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The relative safety of imipenem/cilastatin for 3470 patients was reviewed to see if the safety profile was similar to that seen for the first 1723 patients treated. The most common clinical adverse experiences were local ones related to the site of intravenous infusion. Gastrointestinal adverse experiences included nausea, vomiting, or diarrhoea. The frequency of pseudomembranous colitis was low (0 X 1%). The most common central nervous system abnormality was seizure. The most common background factor was central nervous system abnormality including prior history of seizure. Dermatological adverse experiences included rash, pruritus and urticaria. Bleeding and decreased renal function were uncommon. The most common laboratory changes included transient increased liver function values, eosinophilia, positive Coombs' test (not associated with haemolysis) and increased platelets. The current clinical and laboratory safety data are similar to those obtained in the early part of the clinical trials.
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PMID:The safety profile of imipenem/cilastatin: worldwide clinical experience based on 3470 patients. 346 94

This review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients. In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 3.0% and 6.5%, respectively. An increased incidence (13.4%) has been reported from the U.S.A., possibly relating to the use of higher dosages. Very few reactions have necessitated withdrawal of treatment. The most common adverse effects involve the gastro-intestinal system (2-8% of patients treated) and usually comprise nausea, vomiting, diarrhoea and abdominal discomfort. CNS effects are seen in 1-4% of patients but are usually minor dizziness or mild headache only. Hypersensitivity reactions, most commonly skin rashes or pruritus, affect about 1% of patients. There is little evidence of significant haematological or biochemical toxicity, other than a few reports of transient neutropenia and the finding, in a minority of clinical studies, of equally transient, usually trivial and invariably reversible elevations of serum aminotransferases. Serious, ciprofloxacin-related toxicity has been observed in only three patients: one who developed pseudomembranous colitis, another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline. Ciprofloxacin appears to have an excellent safety profile.
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PMID:Ciprofloxacin: an overview of adverse experiences. 354 45

A middle-aged man presented with diarrhea, fever, and leukocytosis 7 days after discontinuation of clindamycin therapy for a urinary tract infection. Proctosigmoidoscopy showed adherent, raised plaques studding the bowel wall consistent with antibiotic-associated pseudomembranous colitis. Vancomycin therapy was begun, but progressive abdominal distension, nausea, vomiting, and loss of bowel sounds occurred. Serial abdominal radiographs demonstrated colonic wall edema without dilatation. Subtotal colectomy was performed and resulted in complete resolution of symptoms.
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PMID:Fulminant colitis complicating antibiotic-associated pseudomembranous colitis: case report and review of the clinical manifestations and treatment. 355 86

We report here our first experience with the use of a total artificial heart in a human being. The heart was developed at the University of Utah, and the patient was a 61-year-old man with chronic congestive heart failure due to primary cardiomyopathy, who also had chronic obstructive pulmonary disease. Except for dysfunction of the prosthetic mitral valve, which required replacement of the left-heart prosthesis on the 13th postoperative day, the artificial heart functioned well for the entire postoperative course of 112 days. The mean blood pressure was 84 +/- 8 mm Hg, and cardiac output was generally maintained at 6.7 +/- 0.8 liters per minute for the right heart and 7.5 +/- 0.8 for the left, resulting in postoperative diuresis and relief of congestive failure. The postoperative course was complicated by recurrent pulmonary insufficiency, several episodes of acute renal failure, episodes of fever of unidentified cause (necessitating multiple courses of antibiotics), hemorrhagic complications of anticoagulation, and one generalized seizure of uncertain cause. On the 92nd postoperative day, the patient had diarrhea and vomiting, leading to aspiration pneumonia and sepsis. Death occurred on the 112th day, preceded by progressive renal failure and refractory hypotension, despite maintenance of cardiac output. Autopsy revealed extensive pseudomembranous colitis, acute tubular necrosis, peritoneal and pleural effusion, centrilobular emphysema, and chronic bronchitis with fibrosis and bronchiectasis. The artificial heart system was intact and uninvolved by thrombosis or infectious processes. This experience should encourage further clinical trials with the artificial heart, but we emphasize that the procedure is still highly experimental. Further experience, development, and discussion will be required before more general application of the device can be recommended.
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PMID:Clinical use of the total artificial heart. 1476 80

