[Antifungal therapy for infants, children and adolescents with suspected or documented invasive fungal infection]. / Terapia antifungica para neonatos, ninos y adolescentes con micosis invasiva sospechada o documentada.

Fungal nosocomial infections have gradually and consistently increased since the 90s.This increasing threat is closely related with the growing number of people with immune system disorders and their survival. It is also related with the destruction of their physical barriers against infection due to the use of cytotoxic drugs or invasive procedures, such is the case of cancer patients and bone marrow and solid organ transplant patients. Increased survival of patients with congenital or acquired immunodeficiency, premature babies and patients with complex congenital malformations, especially in the gastrointestinal tract, also add up to this scenario. The occurrence of yeast and filamentous fungi infections, especially of the Candida species, has been on the rise. Azole agents overuse, especially fluconazole, for the treatment and prophylaxis of fungal infections has put selective pressure on Candida spp. which resulted in an increase of non-albican species such as C. krusei, C. glabrata and C. famata, among others, as well as their growing resistance to these antifungal agents.

Disseminated histoplasmosis in infants.

BACKGROUND: Disseminated histoplasmosis usually occurs in immunocompromised patients who reside in Histoplasma capsulatum-endemic regions. It has also been described in immunocompetent infants after exposure to a large inoculum of the pathogen resulting in case fatality rates of 40 to 50%. METHODS: From 1983 through 1996 all infants with documented disseminated histoplasmosis were treated with amphotericin B followed by daily ketoconazole for 3 months. Immunologic workups were performed at the time of diagnosis and at 4 to 6 weeks of therapy. Surviving patients were followed for at least 1 year. Time to resolution of signs and symptoms was recorded, as were complications. RESULTS: We managed 40 patients with disseminated histoplasmosis. The age in months at diagnosis was 15.3+/-10.2 (mean +/- SD), and 24 were male. All patients were from endemic regions and they presented with fever, spleen and/or liver enlargement and hematologic abnormalities. Diagnosis was made by histology and culture of bone marrow, spleen, lymph node, bronchoalveolar or liver samples. Twenty patients presented with T cell deficiency that resolved at 4 to 6 weeks of therapy in all of the retested patients, and 10 of 12 tested patients had hyperglobulinemia that resolved. Thirty-five (88%) patients were cured by treatment; 4 died and 1 relapsed. CONCLUSIONS: Disseminated histoplasmosis should be considered in infants from endemic areas who present with fever, hepatosplenomegaly and hematologic abnormalities. These patients develop transient hyperglobulinemia and T cell deficiency that resolve with treatment. Treatment with amphotericin B followed by an oral azole for 3 months is effective in most patients.

Prospective, randomized, investigator-blinded study of the efficacy and safety of meropenem vs. cefotaxime therapy in bacterial meningitis in children. Meropenem Meningitis Study Group.

OBJECTIVES: To compare the efficacy and safety of meropenem with cefotaxime for the treatment of infants and children with bacterial meningitis. METHODS: Infants and children with strongly suspected or documented bacterial meningitis were randomly assigned in a prospective multicenter study to receive either meropenem or cefotaxime. Patients were assessed at the end of therapy and at 5 to 7 weeks and 5 to 7 months after the end of treatment for the presence of neurologic and sensory neural sequelae. RESULTS: A total of 258 children were randomized to either treatment group. A further 8 patients with suspected pneumococcal meningitis were treated with meropenem without randomization. Of the randomized patients 154 were fully evaluable, 79 in the meropenem group and 75 in the cefotaxime group. At the end of treatment there were no significant differences in clinical outcome between the two treatment groups. Clinical cure with or without sequelae was achieved in 97 and 96% of the meropenem- and cefotaxime-treated patients, respectively. At the end of treatment and at 5 to 7 weeks, 46 and 54% of meropenem patients were cured with no sequelae, respectively. Corresponding results for cefotaxime patients were 56 and 58%. All pathogens were eradicated. In total 37 patients had seizures during treatment, 15 (12%) in the meropenem and 22 (17%) in the cefotaxime group. None of the seizures was considered to be drug-related. CONCLUSIONS: This trial shows that meropenem is suitable therapy for bacterial meningitis in infants and children and that it offers an efficacy and safety profile similar to that of cefotaxime.

