Carbapenem-resistant Pseudomonas Aeruginosa Isolates Research Articles

Investigation of Carbapenemase-Producing Pseudomonas aeruginosa at Secondary Care Hospital in Bolu, Turkey.

The global increase in carbapenem resistance poses a significant public health threat due to the potential emergence of multidrug-resistant pathogens and limited treatment options. To learn more about this issue and offer potential solutions, we conducted a study of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections in a secondary care hospital setting. The study utilized the carbapenem inactivation method (CIM), a leading phenotypic analysis, to determine carbapenemase activity in 63 CRPA isolates. Additionally, polymerase chain reaction (PCR) analysis was conducted to test for the presence of carbapenemase genes associated with the production or expression of various carbapenemase enzymes, including blaKPC, blaNDM, blaVIM, blaOXA-48, blaIMP, and blaGES. Arbitrary primed PCR (AP-PCR) was performed to assess the clonal relationship between different isolates. The isolates were also classified as either health care-associated infections or community-acquired infections, and their clonal relationship and gene positivity were evaluated. A total of 63 CRPA samples underwent evaluation, with 14 isolates determined to be carbapenemase producers via CIM tests. PCR assays revealed that 14 isolates carried carbapenemase genes, with 9 carrying blaNDM, 2 carrying blaGES, 2 carrying blaVIM, and 1 carrying blaIMP. CRPA exhibited a 22% prevalence of carbapenemase genes, of which 64% were attributed to the NDM gene responsible for multidrug resistance. AP-PCR revealed high clonal diversity among the isolates. Molecular epidemiological evaluation also showed no dominant outbreak strain among PA isolates. This study presents significant data on the prevalence and distribution of carbapenemase-producing CRPA strains isolated from secondary health care facilities. Typically, the literature focuses on resistance rates in tertiary care public hospitals. These findings may aid in understanding resistance and its mechanisms, as well as in developing effective treatment strategies and infection control measures.

Study on molecular epidemiology of carbapenem resistant Pseudomonas aeruginosa and related genes of quorum sensing signal system

This study aims to investigate the drug resistance, regulation mechanism of quorum sensing system, expression of related virulence genes, and epidemiological characteristics of carbapenem-resistant Pseudomonas aeruginosa (CRPA).In this study, Polymerase chain reaction amplification was performed to evaluate carbapenemase genes, OprD2 gene, quorum sensing system, and related virulence genes. Bacterial genotypes were analyzed using multilocus sequence typing and evolutionary analysis was conducted based on the goeBURST algorithm. The results demonstrated that a total of 47 CRPA strains were collected in this study, primarily from respiratory specimens in the ICU. Drug sensitivity results showed that the resistance rates of the 47 CRPA strains were highest for imipenem (97.87 %). The loss of OprD2 may be the main factor contributing to carbapenem resistance in our hospital's CRPA strains.All isolates tested positive for the quorum sensing system genes lasI and rhlI/R, and the virulence gene lasB was detected in all isolates, while the algD gene was detected in 19.15 % of the isolates. Among the 47 strains, 6 were untypeable, and the 41 strains with 28 different sequence types were clustered into three clonal complexes (BG1, BG2, and BG3).In conclusion, the CRPA isolates from our hospital exhibit high genetic diversity, with the deletion of the OprD2 gene possibly being the primary determinant of carbapenem resistance in Pseudomonas aeruginosa.Moreover, Las and RhI systems play a key role in quorum sensing signal system. Further research and development of drugs targeting quorum sensing signaling system may provide valuable guidance for the treatment of CRPA.

Molecular Epidemiology of Carbapenemase-Producing Pseudomonas aeruginosa: An Iranian Referral Hospital-Based Study.

