bluuebunny/crossref_metadata_2025 huggingface dataset:
142. Impact of an Antimicrobial Stewardship Intervention on Antibiotic Prescribing in Patients with Obstetric Infection and Penicillin Allergy
Authors: Quartuccio Katelyn , Golden Kelly , Tesini Brenda L , Heintz Eric , Seligman Neil , Stern Jessica
Published: December 2021

Background

Antibiotics are commonly administered in the peripartum period and most patients with penicillin allergy can tolerate beta lactams, which are preferred for the prophylaxis and treatment of several common obstetric infections. The purpose of this study was to evaluate the impact of a stewardship intervention bundle (including updates to institutional antibiotic guidelines, reclassification of severe penicillin allergy, development of order sets, and a physician champion) on the management of obstetric infections in patients with reported penicillin allergy.

Methods

This was a multicenter, retrospective study of adult patients presenting for labor and delivery who received at least one dose of antibiotics for an infectious indication May 1, 2018 to October 31, 2018 (pre-intervention) and May 1 2020 to October 31, 2020 (post-intervention). The primary outcome was the composite rates of patients with a reported penicillin allergy who received a preferred agent for Group B Streptococcus (GBS) prophylaxis, intraamniotic infection, or cesarean surgical site infection (SSI) prophylaxis.

Results

A total of 192 patients with a documented penicillin allergy were evaluated (96 patients each in pre- and post-intervention groups). Hives were the most commonly reported allergy in both groups (40% vs 39%, P=0.883). Following stewardship interventions, there was a significant increase in the rate of preferred antibiotics prescribed to patients with penicillin allergy (34.3% vs 84.3%, P< 0.001), driven mainly by patients with non-severe allergy (18.4% vs 82.9%, P< 0.001). There were non-statistically significant trends toward lower rates of postpartum endometritis, 30-day readmission, 90-day SSI, and neonatal early onset sepsis. Allergic reactions in the post-intervention group were limited to itching and rash in one patient each; both resolved with medical management.

Conclusion

A comprehensive antibiotic stewardship intervention increased preferred antibiotic prescribing for treatment and prophylaxis of obstetric infections. Pregnant patients with non-severe penicillin allergies, even those reporting hives, can tolerate beta-lactam antibiotics. The potential positive impact on clinical outcomes warrants additional investigation.

Disclosures

Neil Seligman, MD, Natera (Consultant)UpToDate (Other Financial or Material Support, Author)
1235. Roles of Tetracyclines for Treatment of Stenotrophomonas maltophilia Pneumonia
Authors: Alhayani Taha , Philpott Carolyn , Liao Siyun , Gentene Anthony , Mueller Eric
Published: December 2021

Background

Stenotrophomonas maltophilia is a multidrug resistant organism with limited antibiotic treatment options. Sulfamethoxazole-trimethoprim (TMP-SMZ) is considered first line agent based on in vitro studies and clinical evidence. Minocycline has been showed to be active on in vitro studies and also has been explored in small retrospective studies However, doxycycline in the same class has variable in susceptibility in in vitro studies and has not been evaluated for efficacy in treatment of S. maltophilia infections The purpose of this research is to compare minocycline and doxycycline to TMP-SMZ for treatment of S. maltophilia pneumonia.

Methods

This retrospective, multi-center study evaluated hospitalized patients treated for S. maltophilia pneumonia with minocycline, doxycycline, or TMP-SMZ for clinical success, microbiologic success, and recurrence or reinfection within 30 days that required treatment. The inclusion criteria were patients ≥18 years old with S. maltophilia confirmed on respiratory culture from January 2013 to November 2020. Patients were classified as treatment with tetracyclines (minocycline or doxycycline) or TMP-SMZ based on definitive agent used for ≥50% of the treatment course and a minimum of four days. Patients with S. maltophilia resistant or intermediate to definitive therapy, and patients with combination therapy for treatment for S. maltophilia pneumonia were excluded.

Results

A total of 21 patients were included in tetracyclines group and 59 patients included in TMP-SMZ group. There was no difference in clinical success (28.6% vs. 25.4%; P = 0.994) or microbiologic success (n=28, 55.6% vs. 66.4%; P= 0.677) between tetracyclines and TMP-SMZ, respectively. Recurrence or reinfection requiring treatment (n=24) was higher in the tetracyclines group but not statistically significant compared to TMP-SMZ (66.7% vs. 26.7%; P= 0.092). A subgroup analysis showed no difference between doxycycline, minocycline, and TMP-SMZ for these three aims.

Conclusion

Clinical and microbiologic success were similar in patients treated with tetracyclines compared to TMP-SMZ for S. maltophilia pneumonia. This data suggests minocycline and doxycycline may be an option to treat S. maltophilia pneumonia, but conclusive clinical data continues to be lacking.

Disclosures

Anthony Gentene, PharmD, advisory board with Theravance Biopharma and Mylan (Consultant)
1245. In Vitro Activities of Ceftaroline and Comparator Agents Against Bacterial Pathogens Collected from Patients with Skin and Skin Structure Infections: ATLAS Global Surveillance Program 2012-2019
Authors: Hackel Meredith , Stone Gregory , Sahm Daniel F
Published: December 2021

Background

Ceftaroline fosamil, the prodrug of ceftaroline, is a parenteral cephem approved for the treatment of patients with skin and skin structure infections (SSSIs) caused by Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] isolates), β-hemolytic streptococci (Streptococcus pyogenes, S. agalactiae, S. dysgalactiae), and select species of Enterobacterales (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). The current study is part of the ATLAS (Antimicrobial Testing Leadership and Surveillance) program and evaluated the current activities of ceftaroline and comparator agents against commonly encountered bacterial isolates associated with SSSIs.

