Clinical characteristics, effectiveness and cost of different treatment methods for invasive Klebsiella pneumoniae liver abscess syndrome. / ä¾µè¢­æ€§è‚ºç‚Žå ‹é›·ä¼¯èŒè‚è„“è‚¿ç»¼åˆå¾çš„ä¸´åºŠç‰¹å¾åŠä¸åŒæ²»ç–—æ–¹å¼çš„æœ‰æ•ˆæ€§ä¸Žè´¹ç”¨åˆ†æž.

OBJECTIVES: Bacterial liver abscess is one of the common infectious diseases of the digestive system. Invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS) refers to cases where, in addition to liver abscess, there are migratory infections foci or other invasive manifestations. The clinical characteristics and risk factors of IKLAS are not fully elucidated, and there is a lack of research on the effectiveness and cost-effectiveness of different treatment methods. This study aims to compare the clinical characteristics of patients with IKLAS and non-IKLAS, and explore effective and economical treatment methods. METHODS: This retrospective study collected medical records of patients with Klebsiella pneumoniae liver abscess treated at Xiangya Hospital of Central South University from January 2010 to December 2023. A total of 201 patients were included, dividing into an IKLAS group (n=37) and a non-IKLAS group (n=164). Differences in demographics, symptoms and signs, laboratory indicators, imaging characteristics, comorbidities, treatment methods, treatment outcomes, and direct treatment costs between 2 groups were analyzed. The study also compared the effectiveness and costs of different treatment methods. RESULTS: Compared with the non-IKLAS group, the proportion of patients with diabetes, Quick Sequential Organ Failure Assessment (qSOFA)≥2, immune deficiency, anemia, and thrombocytopenia in the IKLAS group was higher, and the level of procalcitonin at the onset in the IKLAS group was also higher (all P<0.05). In terms of symptoms and signs, the IKLAS group had a higher proportion of visual abnormalities and a lower proportion of complaints of abdominal pain (both P<0.05). In terms of complications, the incidence of combined pleural effusion, pulmonary infection, acute renal failure, respiratory failure, and multiple organ failure was higher in the IKLAS group (all P<0.05). The IKLAS group had a higher proportion of patients treated with antibiotics alone (24.32% vs 11.59%), while the non-IKLAS group had a higher proportion of patients treated with antibiotics combined with puncture and drainage (86.59% vs 64.86%, both P<0.05). The overall effective rate of the IKLAS group (83.78%) was lower than that of the non-IKLAS group (95.73%), and the treatment and drug costs were higher (all P<0.05). The treatment method of antibiotics combined with surgical resection of infectious foci showed a 100% improvement rate, antibiotics combined with abscess puncture and drainage had an 84.9% improvement rate, and in antibiotics alone had an 82.1% improvement rate, with statistical differences among the 3 treatment methods (P<0.05). In terms of treatment costs, antibiotics alone were the most expensive (P<0.05). CONCLUSIONS: Patients with IKLAS have poorer prognosis and higher direct medical costs. The combination of abscess puncture and drainage or surgery has a higher improvement rate and lower hospitalization costs compared to antibiotics alone, suggesting that surgical intervention may reduce antibiotic costs and save medical expenses.

Emergence of silent NDM-1 carbapenemase gene in carbapenem-susceptible Klebsiella pneumoniae: Clinical implications and epidemiological insights.

The global dissemination of carbapenemase genes, particularly blaNDM-1, poses a significant threat to public health. While research has mainly focused on strains with phenotypic resistance, the impact of silent resistance genes has been largely overlooked. This study documents the first instance of silent blaNDM-1 in a cluster of clonally related carbapenem-susceptible K. pneumoniae strains from a single patient. Despite initial effectiveness of carbapenem therapy, the patient experienced four recurrent lung infections over five months, indicating persistent K. pneumoniae infection. Genomic sequencing revealed all strains harbored blaNDM-1 on the epidemic IncX3 plasmid. A deletion within the upstream promoter region (PISAba125) of blaNDM-1 hindered its expression, resulting in phenotypic susceptibility to carbapenems. However, in vitro bactericidal assays and a mouse infection model showed that K. pneumoniae strains with silent blaNDM-1 exhibited significant tolerance to carbapenem-mediated killing. These findings demonstrate that silent blaNDM-1 can mediate both phenotypic susceptibility and antibiotic tolerance. In silico analysis of 1986 blaNDM sequences showed that 1956 (98.5%) retained the original promoter PISAba125. Given that previous genomic sequencing typically targets carbapenem-resistant strains, accurately assessing the prevalence of silent blaNDM remains challenging. This study highlights the hidden threat of silent resistance genes to clinical antimicrobial therapy and calls for enhanced clinical awareness and laboratory detection.

