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).

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.

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.

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.

Incidence of drug-resistant pathogens in community-acquired pneumonia at a safety net hospital.

The 2019 Infectious Diseases Society of America guideline for the management of community-acquired pneumonia (CAP) emphasizes the need for clinician to understand local epidemiological data to guide selection of appropriate treatment. Currently, the local distribution of causative pathogens and their associated resistance patterns in CAP is unknown. A retrospective observational study was performed of patients admitted to an 870-bed safety net hospital between March 2016 and March 2021 who received a diagnosis of CAP or healthcare-associated pneumonia within the first 48 hours of admission. The primary outcome was the incidence of CAP caused by methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PsA) as determined by comparing the number of satisfactory sputum cultures or blood cultures with these drug-resistant organisms to the total number of reviewed patients. Secondary outcomes studied included risk factors associated with CAP caused by drug-resistant organisms, utilization of broad-spectrum antibiotics, appropriate antibiotic de-escalation within 72 hours, and treatment duration. In this 220-patient cohort, MRSA or PsA was isolated from three sputum cultures and no blood cultures. The local incidence of drug-resistant pathogens among the analyzed sample of CAP patients was 1.4% (n = 3/220). The overall incidence of CAP caused by MRSA or PsA among admitted patients is low at our safety-net county hospital. Future research is needed to identify local risk factors associated with the development of CAP caused by drug-resistant pathogens.IMPORTANCEThis study investigates the incidence of drug-resistant pathogens including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa among community-acquired pneumonia (CAP) patients at a safety net hospital. Understanding local bacteria resistance patterns when treating CAP is essential and supported by evidence-based guidelines. Our findings empower other clinicians to investigate resistance patterns at their own institutions and identify methods to improve antibiotic use. This has the potential to reduce the unnecessary use of broad-spectrum antibiotic agents and combat the development of antibiotic resistance.

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.

[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.

Unveiling the microevolution of antimicrobial resistance in selected Pseudomonas aeruginosa isolates from Egyptian healthcare settings: A genomic approach.

The incidence of Pseudomonas aeruginosa infections in healthcare environments, particularly in low-and middle-income countries, is on the rise. The purpose of this study was to provide comprehensive genomic insights into thirteen P. aeruginosa isolates obtained from Egyptian healthcare settings. Phenotypic analysis of the antimicrobial resistance profile and biofilm formation were performed using minimum inhibitory concentration and microtiter plate assay, respectively. Whole genome sequencing was employed to identify sequence typing, resistome, virulome, and mobile genetic elements. Our findings indicate that 92.3% of the isolates were classified as extensively drug-resistant, with 53.85% of these demonstrating strong biofilm production capabilities. The predominant clone observed in the study was ST773, followed by ST235, both of which were associated with the O11 serotype. Core genome multi-locus sequence typing comparison of these clones with global isolates suggested their potential global expansion and adaptation. A significant portion of the isolates harbored Col plasmids and various MGEs, all of which were linked to antimicrobial resistance genes. Single nucleotide polymorphisms in different genes were associated with the development of antimicrobial resistance in these isolates. In conclusion, this pilot study underscores the prevalence of extensively drug-resistant P. aeruginosa isolates and emphasizes the role of horizontal gene transfer facilitated by a diverse array of mobile genetic elements within various clones. Furthermore, specific insertion sequences and mutations were found to be associated with antibiotic resistance.

Molecular characterization of Pseudomonas aeruginosa from diabetic foot infections in Tunisia.

