The document discusses optimizing the use of colistin, an antibiotic used as a last resort to treat infections caused by multidrug-resistant gram-negative bacteria. It notes the high levels of resistance seen in India to carbapenems, which are commonly used to treat serious bacterial infections. The document recommends a high-dose, extended interval dosing regimen for colistin based on its pharmacokinetic and pharmacodynamic properties. Studies show this dosing achieves better target drug concentrations and has demonstrated higher clinical efficacy and bacteriological clearance rates compared to standard colistin dosing.
Colistin is a polymyxin antibiotic produced by Bacillus polymyxa that is effective against most gram-negative bacteria. It fell out of favor due to nephrotoxicity but remains a treatment of last resort for multidrug-resistant infections. There are two forms, colistin sulfate and colistimethate sodium, which are dosed differently and have different mechanisms of action, pharmacokinetics, and toxicity profiles. Resistance can develop with use but remains relatively rare currently.
This document discusses the use of the old antibiotic colistin for treating infections caused by multidrug-resistant Gram-negative bacteria. It notes that colistin was largely replaced in the 1970s due to toxicity concerns but has been reintroduced for resistant infections. The document summarizes that the current dosing of colistin may be suboptimal, especially in critically ill patients; colistin is likely less nephrotoxic than originally thought; and colistin can be as effective as other antibiotics for treating ventilator-associated pneumonia.
This document discusses the antibiotic polymyxins, specifically colistin. It provides details on the chemical structure and formulations of colistin. It describes how colistin fell out of favor in the 1970s but is now being revived to treat infections caused by multidrug-resistant Gram-negative bacteria. The document discusses colistin's mechanism of action, spectrum of activity, dosing, toxicity, and resistance. It also summarizes studies showing colistin is effective against common multidrug-resistant pathogens and that combinations with other antibiotics can have synergistic effects.
Colistin is a polymyxin antibiotic produced by Bacillus polymyxa that is effective against most gram-negative bacteria. It fell out of favor due to nephrotoxicity but remains a treatment of last resort for multidrug-resistant infections. There are two forms, colistin sulfate and colistimethate sodium, which are not interchangeable. Dosing is complicated due to lack of standardization. Colistin works by disrupting bacterial membranes. While resistance is still rare, its increased use has led to some resistant strains emerging.
Managing MDR/XDR Gram Negative infections in ICUVitrag Shah
The document discusses antimicrobial resistance and multidrug-resistant organisms. It notes certain organisms like Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species have developed resistance to multiple drug classes and have high mortality rates. It defines multidrug resistance, extensive drug resistance, and pan drug resistance based on the number of antimicrobial categories an organism is resistant to. Treating such infections requires less effective, more toxic, and expensive drugs. Combination therapy and optimizing dosing is important to prevent further resistance development.
Best Practice for Colistin Susceptibility Testing: Methods and Evidence (Mini...Abdullatif Al-Rashed
Mini-Review presentation
Best Practice for Colistin Susceptibility Testing: Methods and Evidence
Clinical Microbiology Residency Program, King Fahd Hospital of the University
Al Khobar, Saudi Arabia
This document discusses the increasing problem of antibiotic resistance and potential solutions. It notes the emergence of extensively drug-resistant pathogens and classifications of drug resistance. Potential solutions discussed include developing new antibiotics that target resistant bacteria, rediscovering older antibiotics, and using beta-lactamase inhibitors to enhance existing antibiotics. Several new antibiotics are summarized, including their mechanisms of action, clinical indications, and stages of clinical trials.
Teicoplanin is a glycopeptide antibiotic produced by fermentation of Actinoplanes teichomyceticus. It has bactericidal activity by binding to the bacterial cell wall and inhibiting peptidoglycan formation. It is effective against gram-positive bacteria like Staphylococcus aureus and enterococci. Clinically, it is used to treat potentially serious gram-positive infections such as sepsis, endocarditis, and skin infections. It has a longer half-life than vancomycin and is mainly excreted unchanged in urine. Potential adverse reactions include anaphylaxis, hematologic effects, and nephro- and neurotoxicity.
Colistin is a polymyxin antibiotic produced by Bacillus polymyxa that is effective against most gram-negative bacteria. It fell out of favor due to nephrotoxicity but remains a treatment of last resort for multidrug-resistant infections. There are two forms, colistin sulfate and colistimethate sodium, which are dosed differently and have different mechanisms of action, pharmacokinetics, and toxicity profiles. Resistance can develop with use but remains relatively rare currently.
This document discusses the use of the old antibiotic colistin for treating infections caused by multidrug-resistant Gram-negative bacteria. It notes that colistin was largely replaced in the 1970s due to toxicity concerns but has been reintroduced for resistant infections. The document summarizes that the current dosing of colistin may be suboptimal, especially in critically ill patients; colistin is likely less nephrotoxic than originally thought; and colistin can be as effective as other antibiotics for treating ventilator-associated pneumonia.
This document discusses the antibiotic polymyxins, specifically colistin. It provides details on the chemical structure and formulations of colistin. It describes how colistin fell out of favor in the 1970s but is now being revived to treat infections caused by multidrug-resistant Gram-negative bacteria. The document discusses colistin's mechanism of action, spectrum of activity, dosing, toxicity, and resistance. It also summarizes studies showing colistin is effective against common multidrug-resistant pathogens and that combinations with other antibiotics can have synergistic effects.
Colistin is a polymyxin antibiotic produced by Bacillus polymyxa that is effective against most gram-negative bacteria. It fell out of favor due to nephrotoxicity but remains a treatment of last resort for multidrug-resistant infections. There are two forms, colistin sulfate and colistimethate sodium, which are not interchangeable. Dosing is complicated due to lack of standardization. Colistin works by disrupting bacterial membranes. While resistance is still rare, its increased use has led to some resistant strains emerging.
Managing MDR/XDR Gram Negative infections in ICUVitrag Shah
The document discusses antimicrobial resistance and multidrug-resistant organisms. It notes certain organisms like Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species have developed resistance to multiple drug classes and have high mortality rates. It defines multidrug resistance, extensive drug resistance, and pan drug resistance based on the number of antimicrobial categories an organism is resistant to. Treating such infections requires less effective, more toxic, and expensive drugs. Combination therapy and optimizing dosing is important to prevent further resistance development.
Best Practice for Colistin Susceptibility Testing: Methods and Evidence (Mini...Abdullatif Al-Rashed
Mini-Review presentation
Best Practice for Colistin Susceptibility Testing: Methods and Evidence
Clinical Microbiology Residency Program, King Fahd Hospital of the University
Al Khobar, Saudi Arabia
This document discusses the increasing problem of antibiotic resistance and potential solutions. It notes the emergence of extensively drug-resistant pathogens and classifications of drug resistance. Potential solutions discussed include developing new antibiotics that target resistant bacteria, rediscovering older antibiotics, and using beta-lactamase inhibitors to enhance existing antibiotics. Several new antibiotics are summarized, including their mechanisms of action, clinical indications, and stages of clinical trials.
Teicoplanin is a glycopeptide antibiotic produced by fermentation of Actinoplanes teichomyceticus. It has bactericidal activity by binding to the bacterial cell wall and inhibiting peptidoglycan formation. It is effective against gram-positive bacteria like Staphylococcus aureus and enterococci. Clinically, it is used to treat potentially serious gram-positive infections such as sepsis, endocarditis, and skin infections. It has a longer half-life than vancomycin and is mainly excreted unchanged in urine. Potential adverse reactions include anaphylaxis, hematologic effects, and nephro- and neurotoxicity.
