Nosocomial Pneumonia Dr Suruchi

8/3/2019 Nosocomial Pneumonia Dr Suruchi

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Tracking NI has becomedifficult

Shorter inpatient stays (averagepostoperative stay, now

approximately 5 days, is usuallyshorter than the 5- to 7-dayincubation period for S. aureussurgical wound infections)

Surveillance systems are optional tohospitals with infection-controlprograms


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Prevention ofVentilator

AssociatedPneumonia

(VAP)

AACN VAP Practice Alert


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Lecture Content

Epidemiology ofVAP

Preventionstrategies

HOB elevation

Ventilatorequipment changes

Continuous removalof subglottic

secretions Handwashing



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Epidemiology of Ventilator Associated

Pneumonia (VAP)



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Nosocomial Pneumonias

Account for 15% of all hospitalassociated infections

Account for 27% of all MICUacquired infections

Primary risk factor is mechanicalventilation (risk 6 to 21 times therate for nonventilated patients)

CDC Guideline for Prevention of Healthcare AssociatedPneumonias 2003Cook et al, Ann Intern Med 1998;129:433



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Critical Care Interventions Increase Susceptibility

to Nosocomial Pneumonias

TrachealColonization

AlteredHost

Defenses

IncreasedNosocomialPneumonias

Intubation



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VAP Etiology Most are bacterial pathogens, with

Gram negative bacilli common:

Pseudomonas aeruginosa

Proteus spp Acinetobacter spp

Staphlococcus aureus

Early VAP associated with non-multi-antibiotic-resistant organisms

Late VAP associated with antibiotic-resistant organism



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Significance of NosocomialPneumonias

Mortality ranges from 20 to 41%,depending on infecting organism,

antecedent antimicrobial therapy, andunderlying disease(s)

Leading cause of mortality fromnosocomial infections in hospitals

CDC Guideline for Prevention of Healthcare Associated Pneumonias 2003Heyland et al, Am J Respir Crit Care Med 1999;159:1249Bercault et al, Crit Care Med 2001;29:2303



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Significance of NosocomialPneumonias

Increases ventilatory supportrequirements and ICU stay by 4.3

days Increases hospital LOS by 4 to 9

days

Increases cost -

Heyland et al, Am J Respir Crit Care Med1999;159:1249Craven D. Chest 2000;117:186-187S

Rello et al, Chest 2002;122:2115



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VAP Prevention



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Continuous Removal ofSubglottic Secretions

Use an ET tube with

continuous suctionthrough a dorsal lumenabove the cuff toprevent drainageaccumulation

CDC Guideline for Prevention of Healthcare Associated Pneumonias

2003Kollef et al, Chest 1999;116;1339



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HOB Elevation

HOB at 30-45o

CDC Guideline for Prevention of Healthcare Associated Pneumonias 2003Drakulovic et al, Lancet 1999;354:1851


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Frequency of EquipmentChanges

VentilatorTubing

InnerCannulasof Trachs

AmbuBags

No RoutineChanges

Not Enough

DataBetweenPatients

CDC Guideline forPrevention of Healthcare Associated Pneumonias



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Handwashing

What role does handwashing play innosocomial pneumonias?

Albert, NEJM 1981; Preston, AJM 1981; Tablan, 1994AACN VAP Practice Alert


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VAP Prevention

All recommendations are level IA

CDC Guideline for Prevention of Healthcare Associated

Pneumonias 2003AACN Practice Alert for VAP, 2004

Wash hands before and

after suctioning, touchingventilator equipment,and/or coming intocontact with respiratorysecretions.



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Use a continuous subglotticsuction ET tube for intubationsexpected to be > 24 hours

Keep the HOB elevated to atleast 30 degrees unlessmedically contraindicated

VAP Prevention

All recommendations are level II

CDC Guideline for

Prevention of Healthcare Associated Pneumonias2003



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No Data to Support TheseStrategies

Use of small bore versus large boregastric tubes

Continuous versus bolus feeding Gastric versus small intestine tubes

Closed versus open suctioningmethods

Kinetic beds

CDC Guideline forPrevention of Healthcare Associated



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Potential consequences ofinappropriate antibiotic therapy

Inappropriate empiric antibiotictherapy can lead to increases in:

mortality

morbidity

length of hospital stay

cost burden

resistance selection


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Inappropriate antibiotictherapy