Antimicrobial resistance profiles and genome characteristics of Klebsiella isolated from the faeces of neonates in the neonatal intensive care unit.

Introduction. Klebsiella spp. are important bacteria that colonize the human intestine, especially in preterm infants; they can induce local and systemic disease under specific circumstances, including inflammatory bowel disease, necrotizing enterocolitis and colorectal cancer.Hypothesis. Klebsiella spp. colonized in the intestine of the neonates in the neonatal intensive care unit (NICU) may be associated with disease and antibiotic resistance, which will be hazardous to the children.Aim. Our aim was to know about the prevalence, antimicrobial resistance and genome characteristics of Klebsiella spp. in neonate carriers.Methodology. Genome sequencing and analysis, and antimicrobial susceptibility testing were mainly performed in this study.Results. The isolation rates of Klebsiella spp. strains were 3.7% (16/436) in 2014 and 4.3% (18/420) in 2021. Cases with intestinal-colonized Klebsiella spp. were mainly infants with low birth weights or those with pneumonia or hyperbilirubinemia. According to the core-pan genomic analysis, 34 stains showed gene polymorphism and a sequence type (ST) of an emerging high-risk clone (ST11). Eight strains (23.5%) were found to be resistant to 2 or more antibiotics, and 46 genes/gene families along with nine plasmids were identified that conferred resistance to antibiotics. In particular, the two strains were multidrug-resistant. Strain A1256 that is related to Klebsiella quasipneumoniae subsp. similipneumoniae was uncommon, carrying two plasmids similar to IncFII and IncX3 that included five antibiotic resistance genes.Conclusion. The prevention and control of neonatal Klebsiella spp. colonization in the NICU should be strengthened by paying increased attention to preventing antimicrobial resistance in neonates.

Double trouble: an unusual case of Klebsiella pneumoniae invasive syndrome with liver abscess, gallbladder empyema and infective endocarditis.

BACKGROUND: Klebsiella pneumoniae invasive syndrome (KPIS) is characterized by primary pyogenic liver abscess associated with metastatic infections. Although rare, Klebsiella endocarditis carries a high mortality risk. CASE PRESENTATION: A 60-year-old lady with type II diabetes mellitus presented with fever, malaise, right hypochondriac pain and vomiting for two weeks. Ultrasound abdomen revealed a collection within liver, and distended gallbladder with echogenic debris within. 3 days after ultrasound guided pigtail drainage of gallbladder empyema, newly presence murmur detected. Pus, urine, and blood cultures obtained were positive for Klebsiella pneumonia. Echocardiogram exhibited oscillating mass attached to anterior mitral valve leaflet. After 6 weeks of intravenous ceftriaxone, follow-up echocardiogram and ultrasound showed complete resolution of mitral valve vegetation, hepatic and gallbladder collection. CONCLUSION: Concomitant extrahepatic infective endocarditis (IE) should raise concerns in daily practice for patients with Klebsiella pneumoniae liver abscesses, despite the rarity of Klebsiella endocarditis. In the absence of diagnostic suspicion, antibiotic treatment regimens may be shortened, and adverse effects from IE infection may ensue.

Evolution of blaKPC Under the Pressure of Carbapenems and Ceftazidime/Avibactam in a Patient With Persistent Bacteremia Caused by Klebsiella pneumoniae.

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.

A Case of Klebsiella pneumoniae infection.

