Gut microbes improve prognosis of Klebsiella pneumoniae pulmonary infection through the lung-gut axis.

Background: The gut microbiota plays a vital role in the development of sepsis and in protecting against pneumonia. Previous studies have demonstrated the existence of the gut-lung axis and the interaction between the gut and the lung, which is related to the prognosis of critically ill patients; however, most of these studies focused on chronic lung diseases and influenza virus infections. The purpose of this study was to investigate the effect of faecal microbiota transplantation (FMT) on Klebsiella pneumoniae-related pulmonary infection via the gut-lung axis and to compare the effects of FMT with those of traditional antibiotics to identify new therapeutic strategies. Methods: We divided the mice into six groups: the blank control (PBS), pneumonia-derived sepsis (KP), pneumonia-derived sepsis + antibiotic (KP + PIP), pneumonia-derived sepsis + faecal microbiota transplantation(KP + FMT), antibiotic treatment control (KP+PIP+PBS), and pneumonia-derived sepsis+ antibiotic + faecal microbiota transplantation (KP + PIP + FMT) groups to compare the survival of mice, lung injury, inflammation response, airway barrier function and the intestinal flora, metabolites and drug resistance genes in each group. Results: Alterations in specific intestinal flora can occur in the gut of patients with pneumonia-derived sepsis caused by Klebsiella pneumoniae. Compared with those in the faecal microbiota transplantation group, the antibiotic treatment group had lower levels of proinflammatory factors and higher levels of anti-inflammatory factors but less amelioration of lung pathology and improvement of airway epithelial barrier function. Additionally, the increase in opportunistic pathogens and drug resistance-related genes in the gut of mice was accompanied by decreased production of favourable fatty acids such as acetic acid, propionic acid, butyric acid, decanoic acid, and secondary bile acids such as chenodeoxycholic acid 3-sulfate, isodeoxycholic acid, taurodeoxycholic acid, and 3-dehydrocholic acid; the levels of these metabolites were restored by faecal microbiota transplantation. Faecal microbiota transplantation after antibiotic treatment can gradually ameliorate gut microbiota disorder caused by antibiotic treatment and reduce the number of drug resistance genes induced by antibiotics. Conclusion: In contrast to direct antibiotic treatment, faecal microbiota transplantation improves the prognosis of mice with pneumonia-derived sepsis caused by Klebsiella pneumoniae by improving the structure of the intestinal flora and increasing the level of beneficial metabolites, fatty acids and secondary bile acids, thereby reducing systemic inflammation, repairing the barrier function of alveolar epithelial cells, and alleviating pathological damage to the lungs. The combination of antibiotics with faecal microbiota transplantation significantly alleviates intestinal microbiota disorder, reduces the selection for drug resistance genes caused by antibiotics, and mitigates lung lesions; these effects are superior to those following antibiotic monotherapy.

Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection.

Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.

Bacteriophage cocktail shows no toxicity and improves the survival of Galleria mellonella infected with Klebsiella spp.

Klebsiella spp. are causative agents of healthcare-associated infections in patients who are immunocompromised and use medical devices. The antibiotic resistance crisis has led to an increase in infections caused by these bacteria, which can develop into potentially life-threatening illnesses if not treated swiftly and effectively. Thus, new treatment options for Klebsiella are urgently required. Phage therapy can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria infections. The aim of the present study was to produce a safe and effective phage cocktail treatment against Klebsiella pneumoniae and Klebsiella oxytoca, both in liquid in vitro culture and an in vivo Galleria mellonella infection model. The phage cocktail was significantly more effective at killing K. pneumoniae and K. oxytoca strains compared with monophage treatments. Preliminary phage cocktail safety was demonstrated through application in the in vivo G. mellonella model: where the phage cocktail induced no toxic side effects in G. mellonella. In addition, the phage cocktail significantly improved the survival of G. mellonella when administered as a prophylactic treatment, compared with controls. In conclusion, our phage cocktail was demonstrated to be safe and effective against Klebsiella spp. in the G. mellonella infection model. This provides a strong case for future treatment for Klebsiella infections, either as an alternative or adjunct to antibiotics.IMPORTANCEKlebsiella infections are a concern in individuals who are immunocompromised and are becoming increasingly difficult to treat with antibiotics due to their drug-resistant properties. Bacteriophage is one potential alternative therapy that could be used to tackle these infections. The present study describes the design of a non-toxic phage cocktail that improved the survival of Galleria mellonella infected with Klebsiella. This phage cocktail demonstrates potential for the safe and effective treatment of Klebsiella infections, as an adjunct or alternative to antibiotics.

