[Clinical analysis of candidemia in immunocompetent patients].

OBJECTIVE: To investigate the etiological and clinical characteristics of immunocompetent patients with candidemia. METHODS: The clinical and microbiological data of patients diagnosed as candidemia admitted in Peking University Third Hospital from January 2010 to June 2016 were retrospectively analyzed. Underlying diseases, Candida spp. colonization, clinical manifestations, microbiological data, treatment and the outcome were compared between the HIV-negative immunocompromised (IC) and nonimmunocompromised (NIC) patients. RESULTS: A total of 62 cases diagnosed as candidemia were analyzed including 36 men and 26 women, with 16 to 100 years of age [(66.02±17.65) years]. There were 30 NIC and 32 HIV-negative IC patients respectively. In the NIC patients, there were 19 cases (19/30, 63.33%) with admission in intensive care unit (ICU), 21 (21/30, 70.00%) associated diabetes mellitus or uncontrolled hyperglycemia and 22 (22/30,73.33%) receiving invasive mechanical ventilation, while in the HIV-negative IC patients, there were 8 (8/32, 25.00%), 13 (13/32, 40.63%) and 7 (7/32, 21.88%) respectively (P<0.05). The NIC patients had higher acute physiology and chronic health evaluation (APACHE II) scores and sequential organ failure assessment (SOFA) scores both at admission (19.98±5.81, 6.04±6.14) and candidemia onset (25.61±6.52, 12.75±8.42) than the HIV-negative IC patients (APACHEII 15.09±5.82, 22.15±5.98) and SOFA 2.87±2.73, 7.66±5.64 respectively (P<0.05). In the NIC patients, twenty-one cases (21/30, 70.00%) died in hospital, while 14 cases (14/32, 43.75%) in HIV-negative IC. The crude mortality was significantly different between the two groups (P<0.05). By blood culture, Canidia albicans remained the the most prevalent isolates in all the patients. Clinical manifestation, Candida spp. colonization, etiology and drug susceptibility were also similar between NIC and HIV-negative IC patients (P>0.05). CONCLUSION: Candidemia in NIC patients tends to occur in those who are much more critically ill, more often admitted in ICU, and more frequently have diabetes mellitus or uncontrolled hyperglycemia and receive invasive mechanical ventilation than HIV-negative IC patients. NIC patients also have poorer prognosis than HIV-negative IC patients. Clinical manifestations, and microbiological characteristics are similar between HIV-negative IC and NIC patients.

[The effect of renal clearance on serum trough concentration of vancomycin in elderly patients with severe pneumonia].

OBJECTIVE: To investigate the effect of renal clearance on serum trough concentration of vancomycin in elderly patients with severe pneumonia. METHODS: This was a prospective non-interventional study. Forty-two elderly patients with severe pneumonia and normal level of serum creatinine were enrolled from November 2013 to October 2014. The patients included 25 males and 17 females, aged 60-83 years (median 74 years). The renal clearance was measured, and the vancomycin regimen and rate of serum trough concentration achieving guideline-recommended target of 15-20 mg/L were investigated. The factors influencing trough concentration of vancomycin were analyzed using the general linear model. RESULTS: The vancomycin regimens were 1 g/ 12 h (17 cases), 0.5 g/8 h (14 cases) and 0.5 g/12 h (11 cases), and their median and range of serum concentrations were 14.9(2.4-28.5)mg/L, 16.2(2.8-27.8)mg/L and 11.6 (5.9-19.9) mg/L, respectively. The guideline-recommended target trough concentration of 15-20 mg/L was reached in only 10 patients, while trough concentration lower than 15 mg/L was found in 22 patients and higher than 20 mg/L in 10 patients. General linear model analysis showed that creatinine clearance rate(CCR) and dose of vancomycin per kilogram of body weight per day were independent influencing factors for trough concentration (both P<0.05). There were 8 patients with CCR≥130 ml·min(-1)·(1.73 m(2))(-1) (augmented renal clearance), 22 patients with 70≤CCR<130 ml·min(-1)·(1.73 m(2))(-1) and 12 patients with CCR<70 ml·min(-1)·(1.73 m(2))(-1,) and vancomycin trough concentration below 15 mg/L was found in 7, 11 and 4 patients, respectively. CONCLUSION: CCR was an independent influencing factor for trough concentration of vancomycin, and augmented renal clearance increased the risk of subtherapeutic trough concentration of vancomycin.

Comparison of 12-chloroscoulerine enantiomers on animal behavior to dopamine receptors.

AIM: To compare the pharmacological characteristics of 12-chloroscoulerine (CSL) enantiomers to dopamine (DA) receptors. METHODS: Radioligand receptor binding assay with calf striatum and behavioral tests of mice or rats were used. RESULTS: In the competitive binding assay, the affinities (Ki) of l-CSL to D1 and D2 receptors were 5.7 nmol.L-1, while those of d-CSL for D1 and D2 receptors were 135 and 9150 nmol.L-1, respectively. The Ki of dl-CSL to D1 and D2 receptors were 8.9 and 9.6 nmol.L-1, respectively, which were slightly weaker than that of l-CSL. In the behavioral experiments, CSL enantiomers 5-60 mg.kg-1 antagonized the stereotypy induced by apomorphine in rats, and 5-150 mg.kg-1 produced catalepsy. The enantiomers 10-60 mg.kg-1 reduced the mice jumping behavior induced by amphetamine + levodopa. l-CSL 10-80 mg.kg-1 antagonized the spontaneous locomotor activity of normal or amphetamine-treated mice. CONCLUSION: CSL enantiomers are antagonists to DA receptors: l-CSL > dl-CSL >> d-CSL.

[Effect of (+/-)12-chloroscoulerine on brain dopamine receptors].

AIM: To assess potencies of tetrahydroprotoberberines (THPB) and hydrobenzyltetrahydroisoquinolines (HBTI) on DA receptors. METHODS: The receptor binding assay with calf striatum to D1 and D2 receptors, and the animal behavior tests were used. RESULTS: (+/-) 12-Chloroscoulerine (CSL) was the most potent one among the THPB and HBTI. The affinities of CSL to D1 and D2 receptors were 13 and 51 nmol.L-1, respectively. In rats, CSL showed an antagonistic effect on the stereotypy and induced catalepsy. In the 6-OHDA lesioned rats, however, CSL exerted the agonistic effect to DA receptors. CONCLUSION: CSL had dual actions to DA receptors and its effects were similar to that of (-)stepholidine.