The efficacy of human lymphoblastoid interferon (Wellferon) therapy was measured in 20 children with chronic hepatitis B with or without pretreatment with prednisolone. Patients were randomised to receive 0.6 mg/kg/day prednisolone for 3 weeks, then at 0.3 mg/kg for a fourth week or placebo. All patients then received interferon 5 MU/m2 i.m. for 12 weeks; daily for 5 days then three times a week for the remaining 11 weeks. Preliminary results show that 25% of children had a permanent loss of viral markers of replication. However, response to interferon varied widely between individuals and a prolonged follow-up is required in order to determine the influence of prednisolone pretreatment on the efficacy of interferon therapy.
Single dose cefotetan was compared with either a combination of metronidazole and cefazolin given for 24 hours or 3 doses of cefuroxime as prophylaxis in elective abdominal surgery. Wound infections and infections at remote sites (UTI and RTI) were similar in all groups. In a third group prophylaxis of abdominal surgery using a single 2g dose of cefotetan was compared to 2 doses of the same drug, given 12 hours apart. There was no demonstrable advantage to giving 2 doses. The low incidence of post-operative infections seen in all groups indicates the efficacy of cefotetan in the surgical prophylaxis of elective abdominal surgery.
304 strains of R-plasmid harbouring enterobacteria resistant to aminoglycosides were studied for their susceptibilities to a range of antibiotics, including cefotetan. Cefotetan and latamoxef were the most active of the four cephamycins tested and all were stable to the beta-lactamases produced by these strains. No new beta-lactamases (SHV-2, CTX-1, TEM-4, CAZ-1) were found in these strains capable of hydrolysing third generation cephalosporins. The activity of cefotetan against these multi-resistant, beta-lactamase producing strains may be of clinical value.
The in-vitro activity of three long-acting cephalosporins (cefotetan, cefonicid and ceftriaxone) was compared against 206 clinical isolates of Bacteroides fragilis, Peptostreptococcus species and Clostridium perfringens, using an agar dilution procedure to determine minimum inhibitory concentrations (MICs). Clindamycin was included as a comparator. Cefotetan was much more active than the two other cephalosporins against strains of Bacteroides fragilis (MIC90 16 mg/l compared with greater than 128 mg/l for the other two agents). Cefotetan also demonstrated superior activity against anaerobic cocci. All three compounds showed good activity against strains of Clostridium perfringens. Clindamycin was active against all of the test strains.
Sixty-five cancer patients pretreated with chemo or radiotherapy, with granulocytopenia less than 1000/mm3 and without fever, were entered into this study: 30 of them were submitted to prophylaxis with norfloxacin while the remaining 35 patients were used as a control group. 20% of the treated subjects versus 68.6% of the controls presented a subsequent infection (P less than 0.001), the lung representing the most frequent site of the infectious disease in both groups (3/6 and 14/24 respectively). These data strongly suggest the use of norfloxacin as an effective prophylactic drug in nonfebrile, granulocytopenic cancer patients, especially as far as gram-negative infections are concerned. Because of the high prevalence of lung cancer in the patients of our study, and a related prevalence of lung infections, at the present time, a wider use of this antibiotic in every kind of solid tumor cannot be generalized.
Three broad-spectrum cephalosporins (cefotetan, moxalactam, and cefoxitin) proved effective in this randomized, prospective trial for treatment of 303 surgical patients with moderately severe regional peritonitis.
The aim of this study was to compare the effects of the prophylactic use of cefamandole versus oxacillin plus gentamicin on hemostasis in patients undergoing hip replacement with heparin prophylaxis. Twenty-four patients with a normal hemostatic profile were randomly allocated to receive either cefamandole or oxacillin plus gentamicin. All the patients received calcium heparin. Platelet count, bleeding time, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin clotting time (TCT), fibrinogen and serum FDP were assessed before treatment and every day of antibiotic administration. Surgical bleeding was assessed using a four-grade score system. Platelet count, bleeding time, fibrinogen and serum FDP did not show any change with both treatments. PT, aPTT and TCT showed a similar and mild prolongation in the two groups of patients. No difference in the surgical bleeding was observed between the two groups. We conclude that a short-term prophylaxis with cefamandole is a safe regimen in patients undergoing hip replacement with heparin prophylaxis.
Twenty-five children (16 females and 9 males) aged from 8 months to 10 years with clinical and laboratory evidence of UTI were treated with sulbactam + ampicillin (SBT/AMP). Twenty-four of them were suffering from cystitis and one from pyelonephritis. Four of them were treated unsuccessfully prior to entry in the trial. The mean final dose of SBT/AMP was 47.69 mg/kg/die (ratio of SBT-AMP was 1:2). The patients were treated for 3 to 8 days (mean: 4.76 days). 84% were treated by i.m. route. No side effects or adverse experience were reported. Clinical cure was achieved in 25 patients (100%).
