Emerging Infections in Burns

Ludwik Branski

Ahmed Al-Mousawi

Haidy Rivero

Marc Jeschke

Arthur Sanford

David Herndon

Background

Patients who suffer severe burns are at higher risk for local and systemic infections. In recent years, emerging resistant pathogens have forced burn care providers world wide to search for alternative forms of treatment. Multidrug-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter spp., and various fungal strains have been the major contributors to the increase in morbidity and mortality rates. Multi-drug-resistant S. aureus remains the major cause of gram-positive burn wound infections world wide. Treatment strategies include rigorous isolation protocols and new types of antibiotics where necessary.

Methods

We reviewed 398 severely burned patients (burns >40% total body surface area [TBSA]) admitted to our hospital between 2000 and 2006. Patients who did not contract multi-drug-resistant gram-negative organisms during their hospital course and received our standard antibiotic regimen—vancomycin and piperacillin/tazobactam—served as controls (piperacillin/tazobactam; n = 280). The treatment group consisted of patients who, during their acute hospital stay, developed infections with multi-drug-resistant gram-negative pathogens and were treated with vancomycin and colistin for at least three days (colistin; n = 118).

Results

Gram-negative organisms continue to cause the most severe infections in burn patients. Colistin has re-emerged as a highly effective antibiotic against multiresistant Pseudomonas and Acinetobacter infections of burns. Patients who required colistin therapy had a significantly larger average total and full-thickness burn than patients treated with piperacillin/tazobactam and vancomycin, and the mortality rate was significantly higher in the colistin group (p < 0.05). However, there was no significant difference between the colistin and piperacillin/tazobactam groups in the incidence of neurotoxicity, hepatic toxicity, or nephrotoxicity. The main fungal pathogens in burn patients are Candida spp., Aspergillus spp., and Fusarium spp. A definitive diagnosis is more difficult to obtain than in bacterial infections. Amphotericin B and voriconazole remain the two most important anti-fungal substances in our practice.

Conclusions

Innovations in fluid management, ventilatory support, surgical care, and antimicrobial therapy have contributed to a significant reduction in morbidity and mortality rates in burn patients. Vancomycin and clindamycin are the two most important reserve antibiotics for methicillin-resistant Staphylococcus aureus infection. Oxazolidinones and streptogramins have showed high effectiveness against gram-positive infections. Colistin has re-emerged as a highly effective antibiotic against multiresistant Pseudomonas and Acinetobacter infections. Current challenges include Candida, Aspergillus, and molds. The development of new agents, prudent and appropriate use of antibiotics, and better infection control protocols are paramount in the ongoing battle against multi-resistant organisms.

Department of Surgery, The University of Texas Medical Branch and Shriners Hospitals for Children, Galveston, Texas.

^{Corresponding author.}

Address correspondence to: Dr. David N. Herndon, Shriners Hospitals for Children, 815 Market St., Galveston, TX 77550. E-mail:ude.bmtu@nodnrehd

^{These authors contributed equally to this work.}

Address correspondence to: Dr. David N. Herndon, Shriners Hospitals for Children, 815 Market St., Galveston, TX 77550. E-mail:ude.bmtu@nodnrehd

