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Klebsiella pneumoniae are opportunistic bacteria found in the gut. In recent years they have been associated with nosocomial infections. The increased incidence of multiple drug-resistant K . pneumoniae makes it necessary to find new alternatives to treat the disease. In this study, phage UPM2146 was isolated from a polluted lake which can lyse its host K . pneumoniae ATCC BAA-2146. Observation from TEM shows that UPM2146 belongs to Caudoviriales (Order) based on morphological appearance. Whole genome analysis of UPM2146 showed that its genome comprises 160,795 bp encoding for 214 putative open reading frames (ORFs). Phylogenetic analysis revealed that the phage belongs to Ackermannviridae (Family) under the Caudoviriales . UPM2146 produces clear plaques with high titers of 10 10 PFU/ml. The phage has an adsorption period of 4 min, latent period of 20 min, rise period of 5 min, and releases approximately 20 PFU/ bacteria at Multiplicity of Infection (MOI) of 0.001. UPM2146 has a narrow host-range and can lyse 5 out of 22 K . pneumoniae isolates (22.72%) based on spot test and efficiency of plating (EOP). The zebrafish larvae model was used to test the efficacy of UPM2146 in lysing its host. Based on colony forming unit counts, UPM2146 was able to completely lyse its host at 10 hours onwards. Moreover, we show that the phage is safe to be used in the treatment against K . pneumoniae infections in the zebrafish model.

The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing bacteriolytic activities against 81.3% (n = 26) and 78.1% (n = 25) of 32 XDR carbapenemase-producing colistin-resistant K. pneumoniae, with capsular types—K15, K17, K50, K51, K52/ wzi -50 and K2/ wzi -2. Both phages showed short replication times, large burst sizes with rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both phages are genetically distinct phages from Myoviridae and Podoviridae family, with the lack of toxin, virulence, lysogeny and antibiotic resistance genes. These characteristics highlighted their promising potential for utilizing in phage therapy for combating XDR K. pneumoniae . Although phage cocktail combining vB_kpnM_05 and vB_kpnP_08 provided significant bacteriolysis for longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development of phage resistance under phages’ selection pressures. Future study will be undertaken to elucidate the precise mechanisms by which these XDR K. pneumoniae developed phage resistance and their associated fitness cost. Remarkably, combining phage cocktail with amikacin at their sub-inhibitory concentrations produced potent synergy by completely suppressing bacterial regrowth in vitro. Our study demonstrated the significant therapeutic and prophylactic effectiveness of a phage cocktail-amikacin combination as a promising alternative strategy for overcoming bacteremia associated with XDR K. pneumoniae having carbapenemase and colistin resistance in vivo.

The worldwide spread of antimicrobial resistance (AMR) has posed a great challenge to global public health. Phage therapy has become a promising alternative against difficult-to-treat pathogens. One important goal of this study was to optimize the therapeutic efficiency of phage-antibiotic combinations, known as phage-antibiotic synergy (PAS). Through comprehensive analysis of the phenotypic and genotypic characteristics of a large number of CRKp-specific phages, we developed a systematic model for phage cocktail combinations. Crucially, our finding demonstrated that PAS treatments not only enhance the bactericidal effects of colistin and tigecycline against multidrug-resistant (MDR) K. pneumoniae strains in in vitro and in vivo context but also provide a robust response when antibiotics fail. Overall, the optimized PAS therapy demonstrates considerable potential in combating diverse K. pneumoniae pathogens, highlighting its relevance as a strategy to mitigate antibiotic resistance threats effectively.

Capsular polysaccharides are critical virulence factors of Klebsiella pneumoniae, enabling the bacterium to evade host immune recognition and exacerbate infection. Phage-derived depolymerases, which specifically degrade these capsular polysaccharides, are increasingly recognized as a highly promising strategy for the treatment of bacterial infections. In the present study, we isolated and characterized a lytic Klebsiella pneumoniae phage, named phiTH1, and sequenced its genome. The K30-type capsular polysaccharide was identified as the receptor for phiTH1 infection. A tail fiber protein with a pectate lyase domain, Dop5, was then recognized as a potential K30-type depolymerase. Therefore, the recombinant protein Dop5 was expressed in Escherichia coli and purified, and its in vitro capsular depolymerase activity was demonstrated. Further, by using a murine aspiration pneumonia model induced by K30-type Klebsiella pneumoniae TH1, we found that Dop5 protected 80% of mice from lethal challenge with Klebsiella pneumoniae. After Dop5 treatment, the pathological damage in multiple organs of mice was alleviated, the bacterial load was reduced, and serum levels of inflammatory cytokines and complement C3 decreased, along with a significant reduction in the pathological score of the lungs. Hence, this study revealed the potential of the depolymerase Dop5 for the treatment of Klebsiella pneumoniae infections.

