| disease | Burn Infection |
After a burn, the skin, which serves as the body's natural barrier against microbial invasion, is damaged. Additionally, the necrotic skin tissue provides an ideal "culture medium" for microbial growth and reproduction. As a result, burn wounds are highly susceptible to infection. In recent years, with improvements in the treatment of burn shock, the mortality rate from shock has significantly decreased. However, burn infection has become the leading cause of death in severe burn cases. The prevention and treatment of burn infections are crucial in burn care.
bubble_chart Clinical Manifestations
I. Local Symptoms of Wound Infection
Observation of the wound is the primary method for assessing local infection. Medical staff should continuously monitor visible wounds for changes. Common symptoms of wound infection include:
1. Changes in the color, odor, and quantity of wound secretions. Different bacterial infections can cause distinct changes: - *Staphylococcus aureus* infection: pale yellow, viscous secretions. - Hemolytic streptococcus infection: light coffee-colored, thin secretions. - *Pseudomonas aeruginosa* infection: green or blue-green, sweet-smelling, viscous secretions. - Anaerobic bacterial infection: foul, fecal odor.
2. Appearance of dark gray or black necrotic patches on the wound. Gram-negative bacterial infections often cause necrotic patches.
3. Deepening of the wound or delayed healing. Bacterial invasion of deeper blood vessels leads to ischemic necrosis, causing the wound to deepen and delay healing.
4. Premature dissolution or shedding of eschar, or the appearance of moth-eaten-like changes, indicating local infection.
5. Grayish-white spots on the scab or eschar often suggest fungal infection. These spots rapidly spread across the wound, merging into fluffy patches with increasingly noticeable discoloration—grayish-white, pale green, pale yellow, or brown. Within days, a thin powdery layer may form on the wound.6. Pus or abscess formation under the scab. *Staphylococcus aureus* infection may lead to abscesses under the scab, while green, sweet-smelling pus often indicates *Pseudomonas aeruginosa* infection.
7. Edema, redness, swelling, or necrosis of granulation tissue. Both *Staphylococcus aureus* and fungal infections can cause necrosis of granulation tissue. *Pseudomonas* infection may also lead to necrotic patches on granulation tissue.
8. Redness, swelling, petechiae, or necrotic patches around the wound. Hemolytic streptococcus infection often causes significant inflammatory reactions at the wound edges.
II. Manifestations of Systemic Infection After Burns
Despite the continuous introduction of new antibiotics, improvements in treatment protocols, and increased use of nutritional and immunostimulatory supplements, the leading cause of death in patients with extensive burns remains burn sepsis or wound sepsis. Domestic and international statistics indicate that 66.7–75% of deaths are infection-related.
(1) Types and Clinical Significance of Systemic Infection After Burns
1. Septicemia and Bacteremia
(1) Septicemia: The invasion and proliferation of bacteria (or other microorganisms) in the bloodstream, organs, or tissues, accompanied by the production of large amounts of toxins and byproducts, leading to systemic clinical symptoms and hemodynamic and metabolic changes. This condition is termed septicemia. If septic shock occurs, the prognosis is poor. A positive blood culture is typically used to diagnose septicemia. The causative bacteria may originate from burn wounds, intravenous catheter infections, internal organ infections, or gut-derived infections. Septicemia represents an advanced stage of wound sepsis.
(2) Bacteremia: The transient presence of live bacteria in the bloodstream is called bacteremia. This often occurs during eschar excision or shedding in burn wounds, with mild clinical symptoms and no significant hemodynamic or hematologic changes.2. Burn Wound Sepsis and Endotoxemia
(1) Burn Wound Sepsis: Telplitz (1964) first observed the proliferation of *Pseudomonas aeruginosa* in normal tissue surrounding burn wounds, invading lymphatic and blood vessels or forming emboli within vessels. The release of large amounts of endotoxins into the bloodstream leads to clinical symptoms of sepsis, often with negative blood cultures, termed burn wound sepsis. Biopsies of periwound tissue reveal perivascular inflammation or vasculitis. The bacterial load in periwound tissue typically exceeds 10 5 /g of tissue. However, this metric alone is not diagnostic; it must be combined with biopsy findings and systemic symptoms.
The bacteria responsible for wound sepsis include Gram-negative bacteria, Gram-positive bacteria, fungi, and mixed infections.
(2) Endotoxemia: Endotoxins are released from the inner layer of the cell wall of Gram-negative bacteria into the bloodstream, leading to hemodynamic changes and functional alterations in major internal organs, resulting in sepsis-like symptoms. However, blood cultures may be negative. The serum limulus amebocyte lysate (LAL) test can be used to measure endotoxin levels.
