scholarly journals Tobramycin Activity for Pseudomonas Aeruginosa spp. Isolated in Cystic Fibrosis Patients

Doctor Ru ◽  
2021 ◽  
Vol 20 (3) ◽  
pp. 17-23
Author(s):  
A.V. Goryainova ◽  
◽  
S.V. Polikarpova ◽  
S.Yu. Semykin ◽  
N.Yu. Kashirskaya ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
General Group ◽  
Study Objective ◽  
Keywords Cystic Fibrosis ◽  
Study Results ◽  
Before And After ◽  
Comparison Groups ◽  
The Difference

Study Objective: To determine in vitro activity of Tobramycin for Pseudomonas aeruginosa spp. isolated in children with cystic fibrosis (CF); to retrospectively study the efficiency dynamics of inhalative Tobramycin in management of bronchopulmonary process exacerbation in children with CF aged 9 years old (2009–2018). Study Design: retrospective analysis. Materials and Methods. The study included 173 children with cystic fibrosis aged 3 to 17 years old; the median age in the general group was 11 [8; 15] years. Subjects were divided into two comparison groups, depending on various 14-day combined antipseudomonal therapy: 42 children were treated with Cefepime 150 mg/kg + Amikacin 20 mg/kg IV drop infusion; 48 subjects — with Meropenem 100 mg/kg + Amikacin 20 mg/kg IV drop infusion; 83 patients — with Ceftazidime 200 mg/kg IV + Tobramycin (Bramitob) 300 mg twice daily, inhalation + Ciprofloxacin per os 30–40 mg/kg. Study Results. After the two-week therapy of 83 children with Tobramycin inhalations plus oral Ciprofloxacin and Ceftazidime IV, 123 (82%) out of 150 pathogenic P. aeruginosa and Staphylococcus aureus spp. were eliminated (p < 0.001 when compared to bacteriologic test results of pre-therapy bronchial mucus). Comparison groups demonstrated statistically significantly lower number of such subjects: in Cefepime + Amikacin group, 32 (43.8%) out of 73 pathogenic P. aeruginosa and S. aureus spp. were eliminated; whereas in Meropenem + Amikacin group, only 28 (35.4%) pathogens were eliminated out of 79 species. Upon admission in 2013, 50 followed up children underwent antimicrobial therapy with inhalative Tobramycin using the same regimen as in 2009; the P. aeruginosa elimination was the same: 11 (18%) out of 61 pathogenic species remained viable, 50 (82%) species were eliminated, as demonstrated by control sputum. The difference between the number of P. aeruginosa and S. aureus colonies before and after therapy was statistically significant (p < 0.001). Practically the same result after the use of inhalative Tobramycin was observed in 2018: 14 (70%) out 20 children with P. aeruginosa spp. had their control sputum samples sanitised (p < 0.001). Conclusion. Despite a 20-year history of using in patients with cystic fibrosis, inhalative Tobramycin is still clinically efficient and potent for isolated P. aeruginosa as a component of primary eradication and management of chronic Pseudomonal lung infections. Keywords: cystic fibrosis, Pseudomonas aeruginosa, inhalative Tobramycin.

scholarly journals Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa

2019 ◽  
Vol 75 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Odel Soren ◽  
Ardeshir Rineh ◽  
Diogo G Silva ◽  
Yuming Cai ◽  
Robert P Howlin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Clinical Isolates ◽  
Nitric Oxide Donor ◽  
Confocal Laser ◽  
Broth Microdilution Method

Abstract Objectives The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D (‘DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate’) has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. Methods β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. Results DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. Conclusions DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.

scholarly journals In Vitro Newly Isolated Environmental Phage Activity against Biofilms Preformed by Pseudomonas aeruginosa from Patients with Cystic Fibrosis

2021 ◽  
Vol 9 (3) ◽  
pp. 478
Author(s):  
Ersilia Vita Fiscarelli ◽  
Martina Rossitto ◽  
Paola Rosati ◽  
Nour Essa ◽  
Valentina Crocetta ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
In Vitro Test ◽  
Chronic Infections ◽  
Hospital Environments ◽  
Vitro Test ◽  
General Reliability ◽  
Phage Activity

