In 2009, the Scottish government issued a target to reduce Clostridium difficile infection by 30% in 2 years. Consequently, Scottish hospitals changed from cephalosporins to gentamicin for surgical antibiotic prophylaxis. This study examined rates of postoperative AKI before and after this policy change. The study population comprised 12,482 adults undergoing surgery (orthopedic, urology, vascular, gastrointestinal, and gynecology) with antibiotic prophylaxis between October 1, 2006, and September 30, 2010 in the Tayside region of Scotland. Postoperative AKI was defined by the Kidney Disease Improving Global Outcomes criteria. The study design was an interrupted time series with segmented regression analysis. In orthopedic patients, change in policy from cefuroxime to flucloxacillin (two doses of 1 g) and single-dose gentamicin (4 mg/kg) was associated with a 94% increase in AKI (P=0.04; 95% confidence interval, 93.8% to 94.3%). Most patients who developed AKI after prophylactic gentamicin had stage 1 AKI, but some patients developed persistent stage 2 or stage 3 AKI. The antibiotic policy change was not associated with a significant increase in AKI in the other groups. Regardless of antibiotic regimen, however, rates of AKI were high (24%) after vascular surgery, and increased steadily after gastrointestinal surgery. Rates could only be ascertained in 52% of urology patients and 47% of gynecology patients because of a lack of creatinine testing. These results suggest that gentamicin should be avoided in orthopedic patients in the perioperative period. Our findings also raise concerns about the increasing prevalence of postoperative AKI and failures to consistently measure postoperative renal function. Reported rates of postoperative AKI vary because of the heterogeneity of the populations studied. Uncomplicated AKI is associated with a mortality of 10%, rising to 50% in the context of multiorgan failure and up to 80% if RRT is required. 1,2 It was thought that the presence of AKI was a marker of coexisting pathology that increased mortality risk, but recent reports demonstrate AKI as an independent risk factor for mortality. 3,4 The increasing incidence of AKI and its long-term consequences have significant socioeconomic and public health effects globally. 5 Clostridium difficile infection (CDI) is an important healthcare-associated infection. Antibiotic use increases the risk of CDI for at least 3 months 6 and short courses of perioperative antibiotic prophylaxis have also been associated with an increased risk of CDI, particularly in the context of an established outbreak. 7

Ligand-gated ion channels are transmembrane proteins that respond to a variety of transmitters, including acetylcholine, gamma-aminobutyric acid (GABA), glycine, and glutamate [1 and 2]. These proteins play key roles in neurotransmission and are typically found in the nervous system and at neuromuscular junctions [3]. Recently, acetylcholine receptor family members also have been found in nonneuronal cells, including macrophages [4], keratinocytes [5], bronchial epithelial cells [5], and endothelial cells of arteries [6]. The function of these channels in nonneuronal cells in mammals remains to be elucidated, though it has been shown that the acetylcholine receptor alpha7 subunit is required for acetylcholine-mediated inhibition of tumor necrosis factor release by activated macrophages [4]. We show that cup-4, a gene required for efficient endocytosis of fluids by C. elegans coelomocytes, encodes a protein that is homologous to ligand-gated ion channels, with the highest degree of similarity to nicotinic acetylcholine receptors. Worms lacking CUP-4 have reduced phosphatidylinositol 4,5-bisphosphate levels at the plasma membrane, suggesting that CUP-4 regulates endocytosis through modulation of phospholipase C activity.

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A real-world intervention to reduce primary care prescribing of antimicrobials associated with CDI led to large, sustained reductions in the targeted prescribing, largely due to substitution with guideline-recommended antimicrobials rather than by avoiding antimicrobial use altogether. Further research is needed to examine the impact on antimicrobial resistance.

BackgroundIn 2008, the Scottish Antimicrobial Prescribing Group (SAPG) was established to coordinate a national antimicrobial stewardship programme. In 2009 SAPG led participation in a European point prevalence survey (PPS) of hospital antibiotic use. We describe how SAPG used this baseline PPS as the foundation for implementation of measures for improvement in antibiotic prescribing.MethodsIn 2009 data for the baseline PPS were collected in accordance with the European Surveillance of Antimicrobial Consumption [ESAC] protocol. This informed the development of two quality prescribing indicators: compliance with antibiotic policy in acute admission units and duration of surgical prophylaxis. From December 2009 clinicians collected these data on a monthly basis. The prescribing indicators were reviewed and further modified in March 2011. Data for the follow up PPS in September 2011 were collected as part of a national PPS of healthcare associated infection and antimicrobial use developed using ECDC protocols.ResultsIn the baseline PPS data were collected in 22 (56%) acute hospitals. The frequency of recording the reason for treatment in medical notes was similar in Scotland (75.9%) and Europe (75.7%). Compliance with policy (81.0%) was also similar to Europe (82.5%) but duration of surgical prophylaxis <24hr (68.6%), was higher than in Europe (48.1%, OR: 0.41, p<0.001). Following the development and implementation of the prescribing indicators monthly measurement and data feedback in admission units illustrated improvement in indication documented of ≥90% and compliance with antibiotic prescribing policy increasing from 76% to 90%. The initial prescribing indicator in surgical prophylaxis was less successful in providing consistent national data as there was local discretion on which procedures to include. Following a review and a focus on colorectal surgery the mean proportion receiving single dose prophylaxis exceeded the target of 95% and the mean proportion compliant with policy was 83%. In the follow up PPS of 2011 indication documented (86.8%) and policy compliant (82.8%) were higher than in baseline PPS.ConclusionsThe baseline PPS identified priorities for quality improvement. SAPG has demonstrated that implementation of regularly reviewed national prescribing indicators, acceptable to clinicians, implemented through regular systematic measurement can drive improvement in quality of antibiotic use in key clinical areas. However, our data also show that the ESAC PPS method may underestimate the proportion of surgical prophylaxis with duration <24hr.