Carbapenem-resistant Pseudomonas Aeruginosa Research Articles

In-vitro activities of essential antimicrobial agents including aztreonam/avibactam, eravacycline, colistin and other comparators against carbapenem-resistant bacteria with different carbapenemase genes: A multi-centre study in China, 2021

Carbapenem-resistant bacteria (CRB), including carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Enterobacterales (CRE), pose a considerable threat to public health in China. Eravacycline, aztreonam/avibactam and colistin are important antimicrobial agents for the treatment of serious infections caused by CRB. This study aimed to evaluate the prevalence of CRB strains, and the susceptibility of commonly used clinical antimicrobial agents against strains with different carbapenemase genes. In total, 7194 gram-negative bacteria strains were collected from different regions of China, and 924 carbapenem-resistant strains were identified. All strains were from confirmed infections. Antimicrobial susceptibility testing, covering 21 antimicrobial agents including aztreonam/avibactam, eravacycline, colistin and other comparators, was performed using the broth microdilution method. Carbapenemase genes (blaKPC, blaNDM, blaOXA, blaIMP and blaVIM) were screened using polymerase chain reaction amplification and sequence analysis. All statistical analyses were performed using Statistical Package for the Social Sciences Version 23.0. The isolation rates of CRE, CRAB and CRPA were 6.31% (332/5265), 62.95% (440/699) and 15.20% (152/1000), respectively. The predominant carbapenemase in carbapenem-resistant Escherichia coli (CRECO) was NDM, while in carbapenem-resistant Klebsiella pneumoniae (CRKP), it was KPC. All CRAB produced OXA-23, and 85.52% of CRPA did not produce any of the following carbapenemases: NDM, KPC, VIM, IMP and OXA. Aztreonam/avibactam, colistin and eravacycline exhibited high antimicrobial activity against different species producing various carbapenemases. Compared with ceftazidime/avibactam, aztreonam/avibactam demonstrated superior antimicrobial activity, particularly pronounced in CRECO and strains producing metallo-beta-lactamases. In comparisons between tigecycline and eravacycline, the latter maintained higher antimicrobial activity across different species. Antimicrobial agents exhibited varying levels of activity against strains with different resistance mechanisms. Using aztreonam/avibactam, eravacycline and colistin to treat infections caused by CRB offers significant advantages. These findings will guide clinical practice and optimize antimicrobial administration.

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.

Cefepime-Taniborbactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination.