A novel phage putative depolymerase, Depo16, has specific activity against K1 capsular-type Klebsiella pneumoniae.

Klebsiella pneumoniae, especially hypervirulent K. pneumoniae (hvKP), is a common opportunistic pathogen that often causes hospital- and community-acquired infections. Capsular polysaccharide (CPS) is an important virulence factor of K. pneumoniae. Some phages encode depolymerases that can recognize and degrade bacterial polysaccharides. In this study, the lytic bacteriophage vB_KpnP_ZK1 (abbreviated as ZK1) was isolated using serotype K1 hvKP as the host. Although amino acid sequence BLAST analysis indicated that the tail fiber protein Depo16 of phage ZK1 showed no significant similarity to any reported phage depolymerases, it displayed enzymatic activities that are characteristic of phage depolymerases. After expression and purification, Depo16 could efficiently remove the capsular polysaccharide layer that surrounds the surface of serotype K1 K. pneumoniae. Although no bactericidal activity was detected, Depo16 makes serotype K1 K. pneumoniae sensitive to peritoneal macrophages (PMs). In addition, in a mouse bacteremia model of serotype K1 K. pneumoniae, 25 µg of Depo16 was effective in significantly prolonging survival. Depo16 treatment can reduce the bacterial load in blood and major tissues and alleviate tissue damage in mice. This indicates that the putative depolymerase Depo16 is a potential antibacterial agent against serotype K1 K. pneumoniae infections.IMPORTANCEKlebsiella pneumoniae often causes hospital-acquired infections and community-acquired infections. Capsular polysaccharide (CPS) is one of the crucial virulence factors of K. pneumoniae. K1 and K2 capsular-type K. pneumoniae strains are the most prevalent serotypes of hypervirulent K. pneumoniae (hvKP). In this study, a novel K. pneumoniae phage named vB_KpnP_ZK1 was isolated, and its putative depolymerase Depo16 showed low homology with other reported phage depolymerases. Depo16 can specifically degrade the K. pneumoniae K1 capsule making this serotype sensitive to peritoneal macrophages. More importantly, Depo16 showed a significant therapeutic effect in a mouse bacteremia model caused by serotype K1 K. pneumoniae. Thus, Depo16 is a potential antibacterial agent to combat serotype K1 K. pneumoniae infections.

Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae.

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has driven us to explore alternative treatments for the limitation of antimicrobial agents. Lytic phages are considered a promising alternative treatment for CR-hvKP infection. In this study, we reported three novel lytic phages, vB_KpnA_SCNJ1-Z, vB_KpnS_SCNJ1-C, and vB_KpnM_SCNJ1-Y, against a CR-hvKP strain SCNJ1, and they possess genomes of double-stranded DNA with a size of 43,428 bp, 46,039 bp, and 50,360 bp, respectively. Phylogenetic analysis demonstrated that vB_KpnA_SCNJ1-Z belongs to the family Autographiviridae within the class Caudoviricetes, while vB_KpnS_SCNJ1-C and vB_KpnM_SCNJ1-Y are unclassified Caudoviricetes. The phages showed a narrow host range only lysing 1 of 50 tested clinical bacterial strains. The one-step growth curves and stability results showed that the phages displayed relatively short latency periods, with broad pH (pH 3-14) and thermal stabilities (20-60°C). The phages showed significant inhibition of the biofilm formation by SCNJ1 and strong antibacterial activity in vitro. In the mouse model, we demonstrated that administration of a single phage or phage cocktail significantly reduced bacteria loads in the lung, liver, and spleen, and effectively rescued mice from the infection of the SCNJ1 strain, with a survival rate of 70-80%. These findings suggested the three phages have great potential as an alternative therapy with favorable stability and strong antibacterial activity both in vivo and in vitro for the treatment of CR-hvKP infection.

