Immunogenicity of two recombinant hepatitis B vaccines in older individuals.

PURPOSE: Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-micrograms or 20-micrograms doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. PATIENTS AND METHODS: In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. RESULTS: Seroprotection rates for subjects receiving the 20-micrograms dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-micrograms dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p < 0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 micrograms were significantly greater than that for the group receiving Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001). CONCLUSIONS: Immunization with the 20-micrograms dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-micrograms dose. The latter data suggest that the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs titers.

Mediterranean spotted fever in children returning from France.

Although the incidence of Mediterranean spotted fever has increased dramatically in parts of Europe, Africa, and Asia, the disease is only rarely seen in travelers. We describe two children who had traveled in southern France and subsequently had rash and lymphadenopathy develop. Both children were treated with doxycycline and had unequivocal serologic evidence of Mediterranean spotted fever develop. Although this disease is usually mild, in the absence of a tick bite the disease can easily be confused with other febrile exanthems. We describe these patients to reemphasize the influence that international travel has brought to pediatrics.

Randomized clinical trial of aztreonam and aminoglycoside antibiotics in the treatment of serious infections caused by gram-negative bacilli.

Aztreonam was compared with aminoglycoside antibiotics (tobramycin and amikacin) in a randomized, prospective, clinical trial in serious infections caused by gram-negative bacilli (GNB). A total of 43 evaluable patients with 47 infected sites were treated with aztreonam, and 41 evaluable patients were treated with aminoglycosides for 43 infections. Of patients treated with aztreonam, 17 were bacteremic, as were 12 of those treated with aminoglycosides. Clinical and microbiologic response rates were similar, except that only 5 of 11 patients with pneumonia were considered to be clinically cured with aminoglycoside therapy, while 5 of 6 patients with pneumonia treated with aztreonam were cured. Renal impairment was observed in 9 of 54 patients who received aminoglycoside antibiotics, but in only 2 of 53 patients treated with aztreonam. Hearing impairment developed in one patient treated with tobramycin. Transient elevations of serum transaminase levels occurred in 9 of 53 patients treated with aztreonam and in only 2 of 54 aminoglycoside-treated patients. Diarrhea and superinfection occurred with equal frequency in both groups. Serum concentrations of bactericidal activity could not be correlated with the outcome of therapy. Aztreonam appears to have comparable clinical efficacy with aminoglycoside antibiotics for the treatment of serious infections caused by aerobic and facultative GNB. Its use as a single agent for the treatment of serious lower respiratory infections caused by GNB warrants further evaluation.

Treatment of pancreatitis. When do antibiotics have a role?

Experimental and clinical data on the use of antibiotics in treatment of pancreatitis vary widely, depending on the cause of the disease. Antibiotics have little effect on alcoholic or idiopathic pancreatitis, but they play a major role in treatment of bacterial infections in gallstone pancreatitis. Some antibiotics are effective in necrotizing pancreatitis; however, surgery and extensive debridement are often necessary when abscess is present or multiple-organ failure occurs.

Xanthogranulomatous pyelonephritis caused by methicillin-resistant Staphylococcus aureus.

Localized xanthogranulomatous pyelonephritis due to methicillin-resistant Staphylococcus aureus developed in a 41-year-old diabetic patient. She had recurrent bacteremia despite appropriate therapy with vancomycin. Nephrectomy was required for cure and clinical diagnosis. This report emphasizes differences in the clinical presentation and pathogenesis of xanthogranulomatous pyelonephritis caused by S. aureus. Compared with the common form of xanthogranulomatous pyelonephritis caused by gram-negative bacilli, the localized disease due to S. aureus probably results from hematogenous seeding and is not associated with nephrolithiasis or ureteral obstruction. Furthermore, this report indicates that xanthogranulomatous pyelonephritis may be caused by methicillin-resistant S. aureus, a rapidly emerging nosocomial pathogen.

Pseudobacteremia traced to cross-contamination by an automated blood culture analyzer.

Twenty-three episodes of pseudobacteremia occurring over a seven-month period were traced to cross-contamination by the automated blood culture analyzer (BACTEC 460) used in the microbiology laboratory. An epidemiologic investigation of an unusual cluster of three patients with pseudobacteremia caused by oxacillin-resistant Staphylococcus aureus led to the identification of the problem. Mock trials of the blood culture procedure confirmed that the blood culture analyzer was the source of contamination. After the needle sterilizer was replaced by the manufacturer, the problem of cross-contamination abated. Contamination of sterile blood cultures by an instrument intended to identify bacteremia rapidly may lead to incorrect diagnosis, unnecessary administration of antibiotics and prolonged hospitalization. Because of the widespread use of automated blood culture analyzers in the US, physicians, microbiologists, and infection control personnel should be alert to the possibility of cross-contamination and the subtle way in which it may present.

Pathophysiology of bacteremia.

Despite the frequency and importance of both nosocomial and "community-acquired" bacteremia, definitive information concerning crucial pathophysiologic events in human bacteremia remains sparse. An extensive variety of clinical manifestations, such as fever, rigors, shock, altered circulatory dynamics, cutaneous manifestations changes in the coagulation, complement, and other mediator systems, and effects on the lungs, heart, kidney, liver, and other end organs, have been described, but it is difficult to determine the relative frequency of these events in bacteremia caused by different species. The extensive number of bacterial species capable of producing bacteremia and variations in the type of presentation, such as acute, asymptomatic, and chronic, even when bacteremia is produced by the same species, undoubtedly contribute to this difficulty and suggest that a variety of pathophysiologic mechanisms occur in various bacteremias. In contrast, the relative frequency of various manifestations and some pathophysiologic mechanisms have been better delineated in Gram-negative bacteremia. The development of bacteremia enhances the lethality of most types of localized infection and several studies have demonstrated a relation between the magnitude of bacteremia and the outcome of the disease. Among various pathophysiologic alterations, mechanisms involved in the production of fever have been delineated most clearly. Fever appears to reflect a "common pathway" with almost all infectious agents and results from release of endogenous pyrogen from phagocytic cells. Endogenous pyrogen regulates the thermostatic setting of the body through its effect on the anterior hypothalamus. Endogenous pyrogen seems identical with Interleukin 1 and exerts a variety of other biologic activities. An extensive number of bacterial components have been proposed as "effectors" and an equally large number of endogenous substances proposed as "mediators" of the pathophysiologic events in bacteremia. The importance of many of these effectors and mediators has been postulated largely on the basis of in vitro and animal studies. The lack of critical clinical studies hampers extrapolation of these experimental studies to human bacteremia. The development of more effective therapy for the complications of bacteremia, such as shock, will continue to be hampered until the mechanisms involved in the production of those pathophysiologic events that are crucial determinants of outcome have been delineated more precisely in human disease.

Rapid recognition of group B streptococci by pigment production and counterimmunoelectrophoresis.

Streptococci from clinical isolates were studied for their ability to produce pigment in stab cultures in Columbia agar. Serological grouping of these organisms was done by counterimmunoelectrophoresis using Burroughs-Wellcome antisera. In this group of isolates, 66 of the 68 organisms grouped as B by serological testing produced pigment in the Columbia agar stab cultures. Pigment was not produced by any of the other 36 streptococci studied (11 group A, 9 group C, 4 group D, and 12 nongroupable). The use of the Columbia agar stab culture is recommended as a rapid and simple test for recognition of group B streptococci. The counterimmunoelectrophoresis test is also suggested as a convenient, rapid, and sensitive method for grouping the streptococci.