Florence Moulin

Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferon-alpha for differentiation of bacterial vs. viral infections

BACKGROUND Procalcitonin (PCT) concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable, making it a potentially useful marker for distinguishing between bacterial and viral infections. METHODS PCT concentration was determined with an immunoluminometric assay on plasma collected at admission in 360 infants and children hospitalized for bacterial or viral infection. It was compared with C-reactive protein (CRP), interleukin 6 and interferon-alpha measured on the same sample. RESULTS The mean PCT concentration was 46 microg/l (median, 17.8) in 46 children with septicemia or bacterial meningitis. PCT concentration was > 1 microg/l in 44 of 46 in this group and in 59 of 78 children with a localized bacterial infection who had a negative blood culture (sensitivity, 83%). PCT concentration was > 1 microg/l in 16 of 236 children with a viral infection (specificity, 93%). PCT concentration was low in 9 of 10 patients with inflammatory disease and fever. A CRP value > or =20 mg/l was observed in 61 of 236 patients (26%) with viral infection and in 105 of 124 patients (86%) with bacterial infection. IL-6 was > 100 pg/ml in 14% of patients infected with virus and in 53% with bacteria. A secretion of interferon-alpha was found in serum in 77% of viral infected patients and in 8.6% of bacterial infected patients. CONCLUSIONS In this study a PCT value of 1 microg/l or greater had better specificity, sensitivity and predictive value than CRP, interleukin 6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT values are higher in invasive bacterial infections, but the cutoff value of 1 microg/l indicates the severity of the disease in localized bacterial infection and helps to decide antibiotic treatment in emergency room. PCT may be useful in an emergency room for differentiation of bacterial vs. viral infections in children and for making decisions about antibiotic treatments.

Measurement of Procalcitonin Levels in Children with Bacterial or Viral Meningitis

We measured the plasma procalcitonin levels in 59 children who were admitted to the hospital because of bacterial or viral meningitis. Eighteen children with acute bacterial meningitis had elevated procalcitonin levels (mean level, 54.5 micrograms/L; range, 4.8-110 micrograms/L). The procalcitonin levels in 41 children with viral meningitis were low (mean level, 0.32 micrograms/L; range, 0-1.7 micrograms/L; P < .0001). Assay of cerebrospinal fluid (CSF) cells and proteins and serum C-reactive protein showed a zone of overlapping values between the two groups. Procalcitonin was not produced in CSF. Plasma procalcitonin levels decreased rapidly during antibiotic therapy. These data suggest that the measurement of plasma procalcitonin might be of value in the differential diagnosis of meningitis due to either bacteria or viruses.

Procalcitonin as a marker for the early diagnosis of neonatal infection

Serum procalcitonin was determined in newborn infants at the time of admission to the pediatrics or obstetrics unit. Increased levels were found in all neonates with bacterial sepsis. Neonates with viral infection, bacterial colonization, or neonatal distress had normal or slightly increased levels. These data suggest that procalcitonin might be of value in diagnosing neonatal sepsis.

Mycoplasma pneumoniae and Asthma in Children

The aim of this prospective study of a population of children (age, 2-15 years) hospitalized for severe asthma was to test them for acute infection due to Mycoplasma pneumoniae and acute infection due to Chlamydia pneumoniae. Of 119 patients with previously diagnosed asthma, acute M. pneumoniae infection was found in 24 (20%) and C. pneumoniae infection was found in 4 (3.4%) of the patients during the current exacerbation. Of 51 patients experiencing their first asthma attack, acute M. pneumoniae infection was proven in 26 (50%) of the patients (P<.01) and C. pneumoniae in 4 (8.3%). In the control group of 152 children with stable asthma or rhinitis, 8 (5.2%) had M. pneumoniae infection (P<.005). Of the 29 patients experiencing their first asthma attack and infected with M. pneumoniae or C. pneumoniae, 18 (62%) had asthma recurrences but only 6 (27%) of the 22 patients who did not have such infections had asthma recurrences (P<.05). M. pneumoniae may play a role in the onset of asthma in predisposed children and could be a trigger for recurrent wheezing.

