[The reliability of using impenem, meropenem, cefoperazone-sulbactam and piperacillin-tazobactam to treat nosocomial Gram-negative bacterial infections with Monte Carlo simulation].

Objective: To evaluate the reliability of using imipenem, meropenem, cefoperazone-sulbactam, piperacillin-tazobactam in the treatment of hospital-acquired Gram-negative bacterial infections with Monte Carlo simulation(MCS). Methods: The MIC of the four agents collected from hospital-acquired infections were detected in accordance with broth dilution method of Clinical and Laboratory Standard Institute (CLSI). MCS were conducted with MICs and the pharmacokinetics parameters of the four agents based on conventional dose regimens.The cumulative fraction of response (CFR) of time over MIC target attainment in different dosing regimen were generated. Results: A total of 2 541 strains, including 2 093 strains of Enterobacteriaceae and 448 strains of glucose non-fermentative bacilli were collected.The MIC(90) of imipenem and meropenem against Enterobacteriaceae were less than 1 mg/L in general, whereas MIC(90) of two agents with ß-lactamase inhibitors was around 64 mg/L.As to glucose non-fermenting bacteria, MICs of all the four agents were very high, especially to Acinetobacter baumannii, which indicated MIC(50) more than 32 mg/L.MCS revealed that carbapenems had significantly higher CFR than those with ß-lactamase inhibitors.Imipenem and meropenem (1 g, q8 h) obtained CFRs of 74.69% and 81.42%, respectively.The CFR of cefoperazone-sulbactam (2 g, q8 h) and piperacillin-tazobactam (4 g, q6 h) (both excluding ß-lactamase inhibitors) were just 49.59% and 27.66% respectively, which increased after excluding A. baumannii in piperacillin-tazobactam. Conclusions: The conventional dose regimens of imipenem and meropenem are reliable for the empiric therapy of Gram-negative hospital-acquired bacterial infections.Piperacillin-tazobactam is suggested to use with higher doses or prolonged infusion time to satisfy the time of drug concentration exceeded the MIC(T>MIC)requirement.More clinical studies of cefoperazone-sulbactam should be conducted to optimize its regimen and guarantee its efficacy.

The efficiency of continuous regional intra-arterial infusion in the treatment of infected pancreatic necrosis.

OBJECTIVE: Our aim was to investigate the efficiency of continuous regional intra-arterial infusion (CRAI) with antisecretory agents and antibiotics in the treatment of infected pancreatic necrosis. MATERIALS AND METHODS: CRAI was used as a new clinical technique to treat acute pancreatitis patients during a 4-year period at the First Affiliated Hospital, Wenzhou Medical College, China. In this retrospective study, thirty-four patients with proven infected pancreatic necrosis were included. Twelve patients were treated with CRAI, and were matched according to age, sex, APACHE II scores, Ranson scores and remote organ dysfunction, with 22 patients with IPN treated surgically. The clinical outcome following surgery and CRAI were compared. RESULTS: No difference was found between the two groups when comparing age, gender, APACHE II scores, Ranson scores and remote organ dysfunction (p > 0.05). The patients treated with CRAI had a lower incidence of complications (33.3% vs 72.7%), duration of hospitalization (27.1 ± 4.7 days vs 43.0 ± 12.0 days) and cost of hospitalization (4.09 ± 1.64 thousand RMB vs 8.77 ± 3.74 thousand RMB) as compared to patients treated with surgery (p < 0.05). The survival rate was significantly higher in the CRAI group as compared to the surgical group (91.7% vs 63.6%; p < 0.01). However, the two groups had similar rates of concomitant operative treatment and incidence of remote organ dysfunction (p > 0.05). CONCLUSIONS: CRAI or CRAI in combination with abscess drainage seemingly improve the clinical outcome in patients with infected pancreatic necrosis. Further confirmative prospective randomized multicenter studies are warranted prior to broad introduction of the CRAI concept.

[Comparative analysis of the effectiveness and costs of azithromycin and cefoperazone treatment of patients during COPD exacerbation]. / Analiza porównawcza skutecznosci i kosztów leczenia azytromycyna i cefoperazonem w okresie zaostrzenia przewleklej obturacyjnej choroby pluc.

UNLABELLED: The effectiveness and costs of azithromycin and cefoperazone treatment of COPD exacerbation have been analysed in this study. Forty patients at the mean age of 65.9 (+/- 11.5) years were enrolled. The subjects were randomly selected and treated either with cefoperazone 2 x 1.0 g i.v. daily (group I = 20 persons) or with azithromycin 1 x 0.5 g (group II = 20 persons), in sequential method. Body temperature, cough intensity, quality and quantity of expectorated sputum, number of breaths per minute and adverse events were recorded daily. The values of pulmonary function tests and leucocytosis were assessed three times during the study. Statistically significant differences between both groups have been found with respect to the mean time of staying in hospital (9.1 days--group I vs 6.1 days--group II), mean total duration of antibiotic therapy (10.1 days--group I vs. 6.6 days--group II) and duration of intravenous antibiotic therapy only [7.5 days (group I) vs 2.9 days (group II)] (p < 0.05). Taking into account the duration of hospitalization, it was shown that the mean total costs of treatment of COPD exacerbation with azithromycin was significantly lower than that of treatment with cefoperazone (2375.9 PLN and 1663.7 PLN, respectively) (p < 0.05). CONCLUSIONS: The effectiveness of treatment with azithromycin in patients with COPD exacerbation was evident. The total costs of treatment of COPD exacerbation with azithromycin is lower than with cefoperazone. Both azithromycin and cefoperazone are safe in the treatment of exacerbation of COPD.

In vitro assessment of sulbactam plus cefoperazone in the treatment of bacteria isolated from cancer patients.

Cefoperazone is a broad-spectrum cephalosporin that has been used extensively to treat infections in cancer patients. A recent survey demonstrated only a 6% resistance to this drug among Gram-negative bacteria. The combination of cefoperazone plus sulbactam was studied in vitro against consecutive isolates causing bacteremia in cancer patients as well as those selected for resistance to cefoperazone. Both a fixed ratio of sulbactam/cefoperazone (2:1 w/w) and selected concentrations of sulbactam (2, 4, 8, and 16 micrograms/ml) were studied. Sulbactam was shown to increase the susceptibility of various unselected Gram-negative bacilli; this effect increased with larger concentrations of sulbactam. The addition of sulbactam at optimum concentration levels made 29 of 65 cefoperazone-resistant Gram-negative bacilli susceptible. This effect was seen most markedly for Acinetobacter spp.

Assessment of serum bactericidal activity after administration of cefoperazone, cefotaxime, ceftizoxime, and moxalactam to healthy subjects.

Bactericidal activity in serum produced after administration of 1-g intravenous doses of cefoperazone, cefotaxime, ceftizoxime, and moxalactam was ascertained in six healthy subjects. The assay organisms were a strain of Staphylococcus aureus which was moderately susceptible to the drugs (MBC, 2 to 8 micrograms/ml) and an isolate of Escherichia coli which was highly susceptible (MBC, 0.08 to 0.3 microgram/ml). Drug concentrations and bactericidal titers were measured from samples taken for up to 12 h after the dose. No bactericidal activity against the S. aureus strain was found at 4 to 6 h and beyond for any of the drugs. Ranking of the in vivo bactericidal activity of the drugs was cefoperazone = cefotaxime greater than ceftizoxime = moxalactam. Against the E. coli isolate, bactericidal activity was present for 8 h for cefotaxime, and for 12 h for the other drugs. Ranking of the drugs in terms of extent and duration of in vivo bactericidal activity versus E. coli was moxalactam = ceftizoxime greater than cefoperazone greater than cefotaxime. After administration of 1-g doses of these new beta-lactams, bactericidal activity in serum was maintained for 12 h against highly susceptible bacteria. More frequent (6 to 8 h) or higher (greater than or equal to 2 g) dosing appears to be necessary to achieve prolonged serum bactericidal activity against less susceptible isolates (MBC, greater than or equal to 2 to 8 micrograms/ml).

[Clinical assessment of sulbactam/cefoperazone in comparison with ceftizoxime in patients with postoperative infections by well controlled method].

The clinical effectiveness in postoperative infections of sulbactam/cefoperazone (SBT/CPZ, (SBT 0.5 g+ CPZ 0.5 g) X 2/day) was compared to that of ceftizoxime (CZX, 1.0 g X 2/day) by a well controlled comparative study, to have the following results. The overall effectiveness rate of SBT/CPZ and CZX as judged by Judgement Committee was 84.0% (63/75) and 80.6% (50/62), respectively, and the effectiveness of SBT/CPZ and CZX as assessed by the attending surgeons was 84.0% (63/75) and 71.0% (44/62), respectively. No significant difference was noted in both assessments. In a total of 36 SBT/CPZ-treated patients with intraabdominal infections, the clinical efficacy was judged by attending surgeons to be excellent in 13 patients (36.1%), and to be excellent or good in 31 (86.1%). In the 30 CZX treated patients, it was judged to be excellent in 6 patients (20.0%), and to be excellent or good in 19 (63.3%). These results presented a significant difference (P less than 0.05, U-test) between the 2 drug groups. The final global improvement ratio judged by attending surgeons was 85.3% (64/75) for SBT/CPZ, and 79.0% (49/62) for CZX with no significant difference. In assessment of time-course improvement, the improvement ratio of SBT/CPZ on day 4 was significantly better than that of CZX (P less than 0.05, U-test). The usefulness rate of SBT/CPZ and CZX was 84.0% (63/75) and 73.0% (46/63), respectively. There was no significant difference between the 2 drug groups. To assess the bacteriological efficacy, the eradication rate of SBT/CPZ was compared to that of CZX. There was no significant difference between 85.7% (36/42) for SBT/CPZ and 73.5% (25/34) for CZX. After SBT/CPZ administration, 2 patients (2.5%) complained of side effects. In the clinical laboratory tests, abnormality related to SBT/CPZ medication was observed in 6 patients (7.5%), and that related to CZX, in 5 patients (6.4%). As to the types of side effects and frequency, no significant difference was observed between SBT/CPZ and CZX. It is concluded from the above assessments that SBT/CPZ is a useful drug in the treatment of post-operative infections.