The document discusses various classes of antimicrobial agents that act by inhibiting bacterial cell wall synthesis. It begins by describing the different types of bacterial cell walls and then focuses on antibiotics that target cell wall synthesis. Specifically, it covers beta-lactam antibiotics such as penicillins and cephalosporins, which inhibit the final step of peptidoglycan synthesis. It describes the classification, mechanisms of action, and examples within each class. Carbapenems and monobactams, which also inhibit cell wall synthesis, are also discussed.
Glycopeptide antibiotics like vancomycin and teicoplanin inhibit bacterial cell wall synthesis by binding to the terminal dipeptide in peptidoglycan. They are effective against gram-positive bacteria including MRSA but not gram-negatives. Linezolid and tedizolid inhibit bacterial protein synthesis and are effective against VRE and VRSA. Daptomycin is a lipopeptide antibiotic that causes cell membrane damage in gram-positives. Polypeptide antibiotics like polymyxins and bacitracin have detergent-like properties that disrupt bacterial cell membranes but are often toxic. Nitrofurantoin and methenamine are concentrated in urine and used to treat urinary tract infections without systemic effects.
Tigecycline is a broad spectrum antibiotic that is bacteriostatic and derived from tetracycline. It is FDA approved to treat complicated skin infections, complicated intra-abdominal infections, and community acquired bacterial pneumonia. Clinical studies found it to be as effective as vancomycin/aztreonam for skin infections and imipenem/cilastatin for intra-abdominal infections. It has activity against a variety of gram-positive and gram-negative bacteria. Tigecycline's pharmacokinetics involve administration of a 100mg initial dose followed by 50mg every 12 hours, with a long half-life allowing once or twice daily dosing. Its target market includes critical care physicians
Combination antibiotic therapy can provide benefits over monotherapy in some situations. Combining antibiotics may result in synergistic effects against certain pathogens like MDROs or additive effects. It may help prevent resistance. However, combinations can also lead to antagonism or increased side effects. Appropriate combinations depend on the infection and organism. De-escalation of antibiotics is important for improving outcomes and reducing resistance. It involves narrowing therapy based on culture results and clinical response. Regular review and stopping antibiotics when no longer needed are key aspects of de-escalation.
Aminoglycosides are a class of antibiotics that are produced by soil bacteria. They are primarily used to treat infections caused by aerobic gram-negative bacteria and some are used for mycobacterial infections. Aminoglycosides work by binding to bacterial ribosomes which interferes with protein synthesis. They have concentration-dependent bactericidal activity against many gram-negative organisms but limited activity against gram-positive bacteria. Common adverse effects include ototoxicity and nephrotoxicity. Therapeutic drug monitoring is important when using aminoglycosides to minimize toxicity risks.
Piperacillin & tazobactam is effective against nosocomial infections caused by Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. It has shown success in treating lower respiratory tract infections, intra-abdominal infections, complicated urinary tract infections, and fever in neutropenic patients. Piperacillin is an extended spectrum penicillin while tazobactam is a beta-lactamase inhibitor that protects piperacillin from degradation, allowing it to be effective against beta-lactamase producing bacteria. Clinical trials demonstrate piperacillin-tazobactam is superior to other antibiotics for various infections and has a good
FLOW OF THE SEMINAR
1. Definition – antibiotic resistance, Multi-resistance, cross-resistance in antibiotics
2. Evolution of resistance
3. Impact of resistance
4. The scenario of resistance: Global, India
5. Factors causing resistance
6. Mechanisms of resistance: Intrinsic and Acquired
7. Acquired mechanism of resistance
8. Quorum sensing
9. Mechanism of resistance in commonly used antibiotics
10. Methods for determining the resistance
11. Strategies to contain resistance
12. Antibiotic stewardship
13. Role of Pharmacologist
14. Initiatives undertaken by India to control resistance
This document provides an overview of antibiotics, including their classification, mechanisms of action, and common types. It discusses how antibiotics are classified based on their mechanism of action, spectrum of activity, and mode of action. The major classes covered include penicillins, cephalosporins, macrolides, aminoglycosides, fluoroquinolones, and tetracyclines. Specific antibiotics are given within each class with details on their indications, mechanisms, and side effects. Combination antibiotic therapy and developing antibiotic resistance are also summarized.
Antibacterial resistance is a major global problem as many bacterial infections are becoming increasingly difficult to treat due to antibiotic resistance. There are two main issues - increased antibiotic resistance among bacteria and a declining antibiotic pipeline. Bacteria are developing resistance to existing antibiotics, especially gram-negative rods, leaving some infections with no effective treatment options. Meanwhile, the development of new antibiotics has slowed dramatically in recent years. Novel approaches are being explored to address the antibiotic resistance crisis, such as developing antibiotics from non-culturable bacteria and using bacteriophages and their gene products. However, the problem of antibiotic resistance worldwide remains serious without action.
Carbapenems are a class of beta-lactam antibiotics with a fused beta-lactam ring. They include imipenem, meropenem, ertapenem, and aztreonam (a monobactam). Carbapenems have broad spectra of activity against both gram-positive and gram-negative bacteria. Imipenem is inactivated by renal dipeptidases but combined with cilastatin. Meropenem and ertapenem are more stable. Aztreonam only covers gram-negatives but is useful in penicillin allergic patients. Carbapenems are used to treat various infections including respiratory, abdominal, skin and bone infections.
This document provides information on beta-lactam antibiotics including penicillins, cephalosporins, and beta-lactamase inhibitors. It discusses the classes of penicillins such as phenoxymethylpenicillin, methicillin, cloxacillin, aminopenicillins, carboxypenicillins, and ureidopenicillins. It describes the structures, spectra of activity, pharmacokinetics, uses and adverse effects of various penicillin derivatives. The summary focuses on the key classes of beta-lactam antibiotics and their properties.
This document discusses several antibiotics used to treat gram-positive and gram-negative bacteria. It provides details on the mechanisms and spectra of linezolid, vancomycin, teicoplanin, clindamycin, azithromycin, aztreonam, and various generations of cephalosporins. It describes their clinical uses, dosages, side effects and considerations for patients with renal or hepatic impairment.
This document discusses glycopeptide antibiotics, including vancomycin, teicoplanin, telavancin, bacitracin, polymyxin B, and colistin. It describes their mechanisms of action, which generally involve inhibiting bacterial cell wall synthesis. Vancomycin is a first line treatment for MRSA and binds to the D-Ala-D-Ala terminus to prevent cell wall assembly. Teicoplanin and telavancin are similar to vancomycin in mechanism and activity. Bacitracin, polymyxin B, and colistin disrupt bacterial cell membranes through detergent effects. Actinomycin D intercalates DNA to inhibit transcription. The document covers uses
Rifampicin is a broad-spectrum antibiotic used to treat tuberculosis and other bacterial infections. It works by inhibiting bacterial RNA polymerase, preventing RNA transcription and blocking bacterial growth. Rifampicin is well absorbed orally and widely distributed throughout the body, including crossing the blood-brain barrier. It is metabolized in the liver and mainly eliminated through bile with some excretion in urine. Common side effects include upset stomach, headache, and red/orange discoloration of bodily fluids. Rifampicin may interact adversely with some antiviral, anticoagulant, anti-convulsant and hypoglycemic drugs. It is an important first-line treatment for tuberculosis but requires combination therapy to prevent development
Microbiology is the study of microorganisms.
