bluuebunny/crossref_metadata_2025 huggingface dataset:
1559. Methicillin Susceptible Staphylococcus aureus Is The Predominant Organism In Septic Bursitis With The Majority Involving The Olecranon Bursa: A Study Of 61 Cases
Authors: Kannangara Don , Pandya Dhyanesh
Published: January 2021

Background

Bursae are fluid filled structures between mobile parts of the musculoskeletal system to reduce friction between surfaces by lubrication. The most frequently infected are the olecranon and prepatellar bursae. In reported studies there is male preponderance, a relationship to occupational or recreational activities, a mean age of about 50 years and the most frequent organism being Staphylococcus aureus. The frequency of methicillin resistance is not well documented.

Methods

We analyzed approximately 7000 Staphylococcus aureus isolates reported by the laboratory over a 3-year period in 10 of our network hospitals, 9 in Eastern Pennsylvania and one in adjacent Warren County, New Jersey and found 61 cases of S. aureus septic bursitis.

Results

Only 13/61 (21.3%) were caused by methicillin resistant S. aureus (MRSA), 8 olecranon (61.5%), 4 prepatellar (30.8%) and one subacromial (7.7%). Only one in MRSA group (olecranon bursitis) was female. The mean age of MRSA cases was 58.5. Methicillin susceptible S. aureus (MSSA) predominated with 34/48 (70.8%) olecranon bursitis (28M/6F), 11/48 (22.9%) prepatellar bursitis (10M/1F) and 3/48 (6.3%) sub acromial bursitis (1M/2F) with a mean age of 61.9. Overall (MRSA +MSSA), 51/61 (83.6%) were male and 10/61 (16.4%) were female. The olecranon bursa was involved in 42/61 (68.9%), prepatellar bursa 15/54 (24.6%) and subacromial bursa 4/54 (6.6%). The mean age for the entire group was 61.2 with the youngest 23 and the oldest 93. The occupational history was recorded only in a few patients e.g. roofer, floor worker, construction worker. Three in the MSSA group had bacteremia (2 subacromial bursitis and 1 olecranon bursitis). There was 1 death from gram negative sepsis which was unrelated. The majority were successfully treated with a combination of drainage and antibiotics.

Conclusion

In summary, our study shows a predominance of olecranon bursitis, with a higher incidence in males and majority caused by MSSA. The mean age around 61 was higher than the mean age in prior reports around 50 years. Elbows and knees accounted for 57/61 (93%) cases of septic bursitis. Avoidance of activities involving friction or repeated trauma to elbows and knees should help prevention of septic bursitis. As far as we are aware, this is the largest series of septic bursitis reported.

Disclosures

All Authors: No reported disclosures
129. Antimicrobial Stewardship Intervention Bundle Decreases Fluoroquinolone Prescribing for Urinary Tract Infection in Urgent Care and Primary Care Clinics
Authors: Cubillos Ashley L , Caulder Elisabeth , Patch Megan , Saunders Mary B , Lynch Leah W , Gieselman Morris R , Calkins Karen
Published: January 2021

Background

Fluoroquinolone antibiotics are associated with a number of serious adverse effects, and are not recommended for use in uncomplicated infections, including urinary tract infections (UTIs), where other reasonable antibiotic alternatives exist. This analysis describes the impact of a multi-interventional antimicrobial stewardship initiative on outpatient fluoroquinolone prescribing rates for UTI within a large community health system across a variety of practice settings.

Methods

Interventions included prescriber education, standardized order sets, and monthly feedback on fluoroquinolone prescribing rates in UTI at the prescriber level (for urgent care clinics) or clinic level (for primary care/internal medicine/employee health clinics). To assess the impact of these interventions, total fluoroquinolone prescribing rate in UTI patients was compared for defined 6-month time periods pre- and post-intervention implementation.

Results

Fluoroquinolone prescriptions from urgent care clinics within our health system (N=4) for patients with a primary diagnosis of UTI decreased significantly, from 660/3081 (17.6%) in the pre-intervention period to 111/3641 (3%) in the post intervention period (P< 0.0001). Prescribing in primary care, internal medicine, and employee health clinics (N=19) decreased from 492/2071 (23.8%) to 156/2287 (6.8%) (P< 0.0001).

Conclusion

A multi-interventional initiative to reduce the utilization of fluoroquinolone antibiotics resulted in decreased prescribing rates of these agents for UTI across a variety of outpatient practice settings.

Disclosures

All Authors: No reported disclosures
1562. Reduction in Healthcare Utilization and Overdose after Skin and Soft Tissue Infections for Injection Drug Users through Addiction Medicine Consultation
Authors: Bielick Catherine G , Knodle Ryan D , Burrowes Shana , Barlam Tamar F
Published: January 2021

Background

Healthcare encounters for skin and soft tissue infections (SSTIs) due to injection drug use (IDU) may provide opportunities for interventions to improve outcomes. We explored factors that may impact reduction of healthcare utilization and modify other complications of substance use disorder after an IDU-related SSTI.

