Infectious Disease I - 05 (2) - Bone and Joint Infections (Courses in Therapeutics and Disease State Management)

Infectious Disease I:
Bone and Joint Infections

Courses in Therapeutics and Disease State Management
Author: Michael W. Perry PharmD, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy
http://accesspharmacy.mhmedical.com/LearningModuleGroup.aspx?id=8
Copyright © 2017 McGraw-Hill Education. All rights reserved
Learning Objectives (Slide 1 of 3)
• Compare the epidemiology of osteomyelitis when categorized by the
mechanism of the organism reaching the bone
• Differentiate the characteristics of infectious arthritis
• Contrast the most common characteristics of
hematogenous osteomyelitis
• Compare the pathophysiology of osteomyelitis by age group
• Select the most frequent organisms causing
• Contrast the most common characteristics of contiguous-
spread osteomyelitis
• Discuss the organism sources of infectious arthritis
• Differentiate the risk factors for developing adult infectious arthritis
• Compare the etiologies of adult infectious arthritis subgroups
• Design a laboratory monitoring strategy for bone and joint infections
• Contrast the usefulness of culture sites with bone and joint infections
• Choose the preferred duration of therapy for patients with bone and
joint infections
• Discuss the patient selection characteristics for oral antibiotic
regimens treating osteomyelitis
• Critique the use of oral fluoroquinolones in the treatment of bone and
joint infections
• Construct an empiric antibiotic regimen for different patient categories
with bone or joint infections
Required Reading
Armstrong EP, Shehab Z. Chapter 96. Bone and Joint Infections. In:
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds.
Pharmacotherapy: A Pathophysiologic Approach, 9e.
New York, NY: McGraw-Hill; 2014.
Topic Overview
• Bone and Joint infections are divided into two distinct disease
processes with different infecting organisms, signs and symptom
• Septic or infective arthritis is the infection of a joint or synovial fluid
• Osteomyelitis is the infection of a bone
• Early initiation of antibiotic therapy and prolonged courses are
required to reduce long term morbidity
Osteomyelitis: Overview
• Classification
• Manner of a acquisition
• Seeding or direct inoculation of microorganism via the blood into the bone is considered
• Spread of microorganisms from adjacent soft tissues and joints is considered contiguous
osteomyelitis
• Direct inoculation of microorganism via puncture wounds, trauma, or surgery is
considered inoculation osteomyelitis
• Duration
• Acute osteomyelitis has a duration of days to weeks
• Chronic osteomyelitis has a duration of weeks to months
Osteomyelitis: Pathophysiology
• Hematogenous
• Contiguous
• Inoculation
Link to figure of cross section of normal bone
Osteomyelitis: Pathophysiology
Types of Osteomyelitis, Age Distribution, Common Sites, and Risk Factors
Type of Osteomyelitis Typical Age (years) Site(s) Involved Risk Factors
Hematogenous Less than 1 Long bones and joints Prematurity, umbilical or other central venous
catheter or venous cutdown, respiratory
distress syndrome, and perinatal asphyxia
1–20 Long bones (femur, tibia, and humerus) Infection (pharyngitis, cellulitis, and
respiratory infections), trauma, and sickle cell
disease
Older than 50 Vertebrae Diabetes mellitus, blunt trauma to spine, and

