Opportunistic infections in severely burned patients

Opportunistic Infections in Severely Burned Patients

BASIL A. PRUI?T, JR., M.D., F.A.C.S.,

COLONEL, MC.

ALBERT T. McMANUS, Ph.D.

Fort Sam Houston, Texas

From the U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas. The opinions or as- sertioqs contained herein are the private views of the authors and are not to be construed as official or as reflecting ths views of the Department of the Army w the Department of Defense. Requests for reprints should be addressed to Dr. Basil A. Pruitt, Jr., Colonel, MC., U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas 78234.

The risk of infection In burn patients, which is proportional to the extent of burn, reflects the combined effect of impairment of all aspects of the host defense system and microbial factors. The microbial flora colonizing the burn wound changes wlth time followlng injury and provides the organisms causing infections In bum patients. The temporal pattern of the predominant gram-negative organisms causing infecttons In a burn unit resembles that of a successlon of mini-epidemics necessitating an active program of microbial sur- velllance to gulde treatment of infections. Topical chemotherapy has significantly reduced the occurrence of Invasive burn wound infections, but microbial control is imperfect and the burn wound, as well as the patient as a whole, must be closely monitored (using wound biopsies as indicated) to diagnose and treat infection in a timely manner. The treatment of burn wound infections is guided by extent and depth of microbiat Invasion, density of microorganisms, and systemic changes. As a manifestation of immunologic lmpalr- ment, infection in sites other than the burn wound remains the most frequent cause of death in burn patients. The use of broad spectrum serologic agents to enhance immuno-competence in extensively burned patients may reduce the occurrence of life threatening opportunistic infections.

Infection is the most frequent cause of morbidity and mortality in the extensively burned patient [ 11. The susceptibility to infection increases in a sigmoid dose-response fashion as the extent of burn increases. The severity and duration of altered organ function are similarly related to burn size, and the dysfunction of the immune system predisposes the burn patient to septic complications [ 21. The occurrence of infection reflects the combined effect of both the burn-related impairment of host resistance and microbial factors with microorganism- invasive capacity of particular importance in Infections of the burn wound per se.

The burn wound is the site of microbial colonization which, if un- controlled, may progress to invasion with systemic dissemination. Both local wound factors and microbial factors influence the rate of proliferation, and the balance between host defense capacity and the invasive capabilities of the microbial population of the wound deter- mines whether invasive infection will occur. The denatured protein of the burn eschar provides a rich diet for microorganisms, and the avascularity of the burned tissue places the microorganisms within such beyond the reach of both host defense mechanisms and systemically administered antibiotics of low diffusibility [ 31.

146 March 30, 1984 The American Journal of Medicine

WIG AND THE COMPROMISED HOST SYMPOSIUM--PRUITT and MCMANUS

The microorganisms present on the wounds of hos-

pital-treated burn patients change with time postburn,

and the chronologic pattern of predominant organisms

recapitulates the chronologic history of burn wound infections. Gram-positive organisms are initially prev-

alent but are gradually superseded by the gram-negative

opportunists that appear to have greater propensity to

invade [4]. Local factors such as wound maceration,

acidosis, and lack of competitive bacterial pressure as

a result of either antibiotic therapy or topical antimi-

crobial therapy increase the risk of proliferation and

invasion of colonizing fungi. The results of wound cul-

tures are thus influenced by the time following injury at

which they are obtained, and the results should be in-

terpreted with regard to postinjury time of culturing.

A variety of what appear to be organism specific

factors influence the microbial dynamics in the non-

viable burned tissue. Endotoxin, as well as a number of

exotoxins and enzymes with tissue destructive potential,

produced in variable amount by different microorgan-

isms may exert both local effects and also influence the

activity of the immune system and the function of other

organ systems. On the basis of recent studies by

McManus et al [!?I], motility appears to be the most

important microbial factor in terms of penetration of the

burn wound and invasion of underlying viable tissue.

Using a murine model of burn injury, those investigators

found that motile mutants of a Pseudomonas strain

produced a significantly higher incidence of invasive

burn wound infection than a nonmotile mutant of the

same parent strain.