Methods

We conducted a retrospective cohort chart review for 305 patients with IDU-related SSTIs between 10/1/2015 and 6/1/2019 to examine demographic, clinical and healthcare utilization data one year before and after the SSTI encounter. Patients were categorized as a low utilizer if they had < 3 emergency department encounters and as a high utilizer if they had ≥3 encounters in the one-year period before or after the SSTI. For patients that changed utilization categories from the pre- to post-SSTI period, we analyzed demographic and clinical differences using Chi Square tests. We performed a secondary analysis using a Wilcoxon test to examine the relationship between receipt of an addiction consult and change in number of overdoses after SSTI.

Results

131 patients were low utilizers at baseline and 174 were high utilizers. Patients who transitioned from low to high utilization (64 patients) were significantly less likely to have received an addiction consult, 16 (25%), than patients who transitioned from high to low utilization, 15 (48%), p=0.03. However, high utilizers were significantly more likely to remain a high utilizer (p< 0.0001) with no variable predictive of transition to low utilization including addiction consultation, homelessness, insurance type, or treatment with medications for opioid use disorder. Patients who were low utilizers at baseline were more likely to remain low utilizers if they were not homeless, p=0.01. Of the entire sample, 96.2% (p< 0.0001) of those admitted obtained an addiction consult, which significantly reduced rates of overdose in the following year (p=0.0014) for 223 patients for which we had overdose data.

Conclusion

Patients with IDU-related SSTIs who do not receive an addiction consult are more likely to cross from low to high utilization after the event. Preferentially targeting this population for addiction consultation can significantly improve outcomes.

Disclosures

All Authors: No reported disclosures
1569. In Vitro Activity of Ceftazidime-avibactam and Comparator Agents against Enterobacterales and Pseudomonas aeruginosa Collected from Patients with Bloodstream Infections as Part of the ATLAS Global Surveillance Program, 2015-2018
Authors: Kazmierczak Krystyna , Lob Sibylle , Stone Greg , Sahm Daniel F
Published: January 2021

Background

Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2015-2018.

Methods

A total of 57048 Eba and 15813 Pae non-duplicate clinically significant isolates, including 7720 Eba and 1286 Pae isolated from bloodstream infections, were collected in 52 countries in Europe, Latin America, Asia/Pacific (excluding mainland China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/ml AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes.

Results

Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.3-2.9% lower among Eba and Pae from bloodstream infections compared to isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and the CAZ-NS subset (MIC90, 0.5-2 µg/ml, 93.4-98.1% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) because 99% of MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. None of the tested comparators exceeded the activity of CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/ml, 89.4% S). Activity was reduced against CAZ-NS and MEM-NS subsets (54.2-63.8% S), which included isolates carrying MBLs, but exceeded the activity of CAZ and MEM against these subsets by 26-31 percentage points. Amikacin was the only tested comparator that demonstrated comparable activity against Pae bloodstream isolates.

Table

Conclusion

CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates.

Disclosures

Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1570. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales from ICU and Non-ICU Wards Collected in Latin America and Globally as part of the ATLAS Surveillance Program 2017-2018
Authors: Lob Sibylle , Kazmierczak Krystyna , Stone Greg , Sahm Daniel F
Published: January 2021

Background

Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards.

Methods

Non-duplicate clinical isolates were collected in 2017-2018 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC >1 µg/ml.

Results

The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited ≥97% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 66.5% and 68.1% of ICU and non-ICU isolates, respectively (of which 31.8% and 30.8%, respectively, carried metallo-β-lactamases [MBLs]). CAZ-AVI inhibited >97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI and TGC was higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (15.8% and 17.9% in ICU and non-ICUs, respectively). CAZ-AVI inhibited 100% of MEM-NS MBL-negative isolates from LA.

Table

Conclusion

CAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those among patients in ICU wards, where antimicrobial resistance is typically higher.

Disclosures

Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1573. Daptomycin Resistant Enterococcus faecium: Combination Therapy Screening
Authors: Kebriaei Razieh , Stamper Kyle , Lev Katherine , Morrisette Taylor , Arias Cesar A , Rybak Michael J
Published: January 2021

Background

Enterococcus faecium infections are difficult to treat and there is a growing concern regarding the rising occurrence of daptomycin resistance. We have previously demonstrated that only daptomycin plus ampicillin combination was effective against DAP-R E. faecium R497. The efficacy and systematic screening DAP plus β-lactams and DAP plus other combinations against daptomycin-resistant strains of E. faecium has not been investigated. Here, we evaluated 40 selected single, dual and triple combinations of antibacterial regimens against two clinical isolates of DAP-R E. faecium (R497 and R496 (with daptomycin MIC of 16 and 32 µg/ml, respectively).

