Transcript Diabetic Foot Infections

Bacterial Infections in
Hemodialysis Patients
Pathogenesis and Prevention
Sandra A. Kemmerly, MD, MACP, FIDSA
26 June, 2015
Disclosure of Financial Relationship
•
Sandra Kemmerly, Has no relationships with any entity
producing, marketing, re-selling, or distributing health
care goods or services consumed by, or used on,
patients
End Stage Renal Disease (ESDR)
•
•
•
•
•
Bacterial infections common in Hemodialysis (HD) patients
Infection is second leading cause of death ESDR patients
– Cardiovascular disease is 1st
Septicemia in HD patients rose 51% from 1991-1999
Hospitalization for septicemia results in
–
–
–
–
Increased risk of myocardial infarction
CHF
Stoke
Peripheral vascular disease
Evidence suggest HD patients have higher incidence of
infective endocarditis (IE)
J Am Soc Nephrol 15:1038-1045, 2004
Nephrol Dial Transplant 19: 1360-1362, 2004
Annual Death Rate due to Sepsis in HD Patients
Kidney International, Vol. 67, 2005
Pathogenesis of Bacteremia in
Hemodialysis Patients (HD)
Pathogenesis of Bacteremia in HD Patients
Impaired Host Immunity
• Neutrophil dysfunction
–
–
–
–
–
–
Impaired chemotaxis
Oxidative metabolism
Phagocytic activity
Degranulation
Intracellular killing
apoptosis
• Factors
– Malnutrition
– Trace element
deficiencies
– Iron overload
– Impaired glucose
metabolism
– Dialysis
– uremia
Pathogenesis of Bacteremia in HD Patients
Impaired Host Immunity
•
•
•
•
•
Abnormalities in cell-mediated immunity
Primarily involves T-lymphocytes
– Lymphocytopenia
– Impaired delayed skin reactivity
– Decreased in vitro lymphocute proliferation
Alterations in B-lymphocyte function
– Affects humoral immunity
– Decreased immunoglobulin levels
– Depressed antibody response to antigens
Dysregulation of cytokine synthesis
Impaired macrophage receptor function
Lymphocytes
Bacterial Virulence and
Adherence Factors
•
•
•
•
Expression of virulence genes for bacterial survival
– Proteases, superoxide dismutase, catalase inhibits bacterial killing
Bacteria form “SLIME” matrix
–
–
–
–
Extracellular polysaccharides
Biofilm
Acts as barrier between antibiotic and bacteria
More likely with foreign surfaces (central venous catheters)
S.aureus adheres to host proteins on fibronectin (CVC)
Coagulase-negative staphylococci onto polymer surface
The Hemodialysis Procedure
• Disruption of skin
barrier during access
• Dialysis water
treatment system
• Dialyzer reuse
CVC used in Hemodialysis
• Non-tunneled
• Tunneled
• Implantable
Use of Vascular Access
•
Catheters
– Non-tunneled: 1-2 weeks
– Tunneled: months to years
•
Fistula (AVF)
– 8-12 weeks to mature
•
Graft (AVG)
– 2-6 weeks after placement
Hemodialysis Vascular Access Device
(HVAD) Infections
•
•
•
Thrombosis and infection most frequent cause of access
failure
Simple arteriovenous fistula (AVF) preferred device for
chronic dialsyis
– >70% functional after 3 years
– Infection rate is on 2-3% over life of AVF
– Limitations: exhaustion of arteries and veins to create
anastamosis, development of venous aneurysms, stenosis
Alternative: polytetrafluroroethylene synthetic (Gortex)
– Not as durable, 3 yr survival rate is 50%
– Thrombectomy or revision can repair the AVG
Arteriovenous Fistula
Cuffed Central Line Catheters
•
•
•
•
Only use when no other limb option
Should be placed in OR as they are tunneled with
protective cuff
More prone to infection the the AVF or AVG
– Rate of bacteremia 2 times that of AVG
Temporary CVC bedside catheters should be placed in
right internal jugular or subclavian vein as bridge
– 30 days maximum recommendation
– Approximately ½ removed due to infection
Proper Insertion of Central Line
Hemodialysis Vascular Access Device
(HVAD) Infections
