Mónica Trujillo

Etiology and treatment of community-acquired pneumonia in ambulatory children.

OBJECTIVES To determine the etiology of community-acquired pneumonia in ambulatory children and to compare responses to treatment with azithromycin, amoxicillin-clavulanate or erythromycin estolate. METHODS Ambulatory patients with pneumonia were identified at the Childrens Medical Center of Dallas, TX. Children age 6 months to 16 years with radiographic and clinical evidence of pneumonia were enrolled and randomized to receive either azithromycin suspension for 5 days or a 10-day course of amoxicillin-clavulanate for those <5 years or erythromycin estolate suspension for those > or = 5 years. Blood culture was obtained in all patients and we obtained nasopharyngeal and pharyngeal swabs for culture and polymerase chain reaction (PCR) testing for Chlamydia pneumoniae and Mycoplasma pneumoniae and nasopharyngeal swabs for viral direct fluorescent antibody and culture. Acute and convalescent serum specimens were tested for antibodies to C. pneumoniae, M. pneumoniae and Streptococcus pneumoniae. Patients were evaluated 10 to 37 days later when repeat specimens for serology, PCR and culture were obtained. For comparative purposes healthy children attending the well-child clinic had nasopharyngeal and pharyngeal swabs obtained for PCR and culture for C. pneumoniae and M. pneumoniae. RESULTS Between February, 1996, and December, 1997, we enrolled 174 patients, 168 of whom fulfilled protocol criteria for evaluation. There were 55% males and 63% were <5 years of age. All blood cultures were sterile and there was no correlation between the white blood cell and differential counts and etiology of pneumonia. Etiologic agents were identified in 73 (43%) of 168 patients. Infection was attributed to M. pneumoniae in 7% (12 of 168), C. pneumoniae in 6% (10 of 168), S. pneumoniae in 27% (35 of 129) and viruses in 20% (31 of 157). None of the swab specimens from 75 healthy control children was positive for C. pneumoniae or M. pneumoniae. Clinical response to therapy was similar for the three antibiotic regimens evaluated, including those with infection attributed to bacterial agents. CONCLUSION Although a possible microbial etiology was identified in 43% of the evaluable patients, clinical findings and results of blood cultures, chest radiographs and white blood cell and differential counts did not distinguish patients with a defined etiology from those without a known cause for pneumonia. There were no differences in the clinical responses of patients to the antimicrobial regimens studied.

Cerebrospinal fluid values in the term neonate

BACKGROUND Cerebrospinal fluid (CSF) values in the noninfected neonate are not well-delineated. Studies analyzing these values are inconsistent in the criteria used to define the noninfected population. The purpose of our study was to examine CSF values in neonates in the first 30 days of life in whom infection was more thoroughly excluded than in previous reports. Stringent inclusion criteria defined the noninfected population, and the recently available polymerase chain reaction (PCR) for enteroviruses was used in addition to cultures to help exclude viral disease. Results were also stratified by age in weeks to evaluate for any variability that occurs in CSF values during the first month of life. METHODS Neonates were selected from subjects enrolled in two studies on aseptic meningitis. Noninfected infants were identified by the following criteria: (1) atraumatic lumbar puncture (< or = 1000 red blood cells/mm3); (2) no antibiotic therapy before lumbar puncture; (3) sterile blood, CSF and urine bacterial cultures; (4) negative CSF viral culture; and (5) negative CSF PCR for enteroviruses. RESULTS The mean +/- SD total CSF white blood cell count for 108 noninfected neonates was 7.3 +/- 14/mm3 (95% confidence interval 6.6 to 8.0/mm3) with a median of 4/mm3 and a range of 0 to 130/mm3. There were no significant differences in the mean CSF white blood cell counts among age categories. CONCLUSIONS The application of stringent inclusion criteria and the use of the PCR yielded a population of infants that better represents the noninfected neonate than earlier reports. These values can be used for reference in evaluating the febrile or ill neonate.

