Search

Background: Cefotiam, a second-generation cephalosporin, is a broad-spectrum antibiotic with good antibacterial action against both gram-negative and gram-positive bacteria. It is used widely in clinical practice, although bacterial drug resistance makes its clinical use problematic. The authors hypothesized that subtherapeutic concentrations of cefotiam leads to bacterial resistance. The present study was conducted to evaluate whether the standard cefotiam dosing regimen resulted in a subtherapeutic concentrations in children., Method: Data were prospectively collected from pediatric patients with suspected or confirmed community-acquired pneumonia who were receiving cefotiam at the standard dosing regimen (40-80 mg/kg, 2 or 3 times daily). A blood sample was collected after 70%-100% of the dosing interval, and plasma concentrations were determined by high-performance liquid chromatography using an ultraviolet detector., Results: The data from 88 patients (age, 3.0 ± 2.8 years; weight, 15.4 ± 8.3 kg) were used for analysis. The average of cefotiam concentrations was 0.06 mcg/mL (range: <0.05-0.79 mcg/mL). Most patients (n = 72, 81.8%) had concentrations below 0.1 mcg/mL; only 2 patients had concentrations higher than 0.4 mcg/mL., Conclusions: The standard dosing regimen for cefotiam resulted in extremely low plasma concentrations in children; such low concentrations may lead to antimicrobial drug resistance. Thus, an increase in cefotiam dosage in children to 80 mg/kg 4 times daily is recommended (maximum dose on the label).

Background: The aim of this study was to investigate the hypothesis that prevention of surgical site infection (SSI) is equally effective when patients receive single-dose (SD) or three-dose antibiotic prophylaxis with second-generation cephalosporin and metronidazole in elective colorectal surgery., Methods: Ninety-three patients were enrolled from May 2009 to November 2010. The SD group received only one preoperative prophylactic intravenous dose and the three-dose or multiple-dose (MD) group received one preoperative prophylactic and two additional post-operative doses of second-generation cephalosporin and metronidazole. The incidence of infectious complications (SSI of the incision site and organ/space) was compared in the two groups., Results: The overall post-operative infection rate did not differ between the two groups (16.7% in the SD versus 13.3% in the MD, P = 0.653). The incidence of SSI of the incision site and organ/space also did not differ between the groups (6.3% (3/48) versus 4.4% (2/45), P = 0.700; 4.2% versus 6.7%, P = 0.593, respectively). The number of antibiotics administered was not an independent risk factor for SSIs in multivariable analysis., Conclusions: SD antibiotic prophylaxis with second-generation cephalosporin and metronidazole is equivalent to a three-dose prophylaxis for preventing SSI in elective colorectal surgery. But further study would be needed to clarify this because of the small number of participants., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Kingella species including K. kingae are non-motile coccobacilli or short straight rods, and their normal habitats appear to be the upper respiratory and oropharyngeal tracts of humans. In recent years, K. kingae strains have been increasingly recognized as common causes of invasive infections in children at the age of less than 4 years. In Japan, however, invasive K. kingae infections including osteomyelitis have rarely been described. We incidentally encountered isolation of a K. kingae strain from intraoperatively obtained specimens from a previously healthy 44-month-old boy. He first consulted a nearby medical facility and a suspected diagnosis of osteomyelitis was made, after which the patient was then transferred to our Nagano Children's hospital. There was evidence of inflammation in his right calcaneus and toe walking was noted. He was treated with surgical drainage. An isolate grown on sheep blood agar with positive oxidase and negative catalase was biochemically characterized with the ID-Test HN20 (Nissui Pharmaceutical Co., Ltd., Tokyo, Japan) kit system together with genetic examinations involving sequencing the 16S rRNA gene, and the infection was finally identified as K. kingae. The patient was successfully treated with cefotiam (CTM) for the first 7 days followed by the administration of trimethoprim-sulfamethoxazole (ST) for an additional 2 months. The K. kingae isolate was confirmed as a sure causative pathogen by observing that the serum showed high agglutinin titers against the isolate. Accumulation of the case reports in Japan with the isolation of this species is essential for clarifying invasive infections due to K. kingae. Our case report is a noteworthy and useful piece of information.

Pneumatosis intestinalis (PI) is a comparatively rare disease characterized by the presence of intramural gas in the gastrointestinal tract. PI is known to be associated with several clinical conditions, such as pulmonary diseases, gastrointestinal diseases, and traumatic injury, as well as autoimmune disorders. In particular, PI is commonly seen in systemic sclerosis (SSc) but rarely in systemic lupus erythematosus and dermatomyositis (DM). In this report, we present three cases of PI presenting in autoimmune diseases, including DM, Sjögren's syndrome, and limited SSc, and further discuss its background characteristics.

We report a case of severe "bodybuilding acne" in a 22-year-old patient. Treatment with isotretinoin paradoxically led to exaceibation and occurrence of pyogenic granuloma-like lesions.