Based on clinical manifestations, endotoxemia can be classified into four types. The first is the mild type, characterized by transient hypotension, respiratory distress, and blood gas analysis showing grade I decreases in PCO2
and PO2, with a good prognosis. The second is respiratory endotoxic shock, featuring hypotension, respiratory rate exceeding 40 breaths per minute, rapid onset of unconsciousness, oliguria, and metabolic acidosis, with patients often dying from respiratory failure. The third is DIC-type endotoxic shock, typically occurring after debridement of infected wounds, presenting with hemodynamic changes and coagulation dysfunction, accompanied by petechial hemorrhages and microthrombi in unburned skin. Pathological examinations often reveal deep vein thrombosis, as well as petechial hemorrhages in the kidneys and skin. The fourth type often results from the administration of antibiotics that kill large numbers of Gram-negative bacilli, releasing endotoxins and causing hypotension. Body temperature can rise to 41°C, exhibiting a biphasic fever pattern, along with unconsciousness, vomiting, and diarrhea.The symptoms of endotoxemia resemble those of septic shock caused by Gram-negative bacteria. Treatment includes systemic administration of effective antibiotics and comprehensive therapy, along with medications that counteract or neutralize endotoxins: ① Glucocorticoids. They directly antagonize or neutralize the lipopolysaccharides of coliform bacilli and stabilize complement. ② Disodium cromoglycate (DSCG). DSCG stabilizes mast cells and neutrophils, preventing the release of histamine, serotonin, and slow-reacting substances of anaphylaxis, thereby blocking the systemic effects of these mediators. ③ Polymyxin B and other antibiotics. Literature indicates that polymyxin B can neutralize endotoxins, and carbenicillin can also neutralize endotoxins from coliform bacilli.
(II) Clinical Characteristics of Systemic Infections After Burns
1. Onset Periods of Systemic Infections
Systemic infections can be divided into early and late-stage [third-stage] phases based on the time of onset, with different characteristics and influencing factors.
(1) Early-stage infections: Infections occurring within two weeks post-burn are classified as early-stage infections. This phase has a high incidence of invasive infections, representing the peak of systemic invasive infections, accounting for about 60%. The onset is rapid, especially in cases occurring during the shock phase, where clinical manifestations such as rapid pulse, tachypnea, and hypotension can be confused with burn shock, necessitating careful differential diagnosis. Early-stage infections are difficult to treat and have a high mortality rate.
The high incidence of early-stage infections is related to several factors. First, immune function is significantly disrupted within two weeks post-burn. Second, burn patients often experience early complications such as shock, renal injury, and pulmonary injury. Patients with unstable shock phases have a higher incidence of sepsis. Additionally, early edema impairs local blood circulation, granulation tissue has not yet formed, and local defense barriers are incomplete, making invasive infections more likely.
Early-stage infections often manifest as hypothermia, leukopenia, and mental suppression, indicating a hyporesponsive state.
(2) Late-stage [third-stage] infections: Infections occurring more than two weeks post-burn are classified as late-stage [third-stage] infections, with a lower incidence than early-stage infections. These are primarily related to improper wound management and inappropriate antibiotic use. Active wound management and early debridement with skin grafting are key to preventing infections. Large areas of exposed granulation tissue after eschar separation are highly prone to invasive infections. Inappropriate antibiotic use can lead to opportunistic infections. Additionally, inadequate systemic nutritional support, insufficient protein and calorie intake, and prolonged physical depletion are major causes of late-stage infections. Late-stage infections often manifest as hyperthermia, leukocytosis, and mental excitation, indicating a hyperresponsive state.
2. Symptoms of Invasive Infections
The clinical manifestations of invasive infections are complex and can generally be categorized into hyperresponsive and hyporesponsive types. Main symptoms include:
(1) Mental state: Hyperresponsive patients may exhibit extreme excitement, delirium, visual hallucinations, and, in severe cases, mania. Hyporesponsive patients show suppression, manifesting as reduced speech, drowsiness, or even unconsciousness.
(2) Body temperature: The body temperature may present with high fever or decrease due to warm purgation. In severely burned patients, due to hypermetabolism, the body temperature often remains around 37°C to 38.5°C, which does not necessarily indicate the occurrence of invasive infection. However, if the body temperature rises to 39°C or drops below 36°C, attention should be paid to the possibility of infection.
(3) Pulse: Manifested as acceleration up to over 150 beats per minute; a slow pulse during the critical phase indicates poor prognosis.
(4) Respiration: Changes in respiration are a significant feature, presenting as rapid breathing, shallow and fast breathing, or symptoms of dyspnea such as nasal flaring.
(5) Gastrointestinal function: Loss of appetite is a common symptom. Some patients experience nausea, while vomiting and diarrhea are less frequent. If intestinal paralysis occurs, leading to abdominal distension and fullness, it is a specific characteristic.
(6) Blood pressure: A drop in blood pressure often indicates septic shock, suggesting a more critical condition. However, some patients show no significant changes in blood pressure.
