Tuesday, March 21, 2017

Cellulitis--Collaborative care is best practice

    Skin infections encompass many specialty groups, ranging from infectious disease and lymphology societies to wound care specialists and emergency room clinicians, all uniquely aware of the huge personal and financial cost incurred when infections are not handled in a prompt and effective manner.  The collaborative management and treatment of cellulitis, an acute and rapidly progressing bacterial skin infection, is critically important as 2.5% of the general population is impacted by this disorder and its high level of recurrence when not addressed promptly and effectively (Nguyen, Rowland & Mounsey, 2014).
     Cellulitis is a rapidly spreading inflammatory skin infection that specifically affects subcutaneous tissues and is characterized by erythema (redness), swelling and localized tenderness (Goodman & Fuller, 2009).  These authors further defined a sub-category of cellulitis called erysipelas, a surface cellulitis that primarily affects the skin and upper dermis, although it may involve lymphatic vessels with an appearance of redness and sharply defined borders with occasional red colored streaking. Cellulitis presents as warm and painful to touch, reddened and edematous in appearance, but with smooth and ill-defined borders except in severe cases where it may contain pustules or areas of necrosis (Sambrano, Gordon, Mays, Lapolla & Scheinfeld, 2012). According to Mortimer and Rockson (2014), cellulitis and erysipelas are among the most common conditions seen in emergency departments. 
      Erysipelas, usually caused by group A Streptococcus, results in the sudden onset of fever, pain and redness (Koster, Kullberg & Van der Meer, 2007).  The typical scenario that creates a predisposition to infection is the interaction between high bacteria colonization and circulation of the blood, compounded by increased vulnerability in moist areas of the body and on the lower extremities (Erbil et al., 2014).  The predisposition to cellulitis or erysipelas, is increased by the presence of skin disruptions or lymphedema, an abnormal accumulation of fluid in the interstitial space (Koster, Kullberg & Van der Meer, 2007).  This interstitial edema occurs when the capillary filtration rate exceeds the capability of the lymphatic drainage mechanism (Trayes, Studdiford, Pickle & Tully, 2013).  The lymphatic system tends to be one of the most poorly understood body systems, however it has been identified as having three specific functions that include fluid balancing, fatty absorption and host defense (Mortimer & Rockson, 2014).  Their feeling is the lymphatic system maintains volume homeostasis and creates an adaptive immunity through its immune surveillance of antigen and immune cell transport, all important aspects in the maintenance of a healthy body.
     Cellulitis and erysipelas are definitely more prevalent in patients with lymphedema and skin disruptions, but other risk factors include diabetes mellitus, chronic venous insufficiency and skin ulcerations (Perello-Alzamora, Santos-Duran, Sanchex-Barba, Canueto, Marcos & Unamumo, 2012).  These authors feel that rendering a diagnosis of cellulitis is often difficult to provide or problematic in differentiating from other conditions such as an abscess, as gathering cultures for microbiologic analysis or isolating a pathogen is not always accessible or available. 
     When the diagnosis of erysipelas is rendered, studies have found these bacteria respond well to narrow spectrum penicillins, such as benylpenicillin (penicillin G),  or to macrolides such as erythromycin, for patients allergic to penicillin (Koster, Kullberg & Van der Meer, 2007).  According to Ciccone (2013), penicillin G is classified as an anti-infective and falls within the pharmacologic category of penicillins. The anti-infective mechanism is the occurrence of cellular death through its binding action to specific enzymes within the cell wall, making the cellular membrane unable to act as a selective barrier and unable to handle the high internal osmotic pressure of the bacterial cell (Ciccone, 2007, p. 504).  This anti-infective mechanism makes it very effective in treating most gram-positive organisms, some gram-negative organisms and a few anaerobic bacteria and spirochetes (Ciccone, 2013).  Ciccone (2013) further states that Penicillin G, known as a natural occurring penicillin, is particularly helpful with streptococci and staphylococci, as well as some penicillin-susceptible strains of N. gonorrhoeae as it gets widely distributed throughout the body, although poorly distributed in the central nervous system (CNS).
       A common adverse drug reaction (ADR) for penicillin is the frequency of allergic reactions that may include hives, skin rashes, itching and difficulty breathing, although in some cases it may even progress to life-threatening anaphylactic shock (Ciccone, 2007, p. 505).  Other ADRs mentioned were the possibility of seizures, with some milder gastrointestinal side effects like colitis, nausea, vomiting and diarrhea, as well as nephritis, eosinophilia and leukopenia. 
