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Osteomielitis en pie diabético

Renato Ocampo Avello Infectología HRT

“10% de los chilenos padece de diabetes”

“15-25% de los diabéticos tendrá úlceras en los pies”

“un cuarto de las úlceras se infectarán”

“20-50% de las úlceras infectadas tendrá osteomielitis”

http://web.minsal.cl/dia-mundial-de-la-salud-2016/ Ramsey SD, Newton K, Blough D, et al. Diabetes Care 1999;22:382-7

Osteomielitis en pie diabético

• Patología frecuente.

• Diagnóstico puede ser difícil en algunos casos.

• Curación difícil de obtener y documentar.

• Aumenta riesgo de amputación.

• Tratamiento ha evolucionado y tiene controversias

Uckay I, Aragon-Sanchez J, Lew D, Lipsky BA. Int J Infect Dis 2015;40:81-91. Berendt AR, Peters EJ, Bakker K, et al. Diabetes Metab Res Rev 2008;24 Suppl 1:S145-61.

Senneville E, Robineau O. Expert Opin Pharmacother 2017;18:759-65

Caso clínico• Mujer de 60 años

• Diabetes mellitus 2 (13 años de evolución), complicada con retinopatía.

• Úlcera en la cabeza del primer metatarsiano del pie derecho, de 2 meses de evolución.

• Afebril, con discreto eritema rodeando la úlcera. Pulsos palpables en ambas EEII.

• Hueso no visible, pero se palpa con estilete.

• GB: 6.600/mm3, VHS 80 mm/hr.

documents on the importance of prompt surgical intervention inmany DFIs, it is frequently delayed, sometimes leading toamputation.86,87 More conservative surgery for the treatment ofDFIs is now possible because we better understand the compart-mental anatomy of the foot and the ways in which infectionspreads.88,89 Furthermore, it is clear that there are more types offoot infection than just ‘abscesses’ and ‘diabetic gangrene’.90 Wenow also appreciate that combining needed ablative foot surgerywith prompt revascularization can improve the rate of limbsalvage.91 And, finally, new wound therapies have improved thepostoperative care for these patients.92

Any foot compartment affected by infection should be openedquickly to reduce the compartmental pressure.93 Contrary topreviously held beliefs, fascial planes do not constrain the spread of

infection.94 Although unproven, MRI may play a role in planningthe surgical approach.85,95 Unfortunately, there is no classificationthat defines either the point at which surgery is absolutelynecessary, or when it is likely to produce a better outcome thanfurther medical therapy.96–98 It is now clear, however, that in mostcases ‘conservative’ surgery (i.e., resection of just the affected bone,without amputation)96,99–101 or antibiotic therapy alone can treatosteomyelitis successfully.

The optimal timing of surgery for DFI is not well defined, butprompt surgery, including revascularization when necessary, mayreduce the need for above-ankle amputations.102–104 The rate ofsuccess, including avoiding lower extremity amputation, in DFIs,depends on the approach taken by the treating surgeon,105 whichoften reflects his or her experience and skills. When amputation is

Figure 5. Ulcer over the first metatarsal head: X-ray showing cortical destruction of the first metatarsal head.

Figure 6. Postoperative view: X-ray showing the bone that was removed.

I. Uckay et al. / International Journal of Infectious Diseases 40 (2015) 81–9186

Preguntas que uno se hace…• ¿tiene osteomielitis?

• ¿necesito pedir más exámenes?

• ¿solicito cultivos? ¿de qué?

• ¿qué tratamiento indico?

• ¿lo inicio ahora mismo?

• ¿por qué vía?

• ¿por cuánto tiempo la trato?

• ¿requiere tratamiento quirúrgico?

• ¿debe amputarse?

Clínica

• Úlceras ubicadas sobre prominencias óseas.

• Úlceras grandes (>2 cm2) o profundas (>3 mm).

• Úlceras persistentes (>6 semanas).

• Hueso visible o pérdida de fragmentos óseos a través de la herida.

• Hueso palpable a través de la herida.

• Dedo en salchicha.

Lipsky BA, Aragon-Sanchez J, Diggle M, et al. Diabetes Metab Res Rev 2016;32 Suppl 1:45-74. Uckay I, Aragon-Sanchez J, Lew D, Lipsky BA. Int J Infect Dis 2015;40:81-91.

Lipsky BA, Berendt AR, Cornia PB, et al. Clin Infect Dis 2012;54:e132-73.

Dedo en salchicha

Desempeño diagnóstico del examen físico

LR (+) LR (-) Observaciones

Úlcera >2 cm2 7,2 (1,1 - 49)

0,48 (0,31 - 0,76) 1 estudio

Hueso expuesto 9,2 (0,57 - 146)

0,70 (0,5 - 0,92) 1 estudio

Hueso palpable con estilete (PTB)

5,12 (2,4 - 13)

0,16 (0,08 - 0,38) 7 estudios

Impresión clínica 5,5 (1,8 - 17)

0,54 (0,3 - 0,97)

3 estudios Criterio no bien

definido.Butalia S, Palda VA, Sargeant RJ, Detsky AS, Mourad O. JAMA 2008;299:806-13.

Lam K, van Asten SA, Nguyen T, La Fontaine J, Lavery LA. Clin Infect Dis 2016;63:944-8.

