Pharmacokinetic profile of cefbuperazone in healthy Chinese volunteers after single and multiple drip intravenous infusion by HPLC-MS/MS.

A selective and reproducible HPLC-MS/MS method was developed and fully validated for the determination of cefbuperazone in human plasma and urine. Samples were prepared using protein precipitation and separated on a Zorbax Eclipse Plus C18 column (2.1×50mm, 3.5µm). The API-4000 mass spectrometer was operated under multiple reaction monitoring mode (MRM) using the electrospray ionization technique. Linearity was achieved from 0.250 to 250µg/mL in plasma and 20.0-5000µg/mL in urine. The method was successfully applied to a pharmacokinetic study of cefbuperazone in healthy Chinese volunteers after drip intravenous infusion of 0.5, 1.0, 2.0g cefbuperazone sodium injection. Cefbuperazone reached a maximum concentration (Cmax) of 44.7±8.1µg/mL, 86.7±12.7µg/mL and 168±14µg/mL in 0.5, 1.0 and 2.0g dose groups respectively, at 60min after the start of infusion. The half-life (t1/2) was between 1.8-1.9h, and the elimination constant (kel) was between 0.36-0.39h(-1). The results proved that cefbuperazone showed linear pharmacokinetic profile in the dose range of 0.5-2.0g without gender difference. Drug accumulation was not observed. Cefbuperazone reached the maximum excretion rate in urine 2h after the start of infusion. About 60.0% of the administered drug was excreted via urine as unchanged form within 12h. The cumulative excretion of cefbuperazone after single drip intravenous infusion was proportional to the administered dose within the range from 0.5g to 2.0g.

[Correlation analysis on combined medication with of Xiyanping injection in treatment of lung infection in real world].

To analyze the regularity in combined medication with Xiyanping injection (Xiyanping for short) in the real world by as- sociation rules. Totally 5 822 patients using Xiyanping injection was collected from the 18 Class III Grade I hospitals nationwide to study the combined medication information of the patient with lung infection and make the analysis by using association rules and Apriori. According to the results, major drugs combined with Xiyanping in treatment of lung infection included compound amino acid, inosine, coenzyme A, cytidine triphosphate, vitamin C. Common drugs combined with Xiyanping can be divided into 5 categories: nutrition support therapy (vitamin C, compound amino acid) , coenzymes (coenzyme A, cytidine triphosphate, inosine), expectorants and antiasthmatics (ambroxol, salbutamol, doxofylline), hormones (dexamethasone, budesonide), antibiotics (mainly cefminox). The main combined medicines mostly conformed to the regularity for drugs treating lung infection. In addition, there were two most common medical combination models: the model for Xiyanping combined a single medicine is Xiyanping + nutrition support therapy, while the model for Xiyanping combined two or more than two medicines is Xiyanping + nutrition support therapy + coenzyme. Pharmacologically, Xiyanping is mostly combined with western medicines with similar pharmacological effects to substitute or supplement the antibiotic effect in treating lung infection. However, further studies shall be conducted for the safety and rationality of the combined medication based on clinical practices, in order to provide reference for clinical medication.

Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial.

OBJECTIVE: Pelvic inflammatory disease (PID) is a common and morbid intraperitoneal infection. Although most women with pelvic inflammatory disease are treated as outpatients, the effectiveness of this strategy remains unproven. STUDY DESIGN: We enrolled 831 women with clinical signs and symptoms of mild-to-moderate pelvic inflammatory disease into a multicenter randomized clinical trial of inpatient treatment initiated by intravenous cefoxitin and doxycycline versus outpatient treatment that consisted of a single intramuscular injection of cefoxitin and oral doxycycline. Long-term outcomes were pregnancy rate, time to pregnancy, recurrence of pelvic inflammatory disease, chronic pelvic pain, and ectopic pregnancy. RESULTS: Short-term clinical and microbiologic improvement were similar between women randomized to the inpatient and outpatient groups. After a mean follow-up period of 35 months, pregnancy rates were nearly equal (42.0% for outpatients and 41.7% for inpatients). There were also no statistically significant differences between outpatient and inpatient groups in the outcome of time to pregnancy or in the proportion of women with pelvic inflammatory disease recurrence, chronic pelvic pain, or ectopic pregnancy. CONCLUSION: Among women with mild-to-moderate pelvic inflammatory disease, there was no difference in reproductive outcomes between women randomized to inpatient treatment and those randomized to outpatient treatment.

