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Background: Newborns are particularly susceptible to infection in hospitals, with neonatal sepsis being the most common infection symptom and the third leading cause of neonatal death. Klebsiella pneumoniae is a gram-negative bacterium of Enterobacteriaceae, which is a common pathogen of neonatal septicemia. In this study, we will analyze and evaluate the current status, clinical characteristics, and drug resistance of Klebsiella pneumoniaesepsis infection in Neonatal Intensive Care Unit (NICU), with the aim of providing effective basis for timely and accurate clinical diagnosis and treatment in clinical practice. Methods: Statistical analysis was performed on 75 cases of Enterobacteriaceae septicemia in infants admitted to NICU in a special obstetrics and gynecology hospital in Shanghai from January 2020 to June 2022. Based on bacterial identification, isolates were divided into the Klebsiella pneumoniae (KP) group (n = 49) and the non-KP Enterobacteriaceae group (n = 26). The infection, clinical characteristics, and bacterial resistance of the two groups of infected patients were compared. Results: Comparing the clinical characteristics of the two groups, the results showed that most of the subjects in the KP and non-KP groups were premature infants, accounting for 100% and 92.3% of subjects, respectively; late onset was the main disease in both groups, accounting for 93.9% and 80.8% of subjects, respectively. All patients received Peripherally Inserted Central Catheter(PICC). The levels of pro calcitonin and CRP (C-reactive protein) were significantly higher in the KP group compared with those in the non-KP group (p <.05). At the same time, the incidence of thrombocytopenia in the KP group was significantly higher than that in the non-KP group (p <.05). The proportion of antimicrobial drug exposure in the KP group is higher than that in the non-KP group. The drug resistance of the KP group to ceftazidime, ceftriaxone, cefepime, ampicillin/sulbactam, aztreonam, ciprofloxacin and compound sulfamethoxazole was significantly higher than that of the non-KP group, whereas the drug resistance rate to cefotetan, gentamycin and to bramycin was significantly lower than that of the non-KP group, Statistically significant differences (p <.05). 38 cases of Klebsiella pneumoniae producing ESBLs were tested for related resistance genes. The results showed that the main resistance types were SHV and TEM, with detection rates of 60.6% and 28.9%. Conclusions: This study shows that neonatal sepsis caused by Klebsiella pneumoniae infection has a high incidence and drug resistance in premature and low birth weight infants, and has become a serious public health problem; Clinicians should pay attention to differential diagnosis, Reasonable selection of antibiotics to reduce the generation of drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Background: With the continuous advancement of modern medical technology, the survival rate of premature infants has significantly increased. Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens causing neonatal infections, particularly posing a serious risk to premature infants. This study aimed to analyze the clinical characteristics, antibiotic susceptibility profiles, and treatment outcomes of K. pneumoniae infections in these infants. Methods: We retrospectively compared cases of K. pneumoniae infection in premature and term infants admitted in a tertiary hospital from January 2017 to December 2022 in China. Clinical and microbiological characteristics were evaluated. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS), with statistical significance defined as P < 0.05. Results: We enrolled 166 premature infants and 68 term infants. In premature infants, fetal distress, patent ductus arteriosus, patent foramen ovale, enteritis, anemia, hypoproteinemia, bloodstream infections, abdominal infection, mechanical ventilation, nasogastric feeding, drainage tube, parenteral nutrition, and prior exposure to carbapenem antibiotics were identified as significant risk factors for K. pneumoniae infections in univariate analysis. Furthermore, septic shock, bloodstream infections, abdominal infections, indwelling catheters, drainage tubes, parenteral nutrition, and previous exposure to glycopeptide antibiotics were significantly correlated with mortality. Independent risk factors for K. pneumoniae infections in premature infants included fetal distress (OR: 3.702, [95% CI: 1.056–12.986], P = 0.041), enteritis (OR: 4.434, [95% CI: 1.066–18.451], P = 0.041), anemia (OR: 4.028, [95% CI: 1.550-10.466], P = 0.004), bloodstream infections (OR: 1.221, [95% CI: 0.061–1.802], P = 0.022), mechanical ventilation (OR: 4.974, [95% CI: 1.685–14.685], P = 0.004) and prior exposure to carbapenem antibiotic (OR: 14.738, [95% CI: 2.393–90.767], P = 0.004). Additionally, abdominal infections (OR: 8.598, [95% CI: 2.000-36.957], P = 0.004) and indwelling catheters (OR: 7.698, [95% CI: 0.998–59.370], P = 0.050) were positive predictors of mortality. Conclusion: K. pneumoniae isolates exhibit a notable prevalence of infection, poor treatment outcomes, and elevated resistance in preterm neonates. These findings enhance our understanding of K. pneumoniae infections and their association with clinical outcomes among premature infants. [ABSTRACT FROM AUTHOR]

Hypervirulent Klebsiella pneumoniae (hvKp), an emerging Kp subtype, has become a serious global pathogen. However, the information regarding host interactions and innate immune responses during hvKp infection is limited. Here, we found that hvKp clinical strains increased triacylglycerol synthesis, resulting in lipid droplets (LDs) formation via the mammalian target of rapamycin signaling pathway in RAW264.7 cells. Treatment with rapamycin, an inhibitor of this pathway, affected LDs formation and antimicrobial responses against clinical hvKp infections. In accordance with the role of LDs in modulating inflammation, the pharmacological inhibition of lipogenesis reduced proinflammatory cytokine expression during hvKp infections. In addition, inhibition of LDs formation using pharmacological inhibitors and knockdown of lipogenesis regulators decreased the intracellular survival of hvKp in macrophages. Moreover, inhibiting LDs biogenesis reduced mortality, weight loss, and bacterial loads in hvKp-infected mice. Collectively, these data suggest that LDs biogenesis is crucial in linking host immune responses to clinical hvKp infections. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae multidrug-resistant (MDR) high-risk clones drive the spread of antimicrobial resistance (AMR) associated infections, resulting in limited therapeutic options. This study described the genomic characteristics of K. pneumoniae MDR high-risk clones in Gauteng, South Africa. Representative carbapenem-resistant [K. pneumoniae carbapenemase (KPC)-2, New-Delhi metallo-beta (β)-lactamase (NDM)-1, oxacillinase (OXA)-181, OXA-232, OXA-48, Verona integron-encoded metallo-β-lactamase (VIM)-1] K. pneumoniae isolates (n = 22) obtained from inpatient and outpatient's urine (n = 9) and inpatients rectal carriage (n = 13) were selected for short-read whole genome sequencing. Klebsiella pneumoniae population include sequence type (ST)-307 (n = 3), ST2497 (n = 5) and ST17 (n = 4). The ST17 strains were exclusively obtained from rectal screening. Ten isolates co-harboured carbapenemase genes including β-lactamase gene encoding KPC-2 + OXA-181, NDM-1 + OXA-48 and NDM-1 + OXA-181. One ST307 isolate (UP-KT-73CKP) co-harboured three carbapenemase genes (blaNDM-1 + blaOXA-48 + blaOXA-181), while all the ST2497 strains co-harboured (blaNDM-1 + blaOXA-232). Phenotypically, hypermucoviscosity was observed in a single ST307 isolate. The ST307 isolate UP-KT-151UKP harboured colibactin genotoxins. The following mobile genetic elements were detected: plasmids [incompatibility group (Inc)-FIB(K), IncX3], and bacteriophages [e.g. Klebsi_ST16_OXA48phi5.4_NC_049450, Klebsi_3LV2017_NC_047817(36)]. The study highlights the importance of local genomic surveillance systems to characterise K. pneumoniae MDR high-risk clones. This data will aid in designing infection and prevention measures for limiting the spread of carbapenemase-producing K. pneumoniae in Gauteng, South Africa. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae is an opportunistic pathogen causing nosocomial infections, classified into carbapenem-sensitive and carbapenemresistant strains. Understanding the virulence factors and antibiotic resistance of these strains is essential for effective clinical management. Objective: This study compared the virulence genes and antibiotic resistance profiles of 50 CSKP and 50 CRKP strains, examining their expression under antibiotic pressure and the mechanisms contributing to their pathogenicity. Methods: Virulence genes (rmpA, rmpA2, iucA, iutA, Peg-344, ybts, iroB) were detected in both strains using polymerase chain reaction (PCR). Antibiotic susceptibility testing established minimum inhibitory concentrations (MICs) for key antibiotics. Gene expression analysis was performed with quantitative reverse transcription PCR (qRT-PCR) after 10 days of antibiotic exposure. Results: CSKP strains exhibited significantly higher positivity rates for virulence genes compared to CRKP strains. CRKP strains predominantly expressed resistance genes KPC, SHV, and CTX-M3, whereas no resistance genes were found in CSKP. Antibiotic susceptibility tests showed increased MICs, particularly for ciprofloxacin and imipenem, following antibiotic induction. CSKP demonstrated elevated expression of rmpA and rmpA2, while CRKP showed increased expression of SHV, and KPC after antibiotic exposure. Conclusion: This study highlights the intricate relationship between virulence and resistance in Klebsiella pneumoniae. CSKP strains show strong virulence factor expression, while CRKP strains adapt to antibiotic pressure through altered gene expression patterns. These findings underscore the urgent need for continuous surveillance and innovative therapeutic strategies to combat multidrug-resistant Klebsiella pneumoniae infections. [ABSTRACT FROM AUTHOR]

