scholarly journals The Study of Mutation in LasR and PqsR Genes in Extremely Drug Resistant and Multidrug Resistant Strains of Pseudomonas aeruginosa from Burn Wound Infection

2019 ◽  
Vol 12 (10) ◽  
Author(s):  
Seyed Abolfazl Hosseininasab Nodoushan ◽  
Sharareh Moghim ◽  
Nasrin Mirzaei ◽  
Hajieh Ghasemian Safaei
Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 463-477
Author(s):  
Ming Ming Wen ◽  
Ibrahim A. Abdelwahab ◽  
Rania G. Aly ◽  
Sally A. El-Zahaby

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S794-S795
Author(s):  
Mary Francine P Chua ◽  
Syeda Sara Nida ◽  
Jerry Lawhorn ◽  
Janak Koirala

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, >0.5 to <1, >1 to <4, and >4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 >32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures


mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Jake Everett ◽  
Keith Turner ◽  
Qiuxian Cai ◽  
Vernita Gordon ◽  
Marvin Whiteley ◽  
...  

ABSTRACT Environmental conditions affect bacterial behavior and can greatly influence the course of an infection. However, the environmental cues that elicit bacterial responses in specific infection sites are relatively unknown. Pseudomonas aeruginosa is ubiquitous in nature and typically innocuous. However, it is also one of the most prevalent causes of fatal sepsis in burn wound patients. The aim of this study was to determine the impact of environmental factors, specifically the availability of arginine, on the pathogenesis of P. aeruginosa in burn wound infections. Comparison of burned versus noninjured tissue revealed that l-arginine (l-Arg) was significantly depleted in burn wounds as a consequence of elevated arginase produced by myeloid-derived suppressor cells. We also observed that l-Arg was a potent chemoattractant for P. aeruginosa, and while low concentrations of l-Arg increased P. aeruginosa’s swimming motility, high concentrations resulted in diminished swimming. Based on these observations, we tested whether the administration of exogenous l-Arg into the burn wound could attenuate the virulence of P. aeruginosa in thermally injured mice. Administration of l-Arg resulted in decreased P. aeruginosa spread and sepsis and increased animal survival. Taken together, these data demonstrate that the availability of environmental arginine greatly influences the virulence of P. aeruginosa in vivo and may represent a promising phenotype-modulating tool for future therapeutic avenues. IMPORTANCE Despite our growing understanding of the pathophysiology of burn wounds and the evolution of techniques and practices to manage infections, sepsis remains a significant medical concern for burn patients. P. aeruginosa continues to be a leader among all causes of bacteremic infections due to its tendency to cause complications in immunocompromised patients and its ubiquitous presence in the hospital setting. With the unforgiving emergence of multidrug-resistant strains, it is critical that alternative strategies to control or prevent septic infections in burn patients be developed in parallel with novel antimicrobial agents. In this study, we observed that administration of l-Arg significantly reduced bacterial spread and sepsis in burned mice infected with P. aeruginosa. Given the safety of l-Arg in high doses and its potential wound-healing benefits, this conditionally essential amino acid may represent a useful tool to modulate bacterial behavior in vivo and prevent sepsis in burn patients. IMPORTANCE Despite our growing understanding of the pathophysiology of burn wounds and the evolution of techniques and practices to manage infections, sepsis remains a significant medical concern for burn patients. P. aeruginosa continues to be a leader among all causes of bacteremic infections due to its tendency to cause complications in immunocompromised patients and its ubiquitous presence in the hospital setting. With the unforgiving emergence of multidrug-resistant strains, it is critical that alternative strategies to control or prevent septic infections in burn patients be developed in parallel with novel antimicrobial agents. In this study, we observed that administration of l-Arg significantly reduced bacterial spread and sepsis in burned mice infected with P. aeruginosa. Given the safety of l-Arg in high doses and its potential wound-healing benefits, this conditionally essential amino acid may represent a useful tool to modulate bacterial behavior in vivo and prevent sepsis in burn patients.


2021 ◽  
Vol 30 (1) ◽  
pp. 19-28
Author(s):  
Yasser M. Ismail ◽  
Sahar M. Fayed ◽  
Fatma M. Elesawy ◽  
Nora Z Abd El-Halim ◽  
Ola S. El-Shimi

Background: The biggest concern for a burn team is a nosocomial infection in burn patients, which is a significant health issue. Pseudomonas aeruginosa is an extremely troublesome drug-resistant bacterium in the world today. We are now faced with rising P. aeruginosa pan-drug-resistant clones in hospital settings. Objectives: To evaluate the distribution of different virulence factors generated by P. aeruginosa isolated from burn wound infections, together with its antimicrobial susceptibility. Methodology: The isolates reported as P. aeruginosa were further tested for the presence of various phenotypic and genotypic virulence factors including (Biofilm formation, lipase, protease, gelatinase, DNase, bile esculin hydrolysis & hemolysin). Also, genes encoding (nan 1 and Exo A) were investigated by PCR using specific primers. All the isolates were tested for their antimicrobial susceptibility patterns. Results: The study reported that toxins and enzymes were expressed by the tested strains in varying proportions; (92.0%) were producing β-hemolysin, lipase (86%), and protease (86%). The formation of biofilm was observed in 84%. Exo A (70%) was the main virulence gene found in the tested strains. Nan 1 gene was identified in 30% of the samples. 82% of MDRPA isolates were found. There is indeed a relationship between biofilm production and drug resistance, as well as the presence of virulence genes (nan 1 and Exo A) were associated with certain patients and burn wounds characteristics as burn size, burn wound depth, length of hospital stays, and socioeconomic status. Conclusions: Correlation of Pseudomonas aeruginosa virulence profiles with burn wounds and patient-related data can be useful in establishing of an appropriate preventive protocol for hospitalized patients with P. aeruginosa burn serious infections. The targeting of these bacterial virulence arsenals is also a promising approach to developing alternative drugs, which act by attenuating the aggressiveness of the pathogen and reducing its potential to cause vigorous infection.


2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Dee Shortridge ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm

ABSTRACT The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/ml and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/ml; 99.2% susceptible), extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/ml; 97.8% susceptible), and CRE (n = 513; MIC50/90, 0.5/2 μg/ml; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n = 2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n = 1,063) isolates were meropenem susceptible. Among Enterobacter cloacae (22.2% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.3% of the ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC50/90, 2/4 μg/ml; 97.1% susceptible), including MDR (MIC50/90, 4/16 μg/ml; 86.5% susceptible) isolates, and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n = 44,248) of contemporary Gram-negative bacilli isolated from U.S. patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wu Li ◽  
Wanyan Deng ◽  
Jianping Xie

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality globally, with nearly 10.4 million new cases of incidence and over 1.7 million deaths annually. Drug-resistant M. tuberculosis strains, especially multidrug-resistant or extensively drug-resistant strains, have further intensified the problem associated with tuberculosis control. Host-directed therapy is a promising alternative for tuberculosis control. IL-32 is increasingly recognized as an important host molecule against tuberculosis. In this review, we highlight the proinflammatory properties of IL-32 and the mode of action of IL-32 in mycobacterial infections to inspire the development of novel immunity-based countermeasures and host-directed therapies against tuberculosis.


2018 ◽  
Vol 15 ◽  
pp. 136-139 ◽  
Author(s):  
Olga Rodríguez-Núñez ◽  
Marco Ripa ◽  
Laura Morata ◽  
Cristina de la Calle ◽  
Celia Cardozo ◽  
...  

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