AMIT KATOCH’s Post

A Study on the Outcome of Antibiotic Eluting Intramedullary Interlocking Nails in the Primary Fixation of Gustilo and Anderson Grades II and IIIA Open Fractures of Tibia Abstract Introduction: The incidence and outcome of infection in open tibial fractures is adequately recorded in literature. The aim of this study is to find out the deep infection rate, union rate, and functional outcome of open tibial fractures managed by prophylactic antibiotic eluting interlocking nail. Methodology: A total of 18 patients with 20 open tibial fractures who met the study criteria were included and followed up for a minimum of 1 year after surgical intervention. Reamed intramedullary interlocking nailing with antibiotic eluting nail was done followed by adequate skin cover. Results: The outcomes were assessed using lower extremity functional scale and radio logical union scale in tibial fractures both of which showed maximum improvement in initial 3 months followed by a steady improvement till 1 year with a good degree of correlation between the two scales. The total incidence of deep infection in this study was 5% (n = 1). All cases achieved union and independent ambulation by 1 year. Conclusion: Our study shows good radiological and functional outcomes with prophylactic antibiotic-coated nailing of open tibial fractures of Grades II and IIIA. The rate of deep infection is 5% and union rate is 100% in our study. Further comparative studies are required for drawing more conclusions on application of the results in clinical practice. Keywords: Local antibiotic prophylaxis, open tibia fracture, antibiotic eluting implant, antibiotic-coated nail, tibia fracture, deep infection, interlocking nail, gentamycin coating, level of evidence: IV Learning Point of the Article: Sustained local concentration of anti-microbial substance can potentially mitigate deep infections in open fractures of tibia and a careful selection of appropriate anti-microbial may not endanger bone union. Sample size calculation The sample size was is calculated with an assumed deep infection rate of 5% in open tibial fractures Grades II and IIIA based on earlier studies and an expected margin of error (d) of ± 10% and confidence interval of 95%. Eighteen . All participants were started on systemic intravenous antibiotics with a first-generation cephalosporin and an aminoglycoside at the time of initial presentation. All participants were managed by thorough wound debridement done either as a one step or as a staged procedure. All fractures were fixed by antibiotic eluting intramedullary interlocking nail at index surgery (Ossipro Gentamicin Eluting Nails manufactured by Matrix Meditec Pvt. Ltd., India). were followed up at 6 weeks, 12 weeks, 6 months, and 12 months from the date of surgery  

⚠️📝ANTIBIOTICS AND LUNG PENETRATION ✅Antibiotics are pivotal in treating bacterial infections, especially those affecting the respiratory system. In lung infections, the efficacy of antibiotics not only depends on their ability to combat bacterial strains but also on their capacity to penetrate the lungs efficiently. Understanding the dynamics of antibiotic lung penetration is essential for optimizing treatment outcomes against respiratory infections. ✅The Importance of Lung Penetration: The respiratory system poses unique challenges, shielded by layers like airway lining fluid and the pulmonary epithelium. Antibiotics must efficiently penetrate these barriers to ensure efficacy, as insufficient penetration could compromise treatment success. ✅Factors Affecting Lung Penetration: Molecular size, lipophilicity, and protein binding significantly influence antibiotic penetration. Smaller, lipid-soluble molecules tend to penetrate lung tissues more effectively. Protein binding considerations are vital, as only the unbound fraction remains active. ✅Specific Antibiotics and Their Mechanism of Action with Lung Penetration: 1. Fluoroquinolones: - Example:Levofloxacin - Mechanism of Action: Inhibits DNA gyrase, disrupting bacterial DNA replication and repair. - Lung Penetration: Known for excellent lung tissue penetration, achieving a concentration of approximately 60-80%. 2. Macrolides: - Example:Azithromycin - Mechanism of Action:Binds to the 50S subunit of bacterial ribosomes, preventing protein synthesis. - Lung Penetration:Exhibits favorable lung distribution, achieving concentrations around 50-60%. 3. Tetracyclines: - Example: Doxycycline - Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. - Lung Penetration:Demonstrates effectiveness in respiratory infections, with concentrations ranging from 30-60%. 4. Aminoglycosides: - Example:Amikacin - Mechanism of Action: Binds to the 30S ribosomal subunit, causing misreading of mRNA and inhibiting protein synthesis. - Lung Penetration:Effective against Gram-negative bacteria in the respiratory system, achieving concentrations of approximately 70-90%. 5. Cephalosporins: - Example: Ceftriaxone - Mechanism of Action: Inhibits bacterial cell wall synthesis. - Lung Penetration: Demonstrates efficacy in treating respiratory infections, with concentrations varying but often around 40-60%. 6. Carbapenems: - Example: Meropenem - Mechanism of Action: Inhibits bacterial cell wall synthesis. - Lung Penetration: Exhibits good penetration into lung tissues, with concentrations varying but often around 60-80%. ✅Conclusion Optimizing lung penetration is vital for treating respiratory infections. Understanding drug dynamics, mechanisms, and tackling resistance are key. Ongoing research aims at targeted treatments for improved outcomes in the battle against respiratory infections. #drugdiscovery #fda #drug

