Management of nosp|ta|-

Acqu|red neumon|a
8onald Crossman Mu l8CC
rofessor of Medlclne, unlverslLy of 1oronLo
8esplrologlsL, CredlL valley PosplLal
D|sc|osure of otenna| for
Con|ct of Interest
Facilitators Name: Ronald Grossman MD FRCPC
Grants/research support: GSK, Novartis
Speakers bureau/honoraria: Bayer Schering Pharma, GSK, Novartis,
Merck, Pfizer, Abbott, Takeda, Grifols
Consulting fees: Bayer Schering Pharma, GSK, Novartis,
Merck, Abbott, Almirall, Takeda
Other: Nil
Learn|ng Cb[ecnves
Aer Lhls sesslon, learners wlll be able Lo:
uene PCA, PA, vA, vA8l
AppreclaLe Lhe relauve lmporLance of paLhogens ln
Lhese condluons
ldenufy useful prevenuve measures
Comprehend Lhe value of dlagnosuc procedures
8ecognlze Lhe lmpacL of currenL Lherapeuuc
recommendauons
Dehn|nons of Nosocom|a| neumon|a
nospito/-ocquired pneumonio (nA): neumonla
LhaL develops > 48 h aer admlsslon, whlch was noL
lncubaung aL Lhe ume of admlsslon Lo hosplLal
venn/otor-ossocioted pneumonio (VA):
neumonla LhaL arlses > 48 Lo 72 h aer
endoLracheal lnLubauon
Dehn|nons of Nosocom|a| neumon|a
(contd)
neo/th-core ossocioted pneumonio (nCA): auenLs
admlued Lo hosplLal wlLh pneumonla LhaL:
- have recelved lv 8x aL home, wound care or speclallzed
nurslng care
- had self-admlnlsLered lv 8x ln Lhe prevlous 30 days
- have auended a hosplLal or hemodlalysls cllnlc or recelved
lv chemoLherapy ln Lhe prevlous 30 days
- have been admlued Lo an acuLe care hosplLal for 2 or
more days ln Lhe prevlous 90 days or reslded ln a nurslng
home or a long-Lerm care faclllLy
nea|thcare-Assoc|ated Infecnons keported to
the Nanona| nea|thcare Safety Network, 2007-
2010
Lvent No. () of events
reported
2007-2008 (n = 47,S82
No. () of events
reported
2009-2010 (n = 69,47S)
CLA8Sl 18,631 (39.2)

27,766 (40.0)
CAu1l

11,863 (24.9)

19,038 (27.4)

VA

6,290 (13.2)

6,632 (9.S)

SSl

10,778 (22.7)

16,019 (23.1)

SleverL uM, eL al. lnfecuon ConLrol and PosplLal
Lpldemlology , vol. 34, no. 1 (!anuary 2013), pp. 1-14
IS nCA kLALL DIIILkLN1
1nAN CA?
nCA: 1he US Lxper|ence
1. kollef MP, eL al, ChesL 2003, 128:3834-62, 2. Mlcek
S1, eL al, Anumlcrob AgenLs ChemoLher 2007,
31:3368-73, 3. Schrelber M, eL al, ChesL 2010,
137:1283 8
1nL LUkCLAN LkLkILNCL

