Adverse Reactions to Antibiotics in the Critical Care Unit
Cheston B. Cunha, Burke A. Cunha in Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Neuromuscular blockade is a potential side effect of aminoglycosides, particularly after intraperitoneal administration [102]. Polymyxins may also result in neuromuscular blockade. Characteristic signs occur soon after drug administration and include acute paralysis and apnea. Aminoglycosides and polymyxins should be avoided in patients with myasthenia gravis, owing to exacerbation of neuromuscular weakness. Paresthesias can occur in up to 27% of patients on polymyxins and is more common with intravenous versus intramuscular use (7%) [107]. Polymyxin neurotoxicity is theorized to be dose-dependent, with high binding to brain tissue and increased interaction with neurons. Risk factors for polymyxin-induced neurotoxicity include concomitant administration of narcotics, sedatives, anesthetic agents, corticosteroids, and/or muscle relaxants, which are all commonly used in CCU patients. Polymyxins can also cause peripheral neuropathy, visual disturbances, vertigo, confusion, partial deafness, hallucinations, and seizures.
Proteomics Approaches to Uncover the Drug Resistance Mechanisms of Microbial Biofilms
Chaminda Jayampath Seneviratne in Microbial Biofilms, 2017
Another reason for the increased drug resistance could be due to the presence of ‘persister’ cells in biofilms. ‘Persisters’ are a subpopulation of biofilms that are highly resistant to repeated exposure of drugs at high concentrations. Some of the recent proteomics studies have attempted to study this process. Colistin is a last-resort polymyxin antibiotic available for the treatment of infections caused by drug-resistant Gram-negative bacteria such as P. aeruginosa. The antibiotic tolerance of the P. aeruginosa biofilm subpopulation was investigated by a pulsed stable isotope labelling with amino acids (SILAC) approach [57]. P. aeruginosa biofilms were grown under a flow cell setup and then treated with colistin to kill the antibiotic sensitive population. The treated biofilms were then labelled with 13Clysine for 48 h to identify the proteins produced in the antibiotic-tolerant subpopulation. The study identified proteins required for type IV pili assembly and quorum sensing (QS) regulated proteins such as LasB, chitinase and phenazine/pycocyanin synthesis proteins to be highly expressed in the antibiotic-tolerant subpopulation. The study suggested that type IV pili help the antibiotic-tolerant cells to migrate to the top layer of biofilms whereas QS helps in establishing new antibiotic-tolerant subpopulations. Hence, the study proposed that incorporation of QS and motility inhibitors with the traditional antibiotics could prevent persistent infections in affected patient populations.
Bacterial infections after lung transplantation
Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell in LUNG Transplantation, 2016
Directed antimicrobial therapy depends on the pathogen causing the disease and review of the results of antimicrobial susceptibility testing. The emergence of MDR pathogens has made this choice particularly challenging, and susceptibility data should always guide therapeutic decisions. MRSA can be treated with vancomycin, linezolid, or daptomycin, although the use of daptomycin as therapy for MRSA lung infection should be avoided because pulmonary surfactant inactivates it. Vancomycin-resistant Enterococcus can be treated with daptomycin or linezolid. Gram-negative pathogens that produce extended-spectrum ß-lactamases or contain AmpC beta-lactamases (both of which confer resistance to many ß-lactam antibiotics) can be treated with carbapenem.76Acinetobacter isolates are frequently resistant to most antibiotics and are usually treated with carbapenems or colistimethate. Carbapenem-resistant Enterobacteriaceae have limited, nonstandardized treatment options. Polymyxins are commonly used against these isolates; however, they have poor pulmonary penetration when administered intravenously. Adjunctive therapy with aerosolized polymyxins is frequently used for such infection. Consultation with an infectious diseases specialist is recommended. Table 31.1 lists increasingly prevalent MDR pathogens and reasonable empiric antimicrobial coverage. As always, local susceptibility data, culture-specific susceptibility results, and infectious disease guidance should be used.76
The neuroprotective effect of mesenchymal stem cells in colistin-induced neurotoxicity
Published in Toxicology Mechanisms and Methods, 2023
Özlem Öz Gergin, İsmail Şamil Gergin, Sibel Seckin Pehlivan, Ozge Cengiz Mat, Işıl Tuğçe Turan, Adnan Bayram, Zeynep Burçin Gönen, Şeyda Korkmaz, Cihangir Bıcer, Karamehmet Yildiz, Arzu Hanım Yay
It is critical to investigate the mechanism of potential neurotoxicity, one of the most serious side effects of colistin, in order to improve its use in patients. The effect between MSC and colistin-induced neurotoxicity is yet unknown. Concerns have been expressed about the increased risk of toxicity associated with high vancomycin dosages. Neurotoxicity is a critical, yet inadequately clarified, adverse effect related to polymyxin treatment. Therefore, discovering promising neuroprotective preparations to co-administrate throughout colistin treatment is vital to extend the clinical benefit of this critical lipopeptide antibiotic. This study aimed to examine if MSC could prevent or reverse colistin’s pathogenic impact on rats’ brains and if so, whether MSC-produced soluble agents could re-produce this effect.