Data in the literature on the use of ceftazidime-avibactam (CAZ-AVI) in carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are limited especially in OXA-48 (Oxacillinase-48) predominant regions. Our study aimed to evaluate the effect of CAZ-AVI use on outcomes in CRKP-BSIs in Turkey, where OXA-48 is endemic. A multicenter retrospective observational study was conducted between January 2017 and September 2021. The effects of clinical and treatment characteristics on 30-day mortality and relapse in CRKP-BSIs were analyzed. Predictors of outcomes were detected using a Cox regression model. The study enrolled 106 adults with CAZ-AVI-sensitive CRKP-BSIs who received CAZ-AVI for at least 72 h. Patients who received CAZ-AVI as initial therapy had lower mortality rates when compared to those who switched from last resort regimens [14.3% (n = 3/21) vs. 37.7% (n = 32/85), p = 0.04]. In multivariate analysis, older age and severe neutropenia were detected to be associated with higher mortality, significantly. Initiation of CAZ-AVI on the day of blood culture was obtained, was found to be significantly associated with lower mortality (HR: 0.25, CI: 0.07–0.84, p = 0.025). CAZ-AVI monotherapy is an important treatment option for CRKP-BSIs in OXA-48 endemic areas. Early initiation of CAZ-AVI should be preferred rather than switching from a last-resort regimen as it profoundly improves the survival rates. [ABSTRACT FROM AUTHOR]

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. [ABSTRACT FROM AUTHOR]

The spread of carbapenemase-producing gram-negative pathogens, especially those producing metallo-β-lactamases (MBLs), has become a major health concern. MBLs are molecularly the most diverse carbapenemases, produced by a wide spectrum of gram-negative organisms, including the Enterobacterales, Pseudomonas spp., Acinetobacter baumannii, and Stenotrophomonas maltophilia, and can hydrolyze most β-lactams using metal ion cofactors in their active sites. Over the years, the prevalence of MBL-carrying isolates has increased globally, particularly in Asia. MBL infections are associated with adverse clinical outcomes including longer length of hospital stay, ICU admission, and increased mortality across the globe. The optimal treatment for MBL infections not only depends on the pathogen but also on the underlying resistance mechanisms. Currently, there are only few drugs or drug combinations that can efficiently offset MBL-mediated resistance, which makes the treatment of MBL infections challenging. The rising concern of MBLs along with the limited treatment options has led to the need and development of drugs that are specifically targeted towards MBLs. This review discusses the prevalence of MBLs, their clinical impact, and the current treatment options for MBL infections and their limitations. Furthermore, this review will discuss agents currently in the pipeline for treatment of MBL infections. [ABSTRACT FROM AUTHOR]

The specific relationships between total body surface area burned (TBSA), length of stay (LOS), and carbapenem-resistant Klebsiella pneumoniae (CRKP) infection remain unclear. This study aimed to explore the relationship between TBSA and CRKP infection and to examine whether LOS mediates the association between TBSA and the risk of CRKP infection. We retrospectively collected the clinical data of adult burn patients admitted to Nanyang Nanshi Hospital between 2021 and 2023. We used multivariate logistic regression analysis to study the risk factors for CRKP infection; restricted cubic spline analysis to investigate the associations between TBSA, LOS, and CRKP infection; and mediation analysis to examine whether LOS mediated the association between TBSA and CRKP infection. A total of 178 subjects were included in the study; 104 (58.4 %) were male, and the median age was 47 (33−59) years. Thirty-one (17.4 %) subjects developed CRKP infection. Both TBSA and LOS showed a linear positive correlation with the risk of CRKP infection. The LOS mediated the association between TBSA and incident CRKP infection, with a proportion of 17.6 %. The risk of CRKP infection linearly increased as TBSA or LOS increased, and LOS mediated approximately 20 % of the total association between TBSA and CRKP infection. • The risk of CRKP infectionis associated with TBSA, LOS, and carbapenem use. • TBSA and LOS show a linear positive correlation with the risk of CRKP infection. • LOS mediates approximately 20 % of the total association between TBSA and CRKP infection. [ABSTRACT FROM AUTHOR]

Introduction: Infections caused by Klebsiella pneumoniae carbapenemase (KPC) pose a significant clinical challenge due to increasing antibiotic resistance. This study analyzes the effectiveness of ceftazidime/avibactam treatment for KPC infections, focusing on 30-day mortality and comparing results with control groups treated with different antibiotics. Material and methods: We conducted a retrospective analysis of six cohort studies, comparing thirty-day mortality in patients treated with ceftazidime/avibactam with control groups using other antibiotics. The studies included patients infected with KPC, and the analysis focused on therapeutic effectiveness. Aim of the study: The aim of the study is to compare the results in terms of 30-day mortality in groups treated with ceftazidime/avibactam compared to control groups using different antibiotics. Conclusions: Data analysis from various studies revealed varied 30-day mortality outcomes in groups treated with ceftazidime/avibactam compared to control groups using different antibiotics. Ceftazidime/avibactam proved to be more effective in all studies, reducing mortality rates compared to other treatment regimens. We emphasize that emerging antibiotic resistance, especially in the case of KPC, requires a comprehensive therapeutic approach. Despite promising ceftazidime/avibactam results, factors such as overall patient health and treatment delays may influence final therapy outcomes. We also highlight controversies regarding combination therapy vs. monotherapy, necessitating further research. Our work underscores the importance of monitoring the effectiveness of KPC infection treatment and exploring new therapeutic strategies. Further clinical studies are essential to develop a fuller understanding and optimal therapeutic protocols in the face of the growing antibiotic resistance problem. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 patients have been reported to have high rates of secondary Klebsiella pneumoniae infections. K. pneumoniae is a commensal that is typically found in the respiratory and gastrointestinal tracts. However, it can cause severe disease when a person's immune system is compromised. Despite a high number of K. pneumoniae cases reported in SARS-CoV-2 patients, a coinfection animal model evaluating the pathogenesis is not available. In our cohort of COVID-19-positive human patients, 38% exhibited the presence of K. pneumoniae. Therefore we developed a mouse model to study the disease pathogenesis of SARS-CoV-2 and K. pneumoniae co-infection. BALB/cJ mice were inoculated with mouse-adapted SARS-CoV-2 followed by a challenge with K. pneumoniae. Mice were monitored for body weight change, clinical signs, and survival during infection. The bacterial load, viral titers, immune cell accumulation and phenotype, and histopathology were evaluated in the lungs. The co-infected mice showed severe clinical disease and a higher mortality rate within 48 h of K. pneumoniae administration. The co-infected mice had significantly elevated bacterial load in the lungs, however, viral loads were similar between co-infected and single-infected mice. Histopathology of coinfected mice showed severe bronchointerstitial pneumonia with copious intralesional bacteria. Flow cytometry analysis showed significantly higher numbers of neutrophils and macrophages in the lungs. Collectively, our results demonstrated that co-infection of SARS-CoV-2 with K. pneumoniae causes severe disease with increased mortality in mice. [ABSTRACT FROM AUTHOR]

Klebsiella spp. are a genus of Gram-negative, opportunistic bacteria frequently found in the flora of the mucosal membranes of healthy animals and humans, and in the environment. Species of this group can cause serious infections (meningitis, sepsis, bacteraemia, urinary tract infections, liver damage) and possible death in immunocompromised organisms (and even in immunocompetent ones in the case of hypervirulent K. pneumoniae) that are exposed to them. K. pneumoniae is part of the ESKAPE organisms, and so it is important to understand this genus in terms of multidrug-resistant bacteria and as a carrier of antibiotic resistance mechanisms. As it is a durable bacterium, it survives well even in hostile environments, making it possible to colonize all kinds of habitats, even the mucosal flora of wildlife. This systematic review explores the prevalence of Klebsiella spp. bacteria in wild animals, and the possibility of transmission to humans according to the One Health perspective. The isolates found in this review proved to be resistant to betalactams (blaTEM, blaOXA-48...), aminoglycosides (strAB, aadA2...), fosfomycin, tetracyclines, sulphonamides, trimethoprim, phenicols (catB4), and polymyxins (mcr4). [ABSTRACT FROM AUTHOR]

