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Background: New antimicrobials or adjunctive treatments have not substantially reduced mortality from acute childhood bacterial meningitis. Paracetamol seems to have beneficial effects in bacteraemic adults and some experts recommend initial slow β-lactam infusion. We investigated whether these treatments had benefits in children with bacterial meningitis., Methods: We did a prospective, double-blind, single-centre study with a two-by-two factorial design in Luanda, Angola. 723 participants aged 2 months to 13 years were randomly assigned two 12 h intravenous infusions, without loading doses, of 125 mg/kg bodyweight cefotaxime (total dose 250 mg/kg) given over 24 h, or 250 mg/kg bodyweight cefotaxime given as four boluses, one every 6 h over 24 h. Patients also received oral paracetamol at an initial dose of 30 mg/kg then 20 mg/kg every 6 h for 48 h or placebo. Two primary endpoints, death or severe neurological sequelae and deafness, were analysed by intention to treat. The study was registered as ISRCTN62824827., Findings: 183 patients were assigned cefotaxime infusion plus paracetamol and 180 patients to each of the other three treatment groups. Causative agents were identified in 63% of cases and were mostly Haemophilus influenzae type b, Streptococcus pneumoniae, or Neisseria meningitidis. Death or severe neurological sequelae were seen in 340 (47%) of 723 children and deafness in 45 (12%) of 374 tested, both distributed similarly across treatment groups. In a predefined subgroup analysis of death or any sequelae, by causative agent, a benefit was seen in favour of infusion over bolus in children with pneumococcal meningitis (infusion plus placebo, odds ratio 0·18, 95% CI 0·03-0·90, p=0·04). A similar effect was seen for children receiving cefotaxime infusion plus paracetamol, but the difference was not significant (OR 0·22, 95% CI 0·04-1·09, p=0·06). A post-hoc analysis suggested that cefotaxime infusion plus paracetamol lowered mortality at least during the first 3 days, irrespective of cause., Interpretation: Although no tested regimen improved the final outcomes of these very ill children, studies of longer courses of β-lactam infusion plus paracetamol seem warranted., Funding: The Päivikki and Sakari Sohlberg, the Sigrid Jusélius, and the Paediatric Research Foundations, and the daily newspaper Helsingin Sanomat., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment.

Background/aims: Cefotaxime or ceftriaxone were considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing spontaneous bacterial peritonitis. It has been suggested that ciprofloxacin could be an alternative to cefotaxime or ceftriaxone in cirrhotic patients developing spontaneous bacterial peritonitis. The aim of the present study was to compare oral ciprofloxacin with cefotaxime and ceftriaxone in the treatment of spontaneous bacterial peritonitis in cirrhotic patients., Methodology: Fifty-three hospitalized cirrhotic patients with spontaneous bacterial peritonitis were prospectively included and randomized into three groups: group A (n = 16); received orally 500 mg ciprofloxacin every 12 h, group B (n = 18); received intravenous cefotaxime 2 g every 8 h and group C (n = 19) received intravenous ceftriaxone 2 g every 24 h., Results: 15 patients from the ciprofloxacin group, 17 from the cefotaxime group and 17 patients from the ceftriaxone group were finally analyzed. Spontaneous bacterial peritonitis resolution in three groups was found to be 80%, 76%, and 83%, respectively (p = NS). Incidence of complications and hospital mortality was similar in the three groups. No adverse events were observed in any of the three groups. The cost of the treatment was statistically lower in the ciprofloxacin group than in the cefotaxime group and ceftriaxone group (p < 0.001)., Conclusions: These results suggest that orally ciprofloxacin is as effective as cefotaxime and ceftriaxone in the empirical treatment of spontaneous bacterial peritonitis in cirrhotic patients, and is also less expensive and can be administered orally.

