Chemotherapy
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The increasing emergence of serious multidrug-resistant (MDR) Gram-negative infections has led to a new health-care crisis. These infections predominately include MDR Pseudomonas aeruginosa, extended-spectrum beta-lactamase-producing Enterobacteriaceae and MDR Acinetobacter baumannii. ⋯ The increasing use of broad-spectrum antibiotics and lack of good stewardship have contributed to the increase in these MDR organisms. This review focuses on the main MDR Gram-negative infections contributing to the current crisis in health care, their mechanisms of resistance and various treatment options for empiric therapy.
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Mupirocin is a natural antibiotic from Pseudomonas fluorescens which is available as a 2% ointment. The drug has been used mainly for topical treatment of the nasal vestibulum in patients carrying methicillin-resistant Staphylococcus aureus (MRSA). However, mupirocin is also active against methicillin-sensitive S. aureus. Nasal colonization with S. aureus has been identified as a significant risk factor for surgical site infection (SSI). ⋯ Because of the heterogeneity of the studies and the variability of results, no recommendation can be given for the general use of mupirocin in elective surgical patients. Specifically, because of the negative result of a recently published high-quality study, no recommendation can be made for the use of mupirocin in cardiosurgical patients. By contrast, eradication of MRSA before surgery appears to lower SSI rates due to MRSA and is therefore recommended.
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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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Diarrhea is a well-known complication of antibiotic therapy. Rates of antibiotic-associated diarrhea (AAD) vary from 5 to 25%. Some antibiotics are more likely to cause diarrhea than others, specifically, those that are broad spectrum and those that target anaerobic flora. ⋯ Data from clinical trials suggest that poorly absorbed antimicrobials might have a decreased risk of causing AAD and Clostridium difficile-associated disease, as concluded from studies of antibiotics used for preoperative bowel decontamination and poorly absorbed antibiotics used for traveler's diarrhea. Controlled trials would prove this but are not yet available. Probiotics may be a good adjunct to poorly absorbed antibiotics to minimize the risk of diarrhea associated with antibiotics.
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The four major factors predisposing individuals to community-acquired pneumonia (CAP) are chronic obstructive pulmonary disease, congestive heart failure, diabetes, and a high alcohol intake. The elderly are also at increased risk of severe infection. ⋯ Of the fluoroquinolones currently available that have antipneumococcal activity, levofloxacin is well tolerated and effective. It has been approved by the Food and Drug Administration (FDA) for treatment of CAP and widespread use has shown it to be very safe.