Carbapenem-resistant Pseudomonas Aeruginosa Research Articles

Implications of deduplication on the detection rates of multidrug-resistant organism (MDRO) in various specimens: insights from the hospital infection surveillance program

BackgroundCurrently, different guidelines recommend using different methods to determine whether deduplication is necessary when determining the detection rates of multidrug-resistant organisms (MDROs). However, few studies have investigated the effect of deduplication on MDRO monitoring data. In this study, we aimed to investigate the influence of deduplication on the detection rates of MDROs in different specimens to assess its impact on infection surveillance outcomes.MethodsSamples were collected from hospitalized patients admitted between January 2022 and December 2022; four types of specimens were collected from key monitored MDROs, including sputum samples, urine samples, blood samples, and bronchoalveolar lavage fluid (BALF) samples. In this study, we compared and analysed the detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Escherichia coli (CRECO), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA) under two conditions: with and without deduplication.ResultsWhen all specimens were included, the detection rates of CRKP, CRAB, CRPA, and MRSA without deduplication (33.52%, 77.24%, 44.56%, and 56.58%, respectively) were significantly greater than those with deduplication (24.78%, 66.25%, 36.24%, and 50.83%, respectively) (all P < 0.05). The detection rates in sputum samples were significantly different between samples without duplication (28.39%, 76.19%, 46.95%, and 70.43%) and those with deduplication (19.99%, 63.00%, 38.05%, and 64.50%) (all P < 0.05). When deduplication was not performed, the rate of detection of CRKP in urine samples reached 30.05%, surpassing the rate observed with deduplication (21.56%) (P < 0.05). In BALF specimens, the detection rates of CRKP and CRPA without deduplication (39.78% and 53.23%, respectively) were greater than those with deduplication (31.62% and 42.20%, respectively) (P < 0.05). In blood samples, deduplication did not have a significant impact on the detection rates of MDROs.ConclusionDeduplication had a significant effect on the detection rates of MDROs in sputum, urine, and BALF samples. Based on these data, we call for the Infection Prevention and Control Organization to align its analysis rules with those of the Bacterial Resistance Surveillance Organization when monitoring MDRO detection rates.

Multidrug-Resistant Bacteria in Surgical Intensive Care Units: Antibiotic Susceptibility and β-Lactamase Characterization.

Multidrug-resistant (MDR) bacteria of the utmost importance are extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). In this study, an evaluation of MDR bacteria in surgical intensive care units in a tertiary referral hospital was conducted. The study aimed to characterize β-lactamases and other resistance traits of Gram-negative bacteria isolated in surgical intensive care units (ICUs). Disk diffusion and the broth dilution method were used for antibiotic susceptibility testing, whereas ESBL screening was performed through a double disk synergy test and an inhibitor-based test with clavulanic acid. A total of 119 MDR bacterial isolates were analysed. ESBL production was observed in half of the Proteus mirabilis, 90% of the Klebsiella pneumoniae and all of the Enterobacter cloacae and Escherichia coli isolates. OXA-48 carbapenemase, carried by the L plasmid, was detected in 34 K. pneumoniae and one E. coli and Enterobacter cloacae complex isolates, whereas NDM occurred sporadically and was identified in three K. pneumoniae isolates. OXA-48 positive isolates coharboured ESBLs belonging to the CTX-M family in all but one isolate. OXA-23 carbapenemase was confirmed in all A. baumannii isolates. The findings of this study provide valuable insight of resistance determinants of Enterobacterales and A. baumannii which will enhance surveillance and intervention strategies that are necessary to curb the ever-growing carbapenem resistance rates.

Genome analysis of an extensively drug resistant Pseudomonas aeruginosa ST1791 from a patient in China hospitalized for severe pneumonia

The emergence and outbreak of carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a major global public threat. we aimed to characterize the genome of drug-resistant and virulent genes in an extremely drug-resistant Pseudomonas aeruginosa strain to understand its antimicrobial resistance trends and pathogenicity. An XDR Pseudomonas aeruginosa strain was isolated in China from a patient with severe pneumonia. Antimicrobial susceptibility testing, genome sequencing and phylogenetic analysis was performed. Predictions were fulfilled using curated bioinformatics tools. The assembly of the strain (CRPA190) comprised 76 contigs with a total length of 7 009 318 bp. CRPA190 belongs to sequence type 1791 (ST1791) and the O11 serogroup. Nine prophage regions, three CRISPR arrays, and two Cas clusters were identified. However, no plasmids were predicted. Antibiotic susceptibility tests showed that CRPA190 was resistant to all the tested antibiotics, including carbapenem, polymyxin B and ceftazidime-avibactam. Forty antimicrobial resistance genes were predicted in CRPA190, including several carbapenemase genes such as blaPDC-142, blaPME-1, blaNDM-1 and blaOXA-902. The isolate was predicted to be pathogenic and possess strong biofilm-forming ability. It harbors virulence genes that are associated with an arsenal of virulence determinants involved in adherence, motility, exotoxins, exoenzymes, immune modulation, biofilms, nutritional/metabolic factors and effector delivery systems. These findings enhance our understanding of the resistance and pathogenicity of the ST1791 Pseudomonas aeruginosa strain which is unique in China and provide a broader perspective on the global epidemiological landscape, suggesting the emergence of P. aeruginosa ST1971, which requires control measures to limit its dissemination.

