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Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America.

An 8-person subcommittee of the National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group evaluated available data on the treatment of cryptococcal disease. Opinion regarding optimal treatment was based on personal experience and information in the literature. The relative strength of each recommendation was graded according to the type and degree of evidence available to support the recommendation, in keeping with previously published guidelines by the Infectious Diseases Society of America (IDSA). The panel conferred in person (on 2 occasions), by conference call, and through written reviews of each draft of the manuscript. The choice of treatment for disease caused by Cryptococcus neoformans depends on both the anatomic sites of involvement and the host's immune status. For immunocompetent hosts with isolated pulmonary disease, careful observation may be warranted; in the case of symptomatic infection, indicated treatment is fluconazole, 200-400 mg/day for 36 months. For those individuals with non-CNS-isolated cryptococcemia, a positive serum cryptococcal antigen titer >1:8, or urinary tract or cutaneous disease, recommended treatment is oral azole therapy (fluconazole) for 36 months. In each case, careful assessment of the CNS is required to rule out occult meningitis. For those individuals who are unable to tolerate fluconazole, itraconazole (200-400 mg/day for 6-12 months) is an acceptable alternative. For patients with more severe disease, treatment with amphotericin B (0.5-1 mg/kg/d) may be necessary for 6-10 weeks. For otherwise healthy hosts with CNS disease, standard therapy consists of amphotericin B, 0.7-1 mg/kg/d, plus flucytosine, 100 mg/kg/d, for 6-10 weeks. An alternative to this regimen is amphotericin B (0.7-1 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 2 weeks, followed by fluconazole (400 mg/day) for a minimum of 10 weeks. Fluconazole "consolidation" therapy may be continued for as along as 6-12 months, depending on the clinical status of the patient. HIV-negative, immunocompromised hosts should be treated in the same fashion as those with CNS disease, regardless of the site of involvement. Cryptococcal disease that develops in patients with HIV infection always warrants therapy. For those patients with HIV who present with isolated pulmonary or urinary tract disease, fluconazole at 200-400 mg/d is indicated. Although the ultimate impact from highly active antiretroviral therapy (HAART) is currently unclear, it is recommended that all HIV-infected individuals continue maintenance therapy for life. Among those individuals who are unable to tolerate fluconazole, itraconazole (200-400 mg/d) is an acceptable alternative. For patients with more severe disease, a combination of fluconazole (400 mg/d) plus flucytosine (100-150 mg/d) may be used for 10 weeks, followed by fluconazole maintenance therapy. Among patients with HIV infection and cryptococcal meningitis, induction therapy with amphotericin B (0.7-1 mg/kg/d) plus flucytosine (100 mg/kg/d for 2 weeks) followed by fluconazole (400 mg/d) for a minimum of 10 weeks is the treatment of choice. After 10 weeks of therapy, the fluconazole dosage may be reduced to 200 mg/d, depending on the patient's clinical status. Fluconazole should be continued for life. An alternative regimen for AIDS-associated cryptococcal meningitis is amphotericin B (0.7-1 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 6-10 weeks, followed by fluconazole maintenance therapy. Induction therapy beginning with an azole alone is generally discouraged. Lipid formulations of amphotericin B can be substituted for amphotericin B for patients whose renal function is impaired. Fluconazole (400-800 mg/d) plus flucytosine (100-150 mg/kg/d) for 6 weeks is an alternative to the use of amphotericin B, although toxicity with this regimen is high. In all cases of cryptococcal meningitis, careful attention to the management of intracranial pressure is imperative to assure optimal c

AIDS-Related Opportunistic Infections↗

Evaluation of new anti-infective drugs for the treatment of acute pelvic inflammatory disease. Infectious Diseases Society of America and the Food and Drug Administration.

Pelvic inflammatory disease (PID) is a syndrome unrelated to pregnancy or surgery and characterized by lower abdominal pain and tenderness, cervical motion tenderness, and adnexal tenderness. Fever, leukocytosis, and the results of laboratory tests are used to support the diagnosis. Participants in clinical trials should be stratified into two groups: those with and those without tubo-ovarian abscess--i.e., those with complicated and those with uncomplicated PID. Diagnostic studies and treatment should be directed at four major groups of pathogens: Neisseria gonorrhoeae, Chlamydia trachomatis, anaerobic bacteria, and facultative bacteria such as Escherichia coli. Women requiring hospitalization should generally be treated as inpatients for at least 4-7 days; outpatient therapy should then be instituted to complete a 14- to 21-day course. Clinical and laboratory evaluations should be conducted daily during hospitalization and both 2-4 days and 2-4 weeks after the completion of therapy.

