Sartelli et al.

Diario mundo de la cirugía de emergencia (2018) 13:58

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REVISIÓN Acceso abierto

2018 WSES / SIS-E de la conferencia de consenso:

recomendaciones para el tratamiento de las infecciones de piel
y tejidos blandos
Massimo Sartelli 1 *, Xavier Guirao 2, Timothy C. Hardcastle 3, Yoram Kluger 4, Marja. A. Boermeester 5, Kemal Ra þ una 6,
Luca Ansaloni 7, Federico Coccolini 7, Philippe Montravers 8, Fikri M. Abu-Zidan 9, Michele Bartoletti 10,
Matteo Bassetti 11, Offir Ben-Ishay 4, Walter L. Biffl 12, Osvaldo Chiara 13, Massimo Chiarugi 14, Raul Coimbra 15,
Francesco Giuseppe De Rosa dieciséis, Belinda De Simone 17, Salomone Di Saverio 18, Maddalena Giannella 10,
George Gkiokas 19, Vladimir Khokha 20, Francesco M. Labricciosa 21, Ari Leppäniemi 22, Andrei Litvin 23,
Ernest E. Moore 24, Ionut Negoi 25, Leonardo Pagani 26, Maddalena Peghin 11, Edoardo Picetti 27, Pintar tadeja 28,
Guntars Pupelis 29, Ines-Rubio Pérez 30, Boris Sakakushev 31, Helmut Segovia-Lohse 32, Gabriele Sganga 33,
Vishal Shelat 34, Michael Sugrue 35, Antonio Tarasconi 36, Cristian TRANA 1, Ene Ulrych 37, Pierluigi Viale 10 Fausto Catena 33

Resumen

Infecciones de la piel y de tejidos blandos (IPTBs) abarcan una variedad de condiciones patológicas que implican la piel y el tejido subcutáneo subyacente, fascia, o músculo,
que van desde infecciones superficiales simples a infecciones necrotizantes severas. IPTBs son un problema clínico frecuente en los servicios quirúrgicos. Con el fin de
aclarar las cuestiones clave en la gestión de IPTBs, un grupo de trabajo de expertos se reunió en Bertinoro, Italia, el 28 de junio, 2018, para una conferencia de consenso
multidisciplinar especialista bajo los auspicios de la Sociedad Mundial de Cirugía de Emergencia (WSES) y la La infección quirúrgica Sociedad Europa (SIS-E). La naturaleza
polifacética de estas infecciones ha llevado a una colaboración entre cirujanos generales y de emergencia, intensivistas y especialistas en enfermedades infecciosas, que
han compartido estas recomendaciones de práctica clínica.

palabras clave: infecciones de tejidos blandos, infección necrotizante, infección del sitio quirúrgico

Introducción problemas en el manejo de IPTBs, un panel de expertos se reunieron en

Infecciones de la piel y de tejidos blandos (IPTBs) abarcan una variedad de Bertinoro, Italia, el 28 de junio, 2018, para una conferencia de consenso
condiciones patológicas que implican la piel y el tejido subcutáneo multidisciplinar especialista bajo los auspicios de la Sociedad Mundial de
subyacente, fascia, o músculo, que van desde infecciones superficiales Cirugía de Emergencia (WSES) y la Sociedad de Infecciones Quirúrgicas
simples a infecciones necrotizantes severas. IPTBs puede afectar a Europa (SIS -MI).
cualquier parte del cuerpo y son un problema clínico frecuente en los
servicios quirúrgicos [ 1 , 2 ]. Durante la conferencia de consenso, 17 panelistas presentan los
estados desarrollados para cada una de las principales cuestiones
El manejo exitoso de los pacientes con severa IPTBs implica un relativas al diagnóstico y tratamiento de IPTBs. Se llegó a un acuerdo
reconocimiento rápido, un tratamiento antibiótico adecuado, desbridamiento sobre todos los estados.
quirúrgico oportuno o drenaje, y la reanimación cuando sea necesario.
El panel de expertos se reunió por correo electrónico a preparar y revisar el
Varios temas críticos se han debatido en el manejo de estos pacientes. documento de consenso que resulta de la reunión. El manuscrito fue revisado
Con el fin de aclarar estas importantes sucesivamente por todos los miembros y en última instancia revisó como el
presente manuscrito. Este documento representa el resumen de la conferencia
* Correspondencia: [email protected]
1 Departamento de Cirugía, Hospital Macerata, Macerata, Italia Lista completa de información
de consenso que resume las recomendaciones clínicas basadas en el

sobre el autor está disponible al final del artículo

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Sartelli et al. Diario mundo de la cirugía de emergencia (2018) 13:58 Página 2 de 24

La clasificación de las Recomendaciones de Evaluación, desarrollo y Las decisiones de manejo, tratamiento y admisión. En este sistema de
evaluación (grado) criterios de jerarquía resume en la tabla 1 [ 3 ]. clasificación, IPTBs fueron divididos en cuatro clases:

Clase 1: pacientes con SstI, pero no hay signos o síntomas de toxicidad

¿Cómo debe clasificarse IPTBs? sistémica o comorbilidades. Clase 2: pacientes son o bien sistémicamente
El termino “ infecciones de la piel y de tejidos blandos ” describe una malestar con comorbilidades estables o son sistémicamente bien, pero tienen
amplia heterogeneidad de las condiciones clínicas. Se recomienda que el una comorbilidad (por ejemplo, diabetes, obesidad) que pueden complicar o
necrotizante o carácter no necrotizante de la infección, la extensión resolución demora. Clase 3: pacientes parecen tóxico y enfermo (fiebre,
anatómica, las características de la infección (purulenta o no purulenta), y taquicardia, taquipnea, y / o hipotensión). Clase 4: Los pacientes tienen el
la condición clínica del paciente deben ser siempre evaluaron de forma síndrome de sepsis y potencialmente mortales infección; por ejemplo fascitis
independiente para clasificar a los pacientes con infecciones de tejidos necrotizante.
blandos (1C recomendación).

SSTIs abarcar una variedad de condiciones patológicas que implican la

piel y subyacente de tejido subcutáneo, fascia, o músculo y que van SSTIs puede ser también clasificada de acuerdo con las capas de tejido
desde infecciones superficiales simples a infecciones necrotizantes anatómico involucrados [ 7 ]. Las infecciones superficiales tales como erisipela,
severas. impétigo, foliculitis, forúnculos, y carbunclos se encuentran en la capa
Varios sistemas de clasificación se han utilizado para describir SSTIs epidérmica y dérmica, mientras que la celulitis se encuentra en la dermis y el
incluyendo variables tales como la localización anatómica, patógeno (s) tejido subcutáneo. Las infecciones profundas se extienden debajo de la dermis
causante, tasa de progresión, la profundidad de la infección, y la gravedad de y pueden implicar el tejido subcutáneo, planos fasciales, o compartimentos
la presentación clínica. En 1998, la Administración de Alimentos y musculares se presenta como complejo de abscesos, fascitis, o mionecrosis.
Medicamentos de Estados Unidos (FDA) clasifica IPTBs en dos amplias
categorías con el propósito de ensayos clínicos que evalúan nuevos
antimicrobianos para su tratamiento: no complicada y complicada. SSTIs no SSTIs complicada también puede ser clasificado como infecciones no
complicada incluido infecciones superficiales como la celulitis, abscesos necrotizantes o necrotizantes. infecciones necrotizantes más comúnmente
simples, impétigo, y forúnculos y antibióticos requeridos o incisión quirúrgica implican las capas fasciales musculares pero también pueden implicar las
para el drenaje de absceso solo. En contraste, complicada SSTIs incluido capas dérmica, subcutánea, y musculares y garantiza el desbridamiento
infecciones de tejidos blandos profundos tales como infecciones quirúrgico rápido, agresivo.
necrotizantes,
En 2014, la Sociedad de Enfermedades Infecciosas de América (IDSA)
úlceras infectadas, quemaduras infectadas, y la mayor actualiza las guías de práctica para el diagnóstico y tratamiento de
abscesos que requirieron intervención quirúrgica significativa con drenaje y infecciones de la piel y tejidos blandos [ 8 ]. Las directrices divididos
desbridamiento [ 4 ]. Los términos “ Complicado ” y “ sin complicaciones ” persistir infecciones por purulenta y
y puede ser útil en la descripción de SSTIs según lo informado por no purulenta, la gravedad (leve, moderada y grave), y necrosis de los tejidos
Napolitano [ 5 ]. (necrotizante versus no necrotizante). Recientemente, la FDA de Estados Unidos
ha introducido la nueva definición de la piel y la piel-estructura infección bacteriana
IPTBs sencillo llevar bajo riesgo de infección por la vida o la integridad aguda (ABSSSI) para definir más estrechamente la infección de los tejidos blandos
física en peligro a menos que se tratan de forma inadecuada. Los pacientes complicado para los fines de los ensayos de registro. ABSSSIs incluyen celulitis /
que tienen IPTBs sin complicaciones pueden ser tratados con la terapia erisipelas, infecciones de heridas, y los principales abscesos cutáneos. Por lo
antibiótica empírica de acuerdo con el patógeno más probable y los patrones tanto, un ABSSSI se define como una infección bacteriana de la piel con un área
de resistencia locales en el impétigo, erisipela o celulitis suave con drenaje y de tamaño de la lesión de
desbridamiento o drenaje quirúrgico del absceso simple en la piel.
≥ 75 cm 2 ( tamaño de la lesión medida por el área de enrojecimiento, edema o
induración) [ 9 ].
IPTBs complicada se asocian con un alto riesgo de infección En 2015, los WSES publicaron sus directrices para la gestión de IPTBs [ 10 ]
potencialmente mortal. En los pacientes que han complicado IPTBs, es de Proponer una nueva definición dividiendo SSTIs en tres grupos principales:
suma importancia para iniciar el tratamiento empírico inicial de amplio infecciones del sitio quirúrgico (SSI), de no necrotizantes SSTIs, y
espectro apropiado y adecuado de antibióticos y que considere la necrotizantes SSTIs. SSI se clasifican en dos subgrupos: incisional y órgano
necesidad de una intervención quirúrgica para el drenaje y / o y órgano / espacio. El ISQ incisional se dividen además en superficial (piel y
desbridamiento. En 2003, Eron et al. [ 6 ] SSTIs clasificados de acuerdo con tejido subcutáneo) y (músculo de los tejidos blandos de profundidad y fascia)
la gravedad de los signos locales y sistémicos y la presencia o ausencia de de profundidad. infecciones de órganos y órgano / espacio no son
condiciones comórbidas en pacientes que se presentan en el ámbito verdaderamente infecciones de tejidos blandos. SSTIs no necrotizante
ambulatorio para guiar la clínica
incluyendo la erisipela,
Table 1 Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence from Guyatt et al. [ 3 ]

Grade of recommendation Clarity of risk/benefit Quality of supporting evidence Implications

1A
Sartelli et al. Diario mundo de la cirugía de emergencia

Strong recommendation, high-quality Benefits clearly outweigh risk and burdens, or vice versa RCTs without important limitations or overwhelming evidence from Strong recommendation, applies to most patients in
evidence observational studies most circumstances without reservation

1B

Strong recommendation, moderate-quality Benefits clearly outweigh risk and burdens, or vice versa RCTs with important limitations (inconsistent results, methodological Strong recommendation, applies to most patients in
evidence flaws, indirect analyses, or imprecise conclusions) or exceptionally most circumstances without reservation
strong evidence from observational studies
(2018) 13:58

1C

Strong recommendation, low-quality or very lowquality evidence Benefits clearly outweigh risk and burdens, or vice Observational studies or case series Strong recommendation but subject to change
versa when higher quality evidence becomes available

2A

Weak recommendation, high-quality evidence Benefits closely balanced with risks and burden RCTs without important limitations or overwhelming evidence from Weak recommendation, best action may differ
observational studies depending on the patient, treatment circumstances, or
social values

2B

Weak recommendation, moderate-quality Benefits closely balanced with risks and burden RCTs with important limitations (inconsistent results, methodological Weak recommendation, best action may differ
evidence flaws, indirect, or imprecise) or exceptionally strong evidence from depending on the patient, treatment circumstances, or
observational studies social values

2C

Weak recommendation, low-quality or very low-quality Uncertainty in the estimates of benefits, risks, and burden; Observational studies or case series Very weak recommendation; alternative treatments
evidence benefits, risk, and burden may be closely balanced may be equally reasonable and merit consideration
Página 3 de 24
Sartelli et al. Diario mundo de la cirugía de emergencia (2018) 13:58 Página 4 de 24

impétigo, foliculitis, abscesos simple, y absceso complejo pueden ser precauciones tales como asegurar que los pacientes bañarse o ducharse antes de
tratadas por antibióticos o drenaje solo. Necrotizante IPTBs (celulitis, fascitis, la cirugía, de manera adecuada para que los equipos quirúrgicos para limpiar sus
miositis, Fournier ' s gangrena) requieren intervención quirúrgica incluyendo el manos, orientación sobre cuándo usar antibióticos profilácticos, que utilizan
drenaje y el desbridamiento de tejido necrótico, además de la terapia con desinfectantes para antes de la incisión, y el que las suturas de usar. Las
antibióticos. recomendaciones propuestas son las siguientes:

Varios autores y organizaciones han propuesto esquemas de clasificación

para IPTBs basado en variables tales como la localización anatómica, la tasa de “ Fuerte ”- panel de expertos que confía en que los beneficios superan los

progresión, la profundidad de extensión, y la presentación clínica o la gravedad. riesgos, considerados para ser adaptable para su aplicación en la mayoría (si

Cada uno tiene limitaciones clave tanto en la asistencia a la gestión clínica y en no todos) de las situaciones, y los pacientes deben recibir la intervención

proporcionar orientación para el desarrollo de nuevos agentes terapéuticos. como curso de acción.

