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Chin Med J (Engl)

Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria: A Single-center Randomized Controlled Trial.

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Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria: A Single-center Randomized Controlled Trial.

Chin Med J (Engl). 2017 May 20;130(10):1196-1201

Authors: Liu C, Zhang YT, Peng ZY, Zhou Q, Hu B, Zhou H, Li JG

Abstract
BACKGROUND: Aerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB.
METHODS: In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28.
RESULTS: The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P= 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P= 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P= 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P= 0.444), weaning rate (48% vs. 32%, P= 0.236), and mortality (22% vs. 32%, P= 0.427) were detected between the two groups on day 28.
CONCLUSIONS: As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.

PMID: 28485320 [PubMed – in process]

White-opaque Switching in Different Mating Type-like Locus Gene Types of Clinical Candida albicans Isolates.

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White-opaque Switching in Different Mating Type-like Locus Gene Types of Clinical Candida albicans Isolates.

Chin Med J (Engl). 2016 20th Nov;129(22):2725-2732

Authors: Li HM, Shimizu-Imanishi Y, Tanaka R, Li RY, Yaguchi T

Abstract
BACKGROUND: Candida albicans (C. albicans) can become a pathogen causing superficial as well as life-threatening systemic infections, especially in immunocompromised patients. Many phenotypic attributes contribute to its capacity to colonize human organs. In our study, 93 C. albicans isolates from patients of various candidiasis in a hospital of China were surveyed. We aimed to investigate the white-opaque (WO) switching competence, drug sensitivity, and virulence of mating type-like (MTL) a/α isolates.
METHODS: Internal transcribed spacer (ITS) gene and the MTL configuration were detected in all the isolates by reverse transcription-polymerase chain reaction. White/opaque phenotype and doubling time of cell growth were determined. The minimum inhibitory concentrations of antifungal agent were measured using broth microdilution method.
RESULTS: Sixty-four isolates (69.6%) were classified to serotype A, 19 (20.6%) to serotype B, and 9 (9.8%) to serotype C. Moreover, phylogenetic analysis showed that these isolates were divided into four different subgroups of ITS genotypes. Most of our clinical isolates were MTL a/α type, while 6.8% remained MTL a or MTLα type. The frequency of opaque phenotype was 71.0% (66 isolates). Following the guidelines of Clinical and Laboratory Standards Institute M27-A3, all isolates were susceptible to caspofungin and a few (0.6-3.2%) of them showed resistance against amphotericin B, flucytosine, fluconazole, itraconazole, and voriconazole.
CONCLUSIONS: From these analyses, there were comparatively more C. albicans strains classified into serotype B, and the frequency of opaque phase strains was significant in the clinical isolates from China. Genetic, phenotypic, or drug susceptibility patterns were not significantly different from previous studies. MTL a/α isolates could also undergo WO switching which facilitates their survival.

PMID: 27824006 [PubMed – in process]

Antimicrobial susceptibility of Gram-negative bacteria causing intra-abdominal infections in China: SMART China 2011.

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Antimicrobial susceptibility of Gram-negative bacteria causing intra-abdominal infections in China: SMART China 2011.

Chin Med J (Engl). 2014 Jul;127(13):2429-33

Authors: Zhang H, Yang Q, Xiao M, Chen M, Badal RE, Xu Y

Abstract
BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends program monitors the activity of antibiotics against aerobic and facultative Gram-negative bacilli (GNBs) from intra-abdominal infections (IAIs) in patients worldwide.
METHODS: In 2011, 1 929 aerobic and facultative GNBs from 21 hospitals in 16 cities in China were collected. All isolates were tested using a panel of 12 antimicrobial agents, and susceptibility was determined following the Clinical Laboratory Standards Institute guidelines.
RESULTS: Among the Gram-negative pathogens causing IAIs, Escherichia coli (47.3%) was the most commonly isolated, followed by Klebsiella pneumoniae (17.2%), Pseudomonas aeruginosa (10.1%), and Acinetobacter baumannii (8.3%). Enterobacteriaceae comprised 78.8% (1521/1929) of the total isolates. Among the antimicrobial agents tested, ertapenem and imipenem were the most active agents against Enterobacteriaceae, with susceptibility rates of 95.1% and 94.4%, followed by amikacin (93.9%) and piperacillin/tazobactam (87.7%). Susceptibility rates of ceftriaxone, cefotaxime, ceftazidime, and cefepime against Enterobacteriaceae were 38.3%, 38.3%, 61.1%, and 50.8%, respectively. The leastactive agent against Enterobacteriaceae was ampicillin/sulbactam (25.9%). The extended-spectrum β-lactamase (ESBL) rates among E. coli, K. pneumoniae, Klebsiella oxytoca, and Proteus mirabilis were 68.8%, 38.1%, 41.2%, and 57.7%, respectively.
CONCLUSIONS: Enterobacteriaceae were the major pathogens causing IAIs, and the most active agents against the study isolates (including those producing ESBLs) were ertapenem, imipenem, and amikacin. Including the carbapenems, most agents exhibited reduced susceptibility against ESBL-positive and multidrug-resistant isolates.

PMID: 24985578 [PubMed – in process]

Caspofungin versus liposomal amphotericin B for treatment of invasive fungal infections or febrile neutropenia.

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Caspofungin versus liposomal amphotericin B for treatment of invasive fungal infections or febrile neutropenia.

Chin Med J (Engl). 2014 Feb;127(4):753-7

Authors: Zhang J, Gong Y, Wang K, Kong J, Chen Y

Abstract
BACKGROUND: Nowadays, there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B (L-AmB). However, these studies have a modest sample size and convey inconclusive results. The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections (IFIs), compared with L-AmB.
METHODS: Electronic databases (up to July 31, 2013) PubMed and Embase databases, the Cochrane Library, and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB. Analyses of efficacy and adverse outcomes were performed by relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity was assessed by χ(2)-test and the I(2)-statistic.
RESULTS: Three trials were included in this meta-analysis with 1249 modified intention-to-treat (MITT) patients. The results showed that caspofungin produced equal efficacy in favorable overall response (RR = 1.02, 95% CI 0.88-1.18; P = 0.81) and mortality rate (RR = 1.53, 95% CI 0.38-6.27, P = 0.55), safer in clinical adverse events (RR = 0.20, 95% CI 0.08-0.54; P = 0.001), laboratory adverse events (RR = 0.69, 95% CI 0. 57-0.84; P = 0.0002), and discontinuation rate (RR = 0.26, 95% CI 0.08-0.83, P = 0.02), compared with L-AmB in the treatment of patients with IFIs.
CONCLUSION: Based on the results of this meta-analysis, it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.

PMID: 24534235 [PubMed – in process]