mechanism of resistance of antibiotics, ESBL, b lactums, enterobactericae, metallobactums, carbapenemases, types of mechanism of resistance, history of antibiotics and resistance
This document discusses beta lactamases and extended spectrum beta lactamases (ESBLs). It defines beta lactamases as enzymes produced by bacteria that confer resistance to beta lactam antibiotics by hydrolyzing the beta lactam ring. ESBLs are a type of beta lactamase that hydrolyze penicillins, cephalosporins, and aztreonam but are inhibited by beta lactamase inhibitors. The document outlines methods for detecting beta lactamases, such as the penicillin zone edge test, and ESBLs, including disk diffusion and broth microdilution tests. It also discusses
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.
Antimicrobial resistance occurs when microorganisms develop the ability to defeat the drugs designed to treat them. There are natural and acquired forms of resistance. Natural resistance involves mechanisms like preventing drug entry or pumping it out, while acquired resistance occurs through mutation or horizontal gene transfer of resistance genes. These resistance genes can spread between bacteria through mobile genetic elements like plasmids, transforming many strains. As resistant bacteria infect more people, standard treatments become ineffective, necessitating new prevention and treatment approaches like bacteriophage therapy.
beta lactamases : structure , classification and investigationsDr Taoufik Djerboua
this is a simple introduction to the world of beta lactamase enzymes that i had the chance to present during my observership in turkey. it bears some introductive notions necessary to the unverstading of the function fo these enzymes and some tests usually used to invistigate bacteria producing these enzymes. the pictures were taken from Microbe-edu.com Bush et al classification of Beta lactamase, the EUCAST and CLSI recommandation for susceptibility testing documents.
Cephalosporins are a class of antibiotics derived from the fungus Cephalosporium acremonium. They were first isolated in 1948 and are chemically related to penicillins. There are several generations of cephalosporins that have been developed with expanded spectra of activity. First generation cephalosporins such as cefazolin and cephalexin are effective against gram-positive bacteria. Later generations have activity against more gram-negative bacteria with third generation drugs like cefotaxime and ceftriaxone used to treat serious infections. Cephalosporins are generally well-tolerated but can cause adverse effects like diarrhea, rash, bleeding and hypersensitivity reactions in some
Antiprotozoal agents is a class of pharmaceuticals used in treatment of protozoan infection. Protozoans have little in common with each other and so agents effective against one pathogen may not be effective against another
This document discusses beta lactamases and extended spectrum beta lactamases (ESBLs). It defines beta lactamases as enzymes produced by bacteria that confer resistance to beta lactam antibiotics by hydrolyzing the beta lactam ring. ESBLs are a type of beta lactamase that hydrolyze penicillins, cephalosporins, and aztreonam but are inhibited by beta lactamase inhibitors. The document outlines methods for detecting beta lactamases, such as the penicillin zone edge test, and ESBLs, including disk diffusion and broth microdilution tests. It also discusses
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.
Antimicrobial resistance occurs when microorganisms develop the ability to defeat the drugs designed to treat them. There are natural and acquired forms of resistance. Natural resistance involves mechanisms like preventing drug entry or pumping it out, while acquired resistance occurs through mutation or horizontal gene transfer of resistance genes. These resistance genes can spread between bacteria through mobile genetic elements like plasmids, transforming many strains. As resistant bacteria infect more people, standard treatments become ineffective, necessitating new prevention and treatment approaches like bacteriophage therapy.
beta lactamases : structure , classification and investigationsDr Taoufik Djerboua
this is a simple introduction to the world of beta lactamase enzymes that i had the chance to present during my observership in turkey. it bears some introductive notions necessary to the unverstading of the function fo these enzymes and some tests usually used to invistigate bacteria producing these enzymes. the pictures were taken from Microbe-edu.com Bush et al classification of Beta lactamase, the EUCAST and CLSI recommandation for susceptibility testing documents.
Cephalosporins are a class of antibiotics derived from the fungus Cephalosporium acremonium. They were first isolated in 1948 and are chemically related to penicillins. There are several generations of cephalosporins that have been developed with expanded spectra of activity. First generation cephalosporins such as cefazolin and cephalexin are effective against gram-positive bacteria. Later generations have activity against more gram-negative bacteria with third generation drugs like cefotaxime and ceftriaxone used to treat serious infections. Cephalosporins are generally well-tolerated but can cause adverse effects like diarrhea, rash, bleeding and hypersensitivity reactions in some
Antiprotozoal agents is a class of pharmaceuticals used in treatment of protozoan infection. Protozoans have little in common with each other and so agents effective against one pathogen may not be effective against another
The document summarizes a presentation on antimicrobial drug resistance given by Dr. Manas Kr. Nath. It discusses the objectives of the presentation, which were to introduce antimicrobial drug resistance, define it, discuss its timeline and factors, mechanisms of resistance, control strategies, and conclusions. The presentation covered intrinsic and acquired resistance, genetic and biochemical mechanisms of resistance such as mutations, plasmids, conjugation, transduction, transformation, transposons, integrons, and production of antibiotic inactivating enzymes. It emphasized that antimicrobial resistance is a major global health concern.
Mechanism of action of major antibiotic classes including betal lactam agents, aminoglycosides, macrolides, tetracyclines, quinolons, vancomycin, oxazolidionons. Detailed review and illustrations
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.
This document discusses antibiotics and their properties. It describes how antibiotics are chemical substances produced by microorganisms that kill or inhibit pathogenic bacteria without harming host tissue. An ideal antibiotic should have broad-spectrum activity, be effective at low concentrations, kill bacteria rather than just inhibiting growth, selectively target pathogens, and not induce bacterial resistance. The document then discusses specific classes of antibiotics like tetracyclines, penicillins, and cephalosporins, outlining their mechanisms of action, properties, uses, and mechanisms of resistance.
The most common mode of action for antibiotics is the inhibition of cell wall synthesis. Antibiotics that inhibit cell wall synthesis work because of the fact that most eubacteria have peptidoglycan-based cell walls but mammals do not. Growth is prevented by inhibiting peptidoglycan synthesis. Thus these antibiotics only work for actively growing bacteria. The cell wall of new bacteria that grew in the presence of cell-wall-synthesis inhibitors is deprived of peptidoglycan. These bacteria will be subjected to osmotic lysis.In addition, gram-negative bacteria generally are less susceptible to inhibitors of cell wall synthesis than are gram-positive bacteria. In the former cell wall synthesis inhibitors fail to reach the cell wall because they are blocked by the gram-negative outer membrane.Penicillin is the classic example of an inhibitor of cell wall synthesis. Other examples include: ampicillin, bacitracin, carbapenems, cephalosporin, methicillin, oxacillin and vancomycin
This presentation discusses antibiotic resistance. It defines antibiotics as substances produced by microorganisms that inhibit or kill other microorganisms at low concentrations without harming the host. Antibiotic resistance occurs when bacteria no longer respond to an antibiotic. Mechanisms of resistance include preventing antibiotic access, modifying antibiotics, altering antibiotic target sites, and pumping antibiotics out of cells. Causes of increasing resistance include overprescription, patient noncompliance, overuse in animals, poor drug quality, and lack of sanitation. Solutions proposed are only using antibiotics as prescribed, not sharing or saving antibiotics, and increasing education on resistance.