Methods

E.faecium R497 and R496 were tested against an array of antibacterial agents including daptomycin, tigecycline, linezolid, ertapenem, ceftaroline and ceftriaxone using MIC susceptibility tests and 24h time-kill curves (TKC). All susceptibility tests and TKCs were performed in MHB broth containing 50 mg/L calcium. TKCs were performed at half MIC or free peak concentration of each antibacterial (whichever was lower). Synergy was defined as >2 log10 CFU/ml decrease compared to the most potent antibacterial agent.

Results

Susceptibility tests demonstrated resistance to all listed β-lactams for both organisms. TKCs demonstrated that combination of daptomycin-ertapenem, daptomycin-ceftriaxone and daptomycin-ceftaroline was not effective against R497. However, addition of ceftriaxone or linezolid to either daptomycin-ertapenem or daptomycin-ceftaroline combinations resulted in synergy against this organism. Combinations of daptomycin-ertapenem and daptomycin-ceftaroline were synergistic against R496. Addition of linezolid, ceftriaxone or tigecycline to either daptomycin-ceftaroline or daptomycin-ertapenem combination did not increase killing activity against R496.

Conclusion

Differential affinity of β-lactams to specific PBP isotypes seems to be a key parameter for the success of daptomycin- β-lactam combinations against multi-drug resistant E. faecium . The optimized use of double β-lactam therapy in addition to daptomycin can potentially lead to improved patient outcomes and preserving antibiotic therapy for serious enterococcus infections.

Disclosures

Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)
1577. Real-World, Multicenter Experience with Eravacycline for Various Infections
Authors: Alosaimy Sara , Lagnf Abdalhamid M , Molina Kyle , King Madeline , Pullinger Benjamin , Tart Serina , Jones Bruce M , Claeys Kimberly C , Truong James , Andrade Justin A , Biagi Mark , Pierce Michael , Cosimi Reese , Hobbs Athena L V , Perkins Nicholson , Huang Glen , Veve Michael , Morrisette Taylor , Davis Susan L , Davis Susan L , Rybak Michael J
Published: January 2021

Background

Eravacycline (ERV) is Food and Drug Administration approved in patients for the treatment of adults complicated intra-abdominal infections in 2018. Real-world data regarding the indications for ERV use are is limited. We evaluated the clinical/safety outcomes of patients treated with ERV in FDA and non-FDA approved indications.

Methods

Multicenter, retrospective, observational study from September 2018 to June 2020. Adult patients treated with ERV for ³ 72 hours were included. The primary outcome was 30-day survival. Secondary outcomes included a lack of 30-day infection-recurrence, resolution of signs/symptoms of infection and safety. All outcomes were measured from ERV start date.

Results

Overall, 108 patients were included from 12 geographically-distinct medical centers across the United States. The median(IQR) age was 60(52-67) years and 60% were male. Median(IQR) APACHE II and Charlson Comorbidity scores were 15(11-21) and 3 (2-6), respectively. The most common sources of infection were intra-abdominal (32%), and respiratory (24%). Common pathogens included Acinetobacter baumannii (19%), Klebsiella pneumoniae and Enterococcus faecium (16%). Infectious diseases consultation was obtained in 98%, and surgical interventions in 51% of cases. Patients often received active therapy prior to ERV(40%). Median(IQR) ERV therapy duration was 7.7(4.4-14.0) days. Among cases with documented cultures, ERV was initiated within a median(IQR) of 4.8(2.5-9.9) days. Combination therapy ³ 48 hours was given in 45%. The primary endpoint was achieved in 79%(85/108). Of patients who died(n=23), 57% were on monotherapy, 39% were critically ill, 39% had intra-abdominal as a source, and 30% had positive blood cultures. For secondary outcomes, 94%(102/108) lacked 30-day infection-recurrence and 74%(80/108) resolved signs/symptoms of infection. ERV was selected primarily for consolidation of the regimen(40%). Eight patients experienced a probable ERV-related adverse event, mainly gastrointestinal(87.5%) and none experienced clostridium difficile.

Conclusion

30-day survival was achieved in the majority of patients treated with ERV. Studies with longer follow-up are required to confirm these findings.

Disclosures

Madeline King, PharmD, Tetraphase (Speaker’s Bureau) Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)
131. Antimicrobial Usage for Respiratory Infections in Urgent Care Settings within the University of Washington Medicine Network
Authors: Huang Joanne , Escobar Zahra Kassamali , Jain Rupali , Chan Jeannie D , Lynch John B , D’Angeli Marisa A , Fang Victoria , May Larissa , Bryson-Cahn Chloe
Published: January 2021

Background

In an effort to combat antimicrobial resistance and adverse drug events, The Joint Commission mandated expansion of antimicrobial stewardship programs into ambulatory healthcare settings Jan 2020. The most common diagnoses resulting in inappropriate antimicrobial prescribing are respiratory infections. This study aimed to assess the rate of antibiotic prescribing for viral respiratory tract infections within six urgent care clinics affiliated with University of Washington Medicine health system in Seattle, WA.