Abstract

Background

Methods

Results

Conclusions

Abstract

When Doctor G. Tom Shires began his career as a surgeon at the Parkland Memorial Hospital in Dallas, Texas, in 1948, burn care and treatment had only recently emerged from its status as a neglected subspecialty of trauma, becoming under his leadership one of the most prominent fields of clinical and basic research in trauma. On April 16, 1947, two freighters loaded with ammonium nitrate fertilizer exploded at a dock in Texas City, 300 miles south of Dallas, killing 560 people and injuring more than 3,000 in what is still the deadliest industrial accident in American history [1]. Doctor Truman G. Blocker spearheaded the mobilization of the efforts to treat the burn injuries and, subsequently, created the first dedicated burn center in the United States at The University of Texas Medical Branch in Galveston. In the 1960s, when Doctor Shires became Chairman of the Surgery Department at the Southwestern Medical School in Dallas, major improvements were made in burn care; however, shock, sepsis, and multi-organ dysfunction caused a 50% mortality rate in burns exceeding one-half of the total body surface area (TBSA) [2], and the mortality rate attributable to bacterial sepsis in burns >50% TBSA reached 60–80% [1]. Over the next decades, Doctor Shires and his colleagues worked tirelessly to improve the surgical approach to burn wounds, fluid resuscitation, control of infection, support of the hypermetabolic response, nutritional support, treatment of inhalation injury, and rehabilitation [1,3,4]. One of his prominent achievements was the Parkland formula for fluid resuscitation after burn injury [5], today the most widely used schema, which recommends 4 mL of Ringer's lactate/kg/% TBSA in the first 24 h after a burn [5]. Doctor Shires also established burn centers at the University of Washington Harborview Medical Center in Seattle and The New York Hospital-Cornell Medical Center in New York City, where he was Chairman of Surgery from 1976 to 1991 (Fig. 1). Burn survival subsequently improved dramatically, and the size of burn that causes a 50% mortality rate has increased to 98% (Table 1).

FIG. 1.

G. Tom Shires (1926–2007) (with friendly permission from Medical Center Archives of New York-Presbyterian/Weill Cornell.

Table 1.

Percent Total Body Surface Area Burn Associated with an Expected Mortality Rate of 50% in 1952, 1993, and 2006

Age (years)	1953^{^a}	1993^{^b}	2006^{^c}
0–14	49	98	99
15–44	46	72	88
45–65	27	51	75
>65	10	25	33

^{Bull JP, Fisher AJ. A study of mortality in a burns unit: A revised estimate. Ann Surg 1954;139:269–274.}

^{Unpublished data; Shriners Hospital for Children and The University of Texas Medical Branch, Galveston, Texas.}

^{Pereira CT, Barrow RE, Sterns AM, et al. Age-dependent differences in survival after severe burns: A unicentric review of 1,674 patients and 179 autopsies over 15 years. J Am Coll Surg 2006;202:536–548 and unpublished data. Adapted from Herndon DN, ed. Total Burn Care, 3rd edition. Philadelphia: WB Saunders, 2007.}

All progress notwithstanding, infection remains the main cause of death among burn patients [3,4]. The loss of the skin barrier and the immune deficiency associated with large burns make these patients especially susceptible to sepsis [6,7]. The Nosocomial Infection Surveillance System from the U.S. Centers for Disease Control and Prevention (CDC) demonstrated that burn intensive care units (ICUs) have the highest rates of primary blood stream infection in patients with central venous catheters among all ICUs [6,8]. Recently, emerging multi-drug-resistant strains of bacteria and fungi have caused an unexpected rise in burn wound infections, sepsis, and associated death worldwide [9–13]. At the Galveston Shriners Hospital, multiresistant Acinetobacter spp. and Fusarium spp. caused an epidemic in the burn unit in the early 2000s (Fig. 2), and multiresistant Pseudomonas spp. emerged more recently.

FIG. 2.

Incidence of burn wound infections at the Shriners Hospital for Children, Galveston Burn Intensive Care Unit, 1998–2008.

The purpose of this paper is to outline the major contributors to infection-related burn deaths—methicillin-resistant Staphylococcus aureus, Pseudomonas and Acinetobacter spp., and fungal infections—and to describe the development of multiresistant strains and the methods of treatment.

Footnotes

Presented at the Memorial Celebration and Festschrift for Doctor G. Tom Shires, New York, New York, October 25, 2008.

