Multi-Resistant Organisms (MROs)

OVERVIEW

List of multi-resistant bacteria species

• Methicillin Resistant Staphylococcus aureus (community and hospital MRSA)
• Vancomycin-Intermediate Resistant Staphylococcus aureus (VISA) and Heterogeneous Vancomycin-Intermediate-Resistant Staphylococcus aureus (hVISA)
• Methicillin-Resistant Staphylococcus epidermidis (MRSE)
• Vancomycin Resistant Enterococcus (VRE)
• Vancomycin Resistant Staphylococcus aureus (VRSA) and Vancomycin Resistant Staphylococcus epidermidis (VRSE)
• ESCAPPM organisms (Gram negative rods) – Enterobacter species, Serratia species, Citrobacter freundi, Aeromonas, Proteus vulgaris, Providencia, Morganella morganii
• Extended Spectrum Beta-Lactamases (ESBLs) – E coli, Klebsiella, Enterobacteriae
• Stenotrophomonas
• Acinetobacter baumanii
• Pseudomonas aeruginosa
• Streptococcus pneumoniae
• New Delhi metallo-β-lactamase 1 (NDM-1)
• Multi-resistant Acinetobacter baumani

RISK FACTORS

Risk factors for infection with multidrug-resistant Gram-negative organisms (e.g. ESBLs)

• recent international travel to areas with a high prevalence of multidrug-resistant Gram-negative organisms (eg within 6 months)
• prolonged hospitalisation
• residence in a long-term care facility
• previous colonisation or infection with a resistant Gram-negative organism

Hospital-acquired MRSA

• penicillin-binding protein mutation coded by the mecA gene on a transposon
• also produces to multiple other classes (tetracyclines, macrolides, sulphonamides, aminoglycosides)
• treatment: vancomycin, tiecoplanin, rifampicin, fusidic acid, ciprofloxacin

Community-acquired MRSA

• similar mechanism to Hospital-acquired MRSA + additional gene (PVL)
• often seen in Pacific Island born patient and Indigenous communities
• treatment: vancomycin, teicoplanin, clindamycin, sometimes rifampicin, fusidic acid, ciprofloxacin, co-trimoxazole, erythromycin

VISA and hVISA

• genes code for factors such as additional peptidoglycan synthesis and reduced need for peptidoglycan cross-linking
• significance of hVISA is uncertain -> MIC is the same for MRSA but daughter strains have higher MIC
• treatment: teicoplanin, linezolid, quinupristin-dalforpristin, cotrimoxazole

MRSE

• methicillin resistant staphylococcus epidermidis
• penicillin-binding protein mutation coded by the mecA gene as per MRSA

Vancomycin Resistant Enterococcus (VRE)

• Enterococcus faecium and Enterococcus faecalis
• normally low virulence organisms -> but can become significant pathogens in debilitated, immunosuppressed patients receiving broad-spectrum antimicrobial treatment
• in 1990’s in the US vancomycin resistance emerged
• colonise GI tract -> spread by hand contamination by hospital staff
• once established remains endemic
• resistance is passed onto more pathogenic organisms such as Staph aureus
• mechanisms of resistance:

(1) pencillin-binding protein mutations
(2) beta-lactamase production
(3) aminoglycoside-modifying enzymes
(4) antibiotic drug efflux pumps
(5) alterations in cell wall components coded by transposons (Van A to F phenotypes)

Causes

• previous treatment with anti-microbials (especially vancomycin, cephalosporins, and broad spectrums antibiotics)
• increased length of stay
• renal insufficiency
• enteral tube feeding
• prevalence of VRE colonised patients in the unit
• residents of long-term care facilities

Consequences

• potential transmission of resistance to Staph aureus
• determined by presence of infection (UTI, bacteraemia, endocarditis, respiratory infections)
• colonisation and subsequent transmission (requirement for isolation)
• septaecaemia
• intra-abdominal abscesses

Management

• specific antimicrobial therapy if patient develops active infection

Van A: resistant to vancomycin and teicoplanin
Van B: resistant to vancomycin, teicoplanin may be effective but resistance likely to emerge with prolonged use (use linezolid, tigecycline, dalfopristin-quinapristin, daptomycin)
Van C: partly resistant to vancomycin

• treatment: ampicillin, tetracyclines, quinolones, linezolid, teicoplanin (some), quinupristin-dalfopristin (Enterococcus faecium only)
• minimisation of cross contamination (isolation and infection control)
• limitation of broad spectrum antibiotics
• surveillance until patient clear

