A 4-year old with pitchfork injury to his knee

Kelly Henrickson, MD Rodney Willoughby, Jr., MD Pediatric Infectious Diseases [email protected]

• 15 days earlier, stuck in the R knee by a manure-laden pitchfork • Washed w/ soap & water, antiseptic spray, bandaid • D-14, swelling + decreased motion.

PMD: ceftriaxone • D-13, stopped walking. Amox/clavulonate • D-12, hospitalized. Knee aspirated. Pip/tazobactam + tobramycin • D-11, MRI: articular foreign body

PMH FH SH ROS

• Bilateral myringotomy tubes in past • Heart disease, diabetes in family • Lives on dairy farm w/ M,F, 5yo brother, dog • Immunizations up to date

Physical Exam

• Caucasian boy, in pain • T 100.6 VSS • R knee swollen, decreased motion, “half dollar-sized” red patch, medial puncture site • Remainder of exam was normal

Laboratories

• CBC WBC 6,600 Hgb 11.8

• ESR=70 6B 45S 41L 7M 1E Platelets 334,000 • Joint fluid: yellow WBC 34,000 97S 1L 2M RBC 2,300 • Knee XR: Soft tissue swelling • MRI: intra-articular foreign body. No osteomyelitis

Differential diagnosis?

Recommendations?

• D-11, Joint fluid: Bacillus spp.

Blood culture w/o growth • D-10, Increased swelling. I&D • D-9, Joint fluid: Enterococcus fecalis • D-8, sent home on IV pip/tazo + tobra ..... Crawls at home x 6 days ......

• D-2, increased pain.

• D-1, increased warmth. No swelling, redness.

Knee XR: no osteomyelitis • D-0, Increased ESR. Transferred.

Exam at CHW

• Afebrile, VSS • Right lower extremity surgical incision wound is appropriately healed. There is effusion noted. Range of motion of the knee is painful, able to achieve range from 10-100 degrees.

Laboratories at CHW

• WBC 6,600 • ESR 70 5,500 49S 32L 17M >100 • CRP 6.8

• Joint fluid: “many PMNs. No organisms.” • Blood culture: no growth

• Knee XR: There is a mild amount of soft tissue swelling with an effusion and irregularity involving the right tibial epiphysis that is most likely developmental in nature.

• MRI of R leg: Large joint fluid accumulation within the knee with thickening of the suprapatellar bursa. After intravenous administration of gadolinium, there is intense enhancement of the synovium diffusely.

In the medial condyle of the femur, there is a defect going through the cartilaginous component to the bony ossification center. This extends over approximately 1.5 cm length ... and likely reflects fluid tracking along this area. The posterior cartilage component shows mild increased signal on T2's and does enhance slightly. The bone enhances to a slight degree as well.

CHW: Differential diagnosis?

Recommendations?

Hospital course

• Piperacillin/tazobactam started • D1, I&D #2: loculated pus Add vancomycin ... High fevers ..Cultures negative ...

• D2, ID consult: add amikacin • D3, I&D #3: clear ... High fevers • D5, I&D #4: closed wound • ... High fevers ... generalized rash ...

CHW: Differential diagnosis?

Recommendations?

Hospital course

• D5, stop antibiotics for rash. Start clindamycin + ciprofloxacin + cefepime.

Serologies for histo/cocci/blasto/aspergillus • D7, “better” • D8, fever better, patient worse Discharge planning • D9, fever better, pain worse, patient screaming

CHW: Differential diagnosis?

Recommendations?

• MRI: Today's examination shows interval placement of a Penrose drain within the suprapatellar bursa. Diffuse extensive synovial enhancement is redemonstrated. There is a new approximately 4 x 2 x 4 cm fluid collection superior to the suprapatellar bursa and superomedial to the knee which is suspicious for a soft tissue abscess. Although the drain is just adjacent to the inferior border of this fluid collection, there may be septations which prevent appropriate drainage. There is continued abnormal signal and enhancement in the medial femoral condyle consistent with osteomyelitis. There is no evidence of bone abscess.

• D10, I&D #5 Initially the previous incision site was opened on the medial aspect of the right knee, this was extended up approximately 8-10 cm into the area of the vastus medialis. There was a lot of necrotic tissue in this area extending up just anterior to the distal femur and beneath the quadriceps muscle.

There was a large defect in the medial femoral condyle, the edges were débrided and it was evident that the infection carried down into the femoral epiphysis in the area of the medial femoral condyle. This was débrided back to stable bony tissue; all of the necrotic bone in the area was removed using a curet. The articular cartilage of the femoral medial condyle had a full thickness transverse split at the mid aspect of the condyle and this had no bony backing following the bony debridement. The condylar cartilage was left in place in an effort to spare further cartilage loss.

