Bacterial biofilms predominate in both acute and chronic human lung infections

BackgroundA basic paradigm of human infection is that acute bacterial disease is caused by fast growing planktonic bacteria while chronic infections are caused by slow-growing, aggregated bacteria, a phenomenon known as a biofilm. For lung infections, this paradigm has been thought to be supported by observations of how bacteria proliferate in well-established growth media in the laboratory—the gold standard of microbiology.ObjectiveTo investigate the bacterial architecture in sputum from patients with acute and chronic lung infections.MethodsAdvanced imaging technology was used for quantification and direct comparison of infection types on fresh sputum samples, thereby directly testing the acute versus chronic paradigm.ResultsIn this study, we compared the bacterial lifestyle (planktonic or biofilm), growth rate and inflammatory response of bacteria in freshly collected sputum (n=43) from patient groups presenting with acute or chronic lung infections. We found that both acute and chronic lung infections are dominated by biofilms (aggregates of bacteria within an extracellular matrix), although planktonic cells were observed in both sample types. Bacteria grew faster in sputum from acute infections, but these fast-growing bacteria were enriched in biofilms similar to the architecture thought to be reserved for chronic infections. Cellular inflammation in the lungs was also similar across patient groups, but systemic inflammatory markers were only elevated in acute infections.ConclusionsOur findings indicate that the current paradigm of equating planktonic with acute and biofilm with chronic infection needs to be revisited as the difference lies primarily in metabolic rates, not bacterial architecture.

Wheat Yellow Rust Disease Infection Type Classification Using Texture Features

Wheat is a staple crop of Pakistan that covers almost 40% of the cultivated land and contributes almost 3% in the overall Gross Domestic Product (GDP) of Pakistan. However, due to increasing seasonal variation, it was observed that wheat is majorly affected by rust disease, particularly in rain-fed areas. Rust is considered the most harmful fungal disease for wheat, which can cause reductions of 20–30% in wheat yield. Its capability to spread rapidly over time has made its management most challenging, becoming a major threat to food security. In order to counter this threat, precise detection of wheat rust and its infection types is important for minimizing yield losses. For this purpose, we have proposed a framework for classifying wheat yellow rust infection types using machine learning techniques. First, an image dataset of different yellow rust infections was collected using mobile cameras. Six Gray Level Co-occurrence Matrix (GLCM) texture features and four Local Binary Patterns (LBP) texture features were extracted from grayscale images of the collected dataset. In order to classify wheat yellow rust disease into its three classes (healthy, resistant, and susceptible), Decision Tree, Random Forest, Light Gradient Boosting Machine (LightGBM), Extreme Gradient Boosting (XGBoost), and CatBoost were used with (i) GLCM, (ii) LBP, and (iii) combined GLCM-LBP texture features. The results indicate that CatBoost outperformed on GLCM texture features with an accuracy of 92.30%. This accuracy can be further improved by scaling up the dataset and applying deep learning models. The development of the proposed study could be useful for the agricultural community for the early detection of wheat yellow rust infection and assist in taking remedial measures to contain crop yield.

Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria

Antibiotic resistance is a global health threat. There are a few antibiotics under development, and even fewer with new modes of action and no cross-resistance to established antibiotics. Accordingly, reformulation of old antibiotics to overcome resistance is attractive. Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin, potentially enabling parenteral use in deep infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of mupirocin and Nano-mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-mupirocin in a rat model. Nano-mupirocin showed no cross-resistance with other antibiotics and retained full activity against vancomycin-, daptomycin-, linezolid- and methicillin- resistant Staphylococcus aureus, against vancomycin-resistant Enterococcus faecium, and cephalosporin-resistant Neisseria gonorrhoeae. Following Nano-mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for >24 h, and a biodistribution study in mice showed that mupirocin concentrations in vaginal secretions greatly exceeded the MIC90 for N. gonorrhoeae (0.03 µg/mL) for >24 h. In summary, Nano-mupirocin has excellent potential for treatment of several infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established antibiotic and liposomes of the same size and lipid composition as Doxil®, an anticancer drug product now used for the treatment of over 700,000 patients globally.

