The case involves a 55-year-old woman admitted to the ICU with respiratory failure. She was started on vancomycin and meropenem empirically based on local susceptibility trends. Her condition worsened and BAL culture grew Klebsiella pneumoniae. Rapid molecular testing detected OXA-48 carbapenemase. Studies from India have found high rates of OXA-48 producing K. pneumoniae bloodstream isolates. OXA-48 is commonly co-produced with ESBLs and other carbapenemases, complicating treatment.
GCMA-Tackling the menace of MDR gram negative pathogens with a novel BL-BLI-...Jigar Mehta
The patient presented with worsening respiratory status and fever. Klebsiella pneumoniae was isolated from BAL culture and rapid molecular testing detected OXA-48. OXA-48 is commonly reported in India and often co-produced with ESBLs. Given the detection of OXA-48 and the likelihood of ESBL co-production based on local epidemiology, ceftazidime-avibactam was initiated due to its activity against OXA-48 producers and many ESBLs.
This document summarizes sessions from the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held in September 2013 in Denver, Colorado. The conference included workshops, lectures, symposia and poster sessions covering topics in infectious diseases, microbiology, antimicrobial resistance, new antibiotics, and more. One of the highlighted issues was the global rise of carbapenemase-producing organisms, with several presentations focusing on epidemiology and management of carbapenem-resistant Enterobacteriaceae. Other topics included pharmacokinetics/pharmacodynamics of antimicrobials, diagnostics using MALDI-TOF mass spectrometry, and infections such as bloodstream infections and endocarditis. Over 10,000
Accelerating COVID-19 Therapies: How a streamlined biosafety strategy can get...MilliporeSigma
Access the interactive recording: https://bit.ly/2xB2eRs
Abstract:
Vaccine and other biologic developers have long relied on traditional, growth-based methods for the detection of adventitious agents in a biosafety testing package. However, at a time where speed is of the essence, relying on testing methods that take many weeks is a real concern. Fortunately, alternative rapid detection methods can shorten timelines significantly — especially for Phase I testing. Here we will take you through these rapid alternatives and outline a testing strategy that can bring your therapy to the clinic faster.
Accelerating COVID-19 Therapies: How a streamlined biosafety strategy can get...Merck Life Sciences
Access the interactive recording: https://bit.ly/2xB2eRs
Abstract:
Vaccine and other biologic developers have long relied on traditional, growth-based methods for the detection of adventitious agents in a biosafety testing package. However, at a time where speed is of the essence, relying on testing methods that take many weeks is a real concern. Fortunately, alternative rapid detection methods can shorten timelines significantly — especially for Phase I testing. Here we will take you through these rapid alternatives and outline a testing strategy that can bring your therapy to the clinic faster.
The document describes a study that used MALDI-TOF MS to identify mycobacterial isolates. It compared two protein extraction protocols (A and B) on reference strains and clinical isolates, finding protocol A identified 92.1% of isolates to the species level compared to 50% for protocol B. Protocol A was then used to identify 27 environmental mycobacterial isolates, with two isolates misidentified by PRA-hsp65 but correctly identified by MALDI-TOF MS. Sequencing of the hsp65 and 16S rRNA genes confirmed the MALDI-TOF MS identifications. The results support the use of MALDI-TOF MS as a rapid and valuable tool for identifying
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.
This study analyzed burn wound swabs collected from 187 hospitalized patients over 3 years to identify aerobic bacterial pathogens and their antibiotic resistance patterns. The most common isolate was Pseudomonas aeruginosa (49.4% of isolates), followed by Staphylococcus aureus (22.2%) and various Enterobacteriaceae species. P. aeruginosa demonstrated high resistance to many commonly used antibiotics but was most susceptible to piperacillin/tazobactam and imipenem. 59% of S. aureus isolates were methicillin-resistant but all were susceptible to vancomycin and linezolid. The high prevalence of multidrug-resistant bacteria indicates a need for improved infection control and empiric antibiotic strategies tailored to
Ceftazidime-Avibactam Is Superior toOther Treatment Regimens againstCarbape...Abdullatif Al-Rashed
Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia
This study compared outcomes of patients with carbapenem-resistant K. pneumoniae bacteremia treated with ceftazidime-avibactam to other regimens. It found that patients who received ceftazidime-avibactam had significantly higher clinical success and survival rates compared to those who received carbapenem plus aminoglycoside, carbapenem plus colistin, or other therapies. This provides evidence that ceftazidime-avibactam may be superior as first-line treatment for carbapenem-resistant K.
GCMA-Tackling the menace of MDR gram negative pathogens with a novel BL-BLI-...Jigar Mehta
The patient presented with worsening respiratory status and fever. Klebsiella pneumoniae was isolated from BAL culture and rapid molecular testing detected OXA-48. OXA-48 is commonly reported in India and often co-produced with ESBLs. Given the detection of OXA-48 and the likelihood of ESBL co-production based on local epidemiology, ceftazidime-avibactam was initiated due to its activity against OXA-48 producers and many ESBLs.
This document summarizes sessions from the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held in September 2013 in Denver, Colorado. The conference included workshops, lectures, symposia and poster sessions covering topics in infectious diseases, microbiology, antimicrobial resistance, new antibiotics, and more. One of the highlighted issues was the global rise of carbapenemase-producing organisms, with several presentations focusing on epidemiology and management of carbapenem-resistant Enterobacteriaceae. Other topics included pharmacokinetics/pharmacodynamics of antimicrobials, diagnostics using MALDI-TOF mass spectrometry, and infections such as bloodstream infections and endocarditis. Over 10,000
Accelerating COVID-19 Therapies: How a streamlined biosafety strategy can get...MilliporeSigma
Access the interactive recording: https://bit.ly/2xB2eRs
Abstract:
Vaccine and other biologic developers have long relied on traditional, growth-based methods for the detection of adventitious agents in a biosafety testing package. However, at a time where speed is of the essence, relying on testing methods that take many weeks is a real concern. Fortunately, alternative rapid detection methods can shorten timelines significantly — especially for Phase I testing. Here we will take you through these rapid alternatives and outline a testing strategy that can bring your therapy to the clinic faster.
Accelerating COVID-19 Therapies: How a streamlined biosafety strategy can get...Merck Life Sciences
Access the interactive recording: https://bit.ly/2xB2eRs
Abstract:
Vaccine and other biologic developers have long relied on traditional, growth-based methods for the detection of adventitious agents in a biosafety testing package. However, at a time where speed is of the essence, relying on testing methods that take many weeks is a real concern. Fortunately, alternative rapid detection methods can shorten timelines significantly — especially for Phase I testing. Here we will take you through these rapid alternatives and outline a testing strategy that can bring your therapy to the clinic faster.
The document describes a study that used MALDI-TOF MS to identify mycobacterial isolates. It compared two protein extraction protocols (A and B) on reference strains and clinical isolates, finding protocol A identified 92.1% of isolates to the species level compared to 50% for protocol B. Protocol A was then used to identify 27 environmental mycobacterial isolates, with two isolates misidentified by PRA-hsp65 but correctly identified by MALDI-TOF MS. Sequencing of the hsp65 and 16S rRNA genes confirmed the MALDI-TOF MS identifications. The results support the use of MALDI-TOF MS as a rapid and valuable tool for identifying
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.
This study analyzed burn wound swabs collected from 187 hospitalized patients over 3 years to identify aerobic bacterial pathogens and their antibiotic resistance patterns. The most common isolate was Pseudomonas aeruginosa (49.4% of isolates), followed by Staphylococcus aureus (22.2%) and various Enterobacteriaceae species. P. aeruginosa demonstrated high resistance to many commonly used antibiotics but was most susceptible to piperacillin/tazobactam and imipenem. 59% of S. aureus isolates were methicillin-resistant but all were susceptible to vancomycin and linezolid. The high prevalence of multidrug-resistant bacteria indicates a need for improved infection control and empiric antibiotic strategies tailored to
Ceftazidime-Avibactam Is Superior toOther Treatment Regimens againstCarbape...Abdullatif Al-Rashed
Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia
This study compared outcomes of patients with carbapenem-resistant K. pneumoniae bacteremia treated with ceftazidime-avibactam to other regimens. It found that patients who received ceftazidime-avibactam had significantly higher clinical success and survival rates compared to those who received carbapenem plus aminoglycoside, carbapenem plus colistin, or other therapies. This provides evidence that ceftazidime-avibactam may be superior as first-line treatment for carbapenem-resistant K.
Latest Updates in Biosafety Testing for Gene TherapyMilliporeSigma
The document discusses the latest regulatory expectations and challenges for biosafety testing of gene therapies, including how to design a robust safety testing strategy to test for bacteria, fungi, mycoplasma, endotoxins, and adventitious viruses using methods such as sterility testing, PCR assays, and in vivo and in vitro testing. It also covers emerging areas like next generation sequencing, replication competent AAV detection, and characterization of residual DNA levels.
The document discusses the latest regulatory expectations and challenges for biosafety testing of gene therapies, including how to design a robust safety testing strategy to test for bacteria, fungi, mycoplasma, endotoxins, and adventitious viruses using methods such as sterility testing, PCR assays, and in vivo and in vitro testing. It also covers emerging areas like next generation sequencing, replication competent AAV detection, and characterization of residual DNA levels.
Treatment of infections caused by MDR-Gramnegatives: Update (Literature review)PROANTIBIOTICOS
This document summarizes several studies related to the treatment of infections caused by multidrug-resistant Gram-negative bacteria. It reviews literature on carbapenemase-producing Enterobacteriaceae, combinations of "weird" antimicrobials for extremely drug-resistant Gram-negatives, and the optimization of antibiotic dosing. For carbapenemase-producing Enterobacteriaceae, combination therapy is generally recommended but outcomes are heterogeneous. Studies also investigated the efficacy of carbapenems depending on the carbapenemase genotype. The combination of colistin and glycopeptides showed potential benefit for some multidrug-resistant organisms. A randomized trial of colistin plus rifampin for XDR Acinetobacter did not find significant clinical benefit. Extended infusion
This document discusses molecular diagnostic methods for detecting drug resistance in gram-positive bacteria. It covers several key points:
1) Traditional phenotypic methods for antimicrobial susceptibility testing require pure culture and take several days for results, while genotypic methods can provide results within hours directly from patient specimens without culturing.