In recent years, there has been a significant increase in infections caused by carbapenemase-producing strains, with carbapenem-resistant Pseudomonas aeruginosa (CRPA) emerging as a priority pathogen according to the World Health Organization. This study aimed to evaluate the molecular epidemiology of CRPA isolated from patients referred to Children's Medical Center in Tehran, Iran. P. aeruginosa isolates collected from different children's wards were screened for common carbapenem-resistant genes by polymerase chain reaction (PCR). Genetic relatedness between isolates was assessed by pulsed-field gel electrophoresis (PFGE). The study included 133 participants, with 50% being male, and revealed a median age of 2 years (interquartile range: 6 months to 6 years). Carbapenem resistance was detected in 15% of cases (n = 20), with CRPA isolates predominantly found in the emergency ward (60%). The median age of patients with CRPA was significantly higher than those with carbapenem-susceptible P. aeruginosa (6 years vs. 1 year). PCR analysis revealed metallo-β-lactamase production in 45% of CRPA isolates (n = 9), with blaNDM being the most prevalent gene. PFGE analysis of the CRPA isolates identified three clusters (Cluster I, II, and III). Cluster I, comprising 65% of all isolates (n = 13), was predominantly found in the emergency ward. Notably, blaNDM-producing strains were prevalent in the emergency ward. Our study highlights the significant prevalence of CRPA in the emergency ward of our hospital and underscores the importance of targeted surveillance and infection control measures to curb its spread within health care settings.

Antimicrobial susceptibility profile of ceftolozane/tazobactam, ceftazidime/avibactam and cefiderocol against carbapenem-resistant Pseudomonas aeruginosa clinical isolates from Türkiye.

Carbapenem resistant Pseudomonas aeruginosa (CR-PA) is escalating worldwide and leaves clinicians few therapeutic options in recent years, β-lactam/β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of P. aeruginosa infection and have shown potent activity against isolates defined as carbapenem resistant. The aim of this study was to determine the phenotypic profile of these agents against CR-PA in the emerging setting of carbapenemases. CR-PA clinical isolates were collected from three teaching hospitals in different geographical regions between January 2017-December 2021. All isolates were subjected to phenotypic carbapenemase testing using modified carbapenem inactivation method. MICs were determined by reference broth microdilution and evaluated according to EUCAST standards, while genotypic profiling was determined using PCR methods. 244 CR-PA sourced most frequently from the respiratory tract (32.2%), blood (20.4%) and urine (17.5%) were evaluated. Of all isolates, 32 (13.1%) were phenotypically and 38 (15.6%) were genotypically defined as carbapenemase-positive. The most common carbapenemase was GES (63.1%), followed by VIM (15.8%). The MIC50/90(S%) of ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol in all CR-PA isolates were 4 and 32 (80%), 1 and > 64 (69%) and 0.25 and 1mg/L (96%), respectively. Cefiderocol was also the most active agent in carbapenemase-positive isolates (90%). While ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against CR-PA devoid of carbapenemases, cefiderocol provided potent in vitro activity irrespective of carbapenemase production. When considering the potential clinical utility of newer agents against CR-PA, regional variations in carbapenemase prevalence must be considered.

Genomic insights into NDM-1-producing Pseudomonas aeruginosa: Current status in a Bulgarian tertiary hospital and on the Balkans.

The present study aimed to explore the genomic characteristics of eight New Delhi metallo-β-lactamase-1 (NDM-1)-producing carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates from a Bulgarian tertiary hospital (2021-2023) in comparison to blaNDM-1-positive strains originating from the Balkans. Antimicrobial susceptibility testing, phenotypic assays for carbapenemase activity, PCR screening, whole-genome sequencing (WGS), and phylogenomic analysis were performed. Seven of the CRPA isolates investigated (Minimum inhibitory concentration values of imipenem and meropenem >32 mg L-1) were also resistant to piperacillin-tazobactam, ceftazidime, ceftazidime-avibactam, cefepime, ceftolozane-tazobactam, amikacin, tobramycin, ciprofloxacin, and levofloxacin, but were susceptible to colistin (0.5-2 mg L-1) and cefiderocol (0.25-1 mg L-1). The P. aeruginosa Pae57 isolate (designated Pae57) remained susceptible to aminoglycosides as well. WGS uncovered the co-existence of blaNDM-1 and blaGES-1. The isolates belonged to the ST654 high-risk clone, except for Pae57 (ST611). Alignment against reference sequences revealed the presence of a Tn21 transposon harboring bleMBL-blaNDM-1-ISAba125. It was similar to that found in the P. aeruginosa ST654 NDM1_1 strain (GCA_020404785.1) from Serbia. Phylogenomic analysis of our isolates indicated that seven of them (ST654) differed from each other in no more than 44 single-nucleotide polymorphisms (SNPs). Pae57 (ST611) was strikingly different (>21,700 SNPs) compared to all Balkan strains. In conclusion, to our knowledge this is the first report of blaNDM-1-positive P. aeruginosa ST611 isolation, which indicates the transmission dynamics of this determinant between high-risk and potentially high-risk P. aeruginosa clones. Obtained results unveil the dissemination of clonally related NDM-1-producing P. aeruginosa strains in the monitored hospital for approximately a 2-year period.

