Gordon M. Dickinson

Safety and Efficacy of Sulfamethoxazole and Trimethoprim Chemoprophylaxis for Pneumocystis carinii Pneumonia in AIDS

The safety and efficacy of sulfamethoxazole and trimethoprim in the prevention of Pneumocystis carinii pneumonia associated with the acquired immunodeficiency syndrome (AIDS) were evaluated. Sixty patients with a new diagnosis of Kaposis sarcoma and no history of opportunistic infections were randomly assigned to receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice per day or no therapy. None of the 30 patients receiving sulfamethoxazole and trimethoprim developed P carinii pneumonia. Sixteen of the 30 patients receiving no suppressive therapy developed P carinii pneumonia. Development of P carinii pneumonia was associated with the stage of Kaposis sarcoma, B subtype disease, and the presence of 0.20 X 10(9)/L (200/mm3) or fewer CD4 cells at study entry. The proportion of patients surviving and the mean length of survival were significantly greater in the treatment group compared with the control group. Adverse reactions occurred in 15 patients (50%).

Opportunistic Infections and Kaposi's Sarcoma Among Haitians: Evidence of a New Acquired Immunodeficiency State

Twenty Haitian patients, hospitalized from 1 April 1980 to 20 June 1982, had Pneumocystis carinii pneumonia, central nervous system toxoplasmosis, esophageal candidiasis, cryptococcosis, disseminated cytomegalovirus, progressive herpes simplex virus, chronic enteric coccidiosis, or invasive Kaposis sarcoma. Ten patients died. Opportunistic infections were frequently multiple and were recurrent in three patients. In seven patients disseminated tuberculosis preceded the other infections by 2 to 15 months. There was no evidence of an underlying immunosuppressive disease, and no history of homosexuality or intravenous drug abuse. At least three patients probably acquired the syndrome in Haiti. Lymphadenopathy was common. Seventeen patients tested had anergy, and 18 had lymphopenia. Monoclonal antibody analysis of peripheral-blood T-cell subsets done on 11 patients showed a marked decrease in T-helper cells and an inversion of the normal ratio of T-helper cells to T-suppressor cells. This syndrome among heterosexual Haitians is strikingly similar to the syndrome of immunodeficiency described recently among American homosexuals.

A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study.

BACKGROUND Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. METHODS We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. RESULTS During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. CONCLUSIONS In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.

The Epidemiology of Antiretroviral Drug Resistance among Drug-Naive HIV-1-Infected Persons in 10 US Cities

BACKGROUND The prevalence and characteristics of persons with newly diagnosed human immunodeficiency virus (HIV) infections with or without evidence of mutations associated with drug resistance have not been well described. METHODS Drug-naive persons in whom HIV had been diagnosed during the previous 12 months and who did not have acquired immune deficiency syndrome were sequentially enrolled from 39 clinics and testing sites in 10 US cities during 1997-2001. Genotyping was conducted from HIV-amplification products, by automated sequencing. For specimens identified as having mutations previously associated with reduced antiretroviral-drug susceptibility, phenotypic testing was performed. RESULTS Of 1311 eligible participants, 1082 (83%) were enrolled and successfully tested; 8.3% had reverse transcriptase or major protease mutations associated with reduced antiretroviral-drug susceptibility. The prevalence of these mutations was 11.6% among men who had sex with men but was only 6.1% and 4.7% among women and heterosexual men, respectively. The prevalence was 5.4% and 7.9% among African American and Hispanic participants, respectively, and was 13.0% among whites. Among persons whose sexual partners reportedly took antiretroviral medications, the prevalence was 15.2%. CONCLUSIONS Depending on the characteristics of the patients tested, HIV-genotype testing prior to the initiation of therapy would identify a substantial number of infected persons with mutations associated with reduced antiretroviral-drug susceptibility.