Cefotaxime for treatment of neonatal sepsis and meningitis.

Neonatal sepsis is a clinical syndrome characterized by systemic signs and symptoms, and bacteremia during the first month of life. The incidence is relatively low (one to eight cases/1000 live births), yet the risk of mortality is approximately 25%. Meningitis in the neonate is usually a sequela of bacteremia; however, it is discussed with neonatal sepsis, because they commonly share etiology and pathogenesis. The incidence of meningitis is usually a fraction of the number of infants with sepsis, varying in different settings from one-fourth to one-third. The mortality rate is high, varying in some series from 15%-50%. There are two major forms of presentation of neonatal sepsis. Early-onset disease presents as a fulminant, multisystemic illness during the first 5-7 days of life; late-onset disease is more commonly recognized after the first weeks of life. Because different microorganisms are responsible for the two forms of disease, the choice of antimicrobial agents also differs. Some organisms such as Escherichia coli, group B streptococci, and Listeria monocytogenes may be responsible, whereas other pathogens such as Staphylococcus aureus and S. epidermidis, and Pseudomonas aeruginosa are usually associated with late-onset disease. Classic initial (empiric) treatment of neonatal sepsis and meningitis consists of ampicillin and an aminoglycoside. With the advent of the third-generation cephalosporins, however, the empiric antimicrobial approach for neonatal sepsis and meningitis has changed in most centers. Third-generation cephalosporins cover more of the pathogens implicated in neonatal sepsis and meningitis, except for the enterococci and L. monocytogenes.(ABSTRACT TRUNCATED AT 250 WORDS)

An education model for otitis media care field-tested in Latin America.

The World Health Organization has designated the teaching of otitis media management skills a "priority" status. Effective treatment of ear disease requires that the physician be both informationally educated as well as physically trained to use otoscopy. Little is known about how well this education can be provided in a short time and in a foreign country. To more objectively assess teaching effect, results of an education session for rural Mexican pediatric primary-care providers who were given an intensive otitis media lecture and otoscopy skills workshop in 1990 were evaluated. To test immediate cognitive impact, an anonymous written examination was given both before and after the teaching session. Average test scores after the educational sessions improved 24% (p < 0.001) over baseline scores before the sessions. To evaluate long-term impact on clinical practice, a follow-up telephone survey 2 years later was conducted. The use of an otoscope to diagnose otitis media had increased from 40% to 93% of respondents. We conclude that pediatric primary-care providers in rural Mexico possess a baseline level of knowledge about otitis media that can be significantly enhanced with one educational session. Further, this teaching effort produces an impact on practice pattern that lasts at least 2 years.

The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis.

BACKGROUND: In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS: We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS: The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS: The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.

Evaluation of aztreonam and ampicillin vs. amikacin and ampicillin for treatment of neonatal bacterial infections.

In a prospective randomized, open study we evaluated aztreonam (AZ) for treatment of neonatal bacterial infections. There were 147 patients enrolled in the study; 75 received AZ and ampicillin (AMP) and 72 amikacin (AM) and AMP (conventional therapy). Twenty-eight AZ/AMP-treated patients and 32 conventionally treated patients had bacteriologically documented infections caused by gram-negative enteric bacilli or Pseudomonas species. Treatment groups were comparable in age, clinical status, and type and severity of underlying disease at the time of enrollment. Bronchopneumonia and infections caused by Pseudomonas species occurred significantly more often in AM/AMP-treated patients compared with patients given AZ/AMP. Sepsis was documented in 83% of patients in each treatment group and Gram-negative enteric bacilli and Pseudomonas species were the principal pathogens. Median peak serum bactericidal titers against the etiologic agent were 1:64 for the AZ/AMP and 1:16 for AM/AMP-treated patients. Case fatality rates resulting from the primary infection were 7 and 22% (P = 0.011), superinfection occurred in 39% and 34% and treatment failure occurred in 7 and 28% (P = 0.036) of the AZ/AMP and AM/AMP-treated patients, respectively. No clinical adverse reactions were observed in either group. Based on these results aztreonam appears to be at least as effective as and possibly more effective than amikacin when used initially with ampicillin for empiric treatment of neonatal bacterial infections.

