A prospective, open-label noncomparative study with piperacillin-tazobactam monotherapy as management of fever in patients with acute leukemia

We evaluated the efficacy of piperacillin-tazobactam monotherapy as empiric therapy of fever in acute leukemia patients in a total of 80 consecutive febrile episodes. The overall success rate was 75% with success without modification in 34% (afebrile at 72 h) and an overall death rate of 10%. No significant differences were seen in correlation between clinical outcome and phases of underlying disease. The success without modification was higher in patients with fever of unknown origin (FUO) than in those with documented infections (47% and 25% respectively). There were no significant differences in correlations between clinical response and degree of neutropenia. Our study suggests that empirical first-line monotherapy with piperacillin-tazobactam may be a reasonable option in patients with acute leukaemia, although in documented infections the response is frequently inadequate.     

Management of fever in neutropenic patients with acute leukemia: current role of ceftazidime plus amikacin as empiric therapy

To evaluate the current role of ceftazidime plus amikacin as empiric therapy in the management of fever in neutropenic patients with acute leukemia, we examined 172 febrile episodes in 106 patients enrolled during 1996-98. The overall success rate (survival of neutropenia, both with and without protocol modification) was 90%: 39% without modification and 51% with modification. We documented a significant difference in documented infections (DI) and fever of undetermined origin (FUO): success without modification was lower in DI and higher in FUO. Failure (death due to documented or presumed infection) was recorded in 10% of all episodes. Episodes with severe neutropenia were treated in 48% of cases without modification and in 41% with modification. No significant difference was observed in the status of underlying disease. 33% of gram-negative bacteria responsible for bloodstream infections were resistant to ceftazidime, of which 21% were multiresistant strains. We conclude that initial chemotherapy with ceftazidime plus amikacin remains a reasonable option for treating febrile and prolonged neutropenia, although patients with DI are likely to require additional or modified treatment. The emergence of resistant strains is an increasingly important issue.     

Ticarcillin-clavulanic acid plus amikacin versus ceftazidime plus amikacin in the empirical treatment of fever in acute leukemia: a prospective randomized trial

We evaluated the efficacy of ticarcillin-clavulanic acid plus amikacin (TCA) with ceftazidime plus amikacin (CFA) as empiric therapy of fever in acute leukemia in a total of 127 episodes. The overall success rate of the therapy (survival) was 93% in TCA group and 92% in CFA group. Success without therapy modifications (afebrile at 72 hours) was 39% for TCA, 31% for CFA; success with modifications was 55% and 61% respectively. Failure (death due to documented or presumed infection) was 6% for TCA and 8% for CFA. Differences were not statistically significant. The success without modifications was higher in the group of patients with fever of unknown origin (FUO) than in documented infections (DI), mainly with CFA. No differences were documented in the resistance rate and in clinical outcome during severe neutropenia (ANC <100 microl). In our experience TCA is as effective as CFA as first-line treatment in severe neutropenic patients with acute leukemia, although in both regimens patients with DI are likely to require modifications in treatment.     

Meropenem Versus Piperacillin-Tazobactam as Empiric Therapy for Febrile Neutropenia in Pediatric Oncology Patients

Background: Infection is a serious cause of mortality in febrile neutropenia of pediatric cancer patients.Recently, monotherapy has replaced the combination therapy in empirical treatment of febrile neutropenia.Since there has been no reported trial comparing the efficacy of meropenem and piperacillin-tazobactam (PIP/TAZ) monotherapies, the present retrospective study was conducted to compare safety and efficacy in febrileneutropenic children with cancer. Materials and Methods: Charts of febrile, neutropenic children hospitalizedat our center between March 2008 and April 2011 for hemato-oncological malignancies were reviewed. Patientsreceived PIP/TAZ 360 mg/kg/day or meropenem 60 mg/kg/day intravenously in three divided doses. Durationof fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between thetwo groups. Resolution of fever without antibiotic change was defined as success and resolution of fever withantibiotic change or death of a patient was defined as failure. Modification was defined as changing the empiricalantimicrobial agent during a febrile episode. Results: Two hundred eighty four febrile neutropenic episodes weredocumented in 136 patients with a median age of 5 years. In 198 episodes meropenem and in 86 episodes PIP/TAZ were used. Duration of fever and neutropenia, neutrophil count, sex, and primary disease were not differentbetween two groups. Success rates and modification rate between two groups showed no significant differences(p>0.05). Overall success rate in the meropenem and PIP/TAZ groups were 92.4% and 91.9% respectively. Noserious adverse effects occurred in either of the groups. Conclusions: Meropenem and PIP/TAZ monotherapyare equally safe and effective in the initial treatment of febrile neutropenia in children with cancer.     

