Risk factors for Pseudomonas aeruginosa isolation in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Pseudomonas aeruginosa (PA) isolation in patients with chronic obstructive pulmonary disease (COPD) has been associated with a poor prognosis. This meta-analysis aimed to determine significant risk factors for PA isolation among patients with COPD. METHODS: A systematic literature retrieval from PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) was conducted, including studies from January 2003 to September 2024. Case-control and cohort studies exploring the risk factors for PA isolation in patients with COPD were included in this analysis. A random-effects model was applied to estimate the pooled adjusted odds ratio (paOR) or hazard ratio (paHR) with the corresponding 95% confidence intervals (CI). RESULTS: Thirteen eligible studies with a total of 25,802 participants were included in this meta-analysis. Prior systemic steroid therapy (paOR: 2.67; 95% CI: 1.29-5.53; P = 0.008), previous antibiotic treatment (paOR: 2.83; 95% CI: 1.14-6.97; P = 0.02), high "Body mass index, airflow Obstruction, Dyspnea, Exercise capacity" (BODE) index (paOR: 4.13; 95% CI: 1.67-10.23; P = 0.002), 6-min walking distance (6MWD) < 250 m (paOR: 4.27; 95% CI: 2.59-7.01; P < 0.001), COPD assessment test (CAT) score > 20 points (paOR: 2.49; 95% CI: 1.46-4.23; P = 0.001), hypoproteinemia (paOR: 2.62; 95%CI: 1.32-5.19; P = 0.006), hospitalizations in the previous year (paOR: 3.74; 95%CI: 1.22-11.49; P = 0.021), Bronchiectasis (paOR = 4.81; 95% CI: 3.66-6.33; P < 0.001) and prior PA isolation (paOR: 16.39; 95% CI: 7.65-35.10; P < 0.001) were associated with PA isolation in patients with COPD. CONCLUSIONS: Our study identified nine risk factors associated with an increased risk of PA isolation in COPD patients. These findings are significant for the early identification of patients at risk for PA isolation, which might contribute to reducing mortality and improving clinical outcomes.

Molecular investigation of LasA, LasB, and PIV genes in clinical isolates of Pseudomonas aeruginosa in Mazandaran Province, North Iran.

AIMS: Pseudomonasaeruginosa plays an important role in hospital infections caused by several virulence factors, such as elastase and proteases. This study aimed to evaluate the prevalence of LasA, LasB, and PIV genes, encoding these enzymes, in clinical isolates of P.aeruginosa.

Multi-drug resistant Pseudomonas aeruginosa isolation is an independent risk factor for recurrent hemoptysis after bronchial artery embolization in patients with idiopathic bronchiectasis: a retrospective cohort study.

BACKGROUND: Currently, there is a lack of research on multi-drug resistant Pseudomonas aeruginosa (MDR-PA) isolation in bronchiectasis-related hemoptysis. The aim of this study to analyze the risk factors for recurrent hemoptysis following bronchial artery embolization (BAE) and compare the recurrent hemoptysis-free rates between MDR-PA, non-MDR-PA, and non-PA isolation. METHODS: A retrospective study was performed of patients diagnosed with idiopathic bronchiectasis-related recurrent hemoptysis who underwent BAE at an university-affiliated hospital. Patients were categorized based on PA susceptibility tests into non-PA, non-MDR-PA, and MDR-PA groups. Univariate and multivariate Cox regression were conducted to identify independent risk factors for recurrent hemoptysis. The Kaplan-Meier curves was conducted to compare recurrent hemoptysis-free rates after BAE for non-PA, non-MDR-PA, and MDR-PA. RESULTS: A total of 432 patients were included. 181 (41.90%) patients experienced recurrent hemoptysis during a median follow-up period of 25 months. MDR-PA isolation (adjusted hazard ratio (aHR) 2.120; 95% confidence interval (CI) [1.249, 3.597], p = 0.005) was identified as an independent risk factor for recurrent hemoptysis. Antibiotic treatment (aHR 0.666; 95% CI [0.476, 0.932], p = 0.018) reduced the risk of recurrent hemoptysis. The cumulative recurrent hemoptysis-free rates for non-PA, non-MDR-PA, and MDR-PA were as follows: at 3 months, 88.96%, 88.24%, and 75.86%, respectively; at 1 year, 73.13%, 69.10%, and 51.72%; and at 3 years, 61.91%, 51.69%, and 41.10% (p = 0.034). CONCLUSION: MDR-PA isolation was an independent risk factor of recurrent hemoptysis post-BAE. Reducing the occurrence of MDR-PA may effectively decrease the recurrence rates of hemoptysis.

