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Antimicrobial therapy for infants and children: Guidelines for the inpatient and outpatient practice of pediatric infectious diseases

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MAYO CLINIC PROCEEDINGS 2000年第1期75卷 86-97页

作者： Henry, NK Hoecker, JL Rhodes, KH Mayo Clin Sect Pediat Infect Dis Rochester MN 55905 USA Mayo Clin Sect Community Pediat & Adolescent Med Rochester MN USA

In this article, we discuss antimicrobial regimens for both outpatient and inpatient use in infants and children. substantial number of pediatric patient visits annually result in the prescribing of antimicrobial drugs, The emergence of bacteria resistant to commonly used antimicrobial agents is a growing concern. Information on newer drugs such as meropenem, which is active against penicillin-resistant Streptococcus pneumoniae and gram-negative bacilli, and cefepime, which has activity against gramnegative bacilli including Pseudomonas aeruginosa and against gram-positive cocci is also presented. Management of patients with congenital or acquired immunodeficiencies continues to be challenging in regard to the use of antimicrobial drugs to treat various fungal and viral infections. New formulations of older drugs such as aerosolized tobramycin and amphotericin B lipid complex are available. New antiviral agents have been approved, most of which are antiretroviral agents. Childhood tuberculosis is an ongoing concern, and regimens to treat Mycobacterium tuberculosis in children are discussed.

关键词：门诊医疗/标准抗菌药/治疗应用抗真菌药/治疗应用抗病毒药/治疗应用感染/药物疗法诊疗准则(主题) 美国儿童儿童学龄前人类婴儿

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A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer

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AMERICAN JOURNAL OF MEDICINE 2000年第4期108卷 282-289页

作者： Winston, DJ Hathorn, JW Schuster, MG Schiller, GJ Territo, MC Univ Calif Los Angeles Ctr Hlth Sci Dept Med Div Hematol Oncol Los Angeles CA 90024 USA Duke Univ Med Ctr Dept Med Div Hematol Oncol Durham NC 27710 USA Duke Univ Med Ctr Dept Med Div Infect Dis Durham NC 27710 USA Hosp Univ Penn Dept Med Div Infect Dis Philadelphia PA 19104 USA

PURPOSE: To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer. PATIENTS AND METHODS: A total of 317 neutropenic patients (<500 cells/mm(3)) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were randomly assigned to receive either fluconazole (400 mg intravenously once daily) or amphotericin B (0.5 mg/kg once daily). Patients were evaluated for the efficacy and safety of each drug by clinical criteria, frequent cultures and radiological procedures, and laboratory values. A response was classified as satisfactory at the end of therapy if the patient was afebrile, had no clinical or microbiological evidence of fungal infection, and did not require study termination due to lack of efficacy, drug toxicity, or death. RESULTS: A satisfactory response occurred in 68% of the patients treated with fluconazole (107 of 158 patients) and in 67% of patients treated with amphotericin B (106 of 159 patients). Progressive or new fungal infections during therapy occurred in 13 (8%) patients treated with fluconazole (8 with Candida, 5 with Aspergillus) and in 10 (6%) patients treated with amphotericin B (5 with Candida, 3 with Aspergillus, 2 with other fungi). Adverse events related to study drug (especially fryer, chills, renal insufficiency, electrolyte disturbances, and respiratory distress) occurred more often in patients treated with amphotericin B (128 [81%] of 159 patients) than patients treated with fluconazole (20 [13%] of 158 patients, P = 0.001). Eleven (7%) patients treated with amphotericin B but only 1 (1%) patient treated with fluconazole were terminated from the study owing to an adverse event (P = 0.005). Overall mortality (27 [17%] patients treated with fluconazole versus 34 [21%] patients treated with amphotericin B) and mortality from fungal infection (7 [4%] patients treated with fluconazole versus 5 [3%] patients treated with amphotericin

关键词：两性霉素B/治疗应用抗真菌药/治疗应用死亡原因发热/药物疗法发热/病因学氟康唑/治疗应用输注静脉内真菌病/药物疗法真菌病/病因学真菌病/死亡率真菌病/预防和控制肿瘤/并发症中性粒细胞减少/并发症治疗结果女(雌)性人类男(雄)性中年人

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Aspergillus antigen in serum, urine and bronchoalveolar lavage specimens of neutropenic patients in relation to clinical outcome

