scholarly journals Mobile Plasmid Mediated Transition From Colistin-Sensitive to Resistant Phenotype in Klebsiella pneumoniae

2021 ◽  
Vol 12 ◽  
Author(s):  
Baoyue Zhang ◽  
Bing Yu ◽  
Wei Zhou ◽  
Yue Wang ◽  
Ziyong Sun ◽  
...  

Multidrug-resistant bacteria, including carbapenem-resistant Klebsiella pneumoniae (CRKP), are becoming an increasing health crisis worldwide. For CRKP, colistin is regarded as “the last treatment option.” In this study, we isolated a clinical CRKP strain named as K. pneumoniae R10-341. Phenotyping analysis showed that this strain could transit from a colistin-sensitive to a resistant phenotype by inserting an IS4 family ISKpn72 element into the colistin-resistance associated mgrB gene. To investigate the mechanism of this transition, we performed genome sequencing analysis of the colistin-sensitive parental strain and found that 12 copies of ISKpn72 containing direct repeats (DR) are located on the chromosome and 1 copy without DR is located on a multidrug-resistant plasmid pR10-341_2. Both types of ISKpn72 could be inserted into the mgrB gene to cause colistin-resistance, though the plasmid-derived ISKpn72 without DR was in higher efficiency. Importantly, we demonstrated that colistin-sensitive K. pneumoniae strain transferred with the ISKpn72 element also obtained the ability to switch from colistin-sensitive to colistin-resistant phenotype. Furthermore, we confirmed that the ISKpn72-containing pR10-341_2 plasmid was able to conjugate, suggesting that the ability of causing colistin-resistant transition is transferable through common conjugation. Our results point to new challenges for both colistin-resistance detection and CRKP treatment.

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.


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.


Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 424
Author(s):  
Francesco Perrotta ◽  
Marco Paolo Perrini

Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Among them, metallo-β-lactamases (MBLs)-producing Klebsiella pneumoniae are of global concern today. The ceftazidime/avibactam combination and the ceftazidime/avibactam + aztreonam combination currently represent the most promising antibiotic strategies to stave off these kinds of infections. We describe the case of a patient affected by thrombotic thrombocytopenic purpura (TTP) admitted in our ICU after developing a hospital-acquired SarsCoV2 interstitial pneumonia during his stay in the hematology department. His medical conditions during his ICU stay were further complicated by a K. Pneumoniae NDM sepsis. To our knowledge, the patient had no risk factors for multidrug-resistant bacteria exposure or contamination during his stay in the hematology department. During his stay in the ICU, we treated the sepsis with a combination therapy of ceftazidime/avibactam + aztreonam. The therapy solved his septic state, allowing for a progressive improvement in his general condition. Moreover, we noticed that the negativization of the hemocultures was also associated to a decontamination of his known rectal colonization. The ceftazidime/avibactam + aztreonam treatment could not only be a valid therapeutic option for these kinds of infections, but it could also be considered as a useful tool in selected patients’ intestinal decolonizations.


Author(s):  
Fabio Arena ◽  
Anna Rita Daniela Coda ◽  
Valentina Meschini ◽  
Roberto Verzicco ◽  
Arcangelo Liso

Abstract Background In the health care setting, infection control actions are fundamental for containing the dissemination of multidrug-resistant bacteria (MDR). Carbapenemase-producing Enterobacterales (CPE), especially Klebsiella pneumoniae (CR-KP), can spread among patients, although the dynamics of transmission are not fully known. Since CR-KP is present in wastewater and microorganisms are not completely removed from the toilet bowl by flushing, the risk of transmission in settings where toilets are shared should be addressed. We investigated whether urinating generates droplets that can be a vehicle for bacteria and explored the use of an innovative foam to control and eliminate this phenomenon. Methods To study droplet formation during urination, we set up an experiment in which different geometrical configurations of toilets could be reproduced and customized. To demonstrate that droplets can mobilize bacteria from the toilet bowl, a standard ceramic toilet was contaminated with a KPC-producing Klebsiella pneumoniae ST101 isolate. Then, we reproduced urination and attached culture dishes to the bottom of the toilet lid for bacterial colony recovery with and without foam. Results Rebound droplets invariably formed, irrespective of the geometrical configuration of the toilet. In microbiological experiments, we demonstrated that bacteria are always mobilized from the toilet bowl (mean value: 0.11 ± 0.05 CFU/cm2) and showed that a specific foam layer can completely suppress mobilization. Conclusions Our study demonstrated that droplets generated from toilets during urination can be a hidden source of CR-KP transmission in settings where toilets are shared among colonized and noncolonized patients.


mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Elizabeth Diago-Navarro ◽  
Michael P. Motley ◽  
Gonzalo Ruiz-Peréz ◽  
Winnie Yu ◽  
Julianne Austin ◽  
...  

ABSTRACTCarbapenem-resistant (CR) sequence type 258 (ST258)Klebsiella pneumoniaehas become an urgent health care threat, causing an increasing number of high-mortality infections. Its resistance to numerous antibiotics and threat to immunocompromised patients necessitate finding new therapies to combat these infections. Previous successes in the laboratory, as well as the conservation of capsular polysaccharide (CPS) among the members of the ST258 clone, suggest that monoclonal antibody (MAb) therapy targeting the outer polysaccharide capsule ofK. pneumoniaecould serve as a valuable treatment alternative for afflicted patients. Here, we isolated several IgG antibodies from mice inoculated with a mixture of CRK. pneumoniaeCPS conjugated to anthrax protective antigen. Two of these MAbs, 17H12 and 8F12, bind whole and oligosaccharide epitopes of the CPS of clade 2 ST258 CRK. pneumoniae, which is responsible for the most virulent CRK. pneumoniaeinfections in the United States. These antibodies were shown to agglutinate all clade 2 strains and were also shown to promote extracellular processes killing these bacteria, including biofilm inhibition, complement deposition, and deployment of neutrophil extracellular traps. Additionally, they promoted opsonophagocytosis and intracellular killing of CRK. pneumoniaeby human-derived neutrophils and cultured murine macrophages. Finally, when mice were intratracheally infected with preopsonized clade 2 CRK. pneumoniae, these MAbs reduced bacterial dissemination to organs. Our data suggest that broadly reactive anticapsular antibodies and vaccines against clade 2 ST258 CRK. pneumoniaeare possible. Such MAbs and vaccines would benefit those susceptible populations at risk of infection with this group of multidrug-resistant bacteria.IMPORTANCECarbapenem-resistantKlebsiella pneumoniaeis an enteric bacterium that has been responsible for an increasing number of deadly outbreaks and hospital-acquired infections. The pathogen’s resistance to numerous antibiotics, including new drugs, leaves few therapeutic options available for infected patients, who often are too sick to fight the infection themselves. Immunotherapy utilizing monoclonal antibodies has been successful in other medical fields, and antibodies targeting the outer polysaccharide capsule of these bacteria could be a valuable treatment alternative. This study presents two anticapsular antibodies, 17H12 and 8F12, that were found to be protective against the most virulent carbapenem-resistantK. pneumoniaeclinical strains. These antibodies are shown to promote the killing of these strains through several extracellular and intracellular processes and prevent the spread of infection in mice from the lungs to distal organs. Thus, they could ultimately treat or protect patients infected or at risk of infection by this multidrug-resistant bacterium.


Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 332
Author(s):  
Letícia B. Migliorini ◽  
Romário O. de Sales ◽  
Paula C. M. Koga ◽  
Andre M. Doi ◽  
Anja Poehlein ◽  
...  

