November 17th, 2023 - Press notes
Researchers from the Hospital del Mar Research Institute have published a new article in Microbiology Spectrum proposing a novel approach to treating pneumonia caused by antibiotic-resistant Pseudomonas aeruginosa bacteria. The study suggests that increasing the dose of the antibiotic colistin may not only be ineffective but could also increase patient mortality
For this reason, the researchers advocate for using nebulized administration of the treatment instead of intravenous administration. This approach achieves higher concentrations in the lungs, where the infection is located, without causing toxic colistin concentrations in the blood
The World Health Organization considers antibiotic resistance among the top 10 global public health threats
Increasing the dose of colistin, an old antibiotic revived to treat pneumonia caused by drug-resistant Pseudomonas aeruginosa, is ineffective and may lead to an increased mortality rate among patients. This revelation comes from a study led by a Hospital del Mar Research Institute team, recently published in the journal Microbiology Spectrum. The study analyzed data from 75 patients admitted to the Hospital del Mar between 2010 and 2018, making it the most significant study in this field.
The study examined colistin levels in the plasma of patients treated at the center for pneumonia caused by antibiotic-resistant Pseudomonas aeruginosa infection. Colistin is a well-known drug revived due to the bacteria's lack of response to other medications. The challenge is that, at high doses, it can be toxic to the kidneys, requiring careful dosage adjustment. "The margin between being effective and being toxic is very narrow; it is a drug that requires careful management," explains Dr. Lluïsa Sorlí, lead researcher and attending physician in the Infectious Diseases Department at Hospital del Mar.
The results indicate that patients treated with colistin with higher drug levels in their blood did not show better progress and experienced an increased mortality rate. "Patients, when achieving these higher plasma levels of colistin, not only did not improve but significantly showed higher mortality," adds Dr. Sorlí. "This is a paradigm compared to what happens with other antibiotics that perform better against infections when higher plasma levels are achieved," comments Dr. Santi Grau, director of the pharmaceutical area at Hospital del Mar and author of the study.
"Indeed, thanks to this study and others developed by our team, we have learned to use this antibiotic better and how to adjust doses to improve patient safety and avoid the appearance of adverse effects that can worsen their prognosis, such as kidney damage," adds Dr. Sònia Luque, co-author of the article, attending physician in the Pharmacy Department, and researcher at the Hospital del Mar Research Institute.
Given these findings, the study's responsible team believes that changing the drug's administration form is the best approach for this type of patient. They recommend avoiding intravenous administration as a last resort and prioritizing nebulized administration. This change allows for a better concentration of the drug in the lungs, where the infection is located, without entering the bloodstream, avoiding affecting the kidneys.
This change in approach should maximize the benefits of colistin and, at the same time, prevent the development of new treatment resistances. As Dr. Juan Pablo Horcajada, senior author of the study, coordinator of the research group behind it, and head of the Infectious Diseases Department at Hospital del Mar, states, "While it is true that we have new drugs, more tools, to treat multidrug-resistant bacteria, not all hospitals have access to them, and resistance to these new drugs has begun to appear, forcing us, in some cases, to continue using old antibiotics, such as colistin." A recent study indicates that in Spain, Italy, and Greece, 36% of patients with pneumonia associated with the need for mechanical ventilation were caused by Pseudomonas aeruginosa infection resistant to standard treatment.
The study also involved researchers from the CIBER of Infectious Diseases (CIBERINFEC), Monash University in Melbourne, Australia, and the Reference Laboratory of Catalonia.
Sorlí L, Luque S, Li J, Benítez-Cano A, Fernández X, Prim N, Vega V, Gómez-Junyent J, López-Montesinos I, Gómez-Zorrilla S, Montero MM, Grau S, Horcajada JP. Colistin plasma concentrations are not associated with better clinical outcomes in patients with pneumonia caused by extremely drug-resistant Pseudomonas aeruginosa. Microbiol Spectr. 2023 Nov 9:e0296723. doi: 10.1128/spectrum.02967-23. Epub ahead of print. PMID: 37943035.
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