Departmental consumption of antibiotic drugs and subsequent resistance: a quantitative link

Leibovici, Leonard; Berger, Richard E.; Gruenewald, Tara L.; Yahav, Jacob; Yehezkelli, Yoav; Milo, Gai; Samra, Zmira; Pitlik, Silvio

doi:10.1093/jac/48.4.535

Cited by 32 publications

(21 citation statements)

References 18 publications

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“…17 There have been only a few studies combining both levels of information for investigating antibiotic resistance. 18,24,30 In contrast to these studies, we chose to use more detailed information in our statistical models, which included multiple antibiotics and interaction with previous susceptible culture and calculated ward-level use for each patient-day in the hospital. Our results showed some important ward-level associations.…”

Section: Discussionmentioning

confidence: 99%

“…For many antibiotic-bacteria combinations, an individual's risk of resistant infection will increase with the total use of antibiotic in the hospital or ward, during the period preceding their infection. This hypothesis is justified by previous ecological studies 14,18 We hypothesized that an association between population-level use and infection with a resistant organism would be strongest when one or more of the above-mentioned scenarios at the individual level are important AND secondary transmission of the resistant pathogen occurs at an appreciable frequency.…”

Section: Predicted Associations Based On Biological Mechanismsmentioning

confidence: 96%

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A New Approach to the Analysis of Antibiotic Resistance Data from Hospitals

Aşçıoğlu

Samore

Lipsitch

2014

Microbial Drug Resistance

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We aimed to develop a new approach to the analysis of antimicrobial resistance data from the hospitals, which allows simultaneous analysis of both individual- and population-level determinants of bacterial resistance. This was a retrospective cohort study that included adult patients who stayed in the hospital >2 days. We analyzed data using shared frailty Cox models and tested our approach using a priori hypotheses based on biology and epidemiology of antibiotic resistance. For gram-negative bacteria, the use of the major selecting antibiotic by an individual was the main risk factor for acquiring resistant species. Hazard ratios (HRs) were strikingly high for ceftazidime-resistant Enterobacter species (HR=11.17; 95% confidence interval [CI]: 5.67-22.02), ciprofloxacin-resistant Pseudomonas aeruginosa (HR=4.41; 95% CI: 2.14-9.08), and imipenem-resistant P. aeruginosa (HR=7.92; 95% CI: 4.35-14.43). Ward-level use was significant for vancomycin-resistant enterococci (VRE) (HR=1.40; 95% CI: 1.07-1.83) and for imipenem-resistant P. aeruginosa (HR=1.40; 95% CI: 1.08-1.83). Previous incidence of infection in the same ward increased the risk of acquiring methicillin-resistant Staphylococcus aureus (HR=1.22; 95% CI: 1.15-1.30) and VRE (HR=1.53; 95% CI: 1.38-1.70). Our results were consistent with our hypotheses and showed that combining population- and individual-level data is crucial for the exploration of antimicrobial resistance development.

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Section: Discussionmentioning

confidence: 99%

Section: Predicted Associations Based On Biological Mechanismsmentioning

confidence: 96%

A New Approach to the Analysis of Antibiotic Resistance Data from Hospitals

Aşçıoğlu

Samore

Lipsitch

2014

Microbial Drug Resistance

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“…It is not known whether the proportion of patients exposed to antibiotics (irrespective of duration of exposure per patient and length of stay in the unit) or the proportion of patient days exposed to the antibiotics is a better indicator for developing antibiotic resistance. However, Leibovici et al (20) showed that increased consumption of antibiotics as measured by DDDs per 1000 patient days increases the incidence of resistant coliform pathogen among hospital-acquired bloodstream infections. The method of the measuring drug use density must be considered when comparing drug use among various pediatric groups.…”

Section: Discussionmentioning

confidence: 99%

Drug use density in critically ill children and newborns: Analysis of various methodologies

Valcourt

Norozian²,

Lee³

et al. 2009

Pediatric Critical Care Medicine

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In critically ill children, drug use density of vancomycin is significantly less when evaluated by the DDD method compared with the prescribed daily dose method, a more appropriate method in children. However, the simplest and most accurate method of assessing drug use density is the number of days of drug use method, which allows comparison of drug use density between different pediatric facilities or clinical units.

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“…(v) The lack of coresistance to ␤-lactams may weaken the strength of macrolides in the spread of erythromycin resistance in S. pyogenes. The role of antibiotics in the selection of resistance has been studied mostly in the hospital context (17,19). However, in the larger, open, dynamic, and more complex community setting, we need larger and more geographically dispersed samples of clinical isolates to be representative of what is being measured, along with reliable and standardized data on antibiotic consumption.…”

Section: Discussionmentioning

confidence: 99%

Pharmacoepidemiological Analysis of Provincial Differences between Consumption of Macrolides and Rates of Erythromycin Resistance among Streptococcus pyogenes Isolates in Spain

et al. 2002

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The M phenotype is by far the most common mechanism of erythromycin resistance among Streptococcus pyogenes isolates in Spain. A geographic analysis of the relationship between within-country differences in the prevalence of M-type resistance to erythromycin in S. pyogenes and the level of consumption of 14-and 15-membered macrolides within different provinces was carried out. From 1998 to 1999, a nationwide multicenter surveillance study yielded 2,039 consecutive pharyngeal isolates of S. pyogenes. Data on antibiotic consumption for the same period were gathered from IMS Health, and the corresponding daily defined doses per 1,000 inhabitants per day were calculated according to the Anatomic Therapeutic Classification index. Macrolide use was subdivided into dosages given three times a day (TID), twice a day (BID), or once a day (OD). Spearman nonparametric correlation coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were introduced into a linear regression model. The total consumption of macrolides presented a significant correlation with the prevalence of resistance (R ‫؍‬ 0.527; P ‫؍‬ 0.032). Neither TID nor BID macrolide consumption showed significant correlations. Only OD consumption had a significance below 0.1. These data are consistent with the hypothesis that only the total consumption of macrolides influences the local rates of M-type erythromycin resistance in S. pyogenes, and subgroups of macrolides seem to have an additive rather than a selective effect by contributing to increasing the final amount of macrolides used. Local variations in total consumption were associated only with BID consumption (R ‫؍‬ 0.849; P ‫؍‬ 0.004). The simple linear regression with total macrolide consumption showed a considerable determination coefficient (R 2 ‫؍‬ 0.678; P ‫؍‬ 0.006). The model explains up to 68% of the measured variation and is clearly better as a predictor of the prevalence of resistance than the mere mean is. By solving the regression equation, the resultant value of 2.2 defined doses per 1,000 inhabitants per day fits with the existence of a critical threshold of selective pressure.

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Departmental consumption of antibiotic drugs and subsequent resistance: a quantitative link

Abstract: The departmental consumption of cephalosporin drugs and amikacin in six autonomous departments of medicine in the same hospital was associated with a measurable and statistically significant increase in the probability of infection caused by a resistant pathogen.

Cited by 32 publications

References 18 publications

A New Approach to the Analysis of Antibiotic Resistance Data from Hospitals

A New Approach to the Analysis of Antibiotic Resistance Data from Hospitals

Drug use density in critically ill children and newborns: Analysis of various methodologies

Pharmacoepidemiological Analysis of Provincial Differences between Consumption of Macrolides and Rates of Erythromycin Resistance among Streptococcus pyogenes Isolates in Spain

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