The clinical strain of Pseudomonas aeruginosa XM8 harbored multiple RND-type antibiotic efflux pump genes and a novel integron In4881 on its plasmid pXM8-2, rendering it resistant to nearly all conventional antibiotics except colistin. The resistance was primarily attributed to the inactivation of the oprD gene and overexpression of several efflux pump genes, including mexAB-oprM, mexCD-oprJ, oprN-mexFE, and mexXY. In this study, the XM8 strain was comprehensively characterized using various methods. Antimicrobial susceptibility testing was performed using the BioMerieux VITEK2 system and manual double dilution methods. Gene expression levels of efflux pump-related genes were analyzed via quantitative real-time PCR. The bacterial chromosome and plasmid were sequenced using both Illumina and Nanopore platforms, and bioinformatics tools were employed to analyze mobile genetic elements associated with antibiotic resistance. The pXM8-2 plasmid containsed multiple mobile genetic elements, including integrons (In4881, In334, In413) and transposons (Tn3, TnAs1, TnAs3). Notably, In4881 was reported for the first time in this study. The presence of these elements highlights the potential for horizontal gene transfer and further spread of antibiotic resistance. Given the strong resistance profile of the XM8 strain, effective measures should be implemented to prevent the dissemination and prevalence of such multidrug-resistant bacteria.

Pathogenic bacteria, such as Pseudomonas aeruginosa, pose significant threats to public health due to their multidrug resistance and association with severe infections. Rapid and reliable detection methods are crucial for timely treatment and effective infection control, especially in resource-limited settings. In this study, we developed a CRISPR/Cas12a-based colorimetric biosensor that leverages Cas12a's trans-cleavage activity to release left single-stranded DNA (lDNA). The released lDNA facilitates hybridization with clDNA-functionalized gold nanoparticles (AuNPs), resulting in a visible color change. The biosensor achieved a detection limit of 100 CFU/reaction for P. aeruginosa within 2 hours, with excellent specificity and robustness, as validated in spiked sputum and blood samples. Clinical testing using 32 blood samples (13 positive, 19 negative) confirmed its high diagnostic accuracy, achieving an AUC of 1 in ROC curve analysis. The platform's simplicity, robustness, and programmability suggest its broad potential for rapid infectious disease diagnostics, particularly in low-resource settings.

This article provides an overview of the mechanisms behind carbapenem resistance and the antibiotic management for severe infections caused by key carbapenem-resistant gram-negative bacteria, specifically Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa. For Enterobacterales, it highlights the relative advantages of meropenem-vaborbactam and imipenem-relebactam in treating Klebsiella pneumoniae carbapenemase (KPC)-producing strains with resistance to ceftazidime-avibactam, the preference for ceftazidime-avibactam in addressing oxacillin-hydrolyzing carpapenemase (OXA)-48-like -producing organisms, and the combination of ceftazidime-avibactam with aztreonam for metallo-β-lactamase (MBL)-producing Enterobacterales. Regarding A baumannii, sulbactam-durlobactam is identified as the preferred treatment, while ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam are viable options for P aeruginosa. Additionally, cefiderocol is presented as an alternative for MBL-producing carbapenem-resistant gram-negative bacteria.

Emergence of difficult-to-treat-resistance (DTR) P. aeruginosa has significant implications for the selection of empirical therapies. This study aims to compare antimicrobial resistance of P. aeruginosa from ICU and non-ICU patients and to discuss empirical treatment options. Three-hundred-nine P. aeruginosa strains isolated from hospitalized patients in 2023 were included. Antimicrobial susceptibility results for six classes with potential activity against P. aeruginosa were collected. Resistance between strains isolated from ICU and non-ICU was compared. Among 309 strains, 30% were isolated from ICU patients, while 70% from non-ICU. Resistance to ciprofloxacin was significantly higher in non-ICU compared to ICU patients (64% vs. 15%, p-value = 0.0001). Resistance to piperacillin-tazobactam was higher in ICU compared to non-ICU patients (36% vs. 22%, p-value = 0.012). Prevalence of DTR P. aeruginosa was similar between the two groups (21% in ICU and 19% in non-ICU patients). Joint resistance to imipenem and ceftazidime was more prevalent in ICU patients (27% vs. 10%, p-value 0.0001). Additionally, carbapenemase-producing strains were more frequent in ICU patients (20% vs. 5%, p-value = 0.0001). Ceftolozane-tazobactam, whose effectiveness against DTR P. aeruginosa remains preserved, as empirical treatment, would improve its adequacy by 21% in ICU and 19% in non-ICU patients, compared to the currently recommended first-line treatments.

Pseudomonas aeruginosa is an opportunistic bacterium widely distributed in both natural and urban environments, playing a crucial role in global microbial ecology. This article reviews the interactive dynamics of P. aeruginosa across different ecosystems, highlighting its capacity for adaptation and resistance in response to environmental and therapeutic pressures. We analyze the mechanisms of antibiotic resistance, including the presence of resistance genes and efflux systems, which contribute to its persistence in both clinical and nonclinical settings. The interconnection between human, animal, and environmental health, within the context of the One Health concept, is discussed, emphasizing the importance of monitoring and sustainable management practices to mitigate the spread of resistance. Through a holistic approach, this work offers insights into the influence of P. aeruginosa on public health and biodiversity.

Background/Objectives: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an important pathogen associated with high mortality and treatment failure rates. We aimed to assess the susceptibility of CRPA to antipseudomonal agents, identify its resistance mechanisms, and evaluate clinical outcomes in a sample of CRPA isolates. Methods: This was an in vitro study of a clinical isolate of CRPA from hospitalized patients with CRPA infection and a retrospective observational study of these patients, who were diagnosed between 14 February 2021 and 10 August 2023 at Songklanagarind Hospital in Songkhla, Thailand. In vitro experiments were conducted to determine the minimum inhibitory concentrations (MICs) of the antipseudomonal agents using the broth microdilution method. Resistance mechanisms were assessed using the modified carbapenem inactivation method, combined disk tests, and quantitative real-time reverse transcription polymerase chain reaction. Results: A total of 140 CRPA isolates were analyzed. Both traditional and novel β-lactams had high MICs. The most common resistance mechanism was the upregulation of the MexAB-OprM efflux pump (81.3%), followed by the downregulation of the OprD porin (48.9%) and metallo-β-lactamase (MBL) production (45.0%), and the overexpression of blaAmpC (41.0%). The 30-day all-cause mortality rate was 30.5%. The risk factors associated with 30-day mortality included a Charlson Comorbidity Index of ≥5 (OR: 3.43; 95% CI: 1.07-10.99; p = 0.03), sepsis (OR: 10.62; 95% CI: 1.26-89.44; p = 0.03), and septic shock (OR: 4.39; 95% CI: 1.67-11.55; p < 0.01). In contrast, receiving active documented therapy was significantly associated with reduced mortality (OR: 0.17; 95% CI: 0.04-0.74; p = 0.01). Conclusions: This study revealed higher MIC values of all β-lactams for CRPA, while colistin and amikacin remained effective. The resistance mechanisms included MexAB-OprM overexpression, OprD downregulation, MBL production, and blaAmpC overexpression, with a higher prevalence of MBL than in other regions of Thailand. High 30-day mortality was associated with comorbidities, sepsis, and septic shock, but active therapy reduced mortality.

Bacterial DNA gyrase and topoisomerase IV are the major targets of quinolone antibiotic, and mutational alterations in quinolone resistance determining regions (QRDR) serve as major mechanism of resistance in most bacterial species, including P. aeruginosa. The present investigation was aimed to study the molecular mechanism of fluoroquinolone resistance among clinical P. aeruginosa isolated from Dhaka, Bangladesh, including alterations in target sites of the antimicrobial action. Laboratory collection of 53 P. aeruginosa were subjected to conventional cultural and biochemical characterization, followed by molecular identification using 16S rDNA sequencing. Susceptibility to ciprofloxacin and levofloxacin was tested by disc diffusion method followed by MIC assay. Resistant isolates were analyzed for mutation in their QRDR regions of gyrA and parC, and subjected to PCR detection of plasmid mediated quinolone resistance (PMQR) genes qnrA, qnrS and qnrB. Among the isolates, 28% were found to be resistant to both fluoroquinolones tested. All of the fluoroquinolone resistant isolates carried a single mutation in gyrA (Thr-83-Ile), while 20% carried a single parC mutation (Ser-87-Leu). Higher level of MIC was observed in isolates carrying alterations at both sites. None of the isolates harbored any PMQR genes investigated, suggesting that chromosomal mutations in QRDR regions to be the major contributing factor for quinolone resistance in P. aeruginosa under investigation.

Pseudomonas aeruginosa biofilms limit the efficacy of currently available antibacterial therapies and pose significant clinical challenges. Pseudomonal biofilms are complicated further when other markers of persistence such as mucoid and hypermutable phenotypes are present. There is currently a paucity of data regarding the activity of the newer β-lactam/β-lactamase inhibitor combination ceftolozane/tazobactam against P. aeruginosa biofilms.

We evaluated the efficacy of ceftolozane/tazobactam against clinical P. aeruginosa isolates, the laboratory isolate PAO1 and its isogenic mutS-deficient hypermutator derivative (PAOMS) grown under static and dynamic biofilm conditions. The clinical isolate collection included strains with mucoid and hypermutable phenotypes.

Ceftolozane/tazobactam exposure led to a bactericidal (≥3 log cfu/cm2) biofilm reduction in 15/18 (83%) clinical isolates grown under static conditions, irrespective of carbapenem susceptibility or mucoid phenotype, with greater activity compared with colistin (P < 0.05). Dynamically grown biofilms were less susceptible to ceftolozane/tazobactam with active biofilm reduction (≥1 log cfu/cm2) observed in 2/3 isolates. Hypermutability did not affect the antibiofilm efficacy of ceftolozane/tazobactam in either static or dynamic conditions when comparing PAO1 and PAOMS. Consistent with the activity of ceftolozane/tazobactam as a potent inhibitor of PBP3, dramatic impacts on P. aeruginosa morphology were observed.

Our data demonstrate that ceftolozane/tazobactam has encouraging properties in the treatment of P. aeruginosa biofilm infections, and its activity is not diminished against mucoid or hypermutable variants at the timepoints examined.

Infected wounds, refractory to conventional therapy, are a major burden on the healthcare system. Available data show that many commonly used antiseptic agents may be toxic to the cells involved in the healing process and may affect the normal tissue repair. The topical use of different acids to control wound infections effectively and promote healing is well known. The present review aims to summarise the safety and efficacy of various acids as topical agents for treating wound infections.

A literature search was performed in PubMed and manually from other sources (cross references and journal sites).

We reviewed 116 articles, from which data from 86 relevant articles were analysed. The studies showed that various organic acids were clinically effective in treating wound infections.

This study found that various organic acids can act as a substitute for antiseptics to control wound infections refractory to conventional antibiotic therapy and local wound care. Various organic acids differ in efficacy, safety and limitations as topical agents to control wound infections and promote healing. Some acids deliver better results than others, particularly in those cases in which antibiotics and routine antiseptic agents yield little lasting success, especially in controlling hospital strains with multiple antibiotic resistance. Among topically used acids, citric acid and acetic acid are associated with better results.

Respiratory tract infections (RTIs) are one of the leading causes of morbidity and mortality worldwide. The increase in antimicrobial resistance in respiratory pathogens poses a major challenge to the effective management of these infections.

To investigate the distribution of major pathogens of RTIs and their antimicrobial resistance patterns in a tertiary care hospital and to develop a mathematical model to explore the relationship between pathogen distribution and antimicrobial resistance.

Five hundred patients with RTIs were included in the study and 475 bacterial strains were isolated from their respiratory specimens. Antimicrobial susceptibility testing and analysis of influencing factors were performed. A mathematical model was developed to simulate the relationship between pathogen distribution and drug resistance.

The most common pathogens were Streptococcus pneumoniae (30%), Haemophilus influenzae (20%), Pseudomonas aeruginosa (15%), Staphylococcus aureus (10%) and Klebsiella pneumoniae (10%). The distribution of pathogens varied according to age group and type of RTIs, with higher proportions of Pseudomonas aeruginosa and Staphylococcus aureus in hospital-acquired and ventilator-associated pneumonia. Isolated pathogens showed high and increasing rates of resistance to commonly used antibiotics. Model simulations suggest that a shift in the distribution of pathogens toward more resistant strains may lead to a significant increase in overall resistance rates, even if antibiotic use patterns remain unchanged.

