Cloxacillin

Abstract

Before 1980, superficial pyodermas in the US were caused primarily by streptococci. Studies conducted in Miami show that during the early 1980s, the predominant pathogen associated with impetigo in pediatric patients shifted from Streptococcus pyogenes to Staphylococcus aureus. Subsequent reports revealed a trend of increasing resistance of S. aureus to penicillins. By regular monitoring of local sensitivity patterns physicians are more likely to select the appropriate antibiotic. The current recommendation for the treatment of pediatric skin disease is cephalosporins due to their low likelihood of resistance by S. aureus.

Introduction

When diagnosed early and treated with a suitable antibiotic, bacterial skin infections in children can usually be cured. If not treated promptly, nephritis, septicemia, carditis, or arthritis may result. (1) For example, streptococcus infections have been associated with glomerulonephritis (2-6) during the 1960s and 1970s in Jamaica, Trinidad, and Red Lake, Minnesota. Until the early 1980s, therapy for mixed skin infections in children was usually directed at streptococci (group A [beta]-hemolytic Streptococcus pyogenes), the primary causative organism, and staphylococci, the secondary invader. (7-9)

Impetigo

Impetigo is a common skin infection in pre-school and school-aged children. It occurs most frequently in geographic areas with long, hot summers and high humidity. (1,10) Poor hygiene, crowded living conditions, minor skin trauma, and pre-existing infections are also associated with impetigo. (1)

Impetigo contagiosa is caused by Staphylococcus aureus, Streptococcus pyogenes, or both. This highly infectious form is characterized by vesicular lesions that may be preceded by micro or macro trauma. Lesions become thick with honey-colored crust. (Figure 1). Bullous Impetigo is caused by coagulase-positive S. aureus and is more common among infants (Figure 2). Vesicular lesions and superficial flaccid pustules may be present as well as a collarette of scale, often on covered areas of the skin. The exfoliative toxin is produced by phage group II S. aureus.

The Shifting Trend

Before 1980, superficial pyodermas in the US were caused primarily by streptococci. A Miami study reported in 1983, (9) however, uncovered a change. The authors evaluated 101 children (aged 6 months to 3 years) with pyoderma. Samples for culture and sensitivity testing were taken on the initial visit and after 1 week of treatment. After the initial visit, patients randomly received either penicillin V potassium (pen VK) or cloxacillin sodium. Patients not responding after 1 week of treatment were switched to another antibiotic and evaluated 2 weeks later.

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In patients presenting with staphylococcal bullous impetigo, most had vesicular bullous lesions but the predominant lesions were pustules, and most were on the extremities (Figure 4). Conventional expectation at the time was that most lesions of staphylococcus bullous impetigo would appear on the face and genitalia.

Culture revealed S. aureus in 29 patients receiving cloxacillin and S. aureus in 38 patients receiving pen VK. Treatment was successful in all cloxacillin recipients but failed in 47% of pen VK recipients. Nine patients had mixed infections in which both S. aureus and S. pyogenes were isolated. Four had received cloxacillin and 5 had received pen VK. Treatment was successful in all 4 cloxacillin recipients and treatment failed in 2 of the 5 pen VK recipients (40%).

These results showed that the primary invader was no longer S. pyogenes; otherwise the response rate to pen VK would have been higher. The principal pathogen now appeared to be S. aureus, as shown in Figure 3. Two other studies have corroborated these findings. (8,11)

At the University of Miami where this study was conducted, in vitro studies showed resistance of S. aureus against Pen VK at [greater than or equal to]98%, against cloxacillin at [less than or equal to]2 %, and against erythromycin at 10%.

The authors concluded that (1) cloxacillin was effective and pen VK was not; (2) erythromycin was a fair choice but not ideal due to lower efficacy, potential resistance, and GI intolerance; (3) dicloxacillin could also be effective but was not ideal due to its bad taste; and (4) cephalosporins were an ideal alternative because of their efficacy, palatability, and tolerability.

A Decade Later

Later studies in Miami showed a continuing pattern of resistance development. In a retrospective analysis conducted from August 1990 to November 1991, (12) S. aureus was isolated from impetiginized lesions of 111 patients with atopic dermatitis and 23 patients without atopic dermatitis. Antibiotic sensitivity testing revealed pen VK resistance of S. aureus at [greater than or equal to]90%, as in 1983; cloxacillin resistance at 21% compared to [less than or equal to]2% in 1983; and erythromycin resistance at 42% compared to 10% in 1983.

The authors concluded that (1) cloxacillin and/or erythromycin-resistant S. aureus may become a widespread trend, (2) clinical response to in vitro antibiotic susceptibilities needed to be studied, and (3) impetigo patients should also be spot-cultured before antibiotic treatments. The authors also recommended the use of first-generation cephalosporins with consideration of topical agents such as mupirocin as the ideal treatment option.

The Turn of the Century

In a 1999 retrospective study (13) conducted in Miami, bacterial resistance was studied in 105 patients aged 6 months to 12 years. Calcium alginate swabs from skin and asymptomatic nares were plated on trypticase soy agar with 5% sheep blood. Antibiotic susceptibility testing was performed using the Microscan method. The results are shown in Figure 5. Resistance is clearly highest for penicillin.