The overall theme of the Microbiology course is to study the relationship between microbes and our lives.
Microorganisms (microbes) are organisms that are too small to be seen with the unaided eye, and usually require a microscope to be seen.
This relationship involves harmful effects such as diseases and food spoilage as well as many beneficial effects.
I. Teicoplanin is a glycopeptide antibiotic produced by fermentation of Actinoplanes teichomyceticus. It has bactericidal activity by binding to the bacterial cell wall and inhibiting peptidoglycan formation.
II. It is active against gram-positive bacteria including staphylococci, streptococci, enterococci. It has a long half-life of around 150 hours and is primarily excreted unchanged in urine.
III. Teicoplanin is used to treat serious gram-positive infections like sepsis, endocarditis. Dosage is adjusted based on infection severity and patient renal function. It has potential adverse effects like allergic reactions, hemat
This document discusses antimicrobial drugs, including their definition, mechanisms of action, classifications, and examples. The key points are:
- Antimicrobial drugs are either naturally produced by microorganisms (antibiotics) or synthesized in labs (synthetic drugs) and act to selectively inhibit microbial growth without harming the host.
- They have various mechanisms of action including inhibiting cell wall, protein, or nucleic acid synthesis. Examples provided are penicillins, cephalosporins, aminoglycosides.
- Antimicrobials can be classified based on origin, target of action, spectrum, or killing capacity (bacteriostatic vs bactericidal). Broad spectrum drugs like tetracyclines
This document provides guidelines for antibiotic use, including for severe sepsis, septic shock, and other infections. It discusses evaluation of systemic inflammatory response syndrome and organ dysfunction. Choice of antibiotics depends on the suspected causative organism and its susceptibility. Reserve antibiotics like carbapenems and linezolid require meeting certain criteria. The document recommends measures to control multi-drug resistant organisms and emphasizes rational antibiotic use to reduce antimicrobial resistance.
•Describe the role of antibiotic use in the development of resistance
•Review toxicity of commonly used antibiotics
•Understand the prevalence and clinical impact of carbapenem resistant enterobacteriaceae
•State the prognosis antimicrobial resistant Staph aureus infections
• Describe the role of antibiotic use in the
development of resistance
• Review toxicity of commonly used antibiotics
• Understand the prevalence and clinical impact
of carbapenem resistant enterobacteriaceae
• State the prognosis antimicrobial resistant
Staph aureus infections
The document discusses various classes of antimicrobial agents that act by inhibiting bacterial cell wall synthesis. It begins by describing the different types of bacterial cell walls and then focuses on antibiotics that target cell wall synthesis. Specifically, it covers beta-lactam antibiotics such as penicillins and cephalosporins, which inhibit the final step of peptidoglycan synthesis. It describes the classification, mechanisms of action, and examples within each class. Carbapenems and monobactams, which also inhibit cell wall synthesis, are also discussed.
Glycopeptide antibiotics like vancomycin and teicoplanin inhibit bacterial cell wall synthesis by binding to the terminal dipeptide in peptidoglycan. They are effective against gram-positive bacteria including MRSA but not gram-negatives. Linezolid and tedizolid inhibit bacterial protein synthesis and are effective against VRE and VRSA. Daptomycin is a lipopeptide antibiotic that causes cell membrane damage in gram-positives. Polypeptide antibiotics like polymyxins and bacitracin have detergent-like properties that disrupt bacterial cell membranes but are often toxic. Nitrofurantoin and methenamine are concentrated in urine and used to treat urinary tract infections without systemic effects.
Tigecycline is a broad spectrum antibiotic that is bacteriostatic and derived from tetracycline. It is FDA approved to treat complicated skin infections, complicated intra-abdominal infections, and community acquired bacterial pneumonia. Clinical studies found it to be as effective as vancomycin/aztreonam for skin infections and imipenem/cilastatin for intra-abdominal infections. It has activity against a variety of gram-positive and gram-negative bacteria. Tigecycline's pharmacokinetics involve administration of a 100mg initial dose followed by 50mg every 12 hours, with a long half-life allowing once or twice daily dosing. Its target market includes critical care physicians
Combination antibiotic therapy can provide benefits over monotherapy in some situations. Combining antibiotics may result in synergistic effects against certain pathogens like MDROs or additive effects. It may help prevent resistance. However, combinations can also lead to antagonism or increased side effects. Appropriate combinations depend on the infection and organism. De-escalation of antibiotics is important for improving outcomes and reducing resistance. It involves narrowing therapy based on culture results and clinical response. Regular review and stopping antibiotics when no longer needed are key aspects of de-escalation.
Aminoglycosides are a class of antibiotics that are produced by soil bacteria. They are primarily used to treat infections caused by aerobic gram-negative bacteria and some are used for mycobacterial infections. Aminoglycosides work by binding to bacterial ribosomes which interferes with protein synthesis. They have concentration-dependent bactericidal activity against many gram-negative organisms but limited activity against gram-positive bacteria. Common adverse effects include ototoxicity and nephrotoxicity. Therapeutic drug monitoring is important when using aminoglycosides to minimize toxicity risks.
Piperacillin & tazobactam is effective against nosocomial infections caused by Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. It has shown success in treating lower respiratory tract infections, intra-abdominal infections, complicated urinary tract infections, and fever in neutropenic patients. Piperacillin is an extended spectrum penicillin while tazobactam is a beta-lactamase inhibitor that protects piperacillin from degradation, allowing it to be effective against beta-lactamase producing bacteria. Clinical trials demonstrate piperacillin-tazobactam is superior to other antibiotics for various infections and has a good
FLOW OF THE SEMINAR
1. Definition – antibiotic resistance, Multi-resistance, cross-resistance in antibiotics
2. Evolution of resistance
3. Impact of resistance
4. The scenario of resistance: Global, India
5. Factors causing resistance
6. Mechanisms of resistance: Intrinsic and Acquired
7. Acquired mechanism of resistance
8. Quorum sensing
9. Mechanism of resistance in commonly used antibiotics
10. Methods for determining the resistance
11. Strategies to contain resistance
12. Antibiotic stewardship
13. Role of Pharmacologist
14. Initiatives undertaken by India to control resistance
This document provides an overview of antibiotics, including their classification, mechanisms of action, and common types. It discusses how antibiotics are classified based on their mechanism of action, spectrum of activity, and mode of action. The major classes covered include penicillins, cephalosporins, macrolides, aminoglycosides, fluoroquinolones, and tetracyclines. Specific antibiotics are given within each class with details on their indications, mechanisms, and side effects. Combination antibiotic therapy and developing antibiotic resistance are also summarized.
Antibacterial resistance is a major global problem as many bacterial infections are becoming increasingly difficult to treat due to antibiotic resistance. There are two main issues - increased antibiotic resistance among bacteria and a declining antibiotic pipeline. Bacteria are developing resistance to existing antibiotics, especially gram-negative rods, leaving some infections with no effective treatment options. Meanwhile, the development of new antibiotics has slowed dramatically in recent years. Novel approaches are being explored to address the antibiotic resistance crisis, such as developing antibiotics from non-culturable bacteria and using bacteriophages and their gene products. However, the problem of antibiotic resistance worldwide remains serious without action.
