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The shortage of antimicrobials poses a global health threat. In Japan, for instance, the current, critical shortage of cefazolin, a first-line agent for the treatment of common infectious diseases and surgical antimicrobial prophylaxis, has had a substantial impact on inpatient care. A shortage of essential antimicrobial agents like cefazolin leads to increased consumption of alternative antimicrobial agents with broad-spectrum activity, with the unintended consequence of militating against antimicrobial stewardship efforts in inpatient settings and potentially promoting antimicrobial resistance. Although there is global awareness of the shortage of crucial antimicrobials, action to resolve this problem, especially with a view to preventing antimicrobial resistance and promoting antimicrobial stewardship, has been slow, possibly due to the failure to appreciate the urgency of the dilemma. A comprehensive plan for stabilizing antimicrobial access and international collaboration to secure a continuous supply of essential antimicrobials are urgently needed.

BackgroundAn inpatient antimicrobial stewardship program is vital for judicious antimicrobial use. We began a hospital-wide, postprescription review with feedback (PPRF) in 2014; the present study evaluated its impact on antimicrobial consumption and clinical outcomes over 4 years.MethodsOnce-weekly PPRF for carbapenems and piperacillin/tazobactam was implemented. We tracked the data on each antimicrobial use as days of therapy (DOT) per 1000 patient-days (PD). Changes in the incidence of drug-resistant organisms, in-hospital mortality, and length of hospital stay per month were analyzed by an interrupted time series.ResultsCarbapenem use continued to decline in the preintervention and intervention periods (−0.73 and −0.003 DOT/1000 PD, respectively), and although monthly average use remained low in the intervention period (8.3 DOT/1000 PD), more importantly, the postintervention change in the slope diminished significantly. Piperacillin/tazobactam use showed a steeper decline in the intervention period, but the change in the slope was not statistically significant (change in slope: −0.20 DOT/1000 PD per month [P = .16]). Postintervention use of narrower-spectrum antimicrobials including ampicillin/sulbactam (change in slope: +0.58 DOT/1000 PD per month [P < .001]) increased. The antimicrobial cost and the monthly average length of hospital stay also declined (−37.4 USD/1000 PD per month [P < .001] and −0.04 days per month [P < .001], respectively), whereas few postintervention changes in the incidence of drug-resistant organisms were observed.ConclusionsIn our study, the 4-year PPRF for broad-spectrum antimicrobials coincided with a reduction in the use of targeted antimicrobials and resulted in an improvement in 1 patient-centered outcome, thus conferring the additional benefit of reducing expenditures for antimicrobials.

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1. Previous studies have suggested the involvement of arginine vasopressin (AVP) and inflammation in the development of cerebral vasospasm after subarachnoid haemorrhage (SAH). The aim of the present study was to clarify the role of AVP in the arterial narrowing following cerebral haemorrhage by examining the effect of SR 49059 (a V(1) receptor antagonist) on the diameter of rat basilar artery exposed to SAH. The effect of the 5-lipoxygenase inhibitor ZM 230487 on AVP-induced contraction of rat basilar arteries was also investigated. 2. After 1 h and 2 days from SAH induction, brains were removed and pictures of the basilar arteries were taken. The external diameter of the basilar artery was measured in the presence and absence of SR 49059 (1 mg/kg, i.v.). For in vitro experiments, the basilar arteries isolated from control and SAH rats (at 1 h and at 2 days from SAH induction) were cut into spiral preparations and the AVP (0.3 nmol/L)-induced contraction in the presence of ZM 230487 was investigated. Each group analysed (i.e. control, SAH 1 h and SAH 2 days) consisted of eight rats. 3. The diameter of rat basilar arteries decreased by 43 and 25% at 1 h and 2 days from SAH induction, respectively, compared with control. The administration of SR 49059 significantly reduced cerebral vasospasm. After SAH induction, the diameter of the basilar artery in SR 49059-treated groups decreased by only 22% (at 1 h) and by 3% (at 2 days) compared with the control group (P < 0.01). In basilar arterial strips, ZM 230487 attenuated the vasopressin-induced contraction in both control and SAH groups. However, SAH groups showed a significant resistance of the AVP-induced contraction in the presence of ZM 230487 compared with control (P < 0.05). 4. The results suggest that the cerebral vasospasm in SAH rats is due, at least in part, to endogenous AVP and may involve an increase in the activity of 5-lipoxygenase. SR 49059 may represent a potential therapeutic strategy for the treatment of cerebral vasospasm.