Association between use of different antibiotics and trimethoprim resistance: going beyond the obvious crude association

Abstract

Use of amoxicillin/ampicillin explained more of the variance in trimethoprim resistance than trimethoprim use, suggesting that co-selection by these antibiotics is an important driver of trimethoprim resistance levels at the population level. Nitrofurantoin use was consistently associated with lower trimethoprim resistance levels, indicating that trimethoprim resistance levels could be lowered if trimethoprim use is replaced by nitrofurantoin.

Personal clinical history predicts antibiotic resistance in urinary tract infections

“…These inherent correlations among resistances suggest that observed associations between resistance to a given drug A and past purchase of a different drug B may arise indirectly through selection for resistance B and association between resistance to B and resistance to A. Mathematically discerning these direct from indirect effects is not possible when only a single resistance is considered 17,36 . Yet, as our dataset contained measurements of multiple resistances for each sample, we were able to disentangle direct from indirect associations by adjusting the logistic regression for other measured resistances (Methods: Logistic regression "Purchase history adjusted for cross-resistance").…”

“…In practice, though, to save time and resources, drugs are often prescribed empirically in absence of culture susceptibility measurements, risking incorrect and ineffective treatment. difficult to discern the direction of causality 17,35 . Finally, the time extent of these positive and negative associations of resistance with prior antibiotic usage and prior resistant samples is not well resolved, and it is also unclear whether and how these associations vary across resistances to different antibiotics.Here, we present a systematic big-data analysis of a large population of UTI patients to unravel predictive features of antibiotic resistance.…”

“…Treatment of these infections accounts for about 8% of non-hospital usage of antibiotics, often as part of empirical prescription 11,12 . The common etiological agents of UTIs are diverse, including Escherichia coli , Klebsiella pneumoniae and Proteus mirabilis, as well as gram-positive bacteria such as Enterococcus faecalis [13][14][15][16][17][18] . These pathogens are often resistant to several antibiotics, with resistance rates of infections exceeding 20% for commonly used drugs 14,17,19 , emphasizing the challenge of choosing the most appropriate antibiotic treatment for each patient 20 .…”

“…Availability of antibiotic purchase data reveals patterns of antibiotic use and misuse 31 and shows that risk of resistance increases with short-term prior use of antibiotics 5,21,22,29,[32][33][34] . At the population level, a recent large-scale study revealed correlations between risk of trimethoprim/sulfa resistance and the volume of past purchases of the same drug (cognate) as well as of other drugs of different pharmaceutical classes (noncognate) 17 . Such associations of usage of a given antibiotics with future resistance to other antibiotics can appear indirectly through genetic linkage among resistance mechanisms, but mathematically resolving direct and indirect selection for resistance has been challenging.…”

Outpatient antibiotic prescribing and demographic factors associated with state-level septicemia mortality rates in US adults

“…Antibiotic use may also contribute to prevalence of infections resistant to other antibiotics that may lead to severe outcomes. For example, fluoroquinolone use was found to be associated with methicillin-resistant S. aureus (MRSA) infections [16,17], while amoxicillin use was found to be associated with trimethoprim resistance in Enterobacteriaceae [18], with trimethoprim-resistant urinary tract infections (UTIs) leading to bacteremia outcomes [15].…”