Methods

From 2012 to 2019 the ATLAS program received 124,694 bacterial isolates that had been cultured by 493 clinical laboratories in 71 countries from samples of patients diagnosed with SSSIs. All isolates were transported to IHMA, (Schaumburg, IL, USA) where their identities were confirmed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing performed following standardized CLSI broth microdilution methodology (M07). Percent susceptibilities were determined using 2021 CLSI MIC breakpoints. Phenotypic extended-spectrum β-lactamase (ESBL) screening and confirmatory testing were performed using the CLSI M100 method.

Results

The in vitro activity of ceftaroline is summarized in the following table. Overall, >99.9% of MSSA and 92.8% of MRSA from SSSI were susceptible to ceftaroline (MIC ≤1 µg/ml); 7.1% of MRSA isolates were ceftaroline-susceptible dose-dependent (MIC 2-4 µg/ml) with greatest proportion being from Chile (53.3% of 392 isolates), S. Korea (29.3% of 321 isolates), and China (24.7% of 652 isolates). Twelve ceftaroline-resistant MRSA were observed, consisting of 11 of 109 isolates from Thailand (10.1%) and 1 of 161 from China (0.6%). All S. pyogenes and 88.0% of ESBL-negative Enterobacterales were susceptible to ceftaroline.

Results Table

Conclusion

Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs.

Disclosures

Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1252. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales from Patients with Bloodstream Infections collected during the ATLAS Global Surveillance Program, 2015-2019
Authors: Lob Sibylle , Kazmierczak Krystyna , Arhin Francis , Sahm Daniel F
Published: December 2021

Background

Treatment options for β-lactamase-producing Enterobacterales are limited, particularly for infections caused by metallo-β-lactamase (MBL)-producing strains. The β-lactam/non-β-lactam β-lactamase inhibitor combination aztreonam-avibactam (ATM-AVI) is active in vitro against Enterobacterales isolates carrying MBLs, including those co-producing β-lactamases of Class A, C, and some class D enzymes. This study evaluated the in vitro activity of ATM-AVI and comparators against Enterobacterales isolates collected in 2015-2019 from patients with bloodstream infections (BSI) as part of the ATLAS program.

Methods

Non-duplicate clinical isolates were collected in 53 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. ATM-AVI was tested at a fixed concentration of 4 µg/mL AVI. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis phenotypically positive for ESBL activity (2015) or with aztreonam or ceftazidime MIC >1 µg/mL (2016-2019).

Results

ATM-AVI was active in vitro against Enterobacterales isolates from BSI (MIC90, 0.12 µg/mL), with 99.97% of isolates inhibited by ≤8 µg/mL of ATM-AVI, including 100% of isolates that produced MBLs. ATM-AVI tested with MIC90 values of 0.5 µg/mL against subsets of cefepime-nonsusceptible (NS), meropenem-NS, amikacin-NS, colistin-resistant, and MBL-positive Enterobacterales (Table). The tested β-lactam comparators showed susceptibility of < 79% against these subsets of resistant isolates.

Results Table

Conclusion

Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Enterobacterales collected from BSI. The promising in vitro activity of ATM-AVI warrants further development of this combination for treatment of BSI caused by drug-resistant Enterobacterales.

Disclosures

Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1259. Carbapenems Versus Non-carbapenem Beta-Lactams for the Treatment of Ceftriaxone-Susceptible and Piperacillin-Tazobactam-Nonsusceptible Enterobacterales Isolates
Authors: Baalbaki Nadeem , Blum Sharon , Bosco Michael , Akerman Meredith , Zaki Lana , Johnson Diane
Published: December 2021

Background

Ceftriaxone-susceptible (CRO-S) and piperacillin-tazobactam-non susceptible (TZP-NS) Enterobacterales isolates have become a frequently isolated phenotype emerging in practice. The genotypic profile is still not clearly elucidated, although prior genotypic sequencing data of these isolates with this phenotypic profile suggests that they are not extended-spectrum beta-lactamase (ESBL) producers. Due to the unfamiliarity with this phenotype and the potential for overuse of broad-spectrum antibiotics, we investigated the clinical outcomes of CRO-S/TZP-NS isolates with carbapenem versus non-carbapenem beta-lactam (NCBL) therapy.

Methods

This was a retrospective chart review of patients with a diagnosed infection caused by a CRO-S/TZP-NS Enterobacterales isolate admitted to any of the three NYU hospitals: Long Island, Tisch, or Brooklyn campuses, treated with a beta-lactam (BL) antibiotic from October 2015 to October 2020. The primary outcome was treatment failure defined as an escalation of antibiotics due to clinical worsening, 30-day all-cause mortality, or relapse of infection with the same genus and species. Patients who received ≥ 72 consecutive hours of BL antibiotics were considered to be on definitive therapy.

Results

A total of 111 patients were included in this study, 9 in the carbapenem group and 102 in the NCBL group. There was no statistically significant difference in the clinical failure rate between the two groups (0% vs 10.8% respectively, P=0.56). A univariate analysis assessed

the association of clinical failure with TZP, CRO, cefpodoxime, cefepime, and 1st-3rd generation cephalosporins grouped. There were no statistically significant increases in 30-day treatment failure in any of the individual categories.