Taniborbactam (formerly known as VNRX-5133) is a novel bicyclic boronate β-lactamase inhibitor of serine β-lactamases (SBLs) [Ambler classes A, C, and D] and metallo-β-lactamases (MBLs) [Ambler class B], including NDM and VIM, but not IMP. Cefepime-taniborbactam is active in vitro against most isolates of carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA), including both carbapenemase-producing and carbapenemase-non-producing CRE and CRPA, as well as against multidrug-resistant (MDR), ceftazidime-avibactam-resistant, meropenem-vaborbactam-resistant, and ceftolozane-tazobactam-resistant Enterobacterales and P. aeruginosa. The addition of taniborbactam to cefepime resulted in a > 64-fold reduction in MIC90 compared with cefepime alone for a 2018-2021 global collection of > 13,000 clinical isolates of Enterobacterales. In the same study, against > 4600 P. aeruginosa, a fourfold MIC reduction was observed with cefepime-taniborbactam, compared with cefepime alone. Whole genome sequencing studies have shown that resistance towards cefepime-taniborbactam in Enterobacterales arises due to the presence of multiple resistance mechanisms, often in concert, including production of IMP, PBP3 alterations, permeability (porin) defects, and upregulation of efflux pumps. In P. aeruginosa, elevated cefepime-taniborbactam MICs are also associated with the presence of multiple, concurrent mechanisms, most frequently IMP, PBP3 mutations, and upregulation of efflux pumps, as well as AmpC (PDC) overexpression. The pharmacokinetics of taniborbactam are dose proportional, follow a linear model, and do not appear to be affected when combined with cefepime. Taniborbactam's approximate volume of distribution (Vd) at steady state is 20L and the approximate elimination half-life (t½) is 2.3 h, which are similar to cefepime. Furthermore, like cefepime, taniborbactam is primarily cleared renally, and clearance corresponds with renal function. Pharmacodynamic studies (in vitro and in vivo) have reported that cefepime-taniborbactam has bactericidal activity against various β-lactamase-producing Gram-negative bacilli that are not susceptible to cefepime alone. It has been reported that antimicrobial activity best correlated with taniborbactam exposure (area under the curve). A phase III clinical trial showed that cefepime-taniborbactam (2g/0.5g administered as an intravenous infusion over 2h) was superior to meropenem for the treatment of complicated urinary tract infection (cUTI), including acute pyelonephritis, caused by Enterobacterales species and P. aeruginosa while demonstrating similar safety compared with meropenem. The safety and tolerability of taniborbactam and cefepime-taniborbactam has been reported in one pharmacokinetic trial, and in two pharmacokinetic trials and one phase III clinical trial, respectively. Cefepime-taniborbactam appears to be well tolerated in both healthy subjects and patients. Headache and gastrointestinal upset are the most common drug-related adverse effects associated with cefepime-taniborbactam use. Cefepime-taniborbactam will likely have a role in the treatment of infections proven or suspected to be caused by MDR Gram-negative bacteria, including Enterobacterales and P. aeruginosa. In particular, it may be useful in the treatment of infections caused by isolates that harbor an MBL (NDM, VIM) enzyme, although further clinical data are needed. Additional safety and efficacy studies may support indications for cefepime-taniborbactam beyond cUTI.

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.

Phenotypic detection of carbapenem-resistant Enterobacterales and carbapenem-resistant Pseudomonas aeruginosa by mCIM and eCIM and their ceftazidime-avibactam with aztreonam synergy profile in a tertiary care hospital in Eastern India

Background: Worldwide, the emergence of carbapenem-resistant enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global concern to public health as they are responsible for several serious infections that lead to elevated treatment expenses, prolonged hospitalization, and a higher mortality rate. Aims and Objectives: To detect Carbapenem resistance in Enterobacterales and Pseudomonas aeruginosa by phenotypic methods such as mCIM and eCIM. To determine synergism between Ceftazidime-Avibactum and Aztreonum in metallobetalactamase producing isolates. Materials and Methods: Total 217 isolates including enterobacterales and Pseudomonas aeruginosa from patient’s samples such as urine, pus, blood, wound swab, sputum, and ET tube were processed as per standard protocol during the study period from July 2023 to January 2024 at Calcutta National Medical College, Kolkata. Results: Resistance to carbapenem was observed in 110/217 (50.69%) isolates. Phenotypically, 99/110 (90%) produced metallo-β-lactamase and 11/110 (10%) produced serine carbapenemase by mCIM with eCIM test. MBLs producing organisms were most commonly isolated from blood culture samples. On an average, 76% of the MBL producing isolates shows positive synergy result to the combination of CZA+AT by disk elution method. Conclusion: eCIM and mCIM test was performed for identification of carbapenemase producing CRE and CRPA, which causes serious infection in patients with no definitive treatment. The combination of CZA-AT is a potential treatment option to manage CRE and CRPA-associated infections.

