Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis Carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ.

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis carinii pneumonia (PCP) prophylactic agent, but adverse reactions are common among human immunodeficiency virus (HIV)-infected patients and limit its use. This randomized, double-blind controlled trial compared 2 methods of TMP-SMZ reintroduction, 6-day dose escalation and direct rechallenge, for PCP prophylaxis in HIV-infected patients who had experienced previous treatment-limiting reactions. The primary end point was the ability to take single-strength TMP-SMZ daily for 6 months. Seventy-five percent of the dose-escalation group and 57% of the direct-rechallenge group continued to receive daily single-strength TMP-SMZ for 6 months (P= .014). Among premature discontinuations, 58% of the dose-escalation group and 70% of the direct-rechallenge group were due to adverse reactions. None of these reactions was serious. This study provides evidence that it is possible to successfully reintroduce TMP-SMZ to a significant proportion of HIV-infected patients who have experienced mild-to-moderate treatment-limiting adverse reactions.

Toxoplasma serology, parasitemia and antigenemia in patients at risk for toxoplasmic encephalitis.

In order to further characterize the pathogenesis of Toxoplasma gondii infection in patients with AIDS and AIDS-related complex (ARC), a cohort of HIV- and Toxoplasma-infected individuals were identified and prospectively followed. Four hundred and 10 HIV-infected individuals followed in the San Francisco General Hospital AIDS Clinic were screened for antibodies to Toxoplasma between November 1986 and November 1988. Of the 67 (16%) individuals seropositive for Toxoplasma antibodies, 33 (49%) were followed monthly for a mean duration of 7.5 months. One hundred and 11 follow-up blood samples were obtained in order to determine Toxoplasma serology and the incidence of parasitemia. In general, Toxoplasma immunoglobulin (Ig) G antibodies remained stable over time. Detection of Toxoplasma antigenemia and parasitemia was uniformly negative, including those specimens obtained from two individuals within 45 days of their developing toxoplasmic encephalitis.

Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco community prophylaxis trial.

BACKGROUND AND METHODS: Pneumocystis carinii pneumonia (PCP) is the most frequent life-threatening opportunistic infection associated with human immunodeficiency virus (HIV) infection. To assess the possible value of aerosolized-pentamidine prophylaxis in different doses, a controlled clinical trial was begun in 1987 with 408 subjects at 12 treatment centers. The participants were randomly assigned to receive 30 mg of pentamidine every two weeks, 150 mg every two weeks, or 300 mg every four weeks. RESULTS: Eighteen months after randomization, the subjects in the 300-mg arm had had 8 confirmed episodes of PCP while receiving treatment, as compared with 22 in the 30-mg arm (P = 0.0008). The 150-mg arm had intermediate results but ones not significantly different from those of the 300-mg arm. Participants with previous episodes of PCP and CD4-cell counts less than 200 per cubic millimeter were at the highest risk for PCP. CONCLUSIONS: Aerosolized pentamidine was effective for prophylaxis against PCP in patients infected with HIV, according to the dose and schedule of administration. It and zidovudine were well tolerated together and had independent prophylactic benefits.

Occupational exposure to aerosolized pentamidine.

Occupational exposure to aerosolized pentamidine has raised questions regarding transmission of tuberculosis and the effect of the drug itself. To estimate the exposure of a health care worker, we measured the ambient concentration of aerosolized pentamidine in field conditions in 36 m3 unventilated treatment room. The amount of pentamidine averaged in three different environmental air samples over a four-hour period was 4.5 +/- 3.6 x 10(-5) mg/m3. This amount is very small compared to the doses received by the patients in whom long-term adverse effects are few. The greater risk to health care workers is probably transmission of tuberculosis from undiagnosed cases, especially in populations with an increased incidence of tuberculosis. Tuberculosis control measures such as improved ventilation and masks should also decrease exposure to ambient air pentamidine until toxicity studies determine long-term adverse effects, if any, of aerosolized pentamidine.

[Disorders of the nervous system associated with the acquired immunodeficiency syndrome (AIDS)-clinical approach].

The acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) and characterized by disorders of the nervous system in addition to opportunistic infection and cancer. Centers for Disease Control (CDC) recommend the classification system consisting of four major groups. Group I is patients with acute HIV infection, and Group II is asymptomatic carriers. Group III is those with persistent generalized lymphadenopathy (PGL). Group IV includes five subgroups: IVA with constitutional disease, IVB with neurologic disease, IVC with secondary infectious diseases, IVD with secondary cancers and IVE with other conditions. The nervous system disorders are classified into two types: one is produced by HIV itself and not directly related to immunodeficiency, and the other caused by opportunistic infectious agents and cancers. The former is further divided into two kinds: atypical aseptic meningitis and acute inflammatory demyelinating polyneuropathy (AIDP) occur mainly in Group I and II, whereas HIV encephalopathy, distal symmetric polyneuropathy (DSPN) and vacuolar myelopathy in Group III and IV. Group I or II patients have no apparent medical problems. Therefore, when neurologists see patients with risk factors for HIV infection presenting with atypical meningitis or AIDP, it is of utmost importance to have a high index of suspicion and to look for evidence of HIV infection.

Comparison of nosocomial infections due to Staphylococcus aureus and enterococci in a general hospital.

Hospital acquired infections caused by enterococci are increasing in incidence. This increase has been attributed, in part, to widespread use of cephalosporin antibiotics which lack activity against enterococci. To test this hypothesis, we compared patients having nosocomial enterococcal pulmonary and wound infections with those patients having nosocomial staphylococcal infections for antecedant cephalosporin use. In a six month period, we found 14 instances of nosocomial enterococcal wound and respiratory infections; 13 were superinfections (occurring during or up to one week after administration of antimicrobials). Seven had coexisting pathogens noted. In the same six month period, 30 instances of Staphylococcus aureus nosocomial respiratory tract and wound infections were found and only 13 were superinfections (p less than 0.002 compared with enterococcal superinfections). Nine had coexisting pathogens noted. The mean age, gender distribution and underlying illnesses in the Staphylococcus aureus and enterococcal superinfection groups were comparable. Of the 14 instances of enterococcal nosocomial infections, 11 were associated with administration of a cephalosporin compared with seven of 30 for staphylococcal infections (p less than 0.002). Nosocomial enterococcal infections are commonly associated with antimicrobial therapy and the use of cephalosporins may selectively predispose patients to increased risk of enterococcal superinfections.

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.