INTRODUCTION: In recent years, hypervirulent Klebsiella pneumoniae (hvKp) has attracted increasing attention. It usually causes liver abscesses, which spread through the bloodstream to other parts such as the eyes, brain, lungs. 5.5% of all paroxysmal sympathetic hyperactivity syndrome are associated with infection, hydrocephalus, brain tumors, and some unknown causes. Younger patients with focal lesions of the brain parenchyma are at higher risk of paroxysmal sympathetic hyperactivity (PSH). CASE PRESENTATION: This case report details the clinical features of Klebsiella pneumoniae diagnosed in a healthy individual. In addition to liver abscesses, bacteremia, and hyperglycemia, there are also brain abscesses, hernias, and postoperative paroxysmal sympathetic hyperactivity, an unexpected association between diseases or symptoms. The patient stabilized after comprehensive treatment, including early drainage of abscesses, rapid pathogen diagnosis, and timely and appropriate antibiotics. At a two-month follow-up, no signs of infection recurrence were noted, and the patient regained neurological function and could participate in regular physical activity. DISCUSSION: Symptoms of Klebsiella pneumoniae infection usually appear gradually, and misdiagnosis is common. When young patients suddenly develop high fever and abscess at a particular site, Klebsiella pneumoniae infection should be considered routine. Paroxysmal sympathetic hyperactivity syndrome caused by infection is rare, but a clinical score (PSH assessment measure, PSH-AM score) should be performed when clinical features appear. Early diagnosis and treatment can improve the prognosis.

Intracranial dissemination of Klebsiella pneumoniae originating from pulmonary infection: a case report.

BACKGROUND: Metastatic brain abscesses caused by Klebsiella pneumoniae are extremely rare but life-threatening conditions. To depict a unique case of the middle-aged hypertensive man with an unusual presentation of metastatic brain abscesses originating from a pleural abscess caused by Klebsiella pneumoniae and subsequently leading to loss of consciousness (LOC). CASE REPORT: A 52-year-old Iranian man with a history of hypertension presented to the emergency department with a five-day history of worsening cough, high-grade fever, shortness of breath, chest pain, fatigue, and a productive cough. Laboratory tests revealed leukocytosis, elevated C-reactive protein, and respiratory alkalosis. A chest computed tomography scan confirmed pneumonia, and a brain scan revealed multiple hypodense lesions. Despite antibiotic therapy, the patient's condition worsened, leading to confusion, disorientation, and loss of consciousness. Magnetic resonance imaging revealed multiple ring-enhancing lesions, suggesting an abscess formation. Bronchial washings and BAL samples confirmed a lower respiratory tract infection. Cultures from the bronchial washings grew Klebsiella pneumoniae. CONCLUSIONS: Metastatic brain abscesses caused by Klebsiella pneumoniae are exceedingly rare but life-threatening conditions. Timely diagnosis and effective antimicrobial treatment are critical for patient outcomes. This case underscores the significance of recognizing atypical presentations of bacterial infections, as early detection and appropriate management can significantly impact patient outcomes.

In vivo and in vitro efficacy of the ithmid kohl/zinc-oxide nanoparticles, ithmid kohl/Aloe vera, and zinc-oxide nanoparticles/Aloe vera for the treatment of bacterial endophthalmitis.