Critical resistance to carbapenem and aminoglycosides in Pseudomonas aeruginosa: spread of blaNDM/16S methylase armA harboring isolates with intrinsic resistance mechanisms in Kerman, Iran.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is one of the main Gram-negative bacterium causes of infections in hospital settings, and the spread of them is a significant challenge to public health. METHODS: A total of 30 non-duplicate isolates of CRPA were collected. Antibacterial susceptibility of isolates to antibiotic agents, AmpC ß-lactamase production, and biofilm formation were determined. Minimum biofilm inhibitory concentrations (MBIC) of isolates to cefepime (FEP), imipenem (IPM), ceftazidime (CAZ), and meropenem (MEM) were evaluated with/without cloxacillin (CLX). The carbapenemase and 16 S rRNA methylase genes were identified by PCR, and the transcription levels of oprD, ampC, and mexA genes were determined by quantitative real-time PCR (qPCR). ERIC-PCR was used to detect genetic relationships among isolates. RESULTS: All isolates were multidrug resistant (MDR) and strong biofilm producers. The resistance genes including blaNDM, blaIMP, blaVIM, blaSIM, blaGES, and armA were detected in 21 (70%), 6 (20%), 3 (10%), 2 (6.6%), 1 (3.3%), and 17 (56.6%) of the isolates, respectively. CLX at 500 and 1000 µg/mL significantly reduced the level of MIC to MEM, IPM, CAZ, and FEP, also at 2000 µg/mL significantly reduced the level of MBIC to MEM, IPM, CAZ, and FEP. In all isolates, the transcription levels of oprD were significantly downregulated as well as significantly increased for ampC and mexA. ERIC-PCR typing results divided 30 isolates into four clusters A to D. CONCLUSION: In this study, we reported the spread of different clones of CRPA harboring co-existence of various carbapenemase genes with armA 16 S rRNA methylase for the first time in Kerman, Iran. Also, our isolates had several mechanisms of resistance to carbapenems as well as ability biofilm formation along with resistance to aminoglycosides, the further spread of which could cause serious challenges in our hospital settings. Therefore, serious monitoring is necessary to reduce their prevalence.

Metallo-ß-lactamase-producing Pseudomonas aeruginosa Isolates from Two Tertiary Care Centres in a District of Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Pseudomonas aeruginosa isolates producing metallo-ß-lactamase have caused nosocomial outbreaks, severe infections, and ineffective carbapenem therapy worldwide since 1991. Due to their prevalence, hospital infection control techniques are difficult. This study aimed to find out the prevalence of metallo-ß-lactamase among P. aeruginosa isolates from two tertiary care hospitals in Kathmandu. METHODS: A descriptive cross-sectional study was conducted at the Department of Microbiology and Department of Pathology of two tertiary care centres in Kathmandu from 7 December 2021 to 6 April 2023, after receiving ethical approval from the Ethical Review Board. Isolated strains were identified and tested for antibiotic susceptibility by modified Kirby-Bauer Methods. Metallo-ß-lactamase presence was confirmed using an imipenem-imipenem/ ethylenediaminetetraacetic acid disc. A convenience sampling method was used. The point estimate was calculated at 95% Confidence Interval. RESULTS: Among 255, Pseudomanas aeruginosa isolates, the distribution of metallo-ß-lactamase-producing Pseudomanas aeruginosa was 103 (40.39%) (34.32-46.69 at 95% Confidence Interval). Multidrug resistance categories included multidrug resistance 74 (71.80%), extensively drug resistance 32 (31.10%), P. aeruginosa difficult-to-treat 16 (15.53%) and carbapenem-resistant P. aeruginosa was determined to be 82 (79.60%). CONCLUSIONS: The study found a high prevalence of metallo-ß-lactamase-producing Pseudomanas aeruginosa isolates, requiring early identification, infection control measures, and an all-inclusive antimicrobial therapy protocol to reduce their spread in medical settings.

Tn4661-mediated transfer of bla CTX-M-15 from Klebsiella michiganensis to an outbreak clone of Pseudomonas aeruginosa.

