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.     

Efficacy of meropenem as monotherapy in the treatment of ventilator-associated pneumonia

We performed a prospective, open label, randomized study in intensive care unit patients with ventilator-associated pneumonia (VAP) to determine the efficacy and safety of empiric intravenous (i.v.) meropenem monotherapy compared with the combination of ceftazidime plus amikacin. A total of 140 patients receiving mechanical ventilation and diagnosed with pneumonia were included in the study. Patients were randomized to receive either 1 g meropenem i.v. every 8 hours or 2 g ceftazidime i.v. every 8 hours plus 15 mg/kg amikacin daily, administered to patients with normal renal function as two daily doses. Satisfactory clinical responses (cure or improvement) were achieved at the end of treatment in 68.1% of meropenem-treated patients and 54.9% in the ceftazidime/amikacin-treated group (relative risk 1.25; 95% confidence interval >1.00, 1.55). When non-evaluable patients were excluded from the analysis, the satisfactory clinical response was 82.5% and 66.1% for the meropenem and ceftazidime/amikacin patients, respectively (p = 0.044). Logistic regression demonstrated that treatment with meropenem and both the basic traumatic and medical pathologies were significantly associated with a satisfactory response. Adverse events judged to be possibly or probably related to treatment were reported by seven (10.1%) patients in the meropenem group and by eight patients (11.3%) in the ceftazidime/amikacin group. The results of this study confirm that monotherapy with meropenem is well tolerated and provides superior efficacy to the conventional combination of ceftazidime and amikacin in combating VAP.     

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.     

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.     

Strategies for Cost-Containment: Once-Daily Ceftriaxone Plus Amikacin as Empiric Therapy for Febrile Granulocytopenic Children with Cancer

Abstract

Administration of broad-spectrum antibiotics as empiric therapy to febrile granulocytopenic patients has become a widely accepted practice. In order to evaluate the cost-effectiveness of ceftriaxone plus amikacin in single daily doses as empiric treatment for febrile granulocytopenic children with cancer, a retrospective review (January-December 1996) of all febrile episodes at our institution was carried out. Overall, 101 febrile episodes in 89 granulocytopenic children with cancer were empirically treated with a once-daily ceftriaxone plus amikacin combination. 59/101 (59%) patients had absolute granulo-cyte count lower than 100/mm³ at entry; 46 (45%) were affected by solid tumors, 16 (15%) by Hodgkin's disease or lymphoma, and 30 (30%) patients underwent bone marrow transplantation. The ceftriaxone plus amikacin combination was effective in 72/101 (72%) patients with a median time to defervescence of 3 days (range, 1-4). We also evaluated the economic advantages of the ceftriaxone plus amikacin once-daily regimen when compared with another treatment regimen such as ceftazidime plus amikacin requiring three daily doses. Compared with the multiple daily dose regimen of ceftazidime plus amikacin, there is a cost saving of US 11 (17,500 Italian liras) and US 66 (105,000 Italian liras) for both 1-day and 6-day treatments, respectively, by using the single daily dose regimen of ceftriaxone plus amikacin. The potential of ceftriaxone to lower costs in hospitalized patients depends upon its comparable efficacy with other extended-spectrum beta-lactams, in which case it can reduce overall treatment costs because of its once-daily administration schedule.     

Strategies for Cost-Containment: Once-Daily Ceftriaxone Plus Amikacin as Empirical Therapy for Febrile Granulocytopenic Children with Cancer

