bluuebunny/crossref_metadata_2025 huggingface dataset:
1293. In vitro Activity of Ceftibuten in Combination with VNRX-5236 against Clinical Isolates of Enterobacterales from Urinary Tract Infections Collected in 2018-2020
Authors: Hackel Meredith , Wise Mark G G , Sahm Daniel F
Published: December 2021

Background

Increasing resistance among agents commonly prescribed to treat urinary tract infections indicate that new oral agents are urgently needed. Ceftibuten in combination with VNRX-7145 is under development as an oral treatment for complicated urinary tract infections caused by serine β-lactamase-producing Enterobacterales, including isolates carrying ESBLs and carbapenemases. In vivo, VNRX-7145 (VNRX-5236 etzadroxil) is cleaved into to the active inhibitor, VNRX-5236. This study assessed the in vitro activity of ceftibuten/VNRX-5236 against 592 isolates of Enterobacterales from urinary tract infections (UTIs) from a 2018-2020 global culture collection.

Methods

MICs of ceftibuten with VNRX-5236 fixed at 4 µg/mL and comparators were determined following CLSI M07-A11 guidelines against 592 Enterobacterales. Isolates were from community and hospital UTI infections collected from 133 sites in 31 countries in 2018-2020. Resistant phenotypes were based on 2021 CLSI breakpoints.

Results

A substantial percentage of isolates were non-susceptible to extended-spectrum β-lactams, levofloxacin (LVX), trimethoprim-sulfamethoxazole (SXT), and amoxicillin-clavulanate (AMC) (Table). The addition of VNRX-5236 reduced ceftibuten MIC90 values by ≥8-fold to ≥128-fold, depending on the resistant subset. Ceftibuten/VNRX-5236 had potent activity against all Enterobacterales, with MIC50/90 values of 0.06/0.25 µg/mL and 98.3% inhibited at ≤2 µg/mL. Ceftibuten/VNRX-5236 maintained activity against resistant subsets (MIC90 range, 0.5 to 2 µg/mL; 91.5% to 97.1% inhibited at ≤2 µg/mL), including serine carbapenemase-positive isolates (MIC90 0.5 µg/mL; 100% inhibited at ≤1 µg/mL). Ceftibuten/VNRX-5236 in vitro potency was similar to that of newer parenteral and investigational oral therapies.

Results Table

Conclusion

Ceftibuten/VNRX-5236 exhibited promising in vitro activity against recent Enterobacterales from UTIs, and may have potential as an oral treatment option for complicated urinary tract infections, including those caused by serine β-lactamase-expressing Enterobacterales (ESBL, KPC, OXA-48/OXA-48-like) for which there are currently few oral treatment options available.

Disclosures

Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Mark G G. Wise, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1294. Activity of Ceftolozane/Tazobactam and Comparators against Resistant Pseudomonas aeruginosa Isolates from Patients with Respiratory Tract or Bloodstream Infections in ICU and non-ICU settings – SMART United States 2018-2019
Authors: Lob Sibylle , Hackel Meredith , Andrew DeRyke C , Harris Kelly , Young Katherine , Motyl Mary , Sahm Daniel F
Published: December 2021

Background

ICUs are considered hotspots of antimicrobial resistance. Treatment of ICU patients with infections caused by P. aeruginosa (Pa) is especially challenging. When patients fail to improve on therapy with first-line antipseudomonal agents such as piperacillin/tazobactam (P/T) or cefepime (FEP), clinicians often escalate to a carbapenem. Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin (combined with a β-lactamase inhibitor) that was specifically developed to have enhanced antibacterial activity against Pa. We evaluated the activity of C/T and comparators against Pa isolates collected from patients with respiratory tract (RTI) or bloodstream infections (BSI) in ICU and non-ICU settings. Co-resistance (e.g., activity of C/T or meropenem (MEM) when Pa is nonsusceptible (NS) to P/T or FEP) was also evaluated to help inform common clinical scenarios.

Methods

In 2018-2019, 24 US clinical labs each collected up to 100 RTI and 50 BSI consecutive gram-negative pathogens per year as part of the global SMART surveillance program. Only the 1195 Pa isolates collected from patients in ICU or non-ICU hospital wards were included in this report; 1078 and 117 isolates were from patients with RTI and BSI, respectively. MICs were determined using CLSI broth microdilution and breakpoints.

Results

Susceptibility for P/T, FEP, and MEM was generally lower among isolates from patients in ICU than non-ICU wards by 5-14 percentage points, while the difference was ≤3 percentage points for C/T (Table). C/T maintained activity against 96% of ICU isolates, 17-23 percentage points higher than P/T, MEM, or FEP. MEM inhibited 40% of P/T-NS and 34% of FEP-NS ICU isolates, while C/T maintained activity against 81-88% of P/T-NS, FEP-NS, and MEM-NS isolates from ICU patients (Table, Figure).

Results Table

Conclusion

High co-resistance in Pa was seen with P/T, FEP, and MEM especially among ICU isolates. These data suggest that routine escalation to a carbapenem may not be optimal in some critically ill patients not responding to empiric therapy. Among the tested β-lactam antibiotics, C/T showed the highest activity against Pa isolates overall and among resistant phenotypes.

