COMMON ORTHOPAEDIC PATHOGENS
Staphylococcus aureus Dominant | Coagulase-Negative Staph in Implants | Polymicrobial in DFI | Culture-Negative 10-30%
COMMON PATHOGENS BY SCENARIO
Critical Must-Knows
- Staphylococcus aureus is the most common pathogen in acute bone and joint infections (30-50%)
- Coagulase-negative Staphylococci (CoNS) dominate chronic prosthetic joint infections (50-70%)
- MRSA prevalence varies regionally (10-60%) - know your local resistance patterns
- Polymicrobial infections common in diabetic foot, open fractures, and chronic wounds
- Culture-negative infections occur in 10-30% due to prior antibiotics, fastidious organisms, or biofilm
Examiner's Pearls
- "Gram-positive cocci cause 70-80% of orthopaedic infections overall
- "Salmonella osteomyelitis associated with sickle cell disease and hemoglobinopathies
- "Kingella kingae common in pediatric septic arthritis (younger than 4 years)
- "Propionibacterium acnes (Cutibacterium) in shoulder arthroplasty infections (anaerobic culture required)
Critical Pathogen Recognition Points
Staphylococcus aureus
Most common overall (30-50% of infections). Gram-positive cocci in clusters. Produces virulence factors (coagulase, protein A, toxins). MRSA requires vancomycin or alternative agents. Aggressive, destructive infections.
Coagulase-Negative Staph
Dominant in chronic PJI (50-70%). S. epidermidis most common species. Biofilm formation on implants. Often low virulence, indolent presentation. Easily dismissed as contaminant - correlate with clinical picture.
MRSA vs MSSA
MRSA = methicillin-resistant, requires vancomycin, linezolid, or daptomycin. MSSA = methicillin-sensitive, treat with flucloxacillin or cefazolin (beta-lactams superior to vancomycin for MSSA).
Culture Technique Matters
5-7 tissue samples recommended for PJI diagnosis. Hold antibiotics if possible before culture. Extended incubation (7-14 days) for fastidious organisms. Anaerobic culture for shoulder and foot infections.
At a Glance
Staphylococcus aureus is the dominant pathogen in acute orthopaedic infections (30-50%), producing virulence factors including coagulase, protein A, and toxins that cause aggressive tissue destruction. Coagulase-negative Staphylococci (CoNS), particularly S. epidermidis, dominate chronic prosthetic joint infections (50-70%) through biofilm formation on implant surfaces. MRSA prevalence varies regionally (10-60%)—know local patterns and provide vancomycin/linezolid coverage for moderate-severe infections. Diabetic foot and open fractures are typically polymicrobial (Staph, Strep, anaerobes, Gram-negative bacilli). Special associations: Kingella kingae in pediatric septic arthritis (under 4 years), Salmonella in sickle cell osteomyelitis, and Cutibacterium acnes in shoulder arthroplasty infections (requires extended anaerobic culture). Culture-negative rates are 10-30%—hold antibiotics before sampling when possible.
STAPHSTAPH - Staphylococcal Virulence Factors
Memory Hook:STAPH has multiple virulence factors making it the most destructive orthopaedic pathogen
PATHOGENSPATHOGENS - Common Organisms by Clinical Scenario
Memory Hook:Remember the PATHOGENS most likely in each clinical scenario
BIOFILMBIOFILM - How Bacteria Persist on Implants
Memory Hook:BIOFILM explains why implant infections require removal for cure
Overview
Orthopaedic infections are caused by a relatively predictable spectrum of pathogens, with Staphylococcus species accounting for 70-80% of cases.
Why pathogen knowledge matters clinically:
Empiric Therapy Selection
Knowing the most likely pathogens allows rational empiric antibiotic selection while awaiting culture results. S. aureus coverage is essential in most scenarios. Consider local MRSA prevalence when choosing agents.
Treatment Duration and Strategy
Different organisms require different treatment approaches. Staphylococci with biofilm need prolonged therapy (6-12 weeks). Gram-negatives may allow shorter courses. Polymicrobial infections need broad coverage.
Single Positive Culture Interpretation
One positive culture for coagulase-negative Staphylococcus may represent contamination OR true infection. Apply Musculoskeletal Infection Society (MSIS) criteria: greater than or equal to 2 positive cultures of same organism = infected, OR single positive with consistent clinical picture. Consider virulence, clinical context, and inflammatory markers.
Biology of Orthopaedic Pathogens
Pathogen Biology and Clinical Principles
Pathogen Prevalence Patterns:
The distribution of pathogens in orthopaedic infections follows predictable patterns based on clinical context. Understanding these patterns is essential for rational empiric therapy selection.
Pathogen Distribution by Infection Type
| Infection Type | Predominant Pathogens | Key Features |
|---|---|---|
| Acute Native Joint | S. aureus (40-50%), Streptococcus (15-20%) | High virulence, rapid onset, destructive |
| Chronic Prosthetic Joint | CoNS (50-70%), S. aureus (20-30%) | Biofilm formation, indolent, requires removal |
| Hematogenous Pediatric | S. aureus (40%), Kingella (30-50% in under 4yr) | Age-dependent pathogen spectrum |
| Diabetic Foot | Polymicrobial (50-75%) | Aerobes + anaerobes, broad coverage needed |
Virulence Factor Biology:
Understanding bacterial virulence mechanisms explains clinical presentation and guides treatment strategies:
- Adhesins: Surface proteins enabling bacterial attachment to bone matrix, collagen, and prosthetic materials
- Biofilm: Polysaccharide matrix protecting bacteria from antibiotics and immune system (1000-fold increased MIC)
- Toxins: Tissue destruction (alpha-toxin, PVL) and immune evasion (protein A)
- Enzymes: Facilitate tissue invasion (coagulase, hyaluronidase, proteases)
Antibiotic Resistance Mechanisms:
MRSA - mecA Gene
Encodes altered penicillin-binding protein 2a (PBP2a) with low affinity for beta-lactams. Renders ALL beta-lactams ineffective except ceftaroline. Requires vancomycin, daptomycin, or linezolid.