“ Condicional ”- panel de expertos consideran que los beneficios de la intervención,

El consenso llegó a la conclusión de que el necrotizante o carácter no probablemente, eran mayores que los riesgos; un proceso de toma de decisiones

necrotizante de la infección, la extensión anatómica, las características de más estructurado debe llevarse a cabo, sobre la base de consultas con los

la infección (purulenta o no purulenta), y las condiciones clínicas del interesados ​y la participación de los pacientes y los profesionales de la salud.

paciente deben ser siempre evaluaron de forma independiente para

clasificar pacientes con soft- infecciones de tejidos.

Es importante destacar que las directrices recomiendan que la profilaxis

Lo que es nuevo en la prevención de infecciones del sitio quirúrgico? ¿Cuáles son con antibióticos se deben utilizar para prevenir las infecciones antes y
los principios de la prevención de SSI? durante la cirugía solamente. Los antibióticos no deben utilizarse después
Recientes directrices mundiales para la prevención de infecciones del sitio de la cirugía, como se suele hacer. La profilaxis antibiótica se deben
quirúrgico pueden apoyar a los trabajadores de la salud para desarrollar o administrar para procedimientos operativos que tienen una alta tasa de
fortalecer los programas de prevención y control de infecciones, con un infección del sitio quirúrgico postoperatorio, o cuando se implantan
enfoque en la seguridad quirúrgica, así como planes de acción resistencia a materiales extraños. La profilaxis antibiótica debe administrarse dentro de
los antimicrobianos. Recomendamos que todos los trabajadores de la salud 120 minutos antes de la incisión. Sin embargo, la administración de la
adoptan estas recomendaciones basadas en la evidencia en su práctica primera dosis de antibióticos es dependiente de sus características
clínica (1C recomendación). farmacológicas. factores del paciente subyacentes también pueden afectar a
la disposición de fármacos (por ejemplo, la desnutrición, la obesidad, la
Infecciones del sitio quirúrgico son las infecciones más comunes asociadas a la salud caquexia y la enfermedad renal con pérdida de proteínas puede dar lugar a
entre los pacientes quirúrgicos. Evidentemente, es importante para mejorar la seguridad la exposición a antibióticos subóptima a través de aumento de la depuración
del paciente mediante la reducción de la incidencia de infecciones del sitio quirúrgico. La de antibióticos en presencia de normal o función renal aumentada). - 4 h
prevención de infecciones del sitio quirúrgico es una prioridad global. Las bacterias se (típicamente donde duración superior a dos vidas medias del antibiótico). No
están volviendo cada vez más resistentes a los antibióticos, por lo que la prevención de hay evidencia para apoyar el uso de la profilaxis antibiótica postoperatorias.
SSI aún más importante hoy en día. SSI son un problema clínico importante en términos Las recomendaciones basadas en la evidencia clave señalados en las
de morbilidad, mortalidad, duración de la estancia hospitalaria y los costos directos y presentes directrices deberían ser adoptadas por todo el personal de salud
no-directos globales en todo el mundo. A pesar de los avances en el conocimiento de que atienden a pacientes quirúrgicos en todas las etapas de ese paciente ' s
prevención, infecciones del sitio quirúrgico siendo uno de los eventos adversos más atención quirúrgica.
comunes en los hospitales. prevención de SSI es complejo y requiere la integración de

una serie de medidas antes, durante y después de la cirugía. Tanto la Organización

Mundial de la Salud (OMS) [ 11 , 12 ] Y los Centros para el Control y Prevención de

Enfermedades (CDC) [ 13 ] Han publicado recientemente directrices para la prevención de

infecciones del sitio quirúrgico. Las directrices de la OMS de 2016 mundiales para la

prevención de la infección del sitio quirúrgico [ 11 , 12 ] Son incluidas revisiones

sistemáticas que presentan información adicional en apoyo de acciones para mejorar la ¿Cuál es el mejor tratamiento de las infecciones del sitio quirúrgico de
práctica basada en la evidencia. incisión? Cuando se necesitan antibióticos?

Incisionales ISQ requieren apertura rápida y amplia de la incisión quirúrgica.

Recomendamos la terapia con antibióticos para infecciones del sitio quirúrgico de
incisión con cualquier criterio de síndrome de respuesta inflamatoria sistémica o
signos de insuficiencia de órganos tales como hipotensión, oliguria, disminución
Las directrices incluyen 13 recomendaciones para el período de la agudeza mental, o en pacientes inmunocomprometidos (1C
pre-operatorio, y 16 para la prevención de infecciones durante y después recomendación).
de la cirugía. Éstos van desde simples
Sartelli et al. Diario mundo de la cirugía de emergencia (2018) 13:58 Página 5 de 24

SSI se clasifican generalmente de acuerdo con los criterios CDC [ 14 ]. SSI se Es una práctica común para cubrir las heridas quirúrgicas con un
clasifican como infección superficial de la incisión, la infección por incisión profunda, y la apósito. El apósito actúa como una barrera física para proteger la herida
infección por espacio de órganos. infecciones incisionales superficiales son el tipo más de la contaminación del ambiente exterior hasta que la herida se convierte
común de infecciones del sitio quirúrgico. incisional profunda y órgano / espacio son los en impermeable a los microorganismos.
tipos de infecciones del sitio quirúrgico que causan la mayoría de la morbilidad.

infecciones del espacio de órganos no son infecciones de tejidos blandos genuinos. compendios de cuidados postoperatorios recomiendan que los vendajes
Incisional ISQ son el resultado de varios factores [ 15 ]. Todas las heridas quirúrgicas quirúrgicos mantenerse en reposo durante un mínimo de 48 horas después de
están contaminados por bacterias, pero sólo una minoría de hecho se desarrolla una la cirugía a menos que se produce una fuga. Sin embargo, actualmente no
infección clínica. La colonización se produce cuando las bacterias comienzan a existen recomendaciones o directrices específicas sobre el tipo de apósito
replicarse y adherirse al sitio de la herida. Si el host ' s respuesta inmune no es suficiente quirúrgico [ 19 ]. El diagnóstico de la infección del sitio quirúrgico de incisión es
para eliminar o superar los efectos de las bacterias, la infección se produce [ dieciséis ]. clínico. Los síntomas pueden incluir eritema localizado, induración, calor y dolor
En la mayoría de los pacientes, la infección no se desarrolla debido a las defensas del en el sitio de la incisión. Purulenta herida de drenaje y separación de la herida
huésped son eficientes para eliminar los colonizadores en el sitio quirúrgico; Sin puede ocurrir. La mayoría de los pacientes tienen signos sistémicos de
embargo, en algunos pacientes, las defensas del huésped fallan para protegerlos de infección, como fiebre y leucocitosis. La información sobre las especies
infecciones del sitio quirúrgico. Es bien sabido que los mecanismos de trauma quirúrgico microbiológicas presentes en la herida es útil para determinar la elección del
aumenta la respuesta inflamatoria y contra-reguladoras. Tal mecanismo de regulación se antibiótico y la predicción de la respuesta al tratamiento.
puede reducir la respuesta inmune postoperatorio, la promoción de las SSI.

Una ISQ incisional se deben tomar muestras si hay una sospecha clínica de
infección. La falta de criterios estandarizados para el diagnóstico microbiológico de las
Los patógenos aislados de infecciones diferentes, principalmente en infecciones del sitio quirúrgico presentan un desafío para vigilar la epidemiología global
función del tipo de procedimiento quirúrgico. En de infección del sitio quirúrgico. La aparición de resistencia a los antibióticos ha hecho
procedimientos quirúrgicos limpia-contaminada o contaminados, los la gestión de infecciones del sitio quirúrgico difícil. Por otra parte, rápidamente
patógenos aerobios y anaerobios de la microflora endógena normal del emergente patógenos nosocomiales y el problema de la resistencia a múltiples
órgano resecado quirúrgicamente son los patógenos más frecuentemente fármacos hace necesario la revisión periódica de los patrones de aislamiento y su
aislado. En los procedimientos quirúrgicos limpios, en el que el sensibilidad.
gastrointestinal, ginecológico, y no se han entrado en las vías respiratorias, Staphylococcus
aureus desde el entorno exógeno o el paciente ' s la flora de la piel es la El tratamiento adecuado de las ISQ incisional siempre debe incluir:
causa más común de infección. Sin embargo, en algunas áreas específicas
del cuerpo tal como la piel de la ingle podría también ser colonizado por
flora entérica. Por otra parte, es posible que los procedimientos tales como incisión quirúrgica y drenaje de absceso. El desbridamiento del tejido
prótesis de cadera o de derivación vascular, realizan en este anatómica necrótico, si está presente. cuidado apropiado de la herida. Resuscitation
para mejorar la perfusión cuando sepsis está presente.

región, el tiempo podría estar infectada por bacterias

Gram-negativas. Sganga et al. [ 17 ] Han informado recientemente que los terapia antibiótica empírica adecuada cuando esté indicado. De la tensión
factores de riesgo asociados con infecciones del sitio quirúrgico causadas por Staphylococcus
cuando está disponible antibiograma.
aureus resistente a la meticilina ( MRSA), identificado utilizando el método
Delphi eran pacientes de centros de atención de larga estancia, una Incisional ISQ siempre debe ser drenado, regadío, y si es necesario, se abrió
hospitalización dentro de los 30 días anteriores, Charlson puntuación> 5 y un desbridamiento. Si se sospecha que la interrupción de la fascia, el drenaje
puntos, enfermedad pulmonar obstructiva crónica y la cirugía torácica, la debe realizarse siempre. El drenaje percutáneo, la irrigación de heridas y
terapia con antibióticos con betalactámicos (cefalosporinas especialmente), y tratamiento de las heridas asistida por presión negativa son opciones nuevas y
carbapenems y / o quinolonas en los 30 días anteriores, edad 75 años o más, eficaces que reducen la necesidad de una gestión abierta de las heridas
la duración actual de hospitalización> 16 días, y la cirugía con implante de infectadas. En los casos en que es necesaria una gestión abierta, una vez que
prótesis. Un determinante importante de SSI es la integridad de las defensas haya pasado la infección, la herida se puede cerrar. ISQ incisional superficial
del huésped. factores del huésped importantes incluyen los siguientes [ 18 ]: que se han abierto se puede manejar sin antibióticos. En pacientes con
Edad, estado de malnutrición, la diabetes, el tabaquismo, la obesidad, la incisional ISQ con la presencia de cualquier criterio de respuesta inflamatoria
colonización por microorganismos, la duración de la estancia hospitalaria u sistémica o signos de insuficiencia de órganos tales como hipotensión, oliguria,
hospitalización previo, shock e hipoxemia e hipotermia. disminución del estado de alerta mental, o en pacientes inmunocomprometidos,
empírico de amplio espectro de tratamiento antibiótico debe ser
Sartelli et al. Diario mundo de la cirugía de emergencia (2018) 13:58 Página 6 de 24

