Infections In Diabetics NO DISCLOSURES · Case Presentation • A 56 year old diabetic presents with an ulcer on the metatarsal‐phalangeal area of the plantar aspect of the foot

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Infections In Diabetics

Richard A. Jacobs, M.D., PhD.NO DISCLOSURES

Overview

• BASEBALL HISTORY/TRIVIA

• PATHOPHYSIOLOGY

• FRAMEWORK OF HOW TO THINK ABOUT INFECTIONS IN DIABETICS

• CASE PRESENTATIONS

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WHO ARE THEY?? PLAYER # 1

PLAYER #1

Jackie Robinson

PLAYER #1

• Integrated MLB in 1947

Jackie Robinson

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PLAYER #1


• 1st Rookie of the Year

Jackie Robinson

PLAYER #1



• MVP in 1949

Jackie Robinson

PLAYER #1



• MVP in 1949

• Batting Champion 1949

• 2X stolen base leader in

1947,1949

Hall of Fame in 1962

Jackie Robinson

PLAYER #2

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PLAYER #2

Ron Santo

PLAYER #2

• BA .277, Hits 2,254, HRs 342

Ron Santo

PLAYER #2

• BA .277, Hits 2,254, HRs 342

• 1st MLB player to wear a helmet with a protective earflap in 1966

Ron Santo

PLAYER #2

• BA .277, Hits 2,254, HRs 342

• 1st MLB player to wear a helmet with a protective earflap in 1966

• Hall of Fame in 2012

Ron Santo

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PLAYER #3 PLAYER #3

Lou Brock

PLAYER #3

• Traded to the Cardinals in 1964‐‐Led them to WS wins in 1964 and 1967

Lou Brock

PLAYER #3


• Stolen Bases 938—most of any NL player

Lou Brock

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PLAYER #3


• Stolen Bases 938—most of any NL player

• Hall of Fame in 1985

Lou Brock

What Do They Have In Common?

• All in the Hall of Fame



• All had severe diabetes




– Jackie Robinson—nearly blind, renal insufficiency and cardiomyopathy

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– Jackie Robinson—nearly blind, renal insufficiency and cardiomyopathy

– Ron Santo and Lou Brock—BKAs due to diabetic foot infections

Overview


• PATHOPHYSIOLOGY



Pathophysiology

• Adaptive immunity

– T‐cell function and humoral immunity

• Minimal effect

• Normal immunoglobulins and response to vaccinations

Pathophysiology

• Host Factors Predispose To Infection:

– Vascular insufficiency —> tissue ischemia

– Peripheral neuropathy—> skin ulcers/infx

– Autonomic neuropathy—> urinary retention/infx

– Skin colonization (esp. with MRSA)—> cutaneous infections and transient bacteremia

– Mucosal colonization (Candida spp)—> vaginitis/esophagitis

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Pathophysiology

• Real risk for infection is mediated by HYPERGLYCEMIA

– Impairs immune response

• TNF, IL‐6, interferon‐gamma, neutrophil migration to the lungs

– Profound effect on PMN function

• Chemotaxis & phagocytosis

• Oxidative burst

• Intracellular killing

Effect Of Hyperglycemia On Phagocytosis

Alexiewicz, J. M. et. al. Ann Intern Med 1995;123:919-924





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Hyperglycemia and Risk of Infection

• General surgery and risk of SSIs (Arch Surg. 2010;145(9):858‐864)

– Postop hyperglycemia major risk factor for SSIs

– Linear relationship between glucose and SSIs

• < 110 mg/dl —> 1.8%

• 111‐140 mg/dl—> 6%

• 141‐220 mg/dl—> 10%

• >220 mg/dl—> 18%

Hyperglycemia and Risk of Infection

• Cardiothoracic Surgery and SSIs (Infect Control and Hosp Epidemiol 2001;22:607)

– Glucose > 200 mg/dL 48 hours before or after surgery associated with increased risk of SSIs

