Surviving in an endemic situation
Prof George Dimopoulos MD, PhD, FCCP, FCCM
Department of Critical Care, University Hospital ATTIKON
National and Kapodistrian University of Athens, Medical School,
Surviving in an endemic situation Faculty disclosure (2012-17)
Advisory Boards - MERCK USA, Bayer Europe, MSD Europe, Clingier UK, Cardeas USA,
Virogates Denmark, Cempra USA, Tetraphase USA, Gilead UK
Lectures fees
- Pfizer Asian Pacific / USA, Pfizer Korea, Pfizer Taiwan/Australia,
MediaHealth New Delhi –India, Astellas UK / Japan, Baxter France
Research Grants
- EU-FP7 Project
- EU-Horizon FP8 Project
Societies
- ESICM, ERS, ESCMID
- International Society of Chemotherapy
- Asian-Pacific Society of Infectious Diseases
………Mortality, lCU length of stay, Cost
the other
meaning
of MIC ???
Hand hygiene
Treatment of outbreaks
Surveillance
Use of antibiotics
Infection control to minimize infections rates,
resistance emergence and spread
Surviving in an endemic situation The infections in the ICU lead to increased……….
Endemic (from Greek ἐν "in, within" and δῆμος demos "people") An infection is maintained in a population without the need for external inputs
Epidemic (from Greek ἐπί "upon or above" and δῆμος demos "people") The rapid spread of infectious disease to a large number of people in a given
population within a short period of time, usually two weeks or less
Pandemic (from Greek πᾶν "all" and δῆμος demos "people") An epidemic of infectious disease that has spread across a large region (f.i.
multiple continents, or worldwide.
Syndemic or synergistic epidemic The aggregation of two or more concurrent or sequential epidemics or
disease clusters in a population with biological interactions, which exacerbate
the prognosis and burden of disease
Surviving in an endemic situation What is endemic ?
What is outbreak ?
An increase over the
background or 'endemic' rate
of infection in a geographic
area (f.i ICU) with a particular
microbe or of a specific type
of infection such as SSI or BSI.
Only 8% of BSI are related to
an outbreak
How to approach outbrteaks ?
confirmation
multidisciplinary team
literature search
Checko PJ: Text of Infection Control and Epidemiolog T (2000 edition).
Washington DC, 2000, pp 15 15.9,
Doebbeling BN, Prevention and Control of Nosocomial Infections 2), Boston, MA, Little, Brown, 1992, pp 109-134
Surviving in an endemic situation Endemic and Outbreak situation
Molecular epidemiology
I. Genes
f.i. VIM-1 type (gene cassete)
or VIM-2 type base element and
number of nucleotides
II. Integrons
different structure suggests a
different evolution process rather
than a transfer various transposons
III. Plasmids
Rapid detection of resistance
PCR
highly sensitive and specific method
unavailable for daily use in many
laboratories
New Chromogenic medium CHROMagar
KPC CHROMagar orientation supplemented
with agents that inhibit the growth of gram
positive / gram-negative carbapenem-
sensitive bacteria.
Samra et al, J Clin Microb 2008, p. 3110–3111
Surviving in an endemic situation Approaching an endemic / outbreak
Two isolates that were considered as (A) identical are then
considered as (B) different after a third isolate was typed .
Blanc et al, Infection, Genetics and Evolution 4 (2004) 193–197
Surviving in an endemic situation Molecular epidemiology for endemic infections
1. Patient care items medications, enteral feeds, equipment
2. Person-to person transmission\
3. Environmental reservoirs Contamination of infusions, enteral feeds, medications (during
manufacture) is referred as "intrinsic" contamination
Surviving in an endemic situation Finding the Source
Factors contributing to antibiotic resistance in the community
Person-to-person
transmission in
PRIVATE places
Person-to-person
transmission in
PUBLIC places
Antibiotic resistance
within the
community setting
Selection pressures from:
- exposure to antibiotics
- ingestion of antibiotic - treated food-stuffs
Aiello et al. Lancet Infect Dis 2003; 3: 501–06
Surviving in an endemic situation The environment of ICU
Potential reservoirs of infection
- mattresses and pillows= KNOWN
HOWEVER……..
