Treatment Of Febrile Neutropenic Patients Research Articles

Efficacy and Safety of Caspofungin Treatment in Febrile Neutropenic Patients with Hematological Disorders: A Multicenter Consecutive Case Series.

Introduction Invasive fungal infections have been attracting attention as significant fatal complications in patients with febrile neutropenia (FN) who undergo intensive chemotherapy or hematopoietic stem cell transplantation to treat hematological malignancies. Although clinical trials are already underway in other countries, evidence supporting the use of caspofungin (CAS) in FN patients in Japan is still insufficient. Methods A retrospective study of patients treated with CAS for FN associated with hematological diseases between April 2015 and March 2018 was conducted to determine the treatment efficacy and safety. The study was conducted as a multicenter collaboration, and the data of 52 patients who met all of the inclusion criteria were analyzed. A five-composite-endpoint method was used, and the treatment was judged to be effective when all five endpoints (defervescence during neutropenia; no breakthrough fungal infections; resolution of baseline fungal infections; a survival for seven days or more after the completion of therapy; and no discontinuation of therapy due to side effects or invalidity) were met. Results The efficacy rate was 53.8% (28/52), which is close to the average reported efficacy rate. Adverse events included liver dysfunction and electrolyte abnormalities, but no renal dysfunction or serious events were seen. Conclusion These results suggest that the use of CAS in FN patients with hematological diseases is effective and well-tolerated, and we believe that the use of CAS could become a significant treatment in Japan.

How I Treat Febrile Neutropenia.

The management of febrile neutropenia is a backbone of treating patients with hematologic malignancies and has evolved over the past decades. This article reviews my approach to the evaluation and treatment of febrile neutropenic patients. Key topics discussed include antibacterial and antifungal prophylaxis, the initial workup for fever, the choice of the empiric antibiotic regimen and its modifications, and criteria for discontinuation. For each of these questions, I review the literature and present my perspective.

La era de los microorganismos multirresistentes: impacto en pacientes neutropénicos febriles

Introducción: El tratamiento antimicrobiano para los pacientes neutropénicos febriles (NF) se ha convertido en un desafío debido a la emergencia de microorganismos multirresistentes (MOR). El objetivo de este trabajo es analizar las características de estos pacientes y la incidencia de MOR.
 Materiales y métodos: Estudio retrospectivo, observacional y descriptivo desde junio de 2015 hasta agosto de 2017 en adultos neutropénicos febriles hospitalizados en un hospital público de la ciudad de Buenos Aires. Se analizaron características demográficas, clínicas y microbiológicas, incluyendo los siguientes MOR: enterobacterias productoras de carbapenemasas (EPC) y beta-lactamasas de espectro extendido (BLEE), Acinetobacter baumannii complex, Enterococcus vancomicina resistente (EVR) y Stenotrophomonas maltophilia.
 Resultados: Fueron incluidos 32 pacientes, 56% mujeres con 84% de neoplasias hematológicas. Hubo colonización por EPC o EVR en el 59% de los pacientes. Se registraron 148 episodios infecciosos con 41% de documentación microbiológica. Los MOR fueron responsables del 25% de los episodios, siendo los más frecuentes Klebsiella pneumoniae productora de carbapenemasa y BLEE; los focos más frecuentes fueron bacteriemias e infecciones urinarias. Los pacientes con leucemias agudas (67%) presentaron colonización por EPC o EVR en el 80%. El tratamiento fue inadecuado en el 63% de las infecciones por MOR y en el 12% por microorganismos sensibles (MS) (p<0,01). La mortalidad global fue 53% con MOR y del 27% con MS (p=ns).
 Conclusión: las infecciones por MOR fueron frecuentes con predominio de bacteriemias, especialmente EPC y BLEE. Por ello los MOR deben ser tenidos en cuenta para el tratamiento empírico en pacientes neutropénicos febriles.

Empirical antibiotics targeting gram-positive bacteria for the treatment of febrile neutropenic patients with cancer.

The pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment. To assess the effectiveness of empirical anti-gram-positive (antiGP) antibiotic treatment for febrile neutropenic patients with cancer in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment. For the review update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (May 2012 to 2017), Embase (May 2012 to 2017), LILACS (2012 to 2017), conference proceedings, ClinicalTrials.gov trial registry, and the references of the included studies. We contacted the first authors of all included and potentially relevant trials. Randomised controlled trials (RCTs) comparing one antibiotic regimen versus the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic patients with cancer. Two review authors independently assessed trial eligibility and risk of bias, and extracted all data. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated. A random-effects model was used for all comparisons showing substantial heterogeneity (I2 > 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible. Fourteen trials and 2782 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in 12 studies, and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Eight studies were assessed in the overall mortality comparison and no significant difference was seen between the comparator arms, RR of 0.90 (95% CI 0.64 to 1.25; 8 studies, 1242 patients; moderate-quality data). Eleven trials assessed failure, including modifications as failures, while seven assessed overall failure disregarding treatment modifications. Failure with modifications was reduced, RR of 0.72 (95% CI 0.65 to 0.79; 11 studies, 2169 patients; very low-quality data), while overall failure was the same, RR of 1.00 (95% CI 0.79 to 1.27; 7 studies, 943 patients; low-quality data). Sensitivity analysis for allocation concealment and incomplete outcome data did not change the results. Failure among patients with gram-positive infections was reduced with antiGP treatment, RR of 0.56 (95% CI 0.38 to 0.84, 5 studies, 175 patients), although, mortality among these patients was not changed.Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates and were associated with a reduction in documented gram-positive superinfections. Resistant colonisation was not documented in the studies. Based on very low- or low-quality evidence using the GRADE approach and overall low risk of bias, the current evidence shows that the empirical routine addition of antiGP treatment, namely glycopeptides, does not improve the outcomes of febrile neutropenic patients with cancer.

Empiric treatment against invasive fungal diseases in febrile neutropenic patients: a systematic review and network meta-analysis

BackgroundThe most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Our objective was evaluate the relative efficacy of antifungals for all-cause mortality, fungal infection-related mortality and treatment response in this population.MethodsPubmed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs). Two reviewers performed the quality assessment and extracted data independently. Pairwise meta-analysis and network meta-analysis were conducted to compare the antifungals.ResultsSeventeen RCTs involving 4583 patients were included. Risk of bias of included studies was moderate. Pairwise meta-analysis indicated the treatment response rate of itraconazole was significantly better than conventional amphotericin B (RR = 1.33, 95%CI 1.10–1.61). Network meta-analysis showed that amphotericin B lipid complex, conventional amphotericin B, liposomal amphotericin B, itraconazole and voriconazole had a significantly lower rate of fungal infection-related mortality than no antifungal treatment. Other differences in outcomes among antifungals were not statistically significant. From the rank probability plot, caspofungin appeared to be the most effective agent for all-cause mortality and fungal infection-related mortality, whereas micafungin tended to be superior for treatment response. The results were stable after excluding RCTs with high risk of bias, whereas micafungin had the lowest fungal infection-related mortality.ConclusionsOur results highlighted the necessity of empiric antifungal treatment and indicates that echinocandins appeared to be the most effective agents for empiric treatment of febrile neutropenic patients based on mortality and treatment response. However, more studies are needed to determine the best antifungal agent for empiric treatment. Our systematic review has been prospectively registered in PROSPERO and the registration number was CRD42015026629.

Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high-risk hematologic patients with cancer with febrile neutropenia.

Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria. In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment. Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups. The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.