     In the presence of an allergic sensitivity to penicillin, a macrolide antibiotic such as erythromycin is the alternative of choice for treatment of erysipelas and cellulitis (Koster, Kullberg & Van der Meer, 2007).  The role of the macrolide antibiotic is to corrupt the peptide bonding between adjacent amino acids thus disrupting structural and functional features at specific areas of the ribosomes, resulting in the inhibition of bacterial synthesis (Sothiselvam et al., 2014). 
     As with penicillin, erythromycin is an anti-infective that is very effective with gram-positive streptococci and staphylococci, and gets widely distributed throughout the body, although poorly perfused throughout the CNS (Ciccone, 2013).  According to this author there are several strong ADRs that include ventricular arrhythmias, QT prolongation characterized by palpitations, seizures or syncope, as well as pseudomembranous colitis.  Other side effects mentioned were gastrointestinal issues like nausea, vomiting, cramping and diarrhea, as well as rashes, drug induced hepatitis and on rare occasion, drug induced pancreatitis.  Both penicillin and erythromycin cross the placenta and enters into the breast milk (Ciccone, 2013).
     The diagnosis of cellulitis tends to be based mainly on clinical findings versus microbiologic results from needle aspirations due to an issue of unreliable accuracy with organism identification that is common in healthy hosts (Sambrano, Gordon, Mays, Lapolla & Scheinfeld, 2012).  These authors found the most common cause of cellulitis was S. aureus and streptococci, treated initially with beta-lactam, administered intravenously in severe cases.  Ciccone (2007) characterizes beta-lactam antibiotics as cephalosporin drugs that utilize a penicillin-like anti-infective mechanism to adversely impact the integrity of cellular membrane (p. 505).  He states that cephalosporin is commonly used as an alternative for patient’s having difficulty tolerating penicillins, although it should not be used in those having allergic reactions to penicillin.
     The treatment of cellulitis varies in response to the specific causative agent, as methicillin-resistant S. aureus  (MRSA) will typically require interventions with vancomycin, linezolid or daptomycin (Sambrano, Gordon, Mays, Lapolla & Scheinfeld, 2012).  These authors feel that vancomycin should be used with MRSA cellulitis, especially in the presence of a penicillin allergy, but promptly switched to linezolid, an oxazolidinone, if there is a vancomycin-resistant infection. But they all believe that cellulitis, especially those atypical in nature or in the presence of MRSA, should be treated in an empirical manner utilizing patient history, anatomic site and clinical presentation for the most appropriate antibiotic choice.
     Vancomycin, an anti-infective, also has an action of binding to the cell wall, resulting in cell
death (Ciccone, 2013).  He highlighted the most severe ADRs as being hypersensitivity and anaphylaxis, with lesser side effects being ototoxicity, hypotension, nausea, rash, chills and neck or back pain.  This author feels vancomycin is also widely distributed throughout the body and crosses the placenta, but it also allows some permeation into the cerebral spinal fluid (CSF).
     Linezolid, an oxazolidinone, has an anti-infective action that inhibits bacterial protein synthesis at the ribosomal level (Ciccone, 2013).  This author feels it serves as a very effective treatment against streptococci, as well as having a bacteriostatic action against staphylococci.  Side effects of linezolid include headache, insomnia, diarrhea, nausea, lactic acidosis, thrombocytopenia, as well as optic and peripheral neuropathies (Ciccone, 2013).
     Recurrent episodes of cellulitis or erysipelas manifest in spite of antibiotic treatment, whether curative or preventive in nature.  An analysis by Koster, Kullberg and Van der Meer (2007) reported patient noncompliance, incorrect selection of antibiotics, insufficient dosages or antibiotic concentrations, as well as the possibility of other causative agents as reason for recurrence.  According to Cox (2005), 40% of cellulitis cases currently have recurrences. However, in a study summary by Nguyen, Rowland and Mounsey ( 2014), they found the prophylactic use of lower dose penicillin effective in reducing recurrence of leg cellulitis, but feel that more trials are needed to determine if this lower recurrence rate persists upon its discontinuation.    