Introduction: Spontaneous infection of ascitic fluid with Salmonella typhimurium is very rare and exhibits uncommon features., Observation: A Child-Pugh C cirrhotic 47 year-old woman was hospitalised for fever and coma. Norfloxacin 400 mg per day had been introduced three months earlier as secondary prophylaxis for spontaneous bacterial peritonitis. A spontaneous bacterial peritonitis was diagnosed, and an intravenous broad-spectrum antibiotic therapy was started (cefotaxime 1 g/8h). Bacteriologic samples isolated Salmonella typhimurium in ascites, blood and stools; Escherichia coli sensitive to norfloxacin in blood and Escherichia coli resistant to norfloxacin but sensitive to cefotaxime in urine. Despite the initial regression of the hepatic encephalopathy and the decrease in fever, the patient died twenty days after admission to hospital., Discussion: This observation is exceptional because of the simultaneous presence of Salmonella typhimurium in ascites, blood and stools. It underlines the features of spontaneous Salmonella bacterial peritonitis: rare, occurring in immuno-suppressive diseases, virulent despite sensitivity to third generation cephalosporines and of often poor prognosis. Compliance to norfloxacin prophylaxis in cirrhotic patients is a real problem, since in the case of poor compliance such patients are exposed both to sensitive norfloxacin bacteria, and to resistant norfloxacin bacteria selected by the norfloxacin prophylaxis.

Objective: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence., Study Design: Randomized, controlled, community-based trial in Rakai District, Uganda., Methods: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services., Results: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis., Conclusions: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

The checkerboard method was used to determine the antimicrobial activity of the combination cefotaxime/ofloxacin against 217 bacterial isolates involved in serious infections. Synergy or partial synergy was observed against 19 of 34 (55.8%) Staphylococcus aureus methicillin-susceptible isolates, 4 of 47 (8.4%) Streptococcus pneumoniae isolates, 28 of 34 (82.2%) Escherichia coli isolates and 70 of 102 (68.5%) Pseudomonas aeruginosa isolates. Antagonism was not observed with any of the isolates examined.

In a randomized open study, 351 male patients with uncomplicated gonorrhea were given single oral doses of grepafloxacin (400 mg) or cefixime (400 mg). In the 299 microbiologically evaluable patients, urethral infections were cured in 99% (147 of 149) of those receiving grepafloxacin and 97% (145 of 150) of those given cefixime. Eradication rates for both regimens were 100% in the 16% (47 of 299) of participants who were infected with penicillin-resistant Neisseria gonorrhoeae and 97% in the 21% (62 of 299) of participants infected with tetracycline-resistant strains. Grepafloxacin is a well-tolerated alternative to cefixime for treatment of uncomplicated gonorrhea in males.

Patients and Methods: In a prospective protocol 25 consecutive patients with diffuse peritonitis were treated in the Surgical Clinic of the RWT-University in Aachen, Germany, from January to December 1995. According to the "Mannheim Peritonitis Score" three different stages were treated with different surgical procedures and a selective antibiotic regimen. Group-A patients with prognostically favorable peritonitis (MPS 0-20) were treated with the so-called standard procedure, group-B patients (MPS: 21-29) with closed postoperative lavage. The antibiotic regimen was cefotaxime (2 x 2 g) and metronidazole (2 x 500 mg) for both group-A and group-B patients. Severe group-C cases (MPS > 29) were treated with the so-called Etappenlavage (multiple reexplorations and intra-operative lavage) and received a combination of three antibiotics (2 x 2 g cefotaxime; 2 x 500 mg metronidazole and 2 x 200 mg ofloxacin)., Results: Eight patients belonged to group A, 10 to group B, and 7 to group C. The mortality was 0% (group A), 20% (group B), and 29% (group C), respectively. The actual overall mortality of the whole group was 16% (4/25). The statistically expected mortality was 36%, according to the APACHE-II-Score (P = 0.0982).

