Search Results (167)

Klebsiella pneumoniae, a member of the Enterobacterales Order, often colonises the gut and causes diverse infections, including bloodstream, urinary, and respiratory infections. The rise in carbapenem-resistant sFtrains, especially those producing enzymes like K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Oxacillinase 48 (OXA48), or combinations (NDM+OXA48-like), poses a significant threat across Europe, notably in Romania. These strains spread rapidly via mobile genetic elements, complicating treatment. Methods: A retrospective study of multidrug-resistant (MDR) K. pneumoniae strains isolated from clinical samples collected at an infectious diseases hospital in Romania. Results: We analysed the evolution of carbapenemases and their combinations from 2010 to 2024, with the rising antibiotic consumption, particularly during the COVID-19 pandemic. The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) rose from 4.9% in 2010 to 41.6% in 2024. There was an overall antibiotic use increase, especially colistin (186%) between 2019–2024. Additionally, we examined the dynamics of antibiotic susceptibility that decreased in 2023–2024 and found that susceptibility of NDM+OXA48-like isolates to colistin was 16.5% and to cefiderocol 58.5%. Conclusions: The rising prevalence of K. pneumoniae strains with complex resistance mechanisms, coupled with a significant reduction in available treatment options, demands a fundamental paradigm shift in the management of these infections. Full article

Klebsiella pneumoniae, due to its capacity to produce numerous virulence factors and form biofilms, is one of the most significant etiological agents of nosocomial infections. The extensive and often unwarranted use of antibiotic therapy has driven the emergence of various mutations, adaptive mechanisms, and horizontal gene transfer among K. pneumoniae strains, resulting in resistance to most beta-lactam antibiotics, carbapenems, and the last-resort drug—colistin. A promising alternative or adjunctive treatment is the application of rotating magnetic fields (RMFs). The present study aimed to evaluate changes in colistin susceptibility among 20 extended-spectrum beta-lactamases (ESBLs) and 20 K. pneumoniae carbapenemase (KPC)-positive K. pneumoniae strains isolated from hospital infections following exposure to RMF at frequencies of 5 and 50 Hz. Exposure to RMF at 5 Hz resulted in decreased colistin minimum inhibitory concentration (MIC) values in over half of the tested (ESBLs) and (KPC)-positive strains. Additionally, RMF at 50 Hz reduced colistin MIC values in 30% of (ESBL)-positive and 40% of (KPC)-positive strains. Therefore, in the future, RMF may be developed as a supportive therapeutic strategy to improve the efficacy of antibiotics in the treatment of infections caused by multidrug-resistant (MDR) pathogens, including colistin-resistant K. pneumoniae. Full article

The global emergence of multidrug- and pandrug-resistant Klebsiella pneumoniae poses a critical threat to public health, particularly in hospital settings. This study describes a nosocomial outbreak caused by K. pneumoniae in a tertiary-care hospital in Mexico and provides a comprehensive genomic analysis of six clinical isolates. All isolates exhibited pandrug resistance, including carbapenems and colistin. Whole-genome sequencing identified 37 antimicrobial resistance genes, including blaNDM-1, blaOXA-1, blaCTX-M-15, and a pmrB R256G mutation associated with colistin resistance. Two conjugative plasmids (pAA046 and pAA276) carried multiple resistance genes and mobile genetic elements. Although all isolates harbored CRISPR-Cas type I-E systems, no spacers matched resistance plasmids, suggesting functional inactivity. Capsular typing identified the KL27 locus with the wzi187 allele. Phylogenetic and cgMLST analyses confirmed clonal dissemination and close genetic relatedness to strains from Europe and the USA. Despite the absence of classical hypervirulence markers, the presence of kfu, fimH, and mrkD genes indicates adaptation to the hospital environment. These findings confirm the clonal spread of pandrug-resistant K. pneumoniae ST392-KL27 in a Mexican hospital, underscoring the role of plasmid-mediated resistance and the potential for global dissemination. Full article

