Impact of antimicrobial stewardship implementation on the antibiotic use and susceptibility in a Japanese long-term care hospital.

BACKGROUND: Antimicrobial use (AMU) is closely related to the emergence of antimicrobial-resistant (AMR) bacteria. Meanwhile, long-term care hospitals (LTCHs) have been pointed out to be important reservoirs for AMR. However, evidence illustrating the association between AMU and AMR in LTCHs is lacking compared to that of acute care hospitals. METHODS: We evaluated the impact of an antimicrobial stewardship (AS) program implementation, in a LTCH on AMU and antibiotic susceptibility between three periods: the pre-AS-period (pre-AS); the first period after AS implementation (post-AS 1), in which initiated recommendation the blood culture collection and definitive therapy by AS team; and the second period (post-AS 2), implementation of a balanced use of antibiotics was added. RESULTS: After the AS implementation, a significant increase in the number of blood cultures collected was observed. Conversely, the AMU of piperacillin-tazobactam (PIPC/TAZ), which has activity against Pseudomonas aeruginosa, was increased and occupied 43.0% of all injectable AMU in post-AS 1 compared with that in pre-AS (35.5%). In the post-AS 2 period, we analyzed the %AUD and recommended hospital-wide PIPC/TAZ sparing; this resulted in the significant reduction in %AUD of PIPC/TAZ, which was associated with improved susceptibility of P. aeruginosa to PIPC/TAZ. CONCLUSIONS: These results suggest that AS programs aimed at implementing antibiotic sparing may lead to improve AMR, highlighting the necessity of correcting overuse of a single class of antibiotics and usefulness of AMU monitoring in the LTCH setting.

Spontaneous isolated dissection of the superior mesenteric artery and aneurysm formation resulting from segmental arterial mediolysis: a case report.

BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery (SMA) can lead to bowel ischemia, aneurysm rupture, or even death. Studies have suggested that mechanical or hemodynamic stress on the vascular wall of the SMA may be a contributor, but its pathogenesis is unclear. CASE PRESENTATION: A 57-year-old Japanese man with a history of untreated hypertension and hyperuricemia was admitted to our hospital with the sudden onset of severe epigastric pain. Laboratory findings showed elevated white blood cell count and C-reactive protein, and contrast-enhanced computed tomography (CT) of the abdomen demonstrated arterial dissection with luminal stenosis and aneurysm formation at the distal portion of the SMA after the branching of the jejunal artery, and intravenous nicardipine was administered. The patient's epigastric pain resolved spontaneously but recurred on day 6 of his hospital stay. Contrast-enhanced abdominal CT revealed an enlarged aneurysm with wall thinning. Because of the risk of aneurysm rupture, the decision was made to perform aneurysmectomy and bowel resection on day 6. Histologic examinations revealed two separate dissecting lesions: one latent and the other resulting in aneurysm formation. Both lesions showed characteristics of segmental arterial mediolysis (SAM) with lack of arterial media, absence of internal and external elastic laminae and intimal proliferation. CONCLUSIONS: Histologic findings in the present case suggest that mechanical or hemodynamic stress on the vascular wall and SAM-related vascular vulnerability may concomitantly contribute to the onset of isolated SMA dissection.

The effects of a cyclooxygenase-2 inhibitor, FK3311, on total hepatic ischemia-reperfusion injury of the rat.

BACKGROUND/AIMS: This study was designed to investigate the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury of the rat liver. METHODOLOGY: Male Sprague-Dawley rats were used in this experimental study. Total hepatic ischemia was induced with a clamping portal triad. The animals were divided into two groups: the control group and the FK group, in which FK3311 (FK, 1.0 mg/kg) was administered via the penile vein. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured 2 h after reperfusion, while those of thromboxane (Tx) B2 and 6-ketoprostaglandin (PG) F1alpha (stable metabolites of TxA2 and PGI2) were measured 30 min after reperfusion. The liver tissue blood flow was measured at preischemia, end-ischemia, and 30, 60, 90, and 120 min after reperfusion. The liver tissues obtained from animals at 2h after reperfusion were excised for histopathology. RESULTS: The serum levels of AST, ALT, and LDH were significantly lower in the FK group than in the control group. Similarly, in the FK group, the serum levels of TxB2 were significantly lower than in the control group. By contrast, the 6-keto-PG F1a levels were not significantly reduced. The liver tissue blood flow at 120 min after reperfusion was significantly higher in the FK group than in the control group. The histopathological study showed that hepatic tissue damage was milder in the FK group than in the control group. CONCLUSIONS: FK has protective effects on hepatic ischemia-reperfusion injury stemming from the marked inhibition of TxA2.

