Background: This study compared the investigational quadrivalent meningococcal CRM 197 conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. Methods: In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. Results: The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2-to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. Conclusions: MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines.

A 2-week course of ceftriaxone (2 g) plus netilmicin (4 mglkg), administered as one short daily iv infusion, was evaluated for the treatment of streptococcal endocarditis in an open multicenter study. Of the 52 patients, 31 were infected with viridans streptococci, 18 with Streptococcus bovis, two with Gemella morbillorum, and one with group C Streptococcus; 48 patients were assessable.Infection was cured in 42 cases, 35 treated medically and seven treated both medically and surgically. Five patients died without evidence of active infection, and one relapsed. The bacteriologic failure was due to a strain of G. morbillorum against which no synergy of ceftriaxone and netilmicin was evident in vitro. The serum creatinine level increased during treatment in four cases, all involving patients >65 years old who had renal risk factors; in two of these cases, values did not return to baseline during follow-up. Of 40 patients assessed for auditory function, only one developed decreased perception of borderline significance. Other adverse reactions were mild. This regimen was efficacious, safe, and cost-effective for the treatment of streptococcal endocarditis. However, it must be used with caution for patients with preexisting renal impairment or concomitant exposure to other potentially nephrotoxic agents.Four weeks of treatment with iv penicillin alone or 2 weeks oftreatment with iv penicillin plus an aminoglycoside are effective for streptococcal endocarditis [1,2]. However, such regimens require several daily injections, and the use of aminoglycosides carries a risk of renal toxicity and ototoxicity [2,3]. Two recent developments may allow more convenient and safer treatment ofthis condition. First, a single daily dose of ceftriaxone (a cephalosporin with a prolonged serum half-life) given for 4 weeks has been found to be effective against streptococcal endocarditis [4,5]. This regimen has been used successfully on an outpatient basis and without a permanent iv catheter. Second, recent experimental and clinical evidence has suggested that administration of the total daily dose of an aminoglycoside in a single injection is as effective as administration of the same amount of drug in two or three injections and causes equal or less toxicity [6][7][8][9]. Indeed, in the treatment of experimental streptococcal endocarditis, when given in a single daily dose rather than as multiple doses, aminoglycosides were just as synergistic with ,B-Iactam agents such as penicillin and ceftriaxone [10-13].The purpose of the multicenter study reported herein was to test prospectively the efficacy and safety of a 2-week course of therapy for streptococcal (nonenterococcal) endocarditis with a regimen consisting of ceftriaxone plus netilmicin given once a day. The study was noncomparative since streptococcal endocarditis is a rare disease and the outcome of treatment with penicillin is well known. The efficacy of penicillin is so high that it would have been impossible to recruit enough patients to exclude a type II error. Patients and ...

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Influenza is an acute respiratory illness of global importance that causes considerable morbidity and mortality every year. At the beginning of the millennium, influenza will still be an emergent or re-emergent infection because of the viral ability to mutate. Global influenza surveillance indicates that influenza viruses may vary within a country and between countries and continents during an influenza season. Virologic surveillance is of critical importance in monitoring antigenic shift and drift. Disease surveillance is important in assessing the impact of the epidemics. Both types of information provide the basis of vaccine composition and the correct use of antivirals. Laboratory diagnosis is of critical importance for the global surveillance of influenza and may allow the timely use of antiviral drugs. Viral isolation remains the gold standard for laboratory diagnosis; however, several new rapid diagnostic tests are available or in development. The clinical spectrum of the disease varies from asymptomatic infection to the classic flu syndrome, and respiratory and nonrespiratory complications are observed particularly in high-risk groups. Current inactivated influenza vaccines have shown efficacy and effectiveness in preventing influenzalike illness, hospitalization for pneumonia, and death and in reducing health care costs. Because of the annual administration of the vaccine and the short period of time where it can be administered, strategies directed at improving vaccine coverage are of critical importance. In this sense, experiences obtained in different countries, such as with the National Immunization Campaigns developed in Argentina, provide one model of massive vaccine administration. In addition to current vaccines, new live attenuated vaccines will permit a most effective prevention of influenza in the community in the near future. A new type of antiviral, neuraminidase inhibitors, offers valuable benefits in the prevention and treatment of influenza A and B. A future pandemic of influenza seems inevitable. There is wide recognition that preparation for the next pandemic requires that infrastructure be in place during interpandemic periods for implementing preventive and therapeutic measures. The WHO has established a pandemic influenza task force, and a number of countries in Latin America have developed formal pandemic plans. These national and international efforts are essential to reduce the mortality and morbidity in the next influenza pandemic.

MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed.

Assuming a cost of US$602 per treated case and of US$1.50 per dose of vaccine, the total discounted savings from use of vaccine in the targeted groups would be US$132,100. The projected savings would be altered less by vaccine coverage (range 75-90%) or efficacy (60-85%) changes than by disease incidence changes. Our analysis underestimated the true costs of cholera in Argentina because we included only medical expenditures; Indirect losses to trade and tourism had the greatest economic impact. However, vaccination with CVD 103-HgR was still cost-beneficial in the base case.

In this series of burn children age ≤ 4 years, Garces index score 4, colistin use in documented multiresistant infections, mechanical ventilation and graft requirement were identified as independent variables related with mortality.

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