The escalating demographic shift towards an aging population and the widespread occurrence of immunological diseases have contributed to an elevation in the frequency of community-acquired infections. Notably, among these infections, community-acquired bloodstream infections (CABSI) stand out due to their significant lethality. Detailed medical history inquiries, assessment of underlying immune status, detection of the source of infection, and initial precise identification and treatment of the infectious agents can improve the prognosis of CABSI. In this paper, two incidences of severe CABSI with insidious onset and rapid progression are described. Both patients had compromised basic immunity: one developed the infection following unhygienic dietary practices, and the other after repeated enemas leading to intestinal damage. Blood genomic sequencing revealed the presence of and in the respective cases, with the origin of the infection traced back to the gastrointestinal tract. Both patients experienced positive outcomes following targeted antibiotic therapy, fluid resuscitation, support for organ function, and surgical interventions. Nevertheless, one patient manifested dry gangrene in the extremities during the course of treatment, potentially associated with the administration of vasoconstrictor drugs, considering the compromised baseline vascular conditions. Clinicians are advised to expeditiously uncover concealed medical histories and potential sources of infection in patients, thoroughly investigate the origin of the infection, and initiate early genomic testing to ascertain the specific nature of the infection. This proactive approach aims to facilitate precise treatment strategies and, consequently, enhance the overall prognosis.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant pathogen for both hospital-acquired and community-acquired infections, characterized by its strong epidemic potential and high mortality rate, posing a severe threat to global public health. CRKP spreads widely across the globe through the horizontal transfer of plasmid-mediated resistance genes such as *blaKPC*, *blaNDM*, and *blaOXA-48*. The clinical treatment options for this bacterium are limited, and its resistance has been increasing year by year, urgently necessitating the development of new antimicrobial drugs or alternative strategies. In recent years, the CRISPR-Cas system has shown great potential in the diagnosis and treatment of CRKP, including rapid detection and identification, gene editing, antimicrobial strategies, and resistance inhibition. For instance, CRISPR-Cas12a/13a can be used for the rapid detection and identification of CRKP, while CRISPR-Cas9/Cas3 can target resistance genes to reverse the resistance of strains. With the advancement of delivery and biotechnologies, the CRISPR-Cas system is expected to become an important tool against drug-resistant CRKP. This review focuses on the application of the CRISPR-Cas system in the detection and treatment of CRKP, analyzing its technical advantages, limitations, and future development directions.

A 30-year-old bombing victim with a fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term (>700 days) antibiotic therapy is treated with a pre-adapted bacteriophage along with meropenem and colistin, followed by ceftazidime/avibactam. This salvage therapy results in objective clinical, microbiological and radiological improvement of the patient’s wounds and overall condition. In support, the bacteriophage and antibiotic combination is highly effective against the patient’s K. pneumoniae strain in vitro, in 7-day mature biofilms and in suspensions. In this case study of a patient with fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term antibiotic therapy, the authors use a combination therapy of pre-adapted bacteriophage and antibiotics resulting in clinical, microbiological and radiological improvement.

