Добавил:
kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз: Предмет: Файл:

Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 950 - файл

.pdf
Скачиваний:
0
Добавлен:
29.08.2026
Размер:
7 Мб
Скачать
186 M. Papi and E. Fiscarelli
obtained with a fungal culture. In immunocompromised patients, the inhalation of conidia may lead to pulmonary infection and multi-organ involvement.
Mycetoma
The disease is characterised by numerous deformations and disabilities, high morbidity, and in its late stage it is potentially fatal (Sehgal 1990). Mycetoma is endemic in the so-called mycetoma beltthat includes various countries across the world, but it is reported extensively in Sudan, Mexico, and India.
Mycetoma can be caused by bacteria (actinomycete mycetoma) or by soil and plant saprophytic fungi (eufungal mycetoma). Firstly and most frequent in Central and South America, secondly in Africa. Mycetomas have in common some char­acteristics: (a) the penetration of etiological agents through continuous skin swounds caused by thorns, shrubs, wood chips, that is why mycetoma is considered an occupational disease among farmers, (b) the long latency time (months or years), (c) the characteristic, although not exclusive, location to the ankles and feet (Maduras foot) (Sehgal 1990; Verma and Jha 2019) (Fig. 26), (d) the formation of nodular and plaque lesions, poorly inammatory followed by the development of abscesses, stulas and ulcerations: the latter drain a purulent serum exudate con­taining granules, that are, the colonies of etiological agents and may help the histological diagnosis, (e) the not uncommon involvement of muscles tendons ligaments joints and bones, with consequent deformities and functional impotence such as alterations in walking, (f) the chronic clinical course and the frequent
Fig. 26 Maduras foot (with kind permission of Prof. Stefano Veraldi)
Atypical Wounds and Wounds Resulting from Infection 187
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
absence of local symptoms and systemic clinical manifestations, (g) the histopathological picture characterized by granulomas and the frequent resistance to systemic antifungal s drugs. Diagnosis in suspected lesions is made with the help of grain examination, microscopy, imaging (radiography, ultrasonography, magnetic resonance imaging) and culture, and more recently by molecular methods such as PCR and molecular sequencing (Ahmed et al. 2017).
Ecthyma Gangrenosum
Ecthyma gangrenosum is usually seen in immunocompromised patients with leu­kaemia, lymphoma, other malignant diseases, severe burns or organ transplant, or in people receiving immunosuppressive therapy (Singh et al. 2005). It is one of the major dermatologic manifestations of severe, systemic pseudomonas aeruginosa infection (Burnett et al. 2022).
It has ben also reported as the consequence of staphylococcus aureus (San­thaseelan and Muralidhar 2017), group A streptococcus, serratia marcescens, escherichia coli and other bacterial species.
It is characterized by unique or multiple necrotic lesions which tend to enlarge, ulcerate and to be covered by sloughy-purulent material (Fig. 27). If a bacteriemia
Fig. 27 Ecthyma gangrenosum (multiple ulcers of the lower limb) in a patient with leukemia
188 M. Papi and E. Fiscarelli
is excluded antibiotic therapy should be started in accordance with ba cteriological exams. The patient should be investigated for the immunological condition and potential viral infections.
Microbiological Investigations: Methods and Drawing Techniques
Mainly Qualitative Methods
Swab: it is performed by moving the swab in a rotary manner inside the deepest ulcer area or margins and, afterwards, inside the culture medium. It can also be quantitative if performed on a specic lesion area and subsequently shaken in a certain quantity of growth medium for a specic period of time.
Curettage: aspiration with needle: to remove the material from the ulcer surface a disposable curette or a syringe to aspirate material of a purulent sac can be used.
It is advisable that the described techniques are preceded by the ulcer lavage with physiologic salt solution to reduce the risk of developing occasional contaminants.
Qualitative and Quantitative Methods
Biopsy: it is performed after ulcer lavage with physiologic salt solution, local anaesthesia (lidocaine injection, xylocaine), rotary movement and light pressure performed with a disposable 4 mm diam eter punch. The tissue fragment obtained can be homogenized and then weighed before being placed in the culture medium. It allows to evaluate the presence of microbes in depth and to monitor the extent of microbic proliferation. Sometimes, it requires a light compressive haemostasis. Deep-tissue biopsy is a qualitative and quantitative culture of wound tissue.