Drug-induced hemolysis: cefotetan-dependent hemolytic anemia mimicking an acute intravascular immune transfusion reaction.

Numerous cases of drug-induced hemolytic anemia have been described in patients treated with penicillin or cephalosporin. Second and third generation cephalosporins are more commonly implicated in hemolytic reactions than first generation cephalosporins. We report a case of severe cefotetan-induced hemolytic anemia in a previously healthy 46-year-old woman undergoing an elective hysterectomy. The patient received 2 g of intravenous cefotetan intraoperatively and subsequently at 12 and 24 h post-operatively. She complained of diarrhea and fever on the third post-operative day and was seen in her gynecologist's office on the fifth post-operative day (hemoglobin = 10.5 g/dL). On the seventh post-operative day, she complained of fever and soreness around the suprapubic catheter site and was given a prescription for 500 mg oral cephalexin four times a day. The next day she was seen in the gynecologist's office and reported feeling better. Ten days after the operation her fatigue worsened and her hemoglobin was 4.8 g/dL. She was transfused with 3 units of packed red blood cells (PRBC) and was given 1 g of cefotetan intravenously. During the transfusion of the second unit of PRBC nursing staff observed gross hemoglobinuria and she subsequently developed acute renal failure. Laboratory chemistry parameters were consistent with severe acute hemolysis. The patient's direct antiglobulin test was reactive and her serum reacted with cefotetan-coated red blood cells (RBCs) and serum plus soluble cefotetan reacted with untreated RBCs. The titration endpoint of the serum against cefotetan-coated RBCs was 40,960, while the serum plus soluble cefotetan against uncoated RBCs was 2,560. This case of severe cefotetan-induced hemolysis was complicated by an acute hemolytic event that occurred during the transfusion of PRBC. Clinical and transfusion service staff must consider drug-induced hemolysis in the differential diagnosis of acute anemia.

[Combination effect of teicoplanin and beta-lactams on MRSA].

In vitro combination effect of teicoplanin and beta-lactams was investigated against 109 MRSA strains isolated from a variety of clinical specimens at the Social Health Insurance Medical Center during the period from January 1994 through February 2000. TEIC + panipenem (PAPM) was revealed by microbroth dilution method-based checkerboard method, to exhibit synergistic effect of min. FIC index < or = 0.5 against all the 109 strains. The combination of TEIC and flomoxef (FMOX) was shown to have synergistic effect on 108 strains (99.1%). The combination of TEIC and cefepime (CFPM) was shown to have synergistic effect on 96 strains (88.1%). The combination of TEIC and cefmetazole (CMZ) was shown to have synergistic effect on all the 109 strains (100%). The mean value of min. FIC indices obtained from each of the combinations was 0.1259 as to TEIC + PAPM, 0.2019 as to TEIC + FMOX, 0.3257 as to TEIC + CFPM and 0.1995 as to TEIC + CMZ, in other words, the combination of TEIC + PAPM showed the lowest value of all the combinations. While MIC80 was 2.0 micrograms/ml when TEIC was used alone, it was < or = 0.06 microgram/ml when used together with PAPM, and 0.13 microgram/ml when used together with FMOX, respectively. While MIC80 was 3.2 micrograms/ml when PAPM was used alone, it was 0.5 microgram/ml when used together with TEIC. Meanwhile, the value for FMOX was changed from > or = 128 micrograms/ml to 4.0 micrograms/ml. When TEIC was used in combination with CFPM, MIC80 was found to be 0.5 microgram/ml. Similar to the case of the concurrent use with FMOX, the value obtained by combination with CMZ was 0.13 microgram/ml. While MIC80 was 128 micrograms/ml when CFPM was used alone, it was 8.0 micrograms/ml when used together with TEIC, whereas the value for CMZ was decreased from 64 micrograms/ml to 2.0 micrograms/ml. In conclusion, TEIC's antibacterial activity was shown to be accentuated by any of the combinations.