Carriage of CTX-M-type extended-spectrum ß-lactamase (ESBL) is rare in Pseudomonas aeruginosa. During routine surveillance of an endemic ST-621 P. aeruginosa at a large hospital, isolate MRSN 100690 carrying bla CTX-M-15 was cultured from a patient (P2). This was the first detection of this ESBL in the endemic ST-621 lineage. All 1 488 bacterial isolates collected from the same facility in the 12 months prior to the incidence of 100 690 were screened for the presence of bla CTX-M-15. A set of 183 isolates was identified, in which corresponding patient metadata was evaluated for spatiotemporal overlaps with P2. The resulting three isolates, along with 100 690, were long-read sequenced using the Oxford Nanopore MinION platform to determine a potential donor of bla CTX-M-15. The screen revealed a single Klebsiella michiganensis isolate, MRSN 895358, which carried an IncA/C2 plasmid harbouring bla CTX-M-15. Notably, the patient harbouring 895358, P1, occupied the same hospital room as P2 9 months prior. Genomic alignment revealed that both isolates shared an identical 80.8 kb region containing the IncA/C2 plasmid replicon and bla CTX-M-15. This region was plasmid bound in 895 358, but chromosomally bound in 100 690 due to Tn4661-mediated transposition. ESBL bla CTX-M-15 was acquired and subsequently integrated into the chromosome of a ST-621 P. aeruginosa, likely initiated by plasmid transfer from a K. michiganensis strain.

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.

Occurrence of chlorine-resistant Pseudomonas aeruginosa in hospital water systems: threat of waterborne infections for patients.

BACKGROUND: Several healthcare-associated infection outbreaks have been caused by waterborne Pseudomonas aeruginosa exhibiting its ability to colonize water systems and resist conventional chlorine treatment. This study aims to investigate the occurrence of Pseudomonas aeruginosa in hospital drinking water systems and the antimicrobial resistance profiles (antibiotic and chlorine resistance) of isolated strains. METHODS: We investigated the presence of Pseudomonas aeruginosa in water and biofilms developed in nine hospital water systems (n = 192) using culture-based and molecular methods. We further assessed the survival of isolated strains after exposure to 0.5 and 1.5 ppm concentrations of chlorine. The profile of antibiotic resistance and presence of antibiotic resistance genes in isolated strains were also investigated. RESULTS: Using direct PCR method, Pseudomonas aeruginosa was detected in 22% (21/96) of water and 28% (27/96) of biofilm samples. However, culturable Pseudomonas aeruginosa was isolated from 14 samples. Most of P. aeruginosa isolates (86%) were resistant to at least one antibiotic (mainly ß-lactams), with 50% demonstrating multidrug resistance. Moreover, three isolates harbored intI1 gene and two isolates contained blaOXA-24,blaOXA-48, and blaOXA-58| genes. Experiments with chlorine disinfection revealed that all tested Pseudomonas aeruginosa strains were resistant to a 0.5 ppm concentration. However, when exposed to a 1.5 ppm concentration of chlorine for 30 min, 60% of the strains were eliminated. Interestingly, all chlorine-resistant bacteria that survived at 30-minute exposure to 1.5 ppm chlorine were found to harbor the intI1 gene. CONCLUSIONS: The detection of antimicrobial resistant Pseudomonas aeruginosa in hospital water systems raises concerns about the potential for infections among hospitalized patients. The implementation of advanced mitigation measures and targeted disinfection methods should be considered to tackle the evolving challenges within hospital water systems.

Antimicrobial resistance profile of Pseudomonas aeruginosa clinical isolates from healthcare-associated infections in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Antimicrobial-resistant (AMR) bacterial infection is a significant global threat to the healthcare systems. Pseudomonas aeruginosa, the leading infectious agent in the healthcare setting is now one of the major threats due to AMR. A comprehensive understanding of the magnitude of AMR, particularly highly public health important pathogens such as P. aeruginosa, is necessary for the management of infections based on local information. OBJECTIVE: This systematic review and meta-analysis aimed to determine the country-wide AMR of P. aeruginosa. METHODS: Systematic searches were performed to retrieve articles from PubMed, Scopus, Web of Science, ScienceDirect electronic databases, Google Scholar search engine, and repository registrars from 2015 to 31st December 2023. Twenty-three studies that provided important data on AMR in P. aeruginosa were systematically reviewed and analyzed to determine the country-wide magnitude of P. aeruginosa AMR profile from healthcare-associated infections. AMR of P. aeruginosa to 10 different antibiotics were extracted separately into Microsoft Excel and analyzed using STATA 17.0. Cohen's kappa was computed to determine the agreement between reviewers, the Inverse of variance (I2) was used to evaluate heterogeneity across studies, and Egger's test to identify publication bias. A random effect model was used to determine the pooled resistance to each antibiotic. Subgroup analysis was performed by infection type and year of publication. RESULTS: This systematic review and meta-analysis revealed that the pooled prevalence of P. aeruginosa in clinical specimens associated with HAI was 4.38%(95%CI: 3.00-5.76). The pooled prevalence of AMR in P. aeruginosa for different antibiotics varies, ranging from 20.9% (95%CI: 6.2-35.8) for amikacin to 98.72% (95%CI: 96.39-101.4) for ceftriaxone. The pooled resistance was higher for ceftriaxone (98.72%), Trimethoprim-sulfamethoxazole (75.41), and amoxicillin-clavulanic acid (91.2). In contrast relatively lower AMR were observed for amikacin (20.9%) and meropenem (28.64%). The pooled multi-drug resistance (MDR) in P. aeruginosa was 80.5% (95%CI: 66.25-93.84). Upon subgroup analysis by infection types and year of publication, P. aeruginosa isolated from healthcare-associated infections exhibited higher resistance to ceftazidime (94.72%) compared to isolates from mixed types of healthcare-associated infections (70.84%) and surgical site infections (57.84%). Antimicrobial resistance in gentamicin was higher during the periods of 2018-2020 (73.96%), while comparatively lower during 2021-2023 (42.69%) and 2015-2017 (29.82%). CONCLUSIONS: Significantly high AMR and MDR were observed from this systematic review and meta-analysis. AMR obtained from this systematic review and meta-analysis urges the need for improved infection control, antimicrobial stewardship practices, and strengthened surveillance systems to control the spread of AMR and ensure effective treatment of P. aeruginosa infections. PROTOCOL REGISTRATION: This systematic review and meta-analysis was registered on PROSPERO (Registration ID: CRD42024518145).

