Therapeutic role of granulocyte transfusions

Granulocyte transfusions are used as adjuvant therapy for infection in neutropenic patients with underlying neoplastic disease, neutropenic infants, and patients with qualitative white blood cell disorders. In addition, prophylactic leukocyte transfusions have been administered to patients during remission induction for acute leukemia or after bone marrow transplantation. The role of granulocyte therapy will need constant reassessment as new antibiotics and other forms of treatment are developed. At present, granulocyte transfusions are indicated in the treatment of severely neutropenic patients with documented bacterial infection who are unlikely to recover hematopoietic function over the next week and are deteriorating despite 48-72 hr of optimal antibiotic therapy. Under these conditions, they improve the rate of survival from the infectious episode without clearly affecting the longer-term survival of the patient. Only a small minority of neutropenic patients will require granulocyte transfusions.     

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.     

A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.

BACKGROUND--Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS--A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS--The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS--Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.     

After empiric therapy: what to do until the granulocyte comes back

The prompt initiation of empiric broad-spectrum antibiotic therapy when a granulocytopenic patient becomes febrile has become standard practice and has resulted in a significant reduction in the early morbidity and mortality associated with infection. Granulocytopenic patients, however, are at risk for multiple infectious episodes, particularly when the duration of neutropenia is prolonged. Accordingly, the addition of one or more antimicrobial agents to the initial empiric antibiotic regimen is often necessary to deal effectively with these second infections and to help maximize the patient's chance for survival. An organized plan that incorporates modifications of the primary antibiotic regimen (e.g., the addition of another antibiotic or an antifungal agent) into the overall management of the febrile neutropenic patient is important, especially when neutropenia lasts for more than a week.     

Granulocyte transfusions

Laboratory and clinical studies have demonstrated beyond question that granulocyte transfusions can have a beneficial effect on the incidence and course of bacterial infection. The increment of improved survival produced by granulocyte transfusions depends on the effectiveness of the alternative (primarily antibiotic) therapy alone, and this varies with the pattern of bacterial predominance and sensitivity, which is notoriously changeable. The absolute effectiveness of granulocyte transfusion therapy is influenced by the quality of the transfusions and the immune status of both the recipient and the granulocyte donor. The indiscriminate transfusion of inadequate quantities of granulocytes from random donors into sensitized recipients should be discouraged. Severely neutropenic patients with established infection unresponsive to antibiotic therapy are appropriate recipients of granulocyte transfusions. Well-designed programs of prophylactic granulocyte transfusions can reduce the occurrence of bacterial infection in neutropenic patients, but there are few clinical situations in which their use is justified. The use of cytomegalovirus-seropositive granulocyte donors for cytomegalovirus-seronegative recipients should be avoided. There is a need for technical advances that will increase the ease and efficiency of granulocyte procurement.     

Beta-lactam-resistant Enterobacter bacteremia in febrile neutropenic patients receiving monotherapy

Bacteremia with resistant Enterobacter species has been reported in febrile, neutropenic cancer patients receiving beta-lactam antibiotics. To assess the relationship between enterobacter bacteremia and ceftazidime monotherapy, medical records were reviewed and isolates were tested from 16 neutropenic and 35 nonneutropenic patients with Enterobacter bacteremia. Fifteen isolates from the neutropenic patients were resistant to extended spectrum cephalosporins; only 12 of 35 isolates from the nonneutropenic patients were resistant to Enterobacter species. The neutropenic patients also had more beta-lactam therapy, both immediately before bacteremia and in the preceding year, than did nonneutropenic patients. Prior beta-lactam antibiotic exposure may predispose neutropenic patients to develop resistant Enterobacter bacteremia.     

