WEBINAR

May 23, 2016  8 pm EDT

Preventing and Treating
Musculoskeletal Infections

Brought to you by:

Welcome!

Marc Swiontkowski, MD
Editor-in-Chief, JBJS

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 How to Participate
See bios

Ask a question Handouts #jbjswebinar

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Moderator

Jonathan Schoenecker, MD
Departments of Orthopaedics,
Pharmacology, Pathology, and Pediatrics,
Vanderbilt University School of Medicine

Financial Disclosures:
• No related disclosures

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Musculoskeletal Infection
 Musculoskeletal Infection
Epidemiology X Cost X Morbidity X Mortality
 Musculoskeletal Infection
Epidemiology X Cost X Morbidity X Mortality

Health Care Significance

 Musculoskeletal Infection
Epidemiology X Cost X Morbidity X Mortality

Health Care Significance

Therapy
 Musculoskeletal Infection
Epidemiology X Cost X Morbidity X Mortality

Health Care Significance

Therapy

Antibiotics
 Musculoskeletal Infection
Epidemiology X Cost X Morbidity X Mortality

Health Care Significance

Therapy

Antibiotics Surgery
 Musculoskeletal Infection
Epidemiology X Cost X Morbidity X Mortality

Health Care Significance

Impact
Therapy

Antibiotics Surgery
Musculoskeletal Infection
Health Care Significance
Patient Epidemic
Impact
Therapy

Antibiotics Surgery
 Musculoskeletal Infection

Author

Therapy
Dr. Tosti

Antibiotics Surgery
 Musculoskeletal Infection

Author Commentator

Therapy
Dr. Tosti Dr. Thomsen

Antibiotics Surgery
Musculoskeletal Infection

Therapy

Antibiotics Surgery
 Musculoskeletal Infection

Author

Therapy
Dr. Jenkinson

Antibiotics Surgery
 Musculoskeletal Infection

Author Commentator

Therapy
Dr. Jenkinson Dr. Marsh

Antibiotics Surgery
Musculoskeletal Infection
Author Author Commentator Commentator

Dr. Tosti Dr. Jenkinson Dr. Thomsen Dr. Marsh

Therapy

Antibiotics Surgery
Musculoskeletal Infection
Author Author Commentator Commentator

Dr. Tosti Dr. Jenkinson Dr. Thomsen Dr. Marsh

Therapy

Antibiotics Surgery
 AUTHOR

Rick Tosti, MD
Emerging Multidrug Resistance of Methicillin-
Resistant Staphylococcus aureus in Hand Infections
Published in JBJS Sept. 17, 2014

Financial Disclosures:
• No related disclosures

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Introduction
DR. TOSTI

• Methicillin-resistant Staphylococcus Aureus

(MRSA) is the most commonly identified
pathogen in hand infections at urban centers

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Introduction
DR. TOSTI

• MRSA has been associated with higher risk of treatment

failure, lengths of stay, and costs

• A few studies report that this risk can be obviated if an

appropriate empiric antibiotic selected.

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Introduction
DR. TOSTI

• The CDC recommends against selecting an

empiric antibiotic if the local resistance is greater
than 10%

• Beta-lactam antibiotics are usually bypassed for

clindamycin, vancomycin, or trimethoprim sulfa-
methoxazole in MRSA endemic regions

• HOWEVER, the evolving antibiotic sensitivity

profiles of MRSA are not known.

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Introduction
DR. TOSTI

The purposes of this study are to:

1. determine if multi-drug resistance in MRSA is
emerging

2. provide current recommendations for empiric

antibiotic selection for hand infections in
endemic regions.

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Methods
DR. TOSTI

• An 8-year longitudinal, retrospective chart

review was performed on all culture-positive
hand infections encountered by an urban
hospital from 2005-2012.

• The proportions of all major organisms were

calculated for each year.

• MRSA infections were additionally analyzed for

antibiotic sensitivity.

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Results
DR. TOSTI

• A total of 683 culture-positive hand infections were

identified

• Etiology most commonly traumatic or IV drug use

– Mean age – 38-45 yrs (P=0.42)

– IVDU – 12-38% (P=0.03)**
– DM - 12-17% (P=0.78)
– HIV – 1-6% (P=0.71)
– Cancer – 1-2% (P=0.68)

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Results
DR. TOSTI

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Results
DR. TOSTI

• Overall, MRSA was cultured in 49% of cases; the

annual incidence peaked in 2007 at 65% then declined
to 41.8% by 2012
Cultured Organisms per Annum

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Results
DR. TOSTI

• MRSA was universally resistant to penicillin, oxacillin,

and ampicillin. Highly resistant to erythromycin.