Background. Pseudomonas aeruginosa is an invasive organism that frequently causes severe tissue damage in diabetic foot ulcers.Gap statement. The characterisation of P. aeruginosa strains isolated from diabetic foot infections has not been carried out in Tunisia.Purpose. The aim was to determine the prevalence of P. aeruginosa isolated from patients with diabetic foot infections (DFIs) in Tunisia and to characterize their resistance, virulence and molecular typing.Methods. Patients with DFIs admitted to the diabetes department of the International Hospital Centre of Tunisia, from September 2019 to April 2021, were included in this prospective study. P. aeruginosa were obtained from the wound swabs, aspiration and soft tissue biopsies during routine clinical care and were confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing, serotyping, integron and OprD characterization, virulence, biofilm production, pigment quantification, elastase activity and molecular typing were analysed in all recovered P. aeruginosa isolates by phenotypic tests, specific PCRs, sequencing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing.Results. Sixteen P. aeruginosa isolates (16.3 %) were recovered from 98 samples of 78 diabetic patients and were classified into 6 serotypes (O:11 the most frequent), 11 different PFGE patterns and 10 sequence types (three of them new ones). The high-risk clone ST235 was found in two isolates. The highest resistance percentages were observed to netilmicin (69 %) and cefepime (43.8 %). Four multidrug-resistant (MDR) isolates (25 %) were detected, three of them being carbapenem-resistant. The ST235-MDR strain harboured the In51 class 1 integron (intI1 +aadA6+orfD+qacED1-sul1). According to the detection of 14 genes involved in virulence or quorum sensing, 5 virulotypes were observed, including 5 exoU-positive, 9 exoS-positive and 2 exoU/exoS-positive strains. The lasR gene was truncated by ISPpu21 insertion sequence in one isolate, and a deletion of 64 bp in the rhlR gene was detected in the ST235-MDR strain. Low biofilm, pyoverdine and elastase production were detected in all P. aeruginosa; however, the lasR-truncated strain showed a chronic infection phenotype characterized by loss of serotype-specific antigenicity, high production of phenazines and high biofilm formation.Conclusions. Our study demonstrated for the first time the prevalence and the molecular characterization of P. aeruginosa strains from DFIs in Tunisia, showing a high genetic diversity, moderate antimicrobial resistance, but a high number of virulence-related traits, highlighting their pathological importance.

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.

Characterization and genetic analysis of extensively drug-resistant hospital acquired Pseudomonas aeruginosa isolates.

BACKGROUND: The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. RESULTS: Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum ß-lactamases (ESBLs) and metallo ß-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6')-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. CONCLUSION: The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential.

Resistance to ceftazidime-avibactam and other new ß-lactams in Pseudomonas aeruginosa clinical isolates: a multi-center surveillance study.

New ß-lactam-ß-lactamase inhibitor combinations represent last-resort antibiotics to treat infections caused by multidrug-resistant Pseudomonas aeruginosa. Carbapenemase gene acquisition can limit their spectrum of activity, and reports of resistance toward these new molecules are increasing. In this multi-center study, we evaluated the prevalence of resistance to ceftazidime-avibactam (CZA) and comparators among P. aeruginosa clinical isolates from bloodstream infections, hospital-acquired or ventilator-associated pneumonia, and urinary tract infections, circulating in Southern Italy. We also investigated the clonality and content of relevant ß-lactam resistance mechanisms of CZA-resistant (CZAR) isolates. A total of 120 P. aeruginosa isolates were collected. CZA was among the most active ß-lactams, retaining susceptibility in the 81.7% of cases, preceded by cefiderocol (95.8%) and followed by ceftolozane-tazobactam (79.2%), meropenem-vaborbactam (76.1%), imipenem-relebactam (75%), and aztreonam (69.6%). Among non-ß-lactams, colistin and amikacin were active against 100% and 85.8% of isolates respectively. In CZAR strains subjected to whole-genome sequencing (n = 18), resistance was mainly due to the expression of metallo-ß-lactamases (66.6% VIM-type and 5.5% FIM-1), followed by PER-1 (16.6%) and GES-1 (5.5%) extended-spectrum ß-lactamases, mostly carried by international high-risk clones (ST111 and ST235). Of note, two strains producing the PER-1 enzyme were resistant to all ß-lactams, including cefiderocol. In conclusion, the CZA resistance rate among P. aeruginosa clinical isolates in Southern Italy remained low. CZAR isolates were mostly metallo-ß-lactamases producers and belonging to ST111 and ST253 epidemic clones. It is important to implement robust surveillance systems to monitor emergence of new resistance mechanisms and to limit the spread of P. aeruginosa high-risk clones. IMPORTANCE: Multidrug-resistant Pseudomonas aeruginosa infections are a growing threat due to the limited therapeutic options available. Ceftazidime-avibactam (CZA) is among the last-resort antibiotics for the treatment of difficult-to-treat P. aeruginosa infections, although resistance due to the acquisition of transferable ß-lactamase genes is increasing. With this work, we report that CZA represents a highly active antipseudomonal ß-lactam compound (after cefiderocol), and that metallo-ß-lactamases (VIM-type) and extended-spectrum ß-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals. In addition, we reported that such resistance mechanisms were mainly carried by the international high-risk clones ST111 and ST235.

Incidence, Predictors, and Outcomes of Pseudomonas aeruginosa Associated Acute Appendicitis in Children.

