Sandor Feldman

Successful chemoprophylaxis for Pneumocystis carinii pneumonitis.

In a randomized, double-blind, placebocontrolled study to evaluate the efficacy of trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia, we studied 160 patients with cancer who were at high risk for this pneumonia over a two-year period. Seventeen of the 80 patients receiving a placebo acquired P. carinii pneumonitis, whereas none of the 80 given 150 mg of trimethoprim and 750 mg of sulfamethoxazole per square meter per day had the infection P less than 0.01). Bacterial sepsis, pneumonia other than that caused by P. carinii, acute otitis media, upper-respiratory-tract infections, sinusitis and cellulitis occurred less frequently in recipients of the drug than in the placebo group (P less than 0.01 in each case). Oral candidiasis was the only adverse effect ecountered from trimethoprim-sulfamethoxazole administration. The study shows the combination to be highly effective in the prevention of P. carinii pneumonitis.

A Controlled Trial of Acyclovir for Chickenpox in Normal Children

BACKGROUND Chickenpox, the primary infection caused by the varicella-zoster virus, affects more than 3 million children a year in the United States. Although usually self-limited, chickenpox can cause prolonged discomfort and is associated with infrequent but serious complications. METHODS To evaluate the effectiveness of acyclovir for the treatment of chickenpox, we conducted a multicenter, double-blind, placebo-controlled study involving 815 healthy children 2 to 12 years old who contracted chickenpox. Treatment with acyclovir was begun within the first 24 hours of rash and was administered by the oral route in a dose of 20 mg per kilogram of body weight four times daily for five days. RESULTS The children treated with acyclovir had fewer varicella lesions than those given placebo (mean number, 294 vs 347; P less than 0.001), and a smaller proportion of them had more than 500 lesions (21 percent, as compared with 38 percent with placebo; P less than 0.001). In over 95 percent of the recipients of acyclovir no new lesions formed after day 3, whereas new lesions were forming in 20 percent of the placebo recipients on day 6 or later. The recipients of acyclovir also had accelerated progression to the crusted and healed stages, less itching, and fewer residual lesions after 28 days. In the children treated with acyclovir the duration of fever and constitutional symptoms was limited to three to four days, whereas in 20 percent of the children given placebo illness lasted more than four days. There was no significant difference between groups in the distribution of 11 disease complications (10 bacterial skin infections and 1 case of transient cerebellar ataxia). Acyclovir was well tolerated, and there was no significant difference between groups in the titers of antibodies against varicella-zoster virus. CONCLUSIONS Acyclovir is a safe treatment that reduces the duration and severity of chickenpox in normal children when therapy is initiated during the first 24 hours of rash. Whether treatment with acyclovir can reduce the rare, serious complications of chickenpox remains uncertain.

Comparison of pentamidine isethionate andtrimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia†‡

Fifty patients with P. carinii pneumonitis were randomized to receive either pentamidine isethionate or trimethoprim-sulfamethoxazole therapy. Those not responding favorably to the first drug after three or more days of therapy were changed to the alternate drug. Of the 26 patients initially treated with TMP-SMZ, 20 recovered (0.77)-17 after TMP-SMZ alone and three of nine who were crossed over to pentamidine. Of the 24 patients initially treated with pentamidine, 18 recovered (0.75)-14 of 15 who received only pentamidine and four of nine who were crossed over to TMP-SMZ. Abnormal values for blood urea nitrogen, creatinine, or glucose; inflammation at injection sites; or combination of these effects occurred in 14 of the 15 patients treated with pentamidine alone. Only one of the 17 patients treated with TMP-SMZ alone developed any of these abnormalities. This study shows that TMP-SMZ is as effective as pentamidine in the treatment of PCP, and that it offers the advantages of minimal adverse effects, oral administration, and ready availability.

Efficacy of trimethoprim and sulfamethoxazole in the prevention and treatment of Pneumocystis carinii pneumonitis.

A combination of trimethoprim and sulfamethoxazole was effective in the prevention and treatment of Pneumocystis carinii pneumonitis in cortisonetreated rats. Although all of 15 untreated rats died with P. carinii pneumonitis, none of 15 given trimethoprim-sulfamethoxazole prophylactically acquired the infection. After P. carinii pneumonitis was established, 9 of 14 rats recovered after treatment with trimethoprim-sulfamethoxazole compared with only 2 of 14 treated with pentamidine isethionate. Rifampin and clindamycin, separately or in combination with pentamidine, were ineffective in the prevention and treatment of P. carinii infection.

