1、,Bone and Joint Infections,July, 2010,Case 1,A 12 year old female soccer player sustained a nasty bruise below her R knee during a particularly physical game. Two weeks later she complained of increased pain over the area accompanied by a low grade fever and sweats. She didnt tell her parents. Her c
2、oach told her to quit complaining. However, her symptoms persisted and 2 weeks later she went to her pediatrician. Physical exam revealed a temperature of 38 C and a slightly swollen and warm left proximal tibia.,Case 1,What tests would you order?,Plain film, blood culture, ESR,Case 1,,Case 1,What t
3、ests might have been positive 2 weeks earlier?,Bone scan, WBC scan, AB-CD15 scan, Gallium scan, MRI,Case 1,,Case 1,What is the most likely organism?Do you need to perform a needle biopsy for diagnosis?How would you treat this patient? Does she need debridement? Which antibiotics and for how long?,S.
4、 aureus streptococci,BC+: no. Needle biopsy culture sensitivity 80%, Histopathology increases yield,Antibiotics, probably not, many choices; nafcillin, ceftriaxone. Empiric treatment for MRSA?,Case 1,Would oral antibiotics be acceptable?,YES: Zaoutis T, et.al, 2009, Pediatrics;123:636-42 Retrospecti
5、ve cohort of children 2-17 years old, cared for at 29 childrens hospitalsN=1969, IV 1021, oral 948Failure: IV 5%, oral 4% AEs: 3.4% of children on IV therapy admitted with catheter complications,Case 2,A 26 year old thrill-seeker suffered an open fracture of his right tibia and fibula while roller-b
6、lading behind a motorcycle driven by his ex-girlfriend. The fracture was reduced and fixed with the placement of screws, plates and rods. He did remarkably well until 4 months later when he noted a pimple followed by a little drainage from one of wounds. Four days later he was chasing his ex-girlfri
7、end up some stairs and heard a loud crack and looked down to find hardware and bone protruding through his right leg.,Case 2,Why did his leg break (the second time)?What is the most likely bug?What specimens do you want sent to the lab? Can you rely on cultures taken from the sinus tract?,Pathologic
8、 fracture,S. aureus, CoNS GNR,Bone cultures,Generally no If S. aureus or single organism - some + predictive value,Diagnosis - Culture,Gold standard is open bone biopsy for histopathology and culture. Needle biopsy has a sensitivity of 87% and a specificity of 93%. However, in the post-operative or
9、post-trauma setting its performance is compromised. Histopathology of needle biopsy yields diagnosis even if a specific organism is not identified,Diagnosis - Culture,Superficial or sinus tract cultures correlate poorly with bone cultures in most studies ( 50%). Perry (1991) found a 62% correlation
10、between wound swab and operative cultures and a 55% correlation between needle biopsy and operative cultures. Better correlation demonstrated for mono-microbial infections (80 and 76%) and S. aureus infections (69% and 74%). Bottom line: dont trust sinus cultures unless the results yields a single o
11、rganism or S. aureus,Case 2,Should all the hardware be removed or can the leg be set and he be treated with antibiotics alone?What antibiotics would you recommend, by what route and how long would you treat him?,Best: 2 or 3 step procedure: remove hardware, antibiotics, new hardware later Some succe
12、ss without removing hardware if infection detected early, sensitive bug,Vancomycin/rifampin/quinolone A long time,Case 2,Euba, AAC, 2009;53:2672-2676 Prosepctive, randomized trial of S. aureus, non-axial osteomyelitis Randomized to 1) IV cloxacillin for 6 weeks followed by oral cloxacillin for 2 wee
13、ks or 2) oral TMPSMX (3 DS bid) + rifampin 600 mg/d Results: Overall cure rate 89.6% (on protocol 92.9%) no difference b/n the groups Median follow up was 10 years! Relapses: at median of 9 months, associated with FB retention and not following the protocol,Would oral antibiotics be acceptable?,Coch