ESBL - Extended-Spectrum Beta-Lactamase
Enzyme that hydrolyzes penicillins, cephalosporins, and aztreonam. Produced by Enterobacteriaceae (E. coli, Klebsiella). Requires carbapenem therapy (meropenem, ertapenem).
Biofilm Biology and Clinical Implications:
Biofilm is the primary reason prosthetic joint infections are difficult to cure with antibiotics alone:
- Formation stages: Attachment → Irreversible adhesion → Microcolony formation → Maturation with polysaccharide matrix
- Protection mechanisms: Physical barrier to antibiotics, quorum sensing communication, persister cells in dormant state
- Clinical consequence: 1000-fold increase in MIC, antibiotics cannot penetrate, requires implant removal for cure
- Rifampin role: One of few antibiotics that penetrates biofilm, always used in combination to prevent resistance
Culture Interpretation Principles:
Distinguishing true infection from contamination requires integration of microbiology with clinical context:
True Pathogen vs Contamination
| Factor | True Infection | Contamination |
|---|---|---|
| Number of positive cultures | Greater than or equal to 2 (same organism) | Single positive culture |
| Organism type | Virulent (S. aureus, Strep) | Low virulence (CoNS) |
| Clinical correlation | Symptoms, elevated CRP/ESR | Asymptomatic, normal labs |
| Biofilm present | Implant in situ | Native joint, no foreign material |
Understanding these core microbiological concepts is essential for rational antibiotic selection and infection management.
Anatomy
Bacterial Cell Wall Anatomy
Gram-Positive Structure
Cell wall components:
- Thick peptidoglycan layer (20-80nm)
- Teichoic acids embedded in peptidoglycan
- Lipoteichoic acids anchored to membrane
- Single phospholipid membrane
Clinical relevance:
- Retains crystal violet stain (purple)
- Target for beta-lactam antibiotics
- Vancomycin binds to D-Ala-D-Ala
Gram-Negative Structure
Cell wall components:
- Thin peptidoglycan layer (2-7nm)
- Outer membrane with lipopolysaccharide (LPS)
- Periplasmic space between membranes
- Inner phospholipid membrane
Clinical relevance:
- Loses crystal violet, takes safranin (pink)
- Outer membrane limits antibiotic entry
- LPS causes sepsis/endotoxemia
Gram Stain Principle
The Gram stain distinguishes bacteria by cell wall thickness. Gram-positive bacteria have thick peptidoglycan that retains crystal violet (appear purple). Gram-negative bacteria have thin peptidoglycan and are decolorized, taking up the safranin counterstain (appear pink). This simple test guides initial antibiotic selection.
Classification
Classification by Gram Stain
Pathogen Classification by Gram Stain
| Category | Examples | Prevalence in Orthopaedics |
|---|---|---|
| Gram-positive cocci | S. aureus, CoNS, Streptococcus, Enterococcus | 70-80% of all infections |
| Gram-negative bacilli | E. coli, Pseudomonas, Klebsiella, Salmonella | 10-20% of infections |
| Anaerobes | Cutibacterium, Bacteroides, Clostridium | 5-10% (under-recognized) |
| Mycobacteria | M. tuberculosis, atypical mycobacteria | 1-5% globally (endemic areas) |
| Fungi | Candida, Aspergillus, endemic mycoses | less than 2% (immunocompromised) |
Gram-Positive Dominance
Why gram-positives dominate:
- Skin colonization (S. aureus, CoNS)
- Operative contamination source
- Adherence to implant materials
- Biofilm formation capacity
Gram-Negative Indications
When to suspect gram-negatives:
- Elderly, diabetic patients
- Urinary/GI source suspected
- Open fractures (contamination)
- Hospital-acquired infections
- Immunocompromised hosts
Clinical Relevance
Why Pathogen Knowledge Matters in Orthopaedic Practice
Impact on Empiric Antibiotic Selection:
The choice of empiric antibiotics before culture results is a critical clinical decision that directly affects outcomes. Delays in appropriate antibiotic coverage increase morbidity and mortality.
Decision framework:
- Native joint infection in immunocompetent adult: S. aureus most likely → Flucloxacillin or cefazolin (add vancomycin if MRSA risk greater than 20%)
- Prosthetic joint infection: CoNS and S. aureus → Vancomycin plus gram-negative cover (ceftriaxone or cefepime)
- Diabetic foot infection: Polymicrobial → Broad-spectrum (piperacillin-tazobactam or ertapenem)
- Pediatric patient under 4 years: Kingella plus S. aureus → Ceftriaxone
- Sickle cell patient: Salmonella plus S. aureus → Ciprofloxacin or ceftriaxone
Treatment Duration Based on Pathogen:
Different organisms require different treatment durations based on virulence and biofilm potential:
Prognostic Implications:
Pathogen identity predicts treatment success and need for surgery:
- S. aureus PJI: 30-40% failure with DAIR (debridement, antibiotics, implant retention), often needs two-stage
- CoNS PJI: 50-60% success with DAIR if caught early (less than 3 weeks), chronic requires removal
- Pseudomonas: Difficult to eradicate, high recurrence rates, often requires prolonged combination therapy
- Fungi: Almost always require implant removal, 6-12 months therapy, 20-40% recurrence
Special Population Considerations:
Immunosuppressed
Expanded pathogen spectrum: Opportunistic organisms (atypical mycobacteria, fungi), gram-negatives more common. Requires broader empiric coverage and longer treatment.
