Bone marrow suppression--including guidelines for the appropriate use of G-CSF

For previously untreated patients receiving most chemotherapy regimens, primary prophylactic administration of granulocyte colony-stimulating factor (G-CSF) cannot be recommended. Secondary prophylactic G-CSF administration can lessen incidence of febrile neutropenia (FN) in subsequent cycles of chemotherapy in patients with a prior episode of FN. Physicians should consider chemotherapy dose reduction after neutropenic fever or severe or prolonged neutropenia after the previous cycle of treatment. Intervention with G-CSF in afebrile neutropenic patients is not recommended. For the majority of patients with FN, the available data do not clearly support the routine initiation of G-CSF as an adjunct to antibiotic therapy. However, certain FN patients may have prognostic factors that are predictive of clinical deterioration, such as pneumonia, hypotension, multiorgan dysfunction (sepsis syndrome), or fungal infection. The therapeutic use of G-CSF together with antibiotics may be reasonable in such high-risk patients. Empirical antifungal therapy is effective, especially for patients with neutropenia who were treated for seven days with empirical antibiotic therapy but remained febrile, or became afebrile but then had recurrent fever. The patient's overall clinical status and laboratory parameters are both considered when deciding to transfuse a patient. Epoetin may be available for use in the future as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin level less than 10 g/dl. Giving prophylactic platelets at a threshold of 10,000/microliter compared with 20,000/microliter can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.     

Oral fluconazole for empiric treatment of prolonged Fever in neutropenic patients: prospective study in 250 consecutive patients after stem cell transplantation

Neutropenic patients who continue to be febrile despite adequate broad-spectrum antibacterial treatment require empirical antifungal therapy. The aim of the present study was to evaluate the safety and efficacy of oral fluconazole for empirical antifungal therapy in neutropenic patients with persistent fever. A prospective cohort design was used. The study sample included 250 consecutive patients with high-risk stage II, III, or responding metastatic breast cancer who received high-dose chemotherapy (HDC) with autologous peripheral blood progenitor stem cell transplantation. Those with neutropenic fever lasting more than 72 hours despite broad-spectrum antibacterial coverage were treated with fluconazole. Treatment was continued until fever dropped and/or neutrophil count recovered with blood cultures remaining negative. Antifungal treatment was required in 173 patients (69%). There were no cases of documented deep systemic fungal infection. Two patients (<1%) had positive blood cultures for fungi. None of the patients experienced toxicity related to fluconazole. There was one transplant-related death. Thirty-one patients (18%) were unable to complete the oral fluconazole protocol because of severe mucositis, and they received intravenous fluconazole at the same dose, with similar efficacy. Oral fluconazole is a safe and effective alternative to amphotericin B for empirical early antifungal treatment in persistent neutropenic fever in breast cancer patients undergoing HDC with autologous stem cell support. Further study of oral fluconazole and amphotericin B as empirical agents in other groups of patients with persistent neutropenic fever is warranted.     

Candida colonization and systemic infection in neutropenic patients. A retrospective study

The results of surveillance cultures in 424 neutropenic patients with hematologic malignancies were analyzed to evaluate the relationship between colonization and infection by Candida species. Eighteen (32%) of 56 patients with multiple noncontiguous colonized sites developed proven (13 cases) or probable (five cases) systemic candidiasis, versus two patients with proven candidiasis (1.2%) of 170 with one colonized site (P less than 0.00000001), and one patient with proven candidiasis (0.5%) of 198 without any evidence of Candida colonization (P less than 0.00000001). Twenty-two patients with multiple colonized sites who developed a febrile episode resistant to antibiotics were treated with empiric amphotericin B. Nine of 11 given empiric amphotericin B within day 6 survived versus three of 11 receiving antifungal therapy after day 6 (P = 0.014). The above data seem to justify further prospective studies on Candida colonization as indication to early antifungal therapy in febrile neutropenic patients.     

