co., Inc.: employee|Merck & Co., Inc.: Stocks/Bonds Karri A Bauer, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds.
1673. In vitro Activities of Ceftaroline and Comparator Agents against Bacterial Pathogens Frequently Causing Community-Acquired Respiratory Tract Infections in Patients from a Global Population: ATLAS Surveillance Program 2017-2020
Authors: Hackel Meredith , Stone Gregory , Sahm Daniel F 
Published: December 2022

Abstract

Background
Community-acquired bacterial pneumonia (CABP) is a frequent cause of patient morbidity and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent etiologic agents of CABP. Ceftaroline fosamil is a parenteral cephem approved for treatment of patients with CABP caused by S. pneumoniae (including cases with concurrent bacteremia), methicillin-susceptible Staphylococcus aureus (MSSA), H. influenzae, and some species of Enterobacterales. In this study we report the in vitro activity of ceftaroline and comparators against isolates from community-acquired respiratory tract infections (CARTI) collected through a global surveillance program.

Methods
Clinically relevant, non-duplicate, isolates cultured from respiratory specimens by clinical laboratories in 54 countries in 2017-2020 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). In total, 2,284 isolates of S. pneumoniae, H. influenzae, M. catarrhalis, MSSA, and methicillin-resistant S. aureus (MRSA) were tested. The isolates (n/percent of total) originated from Asia/South Pacific (579/25.4%); Europe (1281/56.1%); Latin America (298/13.0%); Middle East/Africa (55/2.4%); and North America (Canada only) (71/3.1%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2022 CLSI M100 MIC breakpoints.

Results
Ceftaroline and comparator agent in vitro activities are summarized in the table. Greater than 98% of S. pneumoniae and &gt;99% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Fifty-eight (31.4%) MRSA were ceftaroline-susceptible-dose-dependent (MIC 2-4 µg/mL) based on a dosage of 600 mg every 8h administered over 2h, with the majority from (n) China (18), S. Korea (8), and Japan (8). Three isolates, all from China, were resistant to CPT (MIC of 8 µg/mL). 99.3% of H. influenzae were susceptible to ceftaroline.

Conclusion
Ceftaroline demonstrated potent in vitro activity against current pathogens associated with CABP from a global collection.

Disclosures
All Authors: No reported disclosures.
1674. Trends in Antimicrobial Susceptibility to Ceftolozane/Tazobactam and Comparators of Pseudomonas aeruginosa from Patients with Respiratory Tract Infections in Five Latin American Countries – SMART 2017-2020
Authors: Lob Sibylle , Hackel Meredith , Siddiqui Fakhar , Pavia Jacqueline , DeRyke Charles A , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: December 2022

Abstract

Background
Ceftolozane is a cephalosporin specifically developed to have enhanced antibacterial activity against P. aeruginosa. Combined with tazobactam, it was approved by FDA and EMA for hospital-acquired/ventilator-associated bacterial pneumonia. We evaluated trends in the activity of ceftolozane/tazobactam (C/T) against P. aeruginosa isolates collected as part of the global SMART surveillance program from patients with lower respiratory tract infections (RTI) in Argentina, Brazil, Chile, Colombia, and Mexico.

Methods
In 2017-2020, 29 clinical labs each collected up to 100 consecutive gram-negative pathogens per year from patients with RTI. A total of 6,036 isolates were collected &lt; 48 or ≥48 hours post-admission, of which 1,679 (27.8%) were P. aeruginosa. MICs were determined using CLSI broth microdilution and breakpoints. C/T- or imipenem-nonsusceptible isolates were screened for genes encoding β-lactamases.

Results
Using only isolates from the 21 sites that participated in all 4 years, variability in susceptibility was seen over the study period among isolates collected &lt; 48h post-admission, with a significant increasing trend in susceptibility only for C/T, while susceptibility was lower and more stable among isolates collected ≥48h (Figure). These patterns correlated with estimated carbapenemase rates, especially among isolates collected &lt; 48h post-admission (9.7%, 4.2%, 8.1%, 1.6% carbapenemase-positive per year 2017-2020). Using isolates from all sites from the two most recent years to assess country-level susceptibility, substantial variability was seen. For example, susceptibility to C/T of isolates collected after 48h ranged from 62.5% for Chile (n=120) to ≥92% for Argentina (n=128) and Brazil (n=183), 12-31 percentage points higher than meropenem and piperacillin/tazobactam. This geographic pattern correlated with estimated carbapenemase rates (36% of isolates collected in Chile 48h post-admission versus ≤4% for Argentina and Brazil).

Conclusion
Variability in antimicrobial susceptibility of P. aeruginosa from RTI was seen across Latin American countries, but overall no significant decreases in susceptibility were found over the study period. C/T remained the most active among the studied agents.