Male Wistar rats received adriamycin, aclacinomycin or thepirubicin at a dose of 4 mg/kg b.w. by slow infusion. Cardiac tissue sections were examined by fluorescence microscopy to evaluate the distribution of the three anthracyclines. The nuclei regularly exhibited a stronger coloring with respect to the cytoplasm for all three drugs. Adriamycin cytoplasm fluoresced intensely, unlike aclacinomycin and thepirubicin. Our results indicate a lower uptake of these last two molecules into cardiac tissue, thus suggesting a different pharmacokinetic profile which might account for their lower cardiotoxicity.
The purpose of this experimental study was to evaluate the possible synergistic effect of hyperthermia (HPT) and methotrexate (MTX) in Wistar rats transplanted with Walker sarcoma. HPT was induced by microwaves of 432 MHZ frequency transmitted through a source of 2 x 5.5 cm2 surface. The temperature in the tumor was maintained at 43 degrees C which was controlled by an intratumor thermocouple connected with an electronic thermometer. Three experiments were performed. First, in 5 rats HPT only was applied and one rat was used as control. Second, HPT and MTX in combination were given to 6 rats. Third, MTX alone was given to 6 rats. In the first experiment all 5 rats had 50% reduction of their tumors compared to control. In the second experiment complete disappearance of the tumor was noticed and in the third experiment the tumor increased in size. Histologically, in the responding tumors extensive necrosis was seen with thrombosed vessels. We conclude that HPT and MTX are synergistic in treating Walker sarcoma in Wistar rats.
Twelve hospitalised patients, affected by biliary tract infections, were treated with cefotetan at dosages ranging between 4 and 6 g daily i.v. In only 11 patients was the aetiological agent identified. Eleven patients (91.67%) completely recovered from their infections and the pathogens were eradicated; the treatment failed in only 1 patient (8.33%). Furthermore, determinations were made of cefotetan concentrations in serum, gallbladder bile, gallbladder wall and gallstones of 14 patients undergoing cholecystectomy: in 7 patients after only 1 injection i.v. of 2 g and in 7 patients after 7 injections i.v. of 2 g at intervals of 12 h. The levels recorded were several times higher than the minimum inhibitory concentrations against bacteria that are most often responsible for biliary infections. Cefotetan is a promising and effective antimicrobial agent in the therapy of biliary tract infections.
We treated 21 patients with advanced breast cancer with buserelin, aminoglutethimide and cortisone acetate in an attempt to obtain a complete estrogen blockade both in premenopausal and postmenopausal patients. Ten patients (47%) obtained an objective response without any relevant side-effects. Dealing with hormonal data, it must be outlined that serum testosterone levels decreased significantly in postmenopausal patients, suggesting a possible explanation for the activity of luteinizing hormone-releasing hormone analogue in this group of patients.
Seventy-one neutropenic patients under cytostatic treatment for malignant hemopathies (neutrophil granulocytes less than or equal to/mm3 with feverish episodes in progress (T greater than or equal to 38.5 degrees C) which were probably of an infectious nature were treated according to two antibiotic protocols (piperacillin + amikacin [P + A] or cefotaxime + amikacin [C + A] in a randomized, comparative, prospective study. Of the 71 patients enrolled, 65 could in the end be evaluated for the purposes of this study (36 treated according to the P + A protocol, 29 according to the C + A protocol). In 16 patients the infection was documented bacteriologically. In these cases the percentages of response were, respectively, 77.7% with the P + A and 71.4% with the C + A protocol. The positive clinical results of the two protocols being studied were, considering the entire survey (bacteriologically documented, clinically documented and FUO infections), respectively, 69.4% in the patients treated with P + A and 62.0% in those treated with C + A. The results of the study seem to indicate that the severity of the neutropenia (N.G. less than 500 or greater than 500) does not affect the response to the antibiotic therapy. Modest and transient side effects (hypokalemia and increase of the ClCr) were noted above all in the patients subjected to the therapy with C + A. The results of this study show, therefore, a superimposable effectiveness of the two therapeutic protocols (P + A and C + A) in the empirical treatment of infections in neutropenic patients with malignant hemopathies.
The in vitro antibacterial activity of teicoplanin, a new glycopeptide antibiotic, previously named teichomycin A2, has been compared to that of five other chemoantibiotics: netilmicin, clindamycin, rifampicin, enoxacin and vancomycin. The minimum inhibitory concentration (MIC) values against 588 gram-positive strains, 561 facultative aerobes and 27 anaerobes, recently isolated from clinical specimens, were evaluated. Teicoplanin showed the highest activity against all the tested strains, with a geometrical mean of the MICs (GMM), a MIC50 and MIC90 of 0.123, 0.12 and 0.5 micrograms/ml respectively.