..all the bed components have to
be adequately decontaminated to
minimise the risk of cross-infection
Creamer et al, Journal of Hospital Infection (2008) 69, 8e23
Surviving in an endemic situation Beds and healthcare-associated infection
X represents VRE culture positive sites
Contaminated surfaces increase cross-transmission The hand of an intensivist in the agar
Surviving in an endemic situation The environment of ICU
“ Transient ” flora
Εnterobacteriacae
E. coli
Klebsiella spp
Proteus spp
Serratia spp
Enterobacter spp
Pseudomonas spp
Acinetobacter spp
MRSA
VRE
“Resident” flora
CοNS
Micrococci,
Propionibacterium spp
Surviving in an endemic situation Hand flora
Prospective, single-centre study in two adult ICUs
Environmental samples from the water fittings of rooms once per week,
during a 8-week period
In 193 (86.2%) of the 224 U-bend samples and in 10 of the 224 samples
from the tap (4.5%) P. aeruginosa
- 17/193 patients were colonized
- 1/17 patients was colonized by a clone present in the water
environment of his room before the patient’s first positive sample
Water fittings seem to play a smaller role in non epidemic situations than
expected
Cholley et al, Intensive Care Med (2008) 34:1428–1433
Surviving in an endemic situation Water environment in the ICU
of resistant strains
amplification and
spread of resistance
- Eradication of the susceptible strains
- Growth of the resistant strains
- Function of antimicrobial activity and
the pharmacokinetics of the antibiotic
- Environmental factors
and fitness of the resistant strain
emergence of the
resistant strain
- Spontaneously
- Independent of antibiotic presence
- A function of the bacterial and of the
antibiotic
Hawkey, BMJ 1998; 317:657–60; Freney, Précis de bactériologie Clinique Ed. ESKA 2000; Andremont,Med Mal Inf.2005;35 sup3:S207-11;
Rice, Clin Infect Dis 2000; 31:762–9; Livermore, Clin Infect Dis 2003;36Sup1:S11-23
• The emergence of bacterial resistance is
through two mechanisms
Mutation Acquisition of
foreign DNA +
Surviving in an endemic situation Outbreaks : Resistance emergence and spread
Polyclonal epidemiology
usually associated with antibiotic use
Clonal epidemiology
may be amenable to infection control
Rahal J et al. Clin Infect Dis 2002;34:499-503.
The type of resistance observed may help determine the
measures that need to be taken to manage resistance
Surviving in an endemic situation Clinically Relevant Considerations in Resistance
Single-center, 2-year study (Guideline to restrict cephalosporin use)
Main outcome : to reduce the incidence of CAZ-resistant Klebsiella
colonization and infection.
80% reduction in cephalosporin use
44% reduction in CAZ-resistant K. pneumoniae (p<0.01)
71% reduction in CAZ-resistant K. pneumoniae in the ICU
88% reduction in the surgical ICU (p<0.001)
Imipenem-resistant P. aeruginosa retained sensitivity to
b- lactams, quinolones, aminoglycosides
Rahal J et al. JAMA 1998;280:1233-1237, Rahal J et al. Clin Infect Dis 2002;34:499-503.
Surviving in an endemic situation Resistance Due To Polyclonal Epidemiology
CAZ = ceftazidime
In vitro results from 15 Brooklyn hospitals showed that:
Cephalosporin use correlated with emergence of a MDR clone
of Acinetobacter spp.
Ribotyping revealed that a single clone accounted for 62%
of the samples and was isolated from patients at all 15 hospitals
This implicated infection control as the source of the problem
Improved infection control is an important component of
managing such outbreaks
Landman D et al. Arch Intern Med 2002;162:1515-1520.