Abstract

Administration of broad-spectrum antibiotics as empiric therapy to febrile granulocytopenic patients has become a widely accepted practice. In order to evaluate the cost-effectiveness of ceftriaxone plus amikacin in single daily doses as empiric treatment for febrile granulocytopenic children with cancer, a retrospective review (January-December 1996) of all febrile episodes at our institutions was carried out. Overall, 101 febrile episodes in 89 granulocytopenic children with cancer were empirically treated with a once-daily ceftriaxone plus amikacin combination. 59/101 (59%) patients had absolute granulo-cyte count lower than 100/mm³ at entry; 46 (45%) were affected by solid tumors, 16 (15%) by Hodgkin's disease or lymphoma, and 30 (30%) patients underwent bone marrow transplantation. The ceftriaxone plus amikacin combination was effective in 72/101 (72%) patients with a median time to defervescence of 3 days (range, 1-4). We also evaluated the economic advantages of the ceftriaxone plus amikacin once-daily regimen when compared with another treatment regimen such as ceftazidime plus amikacin requiring three daily doses. Compared with the multiple daily dose regimen of ceftazidime plus amikacin, there is a cost saving of US 11 (17,500 Italian liras) and US 66 (105,000 Italian liras) for both 1-day and 6-day treatments, respectively, by using the single daily dose regimen of ceftriaxone plus amikacin. The potential of ceftriaxone to lower costs in hospitalized patients depends upon its comparable efficacy with other extended-spectrum beta-lactams, in which case it can reduce overall treatment costs because of its once-daily administration schedule.     

Randomized Study of Cefepime versus Ceftazidime plus Amikacin in Patients with Solid Tumors Treated with High Dose Chemotherapy (HDC) and Peripheral Blood Stem Cell Support (PBSCS) with Febrile Neutropenia

Objective This randomized clinical trial evaluated the efficacy and safety of monotherapy with cefepime for patients with solid tumors treated with high dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) with febrile neutropenia. Subjects Patients with solid tumors treated with HDC and PBSCS, that developed fever and neutropenia (absolute neutrophil count<500 cells/μL) were eligible, and randomly assigned to receive ceftazidime plus amikacin or cefepime. Results Fifty-one episodes were randomized, and all were evaluable (27 received ceftazidime plus amikacin arm, and 24 cefepime). Major efficacy endpoints did not show significant differences, with success rates of 44.4% and 54.2% (p=0.481) for the combination arm and the monotherapy arm, respectively. The proportion of patients that became afebrile in the first 24 hours was significantly higher in the cefepime group (41.7% vs 11.1%, respectively; p=0.012). However, due to its premature closure and small sample size, this study lacks the adequate power to definitely address this question. Conclusions Cefepime monotherapy appeared to have an equivalent efficacy and safety as empiric treatment in febrile neutropenia episodes in a high-risk population compared with ceftazidime and amikacin. Nevertheless, this study is not adequately powered to answer this question. Given the small number of patients randomized and the single-center nature of this study, these results must be cautiously interpreted. Presented in part at the meeting of the American Society of Clinical Oncology, Chicago, Illinois, May 2003 (abstr. 3387). A. Jimeno and A. Arcediano equally contributed to this work.     

Strategies for cost-containment: once-daily ceftriaxone plus amikacin as empiric therapy for febrile granulocytopenic children with cancer

Administration of broad-spectrum antibiotics as empiric therapy to febrile granulocytopenic patients has become a widely accepted practice. In order to evaluate the cost-effectiveness of ceftriaxone plus amikacin in single daily doses as empiric treatment for febrile granulocytopenic children with cancer, a retrospective review (January-December 1996) of all febrile episodes at our institution was carried out. Overall, 101 febrile episodes in 89 granulocytopenic children with cancer were empirically treated with a once-daily ceftriaxone plus amikacin combination. 59/101 (59%) patients had absolute granulocyte count lower than 100/mm3 at entry; 46 (45%) were affected by solid tumors, 16 (15%) by Hodgkin's disease or lymphoma, and 30 (30%) patients underwent bone marrow transplantation. The ceftriaxone plus amikacin combination was effective in 72/101 (72%) patients with a median time to defervescence of 3 days (range, 1-4). We also evaluated the economic advantages of the ceftriaxone plus amikacin once-daily regimen when compared with another treatment regimen such as ceftazidime plus amikacin requiring three daily doses. Compared with the multiple daily dose regimen of ceftazidime plus amikacin, there is a cost saving of US $11 (17,500 Italian liras) and US $66 (105,000 Italian liras) for both 1-day and 6-day treatments, respectively, by using the single daily dose regimen of ceftriaxone plus amikacin. The potential of ceftriaxone to lower costs in hospitalized patients depends upon its comparable efficacy with other extended-spectrum beta-lactams, in which case it can reduce overall treatment costs because of its once-daily administration schedule.     

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.     