Antimicrobial resistance is an increasing problem in Neisseria gonorrhoeae (NG) treatment. Presently, third-generation parenteral cephalosporins, like ceftriaxone and cefotaxime, are the first option. Resistance to oral, but not to parenteral, third-generation cephalosporins has been reported previously. We analysed the microbial susceptibility (as minimum inhibitory concentration - MIC) of NG cultures obtained from high-risk visitors of the largest Dutch outpatient clinic for sexually transmitted infections (STI) in Amsterdam, the Netherlands. Among 1,596 visitors, we identified 102 patients with at least one NG isolate with reduced susceptibility to cefotaxime (0.125 microg/ml < MIC < or = 0.5 microg/ml). The percentage of NG isolates with reduced susceptibility to cefotaxime rose from 4.8% in 2006 to 12.1% in 2008 (chi2 17.5, p<0.001). With multivariate logistic regression, being a man who has sex with men (MSM) was significantly associated with reduced susceptibility to cefotaxime (p<0.001). Compared to susceptible NG isolates, those with decreased susceptiblity to cefotaxime were more often resistant also to penicillin (16.5% vs. 43.3%), tetracycline (21.5% vs. 68.9%) and ciprofloxacin (44.4% vs. 90.0%, all p<0.001). The increased prevalence of NG strains with reduced susceptibility to cefotaxime among MSM may herald resistance to third-generation parenteral cephalosporins. A considerable proportion of these strains show resistance to multiple antibiotics which could limit future NG treatment options.

We assessed the clinical impact of the systemic use of antibiotics on postoperative infection in colorectal surgery. Perioperative administration prevents postoperative infection: a statement which is based on the results of five randomized controlled trials performed in the 1970s and 1980s. Our study design was a randomized controlled trial. We created two groups, one using the systemic antibiotic cefotiam (CTM), and the other using no antibiotic as the control. The primary end point was the overall postoperative infection rate. There were 100 patients assigned to this study. The patients were divided into two groups; the control group consisted of 51 cases and the CTM group had 49 cases. The backgrounds of the patients in the two groups were not significantly different. The overall postoperative infection rate was 28/51 (54.9%) in the control group and 25/49 (51.0%) in the CTM group. The surgical site infection (SSIs) (superficial, deep, and space/organ ) were 23/51 (45.1%) in the control group and 20/49 (40.8%) in the CTM group. No significant difference was observed between the CTM group and the control group regarding postoperative infection after elective colorectal surgery.

We developed breakpoints for cephem antibacterial agents for intraabdominal infections based on pharmacokinetics (PK) and pharmacodynamics (PD) at the target site. Cefepime (CFPM), cefotiam (CTM), cefozopran (CZOP), and flomoxef (FMOX) were each administered to 8-10 patients before abdominal surgery, and venous blood and peritoneal fluid (PF) samples were obtained. The drug concentrations in plasma and PF were determined and analyzed using population pharmacokinetic modeling. Using the pharmacokinetic model parameters, a Monte Carlo simulation was conducted to estimate the probabilities of attaining the bacteriostatic and bactericidal targets (40% and 70% of the time above the minimum inhibitory concentration (T > MIC), respectively) in PF. The bacteriostatic and bactericidal breakpoints were determined as the highest MIC values at which the bacteriostatic and bactericidal probabilities in PF were > or =80%, which values varied with drug and dosing regimen. Site-specific PK-PD-based breakpoints for CFPM, CTM, CZOP, and FMOX are proposed, and should help us to select appropriate cephems and design their dosing regimens for intraabdominal infections.

Most infections after abdominal operations are endogenous and occur by disseminating bacteria present in the intestinal tract during operation. The risk of developing surgical site infection after abdominal operations is related to the extent of intestinal contamination during operation and to the density and type of bacteria in the intestinal tract. Although antimicrobial prophylactic agents must be active against contaminating bacteria during operation, it should not cover all contaminating bacteria but Staphylococcus aureus except MRSA, Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus spp. and Bacteroides spp. As the isolation rate and type of bacteria from primary abdominal infections such as perforated peritonitis and biliary tract infection are resemble to those of bacteria contaminating during operations, antimicrobial prophylactic agents could be chosen considering activities against bacteria isolated from primary infections. According to the isolation rates of these bacteria and antibiotic susceptibilities, cefotiam (CTM) is considered to have most strong activities as prophylactic agent for abdominal surgery, followed by cefmetazole (CMZ) and cefazolin (CEZ), in this order. In order to establish the fundamental principle of antimicrobial prophylaxis in surgery, these results should be evaluated by clinical prospective randomized studies in the near feature.

Objects: Shunt infection is a major complication of shunt implantation. Numerous clinical studies give evidence that antibiotic prophylaxis is efficacious in preventing infections after cerebrospinal fluid shunting. In CSF shunting, antibiotics need to reach sufficient concentrations not only in the blood shielding the operative field but also in tissues and the CSF compartment. Cefotiam is widely used for prophylaxis in neurosurgery. Some clinical trials report that this beta-lactam is able to penetrate considerably into the CSF. However, these studies include disease patterns which are most likely to be associated with a pathological permeability of the blood-brain barrier. Therefore, this study was designed to investigate the extent of penetration of Cefotiam into human CSF in patients without morphological disruption of the blood-brain barrier., Methods: The penetration of Cefotiam into human CSF was investigated in 23 patients without morphological disruption of the blood-brain barrier undergoing CSF shunt surgery. 2 g Cefotiam was administered prior to surgery as a short-term infusion for a period of 15 min. Samples of blood and CSF were collected intraoperatively. The concentrations of Cefotiam were determined by bioassay., Results: All patients (n=23) showed moderate to high plasma levels of Cefotiam (range: 19.8-146.2 mg/L); the pharmacokinetic profiles in blood accorded well with published data. In contrast to earlier studies, no Cefotiam was detected in CSF., Conclusion: This study clearly demonstrates that Cefotiam does not penetrate through an intact blood-brain barrier into human CSF. Although Cefotiam has been shown to be valuable for the perioperative prophylaxis of shunt infection, other antibiotics might be superior if they are capable of entering the CSF. Further studies are required to address this assumption.