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SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES 2000年第5期32卷 485-490页

作者： Salonen, J Lehtonen, OP Teräsjärvi, MR Nikoskelainen, J Turku Univ Cent Hosp Dept Med FI-20520 Turku Finland Turku Univ Cent Hosp Dept Clin Microbiol Turku Finland Turku Univ Dept Med Microbiol Turku Finland

We have used a new, commercial enzyme-linked immunosorbent assay (ELISA, Platelia(R) Aspergillus) to detect Aspergillus antigen in serum, urine and bronchoalveolar lavage (BAL) samples of 105 haematological patients who received empirical amphotericin B treatment for suspected fungal infection. 14% (60/419) of serum and 5% (18/373) of urine samples were positive. Ten-fold concentration of urine increased the number of positive samples to 31 (8%). The antigen was detected in 5 of 20 BAL samples, but fungal culture was negative in all of them. 22 patients had positive antigen test. Serum was positive in 17, urine in 7 and concentrated urine in 12 patients. Six patients had confirmed invasive aspergillosis. In all these patients, antigen was detected in serum, but urine was positive in only 2 patients. Patients whose antigen test turned negative during the amphotericin B treatment had significantly lower mortality than patients with persistently positive antigen test (2/10 vs. 8/8, p = 0.002). We conclude that Aspergillus galactomannan can be detected by ELISA in serum, urine and BAL samples of haematological patients, but the higher sensitivity of serum testing makes it preferable for screening. Disappearance of the antigen during antifungal therapy seems to correlate with good, and persistence with poor, clinical outcome.

关键词：两性霉素B/治疗应用抗真菌药/治疗应用抗原真菌/分析抗原真菌/血液抗原真菌/尿曲霉菌病/诊断曲霉菌病/药物疗法曲霉菌病/死亡率曲霉菌属/免疫学曲霉菌属/分离和提纯支气管肺泡灌洗液/免疫学支气管肺泡灌洗液/微生物学酶联免疫吸附测定中性粒细胞减少/并发症敏感性与特异性治疗结果成年人老年人女(雌)性人类男(雄)性中年人

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Curvularia lunata endophthalmitis with secondary keratitis

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AMERICAN JOURNAL OF OPHTHALMOLOGY 2001年第1期131卷 140-142页

作者： Kaushik, S Ram, J Chakrabarty, A Dogra, MR Brar, GS Gupta, A Postgrad Inst Med Educ & Res Dept Ophthalmol & Microbiol Chandigarh 160012 India

PURPOSE: To report a case of pseudophakic endophthalmitis with secondary keratitis caused by Curvularia lunata. METHODS: A 40 year-old man presented with a fluffy mass in the anterior chamber with low-grade delayed postoperative inflammation in the right eye. RESULTS: The anterior chamber and vitreous aspirate demonstrated C. lunata. A large corneal infiltrate developed after aspiration of the mass. Treatment with systemic, topical, and intraocular antifungal agents cleared the vitreous, but the cornea perforated. CONCLUSION: Delayed low-grade infection with a fluffy mass in the anterior chamber after cataract surgery can rarely be a clinical presentation of dematiaceous fungal infection. Secondary keratitis may result after a diagnostic aspiration. (Am J Ophthalmol 2001;131:140-142. (C) 2001 by Elsevier Science Inc. All rights reserved.).

关键词：抗真菌药/治疗应用眼房水/微生物学白内障摘除术眼内炎/药物疗法眼内炎/微生物学眼感染真菌性/药物疗法眼感染真菌性/微生物学角膜炎/药物疗法角膜炎/微生物学晶体植入眼内有丝分裂孢子真菌/分离和提纯真菌病/药物疗法真菌病/微生物学玻璃体/微生物学成年人人类男(雄)性

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Keratomycosis: Clinical and microbiologic experience with dematiaceous fungi

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OPHTHALMOLOGY 2000年第3期107卷 574-580页

作者： Garg, P Gopinathan, U Choudhary, K Rao, GN L V Prasad Eye Inst Sight Savers Corneal Trainig Ctr Hyderabad 500034 Andhra Pradesh India L V Prasad Eye Inst Devchand Nagardas Jhaveri Microbiol Ctr Hyderabad 500034 Andhra Pradesh India