Surviving in an endemic situation Resistance Due To Clonal Epidemiology
Colonized patients people who carry bacteria without evidence of infection
Infection usually from bacteria that colonize patients
Bacteria that colonize patients can be transmitted from one patient to another by the hands
of healthcare workers
Bacteria can be transmitted even if the patient is not infected
Surviving in an endemic situation Colonization and Infections
Book M et al. Best Pract Res Clin Anaesthesiol. 2013;27:279-88.
Days 1 2 3 4 5 6 7
negative
Only ~10%
are positive
1. Poor specificity (false positive rates: 5 to 50% depending on the methods of collection)
2. Despite optimization of the technique only 15–25% of positive results can be anticipated
3. In up to 30% of the patients with fever clear results cannot be obtained at all
(BC sensitivity for slow growing and fastidious organisms can be poor)
Blood culture (BC)
the gold standard
takes an average 1-2 days
to get a positive result
Surviving in an endemic situation Better diagnosis is needed
Hybridization Amplification Post-amplfication detection strategies
Non-nucleic acid
FISH
PNA FISH
Probe
hybridization
Microarrays
PCR
Broad-range
PCR
Pathogen
specific PCR
Multiplex PCR
PCR +
Proteomics
Spectroscopy
Phage assays
Sequencing
Pyrosequencing
Hybridization
MALTI-TOF-MS
Venkatesh M et al. Expert Rev Anti Infect Ther. 2010;8:1037–1048;
Mancini N et al. Clin Microbiol Rev 2010;23:235–251.
Surviving in an endemic situation Molecular methods of diagnosis
MALDI-TOF-MS Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
• It is based on proteomic profiling of highly
conserved proteins for the rapid (5–15 min)
identification of bacteria and fungi
• Biological material (colony or blood culture
concentrated) is placed on a plate that has a
polymeric matrix
• Irradiated with a laser that vaporizes the sample,
resulting in ionization of molecules, which are
then aspirated into a vacuum flight tube and travel
to a detector
• Protein spectra profile compared with database
Clin Microbiol Infect 2010;16:1604
Surviving in an endemic situation MALDI-TOF-MS
MALDI Sepsityper
• Identification of microorganisms from positive blood culture
bottles in < 30 min.
• Simple preparation protocols using just 1 ml sample material
Schieffer KM, et al. J Appl Microbiol. 2014;116:934-41. Jamal W, et al. Diagn Microbiol Infect Dis. 2013;76(4):404-8.
Meex C, et al. J Med Microbiol. 2012;61(Pt 11):1511-6. Martiny D et al. Eur J Clin Microbiol Infect Dis. 2012;31:2269-81
SE-MALDI accurately
identified 332 (80.8%) of
411 positive BC
Surviving in an endemic situation MALDI Sepsityper Kit
SepsiTest VYOO ®-
Multiplex PCR LightCycler
SeptiFast
Detection limit: 3-30 CFU/mL 20-40 for S. aureus 3-10 CFU/mL
Time: 6 h 8-12 h 8 h
Skvarc M Eur J Microbiol Immunol (Bp). 2013 Jun;3(2):97-104; Paulocci M Intern J Antimicrob Agents 2010;36S:S6
Surviving in an endemic situation Detection of microorganisms directly from whole blood
“Spacer Technology” : A multiplex PCR assay that uses post amplification melting point analysis to
identify microorganisms
16S 23S ITS (Spacer)
Generic Primers (“pan bacteria”) Specific Probes
Group (e.g. Enterobacteriaceae)
Amplification curve
Cycles Tm (melting temperature )
Probe Melting Point(s)
E. coli Enterobacter cloacae
Tm depended upon
- fragment length,
- composition of
sequence and
-degree of homology
between the
hybridization probe
and the target DNA
Surviving in an endemic situation Detection of microorganisms directly from whole blood
● Rapid diagnosis and implementation
of targeted AB treatment
positivity rate significantly higher than
that of BC (x 2 times)
less contaminations due to skin flora
● Diagnosis of invasive fungal infections
detection and identification of 5
Candida spp. & A. fumigatus
● More sensitive than BC in patients
already treated by AB
1. High-risk patients and patients with
presumed sepsis
2. Patients with febrile neutropenia
– Patients with onco-hematological
malignancies
3. Neonates and children
4. Transplants recipients
5. Patients with serious burns
6. Patients with suspected endocarditis
LC-SF is of high rule-in value for early detection of septic patients.