BACKGROUND: Pseudomonas aeruginosa (PSA) is an infectious pathogen associated with acute appendicitis; however, it is not consistently addressed by empirical antibiotic therapy, despite potential complications. OBJECTIVES: To investigate the incidence, predictors, and outcomes of PSA-associated acute appendicitis in children. METHODS: We conducted a retrospective analysis involving pediatric patients who underwent acute appendicitis surgery and had positive peritoneal cultures. Clinical, microbiological, and intraoperative data were extracted from medical records. RESULTS: Among 2523 children with acute appendicitis, 798 (31.6%) underwent peritoneal cultures, revealing 338 positive cases (42.3%), with PSA detected in 77 cases (22.8%). Children with PSA were three times more likely to exhibit high intraoperative grading ≥ 3 (93.4% vs. 76.8%, 95% confidence interval [95%CI] 1.2-8.3, P = 0.023) and nearly four times more likely to have polymicrobial cultures (88.3% vs. 62.1%, 95%CI 1.8-8.0, P < 0.001) than those without PSA in peritoneal cultures. Duration of symptoms did not predict PSA isolation (P = 0.827). Patients with PSA had longer median hospital stays (8 days, interquartile range [IQR] 7-10) than those with other pathogens (7 days, IQR 5-9) (P = 0.004). Antibiotic treatment duration, intensive care unit admission rates, readmission, and mortality were similar between the two groups (P = 0.893, 0.197, 0.760, and 0.761, respectively). CONCLUSIONS: PSA is a common pathogen in children diagnosed with acute appendicitis and positive peritoneal cultures. The likelihood of isolating PSA increases with high-grade intraoperative assessment and in the presence of multiple pathogens in peritoneal cultures, suggests antipseudomonal treatment.

Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial.

BACKGROUND: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes. METHODS: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365. RESULTS: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037. CONCLUSIONS: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25.

Retrospective genome-oriented analysis reveals low transmission rate of multidrug-resistant Pseudomonas aeruginosa from contaminated toilets at a bone marrow transplant unit.

BACKGROUND: Prevention of toilet-to-patient transmission of multidrug-resistant Pseudomonas aeruginosa (MDR PA) poses management-related challenges at many bone marrow transplant units (BMTUs). AIM: To conduct a longitudinal retrospective analysis of the toilet-to-patient transmission rate for MDR PA under existing infection control (IC) measures at a BMTU with persistent MDR PA toilet colonization. METHODS: The local IC bundle comprised: (1) patient education regarding IC; (2) routine patient screening; (3) toilet flushing volume of 9 L; (4) bromination of toilet water tanks, and (5) toilet decontamination using hydrogen peroxide. Toilet water was sampled periodically between 2016 and 2021 (minimum every three months: 26 intervals). Upon MDR PA detection, disinfection and re-sampling were repeated until ≤3 cfu/100 mL was reached. Whole-genome sequencing (WGS) was performed retrospectively on all available MDR PA isolates (90 out of 117 positive environmental samples, 10 out of 14 patients, including nine nosocomial). FINDINGS: WGS of patient isolates identified six sequence types (STs), with ST235/CT1352/FIM-1 and ST309/CT3049/no-carbapenemase being predominant (three isolates each). Environmental sampling consistently identified MDR PA ST235 (65.5% ST235/CT1352/FIM-1), showing low genetic diversity (difference of ≤29 alleles by core-genome multi-locus sequence typing (cgMLST)). This indicates that direct toilet-to-patient transmission was infrequent although MDR PA was widespread (detection on 79 occasions, detection in every toilet). Only three MDR PA patient isolates can be attributed to the ST235/CT1352/FIM-1 toilet MRD PA population over six years. CONCLUSION: Stringent targeted toilet disinfection can reduce the potential risk for MDR PA acquisition by patients.

Prevalence and molecular characterization of colistin resistance in Pseudomonas aeruginosa isolates: insights from a study in Ardabil hospitals.

BACKGROUND: Pseudomonas aeruginosa is a common cause of nosocomial infections. However, the emergence of multidrug-resistant strains has complicated the treatment of P. aeruginosa infections. While polymyxins have been the mainstay for treatment, there is a global increase in resistance to these antibiotics. Therefore, our study aimed to determine the prevalence and molecular details of colistin resistance in P. aeruginosa clinical isolates collected between June 2019 and May 2023, as well as the genetic linkage of colistin-resistant P. aeruginosa isolates. RESULTS: The resistance rate to colistin was 9% (n = 18) among P. aeruginosa isolates. All 18 colistin-resistant isolates were biofilm producers and carried genes associated with biofilm formation. Furthermore, the presence of genes encoding efflux pumps, TCSs, and outer membrane porin was observed in all colistin-resistant P. aeruginosa strains, while the mcr-1 gene was not detected. Amino acid substitutions were identified only in the PmrB protein of multidrug- and colistin-resistant strains. The expression levels of mexA, mexC, mexE, mexY, phoP, and pmrA genes in the 18 colistin-resistant P. aeruginosa strains were as follows: 88.8%, 94.4%, 11.1%, 83.3%, 83.3%, and 38.8%, respectively. Additionally, down-regulation of the oprD gene was observed in 44.4% of colistin-resistant P. aeruginosa strains. CONCLUSION: This study reports the emergence of colistin resistance with various mechanisms among P. aeruginosa strains in Ardabil hospitals. We recommend avoiding unnecessary use of colistin to prevent potential future increases in colistin resistance.

Clinical characteristics and antibiotic treatment of peritoneal dialysis-associated peritonitis caused by Pseudomonas species: a review of 15 years' experience from southern China.

Pseudomonas can lead to peritoneal dialysis-associated peritonitis, which is characterized by a poor prognosis, such as a substantial failure rate and a high death rate. This study aimed to provide an overview of Pseudomonas peritonitis's clinical features, the regimens of antibiotic, antibiotic resistance, and outcomes in peritoneal dialysis (PD) patients. This study observed patients with Pseudomonas peritonitis in two large PD centers in South China from January 2008 to December 2022. The demographics, symptomatology, antibiotics regimens, resistance to common antibiotics, and clinical outcomes of all included patients were reviewed. A total of 3,459 PD patients were included, among them 57 cases of peritonitis caused by Pseudomonas, including 48 cases (84.2%) of Pseudomonas aeruginosa. The incidence rate of Pseudomonas peritonitis was 0.0041 episode per patient-year. Of them, 28.1% (16 cases) of the patients were accompanied by exit site infection (ESI), and all had abdominal pain and turbid ascites at the time of onset. The most commonly used antibiotic combination was ceftazidime combined with amikacin. Approximately 89% of Pseudomonas species were sensitive to ceftazidime, and 88% were sensitive to amikacin. The overall primary response rate was 28.1% (16 patients), and the complete cure rate was 40.4% (23 patients). There was no significant difference in the complete cure rate of peritonitis using three and other antibiotic treatment regimens (44.8% vs 46.4%; P = 0.9). The successful treatment group had higher baseline albumin level (35.9 ± 6.2; P = 0.008) and residual urine volume (650.7 ± 375.5; P = 0.04). Although the incidence of peritonitis caused by Pseudomonas was low, the symptoms were serious, and prognosis was very poor. Pseudomonas was still highly susceptible to first-line antibiotics currently in use against Gram-negative bacteria. Patients with successful treatment had higher albumin levels and higher urine output. IMPORTANCE: Although the incidence of peritoneal dialysis-associated peritonitis caused by Pseudomonas is very low, it seriously affects the technique survival of peritoneal dialysis patients. However, there are few studies and reports on Pseudomonas peritonitis in the Chinese mainland area. Therefore, the purpose of this study is to describe the clinical characteristics, the regimens of antibiotic, drug resistance, and outcome of peritoneal dialysis patients in southern China in the past 15 years and summarize the clinical experience in the treatment of Pseudomonas peritonitis.

Bloodstream infections and multidrug resistant bacteria acquisition among burns patients in Australia and New Zealand: A registry-based study.

INTRODUCTION: This study interrogates infection related data in the Burns Registry of Australia and New Zealand (BRANZ), to examine associations of multi-drug resistant organisms (MDROs) and blood stream infection (BSI). METHODS: Data between July 2016 and June 2021 were analysed to determine prevalence, risk factors and outcomes associated with BSIs and MDROs: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Pseudomonas spp. (CRP), and carbapenem-resistant Enterobacter (CRE). Data completeness and value for quality improvement activity were assessed. RESULTS: We found a low incidence (3.4%) of the resistant organisms of interest, and no change over the study period. Fequency varied between services and increased with age and size of burn. MRSA was the commonest organism in all age groups. A positive BSI result occurred in 1.6% of patients (12.1% of cultures taken) at a median time of 10.2 days post injury. Free text identification of organisms was inconsistently documented. CONCLUSIONS: The low rate and patterns of acquisition of MDROs of interest and BSIs is comparable with reports from countries with low incidence of massive burns. Wider adoption of a standardized laboratory reporting framework would help realise the potential of clinical quality registries to provide data which supports evidence based infection prevention initiatives.