Objectives: This study describes the detection and tracking of emergency neurosurgical cross-transmission infections with carbapenem-resistant Klebsiella oxytoca (CRKO). Methods: We conducted an epidemiological investigation and a rapid screening of 66 surveillance samples using the chromogenic selective medium. Two CRKO isolates from infected patients and three from the preoperative shaving razors had similar resistance profiles identified by the clinical laboratory. Results: The whole genome sequencing (WGS) results identified all isolates as Klebsiella michiganensis (a species in the K. oxytoca complex) with sequence type 29 (ST29) and carrying resistance genes blaKPC-2 and blaOXY-5, as well as IncF plasmids. The pairwise average nucleotide identity values of 5 isolates ranged from 99.993% to 99.999%. Moreover, these isolates displayed a maximum genetic difference of 3 among 5,229 targets in the core genome multilocus sequence typing scheme, and the razors were confirmed as the contamination source. After the implementation of controls and standardized shaving procedures, no new CRKO infections occurred. Conclusion: Contaminated razors can be sources of neurosurgical site infections with CRKO, and standard shaving procedures need to be established. Chromogenic selective medium can help rapidly identify targeted pathogens, and WGS technologies are effective mean in tracking the transmission source in an epidemic or outbreak investigation. Our findings increase the understanding of microbial transmission in surgery to improve patient care quality. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae is a significant global public health burden, especially in low-income countries and regions with fragile healthcare infrastructures, due to its ability to cause severe infections, increase mortality rates, and its rising antimicrobial resistance. This study aimed to estimate the proportion of multidrug-resistant (MDR) K. pneumoniae infections and identify associated risk factors. Methods: Data were retrospectively collected from three academic hospitals in Beirut, Lebanon, between January 2021 and September 2023 using a standardized form. Binary logistic regression was used to determine risk factors associated with MDR, extended-spectrum beta-lactamase (ESBL)-producing, and carbapenem-resistant K. pneumoniae (CRKP) infections. Results: Out of 2,655 K. pneumoniae cases, 410 met the inclusion criteria. The primary infection sources were the urinary tract (58.3%) and the respiratory tract (12.4%). Among the isolates, 61% were MDR K. pneumoniae, with 7.3% being extensively drug-resistant, and 0.5% pandrug-resistant. Additionally, 36.8% were ESBL-producing, while 6.3% were CRKP. Predictors significantly associated with MDR K. pneumoniae infections included male sex (adjusted odds ratio [AOR] = 3.46, 95% CI = 1.01–11.86, P = 0.04), recent antibiotics use (AOR = 4.52, 95% CI = 1.65–12.36, P = 0.003), and recent cancer chemotherapy (AOR = 3.43, 95% CI = 1.25–9.42, P = 0.01). ESBL-producing infections were associated with age ≥ 65 years, higher Charlson Comorbidity Index (CCI), and recent antibiotic use. CRKP infections were linked to male sex, prior antibiotic use, and longer hospital stays prior to infection (all P < 0.05). Conclusions: MDR K. pneumoniae infections are steadily rising in Lebanon, along with an increase in ESBL-producing and CRKP cases. The main risk factors for MDR K. pneumoniae infections were male sex, recent antibiotic use, and cancer chemotherapy. ESBL-producing infections were associated with advanced age, higher CCI, and recent antibiotic use, while CRKP infections were linked to male sex, prior antibiotic use, and prolonged hospital stays. This situation is further exacerbated by inadequate healthcare infrastructure and suboptimal national surveillance. Strengthening local surveillance and implementing effective antibiotic stewardship programs are critical to managing this growing threat.. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP), a significant worldwide public health threat, is common in patients in intensive care units. Methods: A retrospective study was conducted over a period of 22 months to assess the risk factors associated with infection caused by CRKP isolates. Strain identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and antimicrobial sensitivity was assessed using the micro broth dilution method and Kirby–Bauer test. The genes blaKPC, blaOXA-48, blaNDM, blaVIM, and blaGES were amplified using polymerase chain reaction (PCR), followed by sequencing of the PCR products. The polymerase hypermucoviscosity phenotype was determined using the string test. Capsular serotypes (K1, K2) and presence of the virulence gene (rmpA) in positive isolates were investigated using phenotypic tests followed by PCR. Results: Length of hospitalization and use of carbapenems were associated with CRKP infection. CRKP isolates exhibited extensive drug resistance, but retained sensitivity to colistin and ceftazidime–avibactam (CZA). The main gene detected in 35 CRKP isolates was blaKPC-2. In addition, 11 strains were positive in the string test, and two of these strains carried rmpA. Conclusions: Prolonged hospitalization and carbapenem exposure increased the risk of CRKP infection in intensive care unit (ICU) patients. The prevalence of CRKP carrying the blaKPC-2 gene was high, and suspected hypervirulent carbapenem-resistant K. pneumoniae isolates were scattered. [ABSTRACT FROM AUTHOR]

Genes conferring antibiotic resistance phenotype, particularly to last resort antibiotics, pose a significant concern globally. Wastewater treatment plant (WWTP) effluent substantially contributes to antibiotic resistance in receiving rivers, threatening human health. Globally, colistin- and carbapenem-resistant Klebsiella pneumoniae infections cause high morbidity and mortality. We investigated colistin-resistant carbapenemase-producing K. pneumoniae (Co-CRKP) isolates in Kathajodi river receiving WWTP effluent, their resistance genes, and pathogenic potential. Four isolates (Co-CRKP-7, Co-CRKP-8, Co-CRKP-10, and Co-CRKP-15) exhibited extensively drug-resistant (XDR) phenotype, harbouring bla TEM-1, bla CTX-M-15, bla NDM-5, and bla OXA-48 genes. Colistin resistance was attributed to mutations in the pmrA and pmrB genes. Virulence genes (fimH, mrkD, entB, iucA, iutA , and irp1), capsular serotypes (K1, K2) and biofilm formation in the isolates explicated their pathogenicity. Furthermore, Inc plasmid replicons (Y, FrepB, P, K/B, L/M, N, FIA, A/C, and FIB) indicated the dissemination potential of the resistance genes in Co-CRKP isolates. The multi-locus sequence typing showed that Co-CRKP-7 and Co-CRKP-8 belonged to ST42, while Co-CRKP-10 and Co-CRKP-15 were ST16 and ST231, respectively. These high-risk clones carrying multidrug resistance and virulence genes, implicated in numerous outbreaks, have spread worldwide. Our findings emphasize the necessity for effective treatment of hospital wastes to restrict the spread of clinical isolates into aquatic environments. [ABSTRACT FROM AUTHOR]

Background: Clinical significance of Eschericia coli is due to its capacity to develop resistance against many antibiotics specially carbapenem by producing carbapenemase which limits treatment options. blaNDM and blaVIM genes are responsible for this multi-drug-resistance. This is an alarming condition for society as well as clinician because they are very difficult to treat due to limited options of antibiotics and its high virulence. Aims and Objectives: The study was conducted to detect antibiogram pattern and prevalence of blaNDM and blaVIM genes among carbapenem resistant E. coli isolates in a tertiary care hospital. Our study will also help to identify molecular basis of Carbapenem resistance including treatment guideline. Materials and Methods: Cross-sectional study was performed during January'2021 to June'2022 time period. Identification of E. coli was followed by standard protocol and antibiotic sensitivity was done by Kirby-Bauer disk-diffusion method following CLSI guideline, using VITEK-2D-SYSTEM. Detection of genes was done by polymerase chain reaction (PCR). Results: Out of 1867 samples, 161 isolates were identified as E. coli, among which 90 were resistant to carbapenem. Among those, 50 (31%) were resistant to all three carbapenems. Among those, 100% were resistant to ampicillin, amoxycillin-clavulanic acid, cefuroxime, cefuroxime-axetil, cefoperazone-sulbactam, ceftriaxone, cefepime, piperacillin-tazobactam, nalidixic acid, ciprofloxacin; 52% were resistant to amikacin; 54% were resistant to gentamicin; 86% were resistant to cotrimoxazole; 22% were resistant to nitrofurantoin and 96% were sensitive to tigecycline; 100% were intermediate sensitive to colistin. blaNDM gene is detected in 17 (34%) isolates and blaVIM gene is detected in 2 (4%) isolates by PCR. Conclusion: E. coli leads to common clinical presentations such as urinary tract infection, blood stream infection, pneumonia, and wound infection. High burden of carbapenem resistant E. coli was associated with urinary indoor samples. Rising incidence of multi-drug-resistance occurs due to lack of infection control measures, irrational use of antibiotics. Continuous surveillance will prevent development of multi-drug-resistance and help to improve treatment guideline. [ABSTRACT FROM AUTHOR]