Diabetic Patients
Polymicrobial infections common (50-75% of diabetic foot). Anaerobes in deep infections. Often Pseudomonas in chronic wounds. Requires broad-spectrum coverage.
IV Drug Users
High MRSA rates (60-70%). Pseudomonas common (15-20%). Fungal infections (Candida). Unusual sites (sternoclavicular, sacroiliac, cervical spine). Empiric vancomycin plus anti-pseudomonal agent.
Surgical Decision-Making:
Pathogen characteristics influence surgical approach:
- Biofilm-forming organisms (S. aureus, CoNS): Early infection (less than 3 weeks) allows DAIR, chronic requires removal
- Low-virulence organisms (CoNS): May tolerate chronic antibiotic suppression if surgery contraindicated
- High-virulence organisms (S. aureus, Streptococcus): Aggressive surgical debridement essential
- Fungi: Almost always require implant removal for cure
- Polymicrobial: Source control (debridement) as important as antibiotics
Local Resistance Patterns (Antibiogram):
Every institution has unique resistance patterns that must guide empiric therapy:
- Know your hospital's MRSA prevalence (10-60% variation)
- Know ESBL rates in Enterobacteriaceae (influences empiric gram-negative coverage)
- Know VRE prevalence (affects empiric Enterococcus coverage)
- Adjust empiric regimens based on local data, then narrow based on cultures
Antibiotic Stewardship
Start broad, narrow early is the principle. Empiric therapy must cover likely pathogens, but once cultures identify specific organisms, narrow to targeted therapy. Continuing broad-spectrum antibiotics when narrow-spectrum would suffice promotes resistance and increases toxicity. Example: Switch from vancomycin to cefazolin when MSSA identified.
Understanding pathogen patterns, virulence, and resistance informs every clinical decision in orthopaedic infection management.
Gram-Positive Cocci - Dominant Pathogens
Staphylococcus aureus - Most Common Overall
Microbiology:
- Gram-positive cocci in clusters
- Coagulase-positive (distinguishes from CoNS)
- Catalase-positive
- Golden colonies on blood agar (aureus = gold)
Prevalence:
- 30-50% of acute osteomyelitis
- 40-60% of septic arthritis
- 20-30% of prosthetic joint infections (acute)
- 30-50% of surgical site infections
Virulence factors:
- Adhesins: Bind to bone matrix, collagen, fibronectin
- Protein A: Binds IgG, prevents opsonization
- Coagulase: Converts fibrinogen to fibrin (clot formation, walling off)
- Hemolysins: Alpha, beta, gamma toxins (tissue destruction)
- Panton-Valentine leukocidin (PVL): Necrotizing infections, CA-MRSA
- Enzymes: Lipases, nucleases, proteases (tissue invasion)
Clinical features:
- Aggressive, rapid-onset infections
- High fever, systemic toxicity common
- Destructive to bone and cartilage
- Abscess formation typical
- Can cause acute fulminant septic arthritis with cartilage destruction in 24-48 hours
Treatment:
- MSSA (methicillin-sensitive): Flucloxacillin 2g IV q6h, cefazolin 2g IV q8h
- MRSA (methicillin-resistant): Vancomycin 15-20 mg/kg IV q8-12h, or daptomycin, linezolid
- Duration: 4-6 weeks IV for osteomyelitis, 3-4 weeks for septic arthritis
Beta-lactams Superior for MSSA
For MSSA infections, beta-lactams (flucloxacillin, cefazolin) are SUPERIOR to vancomycin in terms of efficacy and outcomes. Never use vancomycin for MSSA just for convenience - it is inferior and promotes resistance. Reserve vancomycin for MRSA only.
Community-Acquired MRSA (CA-MRSA)
CA-MRSA strains often carry PVL toxin, causing necrotizing skin/soft tissue infections and severe pneumonia. More virulent than hospital-acquired MRSA. Common in athletes, children, prisoners. Consider in community patients with severe infections.