This study emphasizes the importance of regular monitoring of respiratory pathogen distribution and antimicrobial resistance patterns and the need for a comprehensive approach to managing RTIs, including implementation of antibiotic stewardship programs, infection control measures, and development of new therapies.

We investigated the drug resistance status of Pseudomonas aeruginosa (P. aeruginosa) focusing on its isolation sites and types of diseases.　Materials and methods: A microbiological laboratory database was searched to identify all clinical cultures positive for P. aeruginosa.　Clinicopathologic features and susceptibility of P. aeruginosa to any antibiotics were evaluated in patients admitted to the division of upper (Upper-GI group) or lower gastrointestinal surgery (Lower-GI group).　In addition, we investigated the susceptibility of P. aeruginosa to any antibiotics based on the isolation site.　Results:P. aeruginosa was frequently detected in the sputum and urine of the Upper-GI and Lower-GI groups, respectively.　Among P. aeruginosa isolates from drain discharge, a significantly higher rate of resistance to imipenem, amikacin, and ciprofloxacin was observed; among P. aeruginosa isolates from wounds, a substantially higher proportion had resistance to imipenem and cefozopran in the Upper-GI group.　However, there was no difference between the two groups in the drug resistance of P. aeruginosa isolated from urine, sputum, blood, and ascites.　P. aeruginosa isolated from sputum showed more resistance to imipenem and ciprofloxacin than those isolated from other sites.　Conclusion: There were significant differences in the drug resistance of P. aeruginosa based on the isolation sites and types of diseases.　.

<b>Background and Objective:</b> It is well documented that Whole Genome Sequencing (WGS) has recently used to explore new resistance patterns and track the dissemination of extensive and pan drug-resistant microbes in healthcare settings. This article explores the link between traumatic infections caused by road traffic accidents (RTAs) leading to coma and the development of chest infections caused by extensively drug-resistant (XDR) <i>Klebsiella pneumoniae</i> and <i>Pseudomonas aeruginosa</i>. <b>Materials and Methods:</b> The study was carried out from March to December 2022 which included a 45-year-old male patient admitted to the ICU of Al Ramadi Teaching Hospitals following a severe RTA that resulted in a TBI and subsequent coma. Two study isolates were diagnosed bacteriologically using the VITEK^®-2 technique including resistant mechanisms like extended-spectrum beta-lactamases and carbapenemases. Whole genome sequencing was performed using a DNA nanoball sequencing platform from BGI-Tech. Genome assembly and annotation were done using the bacterial bioinformatics resource center. The report on Comprehensive Genome Analysis includes a phylogenetic analysis using the reference and representative genomes provided by PATRIC. <b>Results:</b> <i>Klebsiella pneumoniae</i> and <i>P. aeruginosa</i> isolates were XDR, producing ESBLs and carbapenemases. The WGS detection NDM-5 gene in the <i>K. pneumoniae</i> strain is not very common compared to the NDM-1 and blaOXA-181 g. At the same time, a file in <i>P. aeruginosa</i> isolate found genes GES-type ESBL (not reported in Iraq before), blaPAO and blaOXA-396 with NDM-1 all these genes are carbapenemases. In phylogenetic analysis, the <i>K. pneumoniae</i> isolate has an evolutionary relationship with strains originating from China while <i>P. aeruginosa</i> was globally unique. <b>Conclusion:</b> The XDR <i>K. pneumoniae</i> and <i>P. aeruginosa</i> pose a public health threat. The WGS revealed unique virulence and antibiotic-resistance genes associated with nosocomial outbreaks. The XDR isolates carrying NDM-5, blaOXA-181 and GES-type ESBL genes were detected.

The increasing drug resistance of Pseudomonas aeruginosa (PA) poses a serious challenge to the current treatment. Antibiograms of this pathogen often take 3-5 days, and treatment of Pseudomonas aeruginosa keratitis (PAK) is mainly based on preliminary physical examination, clinical experience, and medical guidelines. Pertinent clinical data on the causative agent and antibiotics for high efficacy are essential for early recognition and subsequent treatment.

To report the etiology, risk factors, treatment outcomes, antibiotic susceptibilities, and trends of PAK.

This retrospective study included culture-proven PAK cases at the Ho Chi Minh City Eye Hospital Cornea Department between January 2018 and December 2022. Culture results showing coinfection were excluded from the study.

Among 154 eyes infected by PA (n = 154) of 154 patients, ocular trauma was the leading risk factor (53.2%); only 16 patients had contact lenses (10.4%). Among the 154 eyes, 102/154 required surgical intervention (66.2%); and 31/154 eyes required evisceration (20.1%). PA was sensitive to tobramycin (95.9%), ciprofloxacin (91.9%), levofloxacin (91.9%), ofloxacin (87.4%), and moxifloxacin (20.0%). The prevalence of multidrug resistance (MDR) was 31.8%, and extensive drug resistance (XDR) was 3.9%. Poor outcomes (need for surgical intervention or final visual acuity ≤ CF 3 m) included age > 50 years, ocular surface diseases, deep infiltrate, large infiltrate size ≥ 5 mm, and ring infiltrate (p < 0.05).

PAK, which is associated with increasing drug resistance, poses significant challenges in terms of treatment, with 66.2% of patients requiring surgical intervention. With the rapid progression of PAK, early treatment with broad-spectrum and effective antibiotics is necessary. However, future research should focus on new methods to enhance treatment effectiveness.

Sphingobium sp. SM42 Esterase B (EstB) is an enzyme with a dual function in degrading dibutyl phthalate and catalyzing the cleavage of the C-S bond in C3-sidechains of the dihydrothiazine ring of cephalosporins, generating more active β-lactam derivatives. Global prokaryotic genome analysis revealed the existence of a gene identical to estB in Pseudomonas aeruginosa strain PS1 suggesting a horizontal gene transfer event involving estB. To investigate the effect of ectopic expression of EstB in the periplasm of P. aeruginosa and several Enterobacteriaceae on antibiotic susceptibility levels, plasmid, pEstB, carrying a recombinant EstB fused with the signal peptide from Escherichia coli outer membrane protein A (OmpA) for periplasmic localization was constructed. The expression of EstB in the periplasm of P. aeruginosa and the Enterobacteriaceae: E. coli, Klebsiella pneumoniae, and Salmonella enterica serovar Typhi, increased susceptibility to carbapenems and cephalosporins. EstB reversed the imipenem resistance of P. aeruginosa ΔmexS and restored the changes in susceptibility to cephalosporins conferred by the downregulation of the outer membrane proteins, OmpK35 and OmpK36, in K. pneumoniae ΔramR-ompK36 to wild-type level. The introduction of EstB to the periplasmic space of Gram-negative bacteria can increase carbapenem and cephalosporin susceptibility.

Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a life-threatening infection with limited treatment options. This is the first meta-analysis of recently published data to compare the clinical outcomes of ceftazidime-avibactam (CAZ-AVI) with other antimicrobial agents in treating MDR-PA infections.

Systematic review and meta-analysis.

PubMed, Embase and the Cochrane Library have been systematically reviewed, for publications in the English language, from database inception to July 2023.

Studies comparing CAZ-AVI outcomes with other antimicrobial agents were included. In-hospital mortality & 30-day mortality were assessed as the main outcomes.

Literature screening, data extraction, and the quality evaluation of studies were conducted by two researchers independently, with disagreements resolved by another researcher. The Newcastle-Ottawa Scale was used to assess the bias risk for the included studies. Review Manager V.5.4 was employed for the meta-analysis.

The meta-analysis included four retrospective studies, enrolling 1934 patients. The CAZ-AVI group demonstrated significantly lower in-hospital mortality (risk ratio (RR) = 0.60, 95% CI:0.37-0.97, I2 = 74%, p = 0.04) in three studies with 1444 patients and lower 30-day mortality, in 438 patients from three studies (RR = 0.54, 95% CI:0.28-1.05, I2 = 67%, p = 0.07). No significant difference in clinical success, microbiological success, length of hospital, and ICU stay was observed.

This meta-analysis demonstrated that CAZ-AVI treatment significantly lowered in-hospital mortality compared with other antimicrobial agents in MDR-PA infections. However, the analysis only included a few observational studies and high-quality, randomized controlled trials are needed to investigate further the scope of CAZ-AVI in MDR-PA  infections.

Pseudomonas aeruginosa is a major global threat to human health, and phage therapy has emerged as a promising strategy for treating infections caused by multidrug-resistant pathogens. In this study, we isolated and characterized a Pseudomonas lytic phage, PaTJ, from wastewater. PaTJ belongs to the phage family Mesyanzhinovviridae, and is featured by short latency (30 min) and large burst size (103 PFU per infected cell). Our investigation revealed that PaTJ utilizes the type IV Pili (T4P) as a receptor. Transcriptome analysis of PaTJ infected host at latent stage showed distinct expression patterns of PaTJ encoding genes involved in replication and structure assembly, without expression of the majority of toxic accessory genes responsible for phage release. In addition, host bacteria exhibited specific induction of host metabolism-related genes in response to the PaTJ's infection. Furthermore, our findings demonstrated the PaTJ's potential in degrading biofilms. This work sheds light on the multifaceted impact of this lytic phage PaTJ on P. aeruginosa, presenting potential applications in both gene expression modulation and biofilm management.

Antibiotics targeting the bacterial ribosome are essential to combating bacterial infections. These antibiotics bind to various sites on the ribosome, inhibiting different stages of protein synthesis. This review provides a comprehensive overview of the mechanisms of action of clinically relevant antibiotics that target the bacterial ribosome, including macrolides, lincosamides, oxazolidinones, aminoglycosides, tetracyclines, and chloramphenicol. The structural and functional details of antibiotic interactions with ribosomal RNA, including specific binding sites, interactions with rRNA nucleotides, and their effects on translation processes, are discussed. Focus is placed on the diversity of these mechanisms and their clinical implications in treating bacterial infections, particularly in the context of emerging resistance. Understanding these mechanisms is crucial for developing novel therapeutic agents capable of overcoming bacterial resistance.

Rapid development of antibiotic resistance in pathogenic bacteria and a decline in the pharmaceutical development of new antibiotics are pushing the research community to explore alternative antimicrobials that can replace or complement antibiotics. Bacteriophages (or, phages) are naturally occurring viruses that can kill bacteria with high specificity and can evolve to target resistant bacteria. Phages have been historically employed as antimicrobial agents, but they were overshadowed by the emergence of antibiotics. With a renewed focus on phages, it is important to study their clinical efficacy, safety, and formulation. Pulmonary infections have a large burden of global morbidity and frequently involve multidrug-resistant pathogens such as Acinetobacter baumannii, Klebsiella pneumoniae, Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Therefore, this can be an important area of application of phages. Dry powder inhalers can be an effective strategy to deliver phages to the lungs because they are easy-to-use, portable, and capable of delivering a higher lung dose than oral or intravenous route. They also have longer shelf life and lower cold storage requirements than solutions. Therefore, the aim of the current review is to summarize recent findings on bacteriophage dry powder formulations, particularly focusing on the effect of various excipients and manufacturing factors on phage titer preservation.

New β-lactam-β-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 β-lactam resistance mechanisms of CZA-resistant (CZAR) isolates. A total of 120 P. aeruginosa isolates were collected. CZA was among the most active β-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-β-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-β-lactamases (66.6% VIM-type and 5.5% FIM-1), followed by PER-1 (16.6%) and GES-1 (5.5%) extended-spectrum β-lactamases, mostly carried by international high-risk clones (ST111 and ST235). Of note, two strains producing the PER-1 enzyme were resistant to all β-lactams, including cefiderocol. In conclusion, the CZA resistance rate among P. aeruginosa clinical isolates in Southern Italy remained low. CZAR isolates were mostly metallo-β-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.

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 β-lactamase genes is increasing. With this work, we report that CZA represents a highly active antipseudomonal β-lactam compound (after cefiderocol), and that metallo-β-lactamases (VIM-type) and extended-spectrum β-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.

