Background: Antibiotic resistance in Gram-negative baccilli (GNB) is escalating globally; thus achieving optimal antimicrobial exposures has become considerably more challenging. We used data from ''Tracking Resistance in the United States Today (TRUST) surveillance program'' to compare the probabilities of attaining requisite antibiotic exposures against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa.Methods: Using Monte Carlo simulation, pharmacodynamic profiling was performed for standard and prolonged infusions of cefepime 1&2gq12 h, 2gq8h(0.5h&3 h infusions); ceftazidime 1&2gq8h(0.5&3 h); ceftriaxone; 1&2gq24h(0.5 h); ciprofloxacin 0.4gq8&12h(1 h); doripenem 0.5, 1&2gq8h(1&4 h); ertapenem 1gq24h(0.5 h); imipenem 0.5gq6&8h(0.5 h), 1gq8h(0.5&3 h); levofloxacin 0.75gq24h(1 h); meropenem 0.5gq6&8h(0.5 h) then 1&2gq8h(0.5&3 h); piperacillin/tazobactam 3.375&4.5gq6h(0.5 h), 3.375gq8h(4 h), 4.5gq6h(3 h). MIC data were incorporated from the 2008 TRUST program. Pharmacodynamic targets were defined as fT>MIC >40% for carbapenems, 50% for penicillins and cephalosporins. A total AUC/MIC ≥87 and ≥125 was applied for levofloxacin and ciprofloxacin, respectively. The cumulative fraction of response (CFR) was determined for each regimen against each population of organisms. Optimal CFR was defined a priori as ≥90%.Results: The fluoroquinolones displayed the lowest susceptibilities against all organisms. All cephalosporins, carbapenems and piperacillin/tazobactam had susceptibility rates >90% for Enterobacteriaceae. Against P. aeruginosa, piperacillin/tazobactam portrayed the highest percent susceptibility(90%), followed by meropenem(89.8%), cefepime(88%), and ceftazidime/doripenem(86%). All $lactam regimens achieved optimal CFR against E. coli, and all but piperacillin/tazobactam 3.375 g q6h achieved optimal CFR against K. pneumoniae. The fluoroquinolones achieved the lowest CFRs against all organisms. Against P. aeruginosa, high dose, prolonged infusion doripenem and meropenem achieved CFRs of 97.2% to 98.8%, followed by high dose, prolonged infusion ceftazidime(93.3%) and cefepime(93.2%). No regimens achieved optimal CFR against A. baumannii. Prolonged infusion regimens increased CFR for all $-lactams against the non-fermenting GNB.Conclusion: Standard intravenous doses of many commonly $-lactam regimens have a high probability of achieving optimal exposure against Enterobacteriaceae. For non-fermenting-GNB, higher dose, prolonged infusions of cefepime, ceftazidime, doripenem, and meropenem offered the highest probabilities of achieving bactericidal exposure.
Many haematological issues can complicate end of life care, including cytopenias and venous thromboembolism. Anaemia is very common and can significantly impact quality of life; causes include haemorrhage, iron deficiency, nutritional deficiencies, and bone marrow infiltration. Neutropenia from bone marrow failure as a result of disease infiltration or from chemotherapy effects can result in life-threatening infections. Finally, venous thromboembolism is commonly seen in cancer patients as well as those who require prolonged hospitalization. Symptoms can cause discomfort, mortality is increased, and treatment is associated with major bleeding. Understanding the therapeutic options and their adverse side effects is essential in the management of these complex problems. Despite the presence of effective therapies, it is also important to realize that events such as febrile neutropenia and pulmonary embolism are often seen at the end of life and intervention may not always impact prognosis. The risks of intervention should be weighed against expected benefits when developing appropriate palliative care plans.
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