Measurements of procalcitonin facilitate targeting of endotoxin adsorption treatment in febrile neutropenic patients suffering from shock

Immediate initiation of hemoperfusion treatment with polymixin B immobilized fiber (PMX-DHP) is a potent strategy to improve hemodynamics in septic patients with critical circulatory failure. However, it is often difficult to accurately and rapidly differentiate between bacterial infections and non-infectious causes of shock in acutely critically-ill patients. Procalcitonin (PCT) measurements may assist in the early identification of bacterial infection/sepsis and determination of severity in such patients. We present two febrile neutropenic (FN) patients who developed severe shock after chemotherapy for hematological malignancies. PCT levels were markedly elevated in both patients (≥ 10 ng/ml), suggesting a high likelihood of bacterial infectious etiology as the cause of their shock, and thus they were promptly treated with PMX-DHP. Measurements of PCT may facilitate targeting of PMX-DHP treatment among FN patients suffering from shock, which may lead to better prognosis.

Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients

Fluoroquinolone antibiotics are widely used in our communities and healthcare facilities. This review focuses upon the relationship between fluoroquinolone use and the rising prevalence in neutropenic cancer patients of multidrug resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, Clostridium difficile, and aerobic Gram-negative bacilli. Fluoroquinolones such as ciprofloxacin or levofloxacin are efficacious for the prevention and treatment of neutropenic fever syndromes, including infections due to aerobic Gram-negative bacilli. Recent clinical practice guidelines recommend their prophylactic use in acute leukaemia patients receiving intensive remission-induction, postremission consolidation, or salvage induction therapy, and haematopoietic stem cell transplant recipients during pre-engraftment when the duration of profound neutropenia (absolute neutrophil count <0.1 × 10(9)/l) is at least 7 days. These same agents combined with amoxicillin/clavulanate are recommended for oral outpatient empirical antibacterial treatment of febrile neutropenic patients at low risk for medical complications. Fluoroquinolone-resistant Enterobacteriaceae is linked to community fluoroquinolone consumption. Prophylaxis efficacy is reduced when the prevalence of fluoroquinolone Gram-negative bacillary resistance exceeds 20%. Widespread use encourages the transmissibility of multiclass antimicrobial resistance genes among Gram-negative bacilli. Fluoroquinolone-driven colonization with MRSA enhances the risk of subsequent infection, the use of vancomycin, and risk of colonization by vancomycin-resistant Enterococcus spp. The relative roles of widespread fluoroquinolone use and ineffective infection prevention and control practices in encouraging the spread of virulent C. difficile-associated diarrhoea in healthcare facilities remain controversial. Widespread use of antibacterial agents of one class can encourage multiclass drug resistance, which reduces prophylaxis and treatment efficacy in neutropenic cancer patients.

Initial Management of Fever and Neutropenia in a Child With Cancer—The Past, the Present, and the Future

Fever in a patient with an underlying malignancy who has neutropenia is a relatively common event that requires urgent attention because of the risk of associated morbidity and mortality. Although a clinically suspected or microbiologically documented bacterial infection is present in up to half of such febrile neutropenia episodes, an etiology is not identified in the rest. In a neutropenic patient, signs and symptoms of inflammation can be blunted or atypical, and infections may progress unnoticed, resulting in a life-threatening complication. Often, fever is the only manifestation of infection. For these reasons, empirical intravenous broad-spectrum antibiotics in an inpatient setting have long been the mainstay of treatment for febrile neutropenic patients. However, not all febrile neutropenic patients are at the same risk for developing infection-related complications. Addressing this variability in associated risk, risk-stratified management approaches have been suggested to minimize hospital stay, improve patients' quality of life, and decrease related health care costs. This article reviews some guiding principles of initial management of febrile neutropenic children with cancer with a focus on risk-stratified treatment approaches, including the use of inflammatory markers to discern risk.