Following colonization, the bacteria on the surface

of the wound penetrate the eschar to variable extent,

depending upon their invasive capacity. Bacterial mi-

gration commonly occurs along hair follicles and sweat

glands. Organisms that penetrate the entire thickness

of the eschar further proliferate in the subeschar

space-the interface between viable and nonviable

tissue 161. The proteases produced by bacteria and

released from white blood cells lyse the denatured

collagen of the eschar and thus permit spontaneous

separation or sloughing of the eschar that will occur

over a three-to four-week period. If host defense ca-

pacity is inadequate, the proliferating microorganisms

invade the underlying viable tissue and migrate through

the subcutaneous tissue. Subsequent to invasion, the

pathogenesis of the septic process appears to be or-

ganism specific [7]. Staphylococcal burn wound in-

fection characteristically takes the form of focal or even

multifocal abscess formation. Individual lesions may

extend to the level of the investing fascia; most com-

monly, however, they involve only the superficial sub-

cutaneous tissue. Infections caused by gram-negative

organisms are, as a rule, less well localized than staphylococcal infections. If untreated, any organism

may migrate through the subcutaneous tissue to involve

and even penetrate the investing fascia. Pseudomonas

organisms commonly proliferate around and invade

small vessels and lymphatics from which organisms

may disseminate to produce foci of infection in unin-

jured subcutaneous tissue (ecthyma gangrenosa) and

even to produce septic foci in such remote organs as

the lungs [ 81.

Candidal infections resemble, in their behavior, those

caused by staphylococci, whereas infections caused

by the true fungi have a greater tendency to spread

throughout the subcutaneous tissue 191. The phycom-

ycetes, which readily invade vessels, cause infections

characterized by centrifugally advancing ischemic

necrosis and rapid spread along fascial planes [lo]. Viral infections, most often caused by herpes simplex

virus in the burn patient, typically occur in healing or

recently healed second-degree burns most often in the

nasolabial area, but in the immunocompromised burn

patient these viruses may also involve the upper gas-

trointestinal tract, the pulmonary tree, and even spread

systemically to involve a variety of organs [ 111.

In addition to disrupting the mechanical barrier of the

skin, an extensive burn injury affects the function of all

other components of the immune system. Circulating

levels of the immunoglobulins are altered, and the

functional activity of the complement system is impaired

[ 12,131. Circulatory levels and/or the function of all the

cellular elements of the immune system are also al-

tered. The characteristic early postburn leukopenia is

followed by a leukocytosis with secondary leukopenia,

a common accompaniment of sepsis [ 141. Lymphocyte

subpopulations are altered with the emergence of

suppressor cells occurring five to seven days postburn

[ 15,161. All aspects of granulocyte function are im-

paired with suppression of chemotaxis as well as

phagocytosis and bactericidal activity [ 17-l 91. The

function of the reticuloendothelial system is also in-

fluenced in a variable manner, undergoing changes

related to extent of injury, time postinjury, and the

presence of sepsis [20,21].

The organisms that predominate as causative agents

of infection in any burn treatment facility change across

time and can be viewed as a sequence of mini-epi-

demics. Individual organisms are brought into the burn

ward on the wounds of individual patients. A given or-

ganism persists in the resident flora of the burn treat-

ment facility for a variable period of time, only to be

replaced by a newly arriving organism. The variations in predominant gram-negative organisms on the burn

wounds of patients treated at our burn center throughout

the past 14 years are depicted in Table I in which the

changes in annual frequency of recovery of Providencia species well illustrate the magnitude of year to year

variability. Although members of the genus Staphylo-

March 30, 1994 The American Journal of Medicine 147

WIG AND THE COMPROMISED HOST SYMPOSIUM-PRUITT and MCMANUS

TABLE I Gram-Negative Genera Recovered from Burn Wound Cultures

Annual Percentage of Total Gram-Negative Isolates

Organism 1969 1970 1971 1972 1973 1974 1975 1976 1977 1970 1979 1960 1961 1962

Pseudomonas 20.3 25.6 22.9 19.2 20.4 28.0 44.8 43.3 46.7 45.8 58.3 40.0 46.8 44.1 species