Mapping of Wound Infection Concepts

Wound infection is a serious health care complication. Standardized clinical terminologies could be leveraged to support the early identification of wound infection. The purpose of this study was to evaluate the representation of wound infection assessment and diagnosis concepts (N=26) in SNOMED CT and ICNP, using a synthesized procedural framework. A total of 13/26 (50%) assessment and diagnosis concepts had exact matches in SNOMED CT and 2/7 (29%) diagnosis concepts had exact matches in ICNP. This study demonstrated that the source concepts were moderately well represented in SNOMED CT and ICNP; however, further work is necessary to increase the representation of diagnostic infection types. The use of the framework facilitated a systematic, transparent, and repeatable mapping process, with opportunity to extend.

In situ new variations in Puccinia triticina causing leaf rust on wheat

During the periodic purity checks of pathotypes 107-1(45R35=JCGPL) and 20(5R27=SGQPL) of Puccinia triticina in national repository at Shimla, India, mixtures of infection types were observed on the differential Lr3 and Lr15 , respectively. Single pustule isolations and further pure cultures in both the cases yielded new pathotypes designated as 57(45R39= KGTPL) and 20-2(57R27= SHKPL). Pathotype 57 was one step gain in virulence on Lr3 in 107-1 whereas 20-2 on Lr15 in mother culture of pathotype 20. The difference of virulence on one gene to each mother culture and their non occurrence in the field samples is indicative of mutation for virulence in situ . To ascertain the novelty of new pathotypes, detailed study on differentials, avirulence/virulence structure, DNA polymorphism using SSR markers, and other related information is presented in this publication. The new cultures are being maintained as PrtI 57 and PrtI 20-2 in the repository.

1225. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales Collected from Geriatric Patients in ICU and non-ICU wards, ATLAS Surveillance Program 2016-2019

Background Elevated resistance rates have been reported in ICUs. Aztreonam (ATM) combined with avibactam (AVI) is being developed for use against drug-resistant Enterobacterales (Ebact), including metallo-β-lactamase (MBL)-positive isolates. We examined the activity of ATM-AVI and comparators against Ebact isolates collected from geriatric patients in ICU and non-ICU wards as part of the ATLAS surveillance program. Methods 23754 non-duplicate Ebact isolates were collected in 53 countries in Asia/Pacific (excluding mainland China and India), Europe, Latin America, and Middle East/Africa from patients ≥65 years with lower respiratory tract (LRTI), urinary tract (UTI), skin and soft tissue (SSTI), intra-abdominal (IAI), and bloodstream (BSI) infections. Susceptibility testing was performed by CLSI broth microdilution and values interpreted using CLSI 2021 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL. Results Susceptibility of the studied comparator agents was generally slightly lower among Ebact from BSI than other infection types (Table). Susceptibility was also generally lower among Ebact from ICU than non-ICU wards by up to 10 percentage points, and MIC90 values were up to 32-fold higher. ATM-AVI MIC90 values were within one doubling-dilution across all studied strata (0.12-0.25 µg/mL), were comparable to or lower than for meropenem in all strata, and were 2 to ≥9 dilutions lower than all other tested comparators. MBL-positive Ebact were found in 1.5% of LRTI (n=91), 1.2% of UTI (n=70), 1.1% of SSTI (n=52), 1.3% of BSI (n=49), and 0.7% of IAI isolates (n=22). MBL-positive rates were higher among ICU (1.7%, n=101) than non-ICU isolates (1.0%, n=183). ATM-AVI MIC90 values were 0.5 µg/mL against MBL-positive isolates from all ward and infection types except SSTI (MIC90 0.25 µg/mL) and BSI (MIC90 1 µg/mL), 2-4 dilutions lower than tigecycline and at least 5-10 dilutions lower than the other comparators. Results Table Conclusion ATM-AVI could provide a valuable therapeutic option for treatment of infections caused by Ebact in patients ≥65 years old in both ICU and non-ICU wards. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

