Multiple Infection Sites Research Articles

Evaluating Risk Factors for Clinical Failure Among Tigecycline-Treated Patients.

Clinical trials have documented that tigecycline has a higher mortality risk than other treatments; it continues to be widely used for various infections in real-world settings, where its associated risk factors for clinical failure are understudied. This retrospective analysis included a prospective 2019-2021 cohort of tigecycline-treated patients, excluding those with multiple infection sites. We assessed the outcomes on day 28, with clinical failure defined by mortality, persistent initial infection symptoms, or the requirement for continued antimicrobial treatment. Multivariable logistic regression was used for the outcome analysis. Of 253 patients included in the study, 94 experienced clinical failure. The infection foci included pneumonia (46.3%), bloodstream infection (BSI) (25.3%), and skin/soft tissue infections (10.3%). There were no significant differences in high-dose tigecycline administration or monotherapy rates between patients with favorable outcomes and those with clinical failure. A higher Charlson comorbidity index (adjusted odds ratio [aOR] = 1.20, P = 0.001), Pitt bacteremia score (aOR = 1.25, P = 0.007), and BSI (aOR = 3.94, P < 0.001) were significant predictors of clinical failure. Concomitant use of Pseudomonas aeruginosa-active fluoroquinolone (aOR = 1.97, P = 0.03) and carbapenem (aOR = 2.20, P = 0.01) was linked to increased clinical failure. Multiple comorbidities, BSI, and higher Pitt bacteremia scores are associated with increased risk of clinical failure in tigecycline-treated patients. These results suggest clinicians should consider alternatives to tigecycline for patients with these risk factors. When administering tigecycline, vigilant monitoring is indicated to manage potential clinical failures.

P14 Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam Real-world Analysis (SPECTRA): results from a multinational, multicentre observational study

Abstract Background Ceftolozane/tazobactam (C/T) has demonstrated efficacy to treat complicated intra-abdominal infections (cIAI), complicated urinary tract infections (cUTI) and hospital acquired bacterial and ventilator-associated bacterial pneumonia. However, physicians, providers, and other stakeholders including payers want broader real-world evidence to inform clinical decisions and optimize healthcare resource use. Methods SPECTRA is a multinational, multicentre, retrospective, inpatient, observational study of patients treated with C/T in Australia, Austria, Germany, Italy, Mexico, Spain and the UK. Adult inpatients treated with ≥48 h of C/T were included. Demographics, clinical characteristics, treatment management patterns, and outcomes were analysed. Results There were 687 patients from 38 participating hospitals in 7 countries. The average age was 57.6 years (SD ±17.3), and most were male (456, 66.4%). The majority had at least one comorbidity (563, 82.0%), with the most common being heart disease (208, 30.3%), immunocompromised state (207, 30.1%) and chronic pulmonary disease (195, 28.4%). The most common indications were pneumonia (204, 29.7%), sepsis (147, 21.4%) and cIAI (106, 15.4%); 162 (23.6%) had multiple sites of infection and 245 (35.7%) were polymicrobial infections. Median C/T treatment was 12.0 days (IQR 11.0). Half of the patients were admitted to the ICU (343, 49.9%), 43.4% of which was related to the infection. Clinical success was 66.1%. All-cause in-hospital mortality was 22.0% with 8.7% being infection related. The 30 day all-cause readmission was 9.8% and 4.7% were infection related. Conclusions C/T was used to treat infections among critically ill patients and for multi-source, polymicrobial infections. Despite the complexity of the patients in this real-world analysis, most C/T patients had beneficial outcomes that are similar to results of controlled clinical trials.

Hypervirulent Klebsiella pneumoniae: An update on epidemiology, detection and antibiotic resistance.

Klebsiella pneumoniae is a major human pathogen as it is responsible for various infections. In the past years hypervirulent K. pneumoniae (hvKP) emerged and disseminated worldwide. In this review a summary will be given about epidemiology, detection and antibiotic resistance of hypervirulent K.pneumoniae. A common feature of hypervirulent K. pneumoniae is a combined expression of several virulence factors. A mucoviscosus phenotype, certain capsulare serotypes (e.g.: K1, K2, K28, K47, K63) together with additional genetic markers namely, magA, rmpA or iucABCD, are needed in combinations to achieve the hypervirulent pathotype. Plasmid coded virulence determinants are also detected, that indicates horizontal gene transfer of hypervirulence factors in K. pneumoniae.Interestingly, infections caused by hypervirulent K. pneumoniae occur usually in the community in otherwise healthy people, and during these infections multiple infection sites are detected. Clinical pictures include both invasive infections and local abscess formation. Pyogenic liver abscess is the most frequently reported clinical manifestation and abscess formation in brain, spleen and lung are also diagnosed. Additionally, meningitis, endophthalmitis, trombophlebitis, pneumonia can also develop.In the early reports, hypervirulent K. pneumoniae strains exhibited enhanced virulence but these were susceptible to commonly used antibiotics. However, recently KPC, VIM, NDM and OXA-48 carbapenemase producing hypervirulent K. pneumoniae strains are increasingly reported, furthermore, well-known high-risk K. pneumoniae clones (e.g.: ST11, ST147, ST307) can develop hypervirulent pathotype, that poses an even more alarming challenge.

