PubMed Health⌕ Search

Biomedical subjects

S Safrin

Publications and source records attributed to S Safrin.

At least 55 records · Page 3Linked to original sources
PubMed1992

Interactions and toxicities of drugs used in patients with AIDS.

As clinicians have come to realize, patients who have AIDS are uniquely predisposed to drug-associated toxic effects and allergic reactions. In San Francisco General Hospital's first clinical trial involving patients with pneumonia due to Pneumocystis carinii, only one-third of all patients who were treated initially with either trimethoprim-sulfamethoxazole or pentamidine were able to complete the 3-week course. Because of drug-related toxic effects, most patients required an alteration in therapy. In addition, with the multi-drug approach to management of infection due to human immunodeficiency virus (HIV) and its complications, drug-drug interactions commonly complicate the pharmacokinetics and toxicities of the therapeutic agents used. Both factors make caring for HIV-infected patients a complicated and perplexing process for the clinician. We've invited Drs. Belle Lee and Sharon Safrin of the University of California, San Francisco School of Medicine to contribute the AIDS Commentary this month. Drs. Lee and Safrin are active investigators in the field of pharmacokinetics and conduct clinical trials of agents used in the treatment of patients who have AIDS. In this commentary, they review what is known about the complexities involved in treating patients with AIDS and offer some practical suggestions for management.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Comparison of the Western immunoblot assay and a glycoprotein G enzyme immunoassay for detection of serum antibodies to herpes simplex virus type 2 in patients with AIDS.

Herpes simplex virus type 2 (HSV-2) seroprevalence in 68 patients with AIDS was 77% by Western blot (immunoblot) and 44% by glycoprotein G-2 immunoassay. Each of 16 patients with culture-proven HSV-2 infection was positive by Western blot versus 8 by glycoprotein G-2 immunoassay. No differences in age, race, duration of AIDS, acyclovir usage, or HSV-1 seroprevalence were found to explain differences in sensitivity.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Treatment of acyclovir-resistant herpes simplex virus infections in patients with AIDS.

Resistance to acyclovir in vitro in herpes simplex virus (HSV) isolates has been associated with failure of acyclovir therapy in immunosuppressed patients, and the frequency of reports of clinical resistance in patients with human immunodeficiency virus (HIV) infection is increasing. The primary mechanism of clinical resistance is mutation, producing deficiency in the virus-specified thymidine kinase. A number of case reports and patient series have suggested the efficacy of foscarnet in the treatment of acyclovir-resistant HSV infection in HIV-infected patients. In a recent AIDS Clinical Trials Group study comparing the efficacy of vidarabine and foscarnet in this indication, foscarnet therapy was found to be associated with statistically significant reductions in time to complete healing of lesions, cessation of viral shedding, and 50% reduction in pain, and all patients randomized to receive foscarnet had complete re-epithelialization of lesions. The majority of initial recurrences of herpetic lesions in patients in this study were susceptible to acyclovir; however, all patients ultimately experienced a recurrence due to acyclovir-resistant HSV. A trial comparing acyclovir suppression, foscarnet maintenance therapy, and no chronic antiviral therapy after successful initial treatment of acyclovir-resistant HSV infection would be useful in defining the optimal management of recurrent disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.

BACKGROUND AND METHODS: Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine. RESULTS: The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued. CONCLUSIONS: For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Foscarnet therapy in five patients with AIDS and acyclovir-resistant varicella-zoster virus infection.

OBJECTIVE: To determine whether foscarnet has potential efficacy in the treatment of acyclovir-resistant mucocutaneous varicella-zoster infection in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Open-label study. SETTING: Three university medical centers. PATIENTS: Five patients with AIDS who were infected with thymidine-kinase-deficient or -altered strains of varicella-zoster virus. INTERVENTION: Foscarnet, 40 mg/kg body weight every 8 hours in 1-hour infusions for 10 or more days. MAIN RESULTS: Four patients had healing in response to foscarnet therapy, and each of four tested patients became culture negative for virus during foscarnet therapy. Results of fluorescent antigen testing remained positive during therapy in two patients; one of these patients had concomitant clinical failure but the other patient healed fully. One patient had complete healing despite the emergence of resistance to foscarnet in serial specimens obtained during foscarnet therapy. CONCLUSION: Foscarnet is a potentially effective and tolerable antiviral agent for patients with acyclovir-resistant, varicella-zoster virus infection; however, the optimal dosage and duration of therapy require further study, as does the relation between clinical findings and in-vitro susceptibility results.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Clinical and serologic features of herpes simplex virus infection in patients with AIDS.