Carbapenems are a class of beta-lactam antibiotics with a fused beta-lactam ring. They include imipenem, meropenem, ertapenem, and aztreonam (a monobactam). Carbapenems have broad spectra of activity against both gram-positive and gram-negative bacteria. Imipenem is inactivated by renal dipeptidases but combined with cilastatin. Meropenem and ertapenem are more stable. Aztreonam only covers gram-negatives but is useful in penicillin allergic patients. Carbapenems are used to treat various infections including respiratory, abdominal, skin and bone infections.
This document provides information on beta-lactam antibiotics including penicillins, cephalosporins, and beta-lactamase inhibitors. It discusses the classes of penicillins such as phenoxymethylpenicillin, methicillin, cloxacillin, aminopenicillins, carboxypenicillins, and ureidopenicillins. It describes the structures, spectra of activity, pharmacokinetics, uses and adverse effects of various penicillin derivatives. The summary focuses on the key classes of beta-lactam antibiotics and their properties.
This document discusses several antibiotics used to treat gram-positive and gram-negative bacteria. It provides details on the mechanisms and spectra of linezolid, vancomycin, teicoplanin, clindamycin, azithromycin, aztreonam, and various generations of cephalosporins. It describes their clinical uses, dosages, side effects and considerations for patients with renal or hepatic impairment.
This document discusses glycopeptide antibiotics, including vancomycin, teicoplanin, telavancin, bacitracin, polymyxin B, and colistin. It describes their mechanisms of action, which generally involve inhibiting bacterial cell wall synthesis. Vancomycin is a first line treatment for MRSA and binds to the D-Ala-D-Ala terminus to prevent cell wall assembly. Teicoplanin and telavancin are similar to vancomycin in mechanism and activity. Bacitracin, polymyxin B, and colistin disrupt bacterial cell membranes through detergent effects. Actinomycin D intercalates DNA to inhibit transcription. The document covers uses
Rifampicin is a broad-spectrum antibiotic used to treat tuberculosis and other bacterial infections. It works by inhibiting bacterial RNA polymerase, preventing RNA transcription and blocking bacterial growth. Rifampicin is well absorbed orally and widely distributed throughout the body, including crossing the blood-brain barrier. It is metabolized in the liver and mainly eliminated through bile with some excretion in urine. Common side effects include upset stomach, headache, and red/orange discoloration of bodily fluids. Rifampicin may interact adversely with some antiviral, anticoagulant, anti-convulsant and hypoglycemic drugs. It is an important first-line treatment for tuberculosis but requires combination therapy to prevent development
Microbiology is the study of microorganisms.
The overall theme of the Microbiology course is to study the relationship between microbes and our lives.
Microorganisms (microbes) are organisms that are too small to be seen with the unaided eye, and usually require a microscope to be seen.
This relationship involves harmful effects such as diseases and food spoilage as well as many beneficial effects.
I. Teicoplanin is a glycopeptide antibiotic produced by fermentation of Actinoplanes teichomyceticus. It has bactericidal activity by binding to the bacterial cell wall and inhibiting peptidoglycan formation.
II. It is active against gram-positive bacteria including staphylococci, streptococci, enterococci. It has a long half-life of around 150 hours and is primarily excreted unchanged in urine.
III. Teicoplanin is used to treat serious gram-positive infections like sepsis, endocarditis. Dosage is adjusted based on infection severity and patient renal function. It has potential adverse effects like allergic reactions, hemat
This document discusses antimicrobial drugs, including their definition, mechanisms of action, classifications, and examples. The key points are:
- Antimicrobial drugs are either naturally produced by microorganisms (antibiotics) or synthesized in labs (synthetic drugs) and act to selectively inhibit microbial growth without harming the host.
- They have various mechanisms of action including inhibiting cell wall, protein, or nucleic acid synthesis. Examples provided are penicillins, cephalosporins, aminoglycosides.
- Antimicrobials can be classified based on origin, target of action, spectrum, or killing capacity (bacteriostatic vs bactericidal). Broad spectrum drugs like tetracyclines
This document provides guidelines for antibiotic use, including for severe sepsis, septic shock, and other infections. It discusses evaluation of systemic inflammatory response syndrome and organ dysfunction. Choice of antibiotics depends on the suspected causative organism and its susceptibility. Reserve antibiotics like carbapenems and linezolid require meeting certain criteria. The document recommends measures to control multi-drug resistant organisms and emphasizes rational antibiotic use to reduce antimicrobial resistance.
•Describe the role of antibiotic use in the development of resistance
•Review toxicity of commonly used antibiotics
•Understand the prevalence and clinical impact of carbapenem resistant enterobacteriaceae
•State the prognosis antimicrobial resistant Staph aureus infections
• Describe the role of antibiotic use in the
development of resistance
• Review toxicity of commonly used antibiotics
• Understand the prevalence and clinical impact
of carbapenem resistant enterobacteriaceae
• State the prognosis antimicrobial resistant
Staph aureus infections
The document discusses multi-drug resistant Gram-negative pathogens and current and emerging therapeutic approaches. It provides an overview of colistin, tigecycline, and fosfomycin - discussing their mechanisms of action, pharmacokinetics, clinical efficacy, and safety. Colistin is an old antibiotic that is seeing renewed use for resistant infections. Tigecycline is used off-label for extremely drug resistant infections but has limitations. Fosfomycin has broad-spectrum activity against resistant bacteria including ESBL producers.
2 evaluation of vitamin c as a potential anti tuberculosisshaansshariq
This document summarizes a proposed study to evaluate vitamin C as a potential anti-tuberculosis drug. The study would first test vitamin C in vitro against drug-susceptible and drug-resistant strains of M. tuberculosis, alone and in combination with existing drugs, to determine minimum inhibitory concentrations. It would then evaluate vitamin C pharmacokinetics in guinea pigs at different doses. Finally, it would test vitamin C alone and in combination with other drugs in guinea pig models of acute and chronic tuberculosis infection to assess efficacy. The goal is to explore whether vitamin C's ability to generate oxidative damage could make it useful for treating tuberculosis, including multi-drug resistant forms.
Updated Cefditoren CME Slides for URTIs.pptxNaman Pincha
Cefditoren is a third-generation oral cephalosporin antibiotic with broad-spectrum activity against both gram-positive and gram-negative bacteria. It has a unique structure that enhances its coverage of gram-negative bacteria compared to other oral cephalosporins. Cefditoren has been approved for use in Japan, the US, Spain, India and other countries to treat a variety of respiratory, skin, and other infections. It achieves high concentrations in respiratory tissues and has demonstrated rapid bactericidal activity against respiratory pathogens. Cefditoren also has anti-inflammatory properties and a pharmacokinetic profile supporting its use in respiratory infections.
This document discusses the growing issue of antimicrobial resistance (AMR) and appropriate antibiotic use. It begins by listing several multidrug-resistant organisms of concern. It then discusses common misconceptions around antibiotic use and outlines principles for judicious antibiotic prescribing. The document emphasizes using local antimicrobial susceptibility data to guide empirical therapy and highlights strategies for optimizing antibiotic use, such as de-escalation when culture results are available. It also stresses the importance of antibiotic stewardship programs and following evidence-based guidelines to help curb the rise and spread of drug-resistant infections.
