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A retrospective epidemiological study was conducted in connection with an outbreak of paratyphoid fever at a Peruvian naval installation in Callao. The study sought to determine the magnitude of the outbreak, the source of infection, the attack rates, the persistence of bacilli excretion, and the clinical picture of the disease. The source of Salmonella paratyphi B infection had been a meal of chicken and rice served to around 400 members of the naval police. Over a period of three weeks, 21 persons were hospitalized and 52 received outpatient treatment at the naval hospital. In addition, through a questionnaire it was revealed that 86 unreported cases of diarrhea related to the outbreak had occurred. The most common clinical manifestations were fever, headache, weakness, anorexia, abdominal pain, and diarrhea. The general attack rate was 39.8%. In a follow-up survey carried out 37 days after exposure, fecal cultures indicated that 8.5% of the persons affected continued to excrete the microorganism. The high rates of attack and transmission of S. paratyphi B in this outbreak point up the considerable pathogenicity and virulence of some strains of the microorganism and their impact on public health. It is suggested that preventive measures be taken at naval and other similar installations, including the education of workers who handle and prepare food, in order to ensure proper hygiene.
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PMID:[Outbreak of paratyphoid fever among Peruvian naval personnel]. 161 May 4

In this single-blind study, 579 patients with chronic bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate thrice daily for seven days. Treatment efficacy was evaluated in 129 of the loracarbef-treated patients and 120 amoxicillin/clavulanate-treated patients in whom pretreatment positive cultures of pathogens susceptible to both antibiotics were isolated. Three organisms predominated in either pure or mixed cultures in 57.0% of the evaluable patients: Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella (Branhamella) catarrhalis; H influenzae was isolated in 25.0% of the patients with single pathogens. Among the evaluable patients, favorable clinical responses (cure or improvement) were noted in 93.8% of the loracarbef-treated patients and in 95.0% of the amoxicillin/clavulanate-treated patients. A favorable bacteriologic response (pathogen eliminated or presumed eliminated) was found in 82.2% of loracarbef-treated patients and 90.0% of amoxicillin/clavulanate-treated patients. Six patients in the loracarbef group and 14 in the amoxicillin/clavulanate group discontinued treatment because of adverse events. The events were judged to be drug related in four loracarbef-treated patients and in 11 amoxicillin/clavulanate-treated patients. The incidence of diarrhea and other gastrointestinal symptoms was significantly more frequent in the amoxicillin/clavulanate group (13.5% and 5.6%) than in the loracarbef group (4.5% and 1.7%), while the incidence of severe headaches was significantly more frequent in the loracarbef than the amoxicillin/clavulanate group (7.2% vs 3.1%). It is concluded that loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute bacterial exacerbations of chronic bronchitis.
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PMID:Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute bacterial exacerbations of chronic bronchitis. 161 45

Panipenem/betamipron (PAPM/BP), a new carbapenem, was studied in dermatology. PAPM/BP was used clinically in the treatment of skin and skin structure infections in a multicenter trial. Fifty three patients were enrolled in the trial. Clinical evaluations were made in 50 patients. Most patients received intravenous infusion of PAPM/BP in a dose of 500 mg twice daily. Other dosages were used in some patients. The overall clinical efficacy rate was 78%. When 15 cases of secondary infections were excluded, the rate was 85.7%. Adverse responses were nausea and/or vomiting in 3 patients, redness with itching in 1 patient, headache or head heaviness in 2 patients and diarrhea in 1 patient. The patient with redness and itching had also nausea and vomiting. This occurred 1 hour after the start of the first infusion of this drug. After the discontinuation of the treatment the symptoms went away on the next day. Abnormalities in laboratory test results were observed in 7 out of 53 patients. One patient with liver cirrhosis and hepatocellular carcinoma developed anemia (RBC 372 x 10(4)/mm3----275 x 10(4)/mm3, Hb 11.9 g/dl----8.8 g/dl, 35.1%----26.0%). Other abnormalities were all mild. Penetration of the drug into skin tissues after intravenous infusion of 500 mg of this drug in skin surgery patients was studied. Skin/serum concentration ratios ranged from 0.20 to 0.97. Skin concentrations were higher than the concentration of PAPM inhibiting 80% of clinical isolates over a period of 6 hours. In rats, skin concentrations were much lower than serum concentrations probably due to the difference in in vivo metabolism of PAPM. A few resistant strains of Staphylococcus aureus against PAPM and imipenem (IPM) were isolated. However, PAPM and IPM showed good antibacterial activities compared to other drugs tested. In conclusion, PAPM/BP is considered to be a useful drug in the treatment of skin and skin structure infections.
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PMID:[A multicenter study on panipenem/betamipron in dermatology]. 161 73