Imipenem/Cilastatin Monotherapy as Salvage Treatment in Febrile Neutropenic Patients

Abstract

Imipenem/cilastatin (I/C) monotherapy was used as salvage treatment in 55 neutropenic patients (58 fever episodes) after treatment failure on first-line antibiotic therapy. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiologic evidence of infection on I/C monotherapy alone. Twentyfive out of the 58 episodes (43%) were classified as success, 6 episodes (10%) as initial response but the regimen had to be modified (amphotericin B was added) and 27 episodes (47 %) as failures. In episodes with documented infections 9 out of 23 (39%) were classified as success. All patients survived during the first 72 hours after change to I/C therapy. One patient had to discontinue I/C due to a skin rash.

In conclusion, the use of a treatment algorithm with I/C monotherapy as second-line treatment was safe and effective. Other antimicrobial agents, most often vancomycin and/or amphotericin B, had to be added in half of the patients.     

An Open Evaluation of Triple Antibiotic Therapy Including Vancomycin for Febrile Bone Marrow Transplant Recipients with Severe Neutropenia

Abstract

Infectious complications still represent a major problem in patients submitted to bone marrow transplant (BMT); approximately 40% of febrile episodes are associated with infection and one-third of these are bacteremias. Opinions about the best appropriate empiric regimens are based on evaluation of cost, potential for adverse side-effects, development of bacterial resistance, prevalent nosocomial infections.

In order to assess the clinical and microbiological effectiveness of an aggressive approach, we performed a prospective open study in 72 neutropenic febrile BMT patients, employing a triple antibiotic association including amikacin 500mg x 8h, ceftazidime 2g x 8h, vancomycin 500mg x 8h as first-line empiric treatment. For the purpose of this study, a lasting return of temperature to normal and complete disappearance of either clinical or bacteriological signs of infection without any modification of therapy was considered as success; the persistence of fever after 72 hours or a protocol change was considered as failure. Eighty episodes were enrolled during the course of the study; bacteriological evidence of infection was obtained in 23 (28.7%) febrile episodes. Median duration of antibiotic administration and of febrile episodes were 5 and 2 days respectively. Overall response rate based on clinical responses was 87% and 91% in microbiological documented infections. Death due to sepsis nor toxicity were observed. This triple antibiotic combination appears to be a very effective regimen for the empiric treatment of febrile episodes in severely neutropenic BMT recipients.     

Cost-Effectiveness of Cefepime + Netilmicin or Ceftazidime + Amikacin or Meropenem Monotherapy in Febrile Neutropenic Children with Malignancy in Turkey

Abstract

Infection remains the major cause of morbidity and mortality in immuno-compromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblas-toma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1^st, 2^nd and 3^rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (x²

test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.     

Cefepime as empirical monotherapy in febrile patients with hematological malignancies and neutropenia: a randomized, single-center phase II trial.