Objective: To assess the significance of dematiaceous fungi in the causation of keratomycosis, Design: Retrospective, noncomparative case series. Participants: Eighty-eight cases of dematiaceous fungal keratitis seen at the L. V. Prasad Eye Institute, Hyderabad, India from January 1991 through December 1996. Intervention: Only culture-proven cases were analyzed. Main Outcome Measures: Predisposing factors, clinical characteristics, microbiology, treatment methods, and outcome. Results: Of 557 cases of fungal keratitis seen during the study period, dematiaceous fungi were the etiologic agents in 88 (15.7%), after Fusarium in 210 (37.6%) and Aspergillus species in 170 cases (30.4%), respectively. Trauma was the most common predisposing factor (47.7%). Fifty-three eyes (61.3%) had the classical clinical picture of yellow-white, dry raised infiltrate with feathery hyphate edges at initial examination. The characteristic macroscopic pigmentation was seen in only 24 eyes (27.27%). Septate branching fungal filaments were identified in 78 smears (88.63%) on light microscopy, of which 5 (5.7%) also showed the presence of bacteria. Curvularia species dominated the spectrum (22.7%). Treatment was started in 48 eyes with topical antifungal agents, whereas 37 received both oral and topical antifungal agents. Outcome data were available for 68 cases. Forty-nine (72%) responded to medical therapy, whereas 13 eyes required therapeutic penetrating keratoplasty and 6 eyes had to be eviscerated. Conclusions: This is the largest series of keratitis caused by dematiaceous fungi reported to date. It clearly brings out the clinical importance of this group of corneal infections. (C) 2000 by the American Academy of Ophthalmology.

关键词：抗真菌药/治疗应用角膜/微生物学角膜/病理学眼感染真菌性/诊断眼感染真菌性/药物疗法眼感染真菌性/微生物学角膜炎/诊断角膜炎/药物疗法角膜炎/微生物学有丝分裂孢子真菌/分离和提纯真菌病/诊断真菌病/药物疗法真菌病/微生物学回顾性研究青少年成年人老年人儿童儿童学龄前女(雌)性人类婴儿男(雄)性中年人

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Enhancement of antifungal chemotherapy by interferon-gamma in experimental systemic cryptococcosis

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2000年第3期46卷 437-442页

作者： Lutz, JE Clemons, KV Stevens, DA Santa Clara Valley Med Ctr Dept Med Div Infect Dis San Jose CA 95128 USA Calif Inst Med Res San Jose CA 95128 USA Stanford Univ Sch Med Dept Med Div Infect Dis & Geog Med Stanford CA 94305 USA

The possible enhancement, using immunotherapy with interferon-gamma (IFN-gamma), combined with conventional antifungal therapy, was studied in a murine model of systemic cryptococcosis. Four weeks after intravenous challenge, infection was quantified in brains and livers of survivors. Groups received IFN-gamma every other day beginning 7 days before (prophylaxis), or after infection (14 doses), or amphotericin B post-infection, or combinations of these regimens. IFN-gamma alone was modestly effective, but impressively and significantly potentiated amphotericin in reducing infection in the most important site of infection, the brain. The efficacy was seen after lethal and non-lethal challenges, and when IFN-gamma was given by the intravenous or subcutaneous routes. In non-lethal infection, only the combination amphotericin-IFN-gamma resulted in sterilization of the central nervous system, Potentiation of fluconazole was less impressive. Adding prophylactic IFN-gamma doses to IFN-gamma therapy did not consistently enhance the therapeutic effect. These results suggest IFN-gamma may have a role in potentiating conventional antifungal therapy of cryptococcosis.

关键词：两性霉素B/治疗应用抗真菌药/治疗应用脑/微生物学集落计数微生物隐球菌病/血液隐球菌病/药物疗法隐球菌病/微生物学新型隐球菌/分离和提纯疾病模型动物药物协同作用药物疗法联合氟康唑/治疗应用干扰素γ/治疗应用肝/微生物学小鼠近交BALBC 动物人类男(雄)性小鼠

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In-vivo therapeutic efficacy in experimental murine mycoses of a new formulation of deoxycholate-amphotericin B obtained by mild heating