2) Important resistance mechanisms in clinically relevant gram-positive pathogens include beta-lactamases in Staphylococcus and penicillin-binding protein mutations conferring methicillin resistance.
3) Newer molecular techniques for antimicrobial susceptibility testing include PCR, real-time PCR, and next-generation sequencing, which can more rapidly detect resistance genes compared to traditional phenotypic methods.
Role of the Laboratory in Antimicrobial Resistance DataAnuj Sharma
The document discusses the role of microbiology laboratories in collecting, analyzing, and circulating antimicrobial resistance data. It outlines how laboratories provide antibiograms, which summarize local bacterial susceptibility patterns to guide empiric antibiotic therapy. The data can also be used for quality improvement, infection control, outbreak detection, and surveillance of resistance trends over time. The document recommends following Clinical and Laboratory Standards Institute guidelines for generating high quality antibiograms and discusses how data can be managed and shared using software tools like WHONET.
Vaccines are valuable and specialized products, of great diversity have already achieved great success in controlling many diseases of economics importance in farm and companion animals, but present they do not cover all infections, access to modern techniques are used for designing to new vaccine ,not only prolongation of immunity, but also to better practical aspects, such as product stability and less dependence on cold-storage.
The document summarizes recent updates in tuberculosis (TB) diagnostics and treatment. It discusses improvements and gaps in diagnosing TB infection versus active disease. New World Health Organization recommendations for TB diagnostics are outlined. Challenges in aligning current diagnostics with new multidrug-resistant TB treatment options are described. The future of TB diagnostics includes biomarkers and moving away from reliance on sputum samples for diagnosis. New tests are needed to address diagnostic gaps and better monitor treatment response.
Journal club presentation: by RxVichuZ!! ;)RxVichuZ
My 97th powerpoint... deals with the comparative study of efficacy of piperacillin-tazobactam, as compared to meropenem in the treatment of ESBL(Extended spectrum beta-lactamases) infections.
A summarized insight has been provided, using research article from JAMA.
Journal Presentation on Antibiotic Susceptibility Pattern in Cancer Patientsnayanadiv
This retrospective study analyzed 1178 blood samples from cancer patients with suspected bloodstream infections at a tertiary cancer hospital in India from 2016. The study found a blood culture positivity rate of 27.35% and Gram-negative bacteria accounted for over half of infections. Escherichia coli was the most common organism isolated. Antibiotic resistance was high, especially for cephalosporins. Sensitivity to amikacin was the highest for most Gram-negative bacteria. The study provides important local data on infectious organisms and antibiotic susceptibility to help guide effective treatment of bloodstream infections in cancer patients.
This study analyzed 200 pus samples to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and associated risk factors. 80 samples were found to contain S. aureus, of which 29 tested positive for the mecA gene, confirming MRSA. Testing methods like cefoxitin disk diffusion and oxacillin screen agar were compared to the PCR gold standard. The cefoxitin test showed 96.55% sensitivity and 96.22% specificity for detecting MRSA, outperforming oxacillin tests. Risk factors like hospital acquisition, diabetes, and sex were also analyzed. The study concludes that cefoxitin testing is an effective alternative to PCR for MRSA detection
Background and study aim: During last two decades, there has been a world-wide trend in increasing occurrence of enterococcal infections in the hospitals. The aim of present study was to determine the spectrum of enterococcal infections, species prevalence, antimicrobial and characteristics of vancomycin resistant enterococci (VRE) in a tertiary care hospital, Eastern India.
Patients and Methods: Between January 2013 and July 2014, 152 Enterococcus species were obtained from clinical samples. Enterococci were identified using standard biochemical tests. Antimicrobial susceptibility was tested by Kirby-Bauer disk diffusion according to Clinical resistance
& Laboratory Standards Institute (CLSI) guidelines.VRE agar base was used to screen VRE isolates. Minimum inhibitory concentration (MIC) values of VRE isolates were determined using Epsilometer-test. VRE isolates were also examined by PCR to detect vanA gene.
Results: From 1602 clinical samples, 961 (60%) were culture positive and 152 (15.8%) enterococcal isolates were obtained. Most common species isolated was E. faecalis (63.8%) followed by E. faecium (35.5%). Majority of enterococcal infections were detected from ICUs and surgical wards and clinically presented as UTIs. Disk diffusion method showed 67.1% were resistant to penicillin, 61.2% ampicillin, 58.5% ciprofloxacin, 46.7% high-level gentamicin, 42. 8% high-level streptomycin, 7.9% teicoplanin and none to linezolid. Twenty (13.2%) enterococcal isolates were vancomycin resistant in VRE screen and disk diffusion method. Epsilometer-test of VRE isolates showed 8 (40%) isolates were resistant and 9 (45%) were intermediately resistant. From 20 VRE isolates, six showed VanA and two VanB phenotypes and all six VanA phenotypes had vanA gene cluster.
Conclusion: More accurate and reliable MIC determination tests should be performed in all suspected VRE isolates. Confirmatory PCR is required for identifying resistant gene cluster.
Key words: Enterococci, E. faecalis, E. faecium, VRE, vanA gene
This document describes the validation of a whole genome sequencing (WGS) assay implemented in a public health laboratory to characterize Mycobacterium tuberculosis complex strains. The assay provides rapid identification and comprehensive drug resistance profiles for eight drugs. Validation using 608 clinical isolates found 99% accurate identification and 96% concordance between WGS and culture-based drug susceptibility testing. WGS resistance profiles are reported an average of 9 days sooner for first-line drugs and 32 days sooner for second-line drugs compared to culture-based methods.
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMilliporeSigma
This document discusses approaches for viral safety in AAV processes. It begins with background on the growing gene therapy market and evolving regulatory landscape. It then outlines a risk mitigation strategy using a tripod approach of prevent, remove, and detect. Specific techniques discussed for prevent include using virus-resistant cell lines and pretreated raw materials. Techniques discussed for remove include virus filtration, chromatography, and the use of Benzonase endonuclease to digest DNA. The document emphasizes a layered, multi-pronged approach for complete biosafety assurance in AAV processes.
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/2VRylbi
How can you keep an adventitious virus from contaminating your gene therapy that is delivered by an adeno virus vector? As viral vector bioprocessing advances, regulatory requirements for viral safety will as well. Learn how to define your viral clearance strategy for AAV delivered gene therapies.
How do you define a strategy for viral clearance for a process that inherently aims at purifying a virus?
Gene delivery using AAV has received a boost from two major approvals and the nearly 300 programs in the clinic. Novel gene therapies using viral vectors enable companies to transform the lives of people living with certain rare and ultra-rare diseases where treatments are often not available currently. Amongst a multitude of challenges in viral vector bioprocessing, uncertainty in regulatory expectations is a major challenge to gene therapy developers. Regulatory requirements are evolving as the science and manufacturing matures with more stringent measures for viral safety assurance expected for future approvals.
Learn how to implement techniques for adventitious virus removal in your viral vector process; we will focus on strategies for viral clearance along your journey towards commercial readiness of AAV-based processes.
In this webinar, you will learn:
• AAV process flows and focus areas for viral safety
• Strategies for implementing viral clearance measures in bioprocessing
• Case studies and data driven approaches on log reduction values (LRV) in a viral vector process
• Best practices and evaluation roadmaps on conducting viral clearance studies
Presented by: Ratish Krishnan, Senior Strategy Consultant, Novel Modalities Bioprocessing
Global cancer immunotherapy market outlook 2020KuicK Research
"Global Cancer Immunotherapy Market Outlook 2020" Report Highlight:
Introduction & Classification of Cancer Immunotherapy
Global Cancer Immunotherapy Pipeline by Company, Indication & Phase
Marketed Cancer Immunotherapies Clinical Insight & Patent Analysis by Company & Indication
Global Cancer Immunotherapy Pipeline: 1834 Drugs
Marketed Cancer Immunotherapies: 113 Drugs
Cancer Monoclonal Antibodies Pipeline: 622 Cancer mAb
Cancer Vaccines Pipeline: 312 Vaccines
Marketed Cancer mAb: 36 mAb
Marketed Cancer Vaccines: 12 Vaccines
This research article describes a novel method using high-density peptide microarrays and computational analysis to identify B-cell epitopes in patients with celiac disease. Overlapping peptide sequences from native and deamidated gliadin proteins were synthesized onto silicon wafers. Serum samples from celiac patients and controls were tested on the microarrays. Computational analysis identified distinct epitope sets that differentiated celiac patients from controls with high accuracy. The identified epitopes have potential for developing improved diagnostic tests for celiac disease.
Prediction of antitubercular_peptides_from_sequencShahidAkbar22
This document describes research on developing machine learning models to predict antitubercular peptides from their amino acid sequences. Tuberculosis is a major global health problem and new therapies are needed due to the emergence of drug-resistant strains. The researchers created datasets of known antitubercular peptides and other peptides to train and test their models. They used different machine learning algorithms and peptide sequence features, such as amino acid composition and terminal residues, as inputs. Their best performing ensemble model achieved 73.2% accuracy at predicting antitubercular peptides. They also created a web server to make the models available to other researchers working on designing new antitubercular peptides.
This slide tries to explain and introduce you to the mRNA Vaccine Technology, describes mRNA Vaccines, Mechanism , Delivery, some research and case study of pandemic and advantages disadvantages & application see for yourself in detail.
BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadi...UniversitasGadjahMada
1) The study investigated BRCA1 promoter methylation and its association with clinicopathological characteristics in 56 Indonesian breast cancer patients.