Providencia 19.6 30.4 22.7 30.4 25.3 8.8 2.8 2.8 0.0 0.0 0.0 1.6 31.2 37.9 species

Escherichia coli 22.6 7.2 15.0 13.8 17.0 14.7 8.4 8.2 8.6 17.7 9.3 6.0 6.5 3.6

Proteus species 18.5 14.6 16.3 13.0 4.9 10.6 6.8 6.6 14.7 13.4 7.9 6.2 3.7 5.3

Klebsiella 17.0 16.1 15.9 17.1 24.4 23.5 15.8 10.4 11.2 9.6 6.2 3.9 species 19.0 22.2

Enterobacter (grouped) 6.1 7.5 16.5 20.8 12.8 12.0 10.6 11.3 6.7 14.6 3.1 0.7 species

Other gram- 3.6 3.6 1.4 6.6 22.0 2.5 4.0 negative organisms

coccus appear to persist at a more or less constant level in the burn wound flora, individual strains of staphylococci as well as the members of the gram-negative flora show pronounced temporal variations in prevalence.

The proliferation of bacteria in the burn wound can be limited by the use of topical antimicrobial agents. There are three such topical agents of documented effectiveness, that is, mafenide acetate burn cream, silver sulfadiazine burn cream, and 0.5 percent silver nitrate soaks. The topical antimicrobial agents do not sterilize the burn wound but maintain the microbial density below lo5 organisms per gram of tissue, a level against which even the immunocompromised host can defend [22]. The burns of any given patient may thus escape from microbial control and become infected; this complication most often occurs in patients with burns of more than 30 percent of the total body surface and in pediatric age group burn patients. The systemic signs of invasive burn wound infection include hypo- thermia, ileus, leukopenia, mental obtundation, glucose intolerance, and variable degrees of failure of a variable number of organs. Similar changes may occur as part

TABLE II Local Signs of Bacterial Burn Wound Infection

1. 2.

3. 4. 5.

6. 7. 8.

Focal area(s) of dark brown or black discoloration Conversion of partial-thickness cutaneous injury to full-

thickness necrosis. Hemorrhagic discoloration of subcutaneous tissue Accelerated sloughing of burned tissue Edema and/or violaceous discoloration of skin at wound

margin Appearance of ecthyma gangrenosa Presence of pyocyanin in subeschar tissue Focal subeschar fluctuance and variable-sized abscess

formation

of the systemic response to the burn injury per se, making the diagnosis of infection difficult in patients with such injuries. Systemic signs of infection must, therefore, be interpreted in light of metabolically related hyperthermia, altered neurologic function, injury- and therapy-related alterations in white blood cells, and postresuscitation edema that may occur in the burn patient in the absence of sepsis.

Because of the unreliability of systemic signs of infection in the burn patient, greater emphasis must therefore be placed on early identification of local signs of burn wound infection. The entirety of the burn wound must be examined every day (preferably at the time of the daily wound cleansing) to identify changes in the wound indicative of infection as listed in Table II. If any of those changes are present (Figure l), the microbial status of the wound should be assessed and the diagnosis of infection confirmed or discounted.

Although surface cultures performed in a standard- ized manner can provide information regarding the microorganisms present on the surface of a wound, such culture techniques are of limited value in deter- mining the microbial status of tissues below the surface. Falsely low quantitative surface cultures can result from culture of a nonrepresentative desiccated area of the wound, culture of residual topical agent, and desiccation of the swab due to delayed transport or plating. Addi- tionally, the subeschar space, where microorganisms characteristically proliferate prior to invasion of viable tissue, is inaccessible to surface cultures. Conversely, falsely high quantitative surface cultures can result from culture of pooled secretions or exudates, culture of sloughing eschar, and prolonged incubation of the swab in transport media between the time of culture and the time of culture plating. Monitoring of wound surfaces is perhaps most reliably performed by contact plate cultures which, by use of selective media, provide not



Figure 1. Invasive wound infection developed on the 13th postburn day in the burns of the leg of this 72-year-old man with a 68.5 percent total body surface bum. Note the multiple irregular black lesions slightly-raised above the wound surface on the media/ aspect of the knee as well as the edema and slight discoloration of the unburned skin at the posterior margin of the wound. Pseudomonas burn wound infection grade V/b was confirmed by biopsy of one of the focal lesions.

only quantitative information but also qualitative information including identification of the predominant organism. The limitations of surface cultures make biopsy sampling the best available means of monitoring the microbial status of a burn wound and diagnosing the presence of infection in such wounds [23].