88. Effect of an MDR Enterobacterales Screening Tool on Antibiotic Prescribing for Abdominal Infections Caused by Mixed Bacteria

Background Background: Choosing antibiotics for infections caused by mixed Enterobacterales is challenging. Our microbiology lab implemented a multi-drug resistance (MDR) screen for cultures with mixed gram-negative to direct clinicians to use 3rd generation cephalosporins for screen neg. pathogens, and to use broader beta-lactams for screen-pos. pathogens. Here we report the effect of MDR screen on final antibiotic choice. Methods Methods: We retrospectively reviewed cases with abdominal infections caused by mixed bacteria at UNC Medical Center between August and November 2020. Cultures with non-Enterobacteraeles gram negatives were excluded. MDR screen was done by plating mixed Enterobacterales on HardyCHROM™ ESBL agar. Screen-pos. cases were updated “MDR Enterobacterales present” and pathogens were identified with full susceptibilities. Screen-neg. cases were labeled “MDR Enterobacterales not present”. Definitely covering antibiotics were defined by the use of 3rd generation cephalosporins for screen neg. cases, or based on susceptibilities in case of screen pos. organisms or concomitant bacteremia. Possibly covering antibiotics included regimens whose susceptibility could not be predicted based on the screen (e.g., amox/clav or quinolone+metronidazole). Results Results: 51 cases were identified. Median age was 51 years (range 10 to 87). 54.9% were female and 45.1% male. Infections included intra-abdominal abscesses (n =35), perirectal or scrotal abscesses (10), abdominal wound infections (4), perineal necrotizing fasciitis (1), and cholecystitis (1). Sample types were abscess fluid (43), wound purulence (4) or tissue (3). MDR screen was pos. in 7.8%. Antibiotics were adjusted in 17.6% as a result of the screen report. 31.5% of final antibiotics definitely covered the isolated bacteria, 56.9% possibly covered, and 5.9% did not have an active antibiotic. Among screen pos. cases, final antibiotics definitely covered in 75% and possibly in 25%. Conclusion Conclusions: The MDR Enterobacterales screening tool for abdominal infections had limited impact on final antibiotic choice, but was useful when positive. Further directions include assessment of provider understanding of the MDR screen results and investigation of utility of screen in other infection types. Disclosures All Authors: No reported disclosures

1274. Activity of Ceftolozane/Tazobactam, Imipenem/Relebactam, and Comparators Against Pseudomonas aeruginosa Isolates from Patients with Bloodstream and Other Infection Types—SMART United States/Canada 2018-2019

Background Ceftolozane/tazobactam (C/T), an antipseudomonal cephalosporin combined with a β-lactamase inhibitor, was approved for treatment of complicated urinary tract (cUTI) and intraabdominal infections (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonia (HAP/VAP). Imipenem/relebactam (IMI/REL) is a combination of imipenem/cilastatin with relebactam, an inhibitor of class A and C β-lactamases. IMI/REL was approved for HAP/VAP and for infections due to aerobic gram-negative organisms in adults with limited treatment options (e.g., cUTI, cIAI). We compared the activity of C/T and IMI/REL against P. aeruginosa from bloodstream infections (BSI) to those from other infection types. Methods As part of the SMART program, 24 hospitals in the US and 8 in Canada each collected up to 250 consecutive gram-negative isolates per year in 2018-2019 from patients with BSI, lower respiratory tract infections (LRTI), IAI, and UTI. A total of 2351 Pa isolates were collected. MICs were determined using CLSI broth microdilution and breakpoints. Results Pa isolates from BSI tended to show higher susceptibility than IAI, UTI, and especially LRTI isolates (Table). Susceptibility to the tested comparator β-lactams was 11-12 percentage points lower among LRTI than BSI isolates, while C/T and IMI/REL susceptibility was only 2-5% lower. Even among BSI isolates, the comparator β-lactams were active against only 75-88% of isolates, while C/T and IMI/REL were active against >95%. Only amikacin showed higher activity. Analyzing coverage by either C/T or IMI/REL, 98.7% of Pa isolates from BSI were susceptible to one or both agents. C/T and IMI/REL maintained activity against 89% and 69% of meropenem-nonsusceptible (MEM-NS) Pa isolates from BSI (n=36), respectively, and 87% and 76% of piperacillin/tazobactam (P/T)-NS Pa (n=38). Results Table Conclusion Even among BSI isolates, which were generally more susceptible than those from other infection types, Pa susceptibility to commonly used β-lactams like MEM and P/T was < 90%, 7-23% lower than C/T and IMI/REL. Given the desirability of β-lactams among clinicians and the >98% coverage by either C/T or IMI/REL of Pa isolates from BSI, both agents represent important options in the treatment of patients with BSI. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

1264. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa Collected < 48 Hours and ≥48 Hours Post-Admission from Pediatric Patients, ATLAS Surveillance Program 2016-2019

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 presumed community-acquired (CA; cultured &lt; 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program. Methods 6654 non-duplicate isolates were collected in 52 countries in Europe (n=3423), Latin America (n=1323), Middle East/Africa (n=1177), and Asia/Pacific (excluding China; n=731) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1687), urinary tract (UTI; n=1631), bloodstream (BSI; n=1149), skin and soft tissue (SSTI; n=1122), and intra-abdominal (IAI; n=981) infections. Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2021 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (97.8% susceptible (S)) and Psa (92.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 95.4-99.2% among CA Ent from different infection types and were reduced 0.6-1.3% among HA isolates from LRTI, UTI, SSTI, and IAI. Susceptibility to CAZ-AVI was also similar (92.6-95.8% S) among CA Psa from different infection types and was reduced 1.2-7.0% among HA isolates. Larger differences in susceptibility were typically seen for the tested comparator β-lactams. For Ent, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, while the pattern was less clear for Psa. Results Table Conclusion CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

Incidence and predictors of Gram-negative bacilli in hospitalized people who inject drugs with injection drug use-attributable infections

Objective: Quantify incidence and determine predictors of Gram-negative bacilli (GNB) in people who inject drugs (PWID) with injection-drug use (IDU)-related infections. Design: Retrospective cohort of hospitalized PWID from 1/2017-12/2019. Methods: Inclusion criteria: age ≥18 years, active IDU, treated IDU-attributable infection, organism growth from microbiology cultures. Infection types: infective endocarditis (IE), acute bacterial skin/skin structure infection (ABSSSI), osteoarticular infection (OAI), other bloodstream infections (BSI). Primary outcome was GNB identification from microbiologic culture; descriptive statistics were used to describe the cohort. Multivariable regression was used to identify variables associated with GNB infection. Results: 230 PWID included; 65 (28%) GNB infections, 165 (72%) Gram-positive infections. The median (IQR) population age was 38 (31-45) years. Most patients were women (56%); 37% had no insurance. Infection types were: IE (41%), ABSSSI (37%), OAI (20%), other BSI (2%). 278 organisms were isolated from 230 patients; most common organisms were methicillin-resistant Staphylococcus aureus (43%), Streptococcus spp. (19%), methicillin-susceptible S. aureus (17%), Serratia marcescens (8%); 10% were mixed GNB and Gram-positive infections. 80% of patients received empiric Pseudomonas aeruginosa coverage; only 7% had P. aeruginosa infections. In multivariable regression, age >50 years (adjOR, 2.9; 95%CI; 1.2-7.2), prior hospitalization within 90-days (adjOR, 2.2; 95%CI; 1.2-4.3), and OAI (adjOR, 3.2; 95%CI; 1.5-6.6) were associated with GNB infection. Conclusions: GNB in PWID with IDU-attributed infections were more frequently observed in recently hospitalized, older patients with OAI. The majority of patients received empiric anti-pseudomonal antibiotic coverage, but P. aeruginosa was infrequent. PWID are a potential population to target improved empiric antibiotic use.