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Biomedical subjects

D Nadal

Publications and source records attributed to D Nadal.

At least 19 recordsLinked to original sources

[Acute fever in infants].

The body temperature is influenced among other things by time of day or age and exhibits a Gaussian inter-individual distribution. If measured orally, normal values vary between 35.6 degrees C and 38.2 degrees C. Temperature exceeding the 99th percentile (> 37.7 degrees C) can therefore be interpreted as fever. Nevertheless, an universally accepted definition of fever does not exist. Viral infection is the most frequent cause of acute fever in infants, even in the absence of a source. Bacterial infections are by far a rarer reason. Nevertheless, below the age of 3 years, acute fever is a ticklish issue because of the higher risk for rapidly evolving life-threatening invasive bacterial infections. Following introduction of vaccination against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae has advanced to the most frequent cause of invasive bacterial infections in infants. Fever is rarely seen in newborns (age 1-28 days), but when present, it is more frequently serious. Around 12% of these newborns show an invasive bacterial infection. Therefore, a full workup for sepsis is strongly indicated. This includes cultures of blood,urine and cerebrospinal fluid plus a chest radiography. In addition, immediate start of an empirical intravenous antibiotic therapy and monitoring in a hospital setting are necessary. Apart from this exception, primary antibiotic therapy is rarely necessary in fever without a detectable focus and source. Also, routine prescription of antipyretics is not indicated. Though paracetamol may improve well-being and drinking behavior of infants, it does neither shorten the duration of fever duration, nor prevent febrile seizures.

Acute Disease↗

Disseminated Fusarium oxysporum infection in hemophagocytic lymphohistiocytosis.

The portal of entry of disseminated Fusarium spp. infections is still not clearly defined. We report on a disseminated Fusarium oxysporum infection occurring during a long period of severe neutropenia in a child with hemophagocytic lymphohistiocytosis. A nasogastric feeding tube was the possible source of entry of the fungus.

Fusarium↗

Port-A-Cath infections in children with cancer.

Implanted subcutaneous (s.c.) central venous port accesses including Port-A-Cath (PAC) facilitate the administration of chemotherapy or blood products and are frequently used in children with cancer. The incidence of PAC-related infections was determined in 155 consecutive paediatric cancer patients with PAC followed for a total of 134,773 days (median, 738; range, 25-2080). Overall, 48 bloodstream infections occurred in 26 patients. 12 (25%) of these infections and 3 local infections at the insertion site were treatment-resistant and demanded removal of the PAC. Coagulase-negative staphylococci were involved in 12 of these 15 episodes. The rate of clearly PAC-related infections in this so far largest reported series was 0.11 episodes per 1000 PAC days, one of the lowest in the literature. Although catheter-related infections demanded PAC removal in 8% of our patients, the long periods PAC were in use and their benefits argue for continued PAC use in the paediatric cancer population.

Adolescent↗

Cerebral actinomycosis before adolescence.

In a 10-year-old boy presenting with focal seizures and 6 months later with acute right-sided hemiparesis, the diagnosis of a cerebral abscess due to Actinomyces israelii was established. The immunocompetent child suffered from a complex congenital heart disease with pulmonary arteriovenous shunts and pulmonary hypertension causing mild cyanosis. His parents had been reluctant to agree to neuroimaging investigations resulting in a delayed diagnosis. Despite the long interval between first symptoms and commencement of treatment including neurosurgical excision of the abscess followed by a 4-week course of ceftriaxone, a complete recovery of the hemiparesis was observed. This patient is the first case with cerebral actinomycosis before adolescence reported so far.

Actinomycosis↗

Pulmonary and systemic bacterial co-infections in severe RSV bronchiolitis.

In 127 infants admitted to intensive care for RSV bronchiolitis, concomitant bacterial sepsis was a rare event. However, in the subgroup of intubated patients the incidence of bacterial pneumonia was 43.9% (95% CI 31.0-56.8%), half community acquired and half nosocomial. As clinical signs are not helpful in identifying these patients, tracheal aspirates have to be investigated microbiologically on a routine basis in order to start antibiotics in time.

Anti-Bacterial Agents↗

Prospective survey of antibiotic utilization in pediatric hospitalized patients to identify targets for improvement of prescription.

