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Biomedical subjects

S Safrin

Publications and source records attributed to S Safrin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cost and outcome of intensive care for patients with AIDS, Pneumocystis carinii pneumonia, and severe respiratory failure.

OBJECTIVE: To determine the costs and outcomes associated with intensive care unit (ICU) admission for patients with acquired immunodeficiency syndrome (AIDS)-related Pneumocystis carinii pneumonia (PCP), and severe respiratory failure. DESIGN: Survival and cost-effectiveness analysis. SETTING: A large municipal teaching hospital serving an indigent population. PATIENTS: Consecutive patients intubated and mechanically ventilated for AIDS, PCP, and respiratory failure from 1981 through 1991 (n = 113). The cohort was separated into three groups for analysis: patients admitted to the ICU in 1981 through 1985 (era I, n = 43), those admitted in 1986 through 1988 (era II, n = 33), and those admitted in 1989 through 1991 (era III, n = 37). MAIN OUTCOME MEASURES: Hospital charges and survival time; cost per year of life saved, using a zero-cost, zero-life assumption. RESULTS: Twenty-eight (25%) of the 113 patients mechanically ventilated for PCP and respiratory failure survived to hospital discharge: six (14%) of 43 in era I, 13 (39%) of 33 in era II, and nine (24%) of 37 in era III (P = .04). Post-ICU admission charges averaged $57,874 for the entire cohort, remaining relatively stable across the three eras. Cost of care for survivors was significantly more expensive than for those dying before discharge. The cost of ICU admission and subsequent hospitalization averaged $174,781 per year of life saved; $305,795 in era I, $94,528 in era II, and $215,233 in era III. Improved survival rates and shorter lengths of ICU stay led to the improved cost-effectiveness in era II, while the opposite trends resulted in worsening cost-effectiveness in recent years. The strongest predictors of hospital mortality in era III were low CD4 cell counts on hospital admission and the development of pneumothorax during mechanical ventilation. CONCLUSIONS: The cost-effectiveness of intensive care for patients with PCP and severe respiratory failure improved during the first 8 years of the AIDS epidemic but fell in recent years such that it is now below that of many accepted medical interventions.

AIDS-Related Opportunistic Infections↗
PubMed1995

A comparative evaluation of three methods of antiviral susceptibility testing of clinical herpes simplex virus isolates.

BACKGROUND: Current methods of antiviral susceptibility testing for herpes simplex virus (HSV) are poorly standardized and have rarely been compared critically. OBJECTIVES: To compare the three most commonly utilized HSV susceptibility assays for accuracy of result, method of implementation, and time required. STUDY DESIGN: We compared susceptibility results for acyclovir and foscarnet using the plaque reduction, dye uptake and DNA hybridization assays in 30 patient isolates of HSV, of varying susceptibility pattern. Compared parameters included: values for ID(50) (the concentration of drug required to inhibit virus growth by 50% or more), ratio of ID(90) to ID(50), and correlation of susceptibility result with clinical response to antiviral therapy, when available. In addition, we compared ease of the assay, presence of objective endpoint, time required to generate the susceptibility result, and necessary equipment for implementation. RESULTS: The dye uptake yielded ID(50) results that were approximately two-fold greater than those from the plaque reduction assay, while ID(50) values from the DNA hybridization assay were one-half those from the plaque reduction assay. Comparison of the correlation of susceptibility result with clinical response to acyclovir therapy in 17 instances and to foscarnet therapy in 10 instances suggested the possibility of a somewhat greater discriminative ability of the dye uptake assay, and a somewhat lesser discriminative ability of the DNA hybridization assay, when compared with results from the plaque reduction assay in isolates with borderline acyclovir susceptibility. CONCLUSIONS: Larger comparative studies are necessary to further differences in discriminative ability of the three assays for HSV. All three assays were deemed suboptimal due to an overly long turnaround time, associated expense, and/or level of equipment required for their performance. Continued evaluation of alternative, more rapid assays is therefore warranted.

Journal Article↗
PubMed1994

Treatment of acyclovir-unresponsive cutaneous herpes simplex virus infection with topically applied SP-303.

The naturally occurring polyphenolic biopolymer SP-303 has in vitro activity against both HSV-1 and HSV-2, including strains that are resistant to acyclovir. Nine AIDS patients with acyclovir-unresponsive mucocutaneous herpes simplex virus infection were treated with thrice daily topical SP-303T ointment in an open-label pilot study. Although a transient decrease in lesion size was observed in 4 patients during study drug therapy, and 3 patients sustained a quantitative decrease in virus burden, neither complete healing nor cessation of virus shedding occurred in any patient. Seven patients complained of pain or burning upon application of the study ointment, causing 1 patient to terminate the study. In summary, application of SP-303T ointment effected no significant improvement in the clinical course of 9 AIDS patients with acyclovir-unresponsive HSV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The hydroxylamine of sulfamethoxazole and adverse reactions in patients with acquired immunodeficiency syndrome.

