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

2021 ◽  
pp. 1-15
Author(s):  
Clement Opoku-Temeng ◽  
Natalia Malachowa ◽  
Scott D. Kobayashi ◽  
Frank R. DeLeo

<i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) is a Gram-negative commensal bacterium and opportunistic pathogen. In healthy individuals, the innate immune system is adept at protecting against <i>K. pneumoniae</i> infection. Notably, the serum complement system and phagocytic leukocytes (e.g., neutrophils) are highly effective at eliminating <i>K. pneumoniae</i> 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 <i>K. pneumoniae</i> 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 <i>K. pneumoniae</i> and discuss recent therapeutic measures and vaccine approaches directed to treat and prevent severe disease caused by MDR <i>K. pneumoniae</i>.

2021 ◽  
Vol 9 (7) ◽  
pp. 1353
Author(s):  
Arianna Pompilio ◽  
Daniela Scribano ◽  
Meysam Sarshar ◽  
Giovanni Di Bonaventura ◽  
Anna Teresa Palamara ◽  
...  

Bacterial biofilms are a serious public-health problem worldwide. In recent years, the rates of antibiotic-resistant Gram-negative bacteria associated with biofilm-forming activity have increased worrisomely, particularly among healthcare-associated pathogens. Acinetobacter baumannii is a critically opportunistic pathogen, due to the high rates of antibiotic resistant strains causing healthcare-acquired infections (HAIs). The clinical isolates of A. baumannii can form biofilms on both biotic and abiotic surfaces; hospital settings and medical devices are the ideal environments for A. baumannii biofilms, thereby representing the main source of patient infections. However, the paucity of therapeutic options poses major concerns for human health infections caused by A. baumannii strains. The increasing number of multidrug-resistant A. baumannii biofilm-forming isolates in association with the limited number of biofilm-eradicating treatments intensify the need for effective antibiofilm approaches. This review discusses the mechanisms used by this opportunistic pathogen to form biofilms, describes their clinical impact, and summarizes the current and emerging treatment options available, both to prevent their formation and to disrupt preformed A. baumannii biofilms.


2021 ◽  
Author(s):  
Mattia Palmieri ◽  
Kelly L. Wyres ◽  
Caroline Mirande ◽  
Zhao Qiang ◽  
Ye Liyan ◽  
...  

Klebsiella pneumoniae is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical K. pneumoniae isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.


2019 ◽  
Vol 40 (8) ◽  
pp. 904-909 ◽  
Author(s):  
Isabelle Vock ◽  
Sarah Tschudin-Sutter

AbstractIn the past several decades, the incidence of Klebsiella pneumoniae harboring resistance mechanisms against multiple antibiotic agents has increased on a global scale. We discuss reasons for ongoing transmission of multidrug-resistant K. pneumoniae in healthcare settings, which has resulted in the successful spread and establishment of this pathogen. It is now one of the most important causes of healthcare-associated infections worldwide.


2019 ◽  
Author(s):  
Matthias I Gröschel ◽  
Conor J Meehan ◽  
Ivan Barilar ◽  
Margo Diricks ◽  
Aitor Gonzaga ◽  
...  

AbstractRecent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analysed an international collection of the emerging, multidrug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harboured strains of all degrees of human virulence. Lineage Sm6 comprised the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identified potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals.One Sentence SummaryThe S. maltophilia complex comprises genetically diverse, globally distributed lineages with evidence for intra-hospital transmission.


2021 ◽  
Vol 12 (3) ◽  
pp. 1-5
Author(s):  
Tarek El-Said El-Banna ◽  
Fatma Ibrahim Sonbol ◽  
Heba M El-Dawy ◽  
Lamiaa A Al-Madboly

Nosocomial and community acquired infections that caused by multidrug-resistant (MDR) Klebsiella pneumoniae isolates are widespread recently resulting in high morbidity and mortality due to limited number of treatment options with effective antibiotics. The aim of this study is to evaluate the antibiotic resistance profile, biofilm formation and efflux pump activity of MDR K. pneumoniae isolates collected from different hospitals in Tanta, Egypt. A total of 70 K. pneumoniae isolates characterized by standard biochemical tests and confirmed by MALDI-TOF/MS were screened for antibiotic susceptibility, efflux pump activity and biofilm formation. Isolates displayed high resistance to penicillins, cephalosporins, trimethoprim-sulfamethoxazole and the majority of tested fluoro/-quinolones and decreased resistance to imipenem, amikacin, chloramphenicol, tigecycline and colistin. Out of 70 K. pneumoniae isolates, 2 isolates exhibited Pan Drug-Resistance (PDR) profile while 57 (81.4%) and 11 (15.7%) exhibited MDR and Extensively drug-resistance (XDR) profiles, respectively. Sixty-four (91.4%) isolates exhibited efflux pump activity while all tested isolates had the ability to form biofilm with varied degrees as 40 (57.1%), 26 (37.1%), and 4 (5.7%) isolates were strong, moderate and weak biofilm producers, respectively. Also, a strong relation between efflux pump activity and biofilm formation per isolate was detected. In conclusion, Multidrug resistance, biofilm formation and efflux pump capabilities in K. pneumoniae have serious public health implications in the management and control of infections caused by this bacterium. Therefore, a multifaceted approach and precise planning are recommended in controlling these infections


2019 ◽  
Vol 8 (7) ◽  
pp. 934 ◽  
Author(s):  
Petrosillo ◽  
Taglietti ◽  
Granata

Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies.