Footnotes

References

1. Herndon DN. Barrow RE. History of treatments of burns. In: Herndon DN, editor. Total Burn Care. 3rd. Philadelphia: WB Saunders; 2007. pp. 1–8. [PubMed]
2. Bull JP. Fisher AJ. A study of mortality in a burns unit: A revised estimate. Ann Surg. 1954;139:269–274.
3. Muller MJ. Herndon DN. The challenge of burns. Lancet. 1994;343:216–220.[PubMed]
4. Saffle JR. Davis B. Williams P. Recent outcomes in the treatment of burn injury in the United States: A report from the American Burn Association Patient Registry. J Burn Care Rehabil. 1995;16:219–232.[PubMed]
5. Baxter CR. Shires T. Physiological response to crystalloid resuscitation of severe burns. Ann NY Acad Sci. 1968;150:874–894.[PubMed]
6. Richards C. Emori TG. Edwards J, et al. Characteristics of hospitals and infection control professionals participating in the National Nosocomial Infections Surveillance System 1999. Am J Infect Control. 2001;29:400–403.[PubMed]
7. Schwacha MGMacrophages and post-burn immune dysfunction. Burns. 2003;29:1–14.[PubMed][Google Scholar]
8. Pruitt BA., Jr McManus AT. Kim SH, et al. Burn wound infections: Current status. World J Surg. 1998;22:135–145.[PubMed]
9. Gallagher JJ. Williams-Bouyer N. Villarreal C, et al. Treatment of infection in burns. In: Herndon DN, editor. Total Burn Care. 3rd. Philadelphia: WB Saunders; 2007. pp. 136–176. [PubMed]
10. Greenhalgh DG. Saffle JR. Holmes JHT, et al. American Burn Association consensus conference to define sepsis and infection in burns. J Burn Care Res. 2007;28:776–790.[PubMed]
11. D'Avignon LC. Saffle JR. Chung KK, et al. Prevention and management of infections associated with burns in the combat casualty. J Trauma. 2008;64(3 Suppl):S277–S286.[PubMed]
12. Miranda BH. Ali SN. Jeffery SL, et al. Two stage study of wound microorganisms affecting burns and plastic surgery inpatients. J Burn Care Res. 2008;29:927–932.[PubMed]
13. Wibbenmeyer LA. Kealey GP. Latenser BA, et al. Emergence of the USA300 strain of methicillin-resistant Staphylococcus aureus in a burn-trauma unit. J Burn Care Res. 2008;29:790–797.[PubMed]
14. Durtschi MB. Orgain C. Counts GW, et al. A prospective study of prophylactic penicillin in acutely burned hospitalized patients. J Trauma. 1982;22:11–14.[PubMed]
15. de Macedo JL. Santos JB. Bacterial and fungal colonization of burn wounds. Mem Inst Oswaldo Cruz. 2005;100:535–539.[PubMed]
16. Cook NMethicillin-resistant Staphylococcus aureus versus the burn patient. Burns. 1998;24:91–98.[PubMed][Google Scholar]
17. Phillips LG. Heggers JP. Robson MC. Burn and trauma units as sources of methicillin-resistant Staphylococcus aureus. J Burn Care Rehabil. 1992;13:293–297.[PubMed]
18. Robson MC. Krizek TJ. Heggers JP. Biology of surgical infection. In: Ravitch MM, editor. Current Problems in Surgery. Chicago: Year Book Medical Publishers; 1973. pp. 1–62. [[PubMed]
19. Guggenheim M. Zbinden R. Handschin AE, et al. Changes in bacterial isolates from burn wounds and their antibiograms: A 20-year study (1986–2005) Burns. 2009;35:553–560.[PubMed]
20. Schuster KM. Wilson D. Schulman CI, et al. Continuous-infusion oxacillin for the treatment of burn wound cellulitis. Surg Infect. 2009;10:41–45.[PubMed]
21. de Macedo JL. Rosa SC. Castro C. Sepsis in burned patients. Rev Soc Bras Med Trop. 2003;36:647–652.[PubMed]
22. Thabet L. Turki A. Ben Redjeb S, et al. [Bacteriological profile and antibiotic resistance of bacteria isolates in a burn department](Fre) Tunis Med. 2008;86:1051–1054.[PubMed]
23. Prasanna M. Thomas C. A profile of methicillin-resistant Staphylococcus aureus infection in the burn center of the Sultanate of Oman. Burns. 1998;24:631–636.[PubMed]