2132. Surveillance of Eravacycline Against Enterobacterales and Non-Fermenter Clinical Isolates, Including Resistant Isolates, Collected Worldwide from Multiple Infection Sites During 2021

Abstract Background Eravacycline is a fully synthetic, fluorocycline approved for the treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age in Europe, Singapore, Hong Kong, mainland China, the US, and the UK. The purpose of this study was to monitor the in vitro activity of eravacycline against 2,942 Gram-negative clinical isolates, including multidrug-resistant (MDR) isolates, collected worldwide in 2021. Methods As part of a worldwide surveillance study, a total of 2,942 Gram-negative isolates were collected during 2021 from various infections including IAI, body fluids, respiratory and other sources. Of the 2,942 isolates, 654, 1263, and 1025 were from Asia/Pacific, Europe, and North America, respectively. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. Antibiotic susceptibility was determined with FDA or CLSI breakpoints. Results Summary MIC data for tested antimicrobials are shown in the Table. Susceptibility to eravacycline for Enterobacterales was 93.9%, 85.7%, 90.0%, and 96.8% for all isolates, MDR Enterobacterales, ESBL-positive, and ESBL-negative isolates, respectively. Although there are no clinical breakpoints for Acinetobacter baumannii or Stenotrophomonas maltophilia, eravacycline exhibited promising activity against these species with MIC50 / MIC90 of 0.5 &amp; 1 and 1 &amp; 2 µg/ml, respectively. Conclusion Eravacycline exhibited sustained high susceptibility against multiple Enterobacterales species, including MDR and ESBL-positive isolates. While breakpoints are not defined for A. baumannii or S. maltophilia, eravacycline demonstrated promising activity against these species. These results suggest that, following several years of clinical use, susceptibility to eravacycline remains high. Disclosures Stephen Hawser, PhD, Allecra: study funding|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Nimmi Kothari, PhD, Allecra: Allecra (study funding)|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Federica Monti, PhD, Allecra: Study funded|Innoviva Specialty Therapeutics, Inc.: Honoraria Tony Hodges, MD, La Jolla Pharmaceutical Company: Employee|La Jolla Pharmaceutical Company: Stocks/Bonds Kristie Zappas, PhD, La Jolla Pharmaceutical Company: employee|La Jolla Pharmaceutical Company: Stocks/Bonds

2133. Surveillance of Eravacycline Against Gram-positive Clinical Pathogens, Including Resistant Isolates, Collected Worldwide From Multiple Infection Sites During 2021

Abstract Background Eravacycline is a fully synthetic, fluorocycline approved for the treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age in Europe, Singapore, Hong Kong, mainland China, the US, and the UK. Previous surveillance studies of eravacycline have demonstrated potent in vitro activity against specific Gram-positive pathogens. The purpose of this study was to further monitor the in vitro activity of eravacycline against Staphylococcus aureus (including methicillin-resistant S. aureus, MRSA), Enterococcus spp. (including vancomycin-resistant Enterococcus, VRE) and Streptococcus spp. Methods A total of 1,557 clinical isolates were collected worldwide during 2021 from multiple infection sources, including bodily fluids, gastrointestinal, genitourinary, and respiratory. Of the 1,557 isolates, 316, 649, and 592 were from Asia/Pacific, Europe, and North America, respectively. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. For comparative purposes, antibiotic susceptibility for eravacycline and tigecycline was determined with both FDA and EUCAST breakpoints, where available. Results Summary MIC data for eravacycline and tigecycline, as a selected comparator, are shown in the Table. Susceptibility to eravacycline in all Gram-positive pathogens was greater than 90% for most species/phenotypes though was notably higher when EUCAST breakpoints were applied to the analysis. Conclusion Eravacycline demonstrated sustained high susceptibility rates against clinically important Gram-positive pathogens, including resistant isolates. Importantly, no CLSI breakpoint exists to date for eravacycline, though the use of EUCAST breakpoints showed higher susceptibilities compared with the use of FDA breakpoints. Harmonization of clinical breakpoints for eravacycline would be desirable. Disclosures Stephen Hawser, PhD, Allecra: study funding|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Nimmi Kothari, PhD, Allecra: Allecra (study funding)|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Federica Monti, PhD, Allecra: Study funded|Innoviva Specialty Therapeutics, Inc.: Honoraria Tony Hodges, MD, La Jolla Pharmaceutical Company: Employee|La Jolla Pharmaceutical Company: Stocks/Bonds Kristie Zappas, PhD, La Jolla Pharmaceutical Company: employee|La Jolla Pharmaceutical Company: Stocks/Bonds