Hospital course

• D10, new rash following surgery Stop cefepime and cipro. Keep clinda.

Start meropenem • D11, fungus reported from epiphyseal culture(s)

Hospital course

• D12, I&D #6: no additional curettage • D13, probable Trichophyton spp.

Add terbinafine antifungal PO • D14, I&D #7: primary closure • D15, afebrile, “better” • D16, patient again better, smiling Discontinue antibacterials

Cow paddy microbiology

• Rumen as very complex ecosystem – bacteria, archaea, yeasts, ciliates • Methane; Waste treatment of cow effluent – Crops and E.coli 0157: H7 • M. avium subsp. paratuberculosis – Crohn’s disease?

– present in 3% of retail whole milk (CA, MN, WI)

Cow paddy microbiology

• Pseudallescheria boydii • Trychophyton verrucosum • Trychophyton mentagrophytes

Use of CRP

• Predictor of infection • Predictor of complications

CRP in

bone

& joint infections

Kallio, MJ Pediatr Infect Dis J 1997; 16: 411-413 Peltola, H. Pediatrics 1997;99:846-850 see also: Roine, I Pediatr Infect Dis J 1995; 14 40-44 Unkila-Kallio, L Pediatrics 1994; 93: 59-62

Our patient

14 12 10 8 6 4 2 0 -21 I & D Cultures positive CRP -14 -7 0 7 Day of CHW hospitalization 14 21

When septic arthritis doesn’t respond

• Osteomyelitis!

• Foreign body?

• Pharmacokinetics/dynamics – Piperacillin/tazobactam • Polymicrobial infection (this patient) – Enterococcus – Bacillus spp.

– Trychophyton mentagrophytes – M. avium subsp. paratuberculosis

Long term plan

• Terbinafine x 3 months – Safer, cheaper alternative after that: griseofulvin, fluconazole, itraconazole, voriconazole • Duration for septic arthritis + osteomyelitis?

– Concern? relapse >5%, abnormal growth, loss of function, malignancy, amyloidosis – > 3 weeks, always – subacute/chronic presentation: longer

Medicine as science

• Need for competing hypothesis (p=0.05) – Joint is sterile, but patient is worse • Use the bioassay in front of you – Laboratory tests confirm or rebut

your hypothesis

• Know your assays – Lag in CRP – Range of CRP • Practice due diligence – Cow paddy microbiology

Cow paddy microbiology

1: Chatterjee A, Chakrabarti A, Chatto-Padhyay D, Sen Gupta DN. Isolation of dermatophytes from dung.

Vet Rec. 1980 Oct 25;107(17):399. No abstract available. 2: Bernstein CN, Blanchard JF, Rawsthorne P, Collins MT. Population-based case control study of seroprevalence of Mycobacterium paratuberculosis in patients with Crohn's disease and ulcerative colitis.

J Clin Microbiol. 2004 Mar;42(3):1129-35. 3: Collins MT, Sockett DC, Goodger WJ, Conrad TA, Thomas CB, Carr DJ. Herd prevalence and geographic distribution of, and risk factors for, bovine paratuberculosis in Wisconsin.

J Am Vet Med Assoc. 1994 Feb 15;204(4):636-41. 4: Ellingson JL, Cheville JC, Brees D, Miller JM, Cheville NF. Absence of Mycobacterium avium subspecies paratuberculosis components from Crohn's disease intestinal biopsy tissues.

Clin Med Res. 2003 Jul;1(3):217-26.

Cow paddy microbiology

5: Ellingson JL, Anderson JL, Koziczkowski JJ, Radcliff RP, Sloan SJ, Allen SE, Sullivan NM. Detection of viable Mycobacterium avium subsp. paratuberculosis in retail pasteurized whole milk by two culture methods and PCR.

J Food Prot. 2005 May;68(5):966-72. 6: Verweij PE, Cox NJ, Meis JF. Oral terbinafine for treatment of pulmonary Pseudallescheria boydii infection refractory to itraconazole therapy.

Eur J Clin Microbiol Infect Dis. 1997 Jan;16(1):26-8. No abstract available. 7: Franz E, van Diepeningen AD, de Vos OJ, van Bruggen AH. Effects of cattle feeding regimen and soil management type on the fate of Escherichia coli O157:H7 and salmonella enterica serovar typhimurium in manure, manure-amended soil, and lettuce.