comenzado con la cobertura para cocos gram-positivos y / o la flora esperados trastornar con fiebre elevada y recuento de glóbulos blancos [ 26 ]. Como ya se
en el lugar de operación. tratamiento antibiótico definitivo es guiado por la informó en un párrafo anterior, la celulitis se ha clasificado recientemente
respuesta clínica del paciente y, cuando estén disponibles, los resultados de la como un ABSSSI junto con la erisipela, infecciones del sitio quirúrgico, y
tinción de Gram, la cultura de la herida, y antibiograma. grandes abscesos. En un gran estudio multicéntrico europeo, Garau et al. [ 27 ]
Analizó una población de pacientes con diagnóstico complicado SSTI
hospitalizado entre diciembre de 2010 y enero de 2011 informando de que la
¿Cuál es el tratamiento adecuado de las infecciones celulitis es el diagnóstico más frecuente que representa el 59,1% del total.
superficiales (impétigo, erisipela y celulitis y abscesos Streptococci causa difusa, extendiéndose rápidamente la infección; celulitis
superficiales)? estafilocócica es típicamente más localizada. El tratamiento debe
Recomendamos que el impétigo, erisipela y celulitis deben ser comenzarse rápidamente con agentes eficaces contra los patógenos
manejados por los antibióticos contra las bacterias Gram-positivas Gram-positivos típicos, especialmente los estreptococos. Si la celulitis es muy
(recomendación 1C). Tratamiento empírico de SARM adquirida en la temprano y leve y no hay comorbilidades significativas están presentes, los
comunidad (CA-MRSA) se debe recomendar a los pacientes en riesgo betalactámicos orales podrían ser suficientes en las zonas donde la
de CA-MRSA o que no responden a la terapia de primera línea CA-MRSA no es frecuente. Otras opciones disponibles son macrólidos y
(recomendación 1C). lincosamidas; sin embargo, la resistencia a la eritromicina y clindamicina
están aumentando. Las fluoroquinolonas han sido aprobados para el
Incisión y el drenaje es el tratamiento principal para los abscesos tratamiento de la celulitis más complicado, pero no son adecuados para el
simples o forúnculos. Se recomienda no usar antibióticos para los tratamiento de las infecciones por SARM. Para infecciones más graves, vía
abscesos o forúnculos simples (recomendación 1C). parenteral es la primera opción. Si se sospecha MRSA (MRSA adquiridas en
el hospital, tanto [HA-MRSA] y CA-MRSA), glucopéptidos y nuevos
Superficial infecciones abarcan ya sea superficial antimicrobianos son las mejores opciones [ 25 , 28 , 29 ]. Para un simple
propagación de la infección y la inflamación dentro de la epidermis y la absceso superficial o ebullición, incisión y drenaje es el tratamiento primario,
dermis que se pueden tratar con antibióticos solos o un absceso bien y no se necesitan antibióticos. Para ser considerado un absceso simple,
circunscrita que puede ser entendido por el drenaje solo. induración y eritema debe limitarse únicamente a un área definida del
absceso y no debe extenderse más allá de sus fronteras. Además, abscesos
El examen físico por lo general revela eritema, dolor e induración. La simples no extenderse a los tejidos más profundos o tienen extensión
mayoría de IPTBs superficiales son causadas por bacterias multiloculada. abscesos cutáneos son causadas por bacterias que
Gram-positivas, particularmente estreptococos y S. aureus. Los tres representan la flora cutánea regionales normales de la zona afectada [ 30 ].
presentaciones comunes de infecciones superficiales constan de
impétigo, erisipelas, y celulitis. Ellos son gestionados por la terapia con
antibióticos contra las bacterias Gram-positivas.

El impétigo es una infección bacteriana altamente contagiosa de las

capas superficiales de la epidermis. El impétigo afecta principalmente a
los niños, y es uno de los SSTI más común en niños en todo el mundo [ 20
]. Se caracteriza por lesiones purulentas discretas casi siempre causadas ¿Cuál es el tratamiento apropiado de los abscesos complejos (perianal
por y perirrectal, y abscesos en los sitios de inyección de drogas por vía
β- hemolítica Estreptococo spp. y / o S. aureus. Por otra parte, de especial intravenosa)?
preocupación es el papel creciente de CA-MRSA como el impétigo ' s agente piel Complex y abscesos subcutáneos son bien circunscrito y responden
etiológico [ 21 - 23 ]. La erisipela es una roja, tierna, dolorosa placa de fuego a la incisión y el drenaje. Recomendamos la terapia con antibióticos si los
con bordes bien delimitados y es comúnmente causada por especies de signos sistémicos de infección están presentes, en pacientes
estreptococos, por lo general Staphylococcus pyogenes. S. aureus rara vez inmunocomprometidos, si el control de fuente es incompleta o en casos
causa la erisipela [ 24 ]. Los estreptococos son la causa principal de la de absceso con celulitis significativa (recomendación 1C).
erisipela. La mayoría de las infecciones faciales se atribuyen al grupo A Streptococcus
( GAS), con un porcentaje creciente de infecciones de las extremidades
inferiores causada por no GAS. El rol de S. aureus, y específicamente MRSA, Recomendamos la terapia con antibióticos de amplio espectro empírico
sigue siendo controvertida [ 25 ]. con la cobertura de las bacterias Gram positivas, Gram negativas y
anaerobias (recomendación 1C).
Los sitios comunes de origen de los abscesos complejos pueden ser
La celulitis es una infección bacteriana aguda de la dermis y el tejido perineal o perianal, perirrectal, y abscesos en los sitios de inyección de
subcutáneo que afecta más comúnmente a las extremidades inferiores, drogas por vía intravenosa. complicadas de la piel y abscesos subcutáneos
aunque puede afectar a otras áreas. Provoca signos locales de son bien circunscrito y responden a la incisión y el drenaje con la terapia de
inflamación, tales como el calor, eritema, dolor, linfangitis, y con antibiótico adyuvante.
frecuencia sistémica
Sartelli et al. Diario mundo de la cirugía de emergencia (2018) 13:58 Página 7 de 24

Perianal y abscesos perirrectales originan más a menudo de una glándula Siempre descartado. antibióticos de amplio espectro eficaces contra
cripta anal obstruido, con la recogida de pus resultante en el tejido organismos aeróbicos y anaeróbicos deben administrarse en pacientes
subcutáneo, avión interesfinteriano, o más allá de (espacio isquiorectal o con estos infecciones.
espacio supraelevador) donde varios tipos de anorrectal abscesos forma. Una agentes de amplio espectro con cobertura de gérmenes Gram-positivos,
vez diagnosticada, abscesos anorrectales deben drenarse rápidamente Gram-negativas, y anaerobios pueden ser necesarios en función de la
quirúrgicamente. Un absceso anorrectal sin drenaje puede continuar para situación clínica. Dada la alta frecuencia de MRSA en algunas áreas,
expandirse en espacios adyacentes así como el progreso de la infección este patógeno se debe cubrir empíricamente si se sospecha, pero no se
sistémica generalizada. Absceso anorrectal es más frecuente en hombres que dispone de estudios aleatorizados para el tratamiento de SSTI causada
en mujeres. La mayoría de los pacientes se presentan entre las edades de 20 específicamente por CA-MRSA [ 1 ].
a 60 con la media de edad de 40 en ambos sexos [ 31 ].

El diagnóstico de absceso anorrectal se basa generalmente en el ¿Cuál es el tratamiento adecuado de desarrollar infecciones en la piel
paciente ' s la historia y examen físico. El síntoma más común de un dañada (heridas por quemaduras, picaduras de animales y humanos, y
absceso anorrectal es el dolor. Como tal, tiene que ser diferenciada de úlceras de decúbito)?
otras causas de dolor anal incluyendo fisura anal, hemorroides La irrigación de la herida y el desbridamiento de tejido necrótico son los
trombosadas, espasmo del elevador, enfermedades de transmisión factores más importantes en la prevención de la infección y puede reducir
sexual, proctitis, y el cáncer. Bajas (interesfintérica, perianal y sustancialmente la incidencia de infección invasiva herida. La profilaxis
isquiorrectales) abscesos generalmente están asociados con la con antibióticos no se recomienda en general (1C recomendación).
inflamación, celulitis, y la exquisita ternura, pero pocos síntomas
sistémicos. Altas (submucosa, supraelevador) abscesos pueden tener
pocos síntomas locales, pero los síntomas sistémicos significativos. Para los pacientes con signos sistémicos de infección, el estado
abscesos más profundos, tales como los que se forman en la inmune comprometido, comorbilidades graves, celulitis severa asociada,
supraelevador o alto espacio isquiorectal, también pueden presentar dolor heridas graves y profundo, un antibiótico de amplio espectro eficaces
referido al perineo, baja de la espalda, o nalgas. contra aeróbica, y organismos anaerobios siempre se requiere (1C
recomendación).

El objetivo del tratamiento quirúrgico de un absceso es drenar el absceso Infecciones en desarrollo en la piel dañada son un grupo heterogéneo que
expedita, identificar un tracto de la fístula, y, o bien proceder con fistulotomía incluye las heridas por mordedura (animales y picaduras de humanos), heridas
primaria para prevenir la recurrencia o colocar un sedal de drenaje para su por quemaduras y úlceras por presión. Si se maneja de forma incorrecta, estas
examen futuro. Un gran absceso debe ser drenado con múltiples incisiones de infecciones pueden convertirse en infecciones de tejidos blandos más
contador en lugar de una incisión larga, lo que creará una deformidad paso-off complicados. infección de tejidos blandos es la complicación más común de
y el retardo de cicatrización de la herida. abscesos complicados pueden animales y picaduras humanos. El riesgo de infección depende del tipo de
implicar una variedad de patógenos y son frecuentemente polimicrobiana en mordida, el sitio de la lesión, el tiempo transcurrido desde la picadura hasta la
origen. Aunque la mayoría de los casos pueden ser manejados por incisión y presentación, los factores del huésped, y la gestión de la herida [ 38 - 40 ]. En
drenaje, abscesos en los usuarios de drogas inyectables requieren especial general, 10 - 20% de las heridas por mordedura se infecta, incluyendo 30 -

consideraciones en comparación con 50% de gato muerde, 5 - 25% de las mordeduras de perro, y 20 - 25% de las mordeduras humanos,

infecciones de los tejidos blandos, que no son causadas por el abuso de respectivamente [ 41 ].

drogas por vía intravenosa [ 32 - 35 ]. Hay dos fuentes principales de Los patógenos predominantes en estas heridas son parte de la flora
organismos: los propios usuarios de drogas inyectables (sus orofaringe, la oral normal del animal muerde, junto con organismos de la piel humanos
piel o heces), y el medio ambiente. se puede producir la contaminación y invasores secundarios ocasionales (por ejemplo, S. aureus y GAS).
cuando el usuario prepara o se inyecta la droga, utiliza agujas compartidas, Junto con Estafilococo ssp. (Incluyendo MRSA) y Estreptococo ssp.
o vuelve a utilizar material de inyección. Fabricación y manipulación de los (incluso S. pyogenes), los patógenos comúnmente aisladas incluyen Pasteurella
medicamentos inyectables pueden estar lejos de las normas de higiene [ 36 ]. spp. ( Pasteurella multocida, Pasteurella canis, dagmatis Pasteurella),
señales persistentes de infección sistémica requieren evaluación para Capnocytophagia canimorsus, (anaerobios Fusobacterium spp., Prevotella spp.,
Bacteroides spp., Porphyromonas spp.), y otros. Streptococci puede ser
la presencia de aislado de 50% de las heridas por mordedura humanos, S. aureus de
endocarditis. Los cuerpos extraños, tales como agujas rotas, deben 40%, y (Eikenella corrodens un bacilo anaerobio facultativo
descartarse por radiografía, y la ecografía dúplex deben llevarse a cabo Gram-negativo) de 30%. Las mordeduras humanas pueden transmitir
para identificar la presencia de complicaciones vasculares [ 37 ]. Viral HBV, HCV, y
(HIV, HCV, HBV) infecciones agudas o crónicas deben estar
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 8 of 24

