Download Streptococcus sp

Mandible Osteomyelitis: Retrospective Analysis of the Bone and Joint
Infection (BAJIO) Database
Julie A. Harting, PharmD1,2, Cheick O. Mariko, CRC1, Rob Kelly, PhD1, and Diana Christensen, MD1
1Division
of Infectious Diseases, University of Louisville School of Medicine and 2 Sullivan College of Pharmacy, both in Louisville, KY
ABSTRACT
Background: Infectious Disease Guidelines for diabetic foot and
prosthetic joint infections have been published, but data are lacking
regarding management of other bone infections, particularly those in the
mandible. The primary objectives were to describe the etiology and
microbiology in patients with mandible osteomyelitis. The secondary
objective was to evaluate the end-of treatment, and 30-day outcomes.
Methods: This was a retrospective cohort study of adult patients at the
University of Louisville Hospital. All patients with a diagnosis of mandible
osteomyelitis by Infectious Disease, confirmed using radiographic or
histopathologic criteria or positive bone culture, from January 2010 to
March 2013 were included. Patients received 4-6 weeks of IV antibiotics
and were followed at the end therapy, and 1-3-6-12 months after
induction therapy. Success was defined as clinical improvement,
decrease in ESR and CRP, and no need for further debridement.
Results: From 300 osteomyelitis cases, 9% (n= 27) were recorded in the
mandible. Etiologies included abscess 63%, prosthetic-related 22%,
postsurgical 85%, tooth extraction 37%, and bisphosphonate usage 26%.
Sixteen (59%) were polymicrobial, In patients with bone cultures, the
most common pathogen was Streptococcus sp, particularly
Streptococcus anginosus. One patient was bacteremic. 21 (78%)
required surgical intervention. 100% had success at end-of-therapy.
Seventeen (63%) patients were seen at 30 days with a success rate of
70%.
Conclusion: Although etiologies vary greatly in this subset of patients,
pathogenic organisms most commonly represented normal flora from the
oral cavity. A combined multi-disciplinary management approach by
Oromaxillofacial Surgery and Infectious Disease led to a high rate of
treatment success.
INTRODUCTION
• Osteomyelitis is an infection of the bone and/or marrow. (1)
• Data are lacking regarding treatment of osteomyelitis beyond diabetic
foot, orthopedic, and vertebral infections. Studies regarding the
mandible are limited to case reports and small case series with
particular pathogens.
• Management of infection relies on a multidisciplinary, collaborative
approach, particularly surgical removal of infected and dead bone. (2)
Oromaxillofacial
Surgery
RESULTS (Cont’d)
• Primary Objective
• Describe the pathogenesis and microbiology
osteomyelitis in this series of patients
• From a total of ~300 cases of osteomyelitis, 9% (n = 27) were in the
mandible.
Microbiology (cont.)
• Infections caused by Actinomyces sp. (n = 3) were always identified by
presence of gram-positive rods on gram stain and/or histopathologic. No
cultures were cultivated in the laboratory.
of
mandible
• Secondary Objective
• Evaluate the end-of-treatment and 30-day outcomes
MATERIALS AND METHODS
Study Design:
• Retrospective case series of patients in the BAJIO database at the
University of Louisville hospital and the Robley Rex Veterans Affairs
Medical Center in Louisville, Kentucky. Cases were collected from
January 2010 to March 2013.
• The BAJIO database is a multi-center, real-time, database of all
patients diagnosed with osteomyelitis (including diabetic foot),
prosthetic joint infection, or septic joint by the Bone & Joint Infectious
Disease Program team.
Members of the team include an ID
Attending, ID Fellow, Pharmacist, Podiatry Resident, and Medical and
Pharmacy students. Although data is analyzed retrospectively, patient
cases are created and followed prospectively to capture the most
accurate data and guide clinical decisions.
• IRB approval has been obtained.
Inclusion Criteria:
• ≥18 years of age
• Diagnosis of mandible osteomyelitis confirmed by:
• X-ray, computed tomography, magnetic resonance imaging, and/or
nuclear medicine studies.
• Histologic evaluation of bone documenting presence of
osteomyelitis
• Positive bone cultures collected from the operating room
Study Definitions:
• Clinical Success
• Improvement in clinical symptoms of infection
• Decreased pain, drainage, edema
• Absence of fever during treatment duration
• Closure of a sinus tract or surrounding wound
• Decrease in laboratory markers of infection, ESR and CRP, to
normal range
• No need for further debridement
• Twenty-one (78%) underwent surgical intervention
Pathogenesis
• Pathogenesis of infection was highly varied among the patient
population. Patients could have more than one etiology. (Table 1)
Table 1: Pathogenesis of infection
Etiology
Adjacent SSTI/Abscess
Prosthetic-related
Post-surgical
Following tooth extraction
Evidence of native pathological fracture
Bisphosphonate-induced osteonecrosis of the jaw
Internal Medicine or
Oncology
• Sixteen (59%) infections were
polymicrobial.