Methods

This was a retrospective observational study from Jan 2019-Feb 2020. We used the MITIGATE toolkit; a resource that meets CDC’s core elements for outpatient stewardship. Patients were identified based upon pre-specified ICD-10 codes for viral respiratory infections. The primary outcome was the rate of unnecessary antimicrobial prescriptions for acute viral respiratory infections. Secondary outcomes evaluated inappropriate prescribing practices based on antibiotic selection, diagnosis, and age.

Results

Of 7,313 patients (6078 adults and 1235 pediatric) included, 23% were inappropriately prescribed antibiotics. The most common antibiotics inappropriately prescribed were azithromycin (62%), amoxicillin (13%), and doxycycline (13%). Fluoroquinolone (FQ) utilization was low (2%). Bronchitis (61%) and nonsuppurative otitis media (NSOM) (24%) were the most common viral diagnoses for which antibiotics were prescribed. Overall, unnecessary prescribing was lower in pediatrics than adults at 13% and 25%, respectively (p< 0.001). Adults were more often prescribed antibiotics inappropriately for bronchitis and NSOM compared to pediatrics (p=0.0013).

Conclusion

Inappropriate prescribing practices across six urgent care clinics varied based upon age and diagnosis. Azithromycin is most often inappropriately prescribed but the low rate of FQ prescribing is encouraging. The lower rate of unnecessary prescribing in pediatrics is promising although there is room for improvement as 1 in 8 children were unnecessarily prescribed antibiotics. These findings support the need for antibiotic stewardship in the outpatient setting, targeting areas for azithromycin use and therapeutic management of bronchitis.

Disclosures

All Authors: No reported disclosures
1580. In Vitro Activity of Ceftazidime-Avibactam Against Enterobacterales and Pseudomonas aeruginosa Collected in Latin America as part of the ATLAS Global Surveillance Program, 2017-2019
Authors: Kazmierczak Krystyna , Valente Maria Lavinea , Lemos Elkin , Baudrit Monique , Quintana Alvaro , Irani Paurus , Stone Greg , Sahm Daniel F
Published: January 2021

Background

Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against isolates collected in Latin America (LA) as part of the ATLAS surveillance program.

Methods

Non-duplicate isolates of Ent (n=8416) and Psa (n=2521) were collected in 10 countries in Central America (CAC; Costa Rica, Dominican Republic, Guatemala, Panama [2018-2019 only]) and South America (SA; Argentina, Brazil, Chile, Colombia, Mexico, Venezuela [2017-2019]). Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2020 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with meropenem (MEM) MICs ≥2 µg/mL (Ent) or ≥4 µg/mL (Psa) were screened for β-lactamase genes.

Results

CAZ-AVI demonstrated potent in vitro activity against Ent collected in LA overall and in the CAC and SA subregions (95-99% susceptible (S)) that was comparable to or exceeded the activity of comparators including MEM, amikacin (AMK) and tigecycline (TGC) (Table). CAZ-AVI retained good activity against MEM non-susceptible (NS) Ent collected in SA (82% S; 6.9% of collected isolates) but activity was reduced against MEM-NS Ent from CAC (10% S; 5.7% of collected isolates), which included a high proportion of isolates carrying NDM-type metallo-β-lactamases (MBL). Among Psa, CAZ-AVI showed greater activity than the tested comparators against both all (86-92% S) and MEM-NS (61-66% S) isolates collected in LA overall and in the two subregions.

Table

Conclusion

CAZ-AVI showed potent in vitro activity against Ent and Psa collected from patients in the CAC and SA subregions of LA. Activity was also good against MEM-NS isolates from SA but was reduced against MEM-NS Ent from CAC that included a high proportion of MBL-positive isolates. The regional and country prevalence of different carbapenem-resistance mechanisms must be considered when evaluating treatment options; however, CAZ-AVI could provide a valuable therapeutic option for treatment of infections caused by Ent and Psa in LA.

Disclosures

Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Maria Lavinea Valente, MD, Pfizer Brazil (Employee) Elkin Lemos, MD, PhD, Pfizer Columbia (Employee) Monique Baudrit, MD, MSc, Pfizer Costa Rica (Employee) Alvaro Quintana, MD MSc, Pfizer, Inc. (Employee) Paurus Irani, MD, Pfizer United Kingdom (Employee) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1581. In Vitro Activity of Ceftolozane/Tazobactam against Pseudomonas aeruginosa from ICU and Non-ICU Patients with Respiratory Tract Infections in the Asia/Pacific region – SMART 2016-2018
Authors: Lob Sibylle , Kazmierczak Krystyna , Chen Wei-Ting , Khoo Yivonne , Balwani Kanchan , Young Katherine , Motyl Mary , Sahm Daniel F
Published: January 2021

Background

Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Elevated antimicrobial resistance rates have been reported among pathogens collected in ICUs. Using isolates collected in Asia/Pacific as part of the global SMART surveillance program, we evaluated the activity of C/T and comparators against P. aeruginosa from patients with respiratory tract infections (RTI) in ICU and non-ICU wards.

