This document discusses the antibiotic polymyxins, specifically colistin. It provides details on the chemical structure of colistin, formulations available, dosing, mechanisms of action, spectrum of activity, and toxicity. It notes that colistin is seeing renewed use for treating infections caused by multidrug-resistant Gram-negative bacteria. While nephrotoxicity and neurotoxicity are risks, colistin remains an important therapeutic option when few others are available.
This document summarizes the increasing problem of antibiotic resistance globally and in India specifically. It notes that over half of K. pneumoniae isolates screened in one study from 2009 were carbapenemase producers, with most being metallo-beta-lactamase producers. There was a significant rise from 2002-2009 in ESBL-producing E. coli and resistance to various antibiotics including carbapenems in K. pneumoniae. Carbapenem resistance is of serious concern as carbapenems are often a last resort for multidrug-resistant infections.
This document provides information on extended spectrum beta-lactamases (ESBLs) in 3 sections. It begins by describing the classification of different types of ESBL enzymes including TEM, SHV, CTX-M, OXA, and less common variants. Next, it outlines laboratory detection methods for ESBLs, including phenotypic and genotypic approaches. It concludes by discussing treatment options against ESBL producers such as carbapenems and piperacillin-tazobactam, as well as infection control measures like isolation, surveillance, and restricting broad spectrum antibiotic use.
Neuro 2a cells are mouse neuroblastoma cells that can be differentiated into neuronal-like cells. In this study, the researchers examined the heat shock response in undifferentiated and differentiated Neuro 2a cells. They found that three heat shock protein genes showed reduced expression following heat shock in differentiated Neuro 2a cells, displaying only 12-43% of expression levels in undifferentiated cells. This suggests differentiated Neuro 2a cells have a weaker heat shock response compared to undifferentiated cells. The researchers propose future experiments to further characterize the heat shock response and improve differentiation protocols for this cell line.
Managment of Resistant Gram Negative InfectionsYazan Kherallah
This document discusses the management of resistant gram-negative infections. It describes various beta-lactamases produced by gram-negative bacteria and their antibiotic resistance profiles. Treatment options for infections caused by extended-spectrum beta-lactamase (ESBL) producing, AmpC, carbapenemase and oxacillinase organisms include beta-lactam/beta-lactamase inhibitor combinations, fluoroquinolones, cefepime, tigecycline, carbapenems and colistin. Carbapenems have good activity against most resistant gram-negatives but ertapenem use may select for resistance. Tigecycline and colistin maintain activity against many multid
Development of strategies for management of infections with carbapenem resist...Bhoj Raj Singh
This document discusses strategies for managing infections caused by carbapenem-resistant bacteria. It begins by outlining the objectives of understanding the epidemiology of carbapenemase resistant infections in animals and identifying management strategies. It then provides background on the increasing issue of antimicrobial drug resistance globally and in India. The document discusses common resistance mechanisms like reduced permeability, target alteration, and enzymatic inactivation. It also summarizes different classes of beta-lactam antibiotics and carbapenemases, and the genetics of beta-lactamase resistance. Finally, it presents the author's observations on increasing drug resistance in veterinary clinical isolates in India.
This document discusses carbapenem-resistant Klebsiella pneumoniae (CRKP) strains. It finds that while the ST258 strain is the most common carrier of the bla-KPC gene responsible for carbapenem resistance, non-ST258 strains like ST514, ST11, and ST13 also play an important role in the dissemination and epidemiology of CRKP worldwide. Multilocus sequence typing (MLST) was used to characterize 70 CRKP isolates, identifying 62 as ST258 and 7 as non-ST258 strains. Rep-PCR clustering found that some non-ST258 strains carried the bla-KPC gene as well, showing the epidemiological significance of non-ST258 CRKP cannot be dismissed
This document summarizes the increasing problem of antibiotic resistance globally and in India specifically. It notes that over half of K. pneumoniae isolates screened in one study from 2009 were carbapenemase producers, with most being metallo-beta-lactamase producers. There was a significant rise from 2002-2009 in ESBL-producing E. coli and resistance to various antibiotics including carbapenems in K. pneumoniae. Carbapenem resistance is of serious concern as carbapenems are often a last resort for multidrug-resistant infections.
This document provides information on extended spectrum beta-lactamases (ESBLs) in 3 sections. It begins by describing the classification of different types of ESBL enzymes including TEM, SHV, CTX-M, OXA, and less common variants. Next, it outlines laboratory detection methods for ESBLs, including phenotypic and genotypic approaches. It concludes by discussing treatment options against ESBL producers such as carbapenems and piperacillin-tazobactam, as well as infection control measures like isolation, surveillance, and restricting broad spectrum antibiotic use.
Neuro 2a cells are mouse neuroblastoma cells that can be differentiated into neuronal-like cells. In this study, the researchers examined the heat shock response in undifferentiated and differentiated Neuro 2a cells. They found that three heat shock protein genes showed reduced expression following heat shock in differentiated Neuro 2a cells, displaying only 12-43% of expression levels in undifferentiated cells. This suggests differentiated Neuro 2a cells have a weaker heat shock response compared to undifferentiated cells. The researchers propose future experiments to further characterize the heat shock response and improve differentiation protocols for this cell line.
Managment of Resistant Gram Negative InfectionsYazan Kherallah
This document discusses the management of resistant gram-negative infections. It describes various beta-lactamases produced by gram-negative bacteria and their antibiotic resistance profiles. Treatment options for infections caused by extended-spectrum beta-lactamase (ESBL) producing, AmpC, carbapenemase and oxacillinase organisms include beta-lactam/beta-lactamase inhibitor combinations, fluoroquinolones, cefepime, tigecycline, carbapenems and colistin. Carbapenems have good activity against most resistant gram-negatives but ertapenem use may select for resistance. Tigecycline and colistin maintain activity against many multid
Development of strategies for management of infections with carbapenem resist...Bhoj Raj Singh
This document discusses strategies for managing infections caused by carbapenem-resistant bacteria. It begins by outlining the objectives of understanding the epidemiology of carbapenemase resistant infections in animals and identifying management strategies. It then provides background on the increasing issue of antimicrobial drug resistance globally and in India. The document discusses common resistance mechanisms like reduced permeability, target alteration, and enzymatic inactivation. It also summarizes different classes of beta-lactam antibiotics and carbapenemases, and the genetics of beta-lactamase resistance. Finally, it presents the author's observations on increasing drug resistance in veterinary clinical isolates in India.