LR (+) = sensibilidad 1 - especificidad

Verdaderos positivosFalsos positivos

LR (-) = 1 - sensibilidadespecificidad

Falsos negativosVerdaderos negativos

excelente bueno regular no sirve

LR (+) >10 5 - 10 2 - 5 1 - 2

LR (-) <0,1 0,1 - 0,2 0,2 - 0,5 0,5 - 1

Guyatt G, Rennie D, Meaden M, Cook D. (2014) Users' Guides to the Medical Literature. Mc Graw-Hill

Desempeño diagnóstico del examen físico


Úlcera >2 cm2 7,2 (1,1 - 49)

0,48 (0,31 - 0,76) 1 estudio

Hueso expuesto 9,2 (0,57 - 146)

0,70 (0,5 - 0,92) 1 estudio

Hueso palpable con estilete (PTB)

5,12 (2,4 - 13)

0,16 (0,08 - 0,38) 7 estudios

Impresión clínica 5,5 (1,8 - 17)

0,54 (0,3 - 0,97)

3 estudios Criterio no bien

definido.Butalia S, Palda VA, Sargeant RJ, Detsky AS, Mourad O. JAMA 2008;299:806-13.

Lam K, van Asten SA, Nguyen T, La Fontaine J, Lavery LA. Clin Infect Dis 2016;63:944-8.

Laboratorio


VHS >70 mm/hr 11 (1,6 - 79) 0,34 (0,06 - 1,9) 2 estudios

Butalia S, Palda VA, Sargeant RJ, Detsky AS, Mourad O. JAMA 2008;299:806-13.

• Otros marcadores no han demostrado utilidad para diferenciar OPD de infecciones de tejidos blandos.

documents on the importance of prompt surgical intervention inmany DFIs, it is frequently delayed, sometimes leading toamputation.86,87 More conservative surgery for the treatment ofDFIs is now possible because we better understand the compart-mental anatomy of the foot and the ways in which infectionspreads.88,89 Furthermore, it is clear that there are more types offoot infection than just ‘abscesses’ and ‘diabetic gangrene’.90 Wenow also appreciate that combining needed ablative foot surgerywith prompt revascularization can improve the rate of limbsalvage.91 And, finally, new wound therapies have improved thepostoperative care for these patients.92

Any foot compartment affected by infection should be openedquickly to reduce the compartmental pressure.93 Contrary topreviously held beliefs, fascial planes do not constrain the spread of

infection.94 Although unproven, MRI may play a role in planningthe surgical approach.85,95 Unfortunately, there is no classificationthat defines either the point at which surgery is absolutelynecessary, or when it is likely to produce a better outcome thanfurther medical therapy.96–98 It is now clear, however, that in mostcases ‘conservative’ surgery (i.e., resection of just the affected bone,without amputation)96,99–101 or antibiotic therapy alone can treatosteomyelitis successfully.

The optimal timing of surgery for DFI is not well defined, butprompt surgery, including revascularization when necessary, mayreduce the need for above-ankle amputations.102–104 The rate ofsuccess, including avoiding lower extremity amputation, in DFIs,depends on the approach taken by the treating surgeon,105 whichoften reflects his or her experience and skills. When amputation is

Figure 5. Ulcer over the first metatarsal head: X-ray showing cortical destruction of the first metatarsal head.

Figure 6. Postoperative view: X-ray showing the bone that was removed.

I. Uckay et al. / International Journal of Infectious Diseases 40 (2015) 81–9186

Radiografía

RADIONUCLIDE BONE SCANS

Bone scans use labeled radiotracers to identify sites of active bone formation and arehelpful in diagnosing OM. The most commonly used radiotracers are the technetium-99m labeled bisphosphonates, such as Tc-99m methylene diphosphonate (MDP) andTc-99m hydroxy diphosphonate. Tracer uptake depends on blood flow and newregional osteoblastic activity.20 For diagnosing OM, a 3-phase bone scan is typicallyperformed. The initial angiogram or blood flow phase is acquired immediately aftertracer bolus and consists of serial 1- to 5-second images of the area. The blood-pooling phase is performed 5 minutes after radiotracer injection. In areas of soft tissueinflammation, such as infection, capillaries will dilate, causing increased blood flow

Fig. 2. Dorsoplantar radiographic view shows gas in the soft tissues, visible as small darkareas (arrow), around the radio-opaque foreign body that is visible as a sharply angulateddensity near the first metatarsal head.

Fig. 3. Dorsoplantar radiographic view shows osseous destruction of the first distal phalanx(arrow), visible as deficiency of the bone of the distal tuft, indicating acute osteomyelitis.

Imaging of Diabetic Foot Infections 45

Uckay I, Aragon-Sanchez J, Lew D, Lipsky BA. Int J Infect Dis 2015;40:81-91. Fridman R, Bar-David T, Kamen S, Staron RB, Clin Podiatr Med Surg 2014;31:43-56

RNM

T1 STIRFridman R, Bar-David T, Kamen S, Staron RB, Clin Podiatr Med Surg 2014;31:43-56

Cintigrama trifásico

The collective study is positive for infection when there is activity on the labeledleukocyte image and no activity on the sulfur colloid marrow image. Palestro andcolleagues25 reported that the overall accuracy of combined leukocyte-marrow imag-ing is approximately 90%.

MRI

MRI has been shown to be very sensitive in detecting cellulitis, soft tissue ab-scesses, and OM.26 Croll and colleagues27 evaluated the accuracy, sensitivity,and specificity of MRI, plain radiography, and nuclear scanning for diagnosingOM and concluded that MRI seemed to be the single best test for identifyingbone infection. MRI uses the body’s natural magnetic properties to help producedetailed anatomic images. The single-proton hydrogen nucleus is used for imagingpurposes because it is found in large quantities in both fat and water in the body.28

During an examination, an MRI magnet aligns the average magnetic moment ofhydrogen protons in a given area along an axis and creates a magnetic vector.As a radiofrequency wave is added to the magnetic field, it deflects the magneticvector. When the radiofrequency wave is turned off, the magnetic vector (measuredas T1 relaxation) and axial spins of the hydrogen molecules (measured as T2 relax-ation) return to their resting state, creating measurable signals that are translatedinto images.28 Most pathologic conditions, including skin and bone infections,have a marked increase in water content; it is for this reason that MRI is very sen-sitive in disease detection.27

Standard variations in imaging parameters, such as echo time and repetition time,allow optimal visualization of relevant anatomy and aid in the recognition of patho-logic conditions. In a T1-weighted image, fat appears brighter than water, and both

Fig. 5. A three phase Tc-99m DMP bone scan demonstrates hyperemia (blood flow phase)and soft tissue inflammation (blood pool phase) involving the right midfoot and left hallux(arrows). On the delayed images, radiotracer accumulates in the left hallux (red arrow), indi-cating osteomyelitis. However, the radiotracer uptake has resolved on the right (greenarrow), indicating cellulitis without underlying osteomyelitis in the right midfoot.


Fridman R, Bar-David T, Kamen S, Staron RB, Clin Podiatr Med Surg 2014;31:43-56

Cintigrama con leucocitos marcados (ej. In-111)

CT/CT (SPECT/CT) was introduced to overcome this challenge. This technique pro-vides a fusion image with precise functional-anatomic correlation.48 The current pro-tocols call for either MDP injection (Fig. 10) or leukocyte labeling (Fig. 11) withsubsequent planar scans (for leukocyte scans, at 30 minutes, 4 hours, and 24 hoursafter administration), with SPECT/CT image gathering at 4 to 6 hours.48 In a study con-ducted by Filippi,48 SPECT/CT changed the interpretation of 52% of images (10 of19 suspected sites) when planar and SPECT images were performed alone. Horgerand colleagues49 showed that SPECT/CT enabled the distinction between soft tissueand bone infections in chronic OM better than SPECT alone, with specificity 89%on SPECT/CT versus 78% on SPECT. Sensitivity was identical for both SPECT andSPECT/CT at 100%. Heiba and colleagues50 recommend the use of dual-isotopeSPECT/CT imaging over single-isotope SPECT/CT alone because it considerablyincreased diagnostic accuracy.50

Fig. 11. A. Three phase bone scan cannot reliably differentiate recent postsurgical changesfrom osteomyelitis. B. In-111 labeling leukocyte differentiates right midfoot infection frompostsurgical changes the right first and second toes, but with poor anatomical correlation.C. Fusion leukocyte SPECT/CT increases specificity as well as anatomical details.


Fridman R, Bar-David T, Kamen S, Staron RB, Clin Podiatr Med Surg 2014;31:43-56

PET-CT

DIAGNOSING DIABETIC FOOT INFECTION ISRAEL

Vol. 57 - No. 1 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 9

of the CT part of the study can add clinically useful information. The semi-quantitative standard uptake value (SUV) index has not been validated, however, in patients with inflammatory and infectious proc-esses.

Interpretation of FDG imaging studies should al-ways be done with consideration of the specific clin-ical setting. In the context of a diabetic foot wound false (positive or negative) FDG imaging results are mainly related to a false or missed diagnosis of os-teomyelitis versus an infectious process involving soft tissues or a reactive Charcot joint. False positive studies can be the result of increased FDG uptake in aseptic inflammatory reactions, such as sterile ar-thritis. False negative studies can occur in the pres-ence of lesions of small size, an infectious process with a low metabolic rate or one located in close proximity to structures with high physiological FDG uptake. Hyperglycemia has been long viewed as a main cause for false negative FDG studies, an issue of particular concern in patients with diabetes. Re-sults of a recent study found, however, that the false negative rates in cases suspected of an infectious or inflammatory process were not statistically sig-nificantly different between patients with or without diabetes mellitus, or in those with high versus nor-mal serum glucose levels at the time of the study.54

Table II shows the results of a number of stud-ies that have assessed the role of FDG imaging for the evaluation of the diabetic foot. In one of these

Figure 5.—A 51-year old female patient with diabetes was referred for further evaluation of an abscess in the great toe of the right foot. Coronal (left), sagittal (center) and axial (right) PET (top), PET/CT (middle) and CT (bottom) slices demonstrate an FDG-avid lesion in the area of soft tissue swelling around and below the proximal phalanx of the right great toe. After local drainage and short-term antibiotic therapy there was no evidence of osteomyelitis on clinical follow-up of 10 months

Figure 4.—A 60-year old male with diabetes presented with a left foot plantar ulcer with suspected underlying osteomyelitis. (a) FDG-PET maximal intensity projection (MIP) image demonstrates a focus of abnormal FDG uptake in the 1st left toe. (b) Coronal and sagittal (c) PET, CT and PET/CT slices demonstrate that the focus of FDG uptake is localized in a fragmented 1st metatarsal bone. Culture of bone obtained at surgery grew Pseudomonas aeruginosa, confirming osteomyelitis.

A B C

PROOF

MIN

ERVA M

EDICAIsrael O, Sconfienza LM, Lipsky BA. Q J Nucl Med Mol Imaging 2014;58:33-45.

Desempeño diagnóstico de exámenes imageneológicos


Radiografía 2,3 (1,56 - 3,3)

0,63(0,51 - 0,68) 16 estudios

RNM 3,8 (2,5 - 5,8)

0,14 (0,08 - 0,26) 11 estudios

Cintigrama 3F 1,13 (0,88 - 1,5)

0,68 (0,31 - 1,5) 6 estudios

Cintigrama (GB marcados)

2,31(1,56 - 3,64)

0,38 (0,26 - 0,58) 6 estudios

PET-CT 5,56(2,02 - 15,27)

0,37*(0,1 - 1,35)

4 estudios *Sens= 0,29 - 1,0

Butalia S, Palda VA, Sargeant RJ, Detsky AS, Mourad O. JAMA 2008;299:806-13. Dinh MT, Abad CL, Safdar N. Clin Infect Dis 2008;47:519-27

Treglia G, Sadeghi R, Annunziata S, et al. Foot 2013;23:140-8.

Biopsia ósea

• Permite:

- a) certificar presencia de OPD.

- b) identificar agente etiológico.

• Puede ser percutánea o abierta (quirúrgica).

• Procedimiento seguro.

Lipsky BA, Aragon-Sanchez J, Diggle M, et al. Diabetes Metab Res Rev 2016;32 Suppl 1:45-74. Senneville E, Melliez H, Beltrand E, et al. Clin Infect Dis 2006;42:57-62.

Ertugrul MB, Baktiroglu S, Salman S, et al. J Am Podiatr Med Assoc 2008;98:290-5.

examination may help to define three types of DFO [112]:acute, defined by necrosis and infiltration of polymorpho-nuclear granulocytes in cortical andmedullary sites, usuallyassociated with congestion or thrombosis of small vessels[1]; chronic, characterized by destroyed bone and infiltra-tion of lymphocytes, histiocytes or plasma cells; and [2]acute exacerbation of chronic osteomyelitis, with abackground of chronic osteomyelitis with infiltration ofpolymorphonuclear granulocytes [113]. However, weneed further evaluation of these findings from othergroups. The concordance among several pathologists in di-agnosing DFO in bone samples was found to be low in onestudy, but this may have been related to a lack of an agreeddefinition of histopathological criteria [114]. A morerecent study, using an agreed DFO classification schemethat included the additional histopathological type ‘fibro-sis’, reported a high correlation in the reading by two inde-pendent pathologists [115]. A review comparing themicrobiological versus histopathological aspects of 44bone specimens of patients with DFI concluded that thetwo methods performed similarly in identifying the pres-ence of pedal osteomyelitis [116].

Unfortunately, both histology and culture results ofbone specimens may be misleading. False-positive resultscaused by skin contamination can be reduced by using adorsal route in case of a plantar ulcer and by keeping aminimal distance of 20 mm from the ulcer peripherywhen introducing the biopsy needle. Culture of a bonespecimen may be falsely negative because of samplingerrors, prior antibiotic therapy or a failure to isolatefastidious organisms. Similarly, bone histopathology maybe falsely negative because of sampling error or falselypositive in patients with some non-infectious inflamma-tory disorders. To reduce the likelihood of false negatives,it is likely best to perform bone biopsy using fluoroscopicor CT guidance and to impose an antibiotic-free period(ideally 2 weeks, but even a couple of days may behelpful) in clinically stable patients [117]. Because DFOin the absence of substantial soft tissue infection is typi-cally a slowly progressive disease, such an antibiotic-freeinterval is usually safe.

In one retrospective multicentre study, using boneculture-guided antibiotic treatment was associated with asignificantly better clinical outcome than using soft tissue

Figure 1. Technique of percutaneous bone biopsy of the foot. This may be carried out at bedside, in a radiology suite or in theoperating theatre. If needed, this can be performed using fluoroscopic or computed tomographic guidance. If bone core is obtained,send to microbiology for aseptic division, with one piece for culture and the other sent to histopathology. (Photographs courtesy of Dr E.Beltrand, Orthopedic Surgery Department, Dron Hospital, Tourcoing, France)

IWGDF Guidance on Foot Infections 53

Copyright © 2015 John Wiley & Sons, Ltd. Diabetes Metab Res Rev 2016; 32(Suppl. 1): 45–74DOI: 10.1002/dmrr

examination may help to define three types of DFO [112]:acute, defined by necrosis and infiltration of polymorpho-nuclear granulocytes in cortical andmedullary sites, usuallyassociated with congestion or thrombosis of small vessels[1]; chronic, characterized by destroyed bone and infiltra-tion of lymphocytes, histiocytes or plasma cells; and [2]acute exacerbation of chronic osteomyelitis, with abackground of chronic osteomyelitis with infiltration ofpolymorphonuclear granulocytes [113]. However, weneed further evaluation of these findings from othergroups. The concordance among several pathologists in di-agnosing DFO in bone samples was found to be low in onestudy, but this may have been related to a lack of an agreeddefinition of histopathological criteria [114]. A morerecent study, using an agreed DFO classification schemethat included the additional histopathological type ‘fibro-sis’, reported a high correlation in the reading by two inde-pendent pathologists [115]. A review comparing themicrobiological versus histopathological aspects of 44bone specimens of patients with DFI concluded that thetwo methods performed similarly in identifying the pres-ence of pedal osteomyelitis [116].

Unfortunately, both histology and culture results ofbone specimens may be misleading. False-positive resultscaused by skin contamination can be reduced by using adorsal route in case of a plantar ulcer and by keeping aminimal distance of 20 mm from the ulcer peripherywhen introducing the biopsy needle. Culture of a bonespecimen may be falsely negative because of samplingerrors, prior antibiotic therapy or a failure to isolatefastidious organisms. Similarly, bone histopathology maybe falsely negative because of sampling error or falselypositive in patients with some non-infectious inflamma-tory disorders. To reduce the likelihood of false negatives,it is likely best to perform bone biopsy using fluoroscopicor CT guidance and to impose an antibiotic-free period(ideally 2 weeks, but even a couple of days may behelpful) in clinically stable patients [117]. Because DFOin the absence of substantial soft tissue infection is typi-cally a slowly progressive disease, such an antibiotic-freeinterval is usually safe.

In one retrospective multicentre study, using boneculture-guided antibiotic treatment was associated with asignificantly better clinical outcome than using soft tissue

Figure 1. Technique of percutaneous bone biopsy of the foot. This may be carried out at bedside, in a radiology suite or in theoperating theatre. If needed, this can be performed using fluoroscopic or computed tomographic guidance. If bone core is obtained,send to microbiology for aseptic division, with one piece for culture and the other sent to histopathology. (Photographs courtesy of Dr E.Beltrand, Orthopedic Surgery Department, Dron Hospital, Tourcoing, France)

IWGDF Guidance on Foot Infections 53

Copyright © 2015 John Wiley & Sons, Ltd. Diabetes Metab Res Rev 2016; 32(Suppl. 1): 45–74DOI: 10.1002/dmrr

Lipsky BA, Aragon-Sanchez J, Diggle M, et al. Diabetes Metab Res Rev 2016;32 Suppl 1:45-74.

(1) Certificar diagnóstico

• OPD definit iva : B iopsia ósea compat ib le (inflamación + respuesta reparativa) + cultivo óseo positivo.

• OPD probable: clínica + laboratorio (incluyendo cultivos) + imágenes compatibles.

Lipsky BA, Aragon-Sanchez J, Diggle M, et al. Diabetes Metab Res Rev 2016;32 Suppl 1:45-74. Lipsky BA, Berendt AR, Cornia PB, et al. Clin Infect Dis 2012;54:e132-73.

(2) Identificación de agente etiológico

• Sensibilidad de cultivo óseo: 86,4 - 91,2%.

• Paciente idealmente sin antibióticos.

• Los cultivos de tejidos blandos no son equivalentes.

• Tratamiento de OPD guiado por cultivos óseos podría estar asociado a mayor probabilidad de remisión (ORaj=4,78 [IC 95% 1,0-22,7], p=0,04).

Lipsky BA, Aragon-Sanchez J, Diggle M, et al. Diabetes Metab Res Rev 2016;32 Suppl 1:45-74. Senneville E, Melliez H, Beltrand E, et al. Clin Infect Dis 2006;42:57-62.

Ertugrul MB, Baktiroglu S, Salman S, et al. J Am Podiatr Med Assoc 2008;98:290-5. Senneville E, Lombart A, Beltrand E, et al. Diabetes Care 2008;31:637-42.

Agentes etiológicos de OPD

• Aunque se aíslen en cultivos, habitualmente no son causa de la infección:

• S. coagulasa negativa, Corynebacterium spp., Bacillus spp.

• Enterococcus spp. Lipsky BA, Berendt AR, Cornia PB, et al. Clin Infect Dis 2012;54:e132-73.

Uckay I, Aragon-Sanchez J, Lew D, Lipsky BA. Int J Infect Dis 2015;40:81-91.

Mayor importancia del biopsia ósea

• No hay certeza diagnóstica.

• Cultivos de tejidos blandos difíciles de interpretar.

• Mala respuesta al tratamiento antibiótico empírico.

• Se usará ant imicrobianos que pueden seleccionar microorganismos resistentes (ej. rifampicina).

• OPD con compromiso de segmento medio o posterior del pie.

• Se requiere realizar implante de dispositivo ortopédico metálico.


Enfoque terapéutico ha evolucionado

Uckay I, Aragon-Sanchez J, Lew D, Lipsky BA. Int J Infect Dis 2015;40:81-91.

Clásico

Antibióticos iv Tiempo prolongado (>6-12 semanas)

Paciente hospitalizado Tratamiento quirúrgico agresivo

Actual

Antibióticos iv por corto tiempo, luego oral Tiempo más limitado (6 semanas)

Paciente ambulatorio Tratamiento quirúrgico conservador / tratamiento médico exclusivo

Tratamiento antibiótico oral versus parenteral en osteomielitis crónica

D A T A A N D A N A L Y S E S

Comparison 1. Oral antibiotic versus parenteral antibiotic (AB)

Outcome or subgroup titleNo. ofstudies

No. ofparticipants Statistical method Effect size

1 Remission at the end oftreatment

4 150 Risk Ratio (M-H, Fixed, 95% CI) 1.04 [0.92, 1.18]

2 Remission at least 12 monthsafter the end of treatment


3 Mild adverse events 3 118 Risk Ratio (M-H, Fixed, 95% CI) 1.08 [0.49, 2.42]

4 Moderate or severe adverseevents


5 Superinfection 3 124 Risk Ratio (M-H, Fixed, 95% CI) 1.08 [0.33, 3.60]

Comparison 2. Oral antibiotic versus parenteral plus oral antibiotic



1 Remission at least 12 monthsafter the end of the treatment

1 Risk Ratio (M-H, Fixed, 95% CI) Totals not selected

2 Adverse events 1 Risk Ratio (M-H, Fixed, 95% CI) Totals not selected

Comparison 3. Parenteral plus oral antibiotics versus parenteral antibiotic



1 Remission at least 12 monthsafter the end of treatment

1 Risk Ratio (M-H, Fixed, 95% CI) Totals not selected

2 Adverse events 1 Risk Ratio (M-H, Fixed, 95% CI) Totals not selected

33Antibiotics for treating chronic osteomyelitis in adults (Review)

Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Conterno LO, Turchi MD. The Cochrane database of systematic reviews 2013:Cd004439.