14、rane Review: 2009, Issue 3: Antibiotics for treating chronic osteomyelitis in adults 8 studies (257 patients), 5 studies compared IV to oral No significant difference in outcome at 12 months AEs: moderated-severe: IV 15.5%, oral 4.8%,Clinical Presentation,Cierny-Mader staging Anatomic stage Stage 1
15、medullary infection only, hematogenous spread or spread through an intramedullary prosthesis Stage 2 superficial infection, due to a contiguous soft tissue infection, could also be termed osteotis Stage 3 localized infection, full thickness infection (one cortex), bone integrity maintained Stage 4 d
16、iffuse infection (both cortexes), destabilizes bone (or resection would destabilize bone),Treatment,Cierny-Mader staging Stage 1 Antibiotics alone. Patients with rods in place require removal. Adults without hardware may require medullary reaming. Stage 2 Debride to bleeding bone and antibiotics Sta
17、ge 3 Follow principles of removal of necrotic bone, elimination of dead space and soft tissue coverage plus antibiotics Stage 4 Same as stage 3 plus fracture stabilization.,Case 3,A 72 yo male who underwent a right THR 6 months ago, then developed an enterococcal UTI 3 months ago and now presents wi
18、th low grade fevers and pain in the right hip that prevents ambulation.,Case 3,How should he be treated?,Two stage replacement with 2 - 6 wks between surgeries. Time between operations for tough-to-treat organisms - 6 to 8 wks. Stop abx 1 -2 wks before 2nd operation - if cultures neg - stop, if cult
19、ures +, continue abx for 3 months (6 months for knees).,Case 3,Imaging reveals a peri-prosthetic fluid collection Culture of this fluid grows MRSA and enterococcus,(Lew, Lancet, 2004),Case 3,If the cultures had been sterile at 3 days, what would you recommend?,Prolonged incubation for 15 days to ide
20、ntify Propionibacterium acnes (Zeller, 2007),Case 3,Are there situations when the prosthesis can be retained after debridement?,Symptoms 3 weeks Stable implant Easy to treat organismSuccess rates 82-100%,Case 3,Are there indications for single stage replacement?,Symptoms 3 weeks Soft tissue in good
21、shape No co-morbidities Easy to treat organismSuccess rates 86-100%,Treatment,Ciprofloxacin/rifampin for Osteomyelitis (Zimmerli, 1998) N=33, stable implants Staphylococcus All treated with debridement and 2 weeks of rifampin + vancomycin or flucloxacin Then either cipro/rifampin or cipro/placebo Pr
22、ostheses retained Median duration of symptoms 5d,Treatment,Prosthesis removed: hips (42%), knees (60%), bone plates (50%) All 11 failures occurred in patients with retained prostheses (8) or resistant staphylococcus (8) or both (6) (Drancourt 1993),Treatment,All had native bone infection or prosthes
23、is removal, all treated with 2 weeks of nafcillin, vancomycin or cefazolin initially - then ceftriaxone 2 gms/d for 4 to 5 weeks (Guglielmo, 2000),Case 4,A 39 year old IVDU reports to the ER with fever and back pain. He mixes his drugs with dirty tap water and does not prep his skin before injecting
24、. On exam his temperature is 39 C, he has a 3/6 holo-systolic murmur and tenderness over his thoracic spine on percussion. Neurological exam is initially normal.,Case 4,Diagnoses?Likely organisms?Initial antibiotics?Imaging studies?,Endocarditis, vertebral OM, epidural abscess,Staphylococcus strepto
25、cocci GNR fungi,Nafcillin and gentamicin or vancomycin and gentamicin,MRI,Case 4,The lab reports that 3/4 blood cultures have turned positive in 4 hours and are growing a GPC, the following day the lab reports that 2 blood cultures are also growing GNR. Likely organisms?The patient starts complainin
26、g of mid-thoracic radicular pain. What does this represent?,S. aureus streptococci; P. aeruginosa other GNR,Spinal ache - first sign of epidural abscess,Case 4,www.xray.2000,Tomogram,CT,MRI,Case 4,What do you recommend?What are indications for debridement of vertebral osteomyelitis?,MRI, decompressi
