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