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By Ximena Vazart Hernández Diana Sofía Serna Corredor

Carbepenem Resistant Klebsiella Pneumoniae

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Page 1: Carbepenem Resistant Klebsiella Pneumoniae

By

Ximena Vazart Hernández

Diana Sofía Serna Corredor

Page 2: Carbepenem Resistant Klebsiella Pneumoniae

INTRODUCTION

-Klebsiella microorganisms belong to Enterobacteriaceae family -They are non motile gram-negative bacilli -The outermost layer of Klebsiella it's formed by a polysaccharide capsule that differentiates these microorganisms from other genders -Edwin Klebs, a German microbiologist

KLEBSIELLA

Page 3: Carbepenem Resistant Klebsiella Pneumoniae

INTRODUCTION

-They make lactose and acetone fermentation -Belongs to bacterias gender Klebsiella -Causes about 1% of bacterial pneumonias, sepsis, soft tissue infections, UTI and surgical wound infections.

K.PNEUMONIAE

Page 4: Carbepenem Resistant Klebsiella Pneumoniae

TYPES OF RESISTANCE

1. Natural Resistance: innate ability of bacteria to

resist the activity of an antimicrobial agent

2. Acquired Resistance: Obtention of the ability to

resist to the activity of an antimicrobial agent to

which was previously susceptible.

BACTERIAL RESISTANCE

INTRODUCTION

Page 5: Carbepenem Resistant Klebsiella Pneumoniae

RESISTANCE

OBTENTION

✓SPONTANEOUS MUTATION

✓GENES TRANSFER

Page 6: Carbepenem Resistant Klebsiella Pneumoniae

RESISTANCE

MECHANISMS

✓ INACTIVATION ENZYMES

✓TARGET MOLECULES

ALTERATIONS

✓DECREASE OF DRUG UPTAKE

✓INCREASED IN DRUG

ELIMINATION

Page 7: Carbepenem Resistant Klebsiella Pneumoniae

ST258 strain is the most representative carrier

of bla-kpc gen, responsible of klebsiella

pneumoniae carbepenem resistance.

NON ST258

ST514

ST11

ST13

KLEBSIELLA

PNEUMONIAE

STRAINS

Page 8: Carbepenem Resistant Klebsiella Pneumoniae

General Objetive

To compare the characteristics and outcomes Carbapenem-Resistant Klebsiella pneumoniae ST258 carriers to carriers of other STs defined using MLST

Page 9: Carbepenem Resistant Klebsiella Pneumoniae

Materiales y Métodos

Se incluyeron los pacientes que asistieron al Detroit Medical Center en septiembre de 2008 a septiembre de 2009 en los cuales se aisló la bacteria, tanto colonizados como infectados Pacientes en los que se aisló Klebsiella

pneumoniae más de una vez, solo se tuvo en cuenta el primer aislamiento

Page 10: Carbepenem Resistant Klebsiella Pneumoniae

Variables: comorbilidades, exposición reciente

a antimicrobianos, procedimientos médicos,

índice de severidad de la enfermedad,

regímenes terapéuticos y desenlaces

Prueba exacta de Fisher

Page 11: Carbepenem Resistant Klebsiella Pneumoniae
Page 12: Carbepenem Resistant Klebsiella Pneumoniae

CONCENTRACIÓN

ESTANDAR DE LA CEPA DISEMINACIÓN EN PLATO CON

AGAR

DISCOS CON ANTIBIOTICO

SOBRE LA SUPERFICIE DEL

MEDIO.

FORMACION DE GRADIENTE DE

FARMACO EN TORNO A DISCOS

ZONA DE INHIBICIÓN

SI? NO? TAMAÑO?

DIFUSIÓN EN DISCO

Page 13: Carbepenem Resistant Klebsiella Pneumoniae

DIFUSIÓN EN DISCO

Determinación de la susceptibilidad de una

cepa bacteriana a un antimicrobiano.