Traditional antibiotics have been effective in many cases. However, the rise in multidrug-resistant bacteria has diminished their therapeutic efficacy, signaling the dawn of an era beyond antibiotics. The challenge of multidrug resistance in Klebsiella pneumoniae is particularly critical, with increasing global mortality and resistance rates. Therefore, the development of alternative therapies to antibiotics is urgently needed. Phages, which are natural predators of bacteria, have inherent advantages. However, comprehensive information on K. pneumoniae phages is lacking in current literature. This review aims to analyze and summarize relevant studies, focusing on the present state of phage therapy for K. pneumoniae infections. This includes an examination of treatment methodologies, associated challenges, strategies, new phage technologies, clinical trial safety and efficacy, regulatory issues, and future directions for phage therapy development. Enhancing phage technology is crucial for addressing the evolving threat of multidrug-resistant K. pneumoniae. [ABSTRACT FROM AUTHOR]

Objectives Pharmacodynamic parameters evaluated under conditions that simulate an infection site volume and microbial load might reveal hidden risks of resistance selection and subsequent treatment failure. The study aimed to investigate the predictive potential of MICs determined at various conditions on the antimicrobial effect and emergence of resistance. Methods We assessed meropenem MICs (microdilution: 0.2 mL, 5 × 105 cfu/mL; macrodilution: 2 mL, 5 × 105 cfu/mL), MICHVs (220 mL, 5 × 105 cfu/mL), MICHIs (0.2 mL, 5 × 107 cfu/mL) and MICHVIs (220 mL, 5 × 107 cfu/mL) for five Klebsiella pneumoniae strains and analysed these values alongside the results of experiments in a dynamic in vitro model. A clinically relevant meropenem dosing regimen was simulated and the starting bacterial inocula were 106 and 108 cfu/mL. Results The effectiveness of meropenem agreed with MICHVs for the 106 cfu/mL inoculum and with MICHIs or MICHVIs for the 108 cfu/mL inoculum. Strains characterized as resistant according to these values grew during meropenem exposure, and resistant mutants were selected. Conclusions Our results suggest that MICHV-based parameters may be suitable for predicting antibacterial effects and the risk of resistance development when the inoculum is 106 cfu/mL, while MICHI- or MICHVI-based parameters are suitable for these purposes when the inoculum is 108 cfu/mL. Also, the correlation between resistance selection and the MICHI-based parameter was as high as one that corresponds with a mutant prevention concentration (MPC)-based parameter; this suggests that the MPC can be replaced by the more easily determined alternative parameter MICHI. [ABSTRACT FROM AUTHOR]

Background: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. Methods: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. Results: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. Conclusions: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients. [ABSTRACT FROM AUTHOR]

A novel KPC variant, KPC-84, identified in a Klebsiella pneumoniae isolate from China, exhibits a threonine (T) to proline (P) amino acid substitution at Ambler position 243(T243P), altering from the KPC-2 sequence. Cloning and expression of blaKPC−84 in Escherichia coli, with subsequent MIC assessments, revealed increased resistance to ceftazidime-avibactam and significantly reduced carbapenemase activity compared to KPC-2. Kinetic measurements showed that KPC-84 exhibited sligthly higher hydrolysis of ceftazidime and reduced affinity for avibactam compared to KPC-2. This study emphasizes the emerging diversity of KPC variants with ceftazidime-avibactam resistance, underscoring the complexity of addressing carbapenem-resistant Klebsiella pneumoniae infections. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is an opportunistic pathogen known for two main pathotypes: classical K. pneumoniae (cKp), often multidrug-resistant and common in hospitals, and hypervirulent K. pneumoniae (hvKp), associated with severe community-acquired infections. The recent emergence of strains combining hypervirulence and resistance is alarming. This study investigates the distribution of sequence types (STs), resistance, and virulence factors in K. pneumoniae strains causing bloodstream and urinary tract infections in Croatia. In 2022, 200 consecutive K. pneumoniae isolates were collected from blood and urine samples across several Croatian hospitals. Whole genome sequencing was performed on 194 isolates. Within the analyzed K. pneumoniae population, the distribution of sequence types was determined with multi-locus sequence typing (MLST) and capsule loci, resistance, and virulence determinants were assessed with the bioinformatics tool Kleborate. The analysis identified 77 different STs, with ST101 (24.6%) being the most prevalent, predominantly linked to the K17 capsular type (CT), invasive device usage, high antimicrobial resistance, and low virulence scores. The highest virulence scores were recorded in ST86 isolates, which were predominantly linked to the K2 CT and included some strains with medium resistance scores. String tests were positive in 19 strains, but only four of those harbored hypermucoviscous genetic determinants. The most prevalent ST101 clone in Croatia demonstrated a diverging association between resistance and virulence. An alarming co-existence of resistance and virulence was recorded in the ST86 strains. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance is a major global public health challenge, particularly with the rise of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA). This study aimed to describe the characteristics of CRE and CRPA infections in Eastern Europe, focusing on Bulgaria, Croatia, Czechia, Greece, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia. Methods: Following MOOSE and PRISMA guidelines, a systematic literature review of articles published between 1 November 2017 and 1 November 2023 was conducted using the MEDLINE, Embase, Web of Science, CDSR, DARE, and CENTRAL databases. The search strategy used a combination of free text and subject headings to gather pertinent literature regarding the incidence and treatment patterns of CRE and CRPA infections. A total of 104 studies focusing on infections in both children and adults were included in this review. Results: This review revealed a significant prevalence of carbapenem-resistant Gram-negative isolates and underscored the effectiveness of imipenem/relebactam and ceftazidime/avibactam (CAZ/AVI) against Klebsiella pneumoniae carbapenemase-producing Enterobacterales and of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against non-metallo-β-lactamase-producing CRPA strains. Conclusions: This study highlights the urgent need for comprehensive measures to combat the escalating threat of CRE and CRPA infections in Eastern European countries. At the same time, it shows the activity of the standard of care and new antimicrobials against carbapenem-resistant Gram-negative pathogens in Eastern Europe. Clinical real-world data on the treatment of carbapenem-resistant infections in Eastern Europe are needed. [ABSTRACT FROM AUTHOR]

Introduction Case Description Discussion Conclusion This case examines the sonographic and clinical challenge of diagnosing a Klebsiella pnumoniae pyogenic liver abscess with systemic metastatic infection.The patient in this case study is an 81‐year‐old man who presented with intermittent rigors. Following radiological and clinical assessments, a Klebsiella pnumoniae pyogenic liver abscess, with evidence of systemic metastatic infection, was diagnosed. Sonographic features of the liver abscess were atypical for a cystic lesion and instead appeared as a solid mass, raising the possibility of malignancy. Treatment of intravenous ceftriaxone infusions resulted in full resolution of the liver lesion.The discussion criticises the terminology when describing hepatic lesions, which result from a Klebsiella pnumoniae infection. The term hepatic phlegmon is appropriate when a liver lesion caused by bacterial infection demonstrates a solid appearance on radiologic imaging. The term hepatic abscess is appropriate in cases where liver lesions caused by bacterial infection demonstrate a fluid filled core on radiologic imaging. Differentiation of these terms is important when treating the underlying lesion as a phlegmon, in contrast to an abscess, cannot be drained because it contains no pus. The variable sonographic appearances of Klebsiella pnumoniae pyogenic abscesses were also examined. Despite reported sonographic appearances in the literature, none are sufficient to distinguish a pyogenic liver abscess from malignancy without further investigation.Ultrasound operators should be aware of the variable sonographic appearances of a Klebsiella pnumoniae liver abscess and how these features, combined with non‐homogenous terminology, can obfuscate the correct diagnosis. [ABSTRACT FROM AUTHOR]

Background Klebsiella pneumoniae is infamous for hospital-acquired infections and sepsis, which have also been linked to Alzheimer disease (AD)-related neuroinflammatory and neurodegenerative impairment. However, its causative and mechanistic role in AD pathology remains unstudied. Methods A preclinical model of K. pneumoniae enteric infection and colonization is developed in an AD model (3xTg-AD mice) to investigate whether and how K. pneumoniae pathogenesis exacerbates neuropathogenesis via the gut-blood-brain axis. Results K. pneumoniae, particularly under antibiotic-induced dysbiosis, was able to translocate from the gut to the bloodstream by penetrating the gut epithelial barrier. Subsequently, K. pneumoniae infiltrated the brain by breaching the blood-brain barrier. Significant neuroinflammatory phenotype was observed in mice with K. pneumoniae brain infection. K. pneumoniae -infected mice also exhibited impaired neurobehavioral function and elevated total tau levels in the brain. Metagenomic analyses revealed an inverse correlation of K. pneumoniae with gut biome diversity and commensal bacteria, highlighting how antibiotic-induced dysbiosis triggers an enteroseptic "pathobiome" signature implicated in gut-brain perturbations. Conclusions The findings demonstrate how infectious agents following hospital-acquired infections and consequent antibiotic regimen may induce gut dysbiosis and pathobiome and increase the risk of sepsis, thereby increasing the predisposition to neuroinflammatory and neurobehavioral impairments via breaching the gut-blood-brain barrier. [ABSTRACT FROM AUTHOR]