Acute Disease↗

Special issues in clinical trials of new anti-infective drugs for the treatment of sexually transmitted diseases. Infectious Diseases Society of America and the Food and Drug Administration.

Several special issues arise in relation to clinical trials of therapy for sexually transmitted diseases. These issues include the desirability of including adolescents and both pregnant and nonpregnant women in the trial, the use of unapproved control regimens, problems with antimicrobial susceptibility testing due to inadequate methodology and the need for prompt treatment, the need to assess agents for treatment of syndromes of unknown microbial etiology, toxicity considerations related to the use of single-dose regimens, management of the sexual partners of the participants in the trial, analysis of data despite the high frequency of minor protocol violations, sexual reexposure to infection during the trial, and the potential for loss, alteration, or falsification of data because of the relative simplicity of the usual protocol design and the diagnostic reliance on specimens that are routinely discarded.

Adolescent↗

[Childhood diseases, infectious diseases, and fever as potential risk factors for cancer?].

OBJECTIVE: We investigated the assertion that past childhood diseases, acute and febrile infections as well as allergies have a preventive effect on cancer. Former studies on this topic show controversial results and methodical deficits. PATIENTS AND METHODS The investigation was conducted as a retrospective case control study with 111 cancer patients and a group of 109 control persons from 3 hospitals in Berlin. RESULTS: A significant change in the risk of developing cancer could only be observed for mumps (OR = 2.6; increased risk), whooping cough (OR = 2.7; increased risk), and colds in the recent past (OR = 0.7; decreased risk). Fever within the last 5 years showed no association with the development of malign tumors. CONCLUSION: We could not confirm the results of former studies which assumed a preventive effect of childhood diseases and fever on the cancer risk. On the contrary, on the basis of this investigation one might postulate a 2- to 3-fold rise of the cancer risk by mumps or whooping cough. Because of divergent study results, deficits in the study designs, and a low evidence of the present findings no final statement on the association between childhood diseases or fever and cancer should be made.

Adult↗

Prevalence and relationship between allergic diseases and infectious diseases.

In order to determine the prevalence of childhood allergic diseases, infectious diseases, and the relationship between them, 8723 children from three junior high schools in Tou-Cheng City, Taipei County, were studied using questionnaires developed according to the International Study of Asthma and Allergies in Childhood (ISAAC) criteria combined with supplementary questions about infectious diseases. Students and their parents completed the questionnaires at home. The age of the children ranged from 10 to 18 years old (14.12 +/- 0.89 years), the majority (96.03%) was aged from 13 to 15 years old. The 12-month prevalences of self-reported allergic disease symptoms were: asthma symptom 8.2%, allergic rhinitis symptom 39.6%, and atopic dermatitis symptom 5.9%. The prevalences of diagnosis of the allergic diseases were: asthma 8.7%, allergic rhinitis 24.1%, and atopic dermatitis 3.9%. The 12-month prevalences of diagnosis of infectious diseases were: pneumonia 0.6%, bronchitis 7.2%, sinusitis 7.2%, purulent conjunctivitis 2.5%, otitis media 4.3%, encephalitis or meningitis 0.4%, gastroenteritis 14.5%, acne 23.9%, purulent dermatitis 1.3%, and other infectious diseases 1.2%. Lifetime admission rates of children due to infectious diseases were: pneumonia 1%, bronchitis 1.8%, sinusitis 0.3%, purulent conjunctivitis 0.2%, otitis media 0.3%, encephalitis or meningitis 0.3%, gastroenteritis 2.1%, and other infectious diseases 0.6%. The prevalence of infectious diseases was significantly higher in children with allergic disease symptoms (defined as asthma, allergic rhinitis, or atopic dermatitis). These results demonstrated the presence of a link between allergic diseases and infectious diseases, which may have some important clinical implications.

Adolescent↗

Structural predestination of individual diversity in the course and severity of infectious diseases.

Infectious diseases can be manifested by a spectrum of clinical signs and resultant clinical courses that range from acute to chronic and possible persistence in the victim in a latent form. Until recently, the origins of this kind of biodiversity were poorly understood, but advances in immunology--especially in identifying the constitutional mechanisms of immunity--have contributed to our understanding of the origins of biodiversity in infectious diseases. Infectious diseases affect only focal areas in the affected organisms, and the amounts and distribution of infectious lesions vary from patient to patient. In a population attacked by an infectious agent, individuals can be conveniently divided into three categories: totally resistant organisms which contain no susceptible structures and are not affected; mildly susceptible organisms in which a few foci appear and in which the infection runs a benign course; organisms in which the number of constitutionally susceptible structures is high and the infectious process develops in a severe form. The diversity is determined by the differences in susceptibility of various parts of the organism under consideration.