Objective: The standard protocol of antibiotic prophylaxis in radical prostatectomy remains to be established. We retrospectively compared the occurrence of perioperative infections following radical prostatectomy between two different protocols of antibiotic prophylaxis., Methods: This study included 106 cases of radical retropubic prostatectomy managed on the clinical pathways. Two different protocols of antibiotic prophylaxis were used in otherwise identical pathways. Between January and December 2004, 50 patients received a second generation cephem, cefotiam, for 4 days, beginning 30 min before surgery (4-day group), whilst between December 2004 and July 2005, only two doses of cefotiam were given on the day of operation in 56 patients (1-day group). The incidence of surgical site infection (SSI) and remote infection (RI) was retrospectively investigated., Results: Superficial incisional SSI occurred in one (1.8%) patient in the 1-day group, whereas no patient in the 4-day group developed SSI. No RI was observed in either the 1-day or 4-day group. Intravenous antibiotics were administered besides the pathway in a patient in the 1-day group because unexplained fever more than 38 degrees C continued postoperative day (POD) 2 through POD 4 without signs of SSI or RI. Excluding this case, postoperative more than 38 degrees C was rare and transient after POD 2., Conclusion: The incidence of SSI and RI was low and not significantly different between the 1-day and 4-day groups. Therefore, the 1-day protocol of prophylactic antibiotic treatment seems adequate for preventing perioperative infections in radical prostatectomy.

Objective: The aim of this multicentric, randomized, double blind study with direct individual benefit, was to compare two therapeutic regimens of cefotiam hexetil administration, 5 days vs 10 days, in acute maxillary sinusitis., Method: The study was conducted in ambulatory patients treated by general practitioners according to AFSAPS (French agency for sanitary safety) guidelines for treatment of acute maxillary sinusitis. Five hundred and fifty three GPs included 1042 patients presenting with acute maxillary sinusitis in the study from December 2000 to July 2001. Patients were randomly treated with cefotiam hexetil 200 mg bid over a 5 day period followed by 5 days of placebo, or with cefotiam hexetil 200 mg bid over a 10 day period., Results: No significant difference was noted in each treatment group. Radiography performed in 72.2% of included patients confirmed the diagnosis in 78.8% of the cases. No significant difference occurred in the number and percentage of cured patients. In the ITT analysis (1018 patients) the clinical cure rates were respectively 85.5% and 85.3% in the 5 day and in the 10 day treatment groups, In the PP analysis (800 patients) the clinical cure rates were respectively 88.6% in each group. The low incidence of adverse effects (3.36%) was confirmed in both groups., Conclusion: A 5 day course of cefotiam hexetil 200 mg bid is as effective as a 10 day course in the treatment of acute maxillary sinusitis in adults.

Background: Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia., Methods: Rats (n = 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h., Results: Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P > or = 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P = not significant for all). Antibody to TNF reduced mortality rates (relative risk of death +/- SEM) with both E. coli (-1.6 +/- 0.6; P = 0.006) and S. aureus (-0.5 +/- 0.04; P = 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P = 0.09). Compared with controls, similarly (P = not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P < or = 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P = 0.04) and increased serum interleukin-6 concentrations (P = 0.003)., Conclusion: Antibody to TNF improved host defense and survival rates with both lethal E. coli and S. aureus pneumonia, but protection was greater with E. coli, where TNF concentrations were higher than with S. aureus. The efficacy of antiinflammatory agents in sepsis may be altered by bacteria type.

A 52-year-old man hospitalized for hoarseness and chest pain was found in chest computed tomography to have an impending aortic arch aneurysm rupture. Laboratory studies showed the presence of severe inflammation. Based on a clinical diagnosis of infected aortic arch aneurysm, we conducted total arch replacement. Salmonella was identified in the aneurismal wall and antibiotics were administered long-term. The postoperative course was uneventful. The patient was discharged on postoperative day 48. He has remained afebrile and asymptomatic in the 10 months since surgery but continues to take 300 mg/d of oral levofloxacin.