As disease worsens in patients with cystic fibrosis (CF), Pseudomonas aeruginosa (PA) colonizes the lungs, causing pulmonary failure and mortality. Progressively, PA forms typical biofilms, and antibiotic treatments determine multidrug-resistant (MDR) PA strains. To advance new therapies against MDR PA, research has reappraised bacteriophages (phages), viruses naturally infecting bacteria. Because few in vitro studies have tested phages on CF PA biofilms, general reliability remains unclear. This study aimed to test in vitro newly isolated environmental phage activity against PA isolates from patients with CF at Bambino Gesù Children’s Hospital (OBG), Rome, Italy. After testing in vitro phage activities, we combined phages with amikacin, meropenem, and tobramycin against CF PA pre-formed biofilms. We also investigated new emerging morphotypes and bacterial regrowth. We obtained 22 newly isolated phages from various environments, including OBG. In about 94% of 32 CF PA isolates tested, these phages showed in vitro PA lysis. Despite poor efficacy against chronic CF PA, five selected-lytic-phages (Φ4_ZP1, Φ9_ZP2, Φ14_OBG, Φ17_OBG, and Φ19_OBG) showed wide host activity. The Φ4_ZP1-meropenem and Φ14_OBG-tobramycin combinations significantly reduced CF PA biofilms (p < 0.001). To advance potential combined phage-antibiotic therapy, we envisage further in vitro test combinations with newly isolated phages, including those from hospital environments, against CF PA biofilms from early and chronic infections.

scholarly journals 1458. Uncharted territories: applying “precision medicine” to understand the treacherous landscape of extensively and multidrug resistant (XDR and MDR) Pseudomonas aeruginosa in a patient with cystic fibrosis and lung transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S731-S731
Author(s):  
Laura J Rojas ◽  
Mohamad Yasmin ◽  
Jacquelynn Benjamino ◽  
Steven Marshall ◽  
Kailynn DeRonde ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Transplantation ◽  
Precision Medicine ◽  
Clinical Sample ◽  
Phylogenetic Reconstruction ◽  
Multidrug Resistant ◽  
Population Diversity ◽  
Before And After ◽  
Research Grant

Abstract Background Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with cystic fibrosis (CF). Herein, we describe our experience managing a young woman suffering from CF with XDR P. aeruginosa who underwent lung transplantation. We highlight the contemporary difficulties reconciling the clinical, microbiological, and genetic information. Methods Mechanism-based-susceptibility disk diffusion synergy testing with double and triple antibiotic combinations aided in choosing tailored antimicrobial combinations to control the infection in the pre-transplant period, create an effective perioperative prophylaxis regimen, and manage recurrent infections in the post-transplant period. Thirty-six sequential XDR and PDR P. aeruginosa isolates obtained from the patient within a 17-month period, before and after a double-lung transplant were analyzed by whole genome sequencing (WGS) and RNAseq in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time Results Our phylogenetic reconstruction demonstrates that these isolates represent a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggests that a group of closely related strains was present in the patient prior to transplantation and continued to evolve throughout the course of treatment regardless of antibiotic usage.Our findings challenge antimicrobial stewardship programs that assist with the selection and duration of antibiotic regimens in critically ill and immunocompromised patients based on single-isolate laboratory-derived resistant profiles. We propose that an approach sampling the population of pathogens present in a clinical sample instead of single colonies be applied instead when dealing with XDR P. aeruginosa, especially in patients with CF. Conclusion In complex cases such as this, real-time combination testing and genomic/transcriptomic data could lead to the application of true “precision medicine” by helping clinicians choose the combination antimicrobial therapy most likely to be successful against a population of MDR pathogens present. Disclosures Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)

Murepavadin antimicrobial activity against and resistance development in cystic fibrosis Pseudomonas aeruginosa isolates

2020 ◽  
Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Spontaneous Mutation ◽  
Lung Surfactant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Agar Dilution

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was &gt;90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to &gt;16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.

scholarly journals Within-Host Evolution of Pseudomonas aeruginosa Reveals Adaptation toward Iron Acquisition from Hemoglobin

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Rasmus Lykke Marvig ◽  
Søren Damkiær ◽  
S. M. Hossein Khademi ◽  
Trine M. Markussen ◽  
Søren Molin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Iron Acquisition ◽  
Chronic Infections ◽  
Content Type ◽  
Mortality And Morbidity ◽  
Airway Infections ◽  
Host Evolution ◽  
Promoter Mutations

