h Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/ liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10-to 28-day therapy for platelet nadirs of <100 ؋10 9 / liter. The risk for toxicity did not differ noticeably between 14 and 28 days of therapy and was significantly higher for patients with lower baseline platelet counts. Due to the increased risk of toxicity after longer durations of linezolid therapy and large between-patient variability, close monitoring of patients for development of toxicity is important. Dose individualization based on plasma linezolid concentration profiles and platelet counts should be considered to minimize linezolid-associated thrombocytopenia. Overall, oxazolidinone therapy over 5 to 7 days even at relatively high doses was predicted to be as safe as 10-day therapy of 600 mg linezolid every 12 h.
The validation of a beta-lactam antibiotic allergy assessment allows non-allergists to effectively phenotype patient-reported antibiotic allergies and direct them to appropriate 'de-labeling' stratergies. To the editor, While patient-reported antibiotic allergies (so-called antibiotic allergy labels [AALs]) are encountered in up to 1 in 4 hospitalized patients they are frequently "unknown" and not
P atient-reported antibiotic allergies (so-called antibiotic allergy labels [AALs]) are associated with suboptimal prescribing and inferior clinical outcomes, especially in the immunocompromised (1, 2). The prevalence, type, and impact of AALs in liver transplant recipients (LTRs) remain ill defined. We report on AALs and their impact on a cohort of Australian LTRs.A retrospective matched-cohort study was conducted over a 5-year period (2010 to 2015) at an Australian liver transplant center (Austin Health). Using a departmental liver transplant database, LTRs with an AAL (AAL group) were identified. The same number of matched controls (LTRs without an antibiotic allergy label [non-AAL group]) were randomly selected for comparison. AALs were evaluated and classified as type A adverse drug reactions (ADRs; nonimmune mediated), type B ADRs (immune mediated), or of unknown type (3). Baseline demographics, transplant history, and infection-related admission data were collected. From the time of transplant until 12 months afterward, antibiotics administered during infection-related admissions and their duration of administration were recorded. Readmission, intensive-care unit (ICU) admission, Clostridium difficile infection (CDI), multidrug-resistant (MDR) organism isolation, and mortality rate were captured. An MDR organism was defined as a bacterium resistant to at least one agent in three or more antibiotic classes (4).Of 313 LTRs, 51 (16%) had Ն1 AAL. Females predominated in the AAL group (75% female versus 25% male; P ϭ 0.003), but there was no statistically significant differences in the rates of ICU admission and mortality between males and females (see Table S1 in the supplemental material). Seventy-seven AALs were recorded; of these, 23% (18/77) were type A ADRs, 66% were type B ADRs (51/77), and 10% (8/77) were of unknown type. Of the type A ADRs, 72% (13/18) were gastrointestinal upset, and of the type B ADRs, 6% (3/51) were severe cutaneous ADRs, 55% (28/51) were maculopapular exanthema, 35% (18/51) were anaphylaxis, urticaria, or angioedema, and 4% (2/51) were other reactions. The antibiotics implicated in AALs are demonstrated in Fig. 1
Background: Effective antimicrobial stewardship programs are vital in an environment of emerging resistance to existing antimicrobials and the limited availability of new antimicrobials. There are institutional barriers to successful implementation of these programs. Key performance indicators (KPI) are useful for determining the success of antimicrobial stewardship programs and for benchmarking purposes. Aim: To identify barriers to implementation of antimicrobial stewardship programs, KPI used to measure program outcomes and the perceived usefulness of these KPI in Australian hospitals. Method: Australian Directors of Pharmacy in private and public hospitals or their nominees (n = 281) were surveyed by mail to identify barriers to, and KPI used for antimicrobial stewardship programs at their hospitals. Hospital pharmacists, infectious diseases clinicians and infection control nurses were interviewed until saturation of themes was reached. Results: Response rate for the postal survey was 29% (n = 80). Main barriers to implementing antimicrobial stewardship programs encountered by respondents included: lack of education and training related to antimicrobial usage; prescribing culture at the hospital which was resistant to change; lack of resources to conduct stewardship activities; and lack of feedback to doctors, nurses and pharmacists on institutional antimicrobial use. Only 14 respondents used KPI to measure program outcomes. The KPI used between institutions were variable. Conclusion: Australian hospitals encounter many barriers to implementing antimicrobial stewardship programs. There were no standard national KPI to measure program outcomes. Most participants agreed that the KPI at their hospitals were useful. J Pharm Pract Res 2010; 40: x-x.
