Meropenem versus ceftazidime plus amikacin in the treatment of febrile episodes in neutropenic patients: a randomized study

BACKGROUND AND OBJECTIVE: Meropenem is the first of a new class of carbapenems which may be administered without cilastatin. This study was performed to assess the clinical efficacy and tolerability of meropenem monotherapy (1 g/8 h) compared with the standard combination of ceftazidime (2 g/8 h) plus amikacin (15 mg/kg/day) for the empirical treatment of infective febrile episodes in neutropenic cancer patients. METHODS: This was a three-center, randomized, non-blind parallel group trial. The primary objective was to compare the clinical efficacy of meropenem monotherapy with that of ceftazidime plus amikacin in the empirical treatment of febrile infective episodes in neutropenic patients. This was evaluated by the number of patients surviving on unmodified therapy at 72 h (primary end point) and by the clinical response at the end of therapy (secondary end point). RESULTS: A total of 93 febrile episodes (46 meropenem, 47 ceftazidime/amikacin) were evaluable. Bone marrow transplant patients accounted for 49.5% of all cases. There was a high incidence of Gram-positive infections but no pseudomonal infections. Microbiologically documented infections, clinically documented infections and unexplained fever accounted for 45%, 10% and 45% of episodes, respectively. There was a similar proportion of patients in the meropenem and ceftazidime/amikacin groups on unmodified empiric therapy at 72 h (80.4% vs 76.6%, p = 0.65,) and cured at the end of therapy (37% vs 36.2%, p = 0.9). No significant difference in tolerability was observed between the groups. Meropenem was well tolerated; of note, there were no cases of nausea/vomiting or seizure related to its use. INTERPRETATION AND CONCLUSIONS: Meropenem monotherapy was well tolerated and produced response rates similar to those obtained with ceftazidime/amikacin. The low overall success rates with both treatments concur with those of other recent studies and are probably due to a combination of several factors, including the adoption of strict assessment criteria.     

Once-daily gentamicin versus once-daily netilmicin in patients with serious infections--a randomized clinical trial

Consecutive patients with serious infections were randomized between gentamicin 4 mg/kg once daily i.v. or netilmicin 5.5 mg/kg once daily i.v. (with dosage reduction in case of renal dysfunction). Exclusion criteria were neutropenia or severe renal failure. Median first serum trough and peak concentrations were 0.4/9.5 mg/L and 0.4/12.2 mg/L, for gentamicin and netilmicin respectively. A good clinical response was observed in 50/54 (92.6%) evaluable patients treated with gentamicin and in 48/52 (92.3%) netilmicin-treated patients. Nephrotoxicity (a rise of serum creatinine > or = 45 mumol/L) developed in 5/72 (6.9%) gentamicin patients treated > or = 48 hours and in 10/69 (14.5%) netilmicin patients (difference 7.5%, 95% CI -3.9% to +16.2%). High-tone audiometry was performed when possible; no significant differences were found between the regimens with regard to hearing loss or prodromal signs of ototoxicity. We conclude that with once-daily dosing no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated.     

多西他赛与吉西他滨分别顺泊治疗晚期非小细胞肺癌的临床研究

Objective: The aim of this study was to evaluate the clinical efficacy and side effects of docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment in the patients with advanced non-small-cell lung cancer (NSCLC). Methods: Seventy six patients with advanced NSCLC who were chemotherapy-naive were enrolled in two groups. In docetaxel group (DP group) the patients received docetaxel 75 mg/m2 and cisplatin 60 mg/m2 on day 1. In gemcitabine group (GP group) the patients received gemcitabine 1000 mg/m2 on day 1 and day 8. The dosage of cisplatin was the same as DP group. The two regiments were administrated intravenously every 21 days as a cycle, each patient received 2-4 cycles. All patients were followed up until disease progressed or patients died. Results: The overall response rates were 43.5% in DP group and 45.9% in GP group. The response rate was significantly different between the initial treated group and retreated group in both two groups (53.8% vs 23.0% in DP group and 56% vs 25% in GP group, P < 0.05, respectively). The main side effects were bone marrow suppression and thrombocytopenia. Conclusion: Docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment for the patients with advanced NSCLC were efficient and well-tolerated chemotherapeutic approachs with low toxicity levels. The efficacy and major toxicity in two groups were similar.     