Characterization of bacteriophage BUCT631 lytic for K1 Klebsiella pneumoniae and its therapeutic efficacy in Galleria mellonella larvae.

Severe infections caused by multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) highlight the need for new therapeutics with activity against this pathogen. Phage therapy is an alternative treatment approach for multidrug-resistant K. pneumoniae infections. Here, we report a novel bacteriophage (phage) BUCT631 that can specifically lyse capsule-type K1 K. pneumoniae. Physiological characterization revealed that phage BUCT631 could rapidly adsorb to the surface of K. pneumoniae and form an obvious halo ring, and it had relatively favorable thermal stability (4-50 â€‹°C) and pH tolerance (pH â€‹= â€‹4-12). In addition, the optimal multiplicity of infection (MOI) of phage BUCT631 was 0.01, and the burst size was approximately 303 â€‹PFU/cell. Genomic analysis showed that phage BUCT631 has double-stranded DNA (total length of 44,812 bp) with a G â€‹+ â€‹C content of 54.1%, and the genome contains 57 open reading frames (ORFs) and no virulence or antibiotic resistance related genes. Based on phylogenetic analysis, phage BUCT631 could be assigned to a new species in the genus Drulisvirus of the subfamily Slopekvirinae. In addition, phage BUCT631 could quickly inhibit the growth of K. pneumoniae within 2 â€‹h in vitro and significantly elevated the survival rate of K. pneumoniae infected Galleria mellonella larvae from 10% to 90% in vivo. These studies suggest that phage BUCT631 has promising potential for development as a safe alternative for control and treatment of multidrug-resistant K. pneumoniae infection.

Clinical manifestations, diagnosis, treatment, and outcome of pyogenic liver abscess: a retrospective study.

OBJECTIVE: The incidence of pyogenic liver abscess (PLA) continues to rise, yet atypical clinical symptoms result in considerable incidence of misdiagnosis. This study was conducted to identify potential warning indicators and summarize efficacious diagnostic and therapeutic approaches for potential clinical guidelines. METHODS: Hospitalized patients aged ≥18 years and diagnosed with PLA were included in this retrospective study. Data were collected from participant's clinical records. Patients were grouped according to type 2 diabetes mellitus status and ultrasound-guided percutaneous drainage (USPD). Between-group differences were analysed with Student's t-test. RESULTS: A total of 104 hospitalized patients were included, 33 of whom (31.73%) had type 2 diabetes. Procalcitonin levels were raised in all patients, suggesting potential effectiveness and sensitivity as a warning marker for PLA. Contrast-enhanced computed tomography was the most frequently used method (63.46% of cases) for diagnosing PLA. Klebsiella pneumoniae was the main pathogen found in patients with PLA in southeast China (isolated in 92.86% [26/28] of positive blood cultures and 90.70% [39/43] of positive abscess fluid cultures). Duration of hospital stay was shorter in patients who received USPD versus those who did not (17.91 ± 6.84 days versus 21.47 ± 9.82 days). CONCLUSION: Types of PLA-susceptible patients, infection markers, highly sensitive imaging techniques and clinical treatment options were identified. These results may help with early accurate diagnosis of patients with PLA, avoiding treatment delay.

Phages against Noncapsulated Klebsiella pneumoniae: Broader Host range, Slower Resistance.

