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ABSTRACT Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0–24) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose (P = 0.045), peak concentration (P = 0.020), and sdrC (P = 0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose (P = 0.009), cardiovascular disease (P = 0.043), sequence type 5 (ST5; P = 0.017), tst (P = 0.050), and sec gene (P = 0.044) associated with bacteriological failure. Although the AUC0–24/MIC was higher in the groups with bacterial eradication, the difference was not statistically significant (P = 0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P = 0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB, tst, and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB, tst, and sec.

Objective: To study the protective effect of Chinese herbs for supplementing Shen to eliminate stone on renal injury induced by extracorporeal shockwave lithotripsy (ESWL) in patients with renal calculus., Methods: Sixty patients with diagnosis of renal calculus confirmed by X-ray film or CT combined with abdominal B ultrasonography but showing no obvious symptoms, were randomized into the treated group and the control group. They all were scheduled to receive ESWL treatment. To the patients in the treated group, prescribed Chinese herbs was orally administered in the three days before and after ESWL, patients in the control group ate and drank as usual. Changes of blood levels of nitric oxide (NO), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-alpha), urinary levels of N-acetyl-D-glucosaminidase (NAG), gamma-glutamyltransferase (gamma-GT) and beta 2-microglobulin (beta 2-MG) before and after ESWL were observed., Results: Blood levels of NO, ET-1, MDA and TNF-alpha significantly increased after ESWL in the control group, higher than the levels in the treated group (P < 0.05); and level of SOD decreased gradually in the control group reaching the valley 72 h after ESWL (P < 0.05), while in the treated group it was unchanged and remained at the level higher than that in the control group (P < 0.05). As for the urinary levels of NAG, gamma-GT and beta2-MG, after ESWL, they were all higher in the control group than those in the treated group, showing statistical significance (P <0. 05)., Conclusion: ESWL could induce renal damage in patients with renal calculus and the Chinese herbs for supplementing Shen to eliminate stone can reduce the renal tubular damage by way of anti-oxidation and regulating the renal hemorrheologic disorder and the release of inflammatory mediators.

Objective: Extracorporeal shock wave lithotripsy (ESWL) is has been shown to reduce renal parenchymal injury subject to application of shock wave lithotripsy in our pervious study. To investigate the protective action of three main components from Astragalus membranaceus, including total saponins of astragalus (TSA), total flavonoids of astragalus (TFA) total polysaccharide of astragalus (TPA) in alleviating shock wave induced kidney damage., Methods: Sixty four male rabbits were randomly assigned to a control group or to 3 groups that were premedicated with TSA TFA and TPA respectively prior to application of ESWL. Each group of animals underwent shock wave lithotripsy (18 kV) to the right kidneys and received a total of 1500 shocks. Peripheral blood samples were collected to evaluate the levels of plasma endothelin-1 (ET-1), plasma nitric oxide (NO) and serum malondialdehyde (MDA) before and after shock wave treatment. The concentrations of these markers in the treated kidney tissues were also detected 3 days, 7 days and 14 days after application of ESWL. The changes of histopathology and cells ultrastructure were observed through light microscope and electron microscope. Untreated contralateral kidneys were evaluated as controls., Results: In control serials the levels of ET-1 and MDA were elevated significantly while the level of NO was significantly decreased after application of shock wave lithotripsy (P < 0.05). The comparison between the controls and premedicated groups demonstrated that all these three components especially TSA and TFA significantly inhibited shock wave induced increasing of ET-1 and MDA (P < 0.05). TSA also significantly suppressed the decrease of NO and made the recovery time earlier compare to the results of controls (P < 0.05). However, TFA and TPA had almost no effects on the change of NO. (P > 0.05). The results in histopathology showed noticeably damage of glomerular and tubular epithelial cells in the treated kidneys in the controls. The histological alterations in the TPA group were similar to those of the controls. These alterations were significantly milder in the TSA and TFA particular the TSA group., Conclusion: TFA and TSA, especially TSA seemed to play the key role in alleviating ESWL induced kidney damage.

Background: Recent studies have revealed the important role of free radicals in renal damage induced by high-energy shock waves (HESW). This study aimed at investigating the effects of Astragalus membranaceus, a traditional Chinese medicinal herb, on free radical-mediated HESW-induced damage to renal tubules in a live rabbit model., Methods: Forty-five healthy male New Zealand white rabbits were randomly divided into three groups: control group (n = 15), sham group (n = 15), and herb-treated group (n = 15). Three days prior to HESW application, the controls received verapamil (0.4 mg/kg), the shams received physiological saline (20 ml), and the herb-treated animals received Astragalus membranaceus (2.4 g/kg) intravenously. HESW (1500 shocks, 18 kV) was applied to the right kidneys of all anesthetized rabbits. We measured superoxide dismutase (SOD) and malondialdehyde (MDA) levels before and after shock treatment in blood and kidney homogenates. Histopathological changes were also observed., Results: MDA levels increased and SOD activity decreased significantly in the sham group (P < 0.05 for both) after shock treatment. MDA levels showed a much less increase in the controls (P < 0.05) and did not increase to statistically significant levels in the group receiving Astragalus membranaceus (P > 0.05). SOD values were significantly higher in the controls than in the shams (P < 0.05). By contrast, SOD levels recovered rapidly in the rabbits receiving Astragalus membranaceus, reaching a nadir within 24 hours, and returning to baseline more quickly than in control and sham rabbits (P < 0.05). Histopathological examinations showed that renal tubular damage in the controls was less severe than in the shams, while damage in the Astragalus membranaceus group was even more mild, with rapid recovery in comparison with the controls., Conclusion: This study provides preliminary evidence indicating that Astragalus membranaceus has strong protective effects on free radical-mediated renal tubular damage induced by HESW and that these effects are superior to the effects of verapamil.

Background & Objective: Total prostate-specific antigen (TPSA) is considered the best marker in diagnosis of carcinoma of prostate (Pca), and FPSA (free prostate specific antigen)/TPSA can improve its specificity in diagnosis of PCa. This study was designed to compare the level of serum TPSA and FPSA/TPSA between PCa and benign prostate hyperplasia (BPH) patients, providing reference for diagnosis of PCa., Methods: Values of serum TPSA and FPSA of 66 BPH cases, 29 BPH with acute urinary retention (AUR) cases, 22 PCa cases were determined by enzyme linked immunosorbent assay (ELISA). The differences of serum TPSA and FPSA/TPSA of the three groups were compared and analyzed., Results: There were significant differences of serum TPSA concentration among the three groups (P< 0.05), when the serum TPSA in the patients with BPH, BPH and AUR, PCa were 4.1+/-1.39 microg/L, 15.5+/-3.34 microg/L, 55+/-13.5 microg/L, respectively. Serum TPSA concentration overlapped in the three groups especially in AUR group when the TPSA level in the three groups were less than 4.0 microg/L, 4.0-10.0 microg/L, and more than 10.0 microg/L. There was no significant difference between BPH group and AUR group when the FPSA/ TPSA of BPH group was 0.32+/-0.13, AUR group was 0.30+/-0.09 (P >0.05). However, there were significant differences between BPH and Pca group, between AUR and PCa group when the FPSA/TPSA of Pca group was 0.11+/-0.05 (P< 0.05). FPSA/TPSA level also overlapped in these three groups when FPSA/TPSA level was less than 0.15, 0.15-0.25, and more than 0.25., Conclusions: The serum TPSA and the level of FPSA/TPSA overlapped in these three groups. They can only be regarded clinically as reference index.