In a population with low pretest probability, LC-SF test can still provide
valuable information for ruling out bacteremia or fungemia.
Surviving in an endemic situation Implementation of SeptiFast Test
Chang S-S et al., (2013) Multiplex PCR System for Rapid Detection of Pathogens in Patients with Presumed Sepsis
– A Systemic Review and Meta-Analysis. PLoS ONE 8(5): e62323
KPC
OXA
VIM IMP
NDM
Other Metallo-β-lactamases:
SPM, GIM, and SIM
Class A (serine based) SME, IMI, NMC, GES
Versatile hydrolytic capacities
Variable phenotypic profiles
Variable fitness expression
Variable virulence
Clonal backbone ST258, ST131 Low Expression in vivo
High Expression in vivo
Surviving in an endemic situation Evolving In Vivo Understanding of Carbapenemases
Test Name Approved
Specimens
Advantages Disadvantages
FilmArray®
BCID Panel
Biofire Dx
Blood Culture
Detects the most prevalent
CP in US – KPC
Comprehensive 27 target panel
for most common causes of BSIs
• Does not detect NDM, VIM, OXA-48, IMP
• Expensive for routine detection
• Limited in sample throughput
Verigene®
System
Nanospher, Inc.
Blood Culture
Comprehensive panel
detects most common
carbapenemases and
CTX-M ESBL
• Limited in sample through put
• Expensive for routine use
Xpert CarbaR
Cepheid, Inc.
Resistant culture
isolates from blood,
urine, sputum, rectal
swabs
Direct detection from
rectal swabs
Rapid – 48 min. to result
Comprehensive – 91 gene
targets for carbapenemase
producing organisms, reported
as 5 gene families
KPC, NDM, VIM, IMP, OXA-48
• Higher cost
• Specific for carbapenemases
• Does not detect ESBLs
http://jac.oxfordjournals.org/content/early/2014/03/26/jac.dku083.full.pdf
Surviving in an endemic situation Endemic arias - Molecular Testing for Carbapenemase
Ignaz P. Semmelweis
(1818-1865)
Allegemeines
Krankenhaus,
University of Vienna
Hand hygiene basin at the Lying-In Women’s Hospital in Vienna, 1847.
Semmelweis’ Hand Hygiene Intervention
Surviving in an endemic situation Hand hygiene
• Handwashing
• Antiseptic handwash
• Alcohol-based handrub
• Surgical hand hygiene /
antisepsis
Washing hands
- plain soap/water
Washing hands - water and soap or detergents
containing an antiseptic agent
Rubbing hands
- alcohol-containing preparation
Handwashing - alcohol-based handrub before
operations
Guideline for Hand Hygiene in Health-care Settings. MMWR 2013;51:RR-16
Surviving in an endemic situation Hand hygiene : Methods and Techniques
Good Better Best
Plain Soap Antimicrobial soap
Alcohol-based handrub
Surviving in an endemic situation Hand hygiene : the right solution
avoiding the
recontamination
Surviving in an endemic situation Hand hygiene : the right way
0.0
1.0
2.0
3.0 0 60 180 minutes
0.0
90.0
99.0
99.9
log %
Bacte
rial
Red
ucti
on
Alcohol-based handrub
(70% Isopropanol)
Antimicrobial soap
(4% Chlorhexidine)
Plain soap
Time After Disinfection
Baseline
Surviving in an endemic situation Hand hygiene : ability of agents to reduce bacteria on hands
ARTIFICIAL
POLISHED
NATURAL
Edel et. al, Nursing Research 1998: 47;54-59
- Avoid wearing artificial nails - Keep natural nails <1/4 inch, if caring for high risk patients
Surviving in an endemic situation Hand hygiene : Use of artificial nails
Make improved hand hygiene an institutional priority
