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The current document bestows an expert synopsis of key new information presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in 2003. Data is presented on the socio-political aspects of and policies on antimicrobial prescribing, novel mechanisms of resistance in Streptococcus pneumoniae, and current epidemiological trends in global resistance. Novel information on new (and existing) antimicrobial agents--new penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides, glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin, aminomethylcyclines, glycylcyclines, and newer formulations of agents such as amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be controlled through use of more potent agents. Improved strategies for the use of existing antimicrobial agents, such as the use of high-dose regimens, short-course therapy, also may delay or reduce the development of resistance and preserve the value of our antibiotic armamentarium.

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Lower respiratory tract infections account for a large proportion of prescribed antibiotics and, with emerging resistance to standard agents, the introduction of the fluoroquinolones, in particular ciprofloxacin, has provided a further component in the armamentarium. This review encompasses 37 published clinical trials which featured ciprofloxacin; 3274 patients with lower respiratory tract infections were treated with this agent; in 94.1% of patients treatment was clinically successful and 90.9% of cases showed eradication of the causative pathogen. When these data were supplemented with previously unpublished information from the clinical trial database, specific organism eradication rates of 86.1%, 96.2% and 94.6% for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, respectively, were observed. These findings suggest that the high respiratory tissue penetration of ciprofloxacin and the achievable minimum inhibitory concentrations lead to acceptable clinical outcomes in lower respiratory tract infections.

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Azithromycin, a novel azalide antibiotic structurally related to erythromycin, has been shown by in vitro studies to have similar activity to erythromycin against Gram-positive pathogens but additionally to have increased activity against some Gram-negative bacteria, notably Haemophilus influenzae. Azithromycin achieves excellent concentrations in tissues, polymorphonuclear leucocytes and alveolar macrophages, and has a prolonged tissue elimination half-life. These properties suggest that short-course, once-daily treatment regimens will be appropriate for a variety of bacterial infections, including those of the respiratory tract, skin and soft tissues. The results of a series of clinical trials using such a regimen are reviewed. It is concluded that azithromycin is clinically and bacteriologically effective in these indications and is well tolerated when compared with regimens using standard antibiotics.

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We treated 193 patients either intravenously (94) or subcutaneously (99) for at least 5 days with porcine intestinal mucosal heparin and followed them up prospectively with frequent platelet counts to determine the incidence of heparin-related thrombocytopenia and arterial thrombosis. None of the patients in the study developed severe thrombocytopenia (platelet count, less than 100 x 10(9)/L) or arterial thrombosis. Eight patients had a platelet count of 100 to 140 X 10(9)/L on one occasion, with a count of greater than 140 x 10(9)/L on the subsequent measurement. The mean (+/- SD) values of the initial and lowest platelet counts during therapy in all patients were 288 +/- 100 x 10(9)/L and 253 +/- 88 x 10(9)/L, respectively, with the lowest counts occurring on day 4.1 +/- 4.2. A least-squares line was computed for each patient to fit the day and counts; the slopes were significantly different from zero and negative in 7.8% of patients and positive in 14.5%. This multicenter study confirms the reports that the incidence of heparin-related severe thrombocytopenia and arterial thrombosis is distinctly low in patients treated with porcine-mucosal heparin.

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The pharmacokinetics of ciprofloxacin following a single 100 mg oral dose were evaluated in elderly patients (mean age 74 years), laboratory staff (30-40 years) and students (less than 20 years). There were no significant differences in serum Tmax (1.2-1.3 h) or in overall serum elimination half-life (3.7-4.0 h) but Cmax in elderly patients was more than double that in young volunteers (P less than 0.005). The serum AUC value was greater both in fasting students (1.4 mg/h/l) compared with the same subjects after food (1.09: P less than 0.01) and, after food, in elderly patients (1.95) compared with students (0.81: P less than 0.005). Urinary recoveries were greater in fasting subjects and in all categories of volunteers compared with elderly patients. However, in the elderly, urinary ciprofloxacin concentrations (0-6 h mean 66 mg/l: range 17.4-200 mg/l) were more than adequate for the eradication of urinary pathogens.

