Multidrug-resistant P. Aeruginosa Research Articles

Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

In-depth analysis of the treatment effect and synergistic mechanism of TanReQing injection on clinical multi-drug resistant Pseudomonas aeruginosa.

Antibiotic resistance is a recognized and concerning public health issue. Gram-negative bacilli, such as Pseudomonas aeruginosa (P. aeruginosa), are notorious for their rapid development of drug resistance, leading to treatment failures. TanReQing injection (TRQ) was chosen to explore its pharmacological mechanisms against clinical multidrug-resistant P. aeruginosa (MDR-PA), given its antibacterial and anti-inflammatory properties. We revealed the expression of proteins and genes in P. aeruginosa after co-culture with TRQ. This study developed an assessment method to evaluate clinical resistance of P. aeruginosa using MALDI-TOF MS identification and Biotyper database searching techniques. Additionally, it combined MIC determination to investigate changes in MDR-PA treated by TRQ. TRQ effectively reduced the MICs of ceftazidime and cefoperazone and enhanced the confidence scores of MDR-PA as identified by mass spectrometry. Using this evaluation method, the fingerprints of standard P. aeruginosa and MDR-PA were compared, and the characteristic peptide sequence (Seq-PA No. 1) associated with flagellum was found. The phenotypic experiments were conducted to confirm the effect of TRQ on the motility and adhesion of P. aeruginosa. A combination of co-immunoprecipitation and proteome analysis was employed, and 16 proteins were significantly differentially expressed and identified as potential candidates for investigating the mechanism of inhibiting resistance in P. aeruginosa treated by TRQ. The candidates were verified by quantitative real-time PCR analysis, and TRQ may affect these core proteins (MexA, MexB, OprM, OprF, OTCase, IDH, and ASL) that influence resistance of P. aeruginosa. The combination of multiple methods helps elucidate the synergistic mechanism of TRQ in overcoming resistance of P. aeruginosa.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen closely associated with various life-threatening acute and chronic infections. The presence of antimicrobial resistance and multidrug resistance in P. aeruginosa infections significantly complicates antibiotic treatment. The expression of β-lactamase, efflux systems such as MexAB-OprM, and outer membrane permeability are considered to have the greatest impact on the sensitivity of P. aeruginosa. The study used a method to assess the clinical resistance of P. aeruginosa using matrix-assisted laser desorption ionization time of flight mass spectrometry identification and Biotyper database search techniques. TanReQing injection (TRQ) effectively reduced the MICs of ceftazidime and cefoperazone in multidrug-resistant P. aeruginosa (MDR-PA) and improved the confidence scores for co-cultured MDR-PA. The study found a characteristic peptide sequence for distinguishing whether P. aeruginosa is resistant. Through co-immunoprecipitation and proteome analysis, we explored the mechanism of TRQ overcoming resistance of P. aeruginosa.

In vitro evaluation of biofilm phenotypic and genotypic characteristics among clinical isolates of Pseudomonas aeruginosa in Hamadan, West of Iran.

Due to high antimicrobial resistance and biofilm-forming ability, Pseudomonas aeruginosa is one of the seriously life-threatening agents causing chronic and nosocomial infections. This study was performed to determine the antibiotic resistance pattern, biofilm formation, and frequency of biofilm-related genes in P. aeruginosa strains. In total, 123 P. aeruginosa isolates were collected from different clinical sources. Antimicrobial susceptibility testing (AST) was performed to detect multidrug-resistant P. aeruginosa (MDRPA) isolates. To evaluate the biofilm-forming isolates, the microtiter plate (MTP) method was carried out. Also, the prevalence of biofilm genotype patterns, including pslA, pslD, pelA, pelF, and algD genes, was detected by polymerases chain reaction (PCR). According to our findings, the highest resistance and susceptibility rates were found in ceftazidime with 74.7% (n = 92) and ciprofloxacin with 42.2% (n = 52), respectively. In our study, the highest level of antibiotic resistance belonged to wound isolates which meropenem had the most antibacterial activity against them. In total, 86.1% (n = 106) P. aeruginosa isolates were determined as MDRPA, of which 61.3% (n = 65) were able to form strong biofilm. The highest and lowest frequency of biofilm-related genes among biofilm producer isolates belonged to pelF with 82.1% (n = 101) and algD with 55.2% (n = 68), respectively. The findings of the conducted study indicate a significant relationship between MDRPA and biofilm genotypic/phenotypic patterns, suggesting the necessity of a careful surveillance program in hospital settings.