This document discusses carbapenem-resistant Klebsiella pneumoniae (CRKP) strains. It finds that while the ST258 strain is the most common carrier of the bla-KPC gene responsible for carbapenem resistance, non-ST258 strains like ST514, ST11, and ST13 also play an important role in the dissemination and epidemiology of CRKP worldwide. Multilocus sequence typing (MLST) was used to characterize 70 CRKP isolates, identifying 62 as ST258 and 7 as non-ST258 strains. Rep-PCR clustering found that some non-ST258 strains carried the bla-KPC gene as well, showing the epidemiological significance of non-ST258 CRKP cannot be dismissed
Role of antimicrobial peptides in plant disease management N.H. Shankar Reddy
It is one of the advanced topics in plant disease management, detailed information about antimicrobial peptides and their role in plant disease management is furnished clearly.
Detection of tetB Gene in Environmental Escherichia coli Strains Using Colony...AnissaBoyers
Tetracycline is a commonly used broad spectrum antibiotic that targets the bacterial ribosome and inhibits protein synthesis. Bacterial resistance to tetracycline can occur via drug efflux from the cell, changes in the ribosomal binding site, or enzymatic modification of the drug. These mechanisms are driven by the expression of tet genes. tet genes can be acquired in pathogenic and commensal Escherichia coli, which is a Gram negative, coliform, rod-shaped bacterium that is found in the intestinal tracts of animals. A particular tet gene of interest is tetB, which is in plasmid DNA or the chromosome and codes for an efflux pump. Our goal was to detect the tetB gene in 14 environmental E. coli strains using the colony polymerase chain reaction (PCR) and to determine the minimum inhibitory concentration (MIC) of tetracycline that would inhibit growth in each strain.
The document summarizes a study that found two fungi isolated from a Brazilian mangrove forest were able to extracellularly synthesize spherical silver nanoparticles (Ag NP) that were 35±10 nm in size. The Ag NP were characterized through various techniques and showed pronounced antimicrobial activity against pathogenic fungi and bacteria. In particular, Ag NP produced by Aspergillus tubingensis were highly effective at inhibiting Pseudomonas aeruginosa growth. This is the first report of extracellular Ag NP synthesis and antimicrobial properties of Ag NP produced by fungi isolated from a Brazilian mangrove, opening possibilities for obtaining biogenic Ag NP with positive surface potential and new applications.
CTZ-AVI shows promise for treating CRE infections based on in vitro studies showing activity against CRE, including KPC producers. However, clinical data is limited to small case studies of bacteremia. Larger clinical trials are still ongoing to evaluate CTZ-AVI for HAP/VAP and bacteremia. Currently, CTZ-AVI should be reserved as a last line option due to limited clinical data and the need to prevent further resistance development. Ongoing research continues to evaluate CTZ-AVI's potential role against CRE and other multidrug resistant pathogens.
This document discusses Staphylococcus aureus and antibiotic resistance. It analyzed 34 isolated S. aureus samples from a hospital in China. Antibiotic susceptibility testing found high resistance to erythromycin (95.2%) but no mutations conferring resistance to fusidic acid or mupirocin. Multilocus sequence typing of resistance genes identified mutations in genes related to macrolide and mupirocin resistance in 23 of 28 samples. The overuse of antibiotics is increasing resistance, demonstrating the need for prudent antibiotic use and resistance monitoring to preserve treatment options.
antimicrobial peptides are class of biological defense molecules which act as a part of our innate immune system.in oral cavity any microbial insult will be resisted by physical,biological and chemical barrier there by maintaining oral homeostasis.these molecules are of low molecular weight with less than 100 amino acids. main antimicrobial peptides include defensin,histatin,cathelicidin and statherin etcc.they develop resistence very slowly,prvrnt biofilm formation and in future they can be used as therapeutic agents
The document discusses the emerging threat of carbapenemase producing enterobacteria and approaches to address it. It provides background on carbapenem antibiotics and the different classes of carbapenemases. It emphasizes that carbapenemases can hydrolyze all beta-lactam antibiotics, making detection and control critical. It recommends surveillance, enhanced infection control practices, and improved laboratory detection methods to help control the spread of these resistant bacteria.
The document summarizes a study that used an integrated molecular approach to examine the response of the Pacific oyster, Crassostrea gigas, to multiple stressors. The study exposed oysters to copper, a common pollutant, and Vibrio tubiashii, a bacterial pathogen. It measured the expression of genes involved in stress response, including heat shock protein 70 (Hsp70), metallothionein IV, and copper oxidase, at the mRNA and protein levels. The results showed that V. tubiashii inhibited the expression of metallothionein IV and copper oxidase, leaving the oysters more vulnerable to copper toxicity. The study demonstrated how one stressor can compromise an
This document discusses drug resistant gram-negative bacteria. It notes that there are currently no new drugs to treat infections from multidrug-resistant gram-negative bacilli such as Acinetobacter baumannii and Pseudomonas aeruginosa. It also discusses extended-spectrum beta-lactamases (ESBLs) which are enzymes produced by bacteria that confer resistance to many beta-lactam antibiotics. The document provides information on detecting and confirming ESBL production in bacteria.
This thesis analyzes alterations in hypersensitive response and senescence rate in BLADE-ON-PETIOLE 1/2 (BOP1/2) mutant Arabidopsis plants. BOP1/2 are involved in plant defense responses. The thesis finds that BOP1/2 mutants exhibit runaway cell death during hypersensitive response to pathogens. It also finds that BOP1/2 mutants have delayed senescence and organ production under short day conditions. This suggests BOP1/2 may regulate senescence rate by modulating plant defense pathways.
This document describes a study examining a synthetic small molecule analogue (SMA-12b) of an immunomodulatory parasitic worm product (ES-62) and its ability to treat experimental arthritis. The key findings are:
1) SMA-12b prevents and treats collagen-induced arthritis in mice by modifying the expression of inflammatory genes, particularly inhibiting IL-1β production.
2) SMA-12b increases the expression of antioxidant response genes regulated by the transcription factor NRF2.
3) SMA-12b is unable to inhibit IL-1β expression in macrophages derived from NRF2-deficient mice, suggesting it acts through NRF2-mediated mechanisms.
Extended spectrum β-lactamases (ESBLs) pose challenges for detection and treatment. ESBLs hydrolyze many penicillins and cephalosporins but are inhibited by β-lactamase inhibitors. Delayed or incorrect detection of ESBL producers can lead to inappropriate cephalosporin treatment and worse outcomes. Laboratory detection of ESBLs is complex, requiring screening methods like combination disks or double disk synergy tests followed by confirmatory tests. Genotypic methods can also detect ESBL genes. Accurate detection is important for infection control and antibiotic stewardship given ESBL producers' resistance and transmission risks.