Malignant Otitis Externa: A persistent challenge.

INTRODUCTION: Although rare, Malignant otitis externa is responsible for a high morbidity and could sometimes be fatal. The management of this condition is still challenging. AIM: To analyse the clinical, microbiological and radiological profile of malignant otitis externa, and the management of this condition. METHODS: A descriptive, cross-sectional study was conducted at ENT Department of Kairouan's hospital including 38 patients hospitalised and treated for malignant otitis externa from January 2013 to August 2021. RESULTS: The mean age of patients was 67.7 ± 12.9 years (35-98). All patients presented with continuous otalgia that resists to usual analgesics. Otorrhea was noticed in 76.3% of cases, facial palsy in 2 cases (5.3%) and dysphonia in one case (2.6%). Pseudomonas Aeruginosa was the main responsible pathogen (42%). Concomitant bacterial and fungal infection was noticed in 6.4% of the cases. First-line intravenous antibiotherapy used was mainly based on an association of Cephalosporins and Fluoroquinolones. Complete remission was noticed in 30 patients (79%). However, 8 cases of recurrences (21%) and 2 cases of deaths (5.2%) were noticed in our series. The mean follow-up was 4.6±6.3 (1-26 months). CONCLUSIONS: Pseudomonas Aeruginosa remains the main responsible pathogen for malignant otitis externa. Nevertheless, fungal infections are rising because of the overuse of antibiotics. Antibiotherapy should be adapted to culture results and resistance profile of pathogens in hospital. Practionners should be aware of the possibility of concomitant fungal infection, especially in the case of unfavorable evolution.

The antibiotic resistance profiles of Pseudomonas aeruginosa in the Asia Cornea Society Infectious Keratitis Study.

PURPOSE: To describe the prevalence and antibiotic resistance profiles of Pseudomonas aeruginosa isolated from the Asia Cornea Society Infectious Keratitis Study (ACSIKS). METHODS: All bacterial isolates from ACSIKS underwent repeat microbiological identification in a central repository in Singapore. Minimum inhibitory concentration (MIC) determination was conducted for isolates of P. aeruginosa against thirteen antibiotics from 6 different classes, and categorized based on Clinical Laboratory Standard Institutes' reference ranges. The percentage rates of resistance (non-susceptibility) to each antibiotic included isolates of both intermediate and complete resistance. Multi-drug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial classes. RESULTS: Of the 1493 unique bacterial specimens obtained from ACSIKS, 319 isolates were of P. aeruginosa. The majority of isolates were from centers in India (n = 118, 37%), Singapore (n = 90, 28.2%), Hong Kong (n = 31, 9.7%) and Thailand (n = 30, 9.4%). The cumulative antibiotic resistance rate was the greatest for polymyxin B (100%), ciprofloxacin (17.6%) and moxifloxacin (16.9%), and lowest for cefepime (11.6%) and amikacin (13.5%). Isolates from India demonstrated the highest antibiotic resistance rates of all the centers, and included moxifloxacin (47.5%) and ciprofloxacin (39.8%). Forty-eight of the 59 MDR isolates also originated from India. Antibiotic resistance rates were significantly lower in the other ACSIKS centers, and were typically less than 10%. CONCLUSIONS: The antibiotic resistance profiles of P. aeruginosa varied between different countries. While it was low for most countries, substantial antibiotic resistance and a significant number of multi-drug resistant isolates were noted in the centers from India.