Distribution and antimicrobial sensitivity pattern of multidrug-resistant Pseudomonas aeruginosa from the clinical specimen in Aceh, Indonesia

The development of P. aeruginosa resistance to antibiotics is increasing globally due to the inappropriate use of antibiotics. This retrospective descriptive study aimed to determine the distribution of multidrug resistant P. aeruginosa (MDRPA) and its antimicrobial sensitivity profiles. Data were taken from the bacterial identification and antibiotic sensitivity testing of clinical specimens in Aceh Provincial Referral Hospital from July 2017 to June 2019, where the VITEK® 2 Compact automatic device was used for the identification. In total, there were 307 P. aeruginosa isolates analyzed in this study. The results of this study revealed that 54.39% of P. aeruginosa isolates were multidrug resistant. The MDRPA were mostly found in sputum and pus cultures (41.91% and 23.95%, respectively). Based on the wardroom as the source, most samples came from the internal medicine unit, intensive care unit, and surgical unit with prevalence of 27.54%, 25.74%, and 20.35%, respectively. High proportion of infected patients were male (52.09%) and aged 56–65 years (23.95%). P. aeruginosa showed the highest sensitivity rate to amikacin (77.1%), followed by meropenem (74.4%), ceftazidime (70.1%), levofloxacin (65.1%), tobramycin (64.9%), piperacillin-tazobactam (64.3%), and gentamicin (61.4%). In conclusion, our data suggest that the MDRPA infection is prevalent in Aceh Province and Amikacin is recommended as the highest standard of therapy for MDRPA.

643. Cefiderocol In vitro Activity Against Molecularly Characterized Pseudomonas aeruginosa and Acinetobacter baumannii-calcoaceticus complex Clinical Isolates Causing Infection in United States Hospitals (2020-2021)

Abstract Background Cefiderocol (CFDC) is a siderophore-conjugated cephalosporin with activity against Gram-negative bacteria. CFDC and comparator activities were analyzed against resistant and molecularly characterized P. aeruginosa (PSA) and A. baumannii-calcoaceticus complex (ACB) as part of the SENTRY Antimicrobial Surveillance Program. Methods 2,241 PSA and 682 ACB were consecutively collected from 63 US sites in 2020-2021. Susceptibility testing was performed by broth microdilution and CFDC testing used iron-depleted media. FDA and CLSI breakpoints were used for CFDC. CLSI criteria were applied to comparators, except for imipenem-relebactam (IMR) that used FDA breakpoints. Isolates with a resistance phenotype to ≥ 3 classes were defined as multidrug resistant (MDR). ACB and PSA with imipenem and/or meropenem (MER) MIC ≥4 μg/mL or ceftazidime (CAZ) and/or cefepime MIC ≥ 16 μg/mL were subjected to next-generation genome sequencing for screening of acquired carbapenemase genes. Results 31.6% (709/2,241) and 16.9% (379/2,241) of PSA met the MIC screening criteria and showed an MDR phenotype, respectively (Table). Carbapenemase genes were detected in 6 (&amp;lt; 1%) PSA. CFDC had similar MIC against PSA that did not (MIC50/90, 0.06/0.25 μg/mL) and did (MIC50/90, 0.12/0.5 μg/mL) meet the MIC screening criteria. CFDC also had similar MIC50 values (0.12 μg/mL) against the MDR and carbapenemase-positive PSA populations, whereas other agents had compromised activity. 42.5% (290/682) of ACB met the MIC screening criteria, while 35.9% (245/682) had an MDR phenotype, and 27.3% carried carbapenemase genes (all OXA carbapenemase, except for 2 blaNDM-1). In general, CFDC, IMR, meropenem-vaborbactam, MER, ceftazidime-avibactam, and CAZ had activity against ACB that did not meet the MIC screening criteria, but only CFDC (MIC50/90, 0.25-0.5/2 μg/mL) was active against the resistant ACB subsets. Conclusion Many PSA showed a resistance phenotype but acquired carbapenemase genes remained rare in this subset. In contrast, resistance and presence of carbapenemase genes were high in ACB. CFDC showed potent activity against PSA and ACB subsets in US hospitals, including across resistant and molecularly characterized subsets, where treatment options were limited. Disclosures Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Cory Hubler, BS, Melinta: Grant/Research Support|Shionogi: Grant/Research Support Valerie Kantro, BA, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Jennifer M. Streit, BS, MT(ASCP), Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1676. Activity of SPR206 and Comparator Agents Against Pseudomonas aeruginosa and Acinetobacter baumannii Causing Infections in United States Hospitals