Objective: The purpose of this study was to investigate the efficacy of perioperative antibiotic administration in the prophylaxis of wound infection in lumbar disc surgery., Methods: In 1989, 541 conventional lumbar discectomies were performed to treat nucleus pulposus prolapse in 533 patients at the neurosurgical department of the Benjamin-Franklin-Hospital (Free University of Berlin). Each patient received 2 g of the antibiotic Cefotiam intravenously at induction of anesthesia. During the previous year no antibiotic was administered in 636 similar operations (in 628 Patients). Acquisition of data was performed retrospectively. After statistical stratification there remained 492 procedures in 461 patients in the prophylaxis group and 538 procedures in 475 patients in the control group. Regarding patients age, duration of the surgical procedure and distribution of individual surgeons there were no significant differences between these two groups., Results: The rate of infection was 0.2 % (n=1) in operations performed after antibiotic administration versus 2.8 % (n=15) in procedures without antibiotic prophylaxis. This difference is statistically significant (p < 0.0001)., Conclusion: In accordance with the reviewed literature, this study confirms that one preoperative intravenous ('single shot') administration of Cefotiam is effective in decreasing the rate of postoperative wound infections in lumbar disc surgery.

The efficacy of the perioperative short-term prophylaxis with cefotiam (CAS 66309-69-1) and cefuroxime axetil (CAS 64544-07-6) was analysed by the assessment of the pharmacological kinetics in the serum and the tonsil tissue in 50 patients with recurrent tonsillitis. Twenty-four patients received 1 g cefotiam by the intravenous route 30 min to 4 h before the tonsillectomy, and 26 patients received 250 mg cefuroxime axetil orally 1 to 6 h before the tonsillectomy. Bactericidal serum levels were reached for cefotiam up to 4 h after intravenous application and for cefuroxime axetil up to 3 h after oral application. In the tissue of the tonsil there were proved levels which were definitely above the MIC 90 (MIC = minimum inhibitory concentration) known for the clinically relevant germs for cefotiam after 30 min up to 2 h, for cefuroxime axetil after only 2 h. Considering the distribution areas, the capacity of the protein binding and the microbiological measuring methods, one can expect an efficient antibiotic coverage after an intravenous one-shot bolus injection of 1 g cefotiam from 30 min to 4 h and after oral application of 250 mg cefuroxime axetil on an empty stomach from 1 to 6 h. Because of the short duration of a tonsillectomy and the serum and tonsil tissue kinetics cefotiam and cefuroxime axetil are suitable for the perioperative antibiotic prophylaxis of high-risk patients.

A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among urologists in Japan in the period from April to July 2000. Sixty-three of the 87 urologists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Escherichia coli, Staphylococcus spp., Klebsiella pneumoniae and Bacteroides fragilis group. Use an AMP agent that achieves a bactericidal concentrations in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. The newer agents should be considered as a therapeutics for postoperative infections. The therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for clean operations are cefazolin (CEZ), followed by cefotiam (CTM) and piperacillin (PIPC), in this order. For clean-contaminated operations, the most commonly used agent is CTM, followed by PIPC and CEZ.

A prospective, randomized study was performed in order to evaluate the effect of cefotiam in the prevention of postoperative infectious morbidity in patients undergoing low-risk elective cesarean section. A total of 146 patients were randomly assigned to receive either intraoperative single-shot prophylaxis with 2 g cefotiam (study group, n =76) or no prophylaxis (control group, n=70). Due to a higher rate of urinary tract infections, the incidence of infectious morbidity after cefotiam prophylaxis was higher in the study group than in the control group (16% vs. 9%, P=0.1). Postoperative infectious morbidity following low-risk elective cesarean section cannot be reduced by intraoperative cefotiam prophylaxis.

Background: Although postoperative infections continue to be a major problem in gynecologic surgery, there is still no consensus on the efficacy of antibiotic prophylaxis., Methods: This prospective randomized trial was conducted to investigate the prevention of major operating site infections after nonlaparotomy surgery, with treatment regimens as follows: the first group of patients received 2 g of intravenous cefotiam dihydrochloride (CTM) on the induction of anesthesia, while the second group received 100 mg of oral cefpodoxime proxetil (CPDX- PR) twice daily, from day 0 to day 2., Results: Nineteen of the 207 patients enrolled developed postoperative infections diagnosed by our simple criteria for postoperative infection. The frequency of febrile morbidity was not significantly less in patients who received CTM (9 cases; 8.6%) as compared with those in the CPDX-PR group (10 cases; 9.8%) (p = 0.56)., Conclusion: The administration of oral CPDX-PR (100 mg, twice daily, for 3 days) appears to be a safe, cost-saving, convenient prophylaxis which reduces overall expense., (Copyright 2000 S. Karger AG, Basel.)

Acute phlegmonous gastritis is a rare disorder in which bacterial infection occurs in the gastric wall. Gastrectomy involving the affected area has been thought to be an effective form of treatment. The authors report a case of a 32-year-old woman who had severe upper abdominal pain without signs of peritoneal irritation. Endoscopy showed edematous and reddened gastric mucosa with a mass lesion in the gastric antrum. Endoscopic ultrasonography showed thickening of the antral wall and a low-echoic mass in the gastric antrum, thought to represent a fluid collection. White pus was aspirated from the mass. Localized type of acute phlegmonous gastritis with a gastric abscess was diagnosed. Culture of the pus showed Streptococcus pneumoniae. Through early diagnosis without laparotomy, the patient's gastritis was successfully treated with antibiotics alone.