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 Results
DR. TOSTI

• Levofloxacin resistance linearly increased from 12% to 50%

(p<0.01)

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Results
DR. TOSTI

• Clindamycin resistance significantly increased

approaching 20% by 2012 (p=0.02)

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Results
DR. TOSTI

• Resistance to trimethoprim-sulfamethoxazole, tetracycline,

gentamicin, and moxifloxacin were only sporadically
observed.

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Results
DR. TOSTI

• Resistance to vancomycin, daptomycin, linezolid, and

rifampin were not observed.

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Results
DR. TOSTI
MRSA Drug Resistance per Annum

The Centers for Disease Control recommend against selecting an

empiric antibiotic if the regional resistance exceeds 10%
(region shaded red). 20
Discussion
DR. TOSTI

• MRSA predominates in urban areas around the

USA ranging from 38-74% of hand infections (49%
in this 8 year series).

• In order to avoid treatment failures and increased

costs we sought to further characterize this
organism and support the following conclusions:
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Conclusions
DR. TOSTI

• Significant increases in resistance to clindamycin and

levofloxacin were observed in recent years, and empiric
therapy with these drugs should be used with caution
especially in urban centers.

• Regional levofloxacin prescriptions have been linked to

MRSA increases in the pulmonary literature.

• In the hand literature “fluoroquinolones” sometimes

recommended as alternative antibiotic for patients with
B-lactam allergy – our study would support moxifloxacin
but not levofloxacin.

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Conclusions
DR. TOSTI

• We suspected increased use of these drugs may be

causative, but this study was not designed to answer
that question

• Clindamycin use at TUH was the most common empiric

drug from 2005-2007.

• Subsequent study by Tosti et al. JHS 2015 showed Prior

hx MRSA was not significant! IVDU (11x more likely) and
nosocomial contact (5x more likely) were only significant
risk factors.

• Would social programs to limit IVDU reduce resistance?

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Conclusions
DR. TOSTI

SO, WHAT STILL WORKS??

• Trimethoprim-sulfamethoxazole,
tetracycline, gentamycin, moxifloxacin
• Sporadic resistance

• Vancomycin, daptomycin, linezolid, and

rifampin
• No resistance

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Limitations/Future Questions
DR. TOSTI

• Retrospective

• USA and especially urban centers may have

disproportionally higher prevalence of MRSA

• Frequency of MRSA subject to change in future

• Is this generalizable to other orthopaedic

infections?
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 COMMENTATOR

Isaac Thomsen, MD
Asst. Prof. of Pediatric Infectious Diseases
Director, Vanderbilt Vaccine Research Program Laboratory
Vanderbilt University School of Medicine

Financial Disclosures:
• No related financial disclosures

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Is Clindamycin Resistance
on the Rise?
DR. THOMSEN

• This is a well designed study that reveals a very

concerning trend.

• Clindamycin is a first line therapy recommended

by the Infectious Disease Society of America
(IDSA) for presumed MRSA infection

• Heavy use of an antimicrobial agent always

provides selection pressure for resistant strains.

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 DR. THOMSEN

• Dr. Tosti and his group found that MSSA isolates represented 21% of
infecting pathogens.

• Mechanisms of clindamycin resistance are independent of methicillin-

resistance

• Therefore, MSSA strains may be just as likely to develop increasing

clindamycin resistance as this is agent is frequently used empirically.

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 DR. THOMSEN

• From this month in Pediatrics

• The relative proportion of MSSA is rising, after years
of MRSA dominance.
• Similar trends have been reported in adults

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Rates of Clindamycin resistance are
rising among MSSA isolates in children
DR. THOMSEN

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To the point of “What do
we use now?”
DR. THOMSEN

• Let’s not throw clindamycin out just yet.