Abstract Background SPR206 is a next generation polymyxin being developed to treat serious infections caused by Gram-negative (GN) multidrug-resistant (MDR) pathogens. The in vitro activity of SPR206 and comparators were monitored against GN pathogens causing infection in US and European hospitals during 2021 as part of the SENTRY Antimicrobial Surveillance Program. This study reports the activity of SPR206 against A. baumannii-calcoaceticus species complex (ACB) and P. aeruginosa (PSA) recovered from patients hospitalized in the USA. Methods A total of 238 ACB and 450 PSA recovered from clinical samples during the SENTRY Program for 2021 were included in the study. Isolates were collected from sites in all 9 US Census Divisions and centrally tested for susceptibility by CLSI broth microdilution method and interpretations. Results A total of 34.9% (83/238) and 14.7% (35/238) ACB displayed an MDR or XDR phenotype, whereas 17.8% (80/450) and 8.0% (36/450) PSA had these phenotypes, respectively. Overall, SPR206 had MIC50/90 of 0.12/0.5 mg/L against all ACB, whereas colistin (COL) had MIC50/90 results of 0.5/1 mg/L. SPR206 and COL inhibited, respectively, 98.0% and 97.0% of ACB at MIC of ≤2 mg/L. Other agents tested against ACB showed MIC90 of &amp;gt;16 mg/L. SPR206 remained active against the MDR (MIC50/90, 0.12/1 mg/L) and XDR (MIC50/90, 0.12/0.25 mg/L) subsets of ACB, as did COL (MIC50/90, 0.5/1 mg/L). MIC50, MIC90, and MIC100 of 0.25 mg/L, 0.25 mg/L, and 2 mg/L were obtained for SPR206 against all PSA, respectively. COL (MIC50/90, 1/1 mg/L), ceftazidime-avibactam (MIC50/90, 2/8 mg/L; 94.9% susceptible), and ceftolozane-tazobactam (MIC50/90, 0.5/2 mg/L; 96.9% susceptible) were active against PSA. SPR206 (MIC50/90, 0.25/0.5 mg/L) and COL (MIC50/90, 1/1 mg/L) remained active against the MDR and XDR PSA subsets. Conclusion SPR206 showed potent in vitro activity against these recent collections of ACB and PSA from the USA. SPR206 potency was consistently greater than clinically available in-class and other comparator agents. These results, and favorable safety and tolerability profiles of SPR206 in Phase 1 studies, support the clinical development of SPR206 for the usually difficult-to-treat infections caused by these pathogens and their resistant subsets. Disclosures Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1672. Antimicrobial Activity of Cefepime-Taniborbactam and Comparators Against Clinical Isolates from ICU and Non-ICU Patients; 2018-2020 Global Surveillance

Abstract Background Taniborbactam is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor with selective direct inhibitory activity against both serine- and metallo-β-lactamases. Taniborbactam restores the activity of cefepime against many difficult to treat organisms, including cephalosporin- and carbapenem-resistant Enterobacterales (EB) and P. aeruginosa (PA). The activity of cefepime-taniborbactam (FTB) and comparator agents was evaluated against clinical isolates of EB and PA from a 2018-2020 global surveillance study. Methods 16,742 isolates of EB and PA were collected from patients in wards designated ICU and non-ICU in 2018-2020. MICs of FTB and comparators were determined by the CLSI reference method. Resistant (R) phenotypes were based on 2022 CLSI breakpoints. Multidrug resistant (MDR) was defined as resistance to at least one agent from ≥3 drug classes. Provisional susceptible (S) breakpoints of ≤8 µg/mL and ≤16 µg/mL were applied for FTB for comparative purposes only. Results FTB had potent activity against EB, with MIC90s of 0.25 µg/mL for isolates from non-ICU patients and 0.5 µg/mL for isolates from ICU patients (Table). At least 99.2% of all EB from both wards were inhibited by ≤8 µg/mL FTB. FTB maintained activity against R phenotypes of EB in both ward types, with 90.3% to 98.1% of isolates inhibited at ≤8 µg/mL. FTB had potent activity against PA, with MIC90 values of 8 µg/mL and inhibiting ≥94.0% of isolates at ≤8 µg/mL for both ICU and non-ICU isolates. FTB maintained activity against R phenotypes of PA in both ward types, with 71.0% to 83.7% of isolates inhibited at ≤8 µg/mL and 84.7% to 92.5% inhibited at ≤16 µg/mL. %S to comparator agents against the R subsets ranged from 1.6% to 92.6% for EB, and 36.0% to 68.4% for PA. Against the particularly challenging subset of MDR PA from ICU patients, FTB was the most active agent tested as it inhibited 73.5/84.7% of isolates at ≤8/≤16 µg/mL compared to 43.1%S to CZA and 36.0%S to C/T. Conclusion Cefepime-taniborbactam demonstrated potent in vitro activity against EB and PA from ICU and non-ICU wards, including resistant subsets of isolates. This supports the continued development of FTB as a potential new treatment option for infections due to resistant Gram-negative pathogens. Disclosures All Authors: No reported disclosures.