Rapid detection of imipenem/relebactam susceptibility/resistance in Pseudomonas aeruginosa

ObjectivesImipenem-relebactam (IPR) has been reported to exhibit a good activity against non-metallo-ß-lactamase carbapenem-resistant Pseudomonas aeruginosa (CRPA), and the rapid detection of susceptibility/resistance to this new therapeutic alternative may be crucial. Therefore, the Rapid IPR Pseudomonas NP test was developed to quickly identify IPR susceptibility/resistance among multidrug-resistant P. aeruginosa. MethodsThe principle of the Rapid IPR Pseudomonas NP test is based on visually detecting glucose metabolization by observing (or not) a color change from yellow to red or orange of the red phenol pH indicator in the presence of imipenem at 2 mg/L and relebactam at 4 mg/L A total of 80 clinical Pseudomonas aeruginosa isolates were analyzed, among which 42 isolates were IPR resistant according to EUCAST guidelines (MICs, susceptible ≤2 mg/L, resistant >2 mg/L). Results obtained with the Rapid IPR Pseudomonas NP test were compared with the reference broth microdilution (BMD). ResultsThe sensitivity, specificity and accuracy of the test were found to be 100 %, 89.5 % and 95 %, respectively, using the BMD reference method as a comparator. Moreover, five out of the IPR-susceptible isolates (n = 38) exhibiting an MIC of IPR close to the breakpoint (MIC = 1 mg/L, n = 2; MIC = 2 mg/L, n = 3) yielded to a major error result, namely a positive result with the rapid IPR Pseudomonas NP test (resistance). By contrast, all IPR-resistant isolates (n = 42) were all correctly categorized. ConclusionsThe Rapid IPR Pseudomonas NP test is sensitive, specific, and easy to perform and interpret. Therefore, it is suitable for implementation in routine clinical laboratories.

Not all carbapenem-resistant Pseudomonas aeruginosa strains are alike: tailoring antibiotic therapy based on resistance mechanisms.

To correlate the resistance mechanisms and the susceptibility to new antibiotics in Pseudomonas aeruginosa . Definition of antibiotic resistance in Pseudomonas aeruginosa is still debated. Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) are used but which of them better correlate with the risk of mortality remains debated. Mechanisms underlying resistance in Pseudomonas aeruginosa are complex and may be combined, resulting in unpredictable phenotype and cross-resistance. Thus, not all CRPA are alike and tailoring antibiotic therapy on resistance mechanisms is challenging. Current guidelines recommend the use of new antipseudomonal agents for CRPA or DTR-PA infections but they don't provide specific information on how tailoring antibiotic therapy on underlying resistance mechanisms. This review may be useful to understand which mechanisms are involved in CRPA and may have practical implications helping clinicians to select an appropriate antibiotic regimen. Several antibiotics are now available for Pseudomonas aeruginosa but their rational use is important to avoid development of future resistance. The knowledge of local epidemiology and most common resistance mechanisms may guide empirical therapy, but targeted antibiotic therapy should be re-evaluated as soon as susceptibility testing profile is available and selected according to Pseudomonas aeruginosa phenotype.

Distribution and Drug Resistance Characteristics of Pathogenic Bacteria in the Elderly Population in China in 2021