Fungemia in the Setting of Acute Lymphocytic Leukemia (FINAL)-1Tamara Bystrak
A 6-year-old male with acute lymphocytic leukemia and febrile neutropenia was initially treated for streptococcal bacteremia. After a week, he developed disseminated fungal infection with Trichosporon species confirmed by culture. Voriconazole was started as it has the best activity against Trichosporon. Close monitoring with ultrasounds and therapeutic drug monitoring of voriconazole trough levels is needed due to its non-linear pharmacokinetics and potential for toxicity.
KIN-219 shows promise for treating oral mucositis and inflammatory bowel disease. In animal studies, KIN-219, a small molecule mimetic of antimicrobial peptides, reduced severe oral mucositis by over 90% and reduced severity of colitis. Kinnear Pharmaceuticals is developing KIN-219 as a rinse for oral mucositis and as a drug for IBD, with plans to conduct preclinical and clinical trials over the next 3 years. If successful, KIN-219 could generate over $500 million annually in sales and help address significant unmet needs in oncology supportive care and gastrointestinal diseases.
Cefdinir and its role in otitis media, clinical study, indications, dosages, advantage, role of clavunalic acid, hepatotoxicity role all the research features are includes here to be prepared for Rajshahi Medical College, Focusing ENT specialist
This document discusses new antibiotic developments for ventilator-associated pneumonia (VAP). It outlines several new drugs in development or approval that show promise for treating multi-drug resistant Gram-negative and Gram-positive pathogens commonly seen in VAP. These include novel beta-lactamase inhibitor combinations like ceftolozane-tazobactam and ceftazidime-avibactam, as well as other classes such as aminoglycosides and tetracyclines. Ongoing and completed clinical trials evaluating some of these new agents for the treatment of VAP are also summarized.
Incidence rate of multidrug-resistant organisms in a tertiary care hospital, ...Apollo Hospitals
Antimicrobial resistance to microorganisms is a growing public health concern globally, especially in developing countries. This study was conducted to study the incidence rate of multidrug-resistant organisms with their antibiotic sensitivity pattern.
The document discusses principles of treating infectious illnesses in critical care, with a focus on antibiotic resistance and choice of antibiotics. It covers several topics: the impact of antibiotic use on resistance; choosing initial antibiotics and tailoring treatment based on culture results; applying pharmacology and pharmacodynamics to optimize bacterial killing; and reviewing guidelines for specific infections. It also provides an overview of antibiotic classes, mechanisms of action, considerations for dosing in renal impairment, and highlights specific agents like penicillins, cephalosporins, and vancomycin.
In this presentation, I discuss a new standard of treatment in cancers which is immunotherapy. I also discuss the few cancers for which it has been approved.
Building Bridges Between Discovery, Preclinical, And Clinical Research 2008tsornasse
The document discusses several case studies highlighting the importance of bidirectional information flow between clinical, preclinical, and discovery research:
1) A study of rituximab immunotherapy in lymphoma patients found that allowing longer B cell recovery time before vaccination improved responses, informed by preclinical studies.
2) Development of an anti-IgVH monoclonal antibody for lymphoma was guided by preclinical toxicology in monkeys to explore depletion of target B cells.
3) Gene expression analysis of pediatric IBD patient biopsies generated hypotheses tested with discovery research and preclinical models.
4) Increased IP-10 levels correlated with clinical response in UC patients treated with anti-CD3 visilizumab, informing the mechanism of
This document discusses antiparasitic agents used to treat various protozoal and helminthic infections. It begins by classifying parasites and listing common protozoal infections and their causative organisms. It then describes various anti-protozoal drugs including their mechanisms of action, pharmacokinetics, therapeutic uses, and adverse effects. Drugs covered include amphotericin B, eflornithine, melarsoprol, nitroimidazoles, miltefosine, nifurtimox/benznidazole, nitazoxanide, paramomycin, pentamidine, sodium stibogluconate, and suramin. The document concludes with a brief section on hel
Bacteriophage therapy for antimicrobial resistant and biofilm forming [Autosa...kamal shrestha
This document discusses bacteriophage therapy as a potential treatment for antibiotic-resistant and biofilm-forming bacteria. It provides background on antibiotic resistance and biofilms, how they form and confer resistance. Bacteriophages are introduced as viruses that infect and replicate within bacteria. The history of bacteriophage therapy is covered, along with its advantages over antibiotics in being non-toxic and specifically targeting bacteria. Recent advances aim to improve efficacy, such as using cocktails of phages with broader host ranges or genetically modifying phages. Overall, the document argues that bacteriophage therapy shows promise as an alternative to antibiotics for resistant bacterial infections.
Biological therapy for Ulcerative colitisDr Amit Dangi
The document discusses biological therapy options for ulcerative colitis (UC), including anti-TNF agents. It summarizes key trials on infliximab, adalimumab, and golimumab. The ACT1 and ACT2 trials found infliximab effective for inducing and maintaining remission in moderate-to-severe UC. The ULTRA1 and ULTRA2 trials showed adalimumab induced remission and was effective for maintenance therapy. The PURSUIT trials found golimumab induced clinical response and remission in UC patients. Anti-TNF agents are effective treatment options for moderate-to-severe UC when conventional therapies are inadequate.
Antimicrobial stewardship to prevent antimicrobial resistanceGovindRankawat1
India is among the nations with the highest burden of bacterial infections.
India is one of the largest consumers of antibiotics worldwide.
India carries one of the largest burdens of drug‑resistant pathogens worldwide.
Highest burden of multidrug‑resistant tuberculosis,
Alarmingly high resistance among Gram‑negative and Gram‑positive bacteria even to newer antimicrobials such as carbapenems.
NDM‑1 ( New Delhi Metallo Beta lactamase 1, an enzyme which inactivates majority of Beta lactam antibiotics including carbapenems) was reported in 2008
The document discusses fungal infections in intensive care unit (ICU) patients. Some key points:
1) Fungal infections are a major cause of illness and death in ICU patients. Candida bloodstream infections cause significant mortality in ICUs. Risk factors for ICU patients include use of antibiotics, catheters, and surgery.
2) A study in India found an incidence of 6.51 ICU-acquired candidemia cases per 1,000 admissions. Candida tropicalis was the most common cause (41.6% of cases). Crude mortality was 44.7% and attributable mortality was 19.6%.
3) Studies show non-albicans Candida species are emerging
Closed or ready-to-hang enteral nutrition systems have several benefits over open systems including reduced risk of contamination, easier administration requiring less nursing time, and improved delivery of nutrients. Major guidelines recommend the use of ready-to-hang liquid nutrition as the preferred method where possible. Using closed systems can improve patient outcomes and reduce healthcare costs.
The document discusses the use of corticosteroids in treating several respiratory conditions, including acute severe asthma, acute exacerbation of COPD, and acute respiratory distress syndrome. It provides definitions and prevalence data for these conditions. Guidelines are presented for using corticosteroids to treat exacerbations, including recommendations from GINA and AAFP. A study is summarized that found intravenous methylprednisolone followed by oral methylprednisolone was more effective and safer than intravenous hydrocortisone followed by oral prednisolone for treating acute asthma exacerbations.
Favipiravir is an antiviral drug being studied for the treatment of COVID-19. The document summarizes several studies on favipiravir including: a randomized controlled trial from China finding favipiravir led to faster viral clearance and improved chest imaging outcomes compared to lopinavir/ritonavir; observational data from Japan showing clinical improvement in most patients, especially those with mild/moderate disease; and a Russian study demonstrating improved viral clearance and fever relief with favipiravir versus standard of care. The document also reviews favipiravir's mechanism of action, potential adverse effects, and prescribing guidelines.
