Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis

doi:10.1016/S0140-6736(01)06124-4

The Lancet

Volume 358, Issue 9286, 22 September 2001, Pages 983-984

https://doi.org/10.1016/S0140-6736(01)06124-4 Get rights and content

Summary

Early antibiotic treatment of airway colonisation with Pseudomonas aeruginosa can delay onset of chronic lung infection in patients with cystic fibrosis. Whether the pathogen is eradicated by this treatment is unclear. We successfully eradicated the organism in 14 of 15 patients with cystic fibrosis who had been colonised by P aeruginosa. Patients inhaled 80 mg tobramycin twice daily for 12 months. Eradication was confirmed by sequential respiratory cultures and serum antibody titres that were negative for P aeruginosa. Our antibiotic therapy regimen maintained pulmonary function at high levels.

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Lancet
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There are more references available in the full text version of this article.

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The development of smart nanoparticles (NPs) became a trend to enhance the delivery of drugs. In the present work, Tobramycin (TB), an aminoglycoside antibiotic that displays several undesirable side effects, has been encapsulated into cationic Eudragit®E100 (E100) NPs for the treatment of infections caused by Pseudomonas aeruginosa. Combination with neutral Eudragit®NE30D (NE30D) NPs containing resveratrol (RSV), a strong natural antioxidant, increased the antimicrobial activity of TB (75% higher than free TB). NPs were stabilized with 1.0% (w/v) poloxamer 188 (P188) or poloxamer 407 (P407) as surfactants. E100 NPs showed 83.3 ± 8.5%, and 70.1 ± 2.7 encapsulation efficiency (EE) of TB with P188 and P407 coatings, respectively. The presence of NPs was confirmed by DLS and TEM studies. TB was controlled released from NPs for 6 h. Hemotoxicity tests of NPs in the range of MIC values on human blood gave negative results. Analysis of Surface Plasmon Resonance verified that NE30D/P407/RSV does not interact with plasma proteins BSA, IgG or fibrinogen, besides E100/P188/TB interact with BSA, findings that are compatible with a negligible in vivo clearance of the nanovehicles. The obtained results show a potential binary fluid composed of two NPs to highly improve the effectiveness of conventional antibiotics.
Scope and limitations on aerosol drug delivery for the treatment of infectious respiratory diseases
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The rise of antimicrobial resistance has created an urgent need for the development of new methods for antibiotics delivery to patients with pulmonary infections in order to mainly increase the effectiveness of the drugs administration, to minimize the risk of emergence of resistant strains, and to prevent patients reinfection. Since bacterial resistance is often related to antibiotic concentration, their pulmonary administration could eradicate strains resistant to the same drug at the concentration achieved through the systemic circulation. Pulmonary administration offers several advantages; it directly targets the site of the infection which allows the inhaled dose of the drug to be reduced compared to that administered orally or parenterally while keeping the same local effect. The review article is made with an objective to compile information about various existing modern technologies developed to provide greater patient compliance and reduce the undesirable side effect of the drugs. In conclusion, aerosol antibiotic delivery appears as one of the best technologies for the treatment of pulmonary infectious diseases and able to limit the systemic adverse effects related to the high drug dose and to make life easier for the patients.
A shell-less hen's egg test as infection model to determine the biocompatibility and antimicrobial efficacy of drugs and drug formulations against Pseudomonas aeruginosa
2020, International Journal of Pharmaceutics
A shell-less hen’s egg based infection test with Pseudomonas aeruginosa was established to investigate the antimicrobial efficacy of drugs and drug formulations close to the in vivo situation. The test system using preincubated fertilized chicken eggs transferred in petri dishes was optimized with respect to the controlled local application of liquid materials and bacteria as well as the bacterial cultivation conditions. The applicability of the ex ovo infection model was confirmed with antimicrobial susceptibility tests using tobramycin, ciprofloxacin and meropenem. The validity of the ex ovo data was demonstrated by correlation with in vitro data of the CellTiter®-Blue and the microplate laser nephelometry assay. Real-time imaging of the progress of infection and the efficacy of the treatment could be realized by the MolecuLight i:X™ technique. Furthermore, in a proof-of-concept efficacy, biocompatibility and even the presence of irritants were determined side-by-side using commercial ophthalmics. In conclusion, this egg based infection model could bridge the gap between in vitro and in vivo models for the evaluation of antimicrobial susceptibility to reduce animal tests according to the 3R concept.
A critical review of definitions used to describe Pseudomonas aeruginosa microbiological status in patients with cystic fibrosis for application in clinical trials
2020, Journal of Cystic Fibrosis
Definition of Pseudomonas aeruginosa (Pa) microbiological status is essential for patients' inclusion in clinical trials. The aim of this study was to agree on the definitions of Pa infection status for initial infection, eradication and chronic infection to be used in clinical trials and to propose additional future study areas.
An exhaustive literature search was performed. The clinimetric properties of different definitions of Pa microbiological status were evaluated.