Place alcohol-based handrubs at entrance to patient room or at bedside
Provide HCWs with pocket-sized containers
Guideline for Hand Hygiene in Health-care Settings. MMWR 2017;51:RR-16
Surviving in an endemic situation Improving Hand hygiene
Surveillance
systematic approach using standaradized definitions for
infection, providing a means to recognize problems and to
effectively target infection control measures
Haas JP et al. Seminars in Perinatology 2002; 26(5 ) 367-378
Surviving in an endemic situation Surveillance cultures for early/appropriate ABs treatment
35 ICUs - microbial resistance, antibiotic consumption, infection control and
stewardship measures were evaluated
Median (range) antibiotic consumption
- 1,254 (range 348–4,992) DDD per 1,000 occupied bed days
The proportion - MRSA median 11.6% (range 0–100)
- ESBL phenotype of E. coli 3.9% (0–80)
- K. pneumoniae 14.3% (0–77.8)
- Carbapenem resistant P. aeruginosa 22.5% (0– 100)
Wide variation in antibiotic consumption, microbial resistance
and infection control measures
Hanberger et al, Intensive Care Med DOI 10.1007/s00134-008-1237-y
Surviving in an endemic situation Surveillance of microbial resistance in European ICUs
Using a surveillance method….
- …concordance between VAP and BSI pathogenic
isolates and prior RTIs or GT colonization
Surveillance cultures Acinetobacter, Pseudomonas,Klebsiella
VAP (PPV 67–94%, NPV 73–100%)
Bacteremia (PPV 43–54%, NPV 88-100%)
Surveillance-guided initial antibiotic Rx
- appropriate in 91% and 86% of patients with
VAP and bacteremia respectively.
Papadomichelakis et al Intensive Care Med (2008) 34:2169–2175
Surviving in an endemic situation Surveillance cultures for appropriate Rx with ABs
Patient A (BSI) -A1 blood, A2 tracheal aspirate, A3 stool, A4 pus
Patient B (VAP) -B5 tracheal aspirate, B6 BAL
Patient C (VAP) -C7 tracheal aspirate, C8 stool, C9 BAL, C10 pus
Patient D (BSI) - D11 stool, D12 blood
Surviving in an endemic situation Surveillance cultures : REP-PCR molecular typing
Papadomichelakis et al Intensive Care Med (2008) 34:2169–2175
Unit-specific antibiograms and results from large-
scale studies in choosing initial appropriate therapy
Certain antibiotics promote resistance to other classes Choose agents that minimize resistance
Consider the impact of outpatient antibiotic therapy on in- patient
antibiotic resistance.
Choose combination therapy in appropriate settings.
Kollef MH. Drugs 2003;63;2157-2168.
Kollef MH. Clin Infect Dis 2000;31(Suppl 4):S131-S138.
Surviving in an endemic situation Selecting Initial Appropriate Antibiotic Therapy
• Infection site
• Possible organisms
• Kill characteristics Concentration vs time dependent
• Penetration
• Highest dose without AEs
• Therapeutic Monitoring (TDM)
The intensivist always
has to answer this
question !!!!!
Surviving in an endemic situation Selecting Initial Adeqaute Antibiotic Therapy
1. Bactericidal vs –static
2. Antibacterial spectrum
targeted to relevant pathogens/ avoiding collateral damages
3. Potency
4. Activity PK/PDs, Dosage
5. Duration of exposure Short vs long duration
6. Half life Duration of sub-inhibitory concentration
Surviving in an endemic situation The use of antibiotics, what we have to consider ?