This document discusses ARDS (acute respiratory distress syndrome), including its history, definitions, pathophysiology, and evidence-based treatment strategies. ARDS is characterized by diffuse pulmonary inflammation and reduced lung compliance. Traditional ventilator strategies have been shown to cause ventilator-induced lung injury, so current recommendations focus on lung-protective ventilation with low tidal volumes and high PEEP. Additional rescue therapies for refractory hypoxemia include recruitment maneuvers, proning, and ECMO. Proper diagnosis requires consideration of alternative conditions and use of diagnostic tools like echocardiogram, bronchoscopy, and chest CT scan.
This document provides an overview of ARDS (acute respiratory distress syndrome) including its history, definition, pathophysiology, assessment, and treatment strategies. ARDS is characterized by acute hypoxemia, stiff lungs, and diffuse pulmonary infiltrates caused by inflammatory lung injury from direct or indirect insults. Key evidence-based treatment strategies discussed include lung protective ventilation with low tidal volumes, higher PEEP levels, targeting driving pressure, prone positioning, and rescue therapies like recruitment maneuvers which can improve oxygenation but their benefits are uncertain. The PROSEVA trial showed a significant reduction in 28-day mortality for prone positioning in severe ARDS patients.
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Challenges in the management of HAP-VAP include multidrug-resistant pathogens becoming more common. Combination antibiotic therapy is recommended for patients with risk factors for multidrug-resistant infections or septic shock. Newer beta-lactam/beta-lactamase inhibitor combinations such as ceftolozane-tazobactam and ceftazidime-avibactam show promise in treating resistant gram-negative bacteria including ESBL, AmpC, KPC, and OXA-48 producers.
This case report describes an adult female patient presenting with fever, cough, joint pain, and skin rash. Laboratory tests revealed elevated white blood cell count with neutrophilia. Imaging showed pulmonary nodules. She fulfilled criteria for adult onset Still's disease (AOSD), which can involve the lungs in 50% of cases. AOSD is diagnosed based on Yamaguchi or Fautrel criteria, which this patient met. Treatment involves corticosteroids and immunosuppressants to control the abnormal cytokine levels caused by AOSD. Pulmonary involvement requires close monitoring for serious complications like acute respiratory distress syndrome.
Asthma is a chronic inflammatory airway disease characterized by recurrent episodes of wheezing, breathlessness, chest tightness and coughing. The chronic inflammation causes airway hyperresponsiveness and airflow obstruction. Genetic and environmental factors contribute to its pathogenesis. Key features include eosinophilic inflammation, mast cell activation, cytokine production, and airway remodeling over time. Ongoing research seeks to better understand the complex immune and structural changes involved in order to develop new targeted treatments.
The document discusses the immunology of tuberculosis. It covers the stages of pathogenesis of M. tuberculosis infection, the host immune response including innate and acquired immunity, and the pro-inflammatory and anti-inflammatory mediators involved in tuberculosis. The key points are:
1) M. tuberculosis is an intracellular pathogen that infects the lungs and can spread to other organs. The host immune response involves phagocytosis by alveolar macrophages and recruitment of other immune cells.
2) Both the innate and acquired immune responses are involved in the host defense against M. tuberculosis. Important components include neutrophils, NK cells, TLR signaling, and the cell-mediated immune response involving CD4 and CD8 T cells.
1. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown cause that primarily affects older adults and is associated with poor prognosis.
2. The diagnosis of IPF requires exclusion of other known causes of lung fibrosis and demonstration of a usual interstitial pneumonia pattern on imaging or lung biopsy.
3. Current treatment recommendations strongly advise against monotherapies with corticosteroids, colchicine, cyclosporine A, or immunomodulators due to lack of proven efficacy and risk of side effects.
The document provides information on ventilation and the anatomy of the respiratory system. It defines ventilation as the mass movement of gas in and out of the lungs. It then describes the anatomy of the airways from the nostrils down to the alveoli. This includes details on structures like the nasal cavity, pharynx, larynx, trachea, bronchi, and terminal bronchioles. It also discusses factors that affect ventilation like pulmonary pressures, the mechanics of breathing, and control of breathing.
Pulmonary rehabilitation is a comprehensive intervention program for patients with chronic respiratory diseases. It aims to reduce symptoms, optimize functional status, and improve quality of life through exercise training, education, psychosocial support, and promotion of long-term self-management. Key components include endurance training, strength training, respiratory muscle training, nutritional therapy, and management of anxiety and depression. Regular exercise is shown to improve exercise tolerance and reduce dyspnea.
This document discusses acid-base balance and disorders. It begins by defining acids and bases, and describing the normal physiology of acid-base balance. It then discusses the four main types of acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. For each disorder it describes the primary disturbance (pH or HCO3-) and the secondary compensatory response. The document goes on to provide details on the causes, mechanisms, and clinical assessments of different metabolic and respiratory acid-base disorders.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
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Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
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In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
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- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
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Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
2. Burden of MDR Infections
• Result in a considerable clinical and economic burden
• Additional cost of multidrug resistance in hospitalized patients with
infections has been estimated at $6,000 to $30,000 (per patient):
– More due to the higher rate of inappropriate empiric antimicrobial
treatment than virulence
– Increased morbidity and length of stay
– Increased mortality up to fivefold when the causal organisms were
MDR
N Engl J Med 2014;370:1198-208
3. Bad Bugs, No Drugs: No ESKAPE !
ESKAP The Effects of Antibacterial
Drugs
ESKAPE
✓ Enterococcus faecium
✓ Staphylococcus aureus
✓ Klebsiella pneumoniae
✓ Acinetobacter baumannii
✓ Pseudomonas aeruginosa
✓ Enterobacter species
Clinical Infectious Diseases 2009;48:1–12
6. Resistance
scenario in India
Carbapenem class of
antibiotics is one of the last-
resort antibiotics to treat
serious bacterial infections
Resistance to carbapenems
among various gram-negative
bacteria -extremely high
Carbapenem (meropenem/ imipenem) resistance among
various bacteria isolated from blood culture
Source: Gandra et al. (2016); ICMR (2015).
1.AMR India Scoping Report. Available from
http://dbtindia.gov.in/sites/default/files/ScopingreportonAntimicrobialresistanceinIndia.pdf Last accessed on 30.12.19
Carbapenem class of antibiotics is one
of the last-resort antibiotics to treat
serious bacterial infections.
Resistance to carbapenems among
various gram-negative bacteria -
extremely high
Resistance to carbapenems among
various gram-negative bacteria -
extremely high
Resistance scenario in India
7. Antimicrobial resistance pattern of the causative
organisms : MDR in ICU
Indian tertiary care hospital
Conditions %
MDR GNB %
63
Pneumonia 49
MDR Acinetobacter baumannii
MDR Pseudomonas aeruginosa
Urosepsis 21.8
10.3 64.4
Bloodstream infection (BSI)
Catheter-related bloodstream infection (CRBSI) 5
Resistance to carbapenems was 35.2% in
this study
Pathog Glob Health. 2015Jul;109(5):228-35
8.
9. Resistance among gram negative bacilli including Acinetobacter spp, E. coli,
Klebsiella, and Pseudomonas
◼ MDR: Resistant to at 3
classes of antimicrobial
agents - all penicillins and
Study of a rural hospital at Sevagram, Maharashtra
Total GN Sensitive
isolates isolates
Resistant isolates
cephalosporins
inhibitor
fluoroquinolones,
aminoglycosides.