Clinical findings of cefoxitin in the treatment of serious infections and the prevention of postoperative infections (author''s transl)

This clinical trial was designed to evaluate the efficacy, safety and patient tolerance of cefoxitin in 23 patients who were admitted to the hospital from March 1980 to November 1980. The daily dose of cefoxitin for 21 adult patients (ages ranged from 26 to 74 years old) were 6 g for the treatment of infections, and 2 to 6 g for the prevention of infections by either direct or intermittent intravenous infusions. Two children were given 100 mg/kg of cefoxitin either by direct or intermittent intravenous infusions 2 to 3 times a day in divided doses. Summary of findings: I. Treatment of intracranial infections 1. A 60-year-old man with a brain abscess was admitted to the hospital after the unsuccessful treatment with a cephalothin for 9 days. After, the initiation of therapy with cefoxitin, given 6 g a day for 3 days, the abscess was surgically removed. On the second day of treatment with cefoxitin following the operation, his highest temperature was 37.0 degrees C and was normal on the third day of treatment. He was discharged after 12 days after the surgical procedure. 2. A 56-year-old woman with cerebrospinal rhinorrhea and meningitis after the transsphenoidal removal of pituitary microadenoma responded satisfactorily to therapy with cefoxitin, given 6 g a day for 14 days after the unsuccessful treatment with a cephalothin. II. The prevention of infections following surgical operation of the central nervous system 1. Seventeen patients undergoing surgical procedures were treated with cefoxitin for the prevention of postoperative infections. None of the 17 patients developed postoperative infections. 2. A 53-year-old man undergoing repair of cerebrospinal rhinorrhea in the possibly contaminated area was successfully treated with cefoxitin, given intravenous 2 g every 8 hours for 10 days without meningitis having developed. III. The treatment and prevention of complications 1. A 74-year-old comatose male with a brain stem concussion, who was expectorating insufficiently and had difficulty swallowing and developed into pneumonia as a complication. He was successfully treated with cefoxitin, given intravenous 6 g a day for 2 weeks. 2. A 26-year-old male with a brain stem concussion complicated by pneumonia and a urinary tract infection was successfully treated with the same dose regimen of cefoxitin as the previous patient. 3. The prevention of complications A 58-year-old male with pontine glioma undergoing a tracheotomy was administered cefoxitin for the prevention of pulmonary complication. He died of pontine glioma after the three-month treatment. IV. Side effects Results of skin sensitivity tests given prior to the administration of cefoxitin were negative in all of the 23 patients. Neither anaphylaxis nor other allergic reactions or thrombophlebitis occurred with the intravenous administration of cefoxitin. No abnormalities in blood, hepatic function or renal function were observed. Anorexia occurred in 1 patient who was given cefoxitin, 6 g a day.     

Optimized release of dexamethasone and gentamicin from a soluble ocular insert for the treatment of external ophthalmic infections

The aziridinium ion of ethylcholine (AF64A), a cholinergic neurotoxin, was injected into the right striatum of a rat. The unilateral injection of 10 nmol AF64A reduced the activity of choline acetyltransferase (CAT) and the tissue content of acetylcholine (ACh) in the striatum. The striatal contents of dopamine (DA), norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA) and gamma-aminobutyric acid (GABA) were unchanged. These results suggest that the cholinospecificity in the striatal lesion was induced by the 10 nmol dose of AF64A. The number of N-methyl-D-aspartic acid (NMDA) receptors in the striatum treated with 10 nmol AF64A was determined by a specific binding assay using [3H](+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP), a selective ligand for NMDA receptors. The number of the NMDA receptors decreased significantly in the injected area. On the other hand, in a microdialysis using normal rats, the perfusion of 50 microM NMDA into the striatum increased ACh release. The perfusion of 100 microM MK801 which is the specific and non-competitive NMDA receptor antagonist, decreased the basal levels of ACh release and blocked NMDA-elicited ACh release. Taken together, the present results strongly suggest that a population of NMDA receptors exists on cholinergic interneurons within the striatum, and it directly regulates ACh release.     