Antimicrobial resistance is a pressing concern that poses a significant threat to global public health, necessitating the exploration of alternative strategies to combat drug-resistant microbial infections. Recently, antimicrobial peptides (AMPs) have gained substantial attention as possible replacements for conventional antibiotics. Because of their pharmacodynamics and killing mechanisms, AMPs display a lower risk of bacterial resistance evolution compared with most conventional antibiotics. However, bacteria display different mechanisms to resist AMPs, and the role of metabolic pathways in the resistance mechanism is not fully understood. This review examines the intricate relationship between metabolic genes and AMP resistance, focusing on the impact of metabolic pathways on various aspects of resistance. Metabolic pathways related to guanosine pentaphosphate (pppGpp) and guanosine tetraphosphate (ppGpp) [collectively (p)ppGpp], the tricarboxylic acid (TCA) cycle, haem biosynthesis, purine and pyrimidine biosynthesis, and amino acid and lipid metabolism influence in different ways metabolic adjustments, biofilm formation and energy production that could be involved in AMP resistance. By targeting metabolic pathways and their associated genes, it could be possible to enhance the efficacy of existing antimicrobial therapies and overcome the challenges exhibited by phenotypic (recalcitrance) and genetic resistance toward AMPs. Further research in this area is needed to provide valuable insights into specific mechanisms, uncover novel therapeutic targets, and aid in the fight against antimicrobial resistance.

The prevalence of antibiotic-resistant pathogens has become a major threat to public health, requiring swift initiatives for discovering new strategies to control bacterial infections. Hence, antibiotic stewardship and rapid diagnostics, but also the development, and prudent use, of novel effective antimicrobial agents are paramount. Ideally, these agents should be less likely to select for resistance in pathogens than currently available conventional antimicrobials. The usage of antimicrobial peptides (AMPs), key components of the innate immune response, and combination therapies, have been proposed as strategies to diminish the emergence of resistance. Herein, we investigated whether newly developed random antimicrobial peptide mixtures (RPMs) can significantly reduce the risk of resistance evolution in vitro to that of single sequence AMPs, using the ESKAPE pathogen Pseudomonas aeruginosa (P. aeruginosa) as a model gram-negative bacterium. Infections of this pathogen are difficult to treat due the inherent resistance to many drug classes, enhanced by the capacity to form biofilms. P. aeruginosa was experimentally evolved in the presence of AMPs or RPMs, subsequentially assessing the extent of resistance evolution and cross-resistance/collateral sensitivity between treatments. Furthermore, the fitness costs of resistance on bacterial growth were studied and whole-genome sequencing used to investigate which mutations could be candidates for causing resistant phenotypes. Lastly, changes in the pharmacodynamics of the evolved bacterial strains were examined. Our findings suggest that using RPMs bears a much lower risk of resistance evolution compared to AMPs and mostly prevents cross-resistance development to other treatments, while maintaining (or even improving) drug sensitivity. This strengthens the case for using random cocktails of AMPs in favour of single AMPs, against which resistance evolved in vitro, providing an alternative to classic antibiotics worth pursuing.

The transcription factor PsrA regulates fatty acid metabolism, the type III secretion system, and quinolone signaling quorum sensing system in Pseudomonas aeruginosa. To explore additional roles of PsrA in P. aeruginosa, this study engineered a P. aeruginosa PAO1 strain to carry a recombinant plasmid with the psrA gene (pMMBpsrA) and examined the impact of elevated psrA expression to the bacterium. Transcriptomic analysis revealed that PsrA significantly downregulated genes encoding the master quorum-sensing regulators, RhlR and LasR, and influenced many quorum-sensing-associated genes. The role of PsrA in quorum sensing was further corroborated by testing autoinducer synthesis in PAO1 [pMMBpsrA] using two reporter bacteria strains Chromobacterium violaceum CV026 and Escherichia coli [pSB1075], which respond to short- and long-chain acyl homoserine lactones, respectively. Phenotypic comparisons of isogenic ΔpsrA, ΔlasR, and ΔpsrAΔlasR mutants revealed that the reduced elastase, caseinase, and swarming activity in PAO1 [pMMBpsrA] were likely mediated through LasR. Additionally, electrophoretic mobility shift assays demonstrated that recombinant PsrA could bind to the lasR promoter at a 5'-AAACGTTTGCTT-3' sequence, which displays moderate similarity to the previously reported consensus PsrA binding motif. Furthermore, the PsrA effector molecule oleic acid inhibited PsrA binding to the lasR promoter and restored several quorum sensing-related phenotypes to wild-type levels. These findings suggest that PsrA regulates certain quorum-sensing phenotypes by negatively regulating lasR expression, with oleic acid acting as a crucial signaling molecule.

Studies on bioaerosol bacterial biodiversity have relevance in both ecological and health contexts, and molecular methods, such as 16S rRNA gene-based barcoded sequencing, provide efficient tools for the analysis of airborne bacterial communities. Standardized methods for sampling and analysis of bioaerosol DNA are lacking, thus hampering the comparison of results from studies implementing different devices and procedures. Three samplers that use gelatin filtration, swirling aerosol collection, and condensation growth tubes for collecting bioaerosol at an aeration tank of a wastewater treatment plant in Trieste (Italy) were used to determine the bacterial biodiversity. Wastewater samples were collected directly from the untreated sewage to obtain a true representation of the microbiological community present in the plant. Different samplers and collection media provide an indication of the different grades of biodiversity, with condensation growth tubes and DNA/RNA shieldTM capturing the richer bacterial genera. Overall, in terms of relative abundance, the air samples have a lower number of bacterial genera (64 OTUs) than the wastewater ones (75 OTUs). Using the metabarcoding approach to aerosol samples, we provide the first preliminary step toward the understanding of a significant diversity between different air sampling systems, enabling the scientific community to orient research towards the most informative sampling strategy.

Due to technological and economic limitations, waste products such as sewage and manure generated in livestock farming lack comprehensive scientific and centralized treatment. This leads to the exposure of various contaminants in livestock wastewater, posing potential risks to both the ecological environment and human health. This review evaluates the environmental and physical health risks posed by common pollutants in livestock wastewater and outlines future treatment methods to mitigate these risks. Residual wastes in livestock wastewater, including pathogenic bacteria and parasites surviving after epidemics or diseases on various farms, along with antibiotics, organic wastes, and heavy metals from farming activities, contribute to environmental damage and pose risks to human health. As the livestock industry's development increasingly impacts society's future negatively, addressing the issue of residual wastes in livestock wastewater discharge becomes imperative. Ongoing advancements in wastewater treatment systems are consistently updating and refining practices to effectively minimize waste exposure at the discharge source, mitigating risks to environmental ecology and human health. This review not only summarizes the "potential risks of livestock wastewater" but also explores "the prospects for the development of wastewater treatment technologies" based on current reports. It offers valuable insights to support the long-term and healthy development of the livestock industry and contribute to the sustainable development of the ecological environment.

Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.

The rise in infections caused by multidrug-resistant (MDR) bacteria has necessitated a variety of clinical approaches, including the use of antibiotic combinations. Here, we tested the hypothesis that drug-drug interactions vary in different media, and determined which in vitro models best predict drug interactions in the lungs. We systematically studied pair-wise antibiotic interactions in three different media, CAMHB, (a rich lab medium standard for antibiotic susceptibility testing), a urine mimetic medium (UMM), and a minimal medium of M9 salts supplemented with glucose and iron (M9Glu) with three Gram-negative ESKAPE pathogens, Acinetobacter baumannii (Ab), Klebsiella pneumoniae (Kp), and Pseudomonas aeruginosa (Pa). There were pronounced differences in responses to antibiotic combinations between the three bacterial species grown in the same medium. However, within species, PaO1 responded to drug combinations similarly when grown in all three different media, whereas Ab17978 and other Ab clinical isolates responded similarly when grown in CAMHB and M9Glu medium. By contrast, drug interactions in Kp43816, and other Kp clinical isolates poorly correlated across different media. To assess whether any of these media were predictive of antibiotic interactions against Kp in the lungs of mice, we tested three antibiotic combination pairs. In vitro measurements in M9Glu, but not rich medium or UMM, predicted in vivo outcomes. This work demonstrates that antibiotic interactions are highly variable across three Gram-negative pathogens and highlights the importance of growth medium by showing a superior correlation between in vitro interactions in a minimal growth medium and in vivo outcomes.

Drug-resistant bacterial infections are a growing concern and have only continued to increase during the SARS-CoV-2 pandemic. Though not routinely used for Gram-negative bacteria, drug combinations are sometimes used for serious infections and may become more widely used as the prevalence of extremely drug-resistant organisms increases. To date, reliable methods are not available for identifying beneficial drug combinations for a particular infection. Our study shows variability across strains in how drug interactions are impacted by growth conditions. It also demonstrates that testing drug combinations in tissue-relevant growth conditions for some strains better models what happens during infection and may better inform combination therapy selection.

In recent years, antimicrobial drug resistance has emerged as a serious global public health concern, according to the World Health Organization data. The emergence of pathogens resistant to multiple drugs has been linked to an increase in morbidity and mortality from microbial infections. The study's main goal is to explore the efficacy of using Solanum xanthocarpum in the green synthesis of molybdenum nanoparticles (Mo NPs) for antibacterial and antioxidant properties.

An eco-friendly method of synthesizing Mo NPs was accomplished using an aqueous extract of Solanum xanthocarpum. Characterization of the synthesized nanoparticles was done by UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). After that, antibacterial and antioxidant activity was further evaluated.

The UV-visible spectrophotometer analysis confirmed the presence of synthesized Mo NPs showing a peak around 320 nm. The presence of functional compounds like C-CI, C-H, C=C, and O=C=O was confirmed by FT-IR spectrum analysis. The positions of diffraction peaks in Mo NP patterns were identified using XRD analysis; they were more crystalline (82.7%) and less amorphous (17.3%). The presence of the elements molybdenum (Mo), carbon (C), and oxygen (O) was confirmed by the EDX spectrum and irregular shapes shown in the SEM images. Further, the antimicrobial study results showed the formation of an inhibition zone against 27 mm for Klebsiella pneumoniae, 24 mm for Pseudomonas aeruginosa, 22 mm for Staphylococcus aureus, and 24 mm for Enterococcus faecalis, respectively, at a high concentration 80 μg/ml of Mo NPs. The maximum antioxidant activity at 100 μg/ml was 73.49%, compared to the standard ascorbic acid (74.25%). Additionally, the moderate activity at 60 μg/ml was 53.21%, compared to the standard (56.5%), and the minimal activity at 20 μg/ml was 30.21%, compared to the standard (36.89%).

The environmentally friendly synthesized Mo NPs from Solanum xanthocarpum exhibited antioxidant activity. Furthermore, the findings show that Mo NPs mediated by Solanum xanthocarpum can inhibit antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis. In order to understand further how nanoparticles work against bacteria that are resistant to many drugs, additional research and clinical studies would be needed.

Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % fT>MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% fT>MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02-245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target fT>MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%.

Pseudomonas aeruginosa is a common cause of urinary tract infections by strains that are often multidrug resistant, representing a major challenge to the world's health care system. This microorganism has a highly adaptable metabolism that allows it to colonize many environments, including the urinary tract. In this work, we have characterized the metabolic strategies used by stationary phase P. aeruginosa cells cultivated in urine-like media to understand the adaptations used by this microorganism to survive and produce disease. Our proteomics results show that cells rely on the Entner-Duodoroff pathway, pentose phosphate pathway, the Krebs cycle/ glyoxylate shunt and the aerobic oxidative phosphorylation to survive in urine-like media and other conditions. A deep characterization of the oxidative phosphorylation showed that the respiratory rate of stationary phase cells is increased 3-4 times compared to cells in the logarithmic phase of growth, indicating that the aerobic metabolism plays critical roles in the stationary phase of cells grown in urine like media. Moreover, the data show that respiratory complex III, succinate dehydrogenase and the NADH dehydrogenase NQR have important functions and could be used as targets to develop new antibiotics against this bacterium.