• Needs to be replicated, and regional differences

warrant exploration

• Outcomes have been shown to be better with

clindamycin vs. TMP/SMX or beta-lactams (e.g.
cephalexin)

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 DR. THOMSEN

Williams et al. Pediatrics 2011

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Other Therapeutic Options
DR. THOMSEN

Proctor et al. Clinical Infectious Diseases 2008

• S. aureus can bypass the site of action of TMP/SMX in

abscesses
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Other therapeutic options
DR. THOMSEN

• Levofloxacin is a poor choice.

– Will often be reported as “susceptible, but rapid development of
resistance while on therapy is common.”

• TMP/SMX, clindamycin, doxycycline (or minocycline), and linezolid

are all first-line empiric options when MRSA is likely to be present.

• Given the study presented today (and others), clindamycin may fall
lower on this list.

• Linezolid is highly effective but limited by cost and adverse effects.

• Guidance by culture / susceptibility data is more critical than ever.

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 AUTHOR
Richard Jenkinson,
MD, MSc, FRCSC
Delayed Wound Closure Increases Deep-Infection
Rate Associated with Lower-Grade Open Fractures
A Propensity-Matched Cohort Study,
Published in JBJS, March 5, 2014

Financial Disclosures:
• Grants: COTS and OTA

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Background
DR. JENKINSON

• Treatment standards for open fractures include a

timely irrigation and adequate debridement

• After debridement and stabilization, traumatic

open fracture wounds have traditionally been left
open
– Established practise from experience in pre-antibiotic
era especially WWI and WWII
– to allow drainage of any collecting infection and for a
universal second look debridement
– Minimize infection with Clostridium

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Background
DR. JENKINSON

• Immediate wound closure provides

immediate soft-tissue cover to the
traumatized limb
– May offer some protection against nosocomial
pathogens

• Avoids potentially unnecessary subsequent

operations

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Methods
DR. JENKINSON

• Institutional Treatment Protocol

– Immediate IV Abx
– Surgical I and D done urgently based on OR
availability/patient stability
– Irrigation via Normal Saline
• Gravity or pulse at surgeons discretion
– Wound cultures not done routinely

– Wound closure was at the discretion of the

treating physicians

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Methods
DR. JENKINSON

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Methods
DR. JENKINSON

• Second Look Debridements routinely done

for delayed closure

• Among primary closure patients, second

look done based on judgement of
adequacy of debridement

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Primary Outcome
DR. JENKINSON

• Deep infection
– defined as infection of the injured bone and
deep tissue necessitating an unplanned
operative irrigation and debridement at
greater than 2 weeks following injury

– Planned repeat debridements and superficial

infections not requiring surgery were not
considered to be deep infections.

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DR. JENKINSON

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Treatment Choices
DR. JENKINSON

• Surgeons chose delayed or primary closure

based on their discretion

• One would predict that more severe injuries

would be chosen for delayed closure

• Confounding by indication
– selection bias where the clinician chooses a treatment
method based on the prognosis

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Prior to Matching
DR. JENKINSON

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Prior to Matching
DR. JENKINSON

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Propensity Matching
DR. JENKINSON

• Propensity score predicting likelihood of

primary closure based on
– patient age
– Sex
– delay to debridement
– Gustillo grade I, II, or IIIA
– gross contamination (foreign material, devitalized
muscle or bone)
– tibial vs. non tibial site
– ASA score (1 or 2 vs. 3 and higher)

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Propensity Matching
DR. JENKINSON

• A one to one matching algorithm matched

similar patients (one injury per patient)
– based on their likelihood of treatment with
primary closure

• 73 matched pairs (146 patients)

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After Matching
DR. JENKINSON

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After Matching
DR. JENKINSON

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Results
DR. JENKINSON

Delayed closure infection rate = 17.8%

Primary closure infection rate = 4.1% p<0.0001 50
Limitations and Caveats
DR. JENKINSON

• All debridements were done by experienced surgeon

at a level one trauma center

• Impossible to capture all of the factors that inform a

surgeon’s judgement
– Often an unconscious intuitive “gut feeling”

• Does Not apply to grade Gustillo-Anderson IIIB or IIIC

fractures

• Tight limbs with evolving or actual compartment

syndrome should not be closed primarily

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Limitations and Caveats
DR. JENKINSON

• Data collected retrospectively

• A propensity score only balances on factors

that are specified (known confounders)

• This is not a randomized trial

– Prospective data collection
– Controls for known and unknown confounding
factors

