Search

Patchrapa Boonmee,1,2 Worapong Nasomsong,3 Narisorn Lorchirachoonkul,4 Supanun Pungcharoenkijkul,5 Piraporn Juntanawiwat,6 Suphatthra Chaemchaeng,7 Wichai Santimaleeworagun8,9 1College of Pharmacotherapy Thailand, Nonthaburi, Thailand; 2Department of Pharmacy, Ratchaburi Hospital, Ratchaburi, Thailand; 3Division of Infectious Diseases, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand; 4Department of Medicine, Ratchaburi Hospital, Ratchaburi, Thailand; 5Pharmacy Unit, Nopparat Rajathanee Hospital, Bangkok, Thailand; 6Division of Microbiology, Phramongkutklao Hospital, Bangkok, Thailand; 7Division of Microbiology, Ratchaburi Hospital, Ratchaburi, Thailand; 8Department of Pharmaceutical Care, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, Thailand; 9Pharmaceutical Initiative for Resistant Bacteria and Infectious Disease Working Group (PIRBIG), Nakorn Pathom, ThailandCorrespondence: Wichai Santimaleeworagun, Department of Pharmaceutical Care, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, 73000, Thailand, Tel +66 3 425 5800, Fax +66 3 425 5801, Email swichai1234@gmail.comPurpose: Stenotrophomonas maltophilia, a multidrug-resistant pathogen can cause hospital-acquired infections such as pneumonia, or bloodstream infection. S. maltophilia infection is associated with high mortality rates. This retrospective study examined the antimicrobial susceptibility profile of clinical S. maltophilia isolates and evaluated clinical outcomes, treatment regimens, and risk factors associated with 30-day mortality or treatment failure of S. maltophilia infections at three tertiary care hospitals in Central Thailand.Patients and Methods: The characteristics, microbiological data, and clinical treatment outcomes were derived from medical records obtained from three tertiary care hospitals in Central Thailand from January 2017 to October 2022. The primary outcomes were treatment failure and 30-day mortality. The antimicrobial susceptibility rates of trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin, and ceftazidime were determined by minimum inhibitory concentration (MIC), which were based on broth microdilution and clear zone diameters using the disk diffusion method. However, we also report the susceptibility of minocycline and tigecycline in some clinical S. maltophilia strains (n = 149) and determined by MIC with E-test method.Results: The antimicrobial susceptibility rates to TMP-SMX, levofloxacin, and ceftazidime were 97.1%, 93%, and 55.3%, respectively. The treatment failure rate and 30-day mortality were 66.3% and 49%, respectively. Significant factors associated with treatment failure included APACHE II score ≥ 15 (OR 3.37, 95% confidence interval (CI) 1.46– 7.76), polymicrobial infections (OR 3.20, 95% CI 1.35– 7.55). The significant factors associated with reduced treatment failure was treatment with TMP-SMX-based regimen (OR 0.29, 95% CI 0.11– 0.76). The 30-day mortality rate was associated with APACHE II score ≥ 15 (OR 3.27, 95% CI 1.45– 7.39) and septic shock (OR 2.53, 95% CI 1.36– 4.69).Conclusion: The results indicate a high mortality rate for S. maltophilia infection. The predictive factors for an unfavourable outcome were severity of illness, septic shock, and non-use of TMP-SMX. Therefore, a TMP-SMX-based regimen is recommended for the treatment of S. maltophilia infections.Keywords: co-trimoxazole, levofloxacin, mortality, Xanthomonas

Korawan Pudpong,1,2 Sutthiporn Pattharachayakul,3 Wichai Santimaleeworagun,4,5 Ozioma F Nwabor,6 Varaporn Laohaprertthisan,7 Thanaporn Hortiwakul,6 Boonsri Charernmak,6 Sarunyou Chusri6 1Department of Pharmacy, College of Pharmacotherapy Thailand, Nontaburi, 11000, Thailand; 2Pharmaceutical Care Unit, Department of Pharmacy, Sunpasitthiprasong Hospital, Ubon Ratchathani, 34000, Thailand; 3Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; 4Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, 73000, Thailand; 5Department of Pharmacy, Pharmaceutical Initiative for Resistant Bacteria and Infectious Disease Working Group (PIRBIG), Nakorn Pathom, 73000, Thailand; 6Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, 90110, Songkhla, Thailand; 7Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, 90110, ThailandCorrespondence: Sarunyou Chusri, Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, 90110, Songkhla, Thailand, Tel +66 8 973 40446, Fax +66 74451033, Email sarunyouchusri@hotmail.comPurpose: Compared with non-carbapenemase producing carbapenem-resistant Enterobacterales (non-CP-CRE), carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) are associated with considerable mortality. However, given that the patients are treated with various therapeutic options, it remains unclear whether differences in types of carbapenemase genes yield different mortality rates. Therefore, this study aims to identify carbapenemase genes and identify whether clinical outcomes differ according to the prevalence of genotype and phenotype of carbapenemase among Enterobacterales clinical isolated.Patients and Methods: A retrospective cohort study was performed to determine whether types of carbapenemase genes have an impact on clinical outcomes. Carbapenem-resistant clinical isolates were collected at a tertiary care university hospital in Songkhla, Thailand, between June 2018 and February 2020. Demographic and microbiological data such as antimicrobial susceptibility, carbapenemase genes, and overall mortality were evaluated.Results: A total of 121 Enterobacterales clinical isolated were evaluated. The blaNDM-1 gene was detected in 44% of the isolates, followed by blaOXA-48 (28%) and blaNDM-1/OXA-48 (28%). NDM-1- or NDM-1/OXA-48- producing isolates were more likely to require meropenem MICs of ≥ 16 mg/L, while OXA-48-producing isolates were more likely to require meropenem MICs of < 16 mg/L. The patients with NDM-1 or NDM-1/OXA-48 had a higher 14 days mortality rate than those with OXA-48 after treating with carbapenem-containing regimens (P-value 0.001) or colistin-containing regimens (P-value < 0.001).Conclusion: Our findings suggest that the mortality for CP-CRE infection in patients with NDM-1 or NDM-1/OXA-48 was higher than the mortality in those with OXA-48, which It seems that the type of carbapenemase gene may affect meropenem MIC levels. Hence, in treatment decisions involving the use of either carbapenem-containing regiment or colistin-containing regiment in patients with CP-CRE infection, especially those in the NDM-1 and NDM-1/OXA-48 groups, the patient symptoms should be closely monitored.Keywords: carbapenemase, carbapenem resistance Enterobacterales, NDM-1, OXA-48, NDM-1/OXA-48