Prevalence of the reversed halo sign in neutropenic patients compared with non‐neutropenic patients: Data from a single‐centre study involving 27 patients with pulmonary mucormycosis (2003‐2016)

Pulmonary mucormycosis (PM) is a life‐threatening infection and the diagnosis can be challenging. The objective was to retrospectively explore the value of the RHS in our cohort of 27 patients with mucormycosis and its relation to neutropenia. This was a retrospective study including all patients with a diagnosis of probable or proven invasive PM according to the 2008 EORTC/MSG criteria between September 2003 to April 2016. Fisher's exact test and Mann‐Whitney test, with a P‐value statistically significant under .05 (P<.05), were used to compare neutropenic and non‐neutropenic groups. 27 patients were eligible. The RHS could be identified in 78% of cases in the neutropenic group, and was less common in the non‐neutropenic group (31%) (P<.05). Reticulations inside ground‐glass opacity in case of RHS were present in 13 out of 15 patients (87%). Mucorales DNA detection by PCR on serum provided, a median time to the first PCR‐positive sample of 3 days (?33 to +60 days) before diagnosis was confirmed. Six patients had IPA co‐infection. In conclusion, RHS is more frequent in case of PM in neutropenic patients compare to non‐neutropenic patients. Its presence in immunocompromised patients should be sufficient to promptly start Mucorales‐active antifungal treatment, while its absence especially in non‐neutropenic cases should not be sufficient to exclude the diagnosis.     

Cefepime versus ticarcillin and clavulanate potassium and aztreonam for febrile neutropenia therapy in high-dose chemotherapy patients

An open labeled randomized trial comparing the efficacy and cost of empirically applied cefepime (C) as monotherapy versus combination therapy consisting of ticarcillin and clavulanate potassium and aztreonam (T/A) was performed in febrile neutropenic patients following high-dose chemotherapy (HDC) +/- radiation, with or without peripheral blood stem cell support. Over a 28-month period, 126 patients were screened and included in the study. Using afebrile status following 3 days of therapy as a primary endpoint, both regimens produced comparable clinical response rates (C = 55% vs. T/A = 61%). Also, the use of vancomycin for resistant gram-positive infections and alteration of gram-negative infection coverage was similar in both groups (C = 40% vs. T/A = 47% and C = 29% vs. T/A = 24%). Both treatment groups had similar needs for empirical antifungal therapy (C = 25% vs. T/A = 22%). There was a postrandomization difference between the two groups in that the "C" group had a significantly higher number of allogeneic transplants and non-stem-cell-supported patients, whereas the "T/A" group had a significantly greater number of autologous peripheral blood stem cell patients (p < 0.0001). Despite this difference, the C group had a significantly lower cost ratio than the T/A group (p = 0.016). In conclusion, we have shown that C treatment of febrile neutropenic patients following HDC results in similar efficacy and lower cost when compared to T/A, despite the inclusion of higher risk patients in the C group.     

Risk-adapted approach for fever and neutropenia in paediatric cancer patients – A national multicentre study

BackgroundIn this national multicentre study, we examined the safety of reducing antibiotics in selected paediatric cancer patients with febrile neutropenia.MethodsPatients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk and received antibiotic therapy. Remaining patients were allocated to low- or medium risk, depending on their interleukin-8 level. Low-risk patients did not receive any antibiotics and were discharged from the hospital after having been afebrile for 12 h. Medium-risk patients were re-evaluated after 72 h of antibiotic treatment and, in selected patients, antibiotics were stopped.ResultsTwo hundred thirty-three febrile neutropenic episodes in 141 paediatric cancer patients were included in the study. Sixty-four episodes were classified high risk (28%), 122 medium risk (52%), and 47 (20%) low risk. In the medium-risk group, antibiotics were stopped after 72 h in 50 in 122 episodes (41%). Median duration of antibiotic treatment and hospital admission was significantly lower in low- and medium-risk episodes with early discharge. No failures were observed in the medium-risk group with early discharge. In the low-risk group, six failures were observed (12.8%), due to coagulase-negative staphylococci-positive blood cultures and recurrent fever.ConclusionWe showed that it is safe to shorten antibiotic treatment to 72 h in selected medium-risk patients with febrile neutropenia, regardless of the neutrophil count. The safety of withholding antibiotics in selected low-risk paediatric cancer patients with febrile neutropenia requires further investigation, using more suitable definitions for safety. Reduction in hospital admissions allows children with cancer more time at home and consequently improves their quality of life.     

