Inpatient Infection

Control of DM

Patients with Open

Wounds

BETTY CORONA MSN, ARNP,

FNP-BC

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Diabetic Foot

Infections

Infection in a diabetic foot is limb threatening

and if untreated can become

life threatening

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Diabetic Foot

Infections

Surgical debridement is essential in acute deep tissue

infections

Podiatrists are experts at debriding and collecting

samples to diagnose infections.

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Diabetic Foot

Infections Superficial infection-confined to skin superficial to fascia

Usually caused by normal skin bacteria

gram positive cocci

Coag neg Staph, strep, Corynebacterium

Deep tissue infection-invasion of

fascia, muscle, tendon, joint or bone Polymicrobial-Gram positives, gram negatives and anaerobes

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Diabetic Foot

Infections

WHAT DO YOU

DO WITH THE

CULTURE

RESULTS???

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Eradicate the Bugs! 6

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How Do We

Eradicate Bugs?

Antimicrobial

Therapy

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How Do We Choose

Antibiotics? Where is the infection? Soft

tissue/gangrene/bone?

Determine length of therapy

What is the infection?

Determine aggressiveness of infection and tailor antibiotics empirically, then to C&S

Know Antibiotic Penetrations

Which antibiotics penetrate bone, joints, etc…?

Appropriate Renal Dosing

DON’T OVERDOSE A RENAL PATIENT!!

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IDSA Guidelines

for DFIReduce emergence of

resistant organisms

Reduce hospital days

Reduce costs

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IDSA Guidelines

for DFI2011-Implementation

Decreased use of blood cx

Decreased advanced imaging

Decreased consultations

Shorter durations of therapy

Decreased use of anti-pseudomonal antibiotics

Decreased use of broader spectrum antibiotics

Decreased costs

No change in adverse outcomes

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Inpatient Hospitalization

Don’t Miss

Sepsis!Should be considered even

when local signs are less

severe

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Inpatient HospitalizationFoot infection determined: Look for s/s of sepsis or SIRS

Systemic Inflammatory Response (SIRS) criteria:

Need 3 for SIRS and 4 for sepsis

Known or suggested infection

Systemic manifestations of sepsis

temperature >38.3°C or <36°C

heart rate >90 beats/min

respiratory rate >20 breaths/min

acutely altered mental status

white blood cell count >12,000 μL (or 12 K/μL) or <4000 μL (or 4 K/μL)

plasma glucose 120 mg/dL in the absence of diabetes

Birriel, 2013, April 2.

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Inpatient

Hospitalization Sepsis: SIRS criteria + organ dysfunction

Indications of new or worsened organ dysfunction:

SBP <90 mm Hg or decrease >40 mm Hg from

baseline

Mean arterial pressure <65 mm Hg

Bilateral pulmonary infiltrates with increasing

oxygen requirements to maintain SpO2 >90%

Creatinine >2.0 mg/dL

Bilirubin >2 mg/dL

Platelet count <100,000/μL (or 100 K/μL)

Coagulopathy

Lactate >2 mmol/L

Birriel, 2013, April 2.

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Other Signs of

Systemic Illness

CRP elevated

Marked left shift

Elevated creatinine

Low serum bicarbonate

Low sodium

CK 2 x the upper limit of normal

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Inpatient

Hospitalization

Patients with SIRS and

sepsis need emergent

debridement of wound

infection

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Diabetic Foot Ulcers 16

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Diabetic Foot Ulcers

Not all diabetic foot ulcers are infected.

Infection if at least 2 present:

Purulent secretions

Redness

Warmth

Swelling/induration

Pain/tenderness

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IDSA Guidelines for

Diabetic Foot Infections

(Many areas need further evaluation for good recommendations)

Keep in mind when choosing treatment.

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IDSA Guidelines

for DFIRoute of therapy based on

severity

Mild & some moderate

DFIs

PO antibiotics with

good bioavailability

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IDSA Guidelines

for DFIRoute of therapy based on

severity

Severe & some moderate DFIs

IV at least initially (weak, low)

Switch to oral agents when

systemically stable and culture

results available

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IDSA Guidelines

for DFI

Continue antibiotics till

resolution of infection but

not through complete

healing of the wound (weak,

low)

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Definitive Therapy

Based on:

Results of appropriately

obtained C&S

Patient's clinical

response to the empiric

regimen (strong, low)

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Is there clinical

evidence of

infection?