Klebsiella pneumoniae carbapenemase (KPC) actively hydrolyzes carbapenems, antibiotics often used a last-line treatment for multidrug-resistant bacteria. KPC clinical relevance resides in its widespread dissemination. In this work, we report the genomic context of KPC coding genes blaKPC-2, blaKPC-3 and blaKPC-30 in multidrug-resistant Klebsiellapneumoniae isolates from Brazil. Plasmids harboring blaKPC-3 and blaKPC-30 were identified. Fifteen additional carbapenem-resistant K. pneumoniae isolates were selected from the same tertiary hospital, collected over a period of 8 years. Their genomes were sequenced in order to evaluate the prevalence and dissemination of blaKPC–harboring plasmids. We found that blaKPC genes were mostly carried by one of two isoforms of transposon Tn4401 (Tn4401a or Tn4401b) that were predominantly located on plasmids highly similar to the previously described plasmid pKPC_FCF3SP (IncN). The identified pKPC_FCF3SP-like plasmids carried either blaKPC-2 or blaKPC-30. Two K. pneumoniae isolates harbored pKpQIL-like (IncFII) plasmids, only recently identified in Brazil; one of them harbored blaKPC-3 in a Tn4401a transposon. Underlining the risk of horizontal spread of KPC coding genes, this study reports the prevalence of blaKPC-2 and the recent spread of blaKPC-3, and blaKPC-30, in association with different isoforms of Tn4401, together with high synteny of plasmid backbones among isolates studied here and in comparison with previous reports.


2021 ◽  
Author(s):  
Yi Li ◽  
Wenjuan Yan ◽  
Qi Zhang ◽  
Nan Jing ◽  
Youhua Yuan ◽  
...  

Abstract Background The increased clinical use of polymyxin led to the emergence of polymyxin-resistant strains, especially those carrying plasmid-borne mobilized colistin resistance (mcr) gene variants. In this study, we aimed to evaluate the prevalence and characteristics of polymyxin-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province, China. Methods A total of 16 polymyxin-resistant isolates among 2301 E. coli and K. pneumoniae isolates collected in 6 local hospitals in the Henan province were studied. The isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the minimum inhibitory concentrations (MICs) were determined using the microbroth dilution technique. Polymyxin-resistant isolates were further analysed for mcr-1 and carbapenemase-mediated resistance using the modified carbapenem inactivation method, the ethylenediaminetetraacetic acid-modified carbapenem inactivation method, and polymerase chain reaction. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed to disclose the phylogenetic relationships of the polymyxin-resistant isolates. The clinical characteristics of patients infected with the polymyxin-resistant isolates were also retrospectively analysed. Results 5/1499 (0.3%) and 11/802 (1.4%) E. coli and K. pneumoniae isolates, respectively, were polymyxin-resistant. The MICs of polymyxin were in the range of 4–64 µg/mL and all of the 16 polymyxin-resistant isolates were susceptible to tigecycline. Additionally, four of the five E. coli polymyxin-resistant isolates were mcr-1 positive; one of them was also carbapenem-resistant, carrying blaNDM−5. Conversely, only 1/11 K. pneumoniae isolates was mcr-1 positive, while 9 polymyxin-resistant isolates were also carbapenem-resistant (PRCRKP), carrying blaKPC−2 but not mcr-1. MLST results showed that the five E. coli isolates belonged to four sequence types (STs), including ST2, ST132, ST632, and ST983, while all PRCRKP isolates belonged to ST11. However, all 16 isolates showed different PFGE types using a genetic similarity of ≥ 95%. Furthermore, 33.3% (5/15) of the patients carrying polymyxin-resistant K. pneumoniae isolates showed a history of polymyxin use, and 10/15 (66.7%) patients displayed good clinical outcomes. Conclusion The polymyxin resistance rate of K. pneumoniae was slightly higher than that of E. coli in the Henan province; however, mcr-1 was only detected in one K. pneumoniae isolate. Thus, close monitoring is needed to prevent and control the spread of PRCRKP.


2020 ◽  
Vol 8 (11) ◽  
pp. 1636
Author(s):  
Jouman Hassan ◽  
Razan Zein Eddine ◽  
David Mann ◽  
Shaoting Li ◽  
Xiangyu Deng ◽  
...  