Irrigationaspiration: it is mainly used in presence of deep ulcers or ulcers caused by pressure. It allows taking material from anfractuous areas or in sites where a biopsy cannot easily be performed. It consists in irrigation, through 1 ml sterile syringe of 0.9% sterile saline solution, followed by a light massage of the ulcer margins. Immediately after, 1 ml of saline solution is again injected through a new syringe and, after a light massage, 0.25 ml of uid is inspired.
It is advisable that the microbiological laboratory carries out culture tests for aerobic and anaerobic germs, especially in the presence of a real infection.
The most often isolated microbial species in the cutaneous ulcers are reported on Table 4.
Particular a diabetic patients where anaerobic germs are frequently present (Clostridium per­frigens, Bac occasionally, gangrene.
tion should be given to the ulcers caused by pressure and in
tten
teroides fragilis, Peptostreptococcus spp). They often cause sepsis and,
Atypical Wounds and Wounds Resulting from Infection 189
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Table 4 Pathogenic microbial species more commonly found in the cutaneous ulcers
Gram+
Staphylococcus aureus
Staphylococcus coagulase neg.
Streptococcus group A, D
Pepto-streptococcus spp
Mycetes
Candida albicans
Gram–
Pseudomonas aeruginosa
Acinetobacter
Escherichia coli
Proteus spp
Bacteroides
spp
As an adjunct to wound cultures, culture-independent investigation of the microbial DNA applying pyrosequencing, polymerase chain reaction (PCR)-dena­turing gradient gel electrophoresis, and quantitative real-time PCR have identied a greater range of bacteria than traditional
culture techniques (Renick and Tang 2021;
Rerkasem and Mani 2015).
Laboratory Markers
In addition to the wound culture techniques, laboratory markers can also be mea­sured to aid the diagnosis of wound infection. These markers include C-reactive protein (CRP), procalcitonin, presepsin, microbial DNA, and bacterial protease activity.
In response to inammation and infection, CRP, a peptide produced in the liver, is stimulated by cytokines, primarily interleukin-6, and employed in complement binding and phagocytosis by macrophages.
The Future
Many new technologies have been created in recent years to diagnose infected wounds. Traditional imaging modalities such as radiography and magnetic reso­nance imaging have still a role in the diagnostics, and new hybrid imaging tech­niques, including single-photon emission computed tomography, computed tomography (CT) and positron emission tomography (PET)/MRI, are being utilized as wound infection diagnostic tools, mainly in research at present.
190 M. Papi and E. Fiscarelli
References
Ahmed AA, van de Sande W, Fahal AH. Mycetoma laboratory diagnosis: review article. PLoS
Negl Trop Dis. 2017;11(8): e0005638. Alavi A, Kirsner R. Hemoglobinopathies and leg ulcers. Int J Low Extrem Wounds. 2015;14
(3):213–6. Alavi A, Mayer D, Hafner
entity. Adv Ski Wound Care. 2012;25(12): 563–72. Alavi A, Hafner J, Dutz JP, et al. Livedoid vasculopathy: an in-depth analysis using a modied
Delphi approach. J Am Acad Dermatol. 2013;69(6):1033–1042. Bilgic A, Ozcobanoglu S, Bozca BC, et al. Livedoid vasculopathy: a multidisciplinary clinical
approach to diagnosis and management. Int J Womens Dermatol. 2021;7(5Part A):588–599. Bulte CA, Hoegler KM, Kutlu O, et al. Hydroxyurea: a reappraisal of its cutaneous side effects and
their management. Int J Dermatol. 2021;60(7):810–7. Burnett JR, DeSalvo J, Halvorson S. Ecthyma gangrenosum, a cutaneous manifestation of
systemic infection. CMAJ. 2022;194(12):E461. https://doi.org/10.1503/cmaj.211430. Clancey JK. Mycobacterial skin ulcers in Uganda: description of a new mycobacterium
(Mycobacterium buruli). J Pathol Bacteriol. 1964;88:175–87. Cohen H, Cuadrado MJ, Erkan D, et al. 16th international congress on antiphospholipid antibodies
task force report on antiphospholipid syndrome treatment trends. Lupus. 2020;29(12):1571–93. Conde Montero E, Guisado Muñoz S, Pérez Jerónimo L, et al. Martorell hypertensive ischemic
ulcer successfully treated with punch skin grafting. Wounds. 2018;30:E9–12. Connor J Jr, Minniti CP, Tisdale JF. Sickle cell anemia and comorbid leg ulcer treated with
curative peripheral blood stem cell transplantation. Int J Low Extrem Wounds. 2017;16
(1):56–9. Croitoru D, Naderi-Azad S, Sachdeva M, et al. A wound care specialists approach to pyoderma
gangrenosum. Adv Wound Care. 2020;9(12):686–94. Flores MG, Herrera-Argaez G, Vazquez-Martinez O, et al. Cutaneous manifestations of
antiphospholipid syndrome. Lupus. 2021;30(4):541–8. Gaisne R, Péré M, Menoyo V, et al. Calciphylaxis epidemiology, risk factors, treatment and
survival among French chronic kidney disease patients: a case-control study. BMC Nephrol.