The purpose of this phase II trial was to evaluate the efficacy and safety of cefepime monotherapy in patients with neutropenia expected to last more than 7 days. Sixty-nine patients with neutropenia (<0.5 x 10(9)/1) were randomized during 94 episodes of fever to receive either cefepime monotherapy (n=76) or combination therapy with trimethoprim/sulfamethoxazole plus amikacin (TMP/SMZ plus AMI, n=18). A successful response to cefepime was seen in 31/76 (41%) episodes, with 10/36 (28%) in microbiologically documented infections, 3/4 (75%) in clinically documented infections and 18/36 (50%) in fever of unknown origin. No patient in either treatment group died due to the presenting infection. One patient in the cefepime group discontinued treatment due to a rash. Susceptibility testing of blood isolates by E-test strip showed low MIC values to cefepime for most isolates. It is concluded that cefepime monotherapy appeared both safe and effective as empirical therapy in patients with febrile neutropenia.     

Ceftaroline fosamil and treatment of acute bacterial skin and skin structure infections: CAPTURE study experience

Abstract

The Clinical Assessment Program and TEFLARO Utilization Registry (CAPTURE) is a multicentre retrospective cohort study in the USA describing treatment of acute bacterial skin and skin structure infection (ABSSSI) with ceftaroline fosamil (CPT-F). Charts for review were chosen by random selection. Among 647 evaluable patients, 52% were obese, 46% had diabetes mellitus (DM), and 19% had peripheral vascular disease (PVD). Methicillin-resistant Staphylococcus aureus (MRSA) was recovered in 28% and methicillin-susceptible S. aureus (MSSA), 11%. Antibiotics were administered prior to CPT-F treatment in 80%, and concurrently in 39%. Clinical success overall was 85%; in patients with DM, 83%; with PVD, 76%; and in obese patients, 88%. Clinical success was ≧ 79% across all infection types; 81% for MRSA and 83% for MSSA; and 86% for ceftaroline monotherapy and 84% for concurrent therapy. These high clinical success rates support CPT-F as an effective treatment option for ABSSSI, including infections due to MRSA and patients with significant co-morbidities.     

Evaluation of imipenem 1.5 g daily in febrile patients with short duration neutropenia after chemotherapy for non-leukemic hematologic malignancies and solid tumors: personal experience and review of the literature

Numerous studies have demonstrated efficacy of imipenem-cilastatin, 50 mg/kg/day, as first line therapy in febrile patients with neutropenia of short duration consecutive to cytostatic chemotherapy. However, only two studies used low dosage of this antibiotic as 1.5 g/day, in prospective, double blind, randomized clinical trials, in this indication. Efficacy and tolerability of imipenem-cilastatin 0.5 g three times daily IV in 30-min infusions, as first-line empiric therapy, were retrospectively evaluated in our hematological unit. From January 1996 to September 2000, 30 neutropenic patients (12 females) with 45 febrile episodes were included. Median age was 57.5 years (31-75). Twenty-four of them had lymphomas, 4 solid tumors and 2 myelomas. There were 13 clinically documented infections, (CD, 28.8%), 16 microbiologically documented infections, (MD, 35.6%) and 16 febrile episodes corresponding to fever of unknown origin, (FUO, 35.6%). The median neutrophils count on nadir ( n =44), was 67/mm 3 (8-369). The median duration of neutropenia was 5 days (3-15). Bacteremia was observed in 10 patients, urinary tract infection in 3 patients. The most frequently isolated microorganism was Escherichia coli . The overall success rate of the first line therapy was 66.7%. Adverse events were observed in 11.1% of the patients without necessity to stop treatment. The MD infections showed a lower rate of success compared with CD infections and FUO. These data were in accordance with the previous studies. The importance of number of microorganisms ( p =0.007) and of infected sites ( p =0.01) appeared as prognostic factors (univariate analysis). Although imipenem-cilastatin has been used in numerous studies as empiric broad-spectrum antibiotic therapy in the treatment of febrile neutropenic cancer patients, the exact dosage of this antibiotic is still not standardized. However, utilization of this antibiotic in monotherapy at low dosage seems to us to be safe and effective as usual dosage in the antimicrobial treatment of the febrile patients with post chemotherapy neutropenia of short duration.     

