Resistant Pseudomonas Research Articles

Hand hygiene intervention in the prevention of healthcare associated infections

Abstract Background Healthcare associated infections are a major cause of morbidity and mortality in intensive care units. Observance hand hygiene is singled out as a key element in interruption of these infections. The present study aimed to assess whether hand hygiene intervention program in intensive care unit at the Sahloul University Hospital of Sousse is able to decrease healthcare associated infections. Methods We carried out a pre-experimental study among patients hospitalized in seven intensive care units at the Sahloul University Hospital of Sousse during two distinct periods of 3 months, the first in 2019 and the second in 2021. During these two periods, we monitored only patients hospitalized in the ICU for more than 48 hours and incidence of healthcare associated infections was compared. Healthcare associted infections were defined as infections occurred at least 48 hours after admission to the intensive care units. The hand hygiene promotion intervention, done during the year 2020, was based on 3 axes (training sessions, procedures writing and professional practicesevaluation). Results Incidence of healthcare associated infections decreased significantly in post-intervention (p = 0.000). The decrease of Ventilator-associated pneumonia was significantly higher than other types of infections(p = 0.042). Extended Spectrum B-Lactamase Producing Enterobacteriaceae infections and Ceftazidim resistant Pseudomonas Aeruginosa infections decreased significantly in after intervention (p = 0.000). Conclusions The results of our study showed that improved hand hygiene resulted in a reduction in healthcare associated infections. Key messages • Observance hand hygiene is singled out as a key element in interruption of healthcare associated infections. • Improved hand hygiene resulted in a reduction in healthcare associated infections.

Duration of antibiotic therapy for multidrug resistant Pseudomonas aeruginosa pneumonia: is shorter truly better?

BackgroundThe 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia.MethodsA single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy.ResultsOf 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups.ConclusionsProlonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP.

A Pilot Analysis for a Multicentric, Retrospective Study on Biodiversity and Difficult-to-Treat Pathogens in Burn Centers across the United States (MICROBE).

Following burn injury, patients are at increased risk of infection and are often cited as having a high incidence of difficult-to-treat pathogens (DTp). The purpose of this study is to determine the incidence of DTp after burn injury, which factors are associated with their development, and subsequent outcomes. This single-center, retrospective study assessed patients with thermal or inhalation injury who had a positive culture resulting in initiation of treatment (i.e., excision, topical, or systemic antimicrobials). Demographic data, pathogen and resistance profiles, and prior exposure to topical and systemic antimicrobials were collected. Pathogens were considered DTp if they were multi-drug-resistant (MDR), extensively drug-resistant (XDR), methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing, AmpC-producing, carbapenem-resistant, difficult-to-treat resistance (DTR) Pseudomonas sp., carbapenem-resistant Acinetobacter baumannii (CRAB), or Stenotrophomonas spp. Sixty-five patients who grew 376 pathogens were included in the final analysis. Two-hundred thirteen (56.7%) pathogens were considered DTp. Prior exposure to 7 of the 11 collected topical antimicrobials and 9 of 11 systemic antimicrobial classes were significantly associated with future development of a DTp. This remained true for six and eight, respectively, after controlling for significant covariates via logistic regression. As there were only four deaths, a Cox-proportional hazard analysis was not feasible. The Kaplan-Meier plot according to DTp revealed a clear divergence in mortality (Log rank p = 0.0583). In this analysis, exposure to topical and systemic antibiotics was associated with the development of DTp. The results from this pilot study will inform the next iteration of multicenter study.