2020;21(63). https://doi.org/10.1186/s12882-020-01722-y. Gardette E, Moguelet P, Bouaziz JD, et al. Livedoid vasculopathy: a french observational study
including therapeutic options. Acta Derm Venereol. 2018;98(9):842. Gil T, Pistunovich Y, Kulikovsky M, et al. A prospective case-control study of non-healing
wounds of the lower limbs-the value of biopsies for ulcerating carcinoma. J Eur Acad Derm
Venereol. 2015;29:337–45. Guarner J. Buruli ulcer: review of a neglected skin mycobacterial disease. J Clin Microbiol.
2018;56(4):e01507–17. Hafner J, Keusch G, Wahl C, et al. Uremic small-artery disease with medial calcication and
intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and benet
of parathyroidectomy. J Am Acad Dermatol. 1995;33:954–62. Handler MZ, Patel PA, Kapila R, et al. Cutaneous and mucocutaneous leishmaniasis: clinical
perspectives. J Am Acad Dermatol. 2015;73(6):897–908. Hoffman MD. Atypical ulcers. Dermatol Ther. 2013;26(3):222– Janowska
Aging. 2019;14:2137–43. Janowska A, Romanelli M, Teresa Oranges T, et al. Prognostic
atypical wounds: a case series. Int J Low Extrem Wounds. 2020. https://doi.org/10.1177/
1534734620970292,(153473462097029).
Johnson P
Mycobacterium ulcerans disease. New York: Springer;2019. p. 61–76. Jorizzo JL. Livedoid vasculopathy: what is it? Arch Dermatol. 1998;134:491.
V, Oranges
A, Dini
D. B
uruli ulcer in Australia. In: Pluschke G, Roltgen K, editors. Buruli ulcer.
J, et al. Martorell hypertensive ischemic ulcer. An underdiagnosed
35.
T, et al. Atypical ulcers: diagnosis and management. Clin Interv
indicators of wound healing in
Atypical Wounds and Wounds Resulting from Infection 191
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Kaul S, Kaur I, Mehta S, et al. Cutaneous tuberculosis. Part I: pathogenesis, classication, and
clinical features. J Am Acad Dermatol. 2022a;S0190-9622(22)00202-X. https://doi.org/10.
1016/j.jaad.2021.12.063.
Kaul S, Jakhar D, Mehta S, et al. Cutaneous tuberculosis. Part II: Complications, diagnostic
workup, histopathological
features, and treatment. J Am Acad Dermatol. 2022b;S0190-9622
(22);00203-1. https://doi.org/10.1016/j.jaad.2021.12.064. Khan K, Giannone AL, Mehrabi E, et al. Marjolins ulcer complicating a pressure sore: the clock is
ticking. Am J Case Rep. 2016;17:111 – 4. Knight JS, Kanthi Y. Mechanisms of immunothrombosis and vasculopathy in antiphospholipid
syndrome. Semin Immunopathol. 2022;44(3):347–362. Kodumudi V, Jeha GM, Mydlo N, et al. Management of cutaneous calciphylaxis. Adv Ther.
