José Cofré

Prospective, Multicenter Evaluation of Risk Factors Associated With Invasive Bacterial Infection in Children With Cancer, Neutropenia, and Fever

PURPOSE To identify clinical and laboratory parameters present at the time of a first evaluation that could help predict which children with cancer, fever, and neutropenia were at high risk or low risk for an invasive bacterial infection. PATIENTS AND METHODS Over a 17-month period, all children with cancer, fever, and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto a prospective protocol. Associations between admission parameters and risk for invasive bacterial infection were assessed by univariate and logistic regression analyses. RESULTS A total of 447 febrile neutropenic episodes occurred in 257 children. Five parameters were statistically independent risk factors for an invasive bacterial infection. Ranked by order of significance, they were as follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2; 95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95% CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to 2.3); platelet count less than or equal to 50,000/mm(3) (RR, 1.7; 95% CI, 1.4 to 2.2); and recent (< or = 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6). Other previously postulated risk factors (magnitude of fever, monocyte count) were not independent risk factors in this study population. CONCLUSION In a large population of children, common clinical and laboratory admission parameters were identified that can help predict the risk for an invasive bacterial infection. These results encourage the possibility of a more selective management strategy for these children.

Prospective Evaluation of a Model of Prediction of Invasive Bacterial Infection Risk among Children with Cancer, Fever, and Neutropenia

A risk prediction model for invasive bacterial infection (IBI) was prospectively evaluated among children presenting with cancer, fever, and neutropenia. The model incorporated assessment of 5 previously identified risk factors: serum level of C-reactive protein (CRP) >/=90 mg/L, hypotension, identification of relapse of leukemia as the cancer type, platelet count of </=50,000 platelets/mm(3), and recent receipt of chemotherapy [16]. Children were uniformly evaluated at enrollment and were classified as having high or low risk for IBI according to a model that considers the number and type of variables present. Of the 263 febrile episodes evaluated during a 17-month period, 140 (53%) were in IBI-positive children. The sensitivity, specificity, and positive and negative predictive values of the model were 92%, 76%, 82%, and 90%, respectively. Identification of these 5 risk factors during the first 24 h of hospitalization was helpful in discriminating between children with a high or low risk for IBI.

Early Hospital Discharge Followed by Outpatient Management Versus Continued Hospitalization of Children With Cancer, Fever, and Neutropenia at Low Risk for Invasive Bacterial Infection

PURPOSE To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection (IBI). PATIENTS AND METHODS Children presenting with febrile neutropenia at six hospitals in Santiago, Chile, were categorized as high or low risk for IBI. Low-risk children were randomly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution. Outcome and cost were determined for each episode and compared between both groups using predefined definitions and questionnaires. RESULTS A total of 161 (41%) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk, of which 149 were randomly assigned to ambulatory (n = 78) or hospital-based (n = 71) treatment. In both groups, mean age (ambulatory management, 55 months; hospital-based management, 66 months), sex, and type of cancer were similar. Outcome was favorable in 74 (95%) of 78 ambulatory-treated children and 67 (94%) of 71 hospital-treated children (P = NS). Mean cost of an episode was US 638 dollars (95% CI, 572 dollars to 703 dollars) and US 903 dollars (95% CI, 781 dollars to 1,025 dollars) for the ambulatory and hospital-based groups, respectively (P =.003). CONCLUSION For children with febrile neutropenia at low risk for IBI, ambulatory management is safe and significantly cost saving compared with standard hospitalized therapy.