Worapong Nasomsong,1 Parnrada Nulsopapon,2,3 Dhitiwat Changpradub,1 Manat Pongchaidecha,2 Supanun Pungcharoenkijkul,4 Piraporn Juntanawiwat,5 Waristha Simsiriporn,5 Wichai Santimaleeworagun2,3 1Division of Infectious Diseases, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 3Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group [PIRBIG], Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 4Pharmacy Unit, Nopparat Rajathanee Hospital, Bangkok, Thailand; 5Division of Microbiology, Department of Clinical Pathology, Phramongkutklao Hospital, Bangkok, ThailandCorrespondence: Wichai SantimaleeworagunDepartment of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, ThailandTel +6634 255 800Fax +6634 255 801Email swichai1234@gmail.comPurpose: MBL and OXA-48 genes in carbapenem-resistant Enterobacterales (CRE) have emerged as a major public health problem worldwide, including Thailand. Due to the lack of susceptibility data and dosing regimens of ceftazidime-avibactam (CZA) against CRE in Thailand, especially in colistin-resistant era, we aimed to demonstrate in vitro susceptibility data of CZA and optimal dose based on Monte Carlo simulation of CZA to expand the treatment options.Patients and Methods: We collected 49 carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates from unique patients at Phramongkutklao Hospital (June–October 2020). CZA disk diffusion and E-test testing were performed to obtain minimum inhibitory concentration (MIC). 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).Results: The most common genotypes of CRKP were blaOXA-48 (53.1%) and blaOXA-48 +blaNDM (42.8%). CZA showed 47.7% and 90.5% susceptible rate against all genotypes of carbapenemases and OXA-48 type CRKP isolates. The MIC50 and MIC90 of CZA against CRKP were 2 and > 256 μg/mL. The categorical agreement (CA) between disk diffusion and E-test testing of CZA against CRKP was 95.4%. The CZA dosing regimens of 2.5 g infused 2– 3 h every 8 h achieved ≥ 90% of the target of free ceftazidime plasma concentration over MIC (%fTime >MIC) ≥ 50% and 100% against isolates MICs of ≤ 8 and ≤ 8 μg/mL, respectively. The avibactam regimens also provided 100%fTime at 0.5 μg/mL. Based on CFR ≥ 90%, no CZA regimens were effective against all of the studied CRKP isolates except CRKP carrying OXA-48.Conclusion: CZA exhibited a fairly susceptible rate among the OXA-48-positive isolates in Thailand. The current suggested dose of CZA with prolonged infusion appears appropriate to achieve the pharmacokinetic/pharmacodynamic targets of ceftazidime and avibactam against CRKP carrying blaOXA-48.Keywords: CRE, metallo-beta-lactamase, Monte Carlo, oxacillinase

Ratchanu Charoenpak, 1 Wichai Santimaleeworagun, 2 Gompol Suwanpimolkul, 3–5 Weerawat Manosuthi, 6 Paweena Kongsanan, 6 Suthidee Petsong, 7 Chankit Puttilerpong 8 1College of Pharmacotherapy Thailand, Nonthaburi, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 3Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Tuberculosis Research Unit, Chulalongkorn University, Bangkok, Thailand; 5Emerging Infectious Diseases Clinical Center, Thai Red Cross, Bangkok, Thailand; 6Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand; 7Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 8Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, ThailandCorrespondence: Chankit PuttilerpongDepartment of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok, ThailandTel|Fax +66 2 218 8403Email Chankit.P@chula.ac.thPurpose: The emergence of isoniazid-resistant tuberculosis (HR-TB) is a global public health problem, causing treatment failure and high mortality rates. This study aimed to determine the minimal inhibitory concentration (MIC) of isoniazid and detect the gene mutation in HR-TB and any association between the level of isoniazid resistance and gene mutation.Methods: We collected 74 clinical HR-TB isolates from two tertiary-care centers in Thailand. MICs were established using broth macrodilution. A line probe assay (LPA) was used to detect gene mutations that confer resistance to isoniazid, rifampicin, aminoglycosides, and fluoroquinolones.Results: Sixty-one (82.4%) isolates were monoresistant to isoniazid and 44 (72.1%) were highly resistant to isoniazid. From the clinical isolates, the range of isoniazid MICs was 0.4– 16 μg/mL. The katG S315T gene mutation was the prominent mutation in both isoniazid-monoresistant TB (70.5%) and multidrug-resistant TB (72.7%) isolates. The positive predictive value (PPV) of katG was 100% in detecting high levels of isoniazid resistance. The PPV of the inhA mutation was 93.8% in detecting low levels of isoniazid resistance. Five isolates (6.8%) exhibited low-level phenotypic resistance, whereas an LPA failed to detect an isoniazid gene mutation. Our study found one HR-TB isolate with a gyrA fluoroquinolone-resistant gene mutation.Conclusion: Most HR-TB isolates had high isoniazid-resistance levels associated with the katG gene mutation. High-dose isoniazid should be used with caution in patients with HR-TB. Early detection of drug resistance by genotypic assay can help determine an appropriate regimen.Keywords: tuberculosis, isoniazid, minimal inhibitory concentration, line probe assay, gene mutation