Background and Objectives: Cancer patients are particularly susceptible to infections caused by multidrug-resistant Gram-negative bacteria (MDR GNB) due to chemotherapy- or radiation therapy-induced immunosuppression. Colistin is often prescribed as a last-resort agent for MDR GNB infection, but its clinical benefit in oncology patients remains unclear. This study aims to evaluate the mortality risk associated with colistin versus non-colistin regimens in cancer patient with MDR GNB infections, stratified by resistance profiles, infection sites, and concomitant medication use. Materials and Methods: A retrospective cohort study was conducted in adult cancer patients with MDR GNB infections that are resistant to at least three antibiotic classes and identified from at least two anatomical sites at a tertiary care hospital in Korea. Propensity score-matched in a 1:3 ratio either to the colistin group or non-colistin group and multivariate Cox hazard regression analyses were used to evaluate mortality in cancer patients with MDR GNB infections, primarily Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Results: A total of 85 patients (29 patients in the colistin and 56 patients in the non-colistin group) were included in the analysis. Overall, colistin use did not show a statistically significant mortality benefit compared to non-colistin regimens (hazard ratio (HR) 0.93, 95% CI 0.47–1.87). However, the subgroup analysis revealed that colistin had a potential association with significantly lower mortality in pneumonia patients with aminoglycoside-resistant infections (HR 0.04, 95% CI 0.002–0.69). Concomitant use of antipsychotics and benzodiazepines in selected resistance profiles also correlated with improved outcomes. In contrast, a potential association was found between concomitant macrolide use and increased mortality in patients with fluoroquinolone- or penicillin-resistant profiles. Conclusions: Colistin may offer survival benefits in selected high-risk cancer patients with MDR GNB pneumonia. Treatment outcomes are influenced by resistance profiles, infection sites, and concomitant medications, indicating the significant importance of individualized antimicrobial therapy and antimicrobial stewardship in oncology patients. Full article

Klebsiella pneumoniae is a major public health concern due to its role in Gram-negative bacteremia, which leads to high mortality and increased healthcare costs. This study characterizes phenotypic and genomic features of K. pneumoniae isolates from clinical samples in Karachi, Pakistan. Among 507 isolates, 213 (42%) were carbapenem-resistant based on disk diffusion and MIC testing. Urine (29.7%) and blood (28.3%) were the most common sources, with infections predominantly affecting males (64.7%) and individuals aged 50–70 years. Colistin was the only antibiotic showing consistent activity against these isolates. The whole-genome sequencing of 24 carbapenem-resistant K. pneumoniae (CR-KP) isolates revealed bla_NDM-5 (45.8%) as the dominant carbapenemase gene, followed by bla_NDM-1 (12.5%) and bla_OXA-232 (54.2%). Other detected bla_OXA variants included bla_OXA-1, bla_OXA-4, bla_OXA-10, and bla_OXA-18. The predominant beta-lactamase gene was bla_CTX-M-15 (91.6%), followed by bla_CTX-M-163, bla_CTX-M-186, and bla_CTX-M-194. Sequence types ST147, ST231, ST29, and ST11 were associated with resistance. Plasmid profiling revealed IncR (61.5%), IncL (15.4%), and IncC (7.7%) as common plasmid types. Importantly, resistance was driven not only by acquired genes but also by chromosomal mutations. Porin mutations in OmpK36 and OmpK37 (e.g., P170M, I128M, N230G, A217S) reduced drug influx, while acrR and ramR mutations (e.g., P161R, G164A, P157*) led to efflux pump overexpression, enhancing resistance to fluoroquinolones and tigecycline. These findings highlight a complex resistance landscape driven by diverse carbapenemases and ESBLs, underlining the urgent need for robust antimicrobial stewardship and surveillance strategies. Full article

Klebsiella pneumoniae can acquire resistance mechanisms to colistin and present a pan-resistant phenotype. Therefore, new alternative agents are imperative to control this pathogen, and the peptide Jelleine-I stands out as a promising prototype. Here, the antibacterial activity of Jelleine-I against clinical isolates of colistin-resistant K. pneumoniae (CRKP) was investigated. Antimicrobial activity was assessed by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time kill-curve assay. The release of 260 nm-absorbing materials (DNA/RNA) and the release of proteins were used in the lysis assay. Anti-biofilm activity was studied in microplates. In vivo activity was determined by the lethality assay using Tenebrio molitor larvae. The results show that the MIC of Jelleine-I ranged from 16 to 128 µM and the MBC was on average 128 µM. Jelleine-I at 200 µM killed all CRKP cells in suspension (10⁶ colony-forming units (CFU)/mL) after 150 min of incubation. Jelleine-I acts on the CRKP cell membrane inducing lysis. Biomass and viability of CRKP-induced biofilms are reduced after treatment with Jelleine-I, and the use of this peptide in T. molitor larvae infected with CRKP reduces lethality and improves overall larval health. In conclusion, Jelleine-I is a potential prototype for the development of new antimicrobial agents. Full article

