A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing cytomegalovirus (CMV) disease in HIV-infected persons at high risk for CMV disease. DESIGN: Double-blind, placebo-controlled, randomized clinical trial in primary care clinics and private practice offices specializing in the care of people with HIV. Interventions were oral GCV (1000 mg three times/day) or placebo. Protocol amendment allowed switch to open-label oral GCV. Main outcome measures were confirmed CMV retinal or gastrointestinal mucosal disease, and death. The study enrolled 994 people co-infected with CMV and HIV, with at least one CD4 count recorded < 100 x 10(6) cells/l. RESULTS: At study completion (15 months median follow-up), CMV event rates in the oral GCV and control groups were 13.1 and 14.6 per 100 person years, respectively, a hazard ratio (HR) of 0.92 [95% confidence interval (CI), 0.65-1.27; P = 0.6]. At protocol amendment event rates were 12.7 and 15.0, respectively (HR, 0.85; 95% CI, 0.56-1.30; P = 0.45). At study completion, event rates for death were 26.6 and 32.0 (HR, 0.84; P = 0.09), and at protocol amendment were 18.9 and 19.6 (HR, 0.95; P = 0.78), respectively. At protocol amendment for the CMV endpoint, the oral GCV treatment effect was associated with baseline use of didanosine (ddI). For patients taking ddI at randomization, HR was 7.48 (P = 0.02). For patients not taking ddI, HR was 0.62 (P = 0.04). These HR were statistically different (P = 0.0006). CONCLUSIONS: In our study, 3 g/day oral GCV did not significantly reduce CMV disease incidence, but there was a suggestion of a death-rate reduction. Furthermore, results suggest that oral GVC decreased risk of CMV disease in patients not prescribed ddI, and increased risk in those prescribed ddI. For the CMV endpoint, our study differs markedly from the only similar study, although for the death endpoint, a combined analysis of studies indicated significant reduction in death rate.

Impact of dressing materials on central venous catheter infection rates.

Transparent, semipermeable, polyurethane dressings have become widely accepted for dressing central venous catheter (CVC) insertion sites. However, there have been differing results in terms of their association with microbial growth under the dressing and the risk of subsequent CVC-associated infection. This study describes our positive experience in terms of the impact of a highly permeable transparent dressing on CVC-associated infection among patients at our facility.

Effect of postdischarge surveillance on rates of infectious complications after cesarean section.

Decreases in length of stay for surgical procedures and increased outpatient surgery affect accuracy of surgical wound infection rates. To assess accuracy of rates for infectious complications after delivery by cesarean section, we implemented postdischarge surveillance at our hospital (4800 annual deliveries). Physician questionnaires were used. Response rate was greater than 90%. During the 5 months before postdischarge surveillance the overall infection rate was 1.6%; afterward the rate increased to 6.3% (p = 0.0003). Approximately 59% of infectious complications would have gone undetected with only inpatient surveillance. We conclude that postdischarge surveillance is necessary for an accurate determination of rates of infectious complications. The need among this population reflects relatively short postpartum hospitalization and emphasis on outpatient management of postoperative complications.

Effects of age on respiratory tract immunity in guinea pigs.

This study examined cell-mediated immune responses of aged guinea pigs following intranasal sensitization with Bacillus Calmette Guérin (BCG). Young adult and aged guinea pigs, one and three years old, respectively, were inoculated intranasally with BCG. Changes in lung cell profile, production of migration inhibition factor (MIF) by lung derived lymphocytes and development of delayed hypersensitivity-skin (DHS) reaction to purified protein derivative (PPD) were evaluated at various time intervals. Normal lung lavage cell profiles were similar in both groups. Significant increases in total lung lavage cells occurred in both groups at 2 and 6 weeks following sensitization and corresponded with significant increases in the number of macrophages. The young adult group had significant increases in the total number of lymphocytes and rosette forming cells at 6 weeks compared to their preimmunization levels. Production of MIF was significantly greater in magnitude in the young adult group at 2 weeks compared to aged groups. The total number of animals mounting immune responses to BCG (MIF production) was also significantly lower in the aged group over the 6 week study period. DHS reaction to PPD was positive in all young adult animals, while only half of the aged guinea pigs were positive at 6 weeks. Data suggest that age adversely affects lung resistance to infection from intracellular microbial agents of the respiratory tract.

Microbicidal activity and superoxide production by macrophages in aging rats.

This study examined the effects of aging on the immunobiological properties of alveolar macrophages in young adult and aged rats. Macrophages, obtained by lung lavage, were enumerated and tested in vitro for yeast phagocytosis and fungicidal activities. Superoxide anion (O2-) generation stimulated by opsonized zymosan was compared between the two groups. Total numbers of alveolar cells and the differential cell distribution were comparable in both the groups. The difference between the groups was not statistically significant, even though the yeast phagocytic capacity in the cells from senescent animals was consistently higher than in the controls. This may be due to the wide degree of variability observed in the aged animals. However, cell fungicidal activity was statistically lower in the aged animals at 90 minutes of incubation which correlated with a significant decline in the O2- production. Aging may adversely affect some of the immunobiologic functions of lung macrophages and thus compromise host defense mechanisms in the respiratory tract.

Respiratory tract immunity in the aged.

In the elderly, respiratory infections are frequent and constitute the leading cause of death. Presumably this is the consequence of reduced local immunity in the respiratory tract. The present knowledge based on investigations in man and laboratory animals, including results of own research, is reviewed. Further research is needed to give a definite answer and to improve immunoprophylaxis in the elderly.

Gram-negative septicemia and shock.

Gram-negative septicemia is an old disease with dramatic changes in the arena of modern medicine. Whereas it was most often the domain of the infectious disease specialist and the abdominal surgeon 25 years ago, it is now managed in most medical practice specialties. It requires thorough understanding by all practitioners. Its physiology is increasingly well understood. The relationships between sepsis and host underlying diseases are important. Nonspecific therapies are important for early management of septicemia and impending shock, but specific application of immunotherapy in the form of antibody or vaccines, antibiotics selected for the most likely organism, and perhaps even pharmacotherapy directed at recognized intrinsic mediators of host responses to bacteremia, hold the greatest promise for a successful outcome.