SlideShare a Scribd company logo
1 of 55
Download to read offline
THE RETURN OF THETHE RETURN OF THE
MICROBES!MICROBES!
DO ANTIBIOTICS HAVE ADO ANTIBIOTICS HAVE A
FUTURE?FUTURE?
David C GrolmanDavid C Grolman
Medical DirectorMedical Director
Head of Medical Affairs:Head of Medical Affairs:
Global Established PharmaGlobal Established Pharma
Pfizer Australia & Pfizer New ZealandPfizer Australia & Pfizer New Zealand
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
BACTERIABACTERIA
• Are almost all our friends!Are almost all our friends!
• Are themselves the best protection we haveAre themselves the best protection we have
against colonisation with pathogensagainst colonisation with pathogens
• Have survival mechanisms which pre-date usHave survival mechanisms which pre-date us
by billions of yearsby billions of years
• Outnumber our cells in & on our own bodiesOutnumber our cells in & on our own bodies
by at least 10-foldby at least 10-fold
• Outnumber us on the planet by a factor ofOutnumber us on the planet by a factor of
billionsbillions
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
Where have all the antibioticsWhere have all the antibiotics
gone?gone?
 Why are there so few antibiotics underWhy are there so few antibiotics under
development by pharmaceuticaldevelopment by pharmaceutical
companies and other stakeholders?companies and other stakeholders?
 Do we believe that we are going to ‘runDo we believe that we are going to ‘run
out’ of antibiotic options?out’ of antibiotic options?
 What do we mean by ‘antibiotics’?What do we mean by ‘antibiotics’?
Antibacterials v AntimicrobialsAntibacterials v Antimicrobials
(Fungi, viruses, parasites)(Fungi, viruses, parasites)
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
ANTIBIOTICSANTIBIOTICS
WONDER DRUGS of the 20WONDER DRUGS of the 20thth
CENTURYCENTURY
 Antimicrobial agents are the single classAntimicrobial agents are the single class
of drugs that have most contributed to theof drugs that have most contributed to the
major improvement in prolonged lifemajor improvement in prolonged life
expectancy achieved over the pastexpectancy achieved over the past
centurycentury
 Numerous previously usually fatalNumerous previously usually fatal
infections became treatable –infections became treatable –
Pneumococcal pneumonia, consumption,Pneumococcal pneumonia, consumption,
scarlet fever, diphtheria, wound sepsis,scarlet fever, diphtheria, wound sepsis,
ANTIBIOTIC HISTORYANTIBIOTIC HISTORY
 1920s = first antibiotics discovered1920s = first antibiotics discovered
 1940s = first commercially available1940s = first commercially available
antibioticsantibiotics
RESISTANCE PREDATES THESERESISTANCE PREDATES THESE
EVENTSEVENTS
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
Gram-positive historyGram-positive history
Bacterial response Human response Bacterial response
New pathogens Broad spectrum penicillin Other new pathogens
β-lactamase production β-lactamase inhibitors New β-lactamases
Newer β-lactamases New ‘shaped’ penicillins Altered PBPs
Altered PBPs Glycopeptides Vancomycin-resistance
Vancomycin-resistance Lipopeptides Lipopeptide-resistance
Glycolipopeptide
resistance
Oxazolidinones Enzymatic lysis
Gram-negative historyGram-negative history
Bacterial response Human response Bacterial response
New pathogens Broad spectrum penicillin Other new pathogens
β-lactamase production β-lactamase inhibitors New β-lactamases
Newer β-lactamases Cephalosporins Extended spectrum B L
ESBLs Carbapenems New pathogens
ESBLs Carbapenems Carbapenem resistance
-Efflux
-Carbapenemases
Carbapenem resistance Colistin, tigecycline Enzymatic lysis, efflux
The ‘Ps’ of resistanceThe ‘Ps’ of resistance
 PumpsPumps
 PorinsPorins
 Penicillin-binding protein (PBP) changePenicillin-binding protein (PBP) change
 Proteases (penicillinases to penemases)Proteases (penicillinases to penemases)
 Point mutations & target modificationsPoint mutations & target modifications
 PRE-DETERMINEDPRE-DETERMINED
 PLASMID-MEDIATEDPLASMID-MEDIATED
The bacterial armamentariumThe bacterial armamentarium
 Resistance genesResistance genes
 Virulence factorsVirulence factors
Why don’t all bacteria have all mechanisms?Why don’t all bacteria have all mechanisms?
 These are all energy intensive!These are all energy intensive!
 However: Resistance + virulence genesHowever: Resistance + virulence genes
have recently been seen in combinationhave recently been seen in combination
There will be new antibiotics inThere will be new antibiotics in
the futurethe future
 There will be numerous new antimicrobialThere will be numerous new antimicrobial
agentsagents
 New pathways and potential targets are beingNew pathways and potential targets are being
discovered dailydiscovered daily
 GOAL IS TO FIND AGENTS WHICHGOAL IS TO FIND AGENTS WHICH
ARE:ARE:
 SaferSafer
 Have less environmental impactHave less environmental impact
 Utilise novel pathwaysUtilise novel pathways
LpxC-1LpxC-1
 Blocks the ability of specificallyBlocks the ability of specifically
Acinetobacter baumaniiAcinetobacter baumanii to activate theto activate the
TLR-4 and hence cause the systemicTLR-4 and hence cause the systemic
inflammatory response usually seen ininflammatory response usually seen in
these infectionsthese infections
 Achieved by inhibiting LPS secretionAchieved by inhibiting LPS secretion
 Does not actually kill theDoes not actually kill the AcinetobacterAcinetobacter
 Has no effect on other receptors orHas no effect on other receptors or
mediators from other bacteriamediators from other bacteria
Lin et al: mBio 3(5):e00312-12. doi:10.1128/mBio.00312-12.Lin et al: mBio 3(5):e00312-12. doi:10.1128/mBio.00312-12.
What does cause the emergence ofWhat does cause the emergence of
resistance mechanisms?resistance mechanisms?
 Minimal evidence that correct andMinimal evidence that correct and
appropriate antibiotic leads to resistanceappropriate antibiotic leads to resistance
 Multitude of evidence that incorrect orMultitude of evidence that incorrect or
inappropriate usage does indeed hasteninappropriate usage does indeed hasten
the development of resistancethe development of resistance
 Resistance accelerated by under-dosingResistance accelerated by under-dosing
and excessive duration of therapyand excessive duration of therapy
 We should not be using antibiotics whereWe should not be using antibiotics where
not indicated, appropriate or effectivenot indicated, appropriate or effective
Historical and ongoingHistorical and ongoing
inappropriate usage of antibioticsinappropriate usage of antibiotics
 Gross usage of antibiotics for viral infectionsGross usage of antibiotics for viral infections
where they have no activity, without goodwhere they have no activity, without good
evidence of secondary bacterial infectionevidence of secondary bacterial infection
 Use of antibiotics for non-infectiveUse of antibiotics for non-infective
inflammatory conditions (e.g. allergies) andinflammatory conditions (e.g. allergies) and
for non-antimicrobial effects (e.g. prokineticfor non-antimicrobial effects (e.g. prokinetic
factors)factors)
 Prolonged usage of antibiotics to ‘prevent’Prolonged usage of antibiotics to ‘prevent’
infectioninfection
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
Ongoing inappropriate use in manyOngoing inappropriate use in many
countries of antibiotics in farmingcountries of antibiotics in farming
 Use of antibiotics as an adjunct to animalUse of antibiotics as an adjunct to animal
farming and in agriculturefarming and in agriculture
 Usually done in a vain effort to preventUsually done in a vain effort to prevent
infections in livestock (mainly poultry)infections in livestock (mainly poultry)
 Real problem is overcrowding of animals byReal problem is overcrowding of animals by
modern farming methods with excessivemodern farming methods with excessive
restriction of free animal movementrestriction of free animal movement