Colistin, a last resort antibiotic, is important for controlling infections with carbapenem-resistant Enterobacteriaceae. The recent emergence of mobile-colistin-resistance (mcr) genes has threatened the effectiveness of colistin. Aquaculture is hypothesized to be a major contributor to the evolution and dissemination of mcr. However, data on mcr in aquaculture are limited. Here, the occurrence of mcr-1 was assessed in Rainbow Trout in Lebanon, a country with developing antimicrobial stewardship and an established use of colistin for medical and farming purposes. mcr-1 was detected in 5 Escherichia coli isolated from fish guts. The isolates were classified as multidrug-resistant and their colistin minimum inhibitory concentration ranged between 16 and 32 μg/mL. Whole genome sequencing analysis showed that mcr-1 was carried on transmissible IncX4 plasmids and that the isolates harbored more than 14 antibiotic resistance genes. The isolates belonged to ST48 and ST101, which have been associated with mcr and can occur in humans and fish. The mcr-1-positive E. coli persisted in 6-day biofilms, but there was a potential fitness cost. Given the status of infrastructure in Lebanon, there is a high potential for the dissemination of mcr via aquatic environments. Urgent actions are needed to control mcr and to enhance antimicrobial stewardship in Lebanon.


mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Matthew A. Crawford ◽  
Debra J. Fisher ◽  
Lisa M. Leung ◽  
Sara Lomonaco ◽  
Christine Lascols ◽  
...  

ABSTRACT The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens. IMPORTANCE As bacterial pathogens become resistant to multiple antibiotics, the infections they cause become increasingly difficult to treat. Carbapenem antibiotics provide an essential clinical barrier against multidrug-resistant bacteria; however, the dissemination of bacterial enzymes capable of inactivating carbapenems threatens the utility of these important antibiotics. Compounding this concern is the global spread of bacteria invulnerable to colistin, a polymyxin antibiotic considered to be a last line of defense against carbapenem-resistant pathogens. As the effectiveness of existing antibiotics erodes, it is critical to develop innovative antimicrobial therapies. To this end, we demonstrate that the chemokines CXCL9 and CXCL10 kill the most concerning carbapenem- and colistin-resistant pathogens. Our findings provide a unique and timely foundation for therapeutic strategies capable of countering antibiotic-resistant “superbugs.” IMPORTANCE As bacterial pathogens become resistant to multiple antibiotics, the infections they cause become increasingly difficult to treat. Carbapenem antibiotics provide an essential clinical barrier against multidrug-resistant bacteria; however, the dissemination of bacterial enzymes capable of inactivating carbapenems threatens the utility of these important antibiotics. Compounding this concern is the global spread of bacteria invulnerable to colistin, a polymyxin antibiotic considered to be a last line of defense against carbapenem-resistant pathogens. As the effectiveness of existing antibiotics erodes, it is critical to develop innovative antimicrobial therapies. To this end, we demonstrate that the chemokines CXCL9 and CXCL10 kill the most concerning carbapenem- and colistin-resistant pathogens. Our findings provide a unique and timely foundation for therapeutic strategies capable of countering antibiotic-resistant “superbugs.”


2021 ◽  
pp. 175717742098203
Author(s):  
Alain Kenfak-Foguena ◽  
Immaculée Nahimana Tessemo ◽  
Claire Bertelli ◽  
Laurent Merz ◽  
Alain Cometta ◽  
...  

The recent increase of migration to Europe represents a risk of increased the prevalence of multidrug-resistant (MDR) bacteria. We conducted a cross-sectional study among asylum seekers admitted at two hospitals in Switzerland. Of the 59 patients included, 9 (14%) were colonised by a MDR bacteria, including 5 (8.5%) methicilin-resistant Staphylococcus aureus (MRSA) and 4 (6.8%) extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. No patient carried both ESBL-producing bacteria and MRSA. None of the patients carried a vancomycin-resistant Enterococcus (VRE) or a carbapenem-resistant Enterobacteriaceae (CRE). Colonisation with MDR bacteria was not associated with hospitalisation abroad or recent arrival in Switzerland. Whole genome sequencing analysis allowed us to exclude transmission between patients. The prevalence of MDR bacteria carriage is moderate among asylum seekers in western Switzerland. Further surveillance studies are necessary to determine if there is a risk of dissemination of pathogens into the local population.


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