Survival of Cholangiocarcinoma Patients in Northeastern Thailand after Supportive Treatment

Thunyaharn, Nut,Promthet, Supannee,Wiangnon, Surapon,Suwanrungruang, Krittika,Kamsa-ard, Supot Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Cholangiocarcinoma (CCA) is a very common cancer in Northeastern Thailand. Most CCA patients see a physician at a late stage when curative surgery is not possible. After diagnosis, they generally are treated by partial surgery/percutaneous drainage, chemotherapy and supportive treatment. Objective: This study aimed to assess the survival rates of CCA patients after supportive treatment. Methods: A retrospective cohort design was applied in this study. Data for 746 CCA patients were extracted from the hospital-based cancer registry of Srinagarind Hospital, Khon Kaen University. The patients were diagnosed (at least by ultrasonography) between 1 January, 2009 and 31 December, 2009 and then followed up for current status until 30 June, 2011. The cumulative survival rate was calculated by the Kaplan-Meier method, and independent prognostic factors were investigated using Cox regression. Results: The total follow-up time was 5,878 person-months, and the total number of deaths was 637. The mortality rate was therefore 10.8 per 100 person-year (95%CI : 10.1-11.7). The cumulative 3, 6, 9, 12 and 24 month survival rates were 59%, 39%, 31%, 24% and 14%, respectively. The median survival time after supportive treatment was 4 months. After adjusting for gender, age, stage, distant metastasis, histological grading and treatment, stage was a significant predictor of survival of CCA patients. Those in stage III and stage IV had a 6.78 fold higher mortality than the stage I and stage II cases (95% CI : 1.6-28.7). Conclusion: It is very important to encourage patients to see health personnel at an early stage.

Variant insertion of the teres major muscle

Sitthichai Iamsaard,Nut Thunyaharn,Kowit Chaisiwamongkol,Porntip Boonruangsri,Nongnut Uabundit,Wiphawi Hipkaeo 대한해부학회 2012 Anatomy & Cell Biology Vol.45 No.3

The teres major (TerMa) muscle has a clinical significance for tendon transfer procedures in patients with massive rotator cuff tears. Individually, it originates from the dorsum of the inferior angle of scapula and inserts into the medial lip of bicepital groove of the humerus. Functionally, TerMa in cooperation with latissimus dorsi (LD) adducts arm, medially rotates arm, and assists in arm extension. The variation of TerMa insertion is very rare. In the shoulder and axillary regions of a 33-year-old Thai male cadaver, the variant insertion of the right TerMa was found. The muscle fibers of TerMa are directly attached at the supero-medial border of LD tendon. Notably, there was no terminal tendon of TerMa. To explain an unusual movement of the arm, this rare variation of the TerMa insertion is necessary to be recognized. This case report is very important for surgeons to preoperatively consider using the terminal tendon of TerMa for tendon transfer in treating patients with irreparable cuff tears.

Optimization of Linezolid Dosing Regimens for Treatment of Vancomycin-Resistant Enterococci Infection

Wichai Santimaleeworagun,Changpradub Dhitiwat,Jatapat Hemapanpairoa,Sudaluck Thunyaharn 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.3

Background: Linezolid, an oxazolidinone antibiotic, is recommended for vancomycinresistant enterococci (VRE). However, 100% free-drug concentration above the minimum inhibitory concentration (fT>MIC) and an area under the curve of free drug to MIC ratio (fAUC24/MIC) >100 were associated with favorable clinical outcome with less emerging resistance. A plasma trough concentration (Ctrough) of linezolid ≥9 µg/mL was also related to hematologic toxicity. Thus, linezolid dose optimization is needed for VRE treatment. The study aimed to determine the in vitro linezolid activity against clinical VRE isolates and linezolid dosing regimens in critically ill patients who met the target pharmacokinetics/ pharmacodynamics (PK/PD) for VRE treatment. Materials and Methods: Enterococcal isolates from enterococcal-infected patients were obtained between 2014 and 2018 at Phramongkutklao Hospital. We used Monte Carlo simulation to calculate the probability of target attainment, and the cumulative fraction of response (CFR) of the free area under the curve to MIC ratio (fAUIC24) was used to calculate the fAUC24/MIC 80 - 100 and fT/MIC >85 - 100% of the interval time of administration for clinical response and microbiological eradication as well as the Ctrough ≥9 µg/mL for the probability of hematologic toxicity. Results: For linezolid MIC determination, the MIC median (MIC50), MIC for 90% growth (MIC90), and range for linezolid were 1.5 µg/mL, 2 µg/mL, and 0.72 - 2 µg/mL, respectively. A dosing regimen of 1,200 mg either once daily or as a divided dose every 12 h gave target attainments of fAUC24/MICs >80 and >100, which exceeded 90% for MICs ≤1 and ≤1 µg/mL, respectively, with a rate of hematologic toxicity <15%. If the expected fT>MICs were >85% and 100%, a 1,200-mg divided dose every 12 h could cover VRE isolates having linezolid MICs ≤1 µg/mL and ≤0.75 µg/mL. Even 600 mg every 8 h and 1,200 mg as a continuous infusion gave a higher target attainment of fAUC24/MIC and a fT>MIC and the target CFR, but those regimens gave Ctrough ≥9 µg/mL rates of 40.7% and 99.6%. Conclusion: The current dosing of 1,200 mg/day might be optimal treatment for infection by VRE isolates with documented MICs ≤1 µg/mL. For treatment of VRE with a MIC of 2 µg/mL or to achieve the target CFR, the use of linezolid with other antibiotic combinations might help achieve the PK/PD target, provide better clinical outcome, and prevent resistance.

Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity?

Saelim Weerayuth,Changpradub Dhitiwat,Sudaluck Thunyaharn,Juntanawiwat Piraporn,Nulsopapon Parnrada,Santimaleeworagun Wichai 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.1

Background: Acinetobacter baumannii has been recognized as a cause of nosocomial infection. To date, polymyxins, the last-resort therapeutic agents for carbapenem-resistant A. baumannii (CRAB). Thus, the small number of effective antibiotic options against CRAB represents a challenge to human health. This study examined the appropriate dosage regimens of colistin alone or in combination with sulbactam or fosfomycin using Monte Carlo simulation with the aims of improving efficacy and reducing the risk of nephrotoxicity. Materials and Methods: Clinical CRAB isolates were obtained from patients admitted to Phramongkutklao Hospital in 2014 and 2015. The minimum inhibitory concentration (MIC) of colistin for each CRAB isolate was determined using the broth dilution method, whereas those of sulbactam and fosfomycin were determined using the agar dilution method. Each drug regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). Nephrotoxicity based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria was indicated by colistin trough concentration exceeding ≥3.3 µg/mL. Results: A total of 50 CRAB isolates were included. The MIC50 and MIC90 were 64 and 128 µg/mL, respectively, for sulbactam, 256 and 2,048 µg/mL, respectively, for fosfomycin, and 1 and 4 µg/mL, respectively, for colistin. In patients with creatinine clearance of 91 – 130 m/min, the dosing regimens of 180 mg every 12 h and 150 mg every 8 h achieved ≥ 90% of target of the area under the free drug plasma concentration–time curve from 0 to 24 hr (fAUC24)/MIC ≥25 against isolates MICs of ≤0.25 and ≤0.5 µg/mL, respectively, and their rates of colistin trough concentration more than ≥3.3 µg/mL were 35 and 54%, respectively. Colistin combined with sulbactam or fosfomycin decreased the colistin MIC of CRAB isolates from 1 – 16 µg/mL to 0.0625 – 1 and 0.0625 – 2 µg/mL, respectively. Based on CFR ≥ 90%, no colistin monotherapy regimens in patients with creatinine clearance of 91 – 130 mL/min were effective against all of the studied CRAB isolates. For improving efficacy and reducing the risk of nephrotoxicity, colistin 150 mg given every 12 h together with sulbactam (≥6 g/day) or fosfomycin (≥18 g/day) was effective in patients with creatinine clearance of 91 – 130 mL/min. Additionally, both colistin combination regimens were effective against five colistin-resistant A. baumannii isolates. Conclusion: Colistin monotherapy at the maximum recommended dose might not cover some CRAB isolates. Colistin combination therapy appears appropriate for achieving the pharmacokinetic/pharmacodynamic targets of CRAB treatment.

Optimizing the Dosing Regimens of Tigecycline against Vancomycin-Resistant Enterococci in the Treatment of Intra-abdominal and Skin and Soft Tissue Infections

Wichai Santimaleeworagun,Jatapat Hemapanpairoa,Dhitiwat Changpradub,Sudaluck Thunyaharn 대한감염학회 2020 Infection and Chemotherapy Vol.52 No.3

Tigecycline was previously considered to have activity against vancomycin-resistant Enterococcus (VRE) isolates, but the optimal dose was not clarified. Thus, this study assessed the in vitro activity of tigecycline against clinical VRE isolates to determine its optimal regimens for complicated intra-abdominal (cIAIs) and complicated skin/soft tissue infections (cSSTIs). We used Monte Carlo simulation to calculate the probability of target attainment (PTA) and the cumulative fraction of response for the ratio of the free area under the curve to the minimum inhibitory concentration (MIC) (fAUIC24), which were 17.9 and 6.9 for treating cSSTIs and cIAIs, respectively. All clinical isolates were Enterococcus faecium. Only a maintenance dose of 200 mg/day tigecycline gave the target attainment of fAUIC24 >17.9, and PTA exceeded 90% for MIC ≤0.38 µg/mL. Meanwhile, this dose gave the target attainment of fAUIC24 >6.9, and PTA exceeded 90% for MIC ≤1 µg/mL. All simulated tigecycline dosing regimens met the fAUIC24 targets more than 90% of the cumulative fraction of response. Despite its apparent efficacy, a daily tigecycline dose of 200 mg is recommended for VRE isolates with MICs of ≤0.38 µg/mL and ≤1 µg/mL for treating cSSTIs and cIAIs, respectively.