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006–May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

Molecular Epidemiology of Multidrug-Resistant Pseudomonas aeruginosa Acquired in a Spanish Intensive Care Unit: Using Diverse Typing Methods to Identify Clonal Types.

The increasing number of infections from multidrug-resistant P. aeruginosa (MDRPA) has compromised the selection of appropriate treatment in critically ill patients. Recent investigations have shown the existence of MDRPA global clones that have been disseminated in hospitals worldwide. We aimed to describe the molecular epidemiology and genetic diversity of the MDRPA acquired by Intensive Care Units (ICU) patients in our hospital. We used phenotypic methods to define the MDRPA and molecular methods were used to illustrate the presence of carbapenemase encoding genes. To characterize the MDRPA isolates, we used MALDI-TOF biomarker peaks, O-antigen serotyping, and multi-locus sequence typing analyses. Our data show that the most widely distributed MDRPA clone in our ICU unit was the ST175 strain. These isolates were further investigated by the whole-genome sequencing technique to determine the resistome profile and phylogenetic relationships, which showed, as previously described, that the MDR profile was due to the intrinsic resistance mechanisms and not the carbapenemase encoding genes. In addition, this study suggests that the combination of environmental focus and cross-transmission are responsible for the spread of MDRPA clones within our ICU unit. Serotyping and MALDI-TOF analyses are useful tools for the early detection of the most prevalent MDRPA clones in our hospital. Using these methods, semi-directed treatments can be introduced at earlier stages and healthcare professionals can actively search for environmental foci as possible sources of outbreaks.

Prevalence of carbapenemase genes among multidrug-resistant Pseudomonas aeruginosa isolates from tertiary care centers in Southern Thailand.

To assess the prevalence of carbapenemase genes among multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) isolates from tertiary care centers in Southern Thailand. The prevalence of carbapenemase genes in P. aeruginosa isolates collected from patients hospitalized between 2015-2017 in 2 tertiary care hospitals in Songkhla Province, Southern Thailand, was investigated. Standard laboratory procedures were followed and disk diffusion test was used for bacterial identification and susceptibility evaluations. Carbapenemase genes were detected using multiplex polymerase chain reaction (PCR) and genotyping by pulsed field gel electrophoresis. Among the 289 P. aeruginosa isolates, 55% was from sputum, 19.4% was from urine, and 8% was from secretions. The prevalence was 55.7% in carbapenem-resistant multidrug-resistant P. aeruginosa (CR-MDR-PA) and 39.4% in multidrug-resistant P. aeruginosa (MDR-PA). Resistance to imipenem, meropenem, gentamicin, and ceftazidime ranged from 50-60%, and amikacin was the most effective antibiotic (38.4%). The carbapenemase genes bla VIM (27.7%), bla IMP (23.9%), and bla OXA48 (4.8%) were detected; however, bla SPM and bla BIC were not detected in any of the isolates. Pulsed field gel electrophoresis analysis revealed clonal diversity among 17 CR-MDR-PA strains. A high percentage of CR-MDR-PA carries carbapenemase genes in our area; therefore, more emphasis on and application of molecular techniques for infection prevention and control may provide useful insights on disease epidemiology.

A photo-thermal nanocomposite capable of relieving inflammatory response to compete multidrug-resistant pseudomonas aeruginosa infection

Lung infection associated with drug-resistant P. aeruginosa and their wide spread have become a serious problem to public health. Effective antibacterial strategy without antibiotics must be developed for treatment of these infections. To combat pneumonia infected by multidrug-resistant P. aeruginosa (MRPA), a novel antibacterial nanocomoposite of AuNRs@PBArPEGMA was prepared. AuNRs@PBArPEGMA could bind with P. aeruginosa through the interaction betweeen PBArPEGMA and bacteria proved by alizarin red assay. The nanocomposite could relieve inflammtory response in MRPA-infected macrophages by downregulating MAPK and NFκB signal-transduction pathways. AuNRs@PBArPEGMA showed well photo-thermal conversion capacity leading to the temperature increasing from 20 to 80 °C under near-infrared (NIR) irradiation for 5 min. The photo-thermal capacity endowed the nanocomposites efficient antibacterial activity against MRPA. Simultaneously, AuNRs@PBArPEGMA with NIR irradiation could kill biofilm bacteria while traditional antibiotics were non-effetive. AuNRs@PBArPEGMA with NIR irradiation could treat MRPA-related lung infection. The nanocomposite with NIR reduced the inflammatory cytokines of TNF-α, IL-1β, and IL-6 by downregulating the MAPK signal pathway in bronchoalveolar lavage fluids. The number of P. aeruginosa and expression of NF-κB p65 in lung also decreased. Above all, our study provides a non-antibiotic therapeutic strategy in clinical application and demonstrated that AuNRs@PBArPEGMA with NIR irradiation showed a potential treatment for drug-resistant P. aeruginosa infection in Lung.