Penetración ósea de algunos antibióticos parenterales

Antibióticos niveles óseos / niveles séricos (%)

Cloxacilina (2 g) 10

Cefazolina (1-2 g) 7,5 - 18

Vancomicina (1 g) 10 - 21

Ceftriaxona (2 g) 19

Imipenem (500 mg) 20 - 48

Meropenem (500 mg) 17

Pipe/tazo (3/0,375 g) 20/25

Adaptado de Spellberg B, Lipsky BA. Clin Infect Dis 2012;54:393-407.

Penetración ósea de antibióticos con alta biodisponibilidad oral

Antibióticos niveles óseos / niveles séricos (%)Ciprofloxacino (500 mg) 30 - 35Ciprofloxacino (750 mg) 27 - 48Levofloxacino (500 mg) 75 - 99Moxifloxacino (400 mg) 49

Linezolid (600 mg) 40 - 51TMP / SMX (forte) 50 / 15

Clindamicina (600 mg) 40 - 67Rifampicina (300 mg) >100Metronidazol (500 mg) 79 - 100

Adaptado de Spellberg B, Lipsky BA. Clin Infect Dis 2012;54:393-407.

Tiempos más cortos de tratamiento total

necrotic bone could not be done for anyreason (8).This prospective randomized study

confirms the possibility of treating se-lected diabetic patients with osteomye-litis of the foot without surgery. A recentprospective randomized study con-ducted by Lazaro-Mart ınez et al. (7)showed that antibiotics and surgicaltreatment have similar outcomes in pa-tients with neuropathic forefoot ulcerscomplicated by osteomyelitis withoutischemia or necrotizing soft tissue infec-tions. According to the Infectious Dis-eases Society of America guidelines,surgical treatment of osteomyelitis isnot necessary when 1) surgery wouldcause unacceptable loss of function, 2)there is an untreatable limb ischemia, 3)the infection is confined to the forefootwith minimal soft tissue loss, or 4) sur-gery is considered inappropriate or un-desirable by the patient and health careprofessional (8). The medical approachto DFO is often criticized for collateraldamage due to antibiotic use, especially

the emergence of bacterial resistance,but also adverse events, in particular,Clostridium difficile–associated diarrhea(CDAD), along with significant cost (1).In this study, gastrointestinal adverseevents were reported in significantlymore patients receiving 12 weeks of an-tibiotic treatment than in those receiv-ing only 6 weeks, but the use of rifampincombinations in the majority of our pa-tients (27/40; 67.5%) may have influ-enced these results. The absence ofany reported case of CDAD in our patientsis consistent with the low incidenceof CDAD episodes described in patientstreated with rifampin, especially in asetting of tuberculosis (13). Reductionin the length of antibiotic courses ap-pears to be the best strategy for effec-tively limiting antibiotic resistance byreducing the selective pressure on bac-terial flora, but the design of this studydid not allow for addressing this ques-tion (14,15).

The overall remission rate of 65% inour patients assessed at least 1 year

after the end of treatment is compara-ble to the results established in previousstudies (2–7,9). It is, however, difficultto compare the remission rates re-ported in the literature since, to date,there exists no consensus concerning re-mission criteria for DFO. We used hardremission criteria, which included theassessment of both the healing of thefoot ulcer and the evolution of bone in-volvement. Indeed, the best way to as-sess the outcome of DFO has not yetbeen clearly defined (16). It is crucialthat complete and sustained healing ofthe ulcer occurs, as it prevents againstany new foot infection and represents astrong argument against the existenceof an active underlying DFO (17). Onthe other hand, it also seems importantto assess the radiological outcome ofthe initial bone abnormalities and to re-port the occurrence of relapsing epi-sodes of DFO during a posttreatmentfollow-up period of at least 1 year, asrecommended for any other type ofchronic osteomyelitis. In our study, theproportion of patients with relapsingDFO at the end of 1 year of posttreat-ment follow-up was 15%, which is simi-lar to that reported by Tice et al. (18).The percentage of our patients who re-quired major amputation during follow-up (10%) was comparable to the resultsreported by Embil et al. (14%) (6), Kordaet al. (5%) (19), and Margolis et al.(6.7%) (20). The overall proportion ofpatients in whom complete healingwas obtained was 85%, with a meanhealing time of 15 weeks, slightlyshorter than the 26 weeks reported inthe study by Kessler et al. (21). Univariateanalysis did not identify any parameterassociated with the patient outcome,especially methicillin-resistant S. aureus–related infections, which is consistentwith a previous study from Aragon-Sanchez et al. (22).