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.

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.

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.

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

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

Evaluation and analysis of multidrug resistance- and hypervirulence-associated genes in carbapenem-resistant Pseudomonas aeruginosa strains among children in an area of China for five consecutive years.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a growing threat. It is urgent to investigate the multidrug resistance and high virulence of CRPA to provide a basis for infection control and rational use of antibiotics. A retrospective study of 56 nonduplicated CRPA isolates was conducted. CRPA mainly came from the intensive care unit (ICU) and was mostly isolated from sputum samples. The carbapenem resistance rates of P. aeruginosa were 21.37% (2016), 10.62, 5.88, 10 and 13.87% from 2016 to 2020, respectively. Carbapenem-resistant enzymes and aminoglycoside-modifying enzyme-encoding genes were detected in all isolates, and extended-spectrum β-lactamase and cephalosporin enzyme-encoding genes were present in 96.43 and 80.38% of isolates, respectively. The detection rate of OprM showed a statistically significant difference (p < 0.05) between the ICU and other wards. Genes related to biofilms, membrane channel proteins, I integrons and efflux systems were detected in all isolates, with detection rates greater than 90%. CRPA was strongly virulent, and over 80% of isolates carried hypervirulence-associated genes (exoU, exoS, exoT, and exoY). The drug resistance rates of cefepime and piperacillin/tazobactam showed a statistically significant difference (p < 0.05) between strains with exoU (+) and exoU (-) (p < 0.05). Notably, out of the 7 individuals who died, 4 had extensively drug-resistant P. aeruginosa (57.14%). The detection rates of various resistance and virulence genes were high, and the coexistence phenomenon was serious. In clinical practice, antibiotics should be used reasonably based on different drug resistance genes to ensure the rationality and safety of patient medication.

Molecular epidemiology and antibiotic resistance of Pseudomonas aeruginosa isolated from blood in a hospital in Shandong Province from 2014 to 2021

Objective: To identify the antibiotic resistance, virulence genes, and sequence types of Pseudomonas aeruginosa (P. aeruginosa) strains isolated from blood. Methods: From November 2014 to December 2021, a total of 94 nonrepetitive P. aeruginosa isolates were obtained from blood samples of patients at the First Affiliated Hospital of Shandong First Medical University in Shandong Province, China. The bacteria were identified using matrix-assisted laser desorption ionization time of flight mass spectrometry. Antibiotic resistance of the P. aeruginosa isolates was detected using Vitek 2 Compact system. Polymerase chain reaction (PCR) was conducted for the 18 virulence genes, and multi locus sequence typing (MLST) was performed to identify the sequence types of the P. aeruginosa strains. The resistance rates and distributions of virulence genes between carbapenem resistant pseudomonas aeruginosa (CRPA) and carbapenem susceptible pseudomonas aeruginosa (CSPA) isolates were compared using the Chi-square test. Results: Among 94 P. aeruginosa isolates, 19 (20.2%) isolates were found to be multidrug resistant (MDR) bacteria, of which 17 were CRPA isolates and 2 were CSPA isolates. All strains contained more than 10 virulence genes. Except for exoU gene, the detection rate of other genes was above 83%. MLST analysis revealed a total of 66 different STs, including 59 existing STs and 7 novel STs. Among them, ST244 (n=11, 11.7%) and ST270 (n=7, 7.4%) were the dominant STs. Although these two types of isolates harbored the same virulence genes, the resistance rates to carbapenem were different. 54.5% (6/11) ST244 isolates were CRPA but all 7 ST270 isolates were CSPA. Conclusion: Although the resistance rates of P. aeruginosa strains isolated from blood were at a low level, some MDR and CRPA isolates were detected. As the high virulence gene detection rates and genetic diversity were found for P. aeruginosa strains isolated from blood, close attention should be paid to avoid transmission and outbreaks.