nCA athogens
Carratala J, et al. Arch Intern Med 2007;
167:1393-9
Only 4% are Gram-negatives
and 2.4% are S. aureus
(n=126)
Prospective,
observational study
Low Inc|dence of MDk Crgan|sms |n anents
w|th nCA kequ|r|ng nosp|ta||zanon |n Spa|n
Cf 2243 pLs wlLh pneumonla hosplLallzed Lhrough Lhe Lu, 377
(23.7) had PCA
Anublouc-reslsLanL organlsms, lncludlng M8SA, reslsLanL
sLralns of lseoJomooos oetoqlooso, and LS8L-produclng
LnLerobacLerlaceae, were scarce ln all groups
no dlerences were found regardlng lnapproprlaLe lnlual
emplrlcal anublouc Lherapy beLween groups
Asplrauon pneumonla was parucularly frequenL
MosL PCA pLs could be LreaLed ln Lhe same way as pLs wlLh
CA, aer carefully rullng ouL Lhe presence of asplrauon
pneumonla
Carcla-vldal C, eL al. Clln Mlcroblol lnfecL 2011,
17:1639-63
8acterem|c neumococca|
neumon|a: nCA vs CA Cohorts
Rello J et al. Chest 2010; 137:1138-1144
anent Character|sncs: nCA vs. CA
PCA cohorL demonsLraLed:
Charlson lndex (2.81 vs 1.23, p < .001)
raLe of lCu admlsslon (11.3 vs 23.3, p < .03)
a Lrend Loward Mv (9 vs 19, p = .17) and vasopressor use
(9 vs 18.4, p = .17)
wlLh a Sl score > 90 (class lv-v, 93 vs 63, p < .001)
30-day morLallLy (29.3 vs 7.6, p < .001)
CA cohorL younger (medlan age 68 yrs vs. 77 yrs, p < .001)
PCA an lndependenL varlable assoclaLed wlLh
morLallLy (C8 = 3.36, 93 Cl, 1.86-16.3), aer ad[usLmenLs for
underlylng condluons and severlLy of lllness varlables)
Rello J et al. Chest 2010; 137:1138-1144

AkL 1nLkL C1nLk S1kA1LGILS
1nA1 MA 8L 8L11Lk?
Stranfy|ng anents for MDk
athogens
observauonal, prospecuve
sLudy of 933 consecuuve
pLs admlued wlLh
pneumonla
31 had aL leasL 1 rlsk
facLor for acqulrlng Mu8
bacLerla on admlsslon
Scorlng sysLem developed
based on rlsk facLors
Var|ab|e Score
no rlsk facLors 0
>1 of Lhe followlng: Cvu, uM, CCu,
anubloucs wlLhln 90 days,
lmmunosuppresslon, home wound
care, home lnfuslon Lherapy
(lncludlng anubloucs)
0.3
8esldence ln a nurslng home or
exLended-care faclllLy
3
PosplLallzauon for >2 days ln Lhe
precedlng 90 days
4
Chronlc renal fallure 3
Allberu S, eL al. Clln lnfecL uls 2012, 34(4):470-8
Stranfy|ng anents for MDk
athogens
Allberu S, eL al. Clln lnfecL uls 2012, 34(4):470-8
PosplLallzauon ln Lhe
precedlng 90 days and
resldency ln a nP or
exLended-care faclllLy are
lndependenLly assoclaLed
wlLh a reslsLanL paLhogen
Chronlc renal fallure ls an
lndependenL rlsk facLor
for Mu8 lnfecuon
red|ctors of kes|stant athogens |n
nCA
Odds Ratio
Shorr AF, et al Arch Intern Med 2008;
168:2205-10
639 pts of whom 45.2% had
resistant pathogens
Standard HCAP definition
misclassified one-third
= 1
= 2
= 3
= 4
> 75%
chance of
having
resistant
pathogens
< 20%
chance of
having
resistant
pathogens
55% chance
of having
resistant
pathogens
A1nCGLNLSIS
athogenes|s
Bacterial colonization (oropharynx/
stomach/sinuses/subglottic space/
ventilator circuit condensate)
Aspiration of contaminated
secretions/circuit condensate/
aerosols into lower airways
Development of VAP and
superinfections or 2
nd
episodes of
VAP
2y bacteremia, empyema, lung
abscess, SIRS, MODS
Death
athogenes|s
Bacterial colonization (oropharynx/
stomach/sinuses/subglottic space/
ventilator circuit condensate)
Aspiration of contaminated
secretions/circuit condensate/
aerosols into lower airways
Development of VAP and
superinfections or 2
nd
episodes of
VAP
2y bacteremia, empyema, lung
abscess, SIRS, MODS
Death
Gastric alkanization, prior antibiotic
administration, nasal intubation,
nasogastric tube, malnutrition,
accumulation of circuit condensate
Supine positioning, nasogastric tube,
large gastric volumes, patient/
ventilator circuit manipulation,
accumulation of circuit condensate,
reintubation
All risk factors listed above
Neutropenia, malnutrition, mechanical
ventilation with high transpulmonary
pressures, inadequate initial antibiotic
therapy
k|sk Iactors
Venn|ator-Assoc|ated
1racheobronch|ns
Dehn|non:
lnLubaLed
Cllnlcal slgns of lower resplraLory LracL lnfecuon (eg. fever,
leukocyLosls, and purulenL spuLum)
Cram sLaln demonsLraung mlcroorganlsms and MnLs,
wlLh elLher semlquanuLauve or quanuLauve culLures
suggesung lnfecuon
Absence of a new or progresslve lnlLraLe on chesL
radlography
Craven D. E., et al. Chest 2009; 135:521-528

