acyclovir and Infections

The treatment of infectious complications in the cancer patient has evolved as a consequence of the developments in cancer chemotherapy, which significantly impair immune function. Broad-spectrum, single-agent antibiotics have replaced more cumbersome multidrug regimens for empiric coverage of fever and neutropenia in many institutions. The use of new, potent oral antibiotics may be a next step toward further simplifications. Several new antivirals have come into clinical use in the past decade, and reports of viral resistance to the standard agent, acyclovir, have come forth. Increasing experience with new (and older) antifungal and antiparasitic agents has given a better understanding of the use of these drugs for both prophylaxis and treatment. This overview includes a critical appraisal of the attributes and limitations of current antibiotics, antivirals, antifungals, and antiparasitic agents for the immunocompromised host.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Azoles; Aztreonam; Cephalosporins; Fluoroquinolones; Foscarnet; Ganciclovir; Humans; Imipenem; Immunocompromised Host; Infections; Neoplasms; Pneumonia, Pneumocystis; Vancomycin

The epidemiology of infections associated with orthotopic liver transplantation is summarized herein, and approaches to prophylaxis are outlined. Infection is a major complication following orthotopic liver transplantation, and more than half of transplant recipients develop at least one infection. The risk of infection is highest in the first month after transplantation, and the most common pathogens are bacteria and cytomegalovirus (CMV). Bacterial infections usually occur in the first month, arise in the abdomen, and are caused by aerobes. The peak incidence of CMV infection is late in the first month and early in the second month after transplantation. CMV syndromes include fever and neutropenia, hepatitis, pneumonitis, gut ulceration, and disseminated infection. Other significant problems are Candida intraabdominal infection, Herpes simplex mucocutaneous infection or hepatitis, adenovirus hepatitis, and Pneumocystis carinii pneumonia. Prophylaxis of infection in liver transplant recipients has not been well-studied. Several different regimens of parenteral, oral absorbable, and/or oral non-absorbable antibiotics active against bacteria and yeast have been used at various centers, but no randomized controlled trials have been conducted. Selective bowel decontamination appears to be a promising approach to the prevention of bacterial and Candida infections, while oral acyclovir may be a relatively convenient and effective agent for CMV prophylaxis.

Topics: Acyclovir; Anti-Bacterial Agents; Bacterial Infections; Cytomegalovirus Infections; Humans; Infections; Liver Transplantation; Mycoses; Parasitic Diseases; Pneumonia, Pneumocystis; Postoperative Complications; Premedication; Risk Factors; Time Factors; Virus Diseases

Topics: Acyclovir; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Blood Transfusion; Bone Marrow Transplantation; Cytomegalovirus Infections; Drug Therapy, Combination; Graft vs Host Disease; Granulocytes; Herpes Simplex; Humans; Immunosuppressive Agents; Infection Control; Infections; Interferons; Intestines; Patient Isolation; Penicillins; Pneumonia; Vaccination; Viral Vaccines; Whole-Body Irradiation

Herpes simplex virus type 1 (HSV-1) is an important pathogen related to epilepsy. We have shown previously that corneal inoculation of mice with HSV-1 causes acute spontaneous behavioral and electrophysiological seizures and increases hippocampal excitability and kainite-induced seizure susceptibility. In this study, we aimed to determine whether early-life HSV-1 infection in mice might cause short- and long-term enhanced susceptibility to pentylenetetrazol (PTZ)-induced seizures and to evaluate whether early antiviral drug therapy was effectively ameliorating this deficit. Seizure threshold was calculated by the latency of onset of the myoclonic jerk, generalized clonus, and maximal tonic-clonic convulsion. We demonstrate that the localization of viral antigens was predominantly within the bilateral temporal areas (amygdala, piriform, and entorhinal cortex) of HSV-1-infected mice. We also present evidence that mice of all HSV-1-infected groups had a shorter latency and higher severity to PTZ-induced seizures than in age-matched, mock-infected controls. Treatment of HSV-1-infected mice with valacyclovir, a potent inhibitor of HSV-1 replication, produced a dose-dependent decrease in the signs of neurological deficits, pathological damages, and PTZ-induced seizure severity. Our results are consistent with the hypothesis that early-life HSV-1 infection leads to persistent enhancement of neuronal excitability in limbic circuits, which could result in an overall increased propensity to induce seizures later in life. Additionally, prompt optimal antiviral therapy effectively decreases seizure susceptibility in HSV-1-infected mice by limiting the level of viral replication and inflammatory response induced by virus. The present study provides not only experimental evidence, but also a new therapeutic strategy in HSV-1-associated human epilepsy.

Topics: Acyclovir; Animals; Antiviral Agents; Behavior, Animal; Body Weight; Disease Susceptibility; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Electromyography; Herpes Simplex; Herpesvirus 1, Human; Hippocampus; Immunohistochemistry; Infections; Male; Mice; Mice, Inbred BALB C; Pentylenetetrazole; Reaction Time; Seizures; Staining and Labeling; Time Factors; Valacyclovir; Valine; Virus Latency

Topics: Acyclovir; Bacterial Infections; Cryptococcosis; Cytomegalovirus Infections; Drug Combinations; Humans; Infection Control; Infections; Kidney Transplantation; Pneumonia, Pneumocystis; Postoperative Complications; Prognosis; Sulfamethoxazole; Toxoplasmosis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases