Nosocomial pneumonia in patients having bone marrow transplant attributable mortality and risk factors

Pannuti, Cláudio Sérgio; Gingrich, Roger D.; Pfaller, Michael A.; Kao, Chi; Wenzel, Richard P.

doi:10.1002/1097-0142(19920601)69:11<2653::aid-cncr2820691106>3.0.co;2-8

Cited by 111 publications

(60 citation statements)

References 21 publications

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“…4,5 With better control of other opportunistic infections, especially CMV, invasive fungal disease has become the leading infectious cause of death during the first 100 days after transplant. 18,19 Late fungal infection is predominantly due to aspergillus, while late candidiasis appears to be less common since introduction of post transplant fluconazole prophylaxis in allograft recipients. 14,20 (4) PCP was a relatively rare complication.…”

Section: Discussionmentioning

confidence: 91%

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

Chen

Boeckh

Seidel

et al. 2003

Bone Marrow Transplant

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Summary:The incidence, etiology, outcome, and risk factors for developing pneumonia late after hematopoietic stem cell transplantation (SCT) were investigated in 1359 patients transplanted in Seattle. A total of 341 patients (25% of the cohort) developed at least one pneumonic episode. No microbial or tissue diagnosis (ie clinical pneumonia) was established in 197 patients (58% of first pneumonia cases). Among the remaining 144 patients, established etiologies included 33 viral (10%), 31 bacterial (9%), 25 idiopathic pneumonia syndrome (IPS, 7%), 20 multiple organisms (6%), 19 fungal (6%), and 16 Pneumocystis carinii pneumonia (PCP) (5%). The overall cumulative incidence of first pneumonia at 4 years after discharge home was 31%. The cumulative incidences of pneumonia according to donor type at 1 and 4 years after discharge home were 13 and 18% (autologous/syngeneic), 22 and 34% (HLA-matched related), and 26 and 39% (mismatched related/unrelated), respectively. Multivariate analysis of factors associated with development of late pneumonia after allografting were increasing patient age (RR 0.5 for o20 years, 1.2 for 440 years, P ¼ 0.009), donor HLA-mismatch (RR 1.6 for unrelated/mismatched related, P ¼ 0.01), and chronic graft-versus-host disease (GVHD; RR 1.5, P ¼ 0.007). Our data suggest that extension of PCP prophylaxis may be beneficial in high-risk autograft recipients. Further study of long-term anti-infective prophylaxis based on patient risk factors after SCT appear warranted.

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Section: Discussionmentioning

confidence: 91%

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

Chen

Boeckh

Seidel

et al. 2003

Bone Marrow Transplant

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“…Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in patients with cancer, hematopoietic stem cell transplantation, solid organ transplantation, and other immunodeficiencies (1,4,8,13,21,36). Despite the use of single agents, such as amphotericin B, its lipid formulations, antifungal triazoles, and echinocandins, mortality associated with invasive pulmonary aspergillosis remains high (22,32).…”

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confidence: 99%

Combination Therapy in Treatment of Experimental Pulmonary Aspergillosis: In Vitro and In Vivo Correlations of the Concentration- and Dose- Dependent Interactions between Anidulafungin and Voriconazole by Bliss Independence Drug Interaction Analysis

Petraitis

Petraitienė

Hope

et al. 2009

Antimicrob Agents Chemother

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We studied the antifungal activity of anidulafungin (AFG) in combination with voriconazole (VRC) against experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits and further explored the in vitro and in vivo correlations by using Bliss independence drug interaction analysis. Treatment groups consisted of those receiving AFG at 5 (AFG5 group) and 10 (AFG10 group) mg/kg of body weight/day, VRC at 10 mg/kg every 8 h (VRC group), AFG5 plus VRC (AFG5؉VRC group), and AFG10 plus VRC (AFG10؉VRC group) and untreated controls. Survival throughout the study was 60% for the AFG5؉VRC group, 50% for the VRC group, 27% for the AFG10؉VRC group, 22% for the AFG5 group, 18% for the AFG10 group, and 0% for control rabbits (P < 0.001). There was a significant reduction of organism-mediated pulmonary injury, measured by infarct scores, lung weights, residual fungal burdens, and galactomannan indexes, in AFG5؉VRC-treated rabbits versus those treated with AFG5 and VRC alone (P < 0.05). In comparison, AFG10؉VRC significantly lowered only infarct scores and lung weights in comparison to those of AFG10-treated animals (P < 0.05). AFG10؉VRC showed no significant difference in other outcome variables. Significant Bliss synergy was found in vivo between AFG5 and VRC, with observed effects being 24 to 30% higher than expected levels if the drugs were acting independently. These synergistic interactions were also found between AFG and VRC in vitro. However, for AFG10؉VRC, only independence and antagonism were observed among the outcome variables. We concluded that the combination of AFG with VRC in treatment of experimental IPA in persistently neutropenic rabbits was independent to synergistic at a dosage of 5 mg/kg/day but independent to antagonistic at 10 mg/kg/day, as assessed by Bliss independence analysis, suggesting that higher dosages of an echinocandin may be deleterious to the combination.