athogenes|s of VA1 and VA
Craven D. E., et.al. Chest 2009;135:521-528
kLVLN1ICN
revennon of VA
Strategy kecommendanon Lv|dence Leve|
Lducauon ?es 2
revenuon of cross-lnfecuon
Pandwashlng ?es 1
LnvlronmenLal deconLamlnauon ?es 1
ApproprlaLe lCu sLamng ?es 2
Mlnlmlze durauon of lnLubauon
nlv over Lracheal lnLubauon ?es 1
Avold re-lnLubauon ?es 2
Cral L11 placemenL preferred ?es 1
Larly LracheosLomy no 1
Morrow LE, Kolleff MH. Eur Respir J
2011; 33:74-82
revennon of VA
Strategy kecommendanon Lv|dence Leve|
Mlnlmlze asplrauon
Seml-recumbenL posluonlng ?es 1
Larly removal of enLeral feedlng Lube ?es 2
Larly gasLrosLomy no recommendauon 1
8ouune venulaLor clrculL changes no 1
Subglomc secreuon dralnlng L11 ?es 1
olyureLhane-cued L11 ?es 2
Mlnlmlse pauenL LransporL ?es 2
8educe blolm colonlzauon
sllver-coaLed L11 ?es 1
klneuc beds no recommendauon 1
Morrow LE, Kolleff MH. Eur Respir J
2011; 33:74-82
Impact of rob|oncs on Morta||ty |n
Cr|nca||y I|| Adu|t anents
Barraud D, et al. CHEST. 2013;143(3):646-655
S|ng|e-Dose Annb|onc to revent Lar|y-
Cnset neumon|a |n Venn|ated, Comatose
anents
rospecuve cohorL of comaLose pLs
(CCS < 8) (n=71) compared Lo 38
hlsLorlcal conLrols
AdmlnlsLered 1 dose of anublouc
wlLhln 4 h of lnLubauon
Clobal lncldence of vA: 10.8 vs
28.4 eplsodes/1,000 days on Mv (p
= .013)
lncldence of LC-vA: 4.4 vs 23.1
eplsodes/1,000 days on Mv(p = .02)
no dlerences ln morLallLy
Valls J, et al. Chest. 2013; 143:1219-1225
Components of the Insntute for
nea|thcare Improvement Venn|ator 8und|e
Intervennon urpose
Llevauon of Lhe head of Lhe bed Lo 43 revenung vA
ually sedauon vacauons and
assessmenL of readlness Lo exLubaLe
revenung vA