Clinical findings indicative of burn wound infection should be confirmed by obtaining a burn wound biopsy specimen from that area or those areas of the wound in which the wound changes characteristic of infection are most pronounced. Using a scalpel, a 500 mg lenti- cular tissue sample, including unburned underlying tissue, is excised from the area of the wound suspected of harboring infection. If the patient’s general status necessitates, a local anesthetic can be used, but the anesthetic agent should be injected at the periphery of the biopsy site and the infused volume kept to a mini- mum to avoid morphologic distortion of the specimen. The specimen is bisected and one-half is sent unfixed for quantitative cultures. As in the case of quantitative surface swab cultures, a report of iOr’ organisms per gram of tissue is compatible with, but not diagnostic of, burn would infection [24]. The reliability of quantitative burn wound biopsy cultures has also been questioned by Woolfrey et al [25] who have reported that in such cultures there is a 25 percent chance of missing microorganisms present in a burn wound and only a 38 percent chance of paired quantitative results agreeing within the same Loglo. Culture results for nonbacterial microorganisms (yeast and fungi) are even more variable with overall positive recovery in only 40 percent of specimens ranging from a 90 percent recovery rate

for yeasts to a meager recovery rate for true fungi [ 71. The positive yield of tissues cultured for fungi is en- hanced by the use of tissue slivers rather than tissue homogenates.

The other half of the biopsy specimen can be pro- cessed either by rapid, nonfrozen section technique within a four-hour period, or a newly described frozen section technique that reduces slide preparation time by two and a half hours [ 261. Bacteria in the tissue are best identified using either Gram stain or hematoxylin and eosin stain whereas periodic acid-Schiff or silver methenamine stains are best for identification of fungi.

The pathologist should examine the tissue slides to identify the histologic signs of burn wound infection and invasion listed in Table III. The identification of microorganisms in unburned or uninjured tissue confirms the diagnosis of wound infection. The pathologist should also look carefully for microbial invasion of the micro- vasculature of the biopsy specimen that is associated with hematogenous dissemination of the infecting

TABLE III Histologic Signs of Burn Wound Infection

1. Presence of microorganisms in unburned subseschar tissue 2. Hemorrhage in unburned tissue 4. Exaggerated inflammatory response in unburned tissue 5. Dense microbial growth at interface of nonviable and viable

tissue, that is, in subeschar space 6. Perivascular, perineural. and perilymphatic proliferation of

organisms



microorganisms to remote tissues and serves as an indication for systemic antimicrobial therapy (Figure

2). Familiarity with the limitations of burn wound biopsy

assists one in interpreting the histologic findings. Since burn wound infections commonly begin as focal pro- cesses, biopsy of a noninfected area can result in an accurate but misleading diagnosis. Conversely, a biopsy specimen that fails to include unburned tissue may be misread as a burn wound infection on the basis of microorganisms present in the invariably colonized eschar. Moreover, errors of histologic interpretation may result in either falsely positive or falsely negative reports. The biopsy report must, therefore, be interpreted in light of both the appearance of the wound and the patient’s general condition. In a patient who is oth- erwise pursuing an uneventful course, a positive biopsy reading should be confirmed by a repeat biopsy. On the