Conclusion

There were no statistically significant differences in 30-day failure with the use of carbapenem vs NCBL antibiotics. No individual BLs or classes were associated with an increased risk of clinical failure. This study suggests that there is a role for NCBL antibiotics for Enterobacterales isolates with this phenotypic presentation and supports prior data that they are less likely to be ESBL producers. Prospective studies are warranted to confirm these findings.

Disclosures

All Authors: No reported disclosures
1261. Antimicrobial Susceptibilities of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) Isolates from a Multi-state Network of Long-term Acute Care Hospitals (LTACHs)
Authors: Zhang Helen L , Han Jennifer , Alby Kevin , Lapp Zena , Snitkin Evan , Goldstein Ellie J C , Muldoon Sean R , Tolomeo Pam C , Lautenbach Ebbing
Published: December 2021

Background

CRKP infection is common among LTACH patients. However, CRKP antimicrobial susceptibility testing (AST) with newer antibiotics has not been described in this population. In this study, we performed AST on CRKP in LTACHs.

Methods

CRKP clinical cultures were collected from 21 Kindred Healthcare LTACHs (12 southern California, 6 Texas, 2 Florida, 1 Kentucky) from 8/1/14-7/25/15. AST was performed using a custom SensititreTM broth microdilution panel (ThermoFisher Scientific, Waltham, MA). 2021 Clinical & Laboratory Standards Institute interpretive criteria were used for all agents except plazomicin (PLZ), for which US Food and Drug Administration breakpoints were used.

Results

459 CRKP clinical isolates were collected, including 254 (55.5%) respiratory, 155 (33.8%) urine, 39 (8.5%) blood, and 10 (2.2%) wound cultures. Most (419, 91.0%) were from southern California. 151 (32.9%) were colistin-resistant. 42 (9.2%) isolates were non-susceptible to meropenem-vaborbactam (MVB), 16 (8.9%) to imipenem-relebactam (IPR), 4 (0.9%) to ceftazidime-avibactam (CZA), and 3 (0.7%) to PLZ. Cross-resistance patterns are shown in Table 1. Among southern California facilities, there was significant inter-facility variation in MVB non-susceptibility (Pearson’s chi-squared test, p=0.005) but not in CZA, IPR, or PLZ non-susceptibility.

Table 1. Cross-resistance to antimicrobials among carbapenem-resistant Klebsiella pneumoniae isolates from 21 Kindred long-term acute care facilities, August 1, 2014 – July 25, 2015 (N=459).

Number of isolates and column percentages reported. 2021 Clinical & Laboratory Standards Institute interpretive criteria are used for all agents except for PLZ, for which US Food and Drug Administration breakpoints are used. Abbreviations: CST = colistin. CZA = ceftazidime-avibactam. I = intermediate. IPR = imipenem-relebactam. MIC = minimum inhibitory concentration. MVB = meropenem-vaborbactam. PLZ = plazomicin. R = resistant. S = susceptible.

Conclusion

In this sample of CRKP isolates from LTACHs in 2014-2015, nearly 10% of isolates were non-susceptible to MVB or IPR, respectively, despite neither agent being commercially available at the time. In contrast, there was a low prevalence of non-susceptibility to CZA, which received initial US Food and Drug Association approval in 2/2015, and PLZ, which was not commercially available during the study period. Cross-resistance between CZA and carbapenem/beta-lactamase combination antibiotics was uncommon. Future studies should evaluate CRKP susceptibilities to new agents in post-marketing cohorts and identify risk factors for resistance.

Disclosures

Jennifer Han, MD, MSCE, GlaxoSmithKline (Employee, Shareholder) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))
147. Defining the Optimal Serial Testing Interval and Features for Identifying Patients with Early SARS-CoV-2 Infection
Authors: Kanjilal Sanjat
Published: December 2021

Background

Serial testing for SARS-CoV-2 is necessary to prevent spread from patients early in infection. Testing intervals are largely derived from viral kinetic studies performed early in the COVID-19 pandemic. Laboratory and epidemiologic data accrued over the past year present an opportunity to use empiric models to define optimal serial testing intervals and features predictive of early infection.

Methods

Retrospective analysis of 15,314 inpatients within the Mass General Brigham healthcare system who had two tests within a 36-hour period between May 1 2020 and May 29 2021. Early infection was defined as having a negative test followed by a positive test. Patients with prior positive tests were excluded. The primary outcome was the proportion of patients in early infection over the total number tested serially, stratified by 4-hour testing intervals from the timestamp of the first test. Multivariate modeling was used to identify features predictive of early infection. Covariates included demographics, body site, PCR assay, location, community incidence, percent positivity, and median / skew of Ct value distributions.

Results

Of 19,971 test pairs, 193 (0.97%) were characterized as a negative followed by a positive within 36 hours. Bivariate analysis showed a close association between negative to positive test pairs during the first surge in spring 2020 that was not present during the winter surge. Negative to positive test pairs were most common in the 12 to 16 hour time interval (51/193, 26%, Figure 1). After controlling for covariates, the Roche cobas assay was more likely to identify patients with a negative to positive test pair relative to the Cepheid Xpert, Hologic Panther Fusion and Roche Liat assays. A second specimen from the lower respiratory tract was more likely to lead to a positive relative to other body sites. Community incidence and Ct value distributions were not predictive and there were no differences between nasal and nasopharyngeal swabs. All 4-hour time intervals from 16 to 36 hours were significant for predicting a negative to positive test pair (Table 1).