 There is scant scientific evidence thatThere is scant scientific evidence that
infections can be prevented by usinginfections can be prevented by using
antibiotics prophylactically in these scenariosantibiotics prophylactically in these scenarios
Appropriate human prophylacticAppropriate human prophylactic
antimicrobial useantimicrobial use
 There is also scant evidence that humanThere is also scant evidence that human
infections can be prevented antibioticsinfections can be prevented antibiotics
used prophylactically or pre-emptivelyused prophylactically or pre-emptively
 Exceptions:Exceptions:
 Surgical prophylaxisSurgical prophylaxis
 Maximum of 24 hours permissibleMaximum of 24 hours permissible
 Fungal prophylaxis in immunosuppressedFungal prophylaxis in immunosuppressed
patientspatients
 Fungal sepsis in limited cIAI scenariosFungal sepsis in limited cIAI scenarios
 SDD ?SDD ?
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
LANDMARK PAPERLANDMARK PAPER
MORTALITYMORTALITY
 Overall for community-acquired infections wasOverall for community-acquired infections was
17,1%17,1%
 Overall for nosocomial infections wasOverall for nosocomial infections was 34,3%34,3%
 Overall for nosocomial sepsis after initial treatmentOverall for nosocomial sepsis after initial treatment
for a community-acquired infection wasfor a community-acquired infection was 45,2%45,2%
Kollef MH, Sherman G, Ward S, et al:Kollef MH, Sherman G, Ward S, et al:
Inadequate antimicrobial treatment of infections:Inadequate antimicrobial treatment of infections:
A risk factor for hospital mortality among critically ill patients.A risk factor for hospital mortality among critically ill patients.
Chest 1999; 115:462– 474Chest 1999; 115:462– 474
MORTALITYMORTALITY
 Mortality in group with inadequate antimicrobialMortality in group with inadequate antimicrobial
therapytherapy 42%42%
 Mortality in the appropriately treated infection groupMortality in the appropriately treated infection group
17,7%17,7%
 (Non-septic patient mortality(Non-septic patient mortality 12,2%12,2%))
Kollef MH, Sherman G, Ward S, et al:Kollef MH, Sherman G, Ward S, et al:
Inadequate antimicrobial treatment of infections: A risk factor for hospital mortalityInadequate antimicrobial treatment of infections: A risk factor for hospital mortality
among critically ill patients.among critically ill patients.
Chest 1999; 115:462– 474Chest 1999; 115:462– 474
MORTALITYMORTALITY
INCREASED WITH:INCREASED WITH:
• No. of acquired organ dysfunctionsNo. of acquired organ dysfunctions
• APACHE ScoreAPACHE Score
• Increasing ageIncreasing age
• Need for inotropic supportNeed for inotropic support
• Non-surgical patientsNon-surgical patients
• MalignancyMalignancy
Kollef MH, Sherman G, Ward S, et al:Kollef MH, Sherman G, Ward S, et al:
Inadequate antimicrobial treatment of infections:Inadequate antimicrobial treatment of infections:
A risk factor for hospital mortality among critically ill patients.A risk factor for hospital mortality among critically ill patients.
Chest 1999; 115:462– 474Chest 1999; 115:462– 474
APPROPRIATE vs INAPPROPRIATE
ANTIBIOTIC THERAPY:
MORTALITY IN INTRA-ABDOMINAL INFECTION
12%
23%
0.0%
10.0%
20.0%
30.0%
40.0%
Empiric Antibiotic Therapy
Appropriate (n=290)
Empiric Antibiotic Therapy
Inappropriate (n=75)
Mortality,%
Bare M et al. 12th
European Congress of Clinical Microbiology and Infectious
Diseases, 2002.
Successful Clinical Outcome withSuccessful Clinical Outcome with
Appropriate AntibioticsAppropriate Antibiotics
in severe IAIin severe IAI
81.9%
58.9%
0.0%
20.0%
40.0%
60.0%
80.0%
100.0%
Empiric Antibiotic
Therapy Appropriate
(n=238)
Empiric Antibiotic
Therapy Inappropriate
(n=56)
Patientswith
ClinicalSuccess,%
p<0.05
*Successful outcome was defined as resolution with no change in treatment.
Davey P et al. Presented at the International Society of Pharmacoeconomics and
Outcomes Research Sixth Annual International Meeting, 2001.
LANDMARK PAPERLANDMARK PAPER
APPROPRIATE ANTIBIOTICSAPPROPRIATE ANTIBIOTICS
vs SURVIVALvs SURVIVAL
in SEPTIC SHOCKin SEPTIC SHOCK
 Appropriate antibiotic within 1 hour of developingAppropriate antibiotic within 1 hour of developing
shock, survivalshock, survival 79,9%79,9%
 SurvivalSurvival droppeddropped by average ofby average of 7,6%7,6% perper
hour thereafter up to 6 hourshour thereafter up to 6 hours
 Statistical significance already after 2 hoursStatistical significance already after 2 hours
 Survival after starting antibiotics only after 6Survival after starting antibiotics only after 6
hours was onlyhours was only 42%42%
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
WHY SO FEW NEWWHY SO FEW NEW
ANTIBIOTICS?ANTIBIOTICS?
 Development costs for a new moleculeDevelopment costs for a new molecule
from preclinical to end phase III nowfrom preclinical to end phase III now
ranging from 700 Million to 1.2 Billion USDranging from 700 Million to 1.2 Billion USD
 No guarantees of success along theNo guarantees of success along the
pathwaypathway
 Reward for developing a new antimicrobialReward for developing a new antimicrobial
= no-one uses it!= no-one uses it!
WHY SO FEW NEWWHY SO FEW NEW
ANTIBIOTICS?ANTIBIOTICS?
 Mode of usage is very different to mostMode of usage is very different to most
other drugs, hence profitability almost non-other drugs, hence profitability almost non-
existent:existent:
 Standard usage is 5 – 10 daysStandard usage is 5 – 10 days
 Compare with medications for diabetes,Compare with medications for diabetes,
hypertension, gout, hyperlipidaemia, etc.hypertension, gout, hyperlipidaemia, etc.
where usage of the drug is for lifewhere usage of the drug is for life
WHY SO FEW NEWWHY SO FEW NEW
ANTIBIOTICS?ANTIBIOTICS?
 Length of patents are the same forLength of patents are the same for
antibiotics as for all other drugsantibiotics as for all other drugs
 A few countries do not respect patentA few countries do not respect patent
rights in any event and allow exportationrights in any event and allow exportation
 No other class of medicines is underNo other class of medicines is under
medical pressure to minimise usagemedical pressure to minimise usage
 ANTIBIOTICS ARE THE ONLYANTIBIOTICS ARE THE ONLY
MEDICINES THAT WHEN GIVEN TO AMEDICINES THAT WHEN GIVEN TO A
SINGLE PATIENT, MAY AFFECTSINGLE PATIENT, MAY AFFECT
OTHER INDIVIDUALSOTHER INDIVIDUALS
WHY SO FEW NEWWHY SO FEW NEW
ANTIBIOTICS?ANTIBIOTICS?
 Costs are progressively increasingCosts are progressively increasing
 New additional costs becoming necessaryNew additional costs becoming necessary
in many countriesin many countries
 Environmental impact studiesEnvironmental impact studies
 Very few blockbuster drugs in otherVery few blockbuster drugs in other
therapeutic areas eithertherapeutic areas either
 Even biologics soon to be challenged withEven biologics soon to be challenged with
biosimilarsbiosimilars
Financial difficulties inherent inFinancial difficulties inherent in
antibiotic developmentantibiotic development
 The reward for developing a novel antibiotic is thatThe reward for developing a novel antibiotic is that
it is reserved for later resistant pathogens and isit is reserved for later resistant pathogens and is
hardly used before patent expiryhardly used before patent expiry
 Patent lives are not longer for antibiotics than forPatent lives are not longer for antibiotics than for
other drug classesother drug classes
 Drugs for chronic illnesses are used for prolongedDrugs for chronic illnesses are used for prolonged
periods and hence R&D costs can be recoupedperiods and hence R&D costs can be recouped
 The use of antibiotics is for a very short course ofThe use of antibiotics is for a very short course of
treatmenttreatment
 No other drug class has medical restrictions forNo other drug class has medical restrictions for
usage or volume of usageusage or volume of usage
 Holding costs for reserved drugs are highHolding costs for reserved drugs are high
Are antibiotics a cost-effectiveAre antibiotics a cost-effective