The Effect of Interleukin-10 on Meningeal Inflammation in Experimental Bacterial Meningitis

Interleukin-10 (IL-10) is a cytokine with antiinflammatory effects. In a rabbit model of meningitis, IL-10 was given intracisternally or intravenously to evaluate the impact on inflammation induced by lipooligosaccharide (LOS), Haemophilus influenzae type b (Hib), or Listeria monocytogenes. Intracisternal IL-10 in concentrations >1 microg significantly reduced tumor necrosis factor-alpha (TNF-alpha) and lactate values in cerebrospinal fluid (CSF). Intravenous IL-10 (1 mg/kg) in two doses after intracisternal LOS significantly reduced CSF TNF-alpha and lactate. When Hib was used, animals were treated with ceftriaxone and dexamethasone with or without IL-10 (1 mg/kg). TNF-alpha was significantly reduced in animals treated with IL-10, dexamethasone, or both compared with levels in rabbits receiving ceftriaxone alone. Comparable results were obtained when L. monocytogenes was inoculated and animals were treated with ampicillin with or without IL-10, dexamethasone, or nothing. In conclusion, IL-10 modulates CSF TNF-alpha concentrations in experimental LOS, Hib, or L. monocytogenes meningitis. The maximal inhibitory effect was seen when IL-10 and dexamethasone were combined.

Evaluation of CP-99,219, a new fluoroquinolone, for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.

CP-99,219 is a new fluoroquinolone that has excellent activity against gram-positive organisms including penicillin- and cephalosporin-resistant Streptococcus pneumoniae strains. In our well-established rabbit model of meningitis, we conducted experiments to determine the concentrations of CP-99,219 in cerebrospinal fluid (CSF) after intravenous administration and its ability to eradicate two penicillin-resistant pneumococcal isolates. The peak and trough concentrations of CP-99,219 in the CSF were from 19 to 25% of the concentrations simultaneously obtained in serum and were unaffected by concomitant dexamethasone administration. Compared with untreated (control) animals, three doses of CP-99,219 given 5 h apart significantly reduced the bacterial count in CSF by 5 to 6 log10 CFU at 10 h. Although 47% of the dexamethasone-treated animals and 18% of those not given the steroid had positive cultures at 24 h (14 h after administration of the last antibiotic dose), the mean bacterial counts did not change from those observed at 10 h. Additionally, only results for animals infected with one of the two pneumococcal strains appeared to be affected by concomitant dexamethasone therapy.

ATP Synthase Is Necessary for Microcin H47 Antibiotic Action

ABSTRACT Microcin H47 is a gene-encoded peptide antibiotic produced by a natural Escherichia coli strain isolated in Uruguay. In order to identify cellular components necessary for its antibiotic action, microcin H47-resistant mutants isolated in this work, as well as previously described mutants affected in membrane proteins, were analyzed. These studies indicated that (i) receptor outer membrane proteins for ferric-catechol siderophores would be involved in microcin-specific binding to the cell surface, (ii) the TonB pathway is needed for microcin H47 uptake, and (iii) the presence of the ATP synthase complex is necessary for microcin action. The possibility that this last structure contains the antibiotic target is discussed.

Suppurative and reactive arthritis in children

Suppurative infections of the joints in children often pose a challenge to the clinician because of difficulties in early recognition of the disease process and subsequent medical and surgical management. A prompt diagnosis is important to institute effective antibiotic therapy and to perform timely surgical procedures to prevent disabling sequelae. Reactive arthritis is a joint inflammation that develops soon after or during an infection elsewhere in the body. A strong association between development of reactive arthritis and HLA-B27 has been known for a long time, but the mechanisms by which this antigen determines the appearance of joint complications remain unclear. This article discusses the microbiological, pathophysiological, clinical, diagnostic, therapeutic, and prognostic aspects of suppurative and reactive arthritis in children.

Clinical Characteristics of Carbapenem-resistant Klebsiella pneumoniae Infections in Ill and Colonized Children in Colombia.