Figure 1. Distribution of negative to positive test pairs by 4 hour time intervals

Table 1. Multivariate regression predicting a negative to positive test pair

Conclusion

The likelihood of detecting early infection is dependent on PCR platform and body site of sampling. A range of time intervals between 16 to 36 hours after the initial test were likely to identify positive cases.

Disclosures

Sanjat Kanjilal, MD, MPH, GlaskoSmithKline (Advisor or Review Panel member)
1279. Risk Factors for Colistin Resistance Among Carbapenem-Resistant Klebsiella pneumoniae (CRKP) in a Network of Long-term Acute Care Hospitals (LTACHs)
Authors: Zhang Helen L , Han Jennifer , Lapp Zena , Snitkin Evan , Goldstein Ellie J C , Muldoon Sean R , Tolomeo Pam C , Lautenbach Ebbing
Published: December 2021

Background

Colistin resistance in CRKP presents a serious clinical challenge for patients of LTACHs. However, risk factors for colistin-resistant CRKP have not been previously characterized in this population. Here, we determined risk factors for colistin resistance among CRKP isolates from a network of LTACHs.

Methods

CRKP clinical cultures were collected from 21 Kindred Healthcare LTACHs in 4 US states (California, Texas, Florida, Kentucky) from 8/1/14-7/25/15. Cultures collected within 30 days of a prior CRKP culture from the same patient were excluded. Colistin resistance (minimum inhibitory concentration ≥4) was determined using a custom SensititreTM broth microdilution assay (ThermoFisher Scientific, Waltham, MA). Multivariate logistic regression was performed to evaluate candidate risk factors of age, sex, cirrhosis, chronic kidney disease, culture source, length of stay, indwelling line or tracheostomy, and antibiotic exposure (colistin, fluoroquinolones, 3rd-5th generation cephalosporins, piperacillin-tazobactam, carbapenems, and aminoglycosides) for ≥48 hours in the prior 30 days.

Results

Among 430 CRKP cultures (237 respiratory, 145 urine, 38 blood, 10 wound) from 375 patients, 144 (33.5%) were colistin-resistant. In multivariate analysis, colistin resistance was associated with prior colistin exposure (odds ratio [OR] = 5.9, 95% CI = 2.5-14.0) and culture source (Wald test for joint significance, p=0.03), with higher odds of colistin resistance among respiratory (OR = 2.9, 95% CI = 1.2-7.2), urine (OR = 1.6, 95% CI = 0.7-4.1), or wound (OR = 2.2, 95% CI = 0.4-11.5) compared to blood cultures.

Conclusion

In this sample of CRKP from LTACHs, colistin resistance was associated with prior colistin exposure and respiratory culture source. Other patient factors such as co-morbidities, indwelling devices or tracheostomy, or exposure to other antibiotics/antibiotic classes were not associated with colistin resistance in CRKP. These findings will help inform strategies to reduce colistin resistance and identify LTACH patients at risk of colistin-resistant CRKP.

Disclosures

Jennifer Han, MD, MSCE, GlaxoSmithKline (Employee, Shareholder) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))
1289. The Challenge of Treating Community-Associated Enterobacterales Infections in a Middle-Income Country: Data from SMART 2018-2019
Authors: Telles João Paulo , Arend Lavinia , Bail Larissa , Ito Carmen , Tuon Felipe
Published: December 2021

Background

Antimicrobial stewardship programs have been used widely in hospital settings due to the rise of resistant bacteria, antibiotic toxicities, and costs. Nevertheless, few efforts are done to prevent the rising antimicrobial resistance in community settings. The aim of our study was to evaluate the antimicrobial resistance from Enterobacterales community- and hospital-acquired infections in Southern Brazil.

Methods

A total of 272 Enterobacterales isolates (i.e., Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Serratia spp., Proteus spp., and Providencia) were collected from 2018 and 2019. Broth microdilution method was used to determine minimum inhibitory concentrations for ceftriaxone, cefepime, levofloxacin, amikacin and ertapenem. Molecular evaluation of beta-lactamases (ESBLs, AmpC, and KPC) was also performed.

Results

Ninety-three, and a hundred and seventy-nine isolates were from community- and hospital-acquired infections, respectively. Similar MIC distribution was found between community and hospital settings (Table 1). Levofloxacin MIC of 8mg/L occurred in 38.7% (n=36) and 30.7% (n=55) of isolates from community- and hospital-acquired infections, respectively (Figure 1). Ceftriaxone MIC of 16mg/L occurred in 39.7%(n=37) and 39.1% (n=70) of isolates from community- and hospital-acquired infections, respectively (Figure 1). At last, cefepime MIC of 32mg/L occurred in 22% (n=21) and 25% (n=46) of isolates from community- and hospital-acquired infections, respectively. The following beta-lactamases were found in isolates from community-acquired group, ACT-MIR, CTX-M, SHV and TEM; while beta-lactamases from the hospital-acquired group were ACT-MIR, CMY II, KPC-2, CTX-M, SHV and TEM.

Table 1. Enterobacterales ceftriaxone, cefepime, levofloxacin, amikacin and ertapenem minimum inhibitory concentrations (mg/L) distribution from community- and hospital-settings.

Figure 1. Enterobacterales ceftriaxone and levofloxacin minimum inhibitory concentrations (mg/L) distribution from community- and hospital-settings.

Conclusion

Similar antimicrobials resistances were found in Enterobacterales from community- and hospital-acquired infections. New anti-infective agents are needed urgently to treat pathogens from the community-acquired infections and hospitals that have resistance to the first line regimen. Additionally, community antimicrobial stewardship programs are required.