Antibiotic strategy after the empiric phase in patients treated for a hematological malignancy

 Empiric broad-spectrum antibiotic therapy has become a generally accepted strategy in the treatment of febrile neutropenic patients. Particularly in patients with prolonged neutropenia, subsequent adaptation of such a regimen will be the rule rather than exception. Since there are no uniformly accepted guidelines for the modification of antibiotic therapy during the post-empiric phase, we assessed the impact of a set of rules that evolved during the first randomized trials. Evaluation of the clinician's compliance with these rules in 1951 febrile neutropenic episodes was the subject of the present analysis. Treatment was modified in 761 (39%) cases, and these changes were made according to the rules in 76%. For 75% of the alterations in treatment during the evening and night shifts, no reasonable explanation was established, while 93% of the modifications during the normal working hours were made for objective reasons. The empiric regimen was more frequently changed in patients with a clinical focus of infection at the onset of fever than in patients who showed fever as the only symptom of a possible infection. The perceived need for modification amounted to 69% in pulmonary infections, to 51% in skin and soft-tissue infections, to 44% in patients with abdominal complaints, and to 37% in upper respiratory tract infections. Glycopeptides constituted 22% of modifications, particularly in patients with a central venous catheter, and systemically active antifungals were administered in 16% of cases. Especially inexperienced clinicians tend to adjust antibiotic therapy, in spite of the fact that persistence of fever alone seldom reflects inadequate treatment when the clinical condition of the patient is stable or improving. On the other hand, the development of subsequent infectious events emphasizes that a genuine need for modification does frequently exist. Received: 4 December 1995 / Accepted: 7 December 1995     

European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia

Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4^th European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient’s risk factors for resistant bacteria and for a complicated clinical course. An ‘escalation’ approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A ‘de-escalation’ approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72–96 h should be based on the patient’s clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance.     

Staphylococcus aureus sepsis in hospitalized non neutropenic patients: retrospective clinical and microbiological analysis

Staphylococcus aureus is one of the leading agents of nosocomial infection among adult patients. The aim of this study was to determine the predisposing factors and secondary complications of Staphylococcus aureus septicemia (SAS) in non neutropenic patients, as well as the predictors of the outcome in non neutropenic patients with SAS. We performed a retrospective study of 56 cases of SAS that occurred from January 1997 through June 2001 in patients hospitalized in medical wards at the Policlinico Umberto I, "La Sapienza" University of Rome; we excluded surgical patients and those admitted to the intensive care unit. The median age was 61.9 years (range 24-89 years), 29 (51%) patients were male, and infection was hospital-acquired in 83.5% of cases. Metastatic infections were found in 12 patients (21.4%), with 6 (10.7%) developing infectious endocarditis; the relapse rate was 8.9%; 30.3% of Staphylococcus aureus isolates were methicillin-resistant. The overall mortality was 41% and the attributable mortality 28.5%. Twenty-nine patients who developed metastatic infections or died for sepsis were compared with 27 patients who did not develop complications. At univariate analysis, the following factors were associated with a complicated course: delay to adequate antibiotic therapy (2.46 vs 1.15 days, p < 0.03), persistent Staphylococcus aureus bacteremia during antibiotic therapy (3.56 vs 1.51 days, p = 0.01), septic shock (58.6 vs 3.7%, p < 0.002), bacteremic pneumonia as the source of bacteremia (17.2 vs 0%, p = 0.02), and the increased severity of illness at the onset of SAS as evaluated using an "illness score" (4.2 vs 2.1, p < 0.002). At multivariate analysis, septic shock (p < 0.01) and delay to adequate antibiotic therapy (p = 0.05) were confirmed as associated with a complicated outcome. SAS in non neutropenic patients is associated with significant morbidity consequent to a high rate of metastatic infectious disease and with a considerable related mortality.     

Imipenem-cilastatin for empirical therapy in neutropenic patients with fever: an open study in patients with hematologic malignancies

In adult neutropenic patients with hematological malignancies, we explored imipenem-cilastatin as empirical antibiotic therapy in a dose of 500 mg four times daily. Changing to second-line treatment was only resorted to if clinical deterioration, new infections or recurrence of fever occurred. A clinically or microbiologically documented infection was apparent in 115 of 150 episodes studied (76.7%). Imipenem-cilastatin was successful in 70.7% of all episodes and in 67.8% of all proven infections. Modification was necessary and successful in 22.0% of all episodes. 11 patients died while still febrile, 6 of them by infection (4%) and 5 because of progressive disease (3.3%). Imipenem-cilastatin is safe initial therapy in neutropenic febrile patients.     

Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial

BACKGROUND: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting. OBJECTIVE: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy. DESIGN: An open randomized, controlled, multicenter trial, powered for equivalence. SETTING: 60 oncology centers in 10 countries. PATIENTS: 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy. INTERVENTION: Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution. MEASUREMENTS: Defervescence, breakthrough fungal infection, drug-related adverse events, and death. RESULTS: For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infections (5 patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar. Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days. CONCLUSIONS: Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.     

Empirical antibiotic therapy in febrile neutropenic patients with acute leukemia

One hundred and ninety-five episodes of fever during the neutropenic phase of chemotherapy in 49 patients with acute leukemia from 1984 to 1987 were analyzed with the following results: 1) Febrile episodes occurred in 80 percent of the neutropenic (less than 500/microliters) phase lasting more than 7 days after chemotherapy. 2) Febrile episodes consisted of 44 (22%) of established septicemia and 111 (57%) of suspected septicemia. 3) The pathogens causing septicemia were 8 GPC, 38 GNB (22 Pseudomonas species) and 6 fungi. Fungemia was confirmed on an average of 4.8 days after the onset of fever. The mortality of septic events was 10 out of 17 episodes (59%) when treated with antibiotics alone, while 8 out 27 (30%) with the combination of antibiotics plus antifungal drugs. 4) The mortality of suspected sepsis was only 2 out of 111 episodes. Eighty-three (75%) of these 111 episodes responded to antibiotics alone, while 26 (23%) cases needed antibiotics plus antifungal drugs. Our results suggest that in febrile neutropenic patient empiric broad-spectrum antibiotic therapy should be initiated which is especially effective for Pseudomonas species, but if fever persists despite more than 4 or 5 days of antibiotic therapy, additional antifungal therapy should be considered.     

肿瘤患者粒细胞缺乏症并感染的经验性抗生素治疗回顾性分析

目的　总结肿瘤患者粒细胞缺乏症并感染的经验性抗生素治疗的临床经验。方法　回顾性分析 119例肿瘤患者 2 4 8例次的临床资料 ,观察头孢哌酮 (CFP)、氧哌嗪青霉素 (PPC)、头孢他定 (CTZ)、亚胺培南 (IMP)与丁胺卡那霉素 (AMK)分别组成BA、PA、CA、TA方案的疗效及副作用。结果　BA、PA、CA、TA方案分别治疗 10 3、87、35和 2 3例次 ,治疗的中位时间为 7～ 8d ,有效率分别为 6 3%、4 8%、6 8%和 74 % ,PA方案明显为低 (P <0 0 5 )。治疗无效者调整治疗 :改用CA或TA方案加减去甲万古霉素 (NVC)及抗真菌治疗 ;总有效率分别为 88%、83%、86 %和 91%。最常见副作用为胃肠功能紊乱 ,腹泻为 12 % ,皮疹和肝转氨酶轻度升高分别为 4 % ;2例NVC和AMK治疗者出现明显的听力下降和肾脏毒性。结论　BA、CA、TA方案具有相似的疗效 ,可作为一线经验性治疗方案。经验性治疗无效者 ,应改用具有更高抗菌活性的方案或尽早采用NCV和 (或 )抗霉菌治疗     

Antibiotic therapy for gram-negative bacteremia.