Empiric treatment of infection during granulocytopenia

Results from clinical trials conducted over the past 15 years suggest the following: a) Early empiric therapy with broad-spectrum antibiotics directed against Gram-negative bacillary bacteremia is necessary in febrile granulocytopenic cancer patients; b) The level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; c) Most empiric antimicrobial regimens will require therapeutic modifications; these alterations are necessary and contribute to a high overall success rate; d) Only microbiologically documented infections and especially bacteremias are useful for comparison of initial response to antimicrobial regimens; e) The response rate of Gram-negative bacillary bacteremia is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen; emergence of resistance to some beta-lactam antibiotics is quite common and necessitates successive modifications of empiric regimens with time; f) The combination of an anti-pseudomonal beta-lactam with an aminoglycoside is recommended as the standard for empiric therapy in febrile granulocytopenic cancer patients, especially in those with severe and persistent granulocytopenia who are suspected of having Gram-negative bacillary bacteremia; less neutropenic and/or asymptomatic patients may do well with monotherapy; g) Gram-positive pathogens have become a common cause of bacteremia in granulocytopenic cancer patients; the response rate to empiric regimens may be suboptimal but the associated mortality is low; h) Patients with severe granulocytopenia and protracted fever whose blood cultures remain negative are at high risk for contracting fungal infections; in these patients, empiric antifungal agents are probably indicated.     

An open evaluation of triple antibiotic therapy including vancomycin for febrile bone marrow transplant recipients with severe neutropenia.

Infectious complications still represent a major problem in patients submitted to bone marrow transplant (BMT); approximately 40% of febrile episodes are associated with infection and one-third of these are bacteremias. Opinions about the best appropriate empiric regimens are based on evaluation of cost, potential for adverse side-effects, development of bacterial resistance, prevalent nosocomial infections. In order to assess the clinical and microbiological effectiveness of an aggressive approach, we performed a prospective open study in 72 neutropenic febrile BMT patients, employing a triple antibiotic association including amikacin 500 mg x 8h, ceftazidime 2 g x 8 h, vancomycin 500 mg x 8 h as first-line empiric treatment. For the purpose of this study, a lasting return of temperature to normal and complete disappearance of either clinical or bacteriological signs of infection without any modification of therapy was considered as success; the persistence of fever after 72 hours or a protocol change was considered as failure. Eighty episodes were enrolled during the course of the study; bacteriological evidence of infection was obtained in 23 (28.7%) febrile episodes. Median duration of antibiotic administration and of febrile episodes were 5 and 2 days respectively. Overall response rate based on clinical responses was 87% and 91% in microbiological documented infections. Death due to sepsis nor toxicity were observed. This triple antibiotic combination appears to be a very effective regimen for the empiric treatment of febrile episodes in severely neutropenic BMT recipients.     

Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.     

Monotherapy for empirical management of febrile neutropenic patients

New fever in a neutropenic patient mandates prompt institution of empirical broad-spectrum antibiotics. Traditional empirical regimens have relied on combinations that include an aminoglycoside. However, certain classes of newer antibiotics (e.g., third-generation cephalosporins, carbapenems, quinolones) include agents with a broad spectrum and high bactericidal activity that may provide therapeutic alternatives to combination regimens. We previously compared empirical monotherapy with ceftazidime to a combination regimen of cephalothin, gentamicin, and carbenicillin and found the regimens comparable with respect to percentage with success (survival without change of initial regimen; 62% vs 67%), success with modification (survival with additional antibiotics; 33% vs 29%) and failure (death; 5% vs 4%). Imipenem has a broader in vitro spectrum of activity than ceftazidime, particularly against gram-positive organisms and anaerobes, raising the possibility of equivalent or even improved efficacy as monotherapy. Accordingly, we are prospectively randomizing febrile, neutropenic patients to either empirical ceftazidime or imipenem therapy. Imipenem appears to be comparable to ceftazidime in this ongoing study but has not resulted in fewer modifications or secondary infections. Studies assessing the role of quinolones in the management of neutropenic patients are under way.     

