Subhash Chaudhary

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.

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.

Penicillin V and rifampin for the treatment of group A streptococcal pharyngitis: A randomized trial of 10 days penicillin vs 10 days penicillin with rifampin during the final 4 days of therapy

To improve the bacteriologic and clinical cure rates of streptococcal pharyngitis, 79 children were randomly assigned to receive penicillin V alone for 10 days (39 patients) or penicillin for the same duration and rifampin during the last 4 days of penicillin therapy (40 patients). Eleven patients given penicillin had evidence of bacteriologic failure (including eight with relapse of clinical illness) on repeat cultures done 4 to 7 days after treatment, whereas there were no failures in children given combination therapy (P = 0.0015). All eight symptomatic children improved with penicillin-rifampin therapy and subsequent cultures were negative, whereas three asymptomatic children continued to harbor group A streptococci even after combination therapy. Antibody response by antistreptolysin O or antideoxyribonuclease B assay was seen in 50.6% of patients; the antibody responses in both groups were comparable. These results show that addition of rifampin to the penicillin regimen improves the clinical and bacteriologic cure rates in children with streptococcal pharyngitis.

Use of gentamicin serum levels to individualize therapy in children

The value of a one-compartment pharmacokinetic model for calculating gentamicin half-life and predicting steady-state serum concentrations was assessed in 20 children, 32 to 168 months of age, who were receiving the drug intravenously for gram-negative bacterial infections. Actual steady-state serum concentrations measured after the twenty-fourth or twenty-fifth doses were compared with corresponding values predicted by the model. The mean predicted steady-state serum concentration at 30 minutes after the intravenous dose, 3.6 μg/ml, was 13% less than the mean measured value, 4.15 μg/ml. The mean predicted steady-state nadir serum concentration was 0.152 μg/ml, or 54% less than the mean measured value, 0.33 μg/ml. The mean t 1/2 for decline in serum concentrations following the first dose was 66.9 minutes, which was significantly different ( P 1/2 at steady state (84.9 minutes). Serum concentrations measured in four patients during the washout phase following the last dose of gentamicin declined in a biphasic manner, indicating two-compartment distribution of the drug. The error in predicted-versus-measured serum levels and the change in t 1/2 resulted from the use of the currently accepted but inappropriate one-compartment model to characterize gentamicin disposition. The change in t 1/2 with multiple dosing was attributable to tissue accumulation and not to impaired excretion of gentamicin. Alternative methods to reduce the error in characterizing gentamicin pharmacokinetics and to improve the utility of measuring gentamicin serum levels are proposed.

Trimethoprim-sulfamethoxazole for cholangitis followinghepatic portoenterostomy for biliary atresia

country can be found in the Table? Because of the potential for salicylate absorption, these products probably should not be given to persons taking oral anticoagulants, probenecid, methotrexate, or medications containing other forms of salicylate such as aspirin. Use of these products probably should be avoided by young children and by persons with hemophilia or with sensitivity to salicylates. Although we detected no bismuth in serum or urine specimens, it is not possible at the present time to state categorically that there is no absorption of bismuth from bismuth subsalicylate preparations. A recent report (10) indicates absorption of bismuth into bone in patients who were receiving long-term therapy with orally administered bismuth salts. This requires additional study. The labels on these products do not indicate the potential for salicylate absorption. Manufacturers should be required by the appropriate regulatory agencies in all countries to include an informative and precautionary statement. The Bureau of Drugs of Canada has recently requested that these label changes be made by the makers of Pepto-Bismol, Rawleigh Pleasant, Watkins Settelz, and Stress liquid, which are bismuth subsalicylate containing compounds available in Canada5 ~ These agencies should also review all data upon which the present label recommendations were made.

Ceftazidime versus ceftazidime plus tobramycin in febrile neutropenic children

SummaryAlthough the effectiveness of antibiotic monotherapy in febrile neutropenic patients remains unproven, ceftazidime has been shown previously to be effective monotherapy for the empiric treatment of selective patients. The efficacy and safety of ceftazidime versus ceftazidime plus tobramycin was evaluated in the treatment of febrile children (range 8 months to 18 years) with neutropenia secondary to cancer chemotherapeutic agents. Of the evaluable 89 patients, 45 received ceftazidime and 44 received ceftazidime plus tobramycin for 5 to 10 days. At the end of therapy, 30 (67%) of the 45 ceftazidime-treated patients were clinically cured compared with 38 (86%) of 44 combination-treated patients. Thirteen (29%) of the patients treated with ceftazidime failed to respond clinically to treatment, versus four (9%) of the patients treated with ceftazidime/tobramycin (p=0.046). This study suggests that ceftazidime as monotherapy in febrile neutropenic children may be inferior to combination therapy for optimal clinical response in these patients.ZusammenfassungCeftazidim hat sich in Monotherapie bei ausgewählten Patienten in der empirischen Behandlung von febriler Neutropenie als wirksam erwiesen, dennoch muß die Effizienz einer Antibiotika-Monotherapie bei neutropenischen Patienten mit Fieber nach wie vor als unbewiesen angesehen werden. Bei neutropenischen Kindern im Alter von 8 Monaten bis 18 Jahren, die eine Krebs-Chemotherapie durchmachten, wurde wegen Fieber eine Behandlung mit Ceftazidim allein oder in Kombination mit Tobramycin durchgeführt. Die Wirksamkeit und Sicherheit dieser beiden Therapieformen wurde verglichen. Von den 89 auswertbaren Patienten erhielten 45 Ceftazidim allein und 44 in Kombination mit Tobramycin. Die Behandlungsdauer lag zwischen 5 und 10 Tagen. Am Ende der Behandlung waren 30 der 45 mit Ceftazidim allein behandelten Patienten (67%) geheilt, in der mit Ceftazidim plus Tobramycin behandelten Gruppe 38 von 44 (86%). 13 der mit Ceftazidim behandelten Patienten (29%) sprachen klinisch nicht auf die Therapie an, in der Ceftazidim/Tobramycin-Gruppe waren 4 Therapieversager (9%) festzustellen (p=0,046). Aus dieser Studie läßt sich ableiten, daß Ceftazidim bei Kindern mit Neutropenie und Fieber in Monotherapie nicht in gleichem Ausmaß optimale Therapieergebnisse erzielen kann wie die Kombination Ceftazidim plus Tobramycin.