Disclosures

Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1295. Susceptibility to Ceftolozane/Tazobactam and Comparators Among Pseudomonas aeruginosa Isolates Collected from Patients in Hospitals in Latin America – SMART 2017-2019
Authors: Lob Sibylle , Hackel Meredith , Andrew DeRyke C , Pavía Jacquleine , Siddiqui Fakhar , Young Katherine , Motyl Mary , Sahm Daniel F
Published: December 2021

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 complicated urinary tract and intraabdominal infections, as well as hospital-acquired/ventilator-associated bacterial pneumonia. We evaluated the activity of ceftolozane/tazobactam (C/T) against P. aeruginosa isolates collected as part of the global SMART surveillance program in 10 countries in Latin America.

Methods

In 2017-2019, 41 clinical labs each collected up to 250 consecutive gram-negative pathogens per year from various infection sources. A total of 21,864 isolates were collected, of which 3,335 (15.3%) were P. aeruginosa. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) P. aeruginosa isolates were screened for genes encoding β-lactamases.

Results

The table shows the antimicrobial susceptibility of P. aeruginosa and β-lactam-NS subsets.

C/T was active against 85.9% of all collected P. aeruginosa, with lowest activity against isolates collected in Chile and Venezuela, where 28.0% and 23.2% of isolates, respectively, carried carbapenemases, and highest activity against isolates from Ecuador and Guatemala, where 2.2% and 4.2%, respectively, were carbapenemase-positive. Substantial variability in the activity of C/T and comparators was observed among β-lactam-NS subsets. In aggregate, however, C/T remained active against 59.9% of all meropenem-NS P. aeruginosa isolates from Latin America (n=1,101), 57.3% of piperacillin/tazobactam-NS isolates (n=1054), 48.9% of cefepime-NS isolates (n=895), and 50.3% of ceftazidime-NS isolates (n=937). Conversely, other common β-lactams (meropenem, cefepime, ceftazidime, and piperacillin/tazobactam) remained active against 8-38% of these resistant isolates.

Results Table

Conclusion

C/T showed the highest activity against P. aeruginosa among the tested β-lactam antibiotics. While amikacin showed similar or better activity in vitro, its toxicities severely limit its clinical use. Given the desirability of β-lactams among clinicians, C/T represents an important option in the treatment of infections caused by P. aeruginosa in Latin America.

Disclosures

Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Jacquleine Pavía, MSc, Merck & Co, Inc (Employee) Fakhar Siddiqui, PhD, Merck & Co, Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1296. Genomic Analysis of Human-Associated Outbreak Caused by Salmonella enterica serovar Infantis in Cali, Colombia
Authors: Rosso Fernando , Rojas olga Lucia agudelo
Published: December 2021

Background

Salmonella enterica serovar Infantis is emerging as a leading cause of foodborne infections. The Colombian National Health Institute reported 263 Infantis among all received Salmonella(n=12,966) from 1997 to 2018 being the 5th most frequent serovar in human clinical samples during this period. In this study, Infantis outbreak-associated isolates were sequenced and collectively analysed with global strains from different sources to compare their genomic content and phylogeny

Figure 1. Genomic Comparisons

Methods

Between September 15-20 of 2019, 160 patients with gastroenteric symptoms resulting from the ingestion of a common food, arrived at Fundación Valle del Lilí. Salmonella spp were cultured from stool specimens of patients and 15 isolates were sent to the Genomic Unit of Agrosavia for whole-genome sequencing. Genomic DNA was sequenced using an Illumina®MiSeqX10 platform. Genome assembly was performed with standardized bioinformatics pipelines and in-silico serotyping with SISTR. Genomic comparisons included newly-sequenced isolates of Infantis(n=6) from a Colombian poultry farms as well as datasets from Patric(n=441) and EnteroBase(n=54).

Results

The 15 outbreak isolates were identified by in silico serotyping as S. Infantis, these isolates showed phenotypic sensitivity to all tested antibiotics except by tetracycline. Antimicrobial resistance plasmids IncFIBKpn3, IncX4 and the host-environment persistence plasmid pSL483 were only detected in 2 outbreak-related and 1 in poultry isolates. Out of a total of 511 high-quality sequences, ST32 was the most prevalent and were phylogenetically grouped into a single non-host specific clade. Outbreak-isolates were included in a monophyletic group with some genomes from the US and Chile, suggesting that the parent strain could have originated in those countries.

Conclusion

The magnitude of the outbreak(288 informed-cases) evidenced a high-virulent potential of outbreak-isolates. Routine sequencing of S.enterica and availability of genomes in Colombia can improve outbreak detection and resolution in the future. The presence of plasmids, although with low frequency, suggests a risk of the appearance of resistant clones.

Disclosures

All Authors: No reported disclosures
1297. Azithromycin vs Beta Lactams in Acute Exacerbations of COPD
Authors: Kale-Pradhan Pramodini , Baalbaki Nour , Aprilliano Bianca , Giuliano Christopher , Hartner Carrie , Johnson Leonard B
Published: December 2021

Background

Bacterial infections cause approximately 50% of Acute Exacerbations of COPD (AECOPD). Current guidelines recommend a wide range of antibiotics, but evidence comparing agents is limited. The purpose of this study is to compare the effectiveness of azithromycin to beta lactams in the treatment of hospitalized patients with AECOPD.

Methods

A multicenter, retrospective, observational study of adult patients admitted with AECOPD who received at least two consecutive days of either a beta lactam or azithromycin were included. The primary endpoint was treatment failure which is a composite endpoint defined as in-hospital mortality, admission to intensive care, initiation of invasive mechanical ventilation, requirement of a new antibiotic, steroid therapy escalation, or readmission due to AECOPD within 30 days. Secondary endpoints included each individual component of the composite endpoint and length of stay.