We report a case of clitoral hypertrophy of unknown origin. A 3-year-old girl showed clitoral hypertrophy at birth. Biochemical analysis of peripheral blood and endocrinological examinations were normal. Other virilizing symptoms were not recognized. Clitoroplasty was carried out, and the clitoris has not enlarged 20 months after the operation. Her mother was administered cefotiam and terbutaline (beta-stimulant) during pregnancy because of threatened abortion. No virilizing agents such as progesterone were used during pregnancy.

Objective: A prospective trial was performed to propose a suitable antimicrobial prophylaxis in patients undergoing transurethral resection of the prostate (TUR-P)., Subjects and Methods: Patients who underwent TUR-P due to symptomatic prostatic hyperplasia between April 1995 and February 1996 were included. Based on the results of urinalysis obtained within preoperative 3 days, the patients were classified into Group I (less than 5 WBC/hpf and bacterial count of less than 10(4) CFU/ml in urine specimen), and Group II (5 or more WBC/hpf or bacterial count of 10(4) or more CFU/ml in urine specimen). Furthermore, each group was randomly subdivided into Group A and Group B according to the period of antimicrobial administration. As prophylactic antimicrobials, cefazolin (CEZ) was used in Group I and CEZ or cefotiam (CTM) in Group II. The antimicrobial was administered only on the day of operation in Group IA (n = 92), for 3 days in Group IB (n = 96), 2 days in Group IIA (n = 37), and 4 days in Group IIB (n = 30). On the day of operation, the antimicrobial was infused immediately before the operation. The presence or absence of pyuria, bacteriuria and febrile infection, and the period required for normalization of the urinalysis were the major points evaluated here., Results: No significant differences were observed in any parameters with respect to the period of administration of antimicrobial between the groups, but in both Group I and Group II, the incidence of febrile infection was higher in the groups with shorter antimicrobial administration periods. The mean period for normalization of the urinalysis required 68.4, 68.6, 65.2 and 58.2 days in Group IA, Group IB, Group IIA and Group IIB, respectively., Conclusion: It is concluded that 3 or 4-day administration of first or second generation parenteral cephems is generally acceptable regimen for antimicrobial prophylaxis in patients undergoing TUR-P.

Case Report: Oleic acid and oleate are pulmonary toxins used to create laboratory models of acute respiratory distress syndrome, but there is little information on human toxicity. We report the intentional ingestion of 50 mL sodium oleate 20% by a 22-year-old woman with no symptoms for the first 2 days after ingestion. Her respiratory status deteriorated rapidly on day 3 progressing to acute respiratory distress syndrome (PaO2/FIO2 < 100 mm Hg) on day 4. Treatment with high-dose steroids and intensive respiratory support including high-frequency jet ventilation were associated with gradual but complete recovery by day 39. The delayed onset of symptoms suggested that the lung injury was due to the systemic circulation of oleate to the lungs rather than to direct aspiration. In oral poisoning by sodium oleate, the lung is the first and most lethally affected target organ in humans. This case demonstrates that ingestion of a relatively small amount of sodium oleate can cause delayed, progressively severe, lung injury.

As perioperative prophylaxis for major orthopedic operations 81 patients were given the fixed combination of ampicillin (1 g)/sulbactam (0.5 g) or cefotiam (2 g) as short infusions. The three beta-lactams were rapidly distributed into the different tissues and their pharmacokinetic profiles were found to be very similar. It was noteworthy that ampicillin, sulbactam and cefotiam penetrated within minutes, not only into skin, fat and muscles, but also into bone. Thus 0.25 h after starting the infusion the following mean concentrations were measured in bone: 21.8 +/- 10.5 mg/kg ampicillin, 4.9 +/- 2.2 mg/kg sulbactam and 19.4 +/- 10.6 mg/kg cefotiam. For a period of at least 2 h the concentrations measured in serum and in the different tissues affected by the operation (skin, fat, muscle, bone) were above the MICs for pathogens which are involved in postoperative wound infections. On the basis of pharmacokinetic data, ampicillin/sulbactam and cefotiam seem about equally suitable for perioperative prophylaxis in major orthopedic operations.

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against chronic lower respiratory tract infections, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as a control drug. RIPM-AC was orally administered at 200 mg, and CTM-HE at 400 mg, t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 202, of which 151 cases (RIPM-AC group: 75, CTM-HE group: 76) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent+good) were 85.3% (64/75) in the RIPM-AC group and 80.3% (61/76) in the CTM-HE group. There was no significant difference between the two groups, hence the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 50.0% (13/26) in the RIPM-AC group and 75.0% (18/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 10 cases (11.0%) of the RIPM-AC group and 10 cases (10.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 8 cases(9.5%) of the RIPM-AC group and in 14 cases (16.7%) of the CTM-HE group. There were no significant differences between the two groups in the incidence of side effects and abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 73 cases (80.2%) and CTM-HE in 71 cases (77.2%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 79.5% (62/78) in the RIPM-AC group and 76.9% (60/78) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of chronic lower respiratory tract infections.