2582. Real-World Analysis of the Outcomes of Patients Treated with Ceftazidime-Avibactam

Abstract Background Ceftazidime-avibactam (CAZAVI) is a novel β-lactam/β-lactamase inhibitor combination with activity against Pseudomonas aeruginosa and some carbapenem-resistant Enterobacterales. CAZAVI has been particularly useful as a carbapenem-sparing strategy to mitigate the selection pressure observed with carbapenems. We aim to perform a real-world analysis of patients treated with CAZAVI for various clinical indications at a tertiary care center in Lebanon. Methods This is a retrospective study conducted at the American University of Beirut Medical Center from 2019-21. We excluded patients who were less than 18 years old, received CAZAVI for less than 48 hours, had severe COVID-19 infection, received more than three courses of CAZAVI, and patients on palliative care before CAZAVI treatment. Data were collected from electronic medical records. The primary endpoint was unfavorable outcome defined as death or incomplete clinical response. Results A total of 301 patients were included contributing 373 infection episodes. The median age was 66 years, with 48% of patients being male, and 55% having a high Charlson Comorbidity Index (CCI) of ≥ 5. A large proportion of patients had been admitted to the intensive care unit and had received antibiotics for more than 48 hours during the preceding 30 days. The majority of infection episodes were hospital-acquired (66%). The most common indication for CAZAVI was respiratory infection (44%) followed by bacteremia (9%). Clinical cultures were positive in 44% of episodes distributed as Enterobacterales 64%, P. aeruginosa 10%, and polymicrobial 26%. Clinical success was 66% and microbiological success was 52%. Mortality was 32%, 65% of which was directly attributable to the infection. The primary endpoint was achieved in 38% of episodes. Multivariate analysis of independent predictors of unfavorable outcome is shown in the Table. Independent Predictors of Unfavorable Outcomes in Patients Receiving CAZAVI Conclusion Results from this highly morbid patient population suggest a good overall response to CAZAVI therapy. The presence of multiple infection sites is an important predictor of unfavorable outcome. Disclosures Souha S Kanj, MD, Gilead: Advisor/Consultant|Menarini: Advisor/Consultant|MSD: Advisor/Consultant|Pfizer: Advisor/Consultant

Characteristics of rare ST463 carbapenem-resistant Pseudomonas aeruginosa clinical isolates from blood

ObjectivesThis study aimed to elucidate resistance to carbapenems and fluoroquinolones, the transmission mechanism of blaKPC-2, and the virulence characteristics of a Pseudomonas aeruginosa strain (TL3773) isolated in East China. MethodsThe virulence and resistance mechanisms of TL3773 were investigated by whole genome sequencing (WGS), comparative genomic analysis, conjugation experiments, and virulence assays. ResultsThis study isolated carbapenem-resistant P. aeruginosa from blood resistant to carbapenems. The patient's clinical data showed poor prognosis compounded by multiple sites of infection. WGS showed that TL3773 carried aph (3′)-IIb, blaPAO, blaOXA-486, fosA, catB7, and two crpP resistance genes on chromosome, and the carbapenem resistance gene blaKPC-2 on plasmid. We identified a novel crpP gene named TL3773-crpP2. Cloning experiments proved that TL3773-crpP2 was not the primary cause of fluoroquinolone resistance in TL3773. GyrA and ParC mutations may confer fluoroquinolone resistance. The blaKPC-2 genetic environment was IS26-TnpR-ISKpn27-blaKPC-2-ISKpn6-IS26-Tn3-IS26, potentially mediating the transmission of blaKPC-2 in P. aeruginosa. The overall virulence of TL3773 was lower than that of PAO1. However, the pyocyanin and biofilm formation of TL3773 was higher than that of PAO1. WGS further indicated that TL3773 was less virulent than PAO1. Phylogenetic analysis showed that TL3773 was most similar to the P. aeruginosa isolate ZYPA29 from Hangzhou, China. These observations further indicate that ST463 P. aeruginosa is rapidly spreading. ConclusionsThe threat of ST463 P. aeruginosa harbouring blaKPC-2 is emergent and may pose a threat to human health. More extensive surveillance and effective actions are urgently needed to control its further spread.

673. Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam Real-world Analysis (SPECTRA): Results from a multi-national, multicenter observational study

