Chemotherapy
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Comparative Study
Urinary bactericidal activity of oral antibiotics against common urinary tract pathogens in an ex vivo model.
In this investigation, the urine samples obtained in a single oral-dose pharmacokinetic study were examined for their bactericidal activity against a range of relevant urinary tract pathogens. ⋯ Average urinary bactericidal activity can be predicted from in vitro susceptibility testing, but we expect that there will be patients with a low level of urinary bactericidal activity.
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Infections in intensive care unit (ICU) patients like severe pneumonia, e.g. nosocomial (NP) and community-acquired pneumonia (CAP), or septicemia must be treated promptly and effectively because of the ensuing high mortality. Treatment is thus empirical and starts before the results of microbiological cultures are known. The risk factors affecting mortality include severity of illness, virulence of etiologic pathogens and the use of inappropriate antibiotic therapy. Several studies have shown that modifying initially inadequate therapy, according to microbiological results, does not result in a better outcome. Due to this, antibiotic treatment requires agents which have an appropriate spectrum covering the likely pathogens causing these infections. In critically ill patients, the need for empirical first-line treatment covering a broad spectrum of Gram-negative and Gram-positive bacteria, as recommended in international guidelines (e.g. those of the American Thoracic Society or the Infectious Diseases Society of America), is justified in the presence of resistant organisms commonly documented in these patients. To choose an appropriate, initial antibiotic regimen, local and national resistance data have to be considered. With respect to new German resistance trends in Gram-negative and Gram-positive bacteria, the Paul Ehrlich Society of Chemotherapy has recently published guidelines for the treatment of infections in hospitalized patients. Especially in ICU patients with severe pneumonia (NP or CAP) or septicemia and risk factors like underlying diseases, antibiotic pretreatment or mechanical ventilation, agents with an appropriate spectrum encompassing Pseudomonas aeruginosa as well as other Gram-negative bacteria like Escherichia coli, Klebsiella spp., Enterobacter spp. and Gram-positive bacteria (e.g. Staphylococcus aureus, pneumococci and streptococci) are recommended as treatment of choice. Combination therapy with an anti-pseudomonal beta-lactam and a fluoroquinolone or an aminoglycoside are recommended for these patients to provide the necessary spectrum of activity and to prevent the emergence of resistant organisms. On the other hand, clinical trials and meta-analyses have shown the efficacy, tolerability and cost-effectiveness of monotherapy regimens even in critically ill and immunocompromised patients. ⋯ Appropriate beta-lactam antibiotics recommended in international and German guidelines for the treatment of severe CAP, NP and septicemia, either as monotherapy or as combination therapy, are the 4th generation cephalosporin cefepime, the carbapenems imipenem and meropenem, and the acylamino-beta-lactamase inhibitor combination piperacillin-tazobactam.
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The aim of our study was to verify if the empiric therapy with a single dose of 3 g fosfomycin tromethamine in patients with uncomplicated urinary tract infections (UTIs) was able to clinically resolveand to microbiologically eradicate the infection. A total of 387 out of the 400 patients (274 cases with acute and 113 cases with recurrent uncomplicated UTIs) were enrolled in the clinical study. ⋯ Gastrointestinal side effects were found in only 4.3% of patients. In conclusion, a single-dose administration regimen of fosfomycin tromethamine should be encouraged as a first choice of drug therapy for uncomplicated UTIs.
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Taxanes cause hypersensitivity reactions, averted by premedication with H1 blockers and high glucocorticoid (GC) doses. Prolonged weekly taxane administration may lead to GC toxicity. ⋯ Patients unreactive to their first PTX infusions, after high-dose and tapering GC premedication, may not require GC prophylaxis for subsequent PTX therapy.
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We performed a phase I study of two fixed dosing schemes of cisplatin, a DNA cross-linker, with intravenous escalating topotecan, a DNA-topoisomerase I inhibitor. ⋯ The schedule B daily cisplatin-topotecan x 3 combination with secondary cytokine support is associated with promising activity and schedule convenience. However, substantial myelosuppression undermines its applicability in the palliative setting, stressing the need for less toxic regimens.