Duration of intravenous antibiotics for patients with neutropenic fever

BACKGROUND:: Standard therapy for febrile neutropenia after chemotherapyhas consisted of intravenous antibiotic until resolution ofboth fever and neutropenia. We attempted to shorten the hospitalstay by discontinuing intravenous antibiotics in blood culturenegative patients who remained clinically stable and afebrilefor 48 hours. PATIENTS AND METHODS:: Febrile neutropenic admissions of non-leukemic patients werereviewed. They were divided by three consecutive six month intervalsinto Group 1 (prior to initiation of the policy), Group 2 (afterthe policy was instituted), and Group 3 (to monitor the implementationof the policy after the initial six months). RESULTS:: There were 134 admissions for neutropenic fever. Median durationof intravenous antibiotic for Group 1 was 7 days (95% ConfidenceInterval 6–9). It was significantly decreased to 5 days(4–6) and 4 days (3–5) for Groups 2 and 3 respectively(p – 0.004 and p < 0.001). Median duration of hospitalstay for Group 1 was 10 days (7–13). It was also significantlydecreased to 7 (5–8) and 6 days (5–7) for Groups2 and 3 respectively (p = 0.04 and p = 0.002). CONCLUSION:: Early discontinuation of intravenous antibiotics in patientswith negative blood culture who remain afebrile and clinicallystable for 48 hours results in shorter duration of hospitalstay with potential for reduction in hospital costs. antibiotics, fever, neutropenia     

Early empiric antifungal therapy of infections in neutropenic patients comparing fluconazole with amphotericin B/flucytosine

We compared the efficacy and tolerability of fluconazole (FCA) with amphotericin B/flucytosine (ABF) in neutropenic patients with haematological malignancies. Antifungal therapy started on day 4 when fever was unresponsive to antibiotics or on day 1 together with the antibiotics, if there was evidence of mycosis. If patients did not respond to FCA after 7 days they switched to ABF. 98 patients, 51 FCA and 47 ABF were included in the study. Response to fever was achieved in 28/51 FCA patients and in another 16 after switching to ABF. So in overall 44/51 (86.2%) of the FCA and 37/47 (78.8%) of the ABF group defervescence was observed. 46 patients (21 FCA, 25 ABF) developed radiological signs of pneumonia. Resolution of infiltrates was achieved in 5/21 FCA and 20/25 ABF patients, and another 10 of 15 initially not responding patients showed regression when switched to ABF, 5 of these had highly suspected aspergillosis. Adverse events occurred in 19.6% of FCA and 97.9% of ABF patients. In conclusion fluconazole and amphotericin B/flucytosine seem to be equally effective. In view of its lower toxicity fluconazole may be preferred as first line empiric antifungal agent, but in case of nonresponse, pneumonia or aspergillosis it may be replaced by amphotericin B combined with flucytosine.     

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.     

Safety and efficacy of itraconazole compared to amphotericin B as empirical antifungal therapy for neutropenic fever in patients with haematological malignancy

BACKGROUND: Safety, tolerability and efficacy of itraconazole and amphotericin B (AMB) were compared for empirical antifungal treatment of febrile neutropenic cancer patients. PATIENTS AND METHODS: In an open, randomised study, 162 patients with at least 72 h of antimicrobial treatment received either intravenous followed by oral itraconazole suspension or intravenous AMB for a maximum of 28 days. Permanent discontinuation of study medication due to any adverse event was the primary safety parameter. Efficacy parameters included response and success rate for both treatment groups. RESULTS: Significantly fewer itraconazole patients discontinued treatment due 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 significantly higher and more drug-related adverse events occurred in the AMB group. Intention-to-treat (ITT) analysis showed favourable efficacy for itraconazole: response and success rate were both significantly higher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, both p < 0.0001). Treatment failure was markedly reduced in itraconazole patients (25.9 vs. 43.2%), largely due to the better tolerability. CONCLUSIONS: Itraconazole was tolerated significantly better than conventional AMB and also showed advantages regarding efficacy. This study confirms the role of itraconazole as a useful and safe agent in empirical antifungal therapy of febrile neutropenic cancer patients.     