– Risk of SSIs correlated with degree of hyperglycemia. Compared with glucose < 200mg/dl

• 200‐249 OR = 2.54

• 250‐299 OR = 2.97

• >300 OR = 3.32

Tight Glucose Control and Risk of Infection

• Meta‐analysis of 10 studies comparing continuous infusion insulin to maintain glucose < 200 mg/dl to standard diabetes management (Heart & Lung 44 (2015) 430‐440)

– Tight control decreased SSIs after cardiac surgery with a P <0.00001

Take Home Points

• Risk of infection due to:

–Host facors

–Hyperglycemia the main driving force

• If well controlled, the risk of infection greatly diminished

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Overview


• PATHOPHYSIOLOGY



General Principles

• Two types of infections:

– Those that occur in diabetics (perhaps with increased frequency) as well as non‐diabetics

General Principles



• Unusual pathogens

General Principles




• More severe

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General Principles




• More severe

• Complications more common

General Principles




• More severe


Be aggressive/RX early

Careful FU/”72 hr rule”

General Principles




• More severe


– Those seen predominantly in diabetics (>50%)

Be aggressive/RX early

Careful FU/”72 hr rule”

Increased Frequency in Diabetics

• Pneumonia

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• Pneumonia—> unusual organisms (Klebsiella, S. aureus, TB); increased risk of bacteremia and death



• Abdominal Infections

– cholecystitis




– Cholecystitis—> c/b emphysematous cholecystitis





• Urinary Tract

– Pyelonephritis

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• Urinary Tract

– Pyelonephritis—>intra‐renal/peri‐nephric abscess; emphysematous pyelonephritis; papillary necrosis



• Abdominal Infections– Cholecystitis—> c/b emphysematous cholecystitis

• Urinary Tract– Pyelonephritis—>intra‐renal/peri‐nephric abscess; emphysematous pyelonephritis; papillary necrosis

• Skin & ST Infections– Foot infections/osteomyelitis

Infections in Diabetics

• Infections seen predominantly in diabetics– Head and neck

• Rhinocerebral mucormycosis

• Malignant (invasive) otitis externa

– Urinary tract• Emphysematous cystitis/pyelitis/pyelonephritis

– Skin and soft tissue• Necrotizing fasciitis

• Fournier’s gangrene

Overview


• PATHOPHYSIOLOGY



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Case Presentation

• A 56 year old diabetic presents with an ulcer on the metatarsal‐phalangeal area of the plantar aspect of the foot. There is surrounding cellulitis with a necrotic base to the ulcer, but no purulent material can be expressed and bone is not showing. He has no F/C.

Questions

• Should cultures be done?

• What is the bacteriology?

• What is appropriate antibiotic therapy and duration of therapy?

• When should you suspect osteomyelitis?

– How do you make the diagnosis of osteomyelitis?

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Clinical Infectious Diseases 2012;54(12):132–173

Initial Evaluation

• Assess the severity of the infection

• Laboratory:– CBC, electrolytes, glucose, renal function

– Inflammatory markers (ESR/CRP)

• Radiographs– Conventional films to R/O gas, FB, bony abn.

– MRI if concern for osteomyelitis

• Consult with wound care specialist– Wound debridement, cultures, dressings, off‐loading

Wound Severity

• International Working Group on the Diabetic Foot has established the “PEDIS” classification for staging severity of foot infections.