2) BRCA1 promoter methylation was detected in 48 of 56 (85%) patients. Lower BRCA1 mRNA expression was associated with higher methylation levels, suggesting epigenetic silencing of BRCA1.
3) However, no significant associations were found between methylation levels, BRCA1 expression, and clinicopathological factors like tumor stage or size. This study provides the first analysis of BRCA1 methylation in an Indonesian breast cancer population.
Dr. Rajni Sharma is a senior professor in the Department of Microbiology at SMS Medical College in Jaipur, India. She has published over 43 papers in national indexed journals and 10 in international journals. She serves as the nodal officer for several national disease surveillance programs in India related to antimicrobial resistance, diphtheria, pertussis, and epidemic infectious diseases. Dr. Sharma has led several research studies in collaboration with institutions in India and the United States focused on antimicrobial resistance, Streptococcus pneumoniae vaccines, and strengthening hospital infection control. She has received recognition and awards for her work in microbiology and serves on committees related to her field.
This document discusses ventilator-associated pneumonia (VAP). It begins with the epidemiology of VAP, including that it is the second most common ICU infection and responsible for half of all ICU antibiotics. Risk factors for VAP include increased duration of mechanical ventilation and prior antibiotic use. Diagnosing VAP is challenging due to the lack of a definitive test. Methods for prevention include keeping the head of the bed elevated, daily sedation vacations, and the use of bundled interventions. Quantitative cultures and invasive diagnostic tests provide more specific diagnosis but do not consistently alter management or improve outcomes.
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Latest Updates in Biosafety Testing for Gene TherapyMilliporeSigma
The document discusses the latest regulatory expectations and challenges for biosafety testing of gene therapies, including how to design a robust safety testing strategy to test for bacteria, fungi, mycoplasma, endotoxins, and adventitious viruses using methods such as sterility testing, PCR assays, and in vivo and in vitro testing. It also covers emerging areas like next generation sequencing, replication competent AAV detection, and characterization of residual DNA levels.
The document discusses the latest regulatory expectations and challenges for biosafety testing of gene therapies, including how to design a robust safety testing strategy to test for bacteria, fungi, mycoplasma, endotoxins, and adventitious viruses using methods such as sterility testing, PCR assays, and in vivo and in vitro testing. It also covers emerging areas like next generation sequencing, replication competent AAV detection, and characterization of residual DNA levels.
Treatment of infections caused by MDR-Gramnegatives: Update (Literature review)PROANTIBIOTICOS
This document summarizes several studies related to the treatment of infections caused by multidrug-resistant Gram-negative bacteria. It reviews literature on carbapenemase-producing Enterobacteriaceae, combinations of "weird" antimicrobials for extremely drug-resistant Gram-negatives, and the optimization of antibiotic dosing. For carbapenemase-producing Enterobacteriaceae, combination therapy is generally recommended but outcomes are heterogeneous. Studies also investigated the efficacy of carbapenems depending on the carbapenemase genotype. The combination of colistin and glycopeptides showed potential benefit for some multidrug-resistant organisms. A randomized trial of colistin plus rifampin for XDR Acinetobacter did not find significant clinical benefit. Extended infusion
This document discusses molecular diagnostic methods for detecting drug resistance in gram-positive bacteria. It covers several key points:
1) Traditional phenotypic methods for antimicrobial susceptibility testing require pure culture and take several days for results, while genotypic methods can provide results within hours directly from patient specimens without culturing.
2) Important resistance mechanisms in clinically relevant gram-positive pathogens include beta-lactamases in Staphylococcus and penicillin-binding protein mutations conferring methicillin resistance.
3) Newer molecular techniques for antimicrobial susceptibility testing include PCR, real-time PCR, and next-generation sequencing, which can more rapidly detect resistance genes compared to traditional phenotypic methods.
Role of the Laboratory in Antimicrobial Resistance DataAnuj Sharma
The document discusses the role of microbiology laboratories in collecting, analyzing, and circulating antimicrobial resistance data. It outlines how laboratories provide antibiograms, which summarize local bacterial susceptibility patterns to guide empiric antibiotic therapy. The data can also be used for quality improvement, infection control, outbreak detection, and surveillance of resistance trends over time. The document recommends following Clinical and Laboratory Standards Institute guidelines for generating high quality antibiograms and discusses how data can be managed and shared using software tools like WHONET.
Vaccines are valuable and specialized products, of great diversity have already achieved great success in controlling many diseases of economics importance in farm and companion animals, but present they do not cover all infections, access to modern techniques are used for designing to new vaccine ,not only prolongation of immunity, but also to better practical aspects, such as product stability and less dependence on cold-storage.
The document summarizes recent updates in tuberculosis (TB) diagnostics and treatment. It discusses improvements and gaps in diagnosing TB infection versus active disease. New World Health Organization recommendations for TB diagnostics are outlined. Challenges in aligning current diagnostics with new multidrug-resistant TB treatment options are described. The future of TB diagnostics includes biomarkers and moving away from reliance on sputum samples for diagnosis. New tests are needed to address diagnostic gaps and better monitor treatment response.
Journal club presentation: by RxVichuZ!! ;)RxVichuZ
My 97th powerpoint... deals with the comparative study of efficacy of piperacillin-tazobactam, as compared to meropenem in the treatment of ESBL(Extended spectrum beta-lactamases) infections.
A summarized insight has been provided, using research article from JAMA.
Journal Presentation on Antibiotic Susceptibility Pattern in Cancer Patientsnayanadiv
This retrospective study analyzed 1178 blood samples from cancer patients with suspected bloodstream infections at a tertiary cancer hospital in India from 2016. The study found a blood culture positivity rate of 27.35% and Gram-negative bacteria accounted for over half of infections. Escherichia coli was the most common organism isolated. Antibiotic resistance was high, especially for cephalosporins. Sensitivity to amikacin was the highest for most Gram-negative bacteria. The study provides important local data on infectious organisms and antibiotic susceptibility to help guide effective treatment of bloodstream infections in cancer patients.
This study analyzed 200 pus samples to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and associated risk factors. 80 samples were found to contain S. aureus, of which 29 tested positive for the mecA gene, confirming MRSA. Testing methods like cefoxitin disk diffusion and oxacillin screen agar were compared to the PCR gold standard. The cefoxitin test showed 96.55% sensitivity and 96.22% specificity for detecting MRSA, outperforming oxacillin tests. Risk factors like hospital acquisition, diabetes, and sex were also analyzed. The study concludes that cefoxitin testing is an effective alternative to PCR for MRSA detection
Background and study aim: During last two decades, there has been a world-wide trend in increasing occurrence of enterococcal infections in the hospitals. The aim of present study was to determine the spectrum of enterococcal infections, species prevalence, antimicrobial and characteristics of vancomycin resistant enterococci (VRE) in a tertiary care hospital, Eastern India.
Patients and Methods: Between January 2013 and July 2014, 152 Enterococcus species were obtained from clinical samples. Enterococci were identified using standard biochemical tests. Antimicrobial susceptibility was tested by Kirby-Bauer disk diffusion according to Clinical resistance
& Laboratory Standards Institute (CLSI) guidelines.VRE agar base was used to screen VRE isolates. Minimum inhibitory concentration (MIC) values of VRE isolates were determined using Epsilometer-test. VRE isolates were also examined by PCR to detect vanA gene.
Results: From 1602 clinical samples, 961 (60%) were culture positive and 152 (15.8%) enterococcal isolates were obtained. Most common species isolated was E. faecalis (63.8%) followed by E. faecium (35.5%). Majority of enterococcal infections were detected from ICUs and surgical wards and clinically presented as UTIs. Disk diffusion method showed 67.1% were resistant to penicillin, 61.2% ampicillin, 58.5% ciprofloxacin, 46.7% high-level gentamicin, 42. 8% high-level streptomycin, 7.9% teicoplanin and none to linezolid. Twenty (13.2%) enterococcal isolates were vancomycin resistant in VRE screen and disk diffusion method. Epsilometer-test of VRE isolates showed 8 (40%) isolates were resistant and 9 (45%) were intermediately resistant. From 20 VRE isolates, six showed VanA and two VanB phenotypes and all six VanA phenotypes had vanA gene cluster.
Conclusion: More accurate and reliable MIC determination tests should be performed in all suspected VRE isolates. Confirmatory PCR is required for identifying resistant gene cluster.
Key words: Enterococci, E. faecalis, E. faecium, VRE, vanA gene
This document describes the validation of a whole genome sequencing (WGS) assay implemented in a public health laboratory to characterize Mycobacterium tuberculosis complex strains. The assay provides rapid identification and comprehensive drug resistance profiles for eight drugs. Validation using 608 clinical isolates found 99% accurate identification and 96% concordance between WGS and culture-based drug susceptibility testing. WGS resistance profiles are reported an average of 9 days sooner for first-line drugs and 32 days sooner for second-line drugs compared to culture-based methods.
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMilliporeSigma
This document discusses approaches for viral safety in AAV processes. It begins with background on the growing gene therapy market and evolving regulatory landscape. It then outlines a risk mitigation strategy using a tripod approach of prevent, remove, and detect. Specific techniques discussed for prevent include using virus-resistant cell lines and pretreated raw materials. Techniques discussed for remove include virus filtration, chromatography, and the use of Benzonase endonuclease to digest DNA. The document emphasizes a layered, multi-pronged approach for complete biosafety assurance in AAV processes.
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/2VRylbi
How can you keep an adventitious virus from contaminating your gene therapy that is delivered by an adeno virus vector? As viral vector bioprocessing advances, regulatory requirements for viral safety will as well. Learn how to define your viral clearance strategy for AAV delivered gene therapies.
How do you define a strategy for viral clearance for a process that inherently aims at purifying a virus?