International Clones of Methicillin-Resistant Staphylococcus aureus in Two Hospitals in Miami, Florida

ABSTRACT A total of 202 methicillin-resistant Staphylococcus aureus (MRSA) single-patient isolates recovered between January and June 1998 in two hospitals in Miami, Florida, were characterized by a combination of several molecular typing techniques: multilocus sequence typing, spaA typing, pulsed-field gel electrophoresis, and determination of the structure of the SCCmec element. The overwhelming majority of the isolates—187of 202, or 93%—belonged to one of three internationally spread epidemic clones which were identified on the basis of their multilocus sequence type (ST) as E-MRSA-16 (ST36), the New York clone V (ST8), and the New York/Japan clone (ST5; SCCmec II) and its single- and double-locus variants. The rest of the isolates (15 of 202, or 7%) were more genetically diverse and were each recovered from a few patients only. Of the 23 MRSA strains isolated from confirmed human immunodeficiency virus-positive patients, as many as 17 (or 70%) belonged to a single ST8 clone carrying SCCmec type IV. The data provide further evidence for the conclusion of earlier studies that most MRSA disease in hospitals is caused by relatively few pandemic clones.

Once Weekly Azithromycin Therapy for Prevention of Mycobacterium avium Complex Infection in Patients with AIDS: A Randomized, Double-Blind, Placebo-Controlled Multicenter Trial

We conducted a randomized, double-blind, placebo-controlled multicenter trial of azithromycin (1,200 mg once weekly) for the prevention of Mycobacterium avium complex (MAC) infection in patients with AIDS and a CD4 cell count of < 100/mm3. In an intent-to-treat analysis through the end of therapy plus 30 days, nine (10.6%) of 85 azithromycin recipients and 22 (24.7%) of 89 placebo recipients developed MAC infection (hazard ratio, 0.34; P = .004). There was no difference in the ranges of minimal inhibitory concentrations of either clarithromycin or azithromycin for the five breakthrough (first) MAC isolates from the azithromycin group and the 18 breakthrough MAC isolates from the placebo group. Of the 76 patients who died during the study, four (10.5%) of 38 azithromycin recipients and 12 (31.6%) of 38 placebo recipients had a MAC infection followed by death (P = .025). For deaths due to all causes, there was no difference in time to death or number of deaths between the two groups. Episodes of non-MAC bacterial infection per 100 patient years occurred in 43 azithromycin recipients and 88 placebo recipients (relative risk, 0.49; 95% confidence interval, 0.33-0.73). The most common toxic effect noted during the study was gastrointestinal, reported by 78.9% of azithromycin recipients and 27.5% of placebo recipients. Azithromycin given once weekly is safe and effective in preventing disseminated MAC infection, death due to MAC infection, and respiratory tract infections in patients with AIDS and CD4 cell counts of < 100/mm3.

Fansidar Prophylaxis of Pneumocystis Pneumonia in the Acquired Immunodeficiency Syndrome

Excerpt To the editor:Pneumocystis cariniipneumonia is a major cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). More than 50% of patients with AIDS d...

