POLYMIXINS COLISTIN POLYMIXIN B ANTIBIOTICS ICU DR KANISHKA DAVDA ID PHYSICIAN











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FOOD FOR THOUGHT🤠🙋‍♂️🙋‍♀️ • why colistin and not poly b is used for urosepsis? • ANS🤷‍♂️✔ • POLY B is not excreted into the kidneys and urinary tractunlike colistin • Summary • DR DAVDA explained that the most sensitive bugs are non-ESBL producing, while ESBL-producing bacteria are resistant to third-generation cephalosporins and require beta-lactamase inhibitors or carbapenems. He further detailed the progression of resistance, from ESBL-producing to carbapenem-resistant Enterobacteriaceae (CRE), which can have multiple mechanisms of resistance. Kanishka also highlighted the role of polymyxins in treating CRE, but noted that newer drugs are now available for this purpose. He concluded by outlining the different enzyme categories in CRE and the need to determine the exact mechanism for appropriate treatment. • Kanishka discussed the use of Ceftazidime-Avibactam, a new drug recommended by IDSA and Indian guidelines for use with every bacterium. He noted that 60% of their hospital isolates have NDM or NDM plus another drug, necessitating the use of Sodim with Septasidim Avibactam. He also mentioned the new drug Cefem Zidobactam, currently in phase 3 trials, which has shown promising results in compassionate use cases. Kanishka emphasized the importance of loading doses for both Colistin and Polymyxin B, and the need for combination therapy in high-risk patients to prevent resistance. He also highlighted the differences and similarities between Colistin and Polymyxin B, and their limitations in treating gram-positive and anaerobic infections. • Kanishka discussed the mechanisms of action of Colistin and Polymexin B, explaining that they are positively charged molecules that attract to the negatively charged surface of gram-negative cell walls, causing cell death. Kanishka also presented a schematic and a graph illustrating the various locations and mechanisms of action of these drugs. Despite treatment with meropenem and polymexin B, the patient did not respond as expected. • He highlighted that Colistin is a prodrug with variable drug levels, potential nephrotoxicity, and requires dose adjustments, making it more suitable for urinary tract infections. In contrast, Polymyxin B is an active drug with predictable protein binding, less nephrotoxicity, and no dose adjustments needed, making it preferable for other indications. Kanishka recommended using Colistin for urinary tract infections and Polymyxin B for other indications, unless the patient is not tolerating it. He also noted that Polymyxin B is gentler on the meninges, making it preferable for intrathecal administration. • The swelling was found to be a diffuse large B-cell lymphoma, and the patient was started on a chemotherapy regimen. However, the patient developed altered sensorium, high-grade fever, and a liver lesion, initially thought to be an infection but later determined to be part of the lymphoma. Kanishka suggested that the significant drop in creatinine levels could be due to the patient's severe neutropenic sepsis, which led to a hyperdynamic circulation and increased glomerular filtration rate. • Augmented Renal Clearance and Antibiotic Dosing • Kanishka discussed the importance of monitoring renal clearance in patients, particularly in cases of neutropenic sepsis. He highlighted the concept of augmented renal clearance and its implications for antibiotic dosing. Kanishka emphasized the need for careful dosing adjustments, especially in patients with normal or reducing creatinine levels, to ensure adequate drug levels. He also mentioned the challenges in achieving good drug levels in such cases and suggested the potential need for higher doses or the use of polymyxins. Kanishka recommended consulting the work of authors Roger Nation, M. Falagas, • Kanishka discussed the concept of antibiotic brachytherapy, a method used to overcome systemic therapy limitations in treating infections. He explained the use of high local concentrations of antibiotics, • Colistin and Polymyxin B Dosing and Infusion Discussion • Kanishka discussed the dosing and infusion of Colistin and Polymyxin B, highlighting that the standard dose for a 60-65 kg person is 9 MIU stat loading for Colistin and 15 lac units loading for Polymyxin B. Hand recommended using online calculators for dosing. Kanishka also addressed concerns about infusion volume, stating that Polymyxin B can be given in 250ml or 100ml volumes, but should be infused slowly to avoid toxicity. He shared two cases of severe neuromuscular weakness possibly caused by Polymyxin B, Lastly, he explained that Colistin's effectiveness is variable and may not work in patients with normal creatinine levels due to insufficient blood levels. • 00 01:34 resistance • 00:05:40 types of CRE • 00:08:50 POLYMIXINS • 00:16:40 case 1 • 00:19:20 comparison ploy and coli • 00:26:00 case2 • )0;37;40 local therapy • 00:46:00 case3 • 00:52:00 case 4 • 00:53:30 discussion

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