Results

Of 11,395 patients screened, 595 met the inclusion criteria (428 were treated with azithromycin and 167 patients were treated with a beta lactam). The most common reason for exclusion was the receipt of both azithromycin and beta-lactam in 9857 patients. The patients were similar except the azithromycin group was more likely to be African-American and less likely to have failed an outpatient antibiotic. Treatment failure rate was 19.6% in the azithromycin group and 32.3% in the beta lactam group (P=0.001). Patients in the beta lactam group were more likely to experience in-hospital mortality (P=0.023), require a new antibiotic during admission (P< 0.001), and were more likely to be readmitted within 30 days of discharge due to AECOPD (P=0.032). Length of stay was significantly shorter in the azithromycin group compared to the beta lactam group. There were no statistically significant differences in the rates of adverse events among both groups.

Conclusion

Treatment failure rate and length of stay were significantly higher in the beta lactam group compared to the azithromycin group. However, there were no differences in the side effect profile among both groups. Further studies should be performed to confirm these findings.

Disclosures

All Authors: No reported disclosures
149. Extraction-free RT-PCR to Detect SARS-CoV-2 Variants of Concern
Authors: Harry Brian L , Qiu Yue , Lu Ling , Couto-Rodriguez Mara , Nagy-Szakal Dorottya , O’Hara Niamh B , Lu Shi-Long
Published: December 2021

Background

SARS-CoV-2 variants of concern (VOC) have challenged real-time reverse transcriptase polymerase chain reaction (RT-PCR) methods for the diagnosis of COVID-19.

Methods

The CDC 2019-Novel Coronavirus real-time RT-PCR panel was modified to create a single-plex extraction-free proxy RT-PCR assay, VOCFast™. This assay uses the nucleocapsid N1 as well as novel primer/probe pairs to target VOC mutations in the Orf1a and spike (S) genes. For analytical validation of VOCFast, synthetic controls for the Wuhan, alpha/B.1.1.7, beta/B.1.351, and gamma/P.1 strains were tested at various concentrations. Clinical validation was performed using patient anterior nares swab and saliva specimens collected in the Denver, CO area between Nov 2020 and Feb 2021 or in March 2021. Orthogonal next-generation sequencing (NGS) was also performed.

Results

Similar N1 quantification cycle (Cq) values corresponding to viral load were observed for all strains, suggesting that VOC mutations do not affect performance of the N1 primer/probe. Orf1a-mut and S1-mut primer/probes generated a stable high Cq value for the Wuhan strain. Conversely, Orf1a-mut Cq values were inversely correlated with viral load for all VOC. The S1-mut Cq was inversely correlated with viral load of the alpha strain, but did not reliably amplify beta/gamma VOC. The limit of detection was 8 copies/uL.

The first set of COVID-19 patient specimens revealed no amplification using Orf1a-mut whereas 53% of specimens collected in Mar 2021 demonstrated amplification by Orf-1a. Orthogonal testing by the SARS-CoV-2 NGS Assay and COVID-DX software demonstrated that 12/12 alpha strains, 2/2 beta/gamma strains, and 33/33 Wuhan strains were correctly identified by VOCFast.

Detection of VOC in clinical specimens and validation by NGS

Conclusion

The combination of the N1, Orf1a-mut, and S1-mut primers/probes in VOCFast can distinguish the Wuhan, alpha, and beta/gamma strains and it consistent with NGS results. Testing of clinical samples revealed that VOC emerged in Denver, CO in March 2021. Future work to discriminate beta, gamma, and emerging VOC is ongoing. In summary, VOCFast is an extraction-free RT-PCR assay for nasal swab and saliva specimens that can identify VOC with a turnaround time suitable for clinical testing.

Disclosures

Brian L. Harry, MD PhD, Summit Biolabs Inc. (Grant/Research Support, Shareholder) Mara Couto-Rodriguez, MS, Biotia (Employee) Dorottya Nagy-Szakal, MD PhD, Biotia Inc (Employee, Shareholder) Niamh B. O’Hara, PhD, Biotia (Board Member, Employee, Shareholder) Shi-Long Lu, MD PhD, Summit Biolabs Inc. (Grant/Research Support, Shareholder)
1302. Duration of Antibiotic Therapy for Pneumonia Among Patients with Advanced Cancer: An Opportunity for Antibiotic Stewardship
Authors: Benson Jemma , Datta Rupak , Quagliarello Vincent , Juthani-Mehta Manisha
Published: December 2021

Background

Antibiotic therapy is common for hospitalized older adults (≥65 years) with advanced cancer.1 Pneumonia is prevalent, but data conflict about the benefits and harms of antibiotics in palliative care settings. To inform antibiotic stewardship protocols, we assessed the duration of therapy for non-ventilator-associated pneumonia (non-VAP) in older adults who received palliative chemotherapy for advanced cancer.

Methods

We identified older adults who received palliative chemotherapy from 1/1/2016 through 9/30/2017 at Yale New Haven Hospital and subsequently developed non-VAP during their index admission following receipt of palliative chemotherapy. Non-VAPs were defined per standardized criteria; 2 complicated pneumonias including those associated with abscess, bacteremia, subsequent VAP, necrotizing and fungal pneumonia, and organizing pneumonia were excluded. We determined the total duration of antibiotics, including both inpatient and post-discharge days of therapy, for each initial episode of non-VAP. Patients were then stratified by total duration of therapy ( >7 days versus ≤ 7 days).

