P&T News: April/May 1998

Current Recommendations for Pneumococcal Vaccine

Summarized from Advisory Committee on Immunization Practices1
Peer Review Status: Internally Peer Reviewed by Todd Wiblin, M.D., Associate Hospital Epidemiologist

Pneumococcal Polysaccharide Vaccine
The currently available pneumonococcal vaccines (Pneumovax[R] 23 - Merck and Pnu-Immune[R] 23 - Lederle) include 23 purified capsular polysaccharide antigens of S. pneumoniae. These vaccines were licensed in the United States in 1983 and replaced an earlier 14-valent formulation that was licensed in 1977. One dose (0.5 mL) of the 23-valent vaccine contains 25 mg of each capsular polysaccharide antigen dissolved in isotonic saline solution with phenol (0. 25 %) or thimerosal (0. 0 1 %) added as preservative. The 23 capsular types in the vaccine represent at least 85% to 90% of the serotypes that cause invasive pneumococcal infections among children and adults in the United States. The six serotypes that most frequently cause invasive drug-resistant pneumococcal infection in the United States are represented in the 23-valent vaccine.

Pneumococcal vaccine is administered intramuscularly or subcutaneously as one 0.5-mL dose. It may be administere at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine. Pneumococcal vaccine also may be administered concurrently with other vaccines. The administration of pneumococcal vaccine with combined diphtheria, tetanus, and pertussis (DTP); poliovirus; or other vaccines does not increase the severity of reactions or diminish antibody responses.

After vaccination, an antigen-specific antibody response, indicated by a twofold or greater rise in serotype-specific antibody, develops within 2 to 3 weeks in 80% or more of healthy young adults. Antibody responses also occur in the elderly and in patients who have alcoholic cirrhosis, COPD, and insulin-dependent diabetes mellitus; however, antibody concentrations and responses to individual antigens may be lower among such persons than among healthy young adults. Persons aged 2 or more years with anatomic or functional asplenia (e.g., from splenectomy or sickle cell disease) generally respond to pneumococcal vaccination with antibody levels comparable with those observed in healthy persons of the same age.

In immunocompromised patients, antibody responses to pneumococcal vaccination are often diminished or absent. In patients with leukemia, lymphoma, or multiple myeloma, antibody response to pneumonococcal vaccination is substantially lower than response among patients who are immunocompetent. Patients who have chronic renal failure requiring dialysis, renal transplantation, or nephrotic syndrome have a diminished immune response to vaccination, resulting in lower antibody concentrations than those observed in healthy adults. In patients with Hodgkin's disease, the antibody response to pneumococcal vaccination is greater if the vaccine is administered before splenectomy, radiation, or chemotherapy; however, during chemotherapy, preexisting pneumococcal antibodies may decrease, and responses to pneumococcal vaccine may be diminished. Patients who have AIDS may have a diminished antibody response to pneumococcal vaccine.

Recommendations for Vaccine Use
The vaccine is both cost effective and protective against invasive pneumococcal infection when administered to immunocompetent persons aged 2 or more years. Therefore, all persons at risk of pneumococcal infection should receive the 23-valent pneumococcal polysaccharide vaccine (see Table 1).

Persons who have conditions associated with decreased immunologic function that increase the risk for severe pneumonococcal disease or its complications should also be vaccinated. Although the vaccine is not as effective for immunocompromised patients as it is for immunocompetent persons, the potential benefits and safety of the vaccine justify its use. These patient populations are outlined in Table 1.

Revaccination

Duration of Antibody Levels
Levels of antibodies to most pneumococcal vaccine antigens remain elevated for at least 5 years in healthy adults. In some persons, antibody concentrations decrease to prevaccination levels by 10 years. A more rapid decline (i.e., within 3 to 5 years after vaccination) in antibody concentrations may occur in certain children who have undergone splenectomy following trauma and in those who have sickle cell disease. Similar rates of decline can occur in children with nephrotic syndrome. Antibody concentrations also have declined after 5 to 10 years in elderly persons, persons who have undergone splenectomy, patients with renal disease requiring dialysis, and persons who have received transplants. Low or rapidly declining antibody concentrations after vaccination also have been noted among patients with Hodgkin's disease and multiple myeloma.

Indications for Revaccination
Routine revaccination of immunocompetent persons previously vaccinated with 23-valent polysaccharide vaccine is not recommended. However, revaccination once is recommended for persons aged 2 or more years who are at highest risk for serious pneumococcal infection and those who are likely to have a rapid decline in pneumococcal antibody levels, provided that 5 years have elapsed since receipt of the first dose of pneumococcal vaccine. Revaccination 3 years after the previous dose may be considered for children at highest risk for severe pneumococcal infection who would be aged 10 or less than years at the time of revaccination. These children include those with functional or anatomic asplenia (e.g., sickle cell disease or splenectomy) and those with conditions associated with rapid antibody decline after initial vaccination (e.g., nephrotic syndrome, renal failure, or renal transplantation). Revaccination is contraindicated for persons who had a severe reaction (e.g., anaphylactic reaction or localized arthus-type reaction) to the initial dose they received. Persons at highest risk and those most likely to have rapid declines in antibody levels include persons with functional or anatomic asplenia (e.g., sickle cell disease or splenectomy), HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure, nephrotic syndrome, or other conditions associated with immunosuppression (e.g., organ or bone marrow transplantation), and those receiving immunosuppressive chemotherapy (including long- term systemic corticosteroids). If vaccination status is unknown, patients in these categories should be administered pneumonococcal vaccine. Persons aged ~!65 years should be administered a second dose of vaccine if they received the vaccine ~!5 years previously and were aged < 65 years at the time of primary vaccination. Elderly persons with unknown vaccination status should be administered one dose of vaccine. The need for subsequent doses of pneumococcal vaccine is unclear and will be assessed when additional data become available. Because data are insufficient concerning the safety of pneumococcal vaccine when administered three or more times, revaccination following a second dose is not routinely recommended.

