scholarly journals An Animal Model to Study Klebsiella pneumoniae Gastro-Intestinal Colonization and Host-to-Host Transmission

2020 ◽  
Author(s):  
Taylor M. Young ◽  
Andrew S. Bray ◽  
Ravinder K. Nagpal ◽  
David L. Caudell ◽  
Hariom Yadav ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Close Contact ◽  
Epidemiological Studies ◽  
Transmission Efficiency ◽  
Oral Route ◽  
Human Infection ◽  
Drug Resistant ◽  
Gi Tract ◽  
Fecal Shedding ◽  
Immunocompetent Mice

AbstractAn important yet poorly understood facet in the life cycle of a successful pathogen is the host-to-host transmission. Hospital-acquired infections (HAI) resulting from the transmission of drug-resistant pathogens affect hundreds of millions of patients worldwide. Klebsiella pneumoniae (Kpn), a gram-negative bacterium, is notorious for causing HAI, with many of these infections difficult to treat as Kpn has become multi-drug resistant. Epidemiological studies suggest that Kpn host-to-host transmission requires close contact and generally occurs through the fecal-oral route. Herein, we describe a murine model that can be utilized to study mucosal (oropharynx and gastrointestinal [GI]) colonization, shedding within feces, and transmission of Kpn through the fecal-oral route. Using an oral route of inoculation, and fecal shedding as a marker for GI colonization, we show that Kpn can asymptomatically colonize the GI tract of immunocompetent mice, and modifies the host GI microbiota. Colonization density within the GI tract and levels of shedding in the feces differed among the clinical isolates tested. A hypervirulent Kpn isolate was able to translocate from the GI tract and cause hepatic infection that mimicked the route of human infection. Expression of the capsule was required for colonization and, in turn, robust shedding. Furthermore, Kpn carrier mice were able to transmit to uninfected cohabitating mice. Lastly, treatment with antibiotics led to changes in the host microbiota and development of a transient super-shedder phenotype, which enhanced transmission efficiency. Thus, this model can be used to determine the contribution of host and bacterial factors towards Kpn dissemination.

scholarly journals Animal Model To Study Klebsiella pneumoniae Gastrointestinal Colonization and Host-to-Host Transmission

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Taylor M. Young ◽  
Andrew S. Bray ◽  
Ravinder K. Nagpal ◽  
David L. Caudell ◽  
Hariom Yadav ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Close Contact ◽  
Epidemiological Studies ◽  
Multidrug Resistant ◽  
Transmission Efficiency ◽  
Oral Route ◽  
Human Infection ◽  
Gi Tract ◽  
Content Type ◽  
Immunocompetent Mice

ABSTRACT An important yet poorly understood facet of the life cycle of a successful pathogen is host-to-host transmission. Hospital-acquired infections (HAI) resulting from the transmission of drug-resistant pathogens affect hundreds of millions of patients worldwide. Klebsiella pneumoniae, a Gram-negative bacterium, is notorious for causing HAI, with many of these infections difficult to treat, as K. pneumoniae has become multidrug resistant. Epidemiological studies suggest that K. pneumoniae host-to-host transmission requires close contact and generally occurs through the fecal-oral route. Here, we describe a murine model that can be utilized to study mucosal (oropharynx and gastrointestinal [GI]) colonization, shedding within feces, and transmission of K. pneumoniae through the fecal-oral route. Using an oral route of inoculation, and fecal shedding as a marker for GI colonization, we showed that K. pneumoniae can asymptomatically colonize the GI tract in immunocompetent mice and modifies the host GI microbiota. Colonization density within the GI tract and levels of shedding in the feces differed among the clinical isolates tested. A hypervirulent K. pneumoniae isolate was able to translocate from the GI tract and cause hepatic infection that mimicked the route of human infection. Expression of the capsule was required for colonization and, in turn, robust shedding. Furthermore, K. pneumoniae carrier mice were able to transmit to uninfected cohabitating mice. Lastly, treatment with antibiotics led to changes in the host microbiota and development of a transient supershedder phenotype, which enhanced transmission efficiency. Thus, this model can be used to determine the contribution of host and bacterial factors toward K. pneumoniae dissemination.

scholarly journals Fecal Shedding of SARS-CoV-2 and Its Potential Role in Person-To-Person Transmission and the Environment-Based Spread of COVID-19

2020 ◽  
Author(s):  
Davey Jones ◽  
Marcos Quintela Baluja ◽  
David Graham ◽  
Alexander Corbishley ◽  
James McDonald ◽  
...  
Keyword(s):  
Potential Role ◽  
Wastewater Treatment Plants ◽  
Care Home ◽  
Genetic Material ◽  
Oral Route ◽  
Gi Tract ◽  
Fecal Matter ◽  
Fecal Shedding ◽  
Gi Symptoms ◽  
Stool Samples