27、on (laminectomy or aspiration),Instability Abscess Cord compression Cervical infection Medical failure Neurological signs or symptoms,Case 4,By what route and for how long should abx be administered?What about follow up imaging?,No advantage of IV over oral abx (usually quinolones) Duration at least
28、 4 weeks Longer if hardware in place or abscesses are not drained,MR less than 4 weeks into Rx often look worse even in patients improving dont order! MR later dont follow bone changes often progress. Focus on epidural and soft tissue changes if these are equivocal or progress suggests failure (Kowa
29、lski, CID, 2006),Case 5,A 56 year old diabetic man visits his PCP for a routine visit. He is noted to have a 2.5 cm ulcer on the plantar surface of his foot at the first metatarsal head, extending up to the great toe. He was unaware of the ulcer although, in retrospect, he recalls that his socks hav
30、e been stained and foul smelling lately. He has not noted fevers or chills. His physician notes a hard, gritty surface at the base of the ulcer.,Case 5,Recommended work-up,In this case, plain films, ESR sufficient Of all imaging modalities - MR is most accurate(sensitivity 90%, specificity 80%) Comb
31、ination of WBC scan or ABscan with MRI can improve specificity,Diagnosis,The gold standard is histopathologic evidence for osteomyelitis with supporting microbiologic data However, in many cases the diagnosis rests on clinical, laboratory and radiographic data,Diagnosis,Sometimes its easy: Compatibl
32、e history and physical exam, elevated ESR, elevated WBC (acute osteomyelitis) Positive blood cultures (50% in cases of acute osteomyelitis) Classic radiographic findings,Diagnosis,In many cases the diagnosis is difficult Atypical presentations Non-specific symptomatology Co-morbid local and generali
33、zed conditions that confound and obscure the infection,Diabetic Foot Infections,What are exam findings that predict bone involvement? Larger ( 2cm, 92% specificity) and deeper ( 3mm) associated with osteomyelitis Probe to bone 66% sensitivity and 85% specificity, PPV around 55%, NPV 98% ESR 70: 100%
34、 specificity (only 28% sensitivity),(Grayson, JAMA,1995;273:721-3) (Newman, JAMA, 1991;266:1246-51) (Kaleta, J Am Pod Med Assoc, 2001;91:445-50) (Dinh, CID, 2008;47:519-27),Diabetic Foot Infections,What are the best imaging modalities? Plain film CT scan MRI scan Nuclear medicine studies,Diabetic Fo
35、ot Infections,Plain films Need 30 to 50% mineral loss for x-ray changes to be evident - takes at least 14 days Sensitivity 43-75%, specificity 75-83% Insensitive with acute osteomyelitis In chronic infection - sclerosis, periosteal elevation and sequestra.,(),(Lipsky, CID, 1997;25:1318-26),Diabetic
36、Foot Infections,CT Best method for detecting small areas of necrosis, gas, foreign bodies Metallic foreign bodies compromise the image,(www.xray.2000),Diabetic Foot Infections,MRI Sensitivity 82-100% Specificity 53-94% (tumors, fractures, post surgery, sympathetic edema, infarction all can look the
37、same; light up on T2 weighted image) BEST SINGLE TEST Location important - Heel and malleoli with ulcer = osteo Midfoot, joint-centered, no ulcer - Charcot Combine with Ind-111 WBC scans or gallium scans to increase specificity,(www.med.harvard.edu),(Eckman, JAMA, 1995;273:712-20) (Croll, J Vasc Sur
38、g,1996:24:266-70) (Craig, Radiology, 1997;203:849-55) (Enderle, Diabetes Care, 1999;22:294-9),Diabetic Foot Infections,Bone scan (TC-99 labeled phosphorus) Soft tissue infection will be positive in the immediate (blood flow) and 15 minute (blood pool) phases while osteomyelitis will be positive in t
39、hese 2 plus the delayed ( 4 hour) images. Sensitivity 69-100% ( 95% in acute osteomyelitis), specificity 38-82% (tumors, fractures, post-surgery, septic arthritis, Pagets disease, Charcot foot),(),(Eckman, JAMA, 1995;273:712-20) (Enderle, Diabetes Care, 1999;22:294-9),Diabetic Foot Infections,AB + W