(including
combinations),
MDR
No.
261 16.2 435 26.9 120
XDR
No.
PDR
No. %
7.4 32 1.9
and
No. % % %
1616
◼
◼
XDR: The isolate that is
resistant to MDR
carbapenems.
+
PDR: The isolate that is
resistant to polymyxins and
tigecycline.
J Global Infect Dis 2010;2:291-304
Int J Cur Res Rev. February 2015;7(3):43-47
10. Three-way Solution
Better infection management & prevention
Rational use of antibiotics
Restocked drug pipeline filled of not only new but the old ones and
Revival of older antibiotics (Colistin)
12. History of Polymyxins
✓ Polypeptide antibiotics from Japan
✓ 5 different chemical components ; B and E were used in clinical practice.
✓ Polymyxin E (colistin) discovered in 1949; Bacillus polymyxa var. colistinus.
✓ 1950s : Used in Japan and Europe.
✓ 1959 : USA as colistimethate sodium (CMS).
✓ Used extensively for two decades ; but then disappeared from clinical use due to
concerns over toxicity and availability of safer alternatives
13. Mechanism of action (PD)
Colistimethate salt is the inactive prodrug
which is hydrolysed to colistin, which acts as a
cationic detergent and damages the bacterial
cytoplasmic membrane causing leaking of
intracellular substances and cell death.
15. Spectrum of activity
Bactericidal action
against
Potentially active against Inactive against
✓ P
. aeruginosa,
✓ Acinetobacter
✓ Stenotrophomonas
maltophilia strains
✓ Several mycobacterial
✓ Gram negative:
▪ Proteus species,
▪ Serratia species,
✓ Gram positive bacteria
✓ Anaerobes
species,
species
✓ Klebsiella species,
✓ Enterobacter species,
✓ Escherichia coli, ✓ Fungi and Parasites
✓ Salmonella species,
✓ Shigella species,
✓ Citrobacter species
In vitro data has shown susceptibility against MDR and XDR GNB
16. Pharmacokinetics
Absorption: Not absorbed from the GI tract, mucous membranes, or intact skin (Note: GI
absorption has been observed in infants).
Distribution: Distributes widely, except for CNS, synovial, pleural, and pericardial fluids
• Healthy volunteer: IV: Colistimethate: V : 8.92 L; Colistin: V : 12.4 L.
d d
• Critically ill: IV: Colistimethate: V : 5.3 to 13.5 L; Colistin: V : 7.2 to 189 L.
d d
• Cystic fibrosis: Adolescents and Adults: IV: Colistimethate: V : 0.09 ± 0.03 L/kg
dss
(Reed 2001)
Protein binding: 50%
17. Pharmacokinetics
Metabolism: Colistimethate sodium (inactive prodrug) is hydrolysed to colistin (active
form).
– Half-life elimination: IV: Colistimethate: 2 to 3 hours
– Critically ill: Infants (including premature infants), Children, Adolescents, and
Adults: IV: Colistimethate: 2.3 hours; Colistin: 14.4 hours (Plachouras 2009)
– Cystic fibrosis: IV: Colistin: ~4 hours (Li 2003)
Elimination:
➢ T in
1/2
– Adults with normal renal function: 1.5 – 8 hrs.
– creatinine clearances < 20 mL/min - 10-20 hours
– anuric patients - 2-3 days.
18. Indications of IV Colistin
✓ Colistimethate sodium (CMS) by intravenous administration is indicated in adults
and children including neonates for the treatment of serious infections due to
selected aerobic Gram-negative pathogens, including those of the:
✓ Lower respiratory tract
✓ Urinary tract in patients with limited treatment options.
✓ Consideration should be given to official guidance on the appropriate use of
antibacterial agents.
19. Concerns : Colistin in India
High prevalence of MDR gram negative infections
Colistin often the most Commonly used last resort drug in Indian ICU
No clear dosing guidelines
Resistance now being reported to colistin, linked to suboptimal
dosing
21. Rationale for High Dose Colistin
Concentration dependent
• Pharmacodynamically potent , against MDR Gram negative
• “Colistin has a concentration dependent activity, a high dose could achieve a
higher C > MIC, which is an important parameter for the in vivo efficacy”.
max
• It appears that peak concentrations of colistin 16 times the MIC or greater are
required for complete in vitro killing of P
. aeruginosa within 24 hours.
Antimicrob Agents Chemother 2009;53(8):3430-6
Journal of Infection 2008;56: 432-436
Critical Care 2003,7:R78-R83
22. INDIAN DATA
Pharmacokinetics of intravenous Colistin in patients with nosocomial
infections caused by Multi Drug Resistant Gram Negative Bacilli (MDRGNB)
PK-PD Parameters
MIC(range)
mcg/ml
AUC /MIC Cmax
N= 15
Dose: 2MIU TID
0-∞ SS
/MIC
Acinetobacter 0.57 ( 0.25- 644.3 15.201
5.787
2.0)
Pseudomonas 1.5 (1-2) 105.03
Presented at ISCCM, Feb 2011
23. Pharmacokinetics of Colistin* after single and multiple doses
in Indian patients with MDR GNB
Multiple doses
10000
9000
8000
Single Dose
Total Colistin
MIC Pseudomonas
Cmaxss 8681.97ng/ml
MIC Acinetobacter
Cmax /MIC
FoColistin IV 2 MIU thrice daily did not reach
the desired PK/PD
4000
3000
2000
1000
0
P: 1.5 mcg/ml
A: 0.571 mcg/ml
*2 MIU every 8 hours
• N=15, VAP
27 years, 62 kg
Eur J Clin Pharmacol (2013)69:1429–1436
24. Results
• Survival was 67%
• AUC/MIC > 125 and Cmax /MIC > 8 was achieved in:
– 7/8 patients with Acinetobacter infection
– 1/4 patients with Pseudomonas
• No renal or other significant side effects attributed
• It appears that current dose may be insufficient for
to the drug were observed
Pseudomonas infections
25. Need of High Loading Dose……………
If loading dose is not given, time taken to reach Css
would be 2 -3 days and concentration attained could be
below MIC
26. Need of High Maintenance Dose……………
High Loading & Maintenance Dose would result in faster
target concentration and need less frequent administration
27. Recent Data from PK/PD Suggests…
HIGH DOSE –EXTENDED INTERVAL
Colistin Regimen
Loading Dose of 9 MU or even 12 MU CMS and a Maintenance dose of 4.5 MU
CMS every 12 hours would result in faster target concentration and need less
frequent administration
29. High Dose, Extended- Interval Colistin regimen
Results in faster target concentration
Loading Dose of 9 MU or even 12 MU CMS and a Maintenance dose of 4.5 MU
CMS every 12 hours would result in faster target concentration and need less
frequent administration
Model-Predicted ,Concentration in a typical patient following the use of the current dosing
regimen(3 MU as a 15 min infusion of CMS every 8 h and alternative dosing regimen with LD of 9 or
12 MU as infusion of 15 min or 2 h and a Maintenance dose of 4.5 MU CMS every 12 h.
Antimicrob Agents Chemother 2009;53(8):3430-6
31. High Dose, Extended- Interval Colistin regimen
offers superior Efficacy
Study Design:
✓ Prospective, Observational, Cohort Study, included 28 critically ill patient with sepsis
due to COS GNB bacteria or minimally susceptible GNB
✓ 18 (64.3%) patients had Bloodstream infections (BSIs) and 10 (35.7%) VAP.