This document outlines a study investigating the effects of statin drugs like Simvastatin on the gut microbiome in relation to clinical obesity. The hypothesis is that certain statins will selectively inhibit bacteria in the Fimicutes phylum, which are more prevalent in obese individuals. The methods test the susceptibility of various bacterial species to different statins in vitro. Results show the statins had varying effects, with some inhibiting Clostridium species. Future experiments will examine changes in fecal microbiome DNA from patients taking Simvastatin.
The document discusses antimicrobial drug resistance (AMDR) and the mechanisms by which microbes develop resistance to antimicrobial medications. It describes classes of AMDR including resistance to antifungal, antiviral, antiprotozoal, and antibacterial drugs. Mechanisms of resistance include altering drug receptors or targets, reducing drug accumulation in cells, inactivating drugs, and developing resistant metabolic pathways. The document also summarizes the cellular and molecular mechanisms of antimicrobial action, including interfering with cell wall synthesis, plasma membrane integrity, nucleic acid synthesis, ribosomal function, and folate synthesis.
Tuberculosis is caused by Mycobacterium tuberculosis and forms granulomas in the lungs. It is diagnosed through physical exams, chest x-rays, sputum tests, tuberculin skin tests, and blood tests. The disease is treated with a combination of anti-tubercular drugs including isoniazid, rifampin, pyrazinamide, and ethambutol over several months to kill the bacteria and prevent relapse. Second line drugs are used if the bacteria develop resistance to the first line treatments.
This study examines the antimicrobial and antibiofilm activity of a 5-kDa peptide fraction isolated from the coelomocytes (immune cells) of the sea urchin Paracentrotus lividus. The peptide fraction, called 5-CC, showed inhibitory activity against both Gram-positive and Gram-negative bacteria, as well as fungi, with minimum inhibitory concentrations ranging from 253.7 to 15.8 mg ml-1. 5-CC also inhibited the formation of Staphylococcus aureus and Staphylococcus epidermidis biofilms. At sub-MIC concentrations, 5-CC inhibited the formation of young (6-hour) and mature (24-hour) biofilms of
Teixobactin is a novel antibiotic discovered using an electronic chip to cultivate previously unculturable soil bacteria. It shows promise in treating infections like tuberculosis and C. difficile. Its mechanism of action involves binding to lipid II and lipid III, inhibiting production of the bacterial cell wall peptidoglycan layer. This discovery demonstrates the potential for developing new antibiotics by accessing the vast reservoir of uncultured microorganisms in the environment.
This document discusses the prevalence of vancomycin-resistant enterococci (VRE) in hospitalized patients in Islamabad and Rawalpindi, Pakistan. It describes how 133 clinical samples were collected from three hospitals and cultured to isolate enterococci species. The enterococci isolates were then tested for vancomycin resistance using selective media. Antibiotic susceptibility testing and minimum inhibitory concentration determination were performed on the vancomycin-resistant enterococci isolates to evaluate resistance patterns.
B. bassiana is an entomopathogenic fungus that is used as a mycoinsecticide to control various insect pests. It naturally infects insects through their cuticles, causing white muscardine disease. Some advantages of using B. bassiana include its wide host range of insect pests, ability to control forest pest insects like pine caterpillars and silkworms, and production of beauvericin which helps transport ions and shows antifungal and antibiotic properties. However, mass production of B. bassiana mycoinsecticides can be expensive and time-consuming.
Imidocarb is an effective treatment for bovine babesiosis and anaplasmosis caused by various pathogens. It works by competitively inhibiting inositol receptors on red blood cells, preventing parasite metabolism and destroying parasites without lysing red blood cells. For babesiosis in cattle, the recommended dose is 1 ml/100 kg IM, providing clinical sterilization within 36-48 hours. Imidocarb also provides chemoprotection for 4-6 weeks when administered prophylactically at 2.5 ml/100 kg. It has shown high cure rates against various Babesia species in cattle and provides protection for months when used prophylactically.
Role of antimicrobial peptides in plant disease management N.H. Shankar Reddy
It is one of the advanced topics in plant disease management, detailed information about antimicrobial peptides and their role in plant disease management is furnished clearly.
Detection of tetB Gene in Environmental Escherichia coli Strains Using Colony...AnissaBoyers
Tetracycline is a commonly used broad spectrum antibiotic that targets the bacterial ribosome and inhibits protein synthesis. Bacterial resistance to tetracycline can occur via drug efflux from the cell, changes in the ribosomal binding site, or enzymatic modification of the drug. These mechanisms are driven by the expression of tet genes. tet genes can be acquired in pathogenic and commensal Escherichia coli, which is a Gram negative, coliform, rod-shaped bacterium that is found in the intestinal tracts of animals. A particular tet gene of interest is tetB, which is in plasmid DNA or the chromosome and codes for an efflux pump. Our goal was to detect the tetB gene in 14 environmental E. coli strains using the colony polymerase chain reaction (PCR) and to determine the minimum inhibitory concentration (MIC) of tetracycline that would inhibit growth in each strain.
The document summarizes a study that found two fungi isolated from a Brazilian mangrove forest were able to extracellularly synthesize spherical silver nanoparticles (Ag NP) that were 35±10 nm in size. The Ag NP were characterized through various techniques and showed pronounced antimicrobial activity against pathogenic fungi and bacteria. In particular, Ag NP produced by Aspergillus tubingensis were highly effective at inhibiting Pseudomonas aeruginosa growth. This is the first report of extracellular Ag NP synthesis and antimicrobial properties of Ag NP produced by fungi isolated from a Brazilian mangrove, opening possibilities for obtaining biogenic Ag NP with positive surface potential and new applications.
CTZ-AVI shows promise for treating CRE infections based on in vitro studies showing activity against CRE, including KPC producers. However, clinical data is limited to small case studies of bacteremia. Larger clinical trials are still ongoing to evaluate CTZ-AVI for HAP/VAP and bacteremia. Currently, CTZ-AVI should be reserved as a last line option due to limited clinical data and the need to prevent further resistance development. Ongoing research continues to evaluate CTZ-AVI's potential role against CRE and other multidrug resistant pathogens.