Gene delivery using AAV has received a boost from two major approvals and the nearly 300 programs in the clinic. Novel gene therapies using viral vectors enable companies to transform the lives of people living with certain rare and ultra-rare diseases where treatments are often not available currently. Amongst a multitude of challenges in viral vector bioprocessing, uncertainty in regulatory expectations is a major challenge to gene therapy developers. Regulatory requirements are evolving as the science and manufacturing matures with more stringent measures for viral safety assurance expected for future approvals.
Learn how to implement techniques for adventitious virus removal in your viral vector process; we will focus on strategies for viral clearance along your journey towards commercial readiness of AAV-based processes.
In this webinar, you will learn:
• AAV process flows and focus areas for viral safety
• Strategies for implementing viral clearance measures in bioprocessing
• Case studies and data driven approaches on log reduction values (LRV) in a viral vector process
• Best practices and evaluation roadmaps on conducting viral clearance studies
Presented by: Ratish Krishnan, Senior Strategy Consultant, Novel Modalities Bioprocessing
Global cancer immunotherapy market outlook 2020KuicK Research
"Global Cancer Immunotherapy Market Outlook 2020" Report Highlight:
Introduction & Classification of Cancer Immunotherapy
Global Cancer Immunotherapy Pipeline by Company, Indication & Phase
Marketed Cancer Immunotherapies Clinical Insight & Patent Analysis by Company & Indication
Global Cancer Immunotherapy Pipeline: 1834 Drugs
Marketed Cancer Immunotherapies: 113 Drugs
Cancer Monoclonal Antibodies Pipeline: 622 Cancer mAb
Cancer Vaccines Pipeline: 312 Vaccines
Marketed Cancer mAb: 36 mAb
Marketed Cancer Vaccines: 12 Vaccines
This research article describes a novel method using high-density peptide microarrays and computational analysis to identify B-cell epitopes in patients with celiac disease. Overlapping peptide sequences from native and deamidated gliadin proteins were synthesized onto silicon wafers. Serum samples from celiac patients and controls were tested on the microarrays. Computational analysis identified distinct epitope sets that differentiated celiac patients from controls with high accuracy. The identified epitopes have potential for developing improved diagnostic tests for celiac disease.
Prediction of antitubercular_peptides_from_sequencShahidAkbar22
This document describes research on developing machine learning models to predict antitubercular peptides from their amino acid sequences. Tuberculosis is a major global health problem and new therapies are needed due to the emergence of drug-resistant strains. The researchers created datasets of known antitubercular peptides and other peptides to train and test their models. They used different machine learning algorithms and peptide sequence features, such as amino acid composition and terminal residues, as inputs. Their best performing ensemble model achieved 73.2% accuracy at predicting antitubercular peptides. They also created a web server to make the models available to other researchers working on designing new antitubercular peptides.
This slide tries to explain and introduce you to the mRNA Vaccine Technology, describes mRNA Vaccines, Mechanism , Delivery, some research and case study of pandemic and advantages disadvantages & application see for yourself in detail.
BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadi...UniversitasGadjahMada
1) The study investigated BRCA1 promoter methylation and its association with clinicopathological characteristics in 56 Indonesian breast cancer patients.
2) BRCA1 promoter methylation was detected in 48 of 56 (85%) patients. Lower BRCA1 mRNA expression was associated with higher methylation levels, suggesting epigenetic silencing of BRCA1.
3) However, no significant associations were found between methylation levels, BRCA1 expression, and clinicopathological factors like tumor stage or size. This study provides the first analysis of BRCA1 methylation in an Indonesian breast cancer population.
Similar to Tacking the menage of gram negative inf with novel bl bli.pptx (20)
Dr. Rajni Sharma is a senior professor in the Department of Microbiology at SMS Medical College in Jaipur, India. She has published over 43 papers in national indexed journals and 10 in international journals. She serves as the nodal officer for several national disease surveillance programs in India related to antimicrobial resistance, diphtheria, pertussis, and epidemic infectious diseases. Dr. Sharma has led several research studies in collaboration with institutions in India and the United States focused on antimicrobial resistance, Streptococcus pneumoniae vaccines, and strengthening hospital infection control. She has received recognition and awards for her work in microbiology and serves on committees related to her field.
This document discusses ventilator-associated pneumonia (VAP). It begins with the epidemiology of VAP, including that it is the second most common ICU infection and responsible for half of all ICU antibiotics. Risk factors for VAP include increased duration of mechanical ventilation and prior antibiotic use. Diagnosing VAP is challenging due to the lack of a definitive test. Methods for prevention include keeping the head of the bed elevated, daily sedation vacations, and the use of bundled interventions. Quantitative cultures and invasive diagnostic tests provide more specific diagnosis but do not consistently alter management or improve outcomes.
This document discusses antibiotic stewardship and the importance of judicious antibiotic use. It notes that nearly half of hospitalized patients receive antibiotics. While antibiotics have been life-saving, there has been misuse through overprescribing for viral infections and lack of understanding of principles. This has led to increased antibiotic resistance. The document advocates for antibiotic stewardship programs in hospitals to optimize use and limit unintended consequences like toxicity and resistance. It describes the goals and elements of effective stewardship programs.
The documents discusses two cases related to medical negligence:
1) Pooja Sharma v/s Maharaj Agrasen hospital - A premature baby was discharged without advising retinal checks, which later revealed retinal damage. This was considered negligence.
2) Kunal Saha Vs. AMRI - A woman died from a rare skin disease after being prescribed steroids. Her family sued the hospital and doctors for negligence. The Supreme Court found the doctors and hospital negligent for improper treatment and lack of expertise.
Both cases highlight the importance of informed consent, following standard procedures, advising on important follow-ups, and having the proper expertise when treating complex cases. Failure to do so can be
CBS endocrinology trics complte draft .pptxaceforum
A 33-year-old man presented with sudden onset of headache, chest pain and hypertension. Imaging revealed a right adrenal mass. He had regional hypokinesia on echocardiogram and elevated troponin, suggesting catecholamine-induced cardiomyopathy from a pheochromocytoma. The patient would be diagnosed with a right adrenal pheochromocytoma and treated with alpha-blockade to control blood pressure prior to tumor removal.
The document announces an upcoming critical care conference that will feature expert lectures on topics like hospital acquired infections, fluid and electrolyte balance in the ICU, and pulmonary embolism. It also lists case presentations from various hospitals. The bimonthly meeting will include an expert lecture and case presentations every alternate month on the first Saturday at 8:30pm sharp. It mentions future critical care events like FCCS and EMCON 2017. The document provides information on the agenda and schedule for an upcoming critical care conference.
This document describes the management of a 45-year-old male patient who presented with polytrauma including a head injury from a motor vehicle accident. Initial resuscitation involved administration of fluids and blood products to stabilize vital signs. Investigations revealed a subarachnoid hemorrhage and fractures. The patient underwent surgery and was transferred to the ICU for further care and monitoring. The document discusses important considerations for fluid choice in neurosurgical patients, noting risks of hypotonic, hypertonic and large volumes of non-balanced fluids, and the benefits of balanced salt solutions for maintaining adequate cerebral perfusion pressure and oxygenation without worsening edema or acid-base status.
Post Covid Lung Fibrosis is an increasing problem, with some COVID-19 survivors experiencing continued symptoms long after testing negative. Risk factors for developing pulmonary fibrosis after COVID-19 include older age, illness severity, length of ICU stay/ventilation, smoking history, and steroid/antiviral therapy. Predictors on CT imaging include interstitial thickening and parenchymal bands. Treatment options include continued steroids, antifibrotics like pirfenidone and nintedanib which may reduce inflammation and fibrosis, with caution regarding anticoagulation risk. Oxygen support, pulmonary rehab and transplant are also used, with long term follow up recommended.
This document describes the case of a 46-year-old male with no prior medical history who presented with chest pain and was found to have an ST elevation myocardial infarction (STEMI). He underwent treatment including thrombolysis and stenting, with resolution of symptoms. Two days later, he tested positive for COVID-19. Despite being asymptomatic, his D-dimer level rose significantly, indicating a COVID-19 associated coagulopathy. He was discharged on rivaroxaban for 3 weeks to prevent thrombosis given his elevated risk. The document then reviews the coagulopathy seen in COVID-19 patients and guidelines for extended thromboprophylaxis on discharge for high-risk medical patients.
This document provides guidelines for nutrition screening and feeding critically ill patients in the ICU. It recommends using validated screening tools like MST or MUST to identify high-risk patients for early, aggressive nutrition intervention. Indirect calorimetry studies show COVID-19 patients have high caloric needs, especially in the first week, ranging from 15-20 kcal/kg and increasing to 26-32 kcal/kg in subsequent weeks. Clinical guidelines recommend 1.2-2 g/kg of protein per day for non-obese patients and 2-2.5 g/kg for obese patients. Early enteral nutrition is best delivered in liquid form using closed systems to meet nutritional needs and reduce risks of contamination.
ECCO2R is a technique that removes carbon dioxide from the blood to correct hypercapnia and respiratory acidosis. It is similar to ECMO but uses lower blood flow, so it has little effect on blood oxygenation. Initially developed for ARDS patients, ECCO2R could now be used to treat hypercapnic respiratory insufficiency in COPD or ARDS patients to allow less invasive mechanical ventilation.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Tacking the menage of gram negative inf with novel bl bli.pptx
1. TACKLING THE
MENACE OF MDR
GRAM NEGATIVE
INFECTIONS WITH
EARLY USE OF
NOVEL BL-BLI: CASE
FILES
2. Disclaimer
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Complex, Bandra (East), Mumbai
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For the use only of Registered Medical Practitioners or a Hospital or a Laboratory
General disclaimer for the presentation
“The Content in this presentation is only intended for healthcare professionals in India. The medical
information in this presentation is provided as an information resource only, and is not to be used or
relied on for any diagnostic or treatment purpose.”
Additional slide by the Speaker
“The views and opinions mentioned in the presentation is strictly that of the author and the individuals
expressing the same and Pfizer may not necessarily endorse the same. Pfizer (including its parent,
subsidiary and affiliate entities) makes no representation or warranties of any kind, expressed or
implied; as to the content used in the presentation and/or the accuracy, completeness of its content.”