Respiratory Pathogens at Exacerbation in Chronic Bronchitis With Airway Bacterial Colonisation: A Cohort Study.

BACKGROUND AND OBJECTIVE: COPD and bronchiectasis are common causes of morbidity, particularly around exacerbation. Colonisation with respiratory pathogens can increase the frequency and severity of exacerbations. However, bacterial and viral presence at exacerbation in people with airway colonisation has not been well studied. METHODS: A 6-month cohort study of participants (n = 30) with chronic bronchitis due to bronchiectasis (n = 26) and/or COPD (n = 13) and colonisation with Pseudomonas aeruginosa or Haemophilus influenzae was proven on two sputum cultures at exacerbation in the previous 12 months. Participants were provided self-management education and collected sputum samples daily. Sputum samples at baseline (at least 14 days before or after an exacerbation) and at each exacerbation were examined for a panel of 34 respiratory pathogens using commercially available RT-PCR kits and compared to results obtained using culture methods for the detection of bacteria. RESULTS: Participants provided 29 baseline samples and 71 samples at exacerbation. In 17/29 baseline samples, RT-PCR analysis confirmed the organism demonstrated by culture, while 12 samples showed a discrepancy from culture results. Most exacerbations (57.7%) were not associated with acquiring new bacteria or viruses, while 19.8% showed new bacteria, 15.7% new viruses and 7% both new viruses and bacteria. CONCLUSION: Over half of exacerbations were not associated with new organisms in this cohort of participants with chronic bronchitis and colonisation. However, 26.8% demonstrated a new bacterial species in sputum, which is relevant for antibiotic therapy. Baseline RT-PCR and culture results were discordant in one-third of participants.

Increased 30-day all-cause mortality associated with Gram-negative bloodstream infections in England during the COVID-19 pandemic.

BACKGROUND: Our aim was to assess the impact of COVID-19 pandemic on mortality in patients hospitalised with Gram-negative bloodstream infections (GNBSIs). METHODS: A retrospective cohort study including cases of Escherichia coli, Klebsiella species and Pseudomonas aeruginosa in England (January 2015-December 2021) reported to UKHSA's Second Generation Surveillance System. The outcome was 30-day all-cause mortality. Multivariable logistic regression models were built, and adjusted Odds Ratios (ORs) with 95% confidence intervals were reported. RESULTS: Total E. coli, Klebsiella spp. and P. aeruginosa infections were 206,030, 53,819 and 21,129, respectively. Compared to the pre-pandemic period, odds of death during the pandemic (March 2020 onwards) in E. coli, Klebsiella spp. and P. aeruginosa infections with no COVID-19 infection within 28-days of onset were 1.13 (1.08-1.18), 1.15 (1.07-1.25) and 1.09 (0.97-1.22), while odds in GNBSIs with an associated COVID-19 infection were 2.45 (2.26-2.66), 2.96 (2.62-3.34) and 3.15 (2.61-3.80), respectively. Asian patients with an associated COVID-19 infection were more likely to die during the pandemic compared to White patients (E. coli: OR 1.28 (0.95-1.71); Klebsiella spp. OR 1.59 (1.20-2.11); P. aeruginosa: OR 2.02 (1.23-3.31)). CONCLUSIONS: Patients suffering from a GNBSI had increased risk of death during the pandemic, with the risk higher in patients with an associated COVID-19 infection.

Tracing the origin of NDM-1-producing and extensively drug-resistant Pseudomonas aeruginosa ST357 in the Netherlands.