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Do not treat clinically

uninfected wounds with

antibiotics

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For clinically

infected wounds

Is there high risk of MRSA?

Include anti-MRSA therapy in empiric regimen if the risk is high or the infection is severe

‐ Has patient received antibiotics in the past month?

If so, include agents active against gram-negative bacilli in regimen If not, agents targeted against just aerobic gram-positive cocci may be sufficient

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For clinically

infected wounds

Are there risk factors for Pseudomonas infection?

If so, consider empiric antipseudomonal agent If not, empiric antipseudomonal treatment is rarely needed

What is the infection severity status?

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MRSA Risk Factors Recent hospitalization last 90 days

Residence in long term care facility

Antibiotics last 90 days

Injection drug use

Hemo- or peritoneal dialysis

Incarceration last 90 days

Home infusion therapy

History of MRSA colonization

Immunosupressive state/medications

Wound care in past 30 days

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Pseudomonas

Risk factors

ICU stay in last 90 days

Immunosuppressive

state/medications

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Immunosuppressive states:

HIV

Solid organ transplants

BMT

Immunosuppressive

medications:

Rejection medications

>20mg/d prednisone x2

weeks

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Mild soft tissue infections 29

1-2 weeks

antibiotics Lipinsky, et al., 2012Wate

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IDSA Guidelines

for DFI Mild and many moderate

DFIs

High bioavailable oral antibiotics alone (strong, moderate)

Selected mild superficial infections

Topical therapy (strong, moderate)

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Empiric TherapyBased on severity and the likely etiologic

agent(s)

Mild to moderate infections in patients who have not recently

received antibiotic treatment

Aerobic gram-positive cocci (GPC) is

sufficient (weak, low)

Severe infections

broad-spectrum empiric antibiotic

therapy, pending culture results and

antibiotic susceptibility data (strong,

low)

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Suggested Empiric

Antibiotic Regimens for

DFIs Mild (usually oral agents)

Staphylococcus aureus (MSSA); Streptococcus spp

Dicloxacillin-QID, narrow specrum, inexpensive

Clindamycin-QID, inexpensive, may cover MRSA,

inhibits protein synthesis of some bacterial toxins

Cephalexin-QID, inexpensive

Levofloxacin-daily dosing, suboptimal against

staph aureus

Amoxicillin-clavulanate-Relatively broad spectrum

with anaerobic coverage

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Suggested Empiric

Antibiotic Regimens for

DFIs Mild (usually oral agents)

Methicillin-resistant S. aureus (MRSA)

Doxycycline-MRSA, some gram

negatives, not reliable against strep

Trimethoprim/sulfamethoxazole-MRSA,

some gram-negatives, not reliable

against strep

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Moderate to severe infections34

2-3 weeks

antibioticsLipinsky, et al., 2012W

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Suggested Empiric

Antibiotic Regimens for

DFIs Moderate (oral or IV) or severe (IV)

MSSA, strep, Enterobacter, anaerobes

Levofloxacin-daily, suboptimal against SA

Cefoxitin-2nd gen cephalosporin w/

anaerobic coverage

Ceftriaxone-daily, 3rd generation

Ampicillin-sulbactam-Adequate if low

suspicion for pseudomonas

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Suggested Empiric Antibiotic

Regimens for DFIs

Moderate (oral or IV) or severe (IV)

MSSA, strep, Enterobacter, anaerobes

Moxifloxacin-daily, Relatively broad

spectrum, covers most anaerobes

Ertapenem-daily, Relativelly broad

spectrum w/ anaerobic coverage;

Tigecycline-MRSA, very broad, high

rates of n/v and increased mortality

warning

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Suggested Empiric Antibiotic

Regimens for DFIs Moderate (oral or IV) or severe (IV)

MSSA, strep, Enterobacter,

anaerobes

Levofloxacin or Cipro w/

clindamycin-limited evidence

supporting coverage for severe

MSSA infections

Imipenem-cilastatin-Very broad

spectrum; Only use when

required

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Empiric Therapy• P. aeruginosa is usually unnecessary

except:

Patients with risk factors for true

infection with this organism

(strong, low)

• MRSA

Prior history of MRSA infection

Local prevalence of MRSA is high

Infection is clinically severe (weak,

low)

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Suggested Empiric Antibiotic

Regimens for DFIs

Moderate (oral or IV) or severe (IV)

Pseudomonas aeruginosa

Piperacillin-tazobactam-TID/QID, anaerobic coverage

Cefepime-BID/TID, no anaerobic or enterococcalcoverage

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Risk of

Nephrotoxicity Piperacillin-tazobactam & vancomycin combination

Increased risk of nephrotoxicity

8.1% vancomycin group

16.3% in combination group

Don’t add fuel to the fired unless absolutely necessary, especially in a

renal patient!

