Pseudomonas aeruginosa is an opportunistic pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals. Eradication of P. aeruginosa has become increasingly difficult due to its remarkable capacity to resist antibiotics
4. INTRODUCTION
Pseudomonas Aeruginosa is a gram negative bacteria. Pseudomonas Aeruginosa is
found in soil and water, associate with the infections of animals, plants and
humans.
Incidence of infection caused by drug resistance Pseudomonas is increasing in
hospital and other clinical care situations. ICU are major cause of creating these
organism due to the increased use of antibiotics to treat patients.
ICU patients have an increased threat of infection due to their host defense
delayed immune response.
5. EPIDEMIOLOGY
Pseudomonas Aeruginosa isolated in 1882 by Gessard from green pus. The
universal life style of this bacterium to contribute to many infections in human
beings.
It is found as a part of normal intestine flora, but do not cause disease in healthy
person but an opportunistic pathogen in immune compromised patients
Because of its high surviving capability it can survive on dry inanimate surfaces of
hospital from 6h to 6 months and frequently contaminated the health care
equipment.
6. BACKGROUND HISTORY
In 1882 Carol Gessard first isolated the bacteria pseudomonas from green pus.
Pseudomonas can cause infections in hospitalized patients.
Experimentation:
From Bichat–Claude Bernard hospital 2613 patients were hospitalized in 3 ICUs and
from these patients pseudomonas is recovered from 370 patients.
Result:
Among these 370 patients Pseudomonas is resistant to each of the following
antibiotics as:
Ceftazidime 21.9%, Imipenem 23.5%, Piperacillin 55.9%
Among these patients the prevalence of MDR pseudomonas is 10.5% (39 out of 370)
In 16 of these 39 patients the isolates are resistant to all the aminoglycosides.
7. TESTS AND EXPERIMENTATION
The clinical specimens were collected aseptically from 150 ICU patients from
February 2012 to October 2013.
Identification and antimicrobial susceptibility was performed according to Clinical
and Laboratory Standard Institute(CLSI)guidelines.
ESBLs and AmpC were detected phenotypically and genotypically.
MBL was detected by modified Hodge and imipenem-EDTA double-disk synergy
test.
8. RESULTS
Pseudomonas spp. 35(28%) was the most prevalent pathogen in ICU infections.
Prevalence of ESBL, AmpC and MBL was 22.9%, 42.8% and 14.4% respectively.
The average hospital stay was 25 days and was associated with 20% mortality.
Conclusions
Regular surveillance is required to detect ESBL, AmpC and MBL.
Carbapenems should be used judiciously.
Use of effective antibiotics
10. ANTIBIOTIC RESISTANCE IN
PSEUDOMONAS
Antimicrobial resistance is the capacity of an organism to resist the action of
antimicrobial agent to which it was earlier susceptible.
Pseudomonas is Multiple drug resistance MDR (resistant to minimum three
antibiotics) organism
Pseudomonas is naturally resistant to various antibiotics because of the
permeability barrier contained by its Gram negative exterior membrane.
11. MECHANISM OF ANTIBIOTIC
RESISTANCE IN PSEUDOMONAS
Mechanisms of P. aeruginosa used to counter antibiotic attack can be categorized into
intrinsic, acquired and adaptive resistance.
Intrinsic Resistance: P. aeruginosa has a high level of intrinsic resistance to
antibiotics through restricted outer membrane permeability, efflux systems and
production of antibiotic-inactivating enzymes.
Acquired resistance: Bacteria can gain antibiotic resistance through mutational
changes or acquisition of resistance genes through horizontal gene transfer
Adaptive resistance: Adaptive resistance increases the ability of a bacterium to
survive antibiotic attack due to transient alterations in gene in response to an
environmental stimulus
12. RESISTANT STRAIN
Pseudomonas spp. A multidrug-resistant strain.
Biofilm production attributes to antimicrobial resistance that permits bacteria to
effectively transfer plasmids.
Multidrug resistance and biofilm production was observed in 80.1% and 60.4%
isolates respectively.
Appearance of ESBL , AmpC and MBL genes and their spread among bacterial
pathogen is a serious matter to concern.
14. DIFFERENT COMBINATIONS OF
ANTIBIOTICS WITH ENHANCED
ACTIVITY AGAINST PSEUDOMONAS
Cephalosporin, Quinolones
Ceftazidime, Colistin
Macrolides, Tobramycin
Meropenem, levofloxacin
Fosfomycin, Colistin
15. RESISTANCE TO DIFFERENT
ANTIBIOTICS
Resistant to Beta Lactam:
Beta lactam include the antibiotics that inhibit the synthesis of bacterial peptidoglycan
cell wall.
This includes Cephalosporin, Carbapenem, penicillin, and Monobactam
Amongst these groups most effective are ceftazimide,3rd generation cephalosporin,
dorepenem
Resistance to Beta Lactam is mediated by the action of β-lactamases, this enzyme
destroy the amide bond of β-lactam ring, and make the antibiotic ineffective.
16. RESISTANCE TO
AMINOGLYCOSIDES
Aminoglycosides are inhibitor of microbial protein synthesis, act by binding to
bacterial 30S ribosomal subunit and inhibits with the initiation of protein
synthesis.
Pseudomonas resist to the aminoglycosides by Amino-glycoside modifying
enzyme (AMEs), Low outer membrane permeability, active efflux pump and
rarely target modification.
17. TREATMENT OPTIONS FOR
PSEUDOMONAS AERUGINOSA
Pseudomonas is commonly resistant to many generally used antibiotics
To achieve synergy a combination of antibiotics are used.
Combination of Colistin with anti-pseudomonal agent such as imipenem or
piperacillin is used.
Fosfomycin is also used for treatment of MDR pseudomonas by inactivating the
pyruvil-transferase enzyme, compulsory for synthesis of cell wall.
Fosfomycin is operative against 90% MDR pseudomonas
No vaccine offered so far
18. COMBINATION THERAPHY FOR
TREATMENT OF PSEUDOMONAS
Combination therapy allows different mechanism for bacterial killing, and
prevention of emergence of resistance
Combination therapy is more significant than mono therapy, because the infecting
pathogen will be susceptible to at least one antimicrobial
Frequently used combinations are β-lactamase (penicillin or cephalosporin) and an
aminoglycoside.
19. CHALLENGES
Overuse of antibiotics is also a important cause for pseudomonas resistance
Constant changes in microbial genome is bigger threat than infection itself.
Microbes utilize several mechanism to alter their genome such as horizontal gene
transfer, transposons mediated genomic alterations and promiscuous nature of
gene and gene product.
Bacterial genome is capable to encode enzyme, which destroy several substrates
by developing affinity against them.
20. CONCLUSION
ICU based infections are major threat for health care and associate with high
mortality rate
Pseudomonas counts for more than 30% of contagious infections.
Pseudomonas is an important nosocomial pathogen because of its intrinsic,
acquired resistance to many antibiotics
These MDR strains occurrence in hospitals make them difficult to treat because
these strains exhibit resistant to essential antipseudomonal antibiotics