Background & Aims: Treatment of spontaneous bacterial peritonitis currently involves intravenous antibiotic administration. To test the possibility of treating spontaneous bacterial peritonitis with oral antibiotics, oral ofloxacin was compared with intravenous cefotaxime in this infection., Methods: One hundred twenty-three cirrhotics with uncomplicated spontaneous bacterial peritonitis (no septic shock, grade II-IV hepatic encephalopathy, serum creatinine level of > 3 mg/dL, and gastrointestinal hemorrhage or ileus) were randomly given oral ofloxacin (64 patients) or intravenous cefotaxime (59 patients)., Results: Infection resolution rate was 84% in the ofloxacin group and 85% in the cefotaxime group. Peak serum levels and trough serum and ascitic fluid levels of ofloxacin and cefotaxime measured on days 3 (23 patients) and 6 (11 patients) of therapy were greater than the minimal inhibitory concentration of isolated organisms. Hospital survival rate was 81% in each group of patients. Blood urea nitrogen and hepatic encephalopathy at diagnosis were associated with prognosis. None of the 36 nonazotemic patients with community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy developed complications during hospitalization, and all were alive at time of discharge., Conclusions: Oral ofloxacin is as effective as intravenous cefotaxime in uncomplicated spontaneous bacterial peritonitis. Nonazotemic cirrhotic patients with uncomplicated community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy have an excellent prognosis and may be treated with oral ofloxacin without requiring hospitalization.

Purpose: Children with sickle cell disease are at increased risk for bacterial sepsis and, when febrile, are usually hospitalized for intravenous antibiotic therapy pending results of blood cultures. In this study, we prospectively identified a group of febrile patients with sickle cell disease who were at low risk for sepsis and treated them with outpatient therapy., Patients and Methods: Children identified as low risk for sepsis were treated with an initial dose of intravenous ceftriaxone, followed by outpatient therapy with oral cefixime, and were monitored for 14 days after the initial visit. Compliance was assessed by phone calls to parents and by analysis of urine samples., Results: In 107 eligible febrile episodes (80 patients) over a 21-month period, no patient developed sepsis. One child developed bacteremia 3 days after completing the course of cefixime, and one had splenic sequestration on the fourth study day. Both patients did well. Side effects of cefixime were modest, and overall compliance was excellent (approximately 95%), although urine samples were returned by only 56% of parents., Conclusion: We conclude that outpatient therapy is safe and effective in febrile patients with sickle cell disease who meet the criteria for a low risk of sepsis.

Pharmacodynamic principles have provided important tools to evaluate and compare antimicrobial agents, and well as to guide dosing. For beta-lactams, time above the minimum inhibitory concentration (MIC) has surfaced as the most important factor. However, the area under the inhibitory serum concentration time-curve (AUIC) may be superior when appropriate dosing intervals are selected. Although the target time over the MIC is unclear in humans even when concentrations remain continuously above the MIC, a higher AUIC predicts better clinical outcome up to a maximum. This article provides a pharmacodynamic assessment of 1- and 2-g doses of cefotaxime every 12 h. AUIC24 values and published MIC values for common pathogens (grouped into four groups based on MIC90) were used to predict organisms suitable for treatment with every-12-h regimes. Cefotaxime was inadequate for group 4 organisms including: Pseudomonas aeruginosa, Acienetobacter sp., and Enterococcus sp. Organisms such as Enterobacter cloacae, Serratia marcescens, Staphylococcus aureus, and B. fragilis may be suboptimally treated with cefotaxime every 12 h. Cefotaxime in doses of 1-2 g every 12 h should be useful in patients with normal renal function infected with organisms having MICs < 0.5 microgram/ml. This regimen should obtain AUIC24 values > 125 and ensure adequate time above the MIC. In patients with impaired renal function, because of a longer half-life and higher area under the curve, pathogens with MIC values in the 0.5-2 micrograms/ml range may be treated with cefotaxime every 12 h while maintaining AUICs > 125. Data are also presented for cefotaxime 2 g every 8 h alone and in combination with ofloxacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To compare the use of once-a-day cefpodoxime proxetil to once-a-day cefixime in the treatment of acute suppurative otitis media., Design: Randomized, multicenter, investigator-blinded., Setting: Outpatient., Patients: A total of 368 patients (age 2 months to 17 years) were randomized to receive either cefpodoxime or cefixime in a 2:1 ratio (245 cefpodoxime, 123 cefixime); 236 patients (155 cefpodoxime, 81 cefixime) were evaluable for drug efficacy., Interventions: Patients received either cefpodoxime proxetil oral suspension (10 mg/kg/day, once daily for 10 days) or cefixime oral suspension (8 mg/kg/day, once daily for 10 days)., Main Outcome Measures: Clinical evaluations were performed before treatment (study day 1), at an interim visit (study day 3 through 6), at the end of therapy (study day 12 through 15), and at final follow-up (study day 25 through 38). Microbiologic evaluations were performed at enrollment and whenever appropriate thereafter., Results: End-of-therapy clinical cure rates in evaluable patients were 56% for the cefpodoxime group and 54% for the cefixime group. Clinical improvement rates were 27% for both groups. Clinical response rates were not significantly different between treatment groups (P = .541; 95% confidence interval = -8.1%, 15.2%). At long-term follow-up, 17% of patients in the cefpodoxime group and 20% in the cefixime group had a recurrence of infection. Drug-related adverse events (eg, diarrhea, diaper rash, vomiting, rash) occurred in 23.3% of cefpodoxime-treated patients and 17.9% of cefixime-treated patients (P = .282)., Conclusions: These findings suggest that cefpodoxime proxetil administered once daily is as effective and safe as cefixime given once daily in the treatment of acute suppurative otitis media in pediatric patients.

