In the Journals

PPI use increases risk for listeriosis

A population-based case-control study conducted in Denmark showed that the use of proton pump inhibitors, or PPIs, was associated with an increased risk for listeriosis.

The findings, published in Clinical Infectious Diseases, further demonstrated that the risk for listeriosis waned with time since the last prescription redemption.

Anne Kvistholm Jensen, PhD, of the department of infectious disease epidemiology at Statens Serum Institut, Copenhagen, Denmark, and colleagues reported that escalating use of PPIs was previously attributed to an upward trend in listeriosis cases in several European countries, including Denmark, since the early 2000s.

“PPIs reduce gastric acid secretion and it is hypothesized that this may enhance survival of acid-sensitive pathogens including L. monocytogenes when passing through the stomach and thus increases the risk of disease,” they wrote.

To further investigate this association, the researchers examined information from Danish health registries and listeriosis surveillance data. Their analysis included 721 case-patients aged 45 years or older with specimens that tested positive for L. monocytogenes from July 1, 1994 to Dec. 31, 2012 and 34,844 matched controls.  

According to the data, 12.9% of case-patients and 2.8% of controls were currently using PPIs and were nearly 3 times more likely to develop listeriosis (OR = 2.81; 95% CI, 2.14-3.69) compared with patients not receiving PPIs. Based on this finding, the researchers estimated that the population attributable fraction of listeriosis due to PPI usage was 8.3%. The association between PPI use and listeriosis remained significant up to 90 days after the last date of prescription redemption (OR = 2.56; 95% CI, 1.62-4.04) and increased with decreasing age and level of comorbidity (P < .001). Patients also receiving glucocorticoid treatment were at an even higher risk for listeriosis (OR = 4.61; 95% CI, 3.01-7.06).

“We find that the frailty of the listeriosis patients cannot entirely explain the observed association with PPI as the ORs for the patient groups expected to include the least frail patients, namely the youngest patients and patients with the lowest [comorbidity index] score, remained statistically significant in the analysis of effect-measure modification,” Jensen and colleagues wrote.

In addition to listeriosis, PPIs have also been linked to an increased risk for acute and chronic kidney disease, hypomagnesemia, bone fracture, community-acquired pneumonia and Clostridium difficile infection, according to the researchers. The FDA had published a safety alert concerning these adverse events.

“PPIs have been regarded as generally safe and without serious adverse effects. However, this perspective is changing,” Jensen and colleagues concluded. “Evidence is mounting that PPI can have a biologic, causal effect on the risk of enteric infections including foodborne infections such as salmonellosis, campylobacteriosis and listeriosis.” – by Stephanie Viguers

Disclosure: The researchers report no relevant financial disclosures.

A population-based case-control study conducted in Denmark showed that the use of proton pump inhibitors, or PPIs, was associated with an increased risk for listeriosis.

The findings, published in Clinical Infectious Diseases, further demonstrated that the risk for listeriosis waned with time since the last prescription redemption.

Anne Kvistholm Jensen, PhD, of the department of infectious disease epidemiology at Statens Serum Institut, Copenhagen, Denmark, and colleagues reported that escalating use of PPIs was previously attributed to an upward trend in listeriosis cases in several European countries, including Denmark, since the early 2000s.

“PPIs reduce gastric acid secretion and it is hypothesized that this may enhance survival of acid-sensitive pathogens including L. monocytogenes when passing through the stomach and thus increases the risk of disease,” they wrote.

To further investigate this association, the researchers examined information from Danish health registries and listeriosis surveillance data. Their analysis included 721 case-patients aged 45 years or older with specimens that tested positive for L. monocytogenes from July 1, 1994 to Dec. 31, 2012 and 34,844 matched controls.  

According to the data, 12.9% of case-patients and 2.8% of controls were currently using PPIs and were nearly 3 times more likely to develop listeriosis (OR = 2.81; 95% CI, 2.14-3.69) compared with patients not receiving PPIs. Based on this finding, the researchers estimated that the population attributable fraction of listeriosis due to PPI usage was 8.3%. The association between PPI use and listeriosis remained significant up to 90 days after the last date of prescription redemption (OR = 2.56; 95% CI, 1.62-4.04) and increased with decreasing age and level of comorbidity (P < .001). Patients also receiving glucocorticoid treatment were at an even higher risk for listeriosis (OR = 4.61; 95% CI, 3.01-7.06).

“We find that the frailty of the listeriosis patients cannot entirely explain the observed association with PPI as the ORs for the patient groups expected to include the least frail patients, namely the youngest patients and patients with the lowest [comorbidity index] score, remained statistically significant in the analysis of effect-measure modification,” Jensen and colleagues wrote.

In addition to listeriosis, PPIs have also been linked to an increased risk for acute and chronic kidney disease, hypomagnesemia, bone fracture, community-acquired pneumonia and Clostridium difficile infection, according to the researchers. The FDA had published a safety alert concerning these adverse events.

“PPIs have been regarded as generally safe and without serious adverse effects. However, this perspective is changing,” Jensen and colleagues concluded. “Evidence is mounting that PPI can have a biologic, causal effect on the risk of enteric infections including foodborne infections such as salmonellosis, campylobacteriosis and listeriosis.” – by Stephanie Viguers

Disclosure: The researchers report no relevant financial disclosures.