S. aureus is the most important orthopaedic pathogen due to prevalence and virulence.
Gram-Negative Bacteria
Enterobacteriaceae (Gram-Negative Bacilli)
Common species in orthopaedics:
- E. coli: Most common GNB (40-50% of GNB infections)
- Klebsiella pneumoniae: Diabetics, elderly
- Proteus mirabilis: Chronic wounds, urinary source
- Enterobacter species: Nosocomial, resistant
Clinical contexts:
- 10-20% of osteomyelitis in adults
- Higher prevalence in elderly, diabetic, immunosuppressed
- Often from hematogenous spread (UTI, intra-abdominal source)
- Diabetic foot infections (polymicrobial with anaerobes)
- Open fractures (environmental contamination)
E. coli:
- Most common GNB in orthopaedic infections
- Often from urinary or GI source
- Vertebral osteomyelitis common (hematogenous spread from UTI)
- Treatment: Ceftriaxone 2g IV daily, ciprofloxacin 400mg IV q12h (if sensitive)
Klebsiella pneumoniae:
- Diabetics, alcoholics, elderly
- Capsule protects from phagocytosis
- ESBL (extended-spectrum beta-lactamase) strains resistant to cephalosporins
- Carbapenem-resistant strains emerging (CRE - carbapenem-resistant Enterobacteriaceae)
- Treatment: Carbapenems (meropenem, ertapenem), or ceftriaxone if sensitive
ESBL and Carbapenem Resistance
ESBL-producing Enterobacteriaceae resistant to penicillins, cephalosporins, aztreonam. Treat with carbapenems. CRE (carbapenem-resistant) are nightmare bacteria with limited options (polymyxins, tigecycline). Risk factors: Healthcare exposure, prior antibiotics, ICU admission.
Enterobacteriaceae are the most common gram-negative pathogens in orthopaedic infections.
Anaerobes and Special Pathogens
Anaerobic Bacteria
Common anaerobes in orthopaedics:
- Cutibacterium acnes (formerly Propionibacterium acnes)
- Bacteroides fragilis
- Peptostreptococcus species
- Clostridium species
- Fusobacterium species
Cutibacterium acnes (Propionibacterium acnes):
- Normal skin flora (sebaceous glands)
- 30-40% of shoulder arthroplasty infections
- Indolent, chronic presentation (months to years)
- Often culture-negative if anaerobic culture not requested
- Requires extended incubation (7-14 days) for growth
- Biofilm formation on implants
- Treatment: Penicillin G, ceftriaxone, clindamycin (usually sensitive)
Bacteroides fragilis:
- Part of GI flora
- Diabetic foot infections (polymicrobial)
- Decubitus ulcers with bone involvement
- Resistant to many antibiotics (produces beta-lactamase)
- Treatment: Metronidazole, amoxicillin-clavulanate, carbapenems
Peptostreptococcus:
- Oral and GI flora
- Human bites, diabetic foot
- Often polymicrobial
- Treatment: Penicillin, amoxicillin-clavulanate
Clostridium species:
- C. perfringens: Gas gangrene (myonecrosis), devastating trauma
- Spore-forming, soil organism
- Produces alpha toxin (lecithinase - cell membrane destruction)
- Clinical: Crepitus, bullae, systemic toxicity, rapid progression
- Treatment: Emergency debridement + penicillin G + clindamycin (toxin suppression)
Gas Gangrene Emergency
Clostridial myonecrosis (gas gangrene) is surgical emergency. Clinical: Severe pain, crepitus, bullae, bronze discoloration, systemic toxicity. X-ray shows gas in tissues. Immediate wide debridement + high-dose penicillin + hyperbaric oxygen if available. Mortality 20-30% even with treatment.
Cutibacterium in Shoulder
Shoulder arthroplasty infections have high rate of Cutibacterium acnes (30-40%). Often culture-negative if only aerobic cultures obtained. Request anaerobic cultures specifically and extended incubation (7-14 days) for shoulder revisions. Low virulence, chronic indolent presentation.
Anaerobes require specific culture conditions and extended incubation - communicate with microbiology lab.
Pathogens by Clinical Scenario
Most Likely Pathogens by Clinical Context
| Clinical Scenario | Most Common Pathogens | Empiric Therapy | Duration |
|---|---|---|---|
| Acute osteomyelitis (adult) | S. aureus (40%), Strep (10%), GNB (10-20%) | Flucloxacillin 2g IV q6h (or vancomycin if MRSA risk) | 4-6 weeks IV |
| Acute septic arthritis | S. aureus (40-50%), Strep (15-20%), GNB (10%) | Flucloxacillin + ceftriaxone (empiric), then narrow | 3-4 weeks |
| Prosthetic joint infection (chronic) | CoNS (50-70%), S. aureus (20-30%), polymicrobial (10%) | Vancomycin + ceftriaxone (empiric), then target | 6-12 weeks |
| Diabetic foot infection | Polymicrobial: S. aureus, Strep, GNB, anaerobes | Pip-tazo or amox-clav + ciprofloxacin | 4-6 weeks (bone) |
| Open fracture (contaminated) | S. aureus, Strep, GNB, Clostridium | Cefazolin + gentamicin (or pip-tazo) | 24-72 hours (prophylaxis) |
| Sickle cell osteomyelitis | Salmonella (50%), S. aureus (30%) | Ciprofloxacin or ceftriaxone (cover both) | 4-6 weeks |
| Pediatric septic arthritis (younger than 4 yr) | Kingella (30-50%), S. aureus (30-40%) | Ceftriaxone (covers both) | 3-4 weeks |
| Shoulder arthroplasty infection | C. acnes (30-40%), CoNS (30%), S. aureus (20%) | Request ANAEROBIC cultures, then target | 6 weeks |
| Vertebral osteomyelitis | S. aureus (40%), E. coli (20%), TB (5%, endemic) | Flucloxacillin + ceftriaxone (empiric) | 6-12 weeks |
| Puncture wound (nail through shoe) | Pseudomonas aeruginosa (classic) | Ceftazidime or ciprofloxacin (antipseudomonal) | 4-6 weeks |
Empiric Therapy Principles
Empiric therapy must cover the most likely pathogens while awaiting cultures. For most acute orthopaedic infections, S. aureus coverage is essential. Add gram-negative coverage for elderly, diabetic, immunosuppressed, or urinary/GI source. Always obtain cultures BEFORE starting antibiotics if possible (delays of 2-4 hours acceptable for cultures).