Jatapat Hemapanpairoa,1–3 Dhitiwat Changpradub,4 Sudaluck Thunyaharn,5 Wichai Santimaleeworagun3,61Department of Pharmacy Practice and Pharmaceutical Care, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand; 2College of Pharmacotherapy Thailand, Nonthaburi 11000, Thailand; 3Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group, Nakorn Pathom 73000, Thailand; 4Division of Infectious Disease, Department of Medicine, Phramongkutklao Hospital, Bangkok 10400, Thailand; 5Faculty of Medical Technology, Nakhonratchasima College, Nakhon Ratchasima 30000, Thailand; 6Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom 73000, ThailandPurpose: The incidence of infections with vancomycin-resistant enterococci (VRE) is increasing, with associated high mortality rates and limited therapeutic choices. We investigated the clinical characteristics and treatment outcomes of VRE infection and also determined the in vitro effect of monotherapy and combined antimicrobials against clinical VRE isolates.Patients and methods: Clinical data and bacterial isolates obtained from patients with VRE infections between January 2014 and April 2018 at Phramongkutklao Hospital were reviewed. The clinical outcomes included in-hospital mortality, 30-day mortality, and microbiological eradication. Clonal relationships were assessed by random amplified polymorphic DNA analysis. In vitro activity of linezolid, tigecycline, fosfomycin, gentamicin, chloramphenicol, and ampicillin were determined by minimum inhibitory concentration (MIC) values. Tests of synergy of fosfomycin- or gentamicin-based combinations by the checkerboard method were reported with the fractional inhibitory concentration index or MIC reduction, respectively.Results: Among 26 cases of VRE infection, nosocomial and gastrointestinal infections were the most common. There were various treatment regimens, but linezolid-containing regimens were generally used. In-hospital and 30-day mortality were 73.1% and 57.7%, respectively. Higher mortality was significantly associated with illness severity. The VRE isolates tested were universally susceptible to linezolid and tigecycline. A synergistic or additive effect was observed for fosfomycin combined with linezolid (100%) and with tigecycline (83.3%). Fourfold or greater MIC reduction was observed for linezolid or fosfomycin plus gentamicin at concentrations 1 (58.3%, 62.5%), 2 (83.3%, 62.5%), and 4 μg/mL (91.6%, 62.5%).Conclusion: In-hospital mortality among patients with VRE infection was high. Linezolid remains a treatment of choice. However, combination therapy such as linezolid plus fosfomycin and linezolid plus gentamicin should be considered in cases of serious infection.Keywords: clinical outcomes, vancomycin-resistant enterococci, minimum inhibitory concentration, synergism

Yongyut Lertsrisatit,1 Wichai Santimaleeworagun,2,3 Sudaluck Thunyaharn,4 Jantima Traipattanakul5 1College of Pharmacotherapy Thailand, Nonthaburi, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, Thailand; 3Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group (PIRBIG) Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, Thailand; 4Faculty of Medical Technology, Nakhonratchasima College, Nakhonratchasima, Thailand; 5Division of Infectious Disease, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand Purpose: Colistin is a drug of last resort for treating multidrug-resistant Acinetobacter baumannii infections. Unfortunately, colistin-resistant A. baumannii (CoR-AB) has been reported. Here, we examined the in vitro effect of mono- and combined antimicrobials against CoR-AB strains and their resistance mechanism, and evaluated the clinical outcomes of CoR-AB-infected patients.Patients and methods: Seventeen clinical CoR-AB strains were isolated from patients at Phramongkutklao hospital, 2011–2015. The mono- and synergistic activities of colistin, tigecycline, sulbactam, imipenem, meropenem, amikacin, fosfomycin, and cotrimoxazole were examined by minimum inhibitory concentration (MIC) and fractional inhibitory concentration index. Clonal relationship and resistance genes were determined by repetitive extragenic palindromic polymerase chain reaction with specific primers. The effect of carbonyl cyanide 3-chlorophenylhydrazone combined with colistin was used to test efflux pump involvement. Patient treatment outcomes were also reported.Results: The most prevalent infection in CoR-AB patients was pneumonia (35.3%), and all patients were administered colistin combined with another agent. The 30-day mortality was 70.6%, and the colistin MIC range and MIC50 was 16–512 µg/mL and 64 µg/mL, respectively. All CoR-AB strains were sensitive to tigecycline. Sporadic isolates were susceptible to sulbactam, imipenem, meropenem, and cotrimoxazole. A synergistic or additive effect was observed for colistin plus imipenem or meropenem (16.7%), sulbactam (66.7%), or tigecycline (66.7%). The CoR-AB isolates could be divided into four different clones (A–D) with a high prevalence of group B (47.1%). Eight isolates harbored blaOXA23, blaIMP, blaKPC, and blaNDM, and one contained blaOXA23, blaIMP, and blaKPC, while the eight remaining isolates carried only blaOXA23. The MIC values of all strains were greatly reduced for colistin plus carbonyl cyanide 3-chlorophenylhydrazone.Conclusion: CoR-AB clinical isolates exhibited very high colistin resistance and a high frequency of resistance genes. The mechanism of colistin resistance appears to be mediated via an efflux pump. Thus, certain antimicrobials could be used as salvage therapy for CoR-AB infection. Keywords: synergism, salvage therapy, clinical outcomes