BACKGROUND: The rise in the use of antibiotics has resulted in increasing health care costs and the emergence of resistant bacteria. Little is known about the general misuse of antibiotics in hospitalized children. We evaluated the utilization of antibiotics in a pediatric teaching hospital aiming to identify targets for improvement of prescription. PATIENTS AND METHODS: Clinical, radiological, laboratory and treatment data of patients hospitalized in a pediatric medical and a pediatric surgery ward were prospectively collected during a 6-week period. A subsequent review of the collected data by a pediatric infectious diseases specialist, taking into consideration existing in-house treatment guidelines, was carried out. RESULTS: A total of 125 (36%) of 349 patients was prescribed 246 antibiotics. The median length of hospital stay for children prescribed antibiotics was 5 days (range, 2-30 days) and for those not prescribed 3 days (1-32 days; p < 0.001). Of 154 patients in the medical ward, 64 (42%) received antibiotics, compared to 61 (31%) of 195 patients in the surgical ward (p < 0.05). Empirical prescriptions were more frequent than prophylactic ones, which were more frequent than therapeutic prescriptions (136 [55%] vs 94 [38%] vs 16 [7%]; p < 0.001). Overall, 85% of the prescriptions were considered justified. The rates of inappropriate prescriptions were similar in the medical and surgical ward, and higher for therapeutic (19%) or prophylactic treatment (18%) than for empirical treatment (12%). Higher inappropriate prescription rates were noted for macrolides than for co-trimoxazole and beta-lactams (50% vs 18% and 15%, respectively; p < 0.05). CONCLUSION: Efforts need to be undertaken towards continuous education of medical staff on judicious antibiotic use, as well as ensuring compliance with existing guidelines. Improvement in the availability of rapid diagnostic methods to discern viral from bacterial infections may help reduce the numbers of empiric therapies in favor of pathogen-targeted therapeutic treatments.

Anti-Bacterial Agents↗

Fosfomycin for the initial treatment of acute haematogenous osteomyelitis.

BACKGROUND AND AIMS: At our institution there has been a dichotomous antimicrobial treatment behaviour for acute haematogenous osteomyelitis (AHOM) since 1984. The surgical department favoured fosfomycin as initial choice and the medical department beta lactams. We aimed to compare the performance of both strategies. METHODS: Data from patients discharged with the diagnosis of AHOM between January 1984 and January 1998 were gathered from the charts by means of a questionnaire. Patients receiving fosfomycin treatment (FT) were compared with those receiving fosfomycin plus other antimicrobials (FT+) and those receiving no fosfomycin treatment (NFT). RESULTS: A total of 103 patients aged 0.1-15.5 years (mean 6.5, median 6.9) with AHOM received no surgical treatment initially. In 23 (22.3%) FT was instilled initially, in 47 (45.6%) FT+, and in 33 (32.0%) NFT. The pathogen was established in 30%, 36%, and 42% of FT, FT+, and NFT patients, respectively, Staphylococcus aureus being the predominant isolate. Mean C reactive protein levels and erythrocyte sedimentation rates normalised in all treatment groups after two and four weeks, respectively. The mean duration of intravenous antimicrobial treatment in FT patients was 2.5 weeks, in FT+ patients 3.1 weeks, and in NFT patients 3.8 weeks (p < 0.05), whereas the mean duration of intravenous plus oral treatment was comparable (7.1 v 6.8 v 6.5 weeks). CONCLUSIONS: The leucocyte penetrating fosfomycin performed similarly to extracellular beta lactams in the treatment of AHOM. Intravenous treatment for longer than 2.5 weeks offered no advantage.

Acute Disease↗

Growth in human immunodeficiency virus type 1-infected children treated with protease inhibitors.

UNLABELLED: To determine the long-term impact of antiretroviral treatment (ART) including a protease inhibitor (PI) on growth in children infected with the human immunodeficiency virus type I (HIV-1), a prospective multi-centre study was conducted in Switzerland on HIV-1-infected children treated with ritonavir (350 mg/m2 twice a day) or nelfinavir (20-30 mg/kg three times a day) in addition to two nucleoside reverse transcriptase inhibitors. Length or height of HlV-1-infected children from before (weeks -72, -48, -24, and 0) and after (weeks +24, +48, and +72) introducing a PI to the ART were compared. To allow for age- and gender-independent assessment, values were expressed in standard deviations from the mean. Complete data sets on body length were available for 44 children after 72 weeks of treatment with a PI. Preceding initiation of a PI, there was an overall decline in growth to -0.3 SD. Following start of a PI, an increase in growth was noted from weeks 0 to +24 (+0.33 SD, P=0.02) and from weeks +48 to +72 (+0.21 SD, P=0.03). The increase in growth was restricted to children with stunting before a PI was introduced (P=0.03), and was more marked in children younger than 3 years of age. CONCLUSION: children infected with human immunodeficiency virus type 1 showed catch-up growth after addition of a protease inhibitor to their antiretroviral treatment, but this phenomenon was observed almost exclusively in children under 3 years of age.