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7. Case
history
• 55-year-old woman
• history of type 2 diabetes mellitus & chronic
obstructive pulmonary disease, along with coronary
artery disease with a 3-vessel bypass 5 years prior
• developed new onset shortness of breath and fever
• On arrival in emergency,
– Respiratory status worsened
– Her ventilation rapidly deteriorated despite the use of
noninvasive positive pressure ventilation and she
became minimally responsive, prompting endotracheal
intubation and admission to the medical intensive care
unit
– Chest X-ray showed lobar infiltrate
Adapted from Maley J.H., Stevens J.P. (2020) Ventilator-Associated Pneumonia. In: Hyzy R., McSparron J. (eds) Evidence-Based Critical Care. Springer, Cham. https://doi.org/10.1007/978-
3-030-26710-0_29
8. WHAT WOULD BE THE NEXT
STEP?
1. START AN APPROPRIATE
ANTIBIOTIC
2. SEND CULTURE SAMPLES
3. ASSESS RISK FACTORS FOR
MDR
Points of discussion
9. Importance
of local
epidemiology
• Prior to prescribing antimicrobial therapy, resistance
patterns within an institution are important to
consider, and close liaison with the microbiology
laboratory facilitates the decision-making process 1
• Awareness of the local epidemiology allows tailoring of
initial therapy according to local trends in pathology
and resistance 2
1. Tamma PD, Cosgrove SE, Maragakis LL. Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev. 2012;25(3):450-470. doi:10.1128/CMR.05041-11
2. Morris S, Cerceo E. Trends, Epidemiology, and Management of Multi-Drug Resistant Gram-Negative Bacterial Infections in the Hospitalized Setting. Antibiotics (Basel). 2020;9(4):196. Published 2020
Apr 20. doi:10.3390/antibiotics9040196
10. Case contd • Patient started on vancomycin and meropenem
• On day 5 of the ICU, , she developed a new fever and
her oxygenation worsened
• A chest radiograph now showed diffuse, bilateral
infiltrates
• BAL sample was sent for culture and sensitivity
Adapted from Maley J.H., Stevens J.P. (2020) Ventilator-Associated Pneumonia. In: Hyzy R., McSparron J. (eds) Evidence-Based Critical Care. Springer, Cham. https://doi.org/10.1007/978-
3-030-26710-0_29
12. Role of laboratory diagnosis in management of
MDR gram negative infections
• Conventional phenotypic
antimicrobial susceptibility testing
(AST) methods- provide results 36-72 h
after patients' sample collection 1
• Novel molecular methods (i.e. no
microbial growth-based methods) are
much faster, and their times to results
are 1-4h 1
• Benefit the individual patient by
enabling timely & targeted
antimicrobial optimization, which, in
turn, may lead to decreased mortality,
shortened hospital stay, and lower
hospitalization costs. 2,3,4
• Decreased use of unnecessary empirical
therapies 3
1. De Angelis G, Grossi A, Menchinelli G, Boccia S, Sanguinetti M, Posteraro B. Rapid molecular tests for detection of antimicrobial resistance determinants in Gram-negative organisms from positive blood
cultures: a systematic review and meta-analysis. Clin Microbiol Infect. 2020;26(3):271-280.; 2. Lutgring JD, Limbago BM. The Problem of Carbapenemase-Producing-Carbapenem-Resistant-Enterobacteriaceae
Detection. J Clin Microbiol. 2016 Mar;54(3):529-34 3. Messacar K, Parker SK, Todd JK, Dominguez SR. Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and
Antimicrobial Stewardship. J Clin Microbiol. 2017;55(3):715-723 4. Bauer KA, Perez KK, Forrest GN, Goff DA. Review of rapid diagnostic tests used by antimicrobial stewardship programs. Clin Infect Dis.
Test method Accuracy Turn-around time * Information provided
Modified Hodge test Moderate Next day Detection of carbapenemase
activity
Carba NP test Moderate Same day Detection of carbapenemase
activity
Carbapenemase inactivation
method
High Next Day Detection of carbapenemase
activity
MALDI-TOF MS (MATRIX
ASSISTED LASER DESORTPTION
INONIZATION – TIME OF FLIGHT
MASS SPECTRA)
High Same Day Detection of carbapenemase
activity
PCR High Same Day Detection of specific
carbapenemase gene
Microarray High Same Day Detection of specific
carbapenemase gene
.
*Turnaround time, time to results from pure culture of isolate
13. Case contd • Culture results- Klebsiella pneumoniae
• On rapid molecular testing, OXA-48 detected
• Disc diffusion test shows susceptibility to ceftazidime
avibactam
Hypothetical scenario
14. Understanding
OXA- 48
(Oxacillinase Beta lactamase )
• 11 enzyme variants have since been identified
across the world
• OXA-48b, OXA-54, OXA-162, OXA-163, OXA-181,
OXA-199, OXA-204, OXA-232, OXA-242, and OXA-
247 (OXA- 48 like variants)
• Mortality remains high in patients infected with
OXA-48-like producers
• OXA-48 - frequently reported
from E. coli and Klebsiella pneumoniae
• High level of OXA-48 resistance is associated with
co-production of extended spectrum β-
lactamase(ESBL)
• Co-production of OXA-48 is also seen with other
carbapenemase including NDM-1andVIM
Bakthavatchalam YD, Anandan S, Veeraraghavan B. Laboratory detection and clinical implication of oxacillinase-48 like carbapenemase: The hidden threat. J Global Infect Dis 2016;8:41-50
15. Identification of
carbapenemase-mediated
resistance among
Enterobacteriaceae
bloodstream isolates: A
molecular study from
India (2017)
Consecutive, non-duplicate isolates of Escherichia coli
(EC) and Klebsiella pneumoniae from clinically
diagnosed bloodstream infections were screened for
the presence of carbapenem resistance by standard
disk-diffusion method and minimum inhibitory
concentration breakpoints
• Carbapenemase encoding genes were amplified by
polymerase chain reaction
Mohanty S, Gajanand M, Gaind R. Identification of carbapenemase-mediated resistance among Enterobacteriaceae bloodstream isolates: A molecular study from India. Indian J Med Microbiol
2017;35:421-5
387 isolates (214 K. pneumoniae, 173 EC)
tested
93 (24.03%) were found to be CRE
71 (76.3%) were positive for at least one
tested carbapenemase gene
New Delhi metallo-β-lactamse-1 (65.6%)
Oxacillinase (OXA)-48 (24.7%)
OXA-181 (23.6%)
Verona integron-encoded metallo-β-lactamase
(6.4%) and
K. pneumoniae carbapenemase (2.1%).
16. Endemicity of
OXA-48 and NDM-
1 Carbapenemase
Producing
Klebsiella
pneumoniae and
Escherichia
coli from a Tertiary
Hospital in
Varanasi, India
(2018)
Total Isolates=293 E. coli and 236 K. pneumoniae
Multidrug resistant isolates = 391.
159 isolates (64 E. coli and 75 K. pneumoniae)= carbapenem
resistant enterobacteriaceae.
• Investigated the prevalence of OXA-48 like and NDM-1 among clinical isolates of
K. pneumoniae and E. coli
• Multiplex PCR-based detection of the blaNDM-1 and blaOXA-48
Filgona, J., Banerjee, T., & Anupurba, S. (2018). Endemicity of OXA-48 and NDM-1 Carbapenemase Producing Klebsiella pneumoniae and Escherichia coli from a Tertiary Hospital in Varanasi,
India. Journal of Advances in Microbiology, 12(3), 1-8.
50/159(31.4%) isolates were positive for NDM-1
44/159(27.7%) for OXA-48, while
17/159(10.7%) co-harboured NDM-1 and OXA-48 like
genes
17. Co-production with other beta lactamases
• Co-carriage of OXA-48 and other beta -
lactamases in 265 OXA-48-positive
Enterobacteriaceae collected in 2012 to
2015
• As many as 80% of OXA-48-positive isolates are
reported to coproduce ESBLs
• In the study, 88.7% of OXA-48-positive isolates
(n = 235) carried additional β-lactamases
capable of hydrolyzing expanded-spectrum
cephalosporins or aztreonam
• % susceptibility to meropenem ranged from 0 to
36.4%
It is important to know the local prevalence of OXA-48 and
OXA-48-like β-lactamases among clinical isolates so that
infections caused by isolates with a higher MIC value for a
carbapenem, even if the MIC does not cross the threshold
of “resistant,” should be considered for treatment options
other than carbapenems.
Kazmierczak KM, Bradford PA, Stone GG, de Jonge BLM, Sahm DF. In Vitro Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam against OXA-48-Carrying Enterobacteriaceae Isolated as Part of the
International Network for Optimal Resistance Monitoring (INFORM) Global Surveillance Program from 2012 to 2015. Antimicrob Agents Chemother. 2018;62(12):e00592-18
19. Case contd • Culture results- Klebsiella pneumoniae
• On rapid molecular testing, OXA-48 detected
May indicate
ESBL production
Rawat D, Nair D. Extended-spectrum β-lactamases in Gram Negative Bacteria. J Glob Infect Dis. 2010;2(3):263-274. doi:10.4103/0974-777X.68531
Hypothetical scenario
20. Ceftazidime- avibactam
Ceftazidime-Third generation cephalosporin
Avibactam- non beta lactam- beta lactamase inhibitor
First-in-class
Inhibition of β-lactamases is covalent but reversible
(characteristic that other known β-lactamase
inhibitors lack)
The activity of AVI is reinstated once acted
Spectrum of activity
in vitro activity against many
important Gram-negative
pathogens
Many ESBL, AmpC KPC and OXA-
48-producing Enterobacterales
Drug-resistant P.aeruginosa
isolates
× Acinetobacter
× Metallo- beta lactamases
Shirley M. Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. Drugs. 2018;78(6):675-692
Dietl B, Martínez LM, Calbo E, Garau J. Update on the role of ceftazidime-avibactam in the management of carbapenemase-producing Enterobacterales. Future Microbiol. 2020;15:473-
21. Avibactam has a broad spectrum of activity2
1. Zhanel GG, Lawson CD, Adam H, Schweizer F, Zelenitsky S, Lagacé-Wiens PR, Denisuik A, Rubinstein E, Gin AS, Hoban DJ, Lynch JP. Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Drugs. 2013 Feb 1;73(2):159-77.