Gentamicin dosage in children: A randomized prospective comparison of body weight and body surface area as dose determinants

Body surface area and body weight were evaluated as gentamicin dose determinants in a randomized prospective study of 35 children with normal renal function. Patients were randomly assigned to receive intravenous gentamicin doses of either 37.5 mg/m 2 (Group I) or 1.25 mg/kg (Group II) administered every six hours, and were studied after their first dose on days one, three, and six of therapy. When the variability in peak concentrations for the two dosage regimens was compared, there was no statistically significant difference ( P =0.45) between the two groups. The gentamicin volume of distribution for all patients correlated only moderately with body weight (r=0.82) and body surface area (r=0.79). The mean volume of distribution on day one was 0.295±0.115 l/kg when expressed as a function of body weight and 7.26±2.62 l/m 2 when expressed as a function of body surface area, and did not change significantly with multiple dosing. The results indicate that the variability in serum concentrations is not significantly reduced when pediatric doses are calculated from body surface area instead of body weight, supporting the need for individualization of doses based on measured serum concentrations.

Characterization of Lymphocytes Responsible for Protective Immunity to Histoplasmosis in Mice/Charakterisierung von Lymphozyten der protektiven Immunität gegen Histoplasmose bei Mäusen*

Summary: Purified thymus‐derived (T) and bone marrow derived (B) lymphocytes were obtained from spleens of C3H/HeN mice immunized with live yeast cells of H. capsulatum. Unfractionated spleen lymphocytes contained 44–46% T cells and 40–43% B cells. Adoptive transfer of unfractionated lymphocytes and T‐enriched lymphocytes conferred significant protection against a lethal challenge with yeast cells of H. capsulatum (p < 0.001) whereas, only a minimal level of protection was observed in mice receiving B‐cell enriched subpopulations. The unfractionated lymphocytes and T and B cells retained their in vitro immunological characteristics in lymphocyte transformation assays. Significant migration inhibition of PEC from recipients of unfractionated and T cells was observed in the presence of Histoplasma antigens (p < 0.01); the inhibition was similar to that seen with PEC from immunized donors. In contrast, the PEC from recipients of B cells did not show inhibition of macrophage migration under similar conditions. These results indicate that the purified lymphocytes retained their immunological characteristic and that the significant protective immunity is conferred only by T cells.

Inosiplex for Localized Herpes Zoster in Childhood Cancer Patients: Preliminary Controlled Study

By multiple criteria, inosiplex—a reputed stimulator of virus-sensitized lymphocytes—had no demonstrable therapeutic effects in a preliminary controlled study of patients with localized herpes zoster and cancer. Lymphocytes from the six drug-treated patients were no more responsive to varicella-zoster antigen and phytohemagglutinin than were lymphocytes from seven patients who received a placebo.

SUCCESSFUL CHEMOPROPHYLAXIS FOR Pneumocystis carinii PNEUMONITIS (PCP)

After demonstrating in animal studies that trimethoprim-sulfamethoxazole (TMP-SMZ) administered prophylactically prevented PCP, a double-blind, placebo-controlled study was done in children with cancer at high risk for PCP. A group of 160 children with an expected attack rate of 20% for PCP, were randomized to receive TMP-SMZ or a placebo from Oct. 1974 to Oct. 1976.PCP occurred in 17/80 (21%) of the placebo group and none of the 80 patients receiving TMP-SMZ. The occurrences of certain other infections in the two groups are tabulated:Serial bacterial and fungal cultures of the pharynx and rectum, tests for renal and liver function and serum folate determinations revealed no adverse effects from TMP-SMZ prophylaxis. The course of the malignancies was not affected. TMP-SMZ prophylaxis is an effective approach to the prevention of PCP as well as certain other infections and, with the exception of oral candidiasis, is not associated with significant adverse effects.