Culture Techniques and Diagnostic Pearls
Optimizing culture yield:
Sample Collection
- 5-7 tissue samples for PJI diagnosis (MSIS criteria)
- Deep tissue, NOT swabs (contamination)
- Multiple sites if osteomyelitis
- Synovial fluid for septic arthritis (send for cell count, culture, crystal analysis)
Timing and Antibiotics
- Hold antibiotics before cultures if possible (2-4 hour delay acceptable)
- If already on antibiotics, stop 2 weeks before revision surgery cultures (if feasible)
- Blood cultures in acute infections (bacteremia common)
Special culture requests:
When to Request Special Cultures
| Organism Type | When to Request | Incubation Time | Clinical Clue |
|---|---|---|---|
| Anaerobes | Shoulder infections, diabetic foot, chronic wounds | 7-14 days | Foul odor, gas in tissues, chronic indolent |
| Fungi | Immunosuppressed, chronic infection not responding | 1-4 weeks | Chronic, indolent, failed antibiotics |
| Mycobacteria | Subacute, endemic area, chronic non-healing | 4-6 weeks (TB) | Subacute onset, disc preservation (spine) |
| Fastidious organisms | Culture-negative septic arthritis, pediatric (Kingella) | Extended (5-7 days) | Young child, culture-negative |
Culture-negative infections (10-30%):
Causes:
- Prior antibiotic therapy (most common)
- Fastidious organisms (Kingella, Cutibacterium, fungi, mycobacteria)
- Biofilm (PJI - organisms in dormant state)
- Inadequate sampling (superficial swabs, single sample)
- Technical issues (transport delay, improper media)
Approach to culture-negative PJI:
- Review antibiotic exposure (stop 2 weeks before if possible)
- Request extended incubation (7-14 days)
- Request anaerobic cultures specifically
- Consider PCR or molecular diagnostics (16S rRNA sequencing)
- Sonication of explanted implant (releases biofilm bacteria)
- Histology showing inflammation supports infection even if culture-negative
Molecular Diagnostics
PCR and next-generation sequencing can identify pathogens in culture-negative infections. 16S rRNA gene sequencing identifies bacteria, ITS sequencing identifies fungi. Expensive, not routine, but helpful in culture-negative PJI or when specific pathogen suspected (TB, Kingella).
Investigations
Microbiological Investigations
Gram Stain
Rapid bedside test (minutes):
- Crystal violet → Iodine → Decolorizer → Safranin
- Gram-positive: Purple (thick peptidoglycan)
- Gram-negative: Pink (thin peptidoglycan)
- Guides initial empiric therapy
- Sensitivity: 60-80% for joint fluid
Bacterial Culture
Gold standard for pathogen identification:
- Blood agar, chocolate agar, MacConkey
- 24-48 hours for common pathogens
- Extended incubation for fastidious organisms
- Provides antimicrobial susceptibility testing (AST)
- Deep tissue preferred over swabs
Sample Collection Principles
Deep tissue samples are superior to swabs. For PJI diagnosis, obtain 5-7 tissue samples from different locations (MSIS criteria). Hold antibiotics for 2 weeks before cultures if feasible. Send samples in sterile containers, not swabs. Blood cultures should accompany all acute infections.
Management
Empirical Antibiotic Selection
Native Joint/Fracture Infections
First-line empirical (before culture):
- Flucloxacillin 2g IV q6h (MSSA coverage)
- ADD Vancomycin 25-30mg/kg load if MRSA risk
- ADD Gentamicin 5-7mg/kg for Gram-negative coverage
MRSA risk factors:
- Previous MRSA colonization/infection
- Recent hospitalization (within 90 days)
- Nursing home residence
- IV drug use
- Chronic wounds
Prosthetic Joint Infection
PJI empirical regimen:
- Vancomycin 25-30mg/kg load, then 15-20mg/kg q12h
- PLUS Piperacillin-tazobactam 4.5g IV q6h
Rationale:
- CoNS and MRSA common (vancomycin)
- Gram-negative coverage (pip-tazo)
- Pseudomonas coverage for chronic wounds
Duration: 4-6 weeks IV therapy typical
Pathogen-Directed Therapy
Antibiotic Selection by Organism
| Pathogen | First Line | Alternative | Duration |
|---|---|---|---|
| MSSA | Flucloxacillin 2g IV q6h | Cefazolin 2g IV q8h | 4-6 weeks |
| MRSA | Vancomycin (trough 15-20) | Daptomycin 6-8mg/kg | 6 weeks |
| Streptococcus | Penicillin G 4MU q4h | Ceftriaxone 2g daily | 4 weeks |
| Enterococcus | Ampicillin + Gentamicin | Vancomycin + Gent | 6 weeks |
| E. coli/Klebsiella | Ceftriaxone 2g daily | Ciprofloxacin 750mg PO | 4-6 weeks |
| Pseudomonas | Ceftazidime + Cipro | Meropenem 1g q8h | 6 weeks |
| C. acnes | Penicillin G | Clindamycin | 6 weeks |
This section covers the fundamental principles of antimicrobial management for orthopaedic infections.