Background: Bariatric surgery currently plays an important role in the treatment of obesity. However, iron deficiency and iron deficiency anemia are long-term complications after bariatric surgery. There have been no studies of prevalence and incidence of iron deficiency and iron deficiency anemia after bariatric surgery among Thai population. Objective: To evaluate the incidence and prevalence of iron deficiency and iron deficiency anemia in Thai post-bariatric surgery patients. Materials and Methods: The present study was a retrospective study. The data were collected from the medical records of 78 patients that underwent bariatric surgery, 12 for laparoscopic sleeve gastrectomy (LSG) and 66 for laparoscopic Roux-en-Y gastric bypass (LRYGB), at Phramongkutklao Hospital between January 2008 and December 2016. Demographic and laboratory data were obtained prior to surgery and at 3, 6, 12, and 24 months after the surgery. Results: The prevalence and incidence of iron deficiency 24 months after LRYGB were 25.8% and 18.7%, respectively. The prevalence and incidence of iron deficiency anemia 24 months after LRYGB were 19.7% and 16.0%, respectively. Increasing time after surgery was also associated with significant abnormal iron profiles (p<0.001); whereas, there were no signs of iron deficiency and iron deficiency anemia among patients who underwent LSG. Conclusion: At 24-month follow-up, the prevalence and incidence of iron deficiency and iron deficiency anemia have significantly increased among the patients who underwent LRYGB. Therefore, serum iron, hemoglobin, and hematocrit should be monitored to prevent and initiate the treatment of iron deficiency anemia. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the incidence of chemotherapy-induced neutropenia and febrile neutropenia (FN) among patients with gynecologic cancer receiving initial chemotherapy and to determine associated risk factors related to neutropenia and FN. Materials and Methods: This retrospective study gathered the available record data of gynecologic cancer patients who received first-line chemotherapy from January 2012 to December 2015 at Siriraj Hospital, Thailand. All gynecologic cancer patients over the age of 18 and who had received initial chemotherapy were included. Results: Four hundred seven gynecologic cancer patients were included and there were 2,249 cycles of chemotherapy (17 regimens). Two hundred nine patients (52.0%) had severe neutropenia and 11 patients (2.7%) of 407 patients (2.7%) were diagnosed as FN. Carboplatin-containing regimens were the only one risk factor for severe neutropenia in the logistic analysis. Meanwhile, the use of myeloid growth factors for the prevention of FN could reduce the risk of FN (odd ratios 0.03; 95% confidence interval 0.005-0.231). Conclusion: The incidences of severe neutropenia and FN were 52.0% and 2.7%, respectively. It was also shown that myeloid growth factor use might act as a prevention among patient with intermediate risks of FN using cisplatin and doxorubicin. [ABSTRACT FROM AUTHOR]

Pathophysiologic changes in the early and late phases of septic shock affect the pharmacokinetic (PK) parameters, varying dose adjustments may be necessary. This study aimed to create the PK models of vancomycin in the early and late phases of septic shock and to describe the association between the area under the curve from 0 to 24 h (AUC 0-24 ) and acute kidney injury (AKI). The data from patients with septic shock receiving vancomycin was collected either prospectively or retrospectively. A nonlinear mixed-effects modeling approach was used to develop the PK models. A total of 208 septic shock patients were enrolled and classified into the early (n = 96) and the late phase (n = 112). A two-compartment PK model is the best base model for both phases of septic shock. The model that best predicted the clearance (CL) of both phases was the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, which was not indexed to body surface area (BSA). Albumin (ALB) was a covariate associated with vancomycin CL only in the late phase. The typical values of CL and volume of distribution (V d ) in the early phase were 1.71 L/h and 68.94 L. In the late phase, CL was 1.65 L/h, and V d was 66.36 L. The AKI was observed in patients with a high simulated AUC 0-24 . The population PK model of vancomycin in the early and late phases of septic shock has been established. The CKD-EPI not indexed to BSA predicts vancomycin CL in both phases. ALB was associated with CL in the late phase., (© 2025, The American College of Clinical Pharmacology.)