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Conclusion
DR. JENKINSON

• Primary wound closure after adequate

irrigation and debridement of lower grade
open fractures by experienced trauma
surgeons is safe and may lower rates of
deep infection

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 COMMENTATOR

J. Lawrence Marsh, MD
Chair and Professor, Department of Orthopaedic
Surgery, University of Iowa Hospitals and Clinics

Financial Disclosures:
• No related disclosures

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Outline
DR. MARSH

• I liked this study and paper

• Why would you leave an open fracture
open? Or not?
• Previous evidence
• Strengths of this study and quality of the
evidence
• A few cautions
• Summary

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 DR. MARSH

Closure at initial debridement has become

common practice but there is little evidence

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Outline
DR. MARSH

• I liked this study and paper

• Why would you leave an open fracture
open? Or not?
• Previous evidence
• Strengths of this study and quality of the
evidence
• A few cautions
• Summary

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Why would you leave it open?
DR. MARSH

• Custom or habit
• Clostridial infection
• Wound drainage
• Decreased infection rate
• Severity of injury
• Residual contamination
• Progressive necrosis

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Why would you close it?
DR. MARSH
• It is closable

• Prevent secondary
contamination

• More expedient cost

effective care

• Decrease the need for more

elaborate coverage

• Antibiotics

• Excellent primary debridement

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Outline
DR. MARSH

• I liked this study and paper

• Why would you leave an open fracture
open? Or not?
• Previous evidence
• Strengths of this study and quality of the
evidence
• A few cautions
• Summary

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 DR. MARSH

There is some previous evidence that early

or even primary closure is safe and effective

– Delong et al - J Trauma 1999

– Gopal et al - JBJSb 2000
– Godina - Plastic Recon Surg 1986

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Outline
DR. MARSH

• I liked this study and paper

• Why would you leave an open fracture
open? Or not?
• Previous evidence
• Strengths of this study and quality of the
evidence
• A few cautions
• Summary

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Current study strengths
DR. MARSH

• Large number of open fractures

• Case matched design

• The results favor early closure

• Better evidence is unlikely

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Outline
DR. MARSH

• I liked this study and paper

• Why would you leave an open fracture
open? Or not?
• Previous evidence
• Strengths of this study and quality of the
evidence
• A few cautions
• Summary

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Cautions
DR. MARSH

• Is there bias that could not be accounted

for?
– Maybe

– What helps?
• Case matched design
• Evidence is weighted to immediate closure

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Does the evidence translate to
other practices?
DR. MARSH

The following assumptions are necessary:

• Case selection
– What would yours be like?
– There may be some cases in this series that
benefited from delayed closure
• Compared to these surgeons
– Debridement and
– Internal/External fixation techniques the same?

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Outline
DR. MARSH

• I liked this study and paper

• Why would you leave an open fracture
open? Or not?
• Previous evidence
• Strengths of this study and quality of the
evidence
• A few cautions
• Summary

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Summary
DR. MARSH

• I liked this study and paper

• It has provided evidence for an important

change in practice

• I doubt there will be better evidence

• There are some cautions in translating the

evidence
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 Questions & Answers
MODERATOR AUTHORS COMMENTATORS

Jonathan Rick Richard Jenkinson J. Lawrence Isaac

Schoenecker, MD Tosti, MD MD, MSc FRCSC Marsh, MD Thomsen, MD
Departments of Hand and Microvascular Orthopaedic Surgeon Chair and Professor, Asst. Prof. of Pediatric
Orthopaedics, Surgeon, Department of Sunnybrook Health Department of Infectious Diseases
Pharmacology, Pathology, Orthopaedic Surgery, Sciences Centre, Orthopaedic Surgery, Director,Vanderbilt Vaccine
and Pediatrics, Massachusetts General Assistant Professor, University of Iowa Research Program
Vanderbilt University School Hospital Hospitals and Clinics Laboratory
University of Toronto
of Medicine Vanderbilt University School
of Medicine
Thank you!

Jonathan Schoenecker, MD
Departments of Orthopaedics,
Pharmacology, Pathology, and Pediatrics,
Vanderbilt University School of Medicine

Financial Disclosures:
• No related disclosures

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Thank You!

Marc Swiontkowski, MD
Editor-in-Chief, JBJS

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