To study the distribution and drug resistance characteristics of pathogenic bacteria in the elderly population of China by collecting and analyzing the standardized case data on the pathogens of infections in elderly patients, and to facilitate the establishment of a standardized layered surveillance system for pathogenic bacteria in China. We collected the case data of elderly patients (≥65 years old) from 62 sentinel hospitals across the country in 2021. Then, we statistically analyzed the data by patient age, their geographical region, the distribution of pathogenic bacteria, and the drug resistance characteristics of main pathogens. A total of 3468 cases from across the country were included in the study. The top three sources of patients were the intensive care unit (13.2%), the department of respiratory medicine (11.2%), and the department of general surgery (8.4%). The top three types of specimens were urine (25.5%), sputum (20.6%), and blood (18.7%). A total of 3468 strains of pathogens were isolated, among which, 78.9% were gram-negative bacteria and 21.1% were gram-positive bacteria. The top five types of bacteria were Escherichia coli (20.9%), Klebsiella pneumoniae (18.3%), Pseudomonas aeruginosa (11.2%), Staphylococcus aureus (9.0%), and Acinetobacter baumannii (7.0%). The isolation rates of common important drug-resistant bacteria were 38.0% for methicillin-resistant Staphylococcus aureus (MRSA), 68.7% for carbapenem-resistant Acinetobacter baumannii (CRAB), and 38.2% for carbapenem-resistant Pseudomonas aeruginosa (CRPA), 20.1% for carbapenem-resistant Klebsiella pneumoniae (CRKP), 5.2% for carbapenem-resistant Escherichia coli (CRECO), and 2.1% for vancomycin-resistant Enterococcus (VRE). There were differences in the isolation rates of CRAB and CRKP in clinical care in the elderly population in seven geographical regions of China (P<0.05). Klebsiella pneumoniae is the most important pathogen in the elderly population ≥85 years old, and the isolation rates of CRKP showed significant differences in different age groups (P<0.05). There are significant differences in the drug resistance of pathogenic bacteria in the elderly populations of different regions and age groups in China. Therefore, monitoring the distribution and drug resistance of pathogenic bacteria in the elderly population and formulating targeted treatment plans according to the characteristics of the specific regions and age groups are of great significance to the improvement in the treatment outcomes and prognosis of the elderly population.

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.

Risk factors and molecular epidemiology of intestinal colonization by carbapenem-resistant Gram-negative bacteria in patients with hematological diseases: a multicenter case‒control study.

Patients with hematological diseases are considered to be at high risk for intestinal colonization by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the epidemiological data regarding risk factors and molecular characteristics of intestinal colonized CR-GNB isolates in this population are insufficient in China. A multicenter case‒control study involving 4,641 adult patients with hematological diseases from 92 hospitals across China was conducted. Following culture of collected rectal swabs, mass spectrometry and antimicrobial susceptibility tests were performed to identify GNB species and CR phenotype. Risk factors were assessed through retrospective clinical information. Whole-genome sequencing was used to analyze the molecular characteristics of CR-GNB isolates. This trial is registered with ClinicalTrials.gov as NCT05002582. Our results demonstrated that among 4,641 adult patients, 10.8% had intestinal colonization by CR-GNB. Of these, 8.1% were colonized by carbapenem-resistant Enterobacterales (CRE), 2.6% were colonized by carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 0.3% were colonized by carbapenem-resistant Acinetobacter baumannii (CRAB). The risk factors for CR-GNB colonization include male gender, acute leukemia, hematopoietic stem cell transplantation, β-lactam antibiotic usage, and the presence of non-perianal infections within 1 week. Compared with CRPA-colonized patients, patients using carbapenems were more likely to be colonized with CRE. NDM was the predominant carbapenemase in colonized CRE. This study revealed a high CR-GNB intestinal colonization rate among adult patients with hematological diseases in China, with CRE being the predominant one. Notably, a significant proportion of CRE exhibited metallo-β-lactamase production, indicating a concerning trend. These findings emphasize the importance of active screening for CR-GNB colonization in patients with hematological diseases.IMPORTANCECarbapenem-resistant Gram-negative bacteria (CR-GNB) has emerged as a significant threat to public health. Patients with hematological diseases are at high risk of CR-GNB infections due to their immunosuppressed state. CR-GNB colonization is an independent risk factor for subsequent infection. Understanding the risk factors and molecular characteristics of CR-GNB associated with intestinal colonization in patients with hematological diseases is crucial for empirical treatment, particularly in patients with febrile neutropenia. However, the epidemiology data are still insufficient, and our study aims to determine the intestinal colonization rate of CR-GNB, identify colonization risk factors, and analyze the molecular characteristics of colonized CR-GNB isolates.

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.