Gut colonization with multidrug resistant organisms in the intensive care unit: a systematic review and meta-analysis

BackgroundGut colonization with multidrug-resistant organisms (MDRO) frequently precedes infection among patients in the intensive care unit (ICU), although the dynamics of colonization are not completely understood. We performed a systematic review and meta-analysis of ICU studies which described the cumulative incidence and rates of MDRO gut acquisition.MethodsWe systematically searched PubMed, Embase, and Web of Science for studies published from 2010 to 2023 reporting on gut acquisition of MDRO in the ICU. MDRO were defined as multidrug resistant non-Pseudomonas Gram-negative bacteria (NP-GN), Pseudomonas spp., and vancomycin-resistant Enterococcus (VRE). We included observational studies which obtained perianal or rectal swabs at ICU admission (within 48 h) and at one or more subsequent timepoints. Our primary outcome was the incidence rate of gut acquisition of MDRO, defined as any MDRO newly detected after ICU admission (i.e., not present at baseline) for all patient-time at risk. The study was registered with PROSPERO, CRD42023481569.ResultsOf 482 studies initially identified, 14 studies with 37,305 patients met criteria for inclusion. The pooled incidence of gut acquisition of MDRO during ICU hospitalization was 5% (range: 1–43%) with a pooled incidence rate of 12.2 (95% CI 8.1–18.6) per 1000 patient-days. Median time to acquisition ranged from 4 to 26 days after ICU admission. Results were similar for NP-GN and Pseudomonas spp., with insufficient data to assess VRE. Among six studies which provided sufficient data to perform curve fitting, there was a quasi-linear increase in gut MDRO colonization of 1.41% per day which was stable through 30 days of ICU hospitalization (R2 = 0.50, p < 0.01).ConclusionsAcquisition of gut MDRO was common in the ICU and increases with days spent in ICU through 30 days of follow-up. These data may guide future interventions seeking to prevent gut acquisition of MDRO in the ICU.

Molecular Detection of Virulence Genes Associated With Multi- Drug Resistant Pseudomonas Aeruginosa Isolated from Clinical and Environmental Samples within Maiduguri

Pseudomonas aeruginosa is an ubiquitous opportunistic pathogen having numerous virulence factors and the ability to acquire multidrug resistant traits. This study aimed to determine the presence of the virulence genes algD and lasB in multidrug resistant Pseudomonas aeruginosa isolated from clinical and environmental samples within Maiduguri. A total of 200 samples were collected from four sources namely; Farm soil at root region of groundnut, abattoir waste water, commercial boreholes and urine of urinary tract infected patients. All positive growths on cetrimide agar were further identified biochemically. Antibiotic profile of confirmed Pseudomonas aeruginosa was determined using Kirby-Baeur disc diffusion method. The genes algD and lasB were detected in the multidrug resistant isolates. The result also showed that 90.90%, 81.81% and 81.81% of the urine isolates were resistant to nalidixic acid, chloramphenicol and tetracycline respectively while highest sensitivity was observed against amikacin at 81.81%. Highest resistance among environmental samples was observed in abattoir wastewater with 95.24% resistance to chloramphenicol while least resistance was observed in borehole isolates with 0.00% resistance to Gentamicin, Amikaicin, Meropenem and Aztreonam. According to the findings of this study also, there is no significant difference in habouring virulence genes among the isolates of the different sources. All the multidrug resistant isolates were found to habour both algD and LasB genes. In conclusion, P. aeruginosa was found in all of the studied sources and widespread of algD and LasB genes in the multidrug resistant isolates from all the sources.

Detection of Pyocin S and the Effects of Lactobacillus Acidophilus Cell-Free Supernatants on Multi-Drug Resistant Pseudomonas AeruginosaIsolated from Patients of Baghdad Hospitals

Detection of Pyocin S and the Effects of Lactobacillus Acidophilus Cell-Free Supernatants on Multi-Drug Resistant Pseudomonas AeruginosaIsolated from Patients of Baghdad Hospitals

Impacts of sulfamethoxazole stress on vegetable growth and rhizosphere bacteria and the corresponding mitigation mechanism.