The aim of this study was to investigate the efficacy of the ithmid kohl/zinc-oxide nanoparticles (ZnONPs), ithmid kohl/Aloe vera, and ZnONPs/Aloe vera in the treatment of bacterial endophthalmitis. The endophthalmitis model was prepared by contaminating both eyes of 24 healthy adult male albino rabbits with a clinical isolate of Klebsiella pneumoniae. The animals were randomly divided into eight groups (A-H) according to the treatment. Group A received 1 ml of ithmid kohl/ZnONPs ointment, group B received 1 ml of ithmid kohl/Aloe vera gel ointment, group C received 1 ml of ZnONPs/Aloe vera gel ointment, and groups D, E, and F were treated with 1 ml of ithmid kohl solution (0.5 g/ml in distilled water), 1 ml of ZnONPs (0.5 g/ml) colloidal dispersion, and 1 ml of Aloe vera gel, respectively. Group G received 100 µl of a tetracycline antibiotic solution (final concentration: 16 µg/ml), and group H received sterile distilled water (no treatment). In vitro antibacterial activity was evaluated against K. pneumoniae using the agar well diffusion. The combination of ithmid kohl/ZnONPs was the most effective formulation for treating endophthalmitis model in infected rabbits within 2 days. In vitro antibacterial assay confirmed the potential of the ithmid kohl/ZnONPs formulation, which had the largest zone of inhibition (31 mm) among the compounds tested. The preparation of the ithmid kohl/ZnONPs formulation and its in vivo experiment in albino rabbits for the treatment of bacterial endophthalmitis was an innovative approach that has shown promise and may potentially serve as a viable alternative in clinical practice.

Gas Chromatography-Ion Mobility Spectrometry Reveals Acetoin as a Biomarker for Carbapenemase-Producing Klebsiella pneumoniae.

BACKGROUND This study aimed to detect the volatile organic compound (VOC), 3-hydroxy-2-butanone (acetoin) using gas chromatography-ion mobility spectrometry (GC-IMS) in antimicrobial-resistant Klebsiella pneumoniae (K. pneumoniae) carbapenemase (KPC)-producing bacteria. MATERIAL AND METHODS Using stromal fluid of blood culture bottles (BacT/ALERT® SA) as the medium, 3-hydroxy-2-butanone (acetoin) released by K. pneumoniae during growth was detected using GC-IMS. The impact of imipenem (IPM) and carbapenemase inhibitors [avibactam sodium or pyridine-2,6-dicarboxylic acid (DPA)] on the emission of 3-hydroxy-2-butanone (acetoin) from various carbapenemase-producing K. pneumoniae was further investigated. Subsequently, VOCal software was used to generate a pseudo-3D plot of 3-hydroxy-2-butanone (acetoin), and the relative peak volumes were exported for data analysis. Standard strains served as references, and the findings were validated with clinical isolates. RESULTS The pattern of temporal changes in the 3-hydroxy-2-butanone (acetoin) release from K. pneumoniae in the absence of IPM was consistent with the growth curve. After the IPM addition, carbapenemase-positive strains released significantly higher contents of 3-hydroxy-2-butanone (acetoin) than carbapenemase-negative strains at the late exponential growth phase (T2). Notably, adding avibactam sodium significantly decreased the 3-hydroxy-2-butanone (acetoin) content released from the class A carbapenemase-producing strains as compared to the absence of the carbapenemase inhibitor. Conversely, adding DPA significantly decreased the 3-hydroxy-2-butanone (acetoin) content released from the class B carbapenemase-producing strains (both standard and clinical strains, all P<0.05). CONCLUSIONS This study demonstrated the potential of 3-hydroxy-2-butanone (acetoin) as a VOC biomarker for detecting carbapenemase-producing K. pneumoniae, as revealed by GC-IMS analysis.

An approach to combat multidrug-resistant K. pneumoniae strain using synergistic effects of Ocotea diospyrifolia essential oil in combination with amikacin.

The natural antimicrobial properties of essential oils (EOs) have contributed to the battle against multidrug-resistant microorganisms by providing new ways to develop more effective antibiotic agents. In this study, we investigated the chemical composition of Ocotea diospyrifolia essential oil (OdOE) and its antimicrobial properties combined with amikacin (AMK). Through gas chromatography-mass spectrometry (GCMS) analysis, the primary constituents of OdOE were identified as α-bisabolol (45.8 %), ß-bisabolene (9.4 %), γ-elemene (7.6 %), (Z)- ß-farnesene (5.2 %), spathulenol (3.5 %), (Z)-caryophyllene (3.3 %), and (E)-caryophyllene (3.1 %). In vitro assessments showed that the combined administration of OdOE and AMK exerted a synergistic antibacterial effect on the multidrug-resistant K. pneumoniae strain. This synergistic effect demonstrated bacteriostatic action. OdEO combined with amikacin showed protein extravasation within 2 h of treatment, leading to bacterial death, which was determined by a reduction in viable cell count. The effective concentrations showed hemocompatibility. In vivo assessments using Caenorhabditis elegans as a model showed the survival of 85 % of infected nematodes. Therefore, the combination OdEO combined with amikacin exhibited antimicrobial activity against a multidrug-resistant K. pneumoniae strain. Thus, OdOE is a promising agent that may be considered for development of antimicrobial treatment.