A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended β-lactam-resistant Pseudomonas aeruginosa.

To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-β-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case-control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa.

Nationwide genome surveillance of carbapenem-resistant Pseudomonas aeruginosa in Japan.

Japan is a country with an approximate 10% prevalence rate of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Currently, a comprehensive overview of the genotype and phenotype patterns of CRPA in Japan is lacking. Herein, we conducted genome sequencing and quantitative antimicrobial susceptibility testing for 382 meropenem-resistant CRPA isolates that were collected from 78 hospitals across Japan from 2019 to 2020. CRPA exhibited susceptibility rates of 52.9%, 26.4%, and 88.0% against piperacillin-tazobactam, ciprofloxacin, and amikacin, respectively, whereas 27.7% of CRPA isolates was classified as difficult-to-treat resistance P. aeruginosa. Of the 148 sequence types detected, ST274 (9.7%) was predominant, followed by ST235 (7.6%). The proportion of urine isolates in ST235 was higher than that in other STs (P = 0.0056, χ2 test). Only 4.1% of CRPA isolates carried the carbapenemase genes: blaGES (2) and blaIMP (13). One ST235 isolate carried the novel blaIMP variant blaIMP-98 in the chromosome. Regarding chromosomal mutations, 87.1% of CRPA isolates possessed inactivating or other resistance mutations in oprD, and 28.8% showed mutations in the regulatory genes (mexR, nalC, and nalD) for the MexAB-OprM efflux pump. Additionally, 4.7% of CRPA isolates carried a resistance mutation in the PBP3-encoding gene ftsI. The findings from this study and other surveillance studies collectively demonstrate that CRPA exhibits marked genetic diversity and that its multidrug resistance in Japan is less prevailed than in other regions. This study contributes a valuable data set that addresses a gap in genotype/phenotype information regarding CRPA in the Asia-Pacific region, where the epidemiological background markedly differs between regions.

Heterogeneity and clinical genomics of blaKPC-2-producing, carbapenem-resistant Pseudomonas aeruginosa

Global transmission of carbapenem-resistant Pseudomonas aeruginosa (CRPA) represents a growing threat to clinic setting. Here we report clinical genomics of diverse blaKPC-2-harboring plasmids distributed in heterogeneous CRPA. Variation in bacterial virulence of clinical CRPA isolates was determined with infection models of murine. The combined data facilitated our understanding of CRPA circulation in clinic settings of China.

Hospital-acquired and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative pathogens: Understanding epidemiology, resistance patterns, and implications with COVID-19

The ongoing spread of antimicrobial resistance has complicated the treatment of bacterial hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Gram-negative pathogens, especially those with multidrug-resistant profiles, including Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Acinetobacter spp., are important culprits in this type of infections. Understanding the determinants of resistance in pathogens causing pneumonia is ultimately stressing, especially in the shadows of the COVID-19 pandemic, when bacterial lung infections are considered a top priority that has become urgent to revise. Globally, the increasing prevalence of these pathogens in respiratory samples represents a significant infection challenge, with major limitations of treatment options and poor clinical outcomes. This review will focus on the epidemiology of HAP and VAP and will present the roles and the antimicrobial resistance patterns of implicated multidrug-resistant (MDR) Gram-negative pathogens like carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Enterobacterales (CRE), as well as colistin-resistant Gram-negative pathogens and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales. While emerging from the COVID-19 pandemic, perspectives and conclusions are drawn from findings of HAP and VAP caused by MDR Gram-negative bacteria in patients with COVID-19.

Antimicrobial Resistance in Qatar: Prevalence and Trends before and Amidst the COVID-19 Pandemic.

