Emerging Multi-Drug Multi Drug (MDR) Resistant Gram Negative Pathogens in ICUs: The Enemies from Within Wafeeq Mahmood Mahmood,, MD, FRCPC Infectious Diseases & Critical Care Consultant Intensivist Department of Adult Critical Care Medicine

Emerging MDR Resistant Gram Negative Pathogens in ICUs 1. Multi-Drug Resistant (MDR) Acinetobacter Baumannii 2. Carbapenem-Resistant Klebsiella pneumoniae (KPC producers) 3. Metallo- lactamase (MBL) producing P. aeruginosa

1

MDR Acinetobacter baumannii Infections in ICU 1 Definition 1. 2. Microbiology 3. Clinical Manifestations 4. Treatment 5. Infection Control

Definition: MDR Acinetobacter Baumannii No standard definition Various terms have been used (sometimes interchangeably) to denote antimicrobial-resistant phenotypes: g resistant (MDR) ( ) Multi-drug Pan-drug resistant (PDR) Extensively drug resistant (XDR)

2

Definitions MDR, PDR & XDR Acinetobacter MDR: Multi-drug resistant strains” are resistant to at least 3 classes of the following 5 drug classes: 1 Antipseudomonal cephalosporins 1. 2. Antipseudomonal carbapenems 3. β-lactam–β-lactamase inhibitor 4. Fluoroquinolones 5. Aminoglycosides  PDR: “Pan-drug “Pan drug resistant strains” are resistant to all standard antimicrobial agents tested except colistin 



XDR: “Extensively drug resistant strains” are resistant to all commercially available antimicrobial N Engl J Med 2008;358:1271-81 drugs, including colistin

Clin Micro Reviews , July 2008, p. 538–582 Drugs 2008; 68 (2) Emerging Infectious Diseases 2009, 15(6): 980-981

Microbiology  Acinetobacter:  Akinetos Aki t (Greek (G k adjective): unable to move  Bakterion (Greek noun) rod

 Non-motile rod  Strictly aerobic  Gram negative coccobacillus Gram’s Staining of Sputum Specimen from a Patient with Suspected VAP

3

Microbiology  Ubiquitous:  Widely distributed in nature (soil, water, food sewage) & the hospital environment food,

 In humans, acinetobacter spp. can colonize skin, wounds, respiratory and GIT  32 species  >2/3 of Acinetobacter infections are due to A. baumannii

 Survive for weeks on moist & dry surfaces  Highly antibiotic resistant  Numerous mechanisms of resistance to β-lactams described in A. baumanii

MDR Acinetobacter: Biofilm Formation Scanning Electron Micrograph

Biofilm on IV catheter developed 24 hours after insertion

4

Mixed bacterial population within a urine catheter

Clin Microbiol Infect, 2007

Evaluated the capacity of 23 MDR clinical isolates of Acinetobacter baumannii to adhere to respiratory epithelial cell surfaces and to form biofilm on a polystyrene surface Bacterial adhesion assay and a biofilm formation assay were used

Clin Microbiol Infect, 2007

All 23 A. baumannii isolates were capable of adhering efficiently to respiratory epithelial cells, and biofilm production was positively associated with epithelial cell adhesiveness (p 32 R

Meropenem 4

cefepime

>32 R

Pip-Tazo

Tobramycin >16

ciproflox

TMP-SXT

gentamicin >16 R 

24

>128 R

ceftriaxone >32 R >4 R

Modified Hodge Test:

S R

>4/76 R

Treatment options: KPC producing bacteria Lancet Infect Dis. 2009 Apr;9(4):228-36

  



Limited therapeutic options Resistant to virtually all β lactams, lactams, including β lactams+ lactams + β lactamase inhibitors Carbapenems (imipenem imipenem,, meropenem meropenem,, and ertapenem)) may become inefficient for treating ertapenem KPC--producing bacteria KPC Most isolates are resistant to fluoroquinolones,, aminoglycosides fluoroquinolones aminoglycosides,, and co co-trimoxazole

Treatment options: KPC producing bacteria Lancet Infect Dis. 2009 Apr;9(4):228-36

    

25

Most isolates remain susceptible to colistin and tigecycline Rx failures with tigecycline have been documented Tigecycline should not be used for treating UTI due to its low urine concentration Colistin resistance in KPC-producing K. pneumoniae has been observed Combination therapies based on in-vitro data, but clinical data are lacking

Infection Control: Carbapenem Carbapenem--Resistant Klebsiella pneumoniae (CRKP) 

Patients with unrecognized CRKP colonization h have served d as reservoirs i for f transmission t i i during health-care associated outbreaks



Cultures performed on 30 patients in ICU revealed two colonized patients who were not previously known to harbor CRKP and were not placed l d in i contact t t precautions ti



All patients colonized or infected with carbapenemase-producing bacteria should be placed on contact precautions

Metallo--lactamases Metallo(MBL) Producing P. P aeruginosa = Carbapenem--Resistant Carbapenem Pseudomonas aeruginosa

26

Metallo--lactamases (MBL) Producing P. aeruginosa MBLs can hydrolyse y y all classes of betalactams except aztreonam  MBLs are widespread in P. aeruginosa, Acinetobacter spp. & Enterobacteriaceae  VIM-2 is the dominant MBL in P. aeruginosa i  Rx: Colistin 

Current Opinion in Infectious Diseases 2008, 21:367–371

Lab Detection: MBL producing Pseudomonas aeruginosa

The isolate is resistant to imipenem (IPM 10) ceftazidime (CAZ 10), tazocin (TZP 55), cefepime (FEP 10), Timentin (TIM 85), and susceptible to aztreonam (ATM 30).

27

Lab Detection: MBL producing Pseudomonas aeruginosa

The blank disc contains 750 μg EDTA. The zone of inhibition of imipenem (IPM 10) and meropenem (MEM 5) is increased with the addition of EDTA indicating the presence of a Metallo-Beta-Lactamase.

Summary

28

MDR Acinetobactor baumannii  ↑ Prevalence of MDR & PDR Acinetobacter baumannii infections in ICUs worldwide  Resistance to all antibiotics is now a reality in many ICUs  Colistin remains the most effective agent in vitro against MDR A. baumannii  Enforcing hand hygiene, enhanced isolation precautions & environmental decontamination are essential measures to prevent Acinetobactor transmission in ICU

Carbapenemase-Producing Klebsiella pneumoniae

29



Emerging as an important challenge in critical iti l care settings tti



Resistant to almost all available antimicrobial agents



Most isolates remain susceptible to colistin li ti and d tigecycline ti li



All patients colonized or infected with KPC producing Enterobacteriaceae should be placed on contact precautions

Metallo--lactamases (MBL) Producing P. aeruginosa

30



MBLs can hydrolyse all beta-lactams beta lactams except aztreonam



MBLs are widespread in P. aeruginosa, Acinetobacter spp. & Enterobacteriaceae



Rx: Colistin