Safety and efficacy of low-dose liposomal amphotericin B as empirical antifungal therapy for patients with prolonged neutropenia

Background

Liposomal amphotericin B (L-AmB) is recommended as an empirical antifungal treatment for patients at increased risk of fungal infections although renal toxicity remains a clinical problem. We therefore conducted a pilot study to evaluate the safety and efficacy of low-dose L-AmB as an empirical antifungal therapy for patients with prolonged neutropenia.

Methods

High-risk patients with hematological malignancies were eligible to enroll in this study provided they had: exhibited neutropenia for at least 1 week; suffered from high-grade fever for 4 days despite treatment with a broad-spectrum antibacterial; and no identified fever-causing pathogen. Low-dose L-AmB (1 mg/kg) was administrated as empirical antifungal therapy.

Results

Sixteen patients were registered and, of these, data from the13 patients who did not receive allogeneic stem cell transplantation were analyzed. The median duration of low-dose L-AmB treatment was 8 days. Hypokalemia was seen in one patient: administration of potassium supplements for 10 days restored potassium levels to the normal range. A two-fold increase in creatinine levels was not found in any patients even those taking concomitant nephrotoxic drugs (e.g., amynoglycoside) during the study. One patient stopped receiving the drug due to an infusion-related adverse event. No patients showed breakthrough fungal infections or died during therapy or within 7 days after the end of the study. Increase in the L-AmB dose was necessary due to persistent fever in three patients who withdrew from the study. The satisfactory response rate for low-dose L-AmB was 69 %.

Conclusion

This study suggests that low-dose L-AmB may be an effective option as empirical antifungal therapy for high-risk patients with febrile neutropenia.     

Piperacillin/Tazobactam Plus Gentamicin as Empirical Therapy for Febrile Neutropenic Patients with Haematological Malignancy

Summary

The efficacy of piperacillin/tazobactam (PIPC/TBT) in combination with gentamicin was assessed as empirical therapy in 44 febrile neutropenic patients with haematological malignancy. A favourable response to therapy was seen in 67% patients overall and in 57% of patients with microbiologically documented infection. PIPC/TBT demonstrated good clinical and in vitro activity against isolated pathogens, particularly Gram positive cocci such as Staphylococcus epidermidis. The MIC of both Gram positive and Gram negative pathogens to PIPC was reduced in the presence of TBT. PIPC/TBT plus gentamicin is a safe and effective combination for empirical therapy in febrile neutropenic patients, even in a unit with a predominance of Gram positive infections.     

Efficacy of intravenous ciprofloxacin in patients with febrile neutropenia refractory to initial therapy

We previously reported that monotherapy with carbapenem or cefepime exhibited efficacy equivalent to cefepime plus an aminoglycoside as initial therapy for febrile neutropenia (FN), achieving an adequate response in two-thirds of the patients. However, only one-third of the remaining poor responders to monotherapy became afebrile after an aminoglycoside was added to the initial carbapenem or cefepime. The present study was designed to evaluate the benefit of intravenous ciprofloxacin for neutropenic patients with fever who were refractory to initial therapy given for the first 3 days. Patients with FN--as defined by an axillary temperature >or=37.5 degrees C and a neutrophil count <1,000/microL-who had no response to initial therapy with carbapenem or cefepime for 72 hours were to receive additional ciprofloxacin 600 mg/day. They were otherwise managed according to the Japanese guidelines for FN. An adequate response was defined as a decline of temperature to <37.5 degrees C within 7 days after initiation of ciprofloxacin treatment. Thirty-one patients with FN (seventeen male and fourteen female; mean age 53.1 +/- 14.8 years) were entered in the study. The initial antibiotics were cefepime (2 - 4 g/day) in twenty and carbapenem (1 - 2 g/day) in eleven. Three patients were excluded from analysis, leaving 28 patients for evaluation of efficacy. The response rate was 16/31 patients (51.6%),with four patients judged non-assessable due to adverse effects, protocol violation or early change to other agents. Adverse events occurred in seventeen patients, but all were mild and reversible. Only three patients had adverse events (skin rash, hepatic dysfunction and elevation of alkaline phosphatase in one patient, respectively) considered related to ciprofloxacin. These findings indicate that addition of intravenous ciprofloxacin is effective against FN refractory to initial antibiotic therapy and has acceptable toxicity.     