(7) Wound changes: Combined with wound changes, invasive infections can be diagnosed. Common manifestations include increased secretions with a peculiar odor, eschar deliquescence and detachment, granulation tissue edema and ulceration, and pus accumulation under the scab.
(8) Necrotic patches: Hemorrhagic spots or necrotic patches may appear on the wound or normal skin, appearing dark red or gray-black. These patches, caused by bacteria or fungi, are indicators of poor prognosis.
(9) Laboratory tests: A sudden rise in white blood cell count to 20×109/L or a drop below 4×109/L is a relatively specific diagnostic marker for infection. A sudden decrease in platelets to low levels has high diagnostic value, and if complicated by DIC, the platelet drop is even more pronounced. Invasive infections lead to organ injuries, manifesting as elevated blood glucose, increased bilirubin, and elevated serum creatinine, among others.
III. Clinical Manifestations of Systemic Fungal Infections
1. Medical History
Predisposing factors for systemic fungal infections commonly include:
Moist wounds, where fungi easily proliferate, often due to humid climates or improper wound management.
Severe conditions, extensive burn areas, and prolonged illness. Due to prolonged debilitation, the body's resistance weakens, and immune function declines, increasing susceptibility to systemic fungal infections. Onset typically occurs around three weeks, though cases within one week also exist.
High-dose antibiotic use or topical silver sulfadiazine on wounds may lead to resistant strains and fungal superinfections. The increased incidence of fungal infections with broad-spectrum antibiotic use supports this observation.
Improper wound management, such as delayed removal of necrotic tissue, can lead to severe fungal infections and sepsis.
Other factors, including corticosteroid therapy, total parenteral nutrition, fungal phlebitis from intravenous catheters, and pre-existing bacterial sepsis, are also predisposing factors for systemic fungal infections.
2. Clinical Manifestations
(1) Mental state: Often characterized by excitement, sometimes with hallucinations, delirium, apathy, or confusion. At times, patients may appear entirely normal and lucid, creating a "seemingly ambiguous" presentation. In severe cases, unconsciousness may eventually occur.
(2) Body temperature: Typically sustained or remittent fever, peaking around midnight, with mild chills preceding the fever. Hypothermia may occur in the advanced stage or before death.
(3) Pulse and heart rate increase in sync with temperature fluctuations, sometimes reaching 140 beats per minute. Late-stage [third-stage] heart failure or cardiac arrest may occur.
(4) Markedly accelerated respiration (40–50 breaths per minute) or even dyspnea. When fungi invade the lungs, dry or moist rales may be heard, and X-ray examinations may show thickened lung markings or cotton-like shadows.
(5) Digestive manifestations: Most patients experience loss of appetite, nausea, difficulty swallowing, watery diarrhea, mucus-like stools, or tarry stools. Oral mucosa may show inflammation, ulcers, or adherent pseudomembranes, with fungi detectable in smears and cultures. Sputum becomes thick and gelatinous.
(6) Blood pressure: Gradually declines before death.
(7) Wound changes: Fungi may form brown or black plaques on wounds, appearing round or irregular. Small hemorrhagic spots or diffuse erythematous nodules may appear on normal skin, with biopsy confirming fungal presence.
3. Laboratory Tests
⑴Blood test: White blood cells are all increased, reaching up to 20,000/mm3 or more. The white blood cells show a leukemoid reaction, with metamyelocytes or myelocytes visible in the peripheral blood smear. The platelet count is normal, while the red blood cell count and hemoglobin levels are decreased.
(2) Urine culture and microscopy: For fungal examination of urine, fresh urinary catheters must be used to collect specimens, or midstream urine must be collected using aseptic techniques. Otherwise, positive results due to contamination are of little significance. Generally, urine cultures turn positive 2–3 days earlier than blood cultures.
Other body fluid cultures, such as feces, sputum, wound surfaces, and secretions, can also serve as references for diagnosing systemic fungal infections.
(3) Blood culture: Stirred pulse blood culture has a higher positive rate. A single positive blood culture combined with positive wound biopsy can serve as diagnostic evidence.
(4) Biopsy: During wound biopsy, aseptic techniques must be observed to prevent contamination. If fungal growth is detected under the eschar or in adjacent viable tissue, a diagnosis of invasive fungal infection can be made.
IV. Clinical Manifestations of Anaerobic Infections
1. Tetanus bacillus infection
Burn patients often have severely contaminated wounds with deep tissue necrosis, making them prone to tetanus. To prevent tetanus, in addition to aggressive debridement and wound management, a routine injection of 1500μ TAT is administered post-injury. For extensive burn patients, a booster dose is given one week after the injury.
If tetanus occurs, treatment involves high-dose TAT, sedatives, and antibiotics.
2. Gas gangrene
Electrical burns or other deep burns, due to fluid loss or shock and deep tissue necrosis, create an environment conducive to the growth of Clostridium, leading to gas gangrene. Clinical manifestations include heaviness in the affected area, a sensation of tight bandaging, significant limb swelling, crepitus, and the presence of gas on local X-ray. Gram-positive spore-forming bacilli may be detected in smear microscopy of secretions.