2. Stachyra T, Péchereau MC, Bruneau JM, Claudon M, Frère JM, Miossec C, Coleman K, Black MT. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-β-lactam β-lactamase inhibitor. Antimicrobial agents and chemotherapy. 2010 Dec
1;54(12):5132-8.;
3. Lagacé-Wiens P, Walkty A, Karlowsky JA. Ceftazidime–avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections. Core evidence. 2014;9:13.
Avibactam
Class A
TEM1,2, SHV1,2
CTX-M1,2
KPC1-3
Class B IMP3, VIM3, NDM13
Class C
AmpC1,2
ACC-13, CMY-13, FOX3,
Class D OXA 483
CTX-M, cefotaxime-β-lactamase; KPC, Klebsiella pneumoniae carbapenemase;
NDM, New Delhi metallo-β-lactamase; TEM, temoneira; SHV, sulfhydryl variable; VIM, Verona integron-encoded metallo-β-lactamase.
24. • The most frequent source of infection were IAI (28%), followed by
respiratory (26%) and UTI (25%)
• 31 (54%) patients had a severe infection
• The was no association between mortality and monotherapy with CAZ–AVI; the
recurrence rate at 90 days was 10%
• CAZ–AVI resistance was not detected in any case and only two patients
developed AEs related to treatment
• Mortality at 14 days was 14%; in multivariate analysis, the only mortality risk
factor was INCREMENT-CPE score >7 (HR 11.7, 95%
CI 4.2–20.6)
• CAZ–AVI showed promising results, even in monotherapy, for the
treatment of patients with severe infections due to OXA-48-producing
Enterobacteriaceae and limited therapeutic options
Effectiveness of CAZ–AVI as salvage therapy for treatment of infections due to OXA-48 carbapenemase-
producing Enterobacteriaceae
Sousa A, et al. J Antimicrob Chemother 2018;73:3170–3175
Study background
• An observational study of a prospectively collected cohort of adult patients
receiving CAZ–AVI
• The first treatment course of each patient was analysed
• Efficacy and safety were evaluated as 14 and 30 day mortality,
recurrence rate at 90 days, resistance development and occurrence
of AEs
• 57 patients were treated with CAZ–AVI
AEs, adverse events; CAZ–AVI, ceftazidime–avibactam; CRE,
carbapenem-resistant Enterobacteriaceae; IAI, intra-abdominal
infection; MIC, minimum inhibitory concentration; OXA, oxacillinase;
UTI, urinary tract infection
Antibiotic Susceptible isolates, n (%)
Colistin 45 (75)
Imipenem 2 (3)
Imipenem MIC <8 mg/L 27 (47)
Meropenem 1 (2)
Fosfomycin 10 (17)
Tigecycline 7 (12)
Amikacin 3 (5)
CAZ–AVI 57 (100)
Adapted from Sousa A, et al. 2018
Antimicrobial susceptibility of isolates (n=57) from patients treated with CAZ–AVI
25. • The median time from admission to isolation of CRE culture was 22.5 days in
the CAZ–AVI group and 17 days in the comparative group (P=0.7)
• A carbapenemase gene was isolated from 35 (92%) patients; the OXA-48
gene was the predominant gene identified in 28 (74%) isolates; 8 out of 10
patients in the CAZ–AVI group and 15 out of 28 in the comparative group
achieved clinical remission (P=0.14)
• At 30 days, all-cause mortality was observed in five patients in the CAZ–AVI group and 16 patients in the comparative group, accounting for 50 and 57%
respectively;
• CAZ–AVI is an alternative standard therapy for OXA-48-type CRE
Efficacy of CAZ–AVI in the treatment of infections due to CRE
Alraddadi BM, et al. BMC Infect Dis 2019;19:772
Study background
• Retrospective cohort study of patients with established CRE infections from
January 2017 until August 2018 was conducted
• All patients who received CAZ–AVI and all cultures with carbapenem-
resistant isolates were screened
• Patients who received CAZ–AVI for CRE infections were compared with
patients who received other agents
• A total of 38 consecutive patients with CRE infections were identified, age
and baseline comorbidities were similar between the two groups
CAZ–AVI, ceftazidime–avibactam;
CLABSI, central line-associated blood stream infections;
cIAI, complicated intra-abdominal infections
CRE, carbapenem-resistant Enterobacteriaceae;
cUTI, chronic urinary tract infections;
HAP, hospital acquired pneumonia; OXA, oxacillinase;
SSTI; soft tissue infection
Type of infection CAZ–AVI Comparative P value
HAP 5 (50) 14 (50) >0.99
cUTI 3 (30) 8 (28.6) >0.99
cIAI 3 (30) 5 (17.8) 0.41
Adapted from Alraddadi, et al. 2019
Baseline characteristics of patients with CRE infections who
received CAZ–AVI or different CRE specific antibiotics
26. • The mortality rate was similar in patients treated with monotherapy or
combination therapy (RR=1.18, 95% CI 0.88–1.58; P=0.259)
• All studies except one reported data on the emergence of resistance to
CAZ–AVI, with a total of eight patients (4.1%) in the monotherapy and six
patients (3%) in the combination group developing
CAZ–AVI resistance
• No difference was found between the two groups when analysing the rate
of microbiological cure (64.9% for combination therapy vs. 63.4% for
monotherapy; RR=1.04, 95% CI 0.85–1.28, P=0.705)
• Meta-analysis suggest that use of CAZ–AVI in monotherapy or combination
for infections due to CRE or CRPa could show a similar effect on mortality
and microbiological cure rates
Efficacy of CAZ–AVI in monotherapy or combination therapy against carbapenem-resistant
Gram-negative bacteria: a meta-analysis
Onorato L, et al. Int J Antimicrob Agents 2019;54(6):735–740
Study background
• Comprehensive computerised literature search was performed based on
CAZ–AVI monotherapy or combination therapy with other active agents for
infections due to CRE or CRPa
• Databases Medline, Google Scholar and the Cochrane Library
were searched
• Inclusion criteria characteristics were:
– Reported sufficient data to calculate RR and 95% CI
– Case-control studies, cohort studies or case series
– Full-text, in English
• Overall, 11 articles were included in the meta-analysis
Outcome No. of
studies
Combination
therapy
(events/total
%)
Monotherapy
(events/total
%)
Risk ration
(95% CI)
P-value Heterog
eneity
test (P-
value)
I2
Mortality (all patients) 11 77/202 (38.1) 60/194 (30.9) 1.18
(0.88-1.58)
0.259 0.987 0
%
Microbiological cure (all
patients)
7 61/94 (64.9) 97/153 (63.4) 1.04
(0.85-1.28)
0.705 0.883 0
%
Mortality (excluding
patients infected with
Pseudomonas )
9 74/191 (38.7) 58/186 (31.2) 1.20
(0.89-1.61)
0.229 0.923 0
%
Microbiological cure
(excluding patients
infected with
Pseudomonas )
6 57/90 (63.3) 91/147 (61.9) 1.05
(0.84-1.31)
0.653 0.687 0
%
CAZ–AVI, ceftazidime–avibactam; CRE, carbapenem-resistant
Enterobacteriaceae; CI, confidence intervals; CRPa, carbapenem-
resistant Pseudomonas aeruginosa;
RR, relative risk
Meta-analysis of clinical outcomes in the overall population
Adapted from Onorato, et al. 2019
27. Ceftazidime–avibactam compared to colistin
• Prospective multicenter cohort
• 137 patients with CRE infection1
o 38 received ceftazidime–avibactam first (monotherapy n=14 [37%])1
o 99 received colistin first (monotherapy n=6 [6%])1
• Baseline characteristics were similar
o Median Charlson comorbidity score 3 (IQR: 1–5)1
o Median Pitt bacteremia score 4 (IQR: 2–6)1
• Types of CRE infection included:
o Respiratory tract infection (n=30)1
o UTI (n=19)1
• Pathogens included: K. pneumoniae (n=133), Enterobacter spp. (n=4)1
BSI, bloodstream infection; CRE, carbapenem-resistant Enterobacteriaceae; IQR, interquartile range; UTI, urinary tract infection.
1. van Duin D, et al. Clin Infect Dis 2018;66:163–71.
28. Ceftazidime–avibactam compared to colistin
CAZ–AVI, ceftazidime–avibactam; CI, confidence interval; IPTW, inverse probability of treatment weighting.
1. van Duin D, et al. Clin Infect Dis 2018;66:163–71.
Ceftazidime–avibactam Colistin
Death rate evaluated at Day 30 after therapy1
3/38 (8%) in CAZ–AVI patients versus 33/99 (33%) in colistin group
difference 23%, P=0.001
At Day 301
+ 64% adjusted probability of a better prognosis with CAZ–AVI than colistin
(CI 95% 57–71%)
Clinical outcomes were better in the patients who were treated first with
ceftazidime-avibactam rather than colistin
The use of ceftazidime-avibactam was associated with improved clinical
outcomes, especially decreased all-cause hospital mortality rate and
improved benefit-risk outcomes.
29. Early use
was
associated
with
improved
outcomes
Temkin E, Torre-Cisneros J, Beovic B et al. Ceftazidime-avibactam as salvage therapy
for infections caused by carbapenem-resistant organisms. Antimicrob. Agents
Chemother. 61(2), e01964–16 (2017). Jorgensen SCJ, Trinh TD, Zasowski EJ et al. Real-
world experience with ceftazidime-avibactam for multidrug-resistant gram-negative
bacterial infections. Open Forum Infect. Dis. 6(12), ofz522 (2019).