Method: In this open, randomized and controlled multicenter study involving a total of 100 hospitalized patients with infections of the lower respiratory tract, including pneumonia, the efficacy and tolerability of sequential treatment with cefotaxime i.v./cefixime oral were compared with those of exclusively parenteral treatment with cefotaxime. The patients received either 2 x 2 g cefotaxime i.v. over a period of 7 to 10 days, or 2 x 2 g cefotaxime over a period of 48 to 72 hours followed by oral cefixime treatment (1 x 400 mg/day) for a further 5 to 8 days., Results: A total of 94 patients were evaluated for efficacy; in 93.6% of the evaluable patients in each treatment group, either a cure or improvement was obtained. In four patients in the cefotaxime group and five patients treated first with cefotaxime and then with cefixime, adverse reactions were observed. For three of these adverse reactions (diarrhea, nausea, aggravation of an pre-existing genital mycosis) an association with the respective test substance was considered to be at least possible.

The in vitro effects of cefixime and cefdinir (CI 983), two so-called third-generation oral cephalosporin derivatives, on human polymorphonuclear and mononuclear phagocyte functions (random migration and chemotaxis, specific and nonspecific phagocytosis, nitroblue tetrazolium reduction, superoxide production, microbicidal activity) were studied. Neither antibiotic, in the range of its attainable therapeutic concentration, exhibited any toxic effect on random migration, chemotaxis, metabolic activation and microbicidal mechanisms of phagocytic cells. Cefixime did not interfere in phagocytosis while cefdinir enhanced both phagocytosis frequency and index. The modulating effect on phagocytosis exerted by cefdinir was achieved at very low antibiotic concentrations (0.06 mg/l for polymorphonuclear leukocytes and 0.03 mg/l for monocytes) when non-opsonized zymosan particles were used as phagocytic challenge. Moreover, the effect was demonstrated both in the presence of cefdinir and after pretreatment of cells with the antibiotic and its removal by washings. As for specific phagocytosis, parameters were slightly increased by cefdinir but only the phagocytosis index was significantly improved in the presence of 2 mg/l of antibiotic.

This double-blind randomized study compared 3-day regimens of cefixime (400 mg once daily) and ofloxacin (200 mg twice a day) in the treatment of urinary tract infections in women. The respective clinical cure rates for the two groups of women were 89 and 92% after 7 days and 81 and 84% after 4 weeks. The respective microbiological cure rates (free of bacteriuria) for the two groups of women were 83 and 86% after 7 days and 77 and 80% after 28 days. A 3-day cefixime regimen seems to be as efficient as a 3-day ofloxacin regimen in the treatment of uncomplicated cystitis in women.

Previous studies using the chinchilla animal model demonstrated that the third generation cephalosporin cefixime (Suprax) with split dosing was as effective as ampicillin in sterilizing the middle ear cleft when infected with S. pneumoniae. In this investigator-blinded, randomized trial, a single daily dose of cefixime (8 mg/kg per day) performed as well as split dosing of cefixime (8 mg/kg every 8 h) and ampicillin (150 mg/kg every 8 h) in the time to sterilization of the middle ear cleft. No statistically significant differences were noted between groups in otoscopy or tympanometry. All antibiotic regimens performed better than saline control (P < 0.0001) with regard to time to sterilization of the middle ear cleft. The results of this study support the daily administration of cefixime as an effective agent for the treatment of otitis media due to its extended half-life and broad antibiotic spectrum.