Methods

In 2016-2018, 55 clinical laboratories in 11 Asia/Pacific countries collected 2530 P. aeruginosa isolates from RTI. MICs were determined using CLSI broth microdilution and interpreted with CLSI breakpoints. C/T-nonsusceptible isolates (except those from India) were screened by PCR and sequencing for genes encoding β-lactamases.

Results

Susceptibility to C/T in Asia/Pacific was 85.3% in ICUs and 92.2% in non-ICUs, 15-23 percentage points and 13-19 percentage points, respectively, higher than to meropenem, cefepime, and piperacillin-tazobactam. C/T maintained activity against 58.8% and 69.4% of meropenem-nonsusceptible isolates from ICU (n=294) and non-ICU patients (n=346), respectively. Acquired β-lactamases were detected in 64% of C/T-nonsusceptible isolates from ICUs (n=90; 54% MBL-positive, 1% GES carbapenemase-positive, 9% ESBL-positive) and in 47% of C/T-NS isolates from non-ICUs (n=86; 33% MBL-positive, 6% GES-carbapenemase-positive, 8% ESBL-positive). The table presents country-level rates of C/T-susceptible and carbapenemase-positive P. aeruginosa for countries with n >20 in both ICU and non-ICU subsets.

Table

Conclusion

In Asia/Pacific overall, C/T maintained susceptibility rates >85% in both ICU and non-ICU wards against P. aeruginosa isolates from RTI, with rates >91% in most countries. Susceptibility was lower in countries with higher rates of carbapenemase-positive P. aeruginosa. C/T could provide an important treatment option for RTI infections caused by P. aeruginosa in the Asia/Pacific region.

Disclosures

Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1582. In Vitro Activity of Ceftolozane/Tazobactam against Enterobacterales and Pseudomonas aeruginosa Isolates from Geriatric Patients in the Asia/Pacific region – SMART 2016-2018
Authors: Lob Sibylle , Hackel Meredith , Chen Wei-Ting , Khoo Yivonne , Balwani Kanchan , Young Katherine , Motyl Mary , Sahm Daniel F
Published: January 2021

Background

Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract and intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. We evaluated the activity of C/T against isolates collected from patients ≥65 years old as part of the SMART surveillance program in Asia/Pacific.

Methods

In 2016-2018, 49 clinical laboratories in Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, Korea, Taiwan, Thailand, and Vietnam each collected up to 250 consecutive gram-negative pathogens per year. Susceptibility was determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales (ENT) and P. aeruginosa (PA) isolates were screened by PCR and sequenced for genes encoding β-lactamases (except ENT from 1 site in Taiwan).

Results

2082 PA (68.3% lower respiratory tract, 12.7% intraabdominal, 15.1% urinary tract, and 3.0% bloodstream infection isolates) and 8181 ENT isolates (29.8%, 27.8%, 32.5%, and 9.2%, respectively) were collected from patients ≥65 years old. In vitro susceptibility of PA and ENT stratified by length of hospital stay at time of specimen collection (LOS) is shown (Table).

C/T maintained activity against 75.5% of 518 P/T-NS, 67.9% of 395 cefepime-NS, and 71.6% of 377 meropenem-NS PA isolates. Among 136 C/T-NS PA isolates, 44.9% carried metallo-β-lactamases (MBL), 0.7% KPC, 1.5% GES carbapenemases, 5.9% only ESBL, and in 47.1% no acquired β-lactamases were detected. Among 878 characterized C/T-NS ENT, 14.1% carried MBL, 5.2% KPC, 3.3% OXA-48-like carbapenemases, and 53.5% AmpC and/or ESBL; no acquired β-lactamases were detected in 23.8% of isolates, of which 89.5% were species with intrinsic AmpC.

Table

Conclusion

Susceptibility of PA and ENT to all studied agents was lower for isolates collected ≥48 than < 48 hours post-admission. C/T was active against >92% of PA in both strata, 7-29 percentage points higher than the studied comparators except amikacin, and against >84% of ENT, 4-30% higher than the comparators except meropenem and amikacin. C/T is a potential new treatment option for older patients with infections caused by ENT and PA in Asia/Pacific.

Disclosures

Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1586. A Comparative Analysis of In Vitro Susceptibilities of Vancomycin-Resistant Enterococci Against Doxycycline, Minocycline, Tigecycline, Eravacycline and Omadacycline
Authors: Chua Mary Francine P , Nida Syeda Sara , Lawhorn Jerry , Sundareshan Vidya
Published: January 2021

Background

Vancomycin-resistant Enterococci (VRE) are nosocomial pathogens that cause significant morbidity and mortality especially among patients with chronic medical conditions, critical illness and prolonged hospitalizations. Majority of human infections are caused by two species— E. faecium and E. faecalis, and which can acquire resistance to ampicillin, aminoglycosides, and vancomycin. Our aim was to study the susceptibility profile of the VRE strains to the tetracycline group of antibiotics on isolates collected from our local hospital. Older tetracyclines and their novel derivatives are included in this study.