We studied the natural history of herpes simplex virus (HSV) infection and its association with specific serum antibody in a sample of 68 HIV-infected patients with a first episode of Pneumocystis carinii pneumonia at San Francisco General Hospital in 1986. Seroprevalence was 66 and 77% for HSV-1 and HSV-2 antibody, respectively, by immunoblot assay. Twenty-seven patients had 45 HSV outbreaks diagnosed during 739 patient-months of follow-up. Median frequency of recurrence resulting in a medical visit was once every 6.5 months, and median duration of treated outbreak was 10 days. Fourteen of 48 evaluable patients seropositive for HSV-2 had no outbreak of HSV during a median follow-up of 7.5 months. Our data suggests that neither frequency nor severity of HSV were substantially increased in this group of patients, despite severe immunosuppression caused by HIV. However, validation of these results by a prospective study is required.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Dapsone as a single agent is suboptimal therapy for Pneumocystis carinii pneumonia.

In a prospective, noncomparative study, seven patients with mild Pneumocystis carinii pneumonia, characterized by room air arterial PO2 greater than 60 mm Hg at the time of presentation, were treated with dapsone alone at a dose of 200 mg daily. Two of the seven patients required mechanical ventilation for respiratory failure on day 5 of dapsone therapy; both died. Four patients experienced major side effects during dapsone therapy. None of the seven patients successfully completed a full course of therapy with dapsone. We conclude that high-dose, single-agent dapsone is not suitable for further study as therapy for Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Foscarnet therapy for acyclovir-resistant mucocutaneous herpes simplex virus infection in 26 AIDS patients: preliminary data.

Mucocutaneous herpes simplex virus (HSV) infections that are resistant to therapy with acyclovir have been recognized with increasing frequency in patients with the acquired immunodeficiency syndrome, although alternative therapies in this setting have not been widely studied. Twenty-six consecutive patients are reported with human immunodeficiency virus infection, who received foscarnet therapy for acyclovir-resistant HSV. Clinical response was noted in 81% of patients; complete reepithelialization of HSV lesions occurred in 73%. Cessation of viral shedding was documented in all of the 11 patients who were recultured. Although adverse effects were frequent, in only 3 patients (12%) did toxicity necessitate discontinuation of therapy. Before foscarnet therapy, 14 patients received vidarabine for acyclovir-resistant HSV. The infection did not resolve in any of the vidarabine-treated patients, and therapy was discontinued in 4 (29%) due to toxicity.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Influenza in patients with human immunodeficiency virus infection.

Although patients infected with human immunodeficiency virus (HIV) might be expected to have more severe illness due to influenza virus infection than normal persons, the course of influenza in such patients has not been well delineated. We describe six consecutive HIV-infected patients at San Francisco General Hospital in whom influenza virus was isolated from induced sputum or bronchoalveolar lavage specimens between December 1988 and March 1989. Although neither clinical presentation of influenza nor rate of secondary complications appeared to be altered from that in healthy individuals, our power of comparison was limited by small sample size. However, a high prevalence of hypoxemia and a trend toward prolonged duration of illness were identified. Larger, controlled studies are needed to define the course of influenza virus infection in HIV-infected patients as compared with nonimmunosuppressed patients.

Adult↗
PubMed1990

Extrapulmonary pneumocystosis: clinical features in human immunodeficiency virus infection.

Pneumocystis carinii infection is reported with increasing frequency as a cause of disease outside of the respiratory tract in patients with human immunodeficiency virus (HIV) infection. Extrapulmonary pneumocystosis is not limited to patients in any discrete risk group for HIV infection. Patients with HIV infection who develop extrapulmonary pneumocystosis frequently do not have concurrent P. carinii pneumonia. Signs and symptoms of extrapulmonary pneumocystosis are nonspecific but when present are frequently referable to the tissues or organs involved. Extrapulmonary pneumocystosis can be diagnosed by examination of tissue biopsies from affected sites using standard histologic techniques. Therapy with antimicrobial agents used to treat P. carinii pneumonia has been effective in some patients. An association between use of aerosolized pentamidine for prevention of P. carinii pneumonia and development of extrapulmonary pneumocystosis has been suggested but remains unconfirmed. Other factors such as the use of zidovudine and duration of immunodeficiency may also be important to the pathogenesis of extrapulmonary pneumocystosis. Further studies are needed to better identify risk factors that may predispose patients to the development of extrapulmonary pneumocystosis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Seroprevalence and epidemiologic correlates of human immunodeficiency virus infection in women with acute pelvic inflammatory disease.

