Meta‐analysis: proton pump inhibitor use and the risk of community‐acquired pneumonia

Aliment Pharmacol Ther 31 , 1165–1177

Summary

Background Observational studies examining the association between proton pump inhibitor (PPI) use and risk of community‐acquired pneumonia are conflicting. Aim To assess systematically the association between risk of community‐acquired pneumonia and PPI use in adults. Methods We searched MEDLINE, EMBASE and CINAHL databases between 1988 and January 2010. Two reviewers independently selected studies based on eligibility criteria and extracted data. Included studies evaluated adults (≥18 years) who took PPIs as an out‐patient. The primary outcome was community‐acquired pneumonia. Only observational studies with a comparison arm were included. Results Over 2600 citations were reviewed. Six studies were included. All were nested case‐control studies. Meta‐analysis found an increased risk of community‐acquired pneumonia associated with PPI use [OR 1.36 (95% CI 1.12–1.65)]; significant heterogeneity remained (I² 92%, P < 0.001). In exploratory subgroup analysis, short duration of use was associated with an increased odds of community‐acquired pneumonia [OR 1.92 (95% CI 1.40–2.63), I² 75%, P = 0.003], whereas chronic use was not [OR 1.11 (95% CI 0.90–1.38), I² 91%, P < 0.001], a significant interaction (P < 0.005). Conclusions Heterogeneity precluded interpretation of the summary statistic. Exploratory analysis revealed that duration of PPI use may impact the risk of community‐acquired pneumonia, a finding that should be explored in future studies.     

Proton pump inhibitor therapy and osteoporosis

Osteoporotic fractures, particularly hip fractures, can have a devastating impact on the well-being of the elderly population. Recently, two population-based observational studies reported a highly important association between the use of potent acid suppressive therapy and an increased risk of hip fractures. The mechanisms underlying such an association are not clear. However, a careful review of the existing evidence seems to suggest that the main physiologic consequences of proton pump inhibitor therapy may each have a theoretical influence on bone metabolism. Specifically, inhibition of the osteoclastic proton pumps may reduce bone resorption, while profound acid suppression could potentially hamper intestinal calcium absorption, and secondary hypergastrinemia may enhance bone resorption through the induction of parathyroid gland hyperplasia. However, the existing data are clearly too limited for us to draw any definitive conclusions, and more studies are urgently needed to delineate the physiologic relevance of these theoretical mechanistic links, individually and collectively.     

Proton pump inhibitor therapy is a risk factor for Clostridium difficile-associated diarrhoea

BACKGROUND: Inhibition of gastric acid removes a defence against ingested bacteria and spores, increasing the risk of some forms of gastroenteritis. Previous studies investigating a possible link between acid suppression therapy and Clostridium difficile-associated diarrhoea have reported conflicting results. AIM: To investigate whether acid suppression therapy is associated with an increased risk of C. difficile-associated diarrhoea. Prospective case-control study of 155 consecutive in-patients with C. difficile-associated diarrhoea. RESULTS: Antibiotics had been received by 143 (92%) of the C. difficile-associated diarrhoea group and 76 (50%) of the controls during the preceding 3 months. Among those receiving antibiotics, 59 (41%) of the C. difficile-associated diarrhoea group had also received acid suppression, compared with 21 (28%) of controls (OR 1.84, CI 1.01, 3.36, chi(2) = 4.0, P = 0.046). Among the entire C. difficile-associated diarrhoea group 64 (41%) had received acid suppression compared with 40 (26%) of controls (OR 1.99, CI 1.19, 3.31, chi(2) = 7.9, P = 0.005). Logistic regression analyses found that C. difficile-associated diarrhoea was independently associated with: antibiotic use (OR 13.1, 95% CI: 6.6, 26.1); acid suppression therapy (OR 1.90, 95% CI: 1.10, 3.29); and female sex (OR 1.79, 95% CI: 1.06, 3.04). CONCLUSIONS: The risk of C. difficile-associated diarrhoea in hospitalized patients receiving antibiotics may be compounded by exposure to proton pump inhibitor therapy.     

Levofloxacin treatment failure in a patient with fluoroquinolone-resistant Streptococcus pneumoniae pneumonia

The frequency of fluoroquinolone-resistant Streptococcus pneumoniae has increased as fluoroquinolone administration for treatment of respiratory tract infections has increased. Levofloxacin treatment failed in a patient who had pneumococcal pneumonia and had received three previous courses of levofloxacin therapy. Susceptibility testing revealed high-level resistance to levofloxacin (minimum inhibitory concentration [MIC] > 32 microg/ml), and cross-resistance to moxifloxacin (MIC 4 microg/ml), trovafloxacin (6 microg/ml), and gatifloxacin (12 microg/ml). Sequencing of the quinolone-resistance determining region revealed a mutation of serine-81 to phenylalanine (Ser81-->Phe) in the gyrA region of DNA gyrase and a Ser79-->Phe mutation in the parC region of topoisomerase IV The patient was treated successfully with intravenous ceftriaxone followed by oral cefprozil. Clinicians must be aware of local resistance patterns and the potential for fluoroquinolone treatment failures in patients with infections caused by S. pneumoniae.     

肺炎链球菌肺炎模型小鼠肺组织趋化因子表达变化

目的检测肺炎链球菌肺炎模型小鼠肺组织趋化因子CXCL1,CXCL2,CCL5和CCL7表达变化,探讨这些趋化因子在肺炎链球菌发生时的病理意义。方法取无特定病原体(SPF)级的小鼠30只,随机分为肺炎链球菌性肺炎实验组与热灭活细菌对照组,利用实时聚合酶链反应和酶联免疫吸附试验法检测实验组和对照组小鼠肺组织CXCL1,CXCL2,CCL5和CCL7的表达差异。结果肺炎链球菌肺炎小鼠肺组织CXCL1和CCL5表达高于热灭活细菌对照组且差异有统计学意义(P<0.05),而CXCL2和CCL7表达在2组之间的比较差异无统计学意义。结论肺炎链球菌肺炎发病时,受感染的肺组织通过过表达趋化因子CXCL1和CCL5,与免疫细胞的相应配体相互作用,募集免疫细胞至感染部位,促进炎症发生。