Duration of antibiotic prophylaxis in high-risk patients with penetrating abdominal trauma: a prospective randomized trial.

To evaluate the effect of varying durations of antibiotic prophylaxis in trauma patients with multiple risk factors for postoperative septic complications, a prospective randomized trial was undertaken at an urban level I trauma center. The inclusion criteria were full-thickness colon injury and one of the following: (1) Penetrating Abdominal Trauma Index > 25, (2) transfusion of 6 units or more of packed red blood cells, or (3) more than 4 hours from injury to operation. Patients were randomly assigned to a short course (24 hours) or a long course (5 days) of antibiotic therapy. All patients received 2 g cefoxitin en route to the operating room and 2 g intravenously piggyback every 6 hours for a total of 1 day vs. 5 days. Sixty-three patients were equally divided into short-course (n = 31) and long-course (n = 32) therapy. This was a high-risk patient population, as assessed by the mean Penetrating Abdominal Trauma Index (33), number of patients with multiple blood transfusions (51 of 63; 81%), number of patients with an Injury Severity Score greater than 15 (37 of 63; 59%), number of patients with destructive colon wounds requiring resection (27 of 63; 43%), and number of patients requiring postoperative critical care (37 of 63; 59%). Differences in intra-abdominal (1-day, 19%; 5-days, 38%) and extra-abdominal (1-day, 45%; 5-days, 25%) infection rates did not achieve statistical significance. There continues to be no evidence that extending antibiotic prophylaxis beyond 24 hours is of benefit, even among the highest risk patients with penetrating abdominal trauma. A large, multi-institutional trial will be necessary to condemn this common practice with statistical validity.

Efficacy of liposomal antibiotic therapy in a rat infusion model of Escherichia coli peritonitis.

OBJECTIVE: To compare the potential therapeutic effect of liposomal vs. free cefoxitin. DESIGN: Randomized, controlled study, using a rat model of peritonitis. SETTING: Government research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats were infused intraperitoneally with 6.5 x 10(8) colony forming units of Escherichia coli over 12 hrs. Animals were then randomized to receive intravenous saline, free cefoxitin, liposomal cefoxitin, or plain liposomes twice daily until they were killed. MEASUREMENTS AND MAIN RESULTS: Free cefoxitin significantly reduced the number of E. coli after 24 hrs compared with saline treatment in both liver and spleen. However, liposomal cefoxitin further decreased the bacterial content by five-fold to ten-fold in these organs. Minimal bactericidal effect was observed in animals injected with plain liposomes. Although administration of liposomal cefoxitin for 7 days further reduced bacterial counts in liver and spleen, there was no apparent beneficial bactericidal effect of free cefoxitin over saline at 7 days. There was approximately a ten-fold reduction in bacterial content in the lungs after 24 hrs in all three treatments, but no further reduction was observed after 7 days. There was no difference in 7-day survival rate in animals treated with plain liposomes or saline (45% vs. 39%). Although survival tended to increase with free cefoxitin treatment (64%), this outcome was significantly improved with the use of liposomal cefoxitin (82%). CONCLUSIONS: Liposomal cefoxitin enhanced bacterial killing in liver and spleen in this model of E. coli peritonitis. It also improved survival outcome relative to no treatment but not compared with free cefoxitin.

The duration of antibiotic administration in penetrating abdominal trauma.