ABSTRACTPseudomonas aeruginosaairway infections are a major cause of mortality and morbidity of cystic fibrosis (CF) patients. In order to persist,P. aeruginosadepends on acquiring iron from its host, and multiple different iron acquisition systems may be active during infection. This includes the pyoverdine siderophore and thePseudomonasheme utilization (phu) system. While the regulation and mechanisms of several iron-scavenging systems are well described, it is not clear whether such systems are targets for selection during adaptation ofP. aeruginosato the host environment. Here we investigated the within-host evolution of the transmissibleP. aeruginosaDK2 lineage. We found positive selection for promoter mutations leading to increased expression of thephusystem. By mimicking conditions of the CF airwaysin vitro, we experimentally demonstrate that increased expression ofphuRconfers a growth advantage in the presence of hemoglobin, thus suggesting thatP. aeruginosaevolves toward iron acquisition from hemoglobin. To rule out that this adaptive trait is specific to the DK2 lineage, we inspected the genomes of additionalP. aeruginosalineages isolated from CF airways and found similar adaptive evolution in two distinct lineages (DK1 and PA clone C). Furthermore, in all three lineages,phuRpromoter mutations coincided with the loss of pyoverdine production, suggesting that within-host adaptation toward heme utilization is triggered by the loss of pyoverdine production. Targeting heme utilization might therefore be a promising strategy for the treatment ofP. aeruginosainfections in CF patients.IMPORTANCEMost bacterial pathogens depend on scavenging iron within their hosts, which makes the battle for iron between pathogens and hosts a hallmark of infection. Accordingly, the ability of the opportunistic pathogenPseudomonas aeruginosato cause chronic infections in cystic fibrosis (CF) patients also depends on iron-scavenging systems. While the regulation and mechanisms of several such iron-scavenging systems have been well described, not much is known about how the within-host selection pressures act on the pathogens’ ability to acquire iron. Here, we investigated the within-host evolution ofP. aeruginosa, and we found evidence thatP. aeruginosaduring long-term infections evolves toward iron acquisition from hemoglobin. This adaptive strategy might be due to a selective loss of other iron-scavenging mechanisms and/or an increase in the availability of hemoglobin at the site of infection. This information is relevant to the design of novel CF therapeutics and the development of models of chronic CF infections.

scholarly journals Effects of two different deep digital flexor tenotomy techniques on distal articular angles of equine cadaver forelimbs

2012 ◽  
Vol 42 (11) ◽  
pp. 2005-2010
Author(s):  
Antonio Cezar de Oliveira Dearo ◽  
Vitor Bruno Bianconi Rosa ◽  
Peter Reichmann ◽  
Milton Luis Ribeiro de Oliveira
Keyword(s):  
Quantitative Data ◽  
Statistical Significance ◽  
Surgical Approaches ◽  
Control Groups ◽  
Before And After ◽  
Distal Interphalangeal ◽  
The Difference ◽  
And Control ◽  
Flexor Tenotomy

Deep digital flexor (DDF) tenotomy is a technique employed for years to treat selected disorders of the musculoskeletal system in horses. Although two different surgical approaches (i.e. mid-metacarpal and pastern) have been described for performing the procedure, in vitro quantitative data regarding the modifications induced by either technique on the distal articular angles is lacking. Therefore, the purpose of the study reported here was to investigate the viability of a proposed biomechanical system of induced-traction used to compare the two DDF tenotomy techniques by measuring the distal articular angles of equine cadaver forelimbs. Ten pairs of forelimbs were collected and mounted to a biomechanical system developed to apply traction at the toe level. Dorsal articular angles of the metacarpophalangeal (MP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints were determined by geometric lines on radiographs taken before and after performing each technique. Comparisons between each tenotomy group and its own control, for each joint, and between the two tenotomy groups using as variable the difference between the tenotomy and control groups were tested. Despite the lack of statistical significance, the DDF tenotomy technique at the pastern level produced extension, to a lesser and greater extent, of the PIP and DIP joints, respectively when compared to the mid-metacarpal level. No remarkable differences could be observed for the MP joint. The developed traction-induced biomechanical construct seemed to be effective in producing valuable quantitative estimations of the distal articular angles of equine cadaver forelimbs subjected to different DDF tenotomy techniques.