TABLE IV Histologic Grading of Burn Wound Infection

Grade I Surface contamination by low numbers of organisms

Grade II Dense microbial proliferation on surface of wound Grade III Variable partial penetration of eschar Grade IV Microbial penetration of full-thickness of eschar Grade V Proliferation of microorganisms in subeschar space,

that is, nonviable/viable tissue interface Grade VI Microbial invasion of unburned subeschar tissue

a. Focal microinvasion (early stage) b. Deep extension into viable tissue (advanced

stages) c. Microvascular or lymphatic invasion

Figure 2. Photomicrograph of biopsy sample taken from site of burn wound infection. Note nonviable burned tissue in upper one-half of photo. The presence of inflammatory cells in the v&b/e tissue, the many gram-negative bacilli evident at periphery of fat cell near center of field at 2 o’clock, and the vasculitic lesion (dense concentration of bacilli surrounding vessel at 5 o’clock) are all characteristic of invasive Pseudomonas burn wound infection.

other hand, in a patient with other signs of sepsis, a negative biopsy report should prompt repeat biopsy from the same area or another area showing signs indicative of wound infection.

The histologic findings in a burn wound biopsy specimen must be related to the previously described pathogenesis of burn wound infection using a grading schema based upon both microbial density and depth of microbial penetration (Table IV). In patients with bum wounds that show clinical changes characteristic of infection, serial burn wound biopsies should be carried out. A rapid increase in the numerical grading of specimens prepared from serial biopsy samples should prompt alteration of wound care to arrest microbial proliferation and penetration, that is, a change of topical agent to use mafenide acetate burn cream which con- tains a diffusible antimicrobial. Confirmation of microbial invasion, by identification of the presence of microorganisms in unburned tissue (grade VI), necessitates both local and systemic intervention.

Focal and even multifocal burn wound infections that involve in the aggregate less than 2 percent of the total body surface should be treated by subeschar infusion of an antibiotic-containing solution. Studies showing that the effectiveness of the antibiotic used for subeschar infusion is related to its ability to diffuse into tissues speak for the use of a semisynthetic penicillin for such infusions [27]. Ten grams of the antibiotic are sus- pended in 150 ml of saline solution and the solution is injected into the subcutaneous tissues in each area of infection using a #20 spinal needle to minimize the number of injection sites. The injection is performed twice a day until the septic process is arrested. With


WIG AND THE COMPROMISED HOST SYMPOSICIM--PRUITT and MCMANUS

such treatment, the infected tissue commonly desic-

cates at which time it can be readily removed from the

surrounding and underlying uninvolved tissue.

Excision of infected burn tissue, using a scalpel, is

indicated if the infection, when diagnosed, involves

more than 2 percent of the total body surface, if existing

lesions extend despite subeschar injections of antibi-

otics, if new foci of infection appear, if there is dis-

semination of the infection to unburned tissue or remote

organs, or if there is persistent systemic sepsis. In those

patients in whom extensive or generalized burn wound

infection is present at the time of diagnosis, two sub-

eschar injections of antibiotic solution should be carried

out six hours apart immediately prior to excision.

In addition to subeschar injection of antibiotic-con-

taining solution, mafenide acetate burn cream, in which

the antimicrobial component is diffusable, should be

applied as the topical agent for patients with infected

burn wounds. If systemic sepsis is present or if there

is evidence of microvascular invasion on histologic

examination of a biopsy specimen, a specific antibiotic

should be administered systemically. General supportive

measures should also be employed to correct cardio-

vascular, pulmonary, or metabolic abnormalities.

The salvage of patients with extensive burn wound

infection is discouragingly small, but if the process is

identified in its early stages when it is localized and

before hematogeneous dissemination has occurred,

subeschar infusion therapy has been an effective ad-

junctive treatment [ 281. During the years 1980 to 1981,

454 burn patients were treated at this Institute; in 19 of

these with an average extent of burn of 63 percent of

the total body surface, invasive burn wound infection

developed. In nine of these 19 patients, subeschar

treatment was ineffective and the patients died with burn

wound infection. Subeschar antibiotic infusion therapy

was associated with clearing of the wound infection in

the remaining 10 patients of whom five survived and five

subsequently died of other causes. The infecting

microorganism was Pseudomonas aeruginosa in all of

the survivors. The importance of the early diagnosis and

treatment of burn wound infection is indicated by the

fact that in none of the survivors was a positive blood

culture recovered. In all of the survivors, subeschar

treatment was followed at a variable interval by excision

of the infected tissue; the subeschar antibiotic infusion

treatment of burn wound infection is best considered

an adjunctive measure.