Antibiotics are an important pharmaceutical class excessively used by humans. Its presence in the soil can impact plant growth and induce antibiotic resistance. This research studies the effect of sulfamethoxazole (SMX) on plant growth, rhizosphere bacteria composition, and resistance genes. Two sets of vegetables (basil, cilantro, and spinach) were treated separately with water and SMX solution. The plant growth data and soil samples were collected and analyzed. The results revealed that SMX increased spinach leaf length (34.0%) while having no significant impacts on basil and cilantro. On the other hand, SMX improved the bacterial diversity in all samples. The shifts in the abundance of plant growth-promoting bacteria could indirectly affect vegetable stem and leaf length. SMX also significantly increased the abundance of resistance genes Sul1 and Sul2. A further study into the correlation between bacteria highlights the importance of Shingomonas and Alfipia for inhibiting the spread of key resistance gene hosts, namely, Pseudomonas, Stenotrophomonas, and Agrobacterium. This research provides insight into SMX's impact on vegetable growth and microbial diversity. It also points out important microbial interactions that could potentially be utilized to mitigate ARG proliferation.

2814. The Impact of Novel Antibiotics on Curbing Antimicrobial Resistance and Infection Spread a Dynamic Modeling Study

Abstract Background Antimicrobial resistance (AMR) is a growing global concern. Novel antibiotics (ABXs) target resistant pathogens causing gram-negative (GN) bacterial infections. This study assesses the broader impact of novel ABX use on the US healthcare system, including preventing the onward spread of infections and reducing the level of high-threat AMR. Methods A stochastic dynamic transmission model was developed to simulate the interaction between infection transmissibility, bacterial resistance development, and multiple lines of ABX. Included infection types were intra-abdominal infections, urinary tract infections and hospital-acquired /ventilator-associated pneumonia. Included AMR types were carbapenem-resistant and ESBL-producing enterobacterales (CRE and ESBLE), and multi-drug resistant pseudomonas aeruginosa (MDRP). The model has compartments for non-infected, colonized, or infected patients, with a sensitive or resistant strain in a US hospital. Infected patients receive antibiotics resulting in infection clearance or use of an alternate ABX class. Sensitive pathogens gain resistance due to drug pressure or conversely could lose resistance. Ordinary differential equations were used to estimate compartment membership. The primary data source was the Premier healthcare database (172 hospitals, 2016-2020). The model examined the potential reduction in AMR levels and avoided hospital infections, by comparing two scenarios: targeted use of novel ABX for specific AMR types and the status quo with limited novel ABX use. Results When even novel ABXs are reserved as the 2nd or 3rd line of treatment, compared to the status quo, it could result in a ∼1.5% reduction in hospital infections and a change in CRE, ESBLE, and MDRP by −2.5%, −3.6%, and −2.1%, respectively, on an annual basis. The cumulative impact of novel ABXs over 5-10 years was much larger but subject to higher prediction uncertainty. The primary driver of results are infection clearance rates, risk of resistance gain on various ABX, and uptake of novel ABX. Conclusion Targeted use of novel ABXs for resistant pathogens could lead to improved, earlier infection clearance with most types of infections and pathogens, thereby reducing infection transmission and rise of high-threat AMR in the long-term. Disclosures Apoorva Ambavane, PhD, Merck &amp; Co., Inc: Grant/Research Support Michal Litkiewicz, MSc, Merck &amp; Co., Inc: Grant/Research Support Aditya Sardesai, MSc, CSL Seqirus: Advisor/Consultant|Merck &amp; Co. Inc: Grant/Research Support|Merck &amp; Co. Inc: Grant/Research Support Diana Teloian, MA, Merck &amp; Co., Inc: Grant/Research Support Engels N. Obi, PhD, Merck &amp; Co Inc: Employee Joe Yang, PhD, Merck &amp; Co., Inc: Employee|Merck &amp; Co., Inc: Stocks/Bonds