Although antibiotic therapy is the mainstay of therapy for gram-negative bacillary bacteremia, the amelioration of the underlying conditions, the correction of predisposing factors, the drainage of abscesses, the removal of infected foreign bodies, and adequate supportive care are also of paramount importance for curing the infection and should not be neglected. Beginning in the late 1960s, most of the clinical work on gram-negative infections has focused on the evaluation of new antibiotics. Numerous studies have shown that early, appropriate antibiotic treatment of gram-negative bacteremia significantly improved patients' outcomes and prevented the development of septic shock. Prescribing standard doses of antibiotics does not necessarily mean that therapeutic levels will be reached in all patients, and relapses of infections or breakthrough bacteremias can occur in patients with subinhibitory serum levels of antibiotics. The monitoring of serum concentrations of antibiotic is therefore recommended in critically ill septic patients. Whereas initial studies on the antibiotic treatment of gram-negative bacteremia were carried out in nonneutropenic patients, more recent clinical investigations have been performed almost exclusively in cancer patients with neutropenia. Studies conducted in the 1970s and 1980s among these patients have shown the following: (1) early empirical therapy reduced the mortality of gram-negative bacteremia; (2) therapy with a combination of two antibiotics, be it an extended spectrum penicillin plus an aminoglycoside or a third-generation cephalosporin, has significantly improved patients' outcomes; and (3) triple-drug combinations (i.e., a penicillin plus a cephalosporin plus an aminoglycoside) are not superior to combinations of beta-lactams and aminoglycosides. For the treatment of gram-negative bacteremia, clinicians today have a choice between well-established antibiotic combinations and broad-spectrum single-agent therapy with third-generation cephalosporins or carbapenem antibiotics. Although recent studies suggested that monotherapy could be as effective as combination therapy for the empirical treatment of fever in the neutropenic host, no definitive study has so far unquestionably demonstrated the equivalence of these treatments in patients with gram-negative bacteremias, especially those caused by P. aeruginosa, or in patients with adverse prognostic conditions, such as persistent and profound granulocytopenia. This literature should however be reviewed with great caution. Indeed, only a minority of studies have included a sufficient number of patients to confidently assess the impact of therapy on patients' outcomes. Obviously, small studies can have a significant risk of type II errors, that is, making false-negative conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Bacteremia in patients with febrile neutropenia after chemotherapy at a university medical center in Malaysia.

OBJECTIVES: This study was initiated to determine the local profile of blood culture isolates and antibiotic sensitivities in febrile neutropenic patients following chemotherapy, and to establish if any modifications to treatment guidelines are necessary. DESIGN: A total of 116 episodes of febrile neutropenia admitted to the adult hematology ward at a university medical center in Malaysia were studied retrospectively from January 2004 to January 2005. RESULTS: The study showed 43.1% of febrile neutropenic episodes had established bacteremia. Gram-negative bacteria accounted for 60.3% of isolates. Sensitivities of Gram-negative bacteria to the antibiotics recommended in the Infectious Diseases Society of America (IDSA) guidelines were 86.1-97.2%. Coagulase-negative staphylococci were the most common Gram-positive organisms isolated (23.3%). The majority of these were methicillin-resistant. CONCLUSIONS: Carbapenem monotherapy, as recommended in the 2002 IDSA guidelines, is effective treatment for the infections most often encountered at our center. Combination therapy with an aminoglycoside should be considered when using ceftazidime, cefepime or piperacillin-tazobactam, particularly in high-risk patients. Vancomycin should be used if a Gram-positive organism is suspected or isolated.     

An evaluation of empirical antibiotic therapy in febrile neutropenic patients

A prospective study was undertaken to determine the effectiveness of an empirical antibiotic therapy regimen in 34 neutropenic patients undergoing bone marrow transplantation or remission-induction chemotherapy for leukaemia. Throughout the study period a total of 90 pyrexial episodes were monitored in which organisms designated to be pathogens were isolated from blood cultures on 38 occasions. The response rate to the combination of a ureidopenicillin with gentamicin fell sharply from 50% during patients' first pyrexial episodes to zero during the third and subsequent episodes. The preponderance of Gram-positive bacteria and the high overall resistance of bacterial isolates to these antibiotics have led us to reconsider our approach to empirical therapy and to include antibiotics with greater activity against Staphylococcus epidermidis. The emergence of fungi as a major cause of morbidity in patients with prolonged neutropenia underlines the necessity to introduce early empirical antifungal therapy in this group of patients.     

Outcome of attempted Hickman catheter salvage in febrile neutropenic cancer patients with Staphylococcus aureus bacteremia

There are limited data on outcomes of Hickman catheter salvage associated with Staphylococcus aureus bacteremia (SAB) in neutropenic cancer patients. We evaluated the outcome of attempted Hickman catheter salvage in these patients who were not given antibiotic lock therapy. Outcomes were retrospectively analyzed in all neutropenic cancer patients with Hickman catheter-related SAB over a 12-year period (56 episodes in 54 patients). Salvage attempts were defined as cases where the catheter was still in place 3 days after initial bacteremia. Salvage attempts were considered successful if catheter was still in place 12 weeks later without recurrent SAB or death. Of the 56 episodes, catheters were immediately removed in eight (14%), and catheter salvage was attempted in 48 (86%). Of these 48 episodes, attempted salvage was successful in 29 (60%) and failed in 14 (29%). Outcome of attempted salvage was indeterminate in five (11%) episodes. In univariate analysis, presence of external signs of catheter infection (p?=?0.03), positive follow-up blood culture (p?=?0.03), and methicillin resistance (p?=?0.04) were significantly associated with catheter salvage failure. In multivariate analysis, presence of external signs of catheter infection (OR 12.0; p?=?0.04) and methicillin resistance (OR 5.1; p?=?0.04) were independently associated with catheter savage failure. In conclusion, attempted catheter salvage without antibiotic lock therapy was successful in 60% of the patients with Hickman catheter-related SAB. External signs of catheter infection and methicillin resistance were independent risk factors for catheter salvage failure.     