An antibiotic is a type of antimicrobial substance active against bacteria and is the most important type of antibacterial agent for fighting bacterial infections. Antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria
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.
Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.
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.
Antifungal drugs are used to treat fungal infections and can be classified as systemic agents or topical agents. Some common systemic antifungals include amphotericin B, griseofulvin, ketoconazole, fluconazole, and flucytosine. They work by binding to ergosterol in the fungal cell membrane or inhibiting ergosterol synthesis. Common topical antifungals include nystatin, clotrimazole, and tolnaftate which also disrupt the fungal cell membrane. These drugs are used to treat conditions like candidiasis, dermatophytosis, and aspergillosis.
To understand the mechanisms of antimicrobial action and the classification of antimicrobial drugs.
To explain the process of microbial resistance.
To understand the spread of resistant microbes.
Outlines the prevention of microbial resistance.
ß-lactam antibiotics like penicillins and cephalosporins contain a ß-lactam ring which is essential for their antibacterial activity. Penicillin was the first antibiotic discovered by Alexander Fleming in 1928. It works by interfering with bacterial cell wall synthesis. There are various generations of cephalosporins that are effective against different bacteria. Both penicillins and cephalosporins can cause hypersensitivity reactions and disrupt gut flora. Other ß-lactam classes include carbapenems and monobactams which have similar mechanisms of action and side effects.
This document provides an overview of antimicrobials (also known as antibiotics). It defines antimicrobials and discusses their classification as bactericidal or bacteriostatic. The document outlines the history of antimicrobial discovery and discusses their sources, selective toxicity, and modes of action. Key topics covered include the classification of antibiotics based on chemical structure and mechanism of action, as well as details on specific classes of antibiotics like penicillins, cephalosporins, carbapenems, and others.
This document provides an overview of anti-fungal drugs. It begins by classifying antifungals based on their chemical structure, sites of action, and mechanisms of action. The major classes discussed include azoles, polyene macrolides, and other antifungals. Azoles like fluconazole and itraconazole are broad-spectrum and inhibit ergosterol synthesis. Amphotericin B binds to ergosterol and forms pores in fungal membranes. Other antifungals discussed are flucytosine, griseofulvin, and nystatin. The document outlines the mechanisms, therapeutic uses, and adverse effects of the main antifungal drug
Antibiotics: classification and spectrum of actionBashar Mudallal
This document provides an overview of different classes of antibiotics, including cell wall inhibitors, protein synthesis inhibitors, topoisomerase inhibitors, anti-metabolites, and anti-mycobacterials. It describes common antibiotics within each class, what types of bacteria they cover, and examples of specific antibiotics. It also briefly discusses empiric antimicrobial therapy and treatment for C. difficile infections.
This document discusses mechanisms of multi-drug resistance in bacteria and cancer cells. It describes how organisms can develop resistance through mutation, gene transfer, decreased membrane permeability, and efflux pumps that remove drugs from cells. Specifically, it explains that bacteria resist antibiotics via enzymatic degradation, altered target sites, and increased efflux. Cancer cells similarly resist chemotherapy through efflux pumps like P-glycoprotein and MDR proteins that transport drugs out of cells. The key mechanisms of multi-drug resistance shared by bacteria and cancer are efflux pumps and enzymatic deactivation of drugs.
This document discusses Methicillin Resistant Staphylococcus aureus (MRSA). It begins by providing taxonomic classification of Staphylococcus and describes MRSA's resistance to beta-lactam antibiotics due to acquisition of mecA or mecC genes. It then distinguishes between healthcare-associated MRSA (HA-MRSA), community-associated MRSA (CA-MRSA), and livestock-associated MRSA (LA-MRSA) based on their environments, infections caused, genetic characteristics, and risk factors. Molecular typing methods are also used to identify major epidemic MRSA clones.
Vancomycin was first discovered in 1950 and approved by the FDA in 1958. It became a standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections in the 1980s. Vancomycin works by inhibiting peptidoglycan biosynthesis in the bacterial cell wall. It has activity against gram-positive bacteria and is used to treat various hospital-acquired infections caused by MRSA such as pneumonia, bloodstream infections, and surgical site infections. Key considerations for vancomycin treatment include monitoring for potential adverse effects like red man syndrome, nephrotoxicity, and ototoxicity. Therapeutic drug monitoring is important to maintain concentrations above the minimum inhibitory concentration for optimal bacterial killing
This document discusses tetracycline antibiotics. It covers their classification, mechanism of action, spectrum of activity, mechanisms of resistance, pharmacokinetics, administration, adverse drug reactions, uses, drug interactions, and storage. Tetracyclines are broad-spectrum antibiotics derived from Streptomyces coelicolor bacteria. They work by inhibiting bacterial protein synthesis and include short, intermediate, and long-acting drugs like tetracycline, doxycycline, and minocycline. Resistance can develop through enzymatic inactivation, efflux pumps, or ribosomal protection mechanisms.
1. Bacteria can develop resistance to antibiotics through several mechanisms including enzymatic inhibition of antibiotics by beta-lactamases, modification of bacterial membranes to reduce drug influx or promote efflux, and alteration of antibiotic target sites like ribosomes.
2. Genetic factors like mutations, inversions, duplications, deletions, and acquisition of foreign DNA via plasmids or transposons can lead to antibiotic resistance by these mechanisms.
3. Specific resistance mechanisms include enzymatic inactivation of beta-lactams by beta-lactamases, modification of antibiotic target sites in the ribosome or cell wall, and efflux pumps that eject antibiotics from bacterial cells.
Antibiotic resistance can occur through several mechanisms:
1. Enzymatic inhibition - bacteria produce enzymes that can degrade antibiotics such as beta-lactamases which break down beta-lactam antibiotics.
2. Alteration of bacterial membranes - changes to outer membrane permeability or efflux pumps can reduce antibiotic uptake or increase antibiotic export from bacteria.
3. Modification of antibiotic target sites - mutations may alter the binding sites of antibiotics, such as changes to ribosomal sites reducing aminoglycoside and macrolide effectiveness.