BACKGROUND: The epidemiology of penetrating abdominal trauma is changing to reflect an increasing incidence of multiple injuries. Not only do multiple injuries increase the risk of infection, a very high risk of serious infection is conferred by immunosuppression from hemorrhage and transfusion and the high likelihood of intestinal injury, especially to the colon. Optimal timing and choice of presumptive antibiotic therapy has been established for penetrating trauma, but duration has not been studied extensively in such seriously injured patients. The purpose of this study was to test the hypothesis that 24 hours of antibiotic therapy remains sufficient to reduce the incidence of infection in penetrating abdominal trauma. METHODS: Three hundred fourteen consecutive patients with penetrating abdominal trauma were prospectively randomized into two groups: Group I received 24 hours of intravenous cefoxitin (1 g q6h) and group II received 5 days of intravenous cefoxitin. The development of a deep surgical site (intra-abdominal) infection as well as any type of nosocomial infection, as defined by the Centers for Disease Control and Prevention, (ie, surgical site infections, catheter-related infections, urinary tract, pneumonia), was recorded. Hospital length of stay was a secondary endpoint. Statistical analysis included chi-square tests for coordinate variables and two-tailed unpaired t tests for continuous variables. The independence of risk factors for the development of infection was assessed by multivariate analysis of variance. Significance was determined when P <0.05. RESULTS: Three hundred patients were evaluable. There was no postoperative mortality, and no differences in overall length of hospitalization between groups. The duration of antibiotic treatment had no influence on the development of any infection (P = 0.136) or an intraabdominal infection (P = 0.336). Only colon injury was an independent predictor of the development of an intraabdominal infection (P = 0.0031). However, the overall infection incidence was affected by preoperative shock (P = 0.003), colon (P = 0.0004), central nervous system (CNS) injuries (P = 0.031), and the number of injured organs (P = 0.026). Several factors, including intraoperative shock (P = 0.021) and injuries to the colon (P = 0.0008), CNS (P = 0.0001), and chest (P = 0.0006), were independent contributors to prolongation of the hospital stay. CONCLUSIONS: Twenty-four hours of presumptive intravenous cefoxitin versus 5 days of therapy made no difference in the prevention of postoperative infection or length of hospitalization. Infection was associated with shock on admission to the emergency department, the number of intra-abdominal organs injured, colon injury specifically, and injury to the central nervous system. Intra-abdominal infection was predicted only by colon injury. Prolonged hospitalization was associated with intraoperative shock and injuries to the chest, colon, or central nervous system.

Distribution of free and liposomal cefoxitin in plasma and peritoneal fluid in a porcine intra-abdominal sepsis model.

The plasma and peritoneal fluid pharmacokinetic parameters obtained after the intravenous administration of free and liposomal cefoxitin were studied in a porcine model of intraabdominal sepsis. No prior assumptions were made to predict the number of compartments pertaining to drug clearance from the administration of either cefoxitin formulation. The experimental data obtained were applied to fit mathematical models of multiexponential drug clearance and the pharmacokinetic data were found to best fit a two-compartment open model. Liposomal encapsulation significantly altered the plasma drug distribution pattern resulting in changes in the magnitude of a number of pharmacokinetic parameters examined. The mean post-distributive half-life of liposomal cefoxitin was substantially longer than that of free cefoxitin by at least 3 times. The peritoneal cavity appeared to provide a reservoir for the initial distributive phase of rapid drug clearance from the plasma compartment followed by a less-rapid post-distributive phase. The cumulative drug level, as determined by the area under the concentration curve (AUC) as a function of time, in the plasma of animals treated with liposomal cefoxitin was about 3-4 fold as high as that of animals treated with free cefoxitin. The differences in pharmacokinetic parameters appeared to account for the improved therapeutic efficacy of liposomal cefoxitin in this animal model.

Treatment of osteomyelitis with antibiotic-soaked porous glass ceramic.

We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum. We evaluated the release concentrations of the antibiotics from the blocks. The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days. The concentrations of CMZ from both materials were lower than those of ISP. An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation. Osteoconduction of the A-W GC block was good. Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results.

Double-blind comparison of single-dose alatrofloxacin and cefotetan as prophylaxis of infection following elective colorectal surgery. Trovafloxacin Surgical Group.