•
•
•
•
•
•
•
Most common cause of
infection in HD population
Erythema / cellulitis
Skin breakdown
Purulent drainage
Bleeding
Fever, drainage, abscess <
50% cases
Organisms: S.aureus,
coagulase-negative
staphylococcus, gramnegative rods
Bacteremia in HD Patients
•
•
HVAD responsible for half of infections resulting in
bacteremia
S.aureus can lead to metastatic soft tissue, bone
infection and endocarditis
– Suggest TEE
– MSSA: cefazolin or nafcillin
– MRSA: vancomycin, daptomycin, linezolide +/- gentamicin or
rifamipin
– Minimal treatment course 4 weeks if NO endocarditis
Causes of Catheter-related Blood
Stream Infections
•
•
•
•
Colonization of cutaneous catheter tract and tip with skin
flora
Intraluminal colonization due to contamination of the hub
Hematogenous seeding to the catheter from another
focus of infection
Intraluminal contamination with solvent or infusate
Prevention of Infections
•
•
•
•
•
•
Central lines higher risk than fistula or graft
Promote fistula use
Get catheters out
Improve catheter care
Clean hands before and after every patient contact
Teach patients about good vascular access care
Catheter Care
•
•
•
•
•
•
•
•
•
Exit site examination
Aseptic technique
Cleans HUB
Mask / eye protection
Fresh sterile gloves
Hub scrubbed with CHG, alcohol, or provodine-iodine
Immediate connection
Same procedure for disconnection
Exit-site care
– After each HD session for gauze/tape
– Every 7 days for transparent dressing
Emerging Bacterial Resistance
• Increasing MRSA,
•
•
VRE in US dialysis
centers
Colonization of VRE
associated with outpt
use of vancomycin
Some strains of VISA
– Vancomycin
intermediate S.aureus
Black: MRSA
Gray: VRE
Source: US national surveillance of dialysis-associated disease
Fever During Hemodialysis
•
•
•
•
•
Must be aggressively evaluated
Indolent vascular access infection
Blood cultures
Usual organisms: graft infection
Waterborne organisms: contamination of water source
– Burkholderia, Stenotrophomonas, Pseudomonas,
Aeromas spp
Fever in HD: Empiric Antibiotics
•
•
•
•
•
Empiric therapy should be initiated
Antibiotics post-dialysis
Cefazolin, in absence of methicillin resistance for grampositive organisms
Cefoxitin or Ceftazidime and aminoglycosides for gramnegative organisms
Reserve vancomycin unless septic, previously
documented MRSA infection
– Minimize spread of vanc-resistant gram-positive organisms
The Diabetic Foot in the Dialyzed Patient
•
•
Independent risk fact for foot ulceration
– 5 fold higher in dialysis-treated patients
– Amputation, peripheral arterial disease, prior ulcer, neuropathy ~
2 fold higher
Contributing factors
–
–
–
–
–
–
–
Physical and psychological health
Mobility
Manual dexterity
Visual acuity
Nutrition
Leg edema and neuropathy
anemia
Diabetes Care, vol 33, no 8, 2010
Diabetic Foot Infections
•
•
•
•
Bacteria gain entry to subcutaneous tissue by disruption
of the normal cutaneous barrier
–
–
–
–
Small fissures between toes
Traumatic wounds
Burns
Chronic pressure ulcers
Infection can be mild and localized
Can spread rapidly via tendon sheaths and fascial
planes
Abscesses in plantar spaces can begin under a
metatarsal head
Epidemiology of Foot Lesions in
Diabetic Patients with Renal Disease
•
•
Rate of lower limb amputation with renal failure
secondary to diabetic nephropathy is ~14%
– 10 times higher than the diabetic population at large
10% of new HD patients have already had above or
below-ankle amputation
J Am Soc Nephrol 11: 2000
Causes of Diabetic Foot Lesions
• Ischemia from
macroangiopathy
(ischemic foot)
• Microangiopathy
(neuropathic foot)
– Neuropathy with loss
of sensory,
autonomous and
motor innervation
Mechanisms leading to the diabetic foot lesion.