The document summarizes a presentation on antimicrobial drug resistance given by Dr. Manas Kr. Nath. It discusses the objectives of the presentation, which were to introduce antimicrobial drug resistance, define it, discuss its timeline and factors, mechanisms of resistance, control strategies, and conclusions. The presentation covered intrinsic and acquired resistance, genetic and biochemical mechanisms of resistance such as mutations, plasmids, conjugation, transduction, transformation, transposons, integrons, and production of antibiotic inactivating enzymes. It emphasized that antimicrobial resistance is a major global health concern.
Mechanism of action of major antibiotic classes including betal lactam agents, aminoglycosides, macrolides, tetracyclines, quinolons, vancomycin, oxazolidionons. Detailed review and illustrations
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.
This document discusses antibiotics and their properties. It describes how antibiotics are chemical substances produced by microorganisms that kill or inhibit pathogenic bacteria without harming host tissue. An ideal antibiotic should have broad-spectrum activity, be effective at low concentrations, kill bacteria rather than just inhibiting growth, selectively target pathogens, and not induce bacterial resistance. The document then discusses specific classes of antibiotics like tetracyclines, penicillins, and cephalosporins, outlining their mechanisms of action, properties, uses, and mechanisms of resistance.
The most common mode of action for antibiotics is the inhibition of cell wall synthesis. Antibiotics that inhibit cell wall synthesis work because of the fact that most eubacteria have peptidoglycan-based cell walls but mammals do not. Growth is prevented by inhibiting peptidoglycan synthesis. Thus these antibiotics only work for actively growing bacteria. The cell wall of new bacteria that grew in the presence of cell-wall-synthesis inhibitors is deprived of peptidoglycan. These bacteria will be subjected to osmotic lysis.In addition, gram-negative bacteria generally are less susceptible to inhibitors of cell wall synthesis than are gram-positive bacteria. In the former cell wall synthesis inhibitors fail to reach the cell wall because they are blocked by the gram-negative outer membrane.Penicillin is the classic example of an inhibitor of cell wall synthesis. Other examples include: ampicillin, bacitracin, carbapenems, cephalosporin, methicillin, oxacillin and vancomycin
This presentation discusses antibiotic resistance. It defines antibiotics as substances produced by microorganisms that inhibit or kill other microorganisms at low concentrations without harming the host. Antibiotic resistance occurs when bacteria no longer respond to an antibiotic. Mechanisms of resistance include preventing antibiotic access, modifying antibiotics, altering antibiotic target sites, and pumping antibiotics out of cells. Causes of increasing resistance include overprescription, patient noncompliance, overuse in animals, poor drug quality, and lack of sanitation. Solutions proposed are only using antibiotics as prescribed, not sharing or saving antibiotics, and increasing education on resistance.
An antibiotic is a type of antimicrobial substance active against bacteria and is the most important type of antibacterial agent for fighting bacterial infections. Antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria
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.
Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.
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.
Antifungal drugs are used to treat fungal infections and can be classified as systemic agents or topical agents. Some common systemic antifungals include amphotericin B, griseofulvin, ketoconazole, fluconazole, and flucytosine. They work by binding to ergosterol in the fungal cell membrane or inhibiting ergosterol synthesis. Common topical antifungals include nystatin, clotrimazole, and tolnaftate which also disrupt the fungal cell membrane. These drugs are used to treat conditions like candidiasis, dermatophytosis, and aspergillosis.
To understand the mechanisms of antimicrobial action and the classification of antimicrobial drugs.
To explain the process of microbial resistance.
To understand the spread of resistant microbes.
Outlines the prevention of microbial resistance.
ß-lactam antibiotics like penicillins and cephalosporins contain a ß-lactam ring which is essential for their antibacterial activity. Penicillin was the first antibiotic discovered by Alexander Fleming in 1928. It works by interfering with bacterial cell wall synthesis. There are various generations of cephalosporins that are effective against different bacteria. Both penicillins and cephalosporins can cause hypersensitivity reactions and disrupt gut flora. Other ß-lactam classes include carbapenems and monobactams which have similar mechanisms of action and side effects.
This document provides an overview of antimicrobials (also known as antibiotics). It defines antimicrobials and discusses their classification as bactericidal or bacteriostatic. The document outlines the history of antimicrobial discovery and discusses their sources, selective toxicity, and modes of action. Key topics covered include the classification of antibiotics based on chemical structure and mechanism of action, as well as details on specific classes of antibiotics like penicillins, cephalosporins, carbapenems, and others.
This document provides an overview of anti-fungal drugs. It begins by classifying antifungals based on their chemical structure, sites of action, and mechanisms of action. The major classes discussed include azoles, polyene macrolides, and other antifungals. Azoles like fluconazole and itraconazole are broad-spectrum and inhibit ergosterol synthesis. Amphotericin B binds to ergosterol and forms pores in fungal membranes. Other antifungals discussed are flucytosine, griseofulvin, and nystatin. The document outlines the mechanisms, therapeutic uses, and adverse effects of the main antifungal drug
Antibiotics: classification and spectrum of actionBashar Mudallal
This document provides an overview of different classes of antibiotics, including cell wall inhibitors, protein synthesis inhibitors, topoisomerase inhibitors, anti-metabolites, and anti-mycobacterials. It describes common antibiotics within each class, what types of bacteria they cover, and examples of specific antibiotics. It also briefly discusses empiric antimicrobial therapy and treatment for C. difficile infections.
This document discusses mechanisms of multi-drug resistance in bacteria and cancer cells. It describes how organisms can develop resistance through mutation, gene transfer, decreased membrane permeability, and efflux pumps that remove drugs from cells. Specifically, it explains that bacteria resist antibiotics via enzymatic degradation, altered target sites, and increased efflux. Cancer cells similarly resist chemotherapy through efflux pumps like P-glycoprotein and MDR proteins that transport drugs out of cells. The key mechanisms of multi-drug resistance shared by bacteria and cancer are efflux pumps and enzymatic deactivation of drugs.
This document discusses Methicillin Resistant Staphylococcus aureus (MRSA). It begins by providing taxonomic classification of Staphylococcus and describes MRSA's resistance to beta-lactam antibiotics due to acquisition of mecA or mecC genes. It then distinguishes between healthcare-associated MRSA (HA-MRSA), community-associated MRSA (CA-MRSA), and livestock-associated MRSA (LA-MRSA) based on their environments, infections caused, genetic characteristics, and risk factors. Molecular typing methods are also used to identify major epidemic MRSA clones.
