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Vaccination for pseudomonas aeruginosa
Vaccination for Pseudomonas Aeruginosa J. WESLEY ALEXANDER, MD, Cincinnati, Ohio MYRON W. FISHER,PhD, Detroit, Michigan
Primary infections caused by Pseudomonas aeruginosa occur with extrcme rarity in the absence of pre-existing disease. However, wtien immunologic defense mcchanisms become depressed in association wi,:h a wide wtriety of human diseases, Pseudomonas is ,i r.athogen of considerable importance, capable of invasive and lethal infection. Life threatening Pseudomonas sepsis is frequently .encountered by the surgeon in patients with extensive thermal injury, prolonged assisted ventilation, immunosuppressive therapy, chemotherapy for malignant lesions, extensive operations, multiple system trauma, antibiotic therapy, certain genitourinary conditions, and other diseases. Several antibiotics have recently been found to be effective in killing Pseudomoans or inhibiting its growth, but antibiotic therapy in clinical cases has often been ineffective, and better means for the prevention or therapy of these serious infections is greatly needed. As a response to this need, a vaccine was developed by Parke-Davts and Co, which consists of a mixture of Purified antigens from seven different immunotypes of Ps aeruginosa. Based upon extensive laboratory investigations, this vaccine was first administered in 1968 to patients with extensive thermal injuries at the Cincinnati General Hospital and the Cincinnati Shriners Burns Institute. Studies in these patients have been designed to evaluate the immunologic response to vaccination and to study the basic mechanisms for immunologic defense against this organism. A gratifying product of this study has been a marked decrease in septic deaths caused by Pseudomonas. Only three of the last ninety-six consecutively immunized patients with burn injuries of greater than 20 per cent who lived for at least five days after admission have died from Pseudomonas sepsis. In contrast, 2 2 (18 per cent) of 128 similar but nonvaccinated patients admitted immediately before the study began died as a result of Pseudomonas infection. "I he incidence of other infections has remained unchanged. Coopera-
512
tive investigations in five other major burn centers are currently being conducted on a double-blind basis to evaluate the vaccine. The preliminary results are most encouraging and support our initial observations of efficacy. Of the various routes of immunization, early test results indicate that the intradermal route induces the highest levels of circulating antibody, the intramuscular route provides slightly less vigorous immunization, and the subcutaneous route induces the poorest protection. Unlike most vaccines, the range between the uniformly effective dosage and the dosage associated with unwanted reactivity (local tenderness and/or fever) is not great, and the vaccine is best administered in a close according to body weight. Since it is administered as a therapeutic adjunct, intensive early immunization is necessary: I n the burn patient ithas been found necessary to continue immunization at weekly intervals to maintain high titers of antibody, but normal human vclunteers have-maintained high titers for long periods after the last injection of antigen. P.csponse to the vaccine has been less vigorous after the sixth postburn day when the patient may have a generalized decrease in immunologic responsiveness. Use of the vaccine in the burned patient is somewhat unique since it is given to seriously ill patients to provide protection in an acute situation whereas most vaccines are given to prevent diseases at a time remote to administration of the immunogen. In man, effective antibody responses are seen on the fifth or sixth day after initial immunization. ContraD' to popular belief, lgG antibody al~pears t o be more important than lgM antibody in resistance to infection from Ps aeruginosa. Perhaps even more important than the actual reduction in deaths which might be accomplished by this vaccine are a better insight into the mechanisms of host resistance and the provision of a new approach to the immunologic control of certain opportunistic infections.
The American Journal of Surgery
Primary infections caused by Pseudomonas aeruginosa occur with extrcme rarity in the absence of pre-existing disease. However, wtien immunologic defense mcchanisms become depressed in association wi,:h a wide wtriety of human diseases, Pseudomonas is ,i r.athogen of considerable importance, capable of invasive and lethal infection. Life threatening Pseudomonas sepsis is frequently .encountered by the surgeon in patients with extensive thermal injury, prolonged assisted ventilation, immunosuppressive therapy, chemotherapy for malignant lesions, extensive operations, multiple system trauma, antibiotic therapy, certain genitourinary conditions, and other diseases. Several antibiotics have recently been found to be effective in killing Pseudomoans or inhibiting its growth, but antibiotic therapy in clinical cases has often been ineffective, and better means for the prevention or therapy of these serious infections is greatly needed. As a response to this need, a vaccine was developed by Parke-Davts and Co, which consists of a mixture of Purified antigens from seven different immunotypes of Ps aeruginosa. Based upon extensive laboratory investigations, this vaccine was first administered in 1968 to patients with extensive thermal injuries at the Cincinnati General Hospital and the Cincinnati Shriners Burns Institute. Studies in these patients have been designed to evaluate the immunologic response to vaccination and to study the basic mechanisms for immunologic defense against this organism. A gratifying product of this study has been a marked decrease in septic deaths caused by Pseudomonas. Only three of the last ninety-six consecutively immunized patients with burn injuries of greater than 20 per cent who lived for at least five days after admission have died from Pseudomonas sepsis. In contrast, 2 2 (18 per cent) of 128 similar but nonvaccinated patients admitted immediately before the study began died as a result of Pseudomonas infection. "I he incidence of other infections has remained unchanged. Coopera-
512
tive investigations in five other major burn centers are currently being conducted on a double-blind basis to evaluate the vaccine. The preliminary results are most encouraging and support our initial observations of efficacy. Of the various routes of immunization, early test results indicate that the intradermal route induces the highest levels of circulating antibody, the intramuscular route provides slightly less vigorous immunization, and the subcutaneous route induces the poorest protection. Unlike most vaccines, the range between the uniformly effective dosage and the dosage associated with unwanted reactivity (local tenderness and/or fever) is not great, and the vaccine is best administered in a close according to body weight. Since it is administered as a therapeutic adjunct, intensive early immunization is necessary: I n the burn patient ithas been found necessary to continue immunization at weekly intervals to maintain high titers of antibody, but normal human vclunteers have-maintained high titers for long periods after the last injection of antigen. P.csponse to the vaccine has been less vigorous after the sixth postburn day when the patient may have a generalized decrease in immunologic responsiveness. Use of the vaccine in the burned patient is somewhat unique since it is given to seriously ill patients to provide protection in an acute situation whereas most vaccines are given to prevent diseases at a time remote to administration of the immunogen. In man, effective antibody responses are seen on the fifth or sixth day after initial immunization. ContraD' to popular belief, lgG antibody al~pears t o be more important than lgM antibody in resistance to infection from Ps aeruginosa. Perhaps even more important than the actual reduction in deaths which might be accomplished by this vaccine are a better insight into the mechanisms of host resistance and the provision of a new approach to the immunologic control of certain opportunistic infections.
The American Journal of Surgery