Background Pyogenic liver abscesses are a fatal condition often seen in emergency departments. The major clinical presentations include weakness, anorexia, fever, chills, ventosity and abdominal pain. They occur in immunocompromised individuals who suffer from diabetes mellitus, malignant tumors, hepatocirrhosis, kidney failure, and solid organ transplantation, or those with long-term administration of glucocorticoids. Invasive Klebsiella pneumoniae liver abscess syndrome resulting from hypervirulent Klebsiella pneumoniae often presents with extrahepatic complications such as endophthalmitis, meningitis, brain enlargement, pneumonia, necrotizing fasciitis, and spondylitis. Prompt diagnosis is crucial for the treatment of invasive Klebsiella pneumoniae liver abscess syndrome. Case report A 75-year-old Han Chinese female patient who presented to the emergency department primarily for fever accompanied by chills was diagnosed with pyogenic liver abscess complicated with pulmonary infection, involving multiple pus emboli in the branches of the right hepatic vein. The patient accepted intravenous imipenem and cilastatin sodium for anti-infection, and subcutaneous insulin to control hyperglycemia. Percutaneous liver puncture and drainage was performed under ultrasound guidance. During the treatment the patient presented with headache, weakness in both lower limbs and lower back pain. Brain magnetic resonance imaging showed intracranial infection and lumbar magnetic resonance imaging showed infection of the vertebral body, intervertebral disc, and soft tissue. The patient had a liver abscess positive for Klebsiella pneumoniae together with infection of other organs, thus she was eventually diagnosed with invasive Klebsiella pneumoniae liver abscess syndrome. The antibiotics were adjusted according to the site of infection and drug sensitivity test. The patient recovered after percutaneous liver puncture and drainage under ultrasound guidance and anti-infection treatment for 3 months. Reexamination of abdominal computed tomography, chest computed tomography, brain magnetic resonance imaging and lumbar magnetic resonance imaging suggested that the infectious lesions had disappeared. Conclusion This medical case report describes a patient with a pyogenic liver abscess caused by Klebsiella pneumoniae who was eventually diagnosed with invasive Klebsiella pneumoniae liver abscess syndrome. Invasive Klebsiella pneumoniae liver abscess syndrome has permanent morbidity, poor quality of life, and lacks warning signs. Despite the complexity of the condition, the patient received effective treatment and the abscess was successfully managed. Through this case, we propose that invasive Klebsiella pneumoniae liver abscess syndrome caused by hypervirulent Klebsiella pneumoniae should be considered for patients with diabetes and fever in the emergency department. Targeted intravenous antibiotics and percutaneous drainage of the abscess are key to the treatment of invasive Klebsiella pneumoniae liver abscess syndrome.

This paper aimed to identify the factors related to Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in neurosurgical patients, and to compare the therapeutic effects of tigecycline versus polymyxin B against CRKP infection, so as to provide a reliable reference for neurosurgery in future prevention and treatment of CRKP infection. One hundred and fifty cases of KPN treated in the neurosurgery department of our hospital from January 1, 2019 to December 31, 2021 were selected, 50 of which were found to be infected with CRKP and the other 100 were detected with carbapenem-sensitive Klebsiella pneumoniae (CSKP) by culture, analysis of factors associated with infection with CRKP. Subsequently, CRKP-infected patients were randomized into a group treated with Ti (group Ti) and a group treated with PB (group PB). The clinical efficacy, bacterial clearance, adverse reactions, and pre- and post-treatment hepatorenal function were comparatively analyzed. Based on the Logistic regression analysis, tracheal intubation (or mechanical ventilation), combination of multiple underlying diseases, presence of impaired consciousness, and use of carbapenem antibiotics are independent risk factors for CRKP infection (P < .05). Ti and PB groups had no evident differences in clinical efficacy and bacterial clearance (P > .05); however, Ti group presented a worse hepatorenal function and a higher incidence of adverse reactions than PB group (P < .05). Tracheal intubation (or mechanical ventilation), multiple underlying diseases, consciousness disturbance, and use of carbapenem antibiotics are related factors affecting CRKP infection in neurosurgical patients. Both Ti and PB have excellent therapeutic efficacy, but the former has more obvious toxicity and side effects.

Klebsiella pneumoniae is a well known human nosocomial pathogen. Most community-acquired K pneumoniae infections cause pneumonia or urinary tract infections. During the past two decades, however, a distinct invasive syndrome that causes liver abscesses has been increasingly reported in Asia, and this syndrome is emerging as a global disease. In this Review, we summarise the clinical presentation and management as well the microbiological aspects of this invasive disease. Diabetes mellitus and two specific capsular types in the bacterium predispose a patient to the development of liver abscesses and the following metastatic complications: bacteraemia, meningitis, endophthalmitis, and necrotising fasciitis. For patients with this invasive syndrome, appropriate antimicrobial treatment combined with percutaneous drainage of liver abscesses increases their chances of survival. Rapid detection of the hypervirulent strain that causes this syndrome allows earlier diagnosis and treatment, thus minimising the occurrence of sequelae and improving clinical outcomes.