Vancomycin was first discovered in 1950 and approved by the FDA in 1958. It became a standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections in the 1980s. Vancomycin works by inhibiting peptidoglycan biosynthesis in the bacterial cell wall. It has activity against gram-positive bacteria and is used to treat various hospital-acquired infections caused by MRSA such as pneumonia, bloodstream infections, and surgical site infections. Key considerations for vancomycin treatment include monitoring for potential adverse effects like red man syndrome, nephrotoxicity, and ototoxicity. Therapeutic drug monitoring is important to maintain concentrations above the minimum inhibitory concentration for optimal bacterial killing
This document discusses tetracycline antibiotics. It covers their classification, mechanism of action, spectrum of activity, mechanisms of resistance, pharmacokinetics, administration, adverse drug reactions, uses, drug interactions, and storage. Tetracyclines are broad-spectrum antibiotics derived from Streptomyces coelicolor bacteria. They work by inhibiting bacterial protein synthesis and include short, intermediate, and long-acting drugs like tetracycline, doxycycline, and minocycline. Resistance can develop through enzymatic inactivation, efflux pumps, or ribosomal protection mechanisms.
1. Bacteria can develop resistance to antibiotics through several mechanisms including enzymatic inhibition of antibiotics by beta-lactamases, modification of bacterial membranes to reduce drug influx or promote efflux, and alteration of antibiotic target sites like ribosomes.
2. Genetic factors like mutations, inversions, duplications, deletions, and acquisition of foreign DNA via plasmids or transposons can lead to antibiotic resistance by these mechanisms.
3. Specific resistance mechanisms include enzymatic inactivation of beta-lactams by beta-lactamases, modification of antibiotic target sites in the ribosome or cell wall, and efflux pumps that eject antibiotics from bacterial cells.
Antibiotic resistance can occur through several mechanisms:
1. Enzymatic inhibition - bacteria produce enzymes that can degrade antibiotics such as beta-lactamases which break down beta-lactam antibiotics.
2. Alteration of bacterial membranes - changes to outer membrane permeability or efflux pumps can reduce antibiotic uptake or increase antibiotic export from bacteria.
3. Modification of antibiotic target sites - mutations may alter the binding sites of antibiotics, such as changes to ribosomal sites reducing aminoglycoside and macrolide effectiveness.
Antibiotic resistance can occur through several mechanisms:
1. Enzymatic inhibition - bacteria produce enzymes that can degrade antibiotics such as beta-lactamases which break down beta-lactam antibiotics.
2. Alteration of bacterial membranes - changes to outer membrane permeability or efflux pumps can reduce antibiotic uptake or increase antibiotic export from bacteria.
3. Modification of antibiotic target sites - mutations may alter the binding sites of antibiotics on ribosomes, cell walls, or metabolic enzymes, preventing the antibiotics from working.
Antibiotic resistance can occur through several mechanisms:
1. Enzymatic inhibition - bacteria produce enzymes that can degrade antibiotics such as beta-lactamases which break down beta-lactam antibiotics.
2. Alteration of bacterial membranes - changes to outer membrane permeability or efflux pumps can reduce antibiotic uptake or increase antibiotic export from bacteria.
3. Modification of antibiotic target sites - mutations may alter the binding sites of antibiotics, such as changes to ribosomal sites reducing aminoglycoside and macrolide effectiveness.
ANTIBIOTIC RESISTANCE in our life and take home messagerasel64
Antibiotic resistance can occur through several mechanisms:
1. Enzymatic inhibition - bacteria produce enzymes that can degrade antibiotics such as beta-lactamases which break down beta-lactam antibiotics.
2. Alteration of bacterial membranes - changes to outer membrane permeability or efflux pumps can reduce antibiotic uptake or increase antibiotic export from bacteria.
3. Modification of antibiotic target sites - mutations may alter ribosomal target sites of antibiotics or modify cell wall precursor targets to prevent antibiotic binding and inhibition.
Antibiotic resistance can occur through several mechanisms:
1. Enzymatic inhibition - bacteria produce enzymes that can degrade antibiotics such as beta-lactamases which break down beta-lactam antibiotics.
2. Alteration of bacterial membranes - changes to outer membrane permeability or efflux pumps can reduce antibiotic uptake or increase antibiotic export from bacteria.
3. Modification of antibiotic target sites - mutations may alter ribosomal target sites of antibiotics or cell wall precursor targets of glycopeptides like vancomycin.
Antimicrobial agents and mechanisms of action 2Bruno Mmassy
The document discusses antibiotic resistance mechanisms in bacteria. It describes several key mechanisms:
1. Production of enzymes that inactivate antibiotics through destruction or modification. This includes beta-lactamases that break down beta-lactam antibiotics.
2. Decreased permeability of the cell membrane, preventing antibiotic penetration.
3. Active efflux of antibiotics from the bacterial cell via efflux pumps.
4. Modification of antibiotic target sites, such as altered penicillin-binding proteins or modifications to ribosomes.
Resistance can arise through mutation or acquisition of resistance genes via horizontal gene transfer. Multiple resistance mechanisms can provide high-level or multidrug resistance.
Drug delivery strategies for combating multiple drug resistancetanimittal
This document discusses strategies for combating multiple drug resistance. It begins with an overview of Darwin's theory of survival of the fittest applying to microbes developing resistance. It then discusses the historical background and definitions of drug and multiple drug resistance. It covers various types and mechanisms of developing resistance, including enzymatic, genetic and acquired resistance. It also discusses specific multidrug resistant organisms like MRSA, VRE and ESBLs. The document then covers various resistance mechanisms like efflux pumps, modified target sites and enzymatic degradation. It discusses applications to diseases like tuberculosis, urinary tract infections and the emergence of "superbugs". It concludes with the need for new strategies like nanotechnology to combat evolving drug resistance.
Mechanism Antibiotic Resistance
Intrinsic (Natural)
Acquired
Chromosomal
Extra chromosomal
Intrinsic Resistance
Lack target : No cell wall; innately resistant to penicillin
2. Drug inactivation: Cephalosporinase in Klebsiella
3. Innate efflux pumps:
It is an active transport mechanism. It requires ATP.
Eg. E. coli, P. aeruginosa
Altered target sites
PBP alteration
Ribosomal target alteration
Decreased affinity by target modification
Beta-lactamase
Beta-lactamases are enzymes produced by bacteria that provide resistance to β-lactam antibiotics such as penicillins, cephamycins, and carbapenems
Major resistant Pathogen
1. PRSP- Penicillin resistant Streptococcus pneumoniae2. MRSA/ORSA- Methicillin-resistant Staphylococcus Aureus (Super bug)3. VRE -Vancomycin-Resistant Enterococci4. Carbapenem resistant pseudomonas aeruginosa5. Carbapenem resistant Carbapenem resistant 6. Extended spectrum beta-lactamase (ESBL)-producing bacteria
This document discusses antibiotic resistance and its mechanisms. It provides four main mechanisms of antibiotic resistance: bacteria producing inactivating enzymes, synthesizing modified drug targets, reducing drug permeability, and actively exporting drugs. The genetic basis includes chromosomal mutations, plasmids, and transposons transferring resistance genes. Specific resistance mechanisms are described for several drug classes like beta-lactams, aminoglycosides, tetracyclines and others. Nongenetic resistance factors include bacteria being in abscesses, resting states, or losing cell walls. Overuse and misuse of antibiotics can select for resistant bacteria.