A Randomized,Open-Labeled,Prospective Controlled Study to Assess the Efficacy of Frontline Empirical Intravenous Piperacillin/Tazobactam Monotherapy in Comparison with Ceftazidime Plus Amikacin for Febrile Neutropenia in Pediatric Oncology Patients

Background: Febrile neutropenia (FN) is the most common complication in pediatric oncology patients. Appropriate empirical antibiotics treatment is essential for treatment outcome. Methods: This study was a randomized prospective controlled study to demonstrate the efficacy of piperacillin/tazobactam (PIP/TZO) monotherapy compared with ceftazidime/amikacin in children with FN. Pediatric oncology patients at Chiang Mai University Hospital, diagnosed with FN, were randomized to receive either PIP/TZO 320 mg/kg/day divided every 8 hours or ceftazidime 100 mg/kg/day divided every 8 hours plus amikacin 15 mg/kg/day once daily. Treatment responses were compared between the two groups. Results: One-hundred and eighteen febrile neutropenic episodes in 70 patients (42 males and 28 females) were enrolled. The median age was 7 (3-10) years. The early response and complete response to initial treatment were achieved in 48/59 (81.4%) episodes and 41/59 (69.5%) episodes in PIP/TZO group compared with 40/59 (67.8%) episodes and 33/59 (55.9%) episodes in ceftazidime/amikacin group (p-value 0.091 and 0.128, respectively). Treatment modification in PIP/TZO group was required in 18/59 (30.5%) compared with 26/59 (44.1%) patients in ceftazidime/amikacin group (p-value 0.128). Similarly, the duration of fever, duration of neutropenia and duration of antibiotics treatment were not significantly different between two groups. No serious adverse events were observed. Conclusion: The treatment responses of PIP/TZO monotherapy and ceftazidime/amikacin therapy were not significantly different. Both therapies were effective for FN in pediatric oncology patients.     

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.     

Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial.

PURPOSE: To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia. PATIENTS AND METHODS: A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events. RESULTS: The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic (相似文献   

Combination and single-agent empirical antibacterial therapy for febrile cancer patients with neutropenia and mucositis

The role of mucositis in infectious complications in the patient with cancer is poorly understood. Consequently, neither the presence nor the severity of mucositis is routinely considered in the selection of specific antibacterial agents for the initial empirical therapy of the febrile cancer patient. In a study of children receiving remission induction chemotherapy for acute nonlymphocytic leukemia, the number of febrile days correlated more closely with the degree of mucositis than with the number of days of neutropenia. Oral mucositis appears to predispose cancer patients to systemic infections with alpha-hemolytic streptococci, Capnocytophaga, and Candida species. Overall, studies of single-drug versus combination therapy for the initial empirical therapy of febrile, neutropenic cancer patients indicate that monotherapy approaches the efficacy of combination therapy, although combination therapy may be preferred for certain cohorts of cancer patients. A concern that is closely related to the issue of combination therapy versus monotherapy is the need for vancomycin in the initial empirical regimen. Vancomycin appears to be the consensus drug of choice for patients with known gram-positive bacterial infections pending antibiotic susceptibility testing; however, there is disagreement as to whether the increased activity of vancomycin against gram-positive bacteria outweighs its expense and potential toxicity for inclusion in the initial empirical regimen. There is an explicit need for continued support of basic and clinical research to address these concerns.     

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.     

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.     

De-escalation antimicrobial chemotherapy in critically III patients: pros and cons

In spite of advances in critical care, nosocomial infections still have a considerable impact on Intensive Care Unit (ICU) and hospital length of stay, mortality and costs. Several authors suggest that antibiotic therapy should be instituted as soon as sepsis is suspected in critically patients. Over the last two decades the rates of occurrence for pathogens have significantly changed under selective pressure from broad-spectrum antimicrobial therapy. Shifts from predominance of gram-negative to gram-positive organisms and outbreaks of resistant pathogens address the need for appropriate empirical regimens. Agents such as ceftazidime, imipenem and, more recently, meropenem and tazobactam have been used successfully as monotherapy. Two different clinical trials have reported that meropenem monotherapy is significantly more effective than ceftazidime-based therapy. Because of the outbreak of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, some investigators suggest adding a glycopeptide to beta-lactamase inhibitor and carbapenem as initial empirical therapy. Such a regimen should be administered before definitive proof of infections and until the results of microbial investigation are available (de-escalation antimicrobial chemotherapy). On the other hand, several authors do not recommend glycopeptide administration in an attempt to limit nosocomial outbreaks of vancomycin-resistant enterococci (VRE) and staphylococci (VRS) and to avoid secondary drawbacks, such as nephrotoxicity and ototoxicity. De-escalation antimicrobial chemotherapy should be tailored to critically ill patients according to their clinical status, severity of illness and suspicion of sepsis or nosocomial pneumonia.     