therapeutic intervention?therapeutic intervention?
 QALYQALY
 ICERICER
 NNTNNT
 Antibiotics are amongst the most cost-Antibiotics are amongst the most cost-
effective and life-altering medicaleffective and life-altering medical
therapeutic interventions availabletherapeutic interventions available
 They are amongst the best value forThey are amongst the best value for
money interventions medical sciencemoney interventions medical science
offers the communityoffers the community
Factors influencing antibioticFactors influencing antibiotic
clinical trials for serious infectionsclinical trials for serious infections
 Almost all clinical trials for new antimicrobialsAlmost all clinical trials for new antimicrobials
are done in ‘not-so-sick’ patientsare done in ‘not-so-sick’ patients
 This follows on trials in human volunteers,This follows on trials in human volunteers,
animal studies and laboratory studiesanimal studies and laboratory studies
 The truly ill patient seldom behavesThe truly ill patient seldom behaves
physiologically as the less sick or well personphysiologically as the less sick or well person
 Ethical limitations are immense in these trialsEthical limitations are immense in these trials
 Statistical significance is near impossible toStatistical significance is near impossible to
achieve (confounding variables)achieve (confounding variables)
Clinical trials:Clinical trials:
Exclusions and confoundersExclusions and confounders
 Disease aetiologyDisease aetiology
 Age extremesAge extremes
 Body mass extremesBody mass extremes
 PregnancyPregnancy
 ChangesChanges
 Volume of distributionVolume of distribution
 Protein bindingProtein binding
 Physiological responsesPhysiological responses
 Organ dysfunctionOrgan dysfunction
 InterventionsInterventions
 Dialysis (IHD / SLEDD / CVVHD)Dialysis (IHD / SLEDD / CVVHD)
 Extra-corporeal circulationsExtra-corporeal circulations
 Drug-drug interactionsDrug-drug interactions
DRUG REGISTRATION ANDDRUG REGISTRATION AND
REIMBURSEMENTREIMBURSEMENT
 Complex processes needed to satisfyComplex processes needed to satisfy
regulatorsregulators
 Drug registration ⇒ Efficacy and SafetyDrug registration ⇒ Efficacy and Safety
 Drug reimbursement ⇒ Cost-effectivenessDrug reimbursement ⇒ Cost-effectiveness
 Registration = usually requires provingRegistration = usually requires proving
equivalenceequivalence
 Reimbursement = usually requires provingReimbursement = usually requires proving
superioritysuperiority
Post-marketingPost-marketing
drug surveillancedrug surveillance
 Extremely important for pharmaceuticalExtremely important for pharmaceutical
companies to have strict, well defined andcompanies to have strict, well defined and
comprehensive pharmacovigilancecomprehensive pharmacovigilance
 This means dedicated and appropriatelyThis means dedicated and appropriately
staffed drug safety unitsstaffed drug safety units
 Many drug toxicities will only becomeMany drug toxicities will only become
evident with prolonged and sustainedevident with prolonged and sustained
usageusage ∝∝ incidence, initial trial designincidence, initial trial design
 COST!COST!
COST IMPLICATIONS OFCOST IMPLICATIONS OF
ETHICAL DRUG COMPANYETHICAL DRUG COMPANY
FUNCTIONINGFUNCTIONING
 Medical Affairs departmentMedical Affairs department
 Clinical Development departmentClinical Development department
 Medical Compliance divisionMedical Compliance division
 Medical Information divisionMedical Information division
 Regulatory Affairs departmentRegulatory Affairs department
 Patient Access departmentPatient Access department
 Drug Safety UnitDrug Safety Unit
Pharmaceutical companies:Pharmaceutical companies:
• Are governed by strict regulatory laws in mostAre governed by strict regulatory laws in most
countriescountries
• Are governed by tight Codes of Conduct in mostAre governed by tight Codes of Conduct in most
countriescountries
• Only can promote medications for their licensedOnly can promote medications for their licensed
indicationsindications
• Are subject to major penalties for infringements inAre subject to major penalties for infringements in
the appropriate marketing of their drugsthe appropriate marketing of their drugs
• Have large numbers of doctors, scientists,Have large numbers of doctors, scientists,
lawyers, compliance officers and qualitylawyers, compliance officers and quality
assurance professionals employed fulltime, whoassurance professionals employed fulltime, who
are not accountable to the commercial arms of theare not accountable to the commercial arms of the
businessbusiness
DETRACTORS FROM ENABLINGDETRACTORS FROM ENABLING
QUICK AND AFFORDABLE NEWQUICK AND AFFORDABLE NEW
DRUG REGISTRATIONDRUG REGISTRATION
 Complexity of new drug registrationComplexity of new drug registration
 Needing to repeat the process in everyNeeding to repeat the process in every
country!country!
 Near impossibility to do trials in ill patientsNear impossibility to do trials in ill patients
 Ethics, consent, enrolment, confounders,Ethics, consent, enrolment, confounders,
exclusions, statistically-significant numbersexclusions, statistically-significant numbers
 Near impossibility of proving cost-Near impossibility of proving cost-
effectiveness of novel agentseffectiveness of novel agents
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
FUTURE ANTIBIOTICFUTURE ANTIBIOTIC
DEVELOPMENT WILL NEED:DEVELOPMENT WILL NEED:
LONGTERM:LONGTERM:
 Private-public-academic partnershipsPrivate-public-academic partnerships
 Government active supportGovernment active support
 Cross-country harmonisationCross-country harmonisation
THE FUTURETHE FUTURE
SHORT-TERM:SHORT-TERM:
 Infection ControlInfection Control
 Good habits – cultures, surveillance,Good habits – cultures, surveillance,
source controlsource control
 Antimicrobial stewardshipAntimicrobial stewardship
 Routine PK / PD considerationsRoutine PK / PD considerations
 Early diagnostic markers for sepsis andEarly diagnostic markers for sepsis and
pathogenspathogens
 Vaccine researchVaccine research
MEDICAL STRATEGIES TO LIMITMEDICAL STRATEGIES TO LIMIT
ANTIBIOTIC PRESCRIPTIONANTIBIOTIC PRESCRIPTION
 Antimicrobial stewardshipAntimicrobial stewardship
 GuidelinesGuidelines
 Formularies?Formularies?
 Antibiotic restriction, protocols,Antibiotic restriction, protocols,
cycling, rotationcycling, rotation
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
Early diagnosis will limit inappropriateEarly diagnosis will limit inappropriate
and inadequate antibiotic therapyand inadequate antibiotic therapy
• Early diagnosisEarly diagnosis
– PCRPCR
– MALDI-TOFMALDI-TOF
• Therapeutic drug monitoring (TDM)Therapeutic drug monitoring (TDM)
• Tissue drug levelsTissue drug levels
– Develop indicators of tissue drug levelsDevelop indicators of tissue drug levels
• BiomarkersBiomarkers
– Confirm definite sepsisConfirm definite sepsis
– Exclude non-septic causes of inflammationExclude non-septic causes of inflammation
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"
The ‘D’s of antibiotic prescribingThe ‘D’s of antibiotic prescribing
 DiagnosisDiagnosis
 Drug choiceDrug choice
 DoseDose
 Dosing intervalDosing interval
 Delivery methodDelivery method
 Delivery kineticsDelivery kinetics
 DynamicsDynamics
 DysfunctionsDysfunctions
 Drug interactionsDrug interactions
 Don’t DamageDon’t Damage
 Don’t DelayDon’t Delay
 DurationDuration
 De-escalationDe-escalation
 DiscontinuationDiscontinuation
Antibiotic pipelineAntibiotic pipeline
 Immediate pipeline is very emptyImmediate pipeline is very empty!!
 TedizolidTedizolid
 AvibactamAvibactam
 Ceftolozane / tazobactamCeftolozane / tazobactam
 DalbavancinDalbavancin
 Medium term – new aminoglycosides,Medium term – new aminoglycosides,
glycylcycline, macrolide, glycopeptidesglycylcycline, macrolide, glycopeptides
 Quorum-sensing inhibitors, anti-biofilm,Quorum-sensing inhibitors, anti-biofilm,
immunomodulatorsimmunomodulators
 Efflux pump blockersEfflux pump blockers