Campylobacter fetus subspecies jejuni was isolated fom the feces of 63 (3.2%) of the 1,953 patients who had stools cultured at the Mayo Clinic in 1979. In contrast, Salmonella and Shigella combined were isolated from 31 (1.6%) patients. Two patients had double infections with Salmonella species and C. fetus subsp jejuni. Three patients had no diarrhea at the time of stool culture. One patient, who had chronic lymphocytic leukemia, had both blood and stool cultures positive for C. fetus subsp jejuni. There was a seasonal incidence that peaked in July when 7.8% of all patients who had stools cultured had C. fetus subsp jejuni isolated. Thirteen cases occurred in children 5 years of age and younger and 29 cases occurred between the ages of 15 and 30 years. Clinical features often included a prodrome of malaise, which preceded the onset of abdominal cramps, diarrhea, anorexia, fever, nausea, and vomiting. Grossly bloody diarrhea occurred in 33 patients, and massive intestinal bleeding occurred in 1 patient as a late complication after diarrhea had resolved. Transient splenomegaly was attributed to C. fetus subsp jejuni on one occasion. Proctoscopic findings may be similar to those seen in inflammatory bowel disease or pseudomembranous colitis. Three patients were referred to this institution with newly diagnosed chronic ulcerative colitis, and one patient was referred with newly diagnosed Crohn's disease. C. fetus subsp jejuni was isolated from their stools, and the diagnosis of inflammatory bowel disease was subsequently dropped. A selected review of cases illustrates the variety of gastrointestinal manifestations seen with this organism.
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PMID:Diarrhea due to Campylobacter fetus subspecies jejuni. A clinical review of 63 cases. 725 3

Ceftibuten suspension was administered to 1312 pediatric patients in clinical trials at a dosage of 9 mg/kg once daily, with a maximal daily dose of 400 mg. Adverse experiences were collected by voluntary reports by physicians from direct observations, parental and/or patient complaints in 1152 patients. In 160 patients gastrointestinal adverse experiences were elicited at each visit in addition to voluntary reports. Patients had a mean age of 4.9 years, the male: female ratio was 1:1 and 72% were white. Fifty-five percent (719 of 1312) of patients were treated in otitis media studies, 33% (438 of 1312) were treated in a pharyngitis study and 12% (155 of 1312) were treated in other studies. Adverse experiences occurred in 10% (138 of 1312) of all patients receiving ceftibuten suspension. The most common voluntarily reported treatment-related adverse events were diarrhea 3% (34 of 1152) and vomiting 2% (22 of 1152). For elicited adverse events related to treatment, the most common were also diarrhea 9% (14 of 160) and vomiting 3% (5 of 160). There were no deaths and only 0.9% (12 of 1312) patients discontinued treatment because of adverse events. Abnormal laboratory values related to therapy were uncommon and no patient discontinued treatment because of abnormal laboratory values. No cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, serum sickness-like reactions or pseudomembranous colitis have been observed with ceftibuten suspension in research studies to date.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Worldwide safety experience with ceftibuten pediatric suspension. 756 13

One-hundred-twenty infants under 1 year of age suffering from intractable diarrhoea were studied. They had received prior treatment in the form of antimicrobials (100 per cent), stool binding substance (50 percent), antimotility agents (50 per cent), and intravenous (IV) fluids (33 per cent). One-third of them had been hospitalised in peripheral hospitals. All of them had diarrhoea of more than 2 weeks' duration, protein energy malnutrition and were very ill. In addition vomiting, dehydration, fever, paralytic ileus, perianal excoriation and rectal prolapse were present in 44, 23, 33, 9, 47, and 3 per cent of the infants, respectively. Anaemia, multiple vitamin deficiencies, and pedal oedema were seen in 70, 10, and 3 per cent of infants, respectively. The infections documented were septicaemia (22 per cent), bronchopneumonia (6 per cent), meningitis (4 per cent), urinary tract infection (3 per cent) and acute supporative otitis media in 2 per cent of infants. Fifty-three per cent of infants had secondary lactose intolerance. Intolerance to milk protein, milk protein and soyabean and milk protein, as well as soyabean and chicken was seen in 4, 2, and 1 per cent cases, respectively. Aetiological agents isolated from stool culture were E. coli, (18 per cent), Klebsiella species (9 per cent), Shigella species (6 per cent), Salmonella typhimurium (2 per cent), Cholera mitschikom (1 per cent), Giardia lamblia (6 per cent), cryptosporidium (1 per cent), and E. histolytica (1 per cent). Candida albicans was grown in 18 per cent of infants. Pseudomembranous colitis was documented in 2 per cent cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intractable diarrhoea of infancy and its management: modified cost effective treatment. 807 14

