Proton Pump Inhibitor Use Is Associated With Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Rectal Carriage at Hospital Admission: A Cross-Sectional Study

Huizinga, Pepijn; Bergh, Marjolein Kluytmans– van den; Rijen, Miranda van; Willemsen, Ina; Veer, Nils van 't; Kluytmans, Jan

doi:10.1093/cid/ciw743

Cited by 31 publications

(46 citation statements)

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“…In the primary analysis, we included the 12 studies that adjusted for confounding. [8][9][10]37,39,40,43,45,47,54,55,57 This showed that acid suppression was associated with MDRO colonization (OR = 1.74; 95% CI, 1.40-2.16) ( Figure 2). Among these studies, heterogeneity, as measured using the I 2 method, was 68%.…”

Section: Risk Of Bias and Primary Analysismentioning

confidence: 92%

“…[8][9][10]37,39,40,43,45,47,54,55,57 Overall, the 12 studies included 22 305 participants (8491 [38.1%] were acid suppressant users; 12 714 [57.0%] were female). Of these, 7 studies were cross-sectional, 9,10,37,43,45,55,57 3 were case control, 39,40,54 and 2 were cohort studies. 8,47 We summarized the study characteristics in the Table. Studies were published between 1996 and 2019; most were of adult populations (age ≥18 years).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…8,47 We summarized the study characteristics in the Table. Studies were published between 1996 and 2019; most were of adult populations (age ≥18 years). Three studies were designed to determine the risk assoc iated w ith ac id suppressants, 9,39,54 whereas the remaining studies evaluated risk factors in general. Most studies were conducted in the World Health Organization European region (13 of 26 studies) and the region of the Americas (11 of 26 studies) (eTable 1 in the Supplement).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Hagel et al, 2019 42 Kuenzli et al, 2014 44 Lee et al, 2018 46 Rodríguez-Baño et al, 2008 51 Vading et al, 2016 56 Őstholm-Balkhed et al, 2013 48 Subtotal (95% CI) Heterogeneity: τ 2 = 0.00; χ 2 = 4.83, df = 5 (P = .44); I 2 = 0 Test for overall effect: z = 0.91 (P = .36) Total (95% CI) Heterogeneity: τ 2 = 0.03; χ 2 = 20.39, df = 13 (P = .09); I 2 = 36% Test for overall effect: z Ben-Ami et al, 2006 37 Hamprecht et al, 2016 43 Huizinga et al, 2017 9 Latour et al, 2019 45 Reuland et al, 2016 10 Søgaard et al, 2017 54 Wielders et al, 2017 57 Subtotal (95% CI) Heterogeneity: τ 2 = 0.04; χ 2 = 15.42, df = 7 (P = .03); I 2 = 55% Test for overall effect: z Okamoto et al, 2017 15 Prasad et al, 2016 49 Seekatz et al, 2018 52…”

Section: Unadjustedmentioning

confidence: 99%

“…[6][7][8] Recent evidence has pointed to the use of acid suppression therapy as a possible risk factor for colonization with MDROs. 9,10 Acid suppressants inhibit stomach acid secretion and can change the composition of the intestinal microbiome [11][12][13] ; stomach acid and a healthy intestinal microbiome protect the gastrointestinal tract against colonization by exogenous bacteria. 14 Whether acid suppression facilitates colonization and infection with MDROs remains unclear.…”

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confidence: 99%

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Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms

et al. 2020

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IMPORTANCE Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome. Whether acid suppression increases the risk of colonization with multidrug-resistant microorganisms (MDROs) is unclear. OBJECTIVES To systematically examine the association of use of acid suppressants with the risk of colonization with MDROs and to perform a meta-analysis of current evidence. DATA SOURCES PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from database inception through July 8, 2019. STUDY SELECTION Study selection was performed independently by 2 authors (R.P.J.W. and C.M.J.E.V.-G.) on the basis of predefined selection criteria; conflicts were resolved by consensus or by an adjudicator (K.v.D.). Human observational studies (case control, cohort, and cross-sectional) and clinical trial designs were selected if they quantified the risk of MDRO colonization in users of acid suppressants in comparison with nonusers. DATA EXTRACTION AND SYNTHESIS The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. Data were extracted independently by the same 2 authors, and adjudication was conducted when necessary. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) were estimated using random-effects models; heterogeneity was evaluated using the I 2 method. MAIN OUTCOMES AND MEASURES The primary outcome measure was intestinal colonization with MDROs of the Enterobacterales order (producing extended-spectrum β-lactamases, carbapenemases, or plasmid-mediated AmpC β-lactamases), vancomycin-resistant enterococci, methicillin-resistant or vancomycin-resistant Staphylococcus aureus, or multidrug-resistant Pseudomonas or Acinetobacter species. RESULTS A total of 26 observational studies including 29 382 patients (11 439 [38.9%] acid suppressant users) met the selection criteria. Primary meta-analysis of 12 studies including 22 305 patients that provided adjusted ORs showed that acid suppression increased the odds of intestinal carriage of MDROs of the Enterobacterales order and of vancomycin-resistant enterococci by roughly 75% (OR = 1.74; 95% CI, 1.40-2.16; I 2 = 68%). The odds were concordant with the secondary pooled analysis of all 26 studies (OR = 1.70; 95% CI, 1.44-1.99; I 2 = 54%). Heterogeneity was partially explained by variations in study setting and the type of acid suppression. CONCLUSIONS AND RELEVANCE Acid suppression is associated with increased odds of MDRO colonization. Notwithstanding the limitations of observational studies, the association is plausible and is strengthened by controlling for confounders. In view of the global increase in antimicrobial resistance, stewardship to reduce unnecessary use of acid suppressants may help to prevent MDRO colonization.