Oral doxifluridine plus levoleucovorin in elderly patients with advanced breast cancer

BACKGROUND: There currently is no agreement regarding the appropriate treatment of elderly patients with advanced breast carcinoma (ABC). Doxifluridine (5-dFUR), a prodrug of 5-fluorouracil, has been found to be effective in this entity, but its use is limited by neurotoxicity and cardiotoxicity that are not observed when the oral formulation is used. The objective of this Phase II trial was to evaluate the effectiveness and tolerability of oral 5-dFUR, biomodulated with levoleucovorin (1-leucovorin), in elderly patients (age > 70 years) with ABC. METHODS: 5-dFUR was administered orally at 600 mg/m2 twice daily for 4 consecutive days every 12 days, and oral 1-leucovorin was administered as 25 mg 2 hours before each 5-dFUR administration. Response was assessed every five cycles according to the World Health Organization criteria. In the presence of response or stable disease, the patients were treated for a maximum of 15 cycles. RESULTS: Seventy-three eligible patients were enrolled, 27 of whom had been pretreated with chemotherapy and/or hormonotherapy; all were assessable for response and toxicity after a median follow-up of 15 months. The objective response rate was 26% (95% confidence interval, 17.4-45.4). Regression predominantly occurred in the presence of soft tissue involvement (skin, lymph nodes, and breast). The median time to response was 2 months (range, 1-2 months) and the median response duration was 7 months (range, 2-17+ months). The median survival was 24 months (range, 2-42+ months). The treatment was very well tolerated, and the side effects were manageable and always reversible. CONCLUSIONS: The results of the current study show that 5-dFUR plus 1-leucovorin, both given orally, are associated with excellent patient compliance. Although the results are suboptimal in terms of an objective response, this characteristic could allow 5-dFUR to be used in elderly patients considered unsuitable for "aggressive" chemotherapy.     

Unipolar versus bipolar hemiarthroplasty for the treatment of femoral neck fractures in the elderly

This paper presents the short term results of an ongoing prospective randomized trial comparing a cemented unipolar with a cemented bipolar hemiarthroplasty for the treatment of displaced femoral neck fractures in the elderly. Forty-seven patients with an average age of 77 years completed 6-month followup. Outcomes at 6 weeks, 3 months and 6 months were assessed by completion of a patient oriented hip outcome instrument and by functional tests of walking speed and endurance. No differences in the postoperative complication rates or lengths of hospitalization were seen between the two groups. Patients treated with a bipolar hemiarthroplasty had greater range of hip motion in rotation and abduction and had faster walking speeds. However, no differences in hip rating outcomes were found. These early results suggest that use of the less expensive unipolar prosthesis for hemiarthroplasty after femoral neck fracture may be justified in the elderly.     