Procalcitonin in children admitted to hospital with community acquired pneumonia

AIMS To assess the sensitivity, specificity, and predictive value of procalcitonin (PCT) in differentiating bacterial and viral causes of pneumonia. METHODS A total of 72 children with community acquired pneumonia were studied. Ten had positive blood culture for Streptococcus pneumoniae and 15 had bacterial pneumonia according to sputum analysis (S pneumoniae in 15,Haemophilus influenzae b in one). Ten patients had Mycoplasma pneumoniae infection and 37 were infected with viruses, eight of whom had viral infection plus bacterial coinfection. PCT concentration was compared to C reactive protein (CRP) concentration and leucocyte count, and, if samples were available, interleukin 6 (IL-6) concentration. RESULTS PCT concentration was greater than 2 μg/l in all 10 patients with blood culture positive for S pneumoniae; in eight of these, CRP concentration was above 60 mg/l. PCT concentration was greater than 1 μg/l in 86% of patients with bacterial infection (includingMycoplasma and bacterial superinfection of viral pneumonia). A CRP concentration of 20 mg/l had a similar sensitivity but a much lower specificity than PCT (40%v 86%) for discriminating between bacterial and viral causes of pneumonia. PCT concentration was significantly higher in cases of bacterial pneumonia with positive blood culture whereas CRP concentration was not. Specificity and sensitivity were lower for leucocyte count and IL-6 concentration. CONCLUSIONS PCT concentration, with a threshold of 1 μg/l is more sensitive and specific and has greater positive and negative predictive values than CRP, IL-6, or white blood cell count for differentiating bacterial and viral causes of community pneumonia in untreated children admitted to hospital as emergency cases.

Fluoroquinolones in paediatrics: a risk for the patient or for the community?

Fluoroquinolones are an important group of antibiotics widely used in adult patients because of their excellent tissue penetration and their bactericidal activity. They are not authorised for paediatric use (except the limited indication of pseudomonas infections in cystic fibrosis), however, because of the potential for joint toxicity reported from experiments with young animals. Despite the absence of official approval, fluoroquinolones are widely used in paediatrics as second-line antibiotics when all other treatments have failed. Most of the information available about paediatric use concerns ciprofloxacin, which is used in children much more often than the other members of this class. The published paediatric series have shown that frequency of articular side-effects varies according to age: all the surveys have reported frequencies of around 0.1% in adults and 2-3% in children. Outside of cystic fibrosis and severe infections in which no other treatment is possible, the only paediatric situations where fluoroquinolones are superior to standard treatments for children, in speed of recovery and comfort as well as in efficacy, are typhoid fever, severe shigella dysenteries, and enterobacteria meningitis. Should the use of new fluoroquinolones active against pneumococci be authorised for upper respiratory infections (including recurrent otitis) in children, the potential emergence and dissemination of pneumococci strains in which multidrug resistance includes fluoroquinolones would create a real risk in the community. It is, therefore, important to continue the policy of second-line use in children, only after failure of an earlier treatment, and when other antibiotics approved for paediatric use cannot be used.

Cognitive stimulation intervention for elders with mild cognitive impairment compared with normal aged subjects: preliminary results

Background and aims: Cognitive training programs have been developed for Alzheimer’s disease patients and the health]; elderly) population. Collective cognitive stimulation programs have been shown to be efficient for subjects with memory complaint. The aim of this study was to evaluate the benefit of such cognitive programs in populations with Mild Cognitive Impairment (MCI). Methods: Twelve patients with MCI and twelve cognitively normal elders were administered a cognitive stimulation program. Cognitive performance (Logical Memory, Word paired associative learning task, Trail Making Test, verbal fluency test) were collected before and after the intervention. A gain score [(post-score — pre-score)/pre-score] was calculated for each variable and compared between groups. Results: The analysis revealed a larger intervention size effect in MCI than in normal elders’ performances on the associative learning task (immediate recall: p<0.05, delayed recall: p<0.01). The intervention was more beneficial in improving associative memory abilities in MCI than in normal subjects. At the end of the intervention, the MCI group had lower results than the normal group only for the delayed recall of Logical Memory. Conclusions: Although further studies are needed for more details on the impact of cognitive stimulation programs on MCI patients, this intervention is effective in compensating associative memory difficulties of these patients. Among non-pharmacological interventions, cognitive stimulation therapy is a repeatable and inexpensive collective method that can easily be provided to various populations with the aim of slowing down the rate of decline in elderly persons with cognitive impairment.