Antimicrobial chemotherapy & bacterial resistance dr. ihsan alsaimarydr.Ihsan alsaimary
This document discusses antimicrobial chemotherapy and antibiotic principles. It covers the major classes of antibiotics including cell wall active agents, protein synthesis inhibitors, nucleic acid synthesis inhibitors, and metabolic pathway inhibitors. It describes their mechanisms of action, spectra of activity, and common resistance mechanisms. Key points covered include the importance of appropriate antibiotic usage to prevent resistance, factors influencing antibiotic choice, and definitions of antibiotic properties.
Antimicrobial chemotherapy & bacterial resistance dr. ihsan alsaimarydr.Ihsan alsaimary
This document discusses antimicrobial chemotherapy and antibiotic resistance. It provides definitions and principles related to antimicrobial agents, including their spectrum of activity, mechanisms of action against bacteria, and factors that influence antibiotic choice. The document addresses various classes of antibiotics like beta-lactams, glycopeptides, macrolides and their mechanisms. It also discusses concepts like minimum inhibitory concentration, combination therapy, and factors that can accelerate the development of antibiotic resistance.
Antimicrobial chemotherapy & bacterial resistance dr. ihsan alsaimarydr.Ihsan alsaimary
This document discusses antimicrobial chemotherapy and antibiotic principles. It covers the major classes of antibiotics including cell wall active agents, protein synthesis inhibitors, nucleic acid synthesis inhibitors, and metabolic pathway inhibitors. It describes their mechanisms of action, spectra of activity, and common resistance mechanisms. Key points covered include the importance of appropriate antibiotic usage to prevent resistance, factors influencing antibiotic choice, and definitions of antibiotic properties.
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.
1. The Kirbybauer method is a disc diffusion test used to determine antibiotic sensitivity. Filter paper discs loaded with antibiotics are placed on inoculated agar and allowed to diffuse. The zone of inhibition around each disc indicates sensitivity.
2. Antibiotics can inhibit bacterial cell wall, protein, or nucleic acid synthesis. Examples are penicillins blocking cell wall synthesis and rifampicin inhibiting bacterial transcription.
3. Antimicrobial resistance arises via mutations altering drug targets, enzymatic drug inactivation, or preventing drug uptake. It spreads between bacteria horizontally via plasmids encoding resistance genes. Prudent antibiotic use helps slow resistance development.
A 41-year-old woman with aplastic anemia was admitted with fever. Blood cultures grew E. coli resistant to ampicillin and narrow-spectrum cephalosporins. Despite treatment with multiple antimicrobials over 4 weeks, the patient's fever and bacteremia persisted. The microbiology lab was contacted to help determine why standard therapies were failing to clear the infection.
The document discusses various aspects of antimicrobial drug resistance. It begins by defining antimicrobial drugs and antimicrobial resistance. It then covers the genetic basis of resistance including chromosome-mediated resistance, plasmid-mediated resistance, and transposon-mediated resistance. Specific mechanisms of resistance to different drug classes such as penicillins, cephalosporins, carbapenems, and quinolones are described. Non-genetic bases of resistance and methods to test antibiotic sensitivity and combat resistance are also summarized.
Multi drug resistance molecular pathogenesisAlagar Suresh
The document discusses multi-drug resistance and antibiotic resistance. It provides background on the history of antibiotics and resistance. It then covers the major topics of how antibacterial resistance develops through various mechanisms like mutations, plasmids, efflux pumps, and inactivating enzymes. The document also discusses the Indian scenario of rising drug resistance and the growing problem of NDM-1 enzyme production. It concludes by outlining some strategies to address resistance like developing new antibiotics, prudent antibiotic use, and alternative approaches like phage therapy and quorum sensing inhibition.
Antimicrobial resistance is a serious global public health threat that causes nearly 700,000 deaths per year. Bacteria develop resistance through natural and acquired mechanisms such as modifying drug targets, inactivating drugs, or pumping drugs out of cells. Resistance is increasing due to overuse and misuse of antibiotics in medicine, agriculture, and consumer products. Effective solutions require coordinated efforts across all sectors to slow the development of antimicrobial resistance.
This document discusses antibiotic resistance. It begins by defining antibiotic resistance and explaining that it is a natural phenomenon accelerated by antibiotic use, allowing resistant bacterial strains to survive and multiply. It then outlines various mechanisms of resistance, including enzymatic modification of antibiotics, decreased bacterial membrane permeability, efflux pumps that remove antibiotics, alterations of antibiotic targets or cell wall precursors, overproduction of targets, and bypassing antibiotic inhibition. The document also discusses how resistance spreads between bacteria through horizontal gene transfer and provides several examples of multidrug-resistant pathogens. It emphasizes the importance of addressing antibiotic resistance due to increased mortality, costs, and few treatment options.
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This document provides an overview of the approach to evaluating patients presenting with headache. It begins by noting that headache is one of the most common reasons patients seek medical attention. It then discusses the structures in the head involved in headache pain. The document outlines criteria for differentiating between primary and secondary headaches. It provides guidance on evaluating acute headaches, including symptoms that suggest a serious underlying disorder requiring further workup. The document concludes by reviewing diagnostic criteria for migraine and discussing some examples of secondary headaches like meningitis, intracranial hemorrhage, and glaucoma.
A 76-year old man with diabetes and hypertension was brought to the emergency room in an unresponsive state. His blood sugar was low at 35 mg/dL. He was given dextrose which caused him to become responsive again. Hypoglycemia can be caused by issues with insulin secretion or counterregulation in diabetes. Symptoms range from autonomic to neuroglycopenic. Treatment involves ingestion of fast-acting carbohydrates for mild episodes or intravenous dextrose for more severe cases. Lifestyle changes and medication adjustments are also important to prevent future hypoglycemia.
The document discusses chronic kidney disease (CKD) and provides guidelines for its treatment and management. It defines CKD as abnormalities of kidney structure or function for over 3 months. It then lists markers used to diagnose CKD and common causes including diabetes, hypertension, glomerulonephritis, and polycystic kidney disease. The document concludes by outlining treatment recommendations for CKD, including controlling blood pressure and protein intake, and monitoring mineral metabolism.
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow characterized by excessive proliferation of immature myeloid cells. It has several subtypes based on genetic abnormalities. Treatment involves chemotherapy to induce remission, often followed by additional chemotherapy or stem cell transplant depending on risk factors like age and genetics. Prognosis depends on factors like specific genetic mutations and how long remission lasts.