ually oral care wlLh chlorhexldlne revenung vA

roLon pump lnhlblLors or P2 recepLor
anLagonlsLs
revenung pepuc ulcer dlsease

AnucoagulanLs or compresslon devlces revenung venous Lhromboembollsm

OGrady NP, et al. JAMA 2012;307:2534-39
Cumu|anve k|sk and Da||y nazard of VA
8efore and Aher a revennve
Intervennon
lnLervenuon:
1. Pand-hyglene
2. glove-and-gown use
3. backresL elevauon
4. Lracheal cu pressure malnLenance
3. orogasLrlc Lube use
6. gasLrlc overdlsLenslon avoldance
7. good oral hyglene
8. nonessenual Lracheal sucuon
ellmlnauon
vA raLes decreased by 43
No d|erence ln Lhe LoLal durauon of
Mv or Lhe lCu and hosplLal deaLh raLe
Bouadma L et al. Clin Infect Dis. 2010;51:1115-1122
A1nCGLNS
D|str|bunon of Most Common
athogens |n ICUs
NNIS, Am J Infect Control 1999; 27:520
C|ass|hcanon of Nosocom|a|
neumon|a
Time from Hospitalization (days)
Time from Intubation (days)
Late-onset HAP
Early-onset VAP Late-onset VAP
Early-onset HAP
0 1 2 3 4 5 6 7
0 1 2 3 4 5 6 7
HAP Guideline Committee of the ATS & IDSA. Am J
Respir Crit Care Med. 2005;171(4):388-416
Lno|ogy of Late-onset VA
Rello, AJRCCM 1999; 160:608
IS INVASIVL 1LS1ING kLUIkLD 1C
MANAGL VLN1ILA1Ck-ASSCCIA1LD
NLUMCNIA?

kandom|zed 1r|a| of Invas|ve Strategy
for VA
413 pLs randomlzed Lo
lnvaslve sLraLegy or non-
lnvaslve sLraLegy
lnvaslve sLraLegy based on
dlrecL examlnauon of S8 or
8AL samples
non-lnvaslve sLraLegy
lncluded cllnlcal crlLerla,
lsolauon of organlsms by
nonquanuLauve analysls of LA
and CCs
Fagon et al, Ann Intern Med 2000;
132:621
CAN WL USL A CLINICAL AkCACn
1C kLDIC1 MICkC8IAL L1ICLCG?

Shorr AF, et al. Crit Care Med. 2005;
33:46-53
Meta-ana|ys|s: Morta||ty Invas|ve vs.
Non-|nvas|ve 1echn|ques
Sanchez-nleLo, eL al. 2.42 (0.73,7.84) 13.0 31
8ulz, eL al. 0.71 (0.28,1.77) 19.3 76
lagon, eL al. 0.71 (0.47,1.06) 30.9 413
Sole-vlolan, eL al. 1.08 (0.39,2.98) 16.3 88
Cverall (93 Cl) 0.89 (0.36,1.41)
Favors Invasive
Approach
Favors Non-Invasive
Approach
Odds Ratio
(95% CI)
% Weight n Study
0.13 1 7.84
Odds Ratio for Mortality
IS 1nLkL AN1nING NLW CN
1nL nCkI2CN?
kCkA1A 1r|a|: Use of roca|c|ton|n
to keduce Annb|oncs |n the ICU
rospecuve open-label Lrlal
Anubloucs sLarLed or sLopped accordlng Lo predened cuL-o
ranges
Lxcluded un8s and SAS score > 63
Ma[orlLy of pLs had pulmonary lnfecuon
rlmary endpolnLs:
uay 28 and day 60 morLallLy
number of days wlLhouL anubloucs by day 28
1313 pauenLs assessed buL 630 enrolled and 621 lncluded ln
Lhe analysls
Bouadma L, et al. Lancet 2010;
375:463-74
kCkA1A 1r|a|: Use of roca|c|ton|n
to keduce Annb|oncs |n the ICU
Bouadma L, et al. Lancet 2010;
375:463-74
kCkA1A 1r|a|: Use of roca|c|ton|n
to keduce Annb|oncs |n the ICU
Bouadma L, et al. Lancet 2010;
375:463-74
p<0.0001 p=0.02
kCkA1A 1r|a|: Use of roca|c|ton|n
to keduce Annb|oncs |n the ICU
Bouadma L, et al. Lancet 2010;
375:463-74
Approach to the D|agnos|s of VAkI
c/inico/ c/ues (fever, ^ wbc, purulenL
spuLum, ClS>6)
vA8l
vA1
Microbio/oqico/ c/ues (C-LA: >10
3-6

