Antibiotic Resistant Hospital Acquired Infections in 2018 · Antibiotic Resistant Hospital Acquired...
Transcript of Antibiotic Resistant Hospital Acquired Infections in 2018 · Antibiotic Resistant Hospital Acquired...
Antibiotic Resistant Hospital Acquired Infections in 2018
37th Annual APACVS Meeting Juan D Diaz, DO, FACP
Infectious DiseasesOrlando, Florida
Objectives
Mechanisms of resistance
Antimicrobial stewardship
Prevention
Antimicrobial treatment choices, including their SE’s, adverse reactions
Isolation requirements
cdc.gov
cdc.gov
Common Isolates
MRSA
VRE
MDR PSA
ESBL Enterbacteriacea
Acinetobacter
CRE
MRSA• Carried in anterior nares by 20-30% of population.
◦ Higher carriage rates seen in diabetics, injection drug users (IDU), HIV or
dialysis patients.
◦ Carriers have > risk of subsequent infection.
• Risk factors: skin disease ( psoriasis), venous catheters, other foreign bodies
(e.g., prosthetic joints, pacemakers), IVDA, hemodialysis, recent surgical
procedure.
• Methicillin resistance increasing. MRSA traditionally associated w/ healthcare
system interaction
CA-MRSA has emerged as significant pathogen, especially in children,
prisoners, IVDA. Did not emerge from hospital strain.
◦ CA-MRSA mostly causes skin/soft tissue infections.
◦ CA-MRSA also a cause of necrotizing pneumonia. Consider diagnosis in
a severe pneumonia with evidence of cavitation/necrosis, particularly
after influenza-like illness.
◦ Probably not a frequent cause of cellulitis in the absence of purulence
(abscess) or wound.
MRSAMethicillin resistance (MRSA) conferred by presence of mecA gene that encodes penicillin
binding protein 2a, an enzyme that has low affinity for beta-lactams and thus leads to
resistance to methicillin, oxacillin, nafcillin, and cephalosporins.
Community-acquired MRSA (CA-MRSA) isolates (strains include USA 300 as most common in
US, also USA 500, USA1000): often maintain susceptibility to tetracyclines (doxycycline,
minocycline) & TMP/SMX.
▪ Clindamycin susceptibilities vary geographically.
If isolate is erythromycin resistant, must confirm clindamycin susceptibility with
MRSA
Recall that oxacillin/Nafcillin are DOC for MSSA.
Severe MRSA infections with vancomycin MIC 1.5-2.0 not responding to
therapy, consider alternative agent. Several studies have worse clinical
outcomes with vancomycin in these settings.
🌵Daptomycin: cidal, q-day dosing. Do not use for pneumonia.
Rhabdomyolysis, rare eosinophilic pneumonia
🌵Ceftaroline: cidal, bid dosing, covers GNR’s - Stewardship!
🌵Linezolid: static, bid dosing, bone marrow suppression, optic neuritis,
peripheral neuropathy. Low levels in blood, avoid in bacteremia.
🌵Telavancin: cidal, q-day dosing, slightly more nephrotoxicity than
vancomycin
Contact Isolation
VRE
Found in normal colonic Flora, oropharyngeal and vaginal secretions. found in soil, water and food.
Produces biofilms.
Exploits opportunity to proliferate once antibiotic susceptible organisms are eradicated.
High-density stool colonization in antibiotic treated patients.
VRE
High-level beta-lactam resistance is uncommon with enterococcus faecalis
Intrinsically resistant to cephalosporins due to inner wall penicillin binding proteins.
Uses exogenous folate to overcome antifolate synthesis mechanism.
Aminoglycosides are relatively impermeable at the cell wall. Hence , beta-lactam agents allow bactericidal at the ribosome a level.
Mutations at the ribosomal level confer high-level aminoglycoside resistance.
VRE
VRE: E. faecium>>E faecalis.
Plasmid mediated vanA and VanB gene complexes result in high-level vancomycin resistance.
Mortality is 30%
VRE
Steps to avoid include:
Avoid Unnecessary use of antibiotics, especially vancomycin, catheter removal, device removal, drainage of fluid collections and surgical debridement
VRE
Daptomycin: cidal. 8-12 mg/kg/day
Linezolid: static. Good CNS penetration.
Tigecycline: static. Does not have adequate GU penetration. Low serum levels. Nausea/Emesis: 20-30%. Black box warning for increased risk of death.
Fosfomycin: oral formulation only. lower tract disease only.
Quinupristin/dalfopristin: static, causes plebitis, must use central line. Myalgias & Arthralgias.
Contact Isolation
MDR PSA
causes severe hospital-acquired infections associated with a high
mortality rate, especially in immunocompromised hosts.
Definitions:
▪ MDR: Non-susceptible to ≥1 agent in ≥3 antimicrobial
categories.
▪ XDR: Non-susceptible to ≥1 agent in all but ≤2 categories.
▪ PDR: Non-susceptible to all listed antimicrobials.