Abstract Background Ceftolozane/tazobactam (C/T) has demonstrated efficacy to treat complicated intra-abdominal infections (cIAI), complicated urinary tract infections (cUTI) and hospital acquired bacterial and ventilator-associated bacterial pneumonia. However, physicians, providers, and other stakeholders including payers want broader real-world evidence to inform clinical decisions and optimize healthcare resource use. Methods SPECTRA is a multi-national, multicenter, retrospective, inpatient, observational study of patients treated with C/T in Australia, Austria, Germany, Italy, Mexico, Spain and The United Kingdom. Adult inpatients treated with ≥48 hours of C/T were included. Demographics, clinical characteristics, treatment management patterns, and outcomes were analyzed. Results There were 687 patients from 38 participating hospitals in 7 countries. The average age was 57.6 years (±17.3 [SD]) and most were male 456 (66.4%). The majority had at least one comorbidity 563 (82.0%), with the most common being heart disease 208 (30.3%), immunocompromised state 207 (30.1%) and chronic pulmonary disease 195 (28.4%). The most common indications were pneumonia 204 (29.7%), sepsis 147 (21.4%), and cIAI 106 (15.4%); 162 (23.6%) had multiple sites of infection and 245 (35.7%) were polymicrobial infections. Median C/T treatment was 12.0 days (11.0 [IQR]). Half of the patients were admitted to the ICU 343 (49.9%), 43.4% of which was related to the infection. Clinical success was 66.1%. All-cause in-hospital mortality was 22.0% with 8.7% being infection related. 30-day all-cause readmission was 9.8% and 4.7% were infection related. Conclusion C/T was used to treat infections among critically ill patients and for multi-source, polymicrobial infections. Despite the complexity of the patients in this real-world analysis, most C/T patients had beneficial outcomes that are similar to results of controlled clinical trials. Disclosures Alex Soriano, MD, MSD, Pfizer, Shionogi, Angelini, Menarini, Gilead: Honoraria Laura A. Puzniak, MPH, PhD, Merck &amp; Co., Inc.: former employee and stockholder David Paterson, MBBS, Accelerate: Honoraria|bioMerieux: Honoraria|Entasis: Advisor/Consultant|Janssen-Cilag: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|PPD: Grant/Research Support|Shionogi: Grant/Research Support|VenatoRx: Advisor/Consultant Stefan Kluge, MD, Astrazeneca: Lecture fees|Biotest: Lecture fees|Cytosorbents: Grant/Research Support|Cytosorbents: Lecture fees|Daiichi Sankyo: Grant/Research Support|Daiichi Sankyo: Lecture fees|Fresenius Medical Care: Advisor/Consultant|Fresenius Medical Care: Lecture fees|Gilead: Advisor/Consultant|Gilead: Lecture fees|Mitsubishi Tanabe Pharma: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Advisor/Consultant|Pfizer: Lecture fees|Phillips: Lecture fees|Zoll: Lecture fees Alexandre H. Watanabe, PharmD, Merck &amp; Co., Inc.: Employee Engels N. Obi, PhD, Merck &amp; Co., Inc.: Employee|Merck &amp; Co., Inc.: Stocks/Bonds Sunny Kaul, BSc, MBChB, PHD, FRCP, FFICM, Chiesi: Speaker fees|Gilead: Speaker fees|GlaxoSmithKline: Speaker fees|MSD: Grant/Research Support|MSD: Speaker fees|Shionogi: Speaker fees|Vifor Pharma: Grant/Research Support.

Can fluconazole be used for inpatient re-treatment of coccidioidomycosis among patients with past fluconazole exposures?

Coccidioides spp. may cause significant disease requiring hospitalisation, but optimal antifungal therapy among inpatients following outpatient fluconazole exposures is unknown. The objective of this study is to describe the effectiveness of fluconazole among patients hospitalised for coccidioidomycosis despite recent outpatient fluconazole treatment. Patients were admitted to an academic medical center in Phoenix, Arizona from 1 January 2013 through 31 December 2020 for coccidioidomycosis following at least 30 days of outpatient treatment and re-initiation of fluconazole upon admission. The primary outcome was the proportion of patients with an improved response per the change in the modified Mycosis Study Group (MSG) score (a composite of symptoms, serology and radiographic findings) and clinician impressions. Sixty-seven patients were included, with most (54%) admitted to the intensive care unit. Meningitis was the most common infectious presentation (55%), 17 patients (25%) had multiple infection sites, and 23 (34%) were culture-positive for Coccidioides. Upon admission, the median (IQR) MSG score was 11 (9-14), which dropped to 4 (1-7) at end of therapy or last follow-up. Overall, after initiation of fluconazole therapy at a median daily dose of 800 mg, 48 patients (72%) improved in overall status, 10 (15%) showed stable disease and 9 (13%) were unresponsive. Improved response rates were high across all infection sites, including meningitis (68%) and bone infection (71%). There was no significant difference in response rates between patients with and without reported outpatient fluconazole nonadherence. The majority of patients admitted to the hospital for coccidioidomycosis appeared responsive to fluconazole therapy despite past outpatient exposures.

In vitro activity of cefiderocol against Gram-negative bacterial pathogens in Germany

Widespread antimicrobial resistance in Gram-negative bacteria (GNB), particularly carbapenem resistance, represents a major clinical challenge. Cefiderocol is a novel siderophore cephalosporin active against all carbapenemase classes. We evaluated the in vitro activity of cefiderocol and other antibacterial agents (ceftazidime/avibactam, ceftolozane/tazobactam, colistin and meropenem) against GNB isolates collected in Germany (2013-2018) as part of two multinational studies. Antimicrobial susceptibility testing was performed by broth microdilution. Minimum inhibitory concentrations were interpreted according to EUCAST breakpoints. Cefiderocol had high activity against GNB isolates (N=2298), encompassing both Enterobacterales (n=1562) and non-fermenter species (n=736), and maintained high activity against carbapenem-resistant strains (n=211). The activity of cefiderocol against Enterobacterales was equivalent to that of ceftazidime/avibactam and colistin, while ceftolozane/tazobactam was somewhat less active. Against non-fermenter species, cefiderocol displayed equivalent activity to colistin; both of these agents were more active than ceftazidime/avibactam and ceftolozane/tazobactam. Colistin had similar activity to cefiderocol against the majority of species. These patterns of activity were echoed in carbapenem-resistant isolates. The high activity of cefiderocol was independent of infection site, whereas other antibacterial agents demonstrated slightly lower activity against isolates causing pneumonia compared with those from other key infection sites. Cefiderocol exhibited consistently high in vitro activity against a variety of GNB isolates collected in Germany, including resistant phenotypes, across multiple infection sites. These data suggest that cefiderocol is an effective choice of antibacterial agent in patients with GNB infection, regardless of species and resistance phenotype to other agents.