The clinical impact of antibacterial prophylaxis and cycling antibiotics for febrile neutropenia in a hematological malignancy and transplantation unit

Febrile neutropenia is an expected complication during treatment of aggressive hematological malignancies and hematopoietic cell transplantation. We conducted a prospective cohort trial to determine the effects and safety of prophylactic fluoroquinolone administration, and rotation of empiric antibiotics for neutropenic fever in this patient population. From March 2002 through 2004, patients were treated with prophylactic levofloxacin during prolonged neutropenia, and a cycling schedule of empiric antibiotic therapy for neutropenic fever was initiated. The rates of bacteremia, resistance and complications were compared to a retrospective cohort of previously treated patients. The rate of gram-negative bacteremia decreased after the initiation of prophylactic levofloxacin (4.7 vs 1.8 episodes/1000 patient days, P<0.05). Gram-positive bacteremia rates remained unchanged, but more isolates of Enterococcus faecium were resistant to vancomycin after the intervention began. Resistance to the antibiotic agents used in the rotation did not emerge. There was no change in mortality during the intervention period. A prophylactic and cycling antibiotic schedule was successfully implemented on a hematological malignancy and hematopoietic cell transplant unit. gram-negative bacteremia was significantly decreased, without emergence of resistance. Concerns with Gram-positive resistance will require further observation.     

Aztreonam therapy in neutropenic patients with cancer

Combinations of aztreonam/vancomycin, aztreonam/vancomycin/amikacin, and moxalactam/ticarcillin were compared in a prospective randomized trial as empiric therapy for febrile neutropenic cancer patients. Vancomycin was added to aztreonam to provide coverage against gram-positive organisms. Of 535 febrile episodes included in the study, 455 were evaluable. The aztreonam/vancomycin and aztreonam/vancomycin/amikacin combinations were both more effective than the moxalactam/ticarcillin combination in a total of 244 episodes of documented infection. The difference was due to the fact that both aztreonam-containing combinations were more effective than the moxalactam/ticarcillin combination in documented gram-positive infections. The three regimens were equally effective in 67 documented infections due to a single gram-negative bacterial species. (The response rates were 87, 86 and 94 percent for the aztreonam/vancomycin, aztreonam/vancomycin/amikacin, and moxalactam/ticarcillin combinations, respectively.) Aztreonam was effective as the single active antibiotic in the treatment of gram-negative infections in neutropenic patients; however, it must be used in combination with another antibiotic to provide gram-positive coverage.     

Antimicrobial management of sepsis and septic shock

Every patient who has sepsis and septic shock must be evaluated appropriately at presentation before the initiation of antibiotic therapy. However, in most situations, an abridged initial assessment focusing on critical diagnostic and management planning elements is sufficient. Intravenous antibiotics should be administered as early as possible, and always within the first hour of recognizing severe sepsis and septic shock. Broad-spectrum antibiotics must be selected with one or more agents active against likely bacterial or fungal pathogens and with good penetration into the presumed source. Antimicrobial therapy should be reevaluated daily to optimize efficacy, prevent resistance, avoid toxicity, and minimize costs. Consider combination therapy in septic shock Pseudomonas infections in neutropenic patients. Combination therapy should be continued for no more than 3 to 5 days and de-escalation should occur following availability of susceptibilities. The duration of antibiotic therapy typically is limited to 7 to 10 days. Longer duration is considered if response is slow, if there is inadequate surgical source control, or if immunologic deficiencies are evident. Antimicrobial therapy should be stopped if infection is not considered the etiologic factor for a shock state.