Risk factors
ICU stay
Bedridden status
Presence of invasive devices
Prior use of broad-spectrum cephalosporins,
aminoglycosides, carbapenems, & fluoroquinolones
Diabetes mellitus
Undergoing surgery
http://www.nejm.org/doi/full/10.1056/NEJMra0904124
MDR PSA🍇 For most infections, definitive therapy with a single active agent is appropriate, as there
is no convincing clinical data that demonstrate a mortality benefit to combination therapy.
🍇 However, using two agents for empiric therapy may increase the likelihood that an active
agent will be used for a potentially resistant organism, and this, in turn, is associated
with better outcomes for serious infection
🍇 Combination therapy may be indicated in certain high-risk patients and in severe
infections.
Examples: neutropenia/bacteremia, septic shock, burn patients , or incidence of
resistance > 10-15%
🍇 Avoid aminoglycoside monotherapy for pneumonia, intra-abdominal infections &
bacteremia. GU exception
🍇 delayed therapy correlates with increased mortality.
🍇 Source control. All infected catheters should be removed, and abscesses
drained and obstructions relieved
MDR PSACipro > Levofloxacin (Delafloxacin)
Cefepime, Ceftazidime
Piperacillin-tazobactam
Aztreonam
Doripenem, meropenem, imipenem
Amikacin, Tobramycin, gentamicin
Ceftazidime-avibactam, ceftolozane-tazobactam
Colistin, Polymyxin B (lower rates of nephrotoxicity than colistin and does not need to be dose-adjusted for renal function but no active drug in urine)
Contact Isolation
ESBL
🌶 enzymes that confer resistance to most beta-lactam antibiotics,
including penicillins, cephalosporins, and monobactams
🌶 Cleave the beta-lactam ring.
🌶 prevalence is likely underestimated.
🌶 found exclusively in gram-negative organisms, primarily in
Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli but
also in Acinetobacter, Burkholderia, Citrobacter, Enterobacter,
Morganella, Proteus, Pseudomonas, Salmonella, Serratia, and
Shigella spp.
🌶 GI tract reservoir
ESBL Risk Factors
🌶 healthcare exposure:
hospitalization ( ICU stay, longer hospitalization)
residence in a long-term care facility
hemodialysis use
presence of a urinary catheter
an intravascular catheter
travel to Asia
ESBL
🌶 associated with higher mortality rates
🌶 longer hospital stays
🌶 greater hospital expenses
🌶 reduced rates of clinical and microbiologic response
compared with similar infections with gram-negative
bacteria that do not produce ESBL
Treatment
Carbapenems
Ceftolozane-Tazobactam Ceftazidime-avibactam
Fosfomycin: oral only, GU tract only.
Tigecycline: approved for CIAI, cSSTI, & CAP. no appreciable GU penetration, poor blood levels
Contact Isolation
http://www.nejm.org/doi/full/10.1056/NEJMra0904124
Risk factors previous use of broad spectrum cephalosporins or
carbapenems
trauma
diabetes
malignancy
organ transplantation
mechanical ventilation
indwelling urinary or venous catheters
overall poor functional status or severe illness
50% mortality
Treatment
Ceftazidime-avibactam
Colistin ( up to 20% nephrotoxicity, 3.5 % neurotoxicity rate) or Polymyxin B
Fosfomycin ( uncomplicated UTI)
Meropenem/Vaborbactam
Tigecycline
Contact Isolation
Acinetobacter
GNR when growing, coccobacillus when not
Common in hospital/Nursing home associated & environmental ( can see in war wounds (Iraq)).
HAP, VAP, CRBSI, wounds, post Neurosurgical Meningitis
Inherent and acquired resistance limits the number of antimicrobial options
Risk factors for infection or colonizationPrior colonization with methicillin-resistant S. aureus (MRSA)
Prior beta-lactam use, particularly carbapenems
Prior fluoroquinolone use
Bedridden status
Current or prior intensive care unit admission
Presence of a central venous catheter
Recent surgery
Mechanical ventilation
Hemodialysis
Malignancy
Acinetobacter:
Ampicillin-sulbactam
Meropenem, Imipenem, Doripenem
Tigecycline, Minocycline
Amikacin
Colistin: cationic detergent, binds to lipids in cytoplasmic membrane causing osmotic leakage
Polymyxin B
TMP/SMX: variable activity
Acinetobacter
environmental cleansing: disinfection is particularly important because of the ability of Acinetobacter to survive on inanimate surfaces and contaminate other surfaces that contact it
Occurs at more frequent rate than that observed for multidrug-resistant Pseudomonas
largely susceptible to disinfectants and antiseptics; occasional reports of failure are more likely to represent failure of personnel to follow cleaning procedures than disinfectant resistance
contact isolation, health care worker compliance with hand hygiene, and aseptic care of vascular catheters and endotracheal tubes
Contact Isolation
References
cdc.gov
UpToDate.com
The Johns Hopkins ABX guide
New England Journal of Medicine