Prevalence of multidrug-resistant bacteria in Ethiopia: a systematic review and meta-analysis

Multidrug-resistant (MDR) bacteria are a significant public-health threat worldwide, especially in low- and middle-income countries. Comprehensive data are important to understand the magnitude of multidrug resistance (MDR), however these are not available in Ethiopia. Five electronic databases and grey literature of Addis Ababa University Repository were searched for data regarding the prevalence of MDR bacteria in Ethiopia. OpenMetaAnalyst R1.3 was used for analysis using a random-effects model to determine the effect size. Heterogeneity among articles was checked using the inconsistency index (I2). Funnel plot was used to check for publication bias. The quality of each article was checked using the Newcastle-Ottawa checklist adapted for cross-sectional studies. Through database searching, 2094 articles were identified, of which 37 fulfilled the study inclusion criteria. This review comprises 6856 bacteria, of which 4949 isolates were MDR. The overall pooled prevalence of MDR was 70.5% (95% CI 64.9-76.1%), with considerable heterogeneity (I2=97.48%, P < 0.001). Funnel plot revealed no publication bias. Sidama (81.7%) had the highest MDR and Tigray (51.1%) the lowest. The greatest source of MDR was from multiple sites of infection (MSI) (76.8%); the least was from bloodstream infections (62.9%). MDR was higher in studies conducted on hospital-acquired infections (72.1%) compared with both hospital- and community-acquired infections (69.8%). Our study indicates a high prevalence of MDR in Ethiopia. Sidama region, MSI and hospital-acquired infections showed the highest MDR in subgroup analysis. Regional hospitals should implement infection prevention and proper use of antibiotics in the community.

1083. Clinical Efficacy of Tedizolid for the Treatment of Mycobacterium abscessus complex Infections in Solid Organ Transplant Recipients

Background Mycobacterium abscessus complex is a rapidly growing mycobacteria notoriously refractory to therapy due to inherent antimicrobial resistance mechanisms. Tedizolid is an oxazolidinone with in vitro activity against many nontuberculous mycobacteria species, including M. abscessus complex. This study describes the clinical outcomes of solid organ transplant (SOT) recipients with M. abscessus complex infection treated with tedizolid at a single medical center.MethodsThis retrospective cohort study included adult SOT recipients who met the ATS/IDSA criteria for nontuberculous mycobacterial infection and were treated with a multi-drug regimen that included tedizolid for at least four weeks between January 1, 2010 to August 31, 2019. Symptomatic improvement was defined as either decreased cough or sputum production for pulmonary infection and decrease in size of the primary lesion for skin or surgical site infection. The criteria for a microbiologic response was more than one negative culture with the causative species and sustained until the end of treatment. Clinical cure was defined as improvement of symptoms without proven negative cultures during and sustained until the end of treatment. A patient was considered cured if both symptomatic (if applicable) and microbiologic criteria were fulfilled. The clinical outcomes were compared from the initiation of tedizolid-containing regimen to the end of any M. abscessus complex treatment.ResultsTwelve patients were included. Mycobacterium abscessus abscessus (7/12, 58%) was the most common subspecies. The distribution of infections were as follows: five (42%) disseminated infections, five (42%) pulmonary infections, five (42%) surgical site infections, and four (33%) skin and soft tissue infections. Six patients were cured or clinically cured for all sites of infection (50%), three patients died (25%), and one patient had two recurrences (Table 1).Table 1. Patient demographics and outcomes of M. abscessus complex infection. ConclusionMost patients had multiple sites of infection, and treatment required combination antimicrobial therapy and appropriate surgical management. In this small cohort, tedizolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement in SOT recipients with M. abscessus complex infection.Disclosures All Authors: No reported disclosures