1. Origin : Semisynthetic tetracycline derivative
2. Registration : (FDA) Rx for minocycline-susceptible Acinetobacter spp
3. Susceptibility : CLSI breakpoints for Acinetobacter a. Susceptibility ≤4 μg/mL b. Intermediate 8 μg/mL c. Resistance ≥16 μg/mL
4. Activity : Inhibits bacterial protein synthesis a. through binding with the 30S subunit of the bacterial ribosome b. bacteriostatic effect c. synergistic and bactericidal activity against MDR Acinetobacter
in combination with colistin or carbapenems
5. Dosing a. IV 200-mg load, followed by 100 mg / 12 h (not to exceed 400 mg in 24 h) b. Renal dosing : Not required
6. Resistance : Mechanisms of Acinetobacter resistance to minocycline a. tet(B) efflux gene b. plasmid- mediated ISCR2 mobile element
Ritchie DJ et al, CID 2014:59 (Suppl 6): S374-80
Surviving in an endemic situation The revival of old antibiotics - Minocycline
A. VAP1,2,3,4 - Retrospective small studies
- Critically ill patients with Acinetobacter spp infections
- Dose 100 mg x 2 after a loading dose of 200 mg
- Monotherapy (S to tetracycline), in combination MDR
- Successful outcomes ranging 70-100% (clinical and microbiological
B. Skin and soft tissue infections with or without osteomyelitis3,4,5 - Retrospective small studies
- Patients with Acinetobacter spp infections, Monotherapy (S to tetracycline)
- Dose 100 mg x 2 after a loading dose of 200 mg
B. Bacteremia3 - Retrospective small studies
- Trauma patients with Acinetobacter spp infections, Monotherapy (S to tetracycline),
- Dose 100 mg x 2 after a loading dose of 200 mg
1,Wood GC et al, Intensive Care Med 2003; 29:2072–6, 2Chan JD et al J Intensive Care Med 2010; 25:343–8, 3Jankowski CA, et al, Infect Dis
Clin Pract 2012; 20:184–7, 4Bishburg E et al Infect Dis Clin Pract 2014; 22:26–31, 5Griffith ME, et al, Infect Dis Clin Pract 2008; 16:16–9.
Surviving in an endemic situation Clinical experience with IV Minocycline
In vitro antimicrobial activity for 24 h (baseline) and durability for up to 3 weeks of different antimicrobial-coated
catheters against A. baumannii, E. cloacae, and E. coli (A) and K. pneumoniae, P. aeruginosa, and S. maltophilia (B).
M/R : minocycline-rifampin, CHX/SS : chlorhexidine silver sulfadiazine
CHX-M/R : chlorhexidine-minocycline- rifampin
Jamal MA et al. AAC 2014;58(2):1179–1182
Surviving in an endemic situation Minocycline against biofilm formation
Phosphonic antibiotic Structurally unrelated to other antibiotics
Broad spectrum through inhibition of
enzyme involved in peptidoglycan
synthesis
Available in 2 dose forms
Parenteral : fosfomycin disodium
Oral : fosfomycin tromethamine
(trometamol) better → absorption
Registration
Not registered in many countries
Shaping the antibiotic therapy in MDR/XDR/PDR era Fosfomycin - Microbiology
Susceptible pathogens
Staphylococci (incl MRSA) and
Enterococci
Heamophilus spp
Enterobacteriaceae Klebsiella spp, Enterobacter, Serratia
spp.
Acinetobacter spp. and
Pseudomonas spp. ?????
highly variable MICs
EUCAST Resistant breakpoint 32
mg/L
• Capillary leak*
• increased body fluid
• Organ dysfunctions
elimination
accumulation of metabolites
• Administration of multiple drugs - drug interactions
- altered protein binding
* Capillary leak important changes in concentrations of
antibiotics with low volumes of distribution
(penicillins, cephalosporins, carbapenems and
aminoglycosides)
Surviving in an endemic situation What is different in critical illness ?
