Novel Antibiotic Treatment for Skin and Soft Tissue Infection

Matthew S. Dryden

Disclosures

Curr Opin Infect Dis. 2014;27(2):116-124. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review. Acute bacterial skin and skin structure infection (ABSSSI) is a common and significant indication for antibiotic treatment. The microbial aetiology is becoming more resistant to available antibiotics and the treatment of patients is additionally challenged by extremes of age, obesity, diabetes and other co-morbidities. This review examines recent antimicrobial developments.

Recent Findings. In many parts of the world, multidrug-resistant (MDR) staphylococci are the predominant cause of ABSSSI in both the community and in hospital. Increasing resistance in Gram-negative organisms presents problems in the management of surgical-site infections. Most new antibiotics have been developed to treat MDR Gram-positive bacteria and there are few agents to treat infections caused by MDR Gram-negative pathogens.

Summary. A number of novel agents are available clinically, with other agents of related chemical structure under development. There are no entirely new classes of antibiotics. Maintaining the efficacy of antimicrobial treatment require effective antibiotic stewardship, good infection prevention and the development of further new antibiotics.

Introduction

Novel antibiotics are required because antibiotic resistance is a major global health hazard. Without novel antibiotics, the further development of medical technology and the future of medical treatment may be at risk unless solutions to global antibiotic resistance are found. Multiresistant organisms are rapidly becoming ubiquitous, selected by uncontrolled antibiotic use and spread by poor infection prevention and public sanitation, and are quietly colonizing the global population. Antibiotics are a finite resource and are life-saving in sepsis.[1] Their overuse is caused by diagnostic limitations, which mean that antibiotics are given to patients who have no infection or a viral infection.[2] Empirical treatment is often very broad, de-escalation rarely occurs and the duration often too long.[3,4] Antibiotic stewardship programmes attempt to address these issues.[2] The solutions to this major problem seem simple but are difficult to achieve.[4,5] Better stewardship would reduce selection pressure; good infection control and improved public hygiene would mean fewer infections and less transmission and less need to use antibiotics; improved diagnostics would mean lower requirement for empirical therapy; and finally reinvigoration of antibiotic discovery would mean greater choice for managing multidrug-resistant (MDR)[6] infections. The British Society of Antimicrobial Chemotherapy has launched Antibiotic Action (www.antibioticaction.com) and the Infectious Diseases Society of America (IDSA) the 10 × '20 initiative to promote novel drug discovery.[7]

Soft tissue infections, now called acute bacterial skin and skin structure infections (ABSSSIs) are common in every medical specialty and are encountered by everyone at some point. ABSSSIs are inflammatory microbial invasions of the epidermis, dermis and subcutaneous tissues, presenting with various combinations of heat, redness, swelling and pain. The skin is the largest organ in the body and, with the underlying soft tissue that includes the fat layers, fascia and muscle, represents the majority of the tissue in the body.[8] Normally, the skin is colonized with an endogenous flora, a variety of species of staphylococci, corynebacteria, propionibacteria and yeasts in numbers that may vary from a few hundred to many thousands per centimetre[2] in the moister areas such as the groin and axillae.[8] The normal flora may act as a competitive inhibitor of pathogenic microbes. Breaks in the skin, such as leg ulcers, burns and surgical or traumatic wounds, allow colonization with a broader range of bacteria. Colonization of ulcers does not usually result in inflammation, but occasionally infection of the surrounding tissues may progress from mere colonization. Clinically, it is important to distinguish between colonization, which does not require antibiotic treatment, and infection, which might.[9] Antibiotic stewardship and appropriate use of this important group of drugs are so important to bacterial ecology and future public health that all physicians must consider in every case whether antibiotics are clinically indicated.[10] Methicillin-resistant Staphylococcus aureus (MRSA) is probably the most common world-wide cause of ABSSSI[11,12] and this may have become more widespread because of selection pressure from antibiotic use. Colonization of skin surfaces or broken skin should never require systemic antibiotics, although it would appear from a major survey on the practice of managing MRSA infection in Europe that a significant proportion of practitioners treat MRSA colonized ulcers with systemic antibiotics.[13]

Clinical management of ABSSSI is achieved using a combination of surgical, supportive and antimicrobial therapies.[14,15] Cutaneous abscess is dealt with primarily by incision and drainage, with antibiotics indicated for patients who do not respond to these initial interventions. Antibiotics are also indicated when there is more extensive disease or the abscess is in an area that is difficult to drain, for rapid progression of infection, and where there are signs of systemic illness, comorbidities or immunosuppression.[15] The antibiotic management of ABSSSI is well reviewed in the published guidelines.[10,16–18] The main choice of antibiotic depends on the clinical presentation. In likely Gram-positive infection wherein MRSA is not suspected, penicillins, antistaphylococcal penicillins, cephalosporins, clindamycin or cotrimoxazole are indicated.[10,16]

Where infection is likely to be polymicrobial such as surgical site infections of the abdominal wall, or in proximity to the genital tract or rectum, diabetic foot infections (DFIs) and bites, antibiotic treatment must cover the broad range of pathogens seen in these ABSSSI. Such treatment may include [beta]-lactam-[beta]-lactamase inhibitors and fluoroquinolones with enhanced Gram-positive activity such as moxifloxacin, cotrimoxazole, tigecycline or ceftaroline.[10,16–18] DFIs in particular require proper wound care and early surgical intervention as well as aggressive appropriate antibiotic therapy.

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