Historical studies have mostly used culture-based definitions, although some have also involved complementary anti-Pa antibodies. Clinimetric analysis showed great variability in the definitions used, leading to differences in reliability, validity, responsiveness to treatment and correlation with outcome measures.
Use of serology for initial Pa infection and successful Pa eradication introduced a greater level of complexity as antibody tests are not standardised. Moreover, the chronology of the immune response to Pa antigenic determinants was not completely clear.
Chronic Pa infection was characterized by high levels of antibodies and good concordance between culture results and serology.
Microbiological monitoring, regular sampling from the airways and standardization of culture methods remain essential requisites for microbiological definitions. Despite limitations, serology should be incorporated in the definitions of initial infection and eradication used in clinical trials to better classify patients at enrolment, mainly in non-expectorating children. This requires standardization of serological testing.
Rapid detection of the bacterial biomarker pyocyanin in artificial sputum using a SERS-active silicon nanowire matrix covered by bimetallic noble metal nanoparticles
2019, Talanta
Early stage detection of Pseudomonas infections is life-saving, especially in the case of patients with cystic fibrosis. Pyocyanin (PYO) is a specific metabolite of the Pseudomonas aeruginosa bacteria, and detection of it directly in the sputum can significantly reduce the diagnosis time of the infection. In the present study, aiming to achieve this goal, a simple and cost-effective surface-enhanced Raman spectroscopy (SERS) detection platform was proposed. For this, a silicon nanowire (SiNW) matrix, produced by metal-assisted chemical etching of silicon substrates was variously modified by noble metal (silver and gold) nanoparticles (NPs) and tested for the detection of the metabolite PYO in the complex matrix of artificial sputum. We found the SERS substrate with Ag NPs on the bottom of SiNWs and deposited bimetallic Ag/Au NPs on the top of them the best suited for the sensitive detection of PYO. The investigated plasmonic substrate showed good point-to-point and batch-to-batch signal reproducibility and allowed for the detection of PYO in artificial sputum down to 6.25 μM, which is the required sensitivity for clinical applications.
Early detection using qPCR of Pseudomonas aeruginosa infection in children with cystic fibrosis undergoing eradication treatment
2018, Journal of Cystic Fibrosis
Citation Excerpt :
Therefore, antibiotic eradication therapy (AET) is often attempted in patients with early Pa infections [3–5]. Tobramycin inhaled solution (TIS) is frequently used for AET, given its safety and efficacy profile [4–6]. However, AET fails in about 10–40% of cases [7].
Infection with Pseudomonas aeruginosa (Pa) with a chronic phenotype is associated with antibiotic eradication therapy (AET) failure. Our objective was to determine whether higher levels of Pa (detected using qPCR) prior to culture positivity were associated with AET failure in pediatric CF patients.
Pa-specific qPCR was performed on stored sputa prior to culture positivity in pediatric CF patients with new-onset culture-positive Pa infections undergoing AET with a 28-day course of tobramycin-inhaled solution (TIS). DNA concentrations were compared in patients in whom AET was successful (Eradicated) to those with persistently positive sputum cultures (Persistent).
Forty-seven patients were included. AET was successful in 32 cases (68%), but failed in 15 cases (32%). Median sputum Pa-specific DNA concentration preceding the positive sputum culture was 2.2 × 10⁻⁶ μg/mL in Eradicated cases compared to 3 × 10⁻⁵ μg/mL in Persistent cases (p = 0.14). There was no significant difference in DNA concentration in the last sputum sample prior to culture positivity, nor in maximal DNA values. There was also no difference in sputum Pa DNA concentrations in patients who had a mucoid (compared to non-mucoid) Pa infection.
Pediatric CF patients with new-onset Pa infections have detectable Pa-specific DNA in the year preceding a positive culture, however, there is no significant difference in Pa DNA concentrations between patients in whom AET is successful compared to those in whom it fails. Therefore, early molecular detection of Pa may not lead to improved eradication success rates.

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Summary

References (5)

Prevention of chronic Pseudomonas aeruginosa colonisation by early treatment

Lancet

Cystic Fibrosis Foundation Patient Registry annual report 1998

Cited by (204)

Binary Medical Nanofluids by Combination of Polymeric Eudragit Nanoparticles for Vehiculization of Tobramycin and Resveratrol: Antimicrobial, Hemotoxicity and Protein Corona Studies

Scope and limitations on aerosol drug delivery for the treatment of infectious respiratory diseases

A shell-less hen's egg test as infection model to determine the biocompatibility and antimicrobial efficacy of drugs and drug formulations against Pseudomonas aeruginosa

A critical review of definitions used to describe Pseudomonas aeruginosa microbiological status in patients with cystic fibrosis for application in clinical trials

Rapid detection of the bacterial biomarker pyocyanin in artificial sputum using a SERS-active silicon nanowire matrix covered by bimetallic noble metal nanoparticles

Early detection using qPCR of Pseudomonas aeruginosa infection in children with cystic fibrosis undergoing eradication treatment

Research LettersEffect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis

Summary

Lancet

Cystic Fibrosis Foundation Patient Registry annual report 1998

Research Letters
Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis