Cefepime in the treatment of infection in neutropenic patients]

Cefepime, a fourth-generation cephalosporin, was used in the treatment of 11 febrile episodes in 8 patients with profound neutropenia. The patients were neutropenic because of high-dose chemotherapy with stem-cell rescue or second-line salvage chemotherapy for malignant lymphomas (5 patients) or solid tumors (3 patients). The median duration of grade-IV neutropenia (according to the WHO classification) was 11 days (7 to 14). Cefepime was used as the monotherapy in a dose of 2 g thrice daily. Disappearance of the infection signs was recorded in 8 episodes (73 per cent). In 3 episodes (23 per cent) cefepime was replaced by another drug. The tolerability of cefepime was good and no adverse events were observed with the exception of 1 event of an allergic reaction.     

The efficacy of cefepime (Maxipime) in the treatment of abdominal sepsis in surgical patients]

The efficacy of cefepime in the treatment of 46 patients operated for general peritonitis of various genesis and severity (APACHE II not greater than 35) was studied. Cefepime was used in a dose of 2 g administered every 12 hours as slow intravenous infusions in 0.9 per cent sodium chloride solution in combination with metronidazole administered intravenously in a dose of 7.5 mg/kg body weight. The treatment course was 4 to 15 days. 45 patients were given diflucan for the prophylaxis of fungal superinfection, 3 patients were given aminoglycoside antibiotics (netilmicin or amikacin) and 2 patients were given vancomycin per os. The favourable clinical effect of the cefepime therapy was stated in 38 patients (82.6 per cent) including 4 out of 10 patients with initial APACHE II > 15. 101 isolates of aerobic gram-negative and gram-positive microbes from 38 patients treated with cefepime in combination with metronidazole were tested to estimate the bacteriological efficacy of the therapy and it was shown that only 5.9 per cent of them was resistant. The pathogen eradication was stated in 84.2 per cent of the patients.     

A trial of using augmentin (amoxicillin/clavulanate) in surgical practice]

The experience with the use of augmentin (amoxycillin/clavulane) in abdominal surgery for prophylaxis of postoperative purulent complications was analyzed. The drug was used in 44 patients after relatively pure operations, 37 of them having various risk factors. In 2 patients (4.5 per cent) of that group postoperative pyoinflammatory complications were recorded. For comparison the results of the prophylactic use of cefoperazone, cefamandole or ceftazidime in the group of 78 patients after relatively pure operations on the abdominal cavity organs were analyzed. Postoperative complications in the latter group amounted to 7.4 per cent (4 patients). The results of the treatment of patients in two groups after contaminated operations were also compared. The patients of one group (41 patients) were treated prophylactically with augmentin in a dose of 1200 mg intraoperatively followed by the drug use in a dose of 600 mg thrice daily for 1 to 2 days after the operation. Postoperative pyoinflammatory complications were recorded in 4 patients of that group (9.7 per cent). 78 patients of the other group were treated prophylactically with ceftazidime or cefoperazone in a dose of 2 g and metronidazole intraoperatively or cefoperazone in a dose of 2 g twice daily and metronidazole in a dose of 500 mg twice daily for 1 to 2 days after the operation. Postoperative infectious complications were recorded in 8 patients of that group (10 per cent). In the group of patients with acute cholecystitis treated with ciprofloxacin in a dose of 400 mg in combination, with metronidazole before the operation and for 1 to 2 days after the operation postoperative complications were recorded in 4 patients (17 per cent).     

Efficacy of moxifloxacin in the treatment of secondary peritonitis]

Moxifloxacin efficacy was studied in a prospective open controlled incomparable surveillance of 22 patients at the age of 24 to 78 years (the average of 56.6 +/- 15.9 years old) with extended secondary peritonitis that developed before the hospitalization or not later than 48 hours after the hospitalization. Moxifloxacin (Avelox) was used in a dose of 400 mg every 24 hours at first intravenously as infusions and then orally in the same dose. The abdominal infection was severe (APACHE II of 6 to 12, the average of 8.0 +/- 2.2), in 6 (27.3%) patients signs of severe sepsis with polyorganic insufficiency were observed. The intravenous therapy was used for 3 to 7 days (the average of 3.91 +/- 0.92 days) and the oral therapy was used for 2 to 7 days (the average of 4.50 + 1.37 days). The total time of the treatment was 7 to 12 days (the average of 8.45 +/- 1.53 days). The recovery was recorded in 20 out of the 22 patients (90.9%), disappearance of the main signs of peritonitis being observed within 3-5 days of the treatment. Before the treatment 34 microbial strains were isolated. The most frequent pathogens were E.coli (35.4%) and Enterococcus faecalis (20.6%). In the etiological structure of the community-acquired peritonitis gramnegative enterobacteria prevailed (65%). All the isolates (except 1 strain of E. faecalis) were susceptible to moxifloxacin. The pathogen eradication was stated in 17 out of 18 patients (94.4%). Moderate adverse reactions were observed in 3 patients. Moxifloxacin evidently showed high clinical and bacteriological efficacies in the hospitalized patients with complicated intraabdominal infection including severe abdominal sepsis with the syndrome of polyorganic insufficiency. It can be used for monotherapy of patients with secondary extended peritonitis.     

Cefepime (maxipime) in the treatment of severe urinary tract infection]

Comparative susceptibility of microflora isolates from patients with complicated urinary tract infections to cefepime, other cephalosporins, amikacin, ciprofloxacin and ofloxacin was studied. Isolates in the diagnostic titers (5 x 10(4)-5 x 10(8)) from the patients treated with cefepime as etiotropic monotherapy were identified. The treatment course was 7 to 14 days. The daily dose was 1 to 2 g. The clinical and bacteriological efficacies of the cefepime therapy equaled to 93.2 and 85.4% respectively.     

Comparative in vitro activity of cefepime and other antibiotics against clinical strains of gram-negative bacteria]

In vitro activity of cefepime against etiologically significant strains of gramnegative microflora of patients treated in the Reanimation and Intensive Care Unit after cardiosurgical operations was evaluated. Sixty four strains of gramnegative aerobic bacteria isolated within the period from October 2001 to April 2002 were tested. The isolates susceptibility was determined by the disk diffusion method. Cefepime had an obvious advantage over the 3rd generation cephalosporins. Low incidence of cefepime resistant strains of the problem organisms in the Reanimation and Intensive Care Unit should be taken into account in empirical therapy of infections due to such pathogens.     

Experience with maxipime in neurosurgical clinic]

Cefepime (Maxipime, Bristol-Myers Squibb), a 4th generation cephalosporin was used in the postoperative treatment of 121 patients of Anesthesiology and Intensive Care Unit of Neurosurgical Clinics. The patients were divided into groups by the risk factor of pyoseptic complications. The results were estimated by the number and nature of the complications such as increasing liquor neutrophilic cytosis, systemic inflammations and others. The findings (increasing liquor neutrophilic cytosis only in 2 patients and endobronchitis in 4 patients) and good tolerance of cefepime (Maxipime) were in favour of its use in a dose of 1 g administered intravenously dropwise during initial narcosis and in 12 hours as an efficient agent for perioperative prophylaxis in neurosurgical patients.     

A trial of using timentin (ticarcillin/clavulanate) in treating abdominal surgical infection]

Efficacy of timentin was studied in the treatment of 19 patients with peritonitis of various etiology and clinical and laboratory signs of systemic inflammatory reaction characteristic of abdominal sepsis. The clinical and bacteriological effects were recorded in 84.2 and 87.5 per cent of the cases respectively. The drug was administered intravenously dropwise for 30 minutes in a dose of 3.1 g every 4 hours. The treatment course was 4-11 days. The treatment failed in 3 patients. One of them had general peritonitis of gynecological etiology. In the other no significant regression of abdominal sepsis was observed, Pseudomonas aeruginosa strains were isolated from the abdominal cavity, the antibiotic was changed, still incurable polyorganic insufficiency developed and the patient died. The third patient had perforation of the large intestine due to tumor. No adverse reactions to the use of timentin in any of the cases was observed.     

动态监测血清降钙素原对多发伤患者并发脓毒症的诊断价值

目的:探讨动态监测血清降钙素原(PCT)对多发伤合并脓毒症的诊断价值。方法:选取我院重症监护室并发脓毒症的多发伤患者21例(Sepsis组)、无并发脓毒症的多发伤患者20例(非Sepsis组),连续检测患者入院第1、3、5、7 d血清中的PCT含量,并测定C反应蛋白和白细胞计数。结果:Sepsis组血清PCT浓度明显高于非Sepsis组(P<0.01);不同程度脓毒症患者间PCT水平有显著差异,随严重程度升高而升高(P<0.01)。结论:血清PCT对多发伤患者合并脓毒症的诊断具有重要价值,且血清PCT水平与脓毒症的严重程度有关,监测其动态变化有助于预后判断。     

Effect of cyclosporine, a P-glycoprotein inhibitor, on the pharmacokinetics of cefepime in rat blood and brain: a microdialysis study.

In clinical application, cefepime and cyclosporine are regularly combined in the treatment of organ transplant patients, so the interaction of these two drugs can be hypothesized. Therefore, the pharmacokinetics of cefepime alone and in combination with cyclosporine in rat using microdialysis coupled with HPLC-UV on-line system was evaluated in the study. Cefepime at three doses (20, 50, and 100 mg/kg) showed linear kinetics. After addition of cyclosporine, the mean residence time was increased from 34.9 min to 48.6 min (p<0.05, n=6), and the area under the concentration versus time curve (AUC) increased from 4775 min microg/ml to 6960 min microg/ml (p<0.01, n=6). While in the brain, AUC increased from 64.3 min microg/ml to 110.2 min microg/ml. In summary, cyclosporine (20 mg/kg) could significantly alter the simultaneously administered cefepime (50 mg/kg) unbound drug pharmacokinetic parameters in both blood and brain.     

The effect of different doses of cisplatin on the pharmacokinetic parameters of cefepime in mice

The simulation of human serum levels is essential in animal models to extrapolate the experimental results to clinical practice. Administration of a nephrotoxic drug such as cisplatin can be used to cause renal dysfunction as an approach to mimic human serum levels of renally excreted drugs. We aimed to determine the dose of cisplatin that did not affect the survival rate of mice and to achieve human-like serum concentrations of cefepime. Different doses of cisplatin (0, 10, 14, 18, 22 and 26 mg/kg) were given by intraperitoneal (i.p.) injection to mice three days prior to the i.p. administration of 80 mg/kg cefepime. With cisplatin doses of 18 and 22 mg/kg, the half-life of cefepime was significantly prolonged (P < 0.001) and all mice survived. The pretreatment with 26 mg/kg cisplatin significantly decreased survival (P = 0.001), but the half-life of cefepime was not significantly longer than of 18 mg/kg cisplatin. Serum levels of cefepime after the pretreatment with 18 mg/kg cisplatin were comparable to published human data. The administration of cisplatin appears to be a suitable method in mice for simulating human serum concentrations of renally excreted drugs.     

Comparative clinical and epidemiological evaluation of beta-lactam antibiotics in the treatment of intraabdominal infections]

We performed a retrospective, comparative study to evaluate efficacy, safety and economic outcomes of empiric cefoperazone/sulbactam monotherapy compared with the meropenem, imipenem/cilastatine and combination of cefepime plus metroindazol in patients with intra-abdominal infection. A total of 468 patients diagnosed with intra-abdominal abscess, peritonitis, pancreatitis were included in the study (the severity of infection according to scale APACHE II was less than 15). Patients were randomized to be treated with either 500 mg meropemen i.v. every 8 hours or 500 mg imipenem/cilastatine i.v. every 8 hours or 2 g cefepime i.v. every 12 hours plus 500 mg metronidazol twice daily or cefoperazone/sulbactam 2 g daily administered every 12 hours. Overall positive clinical responses (cure or improvement) were achieved at the end of treatment for 87.5 patients in meropenem group, 86.6% in the imipenem/cilastatin group, 85.3% in the cefepime group and 86.8% in cefoperazone/sulbactam group. Total cost of the treatment per 100 patients with intra-abdominal infections for cefoperazone/sulbactam was 1957031 roubles, for combinations of cefepime with metronidazol--2497815 roubles. For carbapenem group cost achieved for meropenem--3085291 rub., for imipenem/cilastatin--2653388 roubles. Rate "cost-effectiveness" in total: 784.47$ for cefepime, and 834.39$ for imipenem/cilastatine, 970.21$ for meropenem and 615.4$ for cefoperazone/sulbactam. The most expensive treatment was considered to be with meropenem and imipenem/cilastatine, main share is determined by initial cost of preparations. Less expensive was treatment by cefoperazone/sulbactam with cefepime and by metronidazol.     

Intensity of thrombin activity and surgical trauma

Increased level of in vivo thrombin activity represents the essential mark of prethrombotic state. In order to assess the influence of surgical trauma on the constitution of prethrombotic state immediately after the surgical intervention, dynamic estimations of fibrinopeptide A (FPA) have been done in a group of 18 patients who had undergone abdominal surgery and in the group of 25 patients who underwent the replacement of artificial hip, and who were on preventive treatment with subcutaneous heparin. At the same time the presence of soluble fibrinmonomer complex and, in the group of patients on heparin treatment, the concentration of plasma heparin were examined. The investigations were done before the surgical intervention and on the first, third and seventh postoperative day. Our dynamic study showed the existence of certain relation between the surgical trauma and values of FPA which were the expression of intensity of in vivo thrombin activity. The mean values of FPA increased markedly on the first postoperative day in comparison with the preoperative levels. On the third postoperative day significant reduction of FPA was observed and on the seventh day marked increase was found only in patients who were not on heparin prevention. Although preventive application of subcutaneous heparin did not affect the whole blood coagulability it showed a suppressive impact on the thrombin activity level in examined surgical patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative hypoparathyroidism: long term observation and therapy]

Hundred thirty patients with surgical hypoparathyroidism were followed up. Group I involved 45 patients with mild and group II--85 patients with severe surgical hypoparathyroidism. A delay in vitamin D3 therapy was X +/- SD = 4.2 +/- 8.1 years. A delay in introducing vitamin D3 therapy correlated with the duration of hypoparathyroidism (r = 0.93; 8.9 +/- 9.6 years). Follow up period lasted for 15 years and was 4.3 +/- 3.8 years out of which the attempts to establish ultimate and effective dose of vitamin D3 lasted 1.8 +/- 2.4 years. Dose of vitamin D3 was adjusted 5 times, on the average. Effective daily dose was 4,200-22,500 IU (9,311 +/- 7,252) in group I, and 30,000-195,000 IU (51,385 +/- 32,978) in group II whereas maximum daily dose was 75,000 and 250,000 IU respectively (p < 0.001). Some patients were given 25-OH-D3 in daily doses of 50-225 micrograms or 25(OH)2-D3 in daily dose of 0.10-0.75 micrograms. Calcium oral doses of 400-1600 mg daily were administered to 115 patients. In case of high hypercalciuria (over 350 mg/24 h) hydrochlorothiazide (43 +/- 17 mg a day) or chlorthalidone (60 +/- 22 mg a day) normalized calciuria. Low phosphate diet and aluminium oxide (4.4 +/- 1.7 g a day) were more frequently used in group II. Period of time necessary to establish an effective dose of vitamin D3 is long in patients with surgical hypoparathyroidism. Several dose adjustments are required. Maximum daily vitamin D3 dose required for normocalcemia is approximately higher by 1/3 in the early period of the treatment than the effective maintenance dose. A decrease in diet phosphate content, inhibition of phosphates absorption in the gut or blocking increased calcium loss with the urine are necessary in some patients, only.     

Cefepime/amikacin in the empirical antibacterial therapy for patients with hemoblastosis of different forms]

The results of the use of cefepime (Maxipime) combination with amikacin vs ceftriaxon combination with amikacin in the treatment of 80 patients with different forms of hemoblastosis are presented. Severe infectious complications in the patients were associated with prolonged and deep neutropenia during inductive or antirelapsing chemotherapy. All the patients in the trial were from the group of high risk of infectious complications with the blood neutrophil count under 100 cells/microliter. The duration of neutropenia averaged 12 days (7 to 15). The average period of the treatment with cefepime and amikacin equaled to 13 days (8 to 16). The treatment with cefepime + amikacin was successful in 38 out of 40 patients (95%). The average period of the treatment with ceftriaxon and amikacin equaled to 14 days (7 to 18). The efficacy of the treatment with ceftriaxon + amikacin was 60% (24 patients out of 40).     

Early interleukin-6 and slope of monocyte human leukocyte antigen-DR: a powerful association to predict the development of sepsis after major trauma

Objective

Major trauma is characterized by a pro-inflammatory response, followed by an immunosuppression. Recently, in trauma patients, the lack of recovery of monocyte Human Leukocyte Antigen DR (mHLA-DR, a biomarker of ICU-acquired immunosuppression) between days 1–2 and days 3–4 has been demonstrated to be independently associated with sepsis development. The main objective of this study was to determine whether early measurements of IL-6 (interleukin-6) and IL-10 plasma concentrations (as markers of initial severity) could improve, in association with mHLA-DR recovery, the prediction of sepsis occurrence in severe trauma patients.

Design

Prospective observational study over 24 months in a Trauma ICU at university hospital.

Patients

Trauma patients with an ISS over 25 and age over 18 were included.

Measurements and Main Results

mHLA-DR was assessed by flow cytometry, IL-6 and IL-10 concentrations by ELISA. 100 consecutive severely injured patients were monitored (mean ISS 37±10). 37 patients developed sepsis. IL-6 concentrations and slope of mHLA-DR expression between days 1–2 and days 3–4 were significantly different between septic and non-septic patients. IL-10 was not detectable in most patients. After adjustment for usual clinical confounders, when assessed as a pair, multivariate logistic regression analysis revealed that a slope of mHLA-DR expression (days 3–4/days 1–2)≤1.1 and a IL-6 concentration ≥ 67.1 pg/ml remained highly associated with the development of sepsis (adjusted OR 18.4, 95% CI 4.9; 69.4, p = .00002).

Conclusions

After multivariate regression logistic analysis, when assessed as a pair, a high IL-6 concentration and a persistent mHLA-DR decreased expression were found to be in relation with the development of sepsis with the best predictive value. This study underlines the usefulness of daily monitoring of immune function to identify trauma patients at a high risk of infection.     

Antipyretic effect of Mao-to, a Japanese herbal medicine, for treatment of type A influenza infection in children

Mao-to is a Japanese traditional herbal medicine which has been used since ancient times for the treatment of influenza-like illness. This study was conducted to evaluate the effect of oral Mao-to administration in children with type A influenza, in comparison to Oseltamivir. We performed a controlled trial of 60 children, from 5 months through 13 years of age, with fever and influenza-like symptom of up to 48 h duration. Diagnosis of influenza type A was performed by virus isolation or detection of a viral gene by RT-PCR. Patients assigned into the following 3 groups: oral Mao-to powder (TJ-27) 0.06 g/kg body wt./dose three times daily (n=17), Oseltamivir 2 mg/kg body wt./dose twice daily (n=18) or both oral Mao-to plus Oseltamivir (n=14). The median duration of fever after treatment was significantly shorter in the Mao-to and Mao-to plus Oseltamivir groups, compared with the Oseltamivir only group (15 h [95%CI 13.2-22.1] p<0.01; 18 h[15.2-27.7] p<0.05; 24 h[23.5-43.0], respectively). Oral Mao-to administration was effective in the control of fever due to type A influenza infection in children.     

Plasma proinflammatory cytokine response to surgical stress in elderly patients

We investigated the change of plasma cytokines concentrations in elderly patients during lower abdominal surgery. Plasma interleukin (IL-)6 concentrations (68.0+/-15.4 and 36.1+/-20.7 pg/ml) in elderly patients at 24 h and at 3 days after surgery were significantly higher than those (35.1+/-21.5 and 18.6+/-10.6 pg/ml) of young adults. Plasma IL-6 concentrations (92.3+/- 31.9 pg/ml) in elderly patients anesthetized with propofol and fentanyl were significantly higher at the end of the operation than that (57.9+/-36.7 pg/ml) of elderly patients anesthetized with sevoflurane and fentanyl. In conclusion, elderly patients have an increased and delayed IL-6 response to surgical trauma compared with young adults. Plasma IL-6 production after surgical trauma in elderly patients with total intravenous anesthesia with propofol was significantly higher than that in elderly patients with sevoflurane anesthesia.     

Extended Daily Dialysis in Acute Kidney Injury Patients: Metabolic and Fluid Control and Risk Factors for Death

Intermittent hemodialysis (IHD) and continuous renal replacement therapies (CRRT) are used as Acute Kidney Injury (AKI) therapy and have certain advantages and disadvantages. Extended daily dialysis (EDD) has emerged as an alternative to CRRT in the management of hemodynamically unstable AKI patients, mainly in developed countries.

Objectives

We hypothesized that EDD is a safe option for AKI treatment and aimed to describe metabolic and fluid control of AKI patients undergoing EDD and identify complications and risk factors associated with death.

Study Selection

This is an observational and retrospective study describing introduction of EDD at our institution. A total of 231 hemodynamically unstable AKI patients (noradrenalin dose between 0.3 and 1.0 ucg/kg/min) were assigned to 1367 EDD session. EDD consisted of 6–8 h of HD 6 days a week, with blood flow of 200 ml/min, dialysate flows of 300 ml/min.

Data Synthesis

Mean age was 60.6±15.8 years, 97.4% of patients were in the intensive care unit, and sepsis was the main etiology of AKI (76.2). BUN and creatinine levels stabilized after four sessions at around 38 and 2.4 mg/dl, respectively. Fluid balance decreased progressively and stabilized around zero after five sessions. Weekly delivered Kt/V was 5.94±0.7. Hypotension and filter clotting occurred in 47.5 and 12.4% of treatment session, respectively. Regarding AKI outcome, 22.5% of patients presented renal function recovery, 5.6% of patients remained on dialysis after 30 days, and 71.9% of patients died. Age and focus abdominal sepsis were identified as risk factors for death. Urine output and negative fluid balance were identified as protective factors.

Conclusions

EDD is effective for AKI patients, allowing adequate metabolic and fluid control. Age, focus abdominal sepsis, and lower urine output as well as positive fluid balance after two EDD sessions were associated significantly with death.     

Plasma inflammatory cytokine response to surgical trauma in chronic depressed patients

We investigated inflammatory cytokine response in chronic depressed patients during abdominal surgery. Twenty-five major depressed patients (Group D) and twenty-five patients (Group C) as the control were studied. Plasma interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured before and at 15 min after induction of anesthesia, the end of surgery, 24 h and 3 days after the operation. Plasma IL-6 concentrations in Group D at the end of the operation and 24 h after surgery were significantly lower than those of Group C. The plasma IL-6 concentration (87.1+/-55.3 pg/ml) of patients scoring more than 18 points in the Hamilton depression-rating score at the end of the operation was significantly higher than 57.5+/-76.7 pg/ml of patients scoring less than 18 points. Plasma IL-8 concentration (6.1+/-3.2 pg/ml) in Group D at the end of the operation was significantly lower than 8.7+/-4.2 pg/ml of Group C. We conclude that plasma IL-6 and IL-8 response to surgical trauma is inhibited in chronic depressed patients. The IL-6 response to surgical trauma is depending on the clinical state of depression.