This document discusses Staphylococcus aureus and antibiotic resistance. It analyzed 34 isolated S. aureus samples from a hospital in China. Antibiotic susceptibility testing found high resistance to erythromycin (95.2%) but no mutations conferring resistance to fusidic acid or mupirocin. Multilocus sequence typing of resistance genes identified mutations in genes related to macrolide and mupirocin resistance in 23 of 28 samples. The overuse of antibiotics is increasing resistance, demonstrating the need for prudent antibiotic use and resistance monitoring to preserve treatment options.
antimicrobial peptides are class of biological defense molecules which act as a part of our innate immune system.in oral cavity any microbial insult will be resisted by physical,biological and chemical barrier there by maintaining oral homeostasis.these molecules are of low molecular weight with less than 100 amino acids. main antimicrobial peptides include defensin,histatin,cathelicidin and statherin etcc.they develop resistence very slowly,prvrnt biofilm formation and in future they can be used as therapeutic agents
The document discusses the emerging threat of carbapenemase producing enterobacteria and approaches to address it. It provides background on carbapenem antibiotics and the different classes of carbapenemases. It emphasizes that carbapenemases can hydrolyze all beta-lactam antibiotics, making detection and control critical. It recommends surveillance, enhanced infection control practices, and improved laboratory detection methods to help control the spread of these resistant bacteria.
The document summarizes a study that used an integrated molecular approach to examine the response of the Pacific oyster, Crassostrea gigas, to multiple stressors. The study exposed oysters to copper, a common pollutant, and Vibrio tubiashii, a bacterial pathogen. It measured the expression of genes involved in stress response, including heat shock protein 70 (Hsp70), metallothionein IV, and copper oxidase, at the mRNA and protein levels. The results showed that V. tubiashii inhibited the expression of metallothionein IV and copper oxidase, leaving the oysters more vulnerable to copper toxicity. The study demonstrated how one stressor can compromise an
This document discusses drug resistant gram-negative bacteria. It notes that there are currently no new drugs to treat infections from multidrug-resistant gram-negative bacilli such as Acinetobacter baumannii and Pseudomonas aeruginosa. It also discusses extended-spectrum beta-lactamases (ESBLs) which are enzymes produced by bacteria that confer resistance to many beta-lactam antibiotics. The document provides information on detecting and confirming ESBL production in bacteria.
This thesis analyzes alterations in hypersensitive response and senescence rate in BLADE-ON-PETIOLE 1/2 (BOP1/2) mutant Arabidopsis plants. BOP1/2 are involved in plant defense responses. The thesis finds that BOP1/2 mutants exhibit runaway cell death during hypersensitive response to pathogens. It also finds that BOP1/2 mutants have delayed senescence and organ production under short day conditions. This suggests BOP1/2 may regulate senescence rate by modulating plant defense pathways.
This document describes a study examining a synthetic small molecule analogue (SMA-12b) of an immunomodulatory parasitic worm product (ES-62) and its ability to treat experimental arthritis. The key findings are:
1) SMA-12b prevents and treats collagen-induced arthritis in mice by modifying the expression of inflammatory genes, particularly inhibiting IL-1β production.
2) SMA-12b increases the expression of antioxidant response genes regulated by the transcription factor NRF2.
3) SMA-12b is unable to inhibit IL-1β expression in macrophages derived from NRF2-deficient mice, suggesting it acts through NRF2-mediated mechanisms.
Extended spectrum β-lactamases (ESBLs) pose challenges for detection and treatment. ESBLs hydrolyze many penicillins and cephalosporins but are inhibited by β-lactamase inhibitors. Delayed or incorrect detection of ESBL producers can lead to inappropriate cephalosporin treatment and worse outcomes. Laboratory detection of ESBLs is complex, requiring screening methods like combination disks or double disk synergy tests followed by confirmatory tests. Genotypic methods can also detect ESBL genes. Accurate detection is important for infection control and antibiotic stewardship given ESBL producers' resistance and transmission risks.
This document outlines a study investigating the effects of statin drugs like Simvastatin on the gut microbiome in relation to clinical obesity. The hypothesis is that certain statins will selectively inhibit bacteria in the Fimicutes phylum, which are more prevalent in obese individuals. The methods test the susceptibility of various bacterial species to different statins in vitro. Results show the statins had varying effects, with some inhibiting Clostridium species. Future experiments will examine changes in fecal microbiome DNA from patients taking Simvastatin.
The document discusses antimicrobial drug resistance (AMDR) and the mechanisms by which microbes develop resistance to antimicrobial medications. It describes classes of AMDR including resistance to antifungal, antiviral, antiprotozoal, and antibacterial drugs. Mechanisms of resistance include altering drug receptors or targets, reducing drug accumulation in cells, inactivating drugs, and developing resistant metabolic pathways. The document also summarizes the cellular and molecular mechanisms of antimicrobial action, including interfering with cell wall synthesis, plasma membrane integrity, nucleic acid synthesis, ribosomal function, and folate synthesis.
Tuberculosis is caused by Mycobacterium tuberculosis and forms granulomas in the lungs. It is diagnosed through physical exams, chest x-rays, sputum tests, tuberculin skin tests, and blood tests. The disease is treated with a combination of anti-tubercular drugs including isoniazid, rifampin, pyrazinamide, and ethambutol over several months to kill the bacteria and prevent relapse. Second line drugs are used if the bacteria develop resistance to the first line treatments.
This study examines the antimicrobial and antibiofilm activity of a 5-kDa peptide fraction isolated from the coelomocytes (immune cells) of the sea urchin Paracentrotus lividus. The peptide fraction, called 5-CC, showed inhibitory activity against both Gram-positive and Gram-negative bacteria, as well as fungi, with minimum inhibitory concentrations ranging from 253.7 to 15.8 mg ml-1. 5-CC also inhibited the formation of Staphylococcus aureus and Staphylococcus epidermidis biofilms. At sub-MIC concentrations, 5-CC inhibited the formation of young (6-hour) and mature (24-hour) biofilms of
Teixobactin is a novel antibiotic discovered using an electronic chip to cultivate previously unculturable soil bacteria. It shows promise in treating infections like tuberculosis and C. difficile. Its mechanism of action involves binding to lipid II and lipid III, inhibiting production of the bacterial cell wall peptidoglycan layer. This discovery demonstrates the potential for developing new antibiotics by accessing the vast reservoir of uncultured microorganisms in the environment.