Data are reviewed for safety from worldwide clinical trials of 4000 patients and postmarketing studies of 38,000 patients treated with cefixime, a broad-spectrum, bactericidal, beta-lactam stable, third-generation cephalosporin. Adverse experiences were similar in adults and children in all groups, with the most frequent side effects being gastrointestinal in nature. The reported frequency of gastrointestinal adverse experiences was higher in patients in US clinical trials when compared with French, German, or Canadian clinical trials or Canadian or US postmarketing studies. The overall incidence of side effects ranged from 2.7% to 48.2%, and the incidence of gastrointestinal events reported in these studies ranged from 1.4% to 38.6%. Patients infrequently discontinued treatment due to adverse events. The design and methods of data collection in US clinical trials may have resulted in higher frequencies of adverse experiences being reported in US trials when compared with the experiences reported in postmarketing studies and in clinical trials conducted outside of the United States. This is because of the more rigorous methodology used to elicit patient reporting of adverse events in US clinical trials compared with the methodology in postmarketing studies and foreign clinical trials.

VLBW-infants below 1500 g of birth weight have a quite high risk to acquire a nosocomial sepsis. 20-40% of all infants exhibit signs of nosocomial infection once during neonatal intensive care. The rate of infection is related to technique and amount of used invasive devices as to gestational age. Coagulase-negative staphylococci (CONS) and gram-negative organisms contribute most to these cases of sepsis. In a three phase study we tried to demonstrate the efficacy of different mechanisms to change the rate of nosocomial sepsis. During the first phase a strict hygienical protocol was enforced as isolation, care with sterile gloves and aseptic techniques in introducing and maintaining i.v. lines. In a second phase we started a randomized controlled study of prophylactic vancomycin (10 mg/kg/day in two doses). In a third phase we added an oral antibiotic regime with cefixime for all patients with positive cultures for gramnegative organisms under the hypothesis of translocation from the gut as the way of infection. During the first phase 23.7% of 76 patients enrolled acquired CONS-sepsis, 0.52% gramnegative sepsis. During the second phase (41 patients) 6 patients in the control group acquired CONS-sepsis, none in the vancomycin-group. The rate of gramnegative infections was not different (4 and 3 cases). During the third phase (vancomycin plus cefixime eventually in cases of positive stool cultures) no case of nosocomial sepsis occurred (35 patients, 11 positive cultures). The management used in phase 3 reduced the rate of nosocomial infections in VLBW-infants drastically.

The efficacy and safety of cefixime, the first oral third-generation cephalosporin, were evaluated in a multicenter clinical trial involving 118 adult patients with acute sinusitis or acute exacerbations of chronic sinusitis. Patients received a single daily dose of 400 mg of cefixime for a mean duration of 10 days; 106 patients completed a course of therapy. Clinical cure and improvement were achieved in 90% of these patients (61% cured and 29% improved). Among the patients evaluated again 2 weeks after therapy, 91% had a sustained clinical cure or improvement. Sinus exudate specimens were obtained from all patients by transantral puncture before therapy. Pathogens were isolated from 76 patients (66%), the most common pathogens being Haemophilus influenzae, alpha-hemolytic streptococci, and Streptococcus pneumoniae. Eighty-six percent of pathogens were presumed eradicated. Three patients discontinued therapy because of side effects. The most frequently reported adverse effects were gastrointestinal, with 20% of patients reporting diarrhea. Cefixime was effective in the treatment of bacterial sinus infections in adults and was well tolerated.