Gut community structure as a risk factor for infection in Klebsiella pneumoniae-colonized patients.

The primary risk factor for infection with members of the Klebsiella pneumoniae species complex is prior gut colonization, and infection is often caused by the colonizing strain. Despite the importance of the gut as a reservoir for infectious K. pneumoniae, little is known about the association between the gut microbiome and infection. To explore this relationship, we undertook a case-control study comparing the gut community structure of K. pneumoniae-colonized intensive care and hematology/oncology patients. Cases were K. pneumoniae-colonized patients infected by their colonizing strain (N = 83). Controls were K. pneumoniae-colonized patients who remained asymptomatic (N = 149). First, we characterized the gut community structure of K. pneumoniae-colonized patients agnostic to case status. Next, we determined that gut community data is useful for classifying cases and controls using machine learning models and that the gut community structure differed between cases and controls. K. pneumoniae relative abundance, a known risk factor for infection, had the greatest feature importance, but other gut microbes were also informative. Finally, we show that integration of gut community structure with bacterial genotype data enhanced the ability of machine learning models to discriminate cases and controls. Interestingly, inclusion of patient clinical variables failed to improve the ability of machine learning models to discriminate cases and controls. This study demonstrates that including gut community data with K. pneumoniae-derived biomarkers improves our ability to classify infection in K. pneumoniae-colonized patients.IMPORTANCEColonization is generally the first step in pathogenesis for bacteria with pathogenic potential. This step provides a unique window for intervention since a given potential pathogen has yet to cause damage to its host. Moreover, intervention during the colonization stage may help alleviate the burden of therapy failure as antimicrobial resistance rises. Yet, to understand the therapeutic potential of interventions that target colonization, we must first understand the biology of colonization and if biomarkers at the colonization stage can be used to stratify infection risk. The bacterial genus Klebsiella includes many species with varying degrees of pathogenic potential. Members of the K. pneumoniae species complex have the highest pathogenic potential. Patients colonized in their gut by these bacteria are at higher risk of subsequent infection with their colonizing strain. However, we do not understand if other members of the gut microbiota can be used as a biomarker to predict infection risk. In this study, we show that the gut microbiota differs between colonized patients who develop an infection versus those who do not. Additionally, we show that integrating gut microbiota data with bacterial factors improves the ability to classify infections. Surprisingly, patient clinical factors were not useful for classifying infections alone or when added to microbiota-based models. This indicates that the bacterial genotype and the microbial community in which it exists may determine the progression to infection. As we continue to explore colonization as an intervention point to prevent infections in individuals colonized by potential pathogens, we must develop effective means for predicting and stratifying infection risk.

CircCDC42-encoded CDC42-165aa regulates macrophage pyroptosis in Klebsiella pneumoniae infection through Pyrin inflammasome activation.

The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)-165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice.

miR-486-5p predicted adverse outcomes of SCAP and regulated K. pneumonia infection via FOXO1.