Limb salvaging

Known pseudomonas or enterococcus infection

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Suggested Empiric Antibiotic

Regimens for DFIs Moderate (oral or IV) or severe (IV)

MRSA

Linezolid-Expensive, Increased

rate of toxicities when used > 2

weeks

Daptomycin-Daily, Serial CKs for

potential rhabdomyolysis, Rare

eosinophilic pneumonia

Vancomycin-MICs for MRSA are

gradually rising

Need new options

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Suggested Empiric Antibiotic

Regimens for DFIs

Moderate (oral or IV) or severe (IV)

MRSA, Enterobacter,

pseudomonas & anaerobes

Vancomycin AND ceftazidime,

cefepime, pip/tazo, aztreonam OR a

carbapenem-Very broad spectrum,

usually for empiric therapy for severe

DFIs

Will need metronidazole if using

ceftazidime, cefepime, aztreonam

for anaerobic coverage

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Gangrene

Necrotizing soft tissue infections

of the diabetic foot, including

gas gangrene, are uncommon

and are usually caused by mixed

aerobic (and sometimes

anaerobic) bacteria rather than

Clostridium species.

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Strep Anginosus

Strain of Viridans Strep (Strep milleri)

Multidrug resistant; spreads quickly; abscesses

Ensure susceptibilities are obtained!

Generally susc to ampicillin; tetracycline, erythromycin; Resistance found intermittently to clindamycin, meropenems, some cephalosporins, quinolones, aminoglycosides

Arinto-Garcia, et al., 2015; Stelzmueller, et al., 2007; Gray, 2005;

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Normal Skin Flora

Infections coagulase-negative staphylococci

(CNS), corynebacteria, or Bacillus

spp, and low-virulence organisms

such as enterococci, can usually

be ignored unless cultured from

deep, aseptically collected tissue

or infections involving

osteosynthetic material or

hardware

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IDSA Guidelines

for DFIRadical resection without no

remaining infected tissue

2–5 days (weak, low)

Persistent infected or

necrotic bone

≥4 weeks antibiotic treatment

(weak, low)

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Renally Dosing

Antibiotics Vancomycin

Zosyn

Cephalosporins

Fluoroquinolones

Calculate CrCl every day!

www.globalrph.com CrCl calculator

CrCl < 50 ml/min may need renally dosed

Don’t rely on an EMR to calculate dose

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GlobalRPh.com 48

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GlobalRPh.com 50

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Systemic Antimicrobial

Prescribing

to reduce the spectrum and duration of

antibiotherapy to try to slow the tide of

antibiotic resistance

based on the assessment of infection

severity

knowledge of the local microbial

epidemiology

DFIs can develop rapidly, making early

follow-up after starting therapy

imperative

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Peripheral Artery Disease

(PAD)

Most DFIs occur in the setting of PAD, various antibiotic agents may not penetrate the infected site well, especially bone.

Previous practice was to Rx weeks of antibiotics

Evidence no supports the efficacy of current highly bioavailable oral antibiotics, thus not requiring as long of therapy

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Peripheral Artery Disease

(PAD)

Beta-lactam antibiotics-achieve relatively low (albeit therapeutic) tissue levels,

time-dependent (not concentration-dependent) drugs

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No Strong Oral

Antibiotic

RecommendationsSeveral systematic reviews of antimicrobial treatments for DFI have concluded that there is insufficient evidence to

recommend any particular antimicrobial agent or route of administration.

USE ANTIBIOGRAMS FOR

INSTITUTION OR LOCAL REGION

Nelson, et al., 2006; Peters, et al., 2015; Selva Olid, et al., 2015

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Oral Antibiotics

Clindamycin, fluoroquinolones,

linezolid, rifampicin, and to some

degree, tetracyclines and co-

trimoxazole

Good oral bioavailability

Good penetration in bone, synovia,

biofilm, and necrotic tissue.

Uçkay, 2014.

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Antibiotic misuse Excessive and inappropriate uses of

antibiotics have profound negative effect

For the patient by developing resistance

Health care system due to cost

Society as a whole due to resistance.9

Highly recommend not treating clinically

uninfected ulcers with antibiotic therapy.