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The document discusses the pathophysiology of heart failure, including causes such as coronary heart disease, hypertension, and pulmonary heart disease. It describes how injury to the heart muscle leads to a loss of cardiac myocyte function and decreased contractility, stroke volume, and cardiac output. As a compensatory response, the sympathetic nervous system is stimulated to increase heart rate, vasoconstriction, and fluid retention in an attempt to increase cardiac preload and output. However, over time the increased stress on the heart leads to remodeling of the left ventricle and further decreases in stroke volume and cardiac output, resulting in heart failure.
Congestive heart failure (CHF), also known as heart failure, is a condition where the heart muscle is unable to pump sufficiently to maintain blood flow to meet the body's needs. It is classified by the New York Heart Association system from Class I (no symptoms) to Class IV (symptoms at rest). The American College of Cardiology/American Heart Association categorizes heart failure into four stages from asymptomatic structural heart disease to end-stage disease. Common causes include ischemic heart disease, hypertension, diabetes and obesity. Symptoms vary depending on whether the left or right side of the heart is affected but may include shortness of breath, fatigue, swelling and coughing. Diagnosis involves imaging, blood tests and physical exams.
The document discusses the pathophysiology of heart failure, including causes such as coronary heart disease, hypertension, and pulmonary heart disease. It describes how injury to the heart muscle leads to a loss of cardiac myocyte function and decreased contractility, stroke volume, and cardiac output. As a compensatory response, the sympathetic nervous system and renin-angiotensin-aldosterone system are activated to increase preload and afterload. Over time, this leads to left ventricular remodeling and further worsening of cardiac function, resulting in the symptoms of heart failure.
Atherosclerosis is a disease where plaque builds up inside arteries. It is caused by inflammation in the arteries due to risk factors like high cholesterol, high blood pressure, smoking, and diabetes. Over time, plaque hardens and narrows the arteries, reducing blood flow. This can lead to complications like heart attacks or strokes if a plaque ruptures. Doctors use tests like ultrasounds and angiograms to diagnose atherosclerosis and determine if the arteries are blocked. Treatment involves lifestyle changes and medications to control risk factors and blood pressure. In severe cases, procedures like angioplasty may be needed to open blocked arteries.
This document discusses three diseases of the epithelium - eczema, psoriasis, and vitiligo. Eczema is a chronic inflammatory skin condition causing redness, itching, and scaling. Psoriasis causes skin cells to build up rapidly forming thick silvery scales and red patches. Vitiligo occurs when melanin-producing cells die, causing white patches on the skin. All three diseases affect the skin epithelium and have characteristic signs, patterns, diagnostic tests, and treatments including topical medications and light/laser therapies. Famous people like Princess Kate, Kim Kardashian, and Michael Jackson have suffered from these conditions.
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Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
1. Shumayla Aslam, MD
1st year IM Resident
EMILIO AGUINALDO COLLEGE MEDICAL
CENTER- CAVITE
DEPARTMENT OF INTERNAL MEDICINE
dr.shumaylaaslam@gmail.com
2. A 81 year old male patient known COPD admitted for the 4th
time in a year with complains of DIFFICULTY OF
BREATHING. History started 2 weeks prior to admission
when patients developed cough with whitish to yellowish
sputum not associated with fever. Persistence of symptoms
prompted consult and was hence admitted.
Patient in the last 6 months have been treated with the
following antibiotics, completed 7-14 days
- Levofloxacin
- Cefuroxime
- Ceftriaxone
- Azithromycin
- Pipiracillin tazobactum
- Ciprofloxacin
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3. Antimicrobial Agents Zone of inhibition Interpretation
Amikacin 19 mm sensitive
C0-amoxiclav 12 mm resistant
Ampicillin 6 mm resistant
Ampicillin-Sulbactam 11 mm resistant
Aztreonam 14 mm resistant
Cefazolin 6 mm resistant
Cefepime 13 mm resistant
Cefoxitin 14 mm resistant
Ceftazidime 14 mm resistant
Ceftriaxone 7 mm resistant
Ciprofloxacin 6 mm resistant
Cefuroxime 6 mm resistant
Cefotaxime 9 mm resistant
Ertapenem 16 mm resistant
Gentamicin 18 mm sensitive
Meropenem 6 mm resistant
Piperacillin-Tazobactam 23 mm sensitive
Trimethoprim-SMX 6 mm resistant
Result:
Moderate
growth of
Escherichia coli
(ESBL positive)
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4. Antimicrobial Agents Zone of inhibition Interpretation
Amikacin 16 mm Intermediate
C0-amoxiclav 11 mm Resistant
Ampicillin 6 mm Resistant
Ampicillin-Sulbactam 9 mm Resistant
Aztreonam 21 mm Sensitive
Cefazolin 21 mm Intermediate
Cefepime 30 mm Sensitive
Cefoxitin 23 mm Sensitive
Ceftazidime 26 mm Sensitive
Ceftriaxone 29 mm Sensitive
Ciprofloxacin 21 mm Sensitive
Cefuroxime 23 mm Sensitive
Cefotaxime 29 mm Sensitive
Ertapenem 18 mm Resistant
Gentamicin 6 mm Resistant
Meropenem 11 mm Resistant
Piperacillin-Tazobactam 19 mm Intermediate
Trimethoprim-SMX 6 mm Resistant
Result:
Moderate growth
of Klebsiella
pneumoniae
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5. Source:
1. Mandell, Douglas, and Bennett’s Principles and Practice of INFECTIOUS DISEASES
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6. Understand the type of mechanism by which
a bacteria possesses GeneticVariability
Understand the mechanisms of action of the
β-lactam, Enterobactericae, Klebsiella
pneumoniae .
Understand the mechanisms of resistance
of the β-lactamases, Enterobactericae, KPCs
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8. 1. Microevolutionary change:
- Point mutations may occur in a nucleotide base pair.
-These mutations may alter enzyme substrate
specificity or the target site of an antimicrobial agent,
interfering with its activity.
2. Macroevolutionary change:
- Results in whole-scale rearrangements of large
segments of DNA as a single event.
- include inversions, duplications, insertions, deletions,
or transposition of large sequences of DNA from one
location of a bacterial chromosome or plasmid to
another.
- integron, transposons and insertion sequences
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9. 3. Integrative and Conjugative Elements (ICE)
- acquisition of large segments of foreign DNA by
plasmids, bacteriophages, naked sequences of
DNA, or specialized transposable genetic
elements.
- Inheritance of foreign DNA further contributes
to the organism’s genetic variability and its
capacity to respond to selection pressures
imposed by antimicrobial agents.
- These mechanisms endow bacteria with the
seemingly unlimited capacity to develop
resistance to any antimicrobial agent.