This document discusses the prevalence of vancomycin-resistant enterococci (VRE) in hospitalized patients in Islamabad and Rawalpindi, Pakistan. It describes how 133 clinical samples were collected from three hospitals and cultured to isolate enterococci species. The enterococci isolates were then tested for vancomycin resistance using selective media. Antibiotic susceptibility testing and minimum inhibitory concentration determination were performed on the vancomycin-resistant enterococci isolates to evaluate resistance patterns.
B. bassiana is an entomopathogenic fungus that is used as a mycoinsecticide to control various insect pests. It naturally infects insects through their cuticles, causing white muscardine disease. Some advantages of using B. bassiana include its wide host range of insect pests, ability to control forest pest insects like pine caterpillars and silkworms, and production of beauvericin which helps transport ions and shows antifungal and antibiotic properties. However, mass production of B. bassiana mycoinsecticides can be expensive and time-consuming.
Imidocarb is an effective treatment for bovine babesiosis and anaplasmosis caused by various pathogens. It works by competitively inhibiting inositol receptors on red blood cells, preventing parasite metabolism and destroying parasites without lysing red blood cells. For babesiosis in cattle, the recommended dose is 1 ml/100 kg IM, providing clinical sterilization within 36-48 hours. Imidocarb also provides chemoprotection for 4-6 weeks when administered prophylactically at 2.5 ml/100 kg. It has shown high cure rates against various Babesia species in cattle and provides protection for months when used prophylactically.
This document discusses the antimicrobial therapy of neonates. It begins by defining antibiotics and classifying them based on their mode of action, spectrum of activity, and mechanism of action. Common bacterial diseases of neonates include neonatal diarrhea, joint ill, and pneumonia. For neonatal diarrhea, enrofloxacin is the drug of choice. For coccidiosis, sulfonamides are used. Metronidazole treats giardiasis. Penicillin and streptomycin are effective against joint ill. Macrolides like erythromycin and tylosin are useful to treat pneumonia. The document provides market drugs available in Pakistan for the different conditions.
- Compounds 2, 12, and 16 were found to enhance biofilm formation in commensal bacteria (Streptococcus cristatus, Streptococcus gordonii, and Streptococcus sanguinis) without enhancing biofilm in pathogenic bacteria.
- These compounds are structurally similar to other known biofilm/quorum sensing inhibitors.
- Using a combination of these structurally related compounds may selectively reduce pathogenic biofilm while retaining commensal bacteria.
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
Quercetin was found to inhibit quorum sensing in foodborne bacteria both in vitro and in silico. In laboratory experiments, quercetin reduced quorum sensing-dependent phenotypes like biofilm formation, exopolysaccharide production, and motility in a concentration-dependent manner in pathogens like Pseudomonas aeruginosa, Yersinia enterocolitica, and Klebsiella pneumoniae. Molecular docking analysis revealed that quercetin binds strongly to the LasR receptor protein involved in quorum sensing. Molecular dynamics simulations further suggested that quercetin inhibits quorum sensing by inducing conformational changes in the receptor-quercetin complex. The study provides evidence that quercetin can act as a competitive inhibitor of qu
International Journal of Pharmaceutical Science Invention (IJPSI) inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
This document describes three models used to screen for antibacterial activity:
1) The mouse systemic infection model tests compounds against infections caused by E. coli, Klebsiella pneumoniae, and Staphylococcus aureus in mice. One study showed broad-spectrum activity against gram-negative and gram-positive bacteria.
2) The rabbit skin burn infection model assesses compounds' ability to reduce viable E. coli colony counts in burn wounds created on rabbits.
3) The mouse ascending urinary tract infection model evaluates compounds' dose-dependent efficacy against an E. coli bladder infection in mice. Kidneys are examined for reductions in viable bacterial counts compared to controls.
1) Antibiotics are compounds that kill or inhibit the growth of bacteria and are produced by microorganisms. They work by being more toxic to invading bacteria than the human host.
2) The document discusses several classes of antibiotics including penicillin, cephalosporins, aminoglycosides, macrolides, tetracyclines, chloramphenicol, glycopeptides, and fluoroquinolones. It describes their mechanisms of action and antimicrobial spectrums.
3) Antibiotic resistance has become a major problem as bacteria evolve and develop resistance through both natural and acquired mechanisms such as long-term antibiotic use.
This document summarizes research on Saccharomyces boulardii and its use in treating diarrhea. S. boulardii is a probiotic yeast that acts locally in the intestine to help maintain the balance of intestinal microflora. It has several modes of action including inhibiting pathogenic bacteria, enhancing immune defenses, neutralizing toxins, increasing digestive enzyme activity, and releasing polyamines with trophic effects. Studies show S. boulardii is effective against acute diarrhea of various causes as well as antibiotic-associated diarrhea. It helps restore the precarious equilibrium of the intestinal ecosystem.
This document outlines an investigation into the effects of statin drugs like Simvastatin on the gut microbiome in relation to clinical obesity. The hypothesis is that certain statins will selectively inhibit bacteria in the Fimicutes phylum, which are more prevalent in obese individuals. In vitro experiments found that statins like Lovastatin, Lipitor, and Zocor inhibited some species of bacteria including Clostridium and Bacillus. Preliminary in vivo testing of Simvastatin treatment suggested a shift in gut microbiota away from Fimicutes dominance. Further epidemiological studies are needed to understand statins' potential as drugs that target Fimicutes bacteria in obese patients.
This document outlines an investigation into the effects of statin drugs like Simvastatin on the gut microbiome in relation to clinical obesity. The hypothesis is that certain statins will selectively inhibit bacteria in the Fimicutes phylum, which are more prevalent in obese individuals. In vitro experiments found that statins like Lovastatin, Lipitor, and Zocor inhibited the Fimicutes bacteria Bacillus subtilis and Clostridium sordellii. Preliminary in vivo testing also suggests Simvastatin treatment may shift the gut microbiota from Fimicutes-dominant to more Bacteroides-dominant. Further epidemiological studies are needed to better understand statins' potential as obesity drugs that
This document provides information on intracanal medicaments used in endodontic treatment. It defines intracanal medicaments as temporary medications placed in root canals to inhibit bacterial invasion and discusses their ideal requirements. Various commonly used medicaments are described, including their composition, mechanisms of action, and antimicrobial efficacy. In particular, it focuses on chlorhexidine, formocresol, calcium hydroxide, antibiotics, and corticosteroid combinations such as Ledermix paste. The document also reviews the root canal and deciduous tooth microflora that intracanal medicaments aim to eliminate.