Tuberculous adenitis of the thyroid mimicking subacute thyroiditis

Involvement of the thyroid by Mycobacterium tuberculosis was initially described in the late 18OOs, but it has proven to be a rare occurrence. We describe the case of a nurse who was treated for subacute thyroiditis over a prolonged period before tuberculosis was diagnosed. The clinical, laboratory, and radiologic aspects of the case are presented. The pathogenesis and clinical spectrum of tuberculosis of the thyroid are discussed. CASE REPORT A 36-year-old woman experienced the sudden onset of neck tenderness in May 1985 after an upper respiratory tract infection associated with rhinitis, myalgias, and arthralgias. Her thyroid gland was enlarged and tender; a pertechnetate thyroid scan revealed normal uptake except for an area of decreased uptake in the left lobe. Subacute thyroiditis was suspected, and acetylsalicylic acid was prescribed. Failure to respond to treatment led to the addition of L-thyroxine. She remained intermittently symptomatic with a visually prominent thyroid gland. The left lobe was smooth, firm, and tender. Lymph nodes were not enlarged. Results of thyroid function studies were within normal limits, and the Westergren sedimentation rate was 5 mm/hour. Ultrasonography of the gland in October 1985 revealed a normal gland except for a soft tissue nodule connected to the left lobe. Her chest roentgenogram demonstrated clear lung fields without abnormalities. Six months later, her symptoms persisted. In May of 1986, prednisone was begun, with subsequent improvement of the patient’s symptoms. Ultrasonography at that time demonstrated a 5- by 2-cm hyperechogenic structure associated with the lower pole of the left lobe of the thyroid. A cleavage plane between the structure and left lobe was visible. A fine needle biopsy specimen of the left lobe demonstrated clusters of histiocytes mixed with blood. Scant amounts of colloid were noted. In July of 1986, her neck pain, tenderness, and swelling returned. Computed axial tomography of the neck revealed a multiloculated mass 3.5 cm in diameter anterior to a normal-appearing left lobe of the thyroid. The mass enhanced with contrast and appeared to be encapsulated (Figures 1 and 2). Surgical exploration in October 1986 identified an abscess cavity that contained 7 to 10 ml of creamy, yellow pus. The abscess cavity occupied the space of the majority of the isthmus and the left lobe of the thyroid gland. Gram’s stain and culture failed to detect pathogens; no stain or culture for mycobacteria was performed. Histologic examina

Clinical evaluation of piperacillin with observations on penetrability into cerebrospinal fluid.

Piperacillin, a new semisynthetic penicillin, was evaluated for efficacy and safety in 26 patients, most of whom had pneumonia. Included were four patients with gram-negative meningitis in whom the penetration of piperacillin into cerebrospinal fluid was determined. Cure was achieved in 11 of 17 patients with pneumonia; another 4 were improved. One relapse and one failure occurred among nine patients with gram-negative pneumonia. Cure or improvement occurred in seven of nine patients with gram-negative infection in various extrapulmonary sites. Piperacillin given by continuous infusion in a dosage ranging from 324 to 436 mg/kg of body weight per day to four patients with meningitis resulted in a mean cerebrospinal fluid level of 23 micrograms/ml at 24 h; the mean penetration of piperacillin into the cerebrospinal fluid was 32% at this interval. Levels of piperacillin in cerebrospinal fluid collected later during the course of therapy were also adequate. Adverse effects were noted in six patients, but only one episode of granulocytopenia was serious. Emergence of resistance to piperacillin did not occur, and only one superinfection was noted. Piperacillin appeared to be efficacious in the treatment of pneumonia. It penetrated well into the cerebrospinal fluid of patients with meningitis and may be useful for treatment of selected gram-negative infections in extrapulmonary sites.

Genotypic analysis of plasma HIV-1 RNA after influenza vaccination of patients with previously undetectable viral loads

Objective In this study we evaluated the possibility that plasma viral load elevations secondary to influenza vaccination in HIV-1-seropositive individuals with previously undetectable viral loads (< 200 copies/ml) could develop resistance-bearing mutations in the viral reverse transcriptase (RT) and protease regions. Methods Thirty-four patients with undetectable viral burdens on highly active antiretroviral therapy (HAART) were evaluated for elevations in plasma viral load 2 and 4 weeks post-influenza vaccination. Plasma from patients whose viral load increased after vaccination was subject to genotypic resistance analysis by the line probe assay (LiPA) to determine whether primary resistance-bearing mutations developed during this period and at follow-up. Stored plasma was used to evaluate whether RT or protease mutations existed pre-vaccination. Results Seven out of 34 patients were found to experience elevations in their viral load after influenza vaccination. Two of the patients revealed evidence of primary RT or protease mutations not demonstrated in earlier pre-vaccination samples. One patient failed therapy after vaccination, and one patient revealed post-vaccination viral load elevations that eventually led to the progressive development of primary zidovudine mutations. Conclusion Evidence is presented that supports the contention that a small subset of patients who experience viral load elevations after influenza vaccination can develop mutational changes in the RT region of the viral genome either acutely or after a failure of the viral load to return to undetectable levels.