Klebsiella pneumoniae (Kp), a human gut colonizer and opportunistic pathogen, is a major contributor to the global burden of antimicrobial resistance. Virulent bacteriophages represent promising agents for decolonization and therapy. However, the majority of anti-Kp phages that have been isolated thus far are highly specific to unique capsular types (anti-K phages), which is a major limitation to phage therapy prospects due to the highly polymorphic capsule of Kp. Here, we report on an original anti-Kp phage isolation strategy, using capsule-deficient Kp mutants as hosts (anti-Kd phages). We show that anti-Kd phages have a broad host range, as the majority are able to infect noncapsulated mutants of multiple genetic sublineages and O-types. Additionally, anti-Kd phages induce a lower rate of resistance emergence in vitro and provide increased killing efficiency when in combination with anti-K phages. In vivo, anti-Kd phages are able to replicate in mouse guts colonized with a capsulated Kp strain, suggesting the presence of noncapsulated Kp subpopulations. The original strategy proposed here represents a promising avenue that circumvents the Kp capsule host restriction barrier, offering promise for therapeutic development. IMPORTANCE Klebsiella pneumoniae (Kp) is an ecologically generalist bacterium as well as an opportunistic pathogen that is responsible for hospital-acquired infections and a major contributor to the global burden of antimicrobial resistance. In the last decades, limited advances have been made in the use of virulent phages as alternatives or complements to antibiotics that are used to treat Kp infections. This work demonstrates the potential value of an anti-Klebsiella phage isolation strategy that addresses the issue of the narrow host range of anti-K phages. Anti-Kd phages may be active in infection sites in which capsule expression is intermittent or repressed or in combination with anti-K phages, which often induce the loss of capsule in escape mutants.

ISOLATION AND CHARACTERIZATION OF BACTERIOPHAGE WITH LYTIC ACTIVITY AGAINST CARBAPENEM RESISTANCE STRAIN OF KLEBSIELLA PNEUMONIA.

OBJECTIVE: Aim: Klebsiella pneumonia has emerged as an increasingly important cause of community-acquired nosocomial infections and many of these strains are highly virulent and exhibit a strong propensity to spread. Infections cause by K. pneumonia produces carbapen¬emase (KPC) enzyme and can be difficult to treat since only a few antibiotics are effective against them. Bacteriophage targeting this strain can be an alternative treatment. Characterisation of bacteriophage is utmost important in assisting the application of bacteriophage in phage therapy. PATIENTS AND METHODS: Materials and methods: In the present study, the lytic bacteriophage, k3w7, isolated by the host Klebsiella pneumoniae kP2 was characterised using transmission electron microscope (TEM), plaque assay, and restriction digestive enzyme to investigate mor¬phology, host spectrum, bacteriophage life cycle and stability accordingly. RESULTS: Results and conclusions: As shown by TEM, k3w7 was observed to have the characteristic of icosahedral heads 100 nm and contractile sheaths 120 nm suggesting it belongs to the family of myoviridae.The Investigation has done on the phage growth cycle showed a short latent period of 20 min and a burst size of approximately 220 plaque forming units per infected cell. Stability test showed the phage was stable over a wide range of pH and temperatures. According to restriction analysis, k3w7 had 50 -kb double-stranded DNA genome as well as the heterogeneous nature of genetic material. These findings suggest that K3W7 has a potential use in therapy against infections caused by K. pneumonia produces carbapenemase.

Remembrance of infections past.

Host-derived metabolite trains the microbiota to develop colonization resistance.

Klebsiella invasive liver abscess syndrome presenting with a central nervous system manifestation secondary to latent cholecystitis: a case report.