• Similar to IDSA classification

• Severity predicts:– Bacteriology —> antibiotic choice

– Duration of therapy

– Need for hospitalization

– Likelihood of amputation

Wound Severity

• Infection present if 2 of the following are present:

– Swelling or induration

– Erythema

– Local tenderness or pain

– Warmth

– Purulent discharge

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Wound Severity

• PEDIS Grade I/IDSA UNINFECTED

• PEDIS GRADE II/IDSA MILD– Superficial skin and subcutaneous tissue

– < 2 cm erythema around ulcer

• PEDIS Grade III/IDSA MODERATE– Deeper structures (muscle/fascia/bone/joint)

– Erythema > 2 cm

• PEDIS Grade IV/IDSA SEVERE– Systemic toxicity

Wound Severity

Wound Severity Hospitalization Limb Amputation

Uninfected 0% 3%

Mild 4% 3%

Moderate 52% 46%

Severe 89% 70%

Microbiology & TherapyWound Severity

Microbiology Need for culture

Antibiotic Regimen

Duration

GradeI/Uninfected

Not applicable No None None

Grade II/Mild MSSA +β‐hemolytic strep

NO (unless recent abx, failure to respond)

Cephalexin, clindamycin or amoxicillin‐clavulanate

1‐2 weeks

Grade II/Mild MRSA (purulent drainage) +β‐hemolytic strep

NO (unless recent abx, failure to respond)

Clindamycin orTMP‐SMX

1‐2 weeks

Grade III/Moderate (outpatient)

Above organisms +GNRs +anaerobes

Yes Clindamycin + FQ (cipro, levo)

2‐3 weeks

Microbiology and Therapy

Wound Severity

Microbiology Need for culture

Antibiotic Regimen

Duration

Grade III/Moderate (inpatient)

Above organisms +GNRs +anaerobes +enterococcus

Yes Vancomycin + Pip‐tazo or carbepenem;

Vancomycin + metronidazole + cefepime(CTX or ceftazadime

2‐3 weeks

GradeIV/Severe

Aboveorganisms + Bacteroidesspp + Clostridium spp

Yes Same as above 2‐4 weeks

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Therapy‐‐Generalizations

• No data support the superiority of any specific antibiotic agent, route or duration of therapy– Tigecycline—inferior for DFI & DFO

• For moderate to severe infections a switch to oral bioavailable agents is reasonable once improvement has occurred

• If reliable cultures (NOT superficial swabs) have been obtained, targeted therapy is appropriate

Osteomyelitis

• Suspect in any patient with deep tissue involvement (Grade III or IV/Moderate or Severe) or infection over bony prominence

• Certain factors increase likelihood:

– Visible bone or ability to probe to bone

– Ulcer size > 2 cm

– Chronic ulcers (longer than 1‐2 weeks)

– ESR > 70 mm/hr

Osteomyelitis

• Diagnosis

– Bone biopsy—gold standard

– MRI—95% sensitivity and 90% specificity

• Therapy

– Based on cultures

– If cultures not obtained would use empiric regimen for Grade IV/severe infections

– Duration 6weeks (usually with surgery)

Adjunctive Therapy

• VAC (vacuum‐assisted closure) therapy– Advanced wounds (Grade 3) and post‐surgical patients promotes wound closure and shortens hospitalization

• Growth Factors– Becaplermin (a topically applied human recombinant platelet‐derived growth factor)

• FDA approved; increases complete wound closure• High cost; post‐marketing reports of increased risk of cancer

• HBO (Hyperbaric Oxygen)– More data needed—some suggestion that it may be beneficial in wound healing and decreasing amputations

– HBO + Growth Factors currently under study

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Distal lateralsubungual Superficial

Proximal subungual

Etiology and Classification

• Etiology– Dermatophytes‐‐80% (toes>fingers)

• Trichophyton rubrum (proximal and distal)

• Trichophyton mentagrophytes (white superficial)

– Non‐dermatophytes• Candida spp. (fingers > toes)• Molds

– Acremonium

– Aspergillus

– Fusarium

Indications for Therapy

• Patients with cellulitis (especially if recurrent) and ipsilateral onychomycosis

• Diabetics at increased risk of cellulitis (previous cellulitis, venous insufficiency, chronic edema)

• Patients with pain/discomfort

• Patients who want therapy for cosmetic reasons

Principles of Therapy

• Topical

– ciclopirox/Penlac®

– efinaconazole/Jublia®

– amorolfine/Loceryl®

– others

• Systemic

– Terbinafine (Lamisil®)

