Carbapenem-resistant Pseudomonas Aeruginosa Isolates Research Articles

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.

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.

Prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa and association with clinical outcomes in patients: an observational study.

To describe the prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and evaluate the association with clinical outcomes. Colistin heteroresistance was evaluated in CRPA isolates collected from patients without cystic fibrosis in Atlanta, Georgia, USA using two definitions: HR1, growth at 4 and 8 mg/L of colistin at a frequency ≥1 × 10-6 the main population; and HR2, growth at a colistin concentration ≥8× the MIC of the main population at a frequency ≥1 × 10-7. A modified population analysis profile (mPAP) technique was compared with reference PAP for detecting heteroresistance. For adults hospitalized at the time of or within 1 week of CRPA culture, multivariable logistic regression estimated the association between heteroresistance and 90 day mortality. Of 143 colistin-susceptible CRPA isolates, 8 (6%) met the HR1 definition and 37 (26%) met the HR2 definition. Compared with the reference PAP, mPAP had a sensitivity and specificity of 50% and 100% for HR1 and 32% and 99% for HR2. Of 82 hospitalized patients, 45 (56%) were male and the median age was 63 years (IQR 49-73). Heteroresistance was not associated with 90 day mortality using HR1 (0% in heteroresistant versus 22% in non-heteroresistant group; P = 0.6) or HR2 (12% in heteroresistant versus 24% in non-heteroresistant group; P = 0.4; adjusted OR 0.8; 95% CI 0.2-3.4). Colistin heteroresistance was identified in up to 26% of patients with CRPA in our sample, although the prevalence varied depending on the definition. We did not observe an apparent association between colistin heteroresistance and 90 day mortality.

1256. Clinical Response by Minimum Inhibitory Concentrations in Carbapenem-Resistant Pseudomonas aeruginosa Infections under Cefiderocol Compassionate Use Program

BackgroundCefiderocol (CFDC) has been developed for the treatment of serious infections caused by drug-resistant aerobic Gram-negative pathogens, including carbapenem-resistant (CR) Pseudomonas aeruginosa (CRPA). The current CFDC susceptibility breakpoints for P. aeruginosa differ between US Food and Drug Administration (FDA) and Clinical and Laboratory Standards Institute (CLSI) (Table). Data characterizing the impact of CFDC minimum inhibitory concentrations (MICs) on the clinical responses of patients treated with CFDC for CRPA are sparse.MethodsWe reviewed patients treated with compassionate-use CFDC (2 g, q8h or renally adjusted dosages) for infections caused by CRPA with no alternative treatment options. CFDC minimum inhibitory concentrations (MICs) were evaluated according to CLSI guidelines in iron-depleted cation-adjusted Müller–Hinton broth for available CRPA isolates. We then assessed physician-reported clinical responses to CFDC therapy and stratified results by CFDC MIC. ResultsThere were 71 patients overall with CRPA treated with CFDC. Treatment duration ranged from 1 to 132 days. For the subset of 33 patients for whom CFDC MIC values were available, the most common infection sites were the respiratory tract (n=15), blood (n=12), and urinary tract (n=4). Patients could have had an infection at ≥1 sites and in other locations. CFDC MIC range was ≤0.03– >64 µg/mL. The modal MIC value was 2 µg/mL (n=13; Table). CRPA isolates were susceptible to CFDC in 13/33 patients (39.4%) based on the FDA breakpoint (MIC ≤1 µg/mL) and in 31/33 patients (93.9%) based on the CLSI breakpoint (MIC ≤4 µg/mL). Clinical response was reported for 15/18 patients (83.3%) who had infections with CFDC MICs of 2–4 µg/mL, organisms that are considered susceptible by CLSI but not by FDA breakpoints (Table). Clinical response was reported in 6/13 patients (46.1%) with infections with CFDC MIC ≤1 µg/mL and in 1 of 2 patients (50.0%) with CFDC MIC ≥8 µg/mL (Table). 21 (63.6%) patients survived to Day 28 and there were no trends in mortality by CFDC MIC. ConclusionClinical response rate was high for CRPA infections with CFDC MICs of 2–4 µg/mL, supporting the higher CLSI susceptibility breakpoint.Disclosures Michael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Research Grant or Support)BioFire Diagnostics (Research Grant or Support)Merck (Research Grant or Support)Shionogi (Consultant) David Fam, PharmD, Shionogi (Employee) Roger Echols, MD, Shionogi (Consultant) Christopher Longshaw, PhD, Shionogi (Employee) Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Yoshinori Yamano, PhD, Shionogi (Employee)

The Prevalence of blaNDM-1 in Clinical Isolates of Carbapenem-resistant Pseudomonas Aeruginosa: A Systematic Review

