Invasive Pulmonary Fungal Infection Research Articles

Clinical analysis of invasive pulmonary fungal infections

To investigate the clinical characteristics of invasive pulmonary fungal infections (IPFI). The clinical data of 48 patients with confirmed IPFI at Peking Union Medical College Hospital from January 2004 to December 2008 were retrospectively analyzed. Patients were divided into primary IPFI group and secondary IPFI groups based on their disease courses. The most commonly seen fungi were aspergillus species (37.5%) and cryptococcus species (37.5%), and community acquired infections accounted for 87.5%. The secondary IPFI accounted for 66.7% among all cases, in which the major pathogens were aspergillus species; in the primary IPFI group, the major pathogens were cryptococcus species. The symptoms of IPFI were non-specific and mostly presented as cough, fever, hemoptysis, and dyspnea. The common imaging features included multiple nodules, infiltrates and consolidations, or diffused lesions in bilateral lungs, and cavities were found in 11 patients (22.9%). The clinical symptoms and imaging findings were not significantly different between these two groups. A total of 46 patients (95.8%) received antifungal therapies or surgeries. Ten patients (20.8%; all from the secondary IPFI group) died, making the fatality rate significantly different between the primary IPFI group and secondary IPFI group (P=0.033). The major pathogens of IPFI are aspergillus species and cryptococcus species, and most of them are community acquired. The secondary IPFI with aspergillus species tend to be highly fatal. The clinical symptoms and imaging features are non-specific. Early diagnosis with prompt antifungal therapies, or even with surgical intervention, may be beneficial for these patients.

Clinical significance of positive sputum culture for filamentous fungi

To investigate the clinical significance of positive sputum culture for filamentous fungi. The medical data of 140 patients positive for filamentous fungi in sputum culture at Peking Union Medical College Hospital were reviewed retrospectively. Based on the diagnostic criteria by European Organization for Research and Treatment of Cancer/Mycoses Study Group, invasive pulmonary fungal infection (IPFI) was diagnosed. The clinical characteristics of cases with and without IPFI were analyzed respectively. Among all 140 cases positive for filamentous fungi in sputum culture, only 22 cases could be diagnosed as IPFI. Two of 22 IPFI cases were confirmed by post-operative pathology, 1 case was confirmed by positive blood culture for filamentous fungi and the remaining 19 cases were diagnosed clinically according to the nature of hosts, characteristics of pulmonary infections and microbiological evidence (positive sputum culture for filamentous fungi, 2 - 5 times for each case). Most of etiological fungi in IPFI patients belonged to Aspergillus. And the identity of isolated fungal strain was mostly one strain for each patient. In IPFI group, patients who had been treated with broad-spectrum antibiotics (100%), steroids (13, 59.1%) or immunosuppressant (7, 31.8%) or who had pulmonary X-ray imaging changes (100%), primary diseases (21, 95.5%), hypoalbuminemia (18, 81.8%) or hemoptysis (10, 45.5%), were significantly more than those in non-IPFI group (66.9%, 34.7%, 18.6%, 79.7%, 72.0%, 45.8% and 4.2% respectively; P < 0.05 for each item). In IPFI group, itraconazole, amphotericin B and/or voriconazole were administrated, 8 patients (36.4%) were cured and 14 patients (63.6%) passed away. In non-IPFI group, the patients were treated with antibiotics, fluconazole, anti-tuberculosis, steroids or combined with immunosuppressant, chemotherapy or bronchoalveolar lavage; 96 cases (81.4%) were cured or showed improvement, and 22 cases (18.6%) died or gave up further treatment. The clinical significance of positive sputum culture for filamentous fungi are associated with the times of positive culture, the number and species of isolated fungal strains. Meanwhile it is important to determine whether there is IPFI according to the nature and clinical characteristics of patients.

Nursing of patients adopting aerosol inhalation of itraconazole for preventing pulmonary invasive fungal infection

白血病患者随着大剂量化疗、广谱抗生素的应用,侵袭性真菌感染(IFI)的发病率呈逐年上升趋势,过去20年内发病率约增加8倍~([1]).一旦感染并确诊,不仅治疗周期长,而且常常导致患者死亡,这给治疗和护理带来极大的挑战。

Invasive pulmonary fungal infection accompanied by severe hemoptysis in patients with hematologic diseases: a report of nine cases

Severe hemoptysis is the fatal complication of invasive pulmonary fungal infection (IPFI) in patients with hematologic diseases. This report retrospectively analyzed the clinical data of nine IPFI patients with hematologic diseases complicated with severe hemoptysis. Four in nine patients were diagnosed of proven IPFI, probable was established in two and the remaining were diagnosed of possible. Seven patients did not respond to the primary treatment, and four of them also did not respond to the salvage therapy. In these nine patients, seven presented massive hemoptysis and all died of that; other two patients presented severe hemoptysis. The result indicates that ineffective initial treatment and irregular therapy may underlie the concurrence of massive hemoptysis. The prognosis of IPFI patients with massive hemoptysis is very poor. Special attention for IPFI treatment should be prophylaxis, early management as well as sufficient and a whole course administration of effective broad-spectrum antifungal agents.

