Empiric Antibiotic Therapy in 1402 Children With Parapneumonic Effusion/Pleural Empyema in Germany: A Long-term Surveillance Study.

OBJECTIVE: This study investigated empiric antibiotic treatment (EAT), guideline adherence, antibiotic streamlining and clinical outcomes in 1402 hospitalized children with pediatric parapneumonic effusion/pleural empyema (PPE/PE). METHODS: A nationwide surveillance study collected data on EAT, clinical course/outcome, pathogens, susceptibility testing and antibiotic streamlining of children with PPE/PE in Germany between 2010 and 2018. Subgroups were compared using χ2 test/Fisher exact test, Mann-Whitney U test and linear regression analysis adjusting for patient age where appropriate. RESULTS: Complete data on EAT were available for 1402 children. In children with monotherapy (n = 567) and in children with combination therapy of 2 antibiotics (n = 589), the most commonly used antibiotics were aminopenicillin/beta-lactamase inhibitor [138/567 (24.3%) and 102/589 (17.3%)] and cefuroxime [291/567 (51.3%) and 294/589 (49.9%)]. The most common combinations with these beta-lactams were macrolides, aminoglycosides and clindamycin. We observed no difference in clinical severity/outcome between EAT with aminopenicillin/beta-lactamase inhibitor and cefuroxime, neither when used in monotherapy nor when used in combination therapy of 2 antibiotics. Species diagnosis of Streptococcus pneumoniae (n = 192), Streptococcus pyogenes (n = 111) or Staphylococcus aureus (n = 38) in polymerase chain reaction or culture from pleural fluid or blood resulted in a switch to an appropriate narrow-spectrum beta-lactam therapy in 9.4%, 18.9 % and 5.2% of children. In a subset of children with reported bacterial susceptibility testing, penicillin resistance was reported in 3/63 (4.8%) of S. pneumoniae and methicillin resistance in S. aureus was reported in 10/32 (31.3%) of children. CONCLUSION: This study points to antibiotic overtreatment in children with PPE/PE, particularly the frequent use of combinations of antibiotics. Children receiving combinations of antibiotics did not show differences in clinical outcomes. The low rate of children with streamlined antibiotic therapy even upon pathogen detection indicates a necessity for antibiotic stewardship measures in PPE/PE and the need of investigating other potential therapeutic strategies as anti-inflammatory therapy.

Effect of Prehospital Antibiotic Therapy on Clinical Outcome and Pathogen Detection in Children With Parapneumonic Pleural Effusion/Pleural Empyema.

BACKGROUND: Parapneumonic pleural effusion and pleural empyema (PPE/PE) are complications of community-acquired pneumonia. The objective of this study was to analyze prehospital antibiotic therapy (PH-ABT) of children with PPE/PE and investigate its effects on clinical outcome and pathogen detection. METHODS: Prospective nationwide active surveillance in Germany between October 2010 and June 2018. Children and adolescents <18 years of age with pneumonia-associated PE or PPE requiring drainage or with persistence of PPE/PE >7 days were included. RESULTS: A total of 1724 children with PPE/PE were reported, of whom 556 children (32.3% of 1719 with available data) received PH-ABT. Children with PH-ABT had a shorter median hospital length of stay (15 vs. 18 days, P < 0.001), a longer time from onset of symptoms until hospital discharge (25 vs. 23 days, P = 0.002), a lower rate of intensive care unit admission (58.3% vs. 64.4%, P = 0.015) and fewer infectious complications (5.9% vs. 10.0%; P = 0.005). Bacterial pathogens in blood or pleural fluid culture were detected in 597 (34.5%) of 1513 children. Positive culture results were less frequent in children with than without PH-ABT (81/466 [17.4%] vs. 299/1005 [29.8%]; P < 0.001), whereas detection rates in pleural fluid samples by polymerase chain reaction were similar (91/181 [50.3%] vs. 220/398 [55.3%]; P = 0.263). CONCLUSIONS: In children with PPE/PE, PH-ABT significantly reduced the overall rate of bacterial pathogen detection by culture, but not by polymerase chain reaction. PH-ABT was associated with a lower rate of infectious complications but did not affect the overall duration of disease. We therefore speculate that the duration of PPE/PE is mainly a consequence of an infection-induced inflammatory process, which can only partially be influenced by antibiotic treatment.