We measured the urine concentrations of sulfamethoxazole, sulfamethoxazole hydroxylamine, and N-sulfamethoxazole on days 3 and 10 in 15 patients with acquired immunodeficiency syndrome treated with a combination product of trimethoprim (15 mg/kg/day) and sulfamethoxazole (75 mg/kg/day). The percentage of sulfamethoxazole and metabolites excreted on days 3 and 10, respectively, were sulfamethoxazole 17.2% +/- 11.3% versus 15.6% +/- 8.2%; sulfamethoxazole hydroxylamine 2.6% +/- 2.0% versus 5.0% +/- 5.2% (p < 0.05); N-acetylsulfamethoxazole 80.0% +/- 12.9% versus 79.8% +/- 11.8%. The percentage of sulfamethoxazole hydroxylamine excreted was similar between the eight patients who discontinued therapy because of toxicity and the seven patients who did not (2.9% +/- 2.3% versus 2.3% +/- 2.0%, p = 0.7). In two patients who had major liver toxicity the percentage of sulfamethoxazole hydroxylamine excreted was significantly lower than that of the 13 patients who did not (0.8% +/- 0.1% versus 2.9% +/- 2.0%, p < 0.05). This is the first report of the formation and excretion of sulfamethoxazole hydroxylamine in patients with acquired immunodeficiency syndrome. With 15 patients we were unable to show a significant correlation between the percentage of sulfamethoxazole hydroxylamine excreted and adverse reactions. However, patients with liver toxicity excreted less sulfamethoxazole hydroxylamine.

AIDS-Related Opportunistic Infections↗
PubMed1994

Clindamycin and primaquine therapy for mild-to-moderate episodes of Pneumocystis carinii pneumonia in patients with AIDS: AIDS Clinical Trials Group 044.

The objective of this prospective, noncomparative study was to assess the safety and efficacy of clindamycin and primaquine therapy for mild-to-moderate pneumocystis pneumonia (defined as a difference of < 40 mm Hg between the alveolar and the arterial oxygen determinations) in patients with AIDS. In the first part of the study, 22 patients were treated with iv clindamycin (900 mg every 8 hours) for the first 10 days, and then their therapy was switched to oral clindamycin (450 mg every 6 hours) for an additional 11 days. In the second part of the study, 38 patients were treated entirely with oral clindamycin (600 mg every 8 hours). All patients were treated with oral primaquine base (30 mg once daily). Fifty-five (92%) of 60 patients responded to the study treatment. Forty-six (77%) of 60 patients completed a full course of therapy. Of the nine patients with treatment-limiting toxic effects, four had only a mild rash. This study indicates that the combination of clindamycin and primaquine is an effective and well-tolerated therapy for mild-to-moderate pneumocystis pneumonia in patients with AIDS. Entirely oral therapy appears to be as effective as initial therapy with iv clindamycin.

AIDS-Related Opportunistic Infections↗
PubMed1994

Foscarnet-resistant herpes simplex virus infection in patients with AIDS.

Six human immunodeficiency virus-infected patients had clinical lesions of herpes simplex virus (HSV) type 2 that showed in vitro resistance to foscarnet. In each patient, lesions were unresponsive to foscarnet therapy or developed during daily suppressive foscarnet. Five patients had a history of intermittent or chronic foscarnet use for the management of acyclovir-resistant HSV infection, and 1 was receiving daily foscarnet for suppression of cytomegalovirus retinitis. Seven of 10 foscarnet-resistant isolates from 6 patients were susceptible to acyclovir in vitro, and 1 was of borderline susceptibility. In 3 patients, the administration of acyclovir, either alone or in combination with foscarnet, resulted in healing. Clinically significant resistance to foscarnet may occur in immunosuppressed patients with prior foscarnet exposure. Addition or substitution of acyclovir to foscarnet therapy may be a useful strategy for patients in whom foscarnet resistance is suspected, pending the results of in vitro susceptibility testing.

AIDS-Related Opportunistic Infections↗
PubMed1994

A rapid screen test for in vitro susceptibility of clinical herpes simplex virus isolates.