BACKGROUND: In the hospital environment, carbapenemase-producing Pseudomonas aeruginosa (CPPA) may lead to fatal patient infections. However, the transmission routes of CPPA often remain unknown. Therefore, this case study aimed to trace the origin of CPPA ST357, which caused a hospital-acquired pneumonia in a repatriated critically ill patient suffering from Guillain-Barré Syndrome in 2023. METHODS: Antimicrobial susceptibility of the CPPA isolate for 30 single and combination therapies was determined by disk-diffusion, Etest or broth microdilution. Whole-genome sequencing was performed for three case CPPA isolates (one patient and two sinks) and four distinct CPPA ST357 patient isolates received in the Dutch CPPA surveillance program. Furthermore, 193 international P. aeruginosa ST357 assemblies were collected via three genome repositories and analyzed using whole-genome multi-locus sequence typing in combination with antimicrobial resistance gene (ARG) characterization. RESULTS: A Dutch patient who carried NDM-1-producing CPPA was transferred from Kenya to the Netherlands, with subsequent dissemination of CPPA isolates to the local sinks within a month after admission. The CPPA case isolates presented an extensively drug-resistant phenotype, with susceptibility only for colistin and cefiderocol-fosfomycin. Phylogenetic analysis showed considerable variation in allelic distances (mean = 150, max = 527 alleles) among the ST357 isolates from Asia (n = 92), Europe (n = 58), Africa (n = 21), America (n = 16), Oceania (n = 2) and unregistered regions (n = 4). However, the case isolates (n = 3) and additional Dutch patient surveillance program isolates (n = 2) were located in a sub-clade of isolates from Kenya (n = 17; varying 15-49 alleles), the United States (n = 7; 21-115 alleles) and other countries (n = 6; 14-121 alleles). This was consistent with previous hospitalization in Kenya of 2/3 Dutch patients. Additionally, over half of the isolates (20/35) in this sub-clade presented an identical resistome with 9/17 Kenyan, 5/5 Dutch, 4/7 United States and 2/6 other countries, which were characterized by the blaNDM-1, aph(3')-VI, ARR-3 and cmlA1 ARGs. CONCLUSION: This study presents an extensively-drug resistant subclone of NDM-producing P. aeruginosa ST357 with a unique resistome which was introduced to the Netherlands via repatriation of critically ill patients from Kenya. Therefore, the monitoring of repatriated patients for CPPA in conjunction with vigilance for the risk of environmental contamination is advisable to detect and prevent further dissemination.

Three prolonged outbreaks of metallo-ß-lactamase-producing Pseudomonas aeruginosa in an Upper Austrian hospital, 2017-2023.

In spring 2022, an increase in metallo-ß-lactamase-producing Pseudomonas aeruginosa (MBL-Pa) infections was detected in a hospital in Upper Austria. To identify the source of infection and to stop further transmissions, an epidemiological outbreak investigation including whole-genome sequencing (WGS)-based typing was conducted. The final case definition included cases admitted to the hospital between 2020 and 2023 with an MBL-Pa in one of the three genomic clusters identified. In addition, the investigation was extended to include historical cases from 2017. Core genome multilocus sequence typing was performed to assess the genetic relatedness between the isolates. Fifty-four clinical P. aeruginosa isolates and eight P. aeruginosa isolates from the hospital environment were obtained. All but nine isolates grouped into one of three genomic clusters (ST235/blaVIM-1, ST111/blaVIM-2, or ST621/blaIMP-13), which were considered to be distinct, prolonged outbreaks involving 47 out of 52 cases. The most likely source of infection for cluster 1 (ST111/blaVIM-2) and cluster 2 (ST235/blaVIM-1) was sinks in the intensive care unit (ICU) washroom. Cluster 3 clone (ST621/blaIMP-13) could have originated in the urology ward in 2020 and then spread to the ICU years later. However, the nosocomial origin of this clone could not be proven. In March 2023, following the implementation of control measures (gowning, patient isolation, screening, and daily disinfection), no further MLB-Pa was detected, and the outbreaks were considered to be over. As ICUs play an important role in the transmission of P. aeruginosa, emphasis should be placed on genomic surveillance, infection prevention, and control in such wards. IMPORTANCE: The significance of our work lies in the successful resolution of three prolonged outbreaks of MBL-Pa infections in a hospital in Upper Austria. Through a comprehensive epidemiological investigation coupled with WGS-based typing of P. aeruginosa isolates, the study identified three distinct genomic clusters responsible for prolonged outbreaks involving 47 cases. The investigation pinpointed sinks in the ICU washroom as the likely source of infection for two of the clusters. The study demonstrates the effectiveness of control measures such as hand hygiene, gowning, patient isolation, screening, and disinfection in stopping further transmission and bringing the outbreaks to a close. This underscores the critical role of genomic surveillance and control measures, particularly in high-risk settings like ICUs, in reducing nosocomial transmission of MBL-Pa infections.

Factors associated with pulmonary function decline of patients in the cystic fibrosis registry of Turkey: A retrospective cohort study.