Surgical Management of Invasive Pulmonary Fungal Infection in Hematology Patients

The purpose of this study was to analyze our institutional results with pulmonary resection in neutropenic patients with hematologic malignancies and suspected invasive pulmonary fungal infections. We performed a retrospective medical record review of 25 immunocompromised patients with hematologic malignancies who underwent pulmonary resection between 2000 and 2007. We analyzed preoperative diagnostic technique, degree of pulmonary resection, and postoperative morbidity and mortality to determine whether surgery is a viable treatment option in this subset of patients. Twenty-three of 25 patients had a minithoracotomy compared with 2 who had video-assisted thorascopic surgery resection only. Thirteen had wedge resections, 9 had lobectomies, and 3 had segmentectomies. Early surgical morbidity was 2 of 25, involving 1 pneumothorax and 1 empyema. In-hospital mortality was 2, with 1 death primarily related to surgery. Median survival was 342 days, and survival was significantly better in patients with only one lesion. No patient experienced late recurrence of invasive pulmonary fungal infection. Resected pulmonary tissue also provided the best chance for a proven diagnosis in 19 of 25 (76%). This study confirms that pulmonary resection in high-risk immunocompromised patients with suspected invasive fungal infection can be carried out with excellent operative morbidity and mortality.

Reversed Halo Sign in Invasive Pulmonary Fungal Infections

Computed tomography scans of documented pulmonary mold infections were reviewed for the presence of the reversed halo sign, a focus of ground-glass attenuation surrounded by a solid ring. The reversed halo sign was an early sign, seen in approximately 4% of patients with pulmonary mold infections, usually with zygomycosis.

Risk factors for breakthrough invasive fungal infection during secondary prophylaxis

Intensive chemotherapy with severe neutropenia is associated with invasive fungal infections (IFIs) leading to high mortality rates. During leukaemia induction chemotherapy, IFI often prohibited further curative treatment, thus predisposing for leukaemia relapse. Continuing myelosuppressive chemotherapy after diagnosis of IFI has become feasible with the now expanding arsenal of safe and effective antifungals. Secondary prophylaxis of IFI is widely administered, but reliable data on outcome and risk factors for recurrent IFI during subsequent chemotherapy are not available. This study determines risk factors for recurrent IFI in leukaemia patients. From 25 European cancer centres, 166 consecutive patients with acute myelogenous leukaemia (AML) and a recent history of proven or probable pulmonary IFI were included. Patients were followed for recurrence or breakthrough IFI during the subsequent chemotherapy cycle. Of the 166 patients included, 69 (41.6%) were female, the median age was 53 years (range 2-81) the and 3 (1.8%) were <16 years. Recurrent IFI occurred in 26 patients (15.7%). Multiple logistic regressions yielded predisposing factors: duration of neutropenia [per additional day; odds ratio (OR) 1.043, confidence interval (CI) 1.008-1.078], high-dose cytarabine (OR 3.920, CI 1.120-12.706), number of antibiotics (per antibiotic; OR 1.504, CI 1.089-2.086), partial response as outcome of prior IFI (OR 4.037, CI 1.301-12.524) and newly diagnosed AML (OR 3.823, CI 0.953-15.340). Usage of high efficiency particulate air filter appeared protective (OR 0.198, CI 0.036-1.089). Duration of neutropenia, high-dose cytarabine, prior antibiotic therapy and a partial response to the first IFI therapy were risk factors for recurrent IFI and should be considered in AML patients with prior pulmonary IFI undergoing further chemotherapy.

Bronchoalveolar Lavage Fungal Antigen Detection in Critically Ill Children

Bronchoalveolar Lavage Fungal Antigen Detection in Critically Ill Children

A Randomized, Placebo-Controlled, Dose-Escalation, Phase 1 Study of the Safety and Pharmacokinetics of Amphotericin B Inhalation Powder in Healthy Subjects.