The document discusses various classes of antibiotics including their spectrum of activity, mechanisms of action, and examples. It provides classifications of antibiotics such as narrow versus broad spectrum, bacteriostatic versus bactericidal. It describes common mechanisms of action such as inhibition of cell wall synthesis, protein synthesis, and nucleic acid synthesis. Examples of specific antibiotics are given for each class along with their dosages and availability in the Pakistani market.
ISO 15189 2022 standards for laboratory quality and competencePathKind Labs
The fourth edition of standards for laboratory quality and competence are available. Labs need to perform gap analysis to identify areas that need to be developed to fulfill the new requirements.
The document outlines the requirements for medical laboratories to establish and follow quality management standards according to ISO 15189. It describes establishing objectives and policies, managing risks, ensuring adequate resources including personnel, facilities, equipment and processes. Requirements cover pre-examination, examination and post-examination activities including testing, reporting and advisory services. The standard aims to promote quality and competence in medical laboratories to benefit patients.
behaviour changes for success of antimicrobial stewardship program.pptxPathKind Labs
1. A review of behavioral theories identified key barriers to appropriate antimicrobial stewardship including lack of knowledge, resources, and goals.
2. Interventions like training, environmental restructuring, and guidelines were recommended to increase capabilities and opportunities while enabling and persuading behavior change.
3. Audits with feedback, education, and incentives could target motivations by emphasizing consequences and setting clear goals.
management of childhood tuberculosis in 2023.pptxPathKind Labs
diagnosis of childhood TB is a challange, but if we follow a system of screening and then appropriate diagnostic tests following contact tracing, we are likely to identify children with infection or disease and put them on appropriate treatment.
Recently ISO 15189:2022 have become available. This would help laboratories set up processes which would yield reproducible results and improve the quality of work.
viral markers in diagnosis monitoring and treatment of hepatitis b and c.pptxPathKind Labs
Hepatitis B Virus and Hepatitis C Virus infections are transmitted by parentral route. Early diagnosis and treatment can prevent cirrhosis of liver in HCV cases as drugs which can cure the infection are now available.
Covid-19 pandemic has caused over 6 million deaths and has been acknowledged as one of the worst pandemic in living memory. But antimicrobial resistance as invisble pandemic may clain more deaths every year if suitable action is not taken soon.
While MIC is a good measure of antibiotic activity, it is static and reflects in vitro activity. PK and PD of the drug needs to be considered together with MIC if we wish to obtain an in vivo prediction of drug action and success.
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To diagnose and treat drug susceptible pulmonary tuberculosis is of paramount importance in our efforts to eliminate tuberculosis. This describes seven clincal standards which should be practiced to obtain optimum results
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Procalcitonin is an excellent biomarker for antibiotic use in bacterial infections alone. POCT guided PCT levels can help decide whether to add antibiotics or not in opd settings for respiratory tract infection.
Role of neutralizing antibodies in covid 19PathKind Labs
1) Studies on rhesus monkeys found that those who were re-exposed to SARS-CoV-2 after recovering from initial infection did not experience disease recurrence or viral replication, demonstrating protection from reinfection by neutralizing antibodies.
2) Vaccine trials show that neutralizing antibodies induced by mRNA vaccines effectively neutralize emerging variants like B.1.351, and a single vaccine dose can generate neutralizing antibodies in previously infected individuals.
3) The level of neutralizing antibodies required for protection against SARS-CoV-2 in rhesus macaques was found to be 50, with higher RBD and spike IgG titers also correlating with protection.
What is and what is not black fungus and how to diagnose shortPathKind Labs
1. Black fungi, also known as dematiaceous fungi, contain high levels of melanin pigments that cause their cell walls and structures to appear dark brown or black.
2. Important black fungi include genera that produce single-celled or multi-celled conidia, such as Nigrospora, Alternaria, and Cladosporium.
3. Mucor and Aspergillus are not considered black fungi despite sometimes causing black lesions, as they do not contain high melanin levels in their cell walls.
4. When recovering from COVID-19, seek medical help for symptoms like nasal blockage, pain, or swelling that could indicate a fungal infection
24 march short ntep who diagnosis of dr tbPathKind Labs
Robert Koch isolated bacteria from tuberculosis patients in 1882 that caused TB when injected into guinea pigs, rabbits, mice and cats, demonstrating the infectious nature of TB. The document provides guidance on collecting and transporting sputum specimens from TB patients to laboratories for testing, including using proper containers, packaging, storage, and transportation to ensure specimen quality and prevent delays. It emphasizes collecting quality specimens of adequate volume and details the steps needed to properly package and transport specimens in a cool chain within 48-72 hours of collection.
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QMS is essential to run a good laboratory, but the various requirements pose a big challenge. Once you understand the reason for these requirements compliance may be easier.
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The document provides information on Covid-19 vaccination and vaccine development. It discusses how available genome sequence allowed for rapid diagnostic and vaccine development. Multiple vaccine platforms are highlighted, including mRNA, viral vectors, and protein-based. Operation Warp Speed is aiming to deliver hundreds of millions of doses of leading candidates by January 2021. Challenges of vaccine development include safety testing and failure is common. Long-term safety and efficacy data is still needed.
RT PCR is too slow for effective control of spread of cov 2 infection, rapid antigen test by giving results in less than 30 minutes can help identify infected persons leading to quick isolation.Lack of sensitivity can be compensated by repeating RAT after a day or so.
Psaroudakis: Family and Football – The Psaroudakis Success StoryPsaroudakis
Psaroudakis, a name that resonates with football fans around the globe, is a testament to the powerful synergy between familial support and individual passion. Born on March 10, 1992, in the historic city of Heraklion, Crete, Psaroudakis’ journey to international football stardom is a compelling narrative of dedication, perseverance, and unwavering family support. His story not only highlights his athletic prowess but also underscores the crucial role his family played in shaping his career and character.
Psaroudakis’ early life in Heraklion was deeply influenced by a supportive and nurturing family environment. His father, a former semi-professional footballer, recognized Psaroudakis’ potential from an early age. Acting as his first coach, his father’s guidance was instrumental in igniting Psaroudakis’ passion for football. This paternal influence instilled in him a strong work ethic and fundamental skills that would become the foundation of his future success. His mother, a dedicated homemaker, provided a stable and nurturing environment, ensuring that Psaroudakis could pursue his dreams without any hindrances.
From a young age, Psaroudakis showed an innate talent for football. Growing up in Heraklion, he spent countless hours playing football in local parks and streets with friends and family. His natural ability was evident even in these informal settings, and his enthusiasm for the game was infectious. By the age of five, Psaroudakis had joined a local youth football club, where his skills began to flourish. His father’s role as his first coach during these formative years was crucial, as he emphasized not only technical skills but also the importance of discipline and teamwork.