Background: Early detection and proper management of maternal sepsis caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) can significantly reduce severe complications and maternal mortality. This study aimed to describe the epidemiology, antimicrobial resistance profile, and management of carbapenem-resistant K. pneumoniae among sepsis-suspected maternal cases in Ethiopia. Methods: A prospective cross-sectional study was conducted in five tertiary hospitals from June 2021 to December 2023. Isolation, identification, and antimicrobial susceptibility testing of the isolates were carried out following standard microbiological procedures as stated in the CLSI guidelines. Data on socio-demographics, risk factors, and management strategies were collected with structured questionnaires. Associations between variables were determined using logistic regression analysis in STATA-21. A p-value of less than 0.05 was statistically significant. Results: Of the 5613 total women suspected of having maternal sepsis, 609 (10.8%) of them were infected with K. pneumoniae. The prevalence rates of MDR, XDR, and PDR K. pneumoniae strains were 93.9%, 24.3%, and 10.9%, respectively. The resistance rates for the last-resort antibiotics; amikacin, tigecycline, carbapenem, and third-generation cephalosporin were 16.4%, 29.1%, 31.9%, and 93.0%, respectively. The combination of carbapenem with tigecycline or amikacin therapy was used to manage maternal sepsis caused by cephalosporin-and carbapenem-resistant strains. Sepsis associated risk factors, including septic abortion [AOR = 5.3; 95%CI:2.2–14.4]; extended hospitalization [AOR = 3.7; 95%CI: 1.6–19.4]; dilatation and curettage [AOR = 2.2; 95%CI:1.3–13.4]; cesarean wound infection [AOR = 4.1; 95%CI:2.0–9.2]; indwelling catheterization [AOR = 2.1;95%CI: 1.4–6.2]; ICU admission [AOR = 4.3; 95%CI:2.4–11.2]; post abortion [AOR = 9.8; 95%CI:5.7–16.3], and recurrent UTI [AOR = 3.3; 95%CI: 1.6–13.2] were significantly associated with maternal sepsis caused by K. pneumoniae. Conclusions: The prevalence of maternal sepsis caused by carbapenem- resistant K. pneumoniae is high and serious attention needs to be given to combat transmission. Therefore, improving awareness, early diagnosis, IPC, integrated maternal surveillance, improved sanitation and efficient antimicrobial stewardship are crucial to combating bacterial maternal sepsis. [ABSTRACT FROM AUTHOR]

Background: Neutrophil plays a pivotal role in the management of Klebsiella pneumoniae infection. Delineate the clinical characteristics and prognostic utility of neutrophil in severe patients with K. pneumoniae infection are crucial for clinical management and prognostic assessment. Methods: K. pneumoniae patients with different infection sites were enrolled from Medical Information Mart for Intensive Care IV and eICU Collaborative Research Database. Temporal variations of neutrophil counts within 30 days of clinical onset were examined using locally weighted scatterplot smoothing curves. Logistic regression analysis was performed to assess the relationship between neutrophil counts and hospital mortality. Results: A total of 1,705 patients caused by K. pneumonia were included in the study. The non-survivor group exhibited a comparatively older age and a higher proportion of K. pneumoniae infections originating from respiratory and bloodstream sources compared to the survivor group (38.4% vs 21.1%, p<0.0001, and 15.1% vs 10.3%, p=0.021). Patients combined with multiple drug resistance strains, respiratory infection, liver disease, and above 60 years exhibited a specific dynamic process of neutrophil levels. Neutrophils counts peaked at admission and 1-2 weeks later. There was a 'U'-shaped relationship between neutrophil counts and hospital mortality. Conclusions: Neutrophils in K. pneumoniae infected patients have distinctive features and dynamic clinical trajectories. Close monitoring of severe patients infected with K. pneumoniae upon admission and during the first 1-2 weeks after admission is of utmost importance, particularly for patients with a neutrophil count exceeding 8.0×109/L. [ABSTRACT FROM AUTHOR]

Despite its medical relevance, there is no commercial vaccine that protects the population at risk from multidrug-resistant (MDR) Klebsiella pneumoniae infections. The availability of massive omic data and novel algorithms may improve antigen selection to develop effective prophylactic strategies. Up to 133 exposed proteins in the core proteomes, between 516 and 8666 genome samples, of the six most relevant MDR clonal groups (CGs) carried conserved B-cell epitopes, suggesting minimized future evasion if utilized for vaccination. Antigens showed a range of epitopicity, functional constraints, and potential side effects. Eleven antigens, including three sugar porins, were represented in all MDR-CGs, constitutively expressed, and showed limited reactivity with gut microbiota. Some of these antigens had important interactomic interactions and may elicit adhesion-neutralizing antibodies. Synergistic bivalent to pentavalent combinations that address expression conditions, interactome location, virulence activities, and clone-specific proteins may overcome the limiting protection of univalent vaccines. The combination of five central antigens accounted for 41% of all non-redundant interacting partners of the antigen dataset. Specific antigen mixtures represented in a few or just one MDR-CG further reduced the chance of microbiota interference. Rational antigen selection schemes facilitate the design of high-coverage and "magic bullet" multivalent vaccines against recalcitrant K. pneumoniae lineages. [ABSTRACT FROM AUTHOR]

There have been increasing reports of Klebsiella pneumoniae resistant to β-lactam antibiotics. This study aimed to determine the prevalence of some selected carbapenemase genes among clinical isolates of Klebsiella pneumoniae recovered from patients attending a private tertiary hospital in Southwestern Nigeria. The study was conducted over two months (February-March 2024). A total of 50 clinical isolates of Klebsiella pneumoniae from different clinical specimens were obtained from the Medical Microbiology Department, Babcock University Teaching Hospital (BUTH). The clinical isolates were then characterized using standard microbiological procedures and were tested for susceptibility to meropenem and other classes of antibiotics according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Polymerase Chain Reaction (PCR) detection for OXA-48 and NDM-1 carbapenemase genes was performed on the 50 clinical isolates. PCR analysis showed that 9 (18%) clinical isolates were positive for the OXA-48 gene, 22 (44%) were positive for the NDM-1 gene, 4 (8%) possessed both the OXA-48 and NDM-1 genes, and 23 (46%) possessed neither the OXA-48 nor NDM-1 genes. Antibiotic Susceptibility Testing (AST) revealed that all the clinical isolates were resistant to meropenem. In conclusion, this study demonstrates the presence of OXA-48 and NDM-1 genes in clinical isolates of Klebsiella pneumoniae recovered from patients attending a private tertiary hospital in Southwestern Nigeria, highlighting the role of ESBL (extended-spectrum beta-lactamase) as a major resistance mechanism alongside other mechanisms. Population-based surveillance programs should be implemented to monitor the prevalence and epidemiology of Klebsiella pneumoniae infections at the community level, facilitating early detection of outbreaks and identification of emerging antimicrobial resistance patterns. Core Tip: This study highlights the significant prevalence of NDM-1 and OXA-48 carbapenemase genes among Klebsiella pneumoniae clinical isolates in a private tertiary hospital in Southwestern Nigeria, with 44% and 18% of isolates harboring these genes, respectively. Notably, 46% of isolates were resistant to carbapenems despite lacking these genes, suggesting alternative resistance mechanisms. The findings underscore the urgent need for enhanced surveillance, infection control measures, and antibiotic stewardship programs to combat the spread of multidrug-resistant Klebsiella pneumoniae in healthcare settings. [ABSTRACT FROM AUTHOR]