The key to preventing gas gangrene is thorough debridement. Deep necrotic tissue should be irrigated with 3% hydrogen peroxide, and prophylactic penicillin should be administered. Once gas gangrene is confirmed, immediate surgical removal of necrotic tissue is necessary, with amputation performed if required during seasonal epidemics. Systemic penicillin or erythromycin and supportive therapy should be administered.
3. Non-spore-forming anaerobic infections
Anaerobic infections primarily originate from the patient's own body, particularly the intestines. Common anaerobes isolated from infected individuals include Bacteroides fragilis, Bacteroides melaninogenicus, Fusobacterium, and Peptococcus. Anaerobic infections often coexist with aerobic infections. Diagnosis relies on the typical foul odor of secretions and positive culture results from secretions or blood.
V. Clinical Manifestations of Viral Infections
With advancements in viral detection techniques, reports of viral infections have increased. Common viral infections in burn patients include herpes simplex virus infection, which initially presents as vesicular or hemorrhagic herpes, followed by ulceration and necrosis. These lesions typically occur on deep second-degree burn wounds but may also appear on normal skin. Mild cases may resolve spontaneously, while severe cases can lead to invasive infections affecting internal organs and resulting in death. Biopsy may reveal intranuclear inclusions, and the virus can be isolated. Serological tests may detect neutralizing antibodies and complement-fixing antibodies.
Viral infections often follow systemic bacterial or fungal infections. Diagnosis is challenging, and there is no specific treatment.
1. Routes of Invasion
1. Burn Wound Route
Due to the presence of large amounts of necrotic and degenerated tissue, bacterial colonization on burn wounds is inevitable. When bacteria are confined to surface exudate or liquefied necrotic tissue, their systemic impact is minimal. However, if they invade adjacent viable tissue and reach a certain bacterial load, systemic symptoms may arise, commonly referred to as "invasive burn wound infection" or "burn wound sepsis." Debridement can reduce bacterial counts on the wound, and the topical application of sensitive antimicrobial agents can also prevent bacterial invasion and the development of invasive infections.
2. Enterogenic Infection
The bacterial species causing early sepsis sometimes differ from those found on the wound surface, often being resident gut bacteria. Therefore, the enterogenic infection route was proposed early on, and this hypothesis has recently been confirmed.
3. Suppurative Phlebitis
In patients with extensive burns, prolonged intravenous transfusion or fluid therapy occasionally leads to phlebitis. Suppurative thrombophlebitis often becomes a source of systemic infection. Due to the隐蔽 nature of the infection, bacteria continuously enter the bloodstream undetected. The importance of phlebitis as an infection source post-burn should not be overlooked. Autopsies reveal that veins with indwelling catheters often exhibit thrombosis or pus, which went unnoticed during the patient's lifetime.
4. Deep Muscle Tissue Necrosis
Necrosis of muscle tissue due to various causes can easily induce infection, sometimes even leading to life-threatening gas gangrene. Common causes of deep muscle necrosis include: ① Muscle necrosis caused by third-degree burns; ② Progressive muscle ischemia and necrosis due to circumferential eschar; ③ Deep muscle necrosis often caused by electrical burns; ④ Burns combined with crush injuries; ⑤ Muscle necrosis secondary to vascular embolism.
5. Respiratory Tract Infection
Inhalation injuries cause varying degrees of respiratory tract congestion, edema, and necrosis of the tracheal membrane, leading to respiratory tract infection and spread, which becomes a source of infection. Additionally, due to restricted chest eschar, prolonged bed rest, and pooling of sputum, respiratory tract infections are more likely, especially in pediatric and elderly patients.
6. Iatrogenic Infection
Infections caused by improper medical procedures cannot be ignored. Common examples include: ① Contaminated intravenous fluids or blood transfusions; ② Infections due to improper respiratory tract management after tracheostomy; ③ Retrograde infections caused by indwelling urinary catheters; ④ Respiratory tract infections due to aspiration from feeding or vomiting.
2. Classification of Infections
Burn infections can be classified into the following three categories based on the causative pathogens:
1. Bacterial Infections
Bacterial infections are the most common cause of burn infections. Although the incidence of Gram-positive bacterial infections has decreased with the advent of sensitive antibiotics, infections such as Staphylococcus aureus and hemolytic streptococcus still occur. Among Gram-negative bacteria, infections caused by Pseudomonas aeruginosa, Escherichia coli, Edwardsiella, Klebsiella, Proteus (including indole-negative Proteus), and Serratia are increasingly common. With advancements in anaerobic culture techniques, the detection rate of anaerobic infections has also risen in recent years, with common examples including infections caused by non-spore-forming anaerobes such as Bacteroides melaninogenicus and Peptococcus.
