Disseminated fusariosis occurring in two patients despite posaconazole prophylaxis.

Posaconazole is widely used for prophylaxis against invasive fungal infections in patients undergoing myeloablative therapy. Disseminated fusariosis is a serious invasive mold infection in such patients. Preclinical and clinical studies indicate activity of posaconazole against Fusarium. We describe two cases of disseminated fusariosis that occurred despite posaconazole prophylaxis.

Case-control study of statin prevention of mould infections.

Invasive mould infections (IMI) are associated with significant morbidity and mortality. In vitro studies have demonstrated that hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have activity against several pathogenic moulds including Zygomycetes and Aspergillus spp. The aim of our study was to determine if statin use is a preventive factor for the development of IMI. This was a retrospective case-control study of 10 United States Veterans Affairs Medical Centers that comprise the Veterans Integrated Service Network (VISN) 16. Cases with IMI and controls were identified from 2001 to 2008. Controls were matched by age, facility, history of transplantation, presence of chronic steroid use and presence of human immunodeficiency virus infection (HIV). Two hundred and thirty-eight patients were included. Independent variables associated with the development of IMI were history of solid malignant tumours (OR 2.63, 1.41-4.87) and hypertension (OR 2.29, 1.13-4.68). Statin use within 3 months of index date was not an independent variable for prevention or development of IMI. No level of exposure to a statin drug appeared to influence the development of infection. This retrospective case-control study suggests that despite evidence of in vitro activity, statins may not decrease risk of IMI. Prospective, controlled trials may be necessary to investigate any potential clinical benefit.

Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease.

Blood smear analysis is especially useful for diagnosing five infectious diseases: babesiosis, ehrlichiosis, relapsing fever due to Borrelia infection, malaria, and American trypanosomiasis (Chagas disease). It should be performed in patients with persistent or recurring fever or in those who have traveled to the developing world or who have a history of tick exposure, especially if accompanied by hemolytic anemia, thrombocytopenia, or hepatosplenomegaly.

Cutaneous reactions with tenofovir disoproxil fumarate: a report of nine cases.

Adverse drug reactions causing the early discontinuation of therapy are common in patients with HIV infection. Hypersensitivity consisting mainly of a maculopapular rash on the face, extremities and trunk has been observed at a rate higher than expected in patients treated with tenofovir at our clinics. We therefore examined nine patients with suspected tenofovir hypersensitivity reactions in two indigent care HIV clinics. Type I and type IV hypersensitivity may be involved as immunological mechanisms.

Part XIII. Systemic antifungal therapy.

Until the last decade of the 20th century, intravenous amphotericin B deoxycholate was the only agent available to treat the relatively rare occurrence of serious systemic fungal infections. In response to an explosion in the incidence of systemic fungal infections, within a 15 year period, four new classes of antifungal agents were introduced: the triazoles, liposomal amphotericin B preparations, an allylamine, and echinocandins (Table 1). So an updated review of antifungal therapy is in order.

Part XIV. Antiviral agents other than antiretrovirals: therapy for herpesvirus infections, viral hepatitis, and influenza.

The incidences of viral infectious diseases are increasing at an alarming rate in the US and worldwide. Antiviral therapy is challenging because viruses subsume normal host cellular mechanisms for many functions, have rapid replication rates, have poor error scanning when reading genetic code, and undergo frequent drug target mutations. This article will focus on antiviral drugs and principles of treatment for infections due to herpes simplex viruses (HSV1 and HSV2), varicella zoster virus (VZV), cytomegalovirus (CMV), hepatitis B and hepatitis C viruses, and influenza virus. Therapy for human immunodeficiency virus (HIV) infection will be discussed in the next symposium segment.

Gatifloxacin-associated hypoglycemia.

Fluoroquinolone antibiotics are widely employed in treating infectious diseases. Lately, reports of either hyperglycemia or hypoglycemia have appeared in the medical literature. Many patients are elderly and have underlying diabetes and renal insufficiency. Of these antibiotics, dysglycemia occurs more frequently with gatifloxacin (Tequin). While hypoglycemia usually occurs within the first three days of treatment, hyperglycemia often occurs later in the treatment course. The hypoglycemia may be profound and difficult to manage. We report 4 patients with hypoglycemia while taking gatifloxacin and review the relevant literature.

Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins.

In this article we describe antimicrobials that are grouped by their similar mechanism of action, namely inhibition of protein synthesis at the bacterial 50S ribosomal subunit. Macrolides, azalides, and ketolides are primarily used to treat community acquired respiratory tract infections. A lincosamide antibiotic, clindamycin, is primarily used to treat anaerobic infections. A combination of streptogramins, quinupristin/dalfopristin, is used to treat infections due to multiple drug resistant Gram positive cocci.

Part XV. Antiretroviral therapy for human immunodeficiency virus infection.

Twenty six years have passed since the first cases of the acquired immune deficiency syndrome (AIDS) were recognized in the U.S. Since that time, over 25 million people have died worldwide. The Centers for Disease Control and Prevention estimates that 1.1 million individuals in the U.S. are living with human immunodeficiency virus (HIV) infection with or without AIDS. With the advent of effective antiretroviral treatment strategies, HIV infection has now become a chronic disease requiring lifelong therapy. Despite the advances made in treatment, drug resistance, long-term adverse effects, and high adherence requirements continue to represent challenges to patients and clinicians. This overview will provide a summary of current antiretroviral drugs, treatment strategies, and novel therapeutic agents presently in development.

Infectious disease outbreaks in competitive sports: a review of the literature.

Recent outbreaks of infectious diseases in athletes in competitive sports have stimulated considerable interest. The environments in which these athletes compete, practice, receive therapy for injuries, and travel, both domestically and internationally, provide varied opportunities for the transmission of infectious organisms. The purpose of this medical literature review is to identify the agents most commonly reported in the medical literature as responsible for infectious disease outbreaks in specific sports and their modes of transmission and to guide targeted prevention efforts. A literature review of English-language articles in medical publications that reported outbreaks of infectious diseases in competitive athletes was conducted in PubMed MEDLINE from 1966 through May 2005. Outbreaks that were solely food borne were excluded. Fifty-nine reports of infectious disease outbreaks in competitive sports were identified in the published medical literature. Herpes simplex virus infections appear to be common among wrestlers and rugby players, with no single strain responsible for the outbreaks. Methicillin-resistant Staphylococcus aureus was responsible for several recent outbreaks of soft tissue and skin infections among collegiate and professional athletes. The most common mode of transmission in outbreaks was direct, person-to-person (primarily skin-to-skin) contact. Blood-borne exposure was implicated in 2 confirmed outbreaks of hepatitis. Airborne and vector transmissions were rarely reported. This review provides an overview of infectious disease outbreaks thought to be either serious enough or unusual enough to report. Appropriate surveillance of the frequency of infections will allow sports medicine staff to identify outbreaks quickly and take necessary measures to contain further transmission and prevent future outbreaks.

Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment. OBJECTIVE: To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs. DESIGN: A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up. SETTING: 26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers. PARTICIPANTS: 491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood. INTERVENTION: Doxycycline, 200 mg, or matching placebo daily for 12 months. MEASUREMENTS: The primary outcome was the proportion of participants who improved more than 7 units on the Physical Component Summary score of the Veterans Short Form-36 General Health Survey 12 months after randomization. Secondary outcomes were measures of pain, fatigue, and cognitive function and change in positivity for Mycoplasma species at 6, 12, and 18 months after randomization. RESULTS: No statistically significant differences were found between the doxycycline and placebo groups for the primary outcome measure (43 of 238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8 percentage point [95% CI, -6.5 to 8.0 percentage points]; P > 0.2) or for secondary outcome measures at 1 year. In addition, possible differences in outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in the doxycycline group had a higher incidence of nausea and photosensitivity. LIMITATIONS: Adherence to treatment after 6 months was poor. CONCLUSION: Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.

Prevention and treatment of bacterial diseases caused by bacterial bioterrorism threat agents.

There is general consensus that the bacterial agents or products most likely to be used as weapons of mass destruction are Bacillus anthracis, Yersinia pestis, Francisella tularensis and the neurotoxin of Clostridium botulinum. Modern supportive and antimicrobial therapy for inhalational anthrax is associated with a 45% mortality rate, reinforcing the need for better adjunctive therapy and prevention strategies. Pneumonic plague is highly contagious, difficult to recognize and is frequently fatal. Therefore, the development of vaccines against this agent is crucial. Although tularemia is associated with low mortality, the highly infectious nature of aerosolized F. tularensis poses a substantive threat that is best met by vaccine development. Safer antitoxins and a vaccine are required to meet the threat of the use of botulinum toxin as a weapon of mass destruction. In this article, the current status of research in these areas is reviewed.

Preventive and therapeutic approaches to viral agents of bioterrorism.