The median delay of 14 days betweenbone biopsy and the beginning of thedocumented antibiotic therapy in ourpatients is due to the fact that wewaited for the definite results of boneculture (i.e., 14 days) before starting thedocumented antibiotic treatment. In-deed, rifampin combinations are thefirst antibiotic choice in our center forthe treatment of staphylococcal osteo-myelitis of the foot and are debutedonly when the definite results of boneculture are available (i.e., between 10

Table 3—Antibiotic-related gastrointestinal adverse events reported in 40 diabeticpatients with DFO treated nonsurgically according to the duration of antibiotictherapy

Antibiotic-related adverse events6 weeksn = 20

12 weeksn = 20

Nausea 1(5) 2 (10)

Vomiting 1 (5) 2 (10)

Diarrhea 0 2 (10)

Hepatic cytolysis/cholestasis 1 (5) 3 (15)

Total 3 (15) 9 (45)a

Data are number of patients (%). aP = 0.04.

Table 4—Clinical outcome of 40 diabetic patients with osteomyelitis of the foottreated nonsurgically according to the duration of antibiotic therapy

Patient outcome6 weeksn = 20

12 weeksn = 20 P

Overall remission 12 (60) 14 (70%) 0.50

Complete healinga 18 (90) 16 (80) 0.38

Time to complete healing (weeks 6 SD) 13.1 6 12.2 16.8 6 17.4 0.44

Overall failure 8 (40) 6 (30) 0.50

Noncomplete healing 2 (10) 4 (20) 0.37

Relapsing osteomyelitis 2 (15) 3 (15) 1

Worsening radiological bone abnormalities 6 (30) 4 (20) 0.46

Bone resection 2 (10) 2 (10) 1

Spread of osteomyelitis to contiguous sites 4 (20) 2 (10) 0.37

Major amputation 2 (10) 2 (10) 1

Data are number of patients in whom the event was recorded (%). The total number of eachcolumn may exceed the total (overall failure), since more than one event may be recorded ina given patient. aComplete healing of wound sustained for at least 4 consecutive weeks.

care.diabetesjournals.org Tone and Associates 5

Tone A, Nguyen S, Devemy F, et al. Diabetes Care 2015;38:302-7.

necrotic bone could not be done for anyreason (8).This prospective randomized study

confirms the possibility of treating se-lected diabetic patients with osteomye-litis of the foot without surgery. A recentprospective randomized study con-ducted by Lazaro-Mart ınez et al. (7)showed that antibiotics and surgicaltreatment have similar outcomes in pa-tients with neuropathic forefoot ulcerscomplicated by osteomyelitis withoutischemia or necrotizing soft tissue infec-tions. According to the Infectious Dis-eases Society of America guidelines,surgical treatment of osteomyelitis isnot necessary when 1) surgery wouldcause unacceptable loss of function, 2)there is an untreatable limb ischemia, 3)the infection is confined to the forefootwith minimal soft tissue loss, or 4) sur-gery is considered inappropriate or un-desirable by the patient and health careprofessional (8). The medical approachto DFO is often criticized for collateraldamage due to antibiotic use, especially

the emergence of bacterial resistance,but also adverse events, in particular,Clostridium difficile–associated diarrhea(CDAD), along with significant cost (1).In this study, gastrointestinal adverseevents were reported in significantlymore patients receiving 12 weeks of an-tibiotic treatment than in those receiv-ing only 6 weeks, but the use of rifampincombinations in the majority of our pa-tients (27/40; 67.5%) may have influ-enced these results. The absence ofany reported case of CDAD in our patientsis consistent with the low incidenceof CDAD episodes described in patientstreated with rifampin, especially in asetting of tuberculosis (13). Reductionin the length of antibiotic courses ap-pears to be the best strategy for effec-tively limiting antibiotic resistance byreducing the selective pressure on bac-terial flora, but the design of this studydid not allow for addressing this ques-tion (14,15).

The overall remission rate of 65% inour patients assessed at least 1 year

after the end of treatment is compara-ble to the results established in previousstudies (2–7,9). It is, however, difficultto compare the remission rates re-ported in the literature since, to date,there exists no consensus concerning re-mission criteria for DFO. We used hardremission criteria, which included theassessment of both the healing of thefoot ulcer and the evolution of bone in-volvement. Indeed, the best way to as-sess the outcome of DFO has not yetbeen clearly defined (16). It is crucialthat complete and sustained healing ofthe ulcer occurs, as it prevents againstany new foot infection and represents astrong argument against the existenceof an active underlying DFO (17). Onthe other hand, it also seems importantto assess the radiological outcome ofthe initial bone abnormalities and to re-port the occurrence of relapsing epi-sodes of DFO during a posttreatmentfollow-up period of at least 1 year, asrecommended for any other type ofchronic osteomyelitis. In our study, theproportion of patients with relapsingDFO at the end of 1 year of posttreat-ment follow-up was 15%, which is simi-lar to that reported by Tice et al. (18).The percentage of our patients who re-quired major amputation during follow-up (10%) was comparable to the resultsreported by Embil et al. (14%) (6), Kordaet al. (5%) (19), and Margolis et al.(6.7%) (20). The overall proportion ofpatients in whom complete healingwas obtained was 85%, with a meanhealing time of 15 weeks, slightlyshorter than the 26 weeks reported inthe study by Kessler et al. (21). Univariateanalysis did not identify any parameterassociated with the patient outcome,especially methicillin-resistant S. aureus–related infections, which is consistentwith a previous study from Aragon-Sanchez et al. (22).