The efficacy and safety of the antibiotic loracarbef have been demonstrated in a series of 22 clinical trials involving over 9,000 patients. The data compiled from these trials indicate that loracarbef is well tolerated by the majority of patients, including children and elderly patients. Most adverse events in patients receiving loracarbef were mild and transient in nature; only 1.5% of patients discontinued therapy because of drug-related adverse events. The frequency of adverse events associated with this agent compares favorably with that reported for the other antibiotics in these trials. The most commonly reported adverse reaction in the loracarbef study group was diarrhea, but this condition occurred less frequently in patients who received loracarbef than in those treated with the comparative agents. Other gastrointestinal events, such as nausea and vomiting, were reported infrequently. Headache was the second most common adverse event reported and occurred at a slightly higher frequency in the loracarbef-treated group than in patients receiving comparative antibiotics. No clinically significant alterations in laboratory parameters or gastrointestinal flora were observed following loracarbef administration. The compiled data indicate that loracarbef is a safe therapeutic option for the treatment of a wide spectrum of bacterial infections.
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PMID:The safety profile of loracarbef: clinical trials in respiratory, skin, and urinary tract infections. 162 42

Two controlled clinical trials compared loracarbef (LY163892 with amoxicillin/clavulanate or amoxicillin in the treatment of acute exacerbations of chronic bronchitis. Collectively, of 1,057 patients enrolled, 390 qualified for analysis: group 1 comprised 200 patients treated with loracarbef (400 mg twice daily); group 2, 120 patients treated with amoxicillin/clavulanate (500 mg three times daily); and group 3, 70 patients treated with amoxicillin (500 mg three times daily). Symptomatic and bacteriologic outcomes were assessed at post-therapy (within 72 hours of therapy completion), and at late-posttherapy (10-14 days after therapy completion). These evaluations were combined to provide an "overall" evaluation that accounted for all unfavorable outcomes occurring at either the posttherapy or late-posttherapy visit. At the posttherapy evaluation, 93.0% of group 1 patients, 95.0% of group 2 patients, and 88.6% of group 3 patients demonstrated favorable clinical outcomes (cure or improvement). "Overall" favorable clinical outcomes were achieved in 88.0% of group 1 patients, 90.0% of group 2 patients, and 81.4% of group 3 patients. Bacteriologic results from the two studies could not be merged due to marked differences in how posttherapy bacteriologic results were assessed. The clinical significance of positive posttherapy sputum cultures was doubtful: 90% of patients with a positive sputum culture at the posttherapy visit who returned for the late-posttherapy visit had successful clinical outcomes documented at the late-posttherapy evaluation. Loracarbef was associated with a lower incidence of diarrhea and a higher incidence of headache as compared with amoxicillin/clavulanate. These results suggest that 400 mg loracarbef twice daily for 7 days is effective and safe in the treatment of acute exacerbations of chronic bronchitis.
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PMID:Loracarbef (LY163892) in the treatment of acute exacerbations of chronic bronchitis: results of U.S. and European comparative clinical trials. 162 46