Adolescent↗

Community-acquired pneumonia in children due to Mycoplasma pneumoniae: diagnostic performance of a seminested 16S rDNA-PCR.

A 16S rDNA-PCR assay for Mycoplasma pneumoniae applied to nasopharyngeal secretion (NPS) or pharyngeal swab (PS) from children with community-acquired pneumonia (CAP) was prospectively compared to serological tests including complement fixation (CF) test, a mu-capture enzyme immuno assay (EIA) for the detection of specific IgM, and an EIA for the detection of specific IgG. During a 24-months-period diagnosis of active M. pneumoniae infection was established in 32 (12.6%) of 253 patients for whom paired sera were available. In the acute phase, the sensitivities of PCR from NPS and PS, CF test, IgM EIA, and IgG EIA were 90.0%, 79.3%, 46.9%, 78.1%, and 59.4%, respectively. The corresponding specificities were 98.1%, 98.6%, 97.6%, 87.1%, and 72.4%, respectively. Thus, the 16S rDNA-PCR assay provides a highly sensitive and accurate tool for the rapid diagnosis of M. pneumoniae infection in children with CAP.

Adolescent↗

Broad range polymerase chain reaction for diagnosis of rat-bite fever caused by Streptobacillus moniliformis.

An 11-year-old boy presented with fever, vomiting, rash, limping and blisters on his feet after a finger bite by his domestic rat. Although cultures from blood, cerebrospinal fluid and urine remained negative, broad range polymerase chain reaction amplification of a part of the 16S rRNA gene followed by sequencing allowed the detection and identification of Streptobacillus moniliformis in blister fluid, thus confirming the suspected clinical diagnosis of rat-bite fever.

Animals↗

Quantitative detection of Streptococcus pneumoniae in nasopharyngeal secretions by real-time PCR.

Streptococcus pneumoniae is an important cause of community-acquired pneumonia. However, in this setting the diagnostic sensitivity of blood cultures is below 30%. Since during such infections changes in the amounts of S. pneumoniae may also occur in the upper respiratory tract, quantification of these bacteria in nasopharnygeal secretions (NPSs) may offer a suitable diagnostic approach. Real-time PCR offers a sensitive, efficient, and routinely reproducible approach to quantification. Using primers and a fluorescent probe specific for the pneumolysin gene, we were able to detect DNA from serial dilutions of S. pneumoniae cells in which the quantities of DNA ranged from the amounts extracted from 1 to 10(6) cells. No difference was noted when the same DNA was mixed with DNA extracted from NPSs shown to be deficient of S. pneumoniae following culture, suggesting that this bacterium can be detected and accurately quantitated in clinical samples. DNAs from Haemophilus influenzae, Moraxella catarrhalis, or alpha-hemolytic streptococci other than S. pneumoniae were not amplified or were only weakly amplified when there were > or =10(6) cells per reaction mixture. When the assay was applied to NPSs from patients with respiratory tract infections, the assay performed with a sensitivity of 100% and a specificity of up to 96% compared to the culture results. The numbers of S. pneumoniae organisms detected by real-time PCR correlated with the numbers detected by semiquantitative cultures. A real-time PCR that targeted the pneumolysin gene provided a sensitive and reliable means for routine rapid detection and quantification of S. pneumoniae present in NPSs. This assay may serve as a tool to study changes in the amounts of S. pneumoniae during lower respiratory tract infections.

Bacterial Proteins↗

Reliable detection of respiratory syncytial virus infection in children for adequate hospital infection control management.

By using a rapid test for respiratory syncytial virus (RSV) detection (Abbott TestPack RSV), a number of patients were observed, showing repeatedly positive results over a period of up to 10 weeks. A prospective study was initiated to compare the rapid test with an antigen capture enzyme immunoassay (EIA) and a nested reverse transcriptase PCR (RT-PCR) protocol for detection of RSV serotypes A and B. Only respiratory samples from children exhibiting the prolonged presence of RSV (> or =5 days) as determined by the rapid test were considered. A total of 134 specimens from 24 children was investigated by antigen capture EIA and nested RT-PCR. Using RT-PCR as the reference method, we determined the RSV rapid test to have a specificity of 63% and a sensitivity of 66% and the antigen capture EIA to have a specificity of 96% and a sensitivity of 69% for acute-phase samples and the homologous virus serotype A. In 7 (29%) of 24 patients, the positive results of the RSV rapid test could not be confirmed by either nested RT-PCR or antigen capture EIA. In these seven patients a variety of other respiratory viruses were detected. For general screening the RSV rapid test was found to be a reasonable tool to get quick results. However, its lack of specificity in some patients requires confirmation by additional tests to rule out false-positive results and/or detection of other respiratory viruses.