2. Fungal Infections
The concurrent use of multiple antibiotics in large doses or over extended periods has led to an increase in fungal infections. Common fungal pathogens include Candida, herpes simplex virus, cytomegalovirus, and varicella-zoster virus. These are often observed in superficial burn wounds in children.
Based on the site and depth of invasion, burn infections can be classified as follows:
1. Wound Contamination
Bacteria grow on the wound surface but do not invade the post-burn tissue, with no local or systemic symptoms.
2. Wound Infection
A certain amount of bacteria is present in the burn tissue, but they do not invade the surrounding normal tissue, manifesting only as local symptoms.
3. Invasive Infection
refers to systemic infection, which occurs when normal tissues reach a certain bacterial load and exhibit systemic symptoms. This includes burn wound sepsis, a concept first proposed by Teplitz. He pointed out that when the bacterial count in necrotic tissue beneath eschar exceeds 105 per gram and invades adjacent unburned tissue, it is termed burn wound sepsis.
bubble_chart Treatment Measures
1. Topical Medications for Burn Wounds
Due to vascular occlusion in deep burns, systemic antibiotics struggle to reach the affected area, making intravenous therapy alone less effective in controlling bacterial proliferation. Early topical application of bacteriostatic or bactericidal agents is a more effective measure. Although the research and use of topical medications have a long history, no entirely ideal option has yet been developed.
1. Topical Antibacterial Agents
⑴ Mafenide Acetate: In the 1960s, Moncrief first developed a 10% mafenide acetate cream for burn wounds. Clinically, a 10% aqueous solution or cold cream is applied to the wound, penetrating the eschar within 30 minutes. Within 5 hours, 80–90% of the drug leaves the carrier, losing its bacteriostatic effect after 8–10 hours, with excretion via the kidneys. Key characteristics include significant pain upon application and, in large-area use, metabolic acidosis due to carbonic anhydrase inhibition, necessitating caution for pulmonary complications. Hyperosmolarity may also cause polyuria or damage newly formed epidermal cells. Application method: Apply 10% mafenide acetate cream directly to the wound (1–2 mm thick) twice daily, removing the previous dose before reapplication. Daily use should not exceed 450 g. For severe Pseudomonas aeruginosa infections, a 5–10% aqueous solution bath may be used.
⑵ Silver Sulfadiazine (DS-Ag) and N-Sulfadiazine Compounds: Silver sulfadiazine is a weak acid with broad-spectrum inhibitory effects, generally effective against Pseudomonas aeruginosa and other common wound bacteria but less so against Proteus mirabilis. It releases silver ions and sulfadiazine upon penetrating the eschar, forming a light gray film. Most silver ions bind to bacterial DNA, inhibiting growth, with minimal systemic absorption. About 10% of sulfadiazine is absorbed, reaching blood concentrations of 1.5–4 mg% after 3–4 days of application.
Silver sulfadiazine significantly delays and reduces wound infections, proving highly effective for infection control. Despite the emergence of various topical agents, it remains one of the most effective. Side effects include sulfa crystalluria, rashes, scaly dermatitis, and leukopenia.
Among N-metal sulfonamides, silver, zinc, and cerium salts of sulfadiazine, sulfamerazine, and sulfadimidine exist. Zinc salts promote wound healing, while cerium salts exhibit better solubility and lower toxicity but higher minimum inhibitory concentrations than silver salts, confirming silver’s superior antibacterial efficacy. To combine the benefits of zinc and silver, silver-zinc cream has been developed. Due to bacterial resistance to silver sulfadiazine, alternatives like silver nicotinate, silver asparaginate, and silver salts of quinolones (e.g., nalidixic acid, pipemidic acid, norfloxacin) have been explored. Notably, pipemidic acid silver and norfloxacin silver show lower inhibitory concentrations than silver sulfadiazine, promising broader applications.
⑶ Chlorhexidine and Its Mixtures: Chlorhexidine is effective against Gram-positive cocci and Gram-negative bacilli, with good clinical efficacy and minimal irritation. In burn treatment, a 1% chlorhexidine solution is commonly used for wound cleansing or as an inner dressing.
To enhance efficacy, chlorhexidine is often combined with other topical agents, such as: - Chlorhexidine + silver nitrate - Neomycin + polymyxin B + chlorhexidine - Mafenide acetate + silver sulfadiazine + chlorhexidine.
⑷ Povidone-Iodine: A broad-spectrum antimicrobial, previously used as a disinfectant for intact skin and mucous membranes. It has strong bactericidal properties but cannot penetrate eschar. A 1% water-soluble cream is suitable for large-area burns. Side effects include hyperiodinemia (elevated T4 levels) and metabolic acidosis.
⑸ Chloroxylenol (PCMX): The use of 5% chloroxylenol (PCMX) cream is more effective against Staphylococcus aureus and can compensate for the shortcomings of silver sulfadiazine.