2021 ◽  
Vol 22 (8) ◽  
pp. 4042
Author(s):  
Vanessa Arato ◽  
Maria Michelina Raso ◽  
Gianmarco Gasperini ◽  
Francesco Berlanda Scorza ◽  
Francesca Micoli

Klebsiella pneumoniae (Kp) is an opportunistic pathogen and the leading cause of healthcare-associated infections, mostly affecting subjects with compromised immune systems or suffering from concurrent bacterial infections. However, the dramatic increase in hypervirulent strains and the emergence of new multidrug-resistant clones resulted in Kp occurrence among previously healthy people and in increased morbidity and mortality, including neonatal sepsis and death across low- and middle-income countries. As a consequence, carbapenem-resistant and extended spectrum β-lactamase-producing Kp have been prioritized as a critical anti-microbial resistance threat by the World Health Organization and this has renewed the interest of the scientific community in developing a vaccine as well as treatments alternative to the now ineffective antibiotics. Capsule polysaccharide is the most important virulence factor of Kp and plays major roles in the pathogenesis but its high variability (more than 100 different types have been reported) makes the identification of a universal treatment or prevention strategy very challenging. However, less variable virulence factors such as the O-Antigen, outer membrane proteins as fimbriae and siderophores might also be key players in the fight against Kp infections. Here, we review elements of the current status of the epidemiology and the molecular pathogenesis of Kp and explore specific bacterial antigens as potential targets for both prophylactic and therapeutic solutions.


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 302
Author(s):  
Giuseppe Migliara ◽  
Valentina Baccolini ◽  
Claudia Isonne ◽  
Sara Cianfanelli ◽  
Carolina Di Paolo ◽  
...  

Epidemiological research has demonstrated direct relationships between antibiotic consumption and the emergence of multidrug-resistant (MDR) bacteria. In this nested case–control study, we assessed whether prior exposure to antibiotic therapy and its duration affect the onset of healthcare-associated infections (HAIs) sustained by MDR Klebsiella pneumoniae (MDR-Kp) in intensive care unit patients. Cases were defined as patients who developed an MDR-Kp HAI. Controls matched on sex and the length of intensive care unit (ICU) stay were randomly selected from the at-risk population. Any antibiotic agent received in systemic administration before the onset of infection was considered as antibiotic exposure. Multivariable conditional logistic regression analyses were performed to estimate the effect of prior exposure to each antibiotic class (Model 1) or its duration (Model 2) on the onset of HAIs sustained by MDR-Kp. Overall, 87 cases and 261 gender-matched controls were compared. In Model 1, aminoglycosides and linezolid independently increased the likelihood of developing an MDR-Kp HAI, whereas exposure to both linezolid and penicillins reduced the effect of linezolid alone. In Model 2, cumulative exposure to aminoglycosides increased the likelihood of the outcome, as well as cumulative exposures to penicillins and colistin, while a previous exposure to both penicillins and colistin reduced the influence of the two antibiotic classes alone. Our study confirms that aminoglycosides, penicillins, linezolid, and colistin may play a role in favoring the infections sustained by MDR-Kp. However, several double exposures in the time window before HAI onset seemed to hinder the selective pressure exerted by individual agents.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
M Barchitta ◽  
A Maugeri ◽  
C La Mastra ◽  
MC La Rosa ◽  
L Sessa ◽  
...  

Abstract Klebsiella pneumoniae - and especially multidrug-resistant K. pneumoniae - represents a global threat for Public Health, due to its high dissemination in Intensive Care Units (ICUs) and its association with mortality. Here, we investigated the molecular epidemiology of multidrug-resistant K. pneumoniae strains in ICUs from Catania, Italy. We used data and samples from the Italian Nosocomial Infections Surveillance in ICUs - SPIN-UTI project, which has been surveying the epidemiology and the risk of Healthcare-associated infections (HAIs) in Italian ICUs. The SPIN-UTI network adopted the ECDC protocols for patient-based HAI surveillance. In a sample of ICUs the patient-based surveillance was integrated with a laboratory-based surveillance of MDR K. pneumoniae isolates. K. pneumoniae isolates were genotyped by multilocus sequence typing (MLST), and patterns of K. pneumoniae acquisition (i.e. carriage, colonization and infection) were identified using standard definitions. Our analysis included 155 patients who stayed in two ICUs for a total of 2254 days, from October 2016 to March 2017. Trauma patients were more likely to be infected with K. pneumoniae than other patients (OR = 5.9; 95%CI=2.4-14.8; p = 0.004). A total of 109 K. pneumoniae strains were isolated from different sites of 39 patients, which in turn were defined as 45.2% colonization, 25.8% infection, and 29% carriage. 79.3% K. pneumoniae isolates resistant to carbapenems and 100% resistant to penicillins and cephalosporins. The MLST identified two major clonal groups: the ST395 and the ST37, which represented respectively the 65.6% and the 21.3% of typed isolates. Surveillance of colonization and infection by high-risk clones might help in implementing appropriate strategies, which are crucial to reduce the spread of K. pneumoniae in ICUs. *Study Group AOU 'Policlinico-Vittorio Emanuele', Catania, Italy: Patrizia Bellocchi, Giacomo Castiglione, Alida Imbriani, Marinella Astuto, Giuseppa La Camera, Agata Sciacca Key messages Multidrug-resistant K. pneumoniae still represents a threat for Public Health in Italy and globally, due to its high dissemination in intensive care units. Surveillance of colonization and infection by high-risk clones might help in reducing the spread of Klebsiella pneumoniae.


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