cfu/ml. SC-LA: +++/++++ CrowLh, CS:
many 8acLerla/MnL, 8-8AL:>10
4
cfu/
ml, n-8AL:>10
3
cfu/ml, S8: > 10
3
cfu/
ml)
vA
8adlologlc Clues
new lnlLraLe
no new lnlLraLe
Craven DE, et al. Clin Chest Med
2011; 32:547-57
D|agnos|s of VAkI
1racheobronchlal Secreuons may lnclude:
CuanuLauve LA
lnvaslve Lechnlques
8AL
S8
non-bronchoscoplc 8AL or S8
1kLA1MLN1
1herapeunc Approaches
Us|ng Annm|crob|a|s
MonoLherapy
Comblnauon Lherapy
lnLravenous - oral sequenual Lherapy
ue-escalauon
1lme-llmlLed Lherapy
HAP Guideline Committee of ATS and IDSA. Am J
Respir Crit Care Med. 2005;171(4):388-416
Deresinski S Clin Infect Dis. 2007;45:S177-S183
Lar|y In|nanon of Appropr|ate Annb|onc
1herapy for Sepnc Shock and Surv|va|
A|gor|thm for In|nanng Lmp|r|ca| Annb|onc
1herapy for nA, VA, and nCA
Torres A et al. Clin Infect Dis. 2010;51:S48-S53
2010 by the Infectious Diseases Society of America
k|sk Iactors for MDk athogens
Anumlcroblal Lherapy wlLhln 3 monLhs
CurrenL hosplLallzauon of 3 days or more
Plgh frequency of anublouc reslsLance ln Lhe communlLy or
Lhe speclc hosplLal unlL
resence of rlsk facLors for PCA:
PosplLallzauon for > 2 days wlLhln 90 days
8esldence ln a nurslng home or exLended care faclllLy
Pome lnfuslon Lherapy (lncludlng anubloucs)
Chronlc dlalysls wlLhln 30 days
Pome wound care
lamlly member wlLh mulu-drug reslsLanL paLhogen
lmmunosuppresslve dlsease and/or Lherapy
ATS/IDSA Guidelines Am J Respir Crit
Care Med 2005; 171:388
Lmp|r|c 1herapy:
Lar|y-onset nA]VA
nA]VA, ear|y-onset (|.e. no r|sk factors for MDk pathogens), any d|sease sever|ty
otenna| athogen kecommended Annb|onc
5. pneumonioe
n. infuentoe
Meth|c||||n-sens|nve 5. oureus (MSSA)
Annb|onc-sens|nve enter|c Gram-
neganve bac||||:
. co/i
k. pneumonioe
nterobocter sp.
Proteus sp.
5. morcescens
Cehr|axone

or

C|prooxac|n, |evooxac|n or mox|oxac|n

or

Amp|c||||n]su|bactam

or

Lrtapenem
HAP Guideline Committee of the ATS and IDSA.
Am J Respir Crit Care Med. 2005;171(4):388-416.
Lmp|r|c 1herapy: Late-onset nA]VA
nA]VA]nCA, Late-onset (|.e. r|sk factors for MDk athogens), any d|sease sever|ty
otenna| athogen Comb|nanon Annb|onc 1herapy
5. pneumonioe
n. infuentoe
5. oureus
Annb|onc-sens|nve enter|c gram-neganve bac||||:
. coll
k. poeomooloe
otetoboctet sp.
ltoteos sp.
5. motcesceos
MDk athogens:
l. oetoqlooso
k. poeomooloe (LS8L+)*
Acloetoboctet sp.*
MeLhlclllln-reslsLanL 5. ooteos (M8SA)
L. pneumophi/o**
Annpseudomona| cepha|ospor|n
(cefep|me, cehaz|d|me)
or
Annpseudomona| carbepenem
(|m|penem or meropenem)
or
-Lactam]-|actamase |nh|b|tor
(p|perac||||n-tazobactam)
p|us
Annpseudomona| uoroqu|no|one
(c|prooxac|n or |evooxac|n)
or
Am|nog|ycos|de (am|kac|n, gentam|c|n, or
tobramyc|n)
p|us
L|nezo||d or vancomyc|n
Am J Respir Crit Care Med. 2005;171(4):388-416
* A carbapenem is a reliable choice for ESBL+ strains
** A combination antibiotic regimen should include a macrolide (e.g., azithromycin) or a fluoroquinolone (e.g., ciprofloxacin or levofloxacin) rather
than an aminoglycoside.
CAN WL SAILL SnCk1LN 1nL
DUkA1ICN CI 1nLkA IN VA?