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10. A, Genetic exchange may occur by transformation
(naked DNA transfer for dying bacteria to a
competent recipient). This generally results in
transfer of homologous genes located on the
chromosome by recombination enzymes (RecA).
B, Transduction also may transfer antibiotic-
resistance genes (usually from small plasmids)
by imprecise packaging of nucleic acids by
transducing bacteriophages.
C, Conjugation is an efficient method of gene
transfer, requiring physical contact between
donor and recipient. Self-transferable plasmids
mediate direct contact by forming a mating
bridge between cells. Smaller noncon- jugative
plasmids might be mobilized in this mating
process and be trans- ported into the
recipient.
D, Transposons are specialized sequences of DNA
that possess their own recombination enzymes
(transposases), allowing transposition (“hopping”)
from one location to another, independent of
the recombination enzymes of the host
(RecA-independent). They may transpose to
nonhomologous sequences of DNA and spread
antibiotic- resistance genes to multiple plasmids
or genomic locations throughout the host.
Some transposons possess the ability to
move directly from a donor to a recipient,
independent of other gene transfer events
(conjugative transposons or integrative and
conjugative elements).
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11. This is accomplished by at least two mechanisms:
(1) species and strain-specific DNA modifying
enzymes and restriction enzymes that survey
cellular host DNA and degrade foreign DNA that
lacks appropriate DNA modification seqences
(2) a type of adaptive defense system against
foreign DNA known as CRISPR (clustered regularly
spaced short palindromic repeats).
CRISPRs are detectable in nearly 50% of all
bacterial genomes, and this genetic element protects
their genomes from attack by foreign DNA during
transformation, phage invasion, or plasmid insertion.
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12. Examples of plasmid-mediated
carbapenemase-producing Klebsiella
pneumoniae,
vancomycin- resistant
daptomycin-resistant Staphylococcus aureus,
multidrug- resistantYersinia pestis,
transferable quinolone resistance in
enterobacteriae attest to the capacity of
microorganisms to adapt to environmental
stresses such as antibiotic exposure.
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13. 1. Enzymatic Inhibition
2. Decreased Permeability of Bacterial
Membranes
3. Promotion of Antibiotic Efflux
4. Altered Target Sites
5. Protection of Target Site
6. Overproduction of Target
7. Bypass of Antibiotic Inhibition
8. Bind up antibiotic
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18. Beta-lactamases are enzymes that open the beta-
lactam ring, inactivating the antibiotic.
penicillins and narrow spectrum cephalosporins
they are not effective against higher generation
cephalosporins with an oxyimino side chain
Extended-spectrum beta-lactamases (ESBL) are
enzymes that confer resistance to most beta-lactam
antibiotics,
arose by amino acid substitutions that allowed narrower
spectrum enzymes to attack the new oxyimino-beta-
lactams
but cannot attack the cephamycins and the carbapenems
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19. MOLECULAR CLASSIFICATION
(amino acid structure) AMBER
CLASS A
TEM
SHV
OTHERS (CTX-M)
CLASS B
METALLOENZYMES
(carapenemases)
CLASS C
Prototype: chromosomal AmpC
CLASS D
OXA (oxacillin hydrolysing
enzymes)
ENZYMETYPE
(by substrate profile) BJM
Penicillinases
Broad spectrum
Extended spectrum
Carbapenamase
GENETIC CLASSIFICATION
Plasmid Mediated
Chromosomal
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24. TEM beta-lactamases
TEM- the most common β-lactamase in gram-negative
bacteria, and it can hydrolyze penicillins and narrow-
spectrum cephalosporins in Enterobacteriaceae, N.
gonorrhoeae, and H. Influenzae
There are now more than 200TEM-derived ESBLs
The extended-spectrum of activity for TEM-derived
ESBLs the configuration of the enzyme at its active
site, making it more accessible to the bulky R1 oxymino
side chains of third- generation cephalosporins
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25. SHV beta-lactamases
The SHV-1 β-lactamase has a biochemical struc-
ture similar to that ofTEM-1
ESBL derivatives are also produced by point
mutations (one or more amino-acid substitutions)
at its active site.
SHV-type β-lactamases are found primarily in K.
pneumoniae strains.
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26. CTX-M beta-lactamases
they are thought to have been acquired by plasmids
from the chromosomal ampicillin C enzymes
Kluyvera spp, environmental gram- negative rods of
low pathogenic potential.
hydrolyzes cefotaxime and ceftriaxone better than
ceftazidime, and they are inhibited more by
tazobactam than by clavulanic acid.
CTX-M-15 enzymes has emerged as an important
multidrug-resistant pathogen and may have been
responsible for the majority of infections with
multidrug-resistant E. coli infections
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27. OXA beta-lactamases
plasmid derived and hydrolyze oxacillin and its
derivatives;
they are poorly inhibited by clavulanic acid.
OXA-derived ESBLs have been described mainly
in P. aeruginosa, in which they confer high-level
resistance to oxymino-β-lactams
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28. AmpC Enzymes.
primarily chromosomial enzymes that confer
resistance to penicillins, narrow-spectrum
cephalosporins, oxymino-β-lactams, and cephamycins
not susceptible to β-lactamase inhibitors
AmpC β-lactamase production returns to low levels
again after antibiotic exposure is discontinued, unless
spontaneous mutations occur in the ampD locus of the
gene, leading to permanent hyperproduction
(derepression) in these species.
Third-generation cephalosporin use in Enterobacter
spp. infections can therefore select for the overgrowth
of these stably derepressed mutants, leading to the
emergence of antibiotic resistance during treatment.
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29. Carbapenemases
confer the largest antibiotic- resistance spectrum
hydrolyze not only carbapenems but also broad-
spectrum penicillins, oxymino-cephalosporins, and
cephamycins.
The K. pneumoniae carbapenemase (KPC) enzymes
are currently the most important class A serine
carbapenemases.
KPCs have been found worldwide in multiple other
gram-negative species, such as E. coli, Citrobacter,
Enterobacter, Salmonella, Serratia, and P. aeruginosa
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30. Class B metallo-β-lactamases (MBLs)
▪ use a Zn2+ cation for hydrolysis of the β-lactam
ring; are susceptible to ion chelators,
▪ resistant to clavulanic acid, tazobactam, and
sulbtactam.They confer resistance to all β-
lactam antibiotics except monobactams.
The New Delhi metallo-β-lactamase–1
(NDM-1)
▪ These enzymes confer resistance to all β-lactams except
aztreonam.
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31. Schematic representation of the Zn2+-binding site of dinuclear
subclass B1 metallo-β-lactamases such as B. cereus BcII.
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32. class D carbapenemases
described among four subfamilies of OXA-type β-
lactamases (OXA-23, OXA-24, OXA-58, and OXA-
146), primarily in A. baumanii.
intrinsically weaker carbapenemase activity is
augmented by coupling β-lactamase production
with an additional resistance mechanism, such as
decreased membrane permeability or increased
active efflux.
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33. The efficiency of the β-lactamase in hydrolyzing
an antibiotic depends on
(1) its rate of hydrolysis
(2) its affinity for the antibiotic
(3) the amount of β-lactamase produced by the
bacterial cell,
(4) the susceptibility of the target protein
(penicillin-binding protein [PBP]) to the
antibiotic,
(5) the rate of diffusion of the antibiotic into the
periplasm of the cell.
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34. Detection of ESBLs is based upon the
resistance they confer to oxyimino-beta-
lactam substrates and the ability of a beta-
lactamase inhibitor
Problems in identification arise because
ESBLs are heterogeneous
Consequently, susceptibility to several
oxyimino-beta-lactams must be tested.
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35. The Clinical and Laboratory Standards
Institute (CLSI) recommended
screening isolates of E. coli, K. pneumoniae, K.
oxytoca, or Proteus mirabilis by disk diffusion or
broth dilution for resistance
followed by a confirmatory test for increased
susceptibility in the presence of clavulanate
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36. Representation of disk
approximation test.
Flattening of zone of
ceftazidime toward
imipenem disk
(inducing substrate)
showing positive
result.
IMP: Imipenem (10 ìg),
CAZ: Ceftazidime (10
ìg),
AMC: Amoxillin-
clavulanate (20/10 ìg)
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37. In 2010, however, the CLSI published new
minimum inhibitory concentration (MIC) and
disk diffusion breakpoints for the
Enterobacteriaceae
The new MIC breakpoints
one to three doubling dilutions lower than the
original breakpoints,
disk diffusion criteria include larger zone
diameters.
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39. In 2010, the European Committee on
Antimicrobial SusceptibilityTesting
(EUCAST)
changed the breakpoint criteria for susceptibility
by introducing MIC.
Thus, many organisms that previously would have
been categorized as susceptible using the former
breakpoints may now be considered intermediate
or resistant
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40. 1. Automated systems (Vitek, MicroScan, and BD
Diagnostics)
2. The double disk test, in which a disk with
clavulanate placed near a disk with an
oxyimino-beta-lactam enhances susceptibility
to the latter compound
3. An E-test strip with clavulanate added to one
side of a dual oxyimino-beta-lactam gradient
4. Pyrosequencing and microarray technologies
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41. Extended-spectrum beta-lactamase (ESBL)-
producing Enterobacteriaceae have been
reported worldwide
most often in hospital specimens but also in
samples from the community
Community clinics and nursing homes have
also been identified as potential reservoirs for
ESBL-producing K. pneumoniae and E. coli
Wiener J, Quinn JP, Bradford PA, et al. Multiple antibiotic-resistant Klebsiella and Escherichia
coli in nursing homes. JAMA 1999; 281:517.dr.shumaylaaslam@gmail.com
42. ESBL-producing organisms are a growing
cause of nosocomial infections and outbreaks
as well as community-acquired infections
higher in-hospital transmission rates of 4.5
percent for ESBL-producing E. Coli
8.3 percent for ESBL-producing K.
Pneumoniae
Hilty M, Betsch BY, Bögli-Stuber K, et al.Transmission dynamics of extended-spectrum β-
lactamase-producing Enterobacteriaceae in the tertiary care hospital and the household
setting. Clin Infect Dis 2012; 55:967.dr.shumaylaaslam@gmail.com
43. major risk factor colonization with ESBL-
producing Enterobacteriaceae in GI tract
healthcare exposure,
hospitalization,
residence in a long-term care facility,
hemodialysis
presence of an intravascular catheter
community-acquired infections
recent antibiotic therapy,
use of corticosteroids,
presence of a percutaneous feeding tube
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44. chronic indwelling vascular device
age ≥43 years
six or more days of antibiotic exposure within
the prior six months
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45. severe infections caused by extended-
spectrum beta-lactamase (ESBL)-producing
organisms is the carbapenem family
imipenem, meropenem, doripenem,
and ertapenem.
The combination cephalosporin-beta-
lactamase inhibitor agents
ceftolozane-tazobactam and ceftazidime-
avibactam appear promising
dr.shumaylaaslam@gmail.com
46. ESBL-producing K. pneumoniae,
treated with carbapenem monotherapy
piperacillin-tazobactam is NOT RECOMMENED as
resistance may develop during therapy
There are no clear differences in efficacy
between imipenem and meropenem
meropenem is favored in the setting of seizures or
pregnancy
easier to dose in the setting of changing or impaired
renal failure
Ertapenem has the advantage of once-daily dosing
dr.shumaylaaslam@gmail.com
47. severe infections due to ESBL-producing K.
pneumoniae with an oxyimino-beta-lactam
cephalosporin-beta-lactamase inhibitor
combinations (namely ceftolozane-
tazobactam and ceftazidime-avibactam)
susceptible to ciprofloxacin
dr.shumaylaaslam@gmail.com
48. non beta-lactam drug
a potential alternative for treatment of ESBL-
producing strains,
Increasing tigecycline resistance does not yet
appear to be a problem
microbiological surveillance showed unchanged
resistance profiles in 2012 when compared with
2006 isolates
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49. Studies evaluating clinical outcomes in
patients with extended-spectrum beta-
lactamase (ESBL) infections have shown a
trend toward
higher mortality,
longer hospital stay,
greater hospital expenses,
reduced rates of clinical and microbiologic
response
Lautenbach E, Patel JB, BilkerWB, et al. Extended-spectrum beta-lactamase-producing
Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance
on outcomes. Clin Infect Dis 2001; 32:1162.dr.shumaylaaslam@gmail.com
50. The spread of ESBL-producing
organisms within institutions can
be slowed by the
use of barrier protection
restriction of later generation
cephalosporins
dr.shumaylaaslam@gmail.com
51. Treated with
Tigecycline completed 10 days
Ciprofloxacin completed 10 days
Gentamycin completed 10 days
DischargedWell.
dr.shumaylaaslam@gmail.com
Continous exposure to foreign DNA within microbial communities causes bacteria to defend their genomes from exogenous DNA, phages, and plasmid insertion.
β-Lactamases can be classified according to their amino-acid structure into four molecular classes, A through D (Table 18-2), as first suggested by Ambler. Alternatively, the Bush-Jacoby-Medeiros system classifies the enzymes according to their substrate profile and suscep- tibility to β-lactamase inhibitors, such as clavulanic acid, into several functional groups (Table 18-3).42 Class A, C, and D β-lactamases hydrolyze the β-lactam ring through a serine residue at their active site, whereas class B enyzmes are metallo-β-lactamases that use zinc (Zn)2+ to break the amide bond (Fig. 18-4).