40、BC scan (Ind-111) Will be positive prior to bone scan Useful p-surgery (better than MRI) which will always be abnormal When combined with bone scan has specificity in the 90% range, sensitivity in the 70% range and PP value in the 90% range,(www.nuclearonline.org),(Becker, QJ Nuc Med, 1999;43:9-20)
41、(Unal, Clin Nuc Med, 2001;26:1016-21),Newer Imaging Tests,Tc-99 monoclonal (Fab fragments) against CD-15: sensitivity and specificity 85% IND-111 biotin: used and concentrated in bacteria: sensitivity and specificity for vertebral OM 95% PET: better than WBC scans for chronic vertebral OM. Limited u
42、se in patients with diabetes and cancer,Case 5,What organisms are likely responsible for this infection?,(www.erc.montana.edu),Diabetic Foot Infections,Case 5,Recommended treatment,Surgical debridement (with bone cultures) Re-vascularization if needed Long-term abxRecent retrospective studies sugges
43、t abx alone may be sufficient treatment in many cases (Jeffcoate, 04),Diabetic Foot Infections,Which antibiotics should I prescribe and for how long?,(www.erc.montana.edu),Diabetic Foot Infections,Basic principles for choosing antibiotics: Should always include coverage for Gram-positive cocci, espe
44、cially S. aureus Add Gram-negative coverage for chronic wounds, for patients previously treated with abx and for wounds classified as moderate to severe Provide anaerobic coverage for obviously necrotic wounds or those with a feculent odor Narrow coverage based on culture results,(Lipsky, Clin Micro
45、 Infect, 2007;13:351-53),Diabetic Foot Infections,Basic principles for choosing antibiotics: Consider risk factors for MRSA when choosing Gram-positive coverage Coverage for enterococci usually not necessary unless it is the only organism isolated Coverage for Pseudomonas may also not be necessary u
46、nless the wound had been treated with hydrotherapy or Pseudomonas is present and the patient is not improving without anti-Pseudomonal treatment Avirulent organisms (e.g. coagulase negative staphylococci, Corynebacterium species) may become real pathogens in immunocompromised hosts with significant
47、tissue necrosis,(Lipsky, Clin Micro Infect, 2007;13:351-53),Recent Antibiotic Trials for DFI,Ertapenam Vs Piperacillin/tazobactam (SIDESTEP) (Lipsky, Lancet, 2005;366:1695-1702) R,DB,MCT, N=586. Mod-severe DFI (not osteo): 5 days or IV Ertapenam or Pip/tazo - then up to 23 days of amoxacillin-clavul
48、anic acid (could add vanco for MRSA or enterococus) Response rates at DCIV 94%/92%, at 10 day FUA 87%/83% No difference between groups in those with MRSA or PsA even if not on abx active against these organisms Linezolid Vs Amp-sulbactam or Amo-clavulinate (Lipsky, CID, 2004;38:17-24) R,OL,MCT, N=37
49、1, All types of DFI: Could add Vanco for MRSA and Aztreonam for GNR if either not covered by study medication Response rates: L/Pcn: Overall 81%/71% (NS), Subgroups with infected ulcer 81%/68% and those without osteo 87%/72% - both favor linezolid More anemia and thrombocytopenia in the linezolid gr
50、oup - all reversible,Recent Antibiotic Trials for DFI,Daptomycin Vs Vancomycin or Semi-synthetic Pcn (Lipsky, JAC, 2005;55:240-45) Randomized study, N=133, Infected ulcer (no osteo), Comparator was Vanco if MRSA suspected, could add aztreonam for GNR and metronidazole for anaerobes Response rates Da
51、pto/Comparator: Overall 66%/70% (NS), Dapto/SS-PCN 64%/70%, Dapto/Vanco 71%/69% Only one MRSA infection in the daptomycin group Moxifloxacin Vs Pip-Tazo/Amox-clav Subset analysis of P,DB study of 617 patients: only 78 with DFI were evaluable for cure 10-42 days after therapy Response rates Moxi/PT-AC 68%/61% Piperacillin/tazobactam Vs Ampicillin/sulbactam (Harkless, Surg Infect, 2005;6:27-40) P,R,OL,MCT, N=314, Mod-severe DFI (ulcers). If MRSA could use vanco Response rates P-T/A-C 81% 83%,