Study by Jorgensen et al
and
STUDY byTEMKIN et al
30. 1. Bonine NG, et al. Impact of Delayed Appropriate Antibiotic Therapy on Patient Outcomes by Antibiotic Resistance Status from Serious Gram-negative Bacterial Infections. Am J Med Sci. 2019;357(2):103-11
† Defined as no receipt of antibiotic(s) with relevant microbiological activity on or
within 2 days of index date. ‡ Compared with receipt of timely appropriate therapy.
31. Study by Jorgensen et al: Real-World Experience With Ceftazidime-Avibactam for
Multidrug-Resistant Gram-Negative Bacterial Infections
• Multicenter, retrospective, observational cohort study conducted at 6 centers in the United States between
2015 and 2019
• 203 patients included:
1. were ≥18 years of age,
2. received ≥72 hours of CZA therapy
• 57.6% with hospital-acquired infections
– 50.2% (n=102) patients with a high severity of illness at infection onset residing in the ICU and a median
SOFA score of 5 (IQR, 2–8)
• 57.6% Carbapenem-resistant Enterobatceriaceae.
– 63.2% K pneumoniae
– 14.5% Escherichia coli
– 12.8% Enterobacter Spp.
Jorgensen SCJ, Trinh TD, Zasowski EJ et al. Real-world experience with ceftazidime-avibactam for multidrug-resistant gram-negative bacterial infections. Open Forum Infect. Dis. 6(12), ofz522 (2019).
32. Study by Jorgensen et al: Real-World Experience With Ceftazidime-Avibactam for
Multidrug-Resistant Gram-Negative Bacterial Infections
• Primary outcome:
– Clinical failure defined as a composite of
30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of
infection on CZA-AVI
• Study Results:
– Early use of CZA (within 48 hours of infection onset), was associated with improved clinical outcomes in all indications
including bacteraemia
– 30-day mortality rate at 17.2% and recurrence rates at 6%
– 71% Overall clinical success rate*
– Therapy resistance was not detected
– Underscores the important role of rapid diagnostic testing for early pathogen identification and susceptibility testing
Jorgensen SCJ, Trinh TD, Zasowski EJ et al. Real-world experience with ceftazidime-avibactam for multidrug-resistantgram-negative bacterial infections. Open Forum Infect. Dis. 6(12), ofz522 (2019).
*Jorgensen SCJ, et al. Real-world experience with Ceftazidime-Avibactam formultidrug-resistant gram-negative bacterial infections. Open Forum Infect Dis. 2019;6(12):ofz522. (SupplementaryAppendix).
33. STUDY by TEMKIN ET al: 2017
• 38 patients included: Minimum length of treatment with compassionate use CAZ-AVI was 3 days
– 63.2% (n=24) were given the standard dose of CAZ-AVI throughout their treatment (2 g ceftazidime– 0.5 g avibactam
every 8 h)
– 14 patients with renal impairment received adjusted doses.
• Antibiotics before CAZ-AVI
– Received antibiotics before CAZ-AVI for this infection: 36 (94.7)
– Days of antibiotic treatment before CAZ-AVI, median (IQR): 13 (7–31)
– No. of antibiotics before CAZ-AVI, median (IQR): 3 (3–4)
• 34 patients infected with Klebsiella pneumoniae
– 1 with Klebsiella oxytoca
– 1 with Escherichia coli
– 2 with P. aeruginosa
• 89.5% (n=34) hospital-acquired infections
Temkin E, Torre-Cisneros J, Beovic B et al. Ceftazidime-avibactam as salvage therapy for infections caused by carbapenem-resistant organisms. Antimicrob. Agents Chemother. 61(2), e01964–16 (2017
Study Design:
34. STUDY by TEMKIN ET al: 2017
– 79% of patients with negative cultures at the end of treatment survived until discharge
– 73% of patients achieved microbiological cure
– 39.5%All-cause in-hospital mortality
– 24% 30 day all-cause mortality
– 59% Overall clinical success rate
– ‘Waiting to exhaust all other (and potentially more toxic) treatment options before resorting to CAZ-AVI may reduce a
patient’s likelihood of being cured’
Temkin E, Torre-Cisneros J, Beovic B et al. Ceftazidime-avibactam as salvage therapy for infections caused by carbapenem-resistant organisms. Antimicrob. Agents Chemother. 61(2), e01964–16 (2017
Primary Outcomes
Clinical cure at the end of treatment
Microbiological cure at the end of treatment
All-cause in-hospital mortality
Study Results:
35. Population
Pharmacokinetic
Modelling of
Ceftazidime and
Avibactam
in the Plasma and
Epithelial Lining
Fluid of Healthy
Volunteers
• Compartmental modelling analysis
• ELF penetration of both ceftazidime (52%) and
avibactam (42%) was greater than previously
calculated at plasma concentrations relevant for
efficacy (~ 8 mg/l for ceftazidime and ~ 1 mg/l for
avibactam)
• ELF exposures of both drugs exceeded levels
required for efficacy in plasma
Dimelow R et al. Population Pharmacokinetic Modelling of Ceftazidime and Avibactam in the Plasma and Epithelial Lining Fluid of Healthy Volunteers. Drugs in R&D (2018) 18:221–230
36. 1. Vena A, Giacobbe DR, Castaldo N, et al. Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-
Resistant Enterobacterales. Antibiotics (Basel). 2020;9(2):71; 2. Santevecchi BA, Smith TT, MacVane SH. Clinical experience with ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than Klebsiella
pneumoniae. Int J Antimicrob Agents. 2018;51(4):629-635
Outcomes in patients with P.aeruginosa
Study, year Study characteristics Susceptibility to Caz-Avi Outcomes Comments
Vena, 2020, Italy,
Infections other
than CR
Enterobacterales 1
41 pts received 72 h of
ceftazidime-avibactam
for GNB
Nosocomial pneumonia
49%
P.aeruginosa in 33 pts (80.5%); all
MDR isolates
Combination therapy in 80% pts
(colistin,AG, carbapenems)
Clinical success
at the end of the
follow-up period
was 90.5%,
• No
genotyping
done
Santevecci, 2018
USA 2
Infections other
than
K.pneumoniae
10 pts received Caz-AVI;
46% had pneumonia;
Total 21 isolates.
8 isolates (38%) of P.aeruginosa;
60% polymicrobial; Median MIC
1.5mg/L
50% received targeted
combination therapy
Clinical success
was achieved in
70% (n = 7/10) of
patients.
37. Role of
ceftazidime-
avibactam
• One of the most important additions to the
armamentarium for GN infections
• One of the first antibiotics that targets OXA
and KPC
• Post market reports, reflecting real-life use
are very encouraging, in terms of safety,
clinical response, and survival
• Efficacy compared to colistin better with
64% probability of better outcome
• Early use has been associated with better
outcomes
Karaiskos I, Lagou S, Pontikis K, Rapti V, Poulakou G. The "Old" and the "New" Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How. Front Public Health. 2019 Jun 11;7:151.
38. INFECTIOUS DISEASES SOCIETY OF
AMERICA (IDSA) ANTIMICROBIAL
RESISTANT TREATMENT GUIDANCE:
GRAM-NEGATIVE BACTERIAL INFECTIONS
A Focus on Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E),
Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-
Treat Resistance (DTR-P. aeruginosa
Please refer to the complete guideline for more information
39. General
recommendations
• Preferred and alternative treatment
recommendations in this guidance
document assume that the causative
organism has been identified and in
vitro activity of antibiotics has been
demonstrated
• Empiric treatment recommendations
are not provided
• Recommendations on duration of
therapy are not mentioned
Tamma P et al. Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. A Focus on Extended-
Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat
Resistance (DTR-P. aeruginosa). Published by IDSA. Published on 8 Sept 2020. Available at https://www.idsociety.org/practice-guideline/amr-guidance/.
Accessed on 8th Feb 2022
40. Knowledge of whether a
CRE clinical isolate is
carbapenemase-producing
and, if it is, the specific
carbapenemase produced
is important in guiding
treatment decisions
Tamma P et al. Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial Resistant Gram-Negative
Infections. A Focus on Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant
Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Published by IDSA.
Published on 8 Sept 2020. Available at https://www.idsociety.org/practice-guideline/amr-guidance/. Accessed on 8th Feb 2022
41. Recommended antibiotic
treatment options for
carbapenem-resistant
Enterobacterales (CRE),
assuming in vitro
susceptibility to agents
Source of infection Preferred treatment Alternative treatment
Pyelonephritis or cUTI Ceftazidime-avibactam,
meropenem-vaborbactam,
imipenem-cilastatin-
relebactam, and cefiderocol
Once-daily aminoglycosides
Infections outside of the
urinary tract
Resistant to ertapenem,
meropenem, AND
carbapenemase testing
results are either not
available or negative
Ceftazidime-avibactam*,
meropenem-vaborbactam,
and imipenem-cilastatin-
relebactam
Cefiderocol
Tigecycline, eravacycline
(uncomplicated intra-
abdominal infections only)
OXA-48-like
carbapenemase identified
Ceftazidime-avibactam* Cefiderocol
Tigecycline, eravacycline
(uncomplicated intra-
abdominal infections only)
*Ceftazidime-avibactam is approved in adults for treatment of cIAI, cUTI including pyelonephritis and HAP-VAP with susceptible gram
negative organisms
Tamma P et al. Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. A Focus on Extended-Spectrum β-
lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P.
aeruginosa). Published by IDSA. Published on 8 Sept 2020. Available at https://www.idsociety.org/practice-guideline/amr-guidance/. Accessed on 8th Feb 2022
42. Recommended antibiotic
treatment options for
difficult-to-treat (DTR)
Pseudomonas aeruginosa,
assuming in vitro
susceptibility to agents
Source of
infection
Preferred treatment Alternative
treatment
Pyelonephritis or
cUTI
Ceftolozane-tazobactam,
ceftazidime-avibactam,
imipenem-cilastatin-
relebactam, and cefiderocol
Once-daily
aminoglycosides
Infections outside
of the urinary
tract
Ceftolozane-tazobactam,
ceftazidime-avibactam*, or
imipenem-cilastatin-
relebactam
Cefiderocol
Aminoglycoside
monotherapy: limited
to uncomplicated
bloodstream
infections with
complete source
control
Tamma P et al. Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. A Focus on
Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with
Difficult-to-Treat Resistance (DTR-P. aeruginosa). Published by IDSA. Published on 8 Sept 2020. Available at https://www.idsociety.org/practice-
guideline/amr-guidance/. Accessed on 8th Feb 2022
*Ceftazidime-avibactam is approved in adults for treatment of cIAI, cUTI including pyelonephritis and HAP-VAP with susceptible gram
negative organisms
43. Ceftazidime-avibactam & stewardship
• Use of ceftazidime/avibactam in clinical practice requires high levels of antimicrobial stewardship
• Stewardship teams are tasked with minimizing barriers to utilization, but must also be careful not to
promote overuse of these agents
• Minimizing barriers will ensure that these agents can be appropriately used when needed.