Methods

Eighty preserved isolates of VRE were tested against five tetracyclines, i.e. doxycycline, minocycline, tigecycline, eravacycline and omadacycline. Antimicrobial susceptibility testing was performed using the E-test method in accordance to CLSI guidelines. Isolates were then classified as either susceptible, intermediately susceptible or resistant based on established breakpoints.

Results

Eighty isolates (54 VRE. faecium and 26 VRE. faecalis) were included in the study. Out of 54 E. faecium isolates, 52 (96.3%) were susceptible to tigecycline, 15 (27.8%) were susceptible to minocycline, 14 (25.9%) were susceptible to doxycycline, 42 (77.8 %) were susceptible to omadacycline, and 52 (96.3%) were susceptible to eravacycline. Out of 26 E. faecalis isolates, 26 (100%) were susceptible to tigecycline, 2 (7.6%) were susceptible to minocycline, 2 (7.6%) were susceptible to doxycycline, 2 (7.6%) were susceptible to omadacycline, and 25 (96.15%) were susceptible to eravacycline.

Conclusion

Tigecycline and eravacycline exhibited better in vitro antimicrobial activity against vancomycin-resistant E. faecium and E. faecalis when compared to doxycycline and minocycline. Omadacycline showed a relatively favorable susceptibility profile for E. faecium, but less favorable for E. faecalis. Results of this study will be useful to incorporate in the local antibiogram and will guide antimicrobial stewardship efforts. These findings will not only add to existing knowledge on susceptibility profiles of the novel tetracyclines, i.e. eravacycline and omadacycline, but also on their applicability in the clinical setting.

Disclosures

All Authors: No reported disclosures
1587. Activity of Ceftolozane/Tazobactam against Gram-Negative Isolates from Lower Respiratory Tract Infections – SMART United States 2018
Authors: Lob Sibylle , Hackel Meredith , DePestel Daryl , Young Katherine , Motyl Mary , Sahm Daniel F
Published: January 2021

Background

Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. C/T has been approved by the FDA and EMA for complicated urinary tract infections, complicated intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. Using isolates collected in the United States as part of the global SMART surveillance program, we evaluated the activity of C/T and comparators against gram-negative pathogens collected from patients with lower respiratory tract infections (LRTI).

Methods

In 2018, 24 hospitals in the US each collected up to 100 consecutive aerobic or facultative gram-negative bacilli (GNB) from LRTI for a total of 1773 isolates. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales and P. aeruginosa isolates were screened by PCR and sequencing for genes encoding β-lactamases.

Results

The 3 most common species collected from LRTI were P. aeruginosa (35.0% of all collected GNB), K. pneumoniae (10.4%), and E. coli (9.6%). Enterobacterales and P. aeruginosa combined comprised 86.3% of all collected LRTI GNB. The activity of C/T and comparators against GNB from LRTI is shown in the table.

C/T was active against 93% of Enterobacterales isolates from LRTI (activity only exceeded by meropenem and amikacin), as well as against 97% of P. aeruginosa and 94% of all Enterobacterales and P. aeruginosa combined (activity only exceeded by amikacin). C/T maintained activity against 69-83% of β-lactam-NS subsets of Enterobacterales and P. aeruginosa combined.

Among 67 molecularly characterized C/T-NS Enterobacterales isolates, 19.4% carried KPC, 1.5% acquired AmpC, and 16.4% only extended-spectrum β-lactamases. No acquired β-lactamases were detected in the remaining 62.7% of isolates, of which 92.9% were species with intrinsic AmpC. Among 21 molecularly characterized C/T-NS P. aeruginosa, one isolate carried an IMP-type metallo-β-lactamase, and in the remaining isolates no acquired β-lactamases were detected.

Table

Conclusion

With its broad coverage of Enterobacterales and P. aeruginosa, C/T can provide an important empiric therapy option for patients with LRTI in the US.

Disclosures

Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Daryl DePestel, PharmD, BCPS-ID, Merck & Co, Inc (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1592. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa With Overexpression of AmpC β-Lactamase From Phase 3 Clinical Trials
Authors: Lin Lynn-Yao , Debabov Dmitri , Chang William , Rappo Urania
Published: January 2021

Background

AmpC overproduction is a main mechanism of carbapenem resistance, in the absence of acquired carbapenemases. Ceftazidime-avibactam (CAZ-AVI) has potent in vitro activity against AmpC-producing P. aeruginosa and Enterobacterales that are resistant to carbapenems and other β-lactams.

Methods

Activity of CAZ-AVI and comparators was evaluated against AmpC-overproducing Enterobacterales (n=77) and P. aeruginosa (n=53) collected from 4 CAZ-AVI clinical trials: RECLAIM (complicated intra-abdominal infection [cIAI]), REPRISE (cIAI/complicated urinary tract infection [cUTI]), RECAPTURE (cUTI) and REPROVE (hospital-acquired pneumonia/ventilator associated pneumonia). In vitro susceptibility of CAZ-AVI and comparators was performed by broth microdilution using ThermoFisher custom panels. CLSI breakpoints were used to determine susceptibility. Quantitative PCR and microarray data were used to characterize presence and expression of AmpC. Clinical response at test of cure was assessed.