Background: Antimicrobial resistance (AMR) is a global threat in the public healthcare sector. The emergence of carbapenem-resistant Enterobacterales (CRE) has become a serious public health threat in South Africa. The spread of CRE has led to the use of colistin for treating severe infections. Colistin is a cationic, lipopeptide antibacterial agent that is effective against most Gram-negative bacteria through its disruption of the bacterial cell membrane. This study aims to determine the colistin resistance (MIC) and mobile colistin resistance (mcr-1) gene in clinical isolates from healthcare facilities in Mthatha and its surrounding areas. Methods: Fifty-three CRE isolates were collected from health facilities between January 2019 and June 2021 and stored in skim milk 10% and 5% inositol broth. The carbapenemase confirmatory test involved a RESIST-4 O.K.N.V assay (Coris BioConcept, Gembloux, Belgium), which was conducted following manufacturer protocol. Broth microdilution was performed according to the ISO standard method (20776-1) using A ComAspTM colistin 0.25–16 μg/mL MIC Broth. Conventional polymerase reaction (PCR) was performed for the detection of mcr-1. Results: N = 53 (100%) isolates were used. A total of 53% were defined as Klebsiella pneumoniae, Escherichia coli constituted 8%, Enterobacter cloacae 8%, Serratia marcescens 8%, Serratia fonticola 2%, Enterobacter aerogenes 2%, Klebsiella oxytoca 2%, Citrobacter koseri 2%, and Citrobacter freundii 2%. The specimens were from the following wards: Pediatric and Neonatal 38%, Medical 30%, Gynecology, Labour, and Maternity 11%, OPD and A&E 11%, ENT 4%, and Others—Male TB ward, Trauma, and adult ICU 6%. In total, 13% of the isolates were resistant and 86% were sensitive to colistin. The common CRE genes detected were OXA-48 at 47%, NDM at 13%, VIM at 1%, and a combination of OXA-48 and NDM at 5%. Of the isolates, 66% were positive for the production of carbapenamase. In this study, we found that all N = 53 (100%) isolates did not have the mobile colistin resistance gene (mcr-1). Conclusions: Antimicrobial resistance is associated with the emergence of carbapenemases genes. Increasing resistance to colistin in clinical settings can lead to difficulties in treating CRE infections, which may lead to clinical failure. In our study, 13% of isolates were phenotypically resistant to colistin. Full article

Background and Objectives: Bacterial infections amongst COVID-19 patients could be associated with worsened outcomes. This study aimed to investigate the efficacy of colistin antibiotic in multidrug-resistant (MDR) Gram-negative (-ve) secondary bacterial infections among hospitalized COVID-19 patients. Materials and Methods: In this multicentered retrospective study, we analyzed data from the medical records of 116 patients diagnosed with COVID-19 infection and secondary Gram-negative MDR bacterial respiratory infections. Results: We compared those assigned to colistin versus non-colistin-based antimicrobial therapy. The two arms of the study were similar in baseline clinical features, demographics, and Gram-negative pathogens’ distribution. Acinetobacter baumannii (51.7%) was the major pathogen, followed by Klebsiella pneumonia (26.7%). Patients who received colistin-based antimicrobial regimen showed a non-significant difference compared to non-colistin antimicrobial (NCA) therapy (p > 0.05) in the main outcomes. Nephrotoxicity was significantly higher in the IV colistin group, compared to the control (34.1% and 15.3%, p = 0.018). There were substantial differences observed in the levels of serum creatinine and urea among the study arms (p = 0.029 and <0.001, respectively). Conclusions: The combination of colistin with other antimicrobial agents showed comparable results to that of NCA regimens in hospitalized COVID-19 patients with superinfections with multidrug-resistant bacterial isolates; however, there was a notably elevated incidence of nephrotoxicity with colistin antimicrobial therapy. Further randomized controlled trials are needed to assess the therapeutic benefits and tolerability of colistin antimicrobial therapy. Full article