Association between platelet glycoprotein Ib-alpha and myocardial infarction: results of a pilot study performed in male and female patients from Sicily.

Myocardial infarction (AMI) is a complex multifactorial disorder. Platelet adhesion and thrombosis are pivotal events in the development of atherosclerotic lesions. Occlusive thrombus is almost exclusively initiated by plaque rupture and adhesion of platelets to subendothelial von Willebrand factor (vWf) by its specific platelet receptor, the alpha-chain of glycoprotein (GP) Ib-IX-V complex of the human platelet-specific antigens (HPA). Two polymorphisms have been reported in the sequence of GPIb-alpha. The first, a C/T transition at nucleotide 1018 results in an amino acid dimorphism (Thr/Met) at residue 145 of GPIb-alpha, which is located within the vWF-binding domain of the receptor. The second is a T/C polymorphism in the Kozak sequence at position -5 from the initiator ATG. This affects the receptor density on the platelet surface. We assessed 1018 C/T and -5 T/C Kozak polymorphisms to see whether they are associated with AMI in homogeneous populations of Sicilian patients with AMI. To this end, we have analyzed the distribution of 1018 C/T and -5 T/C Kozak polymorphisms in 105 young Sicilian patients (<46 years) and 110 healthy age-related controls, by PCR-SSP and PCR-RFLP. Our results demonstrate no significant differences in the frequency of 1018 C/T and -5 T/C Kozak polymorphism between patients with AMI and controls. Stratifying by gender, there is no difference between male and female patients and control data. Thus, our results indicate that the HPA-2 polymorphisms are not associated with an increased risk for AMI at early onset (< 46 years) both in men and in women.

Genetic control of immune response in carriers of ancestral haplotype 8.1: the study of chemotaxis.

In all caucasian populations the association of an impressive number of autoimmune diseases with genes from the HLA-B8, DR3 haplotype that is part of the ancestral haplotype (AH) 8.1 HLA-A1, Cw7, B8, TNFAB*a2b3, TNFN*S, C2*C, Bf*s, C4A*Q0, C4B*1, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201 has been reported by different research groups. This haplotype, which is more common in northern Europe, is also associated with a number of immune system dysfunctions in healthy subjects. Analyzing the data according to gender, some dysfunctions are observed in women but not in men, in agreement with the role of X-linked genes and/or estrogens in the development and progression of autoimmune diseases. It has been proposed that a small number of genes within the 8.1 AH modify immune responsiveness and hence affect multiple immunopathological diseases. In this article, we demonstrate that neutrophil chemotaxis is significantly decreased in carriers of this AH, suggesting that this impairment may also be related to the increased occurrence of autoimmune diseases in these individuals.

Association between the HFE mutations and unsuccessful ageing: a study in Alzheimer's disease patients from Northern Italy.

Mutations in the class I-like Major Histocompatibility Complex gene HFE are associated with hereditary hemochromatosis (HH), a disorder caused by excessive iron uptake. Three common mutations have been found: C282Y, H63D, and S65C. Moreover, several studies have suggested that HFE mutations may be involved in several age-related chronic diseases such as Alzheimer's disease (AD) and coronary heart disease, but apparently paradoxically also with longevity. In particular, in AD, patients carrying the H63D allele have been suggested to have a mean age at onset of 72 vs. 77 years for those who were homozygous for the wild-type allele. Thus, it seems that H63D mutations may anticipate sporadic AD clinical presentation in susceptible individuals. In the present study, we analysed the HFE genotype in 123 patients with sporadic AD and 152 age-matched controls from Northern Italy. Samples were typed for C282Y, H63D and S65C alleles using the polymerase chain reaction and sequence specific primers. No significant differences were observed in frequencies of the different alleles between controls and AD both for the whole group and when the data were analysed according to gender. In addition, we failed to observe any difference in the age at onset between patients carrying the mutant HFE-H63D allele and those homozygous for the wild-type allele, either in men or women. Also taking into account the presence or absence of the APOE-epsilon 4 allele, no significant differences were observed between carriers of the mutant HFE-H63D allele and those homozygous for the wild-type allele. Thus, our study does not support the suggestion that H63D mutations may anticipate sporadic AD clinical presentation in susceptible individuals.