Disclosures. Orthopedic infections. Case 1. Pen Barnes MBBS PhD. Clinical Associate Professor Departments of Medicine Pathology and Orthopedics OHSU

Transcription

1 Orthopedic infections Disclosures Pen Barnes MBBS PhD I have nothing to disclose Clinical Associate Professor Departments of Medicine Pathology and Orthopedics OHSU Case 1 48 year old woman presents to ED with recurrent cellulitis over lower right shin 25years previously and fractured tibia Plates and screws removed two years later Totally well until 3 episodes of cellulitis over the shin in the past year? What is happening? Bone infection Altered dynamic between osteoblasts and osteoclasts Bacteria invade osteoblasts Differentiaton into osteoclasts rather than blasts Bacteria invade down blood vessels bone infarct TRENDS in microbiology Lancet

2 Normal bone resistant to infection Large inoculum Foreign body Trauma Origins of infection in order of decreasing frequency Acute osteomyelitis < 10 days of clinical signs Pus travels down vascular channels- ischemia Chronic > 10 days: avascular necrosis of bone: formation of sequestrum (dead bone): no osteocytes Contiguous focus of infection after trauma surgery or insertion of a joint prosthesis (1-3%) Secondary to vascular insufficiency (diabetic foot infections) (funny bugs) Hematogenous origin Lancet Lancet What happens to the organisms within infected bone? Areas of dead bone and/or prosthetic material =reduces inoculum by 100,000 1 Intracellular bugs: antibiotics don t penetrate 2 Dead bone/ Prosthetic material Quorum sensing & Biofilm formation 1. J.Orthop Sc : J Infect Dis May;125(5): Nature Reviews Molecular Cell Biology

3 Quorum sensing Bacteria make and release chemicals Chemical concentrations increase with bacterial load Sensed by other bacteria: genes up and down regulated Bacterial colony acts in unison Unicellular Multicellular Biofilm formation Quorum sensing Mating + Fratricide: resistance exchange & diversity Virulence factors: Co-ordinated killing of host cells Cell E.faecalis Cell Biofilm : matrix of extracellular polymeric substance NEJM 351 (16): 1645 Quorum sensing in biofilm.. Nature Reviews Drug Discovery , Am Sci , : 508

4 Small colony variants: Phenotypic resistance Difficult to detect organisms Bacterial growth hidden from human inflammatory response and the lab Osteomyelitis and Prosthetic joint infection Difficult to treat organisms Phenotypic and genotypic resistance Getting at the bugs in their slime Few clinical trials for surgical and antibiotic approaches SCV: Columbia agar: grew 2-3 days: small colonies Decreased pigmentation weak haemolysis CID : Diagnostic techniques Removal of biofilm and Slime busting antibiotics Multidisciplinary team of ID and orthopedics team Osteomyelitis causes S.aureus Coag neg staph Enterobactereacae & Pseudomonas Salmonella Pneumococcus Bartonella Pasturella/ Eikenella TB Brucella /Coxiella/ Meiliodois Pseudomonas Commonest Prosthetic material Hospital acquired Sickle cell HIV Bite TB endemic area Geography Sneaker Lancet Diagnosis of Osteomyelitis Clinical History Risk factors Symptoms of inflammation: redness, erythema pain recurrent ulcer/ drainage Physical Exam Inflammation & pain decreased range of motion Scabs, sinus tracts, ulceration, drainage

5 Radiology Plain films X-ray Bone destruction is not apparent on plain films until after days of infection Eur Radiol 12 (2002), pp Looking for: Periosteal reaction Cortical destruction Articular damage Radiology: should I get an MRI or CT? Both reveal the destruction of medulla as well as periosteal reaction, cortical destruction, articular damage, CT needle biopsy. excellent definition of cortical bone identification of sequestra. MRI early bony edema: early detection of infection. MRI most sensitive: not helpful in assessing the response ( stays positive or a year after infection/ surgery) Lancet Microbiology: negative cultures 1. Recent antibiotics Don t give antibiotics before biopsy unless really sick 2 Unculturable organisms Propionobacteria Fungi AFB Brucella, Bartonella University of Washington 16s Ribosomal Pan-bug scan 3. Enrichment media appropriate work-up Treatment individualized Surgical debridement of dead bone and prosthetic material Antibiotics for a long time Underlying contributing medical conditions: Diabetes Peripheral vascular disease

