Development and Validation of a Risk Scoring System for Cephamycin-Associated Hemorrhagic Events.

Cephamycin-associated hemorrhages have been reported since their launch. This research aimed to determine risk factors for cephamycin-associated hemorrhagic events and produce a risk scoring system using National Taiwan University Hospital (NTUH) database. Patients who were older than 20 years old and consecutively used study antibiotics for more than 48 hours (epidode) at NTUH between January 1st, 2009 and December 31st, 2015 were included. The population was divided into two cohorts for evaluation of risk factors and validation of the scoring system. Multivariate logistic regression was used for the assessment of the adjusted association between factors and the outcome of interest. Results of the multivariate logistic regression were treated as the foundation to develop the risk scoring system. There were 46402 and 22681 episodes identified in 2009-2013 and 2014-2015 cohorts with 356 and 204 hemorrhagic events among respective cohorts. Use of cephamycins was associated with a higher risk for hemorrhagic outcomes (aOR 2.03, 95% CI 1.60-2.58). Other risk factors included chronic hepatic disease, at least 65 years old, prominent bleeding tendency, and bleeding history. A nine-score risk scoring system (AUROC = 0.8035, 95% CI 0.7794-0.8275; Hosmer-Lemeshow goodness-of-fit test p = 0.1044) was developed based on the identified risk factors, with higher scores indicating higher risk for bleeding. Use of cephamycins was associated with more hemorrhagic events compared with commonly used penicillins and cephalosporins. The established scoring system, CHABB, may help pharmacists identify high-risk patients and provide recommendations according to the predictive risk, and eventually enhance the overall quality of care.

Enterococcal liver abscess associated with moxalactam therapy. Review of literature on enterococcal superinfections in association with moxalactam therapy.

Moxalactam, a third-generation cephalosporin, has been demonstrated to have an ultrawide spectrum of antibacterial activity. One important gap in this impressive spectrum is the enterococcus. Superinfections and colonization with enterococci have been reported following moxalactam therapy. Sites involved have included the urinary tract, wounds, middle ear, and blood stream. To our knowledge, we report the first case of enterococcal liver abscess following moxalactam therapy. The abscess was localized by ultrasound examination and microbiologic diagnosis made by aspiration using a skinny needle. Without surgical drainage or therapeutic aspiration, institution of appropriate antibiotic therapy in optimum dosage resulted in complete resolution. The literature on enterococcal superinfections in association with moxalactam therapy and nonsurgical management of liver abscesses is reviewed.

On the disulfiram-like activity of moxalactam.

A three-way crossover study was undertaken in 10 healthy subjects to characterize the reported disulfiram-like activity of moxalactam and to assess its influence on ethanol and acetaldehyde metabolism. On different occasions separated by at least 2 wk subjects were given in random order: 0.5 gm/kg ethanol orally, 0.5 gm/kg ethanol followed in 1 hr by 1.0 gm IV moxalactam, and 1.0 gm IV moxalactam every 8 hr for four doses followed by 0.5 gm/kg ethanol. Mean ethanol elimination rates of 13.1 +/- 0.76, 10.1 +/- 1.11, and 10.9 +/- 1.06 mg/dl/hr (mean +/- SEM) were observed in the three protocols, respectively. Corresponding mean estimated acetaldehyde clearance rates were 103.7 +/- 15.55, 92.8 +/- 13.79, and 97.3 +/- 10.41 l/min (mean +/- SEM). While no consistent moxalactam effect on ethanol or acetaldehyde elimination was observed, two subjects experienced mild disulfiram-like reactions to ethanol after moxalactam pretreatment. In one subject this reaction was associated with markedly elevated blood acetaldehyde concentrations. We conclude that moxalactam pretreatment may induce a disulfiram-like reaction after ethanol ingestion in some, probably due to inhibition of aldehyde dehydrogenase, and that alcoholic beverages are contraindicated in patients receiving moxalactam. We suggest, however, that such reactions will not occur when moxalactam is given after ethanol ingestion.

Moxalactam treatment of serious infections primarily due to Haemophilus influenzae type b in children.

Thirty-eight children completed therapy with moxalactam for a variety of non-CNS infections. Haemophilus influenzae type b (seven ampicillin-resistant strains) was the etiologic agent for 32 children. Doses of moxalactam ranged from 113 to 200 mg/kg/d in three or four divided doses administered parenterally. All children with infections due to H influenzae type b had excellent responses to moxalactam therapy. Children treated for infections due to other agents also responded satisfactorily to moxalactam therapy. Moxalactam concentrations in joint and pleural fluids greatly exceeded the minimal bactericidal concentrations of moxalactam for H influenzae type b. Adverse reactions included neutropenia, eosinophilia, thrombocytosis, and transient elevation of transaminase levels. Moxalactam administered parenterally, at a dose of 113 to 150 mg/kg/d in three or four divided doses is effective therapy for serious infections in children due to H influenzae type b and selected other organisms.