Background: The optimal pharmacokinetic and pharmacodynamic (PK/PD) parameters of vancomycin that can improve outcomes in enterococcal infections remain controversial. To clarify the therapeutic target for this antibiotic, this study aimed to determine vancomycin PK/PD parameters associated with efficacy in the early (during 72 h) or later (after 72 h) phase of treatment and nephrotoxicity in enterococcal bloodstream infection patients., Methods: This multicenter retrospective study reviewed medical records of patients with enterococcal bloodstream infections treated with intravenous vancomycin infusion for at least 72 h between January 2016 and March 2024 at Phramongkutklao Hospital or Nopparatrajathanee Hospital in Bangkok, and Rachaburi Hospital in Rachaburi Province, Thailand. Patients with data available on serum vancomycin concentration were analyzed. The primary outcomes were 30-day mortality and acute kidney injury. The estimates of the mean 24-h area under the curve in the first 72 h (AUC 24 ) and in steady state (AUC ss ) were determined by Bayesian theorem., Results: Overall, 201 vancomycin concentrations were measured within the first 72 h after vancomycin treatment, while 156 were in a steady state (> 72 h). According to Classification and Regression Tree analysis, vancomycin AUC at 420 mg·h/l was the PK/PD target for 30-day mortality. Results reveal that patients with AUC 24 (early phase) and AUC ss  < 420 mg·h/l (later phase) had significantly higher 14-day, 30-day, and in-hospital mortality than AUC ≥ 420 mg·h/l groups. In addition, patients with AUC 24  ≥ 420 mg·h/l in the early phase had significantly reduced microbiological failure (p = 0.004). Patients with AUC ≥ 700 mg·h/l in early and later phases had significantly increased acute kidney injury risk. In addition, patients receiving concomitant nephrotoxic drugs had an AUC cutoff value of 650 mg·h/l. Multivariate Cox regression analysis showed that vancomycin AUC ss  < 420 mg·h/l, unknown source of bacteremia, and acute kidney injury were significantly associated with 30-day mortality., Conclusions: AUC 420-650 mg·h/l in early and later phases was the target of vancomycin's PK/PD in enterococcal bacteremia patients for efficacy and to prevent acute kidney injury. This study suggests close monitoring of vancomycin levels to ensure efficacy and safety., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Review Board of the Royal Thai Army Medical Department at Phramongkutklao College of Medicine and Phramongkutklao Hospital (approval number Q001h/66), Human Research Ethics Committee of Ratchaburi Hospital (approval number RBHEC005/66), and Human Research Ethics Committee of Nopparatrajathanee Hospital (approval number 14/2566). Data were collected after ethics approval and with permission from the hospital director. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: We aimed to use Monte Carlo simulation, based on pharmacokinetic/pharmacodynamic targets, to investigate and determine the optimal dosage of the available combination therapies for carbapenem-resistant Klebsiella pneumoniae (CRKP) in critically ill patients., Methods: We collected CRKP clinical isolates from Phramongkutklao Hospital between October 2020 and June 2022. A molecular study of resistant genes was performed using polymerase chain reaction. Broth microdilution checkerboards were used to evaluate the mono- and synergistic antibiotic activities. Monte Carlo simulation was used to determine the optimal antibiotic regimens, based on the probability of target attainment (PTA) and cumulative fraction of response., Results: The 54 CRKP isolates were resistant to tigecycline (100%), colistin (75.9%), amikacin (70.4%), and gentamicin (63.0%). The most common carbapenemase genotype was bla oxacillinases (OXA)-48-like (42.6%), followed by bla New Delhi metallo beta-lactamase (NDM) (29.6%) and coexistence of bla OXA-48-like and bla NDM (22.2%). Based on the PTA, synergistic and additive activities against CRKP isolates were observed with appropriate dosages of tigecycline-colistin (67.9%), tigecycline-gentamicin (62.2%), and tigecycline-amikacin (51.4%)., Conclusions: Tigecycline-colistin was the best available combination therapy for critically ill patients with CRKP, especially NDM. When used in combination with tigecycline, a colistin creatinine clearance of <90 mL/min can raise the cumulative fraction of response target and less nephrotoxicity., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pseudomonas aeruginosa associated with hospital-acquired infection is often resistant to various antibiotics and is associated with high mortality worldwide. The appropriate treatment of Pseudomonas aeruginosa resistant to carbapenems but susceptible to traditional antipseudomonal non-carbapenem β-lactam agents (Car-R/NonCar-S P. aeruginosa) remains unclear. This retrospective study evaluated risk factors for 14-day and 30-day mortality among treatment regimens against Car-R/NonCar-S P. aeruginosa. This study enrolled 180 patients with Car-R/NonCar-S P. aeruginosa infection at Phramongkutklao Hospital between January 2019 and December 2023. The 14-day and 30-day mortality rates were 18.3% and 28.9%, respectively. Bloodstream infection (OR 1.97, 95% CI 0.88-4.43), septic shock (OR 3.3, 95% CI 1.30-8.40), Acute Physiology and Chronic Health Evaluation (APACHE) II < 14 (OR 0.13, 95% CI 0.03-0.54), Sequential Organ Failure Assessment (SOFA) <7 (OR 0.25, 95% CI 0.11-0.56), and Pitt bacteremia score <4 (OR 0.16, 95% CI 0.05-0.47) were associated with 14-day mortality. There was a higher 14-day and 30-day mortality in patients treated with piperacillin/tazobactam or aminoglycosides but there was no significant difference among antipseudomonal antimicrobial agents in the treatment of Car-R/NonCar-S P. aeruginosa infection. We supported the use of traditional antipseudomonal β-lactam agents to treat Car-R/NonCar-S P. aeruginosa infections, however the use of piperacillin/tazobactam might be concerned in some cases and further investigations were needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Supreeyasakon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Voriconazole is the first-line therapy for invasive aspergillosis (IA). To determine the minimum inhibitory concentration of Aspergillus, a voriconazole pharmacokinetic-pharmacodynamic (PK-PD) model linked to galactomannan response was developed and evaluated, and its clinical correlation for IA treatment was elucidated., Methods: Adult patients with probable or definite IA and at least one serum voriconazole measurement were included. A two-compartment voriconazole PK model was linked to a previously described PD model of galactomannan response. PK and PD parameters were estimated using a nonparametric adaptive grid technique. The relationship between the ratio of voriconazole exposure that induced half-maximum galactomannan response (EC50) and the observed terminal galactomannan concentration was evaluated. The factors associated with the PK-PD parameters and mortality were also determined., Results: Between January 2013 and December 2022, 41 patients were prescribed voriconazole for IA. The 30-day mortality rate was 17%. A high correlation was found for the observed-predicted Bayesian posterior estimates of voriconazole and galactomannan levels. Moreover, a nonlinear relationship was identified between AUC:EC50 and terminal galactomannan. The factors associated with higher AUC:EC50 were intravenous administration and intubation. In the survival analysis, higher EC50 tended to be associated with mortality, higher AUC was significantly associated with increased mortality, and higher AUC:EC50 tended to be associated with higher mortality. After adjusting for the intravenous route, higher AUC and AUC:EC50 were not associated with mortality., Conclusions: Individual EC50 estimation can provide insights into in vivo host and organism responses. Elevated EC50 showed comparable and unfavorable trends to higher minimum inhibitory concentration. Thus, determining EC50 might help guide individualized target serum voriconazole levels., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Biapenem (BIPM) exhibited a less efficient substrate for various metallo-β-lactamase (MBL) than other carbapenems., Objective: We aimed to evaluate in vitro susceptibility data of BIPM and optimal dose based on Monte Carlo simulation to extend treatment options., Methods: We collected 192 carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates from unique patients among multicentres in Thailand, from June 2019 to March 2023. BIPM disk diffusion and broth-microdilution testing were performed to obtain minimum inhibitory concentration (MIC). Each BIPM regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR)., Results: The most common genotypes among 192 CRKP isolates were bla OXA-48 (62.3%), bla OXA-48 +bla NDM (22.6%) and bla NDM (15.1%). BIPM showed 22.4 and 28.6% susceptible rate when interpreted at clinical breakpoints of 1 and 2 mg/L. The MIC 50 and MIC 90 of BIPM against CRKP were 8 and 32 mg/L. The BIPM dosing regimens of 300 mg q 6 h infused 6 h and 600 mg q 8 h infused 8 h met the PTA target of %fTime >MIC at 50%, 75% and 100% against isolates MICs of ≤2 mg/L. Based on CFR ≥90%, no BIPM regimens were effective against all the studied CRKP isolates., Conclusion: BIPM exhibited a partially susceptible rate among the CRKP isolates in Thailand. The current suggested dose of BIPM with prolonged infusion appears appropriate regimen against CRKP MICs of ≤2 mg/L. However, the empirical use of BIPM for severe CRE infection is not recommended unless the susceptibility has been confirmed., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Apixaban and amiodarone are drugs used for non-valvular atrial fibrillation (NVAF) in routine practice. The evidence about apixaban plasma levels in patients who receive apixaban with amiodarone, including bleeding outcomes, has been limited. This study aimed to compare the apixaban plasma levels and bleeding outcomes between apixaban monotherapy and apixaban with amiodarone groups., Methods: This study was a prospective, observational, and single-center research which was conducted from January 2021 to January 2022 in NVAF patients who received apixaban at a tertiary care hospital located in the center of Bangkok, Thailand., Results: Thirty-three patients were measured for their median (5th-95th percentile) apixaban plasma levels. The trough of apixaban plasma level (Ctrough) were 108.49 [78.10-171.52] and 162.05 [87.94-292.88] μg/L in the apixaban monotherapy and apixaban with amiodarone groups, respectively (p = 0.028). Additionally, the peaks of apixaban plasma level (Cpeak) were 175.36 [122.94-332.34] and 191 [116.88-488.21] μg/L in the apixaban monotherapy and apixaban with amiodarone groups, respectively (p = 0.375). There was bleeding that occurred in 7 patients (21.21%); 5 patients in the apixaban monotherapy group and 2 patients in the apixaban with amiodarone group, respectively., Conclusions: Amiodarone may increase the peaks and troughs of apixaban plasma levels. The co-administration of apixaban with amiodarone is generally well tolerated. However, the careful observation of bleeding symptoms in individual cases is necessary to ensure safety., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Limcharoen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immediate hypersensitivity reactions (IHRs) are commonly found in patients receiving paclitaxel. Effects of paclitaxel vary because of variable co-therapy or re-challenge with paclitaxel., Objective: Our objective was to investigate the incidence, patterns, and risk factors for paclitaxel-related IHRs and management of IHRs in gynecologic malignancy patients., Methods: This retrospective study was performed in gynecologic cancer patients receiving paclitaxel-based regimens at Siriraj hospital from January 2012 to December 2017., Results: 416 subjects were included and received ranitidine 50 mg, dexamethasone 20 mg, ondansetron 16 mg intravenously and diphenhydramine 50 mg orally 30 minutes before starting chemotherapy. The incidence of IHRs was 17.79%. IHRs occurring on first exposure to paclitaxel was 81.1% and occurred within 30 minutes after starting paclitaxel. The most commonly found presentation of IHRs were skin reactions (86.5%). In multivariate analysis, age < 54.5 years, stage of cancer < 2, and leukocyte cell count < 7.735 × 109/L were significantly associated with IHRs. Seventy-two out of 74 patients that recovered from IHRs were reintroduced paclitaxel. Forty-seven patients (97.92%) of 48 patients with mild reactions were successfully reintroduced to paclitaxel after treatment with chlorpheniramine or other interventions., Conclusions: The incidence of paclitaxel-related IHRs was about one in five. Skin reactions were the most commonly occurring reactions. Younger age, stage of cancer < 2, and leukocytes < 7.735 × 109/L were significant risk factors for IHRs. Patients with IHRs recovered without the use of dexamethasone and antihistamines before the reintroduction of paclitaxel.

