Is There a Therapeutic or Pharmacokinetic Rationale for Amphotericin B Dosing in Systemic <i>Candida</i> Infections?

Nagata, Maureen P; Gentry, Chris A.; Hampton, Edward M.

doi:10.1177/106002809603000720

Cited by 13 publications

(3 citation statements)

References 48 publications

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“…This is akin to a "democratization" process of the antigen-specific repertoire, whereby the clonal "elite" is culled in favor of the "mediocre" majority [122]. In agreement with this, both mouse and human studies show a dramatic, age-related decline in the diversity of antigen-specific T cells, preferentially losing reactivity over time to epitopes recognized by T cells with low precursor frequencies [123]. This effort to maintain some recognition of a pathogen can sacrifice clonal and antigenic diversity, plausibly generating "gaps" in the immunological repertoire.…”

Section: Altered Peripheral Cd4 T Cell Diversitymentioning

confidence: 83%

Impact of sepsis on CD4 T cell immunity

Cabrera-Pérez¹,

Condotta

Badovinac

et al. 2014

Journal of Leukocyte Biology

154

124

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Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state.

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Section: Altered Peripheral Cd4 T Cell Diversitymentioning

confidence: 83%

Impact of sepsis on CD4 T cell immunity

Cabrera-Pérez¹,

Condotta

Badovinac

et al. 2014

Journal of Leukocyte Biology

154

124

View full text Add to dashboard Cite

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“…However mortality rate has been reported as 10-53% from small case series despite appropriate treatment (5). The therapy for fungal infection of a CSF shunt still consists of externalisation of the shunt, administration of systemic antifungal agents and placement of a new shunt and the elective regimen consists of amphotericin B intravenous (IV) and/or intraventricular (IVT) for a period of at least four weeks (8). We also used the combination therapy of externalisation of the shunt and administration of IV and IVT antifungal agent.…”

Section: Discussionmentioning

confidence: 99%

Persistent Candida albicans Infection of A Cerebrospinal Fluid Shunt Infection Unresponsive to Amphotericin B Treatment Because of Increased Minimum Inhibitory Concentration

Kuzdan¹,

Karaaslan²,

Soysal

et al. 2015

J Pediatr Inf

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Infection is still the most common complication of shunt procedures in children. However fungal infection is considered to be rare, it is also associated with significant morbidity and mortality. The risk is increasing in premature neonates and after neurosurgery. Herein, we present a preterm neonate with persistant Candida albicans cerebrospinal fluid (CSF) shunt infection that was unresponsible to amphotericin B treatment due to increased minimal inhibitory concentration (MIC) during the therapy period and later which was treated by voriconazole plus flucytosine.

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“…The pharmacokinetic rationale for adapting dosage in order to influence clinical outcome has been reviewed elsewhere (21). So far this is partly limited by the fact that currently used AMB bioassays and chromatographic methods require specific equipment not available in all clinical centers, disadvantages that may be circumvented by the assay presented here.…”

Section: Discussionmentioning

confidence: 99%

A Sensitive Amphotericin B Immunoassay for Pharmacokinetic and Distribution Studies

Machard

Théodoro

Bénech

et al. 2000

Antimicrob Agents Chemother

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Since currently used assays of amphotericin B (AMB) lack sensitivity or are not easily adaptable in all laboratories, we have developed an enzyme immunoassay for AMB in biological fluids and tissues. Antibodies to AMB were raised in rabbits after administration of an AMB-bovine serum albumin conjugate. The enzymatic tracer was obtained by coupling AMB via its amino group to acetylcholinesterase (EC 3.1.1.7). These reagents were used for the development of a competitive immunoassay performed on microtitration plates. The limit of quantification was 100 pg/ml in plasma and 1 ng/g in tissues. The plasma assay was performed directly without extraction on a minimal volume of 0.1 ml. The intra-and interassay coefficients of variation were in the range of 5 to 17%, and the recoveries were 92 to 111% for AMB added to human plasma. The assay was applied to a pharmacokinetic study with mice given AMB intraperitoneally at the dose of 1 mg/kg. The drug distribution in selected compartments (plasma, liver, spleen, lung, and brain) was monitored until 72 h after administration. In conclusion, our assay is at least 100-fold more sensitive than previously described bioassays or chromatographic determinations of AMB and may be useful in studying the tissue pharmacokinetics of new AMB formulations and in drug monitoring in clinical situations.Amphotericin B (AMB) has been considered for more than 30 years the major antifungal drug for serious systemic fungal infections, which, owing to AIDS and improved organ transplant immunosuppression drugs, are becoming tragically frequent in immunocompromised individuals (12,20). AMB's spectrum of activity is broad, since antiviral or antiprion effects have also been reported (12). The clinical value of AMB has been reinforced by incorporation in lipid-based carriers, thus reducing its nephro-and hematotoxicity, and these new formulations have been investigated in animals and humans (4,15,25). In parallel with these recent developments, a need arose for suitable analytical methods to monitor AMB levels in tissue or plasma and thus establish pharmacokinetic and pharmacodynamic relationships. Assays based on in vitro biological activity or chromatographic separations have been described and used to monitor AMB in the circulation (3,11,19,22,23). These methods, however, are characterized by a relatively high limit of detection (Ͼ50 ng/ml) and by technological limitations. These disadvantages may be potentially circumvented by antibody-based technology, and enzyme-linked immunosorbent assays for AMB have been developed (6, 18). Although such techniques allow direct assay in a small sample volume, they have not been applied to tissues and have proved to be poorly sensitive since their limits of quantification are above 150 ng/ ml. In this report we describe the development and application of a competitive enzyme immunoassay which allows measurement of AMB in tissues and plasma with sensitivities 1,000-fold greater than those reported elsewhere. The assay is performed with specific AMB antibodies ...

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Is There a Therapeutic or Pharmacokinetic Rationale for Amphotericin B Dosing in Systemic Candida Infections?

Cited by 13 publications

References 48 publications

Impact of sepsis on CD4 T cell immunity

Impact of sepsis on CD4 T cell immunity

Persistent Candida albicans Infection of A Cerebrospinal Fluid Shunt Infection Unresponsive to Amphotericin B Treatment Because of Increased Minimum Inhibitory Concentration

A Sensitive Amphotericin B Immunoassay for Pharmacokinetic and Distribution Studies

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