MICHAEL SCHÖMIG et al. JASN 2000;11:1153-1159
©2000 by American Society of Nephrology
Diabetic Foot Lesions
• Ischemic
– Painful
– Foot cold, cyanotic,
atropic
– Foot pulses absent
– Sensation UNIMPAIRED
– Atrophy of intrinsic foot
muscles
– Acral necrosis
Tip of toe, heel
• Neuropathic
–
–
–
–
–
Painless
Foot warm, pink, dry
Foot pulses present
Sensation IMPAIRED
Atrophy of
subcutaneous fat,
necrosis under callus
or metatarsal ulcer
Examination of Diabetic Foot Lesions
•
•
•
•
•
•
•
History of trauma
Inspection of shoes and stockings
Inspection for callus formation, interdigitial mycosis,
necrosis, ulcers
Neurologic exam (relexes, perception of vibration,
pedography
Angiologic exam (Doppler pressures ankle and toe)
Angiography only prior to interventions
X-rays (2 planes)
Microbiology
•
•
•
1980s and early 1990s virtually all considered
polymicrobial
– Gram positive, gram negative and anaerobes
Recent studies have demonstrated monomicrobial,
similar to non-diabetic patients with skin and soft tissue
infections
– S.aureus and streptococcal species
Chronic infections, previously treated can be
polymicrobial
– S.aureus, streptococci (Group B), Enterocoocus, E.coli,
Klebsiella, Proteus, Pseudomonas
Changing Microbiology
•
Increasing isolation of multidrug-resistant organisms
(MDROs)
– MRSA
•
•
 Associated with higher rate of treatment failure
 Panton-Valentine leukocidin virulence factor
Extended-spectrum beta-lactamase (ESBL)-producing
strains of Enterobacteriaceae
Microbiologic sampling
– Tissue cultures, curettage or biopsy
Drugs
Class
MRSA activity
B.fragilis
activity
Dose adjustment
for renal
impairment
Ampicillin/
sulbactam
ß-lactam/ßlactamase
inhibitor
No
Yes
Yes
Ticarcillin/
clavulanate
ß-lactam/ßlactamase
inhibitor
No
Yes
yes
Pip/tazo
ß-lactam/ßlactamase
inhibitor
No
Yes
Yes
Imp/cilistatin
Carbapenem
No
Yes
Yes
Ertapenem
Carbapenem
No
Yes
Yes
Moxifloxacin
Quinolone
No
Yes
No
Tigecycline
Glycylcyclcine
Yes
Yes
No
Vancomycin
Glycopeptide
Yes
No
Yes
Linezolid
Oxaxolidinone
Yes
No
No
Daptomycin
Cyclic
lipopeptide
Yes
No
Yes
Acute Management of Diabetic
Gangrene
• Control infection
• Assess need for
•
•
revascularization
Assess need for
amputation
Provide long-term
adequate foot care
and foot wear to
prevent recurrences
Treatment Strategies with Gangrene
•
•
•
Treatment
–
–
–
–
–
–
Decide if high amputation is necessary
Bed rest (unloading foot)
Control of hyperglycemia
Surgical debridement
Culture of exudative material
Parenteral antibiotics
If indicated
– Revascularization
– Resection of exostoses, metatarsal heads
Patience
– Wait for demarcation before amputation if possible
Patient Prophylactic Measures
for Prevention
•
•
•
•
•
•
•
•
•
•
Avoid walking barefoot to prevent trauma
Avoid tight footwear
Orthopedic shoes to relieve pressure on deformed foot
Correct trimming of toenails
Corns treated by physician or podiatrist
Treat fungal infections topically
Foot powder for sweaty feet
Lanolin ointment for dry skin
Inspect feet daily
Exercise daily to improve collateral blood flood
Osteomyelitis of Foot with Diabetes
•
•
•
•
•
Contiguous spread from soft tissue
Takes days to weeks
Uncommon in acute infection
20% of diabetic foot infections have underlying bone
involvement
– Some studies suggest up to 2/3
Increases treatment failure and amputations
Diagnosing Osteomyelitis
•
Radiographic studies:
–
–
–
–
•
Plain xray
Scans
CT
MRI
Culture of organisms:
– bone (definitive)
– blood, joint fluid
– sinus tract
Microbiology: Overview
Type of osteo
Organism(s)
•
hematogenous
age - dependent
•
contiguous focus
mixed (staph, GNR)
•
vascular insufficiency
mixed (GPC-strep, Staph,
GNR - Psa, anaerobes)
puncture wound = pseudomonas
Plain X-rays
• In general, osteomyelitis must extend ≥ 1 cm &
compromise 30 - 50% of bone mineral content to
produce noticeable changes in plain
radiographs.