Surgical Technique
Specimen Collection Techniques
Intraoperative Tissue Sampling
Minimum 5 tissue samples for PJI diagnosis:
- Synovium (2 samples from different locations)
- Periprosthetic membrane
- Bone-implant interface tissue
- Capsule
Technique principles:
- Use separate instruments for each sample
- Avoid contamination from skin edges
- Take samples BEFORE antibiotic administration
- Place in sterile containers (not formalin)
Synovial Fluid Aspiration
Preoperative aspiration technique:
- Sterile prep with chlorhexidine (not iodine for culture)
- 18G needle, 20-50mL syringe
- Minimum 2mL for laboratory analysis
- Direct inoculation into blood culture bottles
Sample allocation:
- Cell count and differential (EDTA tube)
- Crystal analysis (plain tube)
- Culture (sterile container/blood culture bottle)
- Alpha-defensin if available
Debridement Principles
Debridement by Infection Type
| Setting | Debridement Goal | Key Steps | Irrigation Volume |
|---|---|---|---|
| Acute native joint | Remove purulent material | Arthrotomy, lavage, drain | 6-9L saline |
| Open fracture | Remove contamination | Serial debridement q48-72h | 6-9L pulsatile lavage |
| PJI DAIR | Preserve implant | Exchange modular parts, scrub | 6-9L minimum |
| Chronic osteomyelitis | Remove dead bone | Sequestrectomy, dead space | Variable |
Proper specimen collection and debridement technique are essential for successful infection management.
Complications
Infection-Related Complications
Local Complications
Soft tissue complications:
- Abscess formation (25-30% of untreated infections)
- Sinus tract development (chronic infection)
- Wound dehiscence
- Skin necrosis
Bone complications:
- Osteomyelitis progression
- Sequestrum formation
- Pathologic fracture
- Joint destruction/ankylosis
Systemic Complications
Sepsis spectrum:
- Bacteremia (15-20% of deep infections)
- Severe sepsis with organ dysfunction
- Septic shock (mortality 20-40%)
Metastatic infection:
- Infective endocarditis
- Septic emboli
- Secondary osteomyelitis at distant sites
- Septic arthritis in other joints
Antibiotic Complications
Drug-Specific Adverse Effects
| Antibiotic | Common Effects | Serious Reactions | Monitoring |
|---|---|---|---|
| Vancomycin | Red man syndrome, phlebitis | Nephrotoxicity, ototoxicity | Trough levels, creatinine |
| Aminoglycosides | Vestibular toxicity | Nephrotoxicity, ototoxicity | Levels, creatinine, audiometry |
| Rifampicin | GI upset, orange secretions | Hepatotoxicity, drug interactions | LFTs, INR if on warfarin |
| Fluoroquinolones | GI upset, photosensitivity | Tendon rupture, QT prolongation | Tendon symptoms, ECG |
| Daptomycin | Myalgia | Rhabdomyolysis, eosinophilic pneumonia | CK weekly |
Understanding potential complications guides antibiotic selection and monitoring protocols.
Postoperative Care
Antibiotic Administration
- Continue empirical IV antibiotics until cultures finalize
- Blood cultures if febrile (temperature greater than 38.5°C)
- Check vancomycin trough (target 15-20 μg/mL)
- Renal function monitoring (creatinine daily)
- Narrow antibiotic spectrum based on sensitivities
- Infectious diseases consultation recommended
- Optimize oral bioequivalent options
- Monitor CRP trend (should decline by 50% weekly)
- Oral switch when: afebrile, CRP declining, tolerating diet
- High bioavailability options: fluoroquinolones, rifampicin combinations
- Weekly CRP/ESR monitoring
- Watch for antibiotic side effects
- Total duration: 6-12 weeks for PJI, 4-6 weeks for native infection
- Consider suppressive therapy if implant retained
- Final inflammatory markers before stopping
- Plan long-term follow-up
Laboratory Monitoring
Monitoring Parameters by Antibiotic
| Antibiotic | Laboratory Tests | Frequency | Action Threshold |
|---|---|---|---|
| Vancomycin | Trough level, creatinine | Twice weekly initially | Trough less than 10 or greater than 25 |
| Aminoglycosides | Peak/trough, creatinine | Every 2-3 days | Rising creatinine, elevated trough |
| Rifampicin | LFTs, FBC | Weekly × 4, then monthly | ALT greater than 3× ULN |
| Daptomycin | CK, creatinine | Weekly | CK greater than 5× ULN or symptoms |
| Cotrimoxazole | FBC, creatinine, K+ | Weekly initially | Cytopenias, hyperkalemia |
Structured postoperative care with close monitoring optimizes antibiotic efficacy while minimizing toxicity.
Outcomes
Treatment Success Rates
Outcomes by Treatment Strategy
| Strategy | Success Rate | Follow-up | Notes |
|---|---|---|---|
| DAIR (early acute) | 65-85% | 2 years | Best with rifampicin combination |
| DAIR (hematogenous) | 55-75% | 2 years | S. aureus has worse outcomes |
| One-stage exchange | 85-95% | 2-5 years | Strict patient selection |
| Two-stage exchange | 85-95% | 2-5 years | Gold standard for complex PJI |
| Suppressive antibiotics | Variable | Ongoing | Symptom control, not cure |
Organism-Specific Outcomes
Favorable Prognosis
Better outcomes with:
- Streptococci (cure rates greater than 90%)
- Susceptible CoNS
- Monomicrobial infections
- Early treatment initiation
Streptococcal advantage:
- Less biofilm formation
- Excellent beta-lactam susceptibility
- Lower recurrence rates
Unfavorable Prognosis
Worse outcomes with:
- S. aureus (cure 60-75% with DAIR)
- MRSA (cure 50-65%)
- Enterococcus (cure 40-60%)
- Polymicrobial infections
- Fungi (cure less than 50%)
Difficult-to-treat organisms:
- Require implant removal for cure
- Prolonged antibiotic courses
- Consider suppression
Successful outcomes depend on appropriate surgical strategy, targeted antibiotics, and patient optimization.