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“…Cancer treatment and bone marrow transplantation/stem cell transplantation (BMT/SCT) regimens involve intensive cytotoxic chemotherapy, which often leads to prolonged myelosuppression and increased risk for opportunistic mycoses (5,30,31,33,39). Graft versus host disease (GVHD) following BMT/SCT may require immunosuppression that also increases the risk of invasive fungal infections.…”

mentioning

confidence: 99%

Safety, Tolerance, and Pharmacokinetics of High-Dose Liposomal Amphotericin B (AmBisome) in Patients Infected withAspergillusSpecies and Other Filamentous Fungi: Maximum Tolerated Dose Study

Walsh

Goodman

Pappas

et al. 2001

Antimicrob Agents Chemother

371

238

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We conducted a phase I-II study of the safety, tolerance, and plasma pharmacokinetics of liposomal amphotericin B (L-AMB; AmBisome) in order to determine its maximally tolerated dosage (MTD) in patients with infections due to Aspergillus spp. and other filamentous fungi. Dosage cohorts consisted of 7.5, 10.0, 12.5, and 15.0 mg/kg of body weight/day; a total of 44 patients were enrolled, of which 21 had a proven or probable infection (13 aspergillosis, 5 zygomycosis, 3 fusariosis). The MTD of L-AMB was at least 15 mg/kg/day. Infusion-related reactions of fever occurred in 8 (19%) and chills and/or rigors occurred in 5 (12%) of 43 patients. Three patients developed a syndrome of substernal chest tightness, dyspnea, and flank pain, which was relieved by diphenhydramine. Serum creatinine increased two times above baseline in 32% of the patients, but this was not dose related. Hepatotoxicity developed in one patient. Steady-state plasma pharmacokinetics were achieved by day 7. The maximum concentration of drug in plasma (C max ) of L-AMB in the dosage cohorts of 7.5, 10.0, 12.5, and 15.0 mg/kg/day changed to 76, 120, 116, and 105 g/ml, respectively, and the mean area under the concentration-time curve at 24 h (AUC 24 ) changed to 692, 1,062, 860, and 554 g ⅐ h/ml, respectively, while mean CL changed to 23, 18, 16, and 25 ml/h/kg, respectively. These data indicate that L-AMB follows dose-related changes in disposition processing (e.g., clearance) at dosages of >7.5 mg/kg/day. Because several extremely ill patients had early death, success was determined for both the modified intent-to-treat and evaluable (7 days of therapy) populations. Response rates (defined as complete response and partial response) were similar for proven and probable infections. Response and stabilization, respectively, were achieved in 36 and 16% of the patients in the modified intent-to-treat population (n ‫؍‬ 43) and in 52 and 13% of the patients in the 7-day evaluable population (n ‫؍‬ 31). These findings indicate that L-AMB at dosages as high as 15 mg/kg/day follows nonlinear saturation-like kinetics, is well tolerated, and can provide effective therapy for aspergillosis and other filamentous fungal infections.

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Nosocomial pneumonia in patients having bone marrow transplant attributable mortality and risk factors

Cited by 111 publications

References 21 publications

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

Combination Therapy in Treatment of Experimental Pulmonary Aspergillosis: In Vitro and In Vivo Correlations of the Concentration- and Dose- Dependent Interactions between Anidulafungin and Voriconazole by Bliss Independence Drug Interaction Analysis

Safety, Tolerance, and Pharmacokinetics of High-Dose Liposomal Amphotericin B (AmBisome) in Patients Infected withAspergillusSpecies and Other Filamentous Fungi: Maximum Tolerated Dose Study

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