24. Barber M. Rozwadowska-Dowzenko M. Infection by penicillin-resistant staphylococci. Lancet. 1948;2:641–644.[PubMed]
25. Jevons MP. Coe AW. Parker MT. Methicillin resistance in staphylococci. Lancet. 1963;1:904–907.[PubMed]
26. Enright MCThe evolution of a resistant pathogen—the case of MRSA. Curr Opin Pharmacol. 2003;3:474–479.[PubMed][Google Scholar]
27. Metzger R. Bonatti H. Sawyer R. Future trends in the treatment of serious gram-positive infections. Drugs Today. 2009;45:33–45.[PubMed]
28. Ben-David D. Mermel LA. Parenteau S. Methicillin-resistant Staphylococcus aureus transmission: The possible importance of unrecognized health care worker carriage. Am J Infect Control. 2008;36:93–97.[PubMed]
29. Dansby W. Purdue G. Hunt J, et al. Aerosolization of methicillin-resistant Staphylococcus aureus during an epidemic in a burn intensive care unit. J Burn Care Res. 2008;29:331–337.[PubMed]
30. Mayhall CGThe epidemiology of burn wound infections: Then and now. Clin Infect Dis. 2003;37:543–550.[PubMed][Google Scholar]
31. Hodle AE. Richter KP. Thompson RM. Infection control practices in U.S. burn units. J Burn Care Res. 2006;27:142–151.[PubMed]
32. Wang Z. Rong XZ. Zhang T, et al. [Distribution and drug resistance analysis of bacteria in different wound infections](Chi) Nan Fang Yi Ke Da Xue Xue Bao. 2009;29:82–83.[PubMed]
33. Zar HJ. Cotton MF. Nosocomial pneumonia in pediatric patients: Practical problems and rational solutions. Paediatr Drugs. 2002;4:73–83.[PubMed]
34. Murray PR. Baron EJ. Jorgensen JH, et al. Manual of Clinical Microbiology. 8th. Washington, DC: ASM Press; 2003. [PubMed]
35. Shoup M. Weisenberger JM. Wang JL, et al. Mechanisms of neutropenia involving myeloid maturation arrest in burn sepsis. Ann Surg. 1998;228:112–122.
36. Walton MA. Villarreal C. Herndon DN, et al. The use of aztreonam as an alternate therapy for multiresistant Pseudomonas aeruginosa. Burns. 1997;23:225–227.[PubMed]
37. Japoni A. Alborzi A. Kalani M, et al. Susceptibility patterns and cross-resistance of antibiotics against Pseudomonas aeruginosa isolated from burn patients in the South of Iran. Burns. 2006;32:343–347.[PubMed]
38. Ozkurt Z. Ertek M. Erol S, et al. The risk factors for acquisition of imipenem-resistant Pseudomonas aeruginosa in the burn unit. Burns. 2005;31:870–873.[PubMed]
39. Mokaddas EM. Sanyal SC. Resistance patterns of Pseudomonas aeruginosa to carbapenems and piperacillin/tazobactam. J Chemother. 1999;11:93–96.[PubMed]
40. Archibald L. Phillips L. Monnet D, et al. Antimicrobial resistance in isolates from inpatients and outpatients in the United States: Increasing importance of the intensive care unit. Clin Infect Dis. 1997;24:211–215.[PubMed]
41. Fass RJ. Barnishan J. Ayers LW. Emergence of bacterial resistance to imipenem and ciprofloxacin in a university hospital. J Antimicrob Chemother. 1995;36:343–353.[PubMed]
42. Evans ME. Feola DJ. Rapp RP. Polymyxin B sulfate and colistin: Old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999;33:960–967.[PubMed]
43. Li J. Nation RL. Turnidge JD, et al. Colistin: The re-emerging antibiotic for multidrug-resistant gram-negative bacterial infections. Lancet Infect Dis. 2006;6:589–601.[PubMed]
44. Storm DR. Rosenthal KS. Swanson PE. Polymyxin and related peptide antibiotics. Annu Rev Biochem. 1977;46:723–763.[PubMed]
45. Nord NM. Hoeprich PD. Polymyxin B and colistin: A critical comparison. N Engl J Med. 1964;270:1030–1035.[PubMed]