Inappropriate antibiotic therapy canbe defined as one or more of the

following: ineffective empiric treatment of

bacterial infectionat the time of its identification

the wrong choice, dose or duration oftherapy

use of an antibiotic to which thepathogen

is resistant

Evidence of improved clinical


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Evidence of improved clinicaloutcomes with appropriateempiric antibiotic therapy

A number of studies havedemonstrated the

benefits of early use ofappropriate empiricantibiotic therapy for patientswith nosocomial infections

Several key clinical studies arereviewed in the followingslides


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Inappropriate antibiotic therapy is a riskfactor for mortality among patients in theintensive care unit (ICU)

Infection-related mortality rates were assessedin a prospective cohort, single-centre study of2000 patients admitted to medical/surgical ICUs

655 patients had a clinically recognisedinfection:

442 (67.5%) had a community-acquiredinfection

286 (43.7%) developed a nosocomial

infection 73 (11.1%) had both community-acquired

and nosocomial infections

169 (25.8%) patients received inappropriate

initial antimicrobial treatment Kollef et al. Chest 1999;115:462474

Inappropriate antibiotic therapy is


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Inappropriate antibiotic therapy isa risk factor for mortality amongpatients in the ICU

Kollef et al. Chest 1999;115:462474

Hospital mortality (%)

0

20

50

60

Appropriate therapyInappropriate therapy

40

30

10

All causes Infectious disease-related

p


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Appropriate antibiotic therapy reducesmortality and complications in patientswith nosocomial pneumonia

The frequency of and reasons for changing empiricantibiotics during the treatment of hospital-acquiredpneumonia were assessed in a prospectivemulticentre study across

30 Spanish hospitals Of the 16 872 patients initially enrolled, 530

developed565 episodes of pneumonia after ICU admission

Empiric antibiotics (administered in 490 [86.7%] of

episodes) were modified in 214 (43.7%) casesbecause of:

isolation of micro-organism not covered by treatment(62.1%)

lack of clinical response (36.0%)

development of resistance (6.6%)Alvarez-Lerma et al. Intensive Care Med 1996;22:387394


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Alvarez-Lerma et al. Intensive Care Med 1996;22:387394

Appropriate antibiotic therapy reducesmortality and complications in patientswith nosocomial pneumonia

Appropriatetherapy

(n=284)

Attributable mortality

No. complications/patient

Shock

Gastrointestinal bleeding

Respiratory failure

Multiple organ failure

Extrapulmonary infection

Inappropriatetherapy

(n=146) p-value

16.2%

1.73 1.82

17.1%

10.7%

24.9%

12.5%

13.2%

24.7%

2.25 1.98

28.8%

21.2%

32.2%

21.2%

17.1%

0.04


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Appropriate early antibiotic therapy reducesmortality rates in patients with suspectedventilator-associated pneumonia (VAP) (Study1)

A prospective observation and bronchoscopy studyof patients with VAP assessed the impact ofbronchoalveolar lavage (BAL) data on the selectionof antibiotics and clinical outcomes in a

medical/surgical ICU 132 mechanically ventilated patients (hospitalised

>72 hours) with clinically confirmed VAP underwentBAL within 24 hours of diagnosis 107 patients received antibiotics prior to

bronchoscopy 25 patients received antibiotics immediately after

bronchoscopy Mortality rates were assessed in relation to the

adequacy and time of initiation of antibiotic therapy

Luna et al. Chest 1997;111:676685

Appropriate early antibiotic therapy reduces


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Luna et al. Chest 1997;111:676685

Appropriate early antibiotic therapy reducesmortality rates in patients with suspectedVAP(Study 1)

Mortality (%)

Pre-BAL Post-BAL Post-cultureresult

0

60

100

20

40

80

p


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ppropr a e ear y an o c erapy re ucesmortality rates and length of hospital stayin patients with bloodstream infection(Study 1)

An observational prospective cohort study of patientswith bloodstream infection examined whetherappropriate antibiotic therapy improved survival rate

Of the 3413 evaluable patients, 2158 (63%) receivedearly appropriate antibiotics

defined as starting within 2 days of the firstpositive blood culture, and if the causativepathogen was susceptiblein vitro to the administered drug

Mortality rates and median duration of hospital stayfor surviving patients were determined

Leibovici et al. J Intern Med 1998;244:379386


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Appropriate early antibiotic therapy reducesmortality rates and length of hospital stay inpatients with bloodstream infection (Study 1)