Abbas, Uçkay & Lipsky, (2015).

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Take HomeChoose antibiotics based on

severity, location and then C&S

Renally dose all antibiotics

Calculate CrCl daily according

to IBW.

Don’t miss sepsis!

Sepsis and SIRS need

emergent debridement.

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Take Home IDSA Guidelines are helpful but not

very specific. Must use clinical

judgement.

MRSA/Pseudomonas risks

IV antibiotics for moderate-severe

infections

Choose oral antibiotics with good

bioavailability

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Take Home

Avoid piperacillin/tazobactamcombination if at all possible to avoid increasing risk of nephrotoxicity.

Use your local antibiogram.

Need good antibiotic stewardship to avoid worsening of resistance. Avoid antibiotics if not infected.

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ReferencesAbbas, M., Uçkay, I., & Lipsky, B. A. (2015). In diabetic foot

infections antibiotics are to treat infection, not to heal wounds.

Expert Opinion on Pharmacotherapy, 16, 821–832.

Arinto-Garcia, R, Pinho, M. D., Carriço, J. A., Melo-Cristino, J., &

Ramirez, M. (2015). Comparing matrix-assisted laser

desorption ionization-time of flight mass spectrometry and

phenotypic and molecular methods for identification of species

within the streptococcus anginosus group. Journal of Clinical Microbiololgy, 53(11), 3580-3588. Epub 2015 Sep 9.

doi:10.1128/JCM.01892-15.

Birriel, B. (2013, April 2). Rapid Identification of Sepsis - The Value

of Screening Tools. Society of Critical Care Medicine,

Retrieved from http://www.sccm.org/Communications/Critical-

Connections/Archives/Pages/Rapid-Identification-of-Sepsis---

The-Value-of-Screening-Tools.aspx

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References

Burgess, L. D., & Drew, R. H. (2014). Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam. Pharmacotherapy, 34(7), 670-676. doi:10.1002/phar.1442.

GlobalRph: The clinicians ultimate reference. (2015.). Multiple creatinine clearance methods. Retrieved from http://globalrph.com/multiple_crcl.htm

Gray, T. (2005). Streptococcus anginosus group: Clinical significance of an important group of pathogens, Clinical Microbiology Newsletter, 27(20), 155–159.

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ReferencesLipinsky, B. A., Berendt, A. R., Cornia, P. B., Pile, J. C., Peters, E. J. G.,

Armstrong, D. G., et al. (2012). 2012 Infectious Diseases Society

of America clinical practice guidelines for the diagnosis and

treatment of diabetic foot infections, Clinical Infectious Diseases,

54, e132-e173.

Nelson, E. A., O’Meara, S., Golder, S., Dalton, J., Craig, D., & Iglesias,

C. (2006). Systematic review of antimicrobial treatments for

diabetic foot ulcers. Diabetic Medicine, 23, 348–359.

Peters, E. J. B., Aragón-Sánchez, J., Bakker, K., Boyko, E. J., Diggle,

M., Embil, J. M., et al. (2015). A systematic review of interventions

in the management of infection in the diabetic foot. Diabetes Metabolism Research & Reviews, [Epub ahead of print] ,

Retrieved from http://dx.doi.org/10.1002/dmrr.2706

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References

Selva Olid, A.,Barajas-Nava, L. A., Gianneo, O.D., Solà, I., Bonfill

Cosp, X., & Lipsky, B.A. (2015). Systemic antibiotics for

treating diabetic foot infections. Cochrane Database Systematic Review, 9, p. CD009061. Retrieved from

http://dx.doi.org/10.1002/14651858.CD009061.pub2

Stelzmueller, I., Berger, N., Wiesmayr, S., Eller, M., Tabarelli, W.,

Fille, M., Margreiter, R., & Bonatti, H. (2007). Transplant International, 20(1), 51-56.

Uçkaya, I., Aragón-Sánchezc, J., Lewa, D., & Lipskya, B. (2015).

Diabetic foot infections: What have we learned in the last 30

years? International Journal of Infectious Diseases, 40, 81-

91. doi:10.1016/j.ijid.2015.09.023

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References

Uçkay, I., Gariani, K., Pataky, Z., & Lipsky, B.A. (2014).

Diabetic foot infections: State-of-the-art. Diabetes Obesity and Metabolism, 16, 305–316.

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