la profilaxis contra el VIH y post-exposición se deben considerar en todos los Las úlceras por presión son áreas localizadas de necrosis de los tejidos que
casos [ 25 ]. tienden a desarrollarse cuando los tejidos blandos se comprime entre una
Existe consenso clínico que los pacientes pueden dividirse en grupos de bajo prominencia ósea y una superficie externa por un período de tiempo prolongado.
y de alto riesgo, dependiendo de la causa, naturaleza y localización de la lesión El daño puede ser relativamente menor, o puede conducir a la destrucción
y las características del paciente, pero no hay directrices basadas en la masiva de los tejidos más profundos. La mayoría de las úlceras por presión se
evidencia están actualmente disponibles. desarrollan en las zonas adyacentes al isquion, el sacro y trocánter mayor. Las
úlceras por presión representan un problema frecuente especialmente en
riego profunda de la herida sirve para eliminar organismos y agentes pacientes ancianos frágiles con comorbilidades crónicas [ 25 ]. Cuando se produce
patógenos extranjeros. No se recomienda el riego bajo presión, ya que puede la infección, es típicamente polimicrobianas e incluye aerobios ( S. aureus,
conducir a la propagación incontrolada de bacterias en las capas de tejido más Enterococcus spp., Proteus mirabilis, Escherichia coli, Pseudomonas spp.) y
profundas. El tratamiento quirúrgico se basa en la eliminación de tejido necrótico anaerobios ( Peptococcus spp., Bacteroides fragilis, Clostridium perfringens) [ 25 ].
y reducción mecánica de la carga de patógenos. No se recomienda la profilaxis
universal con antibióticos. Los amplios metaanálisis de Medeiros et al. en la
base de datos de Cochrane [ 42 ] Demostraron ninguna base probatoria para una
reducción de la tasa de infección por los antibióticos profilácticos, a excepción Combinación de intervenciones quirúrgicas y antibióticos puede ser necesaria
de las heridas de mordeduras en las manos. A pesar del mal estado de la para gestionar las úlceras por decúbito infectadas. El desbridamiento quirúrgico
evidencia, la mayoría de los expertos recomiendan el tratamiento temprano con es necesario para eliminar el tejido necrótico. La terapia con antibióticos se debe
antibióticos durante 3 a 5 días, las heridas y las heridas profundas frescas en utilizar para los pacientes con infecciones úlcera por presión graves, incluyendo
determinadas zonas corporales críticos (manos, pies, áreas cerca de las aquellos con la difusión de la celulitis o en pacientes con signos sistémicos de
articulaciones, cara, genitales), para las personas en situación de riesgo elevado infección. Debido a que tales infecciones generalmente son polimicrobianas,
de la infección, y para personas con implantes, tales como válvulas cardíacas regímenes terapéuticos deben ser dirigidas contra ambos organismos
artificiales [ 43 - 45 ]. Los antibióticos no deben administrarse si el paciente facultativos Gram-positivos y Gram-negativos, así como organismos anaerobios.
presenta 24 h o más después de la picadura y no hay signos clínicos de En muchos casos de úlceras por presión, para cuidados de heridas correcta
infección [ 46 ]. puede evitar en gran medida la aparición de estas infecciones.

lesiones por quemaduras importantes pueden predisponer a complicaciones Cuándo administrar antibióticos para MRSA en IPPBc?
infecciosas. Queman infecciones de heridas son una de las complicaciones más Recomendamos para administrar antibióticos dirigidos contra MRSA
importantes y potencialmente graves que se producen en el período agudo como un complemento a la incisión y el drenaje basado en epidemiología
después de una lesión. gestión precisa de la herida con la escisión temprana de local (área con más de 20% de MRSA en aislamientos hospitalarios
la escara puede disminuir sustancialmente la incidencia de infección invasiva invasivos o alta circulación de MRSA en la comunidad), los factores de
heridas por quemaduras. El daño a esta barrera después de una quemadura riesgo específicos para MRSA, y clínica condiciones (recomendación
interrumpe el sistema inmune innato y aumenta la susceptibilidad a la infección 1C).
bacteriana. Aunque las superficies de la herida por quemadura son estériles
inmediatamente después de la lesión térmica, estas heridas pueden ser La mayoría de IPTBs afectando a la piel sana son causadas por cocos
colonizados con microorganismos. Si el paciente ' s defensas del huésped y las grampositivos aerobios, específicamente S. aureus y estreptococos. Las
medidas terapéuticas (como la escisión del tejido necrótico y los medicamentos cepas de S. aureus y gas puede producir una variedad de toxinas que
de la herida) son inadecuados, los microorganismos pueden colonizar el tejido pueden tanto potenciar su virulencia y afectar a los tejidos blandos y
viable, y puede producirse una infección de la herida quemadura. Quemar permitir la invasión de la dermis. gestión IPTBs se ha vuelto más
infecciones de la herida por lo general son polimicrobianas. Ellos pueden ser complicada debido a la creciente prevalencia de patógenos resistentes a
colonizados inmediatamente por bacterias Gram-positivas del paciente ' s flora de múltiples fármacos. una variación considerable en las tasas de
la piel endógenos o el ambiente externo. Sin embargo, también pueden ser resistencia de S. aureus to methicillin (or oxacillin) in patients with SSTIs
colonizados rápidamente por bacterias Gram-negativas, por lo general una has been noted between continents, with the highest rates in North
semana después de la lesión por quemadura. Los cultivos bacterianos pueden America (35.9%), followed by Latin America (29.4%) and Europe (22.8%)
ayudar en la selección de un antibiótico adecuado, especialmente en casos de [ 48 ]. Although MRSA has been usually acquired during exposure in
resistencia a fármacos bacteriano, pero alterados parámetros farmacocinéticos hospitals and other healthcare facilities, there has been a recent increase
en pacientes con quemaduras deben ser considerados y la dosificación debe in MRSA infections presenting in the community (CA-MRSA) [ 49 ].
ajustarse en consecuencia para maximizar antibiótico eficacia [ 47 ]. CA-MRSA strains are genetically and phenotypically distinct from
HA-MRSA. CA-MRSA infections are becoming increasingly common.
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 9 of 24

They can have a rapid and devastating course and may produce the What oral antibiotics can be used for the management of
pathogenic Panton – Valentine leucocidin toxin (PVL), which destroys white MRSA skin and soft-tissue infections (SSTIs)? What
blood cells and is an important virulence factor [ 50 ]. They may be intravenous antibiotics can be used for the management of
susceptible to a wider range of anti-staphylococcal antibiotics (some are MRSA skin and soft-tissue infections?
resistant only to beta-lactams). Populations at increased risk for
CA-MRSA are listed below [ 49 ]: For oral antibiotic coverage of MRSA in patients with SSTI, we suggest
the following agents: linezolid
(recommendation 1A), trimethoprim-sulfamethoxazole (TMP-SMX)
Children < 2 years old. (recommendation 1B), a tetracycline (doxycycline or minocycline)
Athletes (mainly contact-sport participants). Injection (recommendation 1B), or tedizolid (Recommendation 1A). For
drug users. Homosexual males. Military personnel. intravenous (IV) antibiotic coverage of MRSA in patients with SSTI, we
suggest the following agents: daptomycin (10mg/kg/dose IV once daily)
(recommendation 1A), IV linezolid (recommendation 1A), IV ceftaroline
Inmates of correctional facilities, residential homes, or shelters. (recommendation 1A), IV dalbavancin (recommendation 1A), IV
vancomycin (recommendation 1A), IV tigecycline (recommendation 1A),
Vets, pet owners, and pig farmers. Patients with or IV tedizolid (recommendation 1A).
post-flu-like illness and/or severe pneumonia.

Patients with concurrent SSTI.

History of colonization or recent infection with CA-MRSA. Seven to 14 days of therapy is recommended but should be
individualized on the basis of the patient ’ s clinical response
History of antibiotic consumption in the previous year, (recommendation 1A). IV to oral switch should occur when criteria of
particularly quinolones, or macrolides. clinical stability have been reached (recommendation 1C).

MRSA poses a significant and enduring problem to the treatment of For CA-MRSA, recommended oral agents are clindamycin, although
infection by such strains. Resistance is usually conferred by the clindamycin resistance is now very common [ 52 ], tetracyclines,
acquisition of a non-native gene encoding a penicillin-binding protein TMP-SMX, linezolid, tedizolid, and occasionally, fluoroquinolones.
(PBP2a), with significantly lower affinity for beta-lactams. This resistance Several observational studies and one small randomized trial [ 53 , 54 ]
allows cell-wall biosynthesis, the target of beta-lactams, to continue even suggest that TMP-SMX, doxycycline, and minocycline are effective for
in the presence of typically inhibitory concentrations of antibiotic. PBP2a such infections. If coverage for both streptococci and MRSA is desired for
is encoded by the mecA gene, which is carried on a distinct mobile oral therapy, options include clindamycin alone, or the combination of
genetic element (SCC mec). These genetic elements contain two required either TMP-SMX or doxycycline with a beta-lactam (e.g., penicillin,
components: the mec cephalexin, or amoxicillin). Glycopeptides have been for many years the
microbiological agents of choice used in complicated Gram-positive
infections. Fortunately, staphylococcal resistance to glycopeptides
gene complex and the ccr gene complex (which contains site-specific remains rare, although rising minimal inhibitory concentrations (MICs) of
recombinase genes). The SCC mec elements have been classified into glycopeptides may affect the efficacy of these antibiotics [ 55 , 56 ].
eight types (I – VIII) based on the structure and combination of mec and ccr Increased resistance to glycopeptides has encouraged the development
of new agents active against Gram-positive bacteria,
gene complexes present. These elements also differ in what other
antimicrobial resistance genes are carried on them. Types I, IV, V, VI, and
VII generally do not carry other resistance genes. Types II, III, and VIII
may contain one or more other resistance genes, such as
particularly for severe soft-tissue
ermA ( erythromycin), aadD ( tobramycin), and tetK infections where aggressive antimicrobial management is always
(tetracycline). These types are also used to help distinguish CA-MRSA recommended, such as linezolid and
and HA-MRSA strains. Most HA-MRSA strains carry SCC mec types I, II, daptomycin. Linezolid has been considered an agent of choice in
III, VI, and VIII; while most CA-MRSA strains carry types IV, with some complicated skin and soft-tissue infections (cSSTIs). It has the
carrying types V and VII [ 51 ]. If MRSA is suspected (both HA and advantages of early intravenous-to-oral switch with the oral preparation
CA-MRSA), glycopeptides and other antimicrobial options are available having very high bioavailability and excellent tissue penetration [ 57 ].
agents. Also, new options such as dalbavancin and tedizolid also can be
administered.
In 2010, an open-label study compared oral or intravenous linezolid
with intravenous vancomycin for
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 10 of 24

treatment of cSSTIs caused by MRSA [ 58 ]. Patients receiving linezolid Minocycline100 mg q12h Trimethoprim and sulfamethoxazole
had a significantly shorter length of stay and duration of intravenous 160/800 mg q12h Doxycycline 100 mg q12h Clindamycin 300 – 600
therapy than those receiving vancomycin. Both agents were well mg q8h (high resistance rate) Linezolid 600 mg q12h Tedizolid
tolerated. Adverse events were similar to each drug ’ s established safety 200 mg q24 h
profile [ 58 ].

Recently, a Cochrane meta-analysis included all randomized controlled

trials comparing linezolid with vancomycin in the treatment of SSTIs [ 59 ].
Linezolid was associated with a significantly better clinical (risk ratio [RR] Intravenous options:
= 1.09, 95% CI, 1.03 – 1.16) and microbiological cure rate in adults (RR=
1.08; 95% CI, 1.01 – 1.16). For infections caused by MRSA, linezolid was Vancomycin 15 mg/kg IV q12h Teicoplanin LD 12 mg/kg IV q12h
significantly more effective than vancomycin in clinical (RR = 1.09; 95% for 3 doses, then 6 mg/kg q12h
CI, 1.03 – 1.17) and microbiological cure rates (RR= 1.17; 95% CI, 1.04 – 1.32).
The daily cost of outpatient therapy was less with oral linezolid than with Tigecycline 100 mg IV as a single dose, then 50 mg IV q12h
intravenous vancomycin. Although inpatient treatment with linezolid cost Linezolid 600 mg q12h Daptomycin 4 – 6 mg/kg q24h Ceftaroline
more than inpatient treatment with vancomycin per day, the median 600 mg q12h
length of hospital stay was 3 days shorter with linezolid. Daptomycin has
proven efficacy in patients with Gram-positive complicated ©SSTIs,
including those caused by S. aureus resistant to methicillin [ 60 ]. Dalbavancin 1000 mg once followed by 500 mg after 1 week or
Daptomycin has been shown to achieve very good concentrations in the 1500 mg one dose Tedizolid 200 mg q24h
skin and soft tissues. In 2010, a meta-analysis compared effectiveness
and toxicity of daptomycin with that of other antimicrobials for the
treatment of SSTIs. Four studies were included in the analysis (three The decision to use intravenous or oral agents has been debated.
were randomized RCTs). Vancomycin and semisynthetic penicillins were Currently, oral therapy is recommended for mild infections and
used in the comparator arm. Three studies reported on patients with intravenous therapy for severe infections. Moderate infections may be
cSSTIs. Daptomycin tissue penetration supports its use in the treatment treated via the oral route, or with one to two intravenous doses and then
of cSSTIs, and it has been shown to be non-inferior to vancomycin and transitioning to oral therapy. For patients with severe infections who are
semisynthetic penicillins [ 61 ]. able to tolerate oral therapy and in whom clinical improvement has been
documented, the goal should be to transition to the oral route as soon as
possible. There is evidence to suggest that this approach positively
impacts length of stay as well [ 69 ].