As the number of women with acquired immunodeficiency syndrome (AIDS) continues to rise in the United States, it becomes important to target preventive interventions as effectively as possible toward those groups at highest risk of acquiring human immunodeficiency virus (HIV) infection. We analyzed the prevalence of serum antibody to HIV in 333 women admitted to the Gynecology Service at San Francisco General Hospital with acute pelvic inflammatory disease in the years 1985-1988. The proportion of women with HIV infection in our sample rose incrementally over this 4-year period, from 0 to 6.7%. A history of intravenous (IV) drug use conferred a 23-fold risk of HIV seropositivity. In contrast, markers of the level of sexual activity did not correlate significantly with the presence of HIV infection, although the power to detect such an association was limited by the small sample size. An intensification of educational efforts directed at IV drug-using women in San Francisco is necessary to prevent further increases in the rate of HIV infection and further spread into the heterosexual population.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Foscarnet therapy for severe acyclovir-resistant herpes simplex virus type-2 infections in patients with the acquired immunodeficiency syndrome (AIDS). An uncontrolled trial.

STUDY OBJECTIVE: To determine whether trisodium phosphonoformate (foscarnet) is efficacious in treating severe mucocutaneous disease due to acyclovir-resistant herpes simplex virus type-2 (HSV-2) infection in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Open-labeled drug administration to patients with AIDS and severe ulcerative disease due to acyclovir-resistant HSV-2 infection. SETTING: Medical floors of acute care hospital. PATIENTS: Four patients with AIDS who developed progressive ulcerative mucocutaneous lesions of the genitals, perineum, perianal region, or finger due to acyclovir-resistant, thymidine-kinase (TK)-negative strains of HSV-2. INTERVENTION: Foscarnet, 60 mg/kg body weight intravenously every 8 hours (with reduced dosage for renal impairment), for 12 to 50 days. MEASUREMENT AND MAIN RESULTS: All patients receiving foscarnet had dramatic improvement in their clinical findings with marked clearing of mucocutaneous lesions and eradication of HSV from mucosal surfaces. CONCLUSION: Foscarnet may be an effective treatment for severe mucocutaneous disease due to acyclovir-resistant, TK-negative strains of HSV-2.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Pyelonephritis in adult women: inpatient versus outpatient therapy.

PURPOSE: The traditional treatment of acute pyelonephritis has been hospitalization and parenteral administration of antibiotics. No previous study, however, has attempted to differentiate between those patients with pyelonephritis who might be safely managed as outpatients and those in whom hospitalization is required. We therefore decided to determine whether women with pyelonephritis can be effectively and safely managed outside the hospital. PATIENTS AND METHODS: The medical records of 94 female outpatients and 100 hospitalized women treated for acute pyelonephritis at San Francisco General Hospital were reviewed. Utilizing baseline clinical and laboratory data, we compared outcome in the two groups, and computed the cost-benefit of managing pyelonephritis on an outpatient basis. RESULTS: We observed a similarity in the frequency of successful outcomes (approximately 90 percent in each group) and absence of serious adverse outcome in any outpatient. Results of urine culture were comparable in inpatients and outpatients, with Escherichia coli identified as the most common urinary pathogen in both groups. The frequency of resistance to ampicillin of E. coli and other urinary pathogens was nearly 30 percent. A cost analysis demonstrated a 7.5-fold difference between the inpatient and outpatient groups. CONCLUSION: Our findings suggest that treatment of pyelonephritis with oral antibiotics poses a safe and effective method of therapy in immunocompetent women without underlying illness. The use of ampicillin as a single agent for the treatment of pyelonephritis, however, is inadvisable. Our study also demonstrates the potential savings in managing selected patients with pyelonephritis as outpatients.

Acute Disease↗
PubMedDate not supplied

Non-O:1 Vibrio cholerae bacteremia: case report and review.

A case of non-O:1 Vibrio cholerae bacteremia and prostatic abscess in a patient with idiopathic aplastic anemia was studied, and the data were compared with those from 23 previously reported cases of non-O:1 V. cholerae bacteremia. The case-fatality rate for the 13 cases for which the outcome is known is 61.5%. The majority of known cases have occurred in immunocompromised patients, particularly those with hematologic malignancy or cirrhosis. Host susceptibility is potentially important in this condition. Bacterial products such as a cholera-like toxin and El Tor hemolysin also may play a role in the disease process. The incidence of enteritis due to non-O:1 V. cholerae is unclear because of the methods used for routine stool culture; however, the small number of reported isolates from blood is likely to reflect the infrequency of bacteremia, since Vibrio species are readily identifiable on sheep blood agar. While non-O:1 V. cholerae is sensitive to most antibiotics in vitro, no data are available on antibiotic efficacy.

Abscess↗