Activities of Tobramycin and Six Other Antibiotics against Pseudomonas aeruginosa Isolates from Patients with Cystic Fibrosis

1999 ◽  
Vol 43 (12) ◽  
pp. 2877-2880 ◽  
Author(s):  
Ribhi M. Shawar ◽  
David L. MacLeod ◽  
Richard L. Garber ◽  
Jane L. Burns ◽  
Jenny R. Stapp ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Active Drug ◽  
Resistance Mechanisms ◽  
Phase Iii ◽  
In Vitro Activity ◽  
Phase Iii Clinical Trials ◽  
Multiple Antibiotics

ABSTRACT The in vitro activity of tobramycin was compared with those of six other antimicrobial agents against 1,240 Pseudomonas aeruginosa isolates collected from 508 patients with cystic fibrosis during pretreatment visits as part of the phase III clinical trials of tobramycin solution for inhalation. The tobramycin MIC at which 50% of isolates are inhibited (MIC50) and MIC90 were 1 and 8 μg/ml, respectively. Tobramycin was the most active drug tested and also showed good activity against isolates resistant to multiple antibiotics. The isolates were less frequently resistant to tobramycin (5.4%) than to ceftazidime (11.1%), aztreonam (11.9%), amikacin (13.1%), ticarcillin (16.7%), gentamicin (19.3%), or ciprofloxacin (20.7%). For all antibiotics tested, nonmucoid isolates were more resistant than mucoid isolates. Of 56 isolates for which the tobramycin MIC was ≥16 μg/ml and that were investigated for resistance mechanisms, only 7 (12.5%) were shown to possess known aminoglycoside-modifying enzymes; the remaining were presumably resistant by an incompletely understood mechanism often referred to as “impermeability.”

scholarly journals Comparison of the Remineralizing Effect of Brushing with Aloe vera versus Fluoride Toothpaste

2020 ◽  
Author(s):  
Teresa Al Haddad ◽  
Elie Khoury ◽  
Nada Farhat Mchayleh
Keyword(s):  
Repeated Measures ◽  
Aloe Vera ◽  
In Vitro Study ◽  
P Value ◽  
Fluoride Toothpaste ◽  
Before And After ◽  
The Difference ◽  
Group B ◽  
Ca:P Ratio

Abstract Objectives The aim of the present in vitro study is to compare the remineralization brushing effect of three toothpastes and Aloe vera (AV) gel. Materials and Methods Forty sound extracted teeth were placed in a demineralizing solution for 4 days and randomly assigned to four groups: group A: 1,450-ppm fluoride toothpaste; group B: AV nonfluoridated toothpaste; group C: AV 1,000-ppm fluoridated toothpaste; and group D: AV gel. A 3-minute pH cycling was performed twice a day for each group for 12 days. Specimens were analyzed before and after by scanning electron microscope—energy dispersive X-ray. Statistical analysis The outcomes were analyzed by Kolmogorov–Smirnov’s tests, repeated-measures analyses of variance followed by univariate analyses, and Bonferroni’s multiple comparisons tests to compare the calcium-to-phosphorus (Ca:P) ratio within time among toothpaste groups. Results Following remineralization, the Ca:P ratio increased in all groups. The difference of the Ca:P ratio was not significant between groups C, D, and A. The mean ratio was significantly lower in group B (p-value = 0.026). Conclusions The AV gel demonstrated a remineralization capacity equal to that of the 1,450-ppm fluoride toothpaste. In contrast, fluoride-free AV toothpaste showed a lower remineralization efficiency. Further studies are required to understand its mechanism.

scholarly journals Prevalence and impact of oprD mutations in Pseudomonas aeruginosa strains in cystic fibrosis

2019 ◽  
Author(s):  
Laura J. Sherrard ◽  
Bryan A. Wee ◽  
Christine Duplancic ◽  
Kay A. Ramsay ◽  
Keyur A. Dave ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Hazard Rate ◽  
Carbapenem Resistance ◽  
Adverse Outcomes ◽  
Nonsense Mutations ◽  
Allelic Variants ◽  
Novel Variants

ABSTRACTDefective OprD porins contribute to carbapenem resistance and may be important in Pseudomonas aeruginosa adaptation to cystic fibrosis airways. It is unclear whether oprD mutations are fixed in populations of shared strains that are transmitted between patients or whether novel variants arise during infection. We investigated oprD sequences and antimicrobial resistance of two common Australian shared strains, constructed P. aeruginosa mutants with the most common oprD allelic variants and compared characteristics between patients with or without evidence of infection with strains harbouring these variants. Our data show that three independently acquired nonsense mutations arising from a 1-base pair substitution are fixed in strain sub-lineages. These nonsense mutations are likely to contribute to reduced carbapenem susceptibility in the sub-lineages without compromising in vitro fitness. Not only was lung function worse among patients infected with strains harbouring the nonsense mutations than those without, but they also had an increased hazard rate of lung transplantation/death. Our findings further highlight that understanding adaptive changes may help to distinguish patients with greater adverse outcomes despite infection with the same strain.

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