Five-year Surveillance of Antimicrobial Resistance Changes and Epidemiological Characteristics in Pseudomonas aeruginosa: A Retrospective Study in a Chinese City Hospital

Background: In recent years, the widespread use of antibiotics has resulted in increased rates of antibiotic resistance (ABR). Pseudomonas aeruginosa is one of the most important opportunistic pathogens causing hospital-acquired infections. Pseudomonas aeruginosa has continuously increased resistance to commonly used clinical antimicrobial drugs, bringing great difficulties to clinical treatment. Objectives: This retrospective study investigated the epidemiological characteristics of P. aeruginosa and changes in ABR over a 5-year period at a hospital in Shandong Province, China. Methods: Pseudomonas aeruginosa strains were collected from 2015 to 2019. The antimicrobial susceptibility testing employed the Kirby-Bauer disk diffusion method and the broth microdilution method (VITEK-2 compact system), according to the guidelines by the Clinical and Laboratory Standards Institute. Data were analyzed using WHONET 5.6 and SPSS V. 21.0 software. Results: A total of 3,324 P. aeruginosa strains were isolated from clinical specimens (604, 631, 700, 595, and 794 strains from 2015 to 2019, respectively). The highest P. aeruginosa detection rates were from respiratory tract specimens (72.54%). The highest resistance was seen in aztreonam, followed by ciprofloxacin, levofloxacin, and imipenem. The isolation rates for carbapenem-resistant P. aeruginosa (CRPA) and multidrug-resistant P. aeruginosa (MDRPA) ranged from 15.21 - 18.38% and 17.31 - 27.31%, respectively. Also, the isolation rates for extensively drug-resistant P. aeruginosa (XDRPA) ranged from 1.86 - 3.52%. Conclusions: The main sources of the P. aeruginosa isolates were older adult patients with chronic respiratory diseases. The isolation rates for CRPA, MDRPA, and XDRPA strains decreased over the 5-year period. However, the drug resistance situation remains a serious concern. Hence, continued infection control and antimicrobial stewardship and basic and clinical research on bacterial resistance are essential.

1272. Cefiderocol In Vitro Activity Against Molecularly Characterized Acinetobacter baumannii-calcoaceticus Complex and Pseudomonas aeruginosa Clinical Isolates Causing Infection in United States Hospitals (2020)

1272. Cefiderocol <i>In Vitro</i> Activity Against Molecularly Characterized <i>Acinetobacter baumannii-calcoaceticus</i> Complex and <i>Pseudomonas aeruginosa</i> Clinical Isolates Causing Infection in United States Hospitals (2020)