Results

We identified a total of 118 older adults who developed non-VAP during their index admission following receipt of palliative chemotherapy (Figure). Median age was 77.6 (range, 65.2 to 92.5), 37.2% were female sex, and the most common malignancies included lung (n=42/118; 35.5%), hematologic (n=28/118; 23.7%), gastrointestinal (n=17/118; 14.4%), and genitourinary (n=17/118; 14.4%) tumors. Overall, 83.0% (n=98/118) were prescribed >7 days of therapy.

Figure. Duration of therapy for non-VAP

Conclusion

83.0% of older adults who developed non-VAP during the index hospitalization following receipt of palliative chemotherapy received a duration of antibiotics that exceeded guideline recommendations. This finding provides an opportunity for intervention to improve patient care and antibiotic stewardship in patients receiving palliative chemotherapy. Future studies are needed in larger cohorts to evaluate the implications of guideline-discordant therapy on readmissions and mortality.

References

1. Marra et al. Antibiotic use during end-of-life care: A systematic literature review and meta-analysis. ICHE 2021;42:523-9.

2. CDC NHSN Patient Safety Component Manual, 2021.

Disclosures

All Authors: No reported disclosures
1303. A Rare Case of Legionella micdadei Lung Abscess in an Immunocompromised Patient
Authors: Samaan Fadi , Barchuk Andriy , Bata Yasmin , Biancuzzo Rachael , Jabbour Elias , Zainah Hadeel
Published: December 2021

Background

Legionella micdadei is the most common legionella species causing infection after L. pneumophila. It usually causes infection in immunocompromised hosts and leads to nodules with tendency to cavitate. It is difficult to culture which makes diagnosis challenging. We report a case or L. micdadei in an immunocompromised host with cavitary pneumonia.

Methods

Case Report. An 82 year-old female presented with upper abdominal pain for one day duration. She has history of hypertension, coronary artery disease, hyperlipidemia, heart failure, and hypothyroidism. She was diagnosed with hypersensitivity pneumonia 5 months prior, treated with prednisone (40 mg daily). The pain was not associated with nausea, vomiting or diarrhea. She was found with hypoxia despite she denied shortness of breath, cough, hemoptysis or chest pain. There was no fever, chills, headache, myalgia or upper respiratory symptoms. She was afebrile, tachycardic 134/min and hypoxic to 88% on room air. White cell count was 22x10(3) /mcL (90% neutrophils), hemoglobin was 10.4 g/dL, creatinine was 1.23 mg/dL and lactic acid was 3.6 mmol/L. Chest CT scan showed left lower lobe cavitary lesion with surrounding infiltrates (image 1). Quantiferon gold, serum galagtomannan, B-D-glucan, and vasculitis work-up were negative. Bronchoscopy showed a patent airway. Bronchial smears and cultures were negative for bacteria, fungi and mycobacteria. The patient was treated with ceftriaxone and metronidazole with de-escalation to amoxicillin/clavulanate. Bronchial culture was positive for legionella micdadei after discharge, azithromycin was added.

Image 1. Cavitary lesion on thoracic CT

Results

Our patient was considered immunocompromised given steroid use, predisposing her for L. micdadei infection. L. micdadei is considered an opportunistic infection and was reported in hematologic malignancy population. It can cause an invasive lung disease with lung cavities. It needs special media for growth making it difficult to diagnose especially it is not detected by legionella urine antigen.

Conclusion

L. micdadei should be considered in the differential diagnosis for cavitary lung lesions in immunocompromised patients.

Disclosures

All Authors: No reported disclosures
1304. Antimicrobial Management of Stenotrophomonas maltophilia Pneumonia: Does TMP-SMX Dose Affect Treatment Failure?
Authors: Keck J Myles , Perkins Nicholson , Adams Delaney , Warner Mia , McCommon Julanne , Hobbs Athena L
Published: December 2021

Background

Limited literature exists to guide the appropriate antimicrobial choice, dose, and duration for Stenotrophomonas maltophilia (S. maltophilia) pneumonia.

Methods

This multi-center, retrospective cohort study was conducted in adults diagnosed with S. maltophilia pneumonia in eight hospitals between March 1, 2014 and August 31, 2020. Patients were enrolled into one of two arms: those treated with TMP-SMX and those treated with alternative antibiotics. The primary outcome was a composite of treatment failure, defined as the need for alternative antibiotics with in vitro activity against S. maltophilia, isolation of S. maltophilia on repeat cultures drawn greater than 72 hours from the index culture, or in-hospital mortality. Other clinical outcomes that were accessed include the TMP-SMX dosing regimen, and 30- and 90-day mortality rates. This study was approved by the local Institutional Review Board (IRB).