VRSA and VRSE

• alterations in cell components coded by transposons – Van A gene transferred from VRE
• treatment: linezolid, quinupristin-dalfopristin, cotrimoxazole, chloramphenicol

ESCAPPM

• Gram negative rods
  • Enterobacter species
  • Serratia species
  • Citrobacter freundi
  • Aeromonas
  • Proteus vulgaris (non-mirabilus) + Pseudomonas
  • Providencia
  • Morganella morganii

• rapidly inducible production of beta-lactamase during therapy with cephalosporins (especially third-generation agents)
• treatment: carbapenems, fourth generation cephalosporins, ciprofloxacin, aminoglycosides

ESBL’s

• Klebsiella pneumoniae, Escherichia coli, other Enterbacteriaceae
• genetically coded resistance to broad-spectrum beta-lactam antibiotics -> extended spectrum pencillins, third generation cephalsporins, aztreonam
• co-resistant to co-trimoxazole, aminoglycosides and quinolones
• in vitro appear to be sensitive to cephalsporins, but have resistance in vivo
• treatment: carbapenems or fourth generation cephalsporins

Stenotrophomonas maltophilia

• intrinsic resistance to many beta-lactam antibiotics, including carbapenems and aminoglycosides
• treatment: co-trimoxazole (drug of choice), ticarcillin-clavulanate, ceftazidime and fluoroquinolones

Acinetobacter baumannii

• intrinsic resistance to beta-lactam and aminoglycosides
• found in soil and sand
• treatment: carbapenems and aminoglycosides (two agents often successfully used even if in-vitro resistance demonstrated)

Pseudomonas aeruginosa

• intrinsically resistance to many antibiotics through:

(1) efflux pumps
(2) loss of porins
(3) altered target enzymes
(4) beta-lactamases
(5) metllocarbapenemases
(6) aminoglycoside-modifying enzymes

• treatment: dual therapy in severe infections -> ciprofloxacin, gentamicin, tobramycin, ceftazidime, piperacillin-tazobactam, ticarcillin disodium and clavulanate potassium, imipenem, meropenem, amikacin, nebulised colistin (chronic bronchiectasis)

Streptococcus pneumoniae

• penicillin and cephalosporin intermediate resistance and some high level resistance
• precise proportions are unknown
• North American data: may be between 40-80%
• normal resistance: penicillin MIC < 0.1microgram/mL
• intermediate resistance: MIC 0.1-1microgram/mL (treat with high dose penicillin)
• high resistance: MIC > 2.0micrograms/mL (treat with vancomycin and/or fluoroquinolones)

New Delhi metallo-Clactamase 1 (NDM-1)

• an enzyme that produces resistance to a broad-range of beta-lactam antibiotics
• produces a carbapenemase
• bacteria involved: E. coli, Klebsiella pneumoniae, Acinetobacter baumannii
• can spread to other bacteria through horizontal gene transfer (via plasmids)
• treatment: tigecycline and colistin

Multi-resistant Acinetobacter baumani

• Gram negative aerobic organism
• inherently resistant, low virulence, opportunistic
• unless risk factors (see below) usually is a colonsier
• risk factors: immunosuppressed, prosthetic material (catheters, lines, tubes, devices)
• resistance via beta-lactamases, metalloproteases, reduced membrane permeability, enhanced efflux
• outbreaks associated with: high use of cephalosporins, quinolones and carbapenems
• difficult to clear because of wide spread colonisation
• treatment:
  — colistimethate sodium (adult and child) 2.5 mg/kg up to 150 mg IV, 12-hourly,or
  — tigecycline 100 mg IV, for the first dose, then 50 mg IV, 12-hourly (in adults)
  — generally 14 to 21 days but requires individual assessment

References and Links

Journal articles

• Dhillon RH, Clark J. ESBLs: A Clear and Present Danger? Crit Care Res Pract. 2012;2012:625170. doi: 10.1155/2012/625170. Epub 2011 Jun 6. PubMed PMID: 21766013; PubMed Central PMCID: PMC3135063.
• Pillai DR, McGeer A, Low DE. New Delhi metallo-β-lactamase-1 in Enterobacteriaceae: emerging resistance. CMAJ. 2011 Jan 11;183(1):59-64. doi: 10.1503/cmaj.101487. Review. PubMed PMID: 21220461; PubMed Central PMCID: PMC3017254.

FOAM and web resources

• ATOTW — Microbiology Challenges in Critical Care (2010)