[Educational and research program on diagnosis and treatment of otitis media in Latin America]. / Programa educacional y de investigación sobre diagnóstico y tratamiento de otitis media en latinoamérica.

Otitis media in Latin America is an important cause of hearing impairment and infectious complications which can be prevented without an inordinate effort or investment of resources. The Latin American Otitis Media Research and Training Program is a multidisciplinary, international project designed to improve the detection an treatment of otitis media in Latin America. Over 200 health care providers have already participated in pilot seminars presented in Brazil, Costa Rica, and Mexico. These sessions were highlighted by audiovisual presentations emphasizing pneumatic otoscopy. We conclude that this focused program of medical education can significantly contribute to improve primary health care in the region.

Spiramycin vs. placebo for treatment of acute diarrhea caused by Cryptosporidium.

The efficacy of spiramycin was evaluated in a double blind, placebo-controlled study of 44 immunocompetent infants ages 2 to 13 months who had acute diarrhea caused by Cryptosporidium. Twenty-one patients received spiramycin (100 mg/kg/day) for 10 days and 23 received placebo. On admission the patients in both groups were comparable regarding demographic and clinical characteristics. The infants who were treated with spiramycin had a shorter duration of diarrhea (mean, 5.2 vs. 7.3 days; P = 0.002) and a shorter duration of excretion of oocysts in the stools (7.1 vs. 8.5 days; P = 0.032) compared with those treated with placebo. No clinical or parasitologic relapses were seen in patients of both groups. Mild adverse effects to spiramycin were observed in 2 patients (10%). Spiramycin appeared to hasten clinical recovery and decrease the duration of oocyst excretion in immunocompetent children with diarrheal illness caused by Cryptosporidium.

Single dose antibiotic therapy is not as effective as conventional regimens for management of acute urinary tract infections in children.

One hundred thirty-two children with acute urinary tract infection were randomly assigned to receive trimethoprim-sulfamethoxazole in one dose, two doses daily for 3 days or two doses daily for 7 days. The patient characteristics, etiologic agents and frequency of roentgenologic abnormalities were similar for the three treatment groups. There was no significant difference in bacteriologic cure rates for the single dose regimen (93%) and multidose regimens (96%). The difference in rates of recurrent urinary tract infection between the single dose (20.5%) and 3-day (5.6%) and 7-day (8%) regimens was statistically significant (P = 0.033). A single dose of trimethoprim-sulfamethoxazole is inadequate treatment for infants and children with acute urinary tract infection.

Comparative efficacy of ceftazidime vs. carbenicillin and amikacin for treatment of neonatal septicemia.

The efficacy and safety of ceftazidime were compared with those of carbenicillin and amikacin in 60 neonates with proved invasive bacterial infections. The two treatment groups of patients were comparable with regard to sex, gestational and chronologic ages, associated risk factors, clinical condition on enrollment, focus of infection and bacteriology. Escherichia coli was isolated from blood cultures of 31%, Pseudomonas aeruginosa from cultures of 25%, Klebsiella sp. from cultures of 13% and other Gram-negative enteric bacilli from cultures of 17% of the patients. Staphylococcus aureus was isolated from 20% (12 of 60), and coagulase-negative staphylococci from 8% (5 of 60) of the patients. All Gram-negative coliform bacilli were susceptible to ceftazidime whereas 10, 56 and 77% were resistant to amikacin, carbenicillin and ampicillin, respectively. Serum bactericidal activity against the offending pathogen was as much as 5-fold greater in ceftazidime-treated compared with conventionally treated patients. Seven patients with infections caused by organisms resistant to the study drugs were excluded from analysis. Case-fatality rates were 6.4% (2 of 31) and 21% (6 of 28) in the ceftazidime- and amikacin/carbenicillin-treated patients, respectively. Total failure rates, including deaths, were significantly higher in patients treated with amikacin/carbenicillin (8 of 28, 28.5%) compared with that of ceftazidime-treated patients (2 of 31, 6.4%). Thirteen percent (5 of 31) and 3% (1 of 28) of the ceftazidime- and amikacin/carbenicillin-treated patients, respectively, developed invasive Candida albicans superinfection while receiving treatment. In this study results of treatment with ceftazidime were superior to results of treatment with amikacin/carbenicillin for invasive bacterial infections of newborn infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotaxime vs. conventional therapy for the treatment of bacterial meningitis of infants and children.