2020;37(12):4797–807. Kumar S, Basu S, Bhartiya SK, et al. The Buruli ulcer. Int J Low Extrem Wounds. 2015;14
(3):217–23. Lanzkron S, Strouse JJ, Wilson R. Systematic review: hydroxyurea for the treatment of adults with
sickle cell disease. Ann Intern Med. 2008;148:939–55. Lee JM, Kim IH. Case series of recalcitrant livedoid vasculopathy treated with rivaroxaban. Clin
Exp Dermatol. 2016;41:559–61. Lima Pinto AP, Silva NA Jr, Osorio CT, et al. Martorells ulcer: diagnostic and therapeutic
challenge. Case Rep Dermatol. 2015;7(2):199–206. Mani R, Margolis D, Shukla V, et al. Optimizing technology use for chronic lower-extremity
wound healing: a consensus document. Int J Low Extrem Wounds. 2016;15(2):102– 19. Manry J. Human genetics of Buruli ulcer. Hum Genet. 2020;139(6–7):847–53. Martí-Carvajal AJ, Knight-Madden JM, Martinez-Zapata MJ. Interventions for treating leg ulcers
in people with sickle cell disease. Cochrane Database Syst Rev. 2021;1(1):CD008394. https://
doi.org/10.1002/14651858.CD008394.pub.
Marzano AV, Borghi A, Meroni PL, et al. Pyoderma gangrenosum and its syndromic forms:
evidence for a link with autoinammation. Br J Dermatol. 2016;175:882–91. Maverakis E, Marzano AV, Le ST, et al. Pyoderma gangrenosum. Nat Rev Dis Primers.
2020;6:81. https://doi.org/10.1038/s41572-020-0213-x. Meireles CB, Maia LC, Soares GC, Teodoro IPP, et al. Atypical presentations of cutaneous
leishmaniasis: a systematic review. Acta Trop. 2017;172:240– 54. Miteva M, Romanelli P. Histopathology of wounds. In: Mani R, Romanelli M, Shukla VK,
editors. Measurements in wound healing: science and practice. Springer; 2012. Monfort JB, Senet P. Leg ulcers in sickle-cell disease: treatment update. Adv Wound Care. 2019;9
(6):348–435. Murad AA, Daly T, Mulligan N, et al. Extensive warfarin-induced skin necrosis successfully
treated with negative pressure wound therapy. BMJ Case Rep. 2014:bcr2013203510 Onesti MG, Fioramonti P, Fino P, et al. Skin ulcer caused by venous extravasation of heroin. Int
Wound J. 2014;11(4):409–411. Panuncialman J, Hammerman S, Carson P, et al. Wound edge biopsy sites in chronic wounds heals
rapidly and do not result in delayed overall healing of the wounds. Wound Repair Regen.
2010;18:21–5. Papi M. Macroangiopathic ulcers of the lower extremities: a daily challenge. Int J Low Extrem
Wounds. 2006;5(2):76–7. Papi M, Didona B. Unusual clinical presentation of vasculitis: what some clinical aspects tell us
about the pathogenesis. Clin Dermatol. 1999;17(5):559–64. Papi M, Papi C. Vasculitic ulcers. Int J Low Extrem Wounds. 2016;15(1):6–16. Papi M, Didona B, Chinni LM, et al. Koebner phenomenon in an ANCA-positive patient with
pyoderma
gangrenosum. J Dermatol. 1997;24(9):583–6.
Papi M, Didona B, De Pità O, et al. Livedo vasculopathy versus small vessel cutaneous vasculitis:
citokyne and platelet P-selectin studies. Arch Dermatol. 1998;134(4):447–52.
192 M. Papi and E. Fiscarelli
Papi M. Le ulcere microangiopatiche. Vasculiti, inammazione e microangiopatie occlusive dei
piccoli vasi cutanei. Marrapese; 2008. Papi M, Papi C. Biologics in Microangiopathic wounds. Int J Low Extrem Wounds.
(4):205–13. Papi M, Didona B, De Pità O et al. Multiple skin tumors on light-exposed areas during long-term
treatment with hydroxyurea. J Am Acad Dermatol. 1993;28(3):485–486. Pranteda G, Grimaldi M, Lombardi M, et al. Basal cell carcinoma: differences according to
anatomic location and clinical-pathological subtypes. G Ital Dermatol Venereol.
