CURRENT CONCEPTS IN MANAGEMENT OF BACTERIAL SKIN INFECTIONS
Dr. Jayakar Thomas, MD, DD, PhD, MNAMS*
Senior Consultant Dermatologist, KK CHILDS Trust Hospital, Chennai.*
The childhood version of Bacterial Dermatoses (BD) differs in many ways from its adult counterpart. It is not uncommon to see these disorders leading on to complications like nephritis, meningitis, and septicemia in children, infants, and neonates respectively. For these reasons, correct diagnosis and early therapeutic intervention are important. The take-home message is - never take BD lightly in children. They could spread horizontally to affect wider areas, or penetrate vertically to involve deeper tissues, or result in a blood spill over to cause bacteremia, septicemia, or sometimes even endocarditis.

This presentation consists of ever-developing methicillin-resistant staphylococcus aureus, which is currently causing immense concern in all parts of the world.
Methicillin-Resistant Staphylococcus aureus
There is an increasing incidence of both hospital and community-acquired methicillin-resistant Staphylococcus aureus (MRSA). Hospital-acquired MRSA was first identified in the 1960s, and it has broad antibacterial resistance. The community-acquired variant (CA-MRSA), which has a narrow spectrum of antibiotic resistance, was identified in 1993 and has been an increasing cause of skin and soft tissue infections (SSTI). This increase in MRSA has not been limited to the developed world alone, but has found its way into India. The number of children becoming infected is also increasing. Although SSTI are the most common infections seen with MRSA, 6% of patients develop more serious infections, including pneumonia and osteomyelitis. These more virulent infections are typically found in variants producing Panton-Valentine leukocidin, which enables the bacteria to lyse white blood cells and causes tissue necrosis. While the isolates were initially seen in Europe, they have now traveled to the rest of the world. Children with atopic dermatitis or asthma have an increased risk of developing MRSA infections, as do children participating in contact sports or living with an infected family member.

MRSA infections are often resistant to commonly prescribed antibiotics for Staphylococcus aureus skin and soft tissue infections, although they are usually susceptible to clindamycin, trimethoprim/ sulfamethoxazole, and vancomycin in severe cases. CA-MRSA often contains the staphylococcal cassette chromosome (SCC) gene which codes for methicillin resistance but not multi-drug resistance. New multidrug-resistant strains of CA-MRSA have been found. Clindamycin resistance has become an increasing problem. While resistance to penicillin is conferred through the mecA gene and production of the penicillin-binding protein 2a, another gene, erm, has been shown to confer resistance to erythromycin (macrolide-lincosamide-streptogramin B resistance). Patients who develop erythromycin-resistant strains of S. aureus often demonstrate clindamycin resistance, as shown through a D-zone test for antibiotic sensitivity. Studies found that 38% of MRSA cultures were erythromycin-resistant and the D-zone test was positive in 31 of the 33 isolates, suggesting possible clindamycin resistance. Those isolates that were resistant were predominantly the hospital-acquired variant. Therefore, if isolates are erythromycin-resistant and clindamycin-sensitive, a D-zone test should be performed by the laboratory to determine whether there is inducible clindamycin resistance. If present, the clinician should follow patients with skin and soft tissue infections closely and consider not using clindamycin for serious infections, because it may not prove effective against this strain of bacteria.

The utility of incision and drainage of MRSA abscesses has been proven in several studies and is essential in treating these infections. Pediatric patients treated with incision and drainage of small abscesses (< 5 cm) with MRSA showed similar clearance rates regardless of whether appropriate antibiotics were added. Treatment with antibiotics to which the organism is not sensitive do not adversely affect patient outcome if the area is drained. These suggest that drainage may be as important as antibiotics in treating MRSA infections. It is recommended incising abscesses but avoiding packing the area, which would introduce a foreign body into the infected site. It is preferred to leave the abscess open after drainage and to have the patient irrigate the area.