Nektar is developing Amphotericin B Inhalation Powder (ABIP; NKTR-024) to prevent invasive pulmonary fungal infections in immunocompromised patients. NKTR-024 is a proprietary dry-powder amphotericin B (AmB) formulation that is delivered to the patient's respiratory tract with a proprietary breath-actuated inhalation device (T-326). This study assessed 1) the safety and tolerability and 2) the pharmacokinetics (PK) of AmB in epithelial lining fluid (ELF) and plasma after a loading dose (LD) and 4 weekly maintenance doses (MD) of NKTR-024 in healthy subjects. Thirty-six (36) subjects enrolled in a single center in the US into 2 cohorts 2:1 to receive either NKTR-024 (n=12) or a matching (powder load) placebo inhalation powder (n=6), respectively. Subjects in Cohort 1 (Coh1) received a 25-mg LD and 4 weekly 5-mg MD (25/5) and subjects in Cohort 2 (Coh2) received a 50-mg LD and 4 weekly 10-mg MD (50/10) of NKTR-024 or placebo, respectively. PK assessments used blood [plasma] and bronchoalveolar lavage (BAL) [ELF] samples. Concomitant medications, adverse events (AEs) and other safety parameters were monitored for 17 wk (screening period of up to 28 d, a 4-wk treatment period, and a 9-wk post-treatment period). All 36 subjects received 1 LD and 4 MDs. Subjects were mostly male (n=24, 66.7%) and Caucasian (n=27, 75%). Mean age=28.1 yr, median height=175.3 cm and median weight=77.4 kg. PK data have been previously presented and will not serve as the focus of this abstract. Maximal plasma AmB concentrations occurred at ∼8–12 hr postdose following a ∼1 hr postdose lag. Plasma AmB concentrations (<54.6 ng/mL after the 50-mg NKTR-024 LD) remained well below those typically associated with renal toxicity (plasma AmB concentrations of ≥1000 ng/mL). Mean lung ELF AmB concentrations from the first BAL samples (∼4 hr) were 70.7 and 189 μg/mL for Coh1 and Coh2, respectively. These high lung ELF AmB concentrations show that a large fraction of the nominal NKTR-024 doses were delivered to the lung. Both the NKTR-024 regimens (25/5 and 50/10) were well-tolerated. AEs were mild or moderate. No serious AEs occurred. Most of the AEs across treatment groups were related to bronchoscopy or “other” reasons. Respiratory AEs were most common across treatment groups. Slightly more respiratory AEs (cough, productive cough, increased bronchial secretions, wheezing, dyspnea, and exertional dyspnea) occurred in the NKTR-024 groups versus the placebo groups. AEs were greatest on the day of dosing and for the first 2 days after dosing. Hematology, chemistry, and urinalysis showed no clinically concerning treatment-induced toxicity. No clinically significant abnormalities were noted on physical examination, vital signs, chest x-ray, or electrocardiogram. Spirometry (FVC and FEV1) remained virtually unchanged from predose to postdose at all scheduled visits except for 4 subjects who had transient declines in FVC or FEV1 >20% temporally related to bronchoscopy. Repeated administration of NKTR-024 resulted in high pulmonary and low systemic AmB exposure. Plasma AmB concentrations were well below those associated with renal toxicity; this observation supports an important potential benefit of the NKTR-024 investigational product. Constitutional symptoms and electrolyte abnormalities traditionally seen with systemic administration of AmB were essentially spared.

Itraconazole-Enhanced Vindesine Neurotoxicity in Adult Acute Lymphoblastic Leukaemia.

Severe neurotoxicity following treatment with itraconazole and vincristine has been reported in 25 patients. Here we presented two adult acute lymphoblastic leukemia (ALL) patients developed neurotoxicity after treated with itraconazole and another vinca alkaloids, vindesine. Case 1: A 20-year-old male was diagnosed as having ALL and achieved complete remission (CR) after induction chemotherapy with DVP. He was treated with Hyper-CVAD for consolidation. Because he has a history of pulmonary invasive fungal infection, antifungal prophylaxis with itraconazole solution was started. Nine days after itraconazole was started, some symptom and signs of paralytic ileus were presented. He was diagnosed to have paralytic ileus secondary to neurotoxicity caused by itraconazole and vindesine. After the itraconazole was stopped, his paralytic ileus was improved rapidly. Case 2: A 37-year-old female was diagnosed as having ALL. A diagnosis of B-cell/T-cell biphenotypic acute leukemia was established based on the results of flow cytometry analysis. She was commenced on induction chemotherapy as for ALL (dexamethasone, Idarubicin, and vindesine). The patient presented as pulmonary infection with fever, cough, and expectoration in day 9. Emperical antifungal treatment with itraconazole injection was initiated. Five days after itraconazole injection was started, some symptom of neurotoxicity including limbs anesthesia, and paralytic ileus were presented. After the itraconazole and vindesine were discontinued, these symptoms were resolved. Given the interaction of itraconazole with vinca alkaloids leading to severe and even potentially fatal toxicities, the combination use of these drugs should be avoided.