• Institutions with particularly high rates of CRE, testing of ceftazidime/avibactam susceptibility for
organisms identified as carbapenem-resistant should be considered to further reduce time to
susceptibility information
• Protecting the use of ceftazidime/avibactam will help mitigate development of resistance and maintain
their use as CRE active agents for as long as possible
• Development of criteria for use or a system of protected use is essential to make sure the antibiotic is
safeguarded
Bradley N, Lee Y. Practical Implications of New Antibiotic Agents for the Treatment of Carbapenem-Resistant Enterobacteriaceae. Microbiol Insights. 2019; 12: 1178636119840367.
44. Summary • Resistance among gram negative bacteria is on the
rise, especially for carbapenems
• Rise in the incidence of OXA-48 (either alone or in
combination with other beta lactamases such as
ESBLs)
• Rapid molecular tests will help direct appropriate
antimicrobial therapy
• Ceftazidime-avibactam has shown good efficacy in the
real world studies for carbapenem resistant
enterobacteriaceae and MDR P.aeruginosa
• It has resulted in better outcomes as compared to
colistin in CRE
• Early use is associated with better outcomes
• Good antimicrobial stewardship practices will be
required
45. Case 1* • 55-year-old woman
• history of type 2 diabetes mellitus & chronic
obstructive pulmonary disease, along with coronary
artery disease with a 3-vessel bypass 5 years prior
• developed new onset shortness of breath and fever
• On arrival in emergency,
– Respiratory status worsened
– Her ventilation rapidly deteriorated despite the use of
noninvasive positive pressure ventilation and she
became minimally responsive, prompting endotracheal
intubation and admission to the medical intensive care
unit
– Chest X-ray showed lobar infiltrate
* This is a hypothetical case
46. WHAT WOULD BE THE NEXT
STEP?
1. START AN APPROPRIATE
ANTIBIOTIC
2. SEND CULTURE SAMPLES
3. ASSESS RISK FACTORS FOR
MDR
Points of discussion
47. Case contd • Patient started on vancomycin and meropenem
• On day 5 of the ICU, , she developed a new fever and
her oxygenation worsened
• A chest radiograph now showed diffuse, bilateral
infiltrates
• BAL sample was sent for culture and sensitivity
49. Case contd • Culture results- Klebsiella pneumoniae
• On rapid molecular testing, OXA-48 detected
• Ceftazidime-Avibactam therapy initiated
May indicate
ESBL production
50. Case 2*
• 76 y M patient
• CAD, PTCA in 2013, hypothyroid
• PLWH (virologically suppressed, onTDF/FTC/EFV)
• 17/8/19-Admitted with AcuteAWMI with in stent stenosis of
RCA stent- plan CABG
• Preop- Hb- 8.4,TC- 9670, PC- 2.79 lac, Creatinine- 3.1
• 20/8/19-CABG done- extubated on POD 1
• 24/8- Drowsy, cough with expectoration ? LVF
• Sputum C/S sent- Klebsiella pneumoniae (CR)
• Genotyping sent
* This is a hypothetical case
51. • 30/8- Fever,TC- 22050
• New opacities in CXR, leucocytosis,
BIPAP, drowsy
• ID Reference
• (Old) sputum C/S- Kleb pneumoniae
• No new respiratory culture available
• Blood C/S negative
54. CAZ/AVI – Sensitive (MIC 2 mcg/ml)
Rxed- 10 days of monotherapy with Ceftazidime/avibactam
Patient discharged on day 12 of therapy
55. • Study Name : Novel β-lactam/β-lactamase inhibitor combinations versus
alternative antibiotics in adults with hospital-acquired pneumonia or
ventilator-associated pneumonia: an integrated analysis of three
randomised controlled trial.
This study was published in Journalo f global antibitimicobial resistance
in 2021.
Pubmed, web of science, the cochrane library, ovid MEDLINE, embase
and EBSCO databases were searched for randomised controlled trials
(RCTs) published before 13 september 2020.
Only RCTs comparing the treatment efficacy of novel BL/BLI
combinations with other antibiotics for HAP/VAP in adult patients were
included in this integrated analysis.
PROVEN EFFICACY FOR BL- BLI COMBINATION: Some latest research
56. • Early administration of appropriate antibiotics is key for managing
patients with HAP/VAP.
• The presence of multidrug-resistant organisms (MDROs), such as
carbapenem-resistant Pseudomonas aeruginosa, extended-spectrum
β-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-
resistant Acinetobacter baumannii, is a major factor associated with
the selection of inappropriate antibiotic treatment.
• To overcome the threat of MDROs, new antibiotics with broad-
spectrum activity are urgently required, particularly for use against
antibiotic-resistant bacteria.
57. • Recently, several novel β-lactam/β-lactamase inhibitor (BL/BLI)
combinations, including ceftolozane/tazobactam, ceftazidime/avibactam,
meropenem/vaborbactam and imipenem/cilastatin/relebactam, have been
assessed in largescale randomised controlled trials (RCTs) for clinical use,
such as in cases of complicated intra-abdominal infection (cIAI),
complicated urinary tract infection (cUTI) and HAP/VAP.
• Moreover, several meta-analyses have provided evidence regarding their
efficacy and safety for clinical treatment of cIAIs and cUTIs.
• However, evidence regarding the efficacy and safety of novel BL/BLI
combinations in HAP/VAP treatment is lacking.
• This study provided new evidence for the efficacy and safety of these
BL/BLI combinations in the treatment of adult patients with HAP/VAP
58. • All three RCTs included were phase 3, multicentre and multinational
studies.
• Each study investigated one of the following novel BL/BLI
combinations : imipenem/cilastatin/relebactam;
ceftazidime/avibactam; and ceftolozane/tazobactam.
• The comparative agents were meropenem in two studies and
piperacillin/tazobactam in one study.
59.
60.
61. Results: Three RCTs were included and no significant difference in
clinical cure rate of test of cure was observed between the novel
BL/BLI combinations and comparators [odds ratio (OR) = 1.01, 95%
confidence interval (CI) 0.81–1.27; i 2 = 35%].
The 28-day all-cause mortality was 16.2% and 17.6% for patients
receiving novel BL/BLI combinations and comparators, respectively,
and no significant difference was noted (OR = 0.90, 95% ci 0.69–1.16;
i 2 = 11%).
Compared with comparators, novel BL/BLI combinations were
associated with a similar microbiological response (OR = 1.06, 95% ci
0.73–1.54; I 2 = 64%) and a similar risk of adverse events (AES)
[treatment-emergent AES: OR = 1.04, 95% ci 0.83–1.30; I 2 = 0%;
serious AES: OR = 1.14,
Editor's Notes
The menace of gram negative organisms
Antimicrobial Resistance Surveillance and Research Network. January 2019 to December 2019. Annual Report ICMR. Available at https://main.icmr.nic.in/sites/default/files/upload_documents/Final_AMRSN_Annual_Report_2019_29072020.pdf Accessed on 8th Feb 2022.
1. Tamma PD, Cosgrove SE, Maragakis LL. Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev. 2012;25(3):450-470. doi:10.1128/CMR.05041-11
2. Morris S, Cerceo E. Trends, Epidemiology, and Management of Multi-Drug Resistant Gram-Negative Bacterial Infections in the Hospitalized Setting. Antibiotics (Basel). 2020;9(4):196. Published 2020 Apr 20. doi:10.3390/antibiotics9040196
Hypothetical scenario
387 isolates (214 K. pneumoniae, 173 EC) tested, 93 (24.03%) were found to be CRE
Of these, 71 (76.3%) were positive for at least one tested carbapenemase gene
frequency of carbapenemase genes was New Delhi metallo-β-lactamse-1 (65.6%), oxacillinase
(OXA)-48 (24.7%), OXA-181 (23.6%), Verona integron-encoded metallo-β-lactamase (6.4%) and K. pneumoniae carbapenemase (2.1%).
.
ESBL production
Dimelow R et al. Population Pharmacokinetic Modelling of Ceftazidime and Avibactam in the Plasma and Epithelial Lining Fluid of Healthy Volunteers. Drugs in R&D (2018) 18:221–230
Karlowsky KA et al. In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015. Antimicrob Agents Chemother. 2018;62(7):e02569-17.
Kazmierczak KM et al. In vitro activity of ceftazidime/avibactam against isolates of Pseudomonas aeruginosa collected in European countries: INFORM global surveillance 2012-15. J Antimicrob Chemother. 2018;73(10):2777-2781
For internal use only
Bradley N, Lee Y. Practical Implications of New Antibiotic Agents for the Treatment of Carbapenem-Resistant Enterobacteriaceae. Microbiol Insights. 2019; 12: 1178636119840367.