Results

Against 77 AmpC-overproducing Enterobacterales isolates, meropenem-vaborbactam (MVB) (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (MEM) (96.1% S) had similar in vitro activity (Table), with greater in vitro activity than amikacin (AMK) (84.4% S), gentamicin (61.0% S), and ceftolozane-tazobactam (TZC) (35.1% S). Clinical cures in patients with baseline AmpC-overproducing Enterobacterales were 21/26 (81%) in CAZ-AVI group vs 17/20 (85%) in control groups. Against 53 AmpC-overproducing P. aeruginosa isolates, CAZ-AVI (73.6% S) showed greater in vitro activity than AMK (69.8% S), TZC (58.5% S), and MEM (37.7% S). Clinical cures in patients with baseline AmpC-overproducing P. aeruginosa were 12/14 (86%) in CAZ-AVI group vs 9/12 (75%) in control groups. MIC distributions against the same P aeruginosa isolates were CAZ-AVI (MIC50/90, 4/ >64 µg/mL), MVB (MIC50/90, 8/32 µg/mL), and MEM (MIC50/90, 8/32 µg/mL).

Table

Conclusion

CAZ-AVI was the most active agent against AmpC-overproducing P. aeruginosa with higher proportion of clinical cure than controls. CAZ-AVI was also among the most active agents against AmpC-overproducing Enterobacterales, with >96% isolates susceptible.

Disclosures

Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee) Urania Rappo, MD, MS, PharmD, Allergan (before its acquisition by AbbVie) (Employee)
1597. Ceftolozane-Tazobactam and Meropenem Synergy Testing Against Multi-Drug and Extensively-Drug Resistant Pseudomonas aeruginosa
Authors: Chua Mary Francine P , Nida Syeda Sara , Lawhorn Jerry , Koirala Janak
Published: January 2021

Background

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA.

Methods

We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, >0.5 to <1, >1 to <4, and >4, respectively.

Results

Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 >32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined.

Conclusion

When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections.

Disclosures

All Authors: No reported disclosures
1600. Closing the gap on moxifloxacin breakpoints for Stenotrophomonas maltophilia
Authors: Stone Tyler J , Summers Kate , Williamson John , Palavecino Elizabeth , Palavecino Elizabeth
Published: January 2021

Background

Moxifloxacin (MOX) has in vitro activity against Enterobacterales and Stenotrophomonas maltophilia (SM). Although MOX commonly displays lower minimum inhibitory concentration (MIC)50/90 values against SM when compared to levofloxacin, there are currently no established MOX breakpoints for treatment of SM. The Clinical and Laboratory Standards Institute (CLSI) has established interpretive categories and MIC breakpoints for levofloxacin (S ≤2µg/ml) against SM. The US Food and Drug Administration and European Committee on Antimicrobial Susceptibility Testing provide MOX breakpoints for Enterobacterales with susceptible MICs represented at ≤ 2 µg/mL and ≤ 0.25 µg/mL, respectively. The purpose of this study was to evaluate MOX MIC distribution against SM strains recovered from clinical specimens.

Methods

Clinical samples from patients with suspected infection during calendar year 2018 and 2019 were processed in the microbiology lab of Wake Forest Baptist Medical Center. After incubation, SM colonies were identified by MALDI-TOF system. MOX susceptibility testing was performed for these clinical isolates by gradient diffusion strip methodologies. Results were displayed as MIC (µg/mL) without interpretation. MIC50/90 and susceptibility rates at potential breakpoints were calculated.

Results

A total of 211 isolates were tested, 112 from 2018 and 99 from 2019. MOX MIC50 and MIC90 for all isolates was 0.25 µg/mL and 2 µg/mL, respectively. The range of MIC distribution was ≤ 0.006 µg/mL to ≥ 64 µg/mL. Percent susceptibilities at incremental MICs, including established MOX breakpoints against Enterobacterales and established levofloxacin breakpoints against SM, are represented in Table 1. MIC distribution was plotted in Figure 1.

Table 1. Susceptibility rates of S. maltophilia to moxifloxacin at theoretical breakpoints

Figure 1. Moxifloxacin MIC Distribution against All S. maltophilia Isolates

Conclusion

With no established breakpoint, these data represent one of the largest samples of MOX MICs against SM in the United States. Using the CLSI breakpoint for levofloxacin in SM (MIC of ≤2ug/ml) the overall susceptibility rate is 93%. This finding highlights the importance of performing susceptibility testing to this agent by the microbiology laboratory and the critical need for MOX breakpoints in SM.

