Skin and soft tissue infections (SSTIs) are common infections of the epidermis, dermis or subcutaneous tissue (Stevens 2005). They include impetigo; abscesses, cellulitis and erysipelas; infections following animal and human bites; soft tissue infections following animal contact; infections in people whose immune systems are compromised and infections related to iatrogenic procedures.
SSTIs were described by Celsus in the first century as 'calor, rubor, tumor and dolor' (heat, redness, swelling and pain) (Dryden 2010). They may be accompanied by signs and symptoms of systemic toxicity such as fever, malaise, nausea, hypothermia, tachycardia (more than 100 beats per minute) and hypotension (systolic blood pressure less than 90 mmHg or 20 mmHg below baseline).
For most people the condition is treatable with antibiotics (Morris 2001), but longer-term problems, such as persistent swelling, recurrent episodes, bacterial resistance and side effects of the medication, can occur. Many patients with SSTIs are therefore increasingly turning to complementary and alternative medicine (CAM), including Chinese herbal medicines, in order to alleviate their symptoms and reduce the side effects of medications.
Description of the condition
SSTIs are common and range in severity from minor, self limiting, superficial infections to life-threatening diseases, with or without open wounds/ulcers. There are many important underlying aetiologies, in particular diabetes. Classification of SSTIs can be based on anatomical site, clinical severity or microbial cause, however some classifications (such as that of the US Food and Drug Administration (FDA)) divide SSTIs into 'complicated' and 'uncomplicated' infections. Uncomplicated SSTIs are superficial infections amenable to treatment with antibiotics plus simple surgical incision where appropriate (e.g. simple abscesses, carbuncles, impetigo lesions, furuncles, cellulitis). Complicated SSTIs are infections involving the deeper tissues, such as subcutaneous tissue, fascia and skeletal muscle or SSTIs in people with co-morbidities such as diabetes mellitus, HIV and other immunocompromised states (FDA 1998). Complicated SSTIs can be non-necrotising or necrotising.
The microbial causes of SSTIs have been recorded over some years in the SENTRY Antimicrobial Surveillance Program database. Their report, which presented data over a seven-year period (1998 to 2004) ranked SSTIs by frequency of pathogen: Staphylococcus aureus (42.8%), Pseudomonas aeruginosa (11.1%), Escherichia coli (9.0%), Enterococcus spp. (7.3%), Klebsiella spp. (4.8%), Enterobacter spp. (4.7%), β-haemolytic streptococci (4.3%), coagulase-negative staphylococci (4.0%), Proteus mirabilis (2.5%) and Acinetobacter spp. (2.1%) (Fritsche 2007). However, with the rise in the number of community-acquired methicillin-resistant S. aureus (MRSA)-related infections (Kluytmans-Vandenbergh 2006; Purcell 2005), this picture may change in the future.
SSTIs are frequently encountered in both community and hospital settings, but few published data are found on their incidence. According to the Centers for Disease Control and Prevention (CDC), 562,000 people were discharged with a hospital-acquired SSTIs and SSTIs were the third most common cause of nosocomial infections (Bounthavong 2010). A cohort study conducted in the USA from 1997 to 2002 indicated a higher incidence of 246 per 10,000 person-years (Ellis Simonsen 2006). In England alone, people admitted with a diagnosis of SSTIs took up to 360,000 bed-days (UKDOH 2001). The morbidity and treatment costs associated with SSTIs are high, and treatment has become more complex due to the increasing prevalence of multiple-drug resistant pathogens. During the past decade the prevalence of antibiotic resistance among Gram-positive cocci (particularly S. aureus) has increased sharply. A considerable variation in the MRSA rate has been noted between countries and continents. According to the report of the SENTRY Antimicrobial Surveillance Program, the highest MRSA rate was observed in North America (35.9%), compared with Latin America (29.4%) and Europe (22.8%). However, the MRSA rate varied considerably among European countries, ranging from 0.8% in Sweden to 50% in Portugal (Fritsche 2007). Variability in MRSA rates was also apparent in Latin America: Mexico (50%), Chile (38%), Brazil (29%), Argentina (28%) and Colombia and Venezuela combined (3%) (Moet 2007). Antibiotic resistance increases the length of stay in hospital, costs of treatment and mortality. A review of the epidemiology of severe S. aureus infections in Europe reported that the overall seven-day case fatality rate was 19% (Lamagni 2008). A US study reported that people with MRSA-infected surgical sites had a three times greater 90-day mortality rate and a greater duration of hospitalisation after infection (median additional days = 5; P < 0.001) than people infected by methicillin-sensitive S. aureus (MSSA). Median hospital charges were USD 92,363 for people with MRSA infections (Engemann 2003).