Discontinuation of Antimicrobial Therapy for Febrile, Neutropenic Children with Cancer: A Prospective Study

During a 2-year period, all children with cancer, neutropenia, and fever who were admitted to Hospital de Niños Luis Calvo Mackenna (Santiago, Chile) were enrolled in a study of the safety of stopping antibiotic therapy on day 3 of treatment. Children who met predefined criteria for nonbacterial fever were randomized on day 3 to stop (group A) or continue (group B) antibiotic therapy. A total of 220 children with cancer had 238 episodes of fever and neutropenia; 68 children with 75 episodes met entry criteria for nonbacterial fever (group A, 36; group B, 39). Both groups were comparable in terms of age, gender, oncological disease, chemotherapy status, and initial neutrophil count. Resolution of symptoms occurred in 34 of 36 episodes in group A and 36 of 39 episodes in group B (P > .05). No deaths occurred, and bacterial superinfections were uncommon. For children with cancer as well as episodes of fever and neutropenia without an identifiable bacterial etiology at admission, stopping antibiotic therapy on day 3 was safe and not associated with a higher risk of bacterial superinfections.

Differential time to positivity and quantitative cultures for noninvasive diagnosis of catheter-related blood stream infection in children.

Background: Accurate diagnosis of catheter-related blood stream infection (CRBSI) is necessary to make a decision about removal of the catheter. Differential time to positivity (DTP) and the ratio of quantitative cultures (RQC) between central and peripheral blood cultures have not been evaluated against a strict standard in children, namely catheter tip culture. Objective: Our aim is to compare DTP and RQC in the diagnosis of catheter tip-confirmed catheter-related infection in children. Method: Prospective study performed in 2 large hospitals in Santiago, Chile. Children with clinically suspected CRBSI had 2 peripheral and central vein blood samples obtained for automated culture in Bact/Alert and for quantitative cultures in 5% sheep blood agar plate. The catheter tip was cultured. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios (LR), and accuracy of DTP and RQC were compared against catheter tip-confirmed CRBSI. Results: During a 3-year period, 344 clinically suspected CRBSIs were diagnosed in children of which 124 episodes met study criteria. Catheter tip culture-confirmed CRBSI in 25 (20%) of 124 episodes. A total of 34 microorganisms were cultured from 25 CRBSI; 8 of 25 (32%) episodes were polymicrobial. Staphylococcus aureus followed by coagulase-negative Staphylococcus were the most common microorganisms. For CRBSI, DTP and RQC reached a sensitivity of 75% versus 24% (P < 0.001), specificity of 86 versus 94%, positive predictive value of 58% versus 50%, negative predictive value of 93% versus 82%, LR of 5.48 versus 4.50, and accuracy of 0.84 versus 0.79. Conclusions: In children, DTP was better than RQC for diagnosis of catheter tip-confirmed CRBSI.

Penicillin resistance is not extrapolable to amoxicillin resistance in Streptococcus pneumoniae isolated from middle ear fluid in children with acute otitis media.

Objectives: We evaluated the in vitro antibacterial activity of amoxicillin against penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae strains isolated from children with acute otitis media (AOM). Methods: Children more than 3 months of age with AOM who were seen in the Dr Sótero del Rio and Luis Calvo Mackenna Hospitals in Santiago, Chile, between July 1998 and December 2002 were subjected to tympanic puncture for middle ear fluid culture. The penicillin and amoxicillin susceptibilities of the S pneumoniae isolates were determined by epsilometer test (E test). Results: A bacterial pathogen was isolated in 432 of 543 children (80%) as follows: S pneumoniae, 40%; Haemophilus influenzae, 29%; Moraxella catarrhalis, 7%; and Streptococcus pyogenes, 4%. Penicillin-susceptible S pneumoniae strains were less common than amoxicillin-susceptible strains (60% versus 95%; odds ratio [OR], 0.08; 95% confidence interval [CI], 0.04 to 0.18). Both intermediate- and high-resistance strains were more common for penicillin (22% versus 4.5%; OR, 5.6; 95% CI, 2.5 to 12.7) than for amoxicillin (18% versus 0.5%; OR, 41.3; 95% CI, 6.0 to 821). Conclusions: Penicillin resistance is not extrapolable to amoxicillin among S pneumoniae strains isolated from middle ear fluid of children with AOM. Our results support the recommendation to evaluate the minimal inhibitory concentrations of penicillin-nonsusceptible S pneumoniae for amoxicillin and to continue use of this antimicrobial as a first-line antimicrobial choice for children with AOM.