Disclosures

All Authors: No reported disclosures
1299. Epidemiology of Invasive Pneumococcal Disease (IPD) in the United States 2011-2019
Authors: Gierke Ryan , Farley Monica M , Schaffner William , Thomas Ann , Reingold Art , Harrison Lee , Holtzman Corinne , Burzlaff Kari , Petit Susan , Barnes Meghan , Torres Salina , Beall Bernard , Pilishvili Tamara
Published: December 2021

Background

Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for U.S. children aged < 5 years in February 2010 and recommended in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥ 65 years in 2014. PCV13 has led to dramatic reductions in invasive pneumococcal disease (IPD) burden. New, higher valency PCVs (PCV15, PCV20) are expected to be licensed for adults in late 2021. We examined remaining PCV13-type IPD among children and adults and assessed IPD burden potentially preventable through PCV15 and PCV20 use.

Methods

IPD cases (isolation of pneumococcus from sterile sites) were identified through CDC’s Active Bacterial Core surveillance during 1998–2019. Isolates were serotyped by Quellung or whole genome sequencing. Incidence rates (cases/100,000) were calculated using U.S. Census Bureau population denominators.

Results

After introduction of PCV13 in children, by 2013–2014, PCV13-type IPD declined 89% (from 15 to 2 cases/100,000) in children age < 5 years and 67% (from 19 to 7 cases/100,000) in adults age ≥ 65 years. During 2014–2019, rates of PCV13-type IPD in children and adults remained stable. In 2018–2019, among children age < 5 years, serotypes 3, 19F, 19A, and 6C accounted for most of the remaining PCV13-type IPD (46%, 32%, 14% and 4% respectively) (Figure 1). Among adults age ≥ 65 years, serotypes 3, 6C, 19A, and 19F accounted for most of the remaining PCV13-type IPD (62%, 12%, 10%, and 9% respectively) (Figure 1). During 2015–2019, rates of PCV15 and PCV20-type IPD have remained stable. In 2018–2019, among adults age ≥ 65 years, PCV15 non-PCV13-type IPD rates were 3.6 cases per 100,000 and accounted for 15% of all IPD. PCV20 non-PCV13-type IPD rates were 6.8 cases per 100,000 and accounted for 29% of all IPD (Figure 2). Among children age < 5 years, PCV15 non-PCV13-type IPD rates were 1.6 cases per 100,000 and accounted for 17% of all IPD. PCV20 non-PCV13-type IPD rates were 2.8 cases per 100,000 and accounted for 39% of all IPD (Figure 2).

Figure 1. Incidence rates of IPD among children < 5 years old, by pneumococcal conjugate vaccine type and individual PCV13 serotypes, 2011–2019

Figure 2. Incidence rates of IPD among adults ≥ 65 years old, by pneumococcal conjugate vaccine type and individual PCV13 serotypes, 2011–2019

Conclusion

Following the dramatic reductions after PCV13 introduction, PCV13-type IPD has remained stable during the past five years. There are opportunities to prevent an additional 30% IPD burden among adults through new PCV use.

Disclosures

William Schaffner, MD, VBI Vaccines (Consultant) Lee Harrison, MD, GSK, Merck, Pfizer, Sanofi Pasteur (Consultant)
1300. Comparison of Narrow vs. Broad Spectrum Antibiotics for Treatment of Community-acquired Aspiration Pneumonia
Authors: Box Maggie , Sophonsri Anthony , Bagsic Samantha
Published: December 2021

Background

Aspiration pneumonia (aspPNA) accounts for 5-15% of pneumonia admissions. Despite the absence of risk factors for organisms such as methicillin-resistant S. aureus (MRSA) or Pseudomonas aeruginosa (PsA), broad-spectrum (BS) antibiotics active against these pathogens are frequently prescribed. We compared outcomes of patients receiving narrow-spectrum (NS) versus BS antibiotics for aspPNA.

Methods

This is a retrospective cohort study of hospitalized patients started on antibiotics for aspPNA upon admission from 1/1/2019 to 12/31/2019. The BS cohort included patients prescribed antibiotics with activity against PsA or MRSA and were on BS antibiotics for > 50% duration of therapy regardless of de-escalation. The primary endpoint was clinical response, defined as resolved, improved, no change, or worsened. Secondary endpoints included 30-day all-cause mortality, duration of therapy, 30-day C. difficile infection, and length of stay. Outcomes were assessed using logistic regression with antibiotic group as a fixed effect, and all analyses were conducted using R v. 4.0.3.

Results

A total of N=95 patients were included in the study, 35 in the NS and 60 in the BS groups. Clinical response was similar in distribution between groups (p > 0.3). 30-day all-cause mortality was lower in the NS (11.4%) as compared to the BS group (33.3%) (OR 0.26; 95% CI 0.09- 0.81; p < 0.04). There were no differences for the secondary endpoints including median duration of therapy (4 [IQR 2.5] days vs. 6 [IQR 6] days, p> 0.2), 30-day C. difficile infection (0% vs 6.7%, p > 0.3), and median length of stay (6 [IQR 5] days vs. 7 [IQR 8.5] days, p > 0.2) in NS vs. BS groups, respectively. A positive blood or respiratory culture was isolated in 37% (35/95) patients. Enteric organisms were the most prevalent bacteria isolated (20%), followed by methicillin susceptible S. aureus (8%), and Streptococcus spp (7%). MRSA and PsA were detected in 2% and 3% of patients, respectively.