Compar|son of 8 vs. 1S Days of
Annb|onc 1herapy for VA
Chastre, J. et al. JAMA
2003;290:2588-2598.
rospecuve randomlzed
double-bllnd Lrlal ln 401 pLs
vA conrmed by lnvaslve
Lechnlques
ApproprlaLe Lherapy
assured
CuLcomes slmllar
CIS Annb|onc Study:
1r|a| Des|gn
CPIS6
Standard
Therapy
(antibiotics for
10-21 days)
(n=42)
Experimental
Therapy
Ciprofloxacin for 3 days (n=39)
CPIS >6
Treat as
pneumonia
Singh N, et al. Am J Respir Crit Care
Med. 2000;162:505-11
CPIS 6
Discontinue
treatment
CPIS calculated at 3 days
CIS Annb|onc Study: Cutcomes
Lxper|menta| 1herapy
(n=39)
Standard 1herapy
(n=42)
p Va|ue
Deaths at 3 days 0 (0]39) 7 (3]42) NS
CIS >6 at 3 days 21 (8]39) 23 (9]39) NS
Lxtrapu|monary |nfecnons 18 (7]39) 1S (6]39) NS
Annb|onc connnuanon >3
days
28 (11]39) 97 (38]39) 0.0001
uaLa for pauenLs wlLh enLry ClS 6 sub[ecL Lo sLandard and experlmenLal
Lherapy
Singh N, et al. Am J Respir Crit Care
Med. 2000;162:505-511.
WnA1 IS 1nL kLVALLNCL AND 1kLND
CI kLSIS1ANCL IN 1nL nCSI1AL
SL11ING?
kes|stance of Se|ected nosp|ta|
athogens 2007 - 2010
8eslsLance
p=.03
SleverL uM, eL al. lnfecuon ConLrol and PosplLal
Lpldemlology , vol. 34, no. 1 (!anuary 2013), pp. 1-14
kes|stance of Se|ected nosp|ta|
athogens 2007 - 2010
8eslsLance
p=.03
SleverL uM, eL al. lnfecuon ConLrol and PosplLal
Lpldemlology , vol. 34, no. 1 (!anuary 2013), pp. 1-14
Cverall, no
slgnlcanL change
kes|stance of Pseudomonos oeroqinoso
2007 - 2010
8eslsLance
SleverL uM, eL al. lnfecuon ConLrol and PosplLal
Lpldemlology , vol. 34, no. 1 (!anuary 2013), pp. 1-14
kes|stance of Pseudomonos oeroqinoso
2007 - 2010
8eslsLance
SleverL uM, eL al. lnfecuon ConLrol and PosplLal
Lpldemlology , vol. 34, no. 1 (!anuary 2013), pp. 1-14
Cverall, no
slgnlcanL change
MkSA
C||n|ca| Cutcome of MkSA VA
reLrospecuve cohorL of 97
pauenLs wlLh MSSA and
74 pauenLs wlLh M8SA
vA
lnlual emplrlc anublouc
Lherapy was approprlaLe
for every pauenL
hyslologlc and funcuonal
score changes from uay 1
(day of bronchoscopy) Lo
uay 28
no dlerence noLed
Combes A, et al AJRCCM 2004; 170:786
Walkey A J et al. Chest 2011;139:1148-1155
Compar|son of 8 vs. 1S Days of
Annb|onc 1herapy for VA
Wunderink R G et al. Clin Infect Dis.
2012;54:621-629
The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases
Society of America. All rights reserved. For Permissions, please e-mail:
journals.permissions@oup.com.
rospecuve, u8, 8C1 ln M8SA
PCA or PA
ln Lhe populauon, 37.6 of
llnezolld-8xed pLs (n=163)and
46.6 of vancomycln-8xed pLs
(n=174) achleved cllnlcal
success aL LCS (93 Cl, 0.3-
21.6, p=.042)
All-cause 60-day morLallLy was
slmllar
C||n|ca| kesponse kates of L|nezo||d
vs. Vancomyc|n |n MkSA neumon|a
Moore C L et al. Clin Infect Dis. 2012;54:51-58
The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases
Society of America. All rights reserved. For Permissions, please e-mail:
journals.permissions@oup.com.
8eLrospecuve case-conLrol sLudy
compared vancomycln (n=118) Lo
dapLomycln (n=39) ln Lhe 8x of M8SA
8Sls wlLh a hlgh vancomycln MlC (>1
g/mL)
Cllnlcal fallure (morLallLy,
mlcroblologlc fallure, and/or
recurrence of lnfecuon) was
numerlcally lower ln dapLomycln
group (31 vs 17, p=.084)
