Safety of Antimicrobials for Postexposure Prophylaxis and Treatment of Anthrax: A Review.

BACKGROUND: Bacillus anthracis, the causative agent for anthrax, poses a potential bioterrorism threat and is capable of causing mass morbidity and mortality. Antimicrobials are the mainstay of postexposure prophylaxis (PEP) and treatment of anthrax. We conducted this safety review of 24 select antimicrobials to identify any new or emerging serious or severe adverse events (AEs) to help inform their risk-benefit evaluation for anthrax. METHODS: Twenty-four antimicrobials were included in this review. Tertiary data sources (e.g. Lactmed, Micromedex, REPROTOX) were reviewed for safety information and summarized to evaluate the known risks of these antimicrobials. PubMed was also searched for published safety information on serious or severe AEs with these antimicrobials; AEs that met inclusion criteria were abstracted and reviewed. RESULTS: A total of 1316 articles were reviewed. No consistent observations or patterns were observed among the abstracted AEs for a given antimicrobial; therefore, the literature review did not reveal evidence of new or emerging AEs that would add to the risk-benefit profiles already known from tertiary data sources. CONCLUSIONS: The reviewed antimicrobials have known and/or potential serious or severe risks that may influence selection when recommending an antimicrobial for PEP or treatment of anthrax. Given the high fatality rate of anthrax, the risk-benefit evaluation favors use of these antimicrobials for anthrax. The potential risks of antimicrobials should not preclude these reviewed antimicrobials from clinical consideration for anthrax but rather guide appropriate antimicrobial selection and prioritization across different patient populations with risk mitigation measures as warranted.

Clinical guidance for smallpox vaccine use in a postevent vaccination program.

This report outlines recommendations for the clinical use of the three smallpox vaccines stored in the U.S. Strategic National Stockpile for persons who are exposed to smallpox virus or at high risk for smallpox infection during a postevent vaccination program following an intentional or accidental release of the virus. No absolute contraindications exist for smallpox vaccination in a postevent setting. However, several relative contraindications exist among persons with certain medical conditions. CDC recommendations for smallpox vaccine use were developed in consideration of the risk for smallpox infection, risk for an adverse event following vaccination, and benefit from vaccination. Smallpox vaccines are made from live vaccinia viruses that protect against smallpox disease. They do not contain variola virus, the causative agent of smallpox. The three smallpox vaccines stockpiled are ACAM2000, Aventis Pasteur Smallpox Vaccine (APSV), and Imvamune. Surveillance and containment activities including vaccination with replication-competent smallpox vaccine (i.e., vaccine viruses capable of replicating in mammalian cells such as ACAM2000 and APSV) will be the primary response strategy for achieving epidemic control. Persons exposed to smallpox virus are at high risk for developing and transmitting smallpox and should be vaccinated with a replication-competent smallpox vaccine unless severely immunodeficient. Because of a high likelihood of a poor immune response and an increased risk for adverse events, smallpox vaccination should be avoided in persons with severe immunodeficiency who are not expected to benefit from vaccine, including bone marrow transplant recipients within 4 months of transplantation, persons infected with HIV with CD4 cell counts <50 cells/mm3, and persons with severe combined immunodeficiency, complete DiGeorge syndrome, and other severely immunocompromised states requiring isolation. If antivirals are not immediately available, it is reasonable to consider the use of Imvamune in the setting of a smallpox virus exposure in persons with severe immunodeficiency. Persons without a known smallpox virus exposure might still be at high risk for developing smallpox infection depending on the magnitude of the outbreak and the effectiveness of the public health response. Such persons will be defined by public health authorities and should be screened for relative contraindications to smallpox vaccination. Relative contraindications include atopic dermatitis (eczema), HIV infection (CD4 cell counts of 50-199 cells/mm3), other immunocompromised states, and vaccine or vaccine-component allergies. Persons with relative contraindications should be vaccinated with Imvamune when available and authorized for use by the Food and Drug Administration. These recommendations will be updated as new data on smallpox vaccines become available and further clinical guidance for other medical countermeasures including antivirals is developed.

Infantile Tubercular Meningitis With Brain Infarct.

A previously healthy 6-month-old Asian girl presented to the emergency department (ED) after 7 to 10 days of fever of 101 to 102°F, cough, and intermittent vomiting. Pneumonia was diagnosed and successfully treated, and the patient was discharged. She returned to the ED after her mother noticed mild facial asymmetry, left upper extremity weakness, and an episode of jerkiness. The mother then revealed that both she and the child's maternal grandmother, who also lived with the patient, had suffered chronic coughs in recent months. The mother's previous chest radiograph showed pulmonary tuberculosis. The patient's magnetic resonance imaging findings were consistent with a cerebrovascular event. Positive results on cerebrospinal fluid analysis, the mother's suspicious tuberculosis-like history, and the patient's clinical symptoms pointed heavily toward a diagnosis of tuberculous meningitis. A 4-drug antituberculosis regimen with dexamethasone was instituted and scheduled to continue for 12 months. However, the patient returned to the ED 2 months later after developing an obstructive hydrocephalus.

Strongyloidiasis in a healthy 8-year-old girl in north-eastern USA.

A previously healthy, white 8-year-old girl presented with a 1-week history of abdominal pain and vomiting after a trip to a lake in Pennsylvania, north-eastern USA. There was marked dehydration. A raised blood eosinophilic count prompted microscopy for ova and parasites which demonstrated a heavy load of larvae of Strongyloides stercoralis. Charcot-Leyden crystals were also detected. The child received oral ivermectin and made a complete recovery.

Bacterial meningitis vaccines: not just for kids.

Bacterial meningitis remains a feared diagnosis that may lead to significant mortality and morbidity in both the developed and developing world; case fatality rates range from 10% to 50% among all age groups. Several vaccines are available (including the Haemophilus influenzae type B polysaccharide conjugate vaccine) that have proven effective in reducing the incidence of bacterial meningitis. Although a 23-valent pneumococcal polysaccharide vaccine has been available for some time, use of the 7-valent pneumococcal conjugate vaccine (PCV) has demonstrated a dramatic reduction in the incidence of invasive pneumococcal disease; despite the increase in the disease caused by nonvaccine-serotype strains, the success of the 7-valent PCV is noteworthy. A quadrivalent conjugate meningococcal vaccine has been available in the United States since 2005; although its true efficacy remains to be determined, there have been dramatic results with declining incidence in certain high-risk populations and in endemic areas.

Changing Risk Factors for Pediatric Infective Endocarditis.

Infective endocarditis in children is an uncommon infection. Three major groups of children are at risk: 1) those with underlying congenital heart disease, 2) those with central vascular catheters, and 3) children infected with certain virulent organisms. Although the overall incidence of infective endocarditis has increased, the population of children involved has changed. Children with corrected congenital heart disease are at risk during the early postoperative period. Children in whom vascular shunts or grafts are employed remain at the highest risk for endocarditis. Use of central vascular catheters increases risk in children with underlying heart disease and those with normal hearts. Finally, certain pathogens attack the heart valves and cause high morbidity and mortality.