Background: Besides hemorrhage, allergic reactions have also been observed in several clinical trials of fibrinolytic agents. These reactions might negatively affect patient outcomes, especially life-threatening type I hypersensitivity reactions such as anaphylaxis. However, there are limited data on the incidence of these reactions., Objective: The aim of study was to analyze the incidence of urticaria, angioedema, and type I hypersensitivity reactions from fibrinolytic agents for various indications., Methods: A retrospective analysis of data from the Thai Vigibase database was conducted. All reports of adverse drug reactions from fibrinolytic agents from 1984 to 2017 were identified using the World Health Organization adverse reaction terminology. The proportion of each suspected adverse drug reaction and the cumulative incidence were calculated., Results: A total of 284 reports were identified in the Thai Vigibase database. The overall incidence of urticaria, angioedema, and type I hypersensitivity reactions for the streptokinase group was 52.64/10,000 persons, with individual incidence rates of 9.64/10,000 persons for urticaria, 8.90/10,000 persons for angioedema, and 34.11/10,000 persons for type I hypersensitivity reactions. In the alteplase group, the overall incidence for all suspected reactions was 18.90/10,000 persons, with individual incidence rates of 3.29/10,000 persons for urticaria, 5.75/10,000 persons for angioedema, and 9.86/10,000 persons for type I hypersensitivity reactions., Conclusions: Type I hypersensitivity reactions were the most common allergic reactions from fibrinolytic agents. It is necessary to take these reactions into consideration when using fibrinolytic therapy.