Leibovici et al. J Intern Med 1998;244:379386

Appropriate

therapy

(n=2158)

Mortality rate

Median duration of

hospital stay

Inappropriate

therapy

(n=1255) p-value

20.2%

9 days

(range 0117)

34.4%

11 days

(range 0209)

0.0001

0.0001


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Summary

Clinical evidence suggests thatearly use of appropriate empiric

antibiotic therapy improvespatient outcomes in terms of:

reduced mortality

reduced morbidity

reduced duration of hospital stay


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Resistance to antibacterialagents

Antibiotic resistance either arises as a resultof innate consequences or is acquired fromother sources

Bacteria acquire resistance by:

mutation: spontaneous single or multiplechanges in bacterial DNA

addition of new DNA: usually via plasmids,which can transfer genes from onebacterium to another

transposons: short, specialised sequencesof DNA that can insert into plasmids orbacterial chromosomes


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Mechanisms of antibacterialresistance (1)

Structurally modified antibiotictarget site, resulting in:

reduced antibiotic binding

formation of a new metabolicpathway preventing metabolism of

the antibiotic

Structurally modified antibiotic


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Structurally modified antibiotictarget site

Interior of organism

Cell wall

Target siteBinding

Antibiotic

Antibiotics normally bind to specific binding

proteins on the bacterial cell surface

Structurally modified antibiotic


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Structurally modified antibiotictarget site


Cell wall

Modified target site

Antibiotic

Changed site: blocked binding

Antibiotics are no longer able to bind to modified

binding proteins on the bacterial cell surface


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Altered uptake of antibiotics,resulting in:

decreased permeability

increased efflux


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Altered uptake of antibiotics:decreased permeability


Cell wall

Porin channel

into organism

Antibiotic

Antibiotics normally enter bacterial cells via

porin channels in the cell wall


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Altered uptake of antibiotics:decreased permeability


Cell wall

New porin channel

into organism

Antibiotic

New porin channels in the bacterial cell wall do

not allow antibiotics to enter the cells


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Altered uptake of antibiotics:increased efflux


Cell wall

Porin channel

through cell wall

Antibiotic

Entering Entering

Antibiotics enter bacterial cells via porin

channels in the cell wall


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Altered uptake of antibiotics:increased efflux


Cell wall

Porin channel

through cell wall

Antibiotic

Entering Exiting

Active pump

Once antibiotics enter bacterial cells, they are

immediately excluded from the cells

via active pumps


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Antibiotic inactivation

bacteria acquire genes encoding

enzymes that inactivate antibiotics Examples include:

-lactamases

aminoglycoside-modifying enzymes chloramphenicol acetyl transferase


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Cell wall

Antibiotic

Target siteBindingEnzyme

Inactivating enzymes target antibiotics


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Cell wall

Antibiotic

Target siteBindingEnzyme

Enzyme

binding

Enzymes bind to antibiotic molecules


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Cell wall

Antibiotic

Target siteEnzyme

Antibiotic

destroyedAntibiotic altered,

binding prevented

Enzymes destroy antibiotics or prevent binding to target sites

Many pathogens possess multiple


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Many pathogens possess multiplemechanisms of antibacterialresistance

+Quinolones++Trimethoprim++Sulphonamide

++Macrolide+Chloramphenicol

+Tetracycline +++Aminoglycoside+Glycopeptide

++++-lactam

Modified target Altered uptake Drug inactivation


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Focus on -lactam antibioticresistance mechanisms

Three mechanisms of-lactamantibiotic resistance are

recognised: reduced permeability

inactivation with -lactamase

enzymesaltered penicillin-binding proteins

(PBPs)


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Multiple antibiotic resistancemechanisms: the -lactams

l ibi i


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-lactam antibioticresistance

AmpC and extended-spectrum -lactamase (ESBL) production are themost important mechanisms of-lactam resistance in nosocomialinfections

The antimicrobial and clinicalfeatures of these resistancemechanisms are highlighted in thefollowing slides


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-lactam resistance:AmpC -lactamase production

Worldwide problem: incidence increased from 1723% between

1991 and 2001 in UK

Very common in Gram-negative bacilli AmpC gene is usually sited on

chromosomes, but can be present onplasmids

Enzyme production is either constitutive(occurring all the time) or inducible (onlyoccurring in the presence of theantibiotic)

Pfaller et al. Int J Antimicrob Agents 2002;19:383388

Sader et al. Braz J Infect Dis 1999;3:97110; Livermore et al. Int J Antimicrob Agents 2003;22:1427

l t i t ESBL


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-lactam resistance: ESBLproduction

An increasing global problem

Found in a small, expanding group of

Gram-negative bacilli, most commonlythe Enterobacteriaceae spp.

