Constance B. Wofsy

Adverse Reactions to Trimethoprim-Sulfamethoxazole in Patients with the Acquired Immunodeficiency Syndrome

We reviewed the charts of 38 patients with the acquired immunodeficiency syndrome who were treated for Pneumocystis carinii pneumonia. Only 5 of 37 patients started on trimethoprim-sulfamethoxazole were able to complete treatment; in 29 patients drug toxicity occurred and in 19 treatment was changed due to adverse reactions that included rash, fever, neutropenia, thrombocytopenia, and transaminase elevation. Pentamidine was given to 30 patients (1 as initial treatment); toxicity occurred in 13 but only 4 required a change in drug. Adverse reactions from pentamidine included fever, rash, neutropenia, transaminase elevation, azotemia, and hypoglycemia. Patients received trimethoprim-sulfamethoxazole a median of 9.5 days, and pentamidine, a median of 12.5 days. Toxicity from trimethoprim-sulfamethoxazole appeared earlier than toxicity associated with pentamidine (7.5 versus 9.5 days of treatment). In patients with the acquired immunodeficiency syndrome, trimethoprim-sulfamethoxazole has a higher incidence of adverse reactions than pentamidine (p less than 0.005).

Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

BACKGROUND Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic. METHODS In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day). RESULTS The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone. CONCLUSIONS In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

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.

Dapsone, Trimethoprim, and Sulfamethoxazole Plasma Levels during Treatment of Pneumocystis Pneumonia in Patients with the Acquired Immunodeficiency Syndrome (AIDS): Evidence of Drug Interactions

STUDY OBJECTIVE To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN Measurement of drug levels as part of an open study of dapsone alone and randomized, double-blind comparison of trimethoprim-dapsone with trimethoprim-sulfamethoxazole in treating Pneumocystis carinii pneumonia in patients with AIDS. SETTING County hospital and AIDS clinic. PATIENTS Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole. INTERVENTION Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg.d; administered for 21 days. MEASUREMENTS AND MAIN RESULTS Concentrations of dapsone were 40% higher in patients treated with trimethoprim-dapsone than in those treated with dapsone alone (2.1 compared with 1.5 micrograms/mL; P less than 0.05). Trimethoprimdapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. The concentration of trimethoprim was 48.4% higher in patients treated with trimethoprim-dapsone than in those treated with trimethoprim-sulfamethoxazole, (18.4 compared with 12.4 micrograms/mL; P less than 0.05). Discontinuation of therapy due to toxicity was commoner in the trimethoprim-sulfamethoxazole group (57% compared with 30%). CONCLUSIONS A bidirectional drug interaction exists between dapsone and trimethoprim, resulting in higher concentrations of each in the presence of the other.

Dapsone-Trimethoprim for Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome

All patients with the acquired immunodeficiency syndrome and a first episode of Pneumocystis carinii pneumonia seen at the San Francisco General Hospital between November 1984 and April 1985 were evaluated for oral treatment with dapsone (100 mg/d) plus trimethoprim (20 mg/kg body weight X d). All 15 patients who met the entry criteria improved clinically and radiographically within 3 to 10 days after starting treatment. Repeat pulmonary function tests and gallium lung scans after 3 weeks of therapy also showed improvement. Although side effects occurred in 14 patients, in only 2 were they severe enough to require stopping therapy. Both of these patients had worsening skin rash, and dapsone-trimethoprim therapy was stopped after 10 days. When compared with trimethoprim-sulfamethoxazole or pentamidine used to treat P. carinii pneumonia in similar patients, oral dapsone-trimethoprim is at least as effective, seems to be better tolerated, and may have a lower frequency of serious side effects.

Differences between women and men in adverse events and CD4+ responses to nucleoside analogue therapy for HIV infection

Objective: To prospectively examine differences in baseline characteristics and study outcomes between HIV‐infected women and men during a clinical trial of nucleoside analogue therapy. Methods: ACTG 175 randomized HIV‐infected patients with CD4+ counts between 200 and 500 cells/mm3 to one of four nucleoside analogue regimens: zidovudine (ZDV), didanosine (ddl), ZDV + ddI, or ZDV + zalcitabine (ddC). Differences in time to first dose modification, voluntary withdrawal, development of toxicity and symptomatology, and AIDS progression were compared by gender. Results: The study included 438 women and 2029 men. Baseline values of HIV RNA plasma concentrations were significantly lower for women (0.3 log10) than men in a subset of patients in whom assays were taken and this difference persisted after adjustment for CD4+ count. Women reported reducing dosage and discontinue ddI‐containing regimens more frequently than men did; adjustment for weight did not completely explain this difference. Women were at lower risk than men for progression to a study endpoint (19% of women versus 24% of men; p < .0001). Among those antiretroviral‐naive study subjects receiving ZDV, men were four times more likely to progress to a study endpoint than women. Conclusions: Differences in pretreatment characteristics and on study experiences were demonstrated between women and men enrolled in this clinical trial. The suggestion of a gender difference in response to ZDV monotherapy by antiretroviral‐naive study subjects and the lower baseline values for HIV RNA in women compared with those in men provides evidence for gender differences in the relationship between virus replication, CD4+ decline, and responses to nucleoside analogue therapy.

Dapsone treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

All patients with the acquired immunodeficiency syndrome treated for their first episode of Pneumocystis carinii pneumonia at San Francisco General Hospital between 1 April 1985 and 15 July 1985 were evaluated for their response to treatment with dapsone (100 mg/day) by mouth for 21 days. Of 44 patients evaluated, 18 were eligible for the study. Of these 18 patients, the conditions of 7 of them worsened or failed to improve during treatment with dapsone and they were considered treatment failures. These patients were changed to standard therapy after 4 to 8 days of dapsone therapy. The remaining 11 patients (61%) improved within 3 to 10 days after dapsone therapy was started. Side effects of dapsone therapy were noted in 6 of 11 patients (of these 11 patients, 5 had a rash, 1 had a rash and abnormal liver enzymes, and 1 had abnormal liver enzymes), but in none of the patients were these side effects severe enough to require the cessation of medication. Based on comparison with historical controls, oral dapsone therapy alone appeared to be less effective than standard therapy or the combination of dapsone plus trimethoprim for P. carinii pneumonia in patients with acquired immunodeficiency syndrome.

The acquired immunodeficiency syndrome. Infection control and public health law.

Because they can be transmitted to others, infectious diseases of all kinds have for many years been the subject of statutes, regulations, and court decisions imposing special constraints on both t...

Cytomegalovirus infection of the laryngeal nerve presenting as hoarseness in patients with acquired immunodeficiency syndrome

C ytomegalovirus (CMV) infection is by far the most common opportunistic viral infection in patients with acquired immunodeficiency syndrome (AIDS) [l] and has been reported to involve virtually every organ in the body [2,3]. Though difficult to treat, some limited success has been observed with ganciclovir therapy for CMV retinitis and gastrointestinal disease [4]. We encountered two patients with AIDS in whom hoarseness developed due to CMV involvement of the recurrent laryngeal nerve during administration of ganciclovir for CMV colitis.

Once-daily ceftriaxone for skin and soft tissue infections.

We prospectively compared once-daily administration of ceftriaxone with cefazolin given every 8 h for the treatment of skin and soft tissue infections. Thirty-one patients received cefazolin for a mean of 4.5 days, and 26 patients received ceftriaxone for a mean of 4.0 days. All patients had a satisfactory response. Adverse reactions were few and reversible. Ceftriaxone given as a single daily intramuscular injection is effective therapy for skin and soft tissue infections.