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Section: Risk Of Bias and Primary Analysismentioning

confidence: 92%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Unadjustedmentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms

et al. 2020

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Use of proton pump inhibitors and cholangitis complicated with multi‐drug resistant bacteria

Hakuta

Nakai

Hamada

et al. 2021

J Hepato Biliary Pancreat

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Background Multidrug‐resistant bacteria (MDRB) has rapidly spread worldwide and become a serious problem. Proton pump inhibitors (PPIs) are a class of commonly prescribed medications, but recent studies have suggested the increased risk of infection with MDRB in PPI users. We evaluated the association between PPI use and incidence of cholangitis with MDRB. Methods Consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between January 2010 and August 2019 were included in this retrospective study. The incidence of cholangitis with MDRB was compared between regular and non‐regular PPI users. Results A total of 1224 regular PPI users and 1528 non‐regular PPI users were identified. There was no clinically significant difference in age and sex between the groups. Indication of ERCP was different between the groups. The number of ERCP sessions during the study periods was higher in regular PPI users. The incidence of cholangitis with MDRB was significantly higher in regular PPI users (3.0% vs 1.1%; P < .001). Multivariable‐adjusted odds ratio for cholangitis with MDRB comparing regular PPI users to non‐regular users was 2.19 (95% confidence interval 1.20‐4.00; P = .01). Conclusions Regular PPI use was associated with a higher risk of cholangitis with MDRB.

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Prevalence and risk factors of extended-spectrum beta-lactamase producing E. coli causing urinary tract infections in Iceland during 2012–2021

Halldórsdóttir,

Hrafnkelsson,

Einarsdóttir

et al. 2024

Eur J Clin Microbiol Infect Dis

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Purpose To investigate the association of potential risk factors for urinary tract infections (UTI) caused by E. coli producing ESBL vs. not producing ESBL in Iceland. Methods Observational, case-control study including a cohort of 27,747 patients (22,800 females, 4,947 males; 1207 cases, 26,540 controls) of all ages with UTI caused by E. coli in 2012 to 2021 at the clinical microbiology laboratory covering about 2/3 of the Icelandic population. Clinical patient data was obtained from three national databases. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as a measure of association between ESBL and exposure variables. Results The proportion of samples with ESBL-producing E. coli increased during the study period, from 2.6% in 2012 to 7.6% in 2021 (p < 0.001). ESBL-positive strains were detected in 1207 individuals (4.4%), 905 females (4.0%) and 302 males (6.1%). The following risk factors were identified: Male sex, higher age, institution type (hospital, nursing home), hospital-associated UTI, Charlson comorbidity index score ≥ 3, history of cystitis or hospitalization in the past year, and prescriptions for certain antibiotics or proton pump inhibitors (PPIs: OR 1.51) in the past half year. The antibiotic associated with the highest risk was ciprofloxacin (OR 2.45). Conclusion The prevalence of UTIs caused by ESBL-producing E. coli has been increasing in Iceland. The strongest risk factors for ESBL production were previous antibiotic use, especially ciprofloxacin, and previous PPI use, both considered to be overprescribed. It is important to promote the prudent use of these drugs.

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Proton Pump Inhibitor Use Is Associated With Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Rectal Carriage at Hospital Admission: A Cross-Sectional Study

Cited by 31 publications

References 11 publications

Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms

Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms

Use of proton pump inhibitors and cholangitis complicated with multi‐drug resistant bacteria

Prevalence and risk factors of extended-spectrum beta-lactamase producing E. coli causing urinary tract infections in Iceland during 2012–2021

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