urinary tract infection
Contiguous Older than 50 Femur, tibia, and mandible Hip fractures and open fractures
Puncture Less than 18 Foot Puncture injury to foot
Vascular insufficiency Older than 50 Feet and toes Diabetes mellitus, peripheral vascular disease,
and pressure sores
Osteomyelitis: Pathophysiology, Most
Common Pathogens
• Contiguous • Hematogenous
• With vascular insufficiency
• Neonates
• Adults > 50
• S. aureus (MRSA) • S. aureus
• Enterobacteriaceae • E. coli
• Pseudomonas aeruginosa
• Group B streptococci
• Enterococcus spp.
• Anaerobes • Pre-pubertal Children
• without vascular insufficiency • S. aureus
• Adult > 50
• S. aureus
• Elderly
• S. aureus
• Inoculation
• E. coli
• S. aureus
• Gram negative pathogens
Osteomyelitis: Clinical Presentation
Signs and Symptoms Laboratory tests
• Systemic • Elevated WBC
• Fevers • Elevated inflammatory markers
• Chills • Erythrocyte sedimentation rate (ESR)
• Malaise • C-reactive protein (CRP)
• Localized • Positive blood cultures
• Pain or tenderness
• Bone biopsy cultures
• Edema
• Erythema • Bone changes on radiograph
• Inflammation • Magnetic resonance imaging
• Decreased range of motion • Technetium scans
Osteomyelitis: Treatment Overview
• Antibiotics must have adequate bone concentrations
• Duration of Antibiotics
• 4 to 6 weeks
• May be able to switch to oral antibiotics
• Monitoring for Efficacy
• Clinical improvement of signs in symptoms in 48 to 72 hours
• Reduction in CRP 1 week after therapy
• Observe for adverse effects associated with long term antimicrobial therapy
Osteomyelitis: Nonpharmacological
Treatment
• Surgical drainage of abscesses
• Hyperbaric oxygen
Osteomyelitis: Pharmacological Treatment
Patient Subtype Likely Infecting Organism Antibiotica Recommendation Gradesb
Newborn Staphylococcus aureus, group B streptococci, Nafcillin or oxacillin 50–150 mg/kg/day IV plus cefotaxime B-3
Escherichia coli 100–200 mg/kg/day IV
Children 5 years of age or younger 1. If vaccinated for Haemophilus influenzae type 1. Nafcillin or oxacillin 150–200 mg/kg/day IV or cefazolin 100 B-3
b: S. aureus or streptococci mg/kg/day IV
2. If not vaccinated against H. influenzae type b 2. Cefuroxime 150 mg/kg/day IV B-3
Children older than 5 years of age S. aureus Nafcillin or oxacillin 150–200 mg/kg/day IV or cefazolin 100 A-3
mg/kg/day IV
Adults S. aureus Nafcillin or oxacillin 2 g IV every 4 hours or cefazolin 2 g IV A-3

every 8 hours
IV drug abusers Pseudomonas Ciprofloxacin 750 mg PO twice daily or ceftazidime or cefepime B-3
2 g IV every 8 hours
Postoperative or posttrauma patients Gram-positive and gram-negative organisms Nafcillin or oxacillin 2 g IV every 4 hours plus ceftazidime B-3
or cefepime 2 g IV every 8 hours or ticarcillin–clavulanate 3.1 g
IV every 4 hours
Patients with vascular insufficiency Gram-positive and gram-negative organisms Nafcillin or oxacillin 2 g IV every 4 hours or cefazolin 2 g IV B-3
every 8 hours plus ceftazidime or cefepime 2 g IV every 8 hours
If anaerobes suspected Cefotetan 2 g IV every 12 hours or clindamycin 900 mg IV every C-3