Background:The diminishing investment into the development of new antimicrobials is of significant global concern. This, coupled with the emergence of anti-infective drug resistance, highlights the need to both prolong and optimise the use of existing antimicrobials. Strategies or programs to optimise antimicrobial use fall under the broad heading of antimicrobial stewardship. Aim: To identify the types of antimicrobial stewardship programs in existence in Australian hospitals and their perceived success. Method: Directors of Pharmacy or their nominees (n = 281) working in Australian hospitals were surveyed to identify their institutional antimicrobial stewardship programs. Infectious disease clinicians, infection control nurses and hospital pharmacists were recruited for the qualitative interviews. They were interviewed until saturation of themes was identified. All of the interviews were transcribed verbatim and analysed for common themes.
Objective:The primary objective of this study was to examine the impact of an electronic medical record (EMR)–driven intensive care unit (ICU) antimicrobial stewardship (AMS) service on clinician compliance with face-to-face AMS recommendations. AMS recommendations were defined by an internally developed “5 Moments of Antimicrobial Prescribing” metric: (1) escalation, (2) de-escalation, (3) discontinuation, (4) switch, and (5) optimization. The secondary objectives included measuring the impact of this service on (1) antibiotic appropriateness, and (2) use of high-priority target antimicrobials.Methods:A prospective review was undertaken of the implementation and compliance with a new ICU-AMS service that utilized EMR data coupled with face-to-face recommendations. Additional patient data were collected when an AMS recommendation was made. The impact of the ICU-AMS round on antimicrobial appropriateness was evaluated using point-prevalence survey data.Results:For the 202 patients, 412 recommendations were made in accordance with the “5 Moments” metric. The most common recommendation made by the ICU-AMS team was moment 3 (discontinuation), which comprised 173 of 412 recommendations (42.0%), with an acceptance rate of 83.8% (145 of 173). Data collected for point-prevalence surveys showed an increase in prescribing appropriateness from 21 of 45 (46.7%) preintervention (October 2016) to 30 of 39 (76.9%) during the study period (September 2017).Conclusions:The integration of EMR with an ICU-AMS program allowed us to implement a new AMS service, which was associated with high clinician compliance with recommendations and improved antibiotic appropriateness. Our “5 Moments of Antimicrobial Prescribing” metric provides a framework for measuring AMS recommendation compliance.
Timely intravenous (IV) to oral antimicrobial switch (IV-oral-switch) is a key antimicrobial stewardship (AMS) strategy. We aimed to explore concordance with IV-oral-switch guidelines in the context of a long-standing, tightly regulated AMS program. Data was retrospectively collected for 107 adult general medical and surgical patients in an Australian hospital. Median duration of IV antimicrobial courses before switching to oral therapy was 3 days (interquartile range [IQR] 2.25-5.00). Timely IV-oral-switch occurred in 57% (n = 61) of patients. The median delay to switching was 0 days (IQR 0 to 1.25). In most courses (92/106, 86.8%), the choice of oral alternative after switching was appropriate. In 45% (47/105) of courses, total duration of therapy (IV plus oral) exceeded the recommended duration by >1.0 day. Excessive IV antimicrobial duration was uncommon at a hospital with a tightly regulated AMS program. Total duration of therapy was identified as an AMS target for improvement.
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