4/15/2014
Objectives
Infections in the Acute
Setting: A Crash Course in Infectious Disease Medicine

Identify common and atypical infections in the acute setting found
in the problem wound

Identify challenges in inpatient infections including multi-drug
resistant bacteria

Recognize management and treatment options of wound
infections in the acute setting
HAN PHAM HULEN, MD, ABPM / UHM
SAWC SPRING 2014
Where do we begin?
Skin and Soft Tissue Infections and
Microbial Cause (The Basics)

How do infectious disease specialists make their decisions?
Anatomical Structure
Infection
Microbial Cause

What’s the “decision tree”?
Epithelium
Varicella
Measles
Varicella zoster virus
Measles virus

Are there guidelines or do we flip a coin?
Keratin layer
Ringworm
Dermatophyte fungi (Microsporum,
Epidermatophyton, Trichophyton)
Epidermis
Impetigo
Streptococcus pyogenes
Staphylococcus aureus
Dermis
Erisipelas
Streptococcus pyogenes
Hair follicles
Folliculitis, boils, carbuncles
Staphylococcus aureus
Sebum glands
Acne
Propionibacterium acnes
Subcutaneous fat
Cellulitis
ß-hemolytic streptococci
Fascia
Necrotizing fasciitis
Streptococcus pyogenes or mixed
anaerobic infections
Muscle
Myositis
Gangrene
Toxigenic strains of S. aureus
Clostridium perfringens
 WHERE DO WE BEGIN???
J Antimicrob Chemother 2010; 65 Suppl 3: iii35 - 44
Skin Manifestations in Systemic
Diseases
Pathogen
Disease
Skin Manifestation
Varicella zoster virus
Chickenpox
Vesicles
Staphylococcus aureus
Toxic shock syndrome
Scalded skin syndrome
Rash and desquamation
Streptococcus pyogenes
Scarlet fever
Erythematous rash
Non-blanching petechiae or
haemorrhagic rash
Neisseria meningitides
Meningococcal sepsis
Salmonella typhi
Enteric fever, typhoid
Pseudomonas aeruginosa
Septicemia
Ecythma gangrenosum
Rickettsia conorii
African tick typhus
Macular rash
Cryptococcus neoformans
Cryptococcus
Papule on face or trunk
Rose spots
J Antimicrob Chemother 2010; 65 Suppl 3: iii35 - 44
Defining complicated skin and soft
tissue infections (cSSTIs)

cSSTIs are among the most rapidly increasing reasons for
hospitalizations

Involves deep soft tissue and is common in patients with underlying
co-morbid issues (e.g., diabetes, intravenous drug use, peripheral
vascular disease, coronary artery disease, cancer, chronic kidney
disease, chronic obstructive pulmonary disease)

cSSTIs may be health care associated or community acquired
Journal of Clinical Microbiology 2012; 50(2): 238 - 245
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cSSTIs
Inpatient Algorithmic Approach

Include deep soft tissue infections requiring surgical intervention,
infected ulcers, burns and major abscesses

Initial assessment:

Blood cultures

Full blood count




Identify the pathogen or potential pathogens

Consider patient risk factors (e.g., diabetes, cancer)

Multi-drug resistant organisms

Determine origin of the infection (e.g. health care or community
acquired) to assist with appropriate empiric therapy
Measurement of inflammatory markers (C-reactive protein)

Empiric treatment
Metabolic profile

Goal – directed treatment
Creatine phosphokinase level

Consider: side effects and / or adverse effects of antibiotic therapy
J Antimicrob Chemother 2010; 65 Suppl 3: iii35 - 44
Identifying the Pathogen or Potential
Pathogen (Things to Consider)


The diabetic foot ulcer (DFU)¹:

In less severe infections, consider gram positive bacteria such as
Staphylococci

Consider methicillin resistant Staphylococcus aureus (MRSA) in areas of
high prevalence or if patient has had prior MRSA infection



Common Pathogen Distribution (cSSTIs in patients presenting
with a positive culture obtained at <24 hours from time of
admission or emergency room visit)
In more severe infections, consider broad spectrum antibiotic coverage
for mixed flora (3 – 5 species) covering both gram-positive cocci and
gram-negative rods
Ischemic disease: consider anaerobic coverage
The immunocompromised patient:

Consider unusual / atypical infection such as fungi or Mycobacterium
¹Clinical Infectious Diseases 2012; 54(12): 132 - 173
Multi-Drug Resistant Infections
Journal of Clinical Microbiology, November 2011: 238 – 245
Pathogen(s)
HCAI (n = 194)
No. [%] of patients
CAI (n = 255)
No. [%] of patients
Total (n = 449)
No. [%] of patients
P value
Staphylococcus
aureus
131 (67.5)
167 (65.5)
298 (66.4)
0.65
MRSA
99 (75.6)
124 (74.3)
223 (74.8)
0.71
MSSA
31 (23.7)
43 (25.7)
74 (24.8)
Streptococcus spp.
44 (22.7)
73 (28.6)
117 (26.1)
0.16
Enterococcus spp.
9 (4.6)
6 (2.4)
15 (3.3)
0.18
Proteus spp.
15 (7.7)
15 (5.9)
30 (6.7)
0.44
Other
Enterobacteriaceae
14 (7.2)
13 (5.1)
27 (6.0)
0.35
Pseudomonas
aeruginosa
11 (5.7)
7 (2.7)
18 (4.0)
0.12
Other Gramnegative bacteria
4 (2.1)
8 (3.1)
12 (2.7)
0.57
Polymicrobial
infection
35 (18.0)
34 (13.3)
69 (15.4)
0.17
*HCAI, health care associated infection; CAI, community acquired infection
Methicillin-resistant
Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA)

Gram positive cocci

Extended spectrum beta lactamase producing organisms (ESBLs)

Majority of strains produce adhesins

Vancomycin resistant Enterococcus (VRE)


Carbapenem resistant Enterobacteriaceae (CRE)
Synthesize and secrete polysaccharides, forming a glycocalyx
(biofilm)

Biofilm protects the pathogen against antibiotics and access of
specific and non-specific immunity

Secretion of hemolysins leading to tissue necrosis

Virulence genes leading to high grade infected diabetic foot ulcers
Int Wound J 2011; 8: 567 - 577
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4/15/2014
Extended spectrum beta
lactamase (ESBLs)
Vancomycin-resistant
Enterococcus (VRE)

Plasmid mediated resistance to cephalosporins


Additionally carry resistance genes to other antibiotics such as
aminoglycosides, chloramphenicol, sulfonamides, trimethoprim, and
tetracycline
Generally a fellow pathogen and not typically relatively low
virulence

Minimum inhibitory concentration (MIC) of 32 microgram / mL or
more

Thus, they are multi-drug resistant


Epidemiologic data suggest that rise of ESBLs are due to widespread
use of 3rd generation cephalosporins as a major risk factor
Antibiotic resistance occurs through mutation and acquisition of
genetic material from other species

Risks: prolonged hospitalization, residence in long-term care
facilities, exposure to antibiotics
Mayo Clin Proc. 2011; 86(12): 1230 - 1242
Journal of Perinatology 2003: 23; 439 - 443
Carbapanem-resistant
Enterobacteriaceae (CRE)

Emerging resistance seen in hospitalized patients (mostly
in diabetics and in ICU settings)

Thought to be due to high carbapenem use in face of
treatment of ESBL producing organisms
Unusual or Atypical Infections:
Nontuberculous Mycobacteria (NTM)

Ubiquitous in soil and water (areas of warmth and humidity)

Disseminated skin infections

Mycobacterium abscessus, Mycobacterium chelonae,
Mycobacterium fortuitum

Check culture and AFB (acid fast bacilli) stain

Consider in elderly patients / female patients, operation history (e.g.
implantable devices), exposure to water, delayed wound healing
Clev Clin J Med. 2013 Apr; 80(4): 225 - 33
Unusual or Atypical Infections:
Fungal Infections


Immunocompromised hosts with cutaneous wounds¹
Infect Chemother 2013; 45(1): 85 - 93
Determining the Origin of the
Infection

Health care-associated infection (HCAI)

Cryptococcus

Mostly studied in hospitalized patients with pneumonia or bacteremia

Histoplasmosis

Coincide closely with nosocomial infections

Inappropriate antibiotic (empiric or initial) therapy may result in worse
outcomes

Due to lack of studies, it is difficult to predict whether worse outcomes
are also seen in cSSTIs in relation to HCAI
Natural disasters²

Contamination of wounds with water, soil or debris

Mucormycosis (may lead to necrotizing fasciitis)

Fusarium

Aspergillus

Community-acquired infection

Infection in relation to community-based or ambulatory setting

May also be a hybrid: community-based patients who have had
contact with the health care (inpatient) setting leading to infections
with potentially resistant pathogens
¹J Antimicrob Chemother 2010; 65 Suppl 3: iii35 - 44
²Emerging Infectious Diseases March 2014: 20(3)
Journal of Clinical Microbiology 2012; 50(2): 238 - 245
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Antibiotic Selection Overview:
2012 Infectious Disease Society of America [IDSA]
Guidelines for Diabetic Foot Ulcers [DFUs]


If positive clinical signs of infection, ask the following:
Is there a high risk of MRSA?