More Related Content

What's hot

Vaccines and antiviral
Vaccines and antiviralVaccines and antiviral
Vaccines and antiviralMahamCh14
 
Parasite Vaccines in Trials and in Use
Parasite Vaccines in Trials and in UseParasite Vaccines in Trials and in Use
Parasite Vaccines in Trials and in Usedranjansarma
 
vaccine resistance
vaccine resistancevaccine resistance
vaccine resistanceJaiShree34
 
LIVE BACTERIA VACCINES actual
LIVE BACTERIA VACCINES actualLIVE BACTERIA VACCINES actual
LIVE BACTERIA VACCINES actualCharlotte Litten
 
hiv vaccine
hiv vaccinehiv vaccine
hiv vaccineDUVASU
 
Newer vaccine new ppt
Newer vaccine new pptNewer vaccine new ppt
Newer vaccine new pptWal
 
Types of vaccine.pptx
Types of vaccine.pptxTypes of vaccine.pptx
Types of vaccine.pptxainnasultana
 
Viral vaccine & it’s effect awkum
Viral vaccine & it’s effect awkumViral vaccine & it’s effect awkum
Viral vaccine & it’s effect awkumWaleed Qadar
 
Impact of biotechnology
Impact of biotechnologyImpact of biotechnology
Impact of biotechnologyAlen Shaji
 
Vaccines What is Vaccine? What are the different types of vaccines?
Vaccines What is Vaccine? What are the different types of vaccines?Vaccines What is Vaccine? What are the different types of vaccines?
Vaccines What is Vaccine? What are the different types of vaccines?Maneesha M Joseph
 
Covid-19 vaccine development
Covid-19 vaccine developmentCovid-19 vaccine development
Covid-19 vaccine developmentRachelMackelprang
 
SIGNIFICANT OF TOXOIDS IN ACTIVE IMMUNITY BY NOM KUMAR NAIK
SIGNIFICANT OF TOXOIDS IN ACTIVE IMMUNITY BY  NOM KUMAR NAIKSIGNIFICANT OF TOXOIDS IN ACTIVE IMMUNITY BY  NOM KUMAR NAIK
SIGNIFICANT OF TOXOIDS IN ACTIVE IMMUNITY BY NOM KUMAR NAIKNOM KUMAR NAIK BHUKYA
 
Immunology of parasitic diseases
Immunology of parasitic diseasesImmunology of parasitic diseases
Immunology of parasitic diseasesHossam Ghoneim
 
Vaccine Development & GMP Manufacturing - Creative Biolabs
Vaccine Development & GMP Manufacturing - Creative BiolabsVaccine Development & GMP Manufacturing - Creative Biolabs
Vaccine Development & GMP Manufacturing - Creative BiolabsCreative-Biolabs
 
Superbugs the bacteria that resists
Superbugs   the bacteria that resistsSuperbugs   the bacteria that resists
Superbugs the bacteria that resistsKushal Grakh
 

What's hot (20)

Rabies ppt rajesh
Rabies ppt rajeshRabies ppt rajesh
Rabies ppt rajesh
 
Vaccines and antiviral
Vaccines and antiviralVaccines and antiviral
Vaccines and antiviral
 
Parasite Vaccines in Trials and in Use
Parasite Vaccines in Trials and in UseParasite Vaccines in Trials and in Use
Parasite Vaccines in Trials and in Use
 
Newer vaccine
Newer vaccineNewer vaccine
Newer vaccine
 
vaccine resistance
vaccine resistancevaccine resistance
vaccine resistance
 
LIVE BACTERIA VACCINES actual
LIVE BACTERIA VACCINES actualLIVE BACTERIA VACCINES actual
LIVE BACTERIA VACCINES actual
 
hiv vaccine
hiv vaccinehiv vaccine
hiv vaccine
 
Newer vaccine new ppt
Newer vaccine new pptNewer vaccine new ppt
Newer vaccine new ppt
 
Vaccine 5 march
Vaccine 5 march Vaccine 5 march
Vaccine 5 march
 
Types of vaccine.pptx
Types of vaccine.pptxTypes of vaccine.pptx
Types of vaccine.pptx
 
Vaccination
VaccinationVaccination
Vaccination
 
Viral vaccine & it’s effect awkum
Viral vaccine & it’s effect awkumViral vaccine & it’s effect awkum
Viral vaccine & it’s effect awkum
 
Vaccinology
Vaccinology Vaccinology
Vaccinology
 
Impact of biotechnology
Impact of biotechnologyImpact of biotechnology
Impact of biotechnology
 
Vaccines What is Vaccine? What are the different types of vaccines?
Vaccines What is Vaccine? What are the different types of vaccines?Vaccines What is Vaccine? What are the different types of vaccines?
Vaccines What is Vaccine? What are the different types of vaccines?
 
Covid-19 vaccine development
Covid-19 vaccine developmentCovid-19 vaccine development
Covid-19 vaccine development
 
SIGNIFICANT OF TOXOIDS IN ACTIVE IMMUNITY BY NOM KUMAR NAIK
SIGNIFICANT OF TOXOIDS IN ACTIVE IMMUNITY BY  NOM KUMAR NAIKSIGNIFICANT OF TOXOIDS IN ACTIVE IMMUNITY BY  NOM KUMAR NAIK
SIGNIFICANT OF TOXOIDS IN ACTIVE IMMUNITY BY NOM KUMAR NAIK
 
Immunology of parasitic diseases
Immunology of parasitic diseasesImmunology of parasitic diseases
Immunology of parasitic diseases
 
Vaccine Development & GMP Manufacturing - Creative Biolabs
Vaccine Development & GMP Manufacturing - Creative BiolabsVaccine Development & GMP Manufacturing - Creative Biolabs
Vaccine Development & GMP Manufacturing - Creative Biolabs
 
Superbugs the bacteria that resists
Superbugs   the bacteria that resistsSuperbugs   the bacteria that resists
Superbugs the bacteria that resists
 

Similar to ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"

broad spectrum antibiotics - Dr Sanjana Ravindra
broad spectrum antibiotics - Dr Sanjana Ravindrabroad spectrum antibiotics - Dr Sanjana Ravindra
broad spectrum antibiotics - Dr Sanjana RavindraDr. Sanjana Ravindra
 
Antibiotic Resistance & Food Borne Diseases
Antibiotic Resistance & Food Borne DiseasesAntibiotic Resistance & Food Borne Diseases
Antibiotic Resistance & Food Borne DiseasesGo Forward Consult
 
Antibiotic resistance : A global concern
Antibiotic resistance : A global concern Antibiotic resistance : A global concern
Antibiotic resistance : A global concern Rohan Jagdale
 
A report on Antibiotics
A report on AntibioticsA report on Antibiotics
A report on Antibioticsitfakash
 
The Pharmacological Effect Of Antibiotics
The Pharmacological Effect Of AntibioticsThe Pharmacological Effect Of Antibiotics
The Pharmacological Effect Of AntibioticsJanet Robinson
 
En atbantibiotics
En atbantibioticsEn atbantibiotics
En atbantibioticsDr P Deepak
 
Endodontic pharmacology /prosthodontic courses
Endodontic pharmacology /prosthodontic coursesEndodontic pharmacology /prosthodontic courses
Endodontic pharmacology /prosthodontic coursesIndian dental academy
 
Vaccine Victories Against Microbial Resistance - Dr. Donald F. Gerson
Vaccine Victories Against Microbial Resistance - Dr. Donald F. GersonVaccine Victories Against Microbial Resistance - Dr. Donald F. Gerson
Vaccine Victories Against Microbial Resistance - Dr. Donald F. GersonPnuVax
 
Typhoid fever ppt
Typhoid fever ppt Typhoid fever ppt
Typhoid fever ppt huraismalik
 
Normal-Human-Microbiota.pptx
Normal-Human-Microbiota.pptxNormal-Human-Microbiota.pptx
Normal-Human-Microbiota.pptxbdmizba
 
Acquired id states&amp;aids
Acquired id states&amp;aidsAcquired id states&amp;aids
Acquired id states&amp;aidsFawzia Abo-Ali
 
Bacterial diseases 2011
Bacterial diseases 2011Bacterial diseases 2011
Bacterial diseases 2011Crystal Rose
 
Immunocompromised patient with sepsis
Immunocompromised patient with sepsisImmunocompromised patient with sepsis
Immunocompromised patient with sepsissteveclaydon1970
 
Presentation on bioterrorism
Presentation on bioterrorismPresentation on bioterrorism
Presentation on bioterrorismBijayKumarMahato1
 

Similar to ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes" (20)

broad spectrum antibiotics - Dr Sanjana Ravindra
broad spectrum antibiotics - Dr Sanjana Ravindrabroad spectrum antibiotics - Dr Sanjana Ravindra
broad spectrum antibiotics - Dr Sanjana Ravindra
 