Lower lncldence of morLallLy ln Lhe
dapLomycln group (20 vs 9, p=.
046)
Daptomyc|n vs. Vancomyc|n |n
8|oodstream Infecnons (8SI) Caused by
Vancomyc|n-kes|stant MkSA
Can ou Safe|y D|sconnnue Lmp|r|c
Vancomyc|n |n the Iace of Neganve Cu|tures?
91 PCA pauenLs wlLh nasal and LhroaL culLures
negauve for M8SA ln Lhe absence of adequaLe
resplraLory culLures had emplrlc vancomycln Lherapy
dlsconunued
97 of pauenLs had a ClS < 6 on Lhe day of Lhe
anublouc sLewardshlp Leam recommendauon
ln-hosplLal morLallLy (7.7) was slmllar Lo a prevlous
sLudy of de-escalauon of anubloucs ln pneumonla
pauenLs wlLhouL adequaLe culLures
!oyce !M, eL al. publlshed onllne ahead of prlnL on 17
uec 2012, Anumlcrob. AgenLs ChemoLher. dol:10.1128/
AAC.01963-12
LS8Ls
Lxtended Spectrum 8-Lactamases (LS8Ls)
8acLerlal enzymes LhaL lnacuvaLe -
lacLam anubloucs by hydrolysls, -
lneecuve compounds
LS8Ls hydrolyse and cause
reslsLance Lo varlous Lypes of Lhe
newer -lacLams, lncludlng Lhe
expanded-specLrum cephalosporlns
(cefoLaxlme, cerlaxone) and
monobacLams (azLreonam), buL noL
Lhe cephamyclns (cefoxlun,
cefoLeLan) and carbapenems (lml/
mero/erLa-penem)
llebslellu
Pltout 'LL, et ul. Luncet lnfect Lls zcc8, 8: -66
Lect of Lxtended-Spectrum -Lactamase
(LS8L) roducnon on Morta||ty
SysLemauc revlew and meLa-
analysls Lo examlne Lhe lmpacL
of LS8L producuon on
morLallLy ln
LnLerobacLerlaceae bacLeremla
SlgnlcanLly lncreased
morLallLy ln LS8L-assoclaLed
bacLeraemla (pooled 88 1.83,
93 Cl 1.39-2.47, l < 0.001).
Schwaber MJ, Carmeli Y. J Antimicrob
Chemother 2007; 60:913-920
C1k-M-type LS8Ls
unul 2000, mosL LS8L producers were hosplLal klebslello
spp. wlLh 1LM and SPv muLanL -lacLamases
now, Lhe domlnanL LS8Ls across mosL of Lurope and Asla
are C1x-M enzymes, whlch orlglnaLed as geneuc escapes
from kloyveto spp
CurrenLly recognlzed as Lhe mosL wldespread and
LhreaLenlng mechanlsm of anublouc reslsLance, boLh ln
cllnlcal and communlLy semngs
80 of LS8L-posluve . coll from bacLeremlas ln Lhe uk and
lreland are reslsLanL Lo uoroqulnolones
40 are reslsLanL Lo genLamlcln
Livermore, DM J. Antimicrob. Chemother 2009
71
C1k-M-type LS8Ls: I|rst keports
1989
1989
Matsumoto et al. AAC 1988; 32:1243
Bauernfeind et al. Infection 1990; 18:294
Power et al. AAC 2002; 46:602
1986
1990s
1he C1k-M andem|c: S|nce 2000
72 Lancet Infect Dis 2008;8:159-66
Carbapenemases
Pave been descrlbed ln all four classes of -
lacLamases
MosL relevanL are:
Class A, kC (k. poeomooloe carbapenemases) ls cllnlcally
and epldemlologlcally Lhe mosL lmporLanL enzyme
Class u lncludes Lhe CxA-Lype carbapenemases
Class 8 lncludes Lhe meLallo--lacLamases
NDM-1 Meta||o--|actamase
nuM-1 (new uelhl meLallo--lacLamase) ls a broad-specLrum
-lacLamase (carbapenemase) LhaL ls able Lo lnacuvaLe all -
lacLams excepL azLreonam, as ls Lyplcal of meLallo--
lacLamases (e.g. lM and vlM)
Llnk beLween hosplLallzauon ln lndla and aklsLan and
developmenL of lnfecuons ln Lhe uk was esLabllshed ln 14/37
pauenLs
ldenued mosLly ln . coll and k. poeomooloe and Lo a lesser
exLenL ln oLher enLerobacLerlal specles
MosL of Lhe nuM-1 producers remaln suscepuble only Lo
collsun and ugecycllne
ln vitro Suscepnb|||ty 1esnng NDM-1