Ceftriaxone as a Single Agent in Empirical Therapy of Unexplained Fever in Granulocytopenic Children with Solid Tumors

Abstract

The optimal management of fever in granulocytopenic cancer patients remains controversial. Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile granulocytopenic patients with solid tumors. Available data show that response to empiric therapy is often more related to disease classification (solid tumors vs. acute leukemia) than to the regimen used. In this study we based empiric monotherapy on the underlying disease (solid tumors) in treating 33 episodes of fever in 26 granulocytopenic children with cancer. We investigated the potential effectiveness of single daily doses of ceftriaxone administered empirically in febrile granulocytopenic children with solid tumors. Fever was treated successfully with ceftriaxone monotherapy in 91% (30/33) of febrile episodes. None of the patients died as a result of primary infection. These results suggest that empirical monotherapy with once-daily ceftriaxone is safe and effective. In addition, when compared with other extended-spectrum cephalosporins such as ceftazidime, once-daily administration of ceftriaxone reduces cost and patient inconvenience, allowing convenient parenteral therapy even on an outpatient basis.     

Ibrutinib Monotherapy in Relapsed or Refractory,Transformed Diffuse Large B-cell Lymphoma

BackgroundHistologic transformation to diffuse large B-cell lymphoma (tDLBCL) occurs in a significant proportion of indolent lymphomas. However, few studies of novel agents inform its management, particularly when relapsed after or refractory (R/R) to prior treatment.Patients and MethodsWe prospectively evaluated ibrutinib monotherapy in pathologically documented patients with R/R tDLBCL in a single-arm study. The primary endpoint was overall response rate.ResultsTwenty patients who had received a median of 4 (range, 2-9) prior lines of therapy overall (median, 2.5; range, 1-9 for tDLBCL) were treated. The overall response rate was 35%, including complete responses in 15%. The median progression-free survival and overall survival were 4.1 months (95% confidence interval, 2.4-6.2 months) and 22.4 months (95% confidence interval, 7.5 months to not reached), respectively. Disease control > 2 months was seen in 75% and > 1 year in 15%. Response was associated with either low tumor bulk or low metabolic tumor volume (P = .05) but not with antecedent lymphoma histology (P = 1.0). Treatment-related adverse events were consistent with prior studies of ibrutinib.ConclusionsIbrutinib showed low toxicity and meaningful efficacy in R/R tDLBCL, including short-term disease control in most cases. Results demonstrate the potential utility of ibrutinib in this challenging clinical setting, including as a potential bridge to more definitive treatments.     

Assessment of procalcitonin as a diagnostic and prognostic marker in patients with solid tumors and febrile neutropenia

BACKGROUND: Cancer patients with fever and neutropenia currently are assessed on clinical grounds only. The current study prospectively evaluated the efficacy of baseline procalcitonin (PCT) in the detection of bacteremia and in the prediction of outcome in patients with solid tumors and febrile neutropenia. METHODS: PCT levels were determined at baseline and every 48 hours in 104 patients undergoing chemotherapy who developed fever (axillary temperature > 38 degrees C on 2 occasions or > 38.3 degrees C in a single record) and neutropenia (absolute neutrophil count < 500 cells/microL). RESULTS: The median baseline PCT values were significantly higher in patients who had microbiologically documented infections (1.24 ng/mL) compared with patients who had clinically documented infections (0.27 ng/mL) or fever of unknown origin (0.21 ng/mL; P < 0.01). Accordingly, a PCT cut-off value of 0.5 ng/mL was reached more frequently in patients who had microbiologically documented infections compared with patients who had clinically documented infections or fever of unknown origin (66.7% vs. 13.4%, respectively; P < 0.001). Furthermore, this threshold also was associated with an increased likelihood of treatment failure (70.0% vs. 14.9%; P < 0.001). All 4 septic patients and all 5 patients who ultimately died presented PCT values 5-fold to 10-fold greater than the median values. Clinical evaluation in combination with baseline PCT assessment appeared to improve clinical risk evaluation alone. CONCLUSIONS: Baseline PCT levels were higher in patients who had febrile neutropenia with bacteremia compared with patients who had clinical infections or fever of unknown origin. PCT helped to identify patients who had microbiologic infections and patients who were at high risk of treatment failure, and PCT may constitute a complementary tool in the initial assessment of such patients.     