Disclosures

Tyler J. Stone, PharmD, Paratek (Research Grant or Support) John Williamson, PharmD, Paratek (Research Grant or Support) Elizabeth Palavecino, MD, Paratek (Grant/Research Support)Paratek (Grant/Research Support)
1601. Combination Therapy versus Monotherapy for Carbapenem-resistant Organisms: Is More Really Better?
Authors: Najia Laila , Carr Amy , Alexander Jose , Minor Sarah B
Published: January 2021

Background

Carbapenem-resistant organisms (CROs) represent an urgent public health threat and associated with mortality rates up to 60%. Pharmacotherapy for these infections remain challenging and historically included multiple agents. Meropenem/vaborbactam and ceftazidime/avibactam are options to treat CRO infections as monotherapy; however, combination therapy is still frequently utilized. Data evaluating outcomes of patients who received combination therapy compared to those receiving monotherapy for CRO infections is limited.

Methods

This retrospective analysis was completed across 7 campuses at AdventHealth Orlando (AHO) from March 2018-October 2019. AHO implemented CRO PCR testing in March 2018, to identify carbapenemase producing CROs (CP-CROs). Inclusion criteria were hospitalization, age ≥ 18 years, culture with CP-CRO detected by PCR, and ≥ 72 hours of either monotherapy or combination therapy. Primary outcome was clinical success, defined as resolution of signs and symptoms of infection and absence of recurrent infection. Secondary outcomes included mean length of therapy, mean length of stay, inpatient mortality, adverse reactions and 30-day all cause readmissions.

Results

CRO was isolated 68 times in 59 unique patients (56% male, mean age 62 years). Most common sources included urine (41%), sputum (24%) and wound (22%). Commonly isolated organisms include K. pneumoniae (44%) and E. cloacae (29%). Thirty infections (44%) were polymicrobial and 28 patients (41%) had a secondary source of infection. Forty-three patients (63%) received definitive treatment therapy with a single antibiotic. Monotherapy treated patients had higher rates of treatment success (79% vs 68%, p=0.39), lower in-hospital mortality (4% vs 9%, p=0.066), less nephrotoxicity (6% vs 10%, p=0.084), shorter length of therapy (9.6 vs 13.4 days, p=0.034) and shorter hospital stay (20 vs 34 days, p=0.056). All-cause readmission rates were higher in the monotherapy group (18% vs 9%, p=0.78). Minimum inhibitory concentrations (MIC) were reported in 97% of patients.

Conclusion

Treatment with a single antibiotic for carbapenem-resistant infections can lead to treatment success, while minimizing adverse events, compared to utilizing combination therapy.

Disclosures

All Authors: No reported disclosures
1604. Cost-Effectiveness of Ceftazidime-Avibactam for Patients with Hospital-Acquired Pneumonia Caused by Multi-Drug Resistant Enterobacteriaceae or Pseudomonas in China
Authors: Furnback Wesley , Chen YiXi , Dong Peng , Wang Bruce , Ansari Wajeeha , Charbonneau Claudie , Dong Hengjing
Published: January 2021

Background

To estimate the cost-effectiveness of ceftazidime-avibactam (CAZ-AVI) for the treatment of hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP) caused by multi-drug resistant enterobacteriaceae (MDRE) or MDR pseudomonas aeruginosa (MDRPA) in China.

Methods

A previously published patient-level simulation model was localized to China to estimate the cost-effectiveness of first-line CAZ-AVI compared to meropenem from a healthcare perspective. Patients flowed through the model which evaluates resistance status, response, and adverse events (AEs), which can all lead to a treatment switch. Second-line therapy of colistin plus high dose meropenem was used for both arms. Resistance rates were 0.7% (CAZ-AVI) and 7.6% (meropenem) for MDRE, and 10.7% (CAZ-AVI) and 35.5% (meropenem) for MDRPA. Effectiveness rates for CAZ-AVI and meropenem were based on a randomized, double-blind, phase 3 clinical trial. All cost data, including drugs, AEs, and hospitalization were localized to China. Utility values were based on response and sourced from the literature. Costs and benefits were discounted at 5% over the five year time horizon.

Results

At a cost-effectiveness threshold of three-times GDP per capita, CAZ-AVI was cost-effective compared to meropenem for HAP/VAP caused by both MDRE and MDRPA with ICERs of ¥147,500 and ¥30,496, respectively. Specifically, CAZ-AVI had ¥13,699 and 0.09 additional total costs and QALYs, respectively, within MDRE; ¥5,207 and 0.17 additional total costs and QALYs, respectively, within MDRPA. Length of stay was reduced by 0.65 days and 1.37 in the CAZ-AVI arms of the MDRE and MDRPA analyses, respectively.

Conclusion

CAZ-AVI is a cost-effective alternative to meropenem in the treatment of HAP/VAP caused by MDRE or MDRPA in China.

Disclosures

Wesley Furnback, BA, Pfizer (Consultant) YiXi Chen, MSc, Pfizer (Employee) Peng Dong, PhD, Pfizer (Employee) Bruce Wang, PhD, Pfizer (Consultant) Wajeeha Ansari, MSc, Pfizer (Employee) Claudie Charbonneau, PhD, Pfizer (Employee) Hengjing Dong, MD, Pfizer (Other Financial or Material Support, Honorarium)