Effects of Antibiotic Restrictions on Resistance in Hospitalized Patients

Restricting the use of selected classes of antibiotics such as carbapenems and third-generation cephalosporins does not necessarily lead to decreased prevalence of antibiotic resistance among Enterobacterales, nonfermenters, or Gram-positive bacteria, according to a paper published in Open Forum Infectious Disease.

Investigators from the Netherlands performed a systematic review and meta-analysis in order to determine the effect of restricting the use of antibiotics on the prevalence of resistant bacterial pathogens. The study authors explained that restricting some selected classes of antibiotics in hospital settings is often believed to contribute to the containment of resistance development. They searched the Embase and Pubmed databases for studies from April 11, 2014 (the last date of the previous study period when they conducted this research) through June 4, 2020 that reported prevalence and resistance and use of antibiotics. Then, the investigators explained, they calculated the overall effect of antimicrobial resistance between post- and pre-intervention periods.

Ultimately the investigators pooled 15 studies with an overall low quality of evidence, they noted. These studies originated from 11 countries on 5 continents, they noted, and had varying duration of implementing restriction policies: 6 months up to 10 years. The study authors said a majority of the publications reported data from hospital wards, while 6 reported on ICUs, and 1 included both settings. Only 1 study in the group reported on more than 1 hospital, but the other studies were conducted in single-center university, general care, and tertiary care hospitals. None of the studies were conducted at long-term care facilities.

For the meta-analysis, the investigators grouped the studies based on the restriction of 3 main antibiotics classes: carbapenems, fluoroquinolones, and third-generation cephalosporins. However, the investigators also observed studies on the use and resistance prevalence of nonrestricted antibiotics for piperacillin-tazobactam and first- and second-generation cephalosporins, but not for cotrimoxazole, they said.

Most studies—including those that reported restricted and nonrestricted antibiotics—reported resistance prevalence in Enterobacterales and nonfermenters, the study authors learned. They also found that only 2 studies reported resistance prevalence in Gram-positive bacteria.

The study authors observed that pre-intervention prevalence of antimicrobial resistance did not significantly change the effect on resistance after a restriction of carbapenems or third-generation cephalosporins, but a higher pre-intervention prevalence of resistance did lead to stronger reductions in resistance after restricting cephalosporins and fluoroquinolones. They did emphasize, though, that the observation among fluoroquinolones was driven by 2 smaller studies with high pre-intervention prevalence.

Additionally, the study authors learned that reducing piperacillin-tazobactam had a significant effect on resistance of nonfermenters, but they said it was not conducted through a restrictive intervention.

The study authors also ruled out other factors, like nosocomial infections, post-intervention antibiotic use, or intervention duration, as possible explanations of the heterogeneity between studies within the same class of antibiotics.

Acknowledging their findings are incongruent with current in-hospital practices and many individual studies, the study authors wrote that “it is therefore important to consider the substantial inconsistencies in the direction of effect sizes between included studies, which led to a high degree of heterogeneity, and the generally low quality of evidence… Based on the present comprehensive overview of the available evidence, it is therefore perhaps too straightforward to conclude that applying a restrictive antibiotic policy is in general ineffective. However, high-quality research is lacking and is clearly needed before concluding otherwise.”