Conclusion

There is no difference in efficacy between NS and BS antibiotics for aspPNA. Microbiologic data confirm the low incidence of PsA or MRSA causing aspPNA despite high empiric prescribing of antibiotics active against these pathogens. These results support the ongoing need for targeted antibiotic stewardship initiatives for aspPNA.

Disclosures

All Authors: No reported disclosures
1313. Disease Burden and Real-world Clinical Practice for the Treatment of Hospital-Acquired Bacterial Pneumonia Using a Japanese Large-scale Claims Database: A Retrospective Cohort Study
Authors: Kimata Masahiro , Aoki Yosuke , Noriaki Adachi , Akiyama Takeshi , Harada Akiko
Published: December 2021

Background

With an aging population and increasing healthcare utilization, the frequency of hospital-acquired pneumonia (HAP) is expected to increase. Since HAP is life threatening, appropriate diagnosis and treatment are required; however, large-scale Japanese data focusing on patient profiles and treatment patterns is lacking.

Methods

The demographics and treatment patterns of HAP were examined using a large-scale Japanese claims database from Jan. 2016 to Apr. 2018. The HAP population included patients who received injection antibiotics ≧3 consecutive days after admission, but not within 2 days after admission, and those whose reason for hospitalization was not pneumonia but had a diagnosis of pneumonia after hospitalization (based on ICD-10 codes).

Results

2,968 HAP patients (mean age 77 years, 64.9% male) contributing 2,979 total HAP episodes were included. The 12-month pre-index mean Charlson Comorbidity Index (CCI) score was 4.0±3.1 (mean±SD), CCI scores ≧4 comprised 44.0%. Most HAP episodes (77.6%) occurred ≧5 days after hospitalization. During the 12month pre-index period including outpatients, 84.9% of patients had some type of pneumonia record, 9.1% had VAP (ventilator associated pneumonia) records, and 7.4% had anti-MRSA prescription records. For post-index HAP treatment, ampicillin/sulbactam (36.4%, 8.2±3.8 days) and piperacillin/tazobactam (22.0%, 8.8±4.4 days) were frequently prescribed as the first antibiotic prescription. Ceftriaxone (19.4%) and meropenem (9.8%) were also frequently prescribed. Examinations prescribed during HAP: 30.5% blood culture tests, 28.2% sputum examinations and 29.2% urine antigen tests. The overall mortality rate of HAP in overall hospitalization post-index was 22.0%, in which 14.4% of deaths occurred within 30 days. The mean (±SD) length of overall hospital stay was 49.9 (±34.2) days (11.3 days for HAP period), with 12.4% ICU use and 17.6% ventilator use. The median total cost during hospitalization was ¥1,924,848.18 (&19,248).

Conclusion

The data revealed patient characteristics, treatment patterns, mortality rates and healthcare costs in Japanese HAP patients. This database approach should prove useful for discussing antibiotics usage trends in highly aging Japan.

Disclosures

Masahiro Kimata, PhD, MSD K.K., Tokyo, Japan (Employee) Yosuke Aoki, MD, PhD, MSD K.K., Tokyo, Japan (Other Financial or Material Support, Honorarium for Lecturing)SHIONOGI & Co., Ltd (Grant/Research Support, Other Financial or Material Support, Honorarium for Lecturing) Adachi Noriaki, n/a, MSD K.K., Tokyo, Japan (Employee) Takeshi Akiyama, MSc, MSD K.K., Tokyo, Japan (Independent Contractor) Akiko Harada, n/a, MSD K.K., Tokyo, Japan (Employee)
151. Simplifying Empiric Antimicrobial Therapy Selection for Lower Respiratory Tract Infections in Intensive Care Unit Patients: Using Resistance Frequency to Guide Decision Making
Authors: Klinker Kenneth , Hidayat Levita K , Andrew DeRyke C , Motyl Mary , Bauer Karri A
Published: December 2021

Background

In the US, the burden of multidrug resistant bacterial infections, including carbapenem-resistant P. aeruginosa (CRPA) and ESBL-producing Enterobacterales (ESBL-E), is substantial. These resistant pathogens may affect the delivery of timely effective therapy. The aim of this study is to evaluate beta-lactam (BL) susceptibility trends based on the aggregate frequency of CRPA and a combined ESBL-E phenotype (K. pneumoniae (KPn) + E. coli (EC)) observed in critically ill patients with lower respiratory tract infections (LRTI).

Methods

In 2016-2019, ~20 US institutions per year submitted up to 250 gram-negative pathogens as part of the Study for Monitoring Antimicrobial Resistance Trends. A total of 871 PA, 380 KPn, and 336 EC isolates were collected from ICU patients with LRTI. MICs were determined using broth microdilution and interpreted using 2021 CLSI breakpoints. ESBL-E phenotype was defined as: ceftriaxone MIC ≥ 2 mcg/mL. Institutions were stratified into two groups based on frequency of CRPA and combined ESBL-E phenotype: Group 1: CRPA ≤ 15% and ESBL-E ≤ 15%; Group 2: CRPA > 15% and ESBL-E > 15%. Based on CLSI guidance, an empiric antibiotic susceptibility threshold of ≥90% was deemed optimal.