In this randomized, investigator-blinded multicenter study, tympanocentesis for acute otitis media with effusion in 137 ears from 108 children, 6 months to 12 years of age, revealed 84 definite pathogens and 32 potential pathogens. Twenty-nine aspirates from 23 subjects were sterile. Of the 116 isolates 42 (36%) were Streptococcus pneumoniae, 24 (21%) were Haemophilus influenzae, 9 (8%) were Moraxella catarrhalis, 9 (8%) were Streptococcus pyogenes and 1 (1%) was Staphylococcus aureus. Twenty-two (19%) definite pathogens produced beta-lactamase. Patients were randomized to cefixime (8 mg/kg/day daily) or cefaclor (40 mg/kg/day divided into two doses). Efficacy was determined by pneumatic otoscopy and tympanometry at the end of therapy visit on Days 11 to 14 and up to 4 weeks of follow-up. At end of therapy subjects with definite pathogens exhibited a satisfactory clinical outcome in 26 of 36 (72%) ears for cefaclor and 40 of 48 (83%) ears for cefixime recipients (P = 0.12). For ears with beta-lactamase-producing isolates there were no (0 to 12) cefixime failures but 4 of 10 cefaclor failures (P = 0.03). Diarrhea/loose stools were more frequent in cefixime (16 of 58) than cefaclor (4 of 50) recipients. One cefixime subject required discontinuation of drug. Overall efficacy for treatment of acute otitis media with effusion was not different; however, cefixime appeared more effective for infections caused by beta-lactamase-producing organisms.

Objective: To compare the efficacy of cefixime with amoxicillin in the treatment of acute otitis media in children., Design: Randomized, nonblinded study., Setting: General pediatric clinic at a university hospital in Texas., Participants: A volunteer sample of 201 children, aged 2 months through 6 years., Interventions: A 10-day oral course of cefixime (8 mg/kg per day administered once daily) or amoxicillin (40 mg/kg per day administered in three divided doses [every 8 hours])., Measurements/main Results: Tympanocentesis for bacterial culture was performed on all affected ears on enrollment and after 4 to 6 days of therapy. The patients were evaluated clinically 4 to 6 days after starting therapy, at the end of therapy, and 3 to 4 weeks after therapy was completed. Using Fisher's Exact Test, no significant difference was found between the two treatment groups for rate of clinical improvement or rate of eradication of Haemophilus influenzae and Streptococcus pneumoniae. However, combining the results from this study and two previously reported studies, cefixime was found to be more effective in eradication of H influenzae and less effective in eradication of S pneumoniae.

The cost-effectiveness of prophylaxis for colonic surgery with single dose cefotaxime plus metronidazole has been compared with that of three doses each of cefuroxime plus metronidazole, by analysing data from a previously published study supplemented with additional data on the hospital and community costs of wound infection after colonic surgery. The original trial included 942 patients having elective colonic surgery in 14 hospitals. The data on costs of wound infection were collected from a further 124 patients undergoing elective colonic surgery at Ninewells Hospital. All these patients received a three dose regimen of cefuroxime plus metronidazole. The Dundee patients received three injections of 0.75 g cefuroxime at 8-hourly intervals whereas the trial patients received a single dose of 1.5 g followed by two further doses of 0.75 g at 8-hourly intervals. The cefuroxime prophylaxis regimen used in the trial cost 24.16 pounds per patient more than the cefotaxime regimen. The components of the excess cost were drugs (15.18 pounds), equipment (6.14 pounds) and staff time (2.84 pounds). The median cost to the hospital of a wound infection was 978.04 pounds (95% CI 482.04 pounds to 1521.22 pounds). The components of the hospital cost of wound infection were: hotel costs 858 pounds (88%), dressing costs 83.02 pounds (8%) and drug costs (excluding prophylaxis) 37.02 pounds (4%). Only five patients received additional antibiotic treatment in the community, and only one required home visits from the District Nurse. Applying the difference in costs of prophylaxis as 21 pounds (costs of drugs plus equipment) and the cost per wound infection as 1000 pounds to the observed wound infection rate of 7% in the cefuroxime group, the wound infection rate in the cefotaxime group would have to be 2.1% higher for the two regimens to be equally cost-effective. The probability that such a difference in efficacy exists is 0.088. A model was developed to calculate the probability of equal cost-effectiveness over a range of costs of wound infection.