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. National Institutes of Health.

Prevalence and susceptibility profile of carbapenem-resistant pseudomonas aeruginosa (CRPA) at Dr. Soetomo Public Hospital, Surabaya, from January to December 2021

Introduction: Pseudomonas aeruginosa is a pathogen that frequently causes healthcare-associated infections (HAI), which has also been associated with high mortality and morbidity rates. Carbapenems have been widely utilized as empiric therapy for P. aeruginosa infections since these organisms have intrinsic resistance to various antibiotics. Therefore, the high rate of CRPA infection became the reason for conducting this study to determine the prevalence and susceptibility pattern of CRPA in Dr. Soetomo Public Hospital, Surabaya, from January to December 2021. Method: The researcher employed descriptive observational study from secondary data with the first isolate sample of P. aeruginosa per specimen per patient that has been identified by the BD Phoenix™ automated identification and susceptibility testing system from specimens of urine, blood, sterile fluid, pus, tissue, and sputum that are phenotypically resistant to meropenem or imipenem antibiotics, examined at the Clinical Microbiology Unit of Dr. Soetomo Public Hospital, Surabaya, from January to December 2021. Result: Of the total P. aeruginosa isolates, 149 CRPA isolates were obtained. The researcher conveyed that the majority of the samples were male (59.1%); the most comorbid cases were diabetes mellitus with complications (22.4%) found in the intensive care unit (40.3%); the majority of specimens were from the respiratory tract (43%); the highest antibiotic susceptibility was amikacin (62.4%); the prevalence of CRPA in Dr. Soetomo Public Hospital, Surabaya, from January to December 2021 reached 21.25%. Conclusion: In this study, CRPA isolates showed the highest sensitivity to amikacin, and the highest distribution of CRPA events was found in the intensive care unit.

Carbapenem-resistant Pseudomonas aeruginosa: an assessment of frequency of isolation from ICU versus non-ICU, phenotypic and genotypic profiles in a multinational population of hospitalized patients

BackgroundHistorically, multi-drug resistant organisms have been associated with the ICU setting. The present study sought to define the frequency of isolation from ICU versus non-ICU, phenotypic and genotypic profiles of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) from a global cohort.MethodsMulticenter surveillance study (17 centers from 12 countries) including 672 CR-PA isolates from 2019 to 2021. Phenotypic carbapenemase testing was assessed. Genotypic carbapenemase testing was conducted (CarbaR and CarbaR NxG) to detect β-lactamases. Broth microdilution MICs were established for ceftazidime, cefepime, ceftolozane/tazobactam, and ceftazidime/avibactam.Results59% of CR-PA were isolated from patients outside the ICU. The most common source in ICU and non-ICU patients was respiratory (55% and 30%, respectively). In the ICU, 35% of isolates were phenotypically carbapenemase-positive versus 29% for non-ICU. VIM was the most common carbapenemase (54% and 44%, respectively) followed by GES (27% and 28%, respectively). Susceptibility to ceftazidime or cefepime were relatively low in ICU (39% and 41% of isolates, respectively) and non-ICU (47% and 52% of isolates, respectively). Ceftolozane/tazobactam and ceftazidime/avibactam were more active with 56% and 66% of isolates susceptible in the ICU while 65% and 76% in non-ICU, respectively. When carbapenemase-negative, 86% and 88% of ICU isolates were susceptible to ceftolozane/tazobactam and ceftazidime/avibactam. Similarly, in the carbapenemase-negative, non-ICU isolates 88% and 92% of isolates were susceptible, respectively.ConclusionAlthough multidrug resistant pathogens are often regarded as a challenge in the ICU population, the majority of CR-PA were isolated from non-ICU patients. Implementing phenotypic/genotypic testing will assist in guiding treatment. Carbapenem-resistance in P. aeruginosa should be regarded as a surrogate for MDR and this phenotype is increasingly prevalent outside the ICU.

Risk factors for mortality in hospitalized patients infected with carbapenem-resistant Pseudomonas aeruginosa in Iran.