• Treatment durations for osteomyelitis are long, ~6 weeks, and require
high-dose intravenous antibiotic therapy. It is difficult to fully eradicate
infection, so there must be an infrastructure for long-term follow-up to
monitor for relapse or recurrence. (3)
• The human oral cavity is normally colonized with a variety of gram
positive, gram negative, and anaerobic bacteria, not all of which are
pathogenic or have been documented to cause bone infections.
Figure 1: Gram Stain Results
• Gram stain results contained
> 2 organisms in over half of
the
patients
(Figure
1),
indicating
presence
of
polymicrobial infection. Gram
positive cocci and gram positive
rods were the most prevalent.
No Organisms on
Gram Stain
Gram Positive
Cocci in Pairs
Gram Positive
Cocci in Clusters
Gram Positive
Rods
Gram Negative
Coccobacilli
Gram Negative
Rods
• The most common species by culture was Streptococcus sp., particularly
Streptococcus anginosus. (Table 2)
Table 2: Number of Isolates Collected in Patients with Mandible
Osteomyelitis
Gram Stain
Gram Positive
Statistics:
• Clinical success was described as the number (%) of those clinically
evaluable who were coded as successes.
• Microsoft Excel™ 2010 for all calculations
# of Patients (%)
n = 27
17 (63%)
6 (22%)
23 (85%)
10 (37%)
1 (4%)
7 (26%)
Microbiology
• Ten (37%) infections were culture-negative.
Infectious Disease
Treatment
Success
Plastics
RESULTS
STUDY OBJECTIVES
Gram Negative
• P-values ≤ 0.05 were considered significant.
Yeast
Pathogen
Streptococcus, Viridans Group
Streptococcus anginosus
Streptococcus, alpha-hemolytic
Streptococcus, beta-hemolytic
Peptostreptococcus sp. (anaerobe)
Staphylococcus aureus
Staphylococcus sp (Coagulase negative)
Enterococcus sp
Prevotella sp. (anaerobe)
Pseudomonas aeruginosa
Klebsiella sp.
Citrobacter sp
E. Coli
Candida sp.
# of Isolates
3
6
2
1
1
5
3
3
4
3
3
1
1
1
Note: Table only lists pathogens grown in the laboratory. Other pathogens, example, Actinomyces sp.,
were diagnosed via other methodologies
• Staphylococcus aureus infections occurred in patients with pre-existing
hardware in the mandible 75% of the time.
Clinical Outcomes
• All patients (100%) had clinical success at the end-of-therapy.
• Seventeen (63%) patients had documentation of outcome at 30-days
with a success rate of 70%
• Ten (37%) patients were considered lost-to-follow-up
CONCLUSIONS
• Osteomyelitis of the mandible can occur from a variety of etologies
causing compromise to the mandible periosteum.
• Organisms inhabiting the human oral cavity were the most common
pathogens associated with mandible osteomyelitis. Streptococcus sp.
were the most common species. Empiric coverage in culture-negative
patients should include coverage against gram positive, gram negative
and anaerobic bacteria.
• Streptococcus anginosus, the most prevalent pathogen, is known to form
abscesses and be invasive. Penicillins are the drug of choice.
• Empiric antimicrobial treatment for Staphylococcus aureus is usually not
necessary unless metallic hardware is present in the mandible.
• Because Actinomyces sp did not grow in culture and are not typically
processed for antimicrobial susceptibility, the presence of gram positive
rods and histopathologic evidence of infection warrants empiric therapy.
Penicillins are the drug of choice.
• Culture negative In these cases, antimicrobial selection was driven by
gram stain, histopathologic evidence of a pathogen, or knowledge of
human oral flora.
• The high frequency of surgical debridement and collaboration with the
Oromaxillofacial Surgery Service at University Hospital contributed to the
clinical success in out patients.
REFERENCES
•
•
•
Ohl, C. Principles and Practice in Infectious Diseases.7th edtn. Philadelphia. Churchill Livingstone.
2010.
Lew D, et al. Osteomyelitis. Lancet 2004;364:369-79
Spellburg B, Lipsky B. Systemic Antibiotic Therapy for Chronic Osteomyelitis in Adults. CID
2012;54(3);393-407