Procalcitonin Predicts Response to Beta-Lactam Treatment in Hospitalized Children with Community-Acquired Pneumonia

BACKGROUND: Antibiotic treatment of community-acquired pneumonia (CAP) in children remains mostly empirical because clinical and paraclinical findings poorly discriminate the principal causes of CAP. Fast response to beta-lactam treatment can be considered a proxy of pneumococcal aetiology. We aimed to identify the best biological predictor of response to beta-lactam therapy in children hospitalized for CAP. METHODS: A retrospective, single-centre cohort study included all consecutive patients 1 month to 16 years old hospitalized in a teaching hospital in Paris, France, because of CAP empirically treated with a beta-lactam alone from 2003 to 2010. Uni- and multivariate analyses were used to study the ability of routine biological parameters available in the Emergency Department to predict a favourable response to beta-lactam (defined as apyrexia within 48 hours of treatment onset). RESULTS: Among the 125 included patients, 85% (106) showed a favourable response to beta-lactam. In multivariate logistic regression, we found procalcitonin (PCT) the only independent predictor of apyrexia (p = 0.008). The adjusted odds ratio for the decadic logarithm of PCT was 4.3 (95% CI 1.5-12.7). At ≥ 3 ng/mL, PCT had 55.7% sensitivity (45.7-65.3), 78.9% specificity (54.4-93.9), 93.7% positive predictive value (84.5-98.2), 24.2% negative predictive value (14.2-36.7), 2.64 positive likelihood ratio (1.09-6.42) and 0.56 negative likelihood ratio (0.41-0.77). In the 4 children with a PCT level ≥ 3 ng/mL and who showed no response to beta-lactam treatment, secondary pleural effusion had developed in 3, and viral co-infection was documented in 1. CONCLUSIONS: PCT is the best independent biologic predictor of favourable response to beta-lactam therapy in children hospitalized for CAP. Thus, a high PCT level is highly suggestive of pneumococcal aetiology. However, a 3-ng/mL cut-off does not seem compatible with daily medical practice, and additional research is needed to further define the role of PCT in managing CAP in children

A Systematic Review on the Diagnosis of Pediatric Bacterial Pneumonia: When Gold Is Bronze

In developing countries, pneumonia is one of the leading causes of death in children under five years of age and hence timely and accurate diagnosis is critical. In North America, pneumonia is also a common source of childhood morbidity and occasionally mortality. Clinicians traditionally have used the chest radiograph as the gold standard in the diagnosis of pneumonia, but they are becoming increasingly aware that it is not ideal. Numerous studies have shown that chest radiography findings lack precision in defining the etiology of childhood pneumonia. There is no single test that reliably distinguishes bacterial from non-bacterial causes. These factors have resulted in clinicians historically using a combination of physical signs and chest radiographs as a 'gold standard', though this combination of tests has been shown to be imperfect for diagnosis and assigning treatment. The objectives of this systematic review are to: 1) identify and categorize studies that have used single or multiple tests as a gold standard for assessing accuracy of other tests, and 2) given the 'gold standard' used, determine the accuracy of these other tests for diagnosing childhood bacterial pneumonia.Search strategies were developed using a combination of subject headings and keywords adapted for 18 electronic bibliographic databases from inception to May 2008. Published studies were included if they: 1) included children one month to 18 years of age, 2) provided sufficient data regarding diagnostic accuracy to construct a 2x2 table, and 3) assessed the accuracy of one or more index tests as compared with other test(s) used as a 'gold standard'. The literature search revealed 5,989 references of which 256 were screened for inclusion, resulting in 25 studies that satisfied all inclusion criteria. The studies examined a range of bacterium types and assessed the accuracy of several combinations of diagnostic tests. Eleven different gold standards were studied in the 25 included studies. Criterion validity was calculated for fourteen different index tests using eleven different gold standards. The most common gold standard utilized was blood culture tests used in six studies. Fourteen different tests were measured as index tests. PCT was the most common measured in five studies each with a different gold standard.We have found that studies assessing the diagnostic accuracy of clinical, radiological, and laboratory tests for bacterial childhood pneumonia have used a heterogeneous group of gold standards, and found, at least in part because of this, that index tests have widely different accuracies. These findings highlight the need for identifying a widely accepted gold standard for diagnosis of bacterial pneumonia in children

Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp

Protein quality control: the who’s who, the where’s and therapeutic escapes

In cells the quality of newly synthesized proteins is monitored in regard to proper folding and correct assembly in the early secretory pathway, the cytosol and the nucleoplasm. Proteins recognized as non-native in the ER will be removed and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied by various changes of cellular organelles and results in protein folding diseases. This review focuses on how the immunocytochemical labeling and electron microscopic analyses have helped to disclose the in situ subcellular distribution pattern of some of the key machinery proteins of the cellular protein quality control, the organelle changes due to the presence of misfolded proteins, and the efficiency of synthetic chaperones to rescue disease-causing trafficking defects of aberrant proteins