To the Editor.—Helicobacter pylori infection is usually contracted in early childhood, before the age of 5 years.1 The infection causes chronic gastritis that is responsible in adulthood for atrophic gastritis, which could lead to gastric carcinoma.2 However, there are very few available data about the natural evolution of H pylori gastritis during childhood.We previously published a prospective 2-year study of 18 asymptomatic H pylori–infected children.3 The study revealed a slight aggravation of the histologic features of H pylori gastritis despite stable H pylori colonization. No glandular atrophy, intestinal metaplasia, or any other lesions that could lead to gastric carcinoma were found in these children during the 2-year study.3We recently had the opportunity to obtain information on long-term natural evolution of H pylori gastritis in a 15-year-old adolescent girl. She had participated in the prospective study mentioned above when she was 2 years old. Because she was free of symptoms during this 2-year study, no eradication treatment was proposed, and she was then lost to follow-up. She remained free of symptoms during >12 years and came back to us 13 years later because of frequent epigastric pain (twice a week for 3 months), with vomiting but no weight loss. A new endoscopy showed persisting nodular gastritis, and gastric biopsies (n = 5) revealed that she remained infected with H pylori (both at histology and culture); chronic inflammation was intense in antrum and moderate in fundus, with slight activity in both locations. There was neither atrophy nor metaplasia. When comparing sequential gastric biopsies over the 13-year follow-up period, gastritis progressed only slightly: initial histologic features in both locations consisted of moderate inflammation with slight activity. Because her H pylori strain was sensitive to all the antibiotics tested, a 7-day treatment with omeprazole, amoxicillin, and clarithromycin was given, which resulted in eradication of the H pylori 6 weeks later.This unique case report shows that untreated H pylori infection acquired during early childhood persists without major progression in gastritis. More than the duration of infection, this suggests that exposure to other gastric aggressors and/or cocarcinogens (such as antiinflammatory drugs, special food habits, tobacco, or alcohol) are responsible for gastric atrophy and metaplasia. Moreover, the nonaggravation in histologic features supports recommendations not to screen and treat asymptomatic H pylori–infected children.4,5
Purpose Infection remains one of the most important complications in cancer therapy. The choice of antibiotics and the method of administration can affect results. Beta-lactam antibiotics can be administered by several short injections per day or by continuous infusion. The latter modality may provide superior pharmacokinetics. Patients and Methods The authors studied the pharmacokinetics of ceftazidime in children treated for malignancy and in febrile aplasia after chemotherapy. They received a continuous infusion of ceftazidime (200 mg/kg/day) after a loading dose (65 mg/kg/day) administered with amikacin (25 mg/kg/day) and vancomycin (50 mg/kg/day). Results Twenty-three pharmacokinetic studies were performed. Mean ceftazidime serum levels were 31.1 ± 11.9, 31.2 ± 10, 32.4 ± 11.6, 33 ± 11.6, and 30.4 ± 12.1 mg/L at 25, 27, 30, 36, and 43 hours, respectively. Treatment was tolerated well. There were no toxic or infectious deaths. Conclusions Ceftazidime's time-dependent pharmacokinetics shows the advantage of continuous infusion. This study confirmed the feasibility and safety of this administration schedule in the empiric treatment of febrile neutropenic children with cancer.
Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes pneumonia in immunocompromised humans and severe pulmonary damage in patients with cystic fibrosis. Imbalanced fatty acid incorporation in membranes, including increased arachidonic acid and decreased DHA concentrations, is known to play a critical role in chronic inflammation associated with bacterial infection. Other lipids, such as EPA and alkylglycerols, are also known to play a role in inflammation, particularly by stimulating the immune system, decreasing inflammation and inhibiting bacterial growth. In this context, the goal of the present study was to assess the effect of dietary DHA/EPA, in a 2:1 ratio, and alkylglycerols, as natural compounds extracted from oils of rays and chimeras, respectively, on the inflammatory reaction induced by P. aeruginosa pulmonary infection in mice. To this end, mice were fed with a control diet or isolipidic, isoenergetic diets prepared with oils enriched in DHA/EPA (2:1) or alkylglycerols for 5 weeks before the induction of acute P. aeruginosa lung infection by endotracheal instillation. In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries. By contrast, alkylglycerols did not affect the outcomes of P. aeruginosa infection. Our findings suggest that supplementation with ray oil enriched in DHA/EPA (2:1) can be considered as a preventive treatment for patients at risk for P. aeruginosa infection.
Pseudomonas aeruginosa is a gram-negative bacilli frequently encountered in human pathology. This pathogen is involved in a large number of nosocomial infections and chronic diseases. Herein we investigated the effects of polyunsaturated fatty acids (PUFA) in chronic Pseudomonas aeruginosa lung infection. C57BL/6 mice were fed for 5 wk with specifically designed diets with high contents in either omega-3 (omega-3) or omega-6 PUFA and compared to a control diet. P. aeruginosa included in agarose beads was then instilled intratracheally, and the animals were studied for 7 days. On the 4th day, the mice fed with the omega-3 diet had a higher lean body mass gain and a lower omega-6:omega-3 ratio of fatty acids extracted from the lung tissue compared with the other groups (P < 0.05). The omega-3 group had the lowest mortality. Distal alveolar fluid clearance (DAFC) as well as the inflammatory response and the cellular recruitment were higher in the omega-3 group on the 4th day. The effect on DAFC was independent of alpha-epithelial Na(+) channels (alpha-ENaC), beta-ENaC, and alpha(1)-Na-K-ATPase mRNA expressions, which were not altered by the different diets. In conclusion, a diet enriched in omega-3 PUFA can change lung membrane composition and improve survival in chronic pneumonia. This effect on survival is probably multifactorial involving the increased DAFC capacity as well as the optimization of the initial inflammatory response. This work suggests that a better control of the omega-6/omega-3 PUFA balance may represent an interesting target in the prevention and/or control of P. aeruginosa infection in patients.
Abstract Background Mucin hypersecretion and mucus plugging in the airways are characteristic features of chronic respiratory diseases like cystic fibrosis (CF) and contribute to morbidity and mortality. In CF, Pseudomonas aeruginosa superinfections in the lung exacerbate inflammation and alter mucus properties. There is increasing evidence that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-inflammatory properties in many inflammatory diseases while n-6 PUFA arachidonic acid (AA) favors inflammatory mediators such as eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) that may enhance inflammatory reactions. This suggests that n-3 PUFAs may have a protective effect against mucus over-production in airway diseases. Therefore, we hypothesized that n-3 PUFAs may downregulate mucins expression. Methods We designed an absolute real-time PCR assay to assess the effect of a 5-week diet enriched either with n-3 or n-6 PUFAs on the expression of large mucins in the lungs of mice infected by P. aeruginosa . Results Dietary fatty acids did not influence mucin gene expression in healthy mice. Lung infection induced an increase of the secreted gel-forming mucin Muc5b and a decrease of the membrane bound mucin Muc4 . These deregulations are modulated by dietary fatty acids with a suppressive effect of n-3 PUFAs on mucin (increase of Muc5b from 19-fold up to 3.6 × 10 5 -fold for the n-3 PUFAs treated group and the control groups, respectively, 4 days post-infection and decrease of Muc4 from 15-fold up to 3.2 × 10 4 -fold for the control and the n-3 PUFAs treated groups, respectively, 4 days post-infection). Conclusion Our data suggest that n-3 PUFAs enriched diet represents an inexpensive strategy to prevent or treat mucin overproduction in pulmonary bacterial colonization.