Intensity of immunosuppressive therapy and the incidence of pneumocystis carinii pneumonitis

One hundred and forty‐nine children with acute lymphocytic leukemia treated according to a prospective protocol were randomized after induction of remission and central nervous system (CNS) irradiation to receive maintenance chemotherapy with 1, 2, 3, or 4 chemotherapy agents. The incidence of P. carinii pneumonitis (PCP) was 5.0, 2.3, 2.2, and 22.4%, respectively, during the period of maintenance therapy. An additional 31 patients enrolled in the same study were placed in special categories to receive three drugs for maintenance plus supplemental chemotherapy or irradiation because of CNS leukemia on admission, remission failure, mediastinal mass, or generalized lymphosarcoma without bone marrow involvement. The incidences of PCP in these groups were 16.7, 30.0, 35.7, and 0%, respectively, during the period of maintenance therapy.

Pneumocystis carinii pneumonitis in children with malignancies

Pneumocystis carinii pneumonitis occurred in 51 (4.1 per cent) of 1,251 children with malignancies. The annual incidence was proportional to the number of patients at risk and was unrelated to season, age, sex, place of residence, or the environmental factors investigated. The disease was characterized by fever, marked tachypnea, flaring of nasal alae, intercostal retraction, frequently cyanosis, and roentgenographic evidence of bilateral diffuse alveolar disease. The diagnosis was established by the identification of P. carinii in material obtained from percutaneous transthoracic needle aspiration of the lung. Three stages of the pathologic pattern were delineated in correlation with clinical manifestations. Forty-one patients were treated with pentamidine isethionate; 28 (68 per cent) of them recovered from the pulmonary infection. A second episode occurred in four. Adverse effects of the drug are usually reversible.

Human Leukocyte Interferon for the Treatment of Varicella in Children with Cancer

Human leukocyte interferon was evaluated as a treatment for varicella in a randomized double-blind, placebo-controlled study carried out in two phases. A total of 44 children being treated for cancer were enrolled within 72 hours of the appearance of the exanthem. The mean number of days of new lesion formation was 3.8 +/- 1.89 (+/- S.D.) in the interferon recipients and 5.3 +/- 2.56 in the placebo recipients (P less than 0.05). Eighty-one per cent of the interferon recipients had had no new lesions for 24 hours by Day 7, as compared with 56 per cent of the placebo recipients (P less than 0.025). In the second, higher-dose phase of the study 92 per cent of the interferon recipients had had no new lesions for 24 hours by Day 6, as compared with 45 per cent of the placebo recipients (P less than 0.025). Three of 21 placebo recipients died of progressive varicella. Two of the 23 interferon recipients died two to three weeks after the onset of varicella; viral cultures were negative in one of these patients, and the second had recurrent viremia at the end of the treatment period. Among the survivors, treatment with interferon reduced the number of patients who had life-threatening dissemination (none of 21 vs. three of 18; P = 0.053). We conclude that interferon had an antiviral effect against varicella virus in immunocompromised patients.

Influenza in children and young adults with cancer. 20 cases

The purpose of this study was to characterize the clinical features of laboratory‐confirmed influenza in 20 children and young adults with cancer who were receiving immunosuppressive therapy. Viruses isolated from pharyngeal and nasopharyngeal cultures were identified as the A/Hong Kong/1/68 strain or one of its variants, either A/England/42/72, A/Port Chalmers/1/73, or A/Victoria/3/75. Although the signs and symptoms of influenza in our patients were not unusual, the clinical course lasted twice as long as in the general population. Complications developed in only 3 patients and were related to secondary bacterial infections rather than influenza. An important sequelae of influenza was the interruption of cancer therapy in 16 patients for periods of 4 days to 3 1/2 weeks. The severity of influenza did not appear related to type or activity of malignancy or to duration or specific form of cancer therapy. Guidelines for the prevention and management of influenza in children with cancer are recommended.

Human leukocyte interferon in the treatment of varicella in children with cancer: a preliminary controlled trial.

Eighteen patients who developed varicella while being treated for malignancy received human leukocyte interferon in a randomized double-blind placebo-controlled trial. Complications of varicella occurred in six of nine placebo recipients, but in only two of nine interferon recipients. Interferon was tolerated without significant side effects.

Immunogenicity of hepatitis B vaccine in healthy very low birth weight infants.

We studied the immunogenic response to hepatitis B vaccine of infants weighing < or = 1500 gm at birth. Infants were divided into two groups: those weighing < or = 1000 gm (n = 22) and those weighing 1001 to 1501 gm (n = 28). When immunized early (3 days of age, n = 25), these infants had a response rate (defined as antibody to hepatitis B surface antigen titer > 10 mIU/ml) of 68%, whereas when the first vaccine was given at 1 month of age (n = 25), a 96% response rate was noted, irrespective of birth weight and weight at the time of immunization (p < 0.02).