The scope of the antibacterial effects of plasma-activated water (PAW) is not yet fully comprehended. We investigated the activity of PAW produced by the in-house 3-pin atmospheric pressure plasma jet against carbapenem-resistant Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecalis, with a focus on PAW’s potential to promote susceptibility to conventional antibiotics in these bacteria. Bacterial inactivation was determined by the colony count after 15 and 60 min PAW treatments. Minimum inhibitory concentrations (MICs) measured following repeated exposures to PAW across multiple generations of bacteria enabled the assessment of changes in susceptibility to antibiotics. The PAW’s efficacy was also analyzed through the detection of intracellular reactive oxygen and nitrogen species in treated bacteria. Time-dependent significant inactivation efficiency against K. pneumoniae was observed (log reduction 6.92 ± 0.24 after 60 min exposure), while effects on E. faecalis were limited. PAW demonstrated potential to decrease the MICs of crucial antibiotics. Namely, a 50 to 62.5% decrease in the MICs of colistin against K. pneumoniae and a 25% reduction in the MICs of vancomycin against enterococci were recorded. We found a significant increase in the superoxide anion concentration in K. pneumoniae and E. faecalis cells after PAW treatments. This study indicates that PAW’s inactivating efficacy coupled with the capacity for the potentiation of antibiotic effects is a promising combination against multidrug-resistant bacteria. Full article

Klebsiella pneumoniae is one of the leading causes of healthcare-associated infections and poses challenges in its treatment owing to its high antibiotic resistance. The development of resistance to colistin, which is used as a last resort, has become a major public health problem worldwide. This study was planned according to the PRISMA guidelines and included studies reporting the prevalence of colistin-resistant K. pneumoniae in Turkey between 2004 and 2024 through a systematic literature review. A total of 28 original research articles were included in the meta-analysis. Data were analyzed using the SPSS and CMA software. The pooled colistin resistance of a total of 8916 K. pneumoniae strains from 28 studies included in this meta-analysis was found to be 1.63% (95% CI: 1.51–3.12). Colistin resistance increased significantly over time. A higher resistance rate was detected in the strains tested using the EUCAST guidelines and broth microdilution method. The year of the study and validation methods contributed to the heterogeneity observed in the studies. This meta-analysis reveals that colistin-resistant K. pneumoniae strains have increased over time in Turkey. Current data show that colistin resistance is not only a laboratory finding but has become a crisis, requiring urgent action in terms of hospital infection management and patient safety. Regional and global measures should be taken to ensure the appropriate use of antibiotics to control the development of resistance. Full article

Carbapenemase-producing Klebsiella pneumoniae is responsible for multiple serious infections with high mortality rates. K. pneumoniae carbapenemases (KPCs) are the most commonly isolated carbapenemases worldwide. To study the epidemiological and molecular characteristics of KPC-producing K. pneumoniae (KPC-KP), we conducted a retrospective study at the University General Hospital of Ioannina, Greece. A total of 177 K. pneumoniae clinical strains from the period 2014–2015 were confirmed as KPC producers by polymerase chain reaction (PCR) and were further examined for the presence of bla_VIM, bla_NDM, bla_TEM, bla_SHV, and bla_CTX-M genes. Using the amplification refractory mutation system (ARMS) method, we identified the presence of the KPC-2 allele in 130 strains and the KPC-9 allele in 47. Strains from both allele groups belonged to the sequence type 258 (ST258). KPC-9 was responsible for a distinct outbreak, considered part of the broader KPC-2 outbreak. Molecular characterization of selected KPC-KP isolates from the period 2021–2022 revealed their continued presence in our hospital. Comparison of the antimicrobial susceptibility profiles of the two alleles showed a statistically significant increase in minimum inhibitory concentration (MIC) for ceftazidime (p = 0.03) and higher resistance to amikacin (p = 0.012) and colistin (p < 0.001) for KPC-9 compared to the KPC-2 allele. The two KPC alleles had similar mortality rates. This study demonstrates the heterogeneity of resistance genes in carbapenem-resistant K. pneumoniae (CR-KP) within a single-hospital setting and underscores the need for immediate containment measures. Full article