Background: Pseudomonas aeruginosa (P. aeruginosa) is a gram negative bacteria that is known to cause nosocomial infections. Carbapenem is used to treat the damage caused by P. aeruginosa, however it is becoming resistant to carbapenems because of the production of β-lactamases. The objectives of the study were to systematically review the prevalence of blaNDM-1 in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and to review and analyze the clinical sources as well as the antibiotic resistance profile of CRPA carrying blaNDM-1. Methods: The researchers systematically searched PubMed, ScienceDirect, and Google Scholar. Studies that met the inclusion criteria were included in the review. In assessing the methodological quality of the included studies, the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data and the JBI Critical Appraisal Checklist for Case Reports were used. Results: A total of nine studies were included in which eight were cross-sectional studies and one was a case report. The highest prevalence rate reported was 54.55% in blaNDM-1 positive CRPA isolates among the cross-sectional studies. The three most frequent sources of clinical isolates of CRPA carrying blaNDM-1 include urine, wound discharge, and tissue, among the included studies. Lastly, this review showed that among the included studies, CRPA isolates carrying blaNDM-1 were most resistant to ceftazidime and gentamicin. Conclusions: There is varying prevalence of blaNDM-1 in CRPA in different countries. Urine, wound discharge, and tissue specimens being the most frequent sources of CRPA isolates carrying blaNDM-1 poses a challenge that must be given attention by the infection control committee, thus the need for proper handling and processing of clinical specimens. Resistance to ceftazidime and gentamicin among the CRPA isolates carrying blaNDM-1highlights the growing challenge of successfully treating infections caused by this bacteria. This challenge reminds us of the importance and purpose of antibiotic stewardship that emphasizes the improvement of proper antibiotic prescription by the physicians and proper antibiotic use by the patients that can help in preventing harm and antibiotic resistance. Doi: 10.28991/SciMedJ-2021-0304-9 Full Text: PDF

Biofilm Production and Antimicrobial Resistance of Clinical and Food Isolates of Pseudomonas spp.

Due to its ubiquity, ability to form biofilms, and acquire resistance mechanisms,Pseudomonasspp. become one of the major challenge for healthcare settings and food industry.The aims of this study were to assess the biofilm production ofPseudomonasspp. recovered from clinical and food specimens and to evaluate their antimicrobial resistance. A total of 108 isolates ofPseudomonasspp. were included in the study, 48 being clinical isolates recovered from patients admitted to four tertiary care hospitals throughout Serbia and 60 were isolated from thebulk tank milk samplesand meat carcasses. Biofilm production was analyzed bymicrotiter plate assay. Antimicrobial susceptibility was evaluated by disk diffusion method according to the CLSI guidelines, while class A and B β-lactamases encoding genes were screened by PCR. A total of 98 (90.7%) strains were biofilm producers (moderate producer: 68, 69.4%; strong producer: 8, 8.2%). Although a slightly higher percentage of clinical isolates were biofilm producers (91.7%) compared to food isolates (90%), statistical significance was not observed (P > 0.05). The proportion of carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates was significantly higher among clinical (42%) isolates compared to food (1.7%)Pseudomonads(P < 0.05).The blaPER andblaNDM genes were found in ESBL (seven isolates) and MBL (two isolates) production, respectively. In the present study, we confirmed that biofilm formation was highly present in both clinical and food Pseudomonas spp. irrespective of the prior existence of resistance genes. Additionally, clinical settings pose a major reservoir of MDR Pseudomonas spp. and especially CRPA isolates.

VIM-CRPA in West Texas: Developing a Regional Multidrug-Resistant Organism Containment Strategy for a Novel Bug

Background: The Texas Department of State Health Services Healthcare Safety (HCS) Investigation Team began investigating a cluster of positive carbapenem-resistant Pseudomonas aeruginosa (CRPA) results in August 2017. These CRPA isolates contained the novel carbapenemase Verona integron-encoded metallo-β-lactamase (VIM). This cluster became an outbreak that spanned &gt;2 years and involved multiple healthcare facilities in and around northern Texas. In response to positive results, infection control assessments were conducted, which exposed common infection control gaps including inadequate hand hygiene performance, environmental cleaning issues, and poor communication during interfacility patient transfers. As part of the ongoing investigation efforts, a regional containment strategy was developed to prevent the spread of multidrug-resistant organisms. Methods: Beginning in October 2018, the HCS Investigation Team made site visits to participating facilities every 6 months to provide targeted infection control support and hand hygiene performance and environmental cleaning observations. An initial kick-off meeting was held in February 2019 for facilities to begin collaboration on the containment strategy. This strategy became known as BOOT, an acronym meaning: Being prompt in response to positive cases, Obtaining isolates for testing, Optimizing infection prevention, and Transferring patients using a designated form. An interfacility transfer form to reduce the risk of transmission of multidrug-resistant organisms when patients are transferred between healthcare facilities was developed by a work group that consisted of the local health department, the Public Health Region healthcare-associated infections epidemiologist, and multiple healthcare facilities. Results: Facilities have increased communication with other facilities and with the health departments since the implementation of the BOOT strategy. The local health department is contacted when facilities do not receive a transfer form, and follow-up is initiated to ensure appropriate understanding and compliance. Facility handwashing rates and environmental cleaning results have improved with each visit, and access to alcohol-based hand sanitizing dispensers has increased in select facilities. Conclusions: The regional containment strategy is dynamic and ongoing, and changes are implemented as obstacles are encountered. Implementation has resulted in a successful decrease of positive VIM results in the local area by ∼50% since the first half of 2019. This program has led to greater collaboration among healthcare facilities, health departments, and a neighboring state. This investigation and its products have been used as a model for the implementation of containment strategies in other regions of Texas. The HCS Investigation Team hopes to create and implement an interfacility transfer form that can be used in healthcare facilities statewide.Funding: NoneDisclosures: None