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 1998年第6期42卷 779-785页

作者： Petit, C Chéron, M Joly, V Rodrigues, JM Bolard, J Gaboriau, F Univ Paris 06 Lab Physicochim Biomol & Cellulaire CNRS UA 2056 F-75252 Paris 05 France Hop Bichat Claude Bernard INSERM U13 F-75018 Paris France Univ Paris Sud Ctr Etud Pharmaceut CNRS URA 1218 F-92296 Chatenay Malabry France

Heat-induced 'superaggregation' of deoxycholate-amphotericin B (AmB-DOC, Fungizone) was shown previously to reduce the in-vitro toxicity of this antifungal agent. We compared AmB-DOC with the formulation obtained by heating the commercial form (Fungizone, Bristol Myers Squibb, Paris, France) for 20 min at 70 degrees C, in the treatment of murine infections. An improvement of antifungal activity was obtained with heated AmB-DOC formulations due to a lower toxicity which allowed the administration of higher drug doses than those achievable with the commercial preparation. Single Intravenous injections of heated AmB-DOC solutions were demonstrated to be two-fold less toxic than unheated ones to healthy mice. For mice infected with Candida albicans, the maximum tolerated dose was higher with heated than with unheated AmB-DOC solutions. In the model of murine candidiasis, following a single dose of heated AmB-DOC 0.5 mg/kg, 85% of mice survived for 3 weeks, whereas at this dose the immediate toxicity of the standard formulation in infected mice restricted the therapeutic efficacy to 25% survival. Both formulations were equally effective in increasing the survival time for murine cryptococcal pneumonia and meningoencephalitis. Injection of heated AmB-DOC solutions at a dose two-fold higher than the maximal tolerated dose observed with the unheated preparation (1.2 mg/kg) increased the survival time by a factor of 1.4 in cryptococcal meningoencephalitis. These results indicate that mild heat treatment of AmB-DOC solutions could provide a simple and economical method to improve the therapeutic index of this antifungal agent by reducing its toxicity on mammalian cells.

关键词：两性霉素B/治疗应用两性霉素B/毒性抗真菌药/治疗应用抗真菌药/毒性念珠菌白色/药物作用念珠菌白色/致病力念珠菌病/药物疗法化学药物隐球菌病/药物疗法隐球菌新型/药物作用隐球菌新型/致病力脱氧胆酸/治疗应用脱氧胆酸/毒性复方合剂小鼠近交BALBC 小鼠近交DBA 真菌病/药物疗法动物男(雄)性小鼠

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PRINCIPLES IN MANAGEMENT OF OCULOMYCOSIS - XXXI JACKSON,E MEMORIAL LECTURE

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AMERICAN JOURNAL OF OPHTHALMOLOGY 1975年第5期79卷 719-751页

作者： JONES, BR MOORFIELDS EYE HOSP INST OPHTHALMOLDEPT CLIN OPHTHALMOLLONDON EC1V 2PDENGLAND

Effective antifungal therapy must be long term, nondamaging, penetrating to the eye, and highly active against each patient's fungus. Results of antifungal sensitivity testing of 61 collected ocular fungal pathogens, and observations in 25 cases treated with one of the nonpolyene antifungal drugs indicated that infection was rapidly controlled and eradicated with restoration of visual acuity, determined by the degree of disorganization present at the time of commencement of rational specific antifungal therapy. Pimaricin has the widest spectrum, a medium level of activity, and rather poor penetration, but is recommended as an antifungal prophylactic and as first line therapy for ocular fungal disease while awaiting identification and sensitivity testing of the fungus. Flucytosine combined with amphotericin B, or possibly with clotrimazole or miconazole, is recommended for Candida infections. Clotrimazole is the drug of choice for Aspergillus species, although miconazole and econazole are more effective with some isolates. Miconazole and econazole are recommended for miscellaneous filamentous fungi although clotrimazole or thiabendazole are superior in some cases. Each of these drugs may be useful in patients, infected with Fusarium, who do not respond to pimaricin. In these cases, drug use should be guided by the results of antifungal sensitivity testing. In addition to medical antifungal therapy, some eyes may require excisional keratoplasty with lens removal and evacuation of the posterior chamber and anterior vitreous cavity.