(6) Aminoglycoside antibiotics: 0.1% gentamicin sulfate solution and 0.5% neomycin solution can penetrate eschar for sterilization when applied topically. In severe infections, the antibiotic concentration can be increased, but attention should be paid to renal and auditory nerve damage, and the emergence of resistant strains also limits its effectiveness.
(7) Iodophor: It has significant bactericidal effects against drug-resistant Staphylococcus aureus, Pseudomonas aeruginosa, molds, etc. Iodophor is a hydrophilic drug, and its aqueous solution is convenient for clinical use without irritating the skin or mucous membranes. Generally, 0.5% iodophor is used for semi-exposure therapy, and it can also be prepared in low concentrations for debridement and disinfection. With its excellent antibacterial effects, iodophor is a good topical medication for treating second-degree burn wounds.
2. Topical antifungal medications
(1) Clotrimazole (triphenylmethylimidazole): A bacteriostatic agent that selectively binds to the lipids of the cytoplasmic membrane, thereby affecting the structure and function of fungal cells. For fungal infections in burn wounds, 3–5% clotrimazole cold cream or 1–4% clotrimazole dimethyl sulfoxide preparations are commonly used.
(2) Econazole: This is one of the imidazole derivatives. Compared to other imidazole derivatives (such as miconazole, clotrimazole, and isoconazole), it has a broad antibacterial spectrum, strong bacteriostatic activity, and high efficacy. It is effective against Candida and Aspergillus infections in burn wounds and superficial fungal infections but ineffective against deep-seated fungal infections. The topical dose includes 1% cream or 1% suspension, applied to the wound 2–3 times daily.
(3) Ketoconazole: A white or light brown, odorless, tasteless adhesive agent effective against both superficial and deep infections caused by various Candida species. Commonly used is 1% ketoconazole solution (prepared with 2% dilute hydrochloric acid) or 1% suspension applied to the wound, with efficacy superior to econazole.
(4) Other topical medications: These include nystatin aqueous suspension or decoctions of Phelloendron Bark and Vietnamese Sophora root, which are effective against Candida albicans.
II. Prevention and Treatment of Systemic Infections
1. Immunotherapy: To prevent and treat Pseudomonas aeruginosa infections, active and passive immunization should be employed. The method is as follows: For patients with extensive burns, the first dose of multivalent Pseudomonas aeruginosa vaccine (20 mg/kg) is administered intramuscularly or intradermally upon admission, followed by injections every 7 days until the wound heals. Concurrently with active immunization, administering 250 ml of immune plasma intravenously or using human serum globulin yields better efficacy.
2. Prophylactic use of antibiotics: Penicillin is administered in the first three days post-burn or before and after skin grafting to prevent hemolytic streptococcal infections.
3. Therapeutic use of antibiotics: When the pathogen is identified, antibiotics should be selected rationally based on drug sensitivity tests.
4. Active prevention and treatment of complications: Infections have a causal relationship with shock, renal failure, or stress ulcers. Proactively preventing and treating these complications can significantly reduce the incidence of infections.
5. Rational wound medication: Topical medications are crucial for controlling wound infections. Commonly used agents include silver sulfadiazine, chlorhexidine, and povidone-iodine.
6. Early eschar excision (or debridement) and skin grafting to cover wounds: In recent years, the successful experience in rescuing patients with extensive burns mainly involves early eschar excision (or debridement) and skin grafting. Necrotic tissue serves as an excellent medium for bacterial growth, and eschar excision removes the source of infection, improving the patient's immune function and controlling invasive infections. Of course, choosing the right timing for skin grafting can improve the survival rate of grafts. It is generally recommended to perform skin grafting after shock stabilizes or other complications are largely controlled to avoid surgical failure and infection spread.
7. Nutritional Support Therapy: Nutrition is a key aspect in preventing and treating invasive infections in patients. After burns, a significant amount of protein is lost through wound exudation (1–2g of protein per 1% of the affected area); the body's hypermetabolic state increases consumption; and wound repair requires substantial protein and energy supply. Therefore, burn patients need to consume high-protein, high-calorie nutrients to maintain nitrogen balance. Otherwise, malnutrition, immune dysfunction, reduced synthesis of immune molecules, physical exhaustion, and the onset of invasive infections may occur. Late stage [third stage] invasive infections are associated with insufficient protein and calorie supply.
The nutritional intake for burn patients includes oral, nasogastric, and intravenous nutrition. One or two methods should be selected based on the situation to supplement nutrients. Oral intake is the optimal route, as it aligns best with physiological requirements and facilitates the recovery of gastrointestinal function. A nutritionist should rationally adjust the intake of nutrients and fluids, including proteins, fats, carbohydrates, vitamins, electrolytes, and trace elements. Patients can take oral medications containing multivitamins, trace elements, and electrolytes, such as 12 Golden Vitamins or Centrum.