Empiric Therapy (an example in
Diabetic Foot Ulcers [DFUs])

Infectious Diseases Society of America (IDSA) 2012 Guidelines for diabetic foot ulcer

Mild to Moderate Infection:

Severe Infection:
Include anti-MRSA therapy in the empiric regimen
Has patient received antibiotics in the past month?

If so, include active agents against gram-negative bacilli

If not, gram positive coverage for DFU may be sufficient
Are there risk factors for Pseudomonas?


(Think warm climate, exposure to wound to water, areas of high prevalence
of Pseudomonas)

Start empiric anti-Pseudomonal coverage

What is the severity of the wound infection?

See following slide . . .

Patient has not received recent antibiotics

Target at least aerobic gram positive cocci

Start with broad spectrum antibiotic coverage pending cultures and susceptibilities

Narrow choice to goal directed therapy if proper culture obtained
Pseudomonal infection coverage?

Usually unnecessary unless thought to be true culprit of infection (i.e., prior cultures)

Area of high local prevalence, warm climate, frequent exposure of the foot to water
MRSA coverage necessary?

Severity of infection

High prevalence area

Prior infection with MRSA
Clinical Infectious Diseases 2012: 54(12): 132 - 173
Antibiotic Therapy (Initiation)


Broad spectrum antibiotic therapy:
Clinical Infectious Diseases 2012: 54(12): 132 - 173
Treatment of Methicillin Resistant
Staphylococcus aureus (MRSA)

Oral antibiotics:

Beta lactamase inhibitors (e.g. ampicillin / sulbactam, piperacillin /
tazobactam)

Doxycycline, minocycline

Clindamycin (D-test)

Third- or fourth-generation cephalosporins (e.g. ceftazidime, cefepime)

Trimethoprim/sulfamethoxazole

Carbapenems (e.g. imipenem, ertapenem)

Linezolid

Quinolones (e.g. levofloxacin, ciprofloxacin)

Antibiotics with activity against MRSA: vancomycin, linezolid,
daptomycin

Clinical Pearl*: always consider bone penetration abilities if concerned
for osteomyelitis; for example, vancomycin is known to have poor bone
penetration
Intravenous antibiotics:

Vancomycin

Daptomycin

Linezolid

Ceftaroline

Tigecycline
Int Wound J 2004; 1(2): 123 - 132
Treatment of Extended Spectrum Beta
Lactamase (ESBL) Producing Organisms



Beta lactamase inhibitors

Piperacillin / tazobactam

Failures: seen in “hyperproduction” of ESBL enzymes by the infecting strain;
mutation leading to decreased antimicrobial access into bacteria
Quinolones

Effective in animal models

Rare plasmids may still produce resistance genes
Int Wound J 2011; 8: 567 - 577
Treatment of Vancomycin Resistant
Enterococcus (VRE)

Surgical debridement and management of the wound bed is the most
important

Keep in mind before treatment consideration: fellow pathogen
traveling with another pathogen

Limited data on effective agents for VRE

Antibiotics:

Daptomycin

Linezolid
Only class with consistent effectiveness against ESBL producing organisms

Tigecycline

Remain stable in the presence of ESBL enzymes

Compact size of carbapenems allows easy passage through porins into
Gram negative bacilli
Quinupristin/dalfopristin (limitations due to myalgias, athralgias,
gastrointestinal side effects)


Fosfomycin (little data)
Carbapenems

Imipenem, meropenem

Journal of Perinatology 2003: 23; 439 - 443
Mayo Clin Proc. 2011; 86(12): 1230 - 1242
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4/15/2014
Treatment of Carbapenemresistant Enterobacteriaceae (CRE)

Limited options on treatment:
Treatment of Atypical Infections: When you might want to call your local infectious disease specialist…

Mycobacterium¹
 Colistin

Wound debridement
 Tigecycline

Combination antibiotics (generally 2 – 3 in combination based on
susceptibilities for an average of 4 – 7 months)

Example regimen: amikacin, clarithromycin, ciprofloxacin
 Aminoglycosides
(variable activity)
 Fosfomycin

Fungal Infections²

Aggressive and early diagnosis and treatment

Surgical debridement

Antifungal medication
¹Infect Chemother 2013; 45(1): 85 - 93
Clev Clin J Med. 2013 Apr; 80(4): 225 - 33
²Emerging Infectious Diseases 2014; 20(3): 349 - 355
Antibiotic Therapy and Factors to
Consider

Clostridium difficile colitis

Bone marrow suppression

Antibiotic adjustment in patients with chronic kidney disease

Selection pressures and multi-drug resistant organisms
5