Results

Overall, CRPA and ESBL-E phenotypes were identified in 28.4% and 21.2% of isolates, respectively. Aggregate BL susceptibility in group 1 was above the 90% threshold for cefepime (FEP), piperacillin/tazobactam (TZP), meropenem (MEM), ceftolozane/tazobactam (C/T), and imipenem/relebactam (I/R) (Table 1). However, as frequency of CRPA and ESBL-E exceeded 15%, aggregate BL susceptibility declined to 77.3%, 79.3%, and 86.2% for FEP, TZP, and MEM, respectively. In contrast, C/T and I/R maintain susceptibility above the empiric susceptibility threshold.

Table 1. Aggregate susceptibility of P. aeruginosa, E. coli, and K. pneumoniae ICU LRTI isolates stratified by resistance frequency: Best- (Group 1) and worst-case (Group 2) scenarios

Conclusion

In ICU patients, exceeding CRPA and combined ESBL-E phenotype frequency of 15% for both classifications, impacts susceptibility to 1st line BL’s resulting in a failure to achieve empiric susceptibility thresholds. This stratification could serve as a decision point for triggering earlier susceptibility testing or modifying empiric therapy recommendations for LRTI to include newer agents pending microbiology results.

Disclosures

Kenneth Klinker, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder)
1319. Assessment of Spectrum Score-Based Antibiotic De-Escalation in Patients with Nosocomial Pneumonia
Authors: Ilges Daniel T , Neuner Elizabeth , Krekel Tamara , Ritchie David J , Hampton Nicholas B , Micek Scott
Published: December 2021

Background

Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant morbidity and mortality. Guidelines recommend broad-spectrum empiric antibiotic therapy, including treatment for Pseudomonas aeruginosa (PSAR) and methicillin-resistant Staphylococcus aureus (MRSA), followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure.

Methods

This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016–2019. Patients were enrolled if they met pre-defined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). Data were compared using chi-square, Mann-Whitney U, or T-tests. The primary outcome was composite treatment failure, defined as all-cause mortality or re-admission for pneumonia within 30 days of diagnosis, analyzed using a Cox proportional hazards analysis to control for confounding variables.

Figure 1. Study Schematic

Table 1. Spectrum Score Assignment

Results

Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs. 1026 NDE). Groups were well-matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs. 50.6%, P=0.011). Patients receiving DE experienced a 65% and 44% reduction in anti-MRSA and anti-PSAR therapies by day 3, respectively. There was no difference in composite treatment failure (35.0% DE vs. 33.8% NDE, P=0.604). DE was not associated with treatment failure on Cox multivariate regression analysis (HR 1.13, 95% CI 0.97-1.33, P=0.149). Patients receiving DE had fewer antimicrobial days (median 9 vs. 11, P< 0.0001), episodes of Clostridioides difficile (2.2% vs. 3.8%, P=0.046), and days of hospitalization (median 20 vs. 22 days, P=0.006).

Figure 2: Median Spectrum Scores (SS) Days 0 to 28

Table 2: Cox Regression Analysis

Conclusion

DE and NDE resulted in similar rates of composite treatment failure at 30 days; however, DE was associated with fewer antimicrobial days, episodes of C. difficile, and days of hospitalization. Spectrum scores can objectively identify DE, but further studies are needed to fully understand their utility in this context.

Disclosures

Tamara Krekel, PharmD, BCPS, BCIDP, Merck (Speaker’s Bureau) David J. Ritchie, PharmD, BCPS (AQ-ID), AbbVie (Speaker’s Bureau)Merck (Speaker’s Bureau)
1324. Identification of Local Risk Factors for P. aeruginosa in Community-acquired Pneumonia in a Veteran Population
Authors: Gibbons Emily A , Hopkins Teri L , Yang Linda , Frei Christopher R , Restrepo Marcos I , Walter Elizabeth , Cadena-Zuluaga Jose
Published: December 2021

Background

The 2019 ATS/IDSA community-acquired pneumonia (CAP) guidelines recommend empiric P. aeruginosa (PSA) coverage if locally validated risk factors are present. They further recommend obtaining local data on CAP pathogens to quantify risk factors and help guide clinical decision-making. To comply with the current guideline recommendations and to determine which patients may benefit from empiric anti-pseudomonal therapy, we aimed to characterize our institution’s local risk factors for CAP caused by PSA.

Methods

This is a retrospective single-center matched cohort study of patients admitted to our institution with a CAP diagnosis and a positive respiratory culture who received antibiotic treatment in the past 19 years. Multivariate logistic regression was performed to assess the relationship between PSA and the following risk factors: severe or very severe COPD (FEV1 < 50% predicted), requiring invasive mechanical ventilation or vasopressor support in the first 24 hours of admission, history of PSA infection/colonization in the previous year, tracheostomy, bronchiectasis, long-term care facility residence and admission with receipt of IV antibiotics in the previous 90 days.

Results

A total of 343 patients were screened and 213 were included. Patients were mostly male (99%) with a median (IQR) age of 70 (63-76) years. Long-term care facility residence was removed from the model to prevent it from being over fit as it was related tracheostomy. In the multivariate analysis the only independently associated risk factor for PSA CAP was evidence during the prior year of PSA infection or colonization (OR 3.66; 95% CI 1.26 – 10.56; p = 0.018). Other risk factors that did not reach statistical significance but may be clinically significant included severe or very severe COPD (OR 2.52; 95% CI 2.52 – 6.38; p = 0.055) and tracheostomy (OR 5.28; 95% CI 0.74 – 38.85; p = 0.098).