6 Excellent OK Systemic antibiotics Bone penetration Rifampin Ciprofloxacin Clindamycin Fusidic acid Tetracycline Beta-lactam Vancomycin Daptomycin Bactrim Biofilm penetration Rifampin Ciprofloxacin Daptomycin Vancomycin Beta-lactam Bactrim Tetracycline Poor Aminoglyc Clindamycin Adapted from J.Infect Quinolones & Rifampin Cidal Intracellular penetration Biofilm busters Good bone penetration Rifampin only useful in Staph Cipro Staph & gram negative rods S.aureus in biofilm Without Rifampin With Rifampin Antimicrob agents Chemother 2002, patients Staphylococus infection stable orthopedic implants < 2 months since implant < 21 days symptoms Debridement + 2 week IV fluclox/vanco+ rifampin then po cipro + Rif (100% cure) or cipro alone (50% cure) JAMA Staphylococcus spontaneous mutation rate is 1 x 10 7 for rifampin and ciprofloxacin A tiny abscess may contain >1x10 10 bacteria Plate containing rifampin or ciprofloxacin inoculated with 10 9 Staphylococcus sensitive to rifampin and cipro Science ; Cause Rifampin and Ciprofloxacin cautions Spontaneous mutations Resistance Drug interactions with rifampin Absorption of cipro Advice NEVER use drugs alone Timing in introducing drugs into antibiotic regime Rifampin 10% cipro 30% resistance in community NEVER use empirically without organism isolation and sensitivity results Increases effect of opiates coumadin Liver enzyme abnormalities Bound in the gut by calcium Iron and magnesium and not absorbed Science ; Antimicrob agents Chemother 2008

7 Why not other oral agents? Clindamycin Good bone penetration but poor biofilm penetration Static : Failure to cure Staph bacteremia -Follow-on/suppressive therapy -Combination for spinal disease Bactrim Tetracycline Cidal & Anecdotal evidence that very effective 2 double strength q 8 hours for 6 months Poorly tolerated Good penetration into bone and possibly biofilm Static Mutational resistance :In combination Follow-on therapy/suppression. No randomized trial Antibiotic treatment < 4 weeks thought to have high likelyhood of failure (10% success rate) Antibiotics: According to the sensitivity of the organism Current standard of care: (largest experience but still failure): IV antibiotics Gram positive: vancomycin or betalactam +/- rifampin Gram negative beta-lactam or quinolone Standard of care 6 weeks IV Lancet year old woman presents to ED with recurrent cellulitis over lower right shin 25 years previously and fractured tibia Plates and screws removed two years later Totally well until 3 episodes of cellulitis over the shin in the past year? What is happening? Our patient Biofilm organisms have woken up in an old screw site MRI Hold antibiotics and obtain deep bone biopsies Remove all dead bone Antibiotics 66 year old man presents to your medicine clinic Had hip replacement 3 months ago Increasing pain Loosening on x-ray ESR 30 CRP normal Scar is well healed with no redness Orthopedic surgeon concerned about infection Your patient asks you What does this mean? It does not look like an infection to me Will I be able to keep the hip?