Table 1. Recommendations for the Use of Pneumococcal Vaccine1
Groups for which vaccination is recommended	Strength of recommendation*	Revaccination~
Immunocompetent persons# Persons aged 65 or more years	A	Second dose of vaccine if patient received vaccine 5 or more years previously and were aged less than 65 years at the time of vaccination.
Persons aged 2-64 years with chronic cardiovascular disease,+ chronic pulmonary disease, or diabetes mellitus	A	Not recommended.
Persons aged 2-64 years with alcoholism, chronic liver disease,~~or cerebrospinal fluid leaks	B	Not recommended.
Persons aged 2-64 years with functional or anatomic asplenia##	A	If patient is aged more than 10 years: single revaccination 5 or more years after previous dose. If patient is aged 10 years or less: consider revaccination 3 years after previous dose.
Persons aged 2-64 years living in special environments or social settings++	C	Not recommended.
Immunocompromised persons# Immunocompromised persons aged ~:2 years, including those with HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure, or nephrotic syndrome; those receiving immunosuppressive chemotherapy (including corticosteroids); and those who have received an organ or bone marrow transplant.	C	Single revaccination if 5 years or more have elapsed since receipt of first dose. If patient is aged 10 years or less: consider revaccination 3 years after previous dose.
*The following categories reflect the strength of evidence supporting the recommendations for vaccination: A=Strong epidemiologic evidence and substantial clinical benefit support the recommendation for vaccine use. B=Moderate evidence supports the recommendation for vaccine use. C =Effectiveness of vaccination is not proven, but the high risk for disease and the potential benefits and safety of the vaccine justify vaccination. ~Strength of evidence for all revaccination recommendations is "C." #If earlier vaccination status is unknown, patients in this group should be administered pneumococcal vaccine. +Including congestive heart failure and cardiomyopathies. **Including chronic obstructive pulmonary disease and emphysema. ~~Including cirrhosis. ##Including sickle cell disease and splenectomy. ++Including Alaskan Natives and certain American Indian populations.

Persons with Uncertain Vaccination Status
|To help avoid the administration of unnecessary doses, every patient should be given a record of the vaccination. However, providers should not withhold vaccination in the absence of an immunization record or complete medical record. The patient's verbal history should be used to determine prior vaccination status. When indicated, vaccine should be administered to patients who are uncertain about their vaccination history.

Adverse Reactions Following Revaccination
Early studies have indicated that local reactions (i.e., arthus-type reactions) among adults receiving the second dose of 14-valent vaccine within 2 years after the first dose are more severe than those occurring after initial vaccination. However, subsequent studies have suggested that revaccination after intervals of 4 years or more is not associated with an increased incidence of adverse side effects. Although severe local reactions may occur following a second dose of pneumococcal vaccine, the rate of adverse reactions is no greater than the rate after the first dose. An evaluation of 1,000 elderly Medicare enrollees who received a second dose of pneumococcal vaccine indicated that they were not significantly more likely to be hospitalized in the 30 days after vaccination than were the approximately 66,000 persons who received their first dose of vaccine. No data are available to allow estimates of adverse reaction rates among persons who received more than two doses of pneumococcal vaccine.

Strategies for Implementing Vaccine Recommendations
The use of pneumococcal polysaccharide vaccine consistently has been recommended by the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American College of Physicians, and the American Academy of Family Physicians. Despite these factors, the vaccine remains underutilized. According to the Health Care Financing Administration, only 21 % of Iowa Medicare beneficiaries received the pneumococcal vaccine between 1991 and 1995.

Barriers to achieving high pneumococcal vaccination levels among adults include: a) missed opportunities to vaccinate adults during contacts with health-care providers in offices, outpatient clinics, and hospitals; b) lack of vaccine delivery systems in the public and private sectors that can reach adults in different settings; c) patient and provider fears concerning adverse events following vaccination; and d) lack of awareness among both patients and providers of the seriousness of pneumococcal disease and benefits of pneumococcal vaccination. Because pneumococcal vaccine effectively reduces the incidence of bacteremia, these barriers must be overcome and the use of vaccine must be increased in accordance with recommendations. Strategies that have shown promise in overcoming these barriers include the use of physician reminder systems and education of patients by their physicians.

Reference
1. MMWR 1997; 46(RR-8):1-24.

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Troglitazone: Update on Hepatic Monitoring
Recent information from the manufacturer of troglitazone (Rezulin[R] - Parke Davis) has clarified the guidelines for hepatic monitoring. The measurement of bilirubin levels is not a requirement. Current recommendations for hepatic monitoring include: "It is recommended that serum transaminase be checked at the start of therapy, monthly for the first six months of therapy, every two months for the remainder of the first year of troglitazone therapy, and periodically thereafter. Liver function tests also should be obtained for patients at the first symptoms suggestive of hepatic dysfunction, e.g., nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine. Rezulin' therapy should not be initiated if the patient exhibits clinical or laboratory evidence of active liver disease (e.g., ALT > 3 times the upper limit of normal) and should be discontinued if the patient has jaundice or laboratory measurements suggest liver injury (e.g., ALT > 3 times the upper limit of normal)."

-Letter,
Parke Davis

Note: The prescribing of troglitazone at UIHC is restricted to Endocrinology. April 15, 1998