Disclosures
Fakhar Siddiqui, MD, MBA, Merck & Co., Inc.: employee|Merck & Co., Inc.: Stocks/Bonds Jacqueline Pavia, MD, MSD COLOMBIA: EMPLOYEE Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds.
1683. Antifungal Activity of Alexidine Dihydrochloride in a Novel Diabetic Mouse Model of Dermatophytosis
Authors: Nabeela Sunna , Ibrahim Ashraf S , Uppuliri Priya 
Published: December 2022

Abstract

Background
Ringworm caused by the dermatophyte species Trichophyton is the foremost superficial fungal infection worldwide. The US alone records over 5 million outpatient visits due to dermatophytosis, with an annual burden of one billion dollars in associated direct medical costs. Patients with diabetes mellitus exhibit a higher incidence rate and a more severe manifestation of the disease. Infections are often recurrent and recalcitrant to most antifungal drugs and new molecules to combat these discomforting infections are sorely needed. Here, we establish a novel model of dermatophytosis, which is clinically relevant, simple to use, and is robust enough for evaluation of antifungal drugs. Using this model, we demonstrate that an FDA-approved small molecule alexidine dihydrochloride has enhanced efficacy against dermatophytes.

Methods
For the animal model, ICR mice (equal gender) were rendered diabetic by treatment with a single intraperitoneal dose of streptozotocin, followed by confirmation of glycosuria and ketonuria. The back of the anesthetized diabetic mice was shaved, skin abraded with sand paper, and inoculated with 50 µl of sterile water containing 5x10^7 conidia. Infected lesions were monitored daily, and graded for erythema, edema, and extent of infection over a period of 2 weeks. For drug treatment, infected mice were separated equally into four groups: topical treatment of 20 µg/ml alexidine dihydrochloride, topical 1% terbinafine, 10 mg/kg terbinafine by oral gavage, and a vehicle control. Treatment was started on day 4 post infection and given once daily for 7 days. Lesions were monitored as above and clearance of infection was confirmed by fungal culture and histopathology.

Results
In the absence of drugs, dry, scaly erythematous legions appeared on day 3 after infection and became progressively worse, persisting for at least 14 days. Terbinafine and Alexidine dihydrochloride were highly efficacious in curbing infections within two days after treatment and no recurrence was observed for up to 10 days post treatment.

Conclusion
The diabetic mouse model was found to be reproducible and applicable for primary evaluation of the anti-dermatophytic efficacy of topical and oral formulations of antifungal agents.

Disclosures
All Authors: No reported disclosures.
1696. Comparison of in vitro activities of linezolid and contezolid against clinical Nocardia isolates
Authors: Wei Ming , Wang Peng , Wang Shuai , Yang Chunxia , Degree Master’s , Gu Li 
Published: December 2022

Abstract

Background
Nocardia is nearly 100% susceptible to linezolid which is one of the first-line agents for all clinical species and isolates reported in the literature. However, adverse reactions related to myelosuppression and monoamine oxidase inhibition have limited linezolid use to some extent. Contezolid, a new oxazolidinone antibiotic that has decreased toxicity compared to linezolid, was launched in China in June 2021. In this study, the in vitro activities of linezolid and contezolid are compared against Nocardia.

Methods
Ninety-four clinical Nocardia isolates from Beijing Chao-Yang Hospital were identified by multilocus sequence analysis, and the in vitro activities of linezolid and contezolid were evaluated using the broth microdilution method. A Wilcoxon Signed Rank Test was performed to determine if linezolid and contezolid are significantly different from each other against clinical Nocardia isolates.

Results
Pulmonary nocardiosis (91.5%) was the most common clinical presentation of Nocardia infections. N. cyriacigeorgica (36.2%) and N. farcinica (16.0%) were the most frequently encountered Nocardia species, followed by N. abscessus (9.6%) and N. otitidiscaviarum (9.6%). The MIC (minimum inhibitory concentration) ranges of all clinical Nocardia isolates for linezolid and contezolid were 0.5-8 μg/mL. The MIC50/MIC90 values for all isolates of Nocardia for linezolid vs contezolid was 2/4 μg/mL vs 2/4 μg/mL, and for N. cyriacigeorgica and N. farcinica were 4/4 μg/mL vs 2/4 μg/mL and 4/4μg/mL vs 2/4 μg/mL, respectively. After a Wilcoxon Signed Rank Test analysis, the P values of all Nocardia isolates was &lt; 0.001, and for N. cyriacigeorgica and N. farcinica were 0.001 and 0.020, respectively.

Conclusion
Though MIC50/MIC90 values for linezolid and contezolid for all Nocardia isolates evaluated appeared to be similar, there was a statistically significant difference between the two antibiotics. Furthermore, the MIC50 values for the most commonly encountered species N. cyriacigeorgica and N. farcinica were lower for contezolid than for linezolid. Therefore, the in vitro activity of contezolid is better than that of linezolid against clinical Nocardia isolates, and contezolid could also be an option for the treatment of Nocardia infections.