Following excision of an infected burn wound, wound

care is dictated by the status of the tissue in the excised

wound. If the adequacy of excision is uncertain, the

wound should be covered with dressings soaked with

an antimicrobial solution, reexamined in 24 hours, and

further excision carried out as necessary. If the ability

of the wound bed to accept autograft skin is question-

able, a biologic dressing should be applied and grafting

delayed until the wound appears to be ready for grafting.

If the excision is deemed to be complete and wound bed

viability certain, the wound should be definitively closed

by autografting.

The wounds of those patients in whom infection does

not develop should be cleansed daily at which time the

wound should be thoroughly examined and debrided of

loose eschar following which the first of the two daily

applications of topical agent is made. In order to avoid

the consequences of iodine absorption (acidosis and

thyroid suppression) [ 29,301 in patients with extensive

burns, a noniodine-containing surgical detergent should

be used for wound cleansing. When sufficient eschar

has been removed to permit grafting, split-thickness

cutaneous autografts are used to close the wound.

Early postinjury burn wound excision is an alternate

method of wound care. Excision not only removes the

nonviable burned tissue, which is subject to infection,

but also by effecting earlier closure of the burn wounds

reduces the duration of organ system dysfunction and

systemic stress. Excision of the burn wound is best used

in the treatment of burns of limited extent, that is, 20

percent or less of the total body surface; there is little

evidence of excision exerting a beneficial effect on

survival of patients with burns of more than 20 percent

of the total body surface. In a recently reported pro-

spective study, mortality in patients with burns of be-

tween 20 and 40 percent of the total body surface was

unaffected by early excision [ 3 11. The current techniques of wound care employing

topical chemotherapy have significantly reduced the

occurrence of burn wound infections, particularly those

caused by Pseudomonas aeruginosa, and has been

associated with reduction in the mortality of patients

with burns of up to 60 percent of the total body surface

[32,33]. The decrease in burn wound infections by

microorganisms has been accompanied by an increase

in burn wound infections caused by yeasts, fungi, and

viruses, but the increase of the latter has been far

overshadowed by the decrease of the former. Infections

in sites other than the burn wound account for the un-

changed mortality of extensively burned patients and

are the most frequent cause of morbidity and mortality

in all burn patients [ 11. The reduction of burn wound

infections has been associated with a change in the

predominant type of pneumonia occurring in burn pa-

tients, that is, a significant reduction in hematogeneous

pneumonia and a relative increase in airborne or bronchopneumonia [34]. The bacteria causing the in-

fections that occur in burn patients reflect the flora of

the burn wound. As in the case of wound surface cul-

tures, the frequency of recovery of individual organisms

from blood cultures and from cultures of the respiratory

tract of burn patients, varies across time and generally



TABLE V Gram-Negative Genera Recovered from Blood Cultures

Organism 1969 1970 1971 1972

Pseudomonas species

Providencia species

Escherichia coli Proteus species Klebsiella

species Enterobacter

species Othergram-

30.8 16.2 29.4 17.1 18.9 17.8 28.5 26.2 37.3 31.9 72.4 47.9 46.4 33.0

26.1 50.8 45.9 47.1 49.7 8.2 0.8 0.5 0.0 0.0 0.0 2.0 31.9 39.6

9.2 9.8 6.4 5.7 15.4 3.4 2.7 12.2

11.9 14.1 18.5 9.8 (grouped) 3.7 3.8

.

Annual Percentage of Total Gram-Negative Isolates 1973 1974 1975 1976 1977 1976 1979 1960 1961 1962

6.2 8.6 2.3 2.0 6.5 25.9 6.3 8.3 4.2 1.9 5.0 6.3 2.3 2.0 6.3 12.9 5.2 8.3 1.0 3.8 10.1 23.5 50.6 46.6 35.0 12.9 6.3 6.3 10.3 18.9

10.1 35.6 15.5 15.3 8.9 10.4 2.5 18.8 1.0 0.0

. . 7.4 6.0 6.0 6.8 8.4 5.2 2.8 negative organisms

parallels that of burn wound cultures (Tables V and VI). The treatment of septicemia and pneumonia in burn patients is the same as for other patients and includes the systemic administration of antibiotics. Since the antibiotic sensitivity of an institution’s resident flora may change across time, the initial antibiotic treatment of an infection is best guided by the results of the institution’s sensitivity testing surveillance program.