Application of a Model Using Prior Healthcare Information to Predict Multidrug-Resistant Organism (MDRO) Carriage

Background: Early identification of patients colonized with MDROs can help healthcare facilities improve infection control and treatment. We evaluated whether a model previously validated to predict carbapenem-resistant Enterobacterales (CRE) carriage on hospital admission (area under the curve [AUC]=0.86, Lin et al. OFID 2019) would generalize to predict a patient’s likelihood of CRE and non-CRE MDRO colonization at the time of medical intensive care unit (MICU) admission. Methods: We analyzed data collected previously in a retrospective observational cohort study of patients admitted to Rush University Medical Center’s MICU from 1/2017-1/2018 and screened within the first two days for rectal MDRO colonization. Organisms of interest included CRE, carbapenem-resistant Pseudomonas aeruginosa (CRPA), vancomycin-resistant enterococci (VRE), and third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization at admission was determined by routine clinical screening. Each patient’s first MICU admission during the study period was linked to Illinois’ hospital discharge database and assigned a CRE colonization risk probability using the existing model. Model covariates were age, and during the prior 365 days, number of short-term acute care hospitalizations (STACH) and mean STACH length of stay, number of long-term acute care hospitalizations (LTACH) and mean LTACH length of stay, prior hospital admission with an ICD-10 diagnosis code indicating bacterial infection, and current admission to LTACH. Predictive value of the model was evaluated by receiver operating characteristic (ROC) curves. Results: We analyzed 1237 MICU admissions. MDRO admission prevalence is shown in the Table. The model performed well to predict carriage of healthcare-associated MDROs, including CRE, CRPA, composite CR-MDROs (CRE &amp; CRPA), and VRE. However, the model performed poorly for MDROs with known community reservoirs, including 3GCR-E and MRSA (Table). In general, MDRO admission prevalence increased in parallel with predicted CRE colonization risk (Figure). The number needed to screen (NNS) to detect one healthcare-associated MDRO carrier was inversely related to the CRE colonization risk score. For example, NNS in the total cohort compared to those with CRE risk score of &gt;0.5% was: CRE 111 vs 32 patients, CRPA 333 vs 42 patients, composite CR-MDRO 83 vs 18 patients, and VRE 12 vs 4 patients. However, higher CRE risk score cutoff was inversely related to screening sensitivity. Conclusion: A prediction model using prior healthcare exposure information successfully discriminated patients likely to harbor healthcare-associated MDROs upon MICU admission. Prediction scores generated by a public-health accessible database could be used to target screening/isolation or enact protective measures for high-risk patients.

Variability of MDRO Reporting Across Tennessee Microbiology Laboratories

Background: Identification and timely reporting of multi-drug resistant organisms (MDROs) drives efficacy of infection prevention efforts. Data on MDRO reporting timeliness and inter-facility variability are limited. Facility-dependent variability in MDRO reporting across Tennessee was examined to identify opportunities for MDRO surveillance improvement. Methods: Data for reported Tennessee MDROs including carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and Candida auris, were obtained from the southeast regional Antibiotic Resistance Laboratory Network (ARLN) from 2018-2022, excluding screening and colonization specimens. Variance in days accrued from specimen collection to ARLN receipt was analyzed using one-way analysis of variance (ANOVA) with Tukey’s test (SAS 9.4). Facilities were categorized as fast (1-10 days), slow (11-20 days), or delayed (21-100 days) reporters. Results: There were 9,569 MDRO isolates reported. CRPA was reported faster than other MDROs (p &lt; 0.001), while specimens from West Tennessee compared to other regions (p &lt; 0.001) (Figure) and blood cultures compared to other specimens were reported more slowly (p &lt; 0.001) (Table). There was no difference in reporting times for facilities using on-site microbiology laboratories versus reference laboratories (P = 0.062). Conclusion: MDRO reporting times varied across Tennessee by region, specimen, and organism. Future work to elucidate drivers of variability will consist of surveys and focused interviews with laboratory personnel to identify shared and unique barriers and opportunities for improvement.