Adolescent↗

Randomised controlled trial of three day versus 10 day intravenous antibiotics in acute pyelonephritis: effect on renal scarring.

BACKGROUND: Acute pyelonephritis often leaves children with permanent renal scarring. AIMS: To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days. METHODS: In a prospective two centre trial, 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy, were randomly assigned to receive intravenous ceftriaxone (50 mg/kg once daily) for 10 or three days, followed by oral cefixime (4 mg/kg twice daily) to complete a 15 day course. After three months, scintigraphy was repeated in order to diagnose renal scars. RESULTS: Renal scarring developed in 33% of the 110 children in the 10 day intravenous group and 36% of the 110 children in the three day group. Children older than 1 year had more renal scarring than infants (42% (54/129) and 24% (22/91), respectively). After adjustment for age, sex, duration of fever before treatment, degree of inflammation, presence of vesicoureteric reflux, and the patients' recruitment centres, there was no significant difference between the two treatments on renal scarring. During follow up, 15 children had recurrence of urinary infection with no significant difference between the two treatment groups. CONCLUSION: In children with acute pyelonephritis, initial intravenous treatment for 10 days, compared with three days, does not significantly reduce the development of renal scarring.

Acute Disease↗

Diagnostic and therapeutic impact of whole body positron emission tomography using fluorine-18-fluoro-2-deoxy-D-glucose in children with chronic granulomatous disease.

AIMS: To compare whole body positron emission tomography (PET) using fluorine-18-fluoro-2-deoxy-D-glucose (FDG) with computed tomography (CT) in detecting active infective foci in children with chronic granulomatous disease. METHODS: We performed 22 whole body FDG PET studies in seven children with X linked (n = 6) or autosomal recessive (n = 1) CGD. All had clinical signs of infection and/or were evaluated prior to bone marrow transplantation (BMT). Nineteen PET studies were also correlated with chest and/or abdominal CT. All PET scans were interpreted blinded to the CT findings. Diagnoses were confirmed histologically and bacteriologically. RESULTS: We detected 116 lesions in 22 FGD PETs and 126 lesions on 19 CTs. Only two of the latter could be classified reliably as active lesions by virtue of contrast enhancement suggesting abscess formation. PET excluded 59 lesions suspicious for active infection on CT and revealed 49 infective lesions not seen on CT. All seven active infective lesions were identified by PET, allowing targeted biopsy and identification of the infective agent followed by specific antimicrobial treatment, surgery, or subsequent BMT. CONCLUSIONS: Identification of infective organisms is more precise if active lesions are biopsied. CT does not discriminate between active and inactive lesions. Whole body FDG PET can be used to screen for active infective lesions in CGD patients.

Adolescent↗

Dynamics of Epstein-Barr virus DNA levels in serum during EBV-associated disease.

A real-time polymerase chain reaction assay for quantitation of Epstein-Barr virus (EBV) DNA in serum was developed. This assay detected EBV DNA in 24 (89%) of 27 sera from patients with infectious mononucleosis, but only in 9 (18%) of 51 sera from EBV carriers (P < 0.001) and in none of the sera from 32 EBV-seronegative individuals. EBV DNA levels were higher in sera from infectious mononucleosis (median 8,000, range 1833-150,069 copies/ml) than from carriers (median < 2, range < 2-2980; P < 0.001). In sera of 36 children with infectious mononucleosis followed prospectively, EBV DNA levels correlated inversely with the duration of symptoms. Among 18 children with tumors including Hodgkin's disease (n = 7), non-Hodgkin's lymphoma (n = 6), Burkitt's lymphoma (n = 1), lymphoproliferative disorder (n = 4), and osteosarcoma (n = 1), EBV DNA was detected in serum from those 9 (100%) expressing EBV in the tumor (Hodgkin's disease, 3; non-Hodgkin's lymphoma, 2; lymphoproliferative disorder, 4), the levels peaking at diagnosis and correlating with disease activity. Quantitation of EBV DNA in serum may offer a simple means of monitoring patients at risk of EBV-associated lymphoproliferation.

Bone Neoplasms↗

[Rational utilization of antibiotics in critically ill children].