Empirical oral antibiotic therapy for low risk febrile cancer patients with neutropenia

For over 30 years, fever and neutropenia in cancer patients has been treated with the utmost urgency, necessitating inpatient evaluation and immediate initiation of empirical broad-spectrum parenteral (IV) antibiotics. This practice is based on the recognition that delays in starting antibiotic therapy in febrile neutropenic patients have been associated with life-threatening infections and sometimes fatal consequences. Over the past decade, it has become evident that neutropenic cancer patients are not a homogeneous group and that practice guidelines may vary on their risk status. In fact, attempts have been made to stratify patients into high-risk and low-risk groups and differentiate treatment options respectively. Recent studies suggest that those neutropenic cancer patients who are at low risk may even be successfully treated with oral therapy, thus opening the possibility for ambulatory or home-based management. Oral antibiotic therapy, especially if safely delivered at home, offers a number of advantages including lower cost, improved quality of life (although the impact of shifting the burden of care from the hospital to the home setting on the patient, parent or care provider needs careful assessment) and a decreased risk for nosocomial infection.     

Early hospital discharge of children with cancer treated for fever and neutropenia: identification and management of the low-risk patient

Children with leukemia and solid tumors are often hospitalized for empiric broad-spectrum antibiotic therapy because of fever during periods of chemotherapy-induced neutropenia. Conventional practice dictates that parenteral antibiotics be continued until the patient is afebrile and has recovered from neutropenia, ie, until the absolute neutrophil count (ANC) exceeds 500 cells per cubic millimeter. However, the practice in our center has been to discontinue parenteral antibiotic therapy and discharge many such patients before resolution of neutropenia. Since the feasibility and safety of this approach has not been studied, we reviewed the records of 114 consecutive hospitalizations for fever and neutropenia in 61 patients during a 13-month period. Seventy-seven children (68%) were discharged to their homes while still neutropenic after they had been afebrile for 1 to 2 days on parenteral antibiotics, had negative blood cultures, appeared well, and usually had some evidence of bone marrow recovery. Five patients (4.4%) developed recurrent fever and required rehospitalization within 7 days of discharge. Only three of the 77 patients (3.9%) who were sent home with neutropenia had recurrent fever. Each had a brief and uneventful second hospitalization. Two of the 37 children discharged with an ANC over 500 cells per cubic millimeter required rehospitalization. A declining ANC and advanced malignancy were risk factors in predicting recurrence of fever following discharge. A rising monocyte count was a predictor of imminent recovery from neutropenia. These results suggest that "early" discharge of an afebrile yet still neutropenic patient is safe when the patient is in remission, has no evidence of serious infection, appears clinically stable, and has indications of bone marrow recovery. The conventional approach of routinely continuing the hospitalization until resolution of neutropenia may be unnecessary in such low-risk patients.     

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.     

Continuously infused amphotericin B deoxycholate for primary treatment of invasive fungal disease in acute myeloid leukaemia

Continuous administration of amphotericin B deoxycholate over 24 hours (24 h‐D‐AmB) is better tolerated than rapid infusions. However, toxicity and outcome have not been assessed in a homogenous patient population with acute myeloid leukaemia (AML). We retrospectively analysed renal function and outcome in all adult patients with AML undergoing intensive chemotherapy between 2007 and 2012 at our institution. We compared a patient group with exposure to 24 h‐D‐AmB to a patient group without exposure to 24 h‐D‐AmB. One hundred and eighty‐one consecutive patients were analysed, 133 (73.5%) received at least 1 dose of 24 h‐D‐AmB, and 48 (26.5%) did not. Reasons for 24 h‐D‐AmB initiation were invasive fungal disease (IFD) in 63.5% and empirical treatment for febrile neutropenia in 36.5% of the cases. Most patients with IFD received an oral triazole drug at hospital discharge. Baseline characteristics were well matched. Amphotericin B deoxycholate over 24 hours was given for a median 7 days (interquartile range 3‐13). Peak creatinine concentration was higher in the 24 h‐D‐AmB‐group (104.5 vs. 76 μmol/L, P < .001) but normalized within 1 month after therapy (65.5 vs. 65 μmol/L, P = .979). In neither of the 2 groups, end‐stage renal disease occurred. There was no difference in 60‐day survival (90% vs. 90%) and 2‐year survival (58% vs. 58%). Invasive fungal disease partial response or better was observed in 68% of the patients. We conclude that antifungal therapy with continuously infused amphotericin B deoxycholate is safe in patients with AML. An antiinfective strategy based on 24 h‐D‐AmB in first line followed by an oral triazole compound represents an economically attractive treatment option.     

