New antifungal compounds and strategies for treatment of invasive fungal infections in patients with neoplastic diseases

Walsh, Thomas J.; Lyman, Caron A.

doi:10.1007/978-1-4613-1239-0_6

Cited by 7 publications

(2 citation statements)

References 199 publications

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“…[303] Amphotericin B, a polyene antifungal, is amphoteric (forming soluble salts in both basic and acidic environments) and virtually insoluble in water. The deoxycholate micellar suspension is the formulation used for intravenous infusion.…”

Section: Amphotericin Bmentioning

confidence: 99%

Commonly Used Antibacterial and Antifungal Agents for Hospitalised Paediatric Patients

et al. 2001

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Due to normal growth and development, hospitalised paediatric patients with infection require unique consideration of immune function and drug disposition. Specifically, antibacterial and antifungal pharmacokinetics are influenced by volume of distribution, drug binding and elimination, which are a reflection of changing extracellular fluid volume, quantity and quality of plasma proteins, and renal and hepatic function. However, there is a paucity of data in paediatric patients addressing these issues and many empiric treatment practices are based on adult data. The penicillins and cephalosporins continue to be a mainstay of therapy because of their broad spectrum of activity, clinical efficacy and favourable tolerability profile. These antibacterials rapidly reach peak serum concentrations and readily diffuse into body tissues. Good penetration into the cerebrospinal fluid (CSF) has made the third-generation cephalosporins the agents of choice for the treatment of bacterial meningitis. These drugs are excreted primarily by the kidney. The carbapenems are broad-spectrum beta-lactam antibacterials which can potentially replace combination regimens. Vancomycin is a glycopeptide antibacterial with gram-positive activity useful for the treatment of resistant infections, or for those patients allergic to penicillins and cephalosporins. Volume of distribution is affected by age, gender, and bodyweight. It diffuses well across serous membranes and inflamed meninges. Vancomycin is excreted by the kidneys and is not removed by dialysis. The aminoglycosides continue to serve a useful role in the treatment of gram-negative, enterococcal and mycobacterial infections. Their volume of distribution approximates extracellular space. These drugs are also excreted renally and are removed by haemodialysis. Passage across the blood-brain barrier is poor, even in the face of meningeal inflammation. Low pH found in abscess conditions impairs function. Toxicity needs to be considered. Macrolide antibacterials are frequently used in the treatment of respiratory infections. Parenteral erythromycin can cause phlebitis, which limits its use. Parenteral azithromycin is better tolerated but paediatric pharmacokinetic data are lacking. Clindamycin is frequently used when anaerobic infections are suspected. Good oral absorption makes it a good choice for step-down therapy in intra-abdominal and skeletal infections. The use of quinolones in paediatrics has been restricted and most information available is in cystic fibrosis patients. High oral bioavailability is also important for step-down therapy. Amphotericin B has been the cornerstone of antifungal treatment in hospitalised patients. Its metabolism is poorly understood. The half-life increases with time and can be as long as 15 days after prolonged therapy. Oral absorption is poor. The azole antifungals are being used increasingly. Fluconazole is well tolerated, with high bioavailability and good penetration into the CSF. Itraconazole has greater activity against aspergillus, blastomycosis,...

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Section: Amphotericin Bmentioning

confidence: 99%

Commonly Used Antibacterial and Antifungal Agents for Hospitalised Paediatric Patients

et al. 2001

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“…Invasive aspergillosis is an increasingly important problem in varied groups of immunocompromised hosts, notably in cancer patients, but also in other vulnerable groups [1–5]. Autopsy series such as that reported by Bodey and colleagues attest to the scale of the problem (fungal infection was detected at post‐mortem (PM) in 25% of leukaemic patients—30% was due to Aspergillus ) [6]; and other observers have noted a dramatic increase in the incidence of invasive aspergillosis detected at PM in a wider ‘tertiary hospital’ inpatient group [7].…”

Section: Introductionmentioning

confidence: 99%

Early investigation and initiation of therapy for invasive pulmonary aspergillosis in leukaemic and bone marrow transplant patients

Barnes

Oppenheim

Chang

et al. 1999

Mycoses

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Invasive fungal infections are an increasingly common problem in cancer patients and in other vulnerable groups. Invasive pulmonary aspergillosis (IPA) in the neutropenic host presents particular challenges in terms of diagnosis and therapy. Against the background of a recognized problem of invasive aspergillosis in haematology/oncology patients treated at the Christie Hospital, we undertook a prospective study in patients at risk for IPA. The aim of the study was to improve outcome by using the linked strategies of first, early diagnosis, and secondly, early aggressive therapy with a lipid-associated formulation of amphotericin B, amphotericin B colloidal dispersion ('Amphocil'). Early investigation comprised the use of high-resolution computerized tomography scanning of the thorax and fibreoptic bronchoscopy to obtain bronchoalveolar lavage specimens, processed using conventional detection and culture methods. Using this approach, the incidence of proven or probable IPA in patients with acute leukaemia was 9%. Prompt initiation of amphotericin B colloidal dispersion therapy led to a successful outcome in 11 of 13 patients, compared with a mortality of 100% in historical controls.

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Invasive Candida infections in the neonate

Smith

Steinbach

Benjamin

2005

Drug Resistance Updates

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New antifungal compounds and strategies for treatment of invasive fungal infections in patients with neoplastic diseases

Cited by 7 publications

References 199 publications

Commonly Used Antibacterial and Antifungal Agents for Hospitalised Paediatric Patients

Commonly Used Antibacterial and Antifungal Agents for Hospitalised Paediatric Patients

Early investigation and initiation of therapy for invasive pulmonary aspergillosis in leukaemic and bone marrow transplant patients

Invasive Candida infections in the neonate

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