Hospital-acquired pneumonia (HAP) is a leading cause of morbidity and mortality, commonly caused by Pseudomonas aeruginosa. Meropenem is a commonly used therapeutic agent, although emergent resistance occurs during treatment. We used a rabbit HAP infection model to assess the bacterial kill and resistance pharmacodynamics of meropenem. Meropenem 5 mg/kg administered subcutaneously (s.c.) q8h (±amikacin 3.33-5 mg/kg q8h administered intravenously[i.v.]) or meropenem 30 mg/kg s.c. q8h regimens were assessed in a rabbit lung infection model infected with P. aeruginosa, with bacterial quantification and phenotypic/genotypic characterization of emergent resistant isolates. The pharmacokinetic/pharmacodynamic output was fitted to a mathematical model, and human-like regimens were simulated to predict outcomes in a clinical context. Increasing meropenem monotherapy demonstrated a dose-response effect to bacterial kill and an inverted U relationship with emergent resistance. The addition of amikacin to meropenem suppressed the emergence of resistance. A network of porin loss, efflux upregulation, and increased expression of AmpC was identified as the mechanism of this emergent resistance. A bridging simulation using human pharmacokinetics identified meropenem 2 g i.v. q8h as the licensed clinical regimen most likely to suppress resistance. We demonstrate an innovative experimental platform to phenotypically and genotypically characterize bacterial emergent resistance pharmacodynamics in HAP. For meropenem, we have demonstrated the risk of resistance emergence during therapy and identified two mitigating strategies: (i) regimen intensification and (ii) use of combination therapy. This platform will allow pre-clinical assessment of emergent resistance risk during treatment of HAP for other antimicrobials, to allow construction of clinical regimens that mitigate this risk.IMPORTANCEThe emergence of antimicrobial resistance (AMR) during antimicrobial treatment for hospital-acquired pneumonia (HAP) is a well-documented problem (particularly in pneumonia caused by Pseudomonas aeruginosa) that contributes to the wider global antimicrobial resistance crisis. During drug development, regimens are typically determined by their sufficiency to achieve bactericidal effect. Prevention of the emergence of resistance pharmacodynamics is usually not characterized or used to determine the regimen. The innovative experimental platform described here allows characterization of the emergence of AMR during the treatment of HAP and the development of strategies to mitigate this. We have demonstrated this specifically for meropenem-a broad-spectrum antibiotic commonly used to treat HAP. We have characterized the antimicrobial resistance pharmacodynamics of meropenem when used to treat HAP, caused by initially meropenem-susceptible P. aeruginosa, phenotypically and genotypically. We have also shown that intensifying the regimen and using combination therapy are both strategies that can both treat HAP and suppress the emergence of resistance.

Pseudomonas aeruginosa (Pa), a WHO priority 1 pathogen, resulted in approximately 559,000 deaths globally in 2019. Pa has a multitude of host-immune evasion strategies that enhance Pa virulence. Most clinical isolates of Pa are infected by a phage called Pf that has the ability to misdirect the host-immune response and provide structural integrity to biofilms. Previous studies demonstrate that vaccination against the coat protein (CoaB) of Pf4 virions can assist in the clearance of Pa from the dorsal wound model in mice. Here, a consensus peptide was derived from CoaB and conjugated to cross-reacting material 197 (CRM197). This conjugate was adjuvanted with a novel synthetic Toll-like receptor agonist (TLR) 4 agonist, INI-2002, and used to vaccinate mice. Mice vaccinated with CoaB-CRM conjugate and INI-2002 developed high anti-CoaB peptide-specific IgG antibody titers. Direct binding of the peptide-specific antibodies to whole-phage virus particles was demonstrated by ELISA. Furthermore, a functional assay demonstrated that antibodies generated from vaccinated mice disrupted the replicative cycle of Pf phages. The use of an adjuvanted phage vaccine targeting Pa is an innovative vaccine strategy with the potential to become a new tool targeting multi-drug-resistant Pa infections in high-risk populations.

Bacterial colonization and biofilm formation on abiotic surfaces are initiated by the adhesion of peptides and proteins. Understanding the adhesion of such peptides and proteins at a molecular level thus represents an important step toward controlling and suppressing biofilm formation on technological and medical materials. This study investigates the molecular adhesion of a pilus-derived peptide that facilitates biofilm formation of Pseudomonas aeruginosa, a multidrug-resistant opportunistic pathogen frequently encountered in healthcare settings. Single-molecule force spectroscopy (SMFS) was performed on chemically etched ZnO11 2 ‾ 0 ${\left(11\bar{2}0\right)}$ surfaces to gather insights about peptide adsorption force and its kinetics. Metal-free click chemistry for the fabrication of peptide-terminated SMFS cantilevers was performed on amine-terminated gold cantilevers and verified by X-ray photoelectron spectroscopy (XPS) and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Atomic force microscopy (AFM) and XPS analyses reveal stable topographies and surface chemistries of the substrates that are not affected by SMFS. Rupture events described by the worm-like chain model (WLC) up to 600 pN were detected for the non-polar ZnO surfaces. The dissociation barrier energy at zero force ΔG(0), the transition state distance xb and bound-unbound dissociation rate at zero force koff (0) for the single crystalline substrate indicate that coordination and hydrogen bonds dominate the peptide/surface interaction.

Carbapenem-resistant Pseudomonas aeruginosa (CrPA) is a leading cause of healthcare-associated urinary tract infections (UTIs). Carbapenemase production is an important mechanism that significantly alters the efficacy of frequently used anti-pseudomonal agents. Reporting the current genotypic distribution of carbapenemase-producing P. aeruginosa (CPPA) isolates in relation to antimicrobial susceptibility, UTI risk factors, and mortality is necessary to increase the awareness and control of these strains.

In total, 1,652 non-duplicated P. aeruginosa strains were isolated from hospitalized patients between 2015 and 2020. Antimicrobial susceptibility, carbapenemase genotypes, risk factors for UTI, and associated mortality were analyzed.

The prevalence of carbapenem-non-susceptible P. aeruginosa isolates showed a decreasing trend from 2015 to 2018 and then increased in the background of the emergence of New Delhi metallo-β-lactamase (NDM)-type isolates since 2019. The CPPA strains showed 100.0% non-susceptibility to all tested antibiotics, except aztreonam (94.5%) and colistin (5.9%). Carbapenems were identified as a risk and common predisposing factor for UTI (odds ratio [OR]=1.943) and mortality (OR=2.766). Intensive care unit (ICU) stay (OR=2.677) and white blood cell (WBC) count (OR=1.070) were independently associated with mortality.

The changing trend and genetic distribution of CPPA isolates emphasize the need for relentless monitoring to control further dissemination. The use of carbapenems, ICU stay, and WBC count should be considered risk factors, and aggressive antibiotic stewardship programs and monitoring may serve to prevent worse outcomes.

