Ceftazidime/avibactam-induced severe neutropenia: A case report.

Ceftazidime/avibactam is an important option for the treatment of infections caused by multidrug-resistant gram-negative bacteria. Haematological abnormalities are rare adverse events. We describe a case of a 63-year-old male who developed severe neutropenia following exposure to ceftazidime/avibactam in the intensive care unit for the treatment of abdominal infections. Six days after ceftazidime/avibactam was prescribed, the patient experienced a sheer drop in absolute neutrophil count, down to a minimum of 0.13 × 109 /L. A bone marrow examination showed neutrophilic maturation arrest. After careful screening of all drugs used by the patient and other potential causes of severe neutropenia, ceftazidime/avibactam was suspected to be the most likely culprit and was therefore replaced by cefoperazone/sulbactam, while a dose of colony-stimulating factor was given. The next day, neutrophils rose to 3.64 × 109 /L. To the best of our knowledge, this is the first case report of severe neutropenia associated with ceftazidime/avibactam. When neutropenia occurs during treatment, the clinician should keep this possibility in mind. Regular monitoring of neutrophil counts for timely recognition, immediate discontinuation of the drug and substitution of antibiotics are key steps in management.

Clinical characteristics and risk factors of tigecycline-associated hypofibrinogenaemia in critically ill patients.

PURPOSE: To analyze the clinical features and risk factors of tigecycline-associated hypofibrinogenaemia and study whether cefoperazone/sulbactam combined with tigecycline aggravates coagulopathy or hypofibrinogenaemia. METHODS: A retrospective case-control study of patients with severe infection who were treated with tigecycline was conducted. Patients were assigned to the hypofibrinogenaemia group (< 2.0 g/L) and normal fibrinogen (normal) group (≥ 2.0 g/L) to assess the clinical features of patients with tigecycline-associated hypofibrinogenaemia. The traits of patients treated with cefoperazone/sulbactam in the hypofibrinogenaemia group were also analyzed. RESULTS: In total, 127 patients were enrolled in the study, including 71 patients with hypofibrinogenaemia and 56 patients with normal fibrinogen levels. Hypofibrinogenaemia developed at a median of 6 (4-8) days after tigecycline treatment, and the fibrinogen level returned to normal at a median of 3 (3-5) days after tigecycline discontinuation. In the multivariate analysis, intra-abdominal infection (p = 0.005), fibrinogen level at tigecycline initiation (p < 0.001), maintenance dose (p = 0.039), and treatment duration (p = 0.002) were found to be related to hypofibrinogenaemia. Treatment with cefoperazone/sulbactam was not associated with hypofibrinogenaemia (p = 0.681), but patients treated with cefoperazone/sulbactam had a higher incidence of coagulopathy (p = 0.009) and needed more blood products (p = 0.003) than those treated without cefoperazone/sulbactam. CONCLUSION: Tigecycline-associated hypofibrinogenaemia often developed on the 6th (4th-8th) day of tigecycline use and was associated with intra-abdominal infection, fibrinogen level at tigecycline initiation, maintenance dose, and treatment duration of tigecycline but not cefoperazone/sulbactam.

Absent Filling of Ipsilateral Superficial Middle Cerebral Vein Is Associated With Poor Outcome After Reperfusion Therapy.

BACKGROUND AND PURPOSE: Our aim was to study the effect of drainage of cortical veins, including the superficial middle cerebral vein (SMCV), vein of Trolard, and vein of Labbé on neurological outcomes after reperfusion therapy. METHODS: Consecutive ischemic stroke patients who underwent pretreatment computed tomographic perfusion and 24-hour computed tomographic perfusion or magnetic resonance perfusion after intravenous thrombolysis were included. We defined "absent filling of ipsilateral cortical vein" (eg, SMCV-) as no contrast filling of the vein across the whole venous phase on 4-dimensional computed tomographic angiography in the ischemic hemisphere. RESULTS: Of 228 patients, SMCV-, vein of Trolard- and vein of Labbé- were observed in 50 (21.9%), 27 (11.8%), and 32 (14.0%) patients, respectively. Only SMCV- independently predicted poor outcome (3-month modified Rankin Scale score of >2; odds ratio, 2.710; P=0.040). No difference was found in reperfusion rate after treatment between patients with and without SMCV- (P>0.05). In patients achieving major reperfusion (≥80%), there was no difference in 24-hour infarct volume, or rate of poor outcome between patients with and without SMCV- (P>0.05). However, in those without major reperfusion, patients with SMCV- had larger 24-hour infarct volume (P=0.011), higher rate of poor outcome (P=0.012), and death (P=0.032) compared with those with SMCV filling. SMCV- was significantly associated with brain edema at 24 hours (P=0.037), which, in turn, was associated with poor 3-month outcome (P=0.002). CONCLUSIONS: Lack of SMCV filling contributed to poor outcome after thrombolysis, especially when reperfusion was not achieved. The main deleterious effect of poor venous filling appears related to the development of brain edema.