Ceftaroline is an oxyimino advanced-generation broadspectrum

cephalosporin which has in vitro activity against
S. aureus and MRSA, both of which are associated with cSSTIs. What are necrotizing infections?
Ceftaroline fosamil has been found to be effective in the treatment of Necrotizing soft-tissue infections (NSTIs) are life-threatening, invasive,
cSSTI when compared with vancomycin plus aztreonam for the treatment soft-tissue infections with a necrotizing component involving any or all
of cSSTI [ 62 – 64 ]. Ceftaroline fosamil was also well tolerated and had a layers of the soft-tissue compartment, from the superficial dermis and
safety profile concordant with other antibiotics in the cephalosporin class. subcutaneous tissue to the deeper fascia and muscle. The latter is most
commonly called “ necrotizing fasciitis ” [ 70 ].

More recently, new drugs have been approved for ABSSSI and have The necrotizing or non-necrotizing character of the infection should be
an important activity against MRSA, especially dalbavancin and tedizolid. always specified when classifying patients with soft-tissue infections
Tedizolid, a novel oxazolidinone with Gram-positive activity including (recommendation 1C).
MRSA, is promising because it can be administered daily in oral or
intravenous forms [ 65 , 66 ], and dalbavancin, a second-generation Delay in diagnosis and delay in treatment of these infections increase
lipoglycopeptide that covers MRSA, can be administered as infrequently the risk of mortality. Because of its aggressive character, NSTIs should
as once weekly [ 67 , 68 ]. always be differentiated from non-necrotizing infection. Several definitions
were published over the last few years, and all these definitions can be
confusing. NSTIs are defined by the presence of a spreading infection in
Antibiotics recommended for MRSA infections are listed below. any of the layers of the soft tissues (skin, subcutaneous tissue, superficial
fascia,
Oral options:
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 11 of 24

deep fascia, or muscles) which is associated with the presence of quality of care for necrotizing infections globally should focus on simple
necrosis of the layer(s) involved and hence requires surgical debridement. diagnostic criteria based on physical examination findings and recognition
All NSTIs fulfill this definition and have common features in their clinical of patients needing timely critical care.
presentation and diagnosis, and most importantly, all of these infections
by definition require surgical debridement. Therefore, labeling them with A classification of patients based on a severity assessment which could
different terms does not serve a useful purpose and may in fact identify cases requiring surgical and critical care may be an important tool
complicate management by delaying diagnosis and/or delaying surgical both in ICU and outside of the ICU. The Laboratory Risk Indicator for
debridement [ 7 , 8 , 10 ]. Necrotizing Fasciitis (LRINEC) score first published in 2004 [ 71 ] is based
on routinely performed parameters and offers a method to identify NSTIs
at early stage. With a score of 8 or higher, there is a 75% risk of a NSTI.
A systematic review of English-language literature from 2004 to 2014 to
How can necrotizing infections be classified? identify articles reporting use of LRINEC score and the incidence of
Patients with NSTIs should be classified into the following: necrotizing fasciitis was recently published [ 72 ]. After application of
inclusion criteria, 16 studies with 846 patients were included. The authors
concluded that the LRINEC score is a useful clinical determinant in the
High risk of poor outcome. Mild/moderate risk of diagnosis and surgical treatment of patients with necrotizing fasciitis, with
poor outcome. a statistically positive correlation between LRINEC score and a true
diagnosis of necrotizing fasciitis. A second meta-analysis including
Scores used for severity assessment of patients with necrotizing English-language studies reporting the diagnostic accuracy of LRINEC
infections may be useful in the emergency room or outside the intensive score was recently published [ 73 ]. Twenty-three studies ( n = 5982) were
care unit (ICU) and may identify patients early, who require surgical included. LRINEC ≥ 6 had sensitivity of 68.2% and specificity of
treatment and perioperative intensive care management
(recommendation 1C).

Several classifications of NSTIs have been proposed; however, none

are universally accepted. Necrotizing infections have been described
according to their anatomical locations (i.e., Fournier gangrene) and the
depth of infections: dermal and subcutaneous components (necrotizing
cellulitis), fascial component (necrotizing fasciitis), and muscular 84.8%, while LRINEC ≥ 8 had sensitivity of 40.8% and specificity of
components (necrotizing myositis). NSTIs may also be classified into 94.9%. The authors concluded that due to poor sensitivity, LRINEC
three types defined by the bacterial pathogens initiating the infection and should not be used to rule-out NSTIs.
their typical clinical characteristics: type 1 —
In the setting of such aggressive infections, a feasible, low-cost method
of rapidly identifying patients requiring critical care is crucial [ 74 ]. Early
polymicrobial, type 2 — mono-microbial pathogenic warning system scores utilize physiological, easy-to-measure parameters,
β- hemolytic streptococci or CA-MRSA, and type 3 — assessing physiological parameters such as systolic blood pressure,
mono-microbial secondary to a variety of pathogenic bacilli. However, pulse rate, respiratory rate, temperature, oxygen saturation, and level of
resolution of these nomenclature issues requires a consensus among consciousness. They are simple, non-invasive, and easy-to-repeat
international infectious disease physicians, surgeons, and intensivists, measurement at the bedside. The Sepsis-3 definitions [ 75 ] suggest that
and probably, these various methods of classification are not clinically patients with at least two of these three clinical variables may be prone for
useful. Although many specific variations of NSTIs have been described, the poor outcome typical of sepsis: (1) low blood pressure (systolic blood
the initial approach to diagnosis, antimicrobial treatment, and surgical pressure ≤ 100 mmHg), (2) high respiratory rate ( ≥ 22 breaths per
intervention is similar for all forms and identifying those infections needing minute), or (3) altered mentation (Glasgow coma scale < 15) (quick SOFA
immediate aggressive management is more important than determining [qSOFA]). It is supposed to be useful in out-of-hospital, emergency
the specific variant. Delay in diagnosis and/or treatment of NSTIs surgery, or general hospital ward settings, and in patients with positive
correlates with a poor outcome, leading to multiple organ failure. Early qSOFA, organ dysfunction should be investigated. The qSOFA score
prognostic evaluation of NSTIs is crucial to assess the severity and should not be regarded as a diagnostic criterion for defining sepsis.
decide the aggressiveness of treatment. Necrotizing infections remain an Rather, it should be regarded as a warning for patients with suspected
important source of patient morbidity and are frequently associated with infection who are likely to have poor
poor clinical prognosis. Any process of improving
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 12 of 24

outcomes. In the setting of patients with necrotizing infections, it may be pathophysiologic mechanisms and include fever,
useful as a warning for patient ’ s severity assessment. hypotension, tachycardia, altered mental status, and signs of organ
dysfunction. In principle, these mechanisms may involve both host and
pathogen factors. Host-related factors are determined by human genes
Is a multidisciplinary approach to necrotizing infections that control release of cytokines and encode pro-inflammatory cytokines
mandatory? eliciting subsequent counter-regulatory mechanisms. Microbial virulence
A multidisciplinary team is mandatory for the management of NSTIs. factors include Gram-positive and Gram-negative bacterial products.
Depending on the time line, various specialties are involved. Specific These toxins are absorbed in the bloodstream. Bacterial superantigens
attention should be given to the long-term management of these patients (pyrogenic exotoxins) directly stimulate and non-specifically activate high
(recommendation 1C). numbers of T cells and macrophages to produce pro-inflammatory
mediators such as TNF- α, IL-1, and IL-6. The massive release of these
NSTIs rank among one of the more difficult disease processes cytokines produces an uncontrolled systemic inflammatory response that
encountered by physicians. The most critical factors for reducing mortality can lead to multisystem organ dysfunction and shock [ 77 ].
in NSTIs are early recognition and urgent operative debridement. Initial
treatment of patients with necrotizing infections should always require
coordination between the surgeons, intensivists, and infectious disease
specialist. Treatment consists of radical debridement associated with
broad-spectrum antimicrobial therapy and hemodynamic support.
How can necrotizing infections be diagnosed?
Clinical signs of NSTI include pain out of proportion, edema extending
Moreover, the magnitude of necrotic tissues that need to be radically beyond the erythema, and fever. A rapidly progressive soft-tissue
debrided, although required to save the patient ’ s life, often create unique infection should always be suspected as a necrotizing infection
and difficult challenges in terms of wound care, preservation of function, (recommendation 1C).
reconstruction, and cosmesis. These problems require time and a
multidisciplinary approach. After an extended hospitalization, multiple The initial differential diagnosis between a cellulitis and a necrotizing
dressing changes, and surgical procedures, the survivor of NSTI faces infection that requires prompt operative intervention may be difficult. Most
months of continued physical therapy to regain functional independence, cases of NSTI are initially diagnosed and begin as cellulitis. However,
whenever possible. Rehabilitation is an essential and integral component since time to operative debridement is an important determinant of
of recovery [ 76 ]. outcome in necrotizing infections, timely diagnosis is essential.

Patients with NSTI usually present with severe pain which is out of
What is the pathophysiology of necrotizing infections proportion to the physical findings [ 78 – 82 ]. Typical local signs are as
follows:
Due to the rapid progression of the inflammatory process, early treatment
of necrotizing infection is always recommended (recommendation 1C). Edema
Erythema
There are two main ways by which bacteria can invade soft tissues. Severe and crescendo pain out of proportion Skin bullae
The most common way is through a break in the skin barrier. In case of or necrosis (at later stage) Swelling or tenderness
contamination by spores of C. perfringens, the anaerobic environment Crepitus
(caused by impairment of the blood supply resulting in tissue hypoxia) is
necessary for maturation and proliferation of Clostridium
Systemic signs are as follows:
strains [ 77 ]. The second way is hematogenous spread of bacteria to the
tissue; however, it is a rare condition. Local and systemic manifestations Fever
are related to specific pathophysiologic mechanisms depending upon the Tachycardia
toxins and enzymes of involved bacteria. Hypotension
Shock
Bacteria proliferate and release toxins, which cause local tissue
damage and impair inflammatory responses. Some toxins produce Laboratory tests are not highly sensitive or specific for NSTIs. A rapidly
thrombosis of larger venules and arterioles, with subsequent ischemic progressive soft-tissue infection should be treated as a necrotizing
necrosis of all tissue layers, from the dermis to the deep muscles [ 77 ]. infection, from the beginning. The clinical picture may worsen very
Systemic manifestations are also related to toxin-mediated quickly, sometimes during a few hours.
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 13 of 24

In order to predict the presence of NSTI, the Laboratory Risk Indicator Magnetic resonance imaging (MRI) has been the imaging modality of
for Necrotizing infection (LRINEC) score was proposed [ 71 ]. LRINEC choice for necrotizing fasciitis. Patients with necrotizing fasciitis usually
score assigns points for abnormalities in six independent variables: serum have a significantly greater frequency of the following MRI findings: thick ( ≥
C-reactive protein level (> 150mg/L), white blood cell (WBC) count (> 3 mm) abnormal signal intensity on fat-suppressed T2-weighted images,
low signal intensity in the deep fascia on fat-suppressed T2-weighted
15,000/ μ L), hemoglobin level (< 13.5 g/dL), serum sodium level (< images, a focal or diffuse non-enhancing portion in the area of abnormal
135mmol/L), serum creatinine level (> 1.6mg/dL [142mmol/l]), and serum signal intensity in the deep fascia, extensive involvement of the deep
glucose level (> 180mg/dL [10 mmol/l]). With a score of 8 or higher, there fascia, and involvement of three or more compartments in one extremity [ 93
is a 75% risk of a NSTI. ]. However, MRI may be difficult to perform under emergency conditions
and is not recommended as the first-choice imaging technique.
Subsequent evaluation of the LRINEC score has demonstrated
conflicting results. Several studies have assessed the utility of LRINEC for
the early diagnosis of necrotizing infections [ 72 , 83 – 88 ].