Evidence Base
Microbiology of Prosthetic Joint Infections
- CoNS account for 30-43% of PJI overall, 50-70% of chronic infections
- S. aureus causes 20-35% of PJI, more common in acute presentations
- Polymicrobial infections in 10-20% of cases
- Culture-negative in 7-12% despite optimal techniques
- Biofilm formation major factor in chronic indolent infections
Kingella kingae in Pediatric Septic Arthritis
- Kingella kingae most common cause in children younger than 4 years (40-50% in some series)
- Fastidious organism - culture-negative in 30-50% even when present
- PCR from synovial fluid improves detection to 70-80%
- Less virulent than S. aureus - lower inflammatory markers, less destruction
- Often follows upper respiratory infection
Salmonella Osteomyelitis in Sickle Cell Disease
- Sickle cell patients have 50-fold increased risk of Salmonella osteomyelitis
- Salmonella accounts for 50% of osteomyelitis in sickle cell (vs 1-2% in general population)
- Mechanism: Splenic dysfunction, bone infarcts, impaired immunity
- Often multifocal involvement
- Treatment: Fluoroquinolones or third-generation cephalosporins
Cutibacterium acnes in Shoulder Arthroplasty
- C. acnes accounts for 20-40% of shoulder arthroplasty infections
- Anaerobic culture and extended incubation (7-14 days) required for detection
- Low virulence, indolent presentation (months to years post-op)
- Often culture-negative if only aerobic cultures obtained
- Biofilm formation on implants
MCQ Practice Points
Exam Pearl
Q: What is the most common organism causing periprosthetic joint infection (PJI) following primary total hip arthroplasty?
A: Staphylococcus aureus (approximately 30-40%), followed by coagulase-negative staphylococci (S. epidermidis, 20-30%). Together, staphylococci cause 60-70% of all PJIs. MRSA accounts for approximately 10-15% of S. aureus infections. Polymicrobial infections occur in 10-15% of cases. Culture-negative PJI occurs in 10-20% despite infection.
Exam Pearl
Q: Which organism is characteristically associated with open fractures with soil contamination?
A: Clostridium perfringens (and other Clostridium species) causing gas gangrene. Also consider: Gram-negatives (E. coli, Pseudomonas in water contamination), anaerobes (Bacteroides), fungi in immunocompromised. This is why metronidazole is added to cefazolin + gentamicin for farm/soil-contaminated open fractures. Gas gangrene has mortality of 25-50%.
Exam Pearl
Q: What organism is most commonly associated with diabetic foot osteomyelitis?
A: Polymicrobial infection is most common (70-80%). Typical organisms: S. aureus (including MRSA), Streptococcus, Enterococcus, Gram-negatives (E. coli, Pseudomonas, Proteus), and anaerobes (Bacteroides, Peptostreptococcus). Deep tissue cultures (not superficial swabs) are essential for accurate identification. Empiric therapy must cover Gram-positives, Gram-negatives, AND anaerobes.
Exam Pearl
Q: What is the typical organism causing chronic osteomyelitis with sinus tract formation?
A: Staphylococcus aureus (50-70% of cases). Coagulase-negative staphylococci (10-20%), Pseudomonas aeruginosa (waterborne exposure), and Gram-negative enterics (decubitus ulcers, genitourinary source) are also common. Sinus tract cultures are unreliable (surface colonizers); deep bone cultures required. Consider TB and fungal osteomyelitis in immunocompromised or endemic areas.
Exam Pearl
Q: Which organism should be suspected in a patient with sickle cell disease presenting with osteomyelitis?
A: Salmonella species (40-50% in sickle cell patients vs 1% in general population). S. aureus remains common (40%) but Salmonella is disproportionately over-represented. Mechanism: functional asplenia and bowel ischemia lead to Salmonella bacteremia. Also consider Streptococcus pneumoniae. Blood cultures and bone biopsy essential for diagnosis.
Australian Context
Australian Antibiotic Guidelines
Therapeutic Guidelines (eTG)
Key Australian references:
- Therapeutic Guidelines: Antibiotic (eTG Antibiotic)
- Updated regularly with Australian resistance data
- PBS prescribing aligns with eTG recommendations
eTG empirical recommendations:
- Septic arthritis: Flucloxacillin 2g IV q6h
- PJI: Vancomycin + piperacillin-tazobactam
- Osteomyelitis: Flucloxacillin (MSSA), vancomycin (MRSA)
Australian Resistance Patterns
MRSA prevalence in Australia:
- Community-acquired MRSA: 15-20% of S. aureus
- Healthcare-associated MRSA: 20-30%
- Higher in remote/Indigenous communities
Unique Australian strains:
- Queensland clone (ST93) - community MRSA
- WA MRSA strains
- Generally susceptible to cotrimoxazole, doxycycline
PBS Antimicrobial Access
PBS Authority Requirements for Key Antibiotics
| Antibiotic | PBS Status | Authority Required | Indication |
|---|---|---|---|
| Vancomycin IV | Authority | Streamlined | Serious Gram-positive infection |
| Daptomycin | Authority | Phone required | MRSA with vancomycin intolerance |
| Linezolid | Authority | Phone required | VRE or MRSA alternatives |
| Meropenem | Authority | Streamlined | Serious Gram-negative infection |
| Rifampicin | Authority | Streamlined | Bone/joint infections |
Australian prescribers should follow eTG recommendations and understand PBS authority requirements for specialized antibiotics.