Results

Overall, 213 patients were included; 100 (46.9%) received TMP-SMX, and 113 (53.0%) received alternative therapy. Though there was no difference in treatment failure between the two groups, more patients in the “alternative” antibiotic group required mechanical ventilation (57% vs. 31%, respectively; p < 0.001) (Table 1). 74% of patients who received TMP-SMX received a “low-dose” regimen, characterized by < 10 mg/kg/day. When evaluating treatment failure based on “high” or “low-dose” TMP-SMX, there was no difference in treatment failure. However, we noted that physicians were more likely to utilize an alternative agent in addition to TMP-SMX (p=0.001) compared to an alternative agent. When removing this confounder from the composite endpoint, high-dose TMP-SMX was associated with significantly less treatment failure compared to low dose 23% vs. 49%, respectively (p=0.023). The average TMP-SMX dose of patients in the “low-dose” group was 5 + 2.2 mg/kg/day vs. 13.9 + 3.5 mg/kg/day in the “high-dose group. Moreover, when serum creatinine was evaluated at baseline, day 3, day 5, and day 7, no increase was seen in patients who received high dose TMP-SMX (Table 1).

Table 1: Clinical Outcomes

Conclusion

These preliminary results suggest that appropriate dosing of TMP-SMX may be more important for clinical success in patients with S. maltophilia pneumonia than the choice of agent.

Disclosures

All Authors: No reported disclosures
1306. Early Transition to Oral Antibiotics, Including Fluoroquinolone Therapy, for Streptococcus milleri Empyema Following Video-Assisted Thoracoscopic Surgery
Authors: Ovalle Anais , Alsalman Ahmad , Millington Timothy , Zuckerman Richard A
Published: December 2021

Background

Pleural empyema from Streptococcus milleri (SM) is often complex and requires a combination of surgery and intravenous (IV) antibiotics. There is a paucity of data on the efficacy of oral (PO) treatment due to concerns about the development of resistance, particularly to fluoroquinolones (FQ). We report outcomes of postoperative antibiotic treatment for SM empyema over 3 years, including PO therapy.

Methods

A single-center retrospective chart review was performed of 20 patients treated with video-assisted thoracoscopic surgery (VATS) from October 2015 to March 2018 and SM diagnosed by thoracentesis or operative culture. We reviewed clinical factors, route and duration of antibiotics, complications (empyema recurrence, repeat surgery, 30-day readmission due to empyema), and mortality (30-day and 1-year)

Results

Of the 20 patients, 12 (60%) received all IV and 8 (40%) transitioned to PO therapy (Table 1). Median age was 60 and 58 in the IV and PO group, respectively. IV treated patients had more comorbidities. Cultures were primarily monomicrobial. Isolates tested were susceptible (S) to penicillin (Table 1), Of 10 tested specimen, all had moxifloxacin MIC < 0.19 μg/mL

and 8/8 specimens tested were S to levofloxacin. The average duration of antibiotic therapy in the IV group was 34 days and 32 days in the PO group. There were no complications in the IV group: however, there were 2 deaths (1 patient died from comorbid complications and 1 patient was readmitted and died due to MSSA endocarditis). There were no complications or deaths in patients treated PO.

Conclusion

Our review suggests that early transition to PO antibiotics may be a viable option for operatively managed empyema caused by SM in certain patients. FQs have been generally avoided due to concerns about the rapid development of resistance that has been shown in-vitro; however, no in-vivo data have been reported regarding this concern. We show excellent outcomes with the use of PO therapy in susceptible isolates, particularly FQs, with no failure or reported resistance in patients with SM empyema treated with VATS. Further study is needed to validate these findings and determine optimal patient characteristics for transition to PO therapy.

Disclosures

All Authors: No reported disclosures
1307. The Mycoplasma Conundrum
Authors: Rand Kenneth
Published: December 2021

Background

Lockdown for Covid 19 between March 15 - 30, 2020 lead to sudden closures of schools, public gatherings, all but essential businesses, and stay-at-home orders. Between then and the end of April 2020, literally all enveloped respiratory viruses declined to virtually undetectable levels, suggesting a successful interruption of transmission. Weekly percentage positivity rates for M. pneumoniae and all other respiratory viruses from BioFire Syndromic Trends for weeks ending 3/7/2020- 4/24/2020.

Weekly percentage positive rates are shown, with the Rhinovirus/Enterovirus rate divided by 3 and the M. pneumoniae rate multiplied by 10 to fit on the same scale.

Methods

We used the percentage positivity rates from BioFire Syndromic Trends and from GenMark Diagnostics to examine the post lockdown response of M. pneumoniae versus other respiratory viruses on the Respiratory Virus Panel (RP 2.0)

Results

As has been reported (Nawrocki J., et al, OFID 2021) and as shown in Figure 1, there was a rapid drop in the positivity rate for all enveloped respiratory viruses by 85.6% from an average rate of 2.014% positive for the week ending 3/14/20 to 0.29% for the week ending 4/18/20, while the positivity rate for M. pneumoniae actually increased by 44% from 0.536 % to 0.772%. The increase in M. pneumoniae positivity rate from its baseline of 0.51 ± 0.38 between 1/25/20 - 3/21/20 vs 0.71 ± 0.09 between 3/28/20 - 4/25/20 was significantly higher by t test, p=0.00574. Data from GenMark was available only monthly but also showed an upward rise from march to April, 2020.

Conclusion

It is well documented that M. pneumoniae is transmitted through respiratory mechanisms, yet lockdown measures sufficient to dramatically reduce ordinary respiratory virus transmission had no comparable effect on transmission of Mycoplasma pneumoniae. It is also well known that M. pneumoniae persists in the respiratory tract as long as months after an infection. Therefore, it is possible that this reservoir continued to be a source of transmission for M. pneumoniae, even though lockdown measures effectively interrupted the enveloped respiratory viruses.