Eighty-five infants and children were prospectively randomized to receive cefotaxime or ampicillin and chloramphenicol for therapy of bacterial meningitis. The two therapy groups of patients were comparable as to sex, age, clinical status on admission, prior administration of antibiotics and etiology. Three infants (7%) died in each therapy group. Mean number of days of positive cerebrospinal fluid cultures, time to defervescence and duration of treatment and of hospital stay and complications developing during treatment were similar for the two treatment regimens. Median cerebrospinal fluid bactericidal titers against the patients' pathogens in cefotaxime-treated patients (1:64) were larger than those in patients who received conventional therapy (1:8). Mild to moderate motor sequelae were more frequent in those given conventional therapy at the time of discharge only, and not at 4 months or longer of follow-up. We conclude that cefotaxime has similar efficacy when compared with conventional therapy for the management of bacterial meningitis in pediatric patients.

Comparative treatment trial of augmentin versus cefaclor for acute otitis media with effusion.

A total of 150 children with acute otitis media were randomly allocated to treatment with amoxicillin-potassium clavulanate (Augmentin) or with cefaclor. Each drug was given in a daily dosage of approximately 40 mg/kg in three divided doses for ten days. Tympanocentesis done before treatment yielded specimens that contained pneumococcus or Haemophilus sp or both in 67% of specimens. Viridans group streptococci were isolated from 10% of specimens and Branhamella catarrhalis from 6%. Patients were scheduled for follow-up examinations at midtreatment, end of therapy, and at 30, 60, and 90 days. Of the 150 children, 130 were evaluable. Five of 60 patients (8%) treated with cefaclor were considered therapeutic failures because of persistent purulent drainage and isolation of the original pathogen or suprainfection. There were no failures among patients treated with Augmentin (P = .019). Rates of relapse, recurrent acute otitis media with effusion, and persistent middle ear effusion were comparable in the two groups of patients. Diaper rash, or loose stools, or both were significantly more common in children treated with Augmentin (34%) than in those taking cefaclor (12%), but in no case was it necessary to discontinue medication because of these mild side effects (P = .002). Cefaclor therapy was discontinued in one patient because of severe abdominal pain and vomiting. In this study, treatment with Augmentin was superior to treatment with cefaclor in the acute phase of acute otitis media with effusion, but Augmentin produced more adverse effects. The rates of persistent middle ear effusion and recurrent acute otitis media with effusion were comparable with the two regimens.

CSF shunt infections in pediatrics. A seven-year experience.

The medical records of children who had had CSF shunt procedures were reviewed for the seven-year period from 1975 through 1981. There were 516 procedures performed in 297 patients. Only three were ventriculoatrial shunts; the remainder were ventriculoperitoneal shunts. Fifty-nine infectious episodes (11%) occurred in 50 patients (17%); there were three relapses and six reinfections. The infecting pathogen was staphylococci in 75% of the infections and gram-negative bacilli in 19%, and there were two or more pathogens in 15% of the infections. The onset of the infection was within 15 days of surgery in 53% of the cases. The main symptoms were fever, irritability, and shunt malfunction. Gram's stain of the CSF was positive in 46% of the episodes and blood cultures were positive in 29%. Nineteen percent of patients had wound infection and 7% had peritonitis; in most of these cases there were no neurologic signs or symptoms. Thirteen episodes were managed with antibiotic therapy alone; among these, there were three relapses and two reinfections. Thirty-seven episodes were treated with antibiotics and immediate removal of the shunt; there were no relapses and three reinfections. Nine episodes were managed with antibiotics and delayed removal of the shunt; there was one reinfection. The median duration of antibiotic treatment was 15 days, and the time to defervescence was 24 hours in those with immediate removal of the shunt and six days in those in whom the shunt was not removed.