Appl Environ Microbiol. 2005 Oct;71(10):6165-74.

Cow paddy microbiology

8: Lebuhn M, Effenberger M, Garces G, Gronauer A, Wilderer PA. Hygienization by anaerobic digestion: comparison between evaluation by cultivation and quantitative real-time PCR.

Water Sci Technol. 2005;52(1-2):93-9. 9: Miyatake F, Iwabuchi K. Effect of high compost temperature on enzymatic activity and species diversity of culturable bacteria in cattle manure compost.

Bioresour Technol. 2005 Nov;96(16):1821-5. 10: Jiang X, Islam M, Morgan J, Doyle MP. Fate of Listeria monocytogenes in bovine manure-amended soil.

J Food Prot. 2004 Aug;67(8):1676-81.

Cow paddy microbiology

11: Dorner SM, Huck PM, Slawson RM. Estimating potential environmental loadings of Cryptosporidium spp. and Campylobacter spp. from livestock in the Grand River Watershed, Ontario, Canada.

Environ Sci Technol. 2004 Jun 15;38(12):3370-80. 12: Bradford SA, Schijven J. Release of Cryptosporidium and Giardia from dairy calf manure: impact of solution salinity.

Environ Sci Technol. 2002 Sep 15;36(18):3916-23. 13: Bell RG. Comparative virulence and immunodiffusion analysis of Petriellidium boydii (Shear) Malloch strains isolated from feedlot manure and a human mycetoma.

Can J Microbiol. 1978 Jul;24(7):856-63. 14: Miller RW, Pickens LG, Gordon CH. Effect of Bacillus thuringiensis in cattle manure on house fly larvae.

J Econ Entomol. 1971 Aug;64(4):902-3. No abstract available.

CRP in bone & joint infections

(1) Hammer HB, Kvien TK, Glennas A, Melby K. A longitudinal study of calprotectin as an inflammatory marker in patients with reactive arthritis. Clin Exp Rheumatol 1995; 13(1):59-64.

(2) Kallio MJT, Unkila-Kallio L, Aalto K, Peltola H. Serum C-reactive protein, erythrocyte sedimentation rate and white blood cell count in septic arthritis in children. Pediatr Infect Dis J 1997; 16(4):411-413.

(3) Khachatourians AG, Patzakis MJ, Roidis N, Holtom PD. Laboratory monitoring in pediatric acute osteomyelitis and septic arthritis. Clin Orthop Relat Res 2003;(409):186-194.

(4) Kocher MS, Mandiga R, Murphy JM, Goldmann D, Harper M, Sundel R et al. A clinical practice guideline for treatment of septic arthritis in children: efficacy in improving process of care and effect on outcome of septic arthritis of the hip. J Bone Joint Surg Am 2003; 85-A(6):994-999.

(5) Levine MJ, McGuire KJ, McGowan KL, Flynn JM. Assessment of the test characteristics of C-reactive protein for septic arthritis in children. J Pediatr Orthop 2003; 23(3):373 377.

(6) Martinot M, Sordet C, Soubrier M, Puechal X, Saraux A, Liote F et al. Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients. Clin Exp Rheumatol 2005; 23(3):303-310.

(7) Peltola H, Unkila-Kallio L, Kallio MJ. Simplified treatment of acute staphylococcal osteomyelitis of childhood. The Finnish Study Group. Pediatrics 1997; 99(6):846-850.

CRP in bone & joint infections

(8) (8) Roine I, Faingezicht I, Arguedas A, Herrera JF, Rodriguez F. Serial serum C-reactive protein to monitor recovery from acute hematogenous osteomyelitis in children. Pediatr Infect Dis J 1995; 14(1):40-44.

(9) Roine I, Arguedas A, Faingezicht I, Rodriguez F. Early detection of sequela-prone osteomyelitis in children with use of simple clinical and laboratory criteria. Clin Infect Dis 1997; 24:849-853.

(10) Unkila-Kallio L, Kallio MJ, Eskola J, Peltola H. Serum C-reactive protein, erythrocyte sedimentation rate, and white blood cell count in acute hematogenous osteomyelitis of children. Pediatrics 1994; 93(1):59-62.

(11) Unkila-Kallio L, Kallio MJ, Peltola H. The usefulness of C-reactive protein levels in the identification of concurrent septic arthritis in children who have acute hematogenous osteomyelitis. A comparison with the usefulness of the erythrocyte sedimentation rate and the white blood-cell count. J Bone Joint Surg Am 1994; 76(6):848-853.