Role of silymarin (Silybum marianum) in the prevention of colistin-induced acute nephrotoxicity in rats
Published in Drug and Chemical Toxicology, 2022
Burak Dumludag, Mehmet Kursat Derici, Osman Sutcuoglu, Betul Ogut, Ozge Tugce Pasaoglu, Ipek Isık Gonul, Ulver Derici
Colistin is a polymyxin group antibiotic. The target of colistin is the bacterial cell membrane. It interacts electrostatically with bacterial outer membranes, passes into the race with divalent cations (calcium and magnesium) in the negatively charged phosphate groups in membrane lipids, causes damage to the outer membrane, increases permeability, releases cell content and causes the death of bacteria (Falagas et al. 2005, Li et al. 2005, Li et al. 2006). Nowadays, antibiotic resistance is increasing. Although the side-effect profile is high, colistin treatment must be used especially to treat Pseudomonas aeruginosa and Acinetobacter baumanii infections due to this resistance. The most common limiting effect of colistin on clinical use is its nephrotoxicity (Falagas et al. 2005, Li et al. 2005, Li et al. 2006). Colistin-induced-nephrotoxicity (CIN) is a consequence of intracellular colistin accumulation, its necrotic nature at the level of the proximal tubule cells and its detergent activity on the cell membrane. It is thought that this damage can be prevented by drugs that feature antioxidant activity (Ghlissi et al. 2013, Gai et al. 2019). In this context, silymarin may be effective in preventing colistin nephropathy due to its antioxidant and anti-inflammatory properties.
Safety considerations of current drug treatment strategies for nosocomial pneumonia
Published in Expert Opinion on Drug Safety, 2021
Adrian Ceccato, Pierluigi Di Giannatale, Stefano Nogas, Antoni Torres
Colistin is a polymyxin with activity against gram-negative microorganisms. Its mechanism of action is by interaction with the lipid A component of the lipopolysaccharide of the bacterial membrane. It has activity against extensive drug-resistant P. aeruginosa and A. baumannii, and it can be used as an alternative for pneumonia caused by microorganisms resistant to carbapenems. Some reports have showed that colistin is effective against susceptible microorganisms [58], and the drug has been included in the latest European and Latin-American guidelines for use as a second-line agent in settings with high incidence of microorganisms resistant to carbapenems, such as A. baumannii [3]. In a randomized controlled trial (RCT) colistin was found to be not non-inferior to meropenem while also being associated with a high incidence of side effects [59]. Therefore, colistin must not replace carbapenems as an empirical treatment in settings with high drug resistance.
Related Knowledge Centers
- Antibiotic
- Colistin
- Nephrotoxicity
- Polymyxin B
- Cell Membrane
- Neurotoxicity
- NONribosomal Peptide
- Gram-Positive Bacteria
- Paenibacillus Polymyxa
- Drug of Last Resort