With increasing resistance to conventional antibiotic treatments, especially among gram-negative bacilli, the search for new antibiotics has become critical on a global scale. Among infections with multidrug-resistant bacteria is hospital-acquired pneumonia (HAP), which is nosocomial pneumonia in patients who have been hospitalized for more than 48 hours. HAP carries a high mortality rate and continues to be a challenge with regard to adequate treatment. The typical multidrug-resistant gram negatives found in HAP include Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Many new antibiotics have been studied and tested against these pathogens as possible solutions, and the search continues. Cefiderocol, a novel siderophore cephalosporin, is effective against these pathogens. Cefiderocol is an iron-chelating agent that makes use of iron pumps on the membrane of bacteria via a catechol moiety on the C3 side chain of the molecule. This allows for easy access into the cytoplasm, where it can inhibit peptidoglycan synthesis by binding to penicillin-binding proteins. Cefiderocol displays linear pharmacokinetics and is mainly excreted through the kidneys. It is well tolerated in healthy individuals but may need adjustments of dosage in patients with impaired renal function. Studies have shown that both healthy subjects and those with impaired renal function experienced some adverse effects, including nausea, diarrhea, abdominal pain, and increased creatinine kinase; however, these adverse effects were limited and experienced in placebo groups. It has demonstrated efficacy in treating infections caused by many multidrug-resistant gram-negative pathogens and has demonstrated high stability against many classes of b-lactamases. There have been multiple phase 3 trials, such as the CREDIBLE-CR trial and the APEKS-NP trial, that demonstrated efficacy in treated nosocomial pneumonia caused by multidrug-resistant gram negatives, such as carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, compared to the best available treatment. While clinical data remain limited, a few studies are showing clinical efficacy and few adverse effects. Cefiderocol demonstrated effectivity in treating multidrug-resistant gram-negative pneumonia in patients with multiple comorbidities, such as chronic kidney disease, chronic-obstructive pulmonary disease, and diabetes mellitus. Cefiderocol shows promise as a novel antimicrobial agent in treating multidrug-resistant gram-negative in HAP.

Changes in expression levels of drug efflux pump genes, mexB and mexY, and porin gene oprD in Pseudomonas aeruginosa were investigated in this study. Fifty-five multidrug-resistant P. aeruginosa (MDRP) strains were compared with 26 drug-sensitive strains and 21 strains resistant to a single antibiotic. The effect of the efflux inhibitor Phe-Arg-β-naphthylamide on drug susceptibility was determined, and gene expression was quantified using real-time quantitative real-time reverse transcription polymerase chain reaction. In addition, the levels of metallo-β-lactamase (MBL) and 6'-N-aminoglycoside acetyltransferase [AAC(6')-Iae] were investigated. Efflux pump inhibitor treatment increased the sensitivity to ciprofloxacin, aztreonam, and imipenem in 71%, 73%, and 29% of MDRPs, respectively. MBL and AAC(6')-Iae were detected in 38 (69%) and 34 (62%) MDRP strains, respectively. Meanwhile, 76% of MDRP strains exhibited more than 8-fold higher mexY expression than the reference strain PAO1. Furthermore, 69% of MDRP strains expressed oprD at levels less than 0.01-fold of those in PAO1. These findings indicated that efflux pump inhibitors in combination with ciprofloxacin or aztreonam might aid in treating MDRP infections.

Infections caused by antimicrobial-resistant (AMR) pathogens are increasing worldwide, representing a serious global public health issue with high morbidity and mortality rates The treatment of Pseudomonas aeruginosa (PA) infections has become a significant challenge due to its ability to develop resistance to many of the currently available antibiotics, especially in intensive care unit (ICU) settings. Among the very few therapeutic lines available against extensively drug-resistant (XDR)-PA and/or with difficult-to-treat resistance (DTR)-PA, cefiderocol is an injectable siderophore cephalosporin not licensed for use in pediatric patients. There are only a few case reports and two ongoing trials describing the administration of this cephalosporin in infants.

This report describes the case of a critically ill 8-month-old girl affected by ventilator-associated pneumonia (VAP) infection complicated by bloodstream infection (BSI) sustained by VIM-producing PA. She was treated with cefiderocol as a salvage therapy during ECMO and CRRT support.

In healthcare settings, treating multidrug-resistant, Gram-negative bacteria poses a serious challenge, especially in pediatric patients. Our findings suggest that cefiderocol can be considered as an off-label rescue therapy in selected pediatric cases.

Bacteria possess a diverse range of mechanisms for inhibiting competitors, including bacteriocins, tailocins, type VI secretion systems and contact-dependent inhibition (CDI). Why bacteria have evolved such a wide array of weapon systems remains a mystery. Here we develop an agent-based model to compare short-range weapons that require cell-cell contact, with long-range weapons that rely on diffusion. Our model predicts that contact weapons are useful when an attacking strain is outnumbered, facilitating invasion and establishment. By contrast, ranged weapons tend to be effective only when attackers are abundant. We test our predictions with the opportunistic pathogen Pseudomonas aeruginosa, which naturally carries multiple weapons, including CDI and diffusing tailocins. As predicted, short-range CDI can function at low and high frequencies, while long-range tailocins require high frequency and cell density to function effectively. Head-to-head competition experiments with the two weapon types further support our predictions: a tailocin attacker defeats CDI only when it is numerically dominant, but then we find it can be devastating. Finally, we show that the two weapons work well together when one strain employs both. We conclude that short- and long-range weapons serve different functions and allow bacteria to fight both as individuals and as a group.

Gram-negative bacteria are infectious and life-threatening agents after hematopoietic stem cell transplantation (HSCT). So, this study aimed to investigate the prevalence of Pseudomonas aeruginosa and its antibiotic resistance in patients who have received Hematopoietic Stem-Cell Transplantation through a systematic review. The systematic search was done with key words; Pseudomonas aeruginosa, hematopoietic stem cell transplantation from 2000 to the end of July 2023 in Google Scholar and PubMed/Medline, Scopus, and Web of Science. Twelve studies were able to include our study. Quality assessment of studies was done by Appraisal tool for Cross-Sectional Studies. The most of the included studies were conducted as allo-HSCT. Infections such as respiratory infection, urinary infection and bacteremia have occurred. The rate of prevalence with P. aeruginosa has varied between 3 and 100%. The average age of the participants was between 1 and 74 years. The rate of prevalence of P. aeruginosa resistant to several drugs has been reported to be variable, ranging from 20 to 100%. The highest antibiotic resistance was reported against cefotetan (100%), and the lowest was related to tobramycin (1.8%) followed by amikacin, levofloxacin and ciprofloxacin with the prevalence of 16.6%. Our findings showed a high prevalence and antibiotic resistance rate of P. aeruginosa in Hematopoietic stem cell transplantation. Therefore, more serious health measures should be taken in patients after transplantation.