Cystic fibrosis and pulmonary biofilms

Cystic fibrosis (CF) is an autosomal recessive disorder that involves the cystic fibrosis transmembrane conductance regulator. This protein is an anion channel that transfers chloride and bicarbonate from an intracellular location to an extracellular location. This transfer supports the formation of a normal periciliary fluid layer that is essential for ciliary function and the clearance of particulates from bronchi. Changes in mucociliary function can result in chronic bronchitis and recurrent infections. Studies using micro computed tomography of explanted lungs from CF patients have demonstrated that there is a significant reduction in the number of terminal bronchi and that approximately 50% of these bronchi are obstructed with secretions. These airways become colonized with bacteria, such as Pseudomonas aeruginosa, which can form biofilms, and this results in chronic inflammation and chronic airway damage. Biofilm formation can be predicted when mucoid colonies of pseudomonas grow out on routine bacterial cultures of sputum. Studies on the prognosis of patients with CF have demonstrated that there is lack of clear genotype-phenotype correlation, but one recent longitudinal study did report an association between more severe CFTR genotypes and clinical outcomes. In addition, the degree of pulmonary dysfunction and pseudomonas colonization, especially with drug resistant pseudomonas, predict poor outcomes. Bacteria in biofilms are more resistant to antibiotics, and the structure of biofilms limits host defense responses. Treatment approaches include the use of more than one antibiotic, the addition of inhaled antibiotics, the use of enzymes that degrade biofilms, and the use of small molecules that inhibit community metabolism in biofilms.&#x0D; &#x0D; Key words: cystic fibrosis transmembrane conductance regulator, extracellular secretions, periciliary fluid, Pseudomonas aeruginosa, biofilms

Efficacy of Colistin with Carbapenems Combination by Checkerboard Assay against Carbapenem Resistant Non Lactose Fermenting Gram Negative Bacteria

Recent emergence of carbapenem resistant non-fermenting Gram negative bacteria (CRNFGNB) predominantly Pseudomonas and Acinetobacter species are responsible for significant proportion of nosocomial infections with increased mortality. Of the various mechanisms known, carbapenemases especially metallo beta lactamase (MBL) mediated resistance is the most concerning because of its easy transmissibility via mobile genetic elements and lack of MBL inhibitors for clinical use. In the present study we determined to estimate the prevalence of carbapenem resistant Pseudomonas and Acinetobacter species, their resistance mechanisms by phenotypic tests and synergistic studies with Colistin and carbapenems combination by checkerboard assay. Carbapenem resistance among these two bacteria is 53.2% being isolated predominantly from pus and endotracheal secretions and from patients within the age group of less than 9 years (44%) and more than 60 years (23%). The incidence of carbapenemase and MBL production in NFGNB is 89.8% and 87.9%, respectively. Only Colistin and Tigecycline show significant antibacterial activity while most of the tested antibiotics were found to be least effective against carbapenem resistant NFGNB. Colistin and Imipenem combination demonstrated synergistic activity in majority of the NFGNB species; however, translation of such in vitro efficacy models into highly variable in vivo conditions could be possible only with strong clinical support.

Central venous catheter (CVC) salvage in case of central line-associated bloodstream infection (CLABSI): A monocentric prospective study in patients on long-term home parenteral nutrition (HPN)

CLABSI is a major complication in HPN and frequently leads to central venous catheter (CVC) removal. We developed a salvaging attitude in long term HPN patients due to the necessity of venous preservation. The main objective of this study is to determine the prognosis of CLABSI. We followed-up for three months, in an approved HPN centre, a cohort of 250 adult patients receiving HPN with CLABSI from 2018 to 2020. CLABSI was defined by a blood culture growth differential [peripheral blood] - [CVC blood]≥2h. A therapeutic approach to conserve CVC was established according to the department's protocol. The primary endpoint was conservation of CVC with negative CVC and peripheral blood cultures at 3 months without complications. Data from 30 CLABSIs were collected for 22 HPN patients. The incidence rate of CLABSIs was 0.28 infections/1000 catheter days. Sixteen CVCs were removed immediately, with causes due to the type of germ (staphylococcus aureus: n=6, candida parapsilosis: n=4, klebsiella: n=2), chronic colonization (n=4) or initial complications (n=4). Among the 14 non-removed CVC, 11 were maintained at 3 months with blood cultures on CVC and peripheral negative for 9 (80%) of them. 3 CVC were removed during the 3 months follow-up (non-CVC-related sepsis n=2, and resistant pseudomonas aeruginosa n=1). The incidence rate of CLABSIs in an expert HPN centre remains low. In case of CLABSIs, according to specific protocol, approximately 50% of CVC were removed immediately (essentially due to bacteriological characteristics). In case of CLABSIs and without initial complication, 80% of CVCs can be maintained at 3 months. These results justify a conservative attitude according to standardized protocol.