BACKGROUND: Brain abscess is a life-threatening event. Moreover, when Klebsiella pneumoniae is the cause, rapid diagnosis and appropriate treatment are required. Klebsiella invasive liver abscess syndrome, a bloodstream metastatic infection of potentially aggressive nature, has been recognized to cause infection in the central nervous system, and concern for Klebsiella liver abscess syndrome is increasing globally. CASE PRESENTATION: A 73-year-old Japanese woman was admitted to the institution complaining of aggravated dysarthria and weakness in the right upper extremities with onset 5 days earlier. Magnetic resonance imaging revealed a brain abscess in the left basal ganglia, and abdominal computed tomography revealed a liver abscess in liver segment 7. The patient's dysarthria symptoms became increasingly worse over the next few days, so surgical drainage via frontotemporal craniotomy was performed on admission day 3, and subsequent culture from the brain abscess showed growth of Klebsiella pneumoniae. On admission day 9, percutaneous transhepatic drainage of the liver segment 7 abscess was undertaken. The pus culture also showed growth of Klebsiella pneumoniae, thus associating the liver abscess with the brain abscess. Following long-term conservative treatment with antibiotics and abscess drainage, the liver abscess disappeared. However, the patient continuously presented with right upper quadrant pain, and abdominal computed tomography showed swelling of the gallbladder. Consequently, percutaneous transhepatic gallbladder drainage was initially administered, and the bile culture was also positive for Klebsiella pneumoniae. For radical treatment, a laparoscopic cholecystectomy was performed on admission day 99. The postoperative period was complicated by an intraabdominal abscess; however, conservative therapy was successful. She was subsequently discharged, and 12-month follow-up revealed no further sequelae. CONCLUSIONS: We describe a rare case of Klebsiella liver abscess syndrome, which first presented with a central nervous system manifestation. Our patient was successfully treated via an early surgical intervention and subsequent antibiotic therapy. Although surgical drainage remains the cornerstone treatment for brain abscess, when a brain abscess is found, and there is a high index of suspicion for the existence of a liver abscess, Klebsiella liver abscess syndrome should be considered as a possible diagnosis.

In Vitro and In Vivo Assessments of Two Newly Isolated Bacteriophages against an ST13 Urinary Tract Infection Klebsiella pneumoniae.

Antibiotic resistance represents a major public health concern requiring new alternatives including phage therapy. Klebsiella pneumoniae belongs to the ESKAPE bacteria and can cause urinary tract infections (UTIs). The aims of this study were to isolate and characterize new bacteriophages against a K. pneumoniae strain isolated from UTIs and to assess their efficacy in vitro and in vivo in a Galleria (G.) mellonella larvae model. For this purpose, two bacteriophages were newly isolated against an ST13 K. pneumoniae strain isolated from a UTI and identified as K3 capsular types by wzi gene PCR. Genomic analysis showed that these bacteriophages, named vB_KpnP_K3-ULINTkp1 and vB_KpnP_K3-ULINTkp2, belong to the Drulisvirus genus. Bacteriophage vB_KpnP_K3-ULINTkp1 had the narrowest host spectrum (targeting only K3), while vB_KpnP_K3-ULINTkp2 also infected other Klebsiella types. Short adsorption times and latent periods were observed for both bacteriophages. In vivo experiments showed their ability to replicate in G. mellonella larvae and to decrease host bacterial titers. Moreover, both bacteriophages improved the survival of the infected larvae. In conclusion, these two bacteriophages had different in vitro properties and showed in vivo efficacy in a G. mellonella model with a better efficiency for vB_KpnP_K3-ULINTkp2.

Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae.

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.

Innate Host Defense against Klebsiella pneumoniae and the Outlook for Development of Immunotherapies.

Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative commensal bacterium and opportunistic pathogen. In healthy individuals, the innate immune system is adept at protecting against K. pneumoniae infection. Notably, the serum complement system and phagocytic leukocytes (e.g., neutrophils) are highly effective at eliminating K. pneumoniae and thereby preventing severe disease. On the other hand, the microbe is a major cause of healthcare-associated infections, especially in individuals with underlying susceptibility factors, such as pre-existing severe illness or immune suppression. The burden of K. pneumoniae infections in hospitals is compounded by antibiotic resistance. Treatment of these infections is often difficult largely because the microbes are usually resistant to multiple antibiotics (multidrug resistant [MDR]). There are a limited number of treatment options for these infections and new therapies, and preventative measures are needed. Here, we review host defense against K. pneumoniae and discuss recent therapeutic measures and vaccine approaches directed to treat and prevent severe disease caused by MDR K. pneumoniae.