Bloodstream infection (BSI) is a critical medical emergency associated with a high mortality rate. Rapid and accurate identification of the causative pathogen and the results of antimicrobial susceptibility testing are crucial for initiating appropriate antimicrobial therapy. The aim of this study was to evaluate the performance of a new rapid PCR Molecular Mouse System (MMS) for the identification of Gram-negative bacteria (GNB) and GNB resistance genes directly from a positive blood culture (BC). The validation of these rapid multiplex assays was carried out in a real hospital setting. A total of 80 BSI episodes were included in our study and the results were compared with culture-based methods. BC samples in which GNB had previously been detected microscopically and which originated from different hospital wards were analysed. The MMS GNB identification assay achieved a sensitivity of 98.7% and a specificity of 100% for the covered pathogens. In one BC sample, Klebsiella aerogenes was identified at the family level (Enterobacteriaceae) with MMS. However, in three polymicrobial samples, MMS identified bacteria that were not detected by culture-based methods (Klebsiella pneumoniae, K. aerogenes and Stenotrophomonas maltophilia). MMS also showed excellent overall performance in the detection of GNB resistance markers (100% sensitivity and 100% specificity). The type of extended-spectrum beta-lactamase (ESBL) resistance gene identified correctly with MMS was CTX-M-1/9 (n = 17/20), alone or in combination with SHV-type β-lactamase or with the different types of carbapenemase genes. MMS detected one carbapenemase gene of each type (KPC, NDM and OXA-23) and six OXA-48 genes. In addition, the colistin resistance gene mcr-1 was detected in one positive BC with Escherichia coli (E. coli). The time to result was significantly shorter for MMS than for routine culture methods. A retrospective analysis of the patients’ medical records revealed that a change in empirical antimicrobial therapy would have been made in around half of the patients following the MMS results. These results support the use of MMS as a valuable complement to conventional culture methods for more rapid BSI diagnosis and adjustment of empirical therapy. Full article

Urinary tract infections (UTIs) are common and are typically treated empirically, based on local antimicrobial resistance (AMR) data, which are often scarce in low- and middle-income countries. This study examines the AMR patterns of pathogens causing community-onset (CO) UTIs in the Bolivian Chaco. Urine samples were collected from subjects with suspected CO-UTIs and analyzed by culture techniques. Significant isolates were tested for their antimicrobial susceptibility. Additionally, bla_CTX-M and mcr genes were searched for using real-time PCR. A total of 361 CO-UTI episodes were diagnosed among 731 subjects from February 2020 to November 2021. The cases included uncomplicated and complicated UTIs (58.2% and 41.8%, respectively), with females accounting for the majority (85.3%) of cases. Escherichia coli was the most prevalent pathogen (86.6%), followed by Klebsiella pneumoniae (5.4%) and Proteus spp. (2.2%). Very high resistance rates (>50%) were observed for ampicillin, trimethoprim–sulfamethoxazole and fluoroquinolones, high resistance rates (>20%) for amoxicillin–clavulanate, third-generation cephalosporins and gentamicin, while lower resistance rates (<10%) were observed for nitrofurantoin and fosfomycin. The prevalence of bla_CTX-M among E. coli was high (26.7%). Colistin resistance was detected in 3.4% of E. coli, mostly associated with mcr genes. CO-UTIs from this area were characterized by high resistance rates to commonly used antibiotics (trimethoprim–sulfamethoxazole, amoxicillin–clavulanic acid and ciprofloxacin), highlighting the importance of knowledge of the local epidemiology to inform the selection of appropriate empirical antibiotic regimens. Full article