Clinical outcomes of ceftolozane-tazobactam dosing in patients with sepsis undergoing renal replacement therapies.

A retrospective descriptive study conducted at our institution between May 1, 2017, and March 15, 2022. The primary endpoint was to determine the clinical cure for patients who received C/T for documented infection while on RRT. The secondary endpoints were the microbiologic cure, 30-day infection recurrence, and 30-day crude mortality. Of the 27 patients who met the inclusion criteria, 17 (63%) were males, median age was 69 (62 - 82) years, and weight 67 (57 - 79) kg. The majority of patients had pneumonia 19 (70.4%) followed by bacteremia 5 (18.5%). Multidrug resistant Pseudomonas spp. was the causative organism of infection in 22 subjects (81.5%). Clinical cure was achieved in 17 subjects (63%). Of the 14 subjects who had their culture repeated, 10 (71.4%) patients had microbiologic cure vs. 4 (28.5%) patients who had a microbiologic failure (p = 0.327). 30-day infection recurrence occurred in 6 (35.3%) patients of the clinical cure group and 2 (20%) patients in the clinical failure group (p = 0.362), while mortality occurred in 5 (29.4%) subjects vs. 7 (70%) in both groups, respectively (p = 0.049). The most frequently used doses of C/T were 1.5 g IV q8h while undergoing continuous venovenous hemodiafiltration and 0.75 g IV q8h while undergoing hemodialysis (p = 0.209). The median duration of therapy was 9 (4.5 - 13) days in the clinically cured group vs. 5 (3.75 - 5.5) days in those who had clinical failure (p = 0.038). There was no adverse event reported using these doses during the study period. The used doses of C/T in this study were higher than those approved by the U.S. FDA, while clinical success is uncertain. Larger outcomes and pharmacokinetics studies are needed to establish effective dosing and therapy duration.

Endophytic Fungus Reshapes Spikelet Microbiome to Reduce Mycotoxin Produced by Fusarium proliferatum through Altering Rice Metabolites.

Rice spikelet rot disease (RSRD) caused by Fusarium proliferatum seriously reduces rice yield and produces mycotoxins that threaten human health. The root symbiotic endophytic fungus Phomopsis liquidambaris reduces RSRD incidence and fumonisins accumulation in grain by 21.5 and 9.3%, respectively, while the mechanism of disease resistance remains largely elusive. Here, we found that B3 significantly reduced the abundance of pathogen from 79.91 to 2.84% and considerably enriched resistant microbes Pseudomonas and Proteobacteria in the spikelet microbial community. Further study revealed that B3 altered the metabolites of spikelets, especially hordenine and l-aspartic acid, which played a key role in reshaping the microbiome and supporting the growth of the functional core microbe Pseudomonas, and inhibited the pathogen growth and mycotoxin production. This study provided a feasibility of regulating the function of aboveground microbial communities by manipulating plant subsurface tissues to control disease and mycotoxin pollutants in agricultural production.

Study of Copper Resistant Pseudomonas Strains Isolated from Soil in Sarcheshmeh Copper Mine, in Iran and Investigation of the Mechanisms Involved in Copper Resistance