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). Overall, severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 102-105 gc/ml) and feces (ca. 102-107 gc/ml) is much lower than in nasopharyngeal fluids (ca. 105-1011 gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the GI tract and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that over eight million global cases of COVID-19 have occurred, but exposure to feces or wastewater has never been implicated as a transmission vector.

scholarly journals Genotyping and Virulence Analysis of Drug Resistant Clinical Klebsiella pneumoniae Isolates in Egypt

2020 ◽  
Vol 14 (3) ◽  
pp. 1967-1975
Author(s):  
Sarah M. Abdelhamid ◽  
Hala Mohamed Abd-Elaal ◽  
Moustafa Osama Matareed ◽  
Kholoud Baraka
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Molecular Typing ◽  
Virulence Genes ◽  
Antimicrobial Agents ◽  
Antibiotic Resistance Genes ◽  
Epidemiological Studies ◽  
Diffusion Method ◽  
Drug Resistant ◽  
Horizontal Spread

Klebsiella pneumoniae is a highly drug-resistant human pathogen responsible for a variety of serious infections. Integrons, mobile genetic elements capable of integrating antibiotic resistance genes, and the capsule are important virulence factors that increase bacteria resistance to phagocytosis and antimicrobial agents. Molecular typing is an effective tool for identifying the likely etiology of infection. This study aimed to investigate the presence of the rmpA, wcaG, intI1, intI2, and intI3 virulence genes in clinical Klebsiella pneumoniae isolates, and explore their molecular genotypes by using ERIC-PCR. Fifty Klebsiella pneumoniae strains were isolated from various specimens. Antimicrobial resistance was evaluated by using the disc diffusion method. Five genes were amplified by conventional PCR. Genotyping was performed molecularly by using ERIC-PCR. Forty-seven isolates were multi-drug resistant. In all, 18%, 36%, and 98% of the 50 K. pneumoniae isolates were positive for rmpA, wcaG, and intI1 genes, respectively; however, all isolates were negative for intI2 and intI3 genes. Dendogram analysis of the ERIC-PCR results showed 49 distinct patterns, arranged in five clusters. Our study demonstrates high levels of antibiotic resistance and virulence among clinical isolates of K. pneumoniae. Such resistance reflects a growing problem for public health. Further, the presence of integrons increases the horizontal spread of antibiotic resistance and virulence genes among bacterial isolates. The ERIC-PCR technique is an effective method for molecular typing and epidemiological studies of hospital-acquired infections.

scholarly journals Genomic insights into multi-drug and extensively drug resistant Klebsiella pneumoniae from India

2020 ◽  
Vol 101 ◽  
pp. 12-13
Author(s):  
C. Shankar ◽  
P. Mathur ◽  
J.J. Jacob ◽  
C. Rodrigues ◽  
K. Walia ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals 1675. Epidemiology of Urinary Tract Infections in the United States, 2009 - 2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S823-S823
Author(s):  
Kendra Foster ◽  
Linnea A Polgreen ◽  
Brett Faine ◽  
Philip M Polgreen
Keyword(s):  
United States ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Antibiotic Use ◽  
The United States ◽  
Drug Resistant ◽  
E Coli ◽  
Tract Infections

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures

scholarly journals Drug Resistance in Filarial Parasites Does Not Affect Mosquito Vectorial Capacity

Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Erik Neff ◽  
Christopher C. Evans ◽  
Pablo D. Jimenez Castro ◽  
Ray M. Kaplan ◽  
Guha Dharmarajan
Keyword(s):  
Drug Resistance ◽  
Transmission Efficiency ◽  
Vectorial Capacity ◽  
Vertebrate Host ◽  
Mosquito Vector ◽  
Drug Resistant ◽  
Vector Borne Diseases ◽  
Asian Tiger ◽  
Significant Difference ◽  
Vector Borne

Parasite drug resistance presents a major obstacle to controlling and eliminating vector-borne diseases affecting humans and animals. While vector-borne disease dynamics are affected by factors related to parasite, vertebrate host and vector, research on drug resistance in filarial parasites has primarily focused on the parasite and vertebrate host, rather than the mosquito. However, we expect that the physiological costs associated with drug resistance would reduce the fitness of drug-resistant vs. drug-susceptible parasites in the mosquito wherein parasites are not exposed to drugs. Here we test this hypothesis using four isolates of the dog heartworm (Dirofilaria immitis)—two drug susceptible and two drug resistant—and two vectors—the yellow fever mosquito (Aedes aegypti) and the Asian tiger mosquito (Ae. albopictus)—as our model system. Our data indicated that while vector species had a significant effect on vectorial capacity, there was no significant difference in the vectorial capacity of mosquitoes infected with drug-resistant vs. drug-susceptible parasites. Consequently, contrary to expectations, our data indicate that drug resistance in D. immitis does not appear to reduce the transmission efficiency of these parasites, and thus the spread of drug-resistant parasites in the vertebrate population is unlikely to be mitigated by reduced fitness in the mosquito vector.