Disclosures
All Authors: No reported disclosures.
1699. Efficacy and Safety by BMI Category and Gender in Contezolid and Contezolid Acefosamil Phase 2 and Phase 3 Skin Infection Clinical Trials
Authors: Fang Edward , Yang Huahui , Yuan Hong 
Published: December 2022

Abstract

Background
Contezolid (CZD; MRX-I) is a novel oral (PO) oxazolidinone with potent activity against multidrug-resistant Gram-positive pathogens. Contezolid acefosamil (CZA; MRX-4) is an intravenous (IV) double prodrug of CZD. Nonclinical and initial clinical data indicate CZA and CZD may cause less myelosuppression, particularly with longer duration therapy, and with reduced risk of monoamine oxidase inhibition compared to linezolid (LZD). In 3 CZD Phase 2 (Ph2) and Phase 3 (Ph3) skin infection trials and 1 CZA Ph2 acute bacterial skin and skin structure infection (ABSSSI) study, primary efficacy and overall safety outcomes were comparable to LZD, and the most common treatment emergent adverse events (TEAEs) were gastrointestinal; however, hematologic laboratory abnormalities and TEAEs were less common with CZD and CZA. In June 2021, CZD was approved in China for complicated skin and soft tissue infections (cSSTI). Sequential therapy with CZA IV followed by CZD PO is being evaluated in global Ph3 diabetic foot infection (DFI) and ABSSSI clinical trials. Body weight and gender can affect drug pharmacokinetics (PK) and potentially efficacy and safety outcomes, though in CZA and CZD Phase 1 (Ph1) pharmacokinetics (PK) studies, PK differences between male and female healthy subjects were not considered to be significant. Efficacy and safety outcomes for male and female patients, and between subjects of different body mass index (BMI) were evaluated in completed Ph2 and Ph3 CZD and CZA studies.

Methods
In 4 CZD and CZA Ph2 and Ph3 skin infection trials, men and women were enrolled with no weight restrictions, and no dose adjustments were made for gender or BMI. Primary efficacy outcomes and occurrence of TEAEs were evaluated for CZD and CZA subjects in 3 BMI categories, and also in male and female subjects.

Results
Primary efficacy outcomes and occurrence of TEAEs appeared to be similar for CZD and CZA male and female subjects, and also subjects in different BMI categories in 4 skin infection trials.

Conclusion
In 4 completed Ph2 and Ph3 skin infection clinical trials, primary efficacy and safety outcomes appeared similar for male and female subjects, and for subjects of varying BMI, supporting current Ph3 global DFI and ABSSSI studies which will enroll men and women with no body weight restrictions.

Disclosures
Edward Fang, MD, MicuRx Pharmaceuticals Inc: Employee Huahui Yang, MS, MicuRx Pharmaceuticals Inc: Employee.
1708. In vitro Activities of Ceftazidime-Avibactam and Comparator Agents against Enterobacterales and Pseudomonas aeruginosa Collected &lt; 48 Hours and ≥48 Hours Post-Admission from Hospitalized Pediatric Patients, ATLAS Global Surveillance Program 2017-2020
Authors: Wise Mark , Stone Gregory , Sahm Daniel F 
Published: December 2022

Abstract

Background
Ceftazidime-avibactam (CAZ-AVI) is a β-lactam combined with a diazabicyclooctane-β-lactamase inhibitor for treatment of infections caused by Gram-negative pathogens. Ceftazidime-avibactam is active against Enterobacterales (Ent) and P. aeruginosa (Psa) isolates that produce Class A, C and some Class D β-lactamases. This study examined the in vitro activity of CAZ-AVI and comparators against Ent and Psa from presumed community-acquired (CA; cultured &lt; 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) infections collected from pediatric patients as part of the ATLAS surveillance program, 2017-2020.

Methods
5765 non-duplicate Ent and 1987 Psa isolates from pediatric patients (≤17 y.o.) were collected from 241 sites in 54 countries as part of ATLAS 2017-2020 (excluding North America) for which the length of hospitalization stay was specified. Antimicrobial susceptibility testing was by broth microdilution according to CLSI guidelines and analyzed using CLSI 2022 breakpoints. Ent isolates testing with meropenem MICs &gt;1 µg/mL and Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. variicola, and Proteus mirabilis testing with ceftazidime and/or aztreonam MICs &gt;1 mg/L were genetically screened for β-lactamases. For Psa, meropenem MIC &gt;2 µg/mL triggered β-lactamase screening. In 2020, approximately 25% of the meropenem non-susceptible isolates were screened.

Results
Against Ent, the in vitro activity of CAZ-AVI exceeded that of meropenem and other tested agents for both the presumed CA- and HA-infection sets. The addition of AVI to CAZ increased the %S from 76.1% to 97.5% for the CA-infection population, and from 62.2% to 96.1% for the HA-infection population. For Psa There was a larger difference between the %S to CAZ-AVI of the presumed CA set (93.3% S) and the HA set (89.8% S). For both Psa populations, CAZ-AVI was the most active drug among the comparators.

Conclusion
CAZ-AVI demonstrated potent in vitro activity against Enterobacterales and P. aeruginosa isolates collected globally from pediatric patients in 2017-2020, regardless of whether is infection was community-or hospital-acquired.

Disclosures
All Authors: No reported disclosures.