In- Vitro Activity of Meropenem,a New Carbapenem,Against Imipenem-Resistant Pseudomonas aeruginosa and Xanthomonas maltophilia

Summary

The activity of meropenem, a new carbapenem, as well as imipenem, ceftazidime, aztreonam, tobramycin, amikacin and ciprofloxacin against 18 strains of Xanthomonas maltophilia and 23 strains of Pseudotnonas aeruginosa resistant to imipenem was tested. All strains of X. maltophilia were resistant to both penems. Ceftazidime, tobramycin and ciprofloxacin were the most active antimicrobial agents against this specie. 17% of imipenem-resistant strains of P. aeruginosa were sensitive to meropenem. Ciprofloxacin, amikacin and aztreonam were the most effective agents against these strains.     

Carbapenems in the Treatment of Severe Community-Acquired Pneumonia in Hospitalized Elderly Patients: A Comparative Study Against Standard Therapy

Abstract

In this open, prospective, study were enrolled 204 hospitalized elderly patients with severe (88 males, 116 females, age range 70-94). Patients were randomized to receive one of the following antibiotic treatment regimens: meropenem 500 mg i.v. t.i.d. (52); imipenem/cilastatin 500 mg i.v. t.i.d. (51), clarithromycin 500 mg + ceftriaxone 1 g i.v. b.i.d. (52), clarithromycin 500 mg + amikacin 250 mg i.v. b.i.d. (49). In 99 cases causative germs were isolated (24 meropenem, 26 imipenem, 23 clarithromycin + ceftriaxone, 26 ceftriaxone + amikacin). A satisfactory clinical, bacteriological response was achieved respectively in 86.5% 77% in meropenem; 86.3% 71% in imipenem/cilastatin; 69% 61% in ceftriaxone + clarithromycin and in 85.7% 77% in clarithromycin + amikacin. The mean total cost for each patient was 1,560; 1,620; 1,760 and 1,792 in meropenem, imipenem/cilastatin, clarithromycin + ceftriaxone and clarithromycin + amikacin respectively. This study shows that treatment with either meropenem or imipenem is as efficacious as conventional therapy in the treatment of community acquired pneumonia (CAP), and that meropenem is the most cost-effective.     

UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study

The aim of the study was to investigate the associations between UGT1A1(*)28 genotype and (1) response rates, (2) febrile neutropenia and (3) dose intensity in patients with metastatic colorectal cancer treated with irinotecan. UGT1A1(*)28 genotype was determined in 218 patients receiving irinotecan (either first-line therapy with capecitabine or second-line as monotherapy) for metastatic colorectal cancer. TA(7) homozygotes receiving irinotecan combination therapy had a higher incidence of febrile neutropenia (18.2%) compared to the other genotypes (TA(6)/TA(6) : 1.5%; TA(6)/TA(7) : 6.5%, P=0.031). TA(7) heterozygotes receiving irinotecan monotherapy also suffered more febrile neutropenia (19.4%) compared to TA(6)/TA(6) genotype (2.2%; P=0.015). Response rates among genotypes were not different for both regimens: combination regimen, P=0.537; single-agent, P=0.595. TA(7) homozygotes did not receive a lower median irinotecan dose, number of cycles (P-values >or=0.25) or more frequent dose reductions compared to the other genotypes (P-values for trend; combination therapy: 0.62 and single-agent: 0.45). Reductions were mainly (>80%) owing to grade >or=3 diarrhoea, not (febrile) neutropenia. TA(7)/TA(7) patients have a higher incidence of febrile neutropenia upon irinotecan treatment, but were able to receive similar dose and number of cycles compared to other genotypes. Response rates were not significantly different.     

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.