ro13-9904 and Cerebral-Hemorrhage

The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients who received intravenous thrombolysis (IVT), patients who received ceftriaxone had a significantly better outcome as compared with the control group. This study aimed to gain more insight into the characteristics of these patients.. In PASS, 2,550 patients were randomly assigned to preventive antibiotic treatment with ceftriaxone or standard care. In current post-hoc analysis, 836 patients who received IVT were included. Primary outcome included functional status on the modified Rankin Scale, analyzed with adjusted ordinal regression. Secondary outcomes included infection rate and symptomatic intracerebral hemorrhage (sICH) rate.. For all patients in PASS, the p value for the interaction between IVT and preventive ceftriaxone regarding functional outcome was 0.03. Of the 836 IVT-treated patients, 437 were administered ceftriaxone and 399 were allocated to the control group. Baseline characteristics were similar. In the IVT subgroup, preventive ceftriaxone was associated with a significant reduction in unfavorable outcome (adjusted common OR 0.77; 95% CI 0.61-0.99; p = 0.04). Mortality at 3 months was similar (OR 0.75; 95% CI 0.48-1.18). Preventive ceftriaxone was associated with a reduction in infections (OR 0.43; 95% CI 0.28-0.66), and a trend towards an increased risk for sICH (OR 3.09; 95% CI 0.85-11.31). Timing of ceftriaxone administration did not influence the outcome (aOR 1.00; 95% CI 0.98-1.03; p = 0.85).. According to the post-hoc analysis of PASS, preventive ceftriaxone may improve the functional outcome in IVT-treated patients with acute stroke, despite a trend towards an increased rate of post-IVT-sICH.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Ceftriaxone; Cerebral Hemorrhage; Disability Evaluation; Drug Administration Schedule; Female; Fibrinolytic Agents; Humans; Infusions, Intravenous; Male; Middle Aged; Odds Ratio; Risk Factors; Stroke; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Treatment Outcome

Topics: Anti-Bacterial Agents; Ceftriaxone; Cerebral Hemorrhage; Humans; Infectious Encephalitis; Lyme Neuroborreliosis; Magnetic Resonance Imaging; Male; Middle Aged; Temporal Lobe

Meningococcal meningitis (MM) is a life-threatening disease associated with approximately 10% case fatality rates and neurological sequelae in 10-20% of the cases. Recently, we have shown that the matrix metalloproteinase (MMP) inhibitor BB-94 reduced brain injury in a mouse model of MM. The present study aimed to assess whether doxycycline (DOX), a tetracycline that showed a neuroprotective effect as adjuvant therapy in experimental pneumococcal meningitis (PM), would also exert a beneficial effect when given as adjunctive therapy to ceftriaxone (CRO) in experimental MM.. BALB/c mice were infected by the intracisternal route with a group C Neisseria meningitidis strain. Eighteen h post infection (hpi), animals were randomised for treatment with CRO [100 mg/kg subcutaneously (s.c.)], CRO plus DOX (30 mg/kg s.c.) or saline (control s.c.). Antibiotic treatment was repeated 24 and 40 hpi. Mouse survival and clinical signs, bacterial counts in cerebella, brain damage, MMP-9 and cyto/chemokine levels were assessed 48 hpi.. Analysis of bacterial load in cerebella indicated that CRO and CRO + DOX were equally effective at controlling meningococcal replication. No differences in survival were observed between mice treated with CRO (94.4%) or CRO + DOX (95.5%), (p > 0.05). Treatment with CRO + DOX significantly diminished both the number of cerebral hemorrhages (p = 0.029) and the amount of MMP-9 in the brain (p = 0.046) compared to untreated controls, but not to CRO-treated animals (p > 0.05). Levels of inflammatory markers in the brain of mice that received CRO or CRO + DOX were not significantly different (p > 0.05). Overall, there were no significant differences in the parameters assessed between the groups treated with CRO alone or CRO + DOX.. Treatment with CRO + DOX showed similar bactericidal activity to CRO in vivo, suggesting no antagonist effect of DOX on CRO. Combined therapy significantly improved mouse survival and disease severity compared to untreated animals, but addition of DOX to CRO did not offer significant benefits over CRO monotherapy. In contrast to experimental PM, DOX has no adjunctive activity in experimental MM.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Ceftriaxone; Cerebral Hemorrhage; Chemokines; Disease Models, Animal; Doxycycline; Drug Therapy, Combination; Female; Humans; Kaplan-Meier Estimate; Matrix Metalloproteinase 9; Meningitis, Meningococcal; Mice; Mice, Inbred BALB C; Neisseria meningitidis, Serogroup C; Random Allocation; Treatment Outcome

Topics: Ceftriaxone; Cerebral Hemorrhage; Emergencies; Ethmoid Sinusitis; Female; Humans; Hydrocephalus; Hyperglycemia; Meningitis, Meningococcal; Metformin; Middle Aged; Sphenoid Sinusitis; Unconsciousness

Cerebral hemorrhage occurs rarely in endocarditis caused by Actinobacillus actinomycetemcomitans. A 51-year-old man with a prosthetic mitral valve, who had been prophylactically treated (7 years) with warfarin, presented with intermittent fever. On admission, a Levine grade II/VI systolic cardiac murmur was detected. A transthoracic echocardiogram was negative for valve vegetation. Cefepime (1 g every 8 hours) was administered intravenously. On day 4, culturing of Gram-negative bacilli from blood and a transesophageal echocardiogram revealed a small oscillating filament attached to lateral mitral prosthetic ring on the atrial side. Ceftriaxone (2 g once daily) was started. Gait instability and left-side weakness developed abruptly 2 weeks later; brain magnetic resonance imaging revealed a hematoma over the right parietal-occipital lobe. Ceftriaxone was adjusted to 2 g every 12 hours. Actinobacillus actinomycetemcomitans was identified 3 weeks later. Recovery was achieved, with significant interval improvement and resolution of the cerebral lesions evident on CT.