Antibiotic Resistance & Food Borne Diseases
Antibiotic Resistance & Food Borne DiseasesAntibiotic Resistance & Food Borne Diseases
Antibiotic Resistance & Food Borne Diseases
 
Antibiotics
AntibioticsAntibiotics
Antibiotics
 
Antibiotics Success and Failures what is our role by Dr.T.V.Rao MD
AntibioticsSuccess and Failureswhat is our role by Dr.T.V.Rao MDAntibioticsSuccess and Failureswhat is our role by Dr.T.V.Rao MD
Antibiotics Success and Failures what is our role by Dr.T.V.Rao MD
 
Antibiotic resistance : A global concern
Antibiotic resistance : A global concern Antibiotic resistance : A global concern
Antibiotic resistance : A global concern
 
A report on Antibiotics
A report on AntibioticsA report on Antibiotics
A report on Antibiotics
 
Abuse of antibiotics
Abuse of antibioticsAbuse of antibiotics
Abuse of antibiotics
 
PERSENTATION ON EMERGING DOMAIN OF ANTIBIOTICS.BY TARANJUM KHAN.
PERSENTATION ON EMERGING DOMAIN OF ANTIBIOTICS.BY TARANJUM KHAN. PERSENTATION ON EMERGING DOMAIN OF ANTIBIOTICS.BY TARANJUM KHAN.
PERSENTATION ON EMERGING DOMAIN OF ANTIBIOTICS.BY TARANJUM KHAN.
 
Antibiotics
Antibiotics Antibiotics
Antibiotics
 
Diagnostic microbiology in Antibiotic policy
Diagnostic microbiology in Antibiotic policyDiagnostic microbiology in Antibiotic policy
Diagnostic microbiology in Antibiotic policy
 
The Pharmacological Effect Of Antibiotics
The Pharmacological Effect Of AntibioticsThe Pharmacological Effect Of Antibiotics
The Pharmacological Effect Of Antibiotics
 
En atbantibiotics
En atbantibioticsEn atbantibiotics
En atbantibiotics
 
Endodontic pharmacology /prosthodontic courses
Endodontic pharmacology /prosthodontic coursesEndodontic pharmacology /prosthodontic courses
Endodontic pharmacology /prosthodontic courses
 
Vaccine Victories Against Microbial Resistance - Dr. Donald F. Gerson
Vaccine Victories Against Microbial Resistance - Dr. Donald F. GersonVaccine Victories Against Microbial Resistance - Dr. Donald F. Gerson
Vaccine Victories Against Microbial Resistance - Dr. Donald F. Gerson
 
Typhoid fever ppt
Typhoid fever ppt Typhoid fever ppt
Typhoid fever ppt
 
Normal-Human-Microbiota.pptx
Normal-Human-Microbiota.pptxNormal-Human-Microbiota.pptx
Normal-Human-Microbiota.pptx
 
Acquired id states&amp;aids
Acquired id states&amp;aidsAcquired id states&amp;aids
Acquired id states&amp;aids
 
Bacterial diseases 2011
Bacterial diseases 2011Bacterial diseases 2011
Bacterial diseases 2011
 
Immunocompromised patient with sepsis
Immunocompromised patient with sepsisImmunocompromised patient with sepsis
Immunocompromised patient with sepsis
 
Presentation on bioterrorism
Presentation on bioterrorismPresentation on bioterrorism
Presentation on bioterrorism
 

More from Intensive Care Network Victoria

Orford - iValidate: Improving End of Life Care in the ICU
Orford -  iValidate:  Improving End of Life Care in the ICUOrford -  iValidate:  Improving End of Life Care in the ICU
Orford - iValidate: Improving End of Life Care in the ICUIntensive Care Network Victoria
 
ICN Victoria: Buck on "Teaching Gen Y Doctors - Should We Bother?"
ICN Victoria: Buck on "Teaching Gen Y Doctors - Should We Bother?"ICN Victoria: Buck on "Teaching Gen Y Doctors - Should We Bother?"
ICN Victoria: Buck on "Teaching Gen Y Doctors - Should We Bother?"Intensive Care Network Victoria
 
ICN Victoria: Davies on "Intensive care for Intensivists"
ICN Victoria: Davies on "Intensive care for Intensivists"ICN Victoria: Davies on "Intensive care for Intensivists"
ICN Victoria: Davies on "Intensive care for Intensivists"Intensive Care Network Victoria
 
ICN Victoria: Burrell on "RV Failure for the Intensivist"
ICN Victoria: Burrell on "RV Failure for the Intensivist"ICN Victoria: Burrell on "RV Failure for the Intensivist"
ICN Victoria: Burrell on "RV Failure for the Intensivist"Intensive Care Network Victoria
 

More from Intensive Care Network Victoria (20)

Orford - iValidate: Improving End of Life Care in the ICU
Orford -  iValidate:  Improving End of Life Care in the ICUOrford -  iValidate:  Improving End of Life Care in the ICU
Orford - iValidate: Improving End of Life Care in the ICU
 
Sue berney cognitive impairment 2016
Sue berney cognitive impairment 2016Sue berney cognitive impairment 2016
Sue berney cognitive impairment 2016
 
Davies - Nutrition in Intensive Care
Davies - Nutrition in Intensive CareDavies - Nutrition in Intensive Care
Davies - Nutrition in Intensive Care
 
Haines- Developing puzzle icu outcomes
Haines- Developing puzzle icu outcomesHaines- Developing puzzle icu outcomes
Haines- Developing puzzle icu outcomes
 
ICN Vic - glucose control in diabetics
ICN Vic - glucose control in diabeticsICN Vic - glucose control in diabetics
ICN Vic - glucose control in diabetics
 
Anderson - Never Ever Die
Anderson - Never Ever DieAnderson - Never Ever Die
Anderson - Never Ever Die
 
Pellegrino - ECMO CPR - Getting it Right
Pellegrino - ECMO CPR - Getting it RightPellegrino - ECMO CPR - Getting it Right
Pellegrino - ECMO CPR - Getting it Right
 
Maclure - ECMO CPR - Making it Work
Maclure - ECMO CPR - Making it WorkMaclure - ECMO CPR - Making it Work
Maclure - ECMO CPR - Making it Work
 
Bernard - Refractory Cardiac Arrest
Bernard - Refractory Cardiac ArrestBernard - Refractory Cardiac Arrest
Bernard - Refractory Cardiac Arrest
 
NOACS and bleeding
NOACS and bleedingNOACS and bleeding
NOACS and bleeding
 
Can we predict bleeding
Can we predict bleedingCan we predict bleeding
Can we predict bleeding
 
Cattigan- Doing it for the Kids
Cattigan- Doing it for the KidsCattigan- Doing it for the Kids
Cattigan- Doing it for the Kids
 
McGloughlin -Good Bugs, Bad Bugs
McGloughlin -Good Bugs, Bad BugsMcGloughlin -Good Bugs, Bad Bugs
McGloughlin -Good Bugs, Bad Bugs
 
Mentoring final copy
Mentoring final copyMentoring final copy
Mentoring final copy
 
ICN Victoria: Cornely on "Being a Fun-gi in ICU"
ICN Victoria: Cornely on "Being a Fun-gi in ICU"ICN Victoria: Cornely on "Being a Fun-gi in ICU"
ICN Victoria: Cornely on "Being a Fun-gi in ICU"
 
ICN Victoria: Buck on "Teaching Gen Y Doctors - Should We Bother?"
ICN Victoria: Buck on "Teaching Gen Y Doctors - Should We Bother?"ICN Victoria: Buck on "Teaching Gen Y Doctors - Should We Bother?"
ICN Victoria: Buck on "Teaching Gen Y Doctors - Should We Bother?"
 
ICN Victoria: Buck on "Resus Room Management"
ICN Victoria: Buck on "Resus Room Management"ICN Victoria: Buck on "Resus Room Management"
ICN Victoria: Buck on "Resus Room Management"
 
ICN Victoria: Davies on "Intensive care for Intensivists"
ICN Victoria: Davies on "Intensive care for Intensivists"ICN Victoria: Davies on "Intensive care for Intensivists"
ICN Victoria: Davies on "Intensive care for Intensivists"
 
ICN Victoria: Iwashyna on "Stop Wasting RCT Data!"
ICN Victoria: Iwashyna on "Stop Wasting RCT Data!"ICN Victoria: Iwashyna on "Stop Wasting RCT Data!"
ICN Victoria: Iwashyna on "Stop Wasting RCT Data!"
 
