Cefotiam Treatment in Children: Evidence of Subtherapeutic Levels.

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).

[A case of osteomyelitis due to Kingella kingae].

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.

Single-dose antibiotic prophylaxis is effective enough in colorectal surgery.

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.

Human Infection of Salmonella Matadi in Korea

No abstract available.

Three cases of pneumatosis intestinalis presenting in autoimmune diseases.

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.

Severe ulcerated 'bodybuilding acne' caused by anabolic steroid use and exacerbated by isotretinoin.

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.

Multidrug-resistant Neisseria gonorrhoeae with reduced cefotaxime susceptibility is increasingly common in men who have sex with men, Amsterdam, the Netherlands.

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.

Systemic use of antibiotics does not prevent postoperative infection in elective colorectal surgery: a randomized controlled trial.

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.

Development of breakpoints of cephems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in the peritoneal fluid of patients.

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.

[Fundamental study on the selection of antimicrobial prophylactic agents in abdominal surgery].

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.

Antibiotic prophylaxis in cerebrospinal fluid shunting: reassessment of Cefotiam penetration into human CSF.

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.

Antibiotic prophylaxis in radical prostatectomy: 1-day versus 4-day treatments.

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.

[Efficacy of cefotiam hexetil in acute maxillary sinusitis, with a short five day vs ten day treatment]. / Efficacité du céfotiam hexétil en cure courte dans le traitement des sinusites maxillaires aiguës. Comparaison de l'efficacité d'un traitement de cinq vs dix jours.

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.

Protection with antibody to tumor necrosis factor differs with similarly lethal Escherichia coli versus Staphylococcus aureus pneumonia in rats.

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.

Successful treatment of a Salmonella aortic arch aneurysm.

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.

Suitability of cefotiam and cefuroxime axetil for the perioperative short-term prophylaxis in tonsillectomy patients.

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.

[Prophylactic antibiotics in lumbar disc surgery: analysis of 1,030 procedures]. / Antibiotikaprophylaxe bei lumbalen Bandscheibenoperationen: Eine Analyse von 1,030 Operationen.

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.