𝐀𝐧𝐭𝐢𝐛𝐢𝐨𝐭𝐢𝐜 𝐃𝐫𝐮𝐠𝐬 𝐂𝐥𝐚𝐬𝐬𝐢𝐟𝐢𝐜𝐚𝐭𝐢𝐨𝐧 📚 𝐋𝐚𝐬𝐭 𝐂𝐡𝐚𝐧𝐜𝐞 -𝐑𝐞𝐪𝐮𝐞𝐬𝐭 𝐒𝐚𝐦𝐩𝐥𝐞 𝐂𝐨𝐩𝐲 𝐨𝐟 𝐑𝐞𝐩𝐨𝐫𝐭: https://lnkd.in/gA-EmRgj Antibiotics are classified based on various criteria, including their chemical structure, mechanism of action, spectrum of activity, and clinical uses. 𝐏𝐞𝐧𝐢𝐜𝐢𝐥𝐥𝐢𝐧𝐬: This class includes antibiotics like penicillin, amoxicillin, and ampicillin. Penicillins work by inhibiting the synthesis of bacterial cell walls. 𝐂𝐞𝐩𝐡𝐚𝐥𝐨𝐬𝐩𝐨𝐫𝐢𝐧𝐬: Cephalosporins, such as cephalexin and ceftriaxone, are structurally related to penicillins. They also target bacterial cell wall synthesis but have a broader spectrum of activity against different types of bacteria. 𝐌𝐚𝐜𝐫𝐨𝐥𝐢𝐝𝐞𝐬: Macrolide antibiotics, such as erythromycin, clarithromycin, and azithromycin, work by inhibiting bacterial protein synthesis. They are often used to treat respiratory tract infections, as well as some sexually transmitted infections. 𝐓𝐞𝐭𝐫𝐚𝐜𝐲𝐜𝐥𝐢𝐧𝐞𝐬: Tetracycline, doxycycline, and minocycline are examples of tetracycline antibiotics. They inhibit bacterial protein synthesis and are commonly used to treat a wide range of infections, including acne, respiratory tract infections, and sexually transmitted diseases. 𝐅𝐥𝐮𝐨𝐫𝐨𝐪𝐮𝐢𝐧𝐨𝐥𝐨𝐧𝐞𝐬: This class includes antibiotics like ciprofloxacin, levofloxacin, and moxifloxacin. Fluoroquinolones act by inhibiting the enzymes responsible for bacterial DNA replication and repair. They are often used to treat urinary tract infections, respiratory tract infections, and some types of skin infections. 𝐒𝐮𝐥𝐟𝐨𝐧𝐚𝐦𝐢𝐝𝐞𝐬 𝐚𝐧𝐝 𝐓𝐫𝐢𝐦𝐞𝐭𝐡𝐨𝐩𝐫𝐢𝐦: These antibiotics inhibit different steps in the bacterial folic acid synthesis pathway. Examples include sulfamethoxazole and trimethoprim, as well as the combination drug co-trimoxazole. They are used to treat urinary tract infections, respiratory infections, and certain types of diarrhea. 𝐀𝐦𝐢𝐧𝐨𝐠𝐥𝐲𝐜𝐨𝐬𝐢𝐝𝐞𝐬: Aminoglycosides, such as gentamicin and amikacin, interfere with bacterial protein synthesis. They are usually reserved for serious infections and are commonly administered intravenously. 𝐂𝐚𝐫𝐛𝐚𝐩𝐞𝐧𝐞𝐦𝐬: Carbapenems, including imipenem and meropenem, are broad-spectrum antibiotics with activity against a wide range of bacteria. They are often used to treat severe infections when other antibiotics may not be effective. 𝐆𝐥𝐲𝐜𝐨𝐩𝐞𝐩𝐭𝐢𝐝𝐞𝐬: Glycopeptide antibiotics, such as vancomycin and teicoplanin, work by inhibiting bacterial cell wall synthesis. They are primarily used to treat infections caused by certain types of bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).

Abstract Staphylococcus aureus is the leading cause of skin and soft tissue infections. With the emergence of antibiotic-resistant bacteria, there is an unmet clinical need to develop immune-based therapies to treat skin infections. Previously, we have shown pan-caspase inhibition as a potential host-directed immunotherapy against community-acquired methicillin-resistant S aureus (CA-MRSA) and other bacterial skin infections. Here, we evaluated the role of irreversible pan-caspase inhibitor emricasan as a monotherapy and an adjunctive with a standard-of-care antibiotic, doxycycline, as potential host-directed immunotherapies against S. aureus skin infections in vivo. We used the established CA-MRSA strain USA300 on the dorsum of WT C57BL/6J mice and monitored lesion size and bacterial burden noninvasively, and longitudinally over 14 days with in vivo bioluminescence imaging (BLI). Mice in four groups placebo (0.5% carboxymethyl cellulose [CMC] solution), placebo plus doxycycline (100 mg/kg), emricasan (40 mg/kg) plus doxycycline, and emricasan only were treated orally twice daily by oral gavage for 7 days, starting at 4 h after injection of S aureus. When compared with placebo, all three groups, placebo plus doxycycline, emricasan plus doxycycline, and emricasan treated group, exhibited biological effect, with reduction of both the lesion size (*p = .0277, ****p < .0001, ****p < .0001, respectively) and bacterial burden (***p = .003, ****p < .0001, ****p < .0001, respectively). Importantly, the efficacy of emricasan against S. aureus was not due to direct antibacterial activity. Collectively, pan-caspase inhibitor emricasan and emricasan plus doxycycline reduced both the lesion size and bacterial burden in vivo, and emricasan is a potential host-directed immunotherapy against MRSA skin infections in a preclinical mouse model.