ICN Victoria: Burrell on "RV Failure for the Intensivist"
ICN Victoria: Burrell on "RV Failure for the Intensivist"ICN Victoria: Burrell on "RV Failure for the Intensivist"
ICN Victoria: Burrell on "RV Failure for the Intensivist"
 

Recently uploaded

BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE Mamatha Lakka
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfDolisha Warbi
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptPradnya Wadekar
 
MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.whalesdesign
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfMedicoseAcademics
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024EwoutSteyerberg1
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismusChandrasekar Reddy
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communicationskatiequigley33
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.aarjukhadka22
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdfHongBiThi1
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptPradnya Wadekar
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyZurück zum Ursprung
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...Shubhanshu Gaurav
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfHongBiThi1
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaSujoy Dasgupta
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationMedicoseAcademics
 

Recently uploaded (20)

BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.ppt
 
MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdf
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismus
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communications
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologyppt
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturally
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 

ICN Victoria: Grolman on "Antibiotic Future: The Return of the Microbes"

  • 1. THE RETURN OF THETHE RETURN OF THE MICROBES!MICROBES! DO ANTIBIOTICS HAVE ADO ANTIBIOTICS HAVE A FUTURE?FUTURE? David C GrolmanDavid C Grolman Medical DirectorMedical Director Head of Medical Affairs:Head of Medical Affairs: Global Established PharmaGlobal Established Pharma Pfizer Australia & Pfizer New ZealandPfizer Australia & Pfizer New Zealand
  • 3. BACTERIABACTERIA • Are almost all our friends!Are almost all our friends! • Are themselves the best protection we haveAre themselves the best protection we have against colonisation with pathogensagainst colonisation with pathogens • Have survival mechanisms which pre-date usHave survival mechanisms which pre-date us by billions of yearsby billions of years • Outnumber our cells in & on our own bodiesOutnumber our cells in & on our own bodies by at least 10-foldby at least 10-fold • Outnumber us on the planet by a factor ofOutnumber us on the planet by a factor of billionsbillions
  • 5. Where have all the antibioticsWhere have all the antibiotics gone?gone?  Why are there so few antibiotics underWhy are there so few antibiotics under development by pharmaceuticaldevelopment by pharmaceutical companies and other stakeholders?companies and other stakeholders?  Do we believe that we are going to ‘runDo we believe that we are going to ‘run out’ of antibiotic options?out’ of antibiotic options?  What do we mean by ‘antibiotics’?What do we mean by ‘antibiotics’? Antibacterials v AntimicrobialsAntibacterials v Antimicrobials (Fungi, viruses, parasites)(Fungi, viruses, parasites)
  • 7. ANTIBIOTICSANTIBIOTICS WONDER DRUGS of the 20WONDER DRUGS of the 20thth CENTURYCENTURY  Antimicrobial agents are the single classAntimicrobial agents are the single class of drugs that have most contributed to theof drugs that have most contributed to the major improvement in prolonged lifemajor improvement in prolonged life expectancy achieved over the pastexpectancy achieved over the past centurycentury  Numerous previously usually fatalNumerous previously usually fatal infections became treatable –infections became treatable – Pneumococcal pneumonia, consumption,Pneumococcal pneumonia, consumption, scarlet fever, diphtheria, wound sepsis,scarlet fever, diphtheria, wound sepsis,
  • 8. ANTIBIOTIC HISTORYANTIBIOTIC HISTORY  1920s = first antibiotics discovered1920s = first antibiotics discovered  1940s = first commercially available1940s = first commercially available antibioticsantibiotics RESISTANCE PREDATES THESERESISTANCE PREDATES THESE EVENTSEVENTS
  • 10. Gram-positive historyGram-positive history Bacterial response Human response Bacterial response New pathogens Broad spectrum penicillin Other new pathogens β-lactamase production β-lactamase inhibitors New β-lactamases Newer β-lactamases New ‘shaped’ penicillins Altered PBPs Altered PBPs Glycopeptides Vancomycin-resistance Vancomycin-resistance Lipopeptides Lipopeptide-resistance Glycolipopeptide resistance Oxazolidinones Enzymatic lysis
  • 11. Gram-negative historyGram-negative history Bacterial response Human response Bacterial response New pathogens Broad spectrum penicillin Other new pathogens β-lactamase production β-lactamase inhibitors New β-lactamases Newer β-lactamases Cephalosporins Extended spectrum B L ESBLs Carbapenems New pathogens ESBLs Carbapenems Carbapenem resistance -Efflux -Carbapenemases Carbapenem resistance Colistin, tigecycline Enzymatic lysis, efflux
  • 12. The ‘Ps’ of resistanceThe ‘Ps’ of resistance  PumpsPumps  PorinsPorins  Penicillin-binding protein (PBP) changePenicillin-binding protein (PBP) change  Proteases (penicillinases to penemases)Proteases (penicillinases to penemases)  Point mutations & target modificationsPoint mutations & target modifications  PRE-DETERMINEDPRE-DETERMINED  PLASMID-MEDIATEDPLASMID-MEDIATED
  • 13. The bacterial armamentariumThe bacterial armamentarium  Resistance genesResistance genes  Virulence factorsVirulence factors Why don’t all bacteria have all mechanisms?Why don’t all bacteria have all mechanisms?  These are all energy intensive!These are all energy intensive!  However: Resistance + virulence genesHowever: Resistance + virulence genes have recently been seen in combinationhave recently been seen in combination
  • 14. There will be new antibiotics inThere will be new antibiotics in the futurethe future  There will be numerous new antimicrobialThere will be numerous new antimicrobial agentsagents  New pathways and potential targets are beingNew pathways and potential targets are being discovered dailydiscovered daily  GOAL IS TO FIND AGENTS WHICHGOAL IS TO FIND AGENTS WHICH ARE:ARE:  SaferSafer  Have less environmental impactHave less environmental impact  Utilise novel pathwaysUtilise novel pathways
  • 15. LpxC-1LpxC-1  Blocks the ability of specificallyBlocks the ability of specifically Acinetobacter baumaniiAcinetobacter baumanii to activate theto activate the TLR-4 and hence cause the systemicTLR-4 and hence cause the systemic inflammatory response usually seen ininflammatory response usually seen in these infectionsthese infections  Achieved by inhibiting LPS secretionAchieved by inhibiting LPS secretion  Does not actually kill theDoes not actually kill the AcinetobacterAcinetobacter  Has no effect on other receptors orHas no effect on other receptors or mediators from other bacteriamediators from other bacteria Lin et al: mBio 3(5):e00312-12. doi:10.1128/mBio.00312-12.Lin et al: mBio 3(5):e00312-12. doi:10.1128/mBio.00312-12.
  • 16. What does cause the emergence ofWhat does cause the emergence of resistance mechanisms?resistance mechanisms?  Minimal evidence that correct andMinimal evidence that correct and appropriate antibiotic leads to resistanceappropriate antibiotic leads to resistance  Multitude of evidence that incorrect orMultitude of evidence that incorrect or inappropriate usage does indeed hasteninappropriate usage does indeed hasten the development of resistancethe development of resistance  Resistance accelerated by under-dosingResistance accelerated by under-dosing and excessive duration of therapyand excessive duration of therapy  We should not be using antibiotics whereWe should not be using antibiotics where not indicated, appropriate or effectivenot indicated, appropriate or effective