The bactericidal activity of cefuroxime, cephaloridine and cephalexin is evaluated in an in vitro model. The inocula are derived from an overnight static culture, or after a pre-incubation period of 1 or 2 hours to allow cell re-growth. The early bactericidal effect of the antibiotics is more evident using pre-incubated cells, especially for Staphylococcus aureus 663. At hour 8, with Escherichia coli 851/E, there is re-growth using the static inoculum, while the antibiotic effect is still evident using the pre-incubated one. The importance arises therefore for considering the phase of growth of the inoculum as a critical parameter when using in vitro models with varying concentrations of beta-lactam antibiotics.
Forty-nine patients with localized osteosarcoma of the extremities were treated with a new protocol of neoadjuvant chemotherapy. Preoperatively the patients received high-dose methotrexate intravenously, followed after a week by cisplatinum intra-arterially for a continuous infusion over a 72-hour period, plus adriamycin intravenously infused over an 8-hour period. In all cases the clinical and radiographic response was good and in 44 cases (89.7%) it was possible to perform conservative surgery. The histologic examination of the surgical specimen resulted in necrosis being "good" (greater than or equal to 90% of necrosis) in 41 patients (83.6%). This percentage of "good necrosis" was significantly higher than the percentage previously obtained in our Center as well as in others for preoperative treatment of this tumor. Up to now, patients with localized osteosarcoma of the extremities who showed a good histologic response to the preoperative chemotherapy have had a very good prognosis (82% of patients are continuously disease-free). These results suggest that this new regimen represents a substantial improvement in the treatment of this disease.
The in vitro activity of pefloxacin, a new fluoroquinolone, was compared with that of 5 other quinolone compounds (nalidixic and pipemidic acids, norfloxacin, ciprofloxacin, and ofloxacin) against 416 strains of Proteae spp. isolated from urine specimens of hospitalized patients with acute urinary tract infections (UTI). Ciprofloxacin was the most active agent. Norfloxacin, ofloxacin, and pefloxacin were similarly active against Proteus strains (MIC90 = 0.39 microgram/ml). Against Providencia spp. pefloxacin and norfloxacin showed similar activity (MIC90 = 3.12 micrograms/ml). There is minimal discrepancy between minimum inhibitory concentrations and minimum bactericidal concentrations exhibited by the quinolones for all urinary tract pathogens tested. Our in vitro studies indicate that pefloxacin is an active antimicrobial agent and suggest that it will prove useful in the treatment of complicated urinary tract infections due to nalidixic acid-resistant Proteae spp.
In a randomised clinical trial, 102 women who underwent vaginal hysterectomy were given a single preoperative 2g dose of cefotetan (CTT) (52 pts) or three perioperative 2g doses of cefoxitin (CFX) plus 0.5g metronidazole (50 pts) as antibiotic prophylaxis. No statistically significant differences between the groups were detected in the clinical response (100% for both groups). The incidence of major wound infection (2% CTT and 0% CFX) were also comparable between the two treatment groups; post-operative changes in body temperature, duration of hospitalisation and post-operative urinary tract infections (16% CTT and 20% CFX) were similar. Both drugs were well tolerated. Twenty nine of the 102 patients were further investigated to determine the pharmacokinetics following a single 2g dose of CTT or CFX, in both serum and tissue. Although both antibiotics provided good concentrations during the early phase of surgery, CTT levels persisted for a longer time period. These results confirm that single dose cefotetan is equally as effective and safe as multiple dose cefoxitin plus metronidazole for prophylaxis in patients undergoing vaginal hysterectomy.
In an open, prospective, non-randomised study involving 112 patients undergoing elective colorectal surgery, the effect of perioperative prophylaxis with cefotetan was investigated. Cefotetan (2g) was administered, pre- and intra-operatively only. Preoperative bowel preparation was done by the standardised "Würzburg Method" i.e. oral metronidazole pre and post orthograde lavage. Mucosal biopsies were obtained from the resected colon and simultaneously serum samples were taken to determine tissue and serum levels respectively. Antibiotic serum and gut mucosal levels were well in excess of the minimum inhibitory concentration (MIC90) levels of the isolated bacteria. Wound infections occurred in only 2 patients. Cefotetan was well tolerated and no adverse events were noted. In prolonged colorectal surgery, an antibiotic such as cefotetan with a long half-life is to be recommended.
Data on the antibacterial activity of cefotetan collected since 1985 have been compiled into a computer database and an analysis of results on more than 100,000 clinical isolates presented. The studies were conducted in 285 hospitals located throughout Europe, South Africa, Australia and the USA. The results demonstrate the effectiveness of cefotetan as a broad spectrum agent with significant activity against clinically important aerobes and anaerobes. This is exemplified by the susceptibility to cefotetan of 92% of 14,315 strains of Staphylococcus aureus, 99% of 24,103 strains of Escherichia coli and 93% of 1,841 strains of Bacteroides fragilis.