BACKGROUND: The decline in pulmonary function is a predictor of disease progression in patients with cystic fibrosis (CF). This study aimed to determine the decline rate of percent predicted forced expiratory volume in 1 s (ppFEV1) based on the data of the CF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1. METHODS: A retrospective cohort study of CF patients over 6 years old, with pulmonary function data over at least 2 years of follow-up was extracted from the national CF registry for years 2017-2019. Patients were classified according to disease severity and age groups. Multivariate analysis was used to predict the decline in ppFEV1 and to investigate the associated risk factors. RESULTS: A total of 1722 pulmonary function test results were available from 574 patients over the study period. Mean diagnostic age was older and weight for age, height for age, and body mass index z scores were significantly lower in the group of ppFEV1 < 40, while chronic Pseudomonas aeruginosa (p < .001) and mucoid P. aeruginosa colonization (p < .001) were significantly higher in this group (p < .001). Overall mean annual ppFEV1 decline was -0.97% (95% confidence interval [CI] = -0.02 to -1.92%). The mean change of ppFEV1 was significantly higher in the group with ppFEV1 ≥ 70 compared with the other (ppFEV1 < 40 and ppFEV1: 40-69) two groups (p = .004). Chronic P. aeruginosa colonization (odds ratio [OR] = 1.79 95% CI = 1.26-2.54; p = .01) and initial ppFEV1 ≥ 70 (OR = 2.98 95% CI = 1.06-8.36), p = .038) were associated with significant ppFEV1 decline in the whole cohort. CONCLUSIONS: This data analysis recommends close follow-up of patients with normal initial ppFEV1 levels at baseline; advocates for early interventions for P. aeruginosa; and underlines the importance of nutritional interventions to slow down lung disease progression.

Pseudomonas aeruginosa epidemic high-risk clones and their association with multidrug-resistant.

OBJECTIVE: In Ecuador, data on molecular epidemiology, as well as circulating clones, are limited. Therefore, this study aims to know the population structure of Pseudomonas aeruginosa by identifying clones in clinical samples in Quito-Ecuador. METHODS: A significant set (45) clinical P. aeruginosa isolates were selected, including multidrug and non-multidrug resistant isolates, which were assigned to sequence types (STs) and compared with their antibiotic susceptibility profile. The genetic diversity was assessed by applying the multilocus sequence typing (MLST) scheme and the genetic relationships between different STs were corroborated by phylogenetic networks. RESULTS: The MLST analysis identified 24 different STs and the most prevalent STs were ST-3750 and ST-253. The majority of the multidrug-resistance (MDR) isolates were included in ST-3750 and ST-253, also 3 singleton STs were identified as MDR isolates. The 21 different STs were found in non-multidrug resistance (non-MDR) isolates, and only 3 STs were found in more the one isolate. CONCLUSIONS: The population structure of clinical P. aeruginosa present in these isolates indicates a significant association between MDR isolates and the clonal types: all ST-3750 and ST-253 isolates were MDR. ST-3750 is a closely related strain to the clonal complex ST111 (CC111). ST-253 and ST111 are a group of successful high-risk clones widely distributed worldwide. The multiresistant isolates studied are grouped in the most prevalent STs found, and the susceptible isolates correspond mainly with singleton STs. Therefore, these high-risk clones and their association with MDR phenotypes are contributing to the spread of MDR in Quito, Ecuador.

[Clinical profiles of community-acquired Pseudomonas aeruginosa infections in children].

Objectives: To investigate clinical characteristics, outcomes and antimicrobial resistance of community-acquired Pseudomonas aeruginosa (CAPA) infections in Chinese pediatric patients. Methods: This retrospective study was conducted at 6 tertiary hospitals in China during January 2016 to December 2018. The clinical and microbiological data of CAPA infected hospitalized children in Hainan and in other regions were collected and compared, and the antimicrobial resistance patterns, clinical characteristics and antibiotic therapy were analyzed. Between different groups were compared using the Chi-square test and Mann-Whitney U test. Results: Among 91 patients, 63 cases were males, 28 cases were females, and 74 cases were from Hainan province, 17 cases were from other regians. The age of consultation was 22.5 (5.4, 44.0) months. Twenty-four cases (26%) had underlying diseases. Fever (79 cases (87%)) and cough (64 cases (70%)) were common initial symptoms. Other concomitant symptoms included wheezing 8 cases (9%), diarrhea 3 cases (3%) and vomiting 4 cases (4%). Twenty-eight cases (31%) had organ infections, including pneumonia 22 cases (24%), skin infection 5 cases (5%), meningitis, intra-abdominal infection and upper urinary tract infection each 1 case (1%). The resistance rate of CAPA isolates to cefepime (4% (4/90)), amikacin (1% (1/90)), ciprofloxacin (2% (2/90)) and levofloxacin (1% (1/89)) was low, and to ceftazidime, piperacillin, piperacillin-azobactam, carbapenem was 12% (11/90), 3/16, 18% (10/56) and 6% (5/90), respectively. Antimicrobial combination therapy accounted for 52% (47/91) of empirical therapy and 59% (52/88) of definite therapy. Two cases (2%) were hopeless discharged, and 3 cases (3%) died during hospitalization. The worse prognosis of CAPA infection is significantly different among children in other regions and in Hainan (4/17 vs. 1% (1/74), χ²=9.74, P<0.05). Conclusions: The invasive CAPA-infection has regional difference in incidence and prognosis in China. Clinical symptoms and signs are non-specific. CAPA strains isolated from pediatric patients display low level of resistance to most of the common antipseudomonal antibiotics. The proportion of poor prognostic outcome is lower in Hainan than in other regions.