     In a study by Morgan and McGuckin (2013), they found that collaboration between dermatology and lymphedema services created a multi-specialist approach that provided prompt and effective management of cellulitis.  The treatment plan they identified began with intravenous antibiotics that progressed to oral antibiotics for 14 days, or until the cellulitis resolved, topical steroids and wound dressings/soaks, if needed, followed by compression. From there they highlighted the progression to multilayer compression wrapping using short stretch bandages, followed by thorough instruction in self-care strategies for good nutrition, hydration, proper skin care and manual lymphatic drainage techniques. The final phase of this treatment plan was the progression to custom or over-the-counter compression garments and the incorporation of appropriate self-care strategies.
     Physical therapists treating patients with lymphedema must always be aware of the potential for cellulitis or erysipelas, carefully monitoring the skin on a daily basis.  Once cellulitis is diagnosed it is important to monitor the involved area of redness, either by measurement or photography, observing the impact and effectiveness of the empiric antibiotic. Those therapists specialized in complex lymphedema management will work with bandaging, skin care, compression garments, manual lymphatic drainage and exercises. However, caution must be utilized during the performance of an active physical therapy (PT) program as these antibiotics possess ADRs  ranging from anaphylaxis and seizures to  pseudomembranous colitis (Ciccone, 2013).  Side effects may include nausea, fatigue, hypotension and neuropathies to name just a few, but all require astute clinical observation for safety while attending the PT appointment (Ciccone, 2013).     
     In conclusion, the benefits of the collaborative management of cellulitis are clearly presented in many studies similar to Morgan and McGuckin (2013), with the education of healthcare professionals being an essential aspect to insuring early antibiotic intervention or early referral to appropriate dermatology or lymphedema services. Early intervention provides significant patient benefits by limiting tissue damage and medical complications, as well as significant cost savings through shorter hospital stays and less frequent recurrences.      

Ciccone, C. D. (2007). Pharmacology in rehabilitation (4th ed). Philadelphia, PA: F. A. Davis
Ciccone, C. D. (2013). Drug guide for rehabilitation professionals. Philadelphia, PA: F. A.
       Davis Company.
Cox, N. H. (2006). Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the
        lower leg: a series with community follow-up. Br J Dermatol, 155(5), 947-50.
Erbil, B., Ersoy, G., Ozkutuk, A., Akarca, F. K., Korkmaz, T., Demir, O. F. & Kiyan, S. (2014).  
        The effects of oral antibiotics on infection prophylaxis in traumatic wounds. Ulus Travma  
        Acil Cerrahi Derg, 20(4), 231-235.
Koster, J. B., Kullberg, B. J. & Van der Meer, J. W. M. (2007).  Recurrent erysipelas despite    
        antibiotic prophylaxis:  An analysis from case studies.  The Netherlands Journal of   
        Medicine, 65(3), 89-94.
Mortimer, P. S. & Rockson, S. G. (2014). New developments in clinical aspects of lymphatic
        disease. The Journal of Clinical Investigation, 124(3), 915-921.
Nguyen, L., Rowland, K. & Mounsey, A. (2014). Low dose penicillin for recurrent cellulitis?
        The Journal of Family Practice, 63(1), E10-E12.
Perello-Alzamora, M. R., Santos-Duran, J. C., Sanchex-Barba, M., Canueto, J., Marcos, M. &
        Unamumo, P. ( 2012). Clinical and epidemiological characteristics of adult patients
        hospitalized for erysipelas and cellulitis. Eur J Clin Microbiol Infect Dis, 31, 2147-2152. 
        DOI 10.1007/s10096-012-1549-2
Sambrano, V.,  Gordon, R., Mays, R., Lapolla, W. & Scheinfeld, N. ( 2012). Intravenous            
        antibiotics used in dermatology. Dermatologic Therapy, 25, 70-81.
Sothiselvam, S., Liu, B., Han, W., Ramu, H.,  Klepacki, D., Atkinson, G. C.,.….     
        Mankin, A. S. (2014 ). Macrolide antibiotics allosterically predispose the ribosome for
        translation arrest. PNAS, 11(27), 9804-9808.    10.1073/pnas.1403586111
Trayes, K. P.,. Studdiford, J. S., Pickle, S. & Tully, A. S. (2013). Edema: Diagnosis and    
        Management. Am Fam Physician, 88(2), 102-110.