Despite extensive knowledge on phage resistance at bacterium level, the resistance of bacterial communities is still not well-understood. Given its ubiquity, it is essential to understand resistance at the community level. We performed quantitative investigations on the dynamics of phage infection in Klebsiella pneumoniae biofilms. We found that the biofilms quickly developed resistance and resumed growth. Instead of mutations, the resistance was caused by unassembled phage tail fibers released by the phage-lysed bacteria. The tail fibers degraded the bacterial capsule essential for infection and induced spreading of capsule loss in the biofilm, and tuning tail fiber and capsule levels altered the resistance. Latent infections sustained in the biofilm despite resistance, allowing stable phage-bacteria coexistence. Last, we showed that the resistance exposed vulnerabilities in the biofilm. Our findings indicate that phage lysate plays important roles in shaping phage-biofilm interactions and open more dimensions for the rational design of strategies to counter bacteria with phage. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a prevalent condition characterized by persistent respiratory symptoms and airflow limitation. Bacterial infections may trigger COPD exacerbations, leading to more severe symptoms as well as increased morbidity and mortality rates. This study aimed to investigate the bacterial profiles and antibiotic resistance in COPD patients who had experienced exacerbation and type 2 respiratory failure at Adam Malik Central General Hospital, Medan, Indonesia. This retrospective study utilized medical records spanning from January 1, 2020, to December 1, 2022. The sample included patients aged 40--90 years who had experienced COPD exacerbation and type 2 respiratory failure. The exclusion criteria were patients who had received antibiotic therapy within 48 hours before admission, were severely immunocompromised, and had severe malignancy. The analysis results were presented in the form of means, standard deviations, and frequency distributions. Additionally, an analysis of the relationship between the categorical variables was performed using the Chi-squared test (p<0.05). The study analyzed 25 subjects with an average age of 63.6 years, primarily consisting of men (84%). It was shown that severe exacerbations were prevalent (92%), accompanied by the presence of common comorbidities including pneumonia (52%), diabetes mellitus (32%), and other non-communicable diseases (44%). Bacterial growth was observed in 76% of the subjects, predominantly involving Gram-negative bacteria (89.4%). Klebsiella pneumoniae (26.3%) and Pseudomonas aeruginosa (21.1%) were the most frequently isolated species. The antibiotic resistance patterns indicated that meropenem and amikacin had the highest resistance rates (100%). Cefepime, ertapenem, and gentamicin exhibited notable resistance rates of 66.7%, 66.7%, and 75.0%, respectively. This study highlights the high prevalence of Gram-negative bacteria and significant antibiotic resistance in COPD patients who exhibit exacerbation and type 2 respiratory failure. [ABSTRACT FROM AUTHOR]

The rise of antibiotic resistance and the dwindling antimicrobial pipeline have emerged as significant threats to public health. The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a global threat, with limited options available for targeted therapy. The CRKP has experienced various changes and discoveries in recent years regarding its frequency, transmission traits, and mechanisms of resistance. In this comprehensive review, we present an in-depth analysis of the global epidemiology of K. pneumoniae, elucidate resistance mechanisms underlying its spread, explore evolutionary dynamics concerning carbapenem-resistant hypervirulent strains as well as KL64 strains of K. pneumoniae, and discuss recent therapeutic advancements and effective control strategies while providing insights into future directions. By going through up-to-date reports, we found that the ST11 KL64 CRKP subclone with high risk demonstrated significant potential for expansion and survival benefits, likely due to genetic influences. In addition, it should be noted that phage and nanoparticle treatments still pose significant risks for resistance development; hence, innovative infection prevention and control initiatives rooted in One Health principles are advocated as effective measures against K. pneumoniae transmission. In the future, further imperative research is warranted to comprehend bacterial resistance mechanisms by focusing particularly on microbiome studies' application and implementation of the One Health strategy. [ABSTRACT FROM AUTHOR]

Background: Emerging carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) (CRKP) bacteremias are presenting significant public health risks due to limited treatment options and increased mortality. K. pneumoniae isolates exhibit carbapenem resistance rates that vary from 25% to 50% throughout the European continent, including our country. Aims: To assess the characteristics of CRKP bacteremia, a condition that has recently demonstrated an increasing prevalence in our center. We sought to ascertain the resistance rates of isolated strains to antibiotics other than carbapenems, identify the responsible carbapenemase genes, evaluate the efficacy of antibiotics, determine mortality rates, explore clonality among strains, and investigate the influence of the COVID-19 pandemic on all these factors. Study Design: Retrospective observational study. Methods: This study included patients aged 18 and older who had experienced meropenem-resistant K. pneumoniae bacteremia. Meropenem resistance was confirmed by employing the Kirby-Bauer disk diffusion method. Meropenem minimum inhibitory concentration (MIC) levels were determined using the gradient test, while colistin MIC levels were ascertained using the disk elution technique. Carbapenemase genes were evaluated via colony polymerase chain reaction (PCR), and clonality analysis was performed using the arbitrarily primed PCR technique. Results: The study comprised 230 patients, with a mean age of 63.1 ± 15.9 years, of whom 58.7% were male. Oxacillinase-48 (OXA-48) was detected in 74.8% of the patients, New Delhi metallo-beta-lactamase (NDM) in 12.6%, OXA-48 + NDM in 7.8%, and KPC in 4.8%. The 14-day and 30-day mortality rates were 57% and 69.6%, respectively. Multivariate analysis of the 30-day mortality revealed several crucial factors, including bacteremia development in the intensive care unit, the occurrence of bacteremia during the COVID-19 pandemic, polymicrobial bacteremia, the use of indwelling intravenous catheters, a platelet count of ≤ 140,000/µl, procalcitonin levels of ≥ 6 µg/l, and a Charlson comorbidity score ≥ 3. Notably, the OXA-48 and KPC genes were upregulated significantly during the COVID-19 pandemic, while the NDM gene groups were downregulated. Additionally, both 14-day and 30-day mortality rates increased significantly. Conclusion: In this study, the most prevalent carbapenemase gene was OXA-48; however, there has been a recent increase in KPC genes. No dominant epidemic strain was identified through clonality analysis. The clustering rate was 68% before the pandemic, increasing to 85.7% during the pandemic. The significance of infection control measures is underscored by the rise in both clustering and mortality rates during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality. In 2020–21, non-pharmaceutical interventions associated with the COVID-19 pandemic reduced not only the transmission of SARS-CoV-2, but also the transmission of other LRI pathogens. Tracking LRI incidence and mortality, as well as the pathogens responsible, can guide health-system responses and funding priorities to reduce future burden. We present estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 of the burden of non-COVID-19 LRIs and corresponding aetiologies from 1990 to 2021, inclusive of pandemic effects on the incidence and mortality of select respiratory viruses, globally, regionally, and for 204 countries and territories. We estimated mortality, incidence, and aetiology attribution for LRI, defined by the GBD as pneumonia or bronchiolitis, not inclusive of COVID-19. We analysed 26 259 site-years of mortality data using the Cause of Death Ensemble model to estimate LRI mortality rates. We analysed all available age-specific and sex-specific data sources, including published literature identified by a systematic review, as well as household surveys, hospital admissions, health insurance claims, and LRI mortality estimates, to generate internally consistent estimates of incidence and prevalence using DisMod-MR 2.1. For aetiology estimation, we analysed multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature data using a network analysis model to produce the proportion of LRI deaths and episodes attributable to the following pathogens: Acinetobacter baumannii, Chlamydia spp, Enterobacter spp, Escherichia coli, fungi, group B streptococcus, Haemophilus influenzae, influenza viruses, Klebsiella pneumoniae, Legionella spp, Mycoplasma spp, polymicrobial infections, Pseudomonas aeruginosa , respiratory syncytial virus (RSV), Staphylococcus aureus, Streptococcus pneumoniae , and other viruses (ie, the aggregate of all viruses studied except influenza and RSV), as well as a residual category of other bacterial pathogens. Globally, in 2021, we estimated 344 million (95% uncertainty interval [UI] 325–364) incident episodes of LRI, or 4350 episodes (4120–4610) per 100 000 population, and 2·18 million deaths (1·98–2·36), or 27·7 deaths (25·1–29·9) per 100 000. 502 000 deaths (406 000–611 000) were in children younger than 5 years, among which 254 000 deaths (197 000–320 000) occurred in countries with a low Socio-demographic Index. Of the 18 modelled pathogen categories in 2021, S pneumoniae was responsible for the highest proportions of LRI episodes and deaths, with an estimated 97·9 million (92·1–104·0) episodes and 505 000 deaths (454 000–555 000) globally. The pathogens responsible for the second and third highest episode counts globally were other viral aetiologies (46·4 million [43·6–49·3] episodes) and Mycoplasma spp (25·3 million [23·5–27·2]), while those responsible for the second and third highest death counts were S aureus (424 000 [380 000–459 000]) and K pneumoniae (176 000 [158 000–194 000]). From 1990 to 2019, the global all-age non-COVID-19 LRI mortality rate declined by 41·7% (35·9–46·9), from 56·5 deaths (51·3–61·9) to 32·9 deaths (29·9–35·4) per 100 000. From 2019 to 2021, during the COVID-19 pandemic and implementation of associated non-pharmaceutical interventions, we estimated a 16·0% (13·1–18·6) decline in the global all-age non-COVID-19 LRI mortality rate, largely accounted for by a 71·8% (63·8–78·9) decline in the number of influenza deaths and a 66·7% (56·6–75·3) decline in the number of RSV deaths. Substantial progress has been made in reducing LRI mortality, but the burden remains high, especially in low-income and middle-income countries. During the COVID-19 pandemic, with its associated non-pharmaceutical interventions, global incident LRI cases and mortality attributable to influenza and RSV declined substantially. Expanding access to health-care services and vaccines, including S pneumoniae, H influenzae type B, and novel RSV vaccines, along with new low-cost interventions against S aureus , could mitigate the LRI burden and prevent transmission of LRI-causing pathogens. Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care (UK). [ABSTRACT FROM AUTHOR]