Antimicrobial resistance (AMR) is a global healthcare challenge with substantial morbidity, mortality, and management costs. During the COVID-19 pandemic, there was a documented increase in antimicrobial consumption, particularly for severe and critical cases, as well as noticeable travel and social restriction measures that might influenced the spectrum of AMR. To evaluate the problem, retrospective data were collected on bacterial infections and antimicrobial susceptibility patterns in Qatar before and after the pandemic from 1 January 2019 to 31 December 2021, covering 53,183 pathogens isolated from reported infection episodes. The findings revealed a significant resistance pattern for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-EBC), carbapenem-resistant Enterobacteriaceae (CR-EBC), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), ciprofloxacin-resistant Salmonella and methicillin-resistant Staphylococcus aureus (MRSA). For correlation with social restrictions, ESBL-EBC and MRSA were positively correlated with changing patterns of international travel (ρ = 0.71 and 0.67, respectively; p < 0.05), while CRPA was moderately correlated with the number of COVID-19 hospitalized patients (ρ = 0.49; p < 0.05). CREBC and CRPA respiratory infections were associated with hospitalized patients (OR: 3.08 and 2.00, respectively; p < 0.05). The findings emphasize the challenges experienced during the COVID-19 pandemic and links to international travel, which probably will influence the local epidemiology of AMR that needs further surveillance and control strategies.

Prevalence and molecular characteristics of ceftazidime-avibactam resistance among carbapenem-resistant Pseudomonas aeruginosa clinical isolates

Resistance against ceftazidime-avibactam (CZA) in carbapenem-resistant Pseudomonas aeruginosa (CRPA) is emerging. This study was aimed at detecting the prevalence and molecular characteristics of CZA-resistant CRPA clinical isolates in Guangdong Province, China. The antimicrobial susceptibility profile of these strains was determined. A subset of 16 CZA-resistant CRPA isolates was analysed by whole-genome sequencing (WGS). Genetic surroundings of carbapenem resistance genes and pan-genome-wide association analysis were further studied. Of the 250 CRPA isolates, CZA resistance rate was 6.4% (16/250). The minimum inhibitory concentration (MIC) of CZA range was from 0.25 to >256 mg/L. MIC50 and MIC90 were 2/4 and 8/4 mg/L, respectively. Among the 16 CZA-resistant CRPA strains, 31.3% (5/16) of them carried class B carbapenem resistance genes, including blaIMP-4, blaIMP-45, and blaVIM-2, located on IncP-2 megaplasmids or chromosomes, respectively. Pan-genome-wide association analysis of accessory genes for CZA-susceptible or -resistant CRPA isolates showed that PA1874, a hypothetical protein containing BapA prefix-like domain, was enriched in CZA-resistant group significantly. Class B carbapenem resistance genes play important roles in CZA resistance. Meanwhile, the PA1874 gene may be a novel mechanism involving in CZA resistance. It is necessary to continually monitor CZA-resistant CRPA isolates.

Epidemiology of carbapenem-resistant organisms in Alameda County, California, 2019-2021.

Carbapenem-resistant organisms (CROs) are an urgent health threat. Since 2017, Alameda County Health Public Health Department (ACPHD) mandates reporting of carbapenem-resistant Enterobacterales (CRE) and encourages voluntary reporting of non-CRE CROs including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Surveillance data from ACPHD were analyzed to describe the epidemiology of CROs and target public health interventions. Healthcare facilities in Alameda County reported CRO cases and submitted isolates to ACPHD to characterize carbapenemase genes; deaths were identified via the California Electronic Death Registration System. CRO cases with isolates resistant to one or more carbapenems were analyzed from surveillance data from July 2019 to June 2021. Four hundred and forty-two cases of CROs were reported to Alameda County from 408 patients. The county case rate for CROs was 29 cases per 100,000 population, and cases significantly increased over the 2-year period. CRPA was most commonly reported (157 cases, 36%), and cases of CRAB increased 1.83-fold. One-hundred eighty-six (42%) cases were identified among residents of long-term care facilities; 152 (37%) patients had died by January 2022. One hundred and seven (24%) cases produced carbapenemases. The high burden of CROs in Alameda County highlights the need for continued partnership on reporting, testing, and infection prevention to limit the spread of resistant organisms. A large proportion of cases were identified in vulnerable long-term care residents, and CRAB was an emerging CRO among this population. Screening for CROs and surveillance at the local level are important to understand epidemiology and implement public health interventions.