8 Microbiology PJI 30% Acute < 12 weeks since surgery pain effusion erythema S.aureus Gram negative rods E.coli 40% Late > 12 weeks 24 month low grade subtle implant loosing? Aseptic failure Indolent and difficult to grow bacteria Coagulase negative Staphylococcus Corynebacteria Propionobacteria 30% Very late Acquired by hematogenous seeding 30% S.aureus E.coli The weird Salmonella Pasturella Distinguishing contamination from infection Swab of sinus tract < 50% concordance with bone cultures BMC Infect Dis 2002; 16:2 8 5 samples per patient with 3 or > positive is highly predictive of infection J Clin Micro 1998; 36: Microbiology Sensitivity only 60% Improving sensitivity Swabs fail to grow fastidious organisms and anaerobes CLSI 2010 Prolonged culture for 10 days improves yields of fastidious organisms Clin Infect Dis : Sonication of prosthetic material 78% sensitivity even after recent antibiotics NEJM 2007 :357; Revision Options and Outcomes for PJI Revision Single stage Debridement & retention of implant or exchange 2 stage Remove all hardware antibiotics for 6 weeks wait and then replace Arthrodesis/ girdle stone) Amputation Success rate 3 years 78% success Stopping antibiotics or S.aureus worse outcome J. Antimicro Chemo : With biofilm active antibiotics 100% success (Swiss mountain goat study) JAMA % hips 97% knees NEJM ; Mobility Time course of two stage infected hip/ knee prosthesis Knee explanted Start IV antibiotics Stop antibiotics Sample knee Knee re-implanted Rehab of less well functioning knee Jan 1st Feb 15th April 1st April 15th October 15th

9 Case 3 44 year old man presents with fever Back pain. ED plain film spine normal. weak all over Admitted to ICU hypotension ARF Blood cultures positive for Staphylococcus aureus MRI scan total spine: no obvious focus He continues to complain of back pain Over next 72 hours is complaining of worse leg weakness However non-cooperative with exam due to pain What should you do next? Bacterial causes Spinal osteo S.aureus most common (15-84%) GNR TB Anerobes: diabetes fungi Discitis S.aureus Coag neg staph- surgery J.Infect GNR Diagnosis Spinal osteomyelitis/discitis Our patient 5 days later Unable to see on plain films for 8 weeks 1 MRI most sensitive ( 93-96%) 1 & visualization of epidural space 50% cases spondylodisctis seen on MRI first 2 weeks 20% in another 2 weeks 2 1.AJR : Med mal Inf : Repeat MRI scan early if still unexplained symptoms

10 Epidural abscess Microbiological diagnosis Collection of pus between dural mater and overlying vertebral column triad of fever, back pain and neurological damage: only seen in 10-15% cases Complication: Direct pressure on the cord Thrombosis of spinal artery Blood cultures positive in 60% cases CT guided biopsy : 60-70% sensitivity Recommend multiple samples & repeat 2x if necessary Open biopsy sensitivity 75% Paralysis SPEED IS THE ESSENCE 1.J.Infect Rheumatology Med mal Inf : Differential diagnosis by MRI findings Should I get an echo on patients with spinal osteo? MRI Finding Contiguous vertebral bodies+ intervertebral disc Contiguous vertebral bodies sparing the disc Non-contiguous vertebral bodies sparing disc Lower thoracic and ant vert body Sacroilietis arthritis + spondoylitis Diagnosis Usual pyogenic infection (Staph Strep) TB Malignancy TB Brucella Spondylodisctis with IE : % cases 1 Appears to be more common with Strep discitis 1 One study 26% of discitis cases with Strep had IE Whilst only 2% o those with Staph had IE 2 1.J.Infect J. Rheum

11 Vertebral osteo treatment 50-75% respond without surgery 6 weeks Abx = 12 weeks of antibiotics Indications for Surgery Neurological deficit Persistently positive blood cultures or sepsis Paraspinal collection if > 5cm should be drained Same antibiotics as for osteomyelitis except clindamycin very good disc penetration Bone infections: Bugs on a camping expedition Adrian Weinbrecht Follow-up imaging: lack of correlation with clinical outcome: looks worse Lancet : J.Infect Rheumatology Med mal Inf : Am J Neuroradiol : Thank you