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The support of Psaroudakis’ family was unwavering during this critical period. His father continued to be a source of guidance and mentorship, while his mother ensured that he had everything he needed to succeed. Their collective efforts created a balanced environment where Psaroudakis could focus entirely on his development as a footballer. This familial support was not just about providing the basics; it was about creating an environment where Psaroudakis felt encouraged and motivated to pursue his dreams relentlessly.
As Psaroudakis transitioned from the youth academy to professional football, the challenges became more significant.
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Coach Domenico Tedesco has managed a tactical shakeup and a regular exit for some of the oldest players. Experienced bests remain, not least the 37-year-old Jan Vertonghen in defense, the 32-year-old De Bruyne himself in midfield, and 31-year-old Romelu Lukaku up visible.
Still, younger actors like De Bruyne’s Manchester City partner Jeremy Doku bring fresh vitality to the team. Euro Cup Germany Qualifying unbeaten with just four goals allowed from eight games was a welcome sign of accomplishment back on track under Tedesco.
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Germany and Scotland will take things off before we get into overdrive in two weeks. Meanwhile, Belgium will be longing to bounce back after a horrendous 2022 FIFA World Cup movement, which ended in the group stage.
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According to the report, the consumption of video content related to IPL 2024 has seen significant growth, nearly 3 times more than the previous season, reflecting an increasing interest of fans.
Here are our Euro 2024 predictions for the group stages
Will England make it through the group stages?, Will Germany use the home advantage to full effect?
Follow our progress, see how many we get right
If you want to join in let us know before the first game kick off and we can invite you to our private league
or join in with our friends at DeeperThanBlue
https://www.linkedin.com/posts/activity-7204868572995538944-qejG
https://www.selectdistinct.co.uk/2024/06/13/euro-2024-match-predictions/
#EURO2024 #Germany2024 #England #EURO2024predictions
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2. Polymyxins
Polypeptide antibiotics first isolated from Bacillus
polymyxa
5 chemically different compounds
(Polymyxin A – E)
Polymyxin B
Polymyxin E (Colistin)
Polymyxin A, C and D too toxic for human use
2
3. Colistin
Cationic cyclic deca peptide
Linked to a fatty acid chain
Through an α amide linkage
Amino acid are:
D leucine,
L threonine,
L α γ diamino butyric acid
Fatty acid could be
6 methyl octon oic acid (colistin A)
6 methyl eptanoic acid (colistin B) 3
5. Formulations:
Colistin sulphate Colistimethate sodium (CMS)
Oral, Tropical, inhalation use Parental, inhalation use
Active drug, not absorbed Inactive prodrug, less toxic,
orally hydrolysed in aqueous
solution to active colistin
Two formulations:
International Unit is defined as
minimal conc that inhibits A. colomycin: 500 k, 1 M, 2 M
growth of E.coli 95 ISM in 1 international units
ml broth at pH 7.2
B. Coly mycin: 150 mg colistin
1 million IU = 80 mg of CMS active base/vial = 360 mg
of CMS
5
6. Available formulations
Colomycin injection Coly-Mycin M Parenteral
Manufacturer Dumex-Alpharma A/S, Parkedale Pharmaceuticals,
Copenhagen, Denmark Rochester, MN, USA
Labelled content per vial 500 000, 1 000 000 or 150 mg colistin base activity
2 000 000 IU;
about 12 500 units/mg
Mass of colistimethate 40 mg, 80 mg, or 160 mg About 400 mg
sodium dry powder per vial
Appearance Creamy-white powder White to slightly yellow lyophilised
cake
Recommended dose* ≤60 kg bodyweight: 50 K 2.5– 5mg/kg per day colistin base
IU– 75 K IU/kg per day in activity in two to four doses, =
three divided doses, = about 6.67–13.3 mg/kg per day
4–6 mg/kg per day colistimethate sodium
colistimethate sodium 6
7. Dose
240 to 720 mg per day (3 to 9 million IU/day)
In 2 – 4 divided doses
CMS Colistin Sulphate
Inactive prodrug Active drug
International Unit is defined as minimal conc that inhibits growth of
E.coli 95 ISM in 1 ml broth at pH 7.2
12 500 IU = 1 mg of CMS
2.67 mg of CMS = 1 mg colistin base activity
2 M IU of CMS = 160 mg of drug = 60 mg colistin base activity
7
8. Fell into disrepute in early 1970s
Ryan KJ et al.
Colistimethate toxicity: report of a fatal case in a previously
healthy child. JAMA 1969; 207 : 2099 - 101
Brown JM et al.
Acute renal failure due to overdosage of colistin. Med J Aust
1970; 2: 923 – 4
Koch Weser J et al.
Adverse effects of sodium colistimethate: manifestations and
specific reaction rates during 317 courses of therapy.
Ann Intern Med 1970; 72: 857 – 68.
8
9. Aminoglycosides, FQs & Penems became the
antibiotic work horse in 1970s - 2000
Gentamicin Amikacin Ciprofloxacin
Meropenem 9
10. Emergence of MDR, XDR &courtesy Dr Chand Wattal
Data PDR
Gram Negative Bacterial Infections
10
11. Bad bugs, no drugs: No ESKAPE
CID 2009; 48: 1 - 12
E nterococcus faecium
S taphylococcus aureus
K lebseilla pneumoniae
A cinetobacter baumanii
P seudomonas aeruginosa
E nterobacter species
Clostridium difficile & E. coli
11
12. We have a basic problem
We must make the best use of what we have
12
15. Colistin: Revival of Polymyxins for the management of
MDR GNB Infections
Falagas & Kasiakou CID 2005; 40: 1333 - 41
Treatment of infections caused by MDR
Acinetobacter baumannii
Pseudomonas aeruginosa
Klebsiella pneumoniae
Cystic Fibrosis
VAP
Nosocomial pneumonia
Bacteriemia
UTI
15
Meningitis
16. Use of Colistin as salvage therapy
Colistin active against P. aeruginosa ,
Acinetobacter spp & Klebseilla spp.