Carbapenem resistance in West Africa: a systematic review

OBJECTIVES: The World Health Organization (WHO) has reported carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAb), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) as critical priority pathogens for human health. Therefore, this study aimed to review clinical carbapenem resistance systematically and comprehensively in West Africa. DATA SOURCES: A total of 102 research articles on carbapenem resistance from the sixteen countries forming the West African region were included in this review. DATA SYNTHESIS: Carbapenem-resistant bacteria (CRB) were isolated mainly from urine 73/300 (24.3%) and pus/wounds of patients 69/300 (23%). The mean prevalence of CRB in West Africa was 4.6% (1902/41635), ranging from 1.6% to 18.6%. CRB identified were mainly Escherichia spp. (34/130; 26.1%), Klebsiella spp. (27/130, 20.8%), Pseudomonas spp. (26/130, 20%), and Acinetobacter spp. (25/130; 19.2%). Bacteria isolated in West African countries produced carbapenemases that belong to the four Ambler classes and include 13 types. The bla OXA-type (34/104; 32.7%), bla NDM (31/104; 29.8%), and bla VIM (13/104; 12.5%) were the most common carbapenemase genes. These genes are carried by plasmids, composite transposons, and integrons. The Kirby-Bauer disc diffusion method (74/172; 43.0%), PCR (38/172; 22.1%), and whole genome sequencing (17/172; 9.9%) were the most common methods for carbapenem resistance detection. The most reported alternative antibiotics active against CRB were amikacin, colistin, and fosfomycin. CONCLUSION: There is an urgent need to take synergistic action to delay, as much as possible, the occurrence of CRB epidemics in West Africa.

Karbapenem dirençli Gram-negatif mikroorganizmalarda seftazidim-avibaktam duyarlılıklarının değerlendirilmesi

Aims: Carbapenem-resistant Gram-negative microorganisms are gradually increasing in hospitalized patients in intensive care units and causes increased morbidity, mortality, and cost. This study aims to investigate the susceptibility of ceftazidime-avibactam (caz-avi), which has recently started to be used for the treatment of infections caused by carbapenem-resistant (CR) Gram-negative bacteria isolated from various samples received from the intensive care unit (ICU) of our hospital.&#x0D; Methods: Carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains isolated from various clinical specimens that were sent to our laboratory between January 1st, 2021, and October 30th, 2022, were retrospectively evaluated in the study. The culture and antibiogram results of the samples were received over the laboratory information system (LIS) and evaluated using statistical analyses. Ceftazidime-avibactam susceptibility was studied using the disc diffusion method. &#x0D; Results: Ceftazidime-avibactam antibiotic susceptibility test results of 352 (69.4%) CRKP and 155 (30.6%) CRPA strains isolated from various clinical samples from the ICU of our hospital were analyzed. Of the CRKP strains, 313 (88.9%) were found to be susceptible and 39 (11.1%) were found to be resistant to ceftazidime-avibactam. Of the CRPA strains, 131 (84.5%) were found to be susceptible and 24 (15.5%) were found to be resistant.&#x0D; Conclusion: Determining the regional susceptibility of carbapenem-resistant strains isolated in our hospital to a new antimicrobial combination such as caz-avi will allow a better understanding of the spread of resistance.

EMERGENCE OF CEFTAZIDIME-AVIBACTAM RESISTANCE IN ENTERO-BACTERALES AND PSEUDOMONAS AERUGINOSA

Objective: The objective of this study is to determine the emergence of resistance to Ceftazidime-Avibactam (CAZ-AVI) by Enterobacterales and Pseudomonas aeruginosa in clinical isolates. Material and Methods: In this cross-sectional study (6-months) March-August 2022 Carbapenem resistant Enterobacterales were tested for Ceftazidime-Avibactam (30/20 µg, Oxoid Pvt Ltd) using Disk diffusion technique and enzymes were identified in resistant strains by Carbapenem Inactivation Method (mCIM, eCIM) as per CLSI M100 Guidelines 2022. Results: CAZ-AVI effectiveness has greatly decreased among Enterobacterales and P. aeruginosa isolates in recent past. Antimicrobial susceptibility testing results were interpreted using CLSI M100 document. Resistance against CAZ-AVI in Enterobacterales was found to be 80.8 % in E. coli and 72.1% in Klebsiella pneumonia isolates. This higher emergence is associated with CRE isolates majorly comprising MBLs in our country. Moreover, it has been observed that Metallo- β-lactamases mediated enzyme resistance is one of the major resistance patterns followed by serine carbapenemases. Conclusion: The high frequency of resistance 77% was observed against CAZ-AVI in CRE and in CRPA, the resistance is 80.1% respectively. In our country this tremendously increase in CAZ-AVI resistance is attributed to the existence of NDM in the region. Keywords: Carbapenem Resistant Enterobacterales (CRE), Metallo beta lactamases (MBLs), Carbapenem Resistant Pseudomonas aeruginosa (CRPA) Ceftazidime-Avibactam (CAZ-AVI), Modified Carbapenem Inactivation Method (mCIM), EDTA-modified Carbapenem Inactivation Method(eCIM), Multiple Drug Resistance (MDR)