BACKGROUND: Alatrofloxacin, the prodrug of trovafloxacin, is a novel fluoroquinolone antimicrobial agent with a broad spectrum, including activity against gram-positive and gram-negative aerobes and anaerobes. Its pharmacokinetic properties (long half-life, excellent tissue distribution, and good safety profile) suggest a role in surgical prophylaxis. This prospective, multicenter, double-blind trial compared alatrofloxacin with cefotetan, an approved drug for surgical prophylaxis, in reducing postoperative infections. METHODS: The efficacy and safety of a single 200-mg intravenous dose of alatrofloxacin were compared to a single 2-g intravenous dose of cefotetan in 492 patients undergoing elective colorectal surgery. The efficacy of alatrofloxacin as a prophylaxis for wound, intra-abdominal, or remote-site postoperative infectious complications was compared with cefotetan in 317 clinically evaluable patients; 161 received alatrofloxacin and 156 received cefotetan. The patients were monitored for infections and safety for 30 days postoperatively. RESULTS: No statistically significant between-treatment difference was detected in successful clinical response rates at the end of the study (72% for each group). The incidence of primary wound infections at the time of hospital discharge was also similar: 21% in patients treated with alatrofloxacin and 18% in those treated with cefotetan. Safety, established by the incidence of adverse events, did not differ statistically between the groups. CONCLUSIONS: A single intravenous dose of alatrofloxacin given within 4 hours prior to surgery was as effective as an intravenous dose of cefotetan in the prevention of postoperative infectious complications in patients undergoing elective colorectal surgery. The safety profiles of the two medications were similar.

Oral trovafloxacin compared with intravenous cefoxitin in the prevention of bacterial infection after elective vaginal or abdominal hysterectomy for nonmalignant disease. Trovafloxacin Surgical Group.

BACKGROUND: Trovafloxacin is a new fourth-generation fluoroquinolone whose pharmacokinetics and in vitro activity suggest that it is well suited for antibiotic prophylaxis in elective hysterectomy. METHODS: In a randomized, double-blind, multicenter study, parallel groups of women 18 years of age or older received either 200 mg trovafloxacin by mouth and intravenous (i.v.) placebo or 2 g cefoxitin by i.v. infusion and placebo by mouth before elective vaginal or abdominal hysterectomy for nonmalignant disease. RESULTS: In the 103 and 97 patients in the trovafloxacin and cefoxitin groups, respectively, who were evaluable for efficacy, the prophylactic success rates at hospital discharge (96% in both groups) and 30 +/- 6 days after hysterectomy (88% and 91% in the trovafloxacin and cefoxitin groups, respectively) were statistically equivalent. Both antibiotics were well tolerated. CONCLUSION: A single oral 200 mg dose of trovafloxacin is as effective and safe as a standard cefoxitin parenteral regimen in the prevention of primary bacterial infection after elective vaginal or abdominal hysterectomy for nonmalignant disease.

Treatment of acute gynecologic infections with trovafloxacin. Trovafloxacin Surgical Group.

BACKGROUND: Trovafloxacin, a broad-spectrum fourth-generation quinolone with gram-positive and gram-negative aerobic and anaerobic bacterial activity, is available in oral and intravenous formulations. The objective of this prospective, multicenter, double-blind, randomized study was to compare the efficacy of trovafloxacin with that of cefoxitin, an approved drug for treatment of acute gynecologic infections, together with amoxicillin/clavulanic acid as oral follow-on treatment. METHODS: Patients with a clinical diagnosis of acute pelvic infection received either intravenous alatrofloxacin with oral trovafloxacin follow-on (trovafloxacin) or a combined regimen of cefoxitin followed by amoxicillin/clavulanic acid for a maximum of 14 days. The primary endpoint was clinical response to therapy on follow-up at day 30. RESULTS: Clinical success rates were comparable between the trovafloxacin (n = 107) and comparative (n = 119) groups at study end (90% vs. 86%, respectively; 95% confidence interval, -4.5, 12.5). Among clinically evaluable patients, clinical success rates for infections involving Enterococcus species were higher with trovafloxacin than with the comparative regimen at the end of treatment (96% and 85%) and at study end (96% and 86%). CONCLUSION: Intravenous alatrofloxacin followed by oral trovafloxacin for a maximum of 14 days of total therapy was efficacious in the treatment of acute pelvic infections.

Incidence of postpartum endomyometritis following single-dose antibiotic prophylaxis with either ampicillin/sulbactam, cefazolin, or cefotetan in high-risk cesarean section patients.