– Itraconazole (Sporanox®)

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Principles of Therapy

• Topical therapy

– Require daily use for a year

– Associated with low cure rates – 10%‐20%

– Mainly beneficial in superficial onychomycosis

◦ Oral Therapy◦ Terbinafine (Lamisil®)

◦ Terbinafine is mycologically superior, clinically comparable and better tolerated than azole regimens

◦ Itraconazole (Sporanox®)

Therapy

• Mycologic cure (clinical cure tends to be less)– Terbinafine (76 + 3 percent)

• 250 mg daily for 6 (fingernails) or 12 (toenails) weeks

– Itraconazole pulse therapy (63 + 7 percent)• 200 mg twice daily for one week per month X 2 months (fingernails)

• 200 mg twice daily for one week per month X 3 months (toenails)

– Itraconazole continuous therapy (59 + 5 percent)• 200 mg daily for 6 (fingernails) or 12 (toenails) weeks

Laser Therapy

•NOMOREFUNGUS.COM

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Cost of Treatment

• Laser Treatment‐‐$780 one foot/$1,170 doe both feet

• Terbinafine (Lamisil®)

– Fingers (6 weeks)‐‐$12

– Toes (12 weeks)‐‐$21

• Itraconazole (Sporanox®)—pulse therapy

– Fingers‐‐$56

– Toes‐‐$84

UTIs in Diabetics

• Sparsity of data

• Bacteriology the same as non‐diabetics

• Treatment same as non‐diabetics★★★

– Nitrofurantoin 100 mg PO BID X 5 D

– TMP‐SMX DS PO BID X 3 D (avoid if resistance > 20%, recent usage

– Fosfomycin 3 gm PO X 1

UTIs in Diabetics

• REMEMBER

– Complications common

– If no response to therapy in 72 hours —> look for them

– Don’t be fooled by normal UA—obstruction present in 30% ‐ 40% with complications

Case Presentation

• A 50 year old female diabetic presents requesting a physical and referral for colonoscopy. As part of the evaluation, at the request of the patient, a UA with culture is obtained‐‐concern about increased risk of infection despite being asymptomatic.– UA > 100 WBCs/HPF– Culture grows 105 E. coli

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Treat?

1. Yes

2. No

1

100%

Asymptomatic Bacteriuria in DM(Harding et al M Engl J Med 2002;347:1576

• 55 received 14 D TMP‐SMX; 50 placebo

• 40% placebo and 42% treated group —> symptomatic UTI

• Time to 1st symptomatic episode the same

• Pyelonephritis and hospitalizations for UTIs the same

Case Presentation

• A 50 year old female diabetic presents with dysuria, urgency, frequency and LGF. Exam shows R CVA tenderness.

• UA + leukocyte esterase

• Culture eventually grows a sensitive E coli

• 4 days into a course of levofloxacin, she calls and says still not feeling well and continues to have fevers

What would you do?

1. Repeat urine C&S & give CTX while awaiting cultures

2. Obtain a CT

3. Admit for IV therapy

4. All of the above

1

100%

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Emphysematous Pyelonephritis

• Seen almost exclusively in diabetics

• Often associated with obstruction

• E. coli and Klebsiella pneumoniae most common organisms

• Treatment—> antibiotics and percutaneous drainage (nephrectomy)

• Suspect if:– Critically ill at presentation

– Fail to respond in 72‐96 hours

Case Presentation

• A 25 y.o. farm worker with DM sustained trauma to his penis 2 days prior to admission. He presented to a local ED where he was found to have a small necrotic area on his penis that progressed while he was in the ED. He was given a dose of ceftriaxone and transferred to UCSF.

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Questions

• What is the diagnosis?

• What is the bacteriology?

• What is appropriate therapy?