ERADICATING PSEUDOMONAS PERSISTENCE IN ADULT PATIENTS WITH CYSTIC FIBROSIS WITH A NEW ALGORITHM OF ANTIBIOTIC SELECTION

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Pseudomonas aeruginosa is a common pathogen, causing chronic and life-threatening infections in airways of patients with cystic fibrosis (CF). Multidrug-resistant P.aeruginosa (MDR-PA), is an important cause of persistent infections due to its ability to form biofilms which display tolerance and high resistance to antimicrobial agents Traditional antibiotic selection tests take days and fail to select effective antibiotics against MDR-PA because not accounting for critical characteristics of “real-life” infections. AtbFinder – a novel culture-based test system addresses these realities by using a novel principle of antibiotic selection, named “populational response”, and has previously proved to be highly effective in selecting antibiotics effective even against MDR bacteria in biofilms, delivering results in 4 hours. Here we present findings from 3-y long microbiological monitoring of P.aeruginosa persistence in patients with CF, that underwent antimicrobial treatment with antibiotics selected using AtbFinder. METHODS: 30 CF patients aged between 18 and 63, with confirmed P.aeruginosa chronic infection, receiving prophylactic antibiotic therapy with antibiotics selected based on AtbFinder results were monitored over 2 years. Sputum was obtained during yearly check-up hospitalisations and the presence of P.aeruginosa was assessed with (i)AtbFinder or (ii) standard microbiological media. RESULTS: First we analyzed the effect of antibiotic therapy selected with the AtbFinder on eradication of P.aeruginosa. By year 1 and 2 after the switch for the use of antibiotics selected with AtbFinder, eradication of P.aeruginosa were noted in 16 (53%) and 22 (73%) out of 30 subjects who had P.aeruginosa infection respectively (p<0.001). We next studied how antibiotics selected with AtbFinder, affected P.aeruginosa sputum load in patients who were still having P.aeruginosa infection. The mean sputum density of P.aeruginosa following a switch in antibiotic therapy selected based on standard methods to those selected with the AtbFinder from baseline (year 0) decreased by 3.2 and 4.1 log10 CFU/g for P.aeruginosa and at year 1 and 2, respectively. Moreover we were able to switch to narrow-spectrum antibiotics in over than 50% of patients. CONCLUSIONS: Our results represent the first study to evaluate the performance of the AtbFinder system in selecting antibiotics that account for the polymicrobial nature of infections within a routine diagnostic setting. Antibiotic optimization with AtbFinder results in progressive eradication of P.aeruginosa from airways of patients with CF. CLINICAL IMPLICATIONS: We have demonstrated that the antibiotics selected using the AtbFinder among patients with CF were more effective than the antibiotics selected for the same patients using routine ASTs. The antibiotics selected have significantly improved critical microbiological and clinical parameters, allowing for a reduction in unnecessary broad-spectrum antibiotic use. DISCLOSURES: No relevant relationships by Christina Kardava, source=Web Response No relevant relationships by George Tetz, source=Web Response No relevant relationships by Victor Tetz, source=Web Response No relevant relationships by Maria Vecherkovskaya, source=Web Response

844. Nosocomial Pseudomonas aeruginosa Blood-Stream Infections; Susceptibility Pattern and Mortality at a Tertiary Care Centre in Edmonton, Alberta, Canada

Background Pseudomonas aeruginosa is one of the leading gram negative nosocomial pathogens, causing severe infections including blood-stream infections (BSI) with high mortality rates. (1). Multi-drug resistant P. aeruginosa (MDRPA) infection rates are reported to be increasing (2) and have been associated with increased mortality (3). This study aims to review the susceptibility pattern and trend of P. aeruginosa BSIs and mortality and identify patients at increased risk of BSI with a resistant P. aeruginosa isolate. This data has important treatment implications.MethodsCases of nosocomial P. aeruginosa bacteremia were prospectively identified at the University of Alberta, Edmonton, Alberta, Canada by the infection prevention and control surveillance program between January 1, 2007 and December 31, 2018. Patient charts were retrospectively reviewed to collect microbiological, clinical, and epidemiological information.Results148 cases of P. aeruginosa BSI were identified over a 12-year period between January 2007 and December 2018. There were 19 cases of MDRPA BSI and 9 cases of XDRPA BSI. The incidence of P. aeruginosa BSI was 0.47 per 10,000 patient days and remained relatively stable over the study period. 66.9% of cases occurred in men. The mean age was 60 years. The average length of stay prior to bacteremia was 42 days. The overall 30-day mortality following P. aeruginosa BSI was 36.4%. Risk factors for increased 30-day mortality included: pulmonary source of infection (OR 4.26, p < 0.001), bacteremia with extremely drug resistant Pseudomonas aeruginosa (XDRPA) (p < 0.0001), and diabetes (OR 2.24, p < 0.05). BSI with MDRPA was not an independent risk factor for increased mortality. Significant risk factors for bacteremia with an MDRPA or XDRPA were length of stay > 28 days (OR 4.22, p < 0.001) and hemodialysis (OR 8.92, p < 0.000001).Annual hospital acquired P. aeruginosa blood-stream infections from 2007-2018 Antibiogram of P. aeruginosa blood-stream isolates from 2007-2018 ConclusionThe incidence of P. aeruginosa BSI as well as the rate of MDRPA and XDRPA BSI have remained stable at our centre between 2007 and 2018. We found that BSI with XDRPA but not MDRPA alone was a significant risk factor for mortality. Risk factors for BSI with a resistant P. aeruginosa strain may be considered to guide empiric therapy.Disclosures All Authors: No reported disclosures

Risk Factors for Mortality of Inpatients with Pseudomonas aeruginosa Bacteremia in China: Impact of Resistance Profile in the Mortality.