Rectal culture could predict carbapenem-resistant organism bloodstream infection and reduce the mortality in haematological patients: A retrospective cohort study

The objective is to explore the correlation between rectal swab culture and the overall 30-d survival of hematologic patients diagnosed with carbapenem-resistant organism (CRO) bloodstream infection. A total of 434 haematological patients who were complicated with Gram-negative bacilli (GNB) bloodstream infections (BSIs) caused by Gram-negative bacteria between January 2020 and December 2021 were included in our retrospective study. Based on their drug susceptibility results, we classified patients into CRO BSIs and non-CRO BSIs cases. Through group comparison, to uncover the correlation between the positive screening of rectal swabs and reducing the mortality of CRO BSI in patients with haematological diseases. Among the 434 cases of Gram-negative bacteria bloodstream infection, 96 were identified as carbapenem-resistant bloodstream infection, which consisted of 57 cases of carbapenem-resistant Klebsiella pneumoniae (CR-KP), 19 cases of carbapenem-resistant Pseudomonas aeruginosa (CR-PA), 11 cases of carbapenem-resistant Escherichia coli (CR-CO), 5 cases of carbapenem-resistant Acinetobacter baumannii (CR-AB), and 4 cases of other Enterobacteriaceae. Before the onset of CRO bloodstream infection, rectal swab cultures were conducted on 36 patients, and the positive result rate was 75.0% (27/36), with 20 cases of CR-KP, 6 cases of CR-CO, and one case of carbapenem-resistant Enterobacter cloacae. It was observed that the rectal and blood cultures had matching outcomes in 75.0% of cases. The mortality rate within 30 d for CRO BSIs was 53.1% (51/96), while for carbapenem-resistant Enterobacteriaceae (CRE) BSIs it was 62.5% (45/72). Univariate analysis showed that 30-d mortality was significantly reduced when there were positive rectal culture results preceding bloodstream infection (P < 0.001), as well as preemptive anti-infection treatment (P < 0.001). Multivariate analysis demonstrated that preemptive adjustment to an effective antibiotic regimen, guided by positive rectal culture results, had a significant effect on decreasing 30-d mortality following CRO BSIs (P= 0.002). Furthermore, for the management of CRE BSIs, antibiotic treatments utilising ceftazidime/avibactam (CAV/AVI) may be more beneficial compared to those that use tigecycline (TGC) or polymyxin (PMB). CRO BSI, especially CRE BSI, can be life-threatening for those with haematological diseases. Utilising rectal culture can effectively identify CRO strains with high sensitivity and specificity. Adjusting antibiotic treatment based on the preemptive positive rectal culture results may significantly decrease 30-d mortality rates for haematological patients with CRO BSIs.

Evolving trends among Pseudomonas aeruginosa: a 12-year retrospective study from the United Arab Emirates.

Pseudomonas is a group of ubiquitous non-fermenting Gram-negative bacteria (NFGNB). Of the several species associated with humans, Pseudomonas aeruginosa (PA) can acclimate to diverse environments. The global frequency of PA infections is rising and is complicated by this organism's high intrinsic and acquired resistance to several clinically relevant antibiotics. Data on the epidemiology, levels, and trends of antimicrobial resistance of PA in clinical settings in the MENA/GCC region is scarce. A retrospective 12-year analysis of 56,618 non-duplicate diagnostic Pseudomonas spp. from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010-2021, collected by trained personnel and reported by participating surveillance sites to the UAE National antimicrobial resistance (AMR) Surveillance program. Data analysis was conducted with WHONET (https://whonet.org/). Among the total isolates (N = 56,618), the majority were PA (95.6%). Data on nationality revealed 44.1% were UAE nationals. Most isolates were from soft tissue (55.7%), followed by respiratory tract (26.7%). PA was more commonly found among inpatients than among outpatients, followed by ICUs. PA showed a horizontal trend for resistance to fluoroquinolones, 3rd- and 4th-generation cephalosporins, and decreasing trends of resistance for aminoglycosides and meropenem. The highest percentage of multidrug resistant (MDR) isolates was reported in 2011 at 35.6%. As an overall trend, the percentage of MDR, extensively drug-resistant (XDR), and possible pandrug-resistant (PDR) isolates generally declined over the study period. Carbapenem-resistant PA (CRPA) were associated with a higher mortality (RR: 2.7), increased admission to ICU (RR: 2.3), and increased length of stay (LOS) (12 excess inpatient days per case), as compared to carbapenem-susceptible PA (CSPA). The resistance trends in Pseudomonas species in the UAE indicated a decline in AMR and in percentages of Pseudomonas isolates with MDR and XDR profiles. The sustained Pseudomonas spp. circulation particularly in the hospital settings highlights the importance of surveillance techniques, infection control strategies, and stewardship to limit the continued dissemination. This data also shows that CRPA are associated with higher mortality, increased ICU admission rates, and a longer hospitalization, thus higher costs due to increased number of in-hospital and ICU days.