Safety and Efficacy of Itraconazole Compared to Amphotericin B as Empirical Antifungal Therapy for Neutropenic Fever in Patients with Haematological Malignancy*

Safety, tolerability and efficacy of itraconazole and amphotericinB (AMB) were compared for empirical antifungal treatmentof febrile neutropenic cancer patients. Patients and Methods:In an open, randomised study, 162 patients with at least 72 h ofantimicrobial treatment received either intravenous followed byoral itraconazole suspension or intravenous AMB for a maximum of28 days. Permanent discontinuation of study medication due to anyadverse event was the primary safety parameter. Efficacy parametersincluded response and success rate for both treatment groups.Results: Significantly fewer itraconazole patients discontinued treatmentdue to any adverse event (22.2 vs. 56.8% AMB; p < 0.0001).The main reason for discontinuation was a rise in serum creatinine(1.2% itraconazole vs. 23.5% AMB). Renal toxicity was significantlyhigher and more drug-related adverse events occurred in the AMBgroup. Intention-to-treat (ITT) analysis showed favourable efficacyfor itraconazole: response and success rate were both significantlyhigher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, bothp < 0.0001). Treatment failure was markedly reduced in itraconazolepatients (25.9 vs. 43.2%), largely due to the better tolerability.Conclusions: Itraconazole was tolerated significantly better thanconventional AMB and also showed advantages regarding efficacy.This study confirms the role of itraconazole as a useful andsafe agent in empirical antifungal therapy of febrile neutropeniccancer patients.

Monotherapy versus dual therapy based on risk categorization of febrile neutropenic patients.

Cefepime monotherapy was compared with cefepime-plus-amikacin dual therapy for treatment of febrile neutropenic patients. Response rates were significantly lower for patients receiving monotherapy who had neutrophil counts of <500 cells/mm3 but did not differ significantly between patients receiving dual therapy who had neutrophil counts of > or =500 cells/mm3 or <500 cells/mm3. Dual therapy is recommended for the initial treatment of patients with neutropenia with <500 cells/mm3. Dual therapy was significantly more effective in patients with neutropenia lasting <5 days. The response rates to monotherapy or dual therapy did not differ significantly when neutropenia persisted for > or =6 days, indicating that sustained neutropenia is a risk factor for failure of initial empirical therapy. The rate of response to monotherapy was lower in leukemic patients, whereas the rate of response to dual therapy did not differ between leukemic and nonleukemic groups. The rate of response to either monotherapy or dual therapy did not differ for patients with temperatures of > or =38 degrees C or 37.5 degrees C-38 degrees C. Overall, defervescence occurred in >80% of patients with mild infections, whereas only 32% of those with moderate to severe infection responded by day 3 and 69.8% by day 7.

Empirical second-line antimicrobial therapy in febrile neutropenic cancer patients

8199 Background:The treatment of infectious complications in cancer patients has evolved as a consequence of the developments in the chemotherapy of cancer patients. Monotherapy with the carbapenems (imipenem/cilastatin and meropenem) represents realistic options for risk-based treatment of febrile neutropenic patients. In the past years, imipenem-cilastatin was the most appropriate choices in our institution. The objective of this trial was to evaluate the potential advantages of the combination of quinolones and vancomycin as second-line antimicrobial therapy. Methods:From January 1999 to November 2001, 114 episodes of fever and neutropenia (neutrophils less than 500/mm3) occurring in 67 patients with cancer received treatment with imipenem/cilastatin and glycosylated G-CSF. Target therapy is mandatory if the culture data become available. If infection continued 72 hours later, patients were randomized to receive vancomycin or vancomycin plus quinolones, and if infection had not disappeared 7 days after...

Meropenem +/− Granulocyte Colony Stimulating Factor in the Treatment of Febrile Neutropenic Patients with Cancer: Prospective Randomized Study

The purpose of this study was to evaluate the impact of granulocyte-colony stimulating factor (G-CSF) on the therapy for febrile neutropenia (FN). Our patient population differed significantly from those of previous studies as no patients received antimicrobial or CSF prophylaxis before randomization and all were solid tumor patients. When the diagnosis of FN was established, patients were started on intravenous meropenem 1 g every 8 hours and randomly assigned to receive G-CSF (5 µg/kg body weight per day subcutaneously) or not. Twenty-eight patients with 30 FN episodes received G-CSF and 25 patients with 30 FN episodes did not receive G-CSF according to randomization. The time to resolution of fever, recovery of neutrophil count over 1000/mm3, duration of hospitalization, need for erythrocyte and platelet transfusion and mortality rate were similar in both study groups. Side effects of therapy were mild. These results provide preliminary evidence that G-CSF administration, in addition to effective antibiotic therapy as treatment of febrile neutropenic patients with solid tumor, does not help improve infection-related morbidity and mortality.