These studies (9,12,13) show that antibiotic sensitivities are constantly changing (Table 1) and that local monitoring of antibiotic sensitivities is crucial to selecting the appropriate antibiotic for a bacterial skin infection. Jegasothy and colleagues (13) recommend oral cephalosporins and/or topical mupirocin for the treatment of impetigo, and add that clinicians should watch for increasing utility of other antibiotics.

Table 2 shows the current sensitivities of S. aureus to frequently used antibiotics.

The 2003 Red Book Treatment Guidelines of Staphylococcus aureus and GABHS Skin Infection (15) recommend mupirocin to treat superficial localized skin infection. For deeper skin infection, first- and second-generation cephalosporins, cloxacillin, and dicloxacillin are recommended with macrolides, and clindamycin for penicillin-allergic patients. Serious invasive skin infections require IV antibiotic treatment barrage (ie, vancomycin and oxacillin, with gentamicin and clindamycin if necessary).

The increasing prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA) is an important development. Lee and colleagues (15) showed that in most of 69 pediatric patients, incision and drainage resulted in clinical improvement, even in patients who did not receive MRSA-active antibiotics. The reports by Fritsche and Jones and by Elston in this supplement provide more detail on MRSA.

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Conclusion

After a half century of streptococcus predominance, S. aureus has been the predominant organism in pediatric skin infections since the early 1980s, but this trend may change. Antibiotic susceptibilities may also change, but for now, cephalosporin and/or topical mupirocin are ideal choices for treatment. Despite reported reluctance by physicians to prescribe cephalosporins for penicillin-allergic patients due to concern about cross-sensitivity, there is substantial evidence supporting the recommendation by the American Academy of Pediatrics to do just that. (17) To be vigilant against changing predominance and to uncover possible geographic differences, regular spot checking of patient populations is recommended.

Dr. Schachner is affiliated with the Speakers Bureau of Abbott Laboratories.

References

1. Hedrick J. Acute bacterial skin infections in pediatric medicine: current issues in presentation and treatment. Paediatr Drugs. 2003;5 Suppl 1:35-46.

2. Balter S, Benin A, Pinto SW, et al. Epidemic nephritis in Nova Serrana, Brazil. Lancet. 2000;355:1776-1780.

3. Barnham M, Thornton TJ, Lange K. Nephritis caused by Streptococcus zooepidemicus (Lancefield group C). Lancet. 1983;1:945-948.

4. Duca E, Teodorovici G, Radu C, et al. A new nephritogenic streptococcus. J Hyg (Lond). 1969;67:691-698.

5. Centers for Disease Control. Group C streptococcal infections associated with eating homemade cheese, New Mexico. Morbid Mortal Weekly Rep. 1983;32:510-516.

6. Nicholson ML, Ferdinand L, Sampson JS, et al. Analysis of immunoreactivity to a Streptococcus equi subsp. zooepidemicus M-like protein To confirm an outbreak of poststreptococcal glomerulonephritis, and sequences of M-like proteins from isolates obtained from different host species. J Clin Microbiol. 2000;38:4126-4130.

7. Dillon HC Jr. Impetigo contagiosa: suppurative and non-suppurative complications. I. Clinical, bacteriologic, and epidemiologic characteristics of impetigo. Am J Dis Child. 1968;115:530-541.

8. Dillon HC Jr. Topical and systemic therapy for pyodermas. Int J Dermatol. 1980;19:443-451.

9. Schachner L, Taplin D, Scott GB, Morrison M. A therapeutic update of superficial skin infections. Pediatr Clin North Am. 1983;30:397-404.

10. Epps RE. Impetigo in pediatrics. Cutis. 2004;73(suppl 5):25-26.

11. Finnerty EF, Folan DW Jr. Changing antibiotic sensitivities of bacterial skin diseases. Office practice 1977-1978. Cutis. 1979;23:227-230.

12. Pruksachatkunakorn C, et al. Pediatr Dermatol. 1992;9:175.

13. Jegasothy S. unpublished data.

14. Gonzalez A, Schachner LA, Cleary T, Scott G, Taplin D, Lambert W. Pyoderma in childhood. Adv Dermatol. 1989;4:127-141.

15. Pickering LK, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, II: American Academy of Pediatrics; 2003.

16. Lee MC, Rios AM, Aten MF, Mejias A, Cavuoti D, McCracken GH Jr, Hardy RD. Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Pediatr Infect Dis J. 2004;23:123-127.

17. Pichichero ME. A review of evidence supporting the American academy of pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005;115:1048-1457.

Address for Correspondence

Lawrence A. Schachner MD

University of Miami School of Medicine

PO Box 16250

Miami, FL 33101-6250

Phone: 305-243-6742

Fax: 305-243-6191

e-mail: lschachn@med.miami.edu

Lawrence A. Schacher MD

University of Miami School of Medicine, Miami, FL

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