A rapid screening test for antiviral susceptibility to acyclovir and foscarnet was evaluated in 320 herpes simplex virus (HSV) isolates from 197 patients. Of the isolates tested (16% HSV-1, 84% HSV-2), 60% were resistant in vitro to acyclovir and 5% were resistant to foscarnet using the plaque reduction assay. The rapid screening test, requiring only 3 days to yield a preliminary susceptibility result, was highly associated with the results of the plaque reduction assay for acyclovir and foscarnet (P < or = .001 for each) and with the clinical response to antiviral therapy (P < .001, P = .001, respectively).

Acyclovir↗
PubMed1994

Treatment with intravenous (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]-cytosine of acyclovir-resistant mucocutaneous infection with herpes simplex virus in a patient with AIDS.

(S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is a nucleotide analogue with potent in vitro and in vivo activity against a broad range of herpesviruses, including acyclovir-resistant herpes simplex virus (HSV). A patient with severe acyclovir-resistant perineal HSV infection received intravenous HPMPC at 5 mg/kg/week, with concomitant oral probenecid and prehydration, and had 95% healing after four infusions. The patient developed a hypersensitivity reaction to probenecid and discontinued HPMPC after the fourth infusion. Recurrence of the perineal lesions 2 weeks later prompted initiation of an oral desensitization program to probenecid and enabled the patient to resume therapy. The lesions again responded to infusions of HPMPC, but the drug was discontinued before complete healing because of transient nephrotoxicity (proteinuria, 2+; creatinine, 1.7 mg/dL). HPMPC is a potent antiviral agent that holds promise as a potential treatment for acyclovir-resistant HSV infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death.

Ninety-two AIDS patients with Pneumocystis carinii pneumonia (PCP) were randomized to receive folinic acid or matching placebo in conjunction with trimethoprim-sulfamethoxazole in a prospective, double-blind trial. Neither frequency of dose-limiting toxicity (26% vs. 37%; P = .4) nor time to occurrence (P = .7) was associated with folinic acid use. Although incidence of neutropenia was lower in patients receiving folinic acid (23% vs. 47%; P = .03), time to occurrence of neutropenia did not differ (P = .4). Seven (7.6%) of 92 patients with confirmed PCP met criteria for therapeutic failure, and 5 (6%) died during therapy. Surprisingly, folinic acid use was associated with a higher rate of both therapeutic failure (15% vs. 0; P = .01) and death (11% vs. 0; P = .06). Time to therapeutic failure was shorter and probability of death greater in patients receiving folinic acid (P = .005, P = .02, respectively), even when adjusted for baseline arterial oxygen pressure, serum lactate dehydrogenase, respiratory rate, CD4 cell count, and peak serum level of trimethoprim or sulfamethoxazole.

AIDS-Related Opportunistic Infections↗
PubMed1994

Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility result for isolates of herpes simplex virus from human immunodeficiency virus-infected patients.

In vitro susceptibility testing of herpes simplex virus (HSV) isolates will play an increasingly important role in guiding the clinical management of immunocompromised hosts who have lesions that are poorly responsive to therapy with standard antiviral agents. We assessed the correlation between the in vitro susceptibility result using a plaque reduction assay in Vero cells and the response to antiviral therapy with acyclovir or foscarnet for 243 clinical isolates of HSV collected from 115 human immunodeficiency virus-infected patients. The in vitro results and clinical responses were highly associated for both acyclovir and foscarnet (P < 0.001 and P < 0.001, respectively). The predictive values of a susceptible result (50% effective concentrations, < 2 micrograms/ml for acyclovir and < 100 micrograms/ml for foscarnet) for complete healing of lesions were 62% for acyclovir and 82% for foscarnet; the predictive values of a resistant result for failure to heal were 95% for acyclovir and 88% for foscarnet. Thus, in vitro testing has clinical utility in guiding therapy, although the 1 to 2 weeks required to derive a definitive result by the plaque reduction assay is a major limitation.

Acyclovir↗
PubMed1994

Management of acyclovir-resistant herpes simplex and varicella-zoster virus infections.

Persons with AIDS who have CD4+ counts < or = 100 and transplant patients, especially bone marrow allograft recipients, may experience clinically significant infections with acyclovir-resistant herpes simplex virus (HSV) or varicella-zoster virus (VZV). Patients who have received prior repeated acyclovir treatment appear to be at the highest risk of harboring acyclovir-resistant strains. Algorithms for the management of these infections were developed at a recent roundtable symposium. The consensus of the panelists was that treatment with foscarnet should be initiated within 7-10 days in patients suspected to have acyclovir-resistant HSV or VZV infections. Foscarnet therapy should be continued for at least 10 days or until lesions are completely healed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS.

BACKGROUND: Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii. METHODS: We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg). RESULTS: Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group. CONCLUSIONS: For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.