Heavy metal contaminated sites are the potential source of metal resistance microorganisms. The major focus of this study is to isolate and identify copper ions resistant Pseudomonas from the soil samples collected from mining and refining sites of Sarcheshmeh copper mine in the Kerman Province of Iran and investigate on possible mechanisms for copper resistance. Isolates were selected based on high level of copper ions resistance. The screened isolate was identified as Pseudomonas putida Cu-2 by morphological, biochemical and 16S rDNA gene sequencing analysis. A high degree of copper ions resistance associated with multiple antibiotic resistances was also detected in the screened isolate. The growth pattern of screened isolate with all the studied Cu concentrations was similar to that of control (without Cu ions) indicating that Cu ions would not affect the growth of isolated strain. A decrease in the amount of exopolysaccharides (EPS) was detected after Cu ions – P. Putida Cu-2 culture supernatant interaction. The Fourier transform infrared spectroscopy (FT-IR) peaks for the EPS extracted from the bacterial culture supernatant and the interacted Cu ions were nearly similar. The EPS covering of the Cu ions was established by FT-IR. The study of bacterial EPS covered Cu ions with E. coli PTCC 1338 and S. aureus PTCC 1113 exhibited less toxicity compared to uncoated Cu ions. The presence of copA gene that encodes for the multi-copper oxidase was investigated in the selected strain. The present study suggests that the capping of Cu ions by bacterially produced EPS and the presence of copA gene serve as the probable mechanisms of copper resistance.

Clinical settings, management and factors affecting outcomes in multi and extensively-drug resistant Pseudomonas endophthalmitis.

To report the clinical settings, management and factors affecting outcomes in multi-drug resistant (MDR) and extensively-drug resistant (XDR) Pseudomonas endophthalmitis. Retrospective, consecutive, non-comparative interventional case series. Cases of MDR and XDR Pseudomonas endophthalmitis from January 2012 to December 2020 treated at our tertiary eye care center were included. Data collected included clinical data, anatomic and functional outcome, isolated micro-organisms, and culture sensitivity. This study included 29 eyes of 29 patients with MDR/XDR Pseudomonas endophthalmitis. Mean age at presentation was 60.27 ± 14.9 years (median 63). Commonest clinical setting was acute post-operative endophthalmitis in 27 cases (93.1%). Concurrent corneal infiltrate was present in 11 eyes (37.9%). Initial intervention in 19 eyes (65.5%) was vitrectomy, 2 of which underwent endoscopic pars plana vitrectomy. Mean number of interventions was 3.34 ± 1.44 (median 4). Mean follow up was 3.25 ± 3.07 months (median 2). Sensitivity to ceftazidime was 48.28%. All isolates were sensitive to colistin. Mean visual acuity at last follow up in logMAR was 2.64 ± 1.48 (median 3.5). Seven eyes (24.13%) were NPL (nil perception of light) at the last follow up. Two eyes (6.9%) underwent evisceration. Nine eyes (31.03%) had a favourable anatomic and functional outcome. Eyes without a corneal infiltrate at presentation were found to have a favourable anatomic and favourable functional outcome (OR 11.91, P < 0.04, CI 1.08 to 130.93). Corneal involvement at presentation is associated with poorer outcomes in MDR and XDR Pseudomonas endophthalmitis. There is a potential role of higher newer antibiotics especially colistin in the management of these cases.

LUPEOL AND LAURIC ACID ISOLATED FROM ETHYL ACETATE STEM EXTRACT OF Justicia secunda AND THEIR ANTIMICROBIAL ACTIVITY

The method of cold maceration was used in the extraction of Justicia secunda starting with a non-polar (hexane) to a more polar solvent. The crude extracts of hexane, ethyl acetate, acetone, and methanol from the stem of were obtained using the polarity guided cold extraction method. Lupeol and Lauric acid are two well-known compounds that were discovered when a portion of the ethyl acetate extract of J. secunda was subjected to spectroscopic (1H NMR) structural elucidation. Based on the presence of Lupeol and Lauric acid in J. secunda stem, the plant could be a viable source of antimicrobial agents in the near future. The results of the antimicrobial activity obtained from the fractions of the Stem inhibited or exhibited activity against Methicillin resist Staph aureus, Vancomycin resistant enterococci, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Helicobacter pylori, Campylobacter fetus, Proteus mirabilis, Pseudomonas aeruginosa, Candida tropicalis, and Candida krusei. The plant J. secunda traditionally employed in the treatment of anemic circumstance, blood boost, wound healing, abdominal pain and fertility issues. The overall results confirm the significance of the use of the plant in traditional medicinal treatment of anamic circumstances, blood boost, wound healing etc, in line with reported claims because of the presence of isolated compounds.