Certain viruses, such as those that cause smallpox and hemorrhagic fevers, have been identified as possible bioterrorism agents by the Centers for Disease Control and Prevention. They have been designated as potential threats because large quantities can be propagated in cell culture, they are transmissible as aerosols and, for the most part, there are only limited vaccine and pharmaceutical strategies for either prevention or treatment of established infection. An additional concern is the potential to genetically modify these agents to enhance virulence or promote resistance to vaccines or identified antivirals. Although the major impact of these agents is human illness, the release of zoonotic agents, such as the Nipah virus, would have consequences for both humans and animals because infected and noninfected animals might need to be sacrificed to control the spread of infection. Continued research is necessary to develop effective strategies to limit the impact of these biological threats.

Therapeutic options for diseases due to potential viral agents of bioterrorism.

The etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. Cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. Ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to Ebola and Marburg infections. Current vaccine strategies for smallpox are effective, but carry significant risk for complications. Licensed vaccines for hemorrhagic fever viruses are limited to yellow fever, but animal studies are promising. Genomic analysis of the viral pathogen and the animal model response to infection may provide valuable information enabling the development of novel treatment and prevention strategies. Current knowledge of these strategies is reviewed.

Current therapy and the development of therapeutic options for the treatment of diseases due to bacterial agents of potential biowarfare and bioterrorism.

An important part of biodefense is the optimization of current therapy and the development of new therapeutic options for the treatment of the diseases most likely encountered in the form of biological weapons. Guidelines for the prevention and treatment of anthrax, plague, tularemia and botulinum toxin intoxication are reviewed. The strategies in development for the prevention of anthrax focus primarily on active and passive immunization against protective antigen, because of its central role as a toxin delivery module. Novel vaccine strategies for plague, tularemia and botulism are also reviewed.

Viral agents as biological weapons and agents of bioterrorism.

Multiple viral agents have been classified by the CDC as potential weapons of mass destruction or agents for biologic terrorism. Agents such as smallpox, viral hemorrhagic fever viruses, agents of viral encephalitis, and others are of concern because they are highly infectious and relatively easy to produce. Although dispersion might be difficult, the risk is magnified by the fact that large populations are susceptible to these agents and only limited treatment and vaccination strategies exist. Although the risk of large-scale bioterrorism using viral agents is small, public health programs and health care providers must be prepared for this potentially devastating impact on public health.

Unconventional biological threats and the molecular biological response to biological threats.

This article concludes this symposium on potential agents of warfare and terrorism with discussion of 3 topics. First, influenza A virus is discussed as a potential biological weapon. Although it does not receive much attention in this role, the potential for mass casualties and public panic certainly exist if an epidemic of a virulent influenza A virus were initiated. Second, agroterrorism, terrorism directed at livestock or poultry or crops, is briefly discussed. Finally, the potential role of techniques of modern molecular biology to create new agents for bioterrorism or enhance the terrorist potential of available agents, and the known roles of these techniques in defense against biological warfare or terrorism are discussed.

Bacterial pathogens as biological weapons and agents of bioterrorism.

Bacterial pathogens have been identified as agents that have been, or could be, used as weapons of biological warfare and/or biological terrorism. These agents are relatively easily obtained, prepared, and dispersed, either as weapons of mass destruction or for more limited terrorist attacks. Although phylogenetically diverse, these agents all have the potential for aerosol dissemination. Physicians in the United States and most of the developed world have never encountered most of these agents and the diseases they produce. Public health programs must be prepared, and individual primary care providers must be able to recognize, diagnose, treat, and prevent infection with these agents.

Microbiological, biological, and chemical weapons of warfare and terrorism.

Microbiological, biological, and chemical toxins have been employed in warfare and in terrorist attacks. In this era, it is imperative that health care providers are familiar with illnesses caused by these agents. Botulinum toxin produces a descending flaccid paralysis. Staphylococcal enterotoxin B produces a syndrome of fever, nausea, and diarrhea and may produce a pulmonary syndrome if aerosolized. Clostridium perfringens epsilon-toxin could possibly be aerosolized to produce acute pulmonary edema. Ricin intoxication can manifest as gastrointestinal hemorrhage after ingestion, severe muscle necrosis after intramuscular injection, and acute pulmonary disease after inhalation. Nerve agents inhibit acetylcholinesterase and thus produce symptoms of increased cholinergic activity. Ammonia, chlorine, vinyl chloride, phosgene, sulfur dioxide, and nitrogen dioxide, tear gas, and zinc chloride primarily injure the upper respiratory tract and the lungs. Sulfur mustard (and nitrogen mustard) are vesicant and alkylating agents. Cyanide poisoning ranges from sudden-onset headache and drowsiness to severe hypoxemia, cardiovascular collapse, and death. Health care providers should be familiar with the medical consequences of toxin exposure, and understand the pathophysiology and management of resulting illness.