Prevalence and mechanisms of aminoglycoside resistance among drug-resistant Pseudomonas aeruginosa clinical isolates in Iran.

BACKGROUND: Aminoglycosides have been a cornerstone of the treatment of nosocomial infections caused by Pseudomonas aeruginosa for over 80 years. However, escalating emergence of resistance poses a significant challenge. Therefore, this study aimed to investigate the prevailing patterns of aminoglycoside resistance among clinical isolates of P. aeruginosa in Iran; as well as the underlying resistance mechanisms observed in patients referred to Ardabil hospitals. METHODS: A total of 200 isolates from five hospitals were evaluated. The resistance profiles of P. aeruginosa isolates to tobramycin, amikacin, and netilmicin were determined using the disk diffusion method. The capacity of aminoglycoside-resistant isolates to form biofilms was assessed through a phenotypic assay, and the results were confirmed using the gene amplification technique. The presence of genes associated with aminoglycoside resistance was detected using polymerase chain reaction (PCR). Quantitative reverse transcription PCR (qRT-PCR) was performed to measure the expression levels of genes encoding the MexXY-OprM efflux pump and PhoPQ two-component system (TCS). RESULTS: The prevalence of aminoglycoside-resistant P. aeruginosa isolates was 48%, with 94.7% demonstrating multidrug resistance (MDR). All aminoglycoside-resistant P. aeruginosa strains exhibited biofilm-forming capabilities and harbored all the genes associated with biofilm production. Among the nine genes encoding 16S rRNA methylase and aminoglycoside-modifying enzymes, three genes were detected in these isolates: aac(6')-Ib (85.4%), ant(2'')-Ia (18.7%), and aph(3')-VI (3.1%). Additionally, all aminoglycoside-resistant P. aeruginosa isolates carried mexY and phoP genes, although the expression levels of mexY and phoP were 75% and 87.5%, respectively. CONCLUSION: Given the considerably high prevalence of aminoglycoside-resistant P. aeruginosa strains, urgent measures are warranted to transition towards the use of novel aminoglycosides and to uphold vigilant surveillance of resistance patterns.

Phenotypic and genotypic assessment of fluoroquinolones and aminoglycosides resistances in Pseudomonas aeruginosa collected from Minia hospitals, Egypt during COVID-19 pandemic.

BACKGROUND: One of the most prevalent bacteria that cause nosocomial infections is Pseudomonas aeruginosa. Fluoroquinolones (FQ) and aminoglycosides are vital antipseudomonal drugs, but resistance is increasingly prevalent. The study sought to investigate the diverse mechanisms underlying FQ and aminoglycoside resistance in various P. aeruginosa strains particularly during the COVID-19 crisis. METHODS: From various clinical and environmental samples, 110 P. aeruginosa isolates were identified and their susceptibility to several antibiotic classes was evaluated. Molecular techniques were used to track target gene mutations, the presence of genes encoding for quinolone resistance, modifying enzymes for aminoglycosides and resistance methyltransferase (RMT). Efflux pump role was assessed phenotypically and genotypically. Random amplified polymorphic DNA (RAPD) analysis was used to measure clonal diversity. RESULTS: QnrS was the most frequently encountered quinolone resistance gene (37.5%) followed by qnrA (31.2%) and qnrD (25%). Among aminoglycoside resistant isolates, 94.1% harbored modifying enzymes genes, while RMT genes were found in 55.9% of isolates. The aac(6')-Ib and rmtB were the most prevalent genes (79.4% and 32.3%, respectively). Most FQ resistant isolates overexpressed mexA (87.5%). RAPD fingerprinting showed 63.2% polymorphism. CONCLUSIONS: Aminoglycosides and FQ resistance observed in this study was attributed to several mechanisms with the potential for cross-contamination existence so, strict infection control practices are crucial.