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Ciprofloxacin is a new 4-quinolone antibacterial agent with an extended antibacterial spectrum, enhanced potency and the ability to produce therapeutic serum, tissue and urine concentrations after oral administration. Unlike earlier 4-quinolones, it is active against gram-positive cocci and opportunistic organisms such as Pseudomonas aeruginosa. This overview demonstrates that the oral formulation has been shown to be clinically effective in a broad range of urinary and respiratory infections, gonorrhoea, gastro-intestinal infections including typhoid fever, surgical infections, skin and soft tissue sepsis and in a variety of infections caused by Pseudomonas aeruginosa, notably cystic fibrosis. Adverse reactions are infrequent and in almost every case have proved mild and transient. Ciprofloxacin has great potential for the oral therapy of infections which have traditionally required parenteral chemotherapy.

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Cefuroxime axetil, an orally absorbed pro-drug of cefuroxime was used to treat a mainly elderly group of patients with symptomatic urinary tract infections. The drug was clinically effective and the bacteriological short term and long term cure rates (55% and 48% respectively) comparable to those of other antibiotics. The study had to be terminated however after the development of three cases of antibiotic associated colitis. Studies of the pharmacokinetics of the drug in volunteers gave inconsistent results suggesting that there may be variable bioavailability of the compound.

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An intravenous formulation of Augmentin was used as sole chemotherapy in the treatment of patients with severe infections. Fourteen of 17 assessable patients (82%) responded satisfactorily including six with bacteraemia. Adverse reactions occurred in 38% of patients but in all but one, withdrawn due to diarrhoea, were trivial. There was no significant intolerance.

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The results of a clinical trial of sultamicillin, a novel mutual pro-drug combination of ampicillin and the beta-lactamase inhibitor sulbactam, in ampicillin-resistant urinary tract infections are reported. The majority of infections treated occurred in elderly geriatric in-patients. Two dosage schedules were investigated, both resulting in the same total daily dosage (1500 mg sultamicillin). These were 750 mg sultamicillin, 12-hourly (series I) and 500 mg sultamicillin, 8-hourly (series II), each administered orally for seven days. Short term cure rates (after exclusion of superinfections and reinfections) of 79.5% (series I) and 82% (series II) were obtained one week after therapy, falling to 69% and 50%, respectively, at three to six week follow up. Sultamicillin was well tolerated. Pharmacokinetic studies confirmed intestinal absorption of both constituents in young volunteers and in the elderly.

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Twenty-six patients with enteric fever treated with amdinocillin and/or its pivaloyloxymethyl ester in 1975 to 1978 were compared with 21 patients with enteric fever treated with trimethoprim-sulfamethoxazole in 1972 to 1974. Diagnosis was based on clinical illness and isolation of Salmonella typhi or S. paratyphi A/B from blood cultures or stool cultures. The dosage of pivamdinocillin in adults was 400 to 800 mg, every 6 hours, for 10 to 16 days; dosage in children was half this amount for 11 to 15 days. Of the 21 patients treated with trimethoprim-sulfamethoxazole, 18 (86 percent) showed a satisfactory clinical response; 13 of these 18 had negative stools immediately after therapy, and two more were negative at the time of discharge (total: 83 percent). Mean hospital stay of these patients was 34.5 days. Of the 26 patients treated with amdinocillin, 23 showed a satisfactory clinical response; 20 of those responding clinically were still excreting the causative organism at the end of therapy; seven of the group remained as convalescent patients who continued to excrete the causative organism in feces at the time of discharge. Mean hospital stay was 43 days. The results of initial trials of amdinocillin and ampicillin in combination suggest that such therapy may be preferable to use of amdinocillin alone, although the excretion of the causative organism during convalescence has not been adequately assessed.

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