  • 17. Historical and ongoingHistorical and ongoing inappropriate usage of antibioticsinappropriate usage of antibiotics  Gross usage of antibiotics for viral infectionsGross usage of antibiotics for viral infections where they have no activity, without goodwhere they have no activity, without good evidence of secondary bacterial infectionevidence of secondary bacterial infection  Use of antibiotics for non-infectiveUse of antibiotics for non-infective inflammatory conditions (e.g. allergies) andinflammatory conditions (e.g. allergies) and for non-antimicrobial effects (e.g. prokineticfor non-antimicrobial effects (e.g. prokinetic factors)factors)  Prolonged usage of antibiotics to ‘prevent’Prolonged usage of antibiotics to ‘prevent’ infectioninfection
  • 19. Ongoing inappropriate use in manyOngoing inappropriate use in many countries of antibiotics in farmingcountries of antibiotics in farming  Use of antibiotics as an adjunct to animalUse of antibiotics as an adjunct to animal farming and in agriculturefarming and in agriculture  Usually done in a vain effort to preventUsually done in a vain effort to prevent infections in livestock (mainly poultry)infections in livestock (mainly poultry)  Real problem is overcrowding of animals byReal problem is overcrowding of animals by modern farming methods with excessivemodern farming methods with excessive restriction of free animal movementrestriction of free animal movement  There is scant scientific evidence thatThere is scant scientific evidence that infections can be prevented by usinginfections can be prevented by using antibiotics prophylactically in these scenariosantibiotics prophylactically in these scenarios
  • 20. Appropriate human prophylacticAppropriate human prophylactic antimicrobial useantimicrobial use  There is also scant evidence that humanThere is also scant evidence that human infections can be prevented antibioticsinfections can be prevented antibiotics used prophylactically or pre-emptivelyused prophylactically or pre-emptively  Exceptions:Exceptions:  Surgical prophylaxisSurgical prophylaxis  Maximum of 24 hours permissibleMaximum of 24 hours permissible  Fungal prophylaxis in immunosuppressedFungal prophylaxis in immunosuppressed patientspatients  Fungal sepsis in limited cIAI scenariosFungal sepsis in limited cIAI scenarios  SDD ?SDD ?
  • 25. MORTALITYMORTALITY  Overall for community-acquired infections wasOverall for community-acquired infections was 17,1%17,1%  Overall for nosocomial infections wasOverall for nosocomial infections was 34,3%34,3%  Overall for nosocomial sepsis after initial treatmentOverall for nosocomial sepsis after initial treatment for a community-acquired infection wasfor a community-acquired infection was 45,2%45,2% Kollef MH, Sherman G, Ward S, et al:Kollef MH, Sherman G, Ward S, et al: Inadequate antimicrobial treatment of infections:Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality among critically ill patients.A risk factor for hospital mortality among critically ill patients. Chest 1999; 115:462– 474Chest 1999; 115:462– 474
  • 26. MORTALITYMORTALITY  Mortality in group with inadequate antimicrobialMortality in group with inadequate antimicrobial therapytherapy 42%42%  Mortality in the appropriately treated infection groupMortality in the appropriately treated infection group 17,7%17,7%  (Non-septic patient mortality(Non-septic patient mortality 12,2%12,2%)) Kollef MH, Sherman G, Ward S, et al:Kollef MH, Sherman G, Ward S, et al: Inadequate antimicrobial treatment of infections: A risk factor for hospital mortalityInadequate antimicrobial treatment of infections: A risk factor for hospital mortality among critically ill patients.among critically ill patients. Chest 1999; 115:462– 474Chest 1999; 115:462– 474
  • 27. MORTALITYMORTALITY INCREASED WITH:INCREASED WITH: • No. of acquired organ dysfunctionsNo. of acquired organ dysfunctions • APACHE ScoreAPACHE Score • Increasing ageIncreasing age • Need for inotropic supportNeed for inotropic support • Non-surgical patientsNon-surgical patients • MalignancyMalignancy Kollef MH, Sherman G, Ward S, et al:Kollef MH, Sherman G, Ward S, et al: Inadequate antimicrobial treatment of infections:Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality among critically ill patients.A risk factor for hospital mortality among critically ill patients. Chest 1999; 115:462– 474Chest 1999; 115:462– 474
  • 28. APPROPRIATE vs INAPPROPRIATE ANTIBIOTIC THERAPY: MORTALITY IN INTRA-ABDOMINAL INFECTION 12% 23% 0.0% 10.0% 20.0% 30.0% 40.0% Empiric Antibiotic Therapy Appropriate (n=290) Empiric Antibiotic Therapy Inappropriate (n=75) Mortality,% Bare M et al. 12th European Congress of Clinical Microbiology and Infectious Diseases, 2002.
  • 29. Successful Clinical Outcome withSuccessful Clinical Outcome with Appropriate AntibioticsAppropriate Antibiotics in severe IAIin severe IAI 81.9% 58.9% 0.0% 20.0% 40.0% 60.0% 80.0% 100.0% Empiric Antibiotic Therapy Appropriate (n=238) Empiric Antibiotic Therapy Inappropriate (n=56) Patientswith ClinicalSuccess,% p<0.05 *Successful outcome was defined as resolution with no change in treatment. Davey P et al. Presented at the International Society of Pharmacoeconomics and Outcomes Research Sixth Annual International Meeting, 2001.
  • 31. APPROPRIATE ANTIBIOTICSAPPROPRIATE ANTIBIOTICS vs SURVIVALvs SURVIVAL in SEPTIC SHOCKin SEPTIC SHOCK  Appropriate antibiotic within 1 hour of developingAppropriate antibiotic within 1 hour of developing shock, survivalshock, survival 79,9%79,9%  SurvivalSurvival droppeddropped by average ofby average of 7,6%7,6% perper hour thereafter up to 6 hourshour thereafter up to 6 hours  Statistical significance already after 2 hoursStatistical significance already after 2 hours  Survival after starting antibiotics only after 6Survival after starting antibiotics only after 6 hours was onlyhours was only 42%42%
  • 33. WHY SO FEW NEWWHY SO FEW NEW ANTIBIOTICS?ANTIBIOTICS?  Development costs for a new moleculeDevelopment costs for a new molecule from preclinical to end phase III nowfrom preclinical to end phase III now ranging from 700 Million to 1.2 Billion USDranging from 700 Million to 1.2 Billion USD  No guarantees of success along theNo guarantees of success along the pathwaypathway  Reward for developing a new antimicrobialReward for developing a new antimicrobial = no-one uses it!= no-one uses it!
  • 34. WHY SO FEW NEWWHY SO FEW NEW ANTIBIOTICS?ANTIBIOTICS?  Mode of usage is very different to mostMode of usage is very different to most other drugs, hence profitability almost non-other drugs, hence profitability almost non- existent:existent:  Standard usage is 5 – 10 daysStandard usage is 5 – 10 days  Compare with medications for diabetes,Compare with medications for diabetes, hypertension, gout, hyperlipidaemia, etc.hypertension, gout, hyperlipidaemia, etc. where usage of the drug is for lifewhere usage of the drug is for life
  • 35. WHY SO FEW NEWWHY SO FEW NEW ANTIBIOTICS?ANTIBIOTICS?  Length of patents are the same forLength of patents are the same for antibiotics as for all other drugsantibiotics as for all other drugs  A few countries do not respect patentA few countries do not respect patent rights in any event and allow exportationrights in any event and allow exportation  No other class of medicines is underNo other class of medicines is under medical pressure to minimise usagemedical pressure to minimise usage  ANTIBIOTICS ARE THE ONLYANTIBIOTICS ARE THE ONLY MEDICINES THAT WHEN GIVEN TO AMEDICINES THAT WHEN GIVEN TO A SINGLE PATIENT, MAY AFFECTSINGLE PATIENT, MAY AFFECT OTHER INDIVIDUALSOTHER INDIVIDUALS
  • 36. WHY SO FEW NEWWHY SO FEW NEW ANTIBIOTICS?ANTIBIOTICS?  Costs are progressively increasingCosts are progressively increasing  New additional costs becoming necessaryNew additional costs becoming necessary in many countriesin many countries  Environmental impact studiesEnvironmental impact studies  Very few blockbuster drugs in otherVery few blockbuster drugs in other therapeutic areas eithertherapeutic areas either  Even biologics soon to be challenged withEven biologics soon to be challenged with biosimilarsbiosimilars
  • 37. Financial difficulties inherent inFinancial difficulties inherent in antibiotic developmentantibiotic development  The reward for developing a novel antibiotic is thatThe reward for developing a novel antibiotic is that it is reserved for later resistant pathogens and isit is reserved for later resistant pathogens and is hardly used before patent expiryhardly used before patent expiry  Patent lives are not longer for antibiotics than forPatent lives are not longer for antibiotics than for other drug classesother drug classes  Drugs for chronic illnesses are used for prolongedDrugs for chronic illnesses are used for prolonged periods and hence R&D costs can be recoupedperiods and hence R&D costs can be recouped  The use of antibiotics is for a very short course ofThe use of antibiotics is for a very short course of treatmenttreatment  No other drug class has medical restrictions forNo other drug class has medical restrictions for usage or volume of usageusage or volume of usage  Holding costs for reserved drugs are highHolding costs for reserved drugs are high