SEPSIS
Increased Cardiac
Index
Leaky Capillaries &/or
altered protein binding End Organ Dysfunction
Increased
Clearances
Increased Volume of
Distribution
Decreased Clearances
Low Serum
Concentrations
High Serum
Concentrations
JA Roberts, J Lipman, Clin Pharmacokinet 2006;45:755-773
Surviving in an endemic situation Sepsis pathophysiology and antibiotic pharmacology
0
50
100
150
200
250
0 50 100 150 200 250 300
Creatinine Clearance (mL/min)
Dru
g C
lea
ran
ce
(m
L/m
in)
Augmented
Renal
Clearance
Cr Cl>130ml/min
Lipman et al Anesth Analg 2003
Surviving in an endemic situation Creatinine clearance
ARC (supranormal glomerular filtration)
ClCr > 130 ml/min/1.73m2
Cockcroft Gault
ClCr = (140-age) x Wt x 1.73
(Scr x 72 x BSA) x 0.85 (female)
Most common in critically ill
Patients with:
SIRS/Sepsis
Trauma
Tro
ug
h c
on
ce
ntr
ati
on
:MIC
1
10
100
50 100 150 200 250 300 350 ClCr (ml/min/1.73m2)
Udy AA et al. Chest 2012;142:30-39. Baptista JP et al. Crit Care 2011;15:R139.
β-lactam underdosing
in patients with ΑRC
Surviving in an endemic situation Augmented Renal Clearance (ARC)
Surviving in an endemic situation Pipeline-new antibiotics
Drug name Drug class Potential indications
Recently
approved
Ceftazidine/Avibactam Cephalosporin/ β-lactamase inhibitor cIAI, cUTI, HAP/VAP
Ceftaroline Extended spectrum cephalosporin Pneumonia, Skin infections
Solithromycin Macrolide (fluoroketolide) CAP
Tedizolid Oxazolidinone HAP/VAP, Skin infections
Ceftolozane/Tazobactam Cephalosporin/β-lactamase inhibitor HAP/VAP, cIAI, cUTI
Aztreonam/Avibactam Monobactam/β-lactamase inhibitor cIAI
Dimopoulos G et al . The ICM research agenda on MDR, antibiotics, and stewardship Intens Care Med 2016
Surviving in an endemic situation New antibiotics
Drug name Drug class Potential indications
Under
development
Aztreonam/Avibactam Monobactam / β-lactamase inhibitor cIAI
Cadazolid Quinolonyl-oxazolidinone C. difficile infection
Ceftaroline/Avibactam Cephalosporin/β-lactamase inhibitor Bacterial infections
Delafloxacin Fluoroquinolone Skin infections, CAP, cUTI
Eravacycline Tetracycline cIAI, cUTI
Finafloxacin11 Fluoroquinolone cUTI, cIAI, Skin infections
Iclaprim Dihydrofolate reductase inhibitor Skin infections, HAP/VAP
Imipenem/Relebactam Carbapenem/β-lactamase inhibitor cUTI, cIAI, HAP/VAP
Meropenem/Vaborbactam Meropenem/boronic β-lactamase inhibitor cUTI, cIAI, HAP/VAP, BSI
Nemonoxacin8 Quinolone CAP, Skin infections
Omadacycline Tetracycline CAP, Skin infections , cUTI
Plazomicin Aminoglycoside cUTI, BSI, HAP/VAP, cIAI
S-649266 Siderophore cephalosporin BSI, HAP/VAP, cUTI
Zabofloxacin Fluoroquinolone CAP
Dimopoulos G et al . The ICM research agenda on MDR, antibiotics, and stewardship Intens Care Med 2016
New class of
antibiotics
Surviving in an endemic situation New antibiotics
………Mortality, lCU length of stay, Cost
the other
meaning
of MIC ???
Hand hygiene
Treatment of outbreaks
Surveillance
Use of antibiotics
Infection control to minimize infections rates,
resistance emergence and spread
Surviving in an endemic situation Conclusions
WE ’RE ALL TIRED – BEER TIME ??
Surviving in an endemic situation THE END !