To address surface carriage in patients with recurrent MRSA infections, patients must bathe twice weekly in water containing sodium hypochlorite (bleach). It is recommended using ¼ cup of bleach in a bathtub filled with water to reduce both gram-positive and gram-negative infections. Sodium hypochlorite is bactericidal in concentrations as low as 0.025%. Patients can also reduce surface carriage of bacteria by using chlorhexidine washes at home or triclosan, which is present in alcohol-based no-rinse sanitizers.
New insights into Antibiotics
New antibiotics have been developed for MRSA infections. Linezolid is an oral antibiotic in the oxazolidinone class. It is effective against gram-positive aerobes, and works through the inhibition of bacterial protein synthesis. In some studies, it has shown efficacy superior to vancomycin in treating MRSA infections, but resistance to this antibiotic is already beginning to develop. The use of linezolid is limited by its expense, and it can cause reversible thrombocytopenia and peripheral neuropathy.

Daptomycin is a parenteral antibiotic that is effective against gram-positive organisms by being the cell membrane and causing destruction of the bacteria through depolarization of the ion concentration gradient. Daptomycin can cause nausea and muscle pain and weakness, and muscle enzyme monitoring is required during treatment. Quinupristin/dalfopristin has shown excellent in-vitro activity but only modest in-vivo clinical efficacy, especially in the treatment of MRSA pneumonia.

Ceftobiprole medocaril is a new cephalosporin that is effective against MRSA and considered comparable to linezolid. Topical mupirocin has often been used to treat infections and intranasally to reduce MRSA carriage, although up to 14% of MRSA isolates may be resistant to this medication. The incidence is higher in some instances.

Clinicians should now consider MRSA as a potential pathogen in patients with suspected S aureus infections in the community setting. Culture and sensitivity should be performed from appropriate material. Chromogenic medium is being developed for more rapid information, but even that will take 24 hours.

The presence of erythromycin resistance may signal inducible resistance to clindamycin. The ability to undergo this induction can be tested by observing rings of growth inhibition of adjacent areas on the agar dish; when there is resistance to erythromycin which extends into the adjacent clindamycin disk so that the inhibition forms a "D" rather than an "O", the test indicates pending clindamycin resistance. If clindamycin is being considered for treatment of erythromycin-resistant S. aureus infection, the D test should be ordered.

The recommended approach to suspected staphylococcal skin infections is to:
  1. Consider MRSA as a potential pathogen in the community setting.

  2. Culture and follow up susceptibility testing of all S. aureus isolates.
  3. Perform surgical drainage of infections when feasible.
  4. Treat seriously ill patients with vancomycin. (Linezolid is also a choice)

Surgical drainage of infections should be done when feasible. Antibiotic treatment without drainage encourages the development of resistance. Modified Dakins solution (0.025% sodium hypochlorite solution) has significant activity against gram-positive bacteria, including S aureus, but may not be as effective as topical antibiotics. Mupirocin resistance is becoming more prevalent.

In dermatology, 65% of antibiotics used come from the tetracycline family, 10% are cephalosporins, and erythromycin accounts for 8%. When examining the activity of cephalosporins, the third-generation cefdinir given at a dose of 300 mg twice daily was found to be the most active against those bacteria that commonly cause skin and soft tissue infections, although it was inactive against MRSA and P aeruginosa. Although approximately 10% of patients with penicillin allergy are thought to have cross-sensitivity to cephalosporins, this may be due to the 7-position side chain on the beta-lactam ring. As a result, 3 cephalosporins (cefdinir, cefuroxime, cefpodoxime) contain different side chains from penicillin and are not thought to cross-react in penicillin-allergic patients even if they are skin-test-positive. These antibiotics can be used in patients with a penicillin allergy, although they should probably not be used in patients with a history of severe reactions. Quinolones work well for selected gram-negative pathogens, such as P aeruginosa, but should not be the first line for skin and soft tissue infections because they have little activity against the usual pathogens causing these infections. In addition, their absorption is decreased if taken with antacids.
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