Based on experimental evidence in animals showing that the oral administration of Saccharomyces boulardii is effective in reducing morbidity and mortality due to Clostridium difficile-induced pseudomembranous colitis, we conducted an open trial to examine the effects of the living yeast, given as primary therapy, in a selected group of infants and children with persistent intestinal symptoms related to toxinogenic C. difficile overgrowth. Over a period of 10 consecutive months, we studied 19 eligible patients (median age 8 months) who presented with enteral symptoms lasting for > 15 days and who had solely C. difficile in stools with positive cytotoxin B assay. Serotyping of the strains and determination in vitro of production of toxins A and B were performed subsequently. The patients presented with persistent or protracted diarrhea, malabsorption, and failure to grow (n = 8), or with repeated attacks of colics, emesis, and hypermeteorism without diarrhea (n = 4), or with both entities (n = 7). Patients with chronic protracted diarrhea (n = 3) had depressed jejunal disaccharidase activities and ultrastructural changes of enterocytes, including sparce and shortened microvilli. None had evidence of colitis. All the strains of C. difficile tested (n = 17) belonged to pathogenic serotypes (A1, A8, C, F, G, H, and K) and produced in vitro high levels of toxins A (n = 16) and B (n = 17). S. boulardii was given orally in a lyophilized form over 15 days (250 mg two to four times per day according to age).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Saccharomyces boulardii for Clostridium difficile-associated enteropathies in infants. 831 51

1. The safety in everyday clinical usage of three 4-quinolone antibiotics, (ciprofloxacin, norfloxacin and ofloxacin), was compared with similar data for azithromycin and cefixime, each agent being examined by Prescription-Event Monitoring (PEM) during the early post-marketing period. 2. In PEM the exposure data are derived from general practitioner prescriptions confidentially provided by the Prescription Pricing Authority. Outcome data are provided by questionnaires (green forms) on which the prescribing medical practitioner records event data. When necessary, further information is obtained from a number of sources which include follow-up of all pregnancies and the patients' life-time medical record. 3. The main outcome measures were demographic information, including the patient's date of birth and sex; the indication for prescribing the drug being monitored; the reason for stopping treatment; the start and stop dates of treatment and the events recorded during and after treatment. 4. The final cohort for each of the five antibiotics exceeded 11000 patients. The only event significantly related to the use of all five antibiotics was nausea/vomiting. This was also the most frequent adverse event causing treatment to be discontinued with norfloxacin, ofloxacin and azithromycin (relevant information was not requested in the studies of ciprofloxacin and cefixime). Vaginal candidiasis was significantly more frequently associated with the use of the three 4-quinolones than with azithromycin and cefixime but it was frequently delayed until the week or two after the cessation of therapy. Within each event, as recorded in these studies, the highest event rates (the number of events per 1000 patients) in the week following the start of therapy were: 9.2 for diarrhoea with cefixime; 4.9 for nausea/vomiting with ofloxacin; 2.4 for rash with azithromycin; 2.2 for abdominal pain with norfloxacin; 1.5 for headache/migraine with ofloxacin; 1.4 for malaise/lassitude with ofloxacin; 1.2 for dizziness with norfloxacin. Uncommon events (reported in less than 1:1000 patients) included rare cases of allergic phenomena, convulsions and pseudomembranous colitis. There were no reports of tendinitis, tenosynovitis or tendon rupture in children but tendon disorders were reported in the two months following the start of treatment in 20 adults. A total of 307 pregnancies were reported. Thirty-eight of the 55 women who received these drugs during the first trimester of pregnancy gave birth to healthy babies. No congenital abnormalities were reported. Apart from one case of unconfirmed pseudomembranous colitis, none of the other 2468 deaths that occurred in these studies was attributed to the antibiotics. 5. These five antibiotics are acceptably safe antimicrobial agents when used in general medical practice. PEM is an effective method for monitoring the safety of recently introduced antimicrobial agents.
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PMID:A comparison of ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by observational cohort studies. 873 Sep 72

Pseudomembranous colitis (PMC) is a rare but potentially severe complication of antibiotic treatment, which is characterized by the proliferation of the bacterium Clostridium difficile in the colon. In this retrospective study, 48 cases of endoscopically confirmed PMC were included. The following variables were analysed: characteristics of the patients, antibiotics, clinical, biological and endoscopic features of PMC and its treatment. The antibiotic treatment was often ambulatory (83 per cent) for a broncho-pulmonary infection (42 per cent). In 90 per cent of the cases, the treatment included a -lactam, frequently amoxicillin with clavulanic acid, and in 25 per cent of the cases, a fluoroquinolone. The PMC generally occurred after more than 4 days of treatment and was associated with diarrhoea, abdominal pain, fever and rarely vomiting (23 per cent). The complications were hypokalaemia (37 per cent), renal failure (27 per cent) and/or hypoproteinaemia (50 per cent). Pseumembranes were found between the rectum and the left angle of the colon. All patients recovered after one week of oral treatment with metronidazole and/or vancomycin, often in association with Saccharomyces boulardii.
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PMID:[Antibiotic-associated pseudomembranous colitis: retrospective study of 48 cases diagnosed by colonoscopy]. 876 25


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