For patients with insufficient oral nutrient intake, nasogastric tube feeding can be employed. Milk, egg soup, or elemental diets can be injected into the stomach via the tube at scheduled times daily. Compared to total parenteral nutrition, gastrointestinal feeding aids in the release of digestive enzymes and endocrine substances, promotes vasodilation and increased blood flow in the gastrointestinal tract, enhances intestinal mucosal thickness, and strengthens the barrier function, reducing the risk of bacterial and toxin absorption from the intestines.
Patients with gastrointestinal dysfunction or inadequate gastrointestinal feeding may receive intravenous nutrition. Peripheral venous catheterization is generally preferred to minimize the risk of infection associated with central venous catheterization. Peripheral venous nutrition requires attention to fluid supplementation, with the general fluid requirement calculated as 1% of body surface area × 50 + physiological needs.
III. Prevention and Treatment of Systemic Fungal Infections
1. Eliminating predisposing factors and strengthening preventive measures are key, such as improving wound care, shortening treatment duration, enhancing nutritional support, preventing and managing complications, and rational use of antibiotics to avoid misuse.
2. Treating fungal sepsis in wounds: When fungi invade viable tissue beneath the eschar, or even muscles and bones, local excision can be performed, extending 3–5 cm beyond the affected margin. Amputation may be considered if the infection occurs in a limb.
3. Discontinue antibiotics, corticosteroids, and immunosuppressive drugs. For mixed infections, narrow-spectrum sensitive antibiotics and antifungal agents may be selected.
4. Systemic and topical application of antifungal drugs
(1) Nystatin: Oral administration only affects gastrointestinal fungi, is not absorbed, and is excreted in feces. Dosage: 500,000–1,000,000 units, four times daily. Trichomycin: 200,000–400,000 units daily, divided into four oral doses.
(2) Clotrimazole: Effective against Candida, Cryptococcus, Aspergillus, and Mucor. Poor oral absorption and significant gastrointestinal side effects limit oral use; it is typically formulated as a 5% clotrimazole cream for topical application.
(3) Ketoconazole: Broad-spectrum with strong antifungal activity, well-absorbed orally. Daily dose: 0.2–0.4 g, divided into two doses. Use with caution in patients with liver dysfunction.
(4) 5-Fluorocytosine (5-FC): A synthetic pyrimidine fluoride primarily effective against Candida and Cryptococcus. Dose: 50 mg/kg/day, administered orally in divided doses or intravenously. Side effects include gastrointestinal reactions and liver damage.
(5) Garlic injection: Adults receive 20–80 ml daily, administered intravenously in divided slow infusions, often combined with 5-FC. Raw garlic can also be taken orally, 2–4 g three times daily.
(6) Amphotericin B: A broad-spectrum antifungal drug with poor and unstable oral absorption, requiring intravenous administration. Side effects are severe, including shivering, high fever, nausea, vomiting, rapid breathing, tachycardia, and hypotension in severe cases, with impacts on the liver, kidneys, and hematopoietic system. Dosage should start at 1–5 mg daily and gradually increase to 1 mg/kg body weight. To mitigate side effects, 5 mg dexamethasone or 25 mg hydrocortisone may be added to the infusion.
5. Systemic Nutritional Support Therapy Enhance nutrition to improve patient resistance, including transfusions of fresh blood. Actively prevent and manage complications, and provide symptomatic treatment as needed.
IV. Treatment of Anaerobic Infections
The treatment of anaerobic infections includes debridement, excision of necrotic tissue, and irrigation with hydrogen peroxide solution; oral or intravenous administration of metronidazole, with a usual dose of 1.5g divided into three doses; appropriate use of antibiotics and systemic supportive therapy.
V. Treatment of Viral Infection
Options include idoxuridine, interferon, or vidarabine.
When local or systemic infections occur, treatment is generally challenging, making prevention even more crucial. Reasonable preventive measures include the following aspects:
1. Debridement, aseptic techniques, and disinfection isolation measures
Although the pathogenic bacteria causing systemic infections do not entirely originate from the wound, the bacteria on the wound are related to infection. Therefore, measures to reduce bacterial load are necessary, commonly including debridement and adherence to aseptic principles. Early upon admission, without interfering with anti-shock treatment, necessary debridement should be performed to remove contaminants and necrotic skin from the wound. The wound should be rinsed with 1% benzalkonium bromide or 0.5% chlorhexidine, followed by a final rinse with 20°C–35°C saline to reduce bacterial count. Aseptic techniques and disinfection must not be overlooked in infection prevention. While placing patients in sterile laminar flow rooms is impractical and generally unnecessary, placing them in wards with disinfection and isolation conditions is essential. All potential cross-infection factors (e.g., ward utensils, items carried by medical staff) should be avoided. Aseptic principles are key to preventing iatrogenic infections.
