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,

gdimop@med.uoa.gr

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 !