Conclusion

The results of this study provide valuable data to help guide empiric CAP treatment at our institution. Based on these results, patients with PSA infection or colonization in the past year are appropriate to provide empiric anti-pseudomonal therapy for CAP. Further evaluation of severe or very severe COPD and tracheostomy would be beneficial to better characterize their role in PSA CAP.

Disclosures

All Authors: No reported disclosures
1331. Seasonality of Common Human Coronaviruses in the United States, 2014-2021
Authors: Shah Melisa , Haynes Amber K , Dahl Rebecca M , Kniss Krista , Silk Benjamin , Killerby Marie E
Published: December 2021

Background

The four common human coronavirus (HCoV) types, including two alpha (NL63 and 229E) and two beta (HKU1 and OC43) coronaviruses, generally cause mild, upper respiratory illness. Common HCoV seroprevalence increases rapidly during the first five years of life and remains high throughout adulthood. HCoVs are known to have seasonal patterns, with variation in predominant types each year, but more defined measures of seasonality are needed.

Methods

We describe laboratory detection, percent positivity, and seasonality of the four common HCoVs during July 2014 to May 2021 in the United States reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS). We also describe age, sex, and co-detection with other respiratory viruses for a subset of specimens available through the Public Health Laboratory Interoperability Project (PHLIP). We used a method previously validated for respiratory syncytial virus, characterized by a centered 5-week moving average and normalization to peak, to define seasonal inflections, including season onset, peak, and offset.

Results

Any HCoV type was detected in 96,336 (3.4%) of 2,487,736 specimens. Predominant common HCoV types fluctuated by surveillance year (Figure 1) and were generally consistent across geographic regions. In a subset of 4,576 specimens with a common HCoV detection, those with type 229E had a higher median age compared to other HCoV types (30.8 versus 24.8 years, p< 0.001), but there were no differences by sex. Influenza was the most commonly co-detected virus. In the last six complete HCoV seasons, onsets ranged from October to November, peaks from January to February, and offsets from April to June; >95% of all HCoV detections occurred within these ranges. The 2020-2021 common HCoV season onset, dominated by types NL63 and OC43, was delayed by approximately two months compared to prior seasons.

Figure 1. The top panel represents total specimens tested and the bottom panel shows percent positivity of the four common human coronavirus (HCoV) types by week starting July 5, 2014 through May 8, 2021. Data are from the National Respiratory and Enteric Virus Surveillance System (NREVSS).

Conclusion

Common HCoVs demonstrate relatively consistent seasonal patterns. The delayed onset of the 2020-2021 season may be attributable to mitigation measures implemented across the US including masking, improved hand hygiene, and social distancing. Better defining HCoV seasonality can inform clinical preparedness and testing practices and may provide insights into the behavior of emerging coronaviruses.

Disclosures

All Authors: No reported disclosures
1339. Impact of COVID-19 Pandemic on Activity of Other Respiratory Viral Pathogen and Norovirus
Authors: DiBiase Lauren , Sickbert-Bennett Emily , Weber David J , Weber David J , Miller Melissa B
Published: December 2021

Background

The COVID-19 pandemic led to the implementation of several strategies (e.g., masking, physical distancing, daycare/school and business closures, hand hygiene, surface disinfection) intended to mitigate the spread of disease in the community. Our objective was to evaluate the impact of these strategies on the activity of respiratory viral pathogens (other than SARS-CoV-2) and norovirus.

Methods

At University of North Carolina (UNC) Hospitals, we compared the percent positivity for respiratory viral pathogens and norovirus by calendar year for 2014-2019 and the first three months of 2020 to the percent positivity in the subsequent months of 2020 and the first quarter of 2021. Patients were included in the study if they had a positive specimen obtained in a clinic, ED or as an inpatient. Three molecular tests were used to detect these viruses: adenoviruses, endemic coronaviruses (OC43, 229E, NL63, HKU1), influenza A (subtypes H3, H1, H1N1pdm), influenza B, metapneumovirus (MPV), parainfluenza viruses 1-4 (PIV), rhinovirus and/or enterovirus (RhV/EV), and respiratory syncytial virus (RSV). Two molecular tests were used to detect norovirus. We calculated point prevalence rates with 95% confidence intervals to assess statistical differences in percent positivity.

Results

There was a statistically significant decline in percent positivity for endemic coronaviruses, influenza, MPV, PIV, RSV and norovirus during the time-periods after March 2020 when compared to all other time-periods (Figure). RhV/EV, followed by adenovirus were the most prevalent types of respiratory viruses circulating during height of COVID-19. There was a statistically significant decline seen in RhV/EV in April-Dec 2020, but activity increased in 2021. There was no difference seen in adenovirus activity across time-periods.

Percent Positivity of Respiratory Viral Pathogens and Norovirus by Time Period

Conclusion

Our study demonstrated statistically significant decreases in the percent positivity of several respiratory viral pathogens, as well as norovirus, during the time-period of high community prevalence of SARS-CoV-2. Strategies put in place to mitigate SARS-CoV-2 transmission likely contributed to these differences. Non-enveloped viruses like rhinovirus and adenoviruses may have been less impacted by these strategies since they are more resistant to disinfection.

Disclosures

David J. Weber, MD, MPH, PDI (Consultant) Melissa B. Miller, PhD, D(ABMM), F(AAM), Abbott Molecular (Grant/Research Support)Agena Bioscience (Consultant)ArcBio (Grant/Research Support)Cepheid (Consultant)Luminex Molecular Diagnostics (Consultant)QIAGEN (Consultant)Sherlock Biosciences (Consultant)Talis Biomedical (Consultant)Werfen (Consultant)