Usually associated with large plasmids

Enzymes are commonly mutants of TEM-andSHV-type -lactamases

Jones et al. Int J Antimicrob Agents 2002;20:426431

Sader et al. Diagn Microbiol Infect Dis 2002;44:273280

A ti i bi l f t f


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Antimicrobial features ofESBLs

Inhibited by -lactamase inhibitors

Usually confer resistance to:

first-, second- and third-generation cephalosporins(eg ceftazidime)

monobactams (eg aztreonam)

carboxypenicillins (eg carbenicillin)

Varied susceptibility to piperacillin/tazobactam

Typically susceptible to carbapenems and

cephamycins Often clinically and/or microbiologically

non-susceptible to fourth-generation cephalosporins


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Clinical features of ESBLs

Even if sensitive to fourth-generationcephalosporinsin vitro, treatment failures occur in clinicalpractice

Create clinical difficulties due to cross-resistancewith other antibiotic classes (egaminoglycosides)

Associated with nosocomial outbreaks of highmorbidity and mortality

Result in overuse of other broad-spectrum

agents

Cli i l f il i th


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Clinical failure in thepresence of ESBLs

Recent data show high clinical failure rates among patientstreated with cephalosporins for serious infections causedby ESBL-producing pathogens

susceptible to cephalosporins in vitro

4/32 patients received cephalosporins to whichpathogens showed intermediate susceptibility and allfailed treatment

15/28 remaining patients with cephalosporin-susceptible pathogens failed treatment and 4 died

11 patients required a change in antibiotic therapy

Paterson et al. J Clin Microbiol 2001;39:22062212

Patients who failed cephalosporin


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Patients who failed cephalosporintherapy for serious infections due toESBL-producing organisms

Paterson et al. J Clin Microbiol 2001;39:22062212

Clinical failure rate (%)

0

60

100

20

1

40

80

2 4 8

Cephalosporin MIC (g/mL)


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Features of methicillin-resistantStaphylococcus aureus (MRSA)

Introduction of methicillin in 1959 wasfollowed rapidly by reports of MRSAisolates

Recognised hospital pathogen since the1960s

Major cause of nosocomial infectionsworldwide contributes to 50% of infectious morbidity in

ICUs in Europe

surveillance studies suggest prevalence hasincreased worldwide, reaching 2550% in

1997 Jones. Chest 2001;119:397S404S

S i i f ti t ti iti f MRSA


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Serious infections testing positive for MRSAisolates among hospitalised patients(1997 SENTRY data)

Patients (%)

0

30

50

10

Pneumonia

20

40

UTI Wound Bloodstream

Infection type

Jones. Chest 2001;119:397S404S

UTI

UTI = urinary tract infection

F t f MRSA id i


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Features of MRSA: epidemicstrains

Problem escalated in the early 1980s withemergence of epidemic strains (EMRSA)

first recognised in the UK

17 EMRSAs identified to date

Impact on hospitals is variable

presence of EMRSA can account for >50%

ofS. aureus isolates

Aucken et al. J Antimicrob Chemother 2002;50:171175

k f f l


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Risk factors for colonisation or

infection with MRSA in hospitals

Chambers. Emerg Infect Dis 2001;7:178182

Admission to an ICU

Surgery

Prior antibiotic exposure

Exposure to an MRSA-colonised patient

E f MRSA i th


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Emergence of MRSA in thecommunity

MRSA in hospitals leads to an associated rise in incidencein the community

Community-acquired MRSA strains may be distinct fromthose in hospitals

In a hospital-based study, >40% of MRSA infections wereacquired prior to admission

Risk factors for community acquisition included:

recent hospitalisation

previous antibiotic therapy

residence in a long-term care facility intravenous drug use

Colonisation and transmission are also seen in individuals(including children) lacking these risk factors

Hiramatsu et al. Curr Opin Infect Dis 2002;15:407413Layton et al. Infect Control Hosp Epidemiol 1995;16:1217; Naimi et al. 2003;290:29762984

Antimicrobial features of


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Antimicrobial features ofMRSA (1)