Improved Outcome of Patients with Invasive Pulmonary Fungal Infection Complicated by Respiratory Failure Due to the Use of New Antimycotis Agens and Early Tracheostomy after Allogeneic Transplantation.

The mortality rate associated with respiratory failure due to invasive fungal infections (IFI) after allogeneic hematopoietic stem cell transplantation (HSCT) is exceedingly high. Here we compared in a retrospective analysis the influence of the antimycotic agents and early tracheostomy on the outcome of patients (pts) with required artificial respiration (AV) due to pulmonary IFI. The first cohort presented pts, who were treated at our center before the new antimycotic agents became available. This cohort consisted 16 pts from 236 consecutive allogeneic transplant recipients (median age 38 years [range 22–59], 88% had a leukemic disorder) died during or soon after weaning from AV (median survival: 64 days). The mean weaning time was 16 days, only one patient could be tracheotomized. In contrast to this, within a second cohort of 24 pts from 279 consecutive allogeneic transplant recipients, who required AV after the introduction of the new antimycotic agents 9 (38 %) pts could be brought back to spontaneous breathing. The median survival of these pts was 370 days. The weaning time was 24 days, 67% of those pts underwent tracheotomy within ten days after initiation of AV. There were no differences between the two cohorts regarding the underlying diseases, engraftment time or the ratio of myeloablative and reduced intensity conditioning regimens. However, the cohort of pts who were transplanted during the era of new antimycotic agents had a higher median age (43 years, range 20–65, not significantly) and included more mismatched and unrelated grafts with a higher incidence of GVHD grade II-IV (79% vs. 69%). To date, four of those pts are still alive and well (mean survival 463 days, range 240 to 732). We propose that our observations reflect an improved management of these pts nowadays mainly due to the use of new antimycotics and more effective antifungal treatment approaches, as well as the advantages of early tracheostomy may contribute to better outcomes in the treatment of respiratory failure due to pulmonary IFI following allogeneic HSCT.

Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies

Invasive Fungal Infections (IFI) remain a severe and major complication among patients with hematologic diseases, but the recent availability of new antifungal agents (echinocandins and new azoles) have improved the chance of cure. Caspofungin (Cancidas-Merck) is a large lipopeptide molecule able to inhibit the enzyme complex 1,3-d-glucan synthetase; this action specifically damages the fungal cell wall. Caspofungin (CAS) is active, in vitro and in vivo, against most Candida species and Aspergillus species. We report on our experience with this drug as first-line therapy for proven or probable pulmonary IFI in immunocompromised patients with hematologic malignancies. Thirty-two consecutive patients (20 males and 12 females, with a median age of 52 yr) have been treated with CAS (27 acute leukemias, 1 chronic leukemia, 3 lymphomas and 1 multiple myeloma). Sixteen patients (50%) had a relapsed or resistant hematologic disease, while 12 patients were in complete remission and 4 were at onset of disease; 8/32 (25%) developed IFI after a hematopoietic stem cell transplant (HSCT) procedure. Seven out of 32 patients (22%) had a proven pulmonary IFI (7/7 Aspergillosis) and 25 (78%) had a probable IFI with pulmonary localization as defined according to international consensus. Thirty-one patients (97%) had less than 1000 granulocytes/mL at onset of infection and at the start of CAS therapy. The CAS was given at the dose of 70 mg on day 1, followed by 50 mg/day. Median duration of CAS therapy was 20 d (range 8-64); all the 31 neutropenic patients received concomitant granulocyte colony-stimulating factor (G-CSF). The overall response rate was 56% (18/32) with 12/18 complete responses and 6/18 partial responses; two patients (6%) had a stable disease. Twelve out of 32 (38%) did not respond and seven died of mycotic infection. Univariate analysis showed that granulocytes recovery (>500/mL vs. <500/mL) and status of hematologic disease (remission/onset vs. refractory/relapsed) were significantly associated to favourable outcome. No clinical adverse events (AE) were reported and only a grades I and II transient increase of serum alkaline phosphatase and/or transaminases occurred in 4/32 (12%) patients. After CAS therapy six non-responders and six cases with a partial or stable response were rescued with voriconazole. Two out of six patients (33%) in the former group and 6/6 (100%) in the latter obtained a complete resolution of IFI. Our experience suggests an efficacy of CAS, in combination with G-CSF, as first-line treatment of proven or probable IFI with pulmonary localization. The drug was well tolerated and there were no significant hepatic AE even in patients receiving CAS with cyclosporine after a HSCT. A significant proportion of non-responders or partial responders to CAS can be rescued with a subsequent voriconazole-based therapy.