Carbapenemase-producing Enterobacterales (CPE) are a serious concern in human clinical settings. Companion animal–origin CPE have been only rarely identified in several countries, but they have not yet been identified in Japan. In this study, we present the first case of a canine infected with CPE in Japan. The patient was hospitalized due to pyometra. The pus discharged from the patient's uterus was subjected to bacteriological analysis. As a result, E. coli was identified in the pus and exhibited resistance to piperacillin, amoxicillin–clavulanic acid, cefazolin, ceftazidime, cefepime, meropenem, amikacin, and sulfamethoxazole–trimethoprim and susceptibility to aztreonam, minocycline, and levofloxacin. Results of the sodium mercaptoacetic acid double-disk synergy test showed that the E. coli isolate was positive for metallo-β-lactamases. Next-generation sequencing identified the bla NDM-5 gene, which was located in the IncFII-type plasmid together with bla TEM-1b , rmtB , aadA2 , ble MBL, sul1 , qacE , and dfrA12. The case was treated successfully with doxycycline and orbifloxacin. Our finding emphasizes that close attention should be paid to the significance of CPE harboring multidrug-resistance plasmid in companion animals, based on the perspective of One Health approach in Japan as well as in other countries. [ABSTRACT FROM AUTHOR]

Sepsis is an uncontrolled reaction of the body to an infection, and if not effectively treated, it can progress to septic shock, multiple organ failure, and ultimately, death. Objective: To determine the resistance profile of Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) strains isolated in sepsis cases diagnosed at the Infectious Diseases Clinic in Craiova, Romania. Methods: The bacteria responsible for sepsis cases were identified using the Vitek 2 Systems version 06.01, which was then employed to assess their antimicrobial susceptibility (Global CLSI and Phenotypic 2017). Results: We have identified 989 patients diagnosed with bacterial sepsis. Among these, 953 cases were caused by Gram-negative rods, with 415 attributed to E. coli and 278 to K. pneumoniae. High levels of resistance to ampicillin were recorded for E. coli strains isolated in sepsis cases (64.6%); adding sulbactam lowers the level of resistance to 41.8%. Resistance to 3rd generation cephalosporins varied between 7.47 and 14.6% and another 3.41 to 11.1% are dose-dependent susceptibility strains. Resistance to carbapenems (i.e., ertapenem, meropenem) is low—2.18–2.42%. More than 95% of the tested K. pneumoniae strains were resistant to ampicillin and adding sulbactam as a β-lactamase inhibitor only halves that level. Resistance to 3rd generation cephalosporins varied between 20.7% and 22.5%; resistance levels for K. pneumoniae were notably higher than those for E. coli. Over 95% of K. pneumoniae strains showed resistance to ampicillin, and resistance to 3rd generation cephalosporins varied between 20.7% and 22.5%. Additionally, K. pneumoniae exhibited higher resistance to carbapenems (13.7–19.5%) compared to E. coli (2.18–2.42%). Conclusions: Antimicrobial resistance levels are generally lower than continental and national data, except for ampicillin and carbapenems (meropenem and ertapenem). K. pneumoniae strains are significantly more resistant than E. coli strains. [ABSTRACT FROM AUTHOR]

Background: This study aimed to establish a method for the rapid detection of highly virulent Klebsiella pneumoniae (hvKP) by using multienzyme isothermal rapid amplification (MIRA) technology. The laboratory can quickly, accurately, and conveniently diagnose highly virulent Klebsiella pneumoniae infection. Methods: For this study, 7 laboratory standard strains and 184 clinical isolates (including 70 strains of Klebsiella pneumoniae) were collected and screened for highly virulent Klebsiella pneumoniae based on its colony morphology, wire drawing test, and next-generation sequencing (NGS) results. Based on the nucleic acid sequence of the peg344 gene of highly virulent Klebsiella pneumoniae on GenBank (no. AP006726.1), specific conserved regions were selected to design MIRA and real-time fluorescence quantitative PCR (qPCR) specific primers and probes. The MIRA and qPCR methods were used to detect the tested strain, and the specificity, sensitivity, and clinical performance of the MIRA method for detecting hvKP were evaluated. Results: In total, 21 cases of hvKP were screened from clinical isolates. The MIRA detection method utilizes specific primers and probes to transmit significant fluorescence signals at 39°C, and the detection process takes 30 minutes. The specificity test results showed that only hvKP had a specific amplification curve, while the rest of nonhighly virulent Klebsiella pneumoniae (non-hvKP) had no specific amplification curve. The sensitivity test results showed that the sensitivity of MIRA for detecting hvKP is 7 × 10² CFU/mL, which is consistent with the sensitivity of the real-time fluorescence qPCR method. A simultaneous detection of 184 clinical isolates was accomplished by using MIRA and qPCR methods. Twenty-one strains of hvKP have specific amplification curves, while the remaining 163 strains of non-hvKP have no specific amplification curves. The accuracy of both methods for detecting hvKP is 100%. Conclusions: The established multienzyme isothermal rapid amplification (MIRA) has the following characteristics: a short detection time, high sensitivity, and a strong specificity, and it can be used as a powerful tool for an early diagnosis and epidemiological monitoring of hvKp. [ABSTRACT FROM AUTHOR]

Background and Aims: There are many difficulties in treating Klebsiella pneumoniae, necessitating the creation of more preventative/therapeutic measures like vaccinations. However, after numerous attempts, there is still no authorized and widely accessible vaccine. The present study aimed to systematically review published studies on K. pneumoniae vaccines in human subjects/samples. Methods: To find published studies, several electronic databases, including Scopus, PubMed, Web of Science, ClinicalKey, ClinicalTrials.gov, and Cochrane Library were searched without time limitation using the appropriate keywords. Studies were scrutinized, and the information from those that met our inclusion criteria was gathered and analyzed. Results: In total, 691 studies were found, of which 14 articles were included for systematic review. Bacterial lysate containing K. pneumoniae was the most studied vaccine candidate. As the main indicator of human immune responses to K. pneumoniae, antibody responses were determined by most studies. The antigen amount, the route of immunization, and the immunization schedule were varying in the studies and were chosen based on several factors such as the disease model, the vaccine type, the vaccination setting (prophylactic or therapeutic), and so on. Conclusion: The majority of studies asserted that their vaccination was efficient and safe, which was demonstrated by a decrease in the rate of infections and the induction of protective antibody, cell‐dependent, and/or cytokine responses. Altogether, the information provided here will help researchers examine the K. pneumoniae vaccine candidates more closely and take future actions that will be more consistently successful. [ABSTRACT FROM AUTHOR]

In vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat Escherichia coli and Klebsiella pneumoniae infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of E. coli and K. pneumoniae. Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with E. coli and K. pneumoniae strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls. At acidic urine pH, both antimicrobials were effective, achieving similar reductions in E. coli concentrations in the kidneys in immunocompetent and immunocompromised mice and in K. pneumoniae in immunocompetent mice. At a neutral urine pH, both therapies reduced the presence of E. coli in the kidneys of immunocompetent mice. However, in immunocompromised mice, antimicrobials were ineffective at treating E. coli infection in the kidneys at a neutral urine pH and showed reduced efficacy against K. pneumoniae at both acidic and neutral urine pH. The results showed no correlation between urine pH and antimicrobial efficacy, suggesting that the reduced effectiveness is associated with the animals' immunocompetence status. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce. A multidisciplinary team conducted a multifaceted intervention in a CR-Kp endemic hospital over a 6-year period. We assessed the monthly long-term impacts of ASPs on carbapenem use, incidence density (ID), and crude death rates of hospital-acquired CR-Kp infections. Other variables potentially related to CR-Kp incidence and healthcare activity indicators were monitored. Carbapenem use showed a sustained reduction over the long term, with a difference of −66.19% (95% CI −87.03 to −45.34) between the expected pre-intervention trend consumption value and that obtained six years after starting the program. The ID of CR-Kp also decreased significantly and was maintained over the long term, with a relative reduction of −88.14% (95% CI; −100.4 to −75.85) at the end of the study period. The crude death rate of CR-Kp at 14 and 28 days decreased significantly after the intervention and remained steady after six years. Infection control indicator trends remained stable. This mixed ASP contributed to reducing the high incidence of infections and mortality rates of CR-Kp, achieving a sustained ecological and clinical effect. [ABSTRACT FROM AUTHOR]