A typical multisite invasive infection caused by hvKP: A case report and literature review.

RATIONALE: Hypervirulent K. pneumoniae (hvKP) is a new variant of K. pneumoniae that can caused metastatic spreading by blood, including Splenic abscess, endogenous endophthalmitis, purulent meningitis. This report described a case of A typical multisite invasive infection caused by hvKP and carry out a historical review of the literature. PATIENT CONCERNS: A 55-year-old man was referred to our hospital due to liver abscess. Diabetes was found during this hospitalization. Because of glycemic was uncontrolled, splenic abscess, endogenous endophthalmitis and purulent meningitis occurred during subsequent treatment. DIAGNOSES: We made s diagnosis of liver abscess and invasive K. pneumoniae liver abscess syndrome through generation sequencing and imaging features. INTERVENTIONS AND OUTCOMES: The patient recovered and was subsequently discharged after mechanical ventilation, continuous renal replacement therapy, laparoscopic exploration and various antimicrobials. LESSONS: HvKP are very aggressive and can disseminate to multiple sites, especially in patient who have diabetes, which is a treatment challenge for clinician.

Osteomielitis por Klebsiella pneumoniae BLEE. Reporte de un caso y revisión de la literatura. / OSTEOMYELITIS DUE TO KLEBSIELLA PNEUMONIAE ESBL. REPORT OF A CASE AND LITERATURE REVIEW

Las betalactamasas de espectro extendido (BLEE) son enzimas producidas por bacilos gram negativos capaces de hidrolizar las cefalosporinas de amplio espectro y los monobactámicos. La mayoría pertenece a la familia de Enterobacteriae, tales como Klebsiella pneumoniae y Escherichia coli: Sin embargo, se asocian también con otras bacterias como Proteus, Serratia, Salmonella, Pseudomonas aeruginosa y Acinetobacter. Las enterobacterias productoras de carbapenemasas no sólo han sido aisladas en el ambiente hospitalario, sino que también provienen de la comunidad. Se presenta una paciente de sexo femenino con antecedentes de sida y osteomielitis secundaria a artritis séptica producida por una Klebsiella pneumoniae BLEE de la comunidad. Un tratamiento oportuno y eficaz puede evitar la opción quirúrgica, disminuyendo la morbimortalidad asociada con esta afección

Extended-spectrum beta-lactamases (ESBL) are enzymes produced by gram-negative rods capable of hydrolyzing broad-spectrum cephalosporins and monobactams. Most belong to the Enterobacteriae family, such as Klebsiella pneumoniae and Escherichia coli. However, they are also associated with other bacteria such as Proteus, Serratia, Salmonella, Pseudomonas aeruginosa and Acinetobacter. Carbapenemase-producing Enterobacteriaceae have not only been isolated from the hospital environment, but also from the community. We present a female patient with a history of AIDS and secondary osteomyelitis to septic arthritis caused by a community Klebsiella pneumoniae ESBL. It is concluded that a timely and effective treatment can avoids the surgical option, reducing the morbidity and mortality of this condition.

Phage Therapy Experience at the Eliava Phage Therapy Center: Three Cases of Bacterial Persistence.

In this retrospective descriptive study we focus on cases of three patients who underwent phage therapy procedures at Eliava Phage Therapy Center (EPTC) in Tbilisi, Georgia. Patients with chronic infectious diseases related to Pseudomonas aeruginosa (two patients, lower respiratory tract infection (LRTI)) and Klebsiella pneumoniae (one patient, urinary tract infection (UTI)) are among those very few EPTC patients whose pathogens persisted through phage therapy. By looking at bacterial strains and personalized phages used against them we tried to point towards possible adaptation strategies that are employed by these pathogens. Genome restriction-based Pulsed Field Gel Electrophoresis (PFGE) profiling of strains isolated before and after phage therapy hints towards two strategies of adaptation. In one patient case (Pseudomonas aeruginosa related lung infection) bacterial strains before and after phage therapy were indistinguishable according to their PFGE profiles, but differed in their phage susceptibility properties. On the other hand, in two other patient cases (Pseudomonas aeruginosa related LRTI and Klebsiella pneumoniae related UTI) bacterial adaptation strategy seemed to have resulted in diversification of infecting strains of the same species. With this work we want to attract more attention to phage resistance in general as well as to its role in phage therapy.