Recent evidence has demonstrated that it lacks the sensitivity to be a Ultrasound has the advantage of being rapidly performed at bedside
useful adjunct for the diagnosis of necrotizing infections [ 73 ]. and may be helpful in differentiating simple cellulitis from necrotizing
fasciitis. In a prospective observational study of 62 patients with clinically
The diagnosis of necrotizing infection is primarily a clinical diagnosis. suspected necrotizing fasciitis, ultrasound had a sensitivity of 88.2%,
However, radiologic imaging may be able to provide useful information specificity of 93.3%, positive predictive value of
when the diagnosis is uncertain. A plain X-ray should not be used to
rule-out necrotizing infection (recommendation 1B). In unstable patients, 95.4%, negative predictive value of 95.4%, and diagnostic accuracy of
ultrasound may be useful to differentiate simple cellulitis from necrotizing 91.9%. The authors considered the findings of diffuse subcutaneous
fasciitis (recommendation 2C). thickening accompanied by fluid accumulation of > 4 mm in depth along
the deep fascial layer predictive of necrotizing fasciitis [ 94 ]. Rapid
performance of frozen-section soft-tissue biopsy, early in the evolution of
Imaging studies should not delay surgical consultation and intervention a suspect lesion, may provide a definitive and life-saving diagnosis. Triple
(recommendation 1A). diagnostics which include an incisional biopsy over the most suspected
Frequently, plain radiographs are normal or with increased soft-tissue area, a fresh frozen section and Gram staining might be an important
thickness and opacity, unless the infection and necrosis are advanced. adjunct in early stages of suspected necrotizing infections
The characteristic finding is gas in the soft tissues, but subcutaneous gas (recommendation 1C). Early frozen-section diagnosis should be limited to
is present only in few cases of necrotizing infection and is not present in those cases in which the clinical or radiographic findings are not
pure aerobic infections such as those caused by S. pyogenes. diagnostic (recommendation 1C). Fascial biopsy with frozen section has
been suggested as a means to achieve earlier diagnosis of NSTIs [ 95 ,

Additionally, subcutaneous gas may not be present in earlier stages of

the disease process and only become manifest as the patient ’ s condition
deteriorates [ 89 , 90 ]. Computed tomography (CT) has a higher sensitivity
than plain radiography in identifying early NSTIs. Findings consistent with 96 ]. However, frozen-section biopsy is not very practical and requires
necrotizing infections are fat stranding, fluid and gas collections that availability and experience of the pathologists, and the time taken to carry
dissect along fascial planes, and gas in the involved soft tissues. out and analyze the sample could be used for debridement [ 97 ]. The
Additionally, fascial thickening and non-enhancing fascia on contrast CT Finger test is another adjunct method described for diagnosing NSTIs. It
suggests fascial necrosis [ 91 ]. In 2010, a case series study [ 92 ] analyzing is performed under local anesthesia. A 2-cm incision is made down to the
the use of CT scanning for the diagnosis of NSTIs was published. Of 67 deep fascia. Minimal tissue resistance to finger dissection (positive Finger
patients with study inclusion criteria, 58 underwent surgical exploration, test), the absence of bleeding, presence of necrotic tissue, and/or murky
and NSTIs was confirmed in 25 (43%). The remaining 42 patients had and grayish ( “ dishwater ”) fluid following incision, all suggest the diagnosis
either non-necrotizing infections during surgical exploration ( n = 33) or of NSTI [ 98 ].
were treated non-operatively with successful resolution of the symptoms ( n
= 9). The sensitivity of CT to identify NSTI was 100%, specificity was 81%,
positive predictive value was 76%, and negative predictive value was
100%. What is the best timing of source control?
Provide (surgical) source control in patients with NSSTI as soon as
possible, but at least within the first 12 h after admission, in patients with
a high suspicion for necrotizing infection. Early source control,
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 14 of 24

antimicrobial therapy, and (organ) supportive measures are the follows: surgical treatment less than 12 h after admission, 12 to 24 h after
cornerstone of treatment in patients with sepsis or septic shock caused by admission, and more than 24 h after admission. Patients who underwent
NSSTI (recommendation 1B). surgery less than 12 h after admission had a significantly lower mortality
compared with those who had surgery either 12 to 24 h after admission
Source control for SSTIs includes drainage of infected fluids, (adjusted hazard ratio [HR], 0.064; 95% CI, 1.6 × 10 − 7 to 0.25; p = 0.037)

debridement of infected soft tissues, and removal of infected devices or or more than 24 h after admission (adjusted HR, 0.0043; 95% CI, 2.1 × 10 −
5
foreign bodies. It should also include definitive measures to correct any
anatomic derangement resulting in ongoing microbial contamination and
restoring optimal function. Early surgical debridement with complete to 0.0085; p = 0.002). There was no difference in mortality risk between
removal of necrotic tissue is essential to decrease mortality and other patients who underwent surgery 12 to 24 h after admission and those
complications in patients with NSTIs. It is the most important determinant who had surgery more than 24 h after admission ( p = 0.8). We suggest to
of outcome in necrotizing infections. This was well described in a study by remove only devitalized/infarcted skin and spare normally perfused skin.
Bilton et al. in which patients with NSTIs, who had adequate surgical In case where skin viability is questionable, skin preservation and
debridement (early and complete), were compared to those with either reassessment at the second operation is indicated (recommendation 1C).
delayed or incomplete debridements. The mortality in the latter group was
38% compared to 4.2% in the group receiving early adequate surgical
treatment [ 99 ]. Delay in source control in patients with NSTIs has been
repeatedly associated with a greater mortality. A retrospective study Once the decision to take the patient for an operation has been made,
including 47 patients with the diagnosis of NSTI admitted to a large the initial incision is done in the compromised area and the wound is
academic hospital from December 2004 to December 2010 was explored for macroscopic findings of NSTIs. Incision should take place
published in 2011 [ 100 ]. Overall mortality was 17.0%. The average along the involved muscular lodges. Removal of all non-viable tissue
number of surgical debridements in patients with surgical treatment should be accomplished including muscle, fascial layers, subcutaneous
delayed > 12 h from the time of emergency department admission was tissue, and skin if they are compromised, and one should extend the
significantly higher than those who had an operation within 12 h after incision until healthy viable tissue is seen. Removal of previously viable
admission (7.4 ± 2.5 versus 2.3 ± 1.2; p < 0.001). Delayed surgical skin or muscle should usually not be done at the initial operation,
debridement was associated with significantly higher mortality, higher attempting skin sparing via multiple incisions (to preserve perforators),
incidence of septic shock and renal failure, and more surgical while accounting for underlying bone, nerve, and vascular structures. Skin
debridements than patients with early surgical debridements. After perfusion and viability can easily be assessed at re-exploration, and
adjusting for possible confounding factors, the average number of removal at that time is easy, if indicated. The wound should always be left
surgical debridements and the presence of septic shock and acute renal open. Amputation of a limb does not add to the acute debridement and
failure were still significantly higher in patients in whom surgery was should be reserved for
delayed > 12 h.

late and extreme

presentations.

What is the best timing of re-exploration?

Consider to plan the first re-exploration within 12 –
A retrospective study including 106 patients with necrotizing infections 24 h and to repeat re-exploration(s) until the patient is free of necrosis
conducted in a medical ICU was published in 2009 [ 101 ]. Overall hospital (recommendation 1C).
mortality was There is a lack of literature examining outcomes in necrotizing
40.6%. In multivariate analysis, underlying cardiovascular disease, SAPS infections when surgical re-debridements are performed in early versus
II, abdomino-perineal compared to limb localization, time from the first delayed intervals. Scheduled re-explorations should be done at least
signs to diagnosis < 72 h, and time from diagnosis to surgical treatment > every 12 – 24 h after the initial operation or sooner if clinical local or
14 h in patients with septic shock were independently associated with systemic signs of worsening infection become evident, as well as with
hospital mortality. worsening laboratory parameters (particularly WBC count).
Re-explorations should be repeated until the time when very little or no
A retrospective study of 121 patients (mean age, 65.2 ± 11.6 years) debridement is required.
with Vibrio vulnificus- related necrotizing infection who underwent surgical
intervention between July 1998 and June 2011 was published in 2011 [ 102
]. The patients were divided into three groups according to the time A prospective observational study by Okoye et al. [ 103 ] showed that
between admission and surgical treatment as delayed re-debridement after initial source control in necrotizing infections
results in worse
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 15 of 24

survival and an increased incidence of acute kidney injury. The authors Intravenous immunoglobulin therapy has been postulated to improve
concluded that further studies to identify the optimal time interval for outcomes in a selected population of patients with NSTIs. Most of the
re-debridement are warranted. reported studies evaluated its use for invasive GAS infections including
GAS-related NSTIs with streptococcal toxic shock syndrome (STSS).

What is the role of hyperbaric oxygen therapy (HBO) for source

control in necrotizing infections? The efficacy and safety of high-dose IVIG as adjunctive therapy in
Consider adjuvant hyperbaric oxygen therapy in patients with NSTI after STSS were evaluated in a multicenter, randomized, double-blind,
prompt debridement (recommendation 2B). placebo-controlled trial [ 106 ]. The trial was prematurely terminated
because of slow patient recruitment, and results were obtained from 21
Despite significant advancements in critical care management as well enrolled patients (10 IVIG recipients and 11 placebo recipients). The
as improved knowledge regarding NSTIs, mortality remains relatively primary end point was mortality at 28 days, and a 3.6-fold non-significant
high. Adjunctive and less conventional treatment options have been higher mortality rate was found in the placebo group. A significant
explored in an effort to improve outcomes in this group of patients. decrease in the sepsis-related organ failure assessment score at days 2 ( p
Hyperbaric oxygen (HBO) is one of these modalities. It is a medical = 0.02) and 3 ( p = 0.04) was noted in the IVIG group. Furthermore, a
treatment that uses delivery of 100% oxygen at a pressure of 2 – 3 significant increase in plasma neutralizing activity against superantigens
absolute atmospheres. Its use is motivated by the fact that oxygen expressed by autologous isolates was noted in the IVIG group after
delivery at these parameters achieves a much higher concentration of treatment ( p = 0.03). Although statistical significance was not reached in
dissolved oxygen in blood which results in higher tissue oxygen tensions. the primary end point, the trial provides some supportive evidence for
At this higher tissue tension, beneficial effects may be seen including IVIG as an efficacious adjunctive therapy in STSS. IVIG therapy role in
improved leukocyte function, improving survival in STSS was also demonstrated in other prospective
studies [ 107 , 108 ].
inhibition of
anaerobic growth, inhibition of toxin production, and enhancement of
antibiotic activity.
The role of HBO as an adjunctive treatment has been debated, and no
prospective randomized clinical trials have been published. In order to
determine the effect of hyperbaric oxygen HBO therapy on mortality, In 2017, a retrospective study of adult patients with necrotizing fasciitis
complication rate, discharge status/location, hospital length of stay, and and vasopressor-dependent shock undergoing surgical debridement from
inflation-adjusted hospitalization cost in patients with NSTIs, a 2010 to 2014 in 130 US hospitals was published [ 109 ]. Of 4127 cases of
retrospective study of 45,913 patients in the Nationwide Inpatient Sample debrided necrotizing infection with shock at 121 centers, only 164 patients
from 1988 to 2009 was published in 2012 [ 104 ]. This retrospective (4%) at 61 centers received IVIG. IVIG subjects were younger with lower
analysis of HBO therapy in NSTI showed that despite the higher comorbidity indices, but higher illness severity. Clindamycin and
hospitalization cost and longer length of stay, the statistically significant vasopressor intensity were higher among IVIG cases, as was coding for
reduction in mortality supports the use of HBO therapy in NSTI (RR = TSS and GAS. In-hospital mortality did not differ between matched IVIG
0.47; 95% CI, 0.30 – 0.74). In 2013, a review about HBO therapy for and non-IVIG groups (crude mortality, 27.3 versus 23.6%; adjusted HR,
treating acute surgical and traumatic wounds was published [ 105 ]. The 1.00 [95% CI,
authors concluded that there is a lack of high-quality, valid research
evidence regarding the effects of HBO therapy on wound healing. HBO
could be useful, if available, but it should not interfere with the standard 0.55 – 1.83]; p = 0.99). Early IVIG ( ≤ 2 days) did not alter this effect ( p = 0.99).
treatment. Furthermore, the patient should not be transferred to carry out Among patients coded for TSS, GAS, and/or S. aureus, IVIG use was still
HBO therapy, thereby delaying standard care. unusual (6.8%) and lacked benefit ( p = 0.63). Median LOS was similar
between IVIG and non-IVIG groups (26 [ 13 – 49 ] versus 26 [ 11 – 43 ]; p = 0.84).