PurposePseudomonas aeruginosa bacteremia presents a severe challenge to hospitalized patients. However, to date, the risk factors for mortality among inpatients with P. aeruginosa bacteremia in China remain unclear.Patients and MethodsThis retrospective multicenter study was performed to analyze 215 patients with culture-confirmed P. aeruginosa bacteremia in five healthcare centers in China during the years 2012–2019.ResultsOf 215 patients with P. aeruginosa bacteremia, 61 (28.4%) died during the study period. Logistic multivariable analysis revealed that cardiovascular disease (OR=3.978, P=0.001), blood transfusion (OR=5.855, P<0.001) and carbapenem-resistant P. aeruginosa (CRPA) phenotype (OR=4.485, P=0.038) constituted the independent risk factors of mortality. Furthermore, both CRPA and multidrug-resistant P. aeruginosa (MDRPA) phenotypes were found to be significantly associated with 5-day mortality (Log-rank, P<0.05).ConclusionThis study revealed a high mortality rate amongst hospitalized patients with P. aeruginosa bacteremia, and those with cardiovascular diseases, CRPA and MDRPA phenotypes, should be highlighted and given appropriate management in China.

Antimicrobial resistance patterns and genotypic diversity between clinical and water systems isolates of Pseudomonas aeruginosa in Cali, Colombia

Pseudomonas aeruginosa is considered an opportunistic pathogen, causing a wide variety of infections in compromised hosts, also frequently develops multi-resistance to antibiotics and can colonize various habitats, including water systems. The main aim of this study was to investigate antibiotics susceptibility pattern, genotypic diversity and detection of resistence genes in P. aeruginosa isolates from clinical and aquatic environment sources. Of the 220 P. aeruginosa isolates examined, 48 were clinical isolates and 172 isolates from wastewater and freshwater. Susceptibility to eight antimicrobial agents was carried out by disk diffusion method. Clinical and environmental isolates were screened for the presence of the genes encoding blaKPC-2, blaCTX-M-9, blaPER-1, blaOXA-10, blaIMP-1, blaVIM-2 and blaampC by polymerase chain reaction (PCR). Isolates were examined with PCR-SSCP analysis of partial DNAr 16S sequence. Isolates were mainly resistant to cefoxitin. Multidrug-resistant P. aeruginosa (MDRPA) strains were found in 70% and 90.3% of the clinical and environmental isolates, respectively. The prevalence rates of â-lactamase genes were recorded (blaKPC-2 41.3%, blaVIM-2 36.8%, blaIMP-1 13.6%, blaCTX-M-9 10.9% and blaampC 10.5%,). The PCR-SSCP analysis showed three conformational patterns. All clinical isolates and most environmental isolates were grouped into a single cluster. In this study, we found that P. aeruginosa strains recovered from city water systems must be considered potential reservoir for ESBL genes, especially blaKPC-2 and blaVIM-2.

MULTIDRUG-RESISTANCE PATTERNS AND DETECTION OF PstS GENE IN CLINICAL ISOLATES OF PSEUDOMONAS AERUGINOSA FROM NSUKKA, SOUTHEAST NIGERIA

Objective: This study was aimed to determine the antibiotic resistance patterns of clinical Pseudomonas aeruginosa isolates and to detect the presence of PstS gene.&#x0D; Methods: One hundred and ninety-two clinical isolates of P. aeruginosa were characterized using polymerase chain reaction (PCR) and 16S rDNA sequencing. Antibiotic resistance patterns were determined using the disk diffusion method, while the minimum inhibitory concentrations (MICs) of selected antibiotics against resistant isolates were determined by macro broth dilution and E-test strip methods. The resistant isolates were screened for the presence of PstS gene using PCR.&#x0D; Results: Of 192 clinical isolates of P. aeruginosa, 136 (70.83%) were resistant to at least two antibiotics. Of these, 135 (99%) could be classified as multidrug-resistant P. aeruginosa (MDR-PA), 63 (46%) were extensively drug-resistant (XDR-PA), while 38 (28%) were pandrug-resistant (PDR-PA). The isolates exhibited high level of resistance to cefotaxime and ticarcillin, and low levels of resistance to meropenem and imipenem. The MIC values for meropenem against the resistant isolates were generally &lt;32 mg/L, while the values for other antibiotics ranged from 32 to &gt;128 mg/L. Multiple antibiotic resistance indexes of the MDR-PA ranged from 0.27 to 0.91 and the most prevalent pattern of resistance was PiperacillinR – TicarcillinR – Piperacillin/TazobactamR – CefotaximeR – CeftazidimeR – GentamicnR – TobramycinR– CiprofloxacinR. About 50% of the resistant isolates possessed the PstS gene.&#x0D; Conclusions: The results confirmed the presence of XDR, PDRPA, and PstS gene in P. aeruginosa strains. There is an urgent need for healthcare practitioners to address the problem of multidrug resistance, by implementing a more rational and appropriate use of antibiotics.