Epidemiology and outcomes of invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients in the era of antifungal prophylaxis: a single‐centre study with focus on emerging pathogens

With increased use of expanded‐spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer‐Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post‐IFI mortality. All patients received antifungal prophylaxis. Fifty‐three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n = 31; 50%) and candidaemia (n = 15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n = 6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp., Cladosporium sp., Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR) = 6.0], graft‐versus‐host disease (OR = 5.3), central venous catheter use (OR = 5.2) and hypoalbuminaemia (OR = 0.3 g^?1 dl^?1 increase in albumin). The 90‐day mortality rate after IFI was 57%. Non‐cytomegalovirus systemic viral co‐infection (OR = 3.5) and stay in an ICU (OR = 2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging.     

Can procalcitonin distinguish infectious fever from tumor‐related fever in non‐neutropenic cancer patients?

BACKGROUND:

Procalcitonin (PCT) has been proposed as a marker of infection and was studied in neutropenic patients. This study investigated its role in non‐neutropenic febrile cancer patients (NNCPs).

METHODS:

Between July 2009 and July 2010, a total of 248 NNCPs with fever were studied. PCT was measured in plasma within 24 hours of fever onset and 4 to 7 days thereafter, using a Kryptor system with a lower limit of quantitation of 0.075 ng/mL. Patients' clinical, microbiological, and radiological data were reviewed to make the diagnosis and were correlated with PCT levels.

RESULTS:

This study included 30 patients with bloodstream infection (BSI), 60 with localized bacterial infection, 141 with no documented infection, and 8 with tumor‐related fever. Most patients (98%) were inpatients or admitted to the hospital during the study. Patients with BSI had significantly higher PCT levels than did those with documented localized infections (P = .048) and no documented infection (P = .011). PCT levels were significantly higher in septic patients than in those without sepsis (P = .012). Patients with stage IV disease or metastasis had significantly higher baseline PCT levels than did those with early stages of cancer (P < .05). PCT levels dropped significantly in patients with bacterial infections in response to antibiotics (P < .0001).

CONCLUSIONS:

Baseline PCT levels are predictive of BSI and sepsis in NNCPs. They may be predictors of metastasis and advanced cancer. Subsequent decrease in PCT levels in response to antibiotics is suggestive of bacterial infection. Larger trials are needed to confirm the results of this pilot study. Cancer 2012. © 2012 American Cancer Society.     

Randomised,multicentre trial of micafungin vs. an institutional standard regimen for salvage treatment of invasive aspergillosis

Invasive aspergillosis remains associated with significant morbidity and mortality, necessitating new options for salvage therapy. The objective of this study was to evaluate the efficacy and safety of micafungin as salvage monotherapy in patients with invasive aspergillosis. Patients with proven or probable invasive aspergillosis, who were refractory or intolerant to previous systemic antifungal therapy, were randomised 2 : 1 to receive 300 mg day^?1 intravenous micafungin monotherapy or an intravenous control monotherapy [lipid amphotericin B (5 mg kg^?1 day^?1), voriconazole (8 mg kg^?1 day^?1) or caspofungin (50 mg day^?1)] for 3–12 weeks. Patients underwent final assessment 12 weeks after treatment start. Seventeen patients with invasive aspergillosis (proven, n = 2; probable, n = 14; not recorded, n = 1) participated in the study (micafungin arm, n = 12; control arm, n = 5). Three patients each in the micafungin (25.0%; 95% CI: 5.5–57.2) and control arm (60.0%; 95% CI: 14.7–94.7) had successful therapy at end of treatment as assessed by an Independent Data Review Board. Eleven patients died; six due to invasive aspergillosis. No deaths were considered related to study treatment. During this study it became increasingly common to use combination treatment for salvage therapy. Consequently, enrolment was low and the study was discontinued early. No clear trends in efficacy and safety can be concluded.