Group A Streptococcal Necrotizing Fasciitis

(“FLESH EATING BACTERIA”)

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BACTERIOLOGY OF NECROTIZING FASCIITIS

• Type I– Anaerobes (peptostreptococcus, bacteroides, anaerobic/microaerophilicstreptococci)

– Enteric gram‐negative bacilli (E. coli, klebsiella, proteus, serratia, etc)

• Type II (hemolytic streptococcal gangrene)– Group A streptococcus + S. aureus

LUMPER VS. SPLITTER

Differential Diagnosis of Deep Tissue Infections

• Progressive Bacterial Synergistic Gangrene

• Synergistic Necrotizing Cellulitis

• Gas Gangrene

• Necrotizing Cutaneous Mucormycosis

• Anaerobic Cellulitis

• Fournier’s Gangrene

• Incubation Period

• Onset (gradual/acute)

• Pain/Swelling

• Exudate (Thin/Thick/Dark/SS/Purulent/Seropurulent/Dishwater

• Gas

• Odor (Sour/Sweet)

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DEEP TISSUE INFECTIONS

• Consider polymicrobial

• Broad spectrum antibiotics– Vancomycin + flagyl + tobramycin

– Flagyl + 3rd generation cephalosporin

– ß‐lactam + ß‐lactamase inhibitor + tobramycin

– Carbapenem

• Surgery

WHEN TO SUSPECT DEEP TISSUE INFECTION

• High risk patient ‐‐ diabetes, trauma, surgery

• Wound necrosis

• Gas

• Exudate (foul smelling)

• Systemic symptoms/signs out of proportion to local findings

• Anesthesia of involved area

Case Presentation

• A 42 y/o diabetic presents with a 3 day h/o sinus congestion w/o preceding viral URI. A diagnosis of acute sinusitis is made and he is treated with amoxicillin‐clavulanate (Augmentin®). 3 days later he calls saying he is no better.

At This Point You Would?

1. Increase the amoxicillin‐clavulanate to 2 gm BID

2. Change to levofloxacin

3. Do a sinus CT

4. Refer to ENT

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Pathogenesis of Acute Bacterial Rhinosinusitis

• It is almost always a pyogenic complication of a viral upper respiratory tract infection

• Viral infection causes mucocilliary dysfunction, allowing bacteria from the nasopharynx to ascend to the sinuses and invade the mucosa

Risk factors for Acute Fungal Rhinosinusitis

• Hematologic malignancies

• Hematopoietic stem cell transplantation

• Chemotherapy‐induced neutropenia

• Solid organ transplantation

• Advanced HIV infection

• Diabetes mellitus

• Glucocorticoids

Endoscopy Was Performed Take Home Point

• Maintain a high degree of suspicion in diabetic patients who present with sinus complaints, especially those without a preceding viral upper respiratory infection

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Case Presentation

• A 65 y/o diabetic man was visiting his son in Marin. They frequently used the hot tub. About 10 days later, both the father and son developed painful, red, swollen external ears. They were treated with topical antibiotic/hydrocorisone. The son improved rapidly, but the father failed to improve despite 3 courses f R

Malignant (Necrotizing) Otitis Externa

• Almost exclusively seen in elderly diabetics

• Usually caused by Psuedomonas (less commonly S aureus or aspergillus)

• Severe pain hallmark; painful, red, swollen external ear with granulation/debris in canal

• Can progress to skull based osteomyelitis (SBO) by invasion through fissure of Santoriniat bone‐cartilage junction– Cranial nerve palsies common

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Malignant (Necrotizing) Otitis Externa

• Rx = 6‐8 weeks (FQ‐cipro/levo if susceptible)

• If develop SBO treat longer and monitor by MRI/radionuclide scans

• No indication for topical antibiotics or surgical intervention

• Hyperbaric oxygen might be helpful in refractory cases

Documents

Infections In Diabetics NO DISCLOSURES · Case Presentation • A 56 year old diabetic presents with an ulcer on the metatarsal‐phalangeal area of the plantar aspect of the foot