多西他赛联合塞替派与多西他赛联合卡培他滨治疗转移性乳腺癌的随机、对照临床研究

目的:比较多西他赛联合塞替派方案和多西他赛联合卡培他滨方案治疗转移性乳腺癌的临床疗效及其安全性.方法:选择北京大学临床肿瘤学院乳腺肿瘤内科2006年8月至2008年9月收治的女性乳腺癌患者共46例,采用多西他赛联合塞替派(A组)或卡培他滨(B组)方案进行随机、对照临床治疗试验,A组第1,8天多西他赛35 mg/衬静脉滴注,第1天塞替派60-65 m岁扩静脉滴注,B组第1,8天多西他赛35 mg/耐静脉滴注,第1~14天卡培他滨1000 mg/m2,口服,每日2次.21 d为1个周期,至少应用2个周期.结果:多西他赛联合塞替派组22例,多西他赛联合卡培他滨组24例,两组患者基线情况一致.可评价疗效多西他赛联合塞替派组21例,多西他赛联合卡培他滨组22例.两组疗效分别为部分缓解9.52%..27.27% (2/21例,6/22例),稳定52.38% vs31.82% (11/21例,7/22例),进展38.10%..40.91% (8/21例,9/22例),疾病控制率分别为61.90% vs.59.09%(13/21例,13/22例),中位无进展生存期分别为7.9个月(95% CI 0.77~15.03)vs.8.3个月(95% C14.01~12.59),1年生存率分别为88.2%..81%,P值均＞0.05,每两组间差异无统计学意义.无化疗相关死亡病例.多西他赛联合塞替派组和多西他赛联合卡培他滨组最常见的不良反应为骨髓抑制,主要不良反应Ⅲ~Ⅳ度发生率分别为白细胞减少45.45% vs..26.09%,中性粒细胞减少45.45%..21.74%,血小板减少9.09% vs.0%,手足综合征0% vs.13.04%.P值均＞0.05,每两组间差异无统计学意义.结论:多西他赛联合塞替派方案治疗转移性乳腺癌有一定近期疗效,不良反应可耐受,可以作为经济、有效的解救方案.     

Delay in administering the first dose of antibiotics in patients admitted to hospital with serious infections

A 66-year old female was admitted to our ICU in septic shock with accompanying signs of gastroenteritis and diabetic-related hyperglycemia. Computer tomography of the abdomen revealed the rare diagnosis of emphysematous pyelonephritis. Immediate nephrectomy led to a favourable outcome in this dramatic case. Although abscess drainage and broad-based antibiotic therapy are generally the first-line therapy today, emergency surgery would seem to be indicated in selected cases.     

Cefixime versus amoxicillin plus netilmicin in the treatment of community-acquired non-complicated acute pyelonephritis

BACKGROUND: Community-acquired non-complicated acute pyelonephritis (APN) is a frequent, occasionally serious infection (around 20% of the cases are bacteremic) that usually requires hospital admission. The third generation oral cephalosporins which are active against more than 95% of E. coli strains should allow the outpatient management of these patients. OBJECTIVE: To evaluate the bacteriological and clinical efficacy of oral cefixime in comparison to amoxicilin plus netilcilin in the treatment of APN. PATIENTS AND METHODS: Patients older than 18 years affected by APN were included in a fourteen month prospective study. According to a random numbers chart, the patients received cefixime (400 mg/24 h in a single daily dose for 12 days) or amoxicilin (1 g/8 h per os) plus netilmicin (4 mg/kg/24 h in a single intramuscular daily dose) during five days followed by 7 days of an oral treatment chosen according to the susceptibility pattern of isolated microorganism. RESULTS: Sixty-one patients received cefixime and 65 amoxicillin plus retilmicin. There were no significant differences between both groups of patients. Thirty-two patients presented bacteremia (25.4%). The mean (SD) eak and trough concentrations of netilmicin were 11.4 (2.8) mg/l and 0.38 (0.4) mg/l, respectively. Clinical response was favorable in 97% of patients treated with cefixime and in 98% of those treated with amoxicilin plus netilmicin (p = NS). The infection recurred in 10 out of 59 patients (16.9%) in the cefixime arm of the study and in 9 out of 64 patients (14%) treated with amoxicillin plus netilmicin (p = NS). Tolerance to the study drugs was good in both arms of the study, and renal function remained normal. CONCLUSION: Cefixime seems to be an acceptable alternative to the regimens containing an aminopenicillin and an aminoglycoside for the treatment of community-acquired non-complicated APN.     

Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients

In a double-blind randomized trial, imipenem/cilastatin (I/C; 500 mg every 6 hours) and ampicillin/sulbactam (A/S; 3 g every 6 hours) were compared in regard to their efficacy for initial empirical and definitive parenteral treatment of limb-threatening pedal infection in diabetic patients. The major endpoints of treatment were cure (resolution of soft-tissue infection), failure (inadequate improvement, necessitating a change in antibiotic therapy), and eradication (clearance of all pathogens from the wound and any bone cultures). Patients in the two treatment groups were similar in regard to the severity of diabetes; presence of neuropathy and peripheral vascular disease; site and severity of infection; pathogen isolated; and frequency of osteomyelitis (associated with 68% of the 48 A/S-treated infections and 56% of the 48 I/C-treated infections). After 5 days of empirical treatment, improvement was noted in 94% of the A/S and 98% of the I/C recipients. At the end of definitive treatment (days' duration [mean +/- SD]: 13 +/- 6.5 [A/S], 14.8 +/- 8.6 [I/C]), outcomes were similar: cure, 81% (A/S) vs. 85% (I/C); failure, 17% (A/S) vs. 13% (I/C); and eradication, 67% (A/S) vs. 75% (I/C). Treatment failures were associated with the presence of antibiotic-resistant pathogens and possible nosocomial acquisition of infections. The number of adverse events among patients in the two treatment groups was similar: 7 in the A/S group (4 had diarrhea and 3 had rash) and 9 in the I/C group (5 had diarrhea, 2 had severe nausea, 1 had rash, and 1 had seizure). Efficacy of A/S and I/C is similar for initial empirical and definitive treatment of limb-threatening pedal infection in patients with diabetes.     

Pyrimethamine plus azithromycin for treatment of acute toxoplasmic encephalitis in patients with AIDS

A prospective study was conducted to evaluate azithromycin in combination with pyrimethamine for treatment of acute Toxoplasma encephalitis in patients with AIDS. Of the 14 patients given 75 mg pyrimethamine and 500 mg azithromycin daily for four weeks, eight were evaluable for clinical response. Five responded favorably, one had an intermediate response and two an unfavorable response. Of the nine patients evaluable for radiological response, six responded favorably, and three had an intermediate response. Eleven adverse events occurred in nine patients: rash (n = 5), abnormal liver function (n = 2), vomiting (n = 3) and hypoacousia (n = 1). This pilot study suggests that the combination of pyrimethamine and azithromycin may be further investigated and that the optimal dosage of azithromycin has yet to be determined.     

Continuation of antibiotic therapy for serious bacterial infections outside of the hospital

Many children hospitalized with serious bacterial infections are candidates for either home oral antibiotic therapy or outpatient parenteral antibiotic therapy. Outpatient antibiotic therapy offers the potential for excellent medical treatment, reduced costs, and improved quality of life for ill children. However, cost considerations must not override good medical judgment. Certain children simply are not candidates for outpatient therapy because of the seriousness of their infection, poor compliance, lack of intravenous access, or poor social situation. In addition, although the few published studies to date all show that outpatient antibiotic therapy is effective, there is further need for properly designed clinical trials to evaluate the efficacy and safety of outpatient antibiotic therapy for serious bacterial infections in children.     

Intratympanic gentamicin injection for the treatment of Meniere''s disease

The past year has brought significant advances in our understanding of the involvement of aquaporins in the regulation of water balance. Besides the identification of new mammalian aquaporins, highlights include the progress in our understanding of their cell-biological regulation and their roles in physiology and pathophysiology as deduced from natural and engineered knockout models.     

Outcome in elderly injured patients: injury severity versus host factors

To evaluate the differences between the outcome of elderly patients with severe injuries and that of their contemporaries with a less severe injury, we reviewed 42 severely injured elderly patients and compared them with 76 patients with a femoral neck fracture. We analysed the influence of injury severity and host factors (age, sex and pre-injury medical status) on outcome. The in-hospital mortality rate was 31 per cent in the severely injured patients and 3 per cent in those with a femoral neck fracture. Home was the main discharge destination in the severely injured elderly (34 per cent) and a nursing home in patients with a femoral neck fracture (65 per cent). Functional outcome 1 year after injury was better in the severely injured elderly group. Long-term survival was mainly determined by host factors and not by injury severity. Physicians and policy makers should be careful in predicting the outcome of elderly injured patients merely on the basis of injury severity, because host factors are of greater importance.