Recently, a Cochrane review on intervention for NSTIs was published [ 110

]. One trial of 100 randomized participants assessed IVIG as an adjuvant
drug, given at a dose of 25 g/day, compared with placebo, given for three
What is the role of intravenous immunoglobulin (IVIG) therapy consecutive days. No clear difference between IVIG and placebo in terms
for source control in necrotizing infections? of mortality within 30 days (RR = 1.17; 95% CI, 0.42 – 3.23), nor serious
adverse events experienced in the ICU (RR = 0.73; 95% CI, 0.32 – 1.65)
Consider intravenous immunoglobulin (IVIG) therapy in patients with were observed.
necrotizing infections caused by GAS (recommendation 2B).
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 16 of 24

What are the resuscitation principles in patients with necrotizing analysis, and 40 met criteria for the modified intent-to-treat analysis;
infection? 15 patients each were included in the high-dose and low-dose treatment
Supportive treatment in managing necrotizing infections must be early arms, and 10 in the placebo arm. Baseline characteristics were
and aggressive to halt progression of the inflammatory process comparable in the treatment groups. The Sequential Organ Failure
(recommendation 1A). Assessment score improved from baseline in both treatment groups
Early detection of sepsis and prompt aggressive treatment of the compared with the placebo group at 14 days (change from baseline
underlying organ dysfunction is an essential component for improving score, − 2.8 in the high-dose, − 2 in the low-dose, and + 1.3 in the
outcomes of critical ill patients [ 111 ]. Necrotizing infections may present placebo groups; p = 0.04). AB103-treated patients had a similar number of
with a fulminant course and may be associated with great morbidity and debridements (mean [SD], 2.2[1.1] for the high-dose, 2.3[1.2] for the
high case-fatality rates, especially when they occur in conjunction with low-dose, and 2.8 [2.1] for the placebo groups; p = 0.56). There were no
TSS. statistically significant differences in ICU-free and ventilator-free days or
in plasma and tissue cytokine levels. No drug-related adverse events
Early blood cultures, empirical antibiotic treatment, and intensive care were detected. A phase 3 trial, also known as the ACCUTE trial
for hemodynamic and metabolic support should be performed as soon as (Reltecimod Clinical Composite Endpoint Study in Necrotizing Soft Tissue
possible. Moreover, patients may lose fluids, proteins, and electrolytes Infections), has been designed as a single pivotal study to assess the
through a large surgical wound [ 112 ]. In addition, hypotension is caused efficacy and safety of Reltecimod versus placebo in patients with
by vasodilation induced by the systemic inflammatory response syndrome necrotizing infections.
to infection [ 113 ]. Fluid resuscitation and analgesia are the mainstays of
support for patients with advanced sepsis usually combined with
vasoactive amines associated with mechanical ventilation and other
organ function supports, if needed. No ideal fluid exists: resuscitation
therapy must be prompt and immediate as in any type of shock.

What antibiotics are recommended for empiric treatment of

clinically suspected necrotizing infections?
What are the new agents to treat necrotizing infections
Antibiotic treatment of necrotizing infections should be prompt and
AB103 (Reltecimod) is a new agent for modulation of inflammation after aggressive (recommendation 1B). The initial empirical antibiotic regimen
necrotizing infections. Further study is warranted to establish efficacy (no should comprise broad-spectrum drugs including anti-MRSA and
recommendation). anti-Gram-negative coverage (recommendation 1C). Vancomycin
treatment should be avoided in patients with renal impairment and when
AB103 (Reltecimod) is a safe and promising new agent for modulation MRSA isolate shows a MIC for vancomycin ≥ 1.5mg/mL
of inflammation after a necrotizing infections. However, further studies are (recommendation 1B).
warranted to establish efficacy.

AB103 (originally p2TA) is a novel synthetic CD28 mimetic octapeptide Daptomycin or linezolid are drugs of choice for empirical anti-MRSA
that selectively inhibits the direct binding of superantigen exotoxins to the coverage. Alternatively, ceftaroline, telavancin, tedizolid, and dalbavacin
CD28 costimulatory receptor on T-helper 1 lymphocytes [ 114 ]. Preclinical can be used (recommendation 2C).
studies demonstrated that AB103 and related superantigen mimetic
peptides are associated with improved survival in animal models of toxic The choice of anti-Gram-negative treatment should be based on local
shock and sepsis. The hypothesis is that AB103 could be administered prevalence of ESBL-producing
safely in patients presenting with NSTI and would modulate the immune Enterobacateriaceae and multidrug-resistant organisms (MDROs)
response to reduce the development or progression of organ failure. non-fermenters (recommendation 1B).

De-escalation of antibiotic therapy should be based on clinical

improvement, cultured pathogens, and results of rapid diagnostic tests
To establish the safety of AB103 in patients with NSTI and evaluate the where available (recommendation 1C).
potential effects on clinically meaningful parameters related to the disease
[ 115 ], a prospective, randomized, placebo-controlled, double-blinded Microbiologically, NSTIs have been classified as either type 1
study was performed in six academic medical centers in the USA. (polymicrobial) or type 2 (mono-microbial) or type 3 (gas gangrene).
Participants included adults with NSTI. Of 345 patients screened, 43 were Occasionally in immunocompromised patients, NSTIs may be also
enrolled for the intent-to-treat caused by mycotic species.
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 17 of 24

NSTIs type I is a polymicrobial infection involving aerobic and and a de-escalation if it is too broad particularly in critically ill patients
anaerobic organisms. It is usually seen in the elderly or in those with where de-escalation strategy is one of the cornerstones of antimicrobial
underlying illnesses [ 77 ]. Type I infection is often associated with gas in stewardship programs [ 116 ]. The choice of anti-Gram-negative treatment
the tissue and thus is difficult to distinguish from gas gangrene. should be based on local prevalence of ESBL-producing Enterobacateriaceae
Non-clostridial anaerobic cellulitis and synergistic necrotizing cellulitis are and MDRO non-fermenters.
type I variants. Both occur in patients with diabetes and typically involve
the feet, with rapid extension into the leg.
Should an antitoxin active drug (clindamycin or oxazolidinon)
be included in the empirical regiment of clinically suspected
NSTI type II is a mono-microbial infection. Among Gram-positive necrotizing infection?
organisms, GAS remains the most common pathogen, followed by
MRSA. Unlike type I infections, type II infections may occur in any age Either clindamycin or linezolid should be included in the empirical
group and in persons without any underlying illness. Other pathogens antibiotic regimen of NSTI (recommendation 1C).
include
Aeromonas hydrophila and V. vulnificus. Mono-microbial necrotizing fasciitis Selection of antibiotics that inhibit toxin production may be helpful,
due to Gram-negative pathogens (bacteroides and E. coli) have also been particularly in those patients who have evidence of TSS, potentially
reported, though these infections are typically seen in immunocompromised, present in patients who have streptococcal and staphylococcal infections.
diabetic, obese, and postoperative patients [ 77 ]. Protein cytotoxins play an important role in the pathogenesis of various
staphylococcal infections, and toxin production should be considered
Gas gangrene (clostridial myonecrosis), or type III NSTI, is an acute when selecting an antimicrobial agent for Gram-positive pathogens.
infection by clostridium or bacillus of healthy living tissue that occurs Linezolid and clindamycin play an important role because they may
spontaneously or as a result of traumatic injury. Recurrent gas gangrene, significantly inhibit exotoxin production from Gram-positive pathogens [ 117
occurring several decades after the primary infection, has also been – 119 ].
described.

The use of antimicrobial therapy is an adjuvant treatment and must be

combined with early surgical debridement. Once the diagnosis is made What is the optimal duration of antibiotic therapy for necrotizing
and blood cultures have been drawn, broad-spectrum coverage should be infections?
urgently commenced. Initial antibiotic therapy for necrotizing infections is In the absence of definitive clinical trials, antibiotic therapy should be
empirical in nature because microbiological data (culture and administered until further debridement is no longer necessary, the patient
susceptibility results) may require > 24 h before they are available for a has improved clinically, and fever has resolved for 48 – 72 h
more detailed analysis. (recommendation 1C).

Procalcitonin monitoring may be useful to guide antimicrobial

Since it is impossible to exclude with certainty a polymicrobial discontinuation (recommendation 2B).
necrotizing infection, an aggressive broad-spectrum empiric antimicrobial There is no direct evidence about optimal duration of antibiotic therapy,
therapy should initially be selected to cover Gram-positive, and the expert panel shares that antimicrobial therapy should be
Gram-negative, and anaerobic organisms until culture-specific results and administered until further debridement is no longer necessary, the patient
sensitivities are available. An acceptable empiric antibiotic regimen has improved clinically, and fever has been resolved for 48 – 72 h. Several
should always include antibiotics, which cover MRSA with the additional controlled clinical studies have evaluated the potential of the infection
benefit of inhibiting invasive GAS virulence proteins. For the treatment of biomarker procalcitonin (PCT) to improve the diagnostic work-up of
MRSA, we refer to the previous paragraphs. patients with bacterial infections and its influence on decisions regarding
antibiotic therapy [ 120 ].

For the treatment of Gram-negative bacteria, the use of

piperacillin-tazobactam in the setting without high local prevalence of In order to develop a PCT ratio indicating successful surgical
ESBL-producing Enterobacateriaceae optimizing intervention in patients with necrotizing infections, Friederichs et al. [ 121 ]
pharmacokinetic/pharmacodynamic parameters is appropriate. Carbapenems,designed a study of 38 patients treated with clinical signs of sepsis
administered in adequate dosage, including meropenem, caused by a NSTI. All patients received radical surgical treatment. Serum
imipenem-cilastatin, or doripenem may be used in the settings with high levels of PCT and C-reactive protein were monitored postoperatively. The
local prevalence of ESBL-producing Enterobacateriaceae. ratio of day 1 to day 2 was calculated. An eradication of the infectious
focus was successfully performed in 84% of patients, averaging 1.9
Culture-specific results and sensitivities can direct both broadening of
antimicrobial regimen if it is too narrow
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 18 of 24

operations (range 1 – 6) to achieve the elimination of the infectious source. MRI may be used to confirm clinical suspicions and to help in identifying
The PCT ratio was significantly higher in the group of patients with the extent of the soft-tissue involvement, particularly in the perirectal and
successful surgical intervention (1.665 versus 0.9, p < 0.001). A ratio retroperitoneal planes. Fournier ’ s Gangrene Severity Index (FGSI) is a
higher than the calculated cutoff of 1.14 indicated successful surgical standard score for predicting outcome in patients with FG and is obtained
treatment with a sensitivity of 83.3% and a specificity of from a combination of physiological parameters at admission including
temperature, heart rate, respiration rate, sodium, potassium, creatinine,
71.4%. The positive predictive value was 75.8%, and the negative leukocytes, hematocrit, and bicarbonate. A FGSI score above 9 has been
predictive value was 80.0%. demonstrated to be sensitive and specific as a mortality predictor in
The PCT ratio of postoperative day 1 to day 2 following major surgical patients with Fournier ’ s gangrene [ 126 , 127 ].
procedures for necrotizing infections represented a valuable clinical tool
indicating successful surgical eradication of the infectious focus and
correlated with the successful elimination of the infectious source and
clinical recovery.
Surgical debridement must be early and aggressive to halt progression
of infection. Cultures of infected fluid and tissues should be obtained
What is the treatment of Fournier ’ s gangrene? during the initial surgical debridement and the results used to tailor
Treatment of Fournier ’ s gangrene includes prompt appropriate antibiotic specific antibiotic management. Radical surgical debridement of the entire
therapy, hemodynamic support, and early debridement (recommendation affected area should be performed, continuing the debridement into the
1C). Early and extensive initial surgical debridement in Fournier ’ s healthy-looking tissue [ 128 , 129 ]. In the setting of FG, diverting colostomy
gangrene patients improves survival (recommendation 1C). has been demonstrated to improve outcomes. It helps in decreasing
sepsis by minimizing bacterial load in the perineal wound, thus controlling
infection [ 130 ]. Diverting colostomy does not eliminate the necessity of
We suggest consideration for fecal diversion — either by colostomy, multiple debridements, nor reduces the number of these procedures [ 131 ].
fecal tube system with or without negative pressure therapy — in cases of Diverting colostomy should be avoided as much as possible mainly when
Fournier ’ s gangrene with fecal contamination (recommendation 2C). there are other methods to avoid wound contamination. Recently, rectal
diversion devices have been marketed. They are silicone tubes designed
to divert fecal matter in patients with diarrhea, local burns, or skin ulcers.
Fournier ’ s gangrene (FG) is a severe type of NSTI involving the genital The devices protect the wounds from fecal contamination and reduce, in
area and or perineum. It was initially described by Baurinne in 1764 and is the same way a colostomy does, both the risk of skin breakdown and
named after Jean Alfred Fournier, a French dermatologist who in 1883 repeated inoculation with colonic microbial flora. Fecal diversion tubes
described it. Due to the complexity of fascial planes, the infection may can be used in combination with negative pressure wound therapy
extend up to the abdominal wall, down into the thigh areas, into the (NPWT) for effective isolation of the wound from fecal contamination.
perirectal and gluteal spaces, and, occasionally, into the retroperitoneum. Estrada et al. showed that this was an effective way for fecal diversion
Advanced FG can extend through the fascial planes ascending as high as and constitutes an attractive alternative to colostomy [ 132 ].
the torso and descending to the thighs. The perineal fascia, Colles ’ fascia,
is continuous with Scarpa ’ s fascia of the anterior abdominal wall and Buck
and Dartos ’ fascia of the penis and scrotum. Testicular involvement is
rare, and this has been attributed to their non-perineal blood supply. It has
a mortality rate that approaches 20 – 50% in many contemporary series [ 122
–