Candida albicans is a predominant species causing candidemia in hospitalized patients. This study aimed to investigate the association of culture medium metabolomic profiles with biofilm formation and invasion properties of clinical bloodstream-isolated C. albicans. A total of twelve isolates and two reference strains were identified by virulent phenotypes. Their susceptibility was determined by the microdilution method, following EUCAST guidelines. Biofilm formation was evaluated with metabolic activity, morphology and agglutinin-like sequence 3 (ALS3) mRNA expression. Invasion into the vascular endothelial EA.hy926 cells was determined by lactate dehydrogenase release and internalization assay. Their metabolomic profiles were assessed by high-resolution accurate-mass spectrometry (HRAMS). The results showed four different phenotypes of C. albicans: high-biofilm/invasive (50%), high-biofilm/non-invasive (7%), low-biofilm/invasive (36%) and low-biofilm/non-invasive (7%). The metabolomic profiles of the culture medium determined strong correlation of the virulent phenotypes and the alteration of metabolites in the methionine metabolism pathway, such as homocysteine, 5-methyltetrahydrofolate and S-adenosylmethioninamine. Moreover, thiamine and biotin levels were significantly increased in Isolate03, representative of a high-biofilm/invasive phenotype. These results suggest that methionine and vitamin B metabolism pathways might be influenced by their virulent phenotypes and pathogenic traits. Therefore, their metabolism pathways might be a potential target for reducing virulence of C. albicans bloodstream infections., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcomes., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Home isolation has been proposed for coronavirus disease 2019 (COVID-19) patients with mild symptoms to avoid hospital overcrowding. This study aimed to describe the drug-related problems (DRPs) and the pharmaceutical care of home-isolating COVID-19 patients in Thailand., Methods: Our cross-sectional study was undertaken from July 1 to September 30, 2021, at the King Chulalongkorn Memorial Hospital, Thailand. Patients who were ≥ 18 years old, were diagnosed with mild COVID-19 by real-time polymerase chain reaction (RT-PCR), and were able to isolate at home while receiving an antiviral agent and standard symptomatic treatment were enrolled. Infectious disease pharmacists provided a telepharmacy service on days 1 and 3 after the COVID-19 diagnosis., Results: A total of 197 patients met the study criteria. Their median age was 45 years, and their most common underlying disease was hypertension (44.29%). All patients exhibited excellent anti-COVID-19 drug adherence. We identified 125 DRPs, including adverse reactions (68%), and the unnecessary use of products (62.40%). Moreover, 91 patients (46.19%) reported the use of supplements or herbs, with vitamin C being the main supplement (37.36%). Pharmacists provided 36 recommendations and received 33 questions from COVID-19 patients., Conclusions: Our study demonstrates that telepharmacy is an essential service for detecting and preventing DRPs in home-isolating COVID-19 patients., (© 2023. The Author(s).)

Stenotrophomonas maltophilia is a multidrug-resistant bacterium that is difficult to treat in hospitals worldwide, leading to high mortality. Published data describing the use of monotherapy or combination therapy and which one is better is still unclear. We aimed to investigate the efficacy of monotherapy and combination therapy in the treatment of S. maltophilia infections. We performed a systematic review of combination therapy and additionally a systematic review and meta-analysis to determine the effects of monotherapy versus combination therapy on mortality in S. maltophilia infections. Electronic databases: Cochrane Library, PubMed, Embase, ClinicalTrials.gov, Scopus, and OpenGrey were accessed. Of the 5030 articles identified, 17 studies were included for a systematic review of combination therapy, of which 4 cohort studies were finally included for meta-analysis. We found there is a trend of favorable outcomes with respect to mortality in the use of combination therapy to treat complex or severe S. maltopholia infections. A meta-analysis of monotherapy showed a statistical significance in the decreasing rate of mortality in hospital-acquired pneumonia (hazard ratio 1.42; 95% confidence interval, 1.04-1.94) compared to combination therapy, but not significant in bacteremia (hazard ratio 0.76; 95% confidence interval, 0.18-3.18). Further studies should continue to explore this association.

Background: Several clinical trials of fibrinolytic agents have reported the occurrence of allergic reactions, in addition to hemorrhage. These reactions might worsen patient outcomes, especially by causing life-threatening type I hypersensitivity reactions, including anaphylaxis; however, there is a scarcity of data in this regard., Objective: This study described and characterized patients with urticaria, angioedema and type I hypersensitivity reactions caused by fibrinolytic agents., Methods: This was a retrospective study in which cases of suspected adverse drug reactions from the use of streptokinase, alteplase, and tenecteplase were evaluated over a period of 10 years at Phramongkutklao and Ratchaburi hospitals in Thailand. In addition, patient characteristics and management were assessed., Results: A total of 824 patients received fibrinolytic agents due to various indications. Of 147 patients who received streptokinase, nine (6.12%) had suspected adverse drug reactions (one case of urticaria, two cases of anaphylactic shock, and six cases of hypotension). The prescription rate of alteplase was the highest, being taken by 547 patients; however, only one patient (0.18%) reported an adverse reaction, angioedema in the face and lips. Similarly, of the 130 patients who received tenecteplase, only one patient (0.77%) developed hypotension., Conclusions: All fibrinolytic agents, either nonfibrin or fibrin-specific, can cause urticaria, angioedema, and type I hypersensitivity reactions due to their mechanism of action.