2. Nutrition
Patients with extensive burns often suffer from malnutrition, compromised immune function, and infection, which are interrelated. Studies show that in severely burned patients with adequate caloric intake, the high-protein treatment group exhibited higher调理指数, serum total protein, transferrin, C3, and IgG levels compared to the control group. Enhanced nutrition and maintaining positive nitrogen balance significantly reduce the incidence and mortality of invasive infections.
3. Immunotherapy
Immunotherapy for Pseudomonas aeruginosa infection has been extensively studied in burn infections. Immunotherapy can be active or passive. Currently, active immunotherapy in clinical practice mainly involves Pseudomonas aeruginosa vaccines, while passive immunotherapy uses Pseudomonas aeruginosa immunoglobulins or hyperimmune serum (or plasma).
(1) Active immunization: Pseudomonas aeruginosa vaccines can be classified into lipopolysaccharide antigens and internal toxin protein antigens based on their antigenic components. The 7-valent and 16-valent Pseudomonas aeruginosa vaccines (PEV-01) belong to the lipopolysaccharide antigen category, while the Pseudomonas aeruginosa vaccine (EP) developed in China is an internal toxin antigen. Pseudomonas aeruginosa vaccines exhibit strong immunogenicity. Burn patients vaccinated with PEV-01 on admission day, day 7, and day 14 showed an increase in antibody titers against 16 components from 1/4–1/32 to an average of 1/64–1/256, lasting for 4 weeks. Agglutinins and hemagglutinins appearing in the serum provided protection against lethal Pseudomonas aeruginosa attacks, whereas unvaccinated patients rarely developed protective antibodies.
Vaccinated patients had lower plasma internal toxin levels, while unvaccinated patients infected with Pseudomonas aeruginosa exhibited high internal toxin titers. Internal toxin depletes the C3 component of complement, impairs nonspecific immune mechanisms, and increases susceptibility to infection. Vaccination with Pseudomonas aeruginosa vaccines reduces internal toxin levels in the blood, indirectly enhancing resistance to other bacterial infections.
After vaccination, neutrophil phagocytic activity increases, enhancing their ability to phagocytose latex particles, Enterobacter aerogenes, and Proteus mirabilis. In the presence of specific antibodies, neutrophils' ability to kill Pseudomonas aeruginosa is significantly enhanced.
The appropriate dose of the vaccine can produce the maximum antibody response level. The generally recommended dose is 25 μg/kg/dose for the 7-valent vaccine, one adult dose (RHD) per dose for PEV-01, and 0.5 RHD for children under 12 years old. Intradermal and intramuscular combined or subcutaneous injection can be used. It generally takes 5 to 7 days to produce an adequate antibody level. Therefore, vaccination should be administered as early as possible. The first vaccination should be administered within 6 days, as the patient's response to the vaccine becomes significantly poorer after 6 days. Active immunity usually takes 5 to 7 days for the IgG antibody level in the serum to reach a protective level, and the duration is relatively short. Continuous immunization is required, with vaccinations administered every 3 to 7 days until the threat of Pseudomonas aeruginosa infection disappears.
After vaccination, local redness and swelling may occur, and body temperature may rise. If the reaction is severe, the vaccine dose should be stopped or reduced.
(2) Passive immunization: Passive immunization involves administering Pseudomonas aeruginosa immunoglobulin or hyperimmune serum (or plasma) to the patient. The preparation of high-titer immune plasma involves vaccinating volunteers and separating the plasma when the antibody titer reaches 1:512, followed by freeze-drying for storage. The adult dosage is 250 ml, and the pediatric dosage is 125 ml, typically administered within one week. Pseudomonas aeruginosa immunoglobulin is administered starting on the day of admission for three consecutive days, with adults receiving 0.5 ml per dose and children receiving 0.2 ml.
Passive immunization compensates for the drawback of the longer time required for active immunity to develop. For immunocompromised individuals, it is generally recommended to administer multivalent Pseudomonas aeruginosa vaccine and high-titer Pseudomonas aeruginosa immunoglobulin or immune plasma immediately after burns.
4. Prophylactic Use of Antibiotics
The principles of prophylactic antibiotic use are early, combined, sufficient, and sensitive. Although some scholars do not advocate the prophylactic use of antibiotics, we believe that rational antibiotic use can reduce the incidence of invasive infections. "Early" refers to administering antibiotics to prevent infection in patients with extensive and deep burns or severe contamination immediately upon admission. "Combined" refers to the simultaneous use of two types of antibiotics to inhibit bacterial proliferation on the wound surface and under the eschar, typically using cephalosporins plus amikacin.
5. Active Wound Treatment
The necrotic tissue of burn wounds provides an excellent medium for bacterial growth, and the wound is the primary source of infection. Moreover, the impairment of immune function after burns mostly returns to normal as the wound heals or is covered by eschar excision and skin grafting. Therefore, active wound management (including eschar excision and skin grafting, as well as topical medications to promote wound healing) is key to preventing infection.