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Classification Viva Question
"How do you classify orthopaedic pathogens and why is this clinically useful?"
COMMON ORTHOPAEDIC PATHOGENS
High-Yield Exam Summary
Overall Most Common Pathogens
- •S. aureus: 30-50% of acute osteomyelitis and septic arthritis (MOST COMMON)
- •Coagulase-negative Staph (CoNS): 50-70% of chronic PJI (S. epidermidis dominant)
- •Streptococcus species: 15-20% (Groups A, B, C, G)
- •Gram-negative bacilli: 10-20% (E. coli, Pseudomonas, others)
- •Polymicrobial: 10-20% (diabetic foot, open fractures, chronic wounds)
Staphylococcus aureus (Most Important)
- •Gram-positive cocci in clusters, coagulase-positive, catalase-positive
- •Virulence: Adhesins, protein A, coagulase, hemolysins, toxins (PVL in CA-MRSA)
- •MSSA treatment: Flucloxacillin 2g IV q6h or cefazolin (SUPERIOR to vancomycin)
- •MRSA treatment: Vancomycin 15-20 mg/kg q8-12h (trough 15-20), or daptomycin, linezolid
- •Never use vancomycin for MSSA - beta-lactams are better
Coagulase-Negative Staph (CoNS)
- •S. epidermidis most common (70-80% of CoNS)
- •Dominant in chronic PJI (50-70%), shoulder infections (30%)
- •Biofilm formation on implants - difficult to eradicate
- •Low virulence, indolent presentation (months to years)
- •Diagnosis: ≥2 positive cultures same organism (MSIS criteria)
- •Treatment: Check susceptibilities, vancomycin if resistant, add rifampicin for biofilm
Gram-Negative Bacilli
- •E. coli: Most common GNB (40-50% of GNB), UTI/GI source, vertebral osteomyelitis
- •Pseudomonas: Puncture wounds (nail through shoe), water contamination, requires antipseudomonal coverage
- •Salmonella: Sickle cell disease (50x increased risk, 50% of osteomyelitis in SCD)
- •Enterobacteriaceae: Elderly, diabetic, immunosuppressed (10-20% overall)
- •ESBL producers: Resistant to cephalosporins, use carbapenems
Special Pathogens by Scenario
- •Kingella kingae: Children under 4 years (30-50% of septic arthritis), fastidious, PCR helps
- •Cutibacterium acnes: Shoulder arthroplasty (30-40%), anaerobic culture + extended incubation required
- •Streptococcus: Group A (necrotizing), Group B (neonates), Groups C/G (septic arthritis)
- •N. gonorrhoeae: Sexually active young adults, DGI (tenosynovitis, polyarticular)
- •Pasteurella: Cat/dog bites, rapid onset (24-48h)
Anaerobes and Fungi
- •Cutibacterium acnes: Shoulder infections, 7-14 day incubation needed
- •Clostridium perfringens: Gas gangrene (emergency - debridement + penicillin + clindamycin)
- •Bacteroides fragilis: Diabetic foot, GI flora
- •Candida: Immunosuppressed, vertebral osteomyelitis in IVDU
- •Request anaerobic cultures specifically (not routine)
MRSA Key Points
- •Prevalence: 10-60% (know your local rates)
- •Two types: HA-MRSA (multidrug resistant), CA-MRSA (PVL+, more virulent)
- •Empiric coverage: If MRSA risk greater than 10-20%, recent healthcare exposure, risk factors
- •Treatment: Vancomycin (first-line), daptomycin (severe), linezolid (oral option)
- •De-escalate to flucloxacillin if MSSA (beta-lactams superior to vancomycin)
Culture Optimization
- •5-7 tissue samples for PJI (MSIS criteria), deep tissue not swabs
- •Hold antibiotics before cultures if possible (2-4 hour delay acceptable)
- •Anaerobic cultures: Shoulder, diabetic foot, chronic wounds (request specifically)
- •Extended incubation: 7-14 days for fastidious (Cutibacterium, Kingella, fungi)
- •Culture-negative 10-30%: Prior antibiotics (most common), fastidious organisms, biofilm
- •PCR/molecular: Culture-negative PJI, Kingella detection, TB diagnosis
Empiric Therapy by Scenario
- •Acute osteomyelitis/septic arthritis: Flucloxacillin (or vancomycin if MRSA risk)
- •Prosthetic joint infection: Vancomycin + gram-negative cover (ceftriaxone)
- •Diabetic foot: Broad-spectrum (pip-tazo or amox-clav + cipro) for polymicrobial
- •Sickle cell: Ciprofloxacin or ceftriaxone (covers Salmonella AND S. aureus)
- •Pediatric under 4 years: Ceftriaxone (covers Kingella, S. aureus, Strep)
- •Open fracture: Cefazolin + gentamicin (or pip-tazo)