Description of the intervention
Uncomplicated and complicated SSTIs are treated differently and have different clinical outcomes. Uncomplicated SSTIs are usually treated with local care with or without antibiotics, while the treatment of the most complicated SSTIs involves timely surgical debridement or drainage, appropriate antibiotic therapy, and resuscitation if required (Dryden 2010). The most frequently used broad-spectrum antibiotics to treat SSTIs are β-lactams, glycopeptides, oxazolidinones (Fung 2003). However, there is variation in practice and treatment options for SSTIs include many different oral and intravenous antibiotics. Infections are diagnosed and treated by general practitioners, emergency department doctors, dermatologists, paediatricians, surgeons and physicians from a variety of sub-specialties (British Lymphology Society 2007; CREST 2005; Eron 2003; Société Française de Dermatologie 2001; Stevens 2005).
Conventional treatments for SSTIs include antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy. Treatment with antibiotics and NSAIDs is limited by high treatment costs, bacterial resistance and side effects. Many people may not be good candidates for these therapies because of their co-morbidities, advancing age or preference for Chinese herbal medicine treatment. Chinese herbal medicines have been shown to have the potential to reduce the adverse effects of medications.(Ernst 1995; Neil 1994; Westphal 1996). Chinese herbal medicines, which are natural substances, have been used to promote healing and alleviate pain in many countries, such as Singapore, Thailand and Japan. In China, many people with SSTIs are increasingly turning to CAM, including Chinese herbal medicines. However, they are not totally without side effects and, for example, some people have reported experiencing diarrhoea (H Maechel 1992), sleep disturbance (Wilkie 1994) and nephropathy (Lin 1994).
Chinese herbal medicines form the main part of Traditional Chinese Medicine (TCM), which has been used for centuries in China. Within the framework of TCM Chinese herbal medicines always include herbs, animal or insect products, or minerals, however they are often combined in one formula. An audit of 117 original research reports involving TCM or other natural products in the Chinese Medical Journal (2000 to 2009) found that there were different materia medica described in these reports: 74.4% were derived exclusively from plant material, 10.3% from animals, 3.4% from fungi, 1.7% from minerals and 10.3% were of mixed (plant/animal/fungal/mineral) composition (Collins 2011). Chinese herbal medicines are now included in the national essential drugs list of China. The Chinese State Food and Drug Administration enforces strict controls on the sale, inspection, and record keeping relating to Chinese herbal medicines ( CPC 2010). Chinese herbal medicines are defined in this review as products derived from raw or refined plants or parts of plants (e.g. leaves, buds, flowers, stems, roots or tubers), minerals (e.g. borneol) and/or animals (e.g. prepared centipede or earthworm), and used for the treatment of disease. There are four kinds of herbal therapies: single herb, Chinese proprietary medicines, mixtures of different herbs and any one of the aforementioned three therapies plus Western pharmaceuticals, also known as integrative medicinal treatment (Liu 2008; Vickers 1999).
TCM has unique theories regarding systems of diagnosis, aetiology and treatment. These theories are vital to its practice and include Yin-Yang, the five elements (fire, earth, metal, water and wood), Qi (vital energy) and blood, Zang-Fu (five viscera and six bowels), and channels and collaterals (meridian doctrine) (Cheng 2000; Liu 1991). Chinese herbalists prescribe the mixture of herbs depending on the signs and symptoms the patient is experiencing and other disease information derived from four examinations. The four examinations include: observation; listening and smelling; inquiring; and feeling the pulse and palpation. Chinese herbalists analyse these to detect the cause and location of the disease and the relationship between pathogenic factors and vital energy; they then prescribe the mixture of herbs. Although based on well-established and long-standing recipes, Chinese proprietary medicines are usually formulated as tablets or capsules for convenience, commercial reasons or palatability.
Herbal medicines have been used for SSTIs, and aim to clear heat and eliminate toxins, improve circulation and dispel blood stasis. They can be used orally or topically, alone or in combination with conventional Western medicine.
How the intervention might work
Depending on the symptoms or causes, various medicinal herbs are used for treating SSTIs. In China, Chinese herbs are generally considered to be effective and are commonly prescribed by physicians for patients with SSTIs. Some Chinese herbs are considered to have antibacterial and anti-inflammatory properties. In pharmacological experiments Radix scutellariae has been shown to have antiphlogistic properties (Huang 1990), Coptis chinensis has antibacterial activity against Gram-positive bacteria (Kim 2004) and Sophora flavescens has anti-inflammatory and antiproliferative activities (Zhou 2009). Although these properties have been observed, it is unclear how they work.
Why it is important to do this review
SSTIs cause a heavy public health and economic burden and many sufferers consult CAM practitioners for their symptoms. Therefore there is a need to review the current clinical evidence systematically to inform current practice and guide future studies on Chinese herbal medicines for SSTIs.