To investigate the characteristics and drug resistance patterns of Klebsiella pneumoniae (K. pneumoniae) infection in pediatric intensive care unit (PICU). Methods: K. pneumoniae strains from 17 domestic PICUs were analyzed for overall condition and drug resistance using WHO-NET software. Results: From 2016 to 2022, there was a linear increase in the detection rate of K. pneumoniae (P< 0.05), with a total of 2591 (9.7%) strains detected. The primary sites of K. pneumoniae detection were the respiratory tract (71.1%), blood (8.6%), and urinary tract (7.1%). K. pneumoniae's resistance to penicillin drugs exceeded 90%, and are over 50% to cephalosporins. Resistance to cefoperazone-sulbactam decreased from 51.7% to 25.7%, and ranged from 9.1% to 20.8% for ceftolozane-tazobactam. Carbapenem-resistant K. pneumoniae strains constituted 32.3%. Resistance to imipenem and meropenem have decreased to 33.8% and 40.2%, while increased to 35.2% for ertapenem. Levofloxacin and amikacin resistance rates have decreased to 25.7% and 9.1%, but remain high at 63.8% for moxifloxacin and 44.6% for ciprofloxacin. K. pneumoniae demonstrated the lowest resistance rates to polymyxin B (0.9%), tigecycline (2.2%), and polymyxin E (3.1%). No strain of K. pneumoniae was resistant to both polymyxin B and meropenem. However, some strains showed co-resistance to meropenem with other antibiotics, including tigecycline (2%), imipenem (16%), amikacin (27%), colistin (37%), and levofloxacin (41%). Conclusion: The rates of isolation and drug resistance of K. pneumoniae in PICU have significantly increased over 7 years. Careful antibiotic use, infection control strategies, and appropriate antibiotic combinations are crucial in addressing this problem. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionCombination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Existing data support the combination of aztreonam and ceftazidime/avibactam (CZA) against class serine-β-lactamase (SBL)- and metallo-β-lactamase (MBL) - producing Enterobacterales. However, data about that combination against SBL- and MBL-producing P. aeruginosa are scarce. The objective of the study was to assess the in vitro activity of CZA and aztreonam alone and in combination against SBL- and MBL-producing XDR P. aeruginosa isolatesThe combination was analyzed by means of the hollow-fiber infection model in three selected carbapenemase-producing P. aeruginosa isolates that were representative of the three most common XDRP. aeruginosa high-risk clones (ST175, ST111, ST235) responsible for global nosocomial infection outbreaks.The three isolates were nonsusceptible to CZA and nonsusceptible to aztreonam. In the dynamic hollow-fiber infection model, the combination of CZA plus aztreonam exerts a bactericidal effect on the isolates, regardless of their resistance mechanism and demonstrates synergistic interactions against three isolates, achieving a bacterial reduction of 5.07 log10 CFU/ml, 5.2 log10 CFU/ml and 4 log10 CFU/ml, respectively.The combination of CZA and aztreonam significantly enhanced the in vitro efficacy against XDR P. aeruginosa isolates compared to each monotherapy. This improvement suggests that the combination could serve as a feasible treatment alternative for infections caused by carbapenemase-producing XDR P. aeruginosa, especially in scenarios where no other treatment options are available. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU. Methods: In the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients. Results: A total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7–96.4%, 25.7–100%, 73.3–100%, and 89.2–100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0–96.8%, 0–100%, and 6.4–100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates. Conclusions: Based on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam–beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this work was to assess dynamic cytokine profiles associated with bloodstream infection (BSI) caused by Klebsiella pneumoniae (Kpn) and investigate the clinical features associated with mortality. Methods: A total of 114 patients with positive BSI-Kpn and 12 sepsis individuals without blood positive bacteria culture were followed up. Cytokine profiles were analyzed by multiplex immunoassay on the first, third, seventh and fourteenth day after diagnosis. The test cytokines included arginase, interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12 (p70), and IL-23. The minimum inhibitory concentration (MIC) of 24 antibiotics were tested for BSI-Kpn. Risk factors associated with the 30-day mortality and 120-day mortality were evaluated using logistic analyses and nomogram. Results: There were 55 out of 114 patients with BSI-Kpn were included. All isolates showed high susceptibility rate to novel avibactam combinations. The level of arginase was the highest in carbapenem-resistant Kpn (CRKP) patients. The AUCs of arginase, TNF-α and IL-4 reached 0.726, 0.495, and 0.549, respectively, whereas the AUC for the combination of these three cytokines was 0.805. Notably, 120-day mortality in patients with CRKP was higher than carbapenem-sensitive K. pneumoniae (CSKP). Furthermore, the long-term and high levels of IL-6 and IL-10 were associated with death. Conclusions: High expression of arginase is correlated with CRKP. In addition, BSI-CRKP could result in indolent clinic course but poor long-term prognosis. Continuous increase of IL-6 and IL-10 were associated with mortality. [ABSTRACT FROM AUTHOR]

One of the most common bacteria that cause nosocomial infections is Klebsiella pneumonia (K. pneumoniae), especially in patients who are very sick and admitted to the intensive care unit (ICU). The frequency of multi-drug-resistant Klebsiella pneumoniae (MDRKP) has dramatically increased worldwide in recent decades, posing an urgent threat to public health. The Western world's bacteriophage (phage) studies have been revitalized due to the increasing reports of antimicrobial resistance and the restricted development and discovery of new antibiotics. These factors have also spurred innovation in other scientific domains. The primary agent in phage treatment is an obligately lytic organism (called bacteriophage) that kills the corresponding bacterial host while sparing human cells and lessening the broader effects of antibiotic usage on commensal bacteria. Phage treatment is developing quickly, leading to many clinical studies and instances of life-saving medicinal use. In addition, phage treatment has a few immunological adverse effects and consequences in addition to its usefulness. Since K. pneumoniae antibiotic resistance has made treating multidrug-resistant (MDR) infections challenging, phage therapy (PT) has emerged as a novel therapeutic strategy. The effectiveness of phages has also been investigated in K. pneumoniae biofilms and animal infection models. Compared with antibiotics, PT exhibits numerous advantages, including a particular lysis spectrum, co-evolution with bacteria to avoid the emergence of phage resistance, and a higher abundance and diversity of phage resources than found in antibiotics. Moreover, phages are eliminated in the absence of a host bacterium, which makes them the only therapeutic agent that self-regulates at the sites of infection. Therefore, it is essential to pay attention to the role of PT in treating these infections. This study summarizes the state of knowledge on Klebsiella spp. phages and provides an outlook on the development of phage-based treatments that target K. pneumoniae in clinical trials. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hypervirulent Klebsiella pneumoniae (HvKP) is an emerging bacterial pathogen causing invasive infection in immune-competent humans. The hypervirulence is strongly linked to the overproduction of hypermucoviscous capsule, but the underlying regulatory mechanisms of hypermucoviscosity (HMV) have been elusive, especially at the post-transcriptional level mediated by small noncoding RNAs (sRNAs). Using a recently developed RNA interactome profiling approach iRIL-seq, we interrogate the Hfq-associated sRNA regulatory network and establish an intracellular RNA-RNA interactome in HvKP. Our data reveal numerous interactions between sRNAs and HMV-related mRNAs, and identify a plethora of sRNAs that repress or promote HMV. One of the strongest HMV repressors is ArcZ, which is activated by the catabolite regulator CRP and targets many HMV-related genes including mlaA and fbp. We discover that MlaA and its function in phospholipid transport is crucial for capsule retention and HMV, inactivation of which abolishes Klebsiella virulence in mice. ArcZ overexpression drastically reduces bacterial burden in mice and reduces HMV in multiple hypervirulent and carbapenem-resistant clinical isolates, indicating ArcZ is a potent RNA inhibitor of bacterial pneumonia with therapeutic potential. Our work unravels a novel CRP-ArcZ-MlaA regulatory circuit of HMV and provides mechanistic insights into the posttranscriptional virulence control in a superbug of global concern. By performing a global RNA-RNA interactome analysis in hypervirulent Klebsiella pneumoniae, the authors identify the small RNA ArcZ targets many capsule genes and a key virulence factor MlaA, inhibiting Klebsiella infection and pathogenesis in mice. [ABSTRACT FROM AUTHOR]