Enterococci are major causes of bacteremia. Although the mortality rate of ampicillin- susceptible enterococci (ASE) bloodstream infections (BSI) is lower, compared with that of ampicillin-resistant enterococci BSI, the role of treatment regimens in ASE BSI remains to be determined. This retrospective study aimed to evaluate the treatment outcomes and factors associated with mortality among patients with ASE BSI. The charts of 145 enrolled patients with ASE BSI between January 2013 and April 2022 at Phramongkutklao Hospital were reviewed. The 30-day and in-hospital mortality rates were 28.8 and 41.9%, respectively. The 30-day mortality rate was higher in the vancomycin treatment group than in the beta-lactam treatment group (61.5 vs. 26%; p = 0.02). Pitt bacteremia score (OR 1.44, 95% CI 1.20-1.71); age-adjusted Charlson Comorbidity Index (OR 1.34, 95% CI 1.14-1.58); and vancomycin treatment (OR 4.07, 95% CI 1.02-16.22) were independent factors associated with 30-day mortality. The severity of illness, comorbidity and definitive therapy with vancomycin increased the mortality rate of patients with ASE BSI. Anti-enterococcal beta-lactams remain the first line antibiotics for ASE bacteremia.

Empiric antibiotic dosing frequently relies on an estimate of kidney function based on age, serum creatinine, sex, and race (on occasion). New non-race-based estimated glomerular filtration rate (eGFR) equations have been published, but their role in supporting dosing is not known. Here, we report on a population pharmacokinetic model of vancomycin that serves as a useful probe substrate of eGFR in critically ill Thai patients. Data were obtained from medical records during a 10-year period. A nonlinear mixed-effects modeling approach was conducted to estimate vancomycin parameters. Data from 208 critically ill patients (58.2% men and 36.0% septic shock) with 398 vancomycin concentrations were collected. Twenty-three covariates including 12 kidney function estimates were tested and ranked on the basis of the model performance. The median (min, max) age, weight, and serum creatinine was 69 (18, 97) years, 60.0 (27, 120) kg, and 1.53 (0.18, 7.15) mg/dL, respectively. The best base model was a 1-compartment linear elimination with zero-order input and proportional error model. A Thai-specific eGFR equation not indexed to body surface area model best predicted vancomycin clearance (CL). The typical value for volume of distribution and CL was 67.5 L and 1.22 L/h, respectively. A loading dose of 2000 mg followed by maintenance dose regimens based on eGFR is suggested. The Thai GFR not indexed to BSA model best predicts vancomycin CL and dosing in the critically ill Thai population. A 5% to 10% absolute gain in the vancomycin probability of target attainment is expected with the use of this population-specific eGFR equation., (© 2022, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Apixaban can significantly prevent stroke events in patients with non-valvular atrial fibrillation (NVAF), as can be observed from the large, randomized, controlled trial conducted in the present study. However, the real-world evidence of bleeding events related to the apixaban plasma levels in Asian populations is limited. This study aimed to investigate the apixaban plasma levels and clinical outcomes among NVAF patients receiving apixaban, including determining the risk factors associated with bleeding during routine care. Seventy-one patients were included in the study. The median values were 112.79 (5-95th percentiles: 68.69-207.8) μg/L and 185.62 (5-95th percentiles: 124.06-384.34) μg/L for the apixaban trough (C trough ) and apixaban peak plasma levels (C peak ), respectively. Stroke and bleeding were found in 8 (11.27%) and 14 patients (19.72%), respectively. There was no statistical significance for C trough and C peak in the stroke and non-stroke groups, respectively. The median of C trough (139.15 μg/L) in patients with bleeding was higher than that in the non-bleeding group (108.14 μg/L), but there was no statistical significance. However, multivariate analyses showed that bleeding history (odds ratio (OR): 17.62; 95% confidence interval (CI): 3.54-176.64; and p -value = 0.002) and C trough (OR: 1.01; 95%: CI 1.00-1.03; and p -value = 0.038) were related to bleeding events. Almost all of the patients presented apixaban plasma levels within the expected range. Interestingly, bleeding events were associated with the troughs of the apixaban plasma levels and bleeding history.

Few studies have analyzed community hospital-based parenteral anti-infective therapy (CohPAT). We aimed to assess the clinical impact of a pharmacist-led implementation of a clinical practice guideline (CPG) for CohPAT, and to determine the pharmacist's role in CohPAT medication management. The prospective-period patients (post-implementation group) were compared with the historical control-period patients (pre-implementation group) for receiving a continuous antimicrobial parenteral injection. A CPG was used for laboratory testing for efficacy and safety, the monitoring of adverse drug events during admission, microbiology results coordination, and dosage adjustment. For any antimicrobial drug-related problems, the pharmacist consulted with the clinicians. Over 14 months, 50 participants were included in each group. In the pre-implementation period, 7 (14%) and 4 (8%) out of 50 patients received an inappropriate dosage and nonlaboratory monitoring for dose adjustment, respectively. The patients received the proper dosage of antimicrobial agents, which increased significantly from 78% pre- to 100% post-implementation ( p = 0.000). The pharmacist's interventions during the prospective-period were completely accepted by the clinicians, and significantly greater laboratory monitoring complying with CPG was given to the postimplementation group than the pre-implementation group (100% vs. 60%; p = 0.000). Significantly less patients with unfavorable outcomes (failure or in-hospital mortality) were observed in the post-implementation than in the pre-implementation (6% vs. 26%; p = 0.006) group. For the logistic regression analysis, lower respiratory