Aging↗

[Future prospects of the specialty of infectious diseases].

Infectious diseases were established as a subspecialty of internal medicine in Denmark in 1982. Ten permanent senior positions in Danish hospitals are at present held by specialists in infectious diseases. Simultaneously, seven specialists in infectious diseases employed in junior positions are qualified for senior positions. This number will increase to 15 by 1995. It is concluded that: 1. There is a serious imbalance in the specialty of infectious diseases between the number of senior positions available and the number of qualified specialists. 2. The reluctance on the part of hospital administrators to create new positions in the specialty of infectious diseases cannot be based on the fear of the lack of qualified applicants.

Clinical Competence↗

Medication use and potential drug interactions in pediatric patients with infectious diseases.

Infectious diseases are the most common type of illness in pediatric patients. Limited data are available, however, about the most frequently prescribed drugs for children in pediatric infectious diseases units. The authors prospectively evaluated medication records of 493 children over a 5-month period to determine the pattern of drug prescribing and incidence of potential drug interactions in children admitted to the infectious diseases unit in a pediatric hospital. Antimicrobial agents were the most frequently prescribed class of drugs, comprising 60% of all drug orders. Of all antibiotics used during this period, ampicillin was the most common (24% of antibiotic orders). Ceftriaxone, cefuroxime, and gentamicin were also used frequently and consisted of 15%, 10%, and 14% of all orders for anti-infective agents, respectively. Other classes of drugs frequently given to patients on the infectious disease unit were antipyretics (14%), bronchodilators (10%), and anticonvulsants (7%). The incidence of potential drug interactions was 3.5%, the majority involving anticonvulsants. A clinically significant drug interaction was not documented in any of these cases. Observations made from this study may assist in developing clinical pharmacy services and educational programs for pharmacy students. In addition, knowledge of drug use patterns may aid in conducting antibiotic use reviews.

Adolescent↗

Combined somatic and psychiatric care--effects on personnel treating drug addicts with infectious diseases.

Infectious disease care, psychiatric care of drug addicts, and social care were combined in a ward for drug addicts with infectious diseases. The aim of this study was to evaluate the effects on the personnel (n = 22). One ward with infectious disease care of HIV and AIDS patients (n = 24) and another with nonsomatic care of drug addicts (n = 18) were selected to make comparisons possible. The questionnaire concerned psychosocial work environment and health. The personnel at the new ward also participated in a semistructured interview. The personnel at the special ward experienced a significantly higher degree of emotional exhaustion and lack of ability to concentrate than the comparison groups. They also reported a higher degree of lack of clarity, more job strain, and more difficulties due to demands from patients. The combined care is probably associated with heavier psychological burdens than other forms of care. In spite of this, the personnel experienced their work as meaningful and mentally stimulating.

AIDS-Related Opportunistic Infections↗

Use of granulocyte colony-stimulating factor in the treatment of acute infectious diseases.

Infectious diseases continue to be a major cause of morbidity and mortality in the United States. Novel strategies directed at amplifying critical components of the host's immune system may be one potential adjuvant therapy. To date, studies with granulocyte colony-stimulating factor (G-CSF) treatment have demonstrated favorable results, decreasing both morbidity and mortality in a variety of infectious disease models in non-neutropenic hosts. The recent completion of two clinical trials has also provided supportive data that G-CSF is effective in patients with serious infections. Most important, G-CSF does not produce any adverse consequences, which were of concern to some because of the capacity of G-CSF to enhance neutrophil production and function. This review focuses on current data suggesting that augmentation of the immune system with G-CSF is a promising new approach to adjuvant therapy in infectious diseases.

Acute Disease↗

New and emerging therapies in infectious diseases.

Infectious diseases account for one-third of all deaths worldwide. The last decade has yielded significant advances in the treatment of infectious skin diseases. This article highlights emerging therapies for viral, fungal, bacterial, and parasitic skin cutaneous infections.

Anthelmintics↗

Immunosenescence and infectious diseases.

Infectious diseases are major causes, with malignancies, of morbidity and mortality in the elderly. Increased susceptibility to infections may result from underlying dysfunction of an aged immune system; moreover, inappropriate immunologic functions associated with aging can determine an insufficient response to vaccines. Impairments of cellular, humoral and innate immunity in the elderly, contributing to increased incidence of infectious diseases, are discussed in this review.

Aging↗