Prevalence of carbapenem resistance in Acinetobacter baumannii and Pseudomonas aeruginosa in sub-Saharan Africa: A systematic review and meta-analysis.

Carbapenems are effective drugs against bacterial pathogens and resistance to them is considered a great public health threat, especially in notorious nosocomial pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa. In this study, we aimed to determine the prevalence of carbapenem resistance in A. baumannii and P. aeruginosa infections in Sub-Saharan Africa. Databases (PubMed, Scopus, Web of Science, and African Journal Online) were systematically searched following the Preferred Reporting Items for Systematic review and meta-analysis protocols (PRISMA-P) 2020 statements for articles reporting carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) prevalence between 2012 and 2022. Pooled prevalence was determined with the random effect model and funnel plots were used to determine heterogeneity in R. A total of 47 articles were scanned for eligibility, among which 25 (14 for carbapenem-resistant A. baumannii and 11 for carbapenem-resistant P. aeruginosa) were included in the study after fulfilling the eligibility criteria. The pooled prevalence of CRPA in the present study was estimated at 8% (95% CI; 0.02-0.17; I2 = 98%; P <0.01). There was high heterogeneity (Q = 591.71, I2 = 98.9%; P<0.0001). In addition, this study's pooled prevalence of CRAB was estimated at 20% (95% CI; 0.04-0.43; I2 = 99%; P <0.01). There was high heterogeneity (Q = 1452.57, I2 = 99%; P<0.0001). Also, a funnel plot analysis of the studies showed high degree of heterogeneity. The carbapenemase genes commonly isolated from A. baumannii in this study include blaOXA23, blaOXA48, blaGES., blaNDM, blaVIM, blaOXA24, blaOXA58, blaOXA51, blaSIM-1, blaOXA40, blaOXA66, blaOXA69, blaOXA91, with blaOXA23 and blaVIM being the most common. On the other hand, blaNDM, blaVIM, blaIMP, blaOXA48, blaOXA51, blaSIM-1, blaOXA181, blaKPC, blaOXA23, blaOXA50 were the commonly isolated carbapenemase genes in P. aeruginosa, among which blaVIM and blaNDM genes were the most frequently isolated. Surveillance of drug-resistant pathogens in Sub-Saharan Africa is essential in reducing the region's disease burden. This study has shown that the region has significantly high multidrug-resistant pathogen prevalence. This is a wake-up call for policymakers to put in place measures to reduce the spread of these critical priority pathogens.

588. Ceftolozane/Tazobactam Susceptibility of Carbapenem-Resistant Pseudomonas aeruginosa and Carbapenem-Resistant Enterobacterales Isolates in a Tertiary Hospital in Korea

Abstract Background Carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are significant nosocomial pathogens that pose significant challenges in treatment due to their multidrug-resistant nature. Ceftolozane/tazobactam (C/T) is a novel antimicrobial agent that has shown promising activity against these pathogens. However, there is limited data available on its susceptibility against these resistant isolates in Korea. The aim of this study is to determine the in vitro susceptibility of C/T against CRE and CRPA isolates in a tertiary hospital in Korea. Methods Blood isolates of CRE and CRPA were collected from a tertiary hospital between September 2017 and September 2022. A carbapenemase test was performed using NG test CARBA-5. For non-carbapenemase-producing CRE and CRPA, the minimum inhibitory concentration of C/T was determined using the Etest and interpreted according to the CLSI breakpoints. Results A total of 120 blood isolates, including 55 CRE and 65 CRPA, were analyzed. Carbapenemase-producing isolates were found in 60.0% of CRE and 27.7% of CRPA samples. Among the CRE isolates, KPC (50.9%), NDM (7.3%), and OXA-48-like (1.8%) carbapenemases were identified, while NDM (21.5%), IMP (3.1%), and VIM (3.1%) were found in CRPA isolates. For the non-carbapenemase-producing isolates, the susceptible, intermediate, and resistant rates to C/T were 9.1%, 7.3%, and 23.6%, respectively, for CRE, and 67.7%, 3.1%, and 1.5%, respectively, for CRPA. Conclusion This study provides important information on the in vitro susceptibility of C/T against CRE and CRPA isolates in Korea. The findings will help guide empirical antibiotic therapy and improve patient outcomes. Further studies are needed to evaluate the clinical efficacy of C/T against these resistant pathogens in Korea. Disclosures All Authors: No reported disclosures

2076. Intestinal colonization with multidrug-resistant organisms, horizontal transmission and risk for bloodstream infection

Abstract Background The association between rectal colonization and subsequent bloodstream infections (BSI) by multidrug-resistant organisms (MDROs) remains to be clarified. We aimed to investigate the relative risk of BSI in rectal carriers of MDROs and in the case of carbapenem-resistant Enterobacteriaceae (CRE), whether BSI was due to the patient’s own colonizing strain. Methods We retrospectively included all adult inpatients hospitalized from Jan 2019 to Dec 2022, in ICUs or medical wards of 3 Greek hospitals (Athens: “Attikon” Hospital, Piraeus: Tzaneio Hospital, Thessaloniki: AHEPA Hospital), who were screened for intestinal MDRO carriage at admission and weekly. Screening was performed by selective media and immunochromatography for the carbapenemase in CRE. Patients were followed up for BSI by the same colonizing organism; relative risk (95% CI) was estimated after adjustment for ICU hospitalization and age. MDROs included CRE, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and vancomycin-resistant enterococci (VRE). The CRE-colonizers and BSI-pathogens were analyzed for carbapenemase type to identify potential similarities. Results Of 4,427 patients screened, 1,321 (29.8%) were colonized by CRE, 1,255 (28.3%) with CRAB, 252 (5.7%) with CRPA and 859 (27.9% of 3,082 patients tested) with VRE. Of those, 207 (15.7%), 247 (19.7%), 23 (9.1%) and 30 (3.5%) subsequently developed CRE-BSI, CRAB-BSI, CRPA-BSI and VRE-BSI, respectively. Intestinal CRE colonization was associated with 4-fold higher risk of subsequent CRE-BSI, after adjusted for ICU stay and age [RR (95%CI): 4.1 (3.2, 5.2)]. The respective relative risk (95%CI) for BSI in patients with colonization by CRAB, CRPA and VRE were 2.3 (1.9, 2.8), 8.2 (5.1, 13.4) and 2.1 (1.3, 3.4). To evaluate possible horizontal transmission, 286 paired CRE strains from 143 patients were analyzed; in 111 (77.6%), both colonizers and BSI pathogens belonged to the same bacterial species and carried the same carbapenemase type.Table 1:Rectal colonization with MDROs and the risk for BSI from the same pathogenTable 2:Carbapenemase types in rectal carriers of CRE who developed subsequent BSI with the same pathogen Conclusion Intestinal colonization by MDROs was associated with increased risk of BSI by the colonizing bacteria. Clinicians should evaluate this information for empiric treatment, while genome-wide data are needed to substantiate horizontal transmission. Disclosures All Authors: No reported disclosures

2163. Prevalence and geographic distribution of mutations in TonB-dependent receptors in the Prospective Observational Pseudomonas aeruginosa (PA) Study