Procalcitonin as a Predictor of Vesicoureteral Reflux in Children With a First Febrile Urinary Tract Infection

Objective. A first febrile urinary tract infection leads to the diagnosis of vesicoureteral reflux in 20% to 40% of children. Systematic voiding cystourethrography then is recommended. However, for 60% to 80% of the children, voiding cystourethrography is a posteriori normal. Moreover, it is irradiating, painful, and expensive. Thus, selective approaches are needed. Because procalcitonin has been shown to be associated with severe pyelonephritis and renal scars, which are correlated to vesicoureteral reflux, we analyzed its relationship with vesicoureteral reflux. Methods. A retrospective hospital-based cohort study included all children who were 1 month to 4 years of age and had a first febrile urinary tract infection. Univariate and multivariate analyses were performed. Results. Among 136 patients included, 25% had vesicoureteral reflux. The median procalcitonin concentration was significantly higher in children with reflux than in those without (1.2 vs 0.6 ng/mL). High procalcitonin (≥0.5 ng/mL) was associated with reflux (odds ratio [OR]: 4.6; 95% confidence interval [CI]: 1.6–16.2). After logistic-regression adjustment for all potential confounders, the association remained significant (OR: 4.9; 95% CI: 1.7–14.0). The relationship was stronger for high-grade (≥3) reflux (OR: 8.7; 95% CI: 1.2–382) than low-grade reflux (OR: 3.6; 95% CI: 1.1–15.3). High procalcitonin sensitivities were 85% (95% CI: 70–94) and 92% (95% CI: 65–99) for all-grade and high-grade reflux, respectively, with 44% specificity (95% CI: 35–54). Conclusion. High procalcitonin is a strong and independent predictor of vesicoureteral reflux and could be used to identify low-risk patients to avoid unnecessary voiding cystourethrography.

Clinical decision rules to distinguish between bacterial and aseptic meningitis

Background: Clinical decision rules have been derived to distinguish between bacterial and aseptic meningitis in the emergency room to avoid unnecessary antibiotic treatments and hospitalisations. Aims: To evaluate the reproducibility and to compare the diagnostic performance of five clinical decision rules. Methods: All children hospitalised for bacterial meningitis between 1995 and 2004 or aseptic meningitis between 2000 and 2004 have been included in a retrospective cohort study. Sensitivity and specificity were calculated by applying each rule to the patients. The best rule was a priori defined as the one yielding 100% sensitivity for bacterial meningitis, the highest specificity, and the greatest simplicity for a bedside application. Results: Among the 166 patients included, 20 had bacterial meningitis and 146 had aseptic meningitis. Although three rules achieved 100% sensitivity (95% CI 84–100), one had a significantly lower specificity (13%, 95% CI 8–19) than those of the other two rules (57%, 95% CI 48–65; and 66%, 95% CI 57–73), which were not statistically different. The ease of manual computation of the rule developed by Nigrovic et al (a simple list of five items: seizure, blood neutrophil count, cerebrospinal fluid (CSF) Gram stain, CSF protein, CSF neutrophil count) was higher than the one developed by Bonsu and Harper. Conclusion: On our population, the rule derived by Nigrovic et al had the best balance between accuracy and simplicity of manual computation and could help to avoid two thirds of unnecessary antibiotic treatments and hospitalisations.

Sequential Colonization by Streptococcus pneumoniae of Healthy Children Living in an Orphanage

A prospective study of nasopharyngeal colonization by Streptococcus pneumoniae in the exceptional conditions of a closed community of abandoned children was done over a 1-year period; 71 children (age <24 months) were studied monthly. S. pneumoniae was isolated from 58 (81.7%), and 94.5% of the 111 isolates were resistant to penicillin. The mean rate of carriage was estimated at 57.4%, ranging from 42.8% to 70.4%. Children were sequentially colonized by a mean of 3 different isolates. The mean duration of carriage for a given isolate was approximately 2.2 months. Serotyping and molecular typing by pulsed-field gel electrophoresis showed that children were colonized by a limited number of clones belonging to only 4 serotypes and 4 pulsotypes. These clones rapidly spread in the community and colonized the children in waves, with a rapid turnover of S. pneumoniae isolates, facilitated by close contact between children.