2014;149:423–6. Renick P, Tang L. Diagnostics for wound infections. 2021;10(6):317–27. Rerkasem K, Mani R. Infection, immune disorders, hemoglobinopathies, and lower extremity
wounds: are we doing enough? Int J Low Extrem Wounds. 2015;14(3):211–2. Roldan-Mari R, Contreras-RuizJ, Arenas R, et al. Fixed sporotrichosis as a cause of a chronic ulcer
on the knee. Int Wound J. 2009;6(1):63–6. Sacchelli L, Baraldi C, Misciali C, et al. Neoplastic leg ulcers. Dermatopathology 2018;5
(3–4):113–6. Santhaseelan RG, Muralidhar V. Non-pseudomonal ecthyma gangrenosum caused by
methicillin-resistant Staphylococcus aureus (MRSA) in a chronic alcoholic patient. BMJ
Case Rep. 2017:bcr2017220983. Published 2017 Aug 3. https://doi.org/10.1136/bcr-2017-
220983.
Sarifakioglu E. Nicolau syndrome after diclofenac injection. J Eur Acad Dermatol Venereol.
2007;21(2):266–7. Sehgal VN. Leg ulcers caused by deep mycotic infection. Clin Dermatol. 1990;8(3–4):157–65. Senet P, Combemale P, Debure C. Malignancy and chronic leg ulcers. The value of systematic
wound biopsies: a prospective, multicenter, cross-sectional study Arch Dermatol. 2012;148
(6):704–8 Shanmugam VK, McNish S, Shara N, et al. Chronic leg ulceration associated to polycythemia vera
responding to Ruxolitinib (Jaka). J Foot Ankle Surg. 2013;52(6):781–5. Shavit E, Alavi A, Sibbald RG. Vasculitis-what do we have to know? A review of literature. Int J
Low Extrem Wounds. 2018;17(4):218–226. Singh N, Devi M, Devi S. Ecthyma gangrenosum: a rare cutaneous manifestation caused by
Pseudomonas aeruginosa without bacteremia in a leukemic patient. Indian J Dermatol Venereol
Leprol. 2005;71:128–9. Sirieix ME, Debure C, Baudot N. Leg ulcers and hydroxyurea. Arch Dermatol. 1999;135
(7):818–20. Sönmez Ergün S, Yildiz K, Baygöl EG, et al. Heroin-induced chronic symmetrical skin ulcers of
the forearms in a young adult. Eur J Dermatol. 2012;22(3):414. Tang J, Kirsner RS. Atypical ulcers. In: Mani R, Romanelli M, Shukla VK, editors. Measurements
in wound healing: science and practice. Springer; 2012. Terrier DR, Durel C-A, et al. French recommendations for the management of systemic
necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides. Orphanet J
Rare Dis. 2020;15(Suppl 2):351. https://doi.org/10.1186/s13023-020-01621-3. Tottoli EM, Dorati R, Genta I, et al. Skin wound healing process and new emerging technologies
for skin wound care and regeneration. Pharmaceutics. 2020;12(8):735. https://doi.org/10.3390/
pharmaceutics12080735.
Tremblay D, Kosiorek HE, Dueck AC, et al. Evaluation of therapeutic strategies to reduce the
number of thrombotic events in patients with polycythemia vera and essential thrombo-
cythemia. Front Oncol. 2021;10:636675. Published 2021 Feb 16. https://doi.org/10.3389/fonc.
2020.636675.
Velasco M
Verma
L, Alegria V, Briz AS, et al. Occlusive nonvasculitic vasculopathy. Am J
Dermatopathol. 2017;39(9):637–62.
A. Mycetoma: reviewing a neglected disease. Clin Exp Dermatol. 2019;44(2):123– 9.
P, Jha
2018;17
Atypical Wounds and Wounds Resulting from Infection 193
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Weishaupt C,
Strolin A, Kahle B, et al. Anticoagulation with rivaroxaban for livedoid vasculopathy (RILIVA): a multicentre, single-arm, open-label, phase 2a, proof-of-concept trial. Lancet Haematol. 2016;3:e72–79.
Wirth K, Schoepf E, Mertelsmann R, et al. Leg ulceration with associated thrombocytosis: healing
of ulceration associated with treatment of the raised platelet count. Br J Dermatol. 1998;138:533–5.