294. Interim Analysis of an Evidence-Based Bundle Intervention for Uncomplicated Enterobacterales Bacteremia

BackgroundUse of evidence-based process bundles for Staphylococcus aureus bacteremia benefit patient outcomes. No studies exist assessing the value of an evidence-based bundle (EBB) in Enterobacterales bacteremia. Recent studies show shorter durations of therapy (DOT) (~ 7 days) result in similar outcomes as longer DOT when treating uncomplicated gram-negative bacteremia. An internal study showed 87% of treatment course durations were > 7 days. This study seeks to determine the impact of an education-based EBB for uncomplicated Enterobacterales bacteremia on patient length of stay (LOS) and DOT.MethodsThis is a quasi-experimental pre- post- analysis conducted across six medical centers. The pre-intervention cohort (n=546) consisted of patients treated for uncomplicated Enterobacterales bacteremia between Jan 1 2016 and Dec 31 2017. The post-EBB education cohort (n=49) consisted of patients treated with the bundle from Jan 1 2020 through Apr 4 2020. Exclusion criteria included immunocompromised state, multiple infection sites, lack of source control, polymicrobial bacteremia, death within 48 hours of treatment, receiving end of life care, < 6 days or > 16 days of therapy, and failure to receive at least one antibiotic with in vitro activity against the organism. The primary outcome was the proportion of patients receiving 6–10 days of therapy. Secondary outcomes included LOS, 30-day readmission rate, 30-day all-cause mortality, time to intravenous to oral conversion, and EBB adherence. Descriptive statistics were used for the baseline characteristics and primary and secondary outcomes. Multiple regression analysis was performed to assess patient covariates.ResultsThere was no difference in the proportion of patients receiving 6–10 days of therapy between the pre- and the post-EBB groups (43.4% vs 53.1%; p = 0.19). There was no association between DOT and covariates. The pre- and post-intervention group had average total DOT of 11.7 ± 2.6 days and 10.6 ± 2.7 days (p = 0.0047), respectively.ConclusionThis interim analysis suggests an education-based EBB for Enterobacterales does not increase the proportion of patients receiving DOT of 6–10 days. Education alone may be insufficient.Disclosures All Authors: No reported disclosures

Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms.

The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms.IMPORTANCEPseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

Evaluation of a pharmacist's impact on antimicrobial prescribing in an urgent care center

AbstractIntroductionThe urgent care (UC) setting is an opportunity for pharmacists to promote antimicrobial stewardship (AS).ObjectivesThe primary objective is to determine compliance with antibiotic prescribing recommendations for the treatment of urinary tract infections (UTI), skin and soft tissue infections (SSTI), upper respiratory tract infections (URI), and lower respiratory tract infections (LRTI) before, during, and after the presence of an AS pharmacist in an UC.MethodsSingle‐center, retrospective, observational, pre‐ (December 10, 2018‐January 6, 2019), intervention (January 7, 2019‐February 3, 2019), and post‐ (February 4, 2019‐March 3, 2019) study. All nonpregnant, adult patients with a chief complaint consistent with UTI, SSTI, URI, or LRTI were included. Patients transferred to another facility, not seen by a provider, presented for a follow‐up visit, with multiple sites of infection, or treated for a bite, wound, or surgical site infection were excluded. Compliance was a composite end point of guideline adherent antibiotic prescribing, empiric selection, duration, and/or dosage. Secondary outcomes included composite outcome components and subgroup analysis of disease states. Logistic regression was performed to evaluate the intervention and other predictors of compliance.ResultsA total of 1930 patients were screened with 439 440, and 430 patients included in the pre‐, intervention, and post‐groups. Demographics were similar between groups, except for age (P = .001) and influenza diagnoses (P &lt; .001). Likelihood of receiving guideline compliant therapy at pre‐intervention (57%), intervention (69%), and post‐intervention (73%) showed substantial improvement (P &lt; .001). Controlling for background variables, participants were almost two times more likely to receive guideline compliant therapy at intervention than at pre‐intervention (odds ratio [OR] = 1.96, P &lt; .001).ConclusionsAn AS pharmacist's presence in an UC significantly increased compliance with antibiotic prescribing recommendations. The largest impact was in reducing antibiotic treatment of viral infections and optimizing antibiotic dosing.

The Effect of Selective and Mass Immunization Against Pneumococcal Infection on the Morbidity and Mortality due to Community-Acquired Pneumonia in Children Under 5 Years of Age