Efficacy of Lactobacillus fermentum Isolated from the Vagina of a Healthy Woman against Carbapenem-Resistant Klebsiella Infections In Vivo.

Carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase are increasingly reported worldwide and have become more and more resistant to nearly all antibiotics during the past decade. The emergence of K. pneumoniae strains with decreased susceptibility to carbapenems, which are used as a last resort treatment option, is a significant threat to hospitalized patients worldwide as K. pneumoniae infection is responsible for a high mortality rate in the elderly and immunodeficient individuals. This study used Lactobacillus fermentum as a candidate probiotic for treating CRE-related infections and investigated its effectiveness. We treated mice with L. fermentum originating from the vaginal fluid of a healthy Korean woman and evaluated the Lactobacilli's efficacy in preventive, treatment, non-establishment, and colonization mouse model experiments. Compared to the control, pre-treatment with L. fermentum significantly reduced body weight loss in the mouse models, and all mice survived until the end of the study. The oral administration of L. fermentum after carbapenemresistant Klebsiella (CRK) infection decreased mortality and illness severity during a 2-week observation period and showed that it affects other strains of CRK bacteria. Also, the number of Klebsiella bacteria was decreased to below 5.5 log10 CFU/ml following oral administration of L. fermentum in the colonization model. These findings demonstrate L. fermentum's antibacterial activity and its potential to treat CRE infection in the future.

Characterization and genome analysis of novel Klebsiella phage BUCT556A with lytic activity against carbapenemase-producing Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) have spread globally and led to the limited choice of antimicrobial treatment of K. pneumoniae-induced infections. Bacteriophages are considered as an effective strategy against bacterial infections. In this study, we isolated a novel Klebsiella phage BUCT556A with lytic activity against KPC-producing K. pneumoniae, which was a multi-drug resistant isolate. Phage BUCT556A had a symmetrical head and a long, non-contractile tail, belonging to the family Siphoviridae, order Caudoviridae. Phage BUCT556A had a relatively narrow host range, and a medium burst size of 91 PFU/cell. It was stable at broad temperature/pH range, and exhibited good tolerance to chloroform. The genome of phage BUCT556A was a 49, 376-bp linear double-stranded DNA molecule with average G + C content of 50.2%, and contained 75 open reading frames. There was no tRNA, antibiotic resistance, toxin, virulence related genes or lysogen-formation gene clusters detected in the genome of phage BUCT556A. Phylogenetic analyses based on the major capsid protein Mcp suggested that this phage had a close relationship with Klebsiella phage KLPN1. Together, through phenotypic combined with genomic DNA sequencing and analyses, our study suggests that phage BUCT556A has the potential to be used as a bacterial treatment tool for multidrug-resistant strains K. pneumoniae.

Thinking of Draining a Renal Abscess? Wait! - Could Be Acute Lobar Nephronia.

Acute Lobar Nephronia (ALN) is a rare infective condition of the kidney currently described only in case reports and small case series. The diagnosis of ALN is made by characteristic clinico-radiological findings. Differentiation from acute pyelonephritis, renal abscess and renal tumor is crucial for proper management and to avoid unnecessary diagnostic interventions. Herein, we report a 58-year-old woman with an uncontrolled diabetes mellitus, who was diagnosed clinically as acute pyelonephritis and treated with standard duration of antibiotics but had recurrence of symptoms. On evaluation, she was found to have ALN which was treated successfully with prolonged antibiotic course.