A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia. A randomized controlled trial of filgrastim for the treatment of hospitalized patients with multilobar pneumonia. [Klebsiella pneumoniae glycoproteins as coadjuvants in the prevention of recurrent respiratory infections in children 1-6 years of age]. Ceftazidime vs. standard therapy for pediatric meningitis: therapeutic, pharmacologic and epidemiologic observations. A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal. Prophylactic human granulocyte colony-stimulating factor after induction therapy in pediatric acute myeloid leukemia. Granulocyte colony-stimulating factor (G-CSF) with or without a quinolone in the prevention of infection in cancer patients. Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study. Prospective comparative trial of ceftriaxone vs. conventional therapy for treatment of bacterial meningitis in children.
Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear.
                We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC).
                Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups.
                The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required. This study assessed the safety and efficacy of filgrastim (r-metHuG-CSF [recombinant human methionine granulocyte colony-stimulating factor]), when combined with intravenous (IV) antibiotics, in the treatment of hospitalized adult patients with multilobar community-acquired pneumonia (CAP). Four hundred eighty patients were randomized to receive placebo (n=243) or filgrastim 300 microg/day (n=237), in addition to standard therapy. Treatment with study drug was continued for 10 days, until the peak white blood cell (WBC) count reached 75x109/L, until discharge from the hospital, until death, or until IV antibiotics were discontinued. Study-related observations continued through day 29. Filgrastim increased WBC counts (baseline median, 13.3x109/L; median peak, 43. 8x109/L). The 2 treatment groups were not statistically different with respect to the study end points; however, there was a trend toward reduction of mortality in patients with pneumococcal bacteremia. Although further studies will be required to validate this observation, filgrastim was safe and well tolerated when administered to patients with multilobar CAP. Forty two children with clinical diagnosis of recurrent high and low respiratory infections, were treated with an extract of P1 and F1 glycoproteins; fraction of Klebsiella pneumoniae, 1 g/day for one week a month for three months, according to a double-blind, randomized, parallel group trial.
                Improvement of clinical and laboratory results were compared with 44 control patients with the same age and similar sex distribution, that were treated with placebo. At the end of study, clinical analysis at 6, 9 and 12 months after the initial dose of Klebsiella pneumoniae, decreased in the number of respiratory infections, sick days, and school assistance were observed in the study group when compared with the control group (p < 0.001 in all parameters). There were not statistical significant changes in hemolytic complement, C3, C4 and immunoglobulins (IgA, IgG, IgM and IgE) levels before and after treatment and between groups. There were not observed adverse reactions to oral treatment with this extract of Klebsiella pneumoniae.
                These results suggested that the extract of Klebsiella can be used as a coadjuvant in the treatment of pediatric patients with recurrent high and low respiratory infections. One hundred patients ages 1 month to 15 years received either ceftazidime (CZ) at a dose of 150 mg/kg/day divided every 8 hours or conventional treatment with chloramphenicol and ampicillin (CA). Seventy-eight had isolates recovered from the cerebrospinal fluid: 40 (51%) were Haemophilus influenzae (all ampicillin-susceptible); 16 (21%) were Streptococcus pneumoniae; 14 (18%) were Neisseria meningitidis; 3 (4%) were salmonellae; 1 (2%) was Pseudomonas; and 1 (2%) was Group B Streptococcus. Six patients with negative cerebrospinal fluid culture had positive latex agglutination (two H. influenzae, three N. meningitidis, one S. pneumoniae). Sixty-one patients had positive blood cultures. CZ inhibited 100% of H. influenzae at 0.78 micrograms/ml, S. pneumoniae at 0.39, N. meningitidis at 0.04 and salmonellae at 0.39 micrograms/ml. The mean peak serum concentration of CZ was 36.4 micrograms/ml with a mean cerebrospinal fluid level of 7.4 micrograms/ml. If one eliminates from the statistics those patients who died less than or equal to 24 hours after admission, five (10%) of 49 patients treated with CZ died, one (2%) improved and 43 (88%) were cured. Overall 29 patients died, 12 receiving CZ (20%) and 8 receiving CA (21%). There were no significant CZ-related toxicities. Gross neurologic sequelae were noted in 5% of 38 CZ patients and 4% of 28 CA patients. CZ compared favorably to CA for treatment of meningitis. Pneumonia is a leading cause of illness and death in young children. Interventions to improve case management of pneumonia are needed.
                Our objective was to measure the effect of zinc supplementation in children with pneumonia in a population in which zinc deficiency is common.
                In a double-blind, placebo-controlled clinical trial, children aged 2-35 mo with severe (n = 149) or nonsevere (n = 2479) pneumonia defined according to criteria established by the World Health Organization were randomly assigned to receive zinc (10 mg for children aged 2-11 mo, 20 mg for children aged > or =12 mo) or placebo daily for 14 d as an adjuvant to antibiotics. The primary outcomes were treatment failure, defined as a need for change in antibiotics or hospitalization, and time to recovery from pneumonia.
                One of 5 children did not respond adequately to antibiotic treatment; the odds ratios between zinc and placebo groups for treatment failure were 0.95 (95% CI: 0.78, 1.2) for nonsevere pneumonia and 0.97 (95% CI: 0.42, 2.2) for severe pneumonia. There was no difference in time to recovery between zinc and placebo groups for nonsevere (median: 2 d; hazard ratio: 1.0; 95% CI: 0.96, 1.1) or severe (median: 4 d; hazard ratio: 1.1; 95% CI: 0.79, 1.5) pneumonia. Regurgitation or vomiting < or =15 min after supplementation was observed more frequently among children in the zinc group than among those in the placebo group during the supplementation period (37% compared with 13%; odds ratio: 0.25; 95% CI: 0.20, 0.30).
                Adjuvant treatment with zinc neither reduced the risk of treatment failure nor accelerated recovery in episodes of nonsevere or severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00148733. Children with acute myelogenous leukemia (AML) have a high risk of infectious complications that might be reduced by prophylactic granulocyte colony-stimulating factor (G-CSF). However, G-CSF could induce AML blast proliferation. The prospective randomized trial AML-BFM 98 investigated the impact of G-CSF on hematopoetic recovery and infectious complications (primary endpoints) and on outcome (secondary endpoint) in children (aged 0-18 years) with de novo AML. Patients with more than 5% blasts in day-15 bone marrow or with FAB M3 were not included. Between 1998 and 2003, 161 children with AML were randomized to receive G-CSF after inductions 1 and 2, whereas 156 patients were assigned to the control group. Time of neutropenia after inductions 1 and 2 was significantly shorter in the G-CSF group (23 vs 18 days and 16 vs 11 days; P=.02 and=.001, respectively). G-CSF did not decrease the incidence of febrile neutropenia (72 and 36 patients vs 78 and 37 patients, respectively), microbiologically documented infections (27 and 25 patients vs 36 and 19 patients, respectively) and infection-associated mortality (5 vs 2 patients). Both groups had similar 5-year event-free survival (EFS; 59%+/-4% vs 58%+/-4%). Since G-CSF does not influence the risk of infectious complications or outcome in children undergoing therapy for AML, one cannot advocate the routine use of G-CSF in this patient group. 59 patients who had earlier developed an infection following antineoplastic chemotherapy were randomised to receive either granulocyte colony-stimulating factor (G-CSF) alone or G-CSF+quinolone as prophylaxis during subsequent identical chemotherapy courses. 30 patients received 48 courses of G+CSF, while 29 patients received 44 courses of G-CSF+ofloxacin or ciprofloxacin. The overall infection rate was 23%. Patients with WHO grade IV leukopenia at the onset of prophylactic treatment developed infection in 61% of cases when on G-CSF, but only in 22% when on G-CSF+quinolone (P = 0.002). Patients with initial leukopenia of grade WHO III-I had only a 11% infection rate showing no significant difference between the treatment groups. The median duration of leukopenia < 1 x 10(9)/l was 4 days for patients receiving G-CSF alone and 3.5 days for those receiving additional quinolone. Patients developing infection had grade IV leukopenia for a median of 5 days. Both prophylactic treatments were well tolerated. We conclude that when prophylactic G-CSF is initiated at WHO grade IV leukopenia, addition of an oral quinolone reduces the risk of infection. Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation. Fifty children with bacterial meningitis were prospectively evaluated in a randomized comparative trial of twice daily ceftriaxone with conventional ampicillin and chloramphenicol therapy. The groups were comparable in age, sex, days of illness before admission, severity of illness at admission, etiology and admission cerebrospinal fluid (CSF) parameters and bacterial colony counts. The pathogens were Haemophilus influenzae type b (34 beta-lactamase-negative, 8 beta-lactamase-positive); Streptococcus pneumoniae (4); Neisseria meningitidis (3); and Streptococcus agalactiae (1). Initial CSF colony counts ranged from 2.5 X 10(2) to 1 X 10(10) colony-forming units/ml. In 44 children a lumbar puncture was repeated 10.5 to 18 hours after starting treatment; 16 of 24 (67%) ceftriaxone patients and 12 of 20 (60%) conventional therapy patients had sterile cultures. The reduction in the CSF bacterial colony counts (6.3 log10 colony-forming units/ml) was similar in both groups. Ceftriaxone CSF levels ranged from 1.0 to 8.0 micrograms/ml, representing a mean CSF penetration of 11.3% (range, 3.0 to 24.5%) of the simultaneous serum concentration. The median ceftriaxone bactericidal titer in CSF was 1:1024 compared with 1:4 achieved with conventional therapy. There were no significant differences in clinical responses or in frequency of complications, except for diarrhea which occurred in 59% of the ceftriaxone group and in 22% of the other (P less than 0.01). Despite one H. influenzae type b relapse occurring in the ceftriaxone group, ceftriaxone appears to be safe and as effective as conventional therapy for bacterial meningitis in children older than 2 months of age.
There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.