Three-day treatment with imipenem for unexplained fever during prolonged neutropaenia in haematology patients receiving fluoroquinolone and fluconazole prophylaxis: A prospective observational safety study

BackgroundGuidelines advocate >7 d of broad-spectrum antibiotics for unexplained fever (UF) during neutropaenia. However, effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. This study evaluates the safety of discontinuing empirical broad-spectrum antibiotics if no microbial source is documented after an initial work-up of 72 h.MethodsProspective observational study at a tertiary-care haematology-unit in patients suffering from haematologic malignancies and treatment-induced prolonged neutropaenia of ?10 d. Oral fluoroquinolone and fluconazole prophylaxis was given from day 1. Fever was empirically treated with imipenem which was discontinued after 72 h if, following a standardised protocol, no infectious aetiology was documented. Duration of fever, antimicrobial therapy and overall mortality were registered.ResultsOne hundred and sixty six patients were evaluated during 276 neutropaenic episodes. One hundred and thirty six patients (82.5%) experienced ?1 febrile episode. A total of 317 febrile episodes were observed, of which 177 (56%) were diagnosed as UF. In 135 febrile episodes (43%), a probable/definite infectious origin was documented. Mean duration of fever in neutropaenic periods with 1 febrile episode was 5 d, and mean time of treatment with imipenem was 4.7 d. In patients without documented infection, mean time of imipenem treatment was only 3.7 d. Overall mortality 30 d after neutrophil recovery was 3.6% (6/166); no patient died from untreated bacterial infection.ConclusionDiscontinuation of broad-spectrum antibiotics during neutropaenia in haematology patients on fluoroquinolone and fluconazole prophylaxis is safe, provided that no infectious aetiology is established after 72 h.     

Ceftazidime and amikacin as empiric antibiotic therapy of febrile granulocytopenic patients with hematological malignancies. Report of 171 consecutive episodes

One hundred and seventy-one consecutive febrile episodes occurring in 130 neutropenic adult patients with hematological malignancies (mainly acute leukemia) were empirically treated with a combination antibiotic therapy consisting of ceftazidime (100 mg/kg/day) + amikacin (15 mg/kg/day). Of these, 161 were evaluable. In the majority of episodes (75 per cent) documented infections were identified as a cause of fever. There were 73 bacteremias (34 Gram-negative, 29 Gram-positive, 10 polymicrobial). One third of patients had pneumonia. Cure without change of the initial regimen was achieved in 45/73 (62 per cent) bacteremic episodes and in 12/13 episodes of microbiologically documented infections without bacteremia. There were 35 clinically documented infections and 26 (74 per cent) of these were cured. Of the 40 patients presenting with possible infections 26 (65 per cent) were cured. Overall, cure without modification of the initial antibiotic combination was achieved in 109/161 episodes (68 per cent). In spite of the frequent occurrence of persistent neutropenia (82 per cent), the infectious mortality was low (8.6 per cent), and often due to superinfection. The deaths due to primary infections were 6/161 (3.7 per cent). Side effects were mild and rare. In our experience ceftazidime + amikacin was an effective and safe empirical regimen for this population of hematologic patients with persistent neutropenia and severe documented infections.     

Imipenem/cilastatin as empirical treatment of severe infections in compromised patients

Imipenem/cilastatin was administered as empirical treatment to 22 patients with severe infections, at dosages of 2 or 4 g/day, either alone or in combination with an aminoglycoside. The majority of patients had underlying diseases causing various degrees of immune system dysfunction. The overall cure rate was 77.2%, without significant differences according to the type of pathogen or dosage schedule; however one of the two observed failures was due to a resistant Pseudomonas aeruginosa. Strains recovered from improved patients were all sensitive to the drug. Only mild adverse effects were evidenced, without any alteration of laboratory parameters. Imipenem/cilastatin may be useful as monotherapy in empirical treatment of severe infections in compromised patients.