BACKGROUND: The high risks associated with untreated infection in critically ill newborns or children lower the threshold for prescription of antibiotic treatment. Inappropriate use of antibiotic therapy promotes the emergence of resistant strains. This study had three aims: to identify sources of inappropriate antibiotic utilisation, to develop revised guidelines and to implement changes. METHODS: An observational study was performed in a tertiary, multidisciplinary, neonatal and paediatric intensive care unit (PICU) of a university teaching hospital during a 7-month period (456 admissions). Guidelines addressing one of the identified sources of inappropriate utilisation (prophylaxis following surgery) were developed according to published evidence and implemented, and the effect on prescription patterns was assessed during a second observation period. RESULTS: Patients received systemic antibiotics during 54.6% of all hospitalisation days. Antibiotics prescribed for suspected or proven infection were often continued 1-2 days beyond the intended duration. Prophylaxis accounted for 28% of all systemic antibiotics given, and postsurgical prophylaxis accounted for 14.6% of all exposure days. The literature search revealed little evidence to support this practice. After new guidelines were introduced with the aim of restricting surgical prophylaxis to a single dose prior to surgery, the rate of postsurgical prophylaxis dropped from 14.6 to 11.2% of all exposure days, accompanied by a significant decline in the overall exposure rate from 54.6 to 50.2% of all hospitalisation days. CONCLUSION: Several sources of inappropriate antibiotic utilisation were identified. These include failure to discontinue treatment and prolonged prophylaxis after surgery. Implementation of new guidelines reduced antibiotic utilisation.

Anti-Bacterial Agents↗

Diagnostic potential of neutrophil elastase inhibitor complex in the routine care of critically ill newborn infants.

UNLABELLED: It has been suggested that determination of the neutrophil elastase alpha1-proteinase inhibitor complex (E-alpha1PI) improves the diagnosis of bacterial infection in newborns. We evaluated the use of E-alpha1PI measurements in 143 newborns, consecutively admitted to a tertiary intensive care unit, employing a new random access assay and a sampling procedure that minimises post-collection artefacts. The 95% range for noninfected newborns was 20-110 microg/l up to the 5th day of life and 20-85 microg/l thereafter. The sensitivity as to the diagnosis of culture-proven bloodstream infection was 80% for E-alpha1PI, 86% for the immature to total neutrophil ratio, 64% for C-reactive protein and 37% for the total white blood cell count. The corresponding specificity amounted to 97%, 85%, 85% and 86%, respectively. E-alpha1PI increases preceded elevations of C-reactive protein by 18 h. Like C-reactive protein, E-alpha1PI levels did not distinguish between bloodstream infection and non-bacterial inflammatory responses. Results of E-alpha1PI became available within 1 h of collection and usually 2-3 h before manual leucocyte counts. CONCLUSION: Determination of neutrophil elastase alpha1-proteinase inhibitor levels yields diagnostic advantages comparable to those of manual differential counts but provide faster turnaround times.

Cohort Studies↗

Long-term responses to treatment including ritonavir or nelfinavir in HIV-1-infected children. Pediatric AIDS Group of Switzerland.

BACKGROUND: Knowledge concerning the long-term antiretroviral and immunological efficacy of protease inhibitors in children is limited. PATIENTS AND METHODS: An open-label, prospective, multicenter clinical trial was conducted over a period of 72 weeks in Switzerland. 60 HIV-1 infected children (aged 0.3-16.9 years) naive to protease inhibitors were enrolled. Ritonavir or nelfinavir and at least one new nucleoside reverse transcriptase inhibitor were introduced into the current treatment regimen. HIV-1 RNA levels and CD4 cell counts were monitored after introducing the protease inhibitor, and the tolerability and safety of the drugs were assessed. RESULTS: Dictated by chronological availability, 37 children received ritonavir and 23 nelfinavir. At baseline, children given ritonavir had higher mean plasma HIV-1 RNA levels (5.03 vs 4.63 log10 copies/ml; p = 0.001) and lower mean CD4 cell counts (277 vs 555 cells/microl; p = 0.009) than children given nelfinavir. Antiretroviral treatment (ART) naive children showed higher mean plasma HIV-1 RNA levels than non-naive (5.18 vs 4.64 log10 copies/ml; p = 0.02). The decline in plasma HIV-1 RNA levels 72 weeks after treatment with ritonavir and nelfinavir was -2.17 and -1.30 log10 copies/ml, respectively (p = 0.006) and in ART-naive vs non-naive patients -2.70 vs -1.39 log10 copies/ml (p < or = 0.01). 69% of ART-naive patients and 32% of non-naive patients achieved sustained plasma HIV-1 RNA levels < 400 copies/ml. Increases in CD4 cells were higher in ART-naive compared to non-naive patients (p < 0.04). CONCLUSION: The antiretroviral and immunologic benefits of protease inhibitors are more profound in ART-naive than in non-naive children.

Adolescent↗