Evaluation of and risk factors for the metallo-beta-lactamase enzyme with respect to production of carbapenem-resistant Pseudomonas and Acinetobacter species

Purpose: To investigate the frequency of MBLs in Pseudomonas and Acinetobacter species with E-test, to determine the risk factors and to evaluate the demographic and clinical features of infected patients. Materials and methods: Imipenem or meropenem resistance of Pseudomonas and Acinetobacter isolated from several clinical samples with conventional methods were evaluated with imipenem EDTA E-test and the presence of Metallo-β-lactameses MBL was examined. Several isolates were screened for VIM-1, VIM-2, IMP-1, and IMP-2 with a PCR test. Results: Of 46 carbapenem resistant Acinetobacter isolates, 41 (89%), as well as of 19 carbapenem resistant Pseudomonas isolates, 5 (26%) had MBL positivity with imipenem-EDTA E-test. A history of Intensive Care Unit stay, mechanical ventilation and cephalosporin use were found to be significant risk factors with respect to MBL production. Conclusion: Detection of MBL production in Acinetobacter and Pseudomonas species especially in ICU patients is of prime importance to control infection rapidly and effectively, which contribute to prevention of outbreaks.

1005. Financial and clinical impact of ceftolozane/tazobactam global recall on the treatment of multi-drug resistant Pseudomonas in a large health system

Abstract Background In December 2020, ceftolozane/tazobactam (CT) was voluntarily recalled due to failed sterility tests. With this recall, clinicians were forced to utilize alternatives for multi-drug resistant (MDR) Pseudomonas (PSA) infections until CT returned in late December, 2021. While many studies have examined the impact of medication shortages, few have evaluated the impact of antimicrobial shortages. We evaluated the impact of the CT recall by assessing cost, clinical outcomes, and utilization of novel alternative agents. Methods This multi-site retrospective cohort study compared patients treated for MDR PSA prior to the CT recall (Jan-Jul 2020) to patients treated during the CT recall (Jan-Jul 2021) across seven AdventHealth Central Florida (AHCF) adult hospitals. The primary outcome was percentage of patients treated with novel therapies (CT, ceftazidime/avibactam, or cefiderocol). Secondary outcomes included length of therapy (LOT), inpatient mortality, 30-day readmissions, length of say (LOS), pharmacy expenditures, and average cost per case. Results A total of 203 patients with MDR PSA were evaluated: 100 in the pre-recall cohort and 103 in the post-recall cohort. The majority (58%) of patients were male with an average age of 64 years. The most common source of infection in both cohorts was pneumonia, followed by complicated urinary tract infection. Significantly more patients were treated with novel agents as definitive therapy in the post-recall cohort (65% vs. 29%, p&amp;lt; 0.0001). Average LOT for all anti-PSA therapy was 12 days in the pre-recall cohort compared to 14 days in the post-recall cohort (p=0.1753). Inpatient mortality and 30-day readmissions were not statistically different between groups. Hospital LOS was significantly different between the two groups (18 days vs. 25 days, p=0.006). Significantly higher pharmacy expenditures were found in the post recall cohort (Figure 1) and the average cost per case was significantly higher in the post-recall cohort ($125,254 vs. $62,249). Figure 1:Pharmacy Expenditures for Novel Agents Novel agents: cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam Conclusion The CT recall had a significant impact on both economic and clinical outcomes, particularly increased length of stay, length of therapy, and cost to both the patient and health system. Higher utilization of novel agents is concerning given rising rates of PSA resistance. Disclosures Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board.