PURPOSE: Severe community-acquired pneumonia (SCAP) is a common respiratory system disease with rapid development and high mortality. Exploring effective biomarkers for early detection and development prediction of SCAP is of urgent need. The function of miR-486-5p in SCAP diagnosis and prognosis was evaluated to identify a promising biomarker for SCAP. PATIENTS AND METHODS: The serum miR-486-5p in 83 patients with SCAP, 52 healthy individuals, and 68 patients with mild CAP (MCAP) patients were analyzed by PCR. ROC analysis estimated miR-486-5p in screening SCAP, and the Kaplan-Meier and Cox regression analyses evaluated the predictive value of miR-486-5p. The risk factors for MCAP patients developing SCAP were assessed by logistic analysis. The alveolar epithelial cell was treated with Klebsiella pneumonia to mimic the occurrence of SCAP. The targeting mechanism underlying miR-486-5p was evaluated by luciferase reporter assay. RESULTS: Upregulated serum miR-486-5p screened SCAP from healthy individuals and MCAP patients with high sensitivity and specificity. Increasing serum miR-486-5p predicted the poor outcomes of SCAP and served as a risk factor for MCAP developing into SCAP. K. pneumonia induced suppressed proliferation, significant inflammation and oxidative stress in alveolar epithelial cells, and silencing miR-486-5p attenuated it. miR-486-5p negatively regulated FOXO1, and the knockdown of FOXO1 reversed the effect of miR-486-5p in K. pneumonia-treated alveolar epithelial cells. CONCLUSION: miR-486-5p acted as a biomarker for the screening and monitoring of SCAP and predicting the malignancy of MCAP. Silencing miR-486-5p alleviated inflammation and oxidative stress induced by K. pneumonia via negatively modulating FOXO1.

Transcriptomic responses of extensively drug resistant Klebsiella pneumoniae to N-acetyl cysteine reveals suppression of major biogenesis pathways leading to bacterial killing and biofilm eradication.

AIMS: Carbapenemase-producing Klebsiella pneumoniae is categorized as a "critical global priority-one" pathogen by WHO and new and efficient treatment options are warranted. This study aims to assess the antibacterial and antibiofilm potential of N-acetyl cysteine (NAC), against clinical isolates of extensively drug resistant (XDR) K. pneumoniae and elucidate the mechanism of killing. METHODS AND RESULTS: XDR-K. pneumoniae were isolated from patients admitted to Madras Medical Mission Hospital, India. Antibiofilm activity of NAC was checked using in vitro continuous flow model and RNA sequencing was done using Illumina Novoseq. Data quality was checked using FastQC and MultiQC software. Our findings revealed that NAC at a concentration of 100 mg/ml was safe, and could inhibit the growth and completely eradicate mature biofilms of all XDR-K. pneumoniae isolates. Transcriptomic responses in XDR-K. pneumoniae to NAC showed significant downregulation of the genes associated with crucial biogenesis pathways, including electron transport chain and oxidoreductase activity besides a specific cluster of genes linked to ribosomal proteins. CONCLUSIONS: Our results indicate that NAC kills the XDR- K. pneumoniae clinical isolates by shutting the overall metabolism and, hence, successfully eradicate in vitro biofilms formed on catheters.

A rare case of hypervirulent Klebsiella pneumoniae liver abscess and bacterial endophthalmitis associated with distal bile duct cancer.

We report a case of a patient with distal bile duct cancer who presented with ocular pain and eye redness due to a liver abscess. The patient developed a liver abscess while waiting for surgery. Since Klebsiella pneumoniae with high viscosity was identified and imaging studies showed systemic infection, a diagnosis of klebsiella invasive syndrome was made. In addition, infectious intraocular inflammation was also observed at the same time. In addition to antibiotic therapy, vitrectomy and percutaneous transhepatic abscess drainage successfully normalized the inflammatory response and negative blood cultures were obtained. Thirty-four days after the start of treatment, surgery was performed and the postoperative course was uneventful, and the patient was discharged from the hospital on the 39th postoperative day. Forty-six months after that surgery, there has been no evidence of recurrence of cholangiocarcinoma or recurrence of infection, but unfortunately, vision loss in the right eye remains. Some Klebsiella pneumoniae are highly pathogenic and are often reported from Southeast Asia, and ocular pain and hyperemic symptoms are important physical findings.

Characterization of mAbs against Klebsiella pneumoniae type 3 fimbriae isolated in a target-independent phage display campaign.