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against bacterial pneumonia, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as the control drug. Both RIPM-AC and CTM-HE were orally administered at 200 mg t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 208, of which 152 cases (RIPM-AC group: 73, CTM-HE group: 79) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent + good) were 91.8% (67/73) in the RIPM-AC group and 94.9% (75/79) in the CMT-HE group. There was no significant difference between the two groups, and the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 84.6% (22/26) in the RIPM-AC group and 91.7% (22/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 9 cases (9.6%) of the RIPM-AC group and 5 cases (4.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 23 cases (26.7%) of the RIPM-AC group and 15 cases (15.6%) of the CTM-HE group. There was no significant differences between the two groups in the incidence of side effects nor of abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 64 cases (68.1%) and CTM-HE in 82 cases (80.4%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 86.5% (64/74) in the RIPM-AC group and 92.5% (74/80) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of bacterial pneumonia.

97 patients undergoing breast surgery received either 2 g cefotiam or 1200 mg clindamycin as i.v. singleshot application in the course of an open randomised comparison of parallel groups to evaluate the efficacy and tolerability of both antibiotic regimens. Both regimens proved to be well to-lerated and equally suitable for the prophylaxis of postoperative infections in breast surgery.

A 55-year-old man was admitted to our department one month after resection of rectal carcinoma, with complaints of fever and general malaise. Shock developed rapidly after admission. The chest X-ray film and computed tomography showed diffuse small nodular shadows and bilateral pleural effusion. Septic lung caused by Methicillin-resistant Staphylococcus epidermidis (MRSE) was diagnosed from the results of a bacteriological study. This bacteria is a Coagulase Negative Staphylococcus (CNS). Chemotherapy with Minocycline and Cefotiam was effective. Characteristic radiologic features of this case may be related to the early stage of adult respiratory distress syndrome (ARDS) and septic pulmonary microembolism.

A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS)

The efficacy of a single dose of cefotiam, a cephalosporin of the second generation, as prophylaxis for postoperative infection was analyzed in a prospective randomized study of 129 patients undergoing cerebrospinal fluid shunting. The main focus of interest was the rate of shunt infection requiring operative shunt removal. Data were evaluated in the total group and subgroups formed for normal and high risk patients, respectively. The overall rate of shunt infection was 7.5% in the cefotiam group and 12.9% in the control group. In the high risk subgroup infection rate was 14.3% with and 26.3% without cefotiam as opposed to 4.3% and 6.9%, respectively, in the normal risk subgroup. Although our results do not reach statistical significance, there is a noticeable difference of infection rate between those patients who receive the antibiotic and those who do not. Therefore, we favor single dose antibiotic prophylaxis in shunting procedures.

The clinical efficacy of a new aminoglycoside antibiotic, arbekacin (ABK), was studied in surgical patients who had been infected with methicillin-resistant Staphylococcus aureus (MRSA). Six cases of pneumonia, 2 of wound infections and 2 of intra-abdominal infections were treated by ABK alone or ABK together with beta-lactam antibiotics such as imipenem/cilastatin or cefotiam. The overall clinical efficacies against these MRSA infections were excellent in one case, good in 6 and poor in 3. In six cases treated by ABK alone, good clinical responses were obtained in 4 cases. Among 4 cases that received combination therapy with ABK, good responses were obtained in 3 cases. No adverse reactions were found in ABK monotherapy or in combined therapy. These data suggested that ABK is an effective antibiotic on surgical infections caused by MRSA.

Silent intrauterine infection as cause of preterm labour should be recognised early by measuring C-reactive protein (CRP) levels in the maternal serum. Ensuing antibiotic therapy may not only cause gestational prolongation, but also has a positive effect on pathology during the puerperal period. Consequently, we examined the rate of infectious puerperal complications of 181 patients who suffered from so-called idiopathic preterm labour. 84 patients showed normal CRP-levels at the onset of tocolysis (< 5 mg/l); an elevated level was found in 97 patients (> 5 mg/l). Patients with elevated CRP-levels and supplemented antibiotic therapy during pregnancy (n = 51) showed significantly fewer symptoms of postpartal endometritis than women with similarly elevated CRP-levels but without antibiotics (n = 46). This effect was not produced when preterm labour was associated with normal CRP-levels. Patients with premature contractions and elevated CRP-values at the onset of tocolysis seem to benefit from the antibiotic therapy during pregnancy because they show reduced infectious complications throughout the puerperal period.

Efficacy and safety of a new oral third generation Cephalosporin, Cefotiam Hexetil (CTM) 200 mg bid were compared with those of Cefixime (CX) 200 mg bid over 10 day duration of treatment. One hundred and twenty two ambulatory adults suffering from chronic sinusitis were randomized by ENT specialists in this multicentre prospective double blind, doubled dummy study. Sinusitis diagnosis evocated in front of fascial pain, purulent nasal discharge and/or obstruction was confirmed with sinus X-ray. Use of antibiotics or corticosteroids concomitantly or 15 days prior inclusion represented one of the major exclusion criterion. One hundred and seventy one patients were evaluated for efficacy analysis (62 and 59 respectively in CTM and CX groups). Regarding demographic data, clinical and radiological signs, the two populations were comparable at inclusion excepted for sex and weight (female: 73% in CTM group versus 47% in CX group). The overall clinical success rate at the end of treatment (cure+improvement) was not significantly different between the two groups (CTM: 82% versus CX: 80%). The incidence of adverse events was less frequent in the CTM group (14.5% versus 19%). In conclusion, CTM 200 mg bid is as efficacious and as well tolerated as CX 200 mg bid in the treatment of chronic sinusitis in adults.