• Findings:
– Osteopenia, periosteal elevation
– Endosteal scalloping
– Loss of trabecular architecture
Radionuclide Studies
• Technesium bone scan: (3 phase)
–
–
–
–
–
–
positive earliest (48 hrs after infection)
positive in inflammation and new bone formation
Can detect multifocal osteo
Pooled sensitivity/specificity 81% / 28%
not useful after surgery (+ up to 2 years)
negative scan in highly-suspected cases may indicate
lack of blood flow to area
Gallium and Indium Scanning
•
•
Gallium scans:
– does not show bone detail well, hard to tell from soft
tissue, also positive in metastatic disease
– 99mTc uptake < gallium – infection
– 99mTc uptake > gallium – reactive
Indium scans:
– positive in 40% of acute & 60% of chronic osteo,
negative in areas of new bone formation
– Pooled sensitivity / specificity 74% / 68%
– Better for diabetic feet infections (no red marrow)
99mTc and Gallium Scans
CT Scanning
•
•
Picks up early disease ( marrow density)
Defines extent of disease
– areas of necrosis/abscess/sinus tracts
– *Superior to x-ray and MRI for bony margins and showing
sequestrae and involucrum
– helpful in planning surgical approach
•
•
 utility if metal in place
False (+)’s: stress fractures, osteoid osteomas
MR Scanning
•
•
Good for distinguishing bone vs soft tissue/joint
Osteomyelitis:
– excellent - detecting abnormal bone marrow
–  signal on T-1 and  signal on T-2
– postsurgical/post-traumatic scarring:
decreased signal on T-1 and no impact on T-2
•
•
Sensitivity/specificity 90-100%/ 80%
False (+)’s: fractures, tumors
T 1 image; enhancement
of calcaneal bone marrow
Contiguous Focus & Vascular
Insufficiency Osteomyelitis
• Symptoms can be delayed for > a month
• Low-grade fever, pain over joint
• Local signs: redness, swelling
• Loss of bone stability
• May/ may not be painless (neuropathy)
• Frequently ulcer, drainage
• Fever and sepsis often absent
Vascular Insufficiency Osteo: Treatment
• Cover for staph aureus – MSSA vs MRSA
• Gram-negative coverage:
– Pseudomonal cephalosporins, pip-tazo
– Quinolones, ampicillin-sulbactam
– carbapenems
• Anaerobic coverage:
– Metronidazole
– Beta-lactams
Clindamycin
Moxifloxacin
Bone Levels for Selected Antibiotics
Drug
Ampicillin
Ceftriaxone, ceftaz; cefipime
Imipenem; meropenem
Pip/tazo
Vancomycin (serum level >35)
Cipro; levofloxacin; moxi
Linezolid
Clindamycin
TMP-SMX
Metronidazole
% levels in bone
10-33
20; 27; 100
26-40; 17
20-25
30 (sternal); axial less
27-48; 38-99; 27-49
37-50
40-67
50/15
79-100
Use of Newer Antibiotics
•
Linezolid: Data not high quality, is accumulating
Compassionate use; N= 89; gram (+) infections
– Cure rate ~80%; including MRSA & VRE w/ surgery/graft removal
•
Daptomycin: EU-CORE registry report
– N = 220 (114 no prosthesis); ≥ 28 d Rx;
– S. aureus 33%, coag-neg Staph 32%
– 55% had other Abxic (Q’s or penems); 52% had surgery
– Overall - Success 75% - 23% cured, 52% improved
•
Telavancin, dalbavancin, oritavancin – no data
Duration of Antibiotic Therapy
Clinical situation
Route of therapy
Duration of therapy
No residual infected
tissue (e.g. postamputation)
Parenteral or oral
2-5 days
Residual infected soft
tissue (but not bone)
Parenteral or oral
2-4 weeks
Residual infected (but
viable bone)
Initial parenteral, then
consider oral switch
4-6 weeks
No surgery, or residual
dead bone
postoperatively
Initial parenteral, then
consider oral switch
> 3 months
Clin infect Dis 39, 2004
Pneumonia
•
•
Common in patients with ESRD
CXR: variable and can be misleading
– Pulmonary edema
– Metastasis
– Fungal disease
•
Predisposing conditions
– Underlying cardiac disease
– Pulmonary fluid overload
– Low albumin
– Suboptimal response from pneumonia and flu vaccines
Pathogens in Pneumonia
•
•
•
•
•
•
S.pneumoniae
H. influenzae
S.aureus
Gram-negative rods
Work up:
– Gram stain and culture
Consider use of fluoroquinolones empirically
Urinary Tract Infection
• Asymptomatic pyuria and bacturia ~30% ESRD
patients
– Does not require treatment
• Gram-negative bacteremia
– Urine may be orgin
– Systemic antibiotics required