1206. Epidemiological interaction of MRSA, ESBL E.coli and C. difficile between ICU/Step-down Unit of University-affiliated Community Hospital and LTACs in Japan: Utility of Molecular Epidemiology Analysis by PCR-based ORF Typing (POT method)

Abstract Background Epidemiological interaction of drug resistant organisms between ICU and surrounding health facilities including LTACs have been of interest in the era of antimicrobial resistance (AMR) and aging society. In addition, conventional molecular epidemiology methods such as pulsed-field gel electrophoresis, and multilocus sequence typing are time-consuming and difficult to perform in a standard microbiology laboratory. Methods Patients admitted to a university-affiliated community hospital in Japan was recruited if their cultures collected clinically during admission grew the following target pathogens: Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin Resistant Enterococci (VRE), ESBL Gram negative rods (GNR), carbapenem-resistant Enterobacteriaceae (CRE), multi-drug resistant Pseudomonas (MDRP) and Clostridioides difficile (C. diff). Their clinical information including admission to ICU/step-down unit vs regular wards and disposition was analyzed with chi-square test for binary outcomes. For the isolates of MRSA, ESBL E. coli, and C. diff, further molecular epidemiology analysis was made, using PCR-based open-reading frame (ORF) Typing (POT method), a more resource-friendly and time-efficient technology originally developed in Japan. Results Among total 9639 hospital admissions in 2018-2019, the above-mentioned target pathogens grew from 233 patients (2.4%). There were 96 MRSA isolates (41.2%, out of 233), followed by 93 ESBL GNR (39.9%), 21 C. diff (9.0%), 13 CRE (5.6%), 10 MDRP (4.3%), and no VRE, respectively. Patients admitted to ICU/step-down unit were more likely to grow the target pathogens (117/1605 vs 116/7801, RR 4.90, 95% CI 3.81-6.30, p&amp;lt; 0.001), and to be discharged to LTACs than patients admitted to regular wards (70/113 vs 32/116, RR 2.17, 95% CI 1.56-3.02). Molecular epidemiology analysis with POT method identified 5, 3 and 3 common strains across 20, 11, and 7 patients with MRSA, ESBL E.coli, C. diff, respectively. Conclusion The study suggests the pathogens of higher priority were more prevalent in ICU/step-down unit and that the discharge from ICU/step-down unit to LTACs could impact on further transmission in the surrounding region. POT method can be utilized for more efficient molecular epidemiology analysis in the era of AMR. Disclosures All Authors: No reported disclosures.

A Self-Forming Hydrogel from a Bactericidal Copolymer: Synthesis, Characterization, Biological Evaluations and Perspective Applications

Objects touched by patients and healthcare workers in hospitals may harbor pathogens, including multi-drug resistant (MDR) staphylococci, enterococci (VRE), Escherichia coli, Acinetobacter, and Pseudomonas species. Medical devices contaminated by these pathogens may also act as a source of severe and difficult-to-treat human infections, thus becoming a critical public health concern requiring urgent resolutions. To this end, we recently reported the bactericidal effects of a cationic copolymer (CP1). Here, aiming at developing a bactericidal formulation possibly to be used either for surfaces disinfection or to treat skin infections, CP1 was formulated as a hydrogel (CP1_1.1-Hgel). Importantly, even if not cross-linked, CP1 formed the gel upon simple dispersion in water, without requiring gelling agents or other additives which could be skin-incompatible or interfere with CP1 bactericidal effects in possible future topical applications. CP1_1.1-Hgel was characterized by attenuated-total-reflectance Fourier transform infrared (ATR-FTIR) and UV-Vis spectroscopy, as well as optic and scanning electron microscopy (OM and SEM) to investigate its chemical structure and morphology. Its stability was assessed by monitoring its inversion properties over time at room temperature, while its mechanical characteristics were assessed by rheological experiments. Dose-dependent cytotoxicity studies performed on human fibroblasts for 24 h with gel samples obtained by diluting CP_1.1-Hgel at properly selected concentrations established that the 3D network formation did not significantly affect the cytotoxic profile of CP1. Also, microbiologic investigations carried out on two-fold serial dilutions of CP1-gel confirmed the minimum inhibitory concentrations (MICs) previously reported for the not formulated CP1.Selectivity indices values up to 12 were estimated by the values of LD50 and MICs determined here on gel samples.