Loracarbef (LY163892), a member of the class of beta-lactam antibiotics known as carbacephems, is characterized by a high level of chemical stability and a broad spectrum of antibacterial activity that persists in the presence of beta-lactamase. The efficacy and safety of loracarbef, 200 mg (twice daily), and cefaclor, 250 mg (three times daily) (one patient received 178 mg of cefaclor suspension, three times daily), were compared in a randomized, double-blind, multicenter trial conducted in adults with skin and skin-structure infections due predominantly to Staphylococcus aureus. Examination within 72 hours after the completion of therapy indicated a favorable clinical response in 84 (93.3%) of the 90 loracarbef-treated patients evaluable for efficacy and in 79 (95.2%) of the 83 evaluable patients treated with cefaclor. Pathogens were eradicated in 83 (92.2%) of the patients in the loracarbef group and 74 (89.2%) of those in the cefaclor group. Only four adverse events--headache/migraine, diarrhea, abdominal pain, and nausea--occurred in greater than 2% of the total study population. The overall incidence of adverse events in the 201 loracarbef-treated and 192 cefaclor-treated patients evaluated for safety was 19.9% and 24.5%, respectively. Adverse events that required hospitalization or discontinuation of treatment occurred in four patients in the cefaclor group but in none of those treated with loracarbef. There were no statistically significant differences in the clinical or bacteriologic response or the incidence of side effects between the two treatment groups. These findings indicate that loracarbef given twice daily is comparable in safety and efficacy to cefaclor given three times daily in the treatment of adults with skin and skin-structure infections.
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PMID:Loracarbef (LY163892) versus cefaclor in the treatment of bacterial skin and skin-structure infections in an adult population. 162 51

Optimal therapy for pyelonephritis requires the immediate administration of an effective broad-spectrum antibiotic. Because conventional oral antibiotics such as the sulfonamides and the aminopenicillins are limited by the development of resistant bacteria associated with this common disease, the therapeutic effectiveness of a new oral carbacephem antibiotic was investigated. Two double-blind, randomized clinical trials of loracarbef (LY163892) were conducted. A total of 245 patients (greater than or equal to 18 years old) with uncomplicated pyelonephritis were enrolled in parallel studies. One study compared loracarbef with cefaclor; the other compared loracarbef with norfloxacin. In the combined patient population, 119 patients were treated with loracarbef (400 mg twice daily), 43 with cefaclor (500 mg three times daily), and 83 with norfloxacin (400 mg twice daily). All treatment regimens continued for greater than or equal to 14 days. A total of 68 patients in the loracarbef group, 25 in the cefaclor group, and 43 in the norfloxacin group qualified for efficacy analysis. Escherichia coli was the causative pathogen in 85.0% of these patients. Successful posttherapy clinical and bacteriologic responses were similar for all three study drugs: 94.1 and 86.8%, 96.0 and 80.0%, 97.7 and 88.4% for loracarbef, cefaclor, and norfloxacin, respectively. Late posttherapy clinical responses were 87.4, 83.3, and 91.7% for the loracarbef, cefaclor, and norfloxacin groups, respectively. Bacteriologic responses for the three groups were 79.6, 60.0, and 88.9%. The most frequent adverse effects (headache, diarrhea, and nausea) were experienced by three patients (2.5%) in the loracarbef group; headaches were noted in two (4.7%) cefaclor patients, diarrhea was noted in three (7.0%) patients in the cefaclor group, and nausea was noted in four (9.3%). Gastrointestinal events were noted in four patients (4.8%) in the norfloxacin group. The data demonstrate that loracarbef is comparable in efficacy and safety to both cefaclor and norfloxacin as oral therapy for uncomplicated pyelonephritis.
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PMID:Loracarbef (LY163892) versus cefaclor and norfloxacin in the treatment of uncomplicated pyelonephritis. 162 52