Encefalitis herpética neonatal: valor de la clínica versusla biología molecular

Herpes simplex encephalitis is a diagnostic challenge and causes high morbidity and mortality in children. Early suspicion of the disease and a rapid, safe and useful diagnostic test are relevant because up to 70% of the cases may die. We report the case of a newborn girl aged 25 days, who presented with a clinical picture that was compatible with herpes simplex encephalitis where the confirmation of the etiological diagnosis was delayed. Only by repeated real-time polymerase chain reaction it was possible to confirm the presence of herpes simplex virus type 1 in the cerebrospinal fluid.

Mal de Pott y diagnóstico inmunológico de tuberculosis, a propósito de un caso pediátrico

La tuberculosis sigue siendo un importante problema en salud en el mundo. Las formas clinicas de TBC en los ninos son muy variadas, presentandose en dos tercios de los casos compromiso pulmonar. En el tercio restante destacan los compromisos ganglionar, meningeo y osteoarticular. Caso clinico: varon de 7 anos que presento una espondilodiscitis L2-L3, asociada a un absceso en musculo psoas-iliaco derecho. Por sospecha de mal de Pott se realizo PPD y T-SPOT®.TB que resultaron positivos. Se inicio tratamiento antimicrobiano asociado con isoniazida, rifampicina, pirazinamida y etambutol. Despues de 30 dias, se aislo Mycobacterium tuberculosis del absceso del psoas. Se discute los metodos de diagnostico de TBC en pediatria, con especial enfasis en los metodos inmunologicos: reaccion de tuberculina y test de liberacion de interferon-gamma, los que son una importante contribucion para el diagnostico de esta enfermedad, permitiendo el pronto inicio de su tratamiento.

Diarrea asociada a Clostridium difficile en niños

INTRODUCTION Clostridium difficile is the most commonly isolated organism in antimicrobial and health care-associated diarrhea and is growing in relevance in community-acquired infections. It is a Gram-positive bacillus acquired via the fecal-oral route in the community and in hospital setting. EPIDEMIOLOGY 0.6 to 2.1% worldwide incidence, mortality ~ 1-5%. COLONIZATION: High rates of asymptomatic colonization in healthy people, 37% in children: its presence in stools is of controversial significance. Risk factors in children are prior exposure to antibiotics, recent hospitalization, immunosuppression or inflammatory bowel disease. CLINICAL MANIFESTATIONS Secondary to intestinal involvement due to toxin production, ranging from asymptomatic colonization to fulminant disease. DIAGNOSIS Clinical diagnostic criteria plus high sensitivity and specificity laboratory certification. Recommendations AAP (American Academy of Pediatrics): under 1 year, avoid routine study, only in Hirschsprung disease and/or nosocomial outbreak, 1-3 year, a (+) result suggests C. difficile associated diarrhea (CDAD) is possible, and in children older than 3 years interpretation is equal to adults. MANAGEMENT Antimicrobial suspension, oral metronidazole as first line in mild to moderate CDAD, and oral or enema vancomycin or associated with intravenous metronidazole only in severe cases. Duration 10 days. PREVENTION Antimicrobial control programs and environmental management. CONCLUSION Given the increasing complexity of pediatric patients it is important to deepen the knowledge on this microorganism and its clinical manifestations, as its incidence, morbidity and mortality are increasing.

[Meningococcal disease: frequently asked questions].

On account of an increase of serogroup W135 meningococcal disease (M.D.) observed in Santiago, Chile, during last two years the medical community has experienced an avidity to update their knowledge about M.D. treatment and its prevention. In a queries and answers mode, the following topics on M.D. are presented: nasopharyngeal carriage and its importance, immunity and protection against the disease, reasons to choice ceftriaxone as the first line antibiotic in treatment, rationality and indications of chemoprophylaxis, fundamentals and advantages of conjugate vaccines, its indications, schedules, contraindications and decisions making in public health.