OBJECTIVE: To assess the efficacy of single-dose antibiotic prophylaxis against postpartum endomyometritis in high-risk cesarean section patients. DESIGN: Patients were administered one of three single-dose antibiotic regimens following umbilical cord clamping after cesarean section delivery. SETTING: Prospective randomized trial at a university-based hospital. PATIENTS: The study evaluated 293 consenting women undergoing cesarean section who had either experienced labor for a duration of > or = 6 hr or rupture of amniotic membranes. MAIN OUTCOME MEASURES: Development of postpartum endomyometritis. RESULTS: The incidence of postpartum endomyometritis was 7/95 (7.4%) following the ampicillin/sulbactam regimen, 14/98 (14.3%) after the cefazolin regimen, and 11/99 (11.1%) after the cefotetan regimen. There was no significant difference in postpartum infection among the three study arms. In addition, the incidence of endomyometritis in the three single-dose study arms was not higher than previously noted in studies where three doses of antibiotic were administered. CONCLUSION: Single-dose antibiotic prophylaxis should replace the standard triple-dose therapy for uninfected women undergoing cesarean section who are at risk for postoperative endomyometritis. Ampicillin/sulbactam, cefazolin, and cefotetan are all reasonable antibiotic choices for single-dose therapy.

The enhancing mechanism of capric acid (C10) from a suppository on rectal drug absorption through a paracellular pathway.

Capric acid (C10) enhanced the absorption of cefoxitin sodium in a concentration-dependent manner following the rectal administration as a suppository in rats. The optimal concentration of C10 was 13%. C10 administered as a suppository also reduced rectal membrane resistance (Rm), showing that the above enhancing effect was induced by widening the paracellular pathway. Both the enhancing effect on the absorption and the reducing effect on Rm were inhibited by W7, an inhibitor of myosin light chain kinase. These results supported that, as shown in the in vitro Caco-2 cell system, the C10 effect on the paracellular pathway is due to activating the contraction of Ca(2+)-calmodulin-dependent actin filament.

[Antibiotic prophylaxis in cesarean section with cefoxitin (Mefoxin)]. / Antibiotichna profilaktika pri tsezarovo sechenie s cefoxitin (Mefoxin).

The ain of this presentation is to show the advantages and disadvantages of a single prophylactic dose of Mefoxin, in comparison to the classical antibiotic prophylaxis with penicillin and gentamicin. The authors conclude that: single dose prophylaxis with Mefoxin significantly reduces the rate of infection morbidity after caesarean section; a single application of 2 g Mefoxin after clamping of the umbilicus is enough for prophylaxis of infectious complications after caesarean section.

Studies on the duration of antibiotic administration for surgical prophylaxis.

Patients undergoing 801 elective, clean-contaminated operations were assigned to one of the three following antibiotic regimens: 1) 1 g of cefazolin preoperatively, 2) 1 g of cefazolin preoperatively and another 1-g dose 3 hours later, and 3) 1 g of cefotetan preoperatively. These antibiotic regimens resulted in similar wound infection rates for procedures completed within 3 hours. When the procedure lasted more than 3 hours, the 6.1 per cent infection rate noted when a single dose of cefazolin was given proved significantly greater than the 1.3 per cent infection rates associated with the use of two doses of cefazolin or a single dose of the longer acting antibiotic, cefotetan (P < 0.01). Another series of 768 patients undergoing biliary and gastrointestinal tract operations were assigned to one of two antibiotic regimens: 1) a preoperative dose of 1 g of cefazolin and another 1-g dose 3 hours later if still in the operating room; 2) same as (1), plus 1-g doses every 8 hours for 24 hours. The longer period of antibiotic administration failed to improve the wound infection rate compared to the use of perioperative coverage only. These studies suggest that a single dose of preoperative antibiotic is sufficient for surgical prophylaxis when the operation is completed within 3 hours. Antibiotic coverage must extend for the duration of longer operations. A second dose of antibiotic or a single preoperative dose of an extended half-life antibiotic are equally effective. There is no value to administering antibiotics after the operation has been completed.