What is the role of negative pressure wound therapy in

124 ]. The origin of the infection is identifiable in the majority of cases and soft-tissue infections and necrotizing fasciitis?
is predominantly from anorectal, genito-urinary, or local cutaneous
sources [ 125 ]. The aggressive nature of the infection requires early We suggest to consider negative pressure wound therapy (NPWT) for
recognition and immediate surgical intervention. wound care after complete removal of necrosis in necrotizing infections
(recommendation 1C).
Diagnosis is based on clinical signs and physical examination.
Including cutaneous manifestations, erythema, subcutaneous The rapidly spreading infection followed by aggressive surgical
crepitations, patches of gangrene, a presence of potential portal of entry, intervention and repeated debridements creates challenges for wound
foul smell, purulence and/or wound discharge, and tenderness to management. NPWT refers to wound dressing systems that continuously
palpitation. Imaging, including conventional radiology, US, CT, and or intermittently apply sub-atmospheric pressure to the surface of a
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 19 of 24

wound. NPWT has become a popular treatment modality for the ideal mesh. Synthetic meshes are easy to handle and well tolerated;
management of many acute and chronic wounds. Sub-atmospheric however, they can be potentially associated with infection when bacteria
pressure has multiple beneficial effects on wound healing in animal adhere to the synthetic material leading to chronic infection. Mesh
models. Animal and human studies have shown that sub-atmospheric infection is a challenging complication of abdominal wall defect repairs [ 147
pressure improves the local wound environment through both direct and – 149 ]. Polypropylene remains the most commonly used material for
indirect effects; these effects accelerate healing and reduce the time to hernia repairs. Synthetic meshes consisting of large pore meshes are
wound closure [ 133 ]. In the setting of necrotizing infections once the more resistant to infection than the firm, smaller pore meshes. Although
necrosis is removed, NPWT can help wound healing physiologically. The biological meshes cost more than synthetic meshes and the long-term
negative pressure leads to an increased blood supply, durability may be less favorable [ 150 , 151 ], they can confer protective
factors such as resistance to infection and high biocompatibility when
implanted [ 148 ]. In order to evaluate the risk factors for mesh-related
increasing tissue perfusion, reducing infections after surgical hernia repair, a systematic search performed in
edema, absorbing fluids and exudates, inhibiting infection, and finally PubMed and Scopus databases was published in 2011 [ 152 ]. The crude
drying the wound and thus the migration of inflammatory cells into the mesh infection rate was 5%. Statistically significant risk factors were
wound. Additionally, it promotes and accelerates the formation of smoking (RR = 1.36 [95% CI 1.07, 1.73]; 1171 hernioplasties), American
granulation tissue by the removal of bacterial contamination and Society of Anesthesiologists (ASA) score ≥ 3 (RR = 1.40 [1.15, 1.70];
exudates. 1682 hernioplasties), and emergency operation (RR = 2.46 [1.56, 3.91];
1561 hernioplasties). Also, mesh infections were significantly correlated
Although evidence of promising results with NPWT is increasing in with patient age (weighted mean difference [WMD] =
other fields [ 134 – 143 ], in NSTIs, the clinical evidence of its superiority
over conventional wound dressing techniques for all wound types has not
been proven [ 144 , 145 ].

A systematic review of PubMed and Cochrane Library databases for

randomized, controlled trials (RCTs) of NPWT for the treatment of acute
or chronic wounds was published in 2011, which did not find clear 2.63 [0.22, 5.04]; 2364 hernioplasties), ASA score (WMD = 0.23 [0.08,
evidence of a beneficial effect of NPWT compared with conventional 0.38]; 1682 hernioplasties), and the duration of the hernioplasty (WMD =
treatment [ 146 ]. However, much evidence of a positive effect of NPWT on 44.92 [25.66,
wound in general has been published since and the 2011 systematic 64.18]; 833 hernioplasties). A trend toward higher mesh infection rates
review is outdated. was observed in obese patients (RR = 1.41 [0.94, 2.11]; 2243
hernioplasties) and in patients operated on by a resident (in contrast to a
consultant; RR =
What is the treatment of infected meshes? 1.18 [0.99, 1.40]; 982 hernioplasties). Mesh infections usually resulted in
Respect prevention strategies to avoid surgical site infection and mesh removal, and Staphylococcus
prosthetic contamination (recommendation 1A). spp., Enterococcus spp., and Gram-negative bacteria were the germs
commonly isolated in the specimen. In 2017, a retrospective review of all
We suggest avoidance of mesh contamination following incisional SSI patients who underwent abdominal wall hernia repair from January 2004
by an early and adequate local source control as well as antibiotic to May 2014 at a tertiary center was published [ 153 ]. From 3470 cases of
treatment (recommendation 1C). abdominal wall hernia repair, 66 cases (1.9%) of mesh infection were
reported, and 48 of these patients (72.7%) required mesh explantation.
In chronic sinuses and infected meshes, we suggest a complete Steroid or immunosuppressive drugs use (odds ratio [OR] 2.22; CI 1.16 to
surgical removal of the mesh which remains the only way to eradicate 3.95), urgent repair (OR 5.06; CI
infection (recommendation 1C).

No clear recommendations on the benefit of biologic versus synthetic 2.21 to 8.60), and postoperative surgical site infection (OR 2.9; CI 1.55 to
mesh in potentially contaminated fields can be proposed 4.10) were predictive of mesh infection. Independent predictors of mesh
(recommendations 1C). explantation were type of mesh (OR 3.13; CI 1.71 to 5.21), onlay position
Hernia repair is one of the most common surgical procedures (OR 3.51; CI 1.23 to 6.12), and associated enterotomy in the same
performed globally. Mesh infection, although infrequent, is a devastating procedure (OR 5.17; CI 2.05 to 7.12). The pathogenesis of mesh infection
complication of mesh hernioplasties, and for this reason, a prevention is a complex process involving many factors including, but not limited to,
strategy is essential. Currently, several types of prosthetic mesh are bacterial virulence, surface physicochemical properties of the prosthetic
widely used for repairing abdominal wall defects; however, there is no material, and alterations in
single universal
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 20 of 24

host defense mechanisms. The result of this interaction is the formation of mesh was found with comparable surgical site complication rates and a
the bacterial biofilm. Embedded in self-secreted extracellular polymeric hernia recurrence rate of 9% for biologic and 9% for synthetic repair. In
substances, biofilm can provide bacteria an effective barrier against host contaminated hernias (CDC wound class 3 and 4), most reports were on
immune cells and antibiotics [ 154 – 156 ]. Early antibiotics and mechanical biologic mesh repair, showing high rates of surgical site complications
scrubbing or irrigation to remove the biofilm before it is consolidated are and a hernia recurrence rate of 30%. Recurrence rates in contaminated
both important. Mesh infections should be distinguished from superficial hernias depended on whether primary fascial closure was achieved, or
incisional SSIs. They occur in the early postoperative period and are not the repair with biologic mesh was bridging. Biologic mesh sublay repair
with primary fascial closure showed lower recurrence rates than bridging
repairs. Non-cross-linked biologic mesh can be used in contaminated
influenced by mesh hernia without mesh infection and subsequent need for mesh
implantation but can cause the infection of the mesh. The diagnosis of explantation. As only one study on synthetic repair of contaminated
wound infection is clinical, with typical symptoms of localized inflammation hernias was available in literature, no recommendation can be given on
and pain at the incision site. Patients with deep mesh infections may the use of synthetic mesh in this setting [ 161 ].
present with signs of local inflammation. However, more frequently, deep
mesh infections tend to be indolent and present chronic signs and
symptoms. They may be initially underestimated.

The management of mesh-site infections is challenging and always Conclusions

requires an individualized approach combining medical and surgical SSTIs encompass a variety of pathological conditions ranging from simple
approaches. Clinical trials have demonstrated that in certain instances, superficial infections to severe necrotizing infections. The multifaceted
non-operative strategies with conservative (non-surgical) management nature of these infections has led to a collaboration among general and
have been successful for salvaging a mesh [ 157 ]. If conservative emergency surgeons, intensivists, and infectious diseases specialists,
treatment fails, complete surgical removal of the mesh is suggested to who have shared these clinical practice recommendations.
reduce the risk of infection recurrence or severe complications, such as
visceral adhesions and fistulae. A conservative surgical approach
including abscess drainage, sinus excision, or partial mesh excision can
Abbreviations
fail and may result in recurrent mesh infections.
NSTIs: Necrotizing soft-tissue infections; SSIs: Surgical site infections; SSTIs: Skin and
soft-tissue infections

Acknowledgements
After removing the infected mesh, the intra-operative options are (a) no
Not applicable.
implant of a new mesh, (b)
re-implantation of a new synthetic light-weight, macroporous mesh, and Funding
Not applicable.
(c) replacement of the infected synthetic by a biological mesh [ 158 , 159 ].
A critical issue in the repair of contaminated abdominal wall defects is the Availability of data and materials
dilemma of choosing between synthetic material, with its presumed risk of The authors are responsible for the data described in the manuscript and assure full
availability of the study material upon request to the corresponding author.
surgical site complications, and biologic material, a costly alternative with
questionable durability. In 2016, Atema et al. published a systematic
review and meta-analysis of the repair of potentially contaminated and Authors ’ contributions

contaminated abdominal wall defects [ 160 ]. Thirty-two studies published MS wrote the first draft of the manuscript. All the authors reviewed the manuscript and
approved the final draft.
between January 1990 and June 2015 on repair of (potentially)
contaminated hernias with ≥ 25 patients were reviewed. Fifteen studies Ethics approval and consent to participate
solely described hernia repair with biologic mesh, 6 non-absorbable Not applicable.

synthetic meshes, and 11 described various techniques. Studies reporting

Consent for publication
direct and prospective comparison of synthetic versus biological mesh in Not applicable.
a cohort were not found. Surgical site complications and hernia
Competing interests
recurrence rates were evaluated per degree of contamination and mesh
In the past 5 years, MB has participated in advisory boards and/or received speaker honoraria from
type by calculating pooled proportions. In potentially contaminated Achaogen, Angelini, Astellas, AstraZeneca, Bayer, Basilea, Cidara, Gilead, Melinta, Menarini,
hernias (CDC wound class 2), no benefit of biologic over synthetic MSD, Nabriva, Paratek, Pfizer, Roche, The Medicine Company, Shionogi, Tetraphase, VenatoRX,
and Vifor. All other authors declared no competing interests.

Publisher ’ s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps
and institutional affiliations.
Sartelli et al. World Journal of Emergency Surgery (2018) 13:58 Page 21 of 24

Author details 6. Eron LJ, Lipsky BA, Low DE, Nathwani D, Tice AD, Volturo GA. Expert panel on managing skin
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Universitari, Sabadell, Spain. 3 Trauma Service, Inkosi Albert Luthuli Central Hospital and
Department of Surgery, Nelson R Mandela School of Clinical Medicine, Durban, South Africa. 4 Department
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and Critical Care Medicine, Paris Diderot Sorbonne Cite University, Bichat-Claude Bernard 8. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice
University Hospital, HUPNSV, Paris, France. 9 Department of Surgery, College of Medicine and guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the
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University of Bologna, Bologna, Italy. 11 Infectious Diseases Division, Department of Medicine
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General, Emergency and Trauma Surgery, Regional Hospital of Perpignan, Perpignan, France. 18 Department
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