8 hours plus ceftazidime or cefepime 2 g IV every 8 hours
PO, orally.
a
Dosage should be adjusted for some agents in patients with renal and/or hepatic dysfunction.
b
Strength of recommendations: A, B, C = good, moderate, and poor evidence to support recommendation, respectively. Quality of evidence: 1 = Evidence from more than one properly randomized, controlled studies or multiple time series; or dramatic results from uncontrolled experiments. 2 = Evidence from more than one well-
designed clinical trial with randomization, from cohort or case-controlled analytic studies. 3 = Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert communities.
Septic Arthritis: Overview
• An inflammatory reaction within the joint space
• Joint Infection that can be caused by several different microorganisms
• Classification by manner of a acquisition
• Seeding or direct inoculation of microorganism via the blood into the bone is considered
hematogenous spread
• Spread of microorganisms from adjacent soft tissues and joints is considered contiguous
spread
• Direct inoculation of microorganism via puncture wounds, trauma, or surgery is
considered inoculation spread
Septic Arthritis: Pathophysiology
Feature Finding
Peak incidence Children younger than 16 years
Adults older than 50 years
Clinical findings Fever of 38–40°C (100.4–104°F) in children; painful swollen joint in the absence of trauma
Physical examination: Effusion, restriction of joint motion, tenderness, redness, and warmth of joint
Most commonly affected joints Knee, hip, ankle, elbow, wrist, and shoulder
Laboratory findings
•Erythrocyte sedimentation rate Elevated in 90% of cases
•White blood cell count Elevated in 30–60% of cases
•Left shift Seen in two thirds of patients
•Blood culture Positive in 40% of cases
Needle aspiration of joint Gram-stain diagnostic in 30–50% of cases. Synovial fluid cultures are positive in 60–80% of cases. Synovial fluid
differential reveals 90% polymorphonuclear leukocytes. Synovial fluid glucose decreased relative to serum glucose. Lactic
acid levels elevated in nongonococcal infectious arthritis, but not in gonococcal infectious arthritis
Septic Arthritis: Pathophysiology, Most
Common Pathogens
• Overall • Specific Groups
• Staphylococcus aureus • Neonates
• Streptococcal infection • S. aureus
• Gram negative pathogens • Group B streptococci
• E. coli • Gram negative pathogens
• Pseudomonas aeruginosa • Pre-pubertal Children
• S. aureus
• Streptococcal infection
• IV drug abusers
Septic Arthritis: Clinical Presentation
Signs and Symptoms Laboratory tests
• Systemic • Elevated WBC is rare
• Fevers • Elevated inflammatory markers are less
• Chills common
• Erythrocyte sedimentation rate (ESR)
• Malaise
• C-reactive protein (CRP)
• Localized • Positive blood cultures
• Joint pain or tenderness • Joint aspiration fluid
• Edema • Presence of purulent fluid
• Erythema • Gram stain
• Inflammation • Culture
• Decreased range of motion • Prosthetic joint material cultures
Septic Arthritis: Treatment Overview
• Antibiotics must have adequate synovial fluid concentrations
• Duration of Antibiotics
• 2 to 3 weeks
• May be able to switch to oral antibiotics
• Clinical improvement of signs in symptoms in is generally rapid after
initiation of antibiotic therapy and joint aspiration
Septic Arthritis:
Nonpharmacological Treatment
• Closed-needle aspiration is recommended for all infected joints except
the hip
• Joint rest
• Passive range of motion exercises once joint pain subsides
Septic Arthritis:
Pharmacological Treatment
• Infants < 1 month of age • Children >5 years of age and
• Nafcillin or Oxacillin adults
Plus • MSSA suspected
• 3rd generation cephalosporin • Nafcillin, Oxacillin, or Cefazolin
• MRSA suspected
• Clindamycin, Vancomycin, or
• Children <5 years of age Linezolid
immunized for Hib
• Nafcillin, Oxacillin, or Cefazolin
Overall Monitoring of Bone and Joint
Infections
Parameter Frequency Notes
Culture and susceptibility At initiation of treatment
White blood cell count One time per week until within normal range
C-reactive protein or erythrocyte Weekly May not decrease to normal range until
sedimentation rate several weeks of therapy
Clinical signs of inflammation (redness, pain, Daily during initiation of therapy

swelling, tenderness, and fever)
Compliance of outpatient therapy Reinforce before starting oral therapy and with Compliance is critical if treatment is to be
each healthcare visit successful
Summary
• Osteomyletitis and septic arthritis are infections of the bone and joints
respectively
• S. aureus is the most common pathogen
• Intravenous Antibiotics
• Bone and joint penetration must be considered
• Narrow antibiotics based on cultures and sensitivities
• Duration of antibiotics
• Osteomyelitis 4 to 6 weeks
• Septic Arthritis 2 to3 weeks
• Initiate oral antibiotics when appropriate
Reference
Armstrong EP, Shehab Z. Chapter 96. Bone and Joint Infections. In: DiP
iro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds.
Pharmacotherapy: A Pathophysiologic Approach, 9e.
New York, NY: McGraw-Hill; 2014.

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Infectious Disease I:

Bone and Joint Infections

Link to figure of cross section of normal bone

Older than 50 Vertebrae Diabetes mellitus, blunt trauma to spine, and

Puncture Less than 18 Foot Puncture injury to foot

2. If not vaccinated against H. influenzae type b 2. Cefuroxime 150 mg/kg/day IV B-3

Adults S. aureus Nafcillin or oxacillin 2 g IV every 4 hours or cefazolin 2 g IV A-3

If anaerobes suspected Cefotetan 2 g IV every 12 hours or clindamycin 900 mg IV every C-3

Peak incidence Children younger than 16 years

Adults older than 50 years

•Erythrocyte sedimentation rate Elevated in 90% of cases

•White blood cell count Elevated in 30–60% of cases

•Left shift Seen in two thirds of patients

•Blood culture Positive in 40% of cases

Culture and susceptibility At initiation of treatment

Clinical signs of inflammation (redness, pain, Daily during initiation of therapy

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