We used phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of Klebsiella pneumoniae. We report the discovery of monoclonal antibodies (mAbs) binding to type 3 fimbrial proteins, including MrkA. We found that anti-MrkA mAbs were cross-reactive to a diverse panel of K. pneumoniae clinical isolates, representing different O-serotypes. mAbs binding to MrkA have previously been described and have been shown to provide prophylactic protection, although only modest protection when dosed therapeutically in vivo in a murine lung infection model. Here, we used a combination of binding and opsonophagocytic killing studies using a high-content imaging platform to provide a possible explanation for the modest therapeutic efficacy in vivo reported in that model. Our work shows that expression of K. pneumoniae type 3 fimbriae in in vitro culture is not homogenous within a bacterial population. Instead, sub-populations of bacteria that do, and do not, express type 3 fimbriae exist. In a high-content opsonophagocytic killing assay, we showed that MrkA-targeting antibodies initially promote killing by macrophages; however, over time, this effect is diminished. We hypothesize the reason for this is that bacteria not expressing MrkA can evade opsonophagocytosis. Our data support the fact that MrkA is a conserved, immunodominant protein that is antibody accessible on the surface of K. pneumoniae and suggest that additional studies should evaluate the potential of using anti-MrkA antibodies in different stages of K. pneumoniae infection (different sites in the body) as well as against K. pneumoniae biofilms in the body during infection and associated with medical devices.IMPORTANCEThere is an unmet, urgent need for the development of novel antimicrobial therapies for the treatment of Klebsiella pneumoniae infections. We describe the use of phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of K. pneumoniae. We discovered monoclonal antibodies (mAbs) binding to the type 3 fimbrial protein MrkA. The anti-MrkA mAbs were found to be highly cross-reactive, binding to all K. pneumoniae strains tested from a diverse panel of clinical isolates, and were active in an opsonophagocytic killing assay at pM concentrations. MrkA is important for biofilm formation; thus, our data support further exploration of the use of anti-MrkA antibodies for preventing and/or controlling K. pneumoniae in biofilms and during infection.

High mortality associated with inappropriate initial antibiotic therapy in hematological malignancies with Klebsiella pneumoniae bloodstream infections.

Bloodstream infections caused by multidrug-resistant organisms such as Klebsiella pneumoniae are a significant challenge in managing hematological malignancies. This study aims to characterize the epidemiology of Klebsiella pneumoniae bloodstream infections specifically in patients with hematological malignancies, delineate the patterns of initial antibiotic therapy, assess the prevalence of resistant strains, identify risk factors for these resistant strains, and evaluate factors influencing patient outcomes. A retrospective analysis was conducted at a single center from January 2017 to December 2020, focusing on 182 patients with hematological malignancies who developed Klebsiella pneumoniae bloodstream infections. We compared the 30-day mortality rates between patients receiving appropriate and inappropriate antibiotic treatments, including the effectiveness of both single-drug and combination therapies. Kaplan-Meier survival analysis and multivariate logistic and Cox regression were used to identify factors influencing mortality risk. The 30-day all-cause mortality rate was 30.2% for all patients. The 30-day all-cause mortality rates were 77.2% and 8.8% in patients who received inappropriate initial treatment and appropriate initial treatment (p < 0.001). Inappropriate initial treatment significantly influenced mortality and was a key predictor of 30-day mortality, along with septic shock and previous intensive care unit (ICU) stays. Patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections exhibited more severe clinical symptoms compared to the CSKP group. The study demonstrates a significant association between empirical carbapenem administration and the escalating prevalence of CRKP and multidrug-resistant K. pneumoniae (MDR-KP) infections. Furthermore, the study identified inappropriate initial antibiotic therapy, septic shock, and ICU admission as independent risk factors for 30-day mortality.

Efficacy of short- versus prolonged-courses of antimicrobial therapy for carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A propensity score-matched cohort study.