Mortality due to carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection has increased worldwide in recent years. The risk factors associated with hospital settings in Iran and the role of strain resistance mechanisms in many studies are unclear. A retrospective study was conducted on consecutive non-repetitive patients with CRPA infections isolated from seven major hospitals from northwest of Iran. We evaluated different risk factors and characteristics of bacteria for the death or survival of patients. In this study, 116 CRPA isolates were obtained from patients admitted to seven hospitals. Forty-one (35.3%) patients were enrolled in the study of mortality risk factors. Significant risk factors associated with mortality included the site of infection, hospitalization in different wards, the use of invasive devices, and the type of carbapenem resistance mechanisms. ICU admission, the use of mechanical ventilation and chest tube and infection with pandrug-resistant strains were the most important factors in increasing mortality due to CRPA infection. These results suggested that the clinicians should emphasize the proper use of antibiotic and invasive procedures.

Susceptibility results discrepancy analysis between NHSN Antibiotic Resistance (AR) Option and laboratory instrument data

Background: The NHSN Antibiotic Resistance (AR) Option can serve as a useful tool for tracking antibiotic-resistant infections and can aid in the development of inpatient antibiograms. We recently described the frequency of antibiotic suppression in NHSN AR Option data. In this analysis, we describe the effects of suppression on practical uses of the NHSN AR Option, specifically selected agent antibiogram development, and detection of reportable conditions. Methods: Antibiotic susceptibility data were collected from the NHSN AR Option and commercial automated antimicrobial susceptibility testing instruments (cASTI) from 3 hospital networks. Data were obtained from January 1, 2017, to December 31, 2018. The clinical susceptibility data for third-generation cephalosporins and carbapenems against carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii were included. Susceptibility results were defined as suppressed when susceptibility results were observed from the laboratory instrument but not from NHSN data. For the overall percentage susceptibility estimation, isolates with &lt;30 susceptibility results were excluded. Percentage susceptibility of NHSN results were compared to their counterparts from cASTI. Results: Of the 852 matched isolates in the primary analysis, 804 had at least 1 suppressed result. Of the 804 isolates, 16.9% were P. aeruginosa, 67.3% by E. coli, and 11.1% by Klebsiella spp. The following pathogen–drug combinations had no difference observed in the percentage susceptible between the 2 systems: ceftazidime tested against P. aeruginosa, ceftriaxone tested against Klebsiella spp, ertapenem tested against Klebsiella spp, imipenem tested against E. coli and P. aeruginosa, and meropenem tested against P. aeruginosa. Significant differences were observed for the following drugs tested against E. coli: ceftazidime (11.1%), cefotaxime (8.6%), and ceftriaxone (8.3%). In the NHSN AR Option, the following isolates showed suppressed results related to their phenotypic case definition: 17 (3%) CRE isolates, 7 (28%) carbapenem-resistant Acinetobacter baumannii (CRAB) isolates, 511 (93.2%) extended spectrum β-lactamase (ESBL) isolates, and 94 (66.7%) carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates. Conclusions: For select isolates, notably E. coli, we observed a large difference in the percentage of susceptible isolates reported into the NHSN AR Option compared to the cASTI data. This difference significantly limits the ability of the AR Option to create valid antibiograms for select pathogen–drug combinations. Moreover, significant numbers of CRAB, ESBL, and CRPA isolates would not be identified from NHSN AR Option because of suppression. This finding warrants the need for antimicrobial stewardship teams to regularly assess the impact of selective reporting in identifying pathogens of public health importance.Funding: NoneDisclosures: None

Isolation and characterisation of carbapenem-resistant Pseudomonas aeruginosa from hospital environments in tertiary care hospitals in Dhaka, Bangladesh