The median delay of 14 days betweenbone biopsy and the beginning of thedocumented antibiotic therapy in ourpatients is due to the fact that wewaited for the definite results of boneculture (i.e., 14 days) before starting thedocumented antibiotic treatment. In-deed, rifampin combinations are thefirst antibiotic choice in our center forthe treatment of staphylococcal osteo-myelitis of the foot and are debutedonly when the definite results of boneculture are available (i.e., between 10

Table 3—Antibiotic-related gastrointestinal adverse events reported in 40 diabeticpatients with DFO treated nonsurgically according to the duration of antibiotictherapy

Antibiotic-related adverse events6 weeksn = 20

12 weeksn = 20

Nausea 1(5) 2 (10)

Vomiting 1 (5) 2 (10)

Diarrhea 0 2 (10)

Hepatic cytolysis/cholestasis 1 (5) 3 (15)

Total 3 (15) 9 (45)a

Data are number of patients (%). aP = 0.04.

Table 4—Clinical outcome of 40 diabetic patients with osteomyelitis of the foottreated nonsurgically according to the duration of antibiotic therapy

Patient outcome6 weeksn = 20

12 weeksn = 20 P

Overall remission 12 (60) 14 (70%) 0.50

Complete healinga 18 (90) 16 (80) 0.38

Time to complete healing (weeks 6 SD) 13.1 6 12.2 16.8 6 17.4 0.44

Overall failure 8 (40) 6 (30) 0.50

Noncomplete healing 2 (10) 4 (20) 0.37

Relapsing osteomyelitis 2 (15) 3 (15) 1

Worsening radiological bone abnormalities 6 (30) 4 (20) 0.46

Bone resection 2 (10) 2 (10) 1

Spread of osteomyelitis to contiguous sites 4 (20) 2 (10) 0.37

Major amputation 2 (10) 2 (10) 1

Data are number of patients in whom the event was recorded (%). The total number of eachcolumn may exceed the total (overall failure), since more than one event may be recorded ina given patient. aComplete healing of wound sustained for at least 4 consecutive weeks.

care.diabetesjournals.org Tone and Associates 5

Tiempos más cortos de tratamiento total

Tone A, Nguyen S, Devemy F, et al. Diabetes Care 2015;38:302-7.

Tratamiento médico exclusivo• Cohortes retrospectivas: remisión en 55-86% de los casos.

• Exclusión: cirugía por otra causas e isquemia (algunas).

• Hospitalización variable (7,7 - 100%): heterogéneas.

• Tratamientos basados en cultivos de tejidos blandos.

• Combinaciones basadas en rifampicina y/o quinolonas por 6-35 semanas.

• Único RCT: cicatrización de herida a 12 semanas (ATB=76,5% vs ATB + CX=86,3%; p=0,33).


Factores a considerar para seleccionar

Quirúrgico Médico- Extensa necrosis ósea.

- Pie no salvable (funcionalmente).

- Sepsis persistente.

- Paciente no autovalente.

- Alto riesgo de efectos adversos por antibióticos.

- Isquemia no corregible.

- Preferencia del paciente.

- Necrosis ósea “limitada”.

- Se espera mala mecánica del pie post operatorio.

- Paciente muy inestable para cirugía.

- Sin necesidad de otros procedimientos quirúrgicos.

- Preferencia del paciente.


Elección del esquema antibiótico

• No hay evidencia de superioridad de un esquema antibiótico sobre los demás.

• Se recomienda:

- Empírico: cobertura a Staphylococcus aureus.

- Idealmente guiado por cultivos (ojalá óseos).

- Buena disponibilidad oral y penetración a hueso.

Peters EJ, Lipsky BA, Berendt AR, et al. Diabetes Metab Res Rev 2012;28 Suppl 1:142-62 Lipsky BA, Aragon-Sanchez J, Diggle M, et al. Diabetes Metab Res Rev 2016;32 Suppl 1:45-74.

Duración definitiva del tratamiento antibiótico

Condición Duración del tratamiento

OPD con resección completa del tejido infectado <2-5 días post amputación

OPD con resección incompleta del tejido infectado. 6 semanas

OPD con persistencia de hueso necrótico

> 6 semanas

(no bien definido. ¿meses?)


Weintrob A, Sexton DJ. UpToDate 2017: Wolters Kluwer; 2017.

Respuestas• ¿tiene osteomielitis? sí

• ¿necesito pedir más exámenes? no

• ¿solicito cultivos? sí ¿de qué? idealmente óseos

• ¿qué tratamiento indico? según cultivos

• ¿lo inicio ahora mismo? no, porque está estable

• ¿por qué vía? puede ser oral

• ¿por cuánto tiempo la trato? 6 semanas, en principio

• ¿requiere tratamiento quirúrgico? no necesariamente

• ¿debe amputarse? no, al menos por ahora

Conclusiones

• La OPD es una patología frecuente.

• Con la historia, examen físico, uso de estilete y radiografía se podrá realizar diagnóstico en muchos casos.

• En casos donde persiste la duda se puede recurrir a RNM con gadolinio.

• Si la RNM no está disponible o está contraindicada: considerar cintigrama con leucocitos marcados, cintigrama trifásico o PET-CT.

Conclusiones

• Diagnóstico de certeza: biopsia ósea.

• Tratamiento: basado en cultivos si paciente estable; empírico si paciente séptico.

• El enfoque terapéutico ha ido evolucionado: no es necesario tratamiento iv prolongado, tiempo total de antibióticos 6 semanas, hay espacio para tratamiento médico o quirúrgico no ablativo.

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