BACKGROUND: As limited antibiotic options are available for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs), the optimal treatment duration for CRKP BSIs is unclear. Our objective was to investigate whether short courses (6-10 days) are as effective as prolonged courses (≥11 days) of active antibiotic therapy for CRKP BSIs. METHODS: A retrospective cohort study comprising adults with monomicrobial CRKP BSI receiving a short or prolonged course of in vitro active therapy at a medical center was conducted between 2010 and 2021. Comparisons of two therapeutic strategies were assessed by the logistic regression model and propensity score analysis. The primary endpoint was 30-day crude mortality. Secondary outcomes included recurrent BSIs, the emergence of multidrug-resistant organisms and candidemia during hospitalization after completing antibiotic therapy for CRKP BSIs. RESULTS: Of 263 eligible adults, 160 (60.8%) were male, and the median (interquartile range) age was 69.0 (53.0-76.0) years. Common comorbidities included diabetes (143 patients, 54.4%), malignancy (75, 28.5%), cerebrovascular accident (58, 22.1%), and hemodialysis (49, 18.6%). The 30-day mortality rate was 8.4% (22 patients). Of 84 propensity score well-balanced matched pairs, the 30-day mortality was similar in the short-course and prolonged-course group (6.0% and 7.1%, respectively; P = 1.00). However, there were less episodes candidemia in the short-course group (1.2% versus 13.1%; odds ratio, 0.08; 95% confidence interval, 0.01-0.63; P = 0.005). CONCLUSION: Short courses of active therapy for CRKP BSIs demonstrate comparable clinical outcomes to prolonged courses and are associated with a lower risk of subsequent candidemia.

Co-occurrence of ST412 Klebsiella pneumoniae isolates with hypermucoviscous and non-mucoviscous phenotypes in a short-term hospitalized patient.

Hypermucoviscosity (HMV) is a phenotype that is commonly associated with hypervirulence in Klebsiella pneumoniae. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eight K. pneumoniae strains were recovered from an inpatient who had been hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with higher biofilm formation than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing (WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity (FastANIb) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, eight of which in the non-HMV variants, including rmpA (c.285delG) and wbaP (c.1305T > A), which are assumed to be associated with the non-HMV phenotype. Mutations in manB (c.1318G > A), dmsB (c.577C > T) and tkt (c.1928C > A) occurred in HMV isolates only. RNA-Seq revealed transcripts of genes involved in energy metabolism, carbohydrate metabolism and membrane transport, including cysP, cydA, narK, tktA, pduQ, aceB, metN, and lsrA, to be significantly dysregulated in the non-HMV strains, suggesting a contribution to HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in membrane transport and central metabolism. IMPORTANCE: K. pneumoniae with a hypermucoviscosity (HMV) phenotype is a community-acquired pathogen that is associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contributing to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These findings provide fresh insight into the mechanisms behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMV K. pneumoniae.

A novel chimeric vaccine containing multiple epitopes for simulating robust immune activation against Klebsiella pneumoniae.

BACKGROUND: Due to antibiotic resistance, the Klebsiella genus is linked to morbidity and death, necessitating the development of a universally protective vaccine against Klebsiella pathogens. METHODS: Core sequence analysis prioritized non-redundant host molecules and expected lipid bilayer peptides from fully sequenced Klebsiella genomes. These proteins were refined to identify epitopes, examining their immunogenicity, toxicity, solubility, and interaction with MHC alleles. Epitopes were linked to CPG ODN C274 via EAAAK, HEYGAEALERAG, and GGGS linkers to enhance immunological responses. The vaccine's tertiary structure was modelled and docked with MHC-I and MHC-II. RESULTS: Fifty-five proteins were recognized in the Vaxign collection as having remarkable features. Twenty-three proteins with potential pathogenicity were then identified. Eight options for vaccines emerged after the immunogenicity of proteins was examined. The best antigens were three proteins: MrkD, Iron-regulated lipid membrane polypeptides, and RmpA. These compounds were selected for their sensitivity. The structural protein sequences of K. pneumoniae were utilized to identify seven CTL epitopes, seven HTL epitopes, and seven LBL epitopes, respectively. The produced immunization displayed a stable contact with the receptors, based on molecular dynamic simulations lasting 250 nanoseconds. Intermolecular binding free energies also indicated the dominance of the van der Waals and electrostatic energies. CONCLUSION: In summary, the results of this study might help scientists develop a novel vaccine to prevent K. pneumoniae infections.