Comparison of Efficacy and Safety of Caspofungin Versus Micafungin in Pediatric Allogeneic Stem Cell Transplant Recipients: A Retrospective Analysis

Maximova, Natalia; Schillani, Giulia; Simeone, Roberto; Maestro, Alessandra; Zanon, Davide

doi:10.1007/s12325-017-0534-7

Cited by 24 publications

(20 citation statements)

References 25 publications

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“…Data from adult studies have shown that caspofungin has a well tolerated and exhibits antifungal activity in a dose-dependent manner (Cornely et al, 2011). Caspofungin can be used with the maximum dose for adults up to 200 mg/d from the previously published data (Maximova et al, 2017). Previously, in a murine model of systemic candidiasis, preclinical data from a dose-fractionation study of caspofungin indicated that AUC predicted efficacy (Shen et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Caspofungin and Dosing Optimization in Children With Allogeneic Hematopoietic Stem Cell Transplantation

Niu

Gao

et al. 2020

Front. Pharmacol.

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Caspofungin is the first echinocandin antifungal agent that licented for pediatric use in invasive candidiasis and aspergillosis. In this study, we evaluated the population pharmacokinetics of caspofungin and investigate appropriate dosing optimization against Candida spp. in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in order to improve therapeutic efficacy. All participants received a recommended caspofungin 70 mg/m 2 loading dose followed by 50 mg/m 2 maintenance dose. A one-compartment model with first-order elimination was best fitted the data from 48 pediatric patients. Body surface area and aspartate aminotransferase had significant influence on caspofungin clearance from covariate analysis. Our results reviewed that dose adjustment is not necessary in patients with mild liver dysfunction. Monte Carlo simulations were performed using pharmacokinetic data from our study to evaluate the probability of target attainment (PTA) of caspofungin regimen in terms of AUC 24 /MIC targets against Candida spp. The results of simulations predicted that a caspofungin 70 mg/m 2 at first dose, 50 mg/m 2 of daily dose may have a high probability of successful outcome against C. albicans and C. glabrata whilst 60 mg/m 2 maintenance dose was required for fungistatic target against C. parapsilosis but may be not sufficient to achieve optimal fungicidal activity. Caspofungin standard regimen had high probability of successful outcome against C. albicans (MIC ⩽ 0.25 mg/L) and C. glabrata (MIC ⩽ 0.5 mg/L) but insufficient for C. parapsilosis with MIC > 0.25 mg/L. That may provide an evidence based support to caspofungin individualized administration and decrease the risk of therapeutic failure in allo-HSCT pediatric patients.

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Caspofungin and Dosing Optimization in Children With Allogeneic Hematopoietic Stem Cell Transplantation

Niu

Gao

et al. 2020

Front. Pharmacol.

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“…Caspofungin and TMP-SMZ co-treatment had been reported to improve PCP patients' outcome and decrease ADRs of sulfamide in China [26]. Caspofungin combined with clindamycin were also reported to successfully replace TMP-SMZ in anti-PCP treatment [27].…”

Section: Discussionmentioning

confidence: 99%

The outcome predictors and therapeutic strategy of pneumocystis pneumonia in North China: a double-center retrospective study

Yang

Zhang³

et al. 2019

Preprint

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Background: Pneumocystis pneumonia (PCP) is common in HIV/AIDS patients with advanced immunosuppression. Trimethoprim/sulfamethoxazole (TMP/SMX) is recommended as the first-line anti-pneumocystis agent as soon as PCP is suspected based on its typical feature. However, the clinical characteristic and therapeutic strategy of Chinese PCP were not well-known. Methods: We retrospectively investigated 473 HIV associated PCPs in North China from double centers, Beijing You An Hospital during 2010 to 2017 and the Infectious Disease Hospital in Harbin during 2015 to 2017. HIV associated PCP were diagnosed as the guideline recommended by CDC, NIH and HIV Medicine Association of IDSA. Demographic and clinic data were collected and statistically analysed as the parameter distribution feature. Results: Among 473 HIV associated PCPs, we found that men were over-represented in PCP due to the high incidence of HIV infection among male homosexuality, and over one-third of them were aware of their HIV infection ago but did not maintain effective antiretroviral therapy. A history of smoking and multi-organism infection or system infection were common among them. In the multivariate analysis, we found lactate dehydrogenase (LDH) (OR 1.020, 95% CI 1.006-1.033, P=0.005), alveolar-arterial O2 difference ([A-a] DO2) and neutrophils counts (OR 1.051, 95% CI 1.005-1.099, P=0.030) were unfavourable predictors and CD4 cell counts (OR 0.900, 95% CI 0.813-0.996, P=0.041) were favourable predictor of PCP outcome. Trimethoprim/sulfamethozole (TMP/SMZ) but not TMP/SMX was used to anti-pneumocystis therapy in these patients with a low side-effect incidence which mainly forcused on epispasis, fever, liver injury and myelosuppression. Caspofungin was the only alternative medicine for those presented poor efficacy or could not tolerate the side-effects of TMP-SMZ and near 30 percent of moderate/severe PCP received glucocorticoid treatment. Conclusion: The present data suggest that high levels of serum-LDH, [A-a] DO2 and neutrophils counts and low CD4 cell counts predict poor outcome of PCP. TMP/SMZ can cure most PCPs with a low side-effect incidence and caspofungin is an effective alternation. A larger prospective study is needed to obtain better estimates of PCP in China.

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“…Allogeneic HSCT was performed after a myeloablative standard conditioning regimen based on oral busulfan (480 mg/m 2 ) or total body irradiation (TBI; 12 Gy total dose in six fractions). Myeloablative conditioning was completed with high dose leukemia-specific therapy and immunoablation therapy as described previously [ 30 ]. GVHD prophylaxis was performed with a calcineurin inhibitor, which was associated with mycophenolate mofetil in the matched unrelated and haploidentical donor groups.…”

Section: Methodsmentioning

confidence: 99%

Total body irradiation and iron chelation treatment are associated with pancreatic injury following pediatric hematopoietic stem cell transplantation

et al. 2018

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Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT.We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge.63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8±100,3 μmol/g vs 28,4±37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2±48,8 μmol/g vs 55,7±10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 μmol/g at follow up had DFO-based chelation therapy, versus 26% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48% vs 4%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1% vs 0,9% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy.Based on our data, we suggest that TBI is detrimental for pancreatic functions, and speculate that DFO may contribute to the rapid pancreatic IO observed in these patients.

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Comparison of Efficacy and Safety of Caspofungin Versus Micafungin in Pediatric Allogeneic Stem Cell Transplant Recipients: A Retrospective Analysis

Abstract: These results demonstrate good efficacy and tolerability for caspofungin and micafungin. However, better results with respect to the incidence and resolution of fever in the micafungin group may suggest its use in preference to that of caspofungin.

Cited by 24 publications

References 25 publications

Population Pharmacokinetics of Caspofungin and Dosing Optimization in Children With Allogeneic Hematopoietic Stem Cell Transplantation

Population Pharmacokinetics of Caspofungin and Dosing Optimization in Children With Allogeneic Hematopoietic Stem Cell Transplantation

The outcome predictors and therapeutic strategy of pneumocystis pneumonia in North China: a double-center retrospective study

Total body irradiation and iron chelation treatment are associated with pancreatic injury following pediatric hematopoietic stem cell transplantation

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