Cefotiam hexetil is a prodrug of cefotiam. The concentrations of cefotiam in plasma and sinus secretions were determined in 18 patients (10 males, 8 females, aged 39.3 +/- 13.0 years) with chronic sinusitis. All patients received two 200 mg oral doses of cefotiam hexetil 12 h apart and were divided into four groups according to the time which elapsed between the last dose and collection of secretion samples. The last dose was given 2 h (group I), 3 h (group II), 4 h (group III) or 6 h (group IV) before sinus puncture. Cefotiam concentrations were measured by high-pressure liquid chromatography and microbiological assay, results being very similar with both methods. Mean concentrations of cefotiam with the standard deviation in sinus exudates were 1.04 +/- 0.60 mg/l at 2 h (n = 6), 1.04 +/- 0.33 mg/l at 3 h (n = 4), 0.75 +/- 0.74 mg/l at 4 h (n = 4) and < 0.10 mg/l at 6 h (n = 4). Mean sinus fluid concentrations were higher than mean plasma concentrations in all groups. These results suggest that cefotiam concentrations higher than the MICs for common pathogens are found in sinus secretions up to 4 h after oral administration of cefotiam hexetil.

Forty-one hospitalized patients were randomized to be treated with cefuroxime (4.05 g/die) or cefotiam (5.30 g/die). Several patients received additionally furosemide (0.5 mg/kg body weight) intravenously. Serum creatinine and creatinine clearance did not show significant differences during versus after treatment in any of the groups. Cefotiam or cefotiam/furosemide treated patients displayed higher proteinuria and higher urinary excretion of lysosomal enzymes (leucine aminopeptidase) than patients treated with cefuroxime or cefuroxime/furosemide. Our data indicate higher tubulotoxicity of cefotiam compared to cefuroxime.

In 60 patients suffering from acute ear, nose and throat infections the efficacy and safety of cefotiam hexetil (SCE-2174, CAS 61622-34-2) which is a pro-drug of cefotiam was studied. The clinical success rate (improvement/cure) achieved with a daily administration of 600 mg was 90%. In 63% of the cases being evaluable for bacteriological response an eradication of the causative pathogens at the end of the treatment period was found. The majority of the patients tolerated well the compound. Side effects which were possibly, likely or definitely related to the treatment were observed in 12 patients. In 7 of these patients the treatment had to be stopped due to side effects which is equivalent to an intolerance rate of 12%. The data obtained in the present study indicate that cefotiam hexetil is a potent drug for the treatment of acute and acute on top of chronic infections of the upper aerodigestive tract.

A prospective randomized trial has compared 3 policies of antibiotic prophylaxis in biliary surgery. Patients considered to be high-risked against postoperative infection were randomly allocated to 2 groups: in group CTM-H, patients were given cefotiam; in group CMX-H, patients were given cefmenoxime. Patients free of risk factors (group CTM-L) were all given cefotiam. The high-risk factors adopted in this trial were; emergency surgery, presence of jaundice or cirrhosis, malignant disease, diabetes mellitus, age over 70, recent biliary tract infection, choledocholithiasis, and previous biliary surgery. Postoperative infection occurred in 2.1% (4/190) in the CTM-L group, which was lower compared to 15.5% (11/71) of the CMT-H group (p less than 0.01), and 11.3% (8/71) of the CTM-H group (p less than 0.01). The rates of bacterial isolation from intraoperative bile culture and wound swab were significantly high in the two high-risk groups compared to the low-risk group, but is was not different within the two high-risk groups. These findings suggest that while cefotiam is appropriate for prophylaxis for the low-risk patients, the utmost care should be taken in the high-risk patients to prevent intraoperative contamination along with prophylactic antibiotic therapy which covers the bacteria isolated from the bile.

Because of the rare incidence of liver abscess in childhood and of extremely rare observed Aeromonas hydrophila as pathogen of such a disease we report on a 14 7/12 year old girl with a liver abscess. For the last 4 years she had to be enrolled in chronic hemodialysis. The treatment comprised opening of the abscess cavity and drainage, and antibiotic therapy with cefotiam. We were unable to isolate Aeromonas hydrophila in the environment of the hemodialysis center. Some aspects of clinical importance of liver abscess in childhood and of Aeromonas spp. as pathogens in human infections are discussed.