Nouveaux antifongiques : voriconazole et caspofungine

Among new available antifungal agents voriconazole is a new triazole with an intravenous (IV) and oral formulation, and caspofungin is an echinocandin, new family with a new mode of action on the cell wall. It is available as an IV preparation. Both drugs have a broad spectrum targeting most of the usual pathogens : Candida and Aspergillus, even with low suceptibility or resistance to other antifungals. Voriconazole is also active on Scedosporium and Fusarium. The efficacy of these molecules was established in vitro and in experimental infections in animals either normal or immunosuppressed. Voriconazole is active in oropharyngeal and esophageal candidiasis, in refractory invasive candidiasis and as a first line treatment of invasive aspergillosis with better results than amphotericine B. It was also effective in scedosporiosis and in fusariosis. Caspofungin is active in oropharyngeal and esophageal candidiasis, in invasive candidiasis ranking among the best drugs in non neutropenic patients. It was shown effective in refractory aspergillosis. As empirical treatment of febrile neutropenic patients, these molecules should probably be restricted to the highest risk-population. Safety is good, side effects are a rare cause of discontinuation of treatment, class specific drug-drug interactions occur with voriconazole. These molecules open an important field of investigations with combination of antifungal agents.

Expanding the Options for Risk-based Therapy in Febrile Neutropenia

Fever in neutropenic cancer patients is often due to the development of an infection. The standard management of febrile neutropenic patients involves the administration of empiric, hospital-based, parenteral antibiotic therapy. Although this treatment strategy has evolved from experience in high-risk patients with hematological malignancies, in whom bacterial infection can result in substantial morbidity and mortality, it has been adopted for all patients with febrile neutropenia, largely because of the inability of clinicians to reliably distinguish between patients who are at high risk for developing such morbidity/mortality and those who are not. The development of risk-assessment models has facilitated the recognition of high-, moderate-, and low-risk subgroups among febrile neutropenic patients and allows the administration of outpatient antibiotic therapy to the moderate- and low-risk groups, with the same degree of efficacy and safety as hospital-based therapy. Monotherapy with the carbapenems (imipenem/cilastatin and meropenem), with their broad spectrum of activity and established efficacy in high-risk patients, represents realistic options for risk-based treatment of febrile neutropenic patients within and outside the hospital setting.

Ototoxicity induced by once-daily gentamicin

Aminoglycosides have traditionally had an adjunctive, synergistic role with β-lactam antibiotics, in the treatment of febrile neutropenic patients. Once-daily dosing regimens have been extensively studied over the past 2 years, and shown to be as effective, and no more toxic, than multiple daily regimens.1 However, very few of these trials involved neutropenic patients.2 This is particularly important as these patients are at higher risk of developing aminoglycoside toxicity due to their severe underlying disease, aggressive chemotherapy treatment, and their need for repeated long courses of antibiotics.

A comparison of aztreonam plus vancomycin and imipenem plus vancomycin as initial therapy for febrile neutropenic cancer patients