Emergence of Multidrug- and Pandrug- Resistant Pseudomonas aeruginosa from Five Hospitals in Qatar

SummaryBackgroundA global rise in multidrug-resistant (MDR) nosocomial infections has led to a significant increase in morbidity and mortality. MDR Gram-negative bacteria (GNB) are recognised for rapidly developing drug resistance. Despite Pseudomonas aeruginosa being the second most common GNB isolated from healthcare associated infections, the magnitude of MDR P. aeruginosa (MDR-PA) has not been evaluated in Qatar.AimTo assess the prevalence and antimicrobial susceptibility patterns of MDR-PA from 5 major hospitals in Qatar.MethodsA total of 2533 P. aeruginosa clinical isolates were collected over a one-year period. MDR-PA was defined as resistance to at least one agent of ≥ 3 antibiotic classes. Clinical and demographic data were collected prospectively.FindingsThe overall prevalence of MDR-PA isolates was 8.1% (205/2533); the majority of isolates were from patients exposed to antibiotics during 90 days prior to isolation (85.4 %, 177/205), and the infections were mainly hospital-acquired (95.1%, 195/205) with only 4.9% from the community. The majority of MDR-PA isolates were resistant to cefepime (96.6%, 198/205), ciprofloxacin, piperacillin/tazobactam (91%, 186/205), and meropenem (90%, 184/205). Patient comorbidities with MDR-PA were diabetes mellitus (47.3%, n=97), malignancy (17.1%, n=35), end-stage renal disease (13.7%, n=28) and heart failure (10.7%, n=22).ConclusionThere was a significant prevalence of MDR-PA in Qatar, primarily from healthcare facilities and associated with prior antibiotic treatment. There was an alarming level of antimicrobial resistance to carbapenems. Our results are part of a national surveillance of MDR to establish effective containment plans.

181. Antimicrobial Susceptibility Trends and Risk Factors for Antibiotic Resistance in Pseudomonas aeruginosa Bacteremia: A 10-Year Experience at a Korean Tertiary Hospital

BackgroundBacteremia due to Pseudomonas aeruginosa is associated with high mortality and inappropriate initial antimicrobial therapy leads to worse outcomes. We aimed to analyze clinical characteristics of P. aeruginosa bacteremia and risk factors for antibiotic resistance and investigate their antimicrobial susceptibility trends.MethodsWe retrospectively reviewed the medical records of patients with P. aeruginosa bacteremia admitted to a tertiary hospital between January 2009 and March 2019.ResultsA total of 242 patients were identified and the median age was 70 years [interquartile range (IQR) 57.6–75.4]. Hepatobiliary tract (28.5%) was most common primary site of infection, followed by respiratory tract (20.2%) and urinary tract (15.7%). Out of 197 (81.4%) patients treated with susceptible antibiotics and the median duration of active antibiotic therapy was 10 days (IQR 4–15.5). The percentages of susceptible P. aeruginosa to amikacin, aztreonam, cefepime, ceftazidime, ciprofloxacin, colistin, gentamicin, imipenem, meropenem, piperacillin–tazobactam, and ticarcillin-clavulanate were 90.1%, 57.9%, 77.3%, 74.8%, 74.4%, 99.2%, 91.3%, 76.0%, 76.0%, 69.4%, and 51.2%. There were 24.8% carbapenem-resistant P. aeruginosa (CRPA), 36.4% multidrug-resistant P. aeruginosa (MDRPA), and 15.3% extensively drug-resistant P. aeruginosa (XDRPA). Susceptible P. aeruginosa to gentamycin and ticarcillin-clavulanate were significantly decreased in 2014–2019 than that in 2009–2013 (both; P < 0.001). Resistance rates to carbapenems and fluoroquinolones tended to increase over time. CRPA, MDRPA, and XDRPA were significantly associated with delayed active therapy (>48 h) (all; P < 0.001). Independent risk factors for CRPA were urinary tract infection (adjusted odds ratio [aOR], 3.4; 95% confidence interval [CI], 1.5–7.8), underlying hematologic malignancy (aOR, 3.0; 95% CI, 1.1–8.3) and cerebrovascular accident (aOR, 2.6; 95% CI, 1.1–5.9), hospital-acquired infection (aOR, 2.5; 95% CI, 1.0–6.1), and co-colonization with multidrug-resistant organisms (aOR, 2.2; 95% CI, 1.1–4.4).ConclusionThe identification of risk factors for antibiotic resistance and analysis of antibiotics susceptibility are useful for early initiation of appropriate antibiotics in patients with P. aeruginosa bacteremia.Disclosures All authors: No reported disclosures.