Variation in antibiotic use among and within different settings: a systematic review

Objectives: Variation in antibiotic use may reflect inappropriate use. We aimed to systematically describe the variation in measures for antibiotic use among settings or providers. This study was conducted as part of the innovative medicines initiative (IMI)-funded international project DRIVE-AB. Methods: We searched for studies published in MEDLINE from January 2004 to January 2015 reporting variation in measures for systemic antibiotic use (e.g. DDDs) in inpatient and outpatient settings. The ratio between a study's reported maximumand minimumvalues of a given measure [maximum: minimumratio (MMR)] was calculated as a measure of variation. Similar measures were grouped into categories and when possible the overall median ratio and IQR were calculated. Results: One hundred and forty-three studies were included, of which 85 (59.4%) were conducted in Europe and 12 (8.4%) in low-to middle-income countries. Most studies described the variation in the quantity of antibiotic use in the inpatient setting (81/143, 56.6%), especially among hospitals (41/81, 50.6%). Themost frequentmeasure was DDDs with different denominators, reported in 23/81 (28.4%) inpatient studies and in 28/62 (45.2%) outpatient studies. For this measure, we found a median MMR of 3.7 (IQR 2.6-5.0) in 4 studies reporting antibiotic use in ICUs in DDDs/1000 patient-days and a median MMR of 2.3 (IQR 1.5-3.2) in 18 studies reporting outpatient antibiotic use in DDDs/1000 inhabitant-days. Substantial variationwas also identified in othermeasures. Conclusions: Our review confirms the large variation in antibiotic use even across similar settings and providers. Data from low-and middle-income countries are under-represented. Further studies should try to better elucidate reasons for the observed variation to facilitate interventions that reduce unwarranted practice variation. In addition, the heterogeneity of reported measures clearly shows that there is need for standardization

Metrics to assess the quantity of antibiotic use in the outpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background The international Innovative Medicines Initiative (IMI) project DRIVE-AB (Driving Reinvestment in Research and Development and Responsible Antibiotic Use) aims to develop a global definition of ‘responsible’ antibiotic use. Objectives To identify consensually validated quantity metrics for antibiotic use in the outpatient setting. Methods First, outpatient quantity metrics (OQMs) were identified by a systematic search of literature and web sites published until 12 December 2014. Identified OQMs were evaluated by a multidisciplinary, international stakeholder panel using a RAND-modified Delphi procedure. Two online questionnaires and a face-to-face meeting between them were conducted to assess OQM relevance for measuring the quantity of antibiotic use on a nine-point Likert scale, to add comments or to propose new metrics. Results A total of 597 articles were screened, 177 studies met criteria for full-text screening and 138 were finally included. Twenty different OQMs were identified and appraised by 23 stakeholders. During the first survey, 14 OQMs were excluded and 6 qualified for discussion. During the face-to-face meeting, 10 stakeholders retained five OQMs and suggestions were made considering context and combination of metrics. The final set of metrics included defined daily doses, treatments/courses and prescriptions per defined population, treatments/courses and prescriptions per defined number of physician contacts and seasonal variation of total antibiotic use. Conclusions A small set of consensually validated metrics to assess the quantity of antibiotic use in the outpatient setting was obtained, enabling (inter)national comparisons. The OQMs will help build a global conceptual framework for responsible antibiotic use

Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use

On Total Domination in the Cartesian Product of Graphs

Ho proved in [A note on the total domination number, Util. Math. 77 (2008) 97–100] that the total domination number of the Cartesian product of any two graphs without isolated vertices is at least one half of the product of their total domination numbers. We extend a result of Lu and Hou from [Total domination in the Cartesian product of a graph and K2or Cn, Util. Math. 83 (2010) 313–322] by characterizing the pairs of graphs G and H for which γt(G□H)=12γt(G)γt(H)$\gamma _t \left( {G\square H} \right) = {1 \over 2}\gamma _t \left( G \right)\gamma _t \left( H \right)$ , whenever γt(H) = 2. In addition, we present an infinite family of graphs Gn with γt(Gn) = 2n, which asymptotically approximate equality in γt(Gn□Hn)≥12γt(Gn)2$\gamma _t \left( {G_n \square H_n } \right) \ge {1 \over 2}\gamma _t \left( {G_n } \right)^2$

On Total Domination in the Cartesian Product of Graphs

Ho proved in [A note on the total domination number, Util. Math. 77 (2008) 97–100] that the total domination number of the Cartesian product of any two graphs without isolated vertices is at least one half of the product of their total domination numbers. We extend a result of Lu and Hou from [Total domination in the Cartesian product of a graph and $K_2$ or $C_n$, Util. Math. 83 (2010) 313–322] by characterizing the pairs of graphs $G$ and $H$ for which $\gamma_t (G \square H)=1/2 \gamma_t (G) \gamma_t (H)$, whenever $\gamma_t (H) = 2$. In addition, we present an infinite family of graphs $G_n$ with $\gamma_t (G_n) = 2n$, which asymptotically approximate equality in $\gamma_t (G_n \square H_n ) \ge 1/2 \gamma_t (G_n)^2$

1-perfectly orientable K[sub]4-minor-free and outerplanar graphs

A graph ▫$G$▫ is said to be 1-perfectly orientable if it has an orientation ▫$D$▫ such that for every vertex ▫$v in V(G)$▫, the out-neighborhood of ▫$v$▫ in ▫$D$▫ is a clique in ▫$G$▫. D. J. Skrien [J. Graph Theory 6, 309--316 (1982)] posed the problem of characterizing the class of 1-perfectly orientable graphs. This graph class forms a common generalization of the classes of chordal and circular arc graphshowever, while polynomially recognizable via a reduction to 2-SAT, no structural characterization of this intriguing class of graphs is known. Based on a reduction of the study of 1-perfectly orientable graphs to the biconnected case, we characterize, both in terms of forbidden induced minors and in terms of composition theorems, the classes of 1-perfectly orientable ▫$K_4$▫-minor-free graphs and of 1-perfectly orientable outerplanar graphs. As part of our approach, we introduce a class of graphs defined similarly as the class of 2-trees and relate the classes of graphs under consideration to two other graph classes closed under induced minors studied in the literature: cyclically orientable graphs and graphs of separability at most 2