The improved efficacy of imipenem over other beta-lactam antibiotics in the treatment of febrile neutropenic patients has been attributed to its broad spectrum of activity. A prospective, randomized, clinical trial was performed comparing vancomycin 1 g every 12 hours plus imipenem/cilassatin 500 mg every 6 hours and the same dose of vancomycin plus aztreonam 2 g every 6 hours for empiric treatment of febrile episodes in neutropenic patients with cancer. The imipenem regimen cured 76% of the 148 evaluable episodes compared with a 67% cure rate for the 152 episodes treated with the aztreonam regimen (p = 0.1). Most of the polymicrobial infections (77% or 10/13) treated with the imipenem responded, whereas only 38% (5/13) of these infections responded to the aztreonam regimen. Although the cost of the imipenem regimen was less than the cost of the aztreonam regimen, it was associated significantly more with skin rashes (12/194 vs 3/189, p = 0.02). In a multivariate analysis, a poor outcome was independently associated in both instances with the persistence of neutropenia and the presence of pneumonia (p < 0.001). Overall, in a multifactorial analysis that included efficacy, toxicity, and cost, the imipenem and aztreonam regimens were comparable.

Outpatient treatment of febrile neutropenic patients with cancer.

Outpatient treatment of febrile neutropenic patients with cancer.

Use of the quinolones for the prophylaxis and therapy of infections in immunocompromised hosts.

The prevention and treatment of infections are major issues of supportive care in patients with haematological malignancies. Because of their broad antimicrobial activity, the use of fluoroquinolones for prophylaxis in neutropenic patients has been extensively studied. In comparison with placebo, norfloxacin reduces the incidence of Gram-negative infections, whereas Gram-positive bacterial and fungal infections remain unaffected. Ofloxacin and enoxacin also bacterial and fungal infections remain unaffected. Ofloxacin and enoxacin also produce a reduction in fever and documented infections. In randomized studies comparing ciprofloxacin with cotrimoxazole (trimethoprim/sulfamethoxazole) plus colistin (each in combination with nonabsorbable antifungal agents), conflicting results were obtained. The incidence of documented Gram-negative bacterial infections was markedly reduced by ciprofloxacin prophylaxis; however, the number of Gram-positive infections may increase dramatically. Combining ciprofloxacin with a macrolide antibiotic in an attempt to prevent streptococcal infections can result in breakthrough bacteraemias due to resistant Gram-positive pathogens. Empirical antimicrobial therapy after quinolone prophylaxis should also be directed against microorganisms susceptible to quinolones, since sustained eradication by oral administration cannot be assumed with certainty. Clinical trials comparing intravenous quinolones in combination with aminoglycosides with widely used standard regimens for the treatment of infections in cancer patients indicate equivalent efficacy; however, in studies of ciprofloxacin alone, response rates were significantly lower compared with standard combinations. Therefore, quinolone monotherapy as empirical treatment in febrile neutropenic patients cannot be recommended.

Piperacillin/tazobactam/amikacin versus piperacillin/amikacin/teicoplanin in the empirical treatment of neutropenic patients

A prospective randomized trial was performed to compare the efficacy of a regimen containing a glycopeptide versus one containing a beta-lactamase inhibitor in the treatment of febrile episodes in neutropenic patients. Fifty-eight patients received piperacillin/amikacin/teicoplanin (group 1) and 56 received piperacillin/amikacin/tazobactam (group 2). In the case of persistence of fever without microbiological documentation of the cause, teicoplanin was also given empirically in group 2 on day 4, and amphotericin B in both groups on day 6. In 114 evaluable febrile episodes, the rate of success without modification of therapy was 60% in patients on piperacillin/amikacin/teicoplanin and 41% in patients on piperacillin/amikacin/tazobactam (p < 0.03). Eleven of 34 patients in the latter group who failed to improve eventually responded upon addition of teicoplanin. Ten and nine patients in group 1 and group 2 respectively required the addition of amphotericin B for definite improvement. There were 14 episodes of gram-positive septicemia in each group: the response rate was 100% in group 1 and 43% in group 2. Three episodes of gram-negative breakthrough septicemia occurred in group 1 versus no cases in group 2 (p = 0.1). Three deaths occurred in each group. Piperacillin/amikacin/tazobactam may be as efficacious as piperacillin/amikacin/teicoplanin in the treatment of febrile neutropenic patients provided the regimen is modified (usually by addition of teicoplanin) in unresponsive cases.