  • 38. Are antibiotics a cost-effectiveAre antibiotics a cost-effective therapeutic intervention?therapeutic intervention?  QALYQALY  ICERICER  NNTNNT  Antibiotics are amongst the most cost-Antibiotics are amongst the most cost- effective and life-altering medicaleffective and life-altering medical therapeutic interventions availabletherapeutic interventions available  They are amongst the best value forThey are amongst the best value for money interventions medical sciencemoney interventions medical science offers the communityoffers the community
  • 39. Factors influencing antibioticFactors influencing antibiotic clinical trials for serious infectionsclinical trials for serious infections  Almost all clinical trials for new antimicrobialsAlmost all clinical trials for new antimicrobials are done in ‘not-so-sick’ patientsare done in ‘not-so-sick’ patients  This follows on trials in human volunteers,This follows on trials in human volunteers, animal studies and laboratory studiesanimal studies and laboratory studies  The truly ill patient seldom behavesThe truly ill patient seldom behaves physiologically as the less sick or well personphysiologically as the less sick or well person  Ethical limitations are immense in these trialsEthical limitations are immense in these trials  Statistical significance is near impossible toStatistical significance is near impossible to achieve (confounding variables)achieve (confounding variables)
  • 40. Clinical trials:Clinical trials: Exclusions and confoundersExclusions and confounders  Disease aetiologyDisease aetiology  Age extremesAge extremes  Body mass extremesBody mass extremes  PregnancyPregnancy  ChangesChanges  Volume of distributionVolume of distribution  Protein bindingProtein binding  Physiological responsesPhysiological responses  Organ dysfunctionOrgan dysfunction  InterventionsInterventions  Dialysis (IHD / SLEDD / CVVHD)Dialysis (IHD / SLEDD / CVVHD)  Extra-corporeal circulationsExtra-corporeal circulations  Drug-drug interactionsDrug-drug interactions
  • 41. DRUG REGISTRATION ANDDRUG REGISTRATION AND REIMBURSEMENTREIMBURSEMENT  Complex processes needed to satisfyComplex processes needed to satisfy regulatorsregulators  Drug registration ⇒ Efficacy and SafetyDrug registration ⇒ Efficacy and Safety  Drug reimbursement ⇒ Cost-effectivenessDrug reimbursement ⇒ Cost-effectiveness  Registration = usually requires provingRegistration = usually requires proving equivalenceequivalence  Reimbursement = usually requires provingReimbursement = usually requires proving superioritysuperiority
  • 42. Post-marketingPost-marketing drug surveillancedrug surveillance  Extremely important for pharmaceuticalExtremely important for pharmaceutical companies to have strict, well defined andcompanies to have strict, well defined and comprehensive pharmacovigilancecomprehensive pharmacovigilance  This means dedicated and appropriatelyThis means dedicated and appropriately staffed drug safety unitsstaffed drug safety units  Many drug toxicities will only becomeMany drug toxicities will only become evident with prolonged and sustainedevident with prolonged and sustained usageusage ∝∝ incidence, initial trial designincidence, initial trial design  COST!COST!
  • 43. COST IMPLICATIONS OFCOST IMPLICATIONS OF ETHICAL DRUG COMPANYETHICAL DRUG COMPANY FUNCTIONINGFUNCTIONING  Medical Affairs departmentMedical Affairs department  Clinical Development departmentClinical Development department  Medical Compliance divisionMedical Compliance division  Medical Information divisionMedical Information division  Regulatory Affairs departmentRegulatory Affairs department  Patient Access departmentPatient Access department  Drug Safety UnitDrug Safety Unit
  • 44. Pharmaceutical companies:Pharmaceutical companies: • Are governed by strict regulatory laws in mostAre governed by strict regulatory laws in most countriescountries • Are governed by tight Codes of Conduct in mostAre governed by tight Codes of Conduct in most countriescountries • Only can promote medications for their licensedOnly can promote medications for their licensed indicationsindications • Are subject to major penalties for infringements inAre subject to major penalties for infringements in the appropriate marketing of their drugsthe appropriate marketing of their drugs • Have large numbers of doctors, scientists,Have large numbers of doctors, scientists, lawyers, compliance officers and qualitylawyers, compliance officers and quality assurance professionals employed fulltime, whoassurance professionals employed fulltime, who are not accountable to the commercial arms of theare not accountable to the commercial arms of the businessbusiness
  • 45. DETRACTORS FROM ENABLINGDETRACTORS FROM ENABLING QUICK AND AFFORDABLE NEWQUICK AND AFFORDABLE NEW DRUG REGISTRATIONDRUG REGISTRATION  Complexity of new drug registrationComplexity of new drug registration  Needing to repeat the process in everyNeeding to repeat the process in every country!country!  Near impossibility to do trials in ill patientsNear impossibility to do trials in ill patients  Ethics, consent, enrolment, confounders,Ethics, consent, enrolment, confounders, exclusions, statistically-significant numbersexclusions, statistically-significant numbers  Near impossibility of proving cost-Near impossibility of proving cost- effectiveness of novel agentseffectiveness of novel agents
  • 47. FUTURE ANTIBIOTICFUTURE ANTIBIOTIC DEVELOPMENT WILL NEED:DEVELOPMENT WILL NEED: LONGTERM:LONGTERM:  Private-public-academic partnershipsPrivate-public-academic partnerships  Government active supportGovernment active support  Cross-country harmonisationCross-country harmonisation
  • 48. THE FUTURETHE FUTURE SHORT-TERM:SHORT-TERM:  Infection ControlInfection Control  Good habits – cultures, surveillance,Good habits – cultures, surveillance, source controlsource control  Antimicrobial stewardshipAntimicrobial stewardship  Routine PK / PD considerationsRoutine PK / PD considerations  Early diagnostic markers for sepsis andEarly diagnostic markers for sepsis and pathogenspathogens  Vaccine researchVaccine research
  • 49. MEDICAL STRATEGIES TO LIMITMEDICAL STRATEGIES TO LIMIT ANTIBIOTIC PRESCRIPTIONANTIBIOTIC PRESCRIPTION  Antimicrobial stewardshipAntimicrobial stewardship  GuidelinesGuidelines  Formularies?Formularies?  Antibiotic restriction, protocols,Antibiotic restriction, protocols, cycling, rotationcycling, rotation
  • 51. Early diagnosis will limit inappropriateEarly diagnosis will limit inappropriate and inadequate antibiotic therapyand inadequate antibiotic therapy • Early diagnosisEarly diagnosis – PCRPCR – MALDI-TOFMALDI-TOF • Therapeutic drug monitoring (TDM)Therapeutic drug monitoring (TDM) • Tissue drug levelsTissue drug levels – Develop indicators of tissue drug levelsDevelop indicators of tissue drug levels • BiomarkersBiomarkers – Confirm definite sepsisConfirm definite sepsis – Exclude non-septic causes of inflammationExclude non-septic causes of inflammation
  • 54. The ‘D’s of antibiotic prescribingThe ‘D’s of antibiotic prescribing  DiagnosisDiagnosis  Drug choiceDrug choice  DoseDose  Dosing intervalDosing interval  Delivery methodDelivery method  Delivery kineticsDelivery kinetics  DynamicsDynamics  DysfunctionsDysfunctions  Drug interactionsDrug interactions  Don’t DamageDon’t Damage  Don’t DelayDon’t Delay  DurationDuration  De-escalationDe-escalation  DiscontinuationDiscontinuation
  • 55. Antibiotic pipelineAntibiotic pipeline  Immediate pipeline is very emptyImmediate pipeline is very empty!!  TedizolidTedizolid  AvibactamAvibactam  Ceftolozane / tazobactamCeftolozane / tazobactam  DalbavancinDalbavancin  Medium term – new aminoglycosides,Medium term – new aminoglycosides, glycylcycline, macrolide, glycopeptidesglycylcycline, macrolide, glycopeptides  Quorum-sensing inhibitors, anti-biofilm,Quorum-sensing inhibitors, anti-biofilm, immunomodulatorsimmunomodulators  Efflux pump blockersEfflux pump blockers