Disclosures

Kenneth Rand, M.D., BioFire Diagnostics (Advisor or Review Panel member, Research Grant or Support)
150. Updated Clinical Guidelines for Treatment and Prophylaxis of Plague
Authors: Nelson Christina , Cooley Katharine , Fleck-Derderian Shannon
Published: December 2021

Background

Plague still occurs naturally in the western United States, Latin America, Asia, and Africa. Yersinia pestis, the causative agent of plague, is a Tier 1 bioterrorism agent due to its potential for aerosol release and high fatality rates. Recommendations for treatment and post-exposure prophylaxis (PEP) of plague were published in 2000 and included limited first-line options for treating plague, namely streptomycin or gentamicin. Doxycycline or ciprofloxacin were recommended for PEP. However, since 2000 new human clinical data and animal data have become available, and the FDA has approved additional antimicrobials for plague.

Methods

CDC developed updated, evidence-based guidelines for treatment and prophylaxis of plague using a comprehensive process. To collect evidence on relative efficacy of various antimicrobials for treatment of plague, the guidelines team conducted systematic literature reviews and analyzed U.S. surveillance data. Results of these investigations were published in Clinical Infectious Diseases in 2020. We also hosted several meetings with subject matter experts and clinical organizations (IDSA, AAP, etc.), federal agencies, and others to review relevant data and gather individual input on treatment and prophylaxis of plague.

Results

The forthcoming plague guidelines will include several important updates. First-line treatment options have been expanded to include ciprofloxacin, levofloxacin, and moxifloxacin in addition to streptomycin and gentamicin. For PEP, levofloxacin and moxifloxacin are now first-line options in addition to doxycycline and ciprofloxacin. Trimethoprim-sulfamethoxazole is now one of several new alternative options for PEP. The updated guidelines also include recommendations for treatment of clinical forms of plague other than pneumonic. Additional special populations such as immunocompromised persons and neonates are also covered.

Conclusion

Plague remains a threat, both as a naturally occurring disease and as a potential bioterrorism weapon, and preparedness and early recognition are key to effective response. The updated clinical guidelines will be a useful tool for clinicians to manage antimicrobial treatment and PEP for plague.

Disclosures

All Authors: No reported disclosures
1310. Provider and Facility Variation in Empiric Broad-Spectrum Antibiotic Use for Hospitalization Pneumonia: A Mixed Methods Study of Veterans Affairs Facilities
Authors: Jones Barbara E , Taber Peter , Ying Jian , Butler Jorie M , Nevers McKenna , Jones Makoto M , Greene Tom , Stevens Vanessa W , Zickmund Susan , Weir Charlene , Samore Matthew
Published: December 2021

Background

We previously found widespread variation in the empiric use of antibiotics against methicillin-resistant Staph aureus (anti-MRSA) and Pseudomonas aeruginosa (anti-PAER) for patients hospitalized for pneumonia. To explore this variation further, we conducted (1) quantitative analyses of facility-level versus provider-level variation, and (2) qualitative interviews with emergency department providers.

Methods

For each hospitalization, we predicted the probability of anti-MRSA and anti-PAER use by fitting machine learning models from 75 patient variables. We estimated the predicted risk of anti-MRSA/anti-PAER and facility features among patients hospitalized at upper versus lower 10% facilities after controlling for patient characteristics. We plotted density curves with the variance attributed to facility and provider alone and together. We then interviewed 16 emergency department (ED) providers at 8 VA facilities using a cognitive task analysis.

Results

Among 215,803 hospitalizations at 128 VA facilities 1/1/2006-12/31/2016, 31% received empiric anti-MRSA and 29% received empiric anti-PAER antibiotics. Hospitalizations at upper-decile facilities had a 50% and 45% adjusted probability of receiving anti-MRSA and anti-PAER antibiotics, compared to 15% and 20% in the lower-decile facilities. Facility features most predictive of anti-MRSA or anti-PAER use after adjusting for patient characteristics were complexity level (33% and 30% in high versus 15% and 20% in low complexity facilities). Variation in empiric anti-MRSA and anti-PAER use was almost completely at the facility level (Figure 1). Providers reported social influences from the opinions of other providers during decision-making and a high trust in guidelines and order sets. Consideration of pathogens was not mentioned by any providers at high-prescribing facilities.

Conclusion

Variation in empiric use of anti-MRSA and anti-PAER antibiotics in pneumonia clustered nearly completely at the facility level. ED providers report social influences during decision-making and a high trust in guidelines and order sets. Guidelines, order sets, and facility-level clinical champions that promote consideration of pathogens could be important strategies for de-adoption.

Disclosures

All Authors: No reported disclosures
1314. Descriptive Epidemiology of 30-day Readmissions among Survivors of Hospitalization with Bacterial Nosocomial Pneumonia in the US, 2012-2019
Authors: Zilberberg Marya , Nathanson Brian , Puzniak Laura A , Zilberberg Noah , Shorr Andrew F
Published: December 2021

Background

Nosocomial pneumonia (NP) remains associated with excess morbidity and mortality. The effect of NP on other measures of outcome and quality, such as re-admission at 30 days, remains unclear. Moreover, differing types of NP may have varying impacts on re-admissions.