The temporal variation in microorganism antibiotic sensitivity and the previously cited burn-related impairment of all components of the immune system limit the effectiveness of antibiotic therapy of infections in burn patients. Similarly, the temporal variation in prevalence of microorganisms causing infections in burn patients at individual burn treatment facilities ex- plains the limited effectiveness of organism-specific immunotherapy and speaks for use of broad-spectrum serologic therapy or prophylaxis. Recognition of these

limitations has led to renewed interest in the use of broad-spectrum nonspecific serologic preparations (for example, gamma globulin [35] and J-5 antiserum [36]) and nonspecific immunomodulators (for example, C. parvum [37] and muramyl dipeptide [38]) for treatment and prophylaxis of infection in burned and other im- munosuppressed patients.

Although early reports on the use of gamma globulin to reduce sepsis in burn patients were enthusiastic 139,401, Stone et al [41] reported that administration of 0.4 ml of gamma globulin per kilogram body weight every third day did not significantly affect the bacteri- ology of wound, blood, or urine, the incidence of sepsis, or the mortality of burn patients. This reported lack of effectiveness can be attributed to the combined effect of the low dosage employed, intravascular micro- aggregation of the globulin preparation used, and the shortened distribution phase half-life of gamma globulin in the burn patient, as documented elsewhere in this

TABLE VI Gram-Negative Genera Recovered from Respiratory Tract Cultures

Organism 1969 1970 1971 1972 Annual Percentage of Total Gram-Negative Isolates

1973 1974 1975 1976 1977 1976 1979 1960 1961 1962

Pseudomonas species

Providencia species

Escherichia coli Proteus species Klebsiella

species Enterobacter

species Other gram-

negative organisms

24.9 25.0 21.7 22.2 18.4 31.7 31.0 44.8 43.9 41.5 34.4 33.3 40.5 25.9

20.0 30.7 21.5 31.6 20.9 4.2 2.9 0.1 0.0 0.0 2.9 17.2 20.6 4.7

10.9 9.7 13.7 8.2 19.5 12.3 10.8 6.4 12.6 5.0 12.1 6.7 3.0 18.4 16.4 7.5 3.4 6.7 4.7 7.6 4.1 13.8 20.5 5.9 4.2 4.3 5.0 8.2

16.1 16.1 21.3 27.3 38.3 24.6 13.3 23.3 21.2 17.9 16.3 13.0 25.5 19.2

(grouped) 8.9 7.3 9.9 10.2 4.8 4.4 6.8 12.5 9.4 8.7 2.6 17.5

2.3 8.0 14.7 8.0 5.4 6.6 8.2 6.0 2.9 11.8 15.8 12.0 11.9 12.5


WIG AND THE COMPROMISED HOST SYMPOSIUM --PHUITT and MCMANUS

symposium issue [42], all of which would limit the ef- material can restore circulating gamma globulin levels fect of such infusions on circulating gamma globulin to normal, even in patients with extensive burns [42]. levels. The breadth of antimicrobial activity of gamma Further studies are required to document that admin- globulin makes it an attractive candidate for serologic istration of sufficient quantities of gamma globulin at treatment and prophylaxis in burn patients and other sufficiently frequent intervals to maintain the circulating critically ill patients with compromised immune ca- concentration of gamma globulin at normal levels will pacity. Current techniques of preparation produce a reduce mortality by providing protection for immuno- gamma globulin that is not subject to aggregate for- suppressed burn patients who are susceptible to life- mation when injected intravenously [35]. Recent threatening infections that can be caused by literally any studies at this Institute have shown that infusions of this opportunistic bacterial or nonbacterial organism.

1.

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10.

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17.

18. Grogan JB: Altered neutrophil phagocytic function in burn

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Questions and answers following this presentation appear on page 227,


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Opportunistic infections in severely burned patients