Topics: Actinobacillus Infections; Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Anticoagulants; Ceftriaxone; Cerebral Hemorrhage; Endocarditis; Humans; Male; Middle Aged; Warfarin

The feasibility and safety of outpatient management of acute promyelocytic leukemia (APL) during the aplastic phase after intensive consolidation chemotherapy, the incidence and types of complications requiring readmission to hospital, and the number of hospital days spared by this policy have been prospectively evaluated. After chemotherapy administration, patients were evaluated on an ambulatory basis. In the event of any complication they referred to the Emergency Unit (EU) of our Department dedicated to outpatients with hematologic diseases. Forty patients with APL observed over a 4 year period were eligible for intensive chemotherapy. After the achievement of complete remission they received a total of 104 consolidation courses and in 98 instances they were followed on an ambulatory basis. There were 41 cases (42%) of rehospitalization for fever (40 cases) or severe anemia (one case). Only one patient died due to a brain hemorrhage. Streptococcus viridans was the organism most frequently isolated from blood. Empiric once-a-day antibacterial therapy with ceftriaxone and amikacin was effective in 87% of the cases and made possible early discharge in 28% of the cases to continue the antibiotic therapy on an outpatient setting. Patients were managed out of the hospital for 76% of the post-consolidation neutropenia period. Thanks to the availability of an EU specifically dedicated to outpatients with hematologic diseases, out-hospital management of APL patients after consolidation therapy appeared to be safe, well accepted, potentially cost-saving, and contributed to saving the risk of developing severe nosocomial infections.

Topics: Adult; Aged; Ambulatory Care; Amikacin; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Ceftriaxone; Cerebral Hemorrhage; Cross Infection; Drug Therapy, Combination; Emergency Service, Hospital; Female; Fever; Hospitalization; Humans; Idarubicin; Incidence; Length of Stay; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neutropenia; Remission Induction; Tretinoin

Increasing attention to quality of life and to health care costs has recently induced several cancer centers to change in-patient management into an out-patient setting even during high risk phases of disease. The aim of this prospective study was to evaluate feasibility and safety, as well as clinical characteristics, of out-hospital management of AML patients during their post-consolidation phase.. All patients who were treated over a three year period by the three following protocols were included in the study: AML10 EORTC/GIMEMA for patients with AML, except for APL, aged 60 years; AIDA GIMEMA for APL patients. All patients submitted to the AML10 and AML13 protocols and those patients submitted to the AIDA protocol with difficult peripheral vein access had a central venous catheter (CVC) sited. Patients treated as in-patients were discharged at the end of consolidation chemotherapy provided they were in a good clinical condition. They were routinely evaluated on an out-patient basis twice weekly. In the event of any complication they were referred to the Emergency Unit of our Department dedicated to out-patients with hematologic diseases.. One hundred and eleven patients with AML were eligible for intensive chemotherapy. After achievement of complete remission they received a total of 133 consolidation courses and in 127 instances they were followed on an out-patient basis during the aplastic phase. There were 69 cases (54%) of rehospitalization, 68 because of fever and only one because of severe anemia. Rehospitalization occurred in 90%,70% and 38% of courses in AML10, AML13 and AIDA protocols, respectively. Only one patient died: the cause of death was a brain hemorrhage. Coagulase negative staphylococci and viridans streptococci were the organisms most frequently isolated from blood. Most coagulase negative staphylococci were isolated in patients submitted to AML10 and AML13 protocols, who had an indwelling CVC. Empiric once-a-day antibacterial therapy with ceftriaxone and amikacin was effective in 75% of the cases and made early discharge possible in 28% of the cases with antibiotic therapy continued in an out-patient setting. Overall, patients were managed out of the hospital for 66% of the period of post-consolidation neutropenia (77%, 48% and 50% of the post-consolidation neutropenia period in patients treated with AIDA, AML10 and AML13 protocols, respectively).. Thanks to the availability of an emergency unit specifically dedicated to out-patients with hematologic diseases, selected out-hospital management of AML patients during post-consolidation cytopenia is a feasible, well accepted and cost-saving option, and can contribute to lower the risk of developing severe nosocomial infections. The empiric therapy with once-a-day ceftriaxone plus amikacin was effective, with the exception of staphylococcal infections, and made it possible to discharge patients early to continue treatment in an out-patient setting.

Topics: Adult; Ambulatory Care; Amikacin; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Ceftriaxone; Cerebral Hemorrhage; Clinical Trials as Topic; Drug Therapy, Combination; Emergency Service, Hospital; Fever; Hospitalization; Humans; Immunocompromised Host; Italy; Leukemia, Myeloid; Leukocyte Count; Middle Aged; Mycoses; Neutropenia; Staphylococcal Infections