A multicenter, randomized, open label study compared the safety and efficacy of a single dose of oral lomefloxacin, a broad-spectrum antimicrobial agent of the quinolone class, to a single parenteral dose of cefotaxime, a third generation cephalosporin, for prophylaxis in transurethral surgery. Of the 230 patients initially recruited 182 were considered evaluable: 92 in the lomefloxacin group and 90 in the cefotaxime group. Both study groups were well balanced with respect to demographics and transurethral procedures. Efficacy and safety were evaluated with urine cultures, clinical laboratory evaluations and monitoring of adverse events. The success rate among the lomefloxacin patients was 98% versus 94% in the cefotaxime patients. The difference was not statistically significant. Adverse events, regardless of attributability, were reported by 16% of the lomefloxacin patients and 17% of the cefotaxime patients, respectively. Our results indicate efficacy and safety profiles of lomefloxacin equivalent to cefotaxime. Lomefloxacin has the economic advantage of an oral route of administration compared to the parenteral route of cefotaxime for prophylaxis in transurethral genitourinary procedures.

In a European open, multicentre, prospective clinical trial, 100 hospitalized adult patients (61 males; 18-91 years old (mean age 62] with bacterial pneumonia, diagnosed clinically and radiographically, were randomized to receive either oral temafloxacin 600 mg twice daily (n = 49) or intravenous cefotaxime 2 g thrice daily (n = 51). Signs, symptoms and chest radiographs were assessed during, at the end of therapy and at follow-up eight to ten days after the last dose. Patients were treated for a maximum of ten days. Sputum was obtained for culture before, during and after therapy. The clinical cure rate for the temafloxacin treatment group was 90%, the bacteriological cure rate was 91% and the radiological response rate was 95%. The respective rates for the cefotaxime-treated group were 92%, 96% and 100%. There were no significant differences between the treatment groups for clinical or microbiological outcome, premature study discontinuation, or adverse events. Oral temafloxacin was clinically and bacteriologically equivalent to intravenous cefotaxime in the treatment of hospitalized adults with bacterial pneumonia.

In a clinical study, 40 patients suffering from acute, recurrent or chronic sinusitis were treated with cefixime. The duration of therapy ranged from seven to 15 days. The dosage was 200 mg bid. In all patients cure or a marked improvement of clinical symptoms was noticed. Ten patients suffered gastrointestinal side effects which were classified as mild to moderate; however, all the patients received a full treatment course.

The pharmacokinetic parameters of cefixime were determined in healthy volunteers following oral administration of 200 mg cefixime as tablet, syrup and dry suspension, respectively. All three galenic formulations showed reliable absorption. Mean peak plasma concentrations amounted to 2.4-3.4 mg/l and were reached after 3.3-3.5 h. Mean terminal half-lives were 2.9-3.1 h. The mean areas under the plasma concentration-time curves ranged between 18 and 26 mg/l.h; 18-24% of the dose administered were recovered unchanged in the urine. The best bioavailability was obtained with the dry suspension followed by the tablet and the syrup. With respect to the ester pro-drug cephalosporins, cefuroxime axetil, cefetamet pivoxyl and cefotiam hexetil, cefixime exhibits higher plasma half-life and area under the curve as well as, comparable absolute bioavailability but consistently lower urinary recovery which indicates higher non-renal clearance.

The peritoneal macrophages of mice treated with lysozyme were studied by cytochemical assay. In single and repeated doses of 0.5-5 mg/kg lysozyme induced an increase in macrophage metabolism. This was evident from an increased activity of succinate dehydrogenase, NADP X N-DH and the enzymes catalyzing glycolysis typical of these cells (lactate dehydrogenase and alpha-glycerophosphate). The changes in the activity of the enzymatic systems were most pronounced in minute and less mature macrophages after repeated administrations of the drugs. In a dose of 50 mg/kg lysozyme somewhat decreased the activity of a number of the enzymes. In the doses optimal for the macrophage activity lysozyme had a low effect on the infection resistance and slightly increased the cephotaxim efficiency in experimental staphylococcal infection. This may be mainly due to the immunomodulating effect of lysozyme and its low effect on the large macrophages having the bactericidal effect.