Determinación de concentración mínima

inhibitoria

✓K Pneumoniae resistentes a cefalosporinas

✓Concentración mínima inhibitoria ≥2 mg/dl

Test de Hodge Modificado (MHT)

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PCR

DESNATURALIZACIÓN

ALINEAMIENTO

AMPLIFICACIÓN

Page 15: Carbepenem Resistant Klebsiella Pneumoniae

PCR

Amplificación directa de un gen o fragmento de DNA

CARBAPENEM RESISTANT KLEPSIELLA PNEUMONIAE

blaKPC

blaIMP

blaVIM

blaOXA

blaNDM

CARBEPENEMASAS

Page 16: Carbepenem Resistant Klebsiella Pneumoniae

rep- PCR

Page 17: Carbepenem Resistant Klebsiella Pneumoniae

MULTILOCUS SEQUENCE

TYPING

PCR SECUENCIACIÓN DE

GENES

NÚMERO ALÉLICO A

CADA SECUENCIA

ÚNICA DENTRO DEL

GEN

CARACTERIZACIÓN DE

CEPAS

DENDROGRAMA

Page 18: Carbepenem Resistant Klebsiella Pneumoniae

RESULTADOS

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RESULTADOS

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RESULTADOS

group 1: 6-17

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RESULTADOS

group 2: 21-62

Page 22: Carbepenem Resistant Klebsiella Pneumoniae
Page 23: Carbepenem Resistant Klebsiella Pneumoniae
Page 24: Carbepenem Resistant Klebsiella Pneumoniae

DISCUSSION AUTHOR WHAT HE SAID

YES/NO

Chen L, Mathema B, Pitout JD

«2 of the non ST258 were

identified as ST11, which

are a single locus variants

of ST258 and are though

to be precursors of blakpc

producing k pneumoniae

ST258»

NO

Addler A, Paikin S, Sterlin Y, et al

«Other mechanisms (eg,

ESLBLs such as blaCTX-M

coupled with porin loss

mutations) might be

involved in current CRKP

epidemiology»

YES

Page 25: Carbepenem Resistant Klebsiella Pneumoniae

DISCUSSION AUTHOR WHAT HE SAID YES/NO

Munoz-Price LS, Poirel L,

Bonomo RA, et al.

A negative MHT, which might represent false-negative tests due

to the presence of carbapene-mases other than KPC. This

observation suggests increased diversity in the current molecular

epidemiology of CRKP at DMC

YES

Katz S, Ford AB, Moskowitz

RW, et al.

Poor outcomes and high prevalence of resistance was

identified among the small sample of non-ST258 cases as well,

including in-hospital mortality among 3 of 7 non-ST258 cases

This underscores the fact that the epidemiological significance and

clinical impact of non-ST258 strains cannot be dismissed

YES

Page 26: Carbepenem Resistant Klebsiella Pneumoniae

CONCLUSIONS

MLST allows to determinate similarity between

gen sequences of bacteria strains and its relation

with expression of b lactamases.

Non ST258 strains have a representative influence

in Carbapenem resistant Klebsiella pneumonie and

its dissemination around the world.

Page 27: Carbepenem Resistant Klebsiella Pneumoniae

CONCLUSIONS

Bla kpc is not determinant for the diagnosis of

Klebsiella pneumoniae but could be determinant

for knowing if it is resistant or not

Negative MHT could be false negative because

carbapenemases can be produced by other thing

different from Klebsiella.

Page 28: Carbepenem Resistant Klebsiella Pneumoniae
Page 29: Carbepenem Resistant Klebsiella Pneumoniae

MLST

69 patients

This patient

was excluded

70 CRKP (plus one from the same person

who had 2)

62 patients with

CRKP ST 258

7 patients with

other

3 ST 514 2 ST 11 1 ST 13 1 ST 248

MHT + except

1

56 analyzed

55 with bla kpc

68 patients

rep-PCR

1 ST 514 was ST 258 42 clone 1 12 clone 2

5 non

ST258 were

bla kpc

1 clone 1 3 clone 4 3 clone 4

Page 30: Carbepenem Resistant Klebsiella Pneumoniae

GRACIAS