Methods

We conducted a multicenter retrospective cohort study within the Premier Research database, a source containing administrative, pharmacy, and microbiology data. The rate of rehospitalization at 30 days following the index discharge served as our primary endpoint. We compared NP patients readmitted with pneumonia (RaP) as the principal diagnosis to those readmitted for other reasons (RaO). We also compared readmission rates as function of the type of NP: ventilator-associated bacterial pneumonia (VABP), ventilated hospital-acquired bacterial pneumonia (vHABP), and non-ventilated HABP (nvHABP).

Results

Among 17,819 patients with NP, 14,123 (79.3%) survived to discharge, of whom 2,151 (15.2%) required an acute readmission within 30 days of index discharge. Of these, 106 (4.9%) were RaP, and the remainder were RaO. At index hospitalization, RaP patients were older (mean age (SD) 67.4 (13.9] vs. 63.0 (15.2) years), more likely medical (44.3% vs. 36.7%), and less chronically ill (median [IQR] Charlson scores (3 [2-5] vs. 4 [2-5]) than persons with RaO. Bacteremia (10.4% vs. 17.5%), need for vasopressors (15.1% vs. 20.0%), dialysis (9.4% vs. 16.5%), and/or sepsis (9.4% vs. 16.5%) or septic shock 14.2% vs. 17.1%) occurred less frequently in the RaP group. With respect to NP type, nvHABP was most common in RaP (47.2%) and VABP in RaO (38.1%).

Conclusion

One in seven survivors of a hospitalization complicated by NP requires an acute rehospitalization within 30 days. However, few of these readmissions had a principal diagnosis of pneumonia, irrespective of NP type. This suggests that short-term readmission does not capture the quality of care initially delivered to patients for their NP. Of the 5% of NP subjects with RaP, the plurality initially suffered from nvHABP.

Disclosures

Marya Zilberberg, MD, MPH, Cleveland Clinic (Consultant)J&J (Shareholder)Lungpacer (Consultant, Grant/Research Support)Merck (Grant/Research Support)scPharma (Consultant)Sedana (Consultant, Grant/Research Support)Spero (Grant/Research Support) Brian Nathanson, PhD, Lungpacer (Grant/Research Support)Merck (Grant/Research Support)Spero (Grant/Research Support) Laura A. Puzniak, PhD, Merck & Co., Inc. (Employee) Andrew F. Shorr, MD, MPH, MBA, Merck (Consultant)
1316. Uncommon Presentations of Common Variable Immunodeficiency
Authors: Alok Akankcha , Greene John , Aslam Sadaf
Published: December 2021

Background

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder which affects B lymphocyte function and differentiation causing decreased levels of Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM).1 The objective of this study is to highlight how hypogammaglobulinemia can lead to respiratory infections with microbes that are lesser known in the background of CVID with the help of a two-case series.

Methods

Medical records of two patients with CVID were reviewed who were found to have mycobacterium avium-complex intracellulare and streptococcus agalactiae lung infections respectively.

Results

Decreased IgG in CVID means reduced antibody production, low IgA leads to mucosal inflammation and increased susceptibility to respiratory infections2 and lower IgM memory B-cells causes infections with encapsulated microorganisms.3 Table 1 highlights the various respiratory infections and their etiologies that have been reported with CVID, the most common being encapsulated organisms like Haemophilus influenza, Streptococcus pneumonia, Neisseria meningitidis along with enterovirus. Table 2 demonstrates our findings. In the first case we have reported a patient with mycobacterium avium-complex intracellulare (MAC-I). This could be because of hypogammaglobulinemia, decreased B and T-cell interaction and reduced T-cell signaling caused by CVID.4 Although, mycobacterium tuberculosis, simiae and hominis lung infections and mycobacterium bovis systemic infections have been reported before, MAC-I is relatively rare in CVID.5 In our second case, the patient developed streptococcus agalactiae or Group-B streptococcus (GBS) empyema. Most cases of GBS have been reported in pregnant women and infants. Infections with other encapsulated organisms have been reported in CVID but GBS empyema is less frequent and can happen due to decreased bacteria-specific CD4 cells, microbial translocation and hypogammaglobulinemia.6 .

Table 1. Respiratory Infections reported in CVID along with their etiologies.

Figure 1. CT image of MAC-I infection.

Conclusion

We encountered two unique cases of CVID with rare infectious etiologies. The cases are intended to create an awareness and vigilance regarding CVID induced hypogammaglobulinemia which can cause respiratory infections with lesser known pathogens where antibodies may be important.

Disclosures

All Authors: No reported disclosures
1317. Prevalence of Pseudomonas aeruginosa as the Causative Organism for Community Acquired Pneumonia
Authors: Haviland Adam D , Szymczak Wendy , Weston Gregory
Published: December 2021

Background

IDSA/ATS guidelines regarding pneumonia diagnosis and treatment changed in 2019. Guidelines recommend determining local prevalence of MRSA and P. aeruginosa to help guide empiric antibiotic coverage. The aim of our study was to determine the prevalence of P. aeruginosa as the causative organism for adult patients admitted to a large urban academic medical center with community acquired pneumonia (CAP).

Methods

A report of urine streptococcus antigen tests collected January 1st-December 31st in 2019 was generated. Six hundred charts were reviewed and two hundred subjects met inclusion criteria (figure 1). Inclusion criteria were age >18, hospital admission, and documented suspicion of pneumonia by a physician.

Results

The average age was 70 and half of the cases were women. The causative organism was identified in 60/200 cases (table 1). No cases of P. aeruginosa were identified. The most commonly isolated organisms were Influenza A and pneumococcus. 66% of cases had age >65yo, 25% were from long term care facilities, 34% had structural lung disease, 20% had dementia, 15% were hospitalized in the prior 90 days and received IV antibiotics, and 30% of cases met severe CAP criteria (table 2).