Background: Multidrug-resistant Gram-negative infections represent a growing problem and a serious global threat. Data in children are scarce. Klebsiella pneumoniae carbapenemases (KPC) are the most common mechanism of resistance this organism has developed. We report the clinical characteristics and outcomes from a cohort of children infected or colonized with carbapenem-resistant K. pneumoniae (CRKp) at a tertiary care center in Medellín, Colombia. Methods: We performed a retrospective chart review of all pediatric cases from whom CRKp isolates were obtained from 2008 to 2013. Clinical characteristics and outcomes were recorded. Results: A total of 34 infected children (median age, 22.8 months) with 43 episodes and 55 colonized patients (median age, 33 months) were identified. All patients had at least 1 risk factor previously related with multidrug-resistant Gram-negative infections (premorbid conditions, previous exposure to antibiotics, prolonged length of stay and use of indwelling devices). Urinary tract infections, abdominal infections and bacteremia were the most common clinical presentations. Overall mortality was 38%, and it was lower when a meropenem-containing regimen was used. Colistin was the most used antibiotic either alone or in combination and was associated with 8.8% of nephrotoxicity. Conclusion: CRKp infections have high mortality in children and usually occur in children with comorbidities, prolonged hospital stay and prior antibiotic exposure. Combined therapy with meropenem-containing regimens seems to be the best option in severely ill children.

Experiencia con el uso compasivo de tigeciclina en pacientes pediátricos infectados por Klebsiella pneumoniae productora de carbapenemasas

INTRODUCTION Infections produced by multidrug-resistant pathogens represent a therapeutic challenge because of the few therapeutic options available. Tigecycline is a relatively new antibiotic, with a wide spectrum of activity including some of these resistant bacteria. In adults is prescribed for the treatment of some infections caused by carbapenem resistant K. pneumoniae, however it has not been approved in children because of potential adverse effects in the dental enamel. MATERIALS AND METHODS Case series study. Medical records were reviewed in all children from 0 to 14 years of age that received tigecycline between January of 2008 and March of 2010. RESULTS 9 patients received Tigecycline mainly for treatment of peritonitis, bacteremia, pneumonia and sepsis caused by carbapenem resistant K. pneumoniae. A dose of 1 mg/kg q 12 hours was administered to all patients. No adverse events were reported and a total of 6 patients had complete resolution of the infection. CONCLUSIONS Tigecycline could be considered a therapeutic option for treating infections produced by multidrug-resistant pathogens in children. The use in children is still compassionate and in this series of cases Tigecycline was well tolerated and safe.Introduction: Infections produced by multidrug-resistant pathogens represent a therapeutic challenge because of the few therapeutic options available. Tigecycline is a relatively new antibiotic, with a wide spectrum of activity including some of these resistant bacteria. In adults is prescribed for the treatment of some infections caused by carbapenem resistant K. pneumoniae, however it has not been approved in children because of potential adverse effects in the dental enamel. Materials and Methods: Case series study. Medical records were reviewed in all children from 0 to 14 years of age that received tigecycline between January of 2008 and March of 2010. Results: 9 patients received Tigecycline mainly for treatment of peritonitis, bacteremia, pneumonia and sepsis caused by carbapenem resistant K. pneumoniae. A dose of 1 mg/kg q 12 hours was administered to all patients. No adverse events were reported and a total of 6 patients had complete resolution of the infection. Conclusions: Tigecycline could be considered a therapeutic option for treating infections produced by multidrug-resistant pathogens in children. The use in children is still compassionate and in this serie of cases Tigecycline was well tolerated and safe.

Fungemia due to Kodamaea ohmeri in a young infant and review of the literature.

Fungal infections have become an important cause of morbidity and mortality in hospitalized children due to many complicating and underlying conditions. We present the case of a newborn infant with fungemia due to Kodamaea ohmeri who had a good outcome of the infection after using the combination of antifungal treatment and central venous catheter removal.

Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient

PurposeCARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C. cassiicola. We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C. cassiicola and we searched for mutations in CARD9.MethodsWe reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting.ResultsThe patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C. cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient.ConclusionWe describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C. cassiicola in a Colombian child.