A double-blind comparative study of the nonionic contrast medium iopentol and the ionic contrast medium metrizoate for urography was carried out in 200 adult outpatients. Significantly less discomfort and other side effects were observed following iopentol than following metrizoate. No serious adverse reactions and no clinically significant alterations in heart rate or blood pressure were observed. A questionnaire was used to record delayed symptoms, from 30 min after contrast medium injection and for one week. The response rate was 92% and delayed adverse events were reported by 45%. The incidence of delayed reactions was significantly lower following iopentol than following metrizoate, i.e., delayed arm pain, fatigue, headache, diarrhea, nasal congestion, and rash. Delayed arm pain was probably due to contrast medium induced thrombosis in 1% following iopentol and in 8% following metrizoate. Most other symptoms were probably related to a combination of nocebo effect and coincidentally occurring symptoms. The urograms with both media were of similar high quality. Iopentol was found a suitable contrast medium for urography.
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PMID:Iopentol in urography. A clinical comparison between iopentol and metrizoate including delayed reactions. 163 50

A phase I trial of 5-fluorouracil (FUra) and leucovorin (LV) given with and without dipyridamole (DP) by concurrent 120-h continuous infusion was performed in 27 patients with advanced solid malignancies, 8 of whom had previously received FUra. The LV and DP doses were fixed at 500 mg/m2 daily and 7.7 mg/kg daily, respectively, whereas the FUra dose was escalated. Level 3 (450 mg/m2 FUra daily) represented the maximum tolerated dose for both FUra/LV+DP and FUra/LV. Dose-limiting stomatitis (greater than or equal to grade 3 or grade 2 occurring during the infusion) was encountered in 75% of the first courses given at level 4 (600 mg/m2 daily). Stomatitis was observed in 44/78 (56%) courses. Diarrhea was infrequent and mild. DP infusions were complicated by mild to moderate headache, which was controlled with narcotic analgesics, and mild to moderate nausea/vomiting. FUra-related toxicity was not enhanced by DP administration. Limited pharmacokinetic sampling at levels 3 and 4 revealed mean steady-state FUra concentrations of around 1.0 microM with infusions of FUra/LV+DP. Among three paired courses given with and without DP, no statistically significant difference was found in the total body clearance of FUra (P = 0.44). One partial response was seen in a patient with metastatic gastric carcinoma. For phase II trials, we recommend that concurrent 120-h continuous infusions of FUra (450 mg/m2 daily) and LV (500 mg/m2 daily) be given with and without DP (7.7 mg/kg daily) every 21 days.
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PMID:A phase I trial of 5-fluorouracil, leucovorin, and dipyridamole given by concurrent 120-h continuous infusions. 164 98

In a randomized single-blind international multicentre trial, two antiemetic regimens were compared in 115 oncology patients undergoing chemotherapy for the first time (cisplatin greater than 15 mg/m2, or ifosfamide greater than 1200 mg/m2 or etoposide greater than 120 mg/m2). One group received granisetron, a 5-hydroxytryptamine type-3-receptor antagonist, 40 micrograms/kg alone intravenously before chemotherapy, with, if necessary, up to two further doses daily of 40 micrograms/kg. The second group received a combination of alizapride plus dexamethasone (4 mg/kg alizapride and 8 mg/kg dexamethasone before chemotherapy, repeated, if necessary, after 4 and 8 hours up to two additional doses). There was good antiemetic efficacy (a maximum of one episode of vomiting in 24 hours = "major efficacy") in 50 of 62 patients (80.7%) in the granisetron group, and in 37 out of 53 (69.8%) of those treated with alizapride and dexamethasone; failure of antiemetic therapy occurred in 4.8% (granisetron) and 15.1% (combination) of patients. For the first day of each 5-day chemotherapy cycle, there was a higher rate of excellent antiemetic efficacy (no or only mild nausea, and no vomiting) with granisetron (90.3% vs 69.8%, P less than 0.006). The frequency (29% vs 32%) and nature of side effects (obstipation, diarrhoea, headaches, anxiety, vertigo), the causes of which were not differentiated, were similar. No extrapyramidal reactions occurred with granisetron. Of the 62 patients treated with granisetron, 47 did not require any further granisetron after the single daily prophylactic dose.
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PMID:[Comparison of the antiemetic effectiveness of granisetron and alizapride plus dexamethasone in cytostatic therapy]. 165 80


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