Increasing evidence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection in healthcare facilities poses an alarming threat to public health. There is little evidence on the occurrence of this organism in Bangladeshi hospitals. We collected 117 environmental swab samples from two tertiary care hospitals in Dhaka, Bangladesh and tested for Pseudomonas species by nonselective enrichment of swabs followed by plating on Cetrimide agar. We confirmed the isolates as P. aeruginosa by API 20NE test and polymerase chain reaction Polymerase Chain Reaction (PCR) for 16S rRNA gene. We analysed P. aeruginosa isolates for susceptibility against 15 clinically important antibiotics and tested the carbapenem-resistant isolates for metallo β-lactamase (MBL). All CRPA isolates were characterised for carbapenem-resistant genes, virulence genes and biofilm formation genes. Of 117 swab samples, 82 (70%) were tested positive for P. aeruginosa. All P. aeruginosa isolates were multidrug-resistant, and 39% (n=32) of isolates were CRPA. Around 56% (n=18) of CRPA were MBL-producing; 22% (n=7) of isolates were positive for carbapenemase gene blaNDM followed by 16% (n=5) for blaVIM and 13% (n=4) for blaIMP. Sequencing identified these genes as blaNDM-1, blaIMP-13, blaVIM-2 variants. Based on optical density values, 94% (n=30) of CRPA isolates were capable of producing biofilms. All CRPA isolates (n=32) were positive for at least 1 of 6 biofilm-associated genes and 4 of 12 virulence genes tested in the study. Hospital environments in Bangladesh are contaminated with highly virulent CRPA, which might be a potential source of hospital-acquired infections, accentuating the need for strengthening hospital infection control programs.

Optimizing Doses of Ceftolozane/Tazobactam as Monotherapy or in Combination with Amikacin to Treat Carbapenem-Resistant Pseudomonas aeruginosa.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a hospital-acquired pathogen with a high mortality rate and limited treatment options. We investigated the activity of ceftolozane/tazobactam (C/T) and its synergistic effects with amikacin to extend the range of optimal therapeutic choices with appropriate doses. The E-test method is used to determine in vitro activity. The optimal dosing regimens to achieve a probability of target attainment (PTA) and a cumulative fraction of response (CFR) of ≥90% were simulated using the Monte Carlo method. Of the 66 CRPA isolates, the rate of susceptibility to C/T was 86.36%, with an MIC50 and an MIC90 of 0.75 and 24 µg/mL, respectively. Synergistic and additive effects between C/T and amikacin were observed in 24 (40%) and 18 (30%) of 60 CRPA isolates, respectively. The extended infusion of C/T regimens achieved a ≥90% PTA of 75% and a 100% fT > MIC at C/T MICs of 4 and 2 µg/mL, respectively. Only the combination of either a short or prolonged C/T infusion with a loading dose of amikacin of 20–25 mg/kg, followed by 15–20 mg/kg/day amikacin dosage, achieved ≥90% CFR. The C/T infusion, combined with currently recommended amikacin dose regimens, should be considered to manage CRPA infections.

Antibiotic resistance, biofilm production ability and genetic diversity of carbapenem-resistant Pseudomonas aeruginosa strains isolated from nosocomial infections in southwestern Iran.

BackgroundThis study was aimed to evaluate the antibiotic resistance, biofilm formation, and genetic diversity of carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains isolated from four types of nosocomial infections (NIs) including urinary tract infection (UTI), ventilator-associated pneumonia (VAP), surgical site infection (SSI), and bloodstream infection (BSI).Methods and resultsIn total, 115 isolates of NIs-causing P. aeruginosa were collected from NIs. Antibiotic susceptibility testing (AST) was performed using disk diffusion method and minimum inhibitory concentrations. Biofilm formation was tested on 96-well polystyrene microtiter plates (MTP). CRPA isolates were genotyped using multiple-locus variable number of tandem repeat analysis (MLVA). The most resistance and susceptibility rates were observed to amikacin (70.6%) and colistin (96.1%), respectively. Colistin and meropenem were the most active antimicrobial agents in VAP, SSI, and BSI. While, colistin and cefepime were the most active in UTIs. In total, 52.2% (n = 60/115) of P. aeruginosa isolates were carbapenem resistant, of which 95.0%, 55.0%, and 5.0% were multidrug-resistant, extensively drug-resistant, and pandrug-resistant, respectively. There was a significant association between resistance to carbapenem and resistance to other antibiotics except for piperacillin/tazobactam. The biofilm production of CRPA isolates was 95.0%, of which 23.3% were strong biofilm producers. Based on MLVA, there were 34 different types of CRPA isolates classified into three main clusters and 5 sub clusters.ConclusionThe association of CRPA with other antibiotic resistance, the high rates of biofilm production, and the high genetic diversity of the isolates may be a warning of the need for a careful surveillance program.