Late recanalisation beyond 24 hours is associated with worse outcome: an observational study.

OBJECTIVES: We evaluated the rate of late recanalisation beyond 24 h after intravenous thrombolysis (IVT) and its relationship with haemorrhagic transformation and outcome. METHODS: We reviewed prospectively collected clinical and imaging data from acute ischaemic stroke patients with distal internal carotid artery or proximal middle cerebral artery occlusion who underwent angiography on admission, 24 h and 1 week after IVT. Patients were trichotomised according to vascular status: timely recanalisation (<24 h), late recanalisation (24 h-7 days), and no recanalisation. RESULTS: Non-invasive angiography revealed timely recanalisation in 52 (50.0 %) patients, late recanalisation in 25 (24.0 %) patients, and no recanalisation in 27 (26.0 %) patients. Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation (odds ratio 6.674; 95 % CI: 1.197 to 37.209; p = 0.030). In patients without timely recanalisation, shift analysis indicated that late recanalisation led to a worse modified Rankin Scale score (odds ratio 6.787; 95 % CI: 2.094 to 21.978; p = 0.001). CONCLUSIONS: About half of all patients without recanalisation by 24 h after IVT may develop late recanalisation within 1 week, along with higher mRS scores by 3 months. Pre-existing atrial fibrillation is an independent predictor for late recanalisation. KEY POINTS: • About half of patients may develop late recanalisation within 1 week. • Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation. • Late recanalisation led to a higher mRS score than no recanalisation.

The velocity of collateral filling predicts recanalization in acute ischemic stroke after intravenous thrombolysis.

The aim of this study was to evaluate the impact of pretreatment quality of collaterals, involving velocity and extent of collateral filling, on recanalization after intravenous thrombolysis (IVT). A retrospective analysis was performed of 66 patients with acute middle cerebral artery (MCA) M1 segment occlusion who underwent MR perfusion (MRP) imaging before IVT. The velocity of collateral filling was defined as arrival time delay (ATD) of contrast bolus to Sylvian fissure between the normal and the affected hemisphere. The extent of collateral filling was assessed according to the Alberta Stroke Program Early CT (ASPECT) score on temporally fused maximum intensity projections (tMIP). Arterial occlusive lesion (AOL) score was used to assess the degree of arterial recanalization. ATD (OR = 0.775, 95% CI = 0.626-0.960, p = 0.020), but not tMIP-ASPECT score (OR = 1.073, 95% CI = 0.820-1.405, p = 0.607), was independently associated with recanalization (AOL score of 2 and 3) at 24 hours after IVT. When recanalization was achieved, hemorrhagic transformation (HT) occurred more frequently in patients with slow collaterals (ATD ≥ 2.3 seconds) than those with rapid collaterals (ATD < 2.3 seconds) (88.9% vs 38.1%, p = 0.011). In conclusion, the velocity of collaterals related to recanalization, which may guide the decision-making of revascularization therapy in acute ischemic stroke.

Association between Leukoaraiosis and Poor Outcome is not due to Reperfusion Inefficiency after Intravenous Thrombolysis.

Leukoaraiosis (LA) is associated with structural and functional cerebrovascular impairment, which may compromise the capacity of ischemic tissue to maximize reperfusion after intravenous thrombolysis (IVT). We aimed to determine whether severe LA is correlated with reperfusion inefficiency, which contributes to infarct growth and poor functional outcome. We analyzed data from our consecutive acute ischemic stroke (AIS) patients who had acquired baseline and 24-h follow-up diffusion- and perfusion-weighted imaging. Reperfusion was defined as reduction of ≥70 % of hypoperfusion lesion at 24 h from baseline. Severe LA was defined as Fazekas score 2 or 3 on FLAIR images. We investigated the relationship between severity of LA and reperfusion status. Multivariate statistical analysis was carried out for modeling the independent predictors of reperfusion, infarct growth, and functional outcome. Finally, 79 patients were included, among them 30 (37.97 %) had severe LA. Reperfusion was observed in 41 (51.89 %) patients, the proportion of reperfusion was very similar in patients with and without severe LA (53.33 vs 51.02 %, p = 1.000). Large artery occlusion was the only independent unfavorable predictor for reperfusion (OR = 0.202, 95 % confidence interval, 0.060-0.673; p = 0.014). Multiple linear regression analysis revealed that severe LA was independently associated with infarct growth (standardized coefficients = 0.191, p = 0.040). Severe LA was also an independent predictor of poor outcome (mRS ≥ 3) (OR = 4.004, 95 % confidence interval, 1.267-12.656, p = 0.018) after adjusting for reperfusion and baseline severity of stroke. Severe LA was associated with infarct growth and poor outcome independent of reperfusion status, which may expand the notion that LA contributes the intrinsic vulnerability of brain tissue to acute ischemic insults. The burden of LA may not serve as an imaging indicator of reperfusion inefficiency after IVT for AIS patients.