Introduction: Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are resistant to third-generation cephalosporins (3GCs), carbapenems, colistin, and tigecycline, making them a major public health priority, mainly within the developing world. However, their genomic epidemiology and possible determinants of resistance remain to be elucidated. Thus, this study aimed to perform a genomic characterization of E. coli and K. pneumoniae, both of which are resistant to last-line antibiotics, isolated from humans, poultry, and a dairy farm environment within Ecuador. Methods: This study analyzed nine 3GC-resistant E. coli isolates harboring the mcr-1 gene (six from poultry farms, two from human infections, and one from dairy farm compost), together with ten isolated colistin- and carbapenem-resistant K. pneumoniae clinical samples. Results: The E. coli isolates of human origin belonged to ST609 and phylogroup A, while the poultry and compost isolates belonged to phylogroups A, B1, E, and F. Diverse STs of the K. pneumoniae isolates included ST13 (five isolates), ST258 (four isolates), and ST86 (one isolate). Within the E. coli isolates, bla_CTX-M-55, bla_CTX-M-65, bla_CTX-M-15, and bla_CTX-M-2 genes were identified. This study also identified bla_CMY-2 and bla_KPC-3 (the latter in a carbapenem-susceptible isolate). In E. coli, the plasmid-borne mcr-1.1 gene was identified across all E. coli isolates within an IncI2 plasmid. Tigecycline-reduced susceptibility or resistance was related to missense amino acid substitutions coded in the marA and acrA genes. Within K. pneumoiae, bla_CTX-M-15 and bla_CTX-M-65, on the one hand, and bla_KPC-2 and bla_KPC-3, on the other, were associated with 3GC and carbapenem resistance, respectively. The bla_KPC-2 allele was identified in a ~10 kb Tn4401 transposon (tnpR–tnpA–istA–istB–bla_KPC-2–tnpA). In K pneumoniae, sequence data and phenotypic analysis linked a nonsense amino acid substitution coded in the mgrB (K3*) gene and missense amino acid substitutions coded in the marA, acrA, arnB, eptA, pmrB, pmrJ, and phoQ genes to colistin resistance. Meanwhile, tigecycline resistance was linked to nonsense and missense amino acid substitutions coded within the ramR sequence. Additionally, this study identified several integron structures, including Int191 (5′CS-dfrA14-3′CS), which was the most prevalent integron (Int) among E. coli and K. pneumoniae isolates in this study, followed by Int0 (5′CS-3′CS) and Int18 (5′CS-dfrA1-3′CS). Conclusions: These results contribute to the genomic epidemiology of MDR E. coli and K. pneumoniae in our setting and to the worldwide epidemiology in the One Health approach. Full article

Background: Antimicrobial resistance (AMR) is an escalating global health threat, projected to cause over 40 million deaths by 2050. ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) are major contributors to nosocomial infections and AMR. We evaluated the epidemiology and AMR prevalence of ESKAPE pathogens at the University Hospital in Palermo between January 2018 and July 2023, analyzing factors associated with mortality in patients with positive blood cultures. Methods: Microbiological data from all specimen types were collected using the Business Intelligence system Biwer, excluding duplicates. We assessed the prevalence and trends of ESKAPE isolates and AMR over time. Clinical data from hospital discharge forms were used to evaluate factors associated with mortality in patients with ESKAPE-positive blood cultures. Differences in AMR prevalence between blood and non-blood isolates were examined. Results: A total of 11,607 specimens from 4916 patients were analyzed. Most patients were admitted to Internal Medicine (19.4%), the ICU (13.2%), and General Surgery (9.9%). Additionally, 21.5% of the specimens were collected from ICU-admitted patients. Blood cultures accounted for 14.3% of the specimens, urine for 25.3%, respiratory secretions for 22.1%, and skin and mucosal swabs for 20.9%. The prevalence of all isolates increased progressively, peaking in 2021. The vancomycin-resistant E. faecium prevalence was 19.4%, with a significant upward trend, while oxacillin-resistant S. aureus prevalence was 35.0%, showing a significant decline. A. baumannii exhibited high resistance to all antibiotics tested except for colistin and cefiderocol. Carbapenemase resistance was 55.0% in K. pneumoniae, 20.4% in P. aeruginosa, and 4.6% in Enterobacter spp. P. aeruginosa showed a significant decrease in meropenem resistance. K. pneumoniae and A. baumannii bloodstream infections were linked to higher mortality risk. Full article