Abstract Background Cefiderocol (FDC) is a last line treatment for carbapenem-resistant Pseudomonas aeruginosa (CR-PA). FDC retains activity against CR-PA by inhibition of penicillin-binding proteins facilitated by active uptake of drug via TonB-dependent receptors (TBDR). Prior, we have shown an association between mutations in TBDR genes and loss of FDC susceptibility, particularly in association with changes at the PA-derived cephalosporinase (PDC/AmpC) active site. Here, we outline geographic variation and prevalence of TBDR mutations in the Prospective Observational Pseudomonas (POP) study.Figure 1.SNP frequency in the pirR, pirS, pirA, and piuA/piuD genes across geographic location.Figure 2.Genotypic variation of PirRS and PiuA/D genes in the 972 P. aeruginosa isolates of the POP cohort. Black versus gray differentiates presence of either PiuA versus PiuD homologous proteins. Color legend corresponds to presence of TBDR gene variants/SNPs per gene pirR, pirS, pirA, piuA/piuD, and ampC. Methods The genomes of 972 CR-PA isolates collected across 10 countries in North America, South America, Asia, and Oceania were screened for single nucleotide polymorphisms (SNP) resulting in missense, insertion/deletion (indel), frameshift, and early stop codon mutations in the TBDR genes pirR, pirS, pirA, piuA/piuD, and ampC using PAO1 as a reference. SNPs were defined as variant mutations occurring in ≤10% of isolates. A core genome maximum likelihood phylogenetic tree was used to assess distribution and prevalence of genotypic variants. Neighbor-joining trees of the variants in each gene were used to analyze clusters across lineages. Results Across all regions except Oceania, SNPs were most frequently seen in pirS and pirA (Fig 1). Gene variants comprised from 8% up to 50% of each geographic population. On phylogenetic mapping, isolates within the same lineage tended to have clustering of shared mutations across the TBDR genes pirS, pirR, and pirA, and the majority of piuA/piuD mutations clustered within two distinct lineages (Fig 2). Major mutations, including indel, frameshift, and early stop codon mutations occurred in 16 isolates (1.6%), predominantly in isolates from the United States (n=14). Variations in PDC were frequently observed, with 57 different variants across 35.8% of the population. Seven of the PDC variants (n=10 isolates) have been associated with decreased susceptibility to ceftolozane/tazobactam, but these variants did not co-occur with major TBDR mutations. Conclusion TBDR mutations occur in PA isolates worldwide. Mutations previously associated with reduced susceptibility to FDC occurred most frequently in isolates from the United States. Disclosures Michael J. Satlin, MD, AbbVie: IDMC member|Biomerieux: Grant/Research Support|Merck: Grant/Research Support|Shionogi: Advisor/Consultant|SNIPRBiome: Grant/Research Support William R. Miller, M.D., Merck: Grant/Research Support|UpToDate: Honoraria

728. Potential Reservoirs for Additional Carbapenemase Gene Spread: Detection of Carbapenemase Genes in non-Pseudomonas aeruginosa and non-Acinetobacter baumannii isolates

Abstract Background Public Health Laboratories (PHL) across 50 U.S. states, several cities and Puerto Rico participate in CDC’s Antimicrobial Resistance Laboratory Network (AR Lab Network), to test clinical isolates of carbapenem-resistant Pseudomonas aeruginosa (CRPA) and Acinetobacter baumannii (CRAB) for the presence of targeted carbapenemase (CP) genes. PHLs have submitted reports of these targeted genes in CR non-aeruginosa Pseudomonas (CR-NAP) and non-baumannii Acinetobacter (CR-NBA) isolates. Here we describe the ad-hoc detection of targeted CP genes in CR-NAP and CR-NBA species tested by the Network. Methods Clinical laboratories submitted CR isolates to PHLs for organism identification. Isolates were deemed suspected CR-NAP and CR-NAB when a PHL ruled out aeruginosa or baumannii, respectively, but their MALDI ToF MS database prevented further speciation. PHLs used real-time polymerase chain reaction or whole genome sequencing to detect the presence of targeted CP genes: blaKPC,blaNDM,blaOXA-48-like,blaIMP, and blaVIM in Pseudomonas and Acinetobacter, and blaOXA-23-like,blaOXA-24/40-like, and blaOXA-58-like in Acinetobacter. Results During 2017–2021, the AR Lab Network tested 56,092 CR-Pseudomonas isolates, 71 of which were CR-NAP; P. putida (n=15; 21%), P. fluorescens (12; 17%) P. otitidis (5; 7%), P. monteilii (3; 4%), 1 (1%) each of P. koreensis and P. mosselii, and 34 (48%) other suspected CR-NAP. Three (4%) of the 71 CR-NAP isolates tested carried a targeted CP gene: 1 P. fluorescens with blaIMP, 1 P. putida with blaVIM, and 1 P. Japonica with blaKPC. Of 13,624 CR-Acinetobacter isolates tested, 25 (&amp;lt; 1%) were CR-NBA; A. pitti (10; 40%), A. radioresistens (6; 24%), A. variabilis (2; 8%), 1 (4%) each of A. berezinaiae, A. lwoffii, and A. ursingii, and 4 (16%) other suspected CR-NBA. The A. variabilis isolates each harbored both blaNDM and blaOXA-58-like genes. Conclusion Although CR-NAP and CR-NBA isolates are not solicited by the Network, some of these species are submitted for characterization. Our findings suggest these other species do harbor some targeted CP genes and may represent unmonitored reservoirs for CP gene spread in the U.S. An expansion of testing to include these species in the AR Lab Network may improve our ability to slow the spread of antimicrobial resistance. Disclosures All Authors: No reported disclosures