Multidrug-resistant Organism and Antibiotic Sensitivity Patterns, before, during, and after the Coronavirus Disease 2019 Pandemic in the Dr. M. Djamil Central General Hospital, Padang, Indonesia

Abstract Background: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the prevalence and antibiotic sensitivity patterns of multidrug-resistant organisms (MDROs). This study aimed to investigate the MDRO incidence and antibiotic sensitivity trends before, during, and after the COVID-19 pandemic at Dr. M. Djamil Central General Hospital in Padang, Indonesia. Methods: A total of 5539 clinical samples were collected and analyzed using the VITEK2 system to identify MDRO types. The study periods were defined as before (prepandemic), during, and after the COVID-19 pandemic. Results: The incidence of MDROs increased significantly during and after the pandemic, with 1.64 and 1.42 times higher rates compared to the prepandemic period, respectively. Specific MDRO types that showed increased prevalence included Escherichia coli-producing extended-spectrum β-lactamases (Eco-ESBL), carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant E. coli (CREC), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), and methicillin-resistant Staphylococcus aureus (MRSA). Antibiotic sensitivity decreased during and after the pandemic for K. pneumoniae-producing ESBL s, CRKP, and CRAB, as well as for CREC and CRPA during the pandemic. In contrast, antibiotic sensitivity increased for Eco-ESBL and MRSA during and after the pandemic. Conclusion: The COVID-19 pandemic has significantly contributed to the increased incidence of MDROs and decreased antibiotic effectiveness against these pathogens in the study setting. These findings highlight the need for comprehensive infection control measures and antimicrobial stewardship programs to mitigate the impact of the pandemic on MDRO epidemiology.

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 extensively drug-resistant Pseudomonas aeruginosa ST1971 from a patient in China hospitalized for severe pneumonia

The emergence and outbreak of carbapenem-resistant Pseudomonas aeruginosa are a major global public threat. In this study we aimed to characterize the genome of drug-resistant and virulent genes in an extremely drug-resistant (XDR) P. aeruginosa strain to understand its antimicrobial resistance trends and pathogenicity. An XDR P. aeruginosa strain was isolated in China from a patient with severe pneumonia. Antimicrobial susceptibility testing, genome sequencing, and phylogenetic analysis were performed. Predictions were fulfilled using curated bioinformatics tools. Assembly of the strain (CRPA190) comprised 76 contigs with a total length of 7 009 318 bp. CRPA190 belongs to sequence type 1971 (ST1971) 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 harbours 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 ST1971 P. aeruginosa strain that 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.

Whole-genome sequencing, multilocus sequence typing, and resistance mechanism of the carbapenem-resistant Pseudomonas aeruginosa in China

Pseudomonas aeruginosa is a significant pathogen responsible for severe multisite infections with high morbidity and mortality rates. This study analyzed carbapenem-resistant Pseudomonas aeruginosa (CRPA) at a tertiary hospital in Shandong, China, using whole-genome sequencing (WGS). The objective was to explore the mechanisms and molecular characteristics of carbapenem resistance. A retrospective analysis of 91 isolates from January 2022 to March 2023 was performed, which included strain identification and antimicrobial susceptibility testing. WGS was utilized to determine the genome sequences of these CRPA strains, and the species were precisely identified using average nucleotide identification (ANI), with further analysis on multilocus sequence typing and strain relatedness. Some strains were found to carry the ampD and oprD genes, while only a few harbored carbapenemase genes or related genes. Notably, all strains possessed the mexA, mexE, and mexX genes. The major lineage identified was ST244, followed by ST235. The study revealed a diverse array of carbapenem resistance mechanisms among hospital isolates, differing from previous studies in mainland China. It highlighted that carbapenem resistance is not due to a single mechanism but rather a combination of enzyme-mediated resistance, AmpC overexpression, OprD dysfunction, and efflux pump overexpression. This research provides valuable insights into the evolutionary mechanisms and molecular features of CRPA resistance in this region, aiding in the national prevention and control of CRPA, and offering references for targeting and developing new drugs.

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.

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.