46. Kunin CM. Bugg A. Binding of polymyxin antibiotics to tissues: The major determinant of distribution and persistence in the body. J Infect Dis. 1971;124:394–400.[PubMed]
47. Kunin CM. Bugg A. Recovery of tissue bound polymyxin B and colistimethate. Proc Soc Exp Biol Med. 1971;137:786–790.[PubMed]
48. Martin GS. Mannino DM. Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–1554.[PubMed]
49. Wisplinghoff H. Bischoff T. Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39:309–317.[PubMed]
50. Banerjee SN. Emori TG. Culver DH, et al. Secular trends in nosocomial primary bloodstream infections in the United States, 1980–1989. National Nosocomial Infections Surveillance System. Am J Med. 1991;91:86S–89S.[PubMed]
51. Burchard KW. Minor LB. Slotman GJ, et al. Fungal sepsis in surgical patients. Arch Surg. 1983;118:217–221.[PubMed]
52. Fraser VJ. Jones M. Dunkel J, et al. Candidemia in a tertiary care hospital: Epidemiology, risk factors, and predictors of mortality. Clin Infect Dis. 1992;15:414–421.[PubMed]
53. Wey SB. Mori M. Pfaller MA, et al. Hospital-acquired candidemia: The attributable mortality and excess length of stay. Arch Intern Med. 1988;148:2642–2645.[PubMed]
54. Edwards JR. Peterson KD. Andrus ML, et al. National Healthcare Safety Network (NHSN) Report, data summary for 2006, issued June 2007. Am J Infect Control. 2007;35:290–301.[PubMed]
55. Ballard J. Edelman L. Saffle J, et al. Positive fungal cultures in burn patients: A multicenter review. J Burn Care Res. 2008;29:213–221.[PubMed]
56. Mousa HA. Al-Bader SM. Hassan DA. Correlation between fungi isolated from burn wounds and burn care units. Burns. 1999;25:145–147.[PubMed]
57. Al-Mousawi AM. Jeschke MG. Herndon DN. History of metabolic treatments in burn care. Wounds. 2008;20:185–191.[PubMed]
58. Fox CL., Jr Rappole BW. Stanford W. Control of Pseudomonas infection in burns by silver sulfadiazine. Surg Gynecol Obstet. 1969;128:1021–1026.[PubMed]
59. Lindberg RB. Moncrief JA. Switzer WE, et al. The successful control of burn wound sepsis. J Trauma. 1965;5:601–616.[PubMed]
60. Moyer CA. Brentano L. Gravens DL, et al. Treatment of large human burns with 0.5 per cent silver nitrate solution. Arch Surg. 1965;90:812–867.[PubMed]
61. Becker WK. Cioffi WG., Jr McManus AT, et al. Fungal burn wound infection: A 10-year experience. Arch Surg. 1991;126:44–48.[PubMed]
62. Schofield CM. Murray CK. Horvath EE, et al. Correlation of culture with histopathology in fungal burn wound colonization and infection. Burns. 2007;33:341–346.[PubMed]
63. Dean DA. Burchard KW. Fungal infection in surgical patients. Am J Surg. 1996;171:374–382.[PubMed]
64. Munoz P. Burillo A. Bouza E. Criteria used when initiating antifungal therapy against Candida spp. in the intensive care unit. Int J Antimicrob Agents. 2000;15:83–90.[PubMed]
65. Bochud PY. Bonten M. Marchetti O, et al. Antimicrobial therapy for patients with severe sepsis and septic shock: An evidence-based review. Crit Care Med. 2004;32(11 Suppl):S495–S512.[PubMed]
66. Herbrecht R. Denning DW. Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–415.[PubMed]
67. . . [Mar 12;2009 ]. [PubMed]
68. Krcmery V. Barnes AJ. Non-albicans Candida spp. causing fungaemia: Pathogenicity and antifungal resistance. J Hosp Infect. 2002;50:243–260.[PubMed]
69. McKinsey DSMaking best use of the newer antifungal agents. Drug Benefit Trends March. 2004:131–147.[PubMed][Google Scholar]
70. Anaissie EJ. Kuchar RT. Rex JH, et al. Fusariosis associated with pathogenic Fusarium species colonization of a hospital water system: A new paradigm for the epidemiology of opportunistic mold infections. Clin Infect Dis. 2001;33:1871–1878.[PubMed]