Early Empiric Antibiotic Research Articles

Empiric antibiotic monotherapy with carbapenems in febrile neutropenia: a review.

Early empiric antibiotic therapy can significantly decrease the risk of mortality and infectious morbidity in patients with hematologic malignancies. Broad-spectrum antibiotics, usually a combination regimen of a beta-lactam and an aminoglycoside, have traditionally been employed against the wide variety of organisms that cause febrile episodes. However, since the 1970's, there has been a shift in epidemiology from Gram-negative to Gram-positive infections, against which traditional combination regimens have only limited efficacy. The carbapenems offer a suitable monotherapeutic alternative as they have a very broad spectrum of antibacterial activity, and equivalent efficacy and safety compared with combination regimes. Trials using imipenem/cilastatin have shown equal efficacy to ceftazidime but neurologic and gastrointestinal toxicity were observed at high doses (1 g 6-hourly). In the largest study to date, meropenem (1 g 8-hourly) provided effective, well tolerated monotherapy for patients with febrile neuropenia, equivalent to a regimen of ceftazidime plus amikacin. It is concluded that meropenem appears to be a realistic option for initial monotherapy in febrile neutropenic patients, providing therapy that is equivalent to a standard regimen of ceftazidime and amikacin.

New beta-lactam antibiotics in granulocytopenic patients: New options and new questions

Infectious complications are a frequent cause of morbidity and, at many centers, the major cause of death in patients with cancer. The increased risk and severity of Infectious sequelae result from profound alterations in normal host defenses that occur secondary to the underlying malignancy and the treatment thereof. During the last decade, early empiric antibiotic therapy has become standard practice in the Initial management of febrile granulocytopenic patients and has contributed significantly to the improved outcome among patients undergoing cancer therapy. Although early death due to unsuspected or inadequately treated bacterial infection has been largely overcome, new problems—also with life-threatening implications—have emerged. As the use of cancer chemotherapy continues to increase, new populations of patients are being placed at increased risk of infection. Defining the host and environmental factors that contribute to this risk assumes central importance for delineating those patients who require the most intense surveillance. Changing medical practices (e.g., increased use of indwelling catheters) have contributed to the emergence of new pathogens. Recent drug developments (e.g., the third-generation cephalosporins and extended-spectrum penicillins) offer new treatment options, as well as generate controversy and confusion. For example, authorities disagree on the optimal duration and modifications in treatment that are required by cancer patients who remain granulocytopenic and who thus are at continued risk of multiple infectious episodes or superinfections. A question of current interest is whether combination therapy with synergistic agents is important in light of the development of the third-generation cephalosporins and extended-spectrum penicillins. Several of these new antibiotics have an exceedingly broad spectrum of activity that includes Pseudomonas aeruginosa, as well as Enterobacterlaceae, Serratia, Citrobacter, indole-positive Proteus, and anaerobes (including Bacteroides fragilis). However, the third-generation cephalosporins are not as active against staphylococci and streptococci as are the first-generation cephalosporins, and none is effective against enterococci. Nonetheless, these agents achieve serum levels that can be 10 to 100 times greater than the minimal inhibitory and bactericidal concentrations of gram-negative bacteria, raising the possibility that these drugs might be effective as single agents. The advantages of the third-generation cephalosporins are their minimal toxicity and long serum half-lives. Although these new drugs are expensive, their cost must be evaluated within the context of their efficacy and clinical application.

Granulocytopenia and cancer therapy. Past problems, current solutions, future challenges.

Granulocytopenia has been closely associated with cancer and its treatment. The risk for a life-threatening infection when the granulocyte count falls below 500/mm3 not only is an important complication of therapy and a major cause of death in cancer patients but also plays an important role in the design, schedule, and doses of cancer treatment regimens. While granulocytopenia remains an unavoidable complication of current therapy, improved recognition of patients at risk and prompt initiation of aggressive supportive care have had a significant impact on reducing its infection-related morbidity and mortality. In particular, early empiric antibiotic therapy when the granulocytopenic patient becomes febrile has resulted in a significant reduction in the early mortality from undiagnosed bacterial infections. New antibiotics (extended-spectrum penicillins, third generation cephalosporins) provide new options because of their broad efficacy and potential for reducing the toxicity of antimicrobial therapy. However, as bacterial infections have become better controlled, fungi have emerged as important pathogens. Early aggressive empiric antifungal therapy appears to have reduced infectious mortality, although the repertoire of effective antifungal agents is quite limited. Considerable efforts have been expended in trying to replenish granulocytes by transfusion in infected patients, but technical deficiencies have limited this approach. Current and future efforts are directed toward refining management as well as to developing methods to improve host defenses and provide prophylaxis against infections. If the full potential of current cancer therapy is to be realized, control of granulocytopenia and the prevention of infections are essential goals.

Infection during remission induction in childhood leukaemia.

We have analysed our experience in the management of suspected infection in a group of 221 children with acute leukaemia undergoing induction of first remission. Patients with suspected infection received early empirical antibiotic therapy with cephalothin and gentamicin pending results of bacteriological investigations. Infection occurred in 17% of children with acute lymphoblastic leukaemia (ALL) whose initial treatment comprised prednisolone and vincristine, and was serious in 6·5%. 27% of children with ALL treated with intensive induction had infections which were serious in 20%; the figures for children with acute myeloblastic leukaemia (AML) were 49% and 22% respectively. The organisms responsible for most infections were Pseudomonas aeruginosa and Staphylococcus aureus; the former being most often associated with bacteraemia. One child (0·5%) died from infection. We conclude that with the use of early empirical antibiotic therapy, and granulocytes when appropriate, infection is no longer a major cause of death during remission induction. No special precautions are necessary to prevent its acquisition in most cases of ALL. In patients receiving early intensive treatment, including those with AML, measures designed to prevent acquisition of infection may reduce morbidity and enable the use of more effective chemotherapy.