✓ Colistin was administered as loading dose of 9 MIU(+4.5 MIU q12 hr).
Clin Infect Dis 2012;54(12):1720–6
32. High Dose, Extended- Interval Colistin regimen offers
superior Efficacy
Results:
✓ Clinical Cure Rate was observed in 23 cases (82.1%).
✓ Bacteriological clearance was achieved in 73.9%(17) of the cured
infectious episodes.
Clin Infect Dis 2012;54(12):1720–6
34. High Dose, Extended- Interval Colistin regimen offers
superior efficacy
Study Design:
✓ Retro-prospective and comparative study of 2 group, included 92
Patients with MDR GNB infections.
✓ High Dose group received IV CMS with loading dose of 9 MIU followed
by maintenance dose 4.5 MIU/12 hourly.
✓ Standard dose group was retrospectively analysed and received CMS
IV without a loading dose at a dosage of 6 MIU/24hrs.
Chemotherapy 2015–16;61:190–196
35. High Dose, Extended- Interval Colistin regimen offers
superior efficacy
Results:
✓ Significantly greater proportion of patients were cured at the end of
treatment in high dose colistin group as compared to standard-dose
colisitn group.
% Cure rate
41.3%
63 %
High Dose Standard Dose
Chemotherapy 2015–16;61:190–196
37. High Dose, Extended- Interval Colistin regimen does
not increase nephrotoxicity
Results:
✓ Risk of nephrotoxicity was similar between
high dose group and standard dose group.
✓ AKI was reported in 15 patients in the high-
dose colistin group (32.2%) and 12 in the
standard-dose colistin group (26%) with p =
0.64.
✓ The necessity for renal replacement therapy
in the subgroups with AKI was similar for the
2 groups (26.6 vs. 41%; p = 1).
Chemotherapy 2015–16;61:190–196
38. High Dose, Extended- Interval Colistin regimen does
not increase nephrotoxicity
Results:
✓ No deterioration of renal function was observed during 23 CMS treatment courses
(82.1%).
✓ AKI developed during 5 CMS treatment courses (17.8%) in 5 different patients
(one with pre-existing renal dysfunction)
✓ One, two, and two patients met the criteria for AKI stages I, II, and III,
respectively.
✓ No patients needed renal replacement therapy
✓ All patients completed CMS therapy by dose reduction.
Clin Infect Dis 2012;54(12):1720–6
39. High Dose, Extended- Interval Colistin regimen does not
increase nephrotoxicity & neurotoxicity
Can be used without increasing Nephrotoxicity and
Neurotoxicity
Chemotherapy 2015–16;61:190–196
40. Dosage and administration of IV Colistin
Adults:
✓Recommended dosage is Maintenance dose 9 million IU/day in 2-3 divided
doses.
✓In patients who are critically ill, a loading dose of 9 MIU should be
administered.
✓The most appropriate time interval to the first maintenance dose has not
been established.
✓Modelling suggests that loading and maintenance doses of up to 12 MIU
may be required in patients with good renal function in some cases.
✓Clinical experience with such doses is however extremely limited, and
safety has not been established
42. Recommendation as per CHMP(EMEA) for Colistin based on
population-Pharmacokinetics data in Critically patients
Adults and adolescents
Loading Dose: of 9 MIU should be administered.
Maintenance Dose: 9MIU/day in 2-3 divided doses.
• Loading and maintenance doses of up to 12 MIU may be required in patients
with good renal function in some cases.
• Clinical experience with such doses is however extremely limited, and safety
has not been established.
• The loading dose applies to patients with normal and impaired renal functions
including those on renal replacement therapy
https://www.medicines.org.uk/emc/medicine/1590
43. Special Population
Hepatic impairment: No data in patients with hepatic impairment.
Renal impairment: Dose adjustments in renal impairment are necessary,
but pharmacokinetic data available for patients with impaired renal
function is very limited.
Children: Children ≤ 40kg: 75,000-150,000 IU/kg/day divided into 3 doses. For
children with a body weight above 40 kg, use of the dosing recommendation
for adults should be considered
45. MIC Breakpoint according to the latest 2020 criteria
Colistin Interpretive Categories and Zone
diameter Breakpoints, nearest
whole mm
Interpretive Categories and MIC
Breakpoints, µg/mL
S
-
I
-
-
R
-
S
-
I R
Acinetobacter
Pseudomonas
≤ 2
≤ 2
≥ 4
≥ 4
- - -
Enterobacteriacea - - - - ≤ 2 ≥ 4
http://em100.edaptivedocs.net/GetDoc.aspx?d
oc=CLSI%20M100%20ED29:2019&scope=user
46. MIC Breakpoint according to the latest 2020 criteria
EUCAST Enterobacterales Pseudomonas Acinetobacter
MIC DISC (mm) MIC (mg/L) DISC (mm) MIC (mg/L) DISC (mm)
(mg/L)
S I R S I R S
- - 2
I R S I R S
- 2 - - - 2
I R S I R
- 2 - - -
Colistin 2 - 2 -
49. Suggested loading and daily doses of CMS in critically
ill patients and those on CRRT
Dose Category of Dosing Suggestions for a Desired Target colistin Css,avg
Critically Ill
Patient
of 2 mg/L
Loadin All patient
g dose categories
300 mg CBA (9 million IU)
The 1st regular daily dose should be administered 12 hr
later.
Daily
dose
Intermittent Nondialysis day: CBA dose of 130 mg/d (3.95 million IU/d),
hemodialysis ie, baseline dosing for a Css,avg of 2 mg/L;
Dialysis day supplement: add 30% or 40% to baseline daily
dose after a 3- or 4-h session, respectively.
CRRT During CRRT: add 10% per 1 hr of CRRT to the baseline
daily dose for a Css,avg of 2 mg/L; the suggested CBA dose
is 440 mg/d (~13 million IU/d).
Clinical Infectious Diseases®
2017;64(5):565–71
50.
51. Key Points
✓ The dosing regimen of colistin should be adapted to the renal function of
patients, and the use of a loading dose is recommended.
✓ Therapeutic drug monitoring of colistin is recommended.
✓ Because the resistance of bacteria to colistin is increasing, its use in
combination seems necessary.
56. COLISTIN RESISTANCE
Resistance
Mortality associated with dual carbapenem and colistin-
resistant Klebsiella pneumoniae bloodstream infections
Kaur et al. (2017).
1.AMR India Scoping Report. Available from
http://dbtindia.gov.in/sites/default/files/ScopingreportonAntimicrobialresistanceinIndia.pdf Last accessed on 30.12.19
With increasing use of colistin for
treatment of carbapenem-resistant
gram-negative bacterial infections,
colistin resistance among gramnegative
bacteria has emerged in India
Bloodstream infections due to dual
carbapenemand colistin-resistant K.
pneumoniae are associated with 69.3%
mortality among Indian patients
With increasing use of colistin for
treatment of carbapenem-
resistant gram-negative bacterial
infections, colistin resistance
among gram negative bacteria
has emerged in India.
Bloodstream infections due to
dual carbapenem and colistin-
resistant K. pneumoniae are
associated with 69.3% mortality
among Indian patients