Can be used for Pneumonia, Bacteremia or UTI
caused by these infections
Acceptable toxicity & effectiveness
16
17. Nephrotoxicity
CMS at 160 mg x 3 has satisfactory safety
CMS maybe safer than aminoglycosides
CMS + AG have increased renal toxicity
RIFLE (Risk, injury, failure,loss,end stage)
66 pt, 45% met criteria for nephrotoxicity
21% stopped CMS, reversible,
toxicity 3.7 x > if dosed for more than 14 days
17
21. Colistin Susceptibility
Break Points
Organization Bacteria MIC Disk Diffusion
S I R S I R
CLSI Acinetobacter spp <2 >4 No Break Points
Pseudomonas <2 4 >8 < 10 > 11
aeruginosa
Enterobacteriaceae No Break Points
EUCAST Acinetobacter spp <2 >4
No Break Points
Pseudomonas <2 >4
aeruginosa
Enterobacteriaceae* <2 >4
Only
E.coli, Klebsiella spp
& Enterobacter spp.
21
24. Recent Recommendations for Dose Calculation
Anti Agents Chemother 2011: 55: 3284 - 3294
Loading dose: 6 M IU
desired target conc. X 2 X body wt
= 300 mg CBA ( 1 mg CBA = 12 500 IU)
Maintenance dose:
desired target conc. X (1.5 X Cr Cl + 30) mg CBA
Useful to add Melatonin or Vit C as nephroprotectants
Not likely to attain AUC/MIC values likely to be
effective for MIC >0.5;
Donot use as monotherapy
24
25. Mechanism of action
1. Polymyxin have strong positive charge & a hydrophobic aryl chain
2. Initial target is LPS component of Outer membrane
3. Displaces divalent cations: Ca & Mg
4. Causes disruption of cell membrane
5. Increased permeability & leakage of cell contents & subsequent cell
death
6. Polymyxin binds to Lipid A
portion of LPS exhibit anti
endotoxin activity
25
26. Routes of administration of colistin
Colistin Methane Sulphonate (CMS)
IV
(IM)
Inhalation
Intrathecal
Intraventricular
Colistin Sulphate
Local application
Oral (for Gut decontamination)
26
27. Colistin by aerosolised route
Naesens R et al. BMS Infect Dis 2011; 11: 317
20 ICU pts with Ps aeruginosa pneumonia
6 received colistin by inhalation only
5 only by IV; 9 combined
All received concomitent β lactam
Clinical response & no deaths in 6/6
3/9 of combined & 5/5 of IV group died
Dose: 2 M IU/by aerosole TID
27
28. Clinical use of colistin in children
Falagas ME et al: Int J Anti Agents 2009; 33: 503 e1 - 13
326 children for treatment & 44 for prophylaxis
271 of 311 children were available for evaluation
235 (86.7%) cured; 10 (3.7%) improved
6 (2.2%) deteriorated; 20 (7.4%) died
No infection in 44 children who received prophylaxis
Nephrotoxicity in 10 children
Systemic Colistin is an effective & acceptable option for
MDR infections
Dose: 25 k IU/kg TID
28
29. Mechanism of resistance
Hetroresistance: Presence of colistin resistant
subpopulation within a microbial population
that is susceptible based on MIC.
1. LPS change or loss
2. Efflux pump/potassium system
3. Colistinase is produced by B. polymyxa that
produces colistin, but has not yet been
detected in clinical isolates
29
30. Mechanism of resistance
Moffatt JH et al: Colistin Resistance in Acinetobacter baumannii Is Mediated by Complete Loss of
Lipopolysaccharide Production . AAC 2010; 54: 4971 - 7
LPS
30
32. Phenotype of resistance by two compartment system
Regulatory Contributing Mechanism or
Gene Effect
System Factors Site of Action
PmrA-PmrB PmrE PhoP-PhoQ Reduces negative Reduced binding
PmrHFIJKLM activation charge of the affinity
Mildly acidic pH bacteria's lipid A
High iron and LPS
concentrations
Low magnesium
concentrations
PhoP-PhoQ OprH Exogenous OprH proteins reduce the
polyamines occupy binding site for
Low magnesium membrane colistin
concentrations magnesium sites
32
33. Resistance in Clinical isolates: Acinetobacter baumannii
Location Findings
Australia 93.8% of 16 clinical isolates were heteroresistant to colistin.
Spain 19.1% of 115 clinical isolates were resistant to colistin.
Korea 27.9% of 214 isolates were resistant to colistin, with most of these
resistant strains susceptible to conventional antibiotics.
Western Pacific 3.3% of 30 isolates were resistant to colistin, 23% of the 30 isolates
were colistin heteroresistant.
United States Ventilator-associated pneumonia in a 55-year-old woman was
initially susceptible to colistin (MIC 0.5 mg/L); after i.v. therapy,
high-level colistin resistance developed (MIC > 1024 mg/L)
Argentina 46.4% of 28 isolates from 28 different patients in an ICU showed
colistin heteroresistance. A 22-year-old man initially susceptible to
colistin developed resistance (MIC 32 mg/L) after receiving 33
intrathecal colistin for 48 hrs.
34. Resistance in Clinical isolates : Pseudomonas aeruginosa
Place Findings
Australia 47.8% of 23 clinical isolates from patients with cystic
fibrosis were resistant to colistin.
Germany 34.9% of nonmucoid and 51.9% of mucoid strains were
susceptible to colistin among 385 isolates obtained
from patients with cystic fibrosis.
United Colistin-resistant isolates were obtained from 6
Kingdom children with cystic fibrosis over a 5-yr period; the
children had previously received aerosolized colistin for
a mean duration of 3.1 yrs.
34
35. Resistance in Clinical isolates : Klebsiella pneumoniae
Location Findings
Greece 18 colistin-resistant isolates were identified in a
tertiary hospital over a 16-mo period.
Australia 27.27% of 22 Clinical isolates colistin resistant;
Resistance in isolates were
colistin heteroresistance was seen in 93.8% of the
16 colistin-susceptible isolates
South Korea 6.8% of 221 isolates were colistin resistant
35
37. Combination by Kill Kinetics & Population analysis
Ps aeruginosa: Imipenem or Rifampicin
Acinetobacter spp.: Doripenem or Cefepime
Kleb pneumoniae: Meropenem or Amikacin
Sulbactam was not tested.
37
41. Take home messages
1. Colistin has emerged as effective treatment for carbapenem
resistant Gram Negative infections
2. Colistin is associated with lower mortality than no effective
treatment in these infections.
3. Colistin is associated with higher mortality than beta lactam
antibiotics in sensitive bacterial infections.
4. Nephrotoxicity rates are not higher with colistin, colistin
induced nephrotoxicity is reversible
5. Emergence of colistin resistance has been described in high
use settings
6. Synergy with carbapenem, rifampicin & sulbactam has been
reported 41