Figure 1. Workflow

Table 1. Organisms Identified

Table 2. Risk Factors

Conclusion

Limitations include a low prevalence of renal failure in the study population, and lack of a standardized respiratory infection evaluation. Our results suggest that empiric coverage for P. aeruginosa may not be needed at our center in this cohort of older patients with clinical characteristics sometimes thought to be risk factors for P. aeruginosa.

Disclosures

Wendy Szymczak, PhD, Premier, Inc (Consultant)Qiagen (Consultant, Scientific Research Study Investigator) Gregory Weston, MD MSCR, Allergan (Grant/Research Support)
1318. Clinical and Molecular Characteristics of Hypermucoviscous Klebsiella pneumoniae Causing Pneumonia in Korea
Authors: Lee Ji Yeon , Kim Hyun Ah , Hyun Miri
Published: December 2021

Background

Invasive Klebsiella pneumoniae (K. pneumoniae) was emerged in Asia, well-known for community-onset liver abscess. Healthcare-associated pneumonia caused by hypervirulent K. pneumoniae has been reported in recent studies. The purpose of this study was to evaluate the clinical and molecular characteristics of hypervirulent K. pneumoniae compared with classic K. pneumoniae in respiratory infection.

Methods

The study was performed on 163 K. pneumoniae isolates of respiratory infections collected from Keimyung University of Dongsan Medical Center from November 2013 to November 2015; group A, as classic K. pneumoniae and group B, as hypervirulent K. pneumoniae. Hypermucoviscous phenotype was confirmed with string test. Capsular serotypes, rmpA, magA, allS, mrkD, entB, kfu, and iutA were identified using specific primers by polymerase chain reaction. The biofilm mass was determined using the microtiter plate assay measured by optical density (OD, 570nm).

Results

A total 163 patients were analyzed, 100 (61.3%) of group A and 68 (38.7%) of group B. Community-acquired pneumonia was observed in 49.2% of group B and 18.0% of group A (p=0.001). Underlying diseases except chronic lung disease were more associated with group A. Mean age (72.6±11.7 vs. 68.8±12.5 years, p=0.051) and antimicrobial resistant rates were higher in group A. Mechanical ventilators (21.0% vs. 36.5%, p=0.030) was more associated with group B. Concordances of initial antibiotics (57.5% vs. 92.1%, p=0.001) were more observed in group B. Biofilm formation and infection related 30-day mortality showed no differences between the two groups.

Conclusion

Contrary to our expectations, hypervirulent K. pneumoniae was more associated with community-acquired pneumonia in this study. Compared to classic K. pneumoniae, hypervirulent K. pneumoniae showed more association with severe pneumonia and less association with underlying diseases. In respiratory infection, biofilm formation was not different according to hypermucoviscousity.

Disclosures

All Authors: No reported disclosures
1321. Acquisition and Transmission of Streptococcus pneumoniae in Individuals Over the Age of 60 Years Residing in New Haven, CT, USA
Authors: Wyllie Anne , Mbodj Sidiya , Yolda-Carr Devyn , Thammavongsa Darani A , Waghela Pari , Nakahata Maura , Vega Noel J , York Anna , Allicock Orchid M , Alexander-Parrish Ronika , Arguedas Adriano , Gessner Bradford D , Weinberger Daniel , Hislop Maikel
Published: December 2021

Background

Despite the widespread use of pneumococcal conjugate vaccines, particularly in children, an important burden of pneumococcal disease remains in older adults. The acquisition and transmission rates of pneumococcus between older adults have not been well characterized.

Methods

Between October 2020-June 2021, couples living in the Greater New Haven Area were enrolled if both individuals were over the age of 60 years and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social patterns and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when qPCR Ct-values for piaB +/- lytA were less than 40.

Results

To date, we have collected 495 saliva samples from 95 individuals (48 households). Of 495 saliva samples, 31 (5.9%) have tested positive for pneumococcus by either piaB only (n=9) or both lytA and piaB (n=22). Of 95 individuals, 16 (16.8%) (representing 13, or 27.1% households) have tested positive at least once. Six of the 16 (37.5%) carriers tested positive at multiple timepoints, though none were colonized at all 6 time points over the course of the 10 weeks of study enrolment. For 3 of the 48 (6.3%) households, both members of the couple were identified as carriers, though not necessarily at the same sampling moment.

Conclusion

The preliminary findings of this longitudinal transmission model demonstrate evidence of pneumococcal acquisition among older adults measured by molecular tools. These transmission patterns and high rates of pneumococcal carriage in adults were observed during a period when the COVID-19 pandemic led to numerous preventative public health measures that may have reduced pneumococcal transmission (e.g., social distancing, mask wearing, bans on mass gatherings, restaurant closures, travel restrictions).

Disclosures

Anne Wyllie, PhD, Global Diagnostic Systems (Consultant)Pfizer (Advisor or Review Panel member, Research Grant or Support)PPS Health (Consultant)Tempus Labs, Inc (Research Grant or Support) Ronika Alexander-Parrish, RN, MAEd, Pfizer (Employee, Shareholder) Adriano Arguedas, MD, Pfizer (Employee) Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) Daniel Weinberger, PhD, Affinivax (Consultant)Merck (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)