A double blind study was conducted to objectively evaluate the usefulness of Cefuzonam (CZON) in the treatment of bacterial pneumonia and lung abscess. Cefotiam (CTM) was used as a control drug. Each drug was administered by intravenous drip infusion at 1 g at a time, twice daily, for 14 days as a rule. The results are as follows: 1. Enrolled in this study were 145 cases in total, comprising 72 of CZON group and 73 of CTM group. Of the total cases, 109 (53 of CZON group and 56 CTM group) were evaluated for clinical efficacy by the evaluation committee. Exclusion rate and background of patients were not significantly different between the two groups. 2. Clinical effectiveness assessed by the committee showed the efficacy rates of 84.9% (45 cases out of 53) for the CZON group and 83.3% (47 cases out of 56) for the CTM group, with no significant difference between the two groups. 3. The bacteriological eradication rates were 89.5% (17 strains out of 19) for the CZON group and 78.3% (18 strains out of 23) for the CTM group, with no significant difference between the two groups. 4. The incidence of side effects was 5 cases (7.5%) for the CZON group and 3 cases (4.2%) for the CTM group. The incidence rate of laboratory test abnormality was 28.4% (19 cases out of 67) for the CZON group and 31.3% (12 cases out of 67) for the CTM group. There was no significant difference between the two groups. 5. Usefulness rates calculated by the committee were 79.2% (42 cases out of 53) for the CZON group and 76.8% (43 cases out of 56) for the CTM group. There was no significant difference between the two groups. These results show that CZON is a useful drug in the treatment of bacterial pneumonia and lung abscess.

The combination of carumonam (CRMN) and cefotiam (CTM), expected to have a broader spectrum of coverage in connection with urinary tract infections, was evaluated for its effectiveness and safety at the Department of Urology, Osaka University Hospital and 17 affiliated hospitals. CRMN and CTM were given together to 109 patients with complicated urinary tract infections (UTI), of whom 65 cases satisfied the "Criteria of UTI Committee for the Evaluation of Drug Efficacy in the UTI (3rd Ed.)", which was modified by adopting the midstream urine data for women. CRMN and CTM were administered by drip or one-shot infusion at a total daily dose of 4 g (equally mixed 1 g plus 1 g each, twice a day) for 5 consecutive days or longer. The overall clinical efficacy rate in the 65 cases of complicated UTI was 72%, estimated by the criteria cited above. The efficacy rate according to the infection type groupings was 72% for the 29 patients in the 1st group, 100% for the 1 patient in the 2nd group, 100% for the 7 patients in the 3rd group, 83% for the 6 patients in the 4th group, 50% for the 14 patients in the 5th group and 75% for the 8 patients in the 6th group. The disappearance rate of both urinary Gram positive cocci and Gram negative bacilli was 83.3%. Fifteen strains appeared after the treatment, only 4 of which were Gram positive cocci. Among the 109 patients treated with CRMN+CTM, no subjective side effects were recorded and the abnormalized laboratory findings observed were: eosinophilia in one patient, increases in both GPT and GOT in one patient, and lowered creatinine clearance in one patient. With a broader spectrum and safe regimen, the combination of CRMN/CTM is recommended as the first choice against complicated UTI.

This prospective, randomized study was carried out in the Orthopaedic Traumatology service, Hôpital Bichat, from March 1987 to June 1989 in order to compare the efficacy of an antibiotic prophylaxis either with cefotiam in "flash" administration or with cefazolin in continued administration (48 hours). This study included 207 patients undergoing a total hip or knee-joint replacement. The both groups (89 patients with cefotiam, 118 patients with cefazolin) were comparable with regard to all criteria. The general and local evolution did not show statistical significant difference in the occurrence of complications in the both groups. No infectious complication occurred after the operation for the two groups. Then, cefotiam, in "flash" administration (2 g with the anesthetic induction) proves to be as effective as a conventional antibiotic prophylaxis with cefazolin in the prevention of infectious complications in orthopaedic surgery.

In 48 patients suffering from giant renal calculi a percutaneous nephrolitholapaxy was done. The use of perioperative antibiotic prophylaxis using aminoglycosides or cephalosporins was effective in reduction of postoperative urinary tract infections.

By using checkerboard titrations the effect of cefotiam combined with different beta-lactam antibiotics on fifty strains of Enterobacteriaceae moderately susceptible (minimal inhibiting concentration greater than or equal to 8 mg/l) or resistant (minimal inhibiting concentration greater than or equal to 64 mg/l) to cefotiam was evaluated. The following compounds were tested: cefamandole, cefazolin, cefmenoxime, cefotaxime, cefotiam, ceftazidime, cefuroxime, mecillinam and piperacillin. The synergistic effect varied markedly. The combination cefotiam-mecillinam showed the highest rate of synergistic activity. Antagonism was found in 1% of the combinations.

Unlabelled: Over a period of 7 months, 50 patients underwent a trans-urethral resection of the prostate (TURP), this intervention is classified as "clear-contamined". The antibiotic prophylactic protocol, the subject of this study, was the following: cefotiam 2 g IV with the induction of anesthesia, 1 g 3 hours later and 1 g IV with the removal of the urethral catheter., Results: there were 3 early post-operative urinary tract infections, one of these patients was symptomatic, at the time of removal of the urethral catheter. Most of these infections were due to Enterococcus faecalis bacteria. There was 4 late post-operative symptomatic urinary tract infections at days 15, 20, 50, and 120 respectively. All these late infections were due to Streptococcus faecalis. In total, there was a 10% rate of urinary tract infections in the critical 30 days period following the TURP. All the blood cultures were negative. These results lead us to conclude that the short term preventive treatment using the cefotiam, cephalosporin which has a strong prostatic tissue penetration, reduces the rate of post TURP urinary tract infections.