AIDS-Related Opportunistic Infections↗
PubMed1993

Potential for combined therapy with 348U87, a ribonucleotide reductase inhibitor, and acyclovir as treatment for acyclovir-resistant herpes simplex virus infection.

Inhibitors of the ribonucleotide reductase of herpes simplex viruses (HSV) potentiate the activity of acyclovir in vitro and in animal studies. In addition, the combination of the ribonucleotide reductase inhibitor 348U87 and acyclovir has synergistic therapeutic effects against infections in mice due to thymidine kinase-deficient, thymidine kinase-altered, and DNA polymerase mutants of HSV. We performed a pilot study of topical combination therapy with 348U87 (3%) and acyclovir (5%) cream for acyclovir-resistant, anogenital HSV infections in ten human immunodeficiency virus (HIV)-infected patients. Our results, with lack of complete reepitheliazation of lesions in all patients and poor virologic response, suggest that this therapy is unlikely to be useful for this indication.

Acyclovir↗
PubMed1993

In vitro activity of penciclovir against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes simplex virus.

We tested 23 clinical isolates of acyclovir-susceptible, acyclovir-resistant, and foscarnet-resistant herpes simplex virus for susceptibility to penciclovir. Isolates showed cross-resistance to penciclovir and acyclovir, but penciclovir retained a relative activity against foscarnet-resistant isolates. Its clinical utility for the treatment of resistant herpes simplex virus infections remains to be studied.

Acyclovir↗
PubMed1993

Topical treatment of infection with acyclovir-resistant mucocutaneous herpes simplex virus with the ribonucleotide reductase inhibitor 348U87 in combination with acyclovir.

The thiocarbonohydrazone 348U87 inactivates herpes simplex virus ribonucleotide reductase and potentiates the activity of acyclovir against wild-type and acyclovir-resistant strains of herpes simplex virus. We treated 10 human immunodeficiency virus-infected patients with acyclovir-resistant anogenital herpes simplex virus infection with a topical preparation of 348U87 (3%) in combination with acyclovir (5%) in an open-labelled study. Transient improvement with combination therapy occurred frequently; however, target lesions reepithelialized completely in only 1 of 10 patients. Termination of study drug therapy was most often due to cessation of therapeutic effect before complete resolution of lesions. As currently formulated, topical 348U87 offers little therapeutic benefit for this indication.

Acyclovir↗
PubMed1993

Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome.

Pneumocystis carinii infection remains extremely common in the immunocompromised patient population, particularly in patients with human immunodeficiency virus (HIV) infection, despite the availability of effective prophylaxis. Although most commonly presenting as an acute pneumonia, the organism can infect a multitude of different organs, and thus may pose difficulty in diagnosis. Because effective treatment regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and parenteral pentamidine are hindered by a high rate of adverse reactions, alternative regimens are continuing to be evaluated. Of greatest promise to date for patients with mild-to-moderate disease are the alternative oral regimens of atovaquone, dapsone with trimethoprim, and clindamycin with primaquine. The addition of corticosteroids to anti-Pneumocystis therapy in patients with severe disease has been shown to improve both the short-term and long-term success of treatment. TMP-SMX and aerosolized pentamidine have been shown to be effective in the primary and secondary prevention of pneumocystosis; prophylactic regimens currently under study include dapsone, dapsone with pyrimethamine, and once-monthly parenteral pentamidine.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Long-term sequelae of acute pelvic inflammatory disease. A retrospective cohort study.

OBJECTIVE: Our objective was to prospectively assess the frequency and predictors of long-term sequelae of acute pelvic inflammatory disease. STUDY DESIGN: We performed a retrospective cohort study of 140 women admitted for treatment of pelvic inflammatory disease to San Francisco General Hospital in 1985, locating and interviewing 51 women by telephone a median of 37 months later. RESULTS: Twelve (24%) women had pelvic pain for 6 months or more after hospitalization, 22 (43%) had subsequent episode(s) of pelvic inflammatory disease, and 40% were involuntarily infertile. A history of pelvic inflammatory disease prior to admission was associated with infertility (p = 0.05), chronic pelvic pain (p = 0.03), and pelvic inflammatory disease subsequent to hospitalization (p = 0.06). Longer duration of abdominopelvic pain before admission and younger age at the time of first sexual intercourse were associated with both infertility (p = 0.02, p = 0.04) and subsequent pelvic inflammatory disease (p = 0.04, p = 0.0008). CONCLUSIONS: Further studies are needed to more accurately assess the incidence and predictors of long-term sequelae of pelvic inflammatory disease. A reduction in adverse outcome will require more stringent efforts at education and reduction of risk-taking behaviors.

Acute Disease↗