Background. It is required to perform estimation of epidemiological and cost efficacy (regarding morbidity rate) of mass routine vaccination against pneumococcal infection in Russian children and carried out earlier selective vaccination of children from high-risk groups on the basis of four-year experience. It is also important to estimate the rate of hospital admissions in this patient group, long-term and annual cycles, morbidity age and etiology structure, and mortality due to community-acquired pneumonia as one of the most common form of pneumococcal disease.The aimis to study the effect of selective and mass immunization against pneumococcal infection on the morbidity and mortality due to community-acquired pneumonia in children under 5 years of age. Methods.The analysis of communityacquired pneumonia morbidity (in 2003–2018) and mortality due to pneumonias (in 2003–2018) in children under the 14 years old in Perm was carried out. Serotypes of circulating pneumococcus, etiology of community-acquired pneumonias and immunization cost efficacy (direct expense on health care) were further studied. The analysis of study indexes was carried out following selective (vaccination of at-risk children in 2011–2014) and mass (vaccination of infants in 2015–2018) immunization strategies. Results. The morbidity rate of community-acquired pneumonias decreased by 4.0 times (from 267.0 to 66.7 for 1000) after performing selective vaccination (2011–2014) in at-risk children (frequently and chronically ill children). The morbidity rate of community-acquired pneumonias in non vaccinated children of the same group increased by 2.0 times (from 40.0 to 80.0 for 1000 non-vaccinated). The prophylactic efficacy index was 46.0. Whereby the antibacterial index among vaccinated frequently and chronically ill children was 0.11 on one child. This index has decreased by 2.6 times (from 0.11 to 0.04 on one child) in a year within the framework of prospective controlled randomized clinical study. The antibacterial index among non-vaccinated children of this group remained slightly the same: 0.09 and 0.12 respectively. During the selective vaccination the mortality rate among infants decreased by 2 times: long-term average index was 17.9 (2011–2014) against 35.2 (2003-2010) on 100 thousand children. Mass vaccination of infants against pneumococcal infection has reduced the incidence of community-acquired pneumonias among children under 2 years of age and has led to absence of multiple sites of pneumococcal infection in children’s organizations. It also has reduced the number of hospitalized children and achieved zero mortality due to pneumonias in infants by the third year of this immunization strategy implementation. The obtained results were achieved mainly due to circulation of 7 pneumococcal serotypes (6A, 6B, 9V, 14, 19A, 19F, 23F) in children under 5 years of age. The threshold level of vaccination against pneumococcal infection advancing morbidity and mortality due to pneumonias in children was specified. The strategy of mass vaccination of infants was cost-effective. Conclusion. The new data on epidemiological and cost efficacy of various immunization strategies against pneumococcal infection in children was obtained.

Prognostic factors influencing the treatment outcome of onychomycosis Candida

Onychomycosis contributes as many as half of all nail disorder cases. In 2017, the incidence of onychomycosis was 15% of all dermatomycosis cases at our hospital, a tertiary hospital in Indonesia, with only 25% of the patients achieving mycological cure. This study aims to identify the prognostic factors influencing the treatment outcome of onychomycosis Candida. This is a retrospective study, using data obtained from outpatient registry at our hospital. Fifty-four onychomycosis patients were included in this study. Potential prognostic factors were analysed by STATA15.0. Retrospective analysis with cox proportional-hazard was used to measure the contribution of each variable to the treatment's outcome. Onset of disease, history of nail disorder, and site of infection were not associated with mycological cure (P>.05). Based on retrospective analysis, age[odds ratio (OR)1.46; 95% confidence interval (CI)1.07-2.03], onset of disease (OR 1.14; 95%CI 1.11-1.17), comorbidities (OR 1.07; 95%CI 1.03-1.11), type of onychomycosis (OR 1.08; 95%CI 1.05-1.16), site of infection (OR 1.12; 95%CI 1.04-1.22) and number of infected nails (OR 1.50; 95%CI 1.25-1.68) were significantly associated with poor treatment outcome, while type of treatment and type of systemic agents showed no significant association with the outcome. Kaplan-Meier curves showed that subjects elderly age and more than 3 infected nails had the lowest median survival. Elderly, longer onset, presence of comorbidities, multiple sites of infection, and high number of infected nails can affect the mycological cure negatively. Unstandardised treatment was associated with the mycological cure despite not affecting the prognosis. Therefore, the management's goal is to identify these specific prognostic features.

2060. Evaluation of a Pharmacist’s Impact on Antimicrobial Prescribing in an Urgent Care Center

BackgroundThe urgent care center (UC) setting is an opportunity for pharmacists to promote antimicrobial stewardship (AS). The primary objective is to determine compliance with antibiotic prescribing recommendations for the treatment of urinary tract infections (UTIs), skin and soft-tissue infections (SSTIs), upper respiratory tract infections (URIs), and lower respiratory tract infections (LRTIs) before, during, and after the presence of an AS pharmacist in an UC.MethodsSingle-center, retrospective, observational, pre (December 10, 2018–January 6, 2019), intervention (January 7–February 3, 2019), and post-intervention (February 4–March 3, 2019) study. All non-pregnant, adult patients with a chief complaint consistent with UTI, SSTI, URI, or LRTI were included. Patients transferred to another facility, presented for a follow-up visit, with multiple sites of infection, or treated for a bite, wound, or surgical site infection were excluded. Noncompliance (NC) was a composite endpoint of non-guideline adherent antibiotic prescribing for viral infections, inappropriate empiric selection, duration, and/or dosage. Secondary outcomes include composite outcome components and subgroup analysis of disease states.ResultsA total of 1,930 patients were screened with 439,440, and 430 patients included in the pre, intervention, and post-intervention group. Demographics were similar between groups, except for age (P = 0.001) and influenza diagnoses (P < 0.001). NC decreased from 43.3% to 31.1% (P = 0.0002) pre-intervention to intervention and from 31.1% to 26.5% (P = 0.14) post-intervention. Pre-intervention to intervention resulted in a change in composite outcome components of non-compliant prescribing (18.9% to 13%, P = 0.02), empiric selection (8.7% to 5.9%, P = 0.12), duration (4.1% to 5.9%, P = 0.28), dosage (3.4% to 0.5%, P = 0.001), and multiple components for NC (8.2% to 6.4%, P = 0.3). Reductions in NC were seen for UTI (83.3% to 69.2%, P = 0.26), SSTI (45.7% to 42.9%, P = 1.0), URI (23.5% to 23.2%, P = 1.0), and LRTI (82.1% to 51.6%, P = 0.0004).ConclusionAn AS pharmacist’s presence in a UC significantly reduced NC to antibiotic prescribing recommendations. The largest impact was in reducing antibiotic treatment of viral infections and optimizing antibiotic dosing.Disclosures All authors: No reported disclosures.

434. Concurrent Gonococcal Infections with Differing Susceptibility Results from the Enhanced Gonococcal Isolate Surveillance Project (eGISP)

BackgroundConcurrent gonococcal infections could impact treatment success in cases of anatomic site-specific strains with different antimicrobial susceptibilities; however, little is known about same-patient differences in susceptibility as most antibiotic resistance surveillance is based on only male urethral isolates.MethodsIn August 2017, the enhanced Gonococcal Isolate Surveillance Project (eGISP) began collecting male and female genital and extragenital gonococcal isolates from patients in 12 STD clinics. Minimum Inhibitory Concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, gentamicin, cefixime, ceftriaxone and azithromycin were determined by agar dilution. We identified patients with isolates from multiple anatomic sites of infection collected during the same clinic visit. Isolate sets were categorized as pairs or triplets based on the number of culture positive anatomic sites. We identified same-patient isolate sets with differing MICs (≥2 dilution difference) for each antibiotic, and identified if the difference affected susceptibility categorization. All isolates in a set were tested in the same batch run by the same laboratory.ResultsFrom August 2017-February 2019, 280 isolates were collected from 135 patients, representing 136 isolate sets (128 pairs and 8 triplets); one patient contributed 2 isolate sets. Of the 136 isolate sets, the majority (72; 53%) were grouped as genital and pharyngeal isolates (Table 1). Overall, 33 isolate sets (24%) had differing MICs for ≥1 antibiotic and 21 sets (15%) for ≥2 antibiotics. Across all anatomical site combinations, differing MICs were most common for ciprofloxacin (10.3%), penicillin (9.6%) and azithromycin (9.6%). Only 18 isolate sets (13%) demonstrated differing MICs where an isolate was considered susceptible and another was considered resistant or reduced-susceptible.ConclusionAmong persons with concurrent gonococcal infections, MICs can vary by ≥2 dilutions between sites and may change susceptibility interpretation. Variation by the anatomic site can result from initial infection with multiple strains or differential development of resistance after infection. Continued surveillance of multi-site infections could help understand resistance development and inform patient management. Disclosures All authors: No reported disclosures.

519. Multidrug-resistant Gram-Negative Bacteremia in Pediatric Patients: Is It Time to Change to Empiric Meropenem?

BackgroundThe rise of antimicrobial resistance among gram-negative (GN) pathogens has been dramatic nationally. Delayed initiation of active antimicrobial agents has been associated with poor outcomes. We aimed at evaluating the prevalence and treatment of multi-drug-resistant gram-negative (MDR-GN) bacteremia in our pediatric patients.MethodsAll episodes of GN bacteremia from 2017–2018 at our institution were retrospectively reviewed. GN defined as MDR in our study were carbapenem-resistant organisms (CRO), extended-spectrum β-lactamase (ESBL) producers, and GN that were resistant to cefepime and ≥2 classes of non-cephalosporin antimicrobial agents. Stenotrophomonas maltophilia was excluded. Ineffective empirical treatment (IET) is defined as an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results.ResultsA total of 292 episodes of GN bacteremia were identified and 6 S. maltophilia were excluded. Of these, 29 bacteremic episodes in 26 patients were caused by MDR-GN organisms including 18 ESBL, 7 CRO, 1 ESBL and CRO, 3 non-ESBL/non-CRO cefepime-resistant MDR-GN. None of the CRO had carbapenemase genes detected. However, there was a patient with multiple sites of infection simultaneously with non-NDM CR Acinetobacter bacteremia and NDM-mediated CR-Klebsiella ventriculitis. The annual rate of MDR-GN bacteremia increased from 8% in 2017 to 12% in 2018. Almost half (48%) of episodes were community onset. Among these, all but one had underlying medical conditions with hospital exposure and most patients had central venous devices at the time of infection. 52% (15/29) episodes of MDR-GN bacteremia had IET. Despite IET, 47% (7/15) had negative blood cultures prior to initiation of effective therapy (6 ESBL and 1 P. aeruginosa). Various antibiotic regimens were used for CRO therapy as shown in Table 1.ConclusionIn our institution, MDR-GN infection is increasing. As such, empiric meropenem is currently recommended in BMT or neutropenic patients with suspected sepsis. However, empiric meropenem must be used judiciously as its widely use will lead to more selection of MDR pathogens. It is essential to continue monitoring of these MDR-GN to guide appropriate empiric regimens. Disclosures All authors: No reported disclosures.