scholarly journals Wastewaters, with or without Hospital Contribution, Harbour MDR, Carbapenemase-Producing, but Not Hypervirulent Klebsiella pneumoniae

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 361
Author(s):  
Adela Teban-Man ◽  
Anca Farkas ◽  
Andreea Baricz ◽  
Adriana Hegedus ◽  
Edina Szekeres ◽  
...  
Keyword(s):  
Principal Component Analysis ◽  
Klebsiella Pneumoniae ◽  
Wastewater Treatment Plants ◽  
Principal Component ◽  
Drug Resistant ◽  
Beta Lactams ◽  
Carbapenemase Gene ◽  
Antibiotic Susceptibility Patterns ◽  
Sequence Types ◽  
Susceptibility Patterns

Carbapenemase-producing Klebsiella pneumoniae (CPKP) isolated from influent (I) and effluent (E) of two wastewater treatment plants, with (S1) or without (S2) hospital contribution, were investigated. The strains belonged to the Kp1 phylogroup, their highest frequency being observed in S1, followed by S2. The phenotypic and genotypic hypervirulence tests were negative for all the strains tested. At least one carbapenemase gene (CRG), belonging to the blaKPC, blaOXA-48, blaNDM and blaVIM families, was observed in 63% of CPKP, and more than half co-harboured two to four CRGs, in different combinations. Only five CRG variants were observed, regardless of wastewater type: blaKPC-2, blaNDM-1, blaNDM-6, blaVIM-2, and blaOXA-48. Sequence types ST258, ST101 and ST744 were common for both S1 and S2, while ST147, ST525 and ST2502 were found only in S1 and ST418 only in S2. The strains tested were multi-drug resistant (MDR), all being resistant to beta-lactams, cephalosporins, carbapenems, monobactams and fluoroquinolones, followed by various resistance profiles to aminoglycosides, trimethoprim-sulphamethoxazole, tigecycline, chloramphenicol and tetracycline. After principal component analysis, the isolates in S1 and S2 groups did not cluster independently, confirming that the antibiotic susceptibility patterns and gene-type profiles were both similar in the K. pneumoniae investigated, regardless of hospital contribution to the wastewater type.

scholarly journals Extensively Drug-Resistant Hypervirulent Klebsiella pneumoniae From a Series of Neonatal Sepsis in a Tertiary Care Hospital, India

2021 ◽  
Vol 8 ◽  
Author(s):  
Tuhina Banerjee ◽  
Jayalaxmi Wangkheimayum ◽  
Swati Sharma ◽  
Ashok Kumar ◽  
Amitabha Bhattacharjee
Keyword(s):  
Klebsiella Pneumoniae ◽  
Neonatal Sepsis ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Plasmid Profile ◽  
Care Hospital ◽  
Drug Resistant ◽  
Maternal Complications ◽  
Extensively Drug Resistant ◽  
Recent Emergence

The recent emergence of multidrug-resistant (MDR) Klebsiella pneumoniae with hypervirulent traits causing severe infections and considerable mortality is a global cause for concern. The challenges posed by these hypermucoviscous strains of K. pneumoniae with regard to their optimal treatment, management, and control policies are yet to be answered. We studied a series of extensively drug-resistant (XDR) and hypervirulent K. pneumoniae ST5235 isolates with resistance to carbapenems and polymyxins causing neonatal sepsis in a tertiary care hospital in India. A total of 9 K. pneumoniae isolates from 9 cases of neonatal sepsis were studied with respect to their clinical relevance, antimicrobial susceptibility profile, presence of extended spectrum β lactamase (ESBL) production, and responsible genes, carbapenemases (classes A, B, and D), and aminoglycoside-resistant genes. Hypervirulence genes encoding hypermucoid nature, iron uptake, and siderophores were detected by multiplex PCR. The plasmid profile was studied by replicon typing. Isolates were typed by multilocus sequence typing (MLST) and enterobacterial repetitive intergenic consensus (ERIC) PCR to study the sequence types (STs) and clonal relation, respectively. The neonates in the studied cases had history of pre-maturity or low birth weight with maternal complications. All the cases were empirically treated with piperacillin–tazobactam and amikacin followed by imipenem/meropenem and vancomycin and polymyxin B as a last resort. However, all the neonates finally succumbed to the condition (100%). The studied isolates were XDR including resistance to polymyxins harboring multiple ESBL genes and carbapenemase genes (blaNDM and blaOXA−48). Hypervirulence genes were present in various combinations with rmpA/A2 genes present in all the isolates. IncFI plasmids were detected in these isolates. All belonged to ST5235. In ERIC PCR, 6 different clusters were seen. The study highlighted the emergence and burden of XDR hypervirulent isolates of K. pneumoniae causing neonatal sepsis in a tertiary care hospital.

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