Cefotetan. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Cefotetan is a new semisynthetic cephamycin antibiotic administered intravenously or intramuscularly. It has a broad spectrum of activity against Gram-negative aerobic and most clinically important Gram-positive and anaerobic bacteria, and is generally more active against Gram-negative bacteria than the 'first and second generation' agents. Cefotetan is particularly active against Enterobacteriaceae but has little activity against Pseudomonas aeruginosa. An extended plasma elimination half-life of about 3.5 hours, and relatively high achievable serum and tissue levels, enables cefotetan to be administered on a twice daily basis in the treatment of mild to severe infections. Cefotetan has shown good clinical efficacy in intra-abdominal, obstetric and gynaecological infections, postoperative wound infections, and infections in immunocompromised patients - all of which are often complicated due to their polymicrobial nature or by the presence of anaerobic pathogens. A satisfactory clinical response is achieved in over 90% of paediatric patients with acute otorhinolaryngological infections, whereas in the treatment of chronic disease, as with other agents, the efficacy is dramatically reduced. Like other cephalosporins, cefotetan is effective in treating patients with complicated urinary tract infections and lower respiratory tract infections. Its efficacy in urinary tract infections is at least as good as cefoxitin, although in this and some other clinical areas its activity relative to that of other cephamycins and cephalosporins remains to be assessed. Thus, with its convenient twice daily dosage schedule, cefotetan would appear to be a useful addition to a rapidly expanding group of antibacterial agents.

Cefotetan compared with gentamicin and tinidazole in acute abdominal surgery.

In a prospective randomised trial 190 consecutive admissions undergoing emergency abdominal surgery were allocated to receive a 24-h peri-operative prophylactic regime of either cefotetan or gentamicin and tinidazole. Wound sepsis developed in 14 patients in each group and one patient in each group developed intra-abdominal abscess. Nine patients in the cefotetan group and 10 patients in the gentamicin and tinidazole group died within 1 month of surgery. The death of one patient in each group was directly related to sepsis. Sixty-five per cent of aerobes isolated at operation were sensitive to cefotetan and 62% sensitive to gentamicin. The in vitro anaerobic cover of tinidazole was complete, whereas 13% of anaerobes isolated at operation were resistant to cefotetan. Anaerobes, predominantly Bacteroides fragilis, were isolated from six of the 14 infected wounds following cefotetan prophylaxis and two of the 14 infected wounds in the gentamicin and tinidazole group. It is therefore recommended that cefotetan should be combined with a nitroimidazole in patients undergoing emergency colo-rectal procedures.

Cutaneous drug reaction case reports: from the world literature.

Skin disorders are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. To help you keep up-to-date with the very latest skin reactions occurring with both new and established drugs, this section of the journal brings you information selected from the adverse drug reaction alerting service Reactions Weekly. The following case reports are selected from the very latest to be published in the world dermatology literature. Any claim of a first report has been verified by a search of AdisBase (a proprietary database of Adis International, Auckland, New Zealand) and Medline. Each case report is assessed for seriousness using the FDA MedWatch definition of serious (patient outcome is: death; life-threatening; hospitalization; disability; congenital anomaly; or requires intervention to prevent permanent impairment or damage).

A comparative evaluation of moxalactam: antimicrobial activity, pharmacokinetics, adverse reactions, and clinical efficacy.

Although moxalactam is not, technically speaking, a cephalosporin it is chemically and microbiologically so closely related to those compounds that it can be viewed as a member of the cephalosporin family. Moxalactam has a spectrum of activity that includes both gram positive and gram negative bacteria. Its gram positive activity is less than earlier cephalosporins, but its activity against the Enterobacteriaceae is similar to that of the aminoglycoside family of antibiotics in most comparative studies. Although moxalactam is considerably less active against gram positive bacteria than cefotaxime, another third generation cephalosporin, its higher and more prolonged serum levels probably offset this disadvantage. Compared to cefoperazone, the stability of moxalactam to many types of beta lactamases produced by gram negative bacteria may be advantageous in the therapy of infections caused by hospital-acquired pathogens. Clinical studies suggest that moxalactam can be used for empiric therapy of suspected gram negative infections when Pseudomonas and other non-fermentative bacteria, such as Acinetobacter, are not suspected. Impressive improvements in the survival of patients with gram negative enteric bacillary meningitis have been reported. Although moxalactam, cefotaxime, and cefoperazone have activity against Pseudomonas aeruginosa, none of these antibiotics should be used alone as therapy for suspected or proven severe systemic infections caused by this pathogen. Cost is a major problem with all of the new cephalosporin-like antibiotics. While this high cost may be partially balanced by the use of a single agent compared to an antibiotic combination for therapy in some situations, these antibiotics are not cost effective for prophylactic use. Superinfection with fungi, such as Candida, and Streptococcus faecalis have occurred, and toxicities, such as bleeding due to vitamin K deficiency and disulfuram-like reactions, have also been reported. Reports of resistance to moxalactam and the other third generation cephalosporins are of major concern and indicate the need to closely monitor antibiotic susceptibility patterns of hospital acquired organisms if these antibiotics are to be used for empiric therapy of suspected gram negative non-pseudomonas sepsis.

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

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

Postmarketing surveillance on side-effects of cefminox sodium (Meicelin).

A postmarketing surveillance of cefminox sodium (Meicelin, CMNX) for intravenous injection was conducted for about 4 years from August 1987 through June 1991, and 13,431 patients were followed up to evaluate the safety of the drug. The incidence of side-effects was 1.76%. By organ, the most frequently observed were hepatic and of the bile duct system (0.87%) followed by those on leukocytes and reticuloendothelial system (0.24%), skin and adnexa (0.24%) and digestive tract (0.16%) indicating a tendency similar to that of other injectable cephalosporins. The incidence of the side-effects among elderly patients (65 years old or older) was 2.12%, whereas among patients 64 years old or younger it was 1.58% with no significant differences between the two groups. No side-effects specific to the elderly were observed. Among children 15 years old or younger the incidence was 0.59%, which was lower than that for patients 16 years old or older (1.90%). Potential side-effects on pregnant women (n = 101) and their babies were also checked. No side-effects occurred among the 52 pregnant women evaluated and no abnormalities were detected in their babies who were followed up for up to 4 years. Cefminox is thus considered to be a highly safe cephalosporin antibiotic.

Cefotetan-induced hemolytic anemia: a case report and review of the literature.

Cefotetan disodium-induced hemolytic anemia has been reported previously, and some of these cases have been severe or fatal. We describe a case of severe hemolytic anemia that occurred in an 80-year-old woman who received cefotetan prophylactically after surgery for a small bowel obstruction. Eight days after the first dose of cefotetan, the patient developed a severe Coomb test-positive hemolytic anemia. Using flow cytometry, we demonstrated cefotetan-specific antibodies in her posttreatment serum, which were detectable at a serum dilution up to 1:10 000. The patient received corticosteroid therapy and blood transfusions, with improvement of her hematologic parameters, but died 54 days after admission for respiratory failure. To our knowledge, this is the first use of flow cytometry for the detection of cefotetan-induced red blood cell antibodies. This technique offers a sensitive, rapid, objective method for detecting drug-induced antibodies.

Efficacy of cefminox in the treatment of bacterial infections.

In an open trial, 1841 patients were treated with mainly 1 g of cefminox twice a day in adults or 20-30 mg/kg three or four times a day in children for up to 14 days. The clinical efficacy was assessed in 1560 patients (1256 adults, 304 children) and the efficacy rates were as follows: 82.3% in respiratory tract infections (n:525), 85.7% in biliary tract infections (n:87), 66.4% in urinary tract infections (n:509), 92.1% in gynaecological infections (n:126), 88.1% in peritonitis (n:84), 74.9% in all infections (n:1560). The overall bacterial response rates in single infections were 81.5% (81.5% for Staphylococcus aureus, 98.4% for Escherichia coli, 98.6% for Haemophilia influenzae and 38.8% for Pseudomonas aeruginosa). The safety of cefminox was assessed in 1831 patients. Adverse side-effects were reported in 35 patients (1.9%), the most frequent being rash.

Cefotetan in the treatment of serious intra-abdominal sepsis: a controlled clinical trial.

Cefotetan has been compared with two regimens of combination antibiotic therapy in the treatment of peritonitis and serious intra-abdominal sepsis. One hundred predominantly elderly patients (median age 66 years) were entered into a prospective randomized surgical trial. Sixty-two per cent had peritonitis. There were seven non-septic deaths. Side-effects were similar in each group and generally of a minor, self limiting nature. Haematological and biochemical factors were closely monitored, and though there were increases in the prothrombin time, there was no statistical difference between cefotetan and comparators. Cefotetan is as effective as combination therapy in the treatment of surgical patients with serious intra-abdominal sepsis.

Role of new cephamycins in the management of obstetric and gynecologic infections.