Invasive pulmonary fungal infections in solid organ transplant recipients: a four-year review

Invasive pulmonary fungal infections in solid organ transplant recipients: a four-year review

Invasive Fungal Infection in Patients with Myelodysplastic Syndrome: A Report of Twelve Cases

In this report we analyse the risk factors, clinical characteristics and outcome of patients with myelodysplastic syndrome (MDS) who developed a invasive fungal infection (IFI). This was a multicentric study involving 14 Italian Haematological Divisions during a 10-year-period whose object was to identify the characteristics of patients with this infection. The study recorded 391 consecutive documented IFI, 12 of which (3%) occurred in MDS patients from five of the participating centres. The primary localisation of infection was the lung in 10 cases and skin and paranasal sinus in one case each. Ten patients died at the end of the follow up. The death was mainly attributable to IFI progression in nine of them. The factors which appeared related to an unfavourable outcome were intensive chemotherapy within 30 days before IFI diagnosis, presence of multiple localisation at chest X-ray in patients with isolated pulmonary IFI and multiple sites of infection.

Surgical aspects of resection for suspected invasive pulmonary fungal infection in neutropenic patients

Background. Morbidity and mortality of early resection of invasive pulmonary fungal disease in neutropenic patients are still considered prohibitive for surgical treatment. Methods. We retrospectively analyzed results of 28 (16 men, 12 women; mean age, 38.9 years) consecutive neutropenic hematologic patients who had lung resections for suspicion of invasive pulmonary fungal disease. Results. We did 28 lung resections (19 lobectomies, one bilobectomy, eight single or multiple wedge resections including three video-assisted wedge resections). The disease was proved histologically in 22 (78.6%) cases. Intraoperative difficulties, such as diffuse oozing or mycotic infiltration, and solid postinflammatory adhesions were encountered in 5 (17.8%) and 6 (21.4%) patients respectively. In one case (3.6%) it lead to a major intraoperative hemorrhage. There were no intraoperative deaths, overall 30-day mortality rate was two of 28 (7.1%), overall 90-day mortality rate was seven of 28 (25%), with one death (3.6%) possibly related to surgery. Minor surgery-related complications were seen in ten (35.7%) cases, major surgery-related complications occurred in three (10.7%) cases. Twelve of 22 patients (54.5%) with proven invasive fungal infection are currently alive (mean follow-up, 32.3 months). Conclusions. Surgery-related complications and mortality are acceptable for this high risk group of patients. Resection should be carried out early for diagnostic as well as therapeutic reasons.

Equine pulmonary mycosis due to Aspergillus niger and Rhizopus stolonifer

Invasive pulmonary mycosis caused by Aspergillus niger and Rhizopus stolonifer is reported in a 2-year-old horse, one of three that died after being housed in a disused, uncleaned stable. Lesions were characterized by thrombosis of the blood vessels with haemorrhage and tissue necrosis. Fungal hyphae were observed both in thrombosed vessels and in adjacent necrotic tissue. In culture media inoculated with lung samples and samples from the bedding hay, two types of colony were recorded and identified as A. niger and R. stolonifer. This study is the first description of equine pulmonary mucormycosis and of A. niger as an aetiological agent in the horse.

Increased lung volume in invasive pulmonary fungal infection.

Increased lung volume in invasive pulmonary fungal infection.H T Winer-Muram, P M Bozeman and B C DesselleAudio Available | Share

Successful treatment of aspergillus pneumonia in hematologic neoplasia.

Patients with acute leukemia and lymphoma are at increased risk of invasive pulmonary fungal infection.1 , 2 Among the opportunistic fungi responsible for these infections, aspergillus species are especially common.3 4 5 6 Invasive aspergillus pneumonia in these patients has with few exceptions been fatal, despite a number of therapeutic attempts with antifungal chemotherapy. In the two cases of aspergillus pneumonia presented below (both in patients with lymphoma) an aggressive diagnostic and therapeutic approach resulted in a successful outcome.Case ReportsCase 1. A 65-year-old woman with poorly differentiated lymphoma entered the hospital because of fever. The white-cell count was 900, with 10 per cent . . .