Importance of circulating antibodies in protection against meningococcal disease.

Neisseria meningitidis infection results in life-threatening illnesses, including bacteremia, sepsis and meningitis. Early diagnosis and treatment are a challenge due to rapid disease progression, resulting in high mortality and morbidity in survivors. Disease can occur in healthy individuals, however, risk of infection is higher in patients with certain risk factors. N meningitidis carriage and case-fatality rates are high in adolescents and young adults. The absolute incidence of meningococcal disease has decreased partially due to increasing meningococcal vaccination rates. Maintaining protective levels of circulating antibodies by vaccination is necessary for clinical protection against disease. The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices guidelines recommend vaccination for all individuals aged 11 through 12 years, followed by a booster dose at age 16 years for maintenance of protective antibody levels throughout the high-risk years. Despite these guidelines, many adolescents remain unvaccinated and susceptible to infection and disease.

Ertapenem.

IMPORTANCE OF THE FIELD: Given their broad-spectrum and safety, carbapenems are a widely used class of antibiotics, especially in the treatment of hospital-acquired infections including infections due to multidrug-resistant organisms. Ertapenem is a unique member of this class, with a narrower spectrum that lacks reliable activity against Pseudomonas and Enterococcus. Given its spectrum and half-life of 4 h it is better suited to use in community-acquired infections and it is particularly well positioned for use in the outpatient setting. AREAS COVERED IN THIS REVIEW: Chemistry, mechanism of action, pharmacokinetics/pharmacodynamics, safety and indications for use will be covered in this review. Similar to other beta-lactams, the carbapenems inhibit cell wall synthesis by binding to and inhibiting penicillin-binding proteins. Their resistance to beta-lactamases including AmpC and extended-spectrum beta-lactamases enhances their usefulness. Similar to other beta-lactams, ertapenem exhibits time-dependent killing. Given this profile, ertapenem has been found to be useful in intra-abdominal infections, acute pelvic infections, complicated skin and skin structure infections, community-acquired pneumonia and complicated urinary tract infections. WHAT THE READER WILL GAIN: This review will enable the reader to understand differences between the different carbapenems, especially with regard to ertapenem. Once an understanding is gained with regard to pharmacology and microbiology, the reader will be positioned to understand better those circumstances in which use of ertapenem should be considered. TAKE HOME MESSAGE: Substantial differences between the carbapenems exist. Ertapenem has unique characteristics that may make it useful in specific clinical circumstances that are detailed in this review.

Ertapenem or ticarcillin/clavulanate for the treatment of intra-abdominal infections or acute pelvic infections in pediatric patients.

BACKGROUND: Ertapenem, a group I carbapenem antibiotic, has been shown to be safe and effective in treating adults with complicated intra-abdominal (cIAI) or acute pelvic infection (API). This study evaluated ertapenem for treating these infections in children. METHODS: In an open-label study, children aged 2 to 17 years with cIAI or API were randomized 3:1 to receive ertapenem or ticarcillin/clavulanate. Children 13 to 17 years of age received 1 g parenterally daily, and those 2 to 12 years of age received 15 mg/kg twice daily. Patients < 60 kg received ticarcillin/clavulanate 50 mg/kg 4 to 6 times daily and 3.1 g 4 to 6 times daily for those > or = 60 kg. Patients were assessed for safety and tolerability throughout the study and for efficacy after the completion of therapy. RESULTS: One hundred five patients, 72 (69%) with cIAI, received > or = 1 dose of study drug and were included in the safety analysis. Eighty-one patients were treated with ertapenem. Infusion site pain was the most common drug-related adverse event in both groups. In the modified intent-to-treat analysis, the age-adjusted posttreatment clinical response rates were 87% (43/50 patients) and 100% (25/25 patients) in the cIAI and API patients, respectively, for ertapenem and 73% (11/15 evaluable patients) and 100% (8/8 evaluable patients), respectively, for ticarcillin/clavulanate. Overall age-adjusted response rates were 91% (68/75 evaluable patients) for ertapenem and 83% (19/23 evaluable patients) for the comparator. CONCLUSIONS: This study suggests that ertapenem is generally safe and efficacious for treating cIAI or API in pediatric patients.

Vaccine shortages eliminate possibility for excess capacity in stockpiles.

The ability to provide vaccines to the entire population stands as one of the greatest achievements of the past century. Many new antigens have been developed, and now more antigens are offered as part of combination vaccines, reducing the number of injections. Vaccines that are routinely administered protect against 11 common childhood diseases. In addition, through herd immunity, immunization even offers some benefit to those who are not immunized. Providing additional protection has come at some additional cost, however. Immunizing a child with the 20 doses of recommended vaccines increased in price from 200 dollars to 400 dollars, (at the discounted government price) between 1997 and 2001. In spite of this impressive record, vaccines shortages have occurred for eight of the routinely recommended vaccines, and the conjugate pneumococcal vaccine is still in short supply, mandating deferral of doses three and four. These shortages have resulted in some harm to the system. Several temporary changes to recommendations were made, and it is not at all clear to what extent children for whom doses were deferred have been called back. School immunization requirements have been modified in 48% of states. Concern has been raised that we may see a reversal in the trend toward improved vaccine coverage, and the possibility of outbreaks is seen as very real. Some, but not all, of the immediate factors that led to the vaccine shortages of 2 years ago have been resolved. Longstanding factors that contributed to the shortages remain. Undervaluation by society, inadequate communication between involved parties, attrition of manufacturers, and the threat of frivolous litigation have not been addressed and may once again threaten the vaccine supply. Currently, four manufacturers are responsible for almost all of the routinely recommended vaccines used in this country. Five vaccines are produced by a single manufacturer. Only one vaccine, conjugate Haemophilus influenzae type b, is produced by three. It will take between 4 and 5 years to improve vaccine stockpiles to the desired levels. With fewer manufacturers, there is no possibility for "excess" capacity that may provide a cushion to augment stockpiles or address any unanticipated shortfalls in supply. In short, the potential for additional shortages remains substantial, and the ability to respond to shortages may actually have worsened. We must hope the return of widespread shortages or even outbreaks will not be necessary before real solutions are implemented.