Antimicrobial
Antimicrobial Susceptibilities
MIC
90
(mg/L) Proportion
Susceptible
Imipenem 128 0
Meropenem 32 3%
Pipercillin-tazobactam >64 0
Cefotaxime >256 0
Ceftazidime >256 0
Ciprofloxacin >8 08%
Gentamicin >32 3%
Tobramycin >32 0
Amikacin >64 0
Tigecycline 4 67%
Colistin 8 100%
Nordmann P et al. J. Antimicrob. Chemother.
2011;66:689-692
Wor|dw|de D|str|bunon of Idennhed
Cases of NDM-1 roducers, 1 December
2010.
C||n|ca| kesponse w|th Co||snn Compared
w|th Contro| Annb|oncs |n VA
Florescu D F et al. Clin Infect Dis. 2012;54:670-680
6 conLrolled sLudles
no dlerence ln:
Cllnlcal response
PosplLal morLallLy
nephroLoxlclLy
Collsun may be as safe
and as emcaclous as
sLandard anubloucs for
Lhe 8x of vA
Clinical
Response
Conc|us|ons
PCA/PA/vA conunue Lo be an exLremely
lmporLanL nosocomlal lnfecuon
lnlual approprlaLe emplrlc Lherapy makes a
dlerence
A rellable Lracheal asplraLe Cram sLaln can be used
Lo dlrecL Lherapy
Choose anubloucs based on Lhe presence or absence
of rlsk facLors for Mu8 paLhogens
A modled ClS score of <6 for 3 days may allow
selecuon of pauenLs for early dlsconunuauon of
anubloucs
Conc|us|ons
Anubloucs should be admlnlsLered aL opumal doses
Lo ensure maxlmum emclency
Comblnauon Lherapy should be chosen for pauenLs
suspecLed of belng lnfecLed wlLh Mu8 paLhogens
8e aware of emerglng new Mu8 paLhogens
uurauon of Lherapy can be shorLened Lo as llule as 8
days lf Lhe lnlual cholce ls correcL and a good cllnlcal
response ensues
revennon Strateg|es for Acute and
Long-1erm Care Iac|||nes
Core Measures for A|| Acute and Long-term Care
Iac|||nes
Pand hyglene
ConLacL precauuons
auenL and sLa cohorung
Mlnlmlze use of lnvaslve devlces
romoLe anumlcroblal sLewardshlp
Screenlng
CDC 2013