A dual inhibitor of TNF-alpha and IL-1 mitigates liver and kidney dysfunction and improves survival in rat endotoxemia.

BACKGROUND/AIMS: Endotoxin shock induces multiple organ dysfunction syndromes that are associated with a substantial increase in mortality. In this study, we evaluated the effect of FR167653, a potent suppressant of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) production, on lipopolysaccharide (LPS)-induced liver and kidney injury and lethality in rats. METHODOLOGY: Male Sprague-Dawley rats weighing from 200 to 270g received an injection of LPS. The FR group received an infusion of FR167653 at 0.2 mg/kg/hr, commencing 30 min prior to the LPS injection and continuing for 5.5 hr, while the control group received an infusion of a vehicle in the same fashion. Separate groups of animals were used for the survival study (n=5 each), and for blood sampling (n=5 each group, each time point). RESULTS: The FR group showed a significantly better survival rate'than the control group. Serum levels of GOT, Cr, and BUN were significantly lower in the FR group than in the control group. The elevation of TNF-alpha and IL-1beta at 2 hr after LPS administration was significantly lower in the FR group than in the control group. CONCLUSIONS: FR167653 administration is effective in decreasing serum TNF-alpha and IL-1beta levels and associated injury to liver and kidney caused by LPS-induced endotoxemia, as well as decreasing mortality.

NO donor ameliorates ischemia-reperfusion injury of the rat liver with iNOS attenuation.

This study investigated the effect of a spontaneous nitric oxide (NO) donor, FK409 (FK), in a rat model of segmental hepatic ischemia. Rats were allocated to four experimental groups. Two of the groups underwent segmental hepatic ischemia of 60 min duration and received FK (0.4 mg/kg, iv) or vehicle alone before inducing ischemia and again 5 min before reperfusion. Sham-FK and sham groups were treated identically, but did not have vascular occlusion. Serum aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) were measured, and the livers were examined for histological evidence of injury, polymorphonuclear neutrophil (PMN) infiltration, and immunohistochemical expression of inducible NO synthase (iNOS) before and 6 h after reperfusion. AST, ALT, and LDH levels were significantly (p < .05) reduced 6 h after reperfusion in the FK-treated group compared with the vehicle-treated control group. FK treatment also reduced the degree of hepatic damage apparent on histopathology and reduced PMN infiltration and iNOS expression. Thus, FK treatment is protective against hepatic ischemia reperfusion injury and attenuates neutrophil infiltration and iNOS expression.

2-Arachidonoylglycerol increases in ischemia-reperfusion injury of the rat liver.

Several studies have implicated endocannabinoids in various forms of shock. However, the role of endocannabinoids in hepatic ischemia-reperfusion injury remains unclear. The purpose of this study was to evaluate the changes of two endocannabinoidsin hepatic ischemia-reperfusion injury: anandamide (ANA) and 2-arachidonoylglycerol (2-AG). Male Sprague-Dawley rats were divided into 2 groups: the short (15 min) ischemic group and the long (60 min)ischemic group in the segmental (70%) hepatic tissue. Blood levels of aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), ANA, and 2-AG were examined. Serum lev-els of AST, ALT, and LDH were significantly higher in the long-ischemia group than in the short-ischemia group. Plasma levels of 2-AG showed similar augmentation prior to and after reperfusion in both the short- and long-ischemia groups, although plasma 2-AG lev-els tended to be higher in the long-ischemia group than in the short-ischemia group. Plasma levels of ANA were augmented in the early phase of reperfusion in the short-ischemia group and did not differ significantly from the normal level with time after reperfusion in the long-ischemia group. These results suggest that the endocannabinoid 2-AG increases in hepatic ischemia-reperfusion injury of rats, rather than ANA.