关键词：肾上腺皮质激素类/治疗应用两性霉素B/治疗应用抗生素类抗真菌/治疗应用抗真菌药/治疗应用曲霉菌病/药物疗法曲霉菌属/药物作用盲/病因学念珠菌属/药物作用念珠菌病/药物疗法克霉唑/治疗应用角膜眼疾病/并发症眼疾病/药物疗法眼疾病/病因学镰刀菌属/药物作用青光眼/病因学青光眼/微生物学咪唑类/治疗应用真菌病/并发症真菌病/药物疗法纳他霉素/治疗应用聚烯类/治疗应用成年人老年人动物女(雌)性人类男(雄)性中年人

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Terbinafine, a unique oral antifungal: current perceptions

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INTERNATIONAL JOURNAL OF DERMATOLOGY 2000年第6期39卷 412-423页

作者： Jain, S Sehgal, VN Sehgal Nursing Home Dermatovenereol Skin VD Ctr Delhi 110033 India Skin Care Clin Delhi India

Terbinafine is a distinct allylamine antifungal agent. It was discovered in the 1970s.(1-5) It was introduced into the market in 1991, and is now available worldwide. The chemical name of terbinafine is (E)-N-(6,6-dimethyl-1,2-hepten-4-inyl)-N-methyl-1-naphthalene-methenamine-hydrochloride. It has a characteristic mechanism of action involving the inhibition of ergosterol biosynthesis at the level of squalene epoxidation,(6) resulting in a deficiency of the essential membrane component ergosterol and the accumulation of squalene. The latter plays an essential role in its fungicidal action. Its spectrum of in vitro activity includes a broad range of dermatophytes, filamentous, dimorphic, and dermatiaceous fungi, and a few yeast species.

关键词：投药口服抗真菌药/投药和剂量抗真菌药/药代动力学抗真菌药/治疗应用临床试验(主题) 足皮肤病/药物疗法手皮肤病/药物疗法萘类/投药和剂量萘类/药代动力学萘类/治疗应用甲癣/药物疗法人类

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Lanoconazole, a new imidazole antimycotic compound, protects MAIDS mice against encephalitis caused by Cryptococcus neoformans

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2000年第3期46卷 443-450页

作者： Furukawa, K Sasaki, H Pollard, RB Suzuki, F Univ Texas Med Branch Galveston TX 77555 USA

The protective effect of a new antifungal compound, lanoconazole, against Cryptococcus neoformans infection in C57BL/6 mice exposed to LP-BM5 murine leukaemia virus (MuLV) (MAIDS mice) was investigated. Mice were infected intratracheally with C. neoformans, strain 613D, 40 days after infection with LP-BM5 MuLV. They were treated orally with various doses of lanoconazole or with fluconazole 10 mg/kg (a positive control) once daily beginning 1 day after the fungal infection and continuing until the end of the experimental period. The number of C. neoformans cells in the lungs and brains of infected mice was determined. Lanoconazole and fluconazole had a similar inhibitory effect on the growth of C. neoformans in the brains and lungs of normal mice. Whereas lanoconazole inhibited the growth of C. neoformans in the brains and lungs of MAIDS mice, the pathogen grew in the brains of MAIDS mice treated with fluconazole. Lanoconazole reduced the number of C. neoformans in the brains of normal mice treated with a type 2 cytokine mixture, whereas fluconazole did not. A predominance of type 2 T-cell responses was demonstrated in MAIDS mice. Splenic T cells from MAIDS mice, but not those from normal mice, released interleukins 4 and 10 into the culture medium when they were stimulated with an anti-CD3 monoclonal antibody. These results suggest that lanoconazole may have the potential to inhibit the growth of C. neoformans in AIDS patients with a predominance of type 2 T-cell responses.

关键词：抗真菌药/治疗应用脑/微生物学隐球菌病/并发症隐球菌病/药物疗法隐球菌病/免疫学隐球菌病/微生物学新型隐球菌/生长和发育细胞因子类/生物合成细胞因子类/治疗应用脑炎/并发症脑炎/药物疗法脑炎/免疫学脑炎/微生物学氟康唑/治疗应用杂环化合物/治疗应用咪唑类/治疗应用肺/微生物学小鼠近交C57BL 鼠获得性免疫缺陷综合征/并发症鼠获得性免疫缺陷综合征/免疫学鼠获得性免疫缺陷综合征/微生物学机会致病菌感染/并发症机会致病菌感染/药物疗法机会致病菌感染/免疫学机会致病菌感染/微生物学脾/细胞学 Th2细胞/免疫学动物小鼠

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