Mechanism involves altered target site

new penicillin-binding protein PBP 2' (PBP 2a)

encoded by chromosomally located mecA gene

Confers resistance to all -lactams Gene carried on a mobile genetic element

staphylococcal cassette chromosome mec(SCCmec)

Laboratory detection requires care

Not all mecA-positive clones are resistant tomethicillin

Hiramatsu et al. Trends Microbiol 2001;9:486493Berger-Bachi & Rohrer. Arch Microbiol 2002;178:165171

Antimicrobial features of


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Antimicrobial features ofMRSA (2)

Cross-resistance common with many otherantibiotics

Ciprofloxacin resistance is a worldwide problemin MRSA:

involves 2 resistance mutations

usually involvesparC and gyrA genes

renders organism highly resistant tociprofloxacin, with cross-resistance to other

quinolones Intermediate resistance to glycopeptides

first reported in 1997

Hiramatsu et al. J Antimicrob Chemother 1997;40:135136Hooper. Lancet Infect Dis 2002;2:530538


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Clinical features of MRSA

Common associations include: underlying chronic disease, especially

repeated

hospital stays prolonged/repeated antibiotics, especially the-lactams

Usually susceptible to at least one other

antibiotic Not all MRSAs behave as EMRSAs

Methicillin resistance is not a marker ofvirulence

Clinical features of MRSA:


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Clinical features of MRSA:transmission

Occurs primarily from colonised or infected patientsvia the hands of healthcare workers

contact transmission to other patients or staff verycommon

Airborne transmission important in the acquisition ofnasal carriage

Infection control measures include:

screening and isolation of new patients suspectedof carrying MRSA or S. aureus with vancomycinresistance

implementing infection control programmes

establishing adequate antibiotic policy to minimisedevelopment of resistance


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Management of MRSA

Educate on risks and control measures

Adhere to strict control measures to prevent

transmission, especially through contact

Treat patient with appropriate empiricand targeted therapy

Consider clearing patient of MRSA carriage

Gl tid i t f


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Glycopeptide resistance: focuson vancomycin resistance

Vancomycin-resistant enterococci(VRE)

Vancomycin-resistant S. aureus(VRSA)


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Features of quinolone resistance:Gram-negative organisms

Resistance most common in organisms associatedwith nosocomial infections

Pseudomonas aeruginosa

Acinetobacterspp.

also increasing among ESBL-producing strains

Meropenem Yearly Susceptibility Test InformationCollection (MYSTIC) surveillance programme(19972000)

13.4% of Gram-negative strains resistant tociprofloxacin

P. aeruginosa andAcinetobacter baumanniiarethe most prevalent resistant strains

increasing prevalence of resistance during

surveillance period Masterton. J Antimicrob Chemother 2002;49:218220Thomson. J Antimicrob Chemother 1999;43(Suppl. A):3140

Gram-negative organisms with


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g gresistance to ciprofloxacin (1997SENTRY data)

Organisms (%)

0

30

50

10

Stenotrophomonasmaltophilia

20

40

Acinetobacterspp. P. aeruginosa Escherichiacoli

All patients (USA)Lower RTI (USA and Canada)

Organism typeJones. Chest 2001;119:397S404S


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Features of quinolone resistance:

Gram-positive organisms

MRSA

S. aureus occurred in 22.9% of pneumonias inhospitalised patients in USA and Canada (1997SENTRY data)

Enterococcus spp. resistance

has developed rapidly, especially among VRE

Streptococcus pneumoniae resistance

emerging in many countries, including

community-acquired resistance Hong Kong (12.1%), Spain (5.3%) and USA

(


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Summary

Antibiotic resistance in the hospitalsetting is increasing at an alarming

rateand is likely to have an importantimpact on infection management

Steps must be taken now to controlthe increase in antibiotic resistance

Cosgrove et al. Arch Intern Med 2002;162:185190


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Summary

The Academy for Infection Management supports theconcept of using appropriate antibiotics early innosocomial infections and proposes:

selecting the most appropriate antibiotic based on the

patient,risk factors, suspected infection and resistance

administering antibiotics at the right dose for theappropriate duration

changing antibiotic dosage or therapy based onresistance and pathogen information

recognising that prior antimicrobial administration is arisk factor for the presence of resistant pathogens

knowing the units antimicrobial resistance profile andchoosing antibiotics accordingly

Nosocomial Pneumonia Dr Suruchi

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