Tel Aviv, Israel—Could drugs that are not antibiotics contribute to antibiotic resistance? A new Israeli study suggests that can occur.

In a presentation at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) this month, three commonly prescribed classes of drugs, none of them antibiotics, are cited for causing antibiotic-resistant infections from bacteria of the Enterobacteriaceae family. Antibiotic-resistant infections occurring because of use of proton-pump inhibitors (PPIs), beta-blockers, and antimetabolites often lead to longer hospital stays and possibly higher mortality, write the researchers from Tel Aviv Medical Center.

The observational study emphasizes that not all antibiotic resistance occurs because of over-prescribing of anti-infectives. The authors point out that nonantimicrobial drugs (NAMDs) also can play a role, noting that some commonly prescribed NAMDs have been found to have a significant impact on the bacterial composition of the gut microbiome. They sought to determine how that affected risks for infection with antibiotic-resistant bacteria.

To do that, the researchers reviewed data from 1,807 adults admitted to a tertiary-level academic hospital in Tel Aviv, Israel between January 1, 2017, and April 18, 2019, with a diagnosis of upper urinary tract infection and a positive urine or blood culture growing Enterobacteriaceae. They also retrieved data about use of 19 nonantimicrobial drug classes prior to hospital admission from electronic medical records.

Researchers identified antimicrobial drug–resistant organisms in more than half of patient samples; multidrug-resistant organisms, defined as being resistant to three or more classes of antibiotics, were identified in about a quarter of them.

Their analyses pinpointed seven common drug categories as being associated with increased resistance to antimicrobial drugs:
• Selective serotonin reuptake inhibitors for depression
• Typical antipsychotics used to treat mental health conditions such as schizophrenia
• Anti-10A inhibitors, i.e., blood thinners, for stroke prevention in patients with atrial fibrillation
• Proton pump inhibitors (PPIs), which reduce the production of stomach acid
• Beta-blockers, which lower blood pressure
• Antimetabolites, common chemotherapy drugs that are often used to treat cancers and inflammatory diseases.

Of those, researchers determined that PPIs, beta-blockers, and antimetabolites were especially associated with resistance to third-generation cephalosporins, trimethoprim-sulfamethoxazole, and fluoroquinolones. The strongest effect on antibiotic resistance was found with antimetabolites, they advise.

“Our findings highlight the importance of non-antimicrobial drug exposure as a risk factor for antibiotic resistance," explained lead author Meital Elbaz, MD, from Tel Aviv Medical Center. “We urgently need larger studies with more drug classes to confirm the discovery and to clarify the biological link between common prescription drugs and antibiotic resistance.”

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