Randomized, double-blind study in healthy adults to assess the boosting effect of Vaqta or Havrix after a single dose of Havrix.

A randomized, double-blind, multicenter study was conducted to investigate the boosting effect of Vaqta or Havrix in 537 healthy adults 18-53 years of age who had received a single dose of Havrix either 24 or 52 weeks earlier. Subjects were randomized in a 2 : 1 ratio to receive either Vaqta or Havrix for their second dose of vaccine and followed for clinical reactions for 14 days after dose 2 was administered. Serum samples were collected immediately before dose 2 was administered and again 4 weeks later and evaluated for hepatitis A antibody (modified hepatitis A virus antibody assay). The booster response rate after administration of the second dose of either vaccine was similar (86.1% for Vaqta vs. 80.1% for Havrix). The geometric mean titers were also similar: 3274 mIU/mL (95% confidence interval [CI], 2776-3858) for Vaqta versus 2423 mIU/mL (95% CI, 1911-3074) for Havrix. The proportion of subjects who reported > or =1 injection-site adverse experiences was lower in the patients receiving Vaqta than in those receiving Havrix (36.6% vs. 59.7%; P<.001). The results of this study indicate that a regimen of Havrix followed by Vaqta is generally well tolerated and highly immunogenic.

Susceptibility of Pseudomonas pseudomallei to new beta-lactam and aminoglycoside antibiotics.

Pseudomonas pseudomallei is resistant to many antimicrobial agents. We determined the susceptibility to twelve beta-lactams and six aminoglycosides of twelve isolates of P. pseudomallei. Imipenem (MIC range 0.5-1.0 mg/l; MIC90 1.0 mg/l), ceftazidime (MIC range 1-8 mg/l; MIC90 8.0 mg/l), amoxycillin/clavulanate (MIC range 4-8 mg/l; MIC90 8.0 mg/l), piperacillin (MIC range 4-16 mg/l; MIC90 8.0 mg/l), and carumonam (MIC range 4-16 mg/l; MIC90 8.0 mg/l) were the most active. Aminoglycosides were relatively inactive, for example, gentamicin (MIC range 16-64 mg/l; MIC90 64 mg/l), netilmicin (MIC range 16-128 mg/l; MIC90 128 mg/l) and amikacin (MIC range 32-64 mg/l; MIC90 64 mg/l).

Assessment of the immune deficit in leprosy patients and the effect of recombinant IL-2 in vitro.

Although the mechanism of immunologic unresponsiveness in lepromatous leprosy remains unknown, it has been shown that interleukin-2 (IL-2) production is defective in these patients. Peripheral blood mononuclear cells (PBMC) were isolated from treated (less than 16 months) and untreated leprosy patients as well as household contacts; age, sex, ethnically matched control subjects; and laboratory staff. PBMC were cultured for 6 days with sonicated Mycobacterium leprae (1-10 micrograms/ml), Dharmendra lepromin (1:10), or phenolic glycolipid-I (PGL-I) (0.05-5.0 micrograms/ml) in medium supplemented with various concentrations of recombinant IL-2 (rIL-2) or cultured for 3 days with one of the three mycobacterial antigens in the presence of concanavalin A (ConA). TT/BT patients and household control subjects had a robust response to M. leprae and lepromin, but were unresponsive to PGL-I delivered in liposomes. PBMC from LL patients did not respond to any of the three antigen preparations. rIL-2 induced proliferation of PBMC both in leprosy patients and control subjects regardless of the presence or absence of the three leprosy antigen preparations. This antigen nonspecific augmentation of proliferation by the wide range of doses of rIL-2 employed makes difficult the interpretation of the enhanced thymidine incorporation noted when rIL-2 is added in the presence of antigen to cultures of lymphocytes from LL patients. Our studies are at variance with reports that leprosy antigens, specifically PGL-I, induce immunological suppression, in that mycobacterial antigens did not cause significant suppression of the ConA-induced proliferations of PBMC from patients.

Cephalosporins in surgery. Prophylaxis and therapy.

Prophylactic antibiotics in surgery are intended to prevent morbidity and mortality, as well as to reduce the duration and cost of hospitalisation. The indications for prophylaxis, and its effectiveness, should be evaluated with these criteria in mind. The basis for antibiotic prophylaxis in surgery is either provision of an effective concentration of antibiotic in the tissue site at the time of potential contamination, or (primarily in the case of colorectal surgery) to reduce the inoculum of potentially contaminating bacteria. Cephalosporins are the antibiotics most widely used for prophylaxis in surgery, and have clearly been shown to reduce postoperative morbidity in vaginal hysterectomy, resection of head and neck cancers, vascular grafting, total joint replacement, repair of hip fractures, and high risk gastroduodenal surgery. They are probably also useful in cardiac surgery, abdominal hysterectomy, caesarean section, and colorectal surgery. For orthopaedic, cardiac, gynaecological, and gastroduodenal procedures it is important to select an antibiotic with proven clinical activity against Gram-positive organisms. For head and neck surgery, the spectrum of activity should also include oral anaerobes and Enterobacteriaceae. For biliary surgery an antibiotic effective against both Gram-positive and Gram-negative organisms may offer at least theoretical advantages, while for appendicectomy a cephamycin represents the most appropriate choice. In colorectal procedures, activity against B. fragilis is the major consideration in selecting an antibiotic for systemic prophylaxis. When intra-abdominal sepsis occurs following surgery, a potentially wide range of bacteria may be implicated, but in practice such infections are due to a small number of species, with B. fragilis most commonly implicated. The most useful cephalosporins in this setting are those active against both aerobic Gram-negative bacteria and anaerobes, especially B. fragilis. In practice, an aminoglycoside is often administered concomitantly. Importantly, prompt surgical treatment is the cornerstone of management of abdominal sepsis, and empirical antibiotic therapy should be adjusted as needed when culture and sensitivity tests become available.

Acquired immunodeficiency syndrome with progressive multifocal leukoencephalopathy and monoclonal B-cell proliferation.

A 34-year-old man who used intravenous drugs developed the acquired immunodeficiency syndrome with lymphadenopathy, Mycobacterium tuberculosis pneumonia, and progressive multifocal leukoencephalopathy. Early biopsy specimens of the lymph node showed hyperplasia without evidence of lymphoma. Later, immunologic analysis of peripheral blood lymphocytes showed inversion of the helper/suppressor T-lymphocyte ratio and persistent monoclonal B-cell proliferation without clinically overt lymphoma. The clinical course of this patient suggests that abnormal immune responses seen in the setting of the acquired immunodeficiency syndrome may evolve into lymphoproliferative disorders detectable by peripheral blood lymphocyte analysis.