The results of in vitro and in vivo studies of cefmetazole, a second-generation cephamycin, were reviewed. Cefmetazole's spectrum of activity includes clinical coverage of many Enterobacteriaceae, staphylococci, streptococci, Haemophilus species, pathogenic Neisseria organisms, Moraxella (Branhamella) catarrhalis and anaerobic bacteria. Cefmetazole is generally two to eight times more potent than cefoxitin against organisms within their spectra and is most active against staphylococci (minimal inhibitory concentration90 = 2.0 micrograms/mL). Methicillin-resistant Staphylococcus aureus strains are more susceptible to cefmetazole, alone or in combination with fosfomycin, than to any other cephamycins, and cefmetazole is remarkably resistant to the beta-lactamases produced by aerobic and anaerobic bacteria. The incidence of adverse drug reactions is low (8.8% in the United States, 2.2% in Japan), and the drug has been demonstrated to have cost-containment potential.

[Cephalosporins and enzymuria]. / Cefalosporine ed enzimuria.

Urinary enzyme excretion was studied in 56 patients treated with cephalosporins in order to evaluate their potential nephrotoxicity. Only in 4 out of 56 patients (7%) was increased NAG, gamma-GT, AlP excretion seen. A rapid return to normal values was observed just after the end of the therapy.

[Clinical evaluation of cefbuperazone in complicated urinary tract infection].

Cefbuperazone, a new cephamycin antibiotic, was used in 13 complicated UTI cases. The drug was given at a dose of 1 g in 100 ml of physiological saline solution twice a day for 5 - 14 days and judged for its clinical effect in 11 cases on days 5 - 7 according to the criteria of the UTI committee. Overall clinical efficacy was excellent in 3 cases, moderate in 2 cases and poor in 6 cases, the effectiveness rate was 45.5%. In laboratory findings, slightly elevated transaminase and A1-P were observed in 2 cases and 1 case, respectively.

[Clinical study of CS-1170 in children (author's transl)].

CS-1170 was administered to 9 cases of the pediatric field. The clinical effect was good in 6 cases, fair in 2, and poor in one. The doses ranged from 80 mg/kg to 100 mg/kg, and an intravenous injection of 300 mg/kg was given in only one case. In the poor case, continuous instillation of 100 mg/kg was given. In the 2 fair cases, the patients with septicemia received 80 mg/kg and 300 mg/kg, respectively. There was no improvement in clinical findings, but the bacteria alone disappeared. As side effects, vasalgia due to intravenous injection was observed in 2 cases, but it disappared by the intravenous injection of 500 mg dissolved in 10 ml. No case showed eruption, diarrhea, or acidophilia. GOT or GPT increased in no case either.

[Clinical evaluation of CS-1170 in pediatric field (author's transl)].

CS-1170 was used for treatment of 26 children who were diagnosed as bacterial infections, and a response rate of 88% was obtained as the drug was effective in 15 of 17 determinable cases. In our evaluation, daily dosage of 75 approximately 270 mg/kg (100 approximately 200 mg/kg in the majority of the cases) was divided into 4 doses, and administered intravenously by one-shot injection over a 10-minute period. The period of drug administration ranged from 1.5 to 25.5 days, but in most cases it was 3 to 6 days. Elevation of GOT and GPT as a side effect of the drug was seen in one case (3.8%), which was reverted to normal level upon cessation of the drug administration.

[Clinical results and pharmacokinetics of 6059-S in the field of pediatrics (author's transl)].

6059-S, a new injectable oxacephem antibiotic, has been investigated to give following results. 1. Clinical results Twenty patients were administrated intravenously 20 approximately 124 mg/kg/day of 6059-S for 2 approximately 14 days. Clinical effect was excellent in 5 cases, good in 7, fair in 3, poor in 1, unknown in 3 and except in 1, and efficacy rate was 75%. Side effect was observed only 1 case of discomfort and chill of hand and foot immediately after intravenous injection and no adverse value in laboratory findings was seen. 2. Pharmacokinetics Blood level and urinary excretion of 6059-S single administration were measured in 4 patients with normal renal function and a patient with renal failure. Half life was 1.27 approximately 1.76 hours in 4 patients with normal function and 4.33 hours in a patient with renal failure. Urinary excretion was 43.4 approximately 50.9% up to 4 hours in 2 patients with normal renal function, and it was delayed to 1.0% up to 12.5 hours in a patient with renal failure.

[Clinical experience of therapeutic use of cefmetazole (cefmetazon) or bronchopneumonia (author's transl)].

1. Therapeutic effects of cefmetazole (cefmetazon, CMZ) were examined in 22 cases of bronchopneumonia. 2. Among the 22 cases, 17 cases (77%) showed better response than 'effective'. However, 10 cases (91%) showed better response than 'effective' if a daily of 4 g (11 cases) was taken into consideration. 3. No particular symptomatic side effect of CMZ was shown. Abnormality in such laboratory tests as transaminase (1 case of GOT, and 2 cases of GPT) and 1 case of alkaline phosphatase were observed, and the abnormality was ascribable to CMZ administration.