Yotsu RR, Richardson M, Ishii N. Drugs for treating Buruli ulcer (Mycobacterium ulcerans
disease). Cochrane Database Syst Rev. 2018;8(8):CD012118. Published 2018 Aug 23. https://
doi.org/10.1002/14651858.CD012118.pub2.
Biofilms and Impaired Wound Healing: How Do We Detect the Presence of Biofilms in Chronic Wounds Non-invasively
Ida C. Thaarup and Thomas Bjarnsholt
Abstract
The pervasive presence of biolms in chronic wounds is a well-acknowledged phenomenon. A recent meta-review estimat ed that 80% of all chronic wounds contain biolms and this number is thought to be an underestimation, as the presence of a biolm can be difcult to establish. The presence of a biolm is believed to prevent a wound from progressing through the normal phases of healing, which are haemostasis, inammation, proliferation, and remodelling. Biolms are thought to arrest the wound in the inammatory state, causing an exaggerated immune response with continuous tissue damage and harmful change to the wound microenvironment. Therefore, a key to successful wound healing is to focus on biolm detection and subsequent biolm eradication. Non-invasive biolm detection methods present a new and challenging eld of study. One of the main chall enges lies within the random spatial dist ribution of wound biolms. Despite the limit ed number of studies in this particular area, biolms are currently thought to exist in an unstructured, heterogeneous fashion within the wound, occupyi ng different spatial regions and both shallow and deeper layers of the wound. Several distinct species are thought to be present within a single wound creating many different microenvironments. Regardless of these challenges, a handful of non-invasive techniques have been developed that
I. C. Thaarup T. Bjarnsholt (&) Costerton Biolm Centre, Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark e-mail: tbjarnsholt@sund.ku.dk
I. C. Thaarup e-mail: icthaarup@sund.ku.dk
T. Bjarnsholt Department of Clinical Microbiology, Copenhagen University Hospital, Juliane Maries Vej 22, 2100 Copenhagen, Denmark
© The Author(s), under R. Mani (ed.), Chronic Wound Management,
https://doi.org/10.1007/978-3-031-26110-7_10
exclusive license to Springer Nature Switzerland AG 2023
195
196 I. C. Thaarup and T. Bjarnsholt
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
attempt to survey and locate biolms in wounds using both direct and indirect methods. In this chapter, we begin by introducing the reader to the devastating effect biolms have in a wound environment. This will incl ude some of the complex interactions between the microbes, their host, and the surrounding microenvironment. We then cover the conventional methods used today to detect wound microbes and subsequently we introduce a number of new, non-invasive methods to de their infancy and have yet to be tested in human subjects, while others are further along in their development. Finally, we discuss the importance of biolm detection in wounds and other concerns which might be just as important to consider.
Keywords
tect the presence of wound biolms. Some methods are still in
Biolms Detection methods Biological markers Imaging techniques
How Biofilms Impair Wound Healing
Disruption of Immune and Skin Cells
Normal wound healing is often described to progress through four overlapping phases of healing: haemostasis, inammation, prolifera tion including tissue regeneration and nally, remodelling (Zhao et al. 2016). In wounds that are pro­gressing normally, the inammatory phase usually only lasts a few days. However, in the case of an infection, the presence of bacteria is thought to cause a deviant and exaggerated immune response, stalling the wound in the inammatory phase of healing (Grice and Segre 2012). A meta-review has estimated that up to 80% of all chronic wounds contain bacterial biolms (Malone et al. 2017a); however, these numbers are often thought to be underestimated since the presence of a biolm can be difficult to prove due to the heterogeneous distribution in the wounds. While biolms have already been shown to slow the healing of trauma-induced wounds (Schierle et al. 2009; Zhao et a l. 2010; Seth et al. 2012), the specic methods by which biolms slow the healing of chronic wounds, and the conclusive proof that they do so, is still being investigated. However, many in vivo and in vitro inves­tigations have been performed, and in combination with clinical observations, they have uncovered several mechanisms by microbial biolms that might lead to delayed healing.
Excessive neutrophil numbers have been observed in many chronic biolm
infections, furthering the belief that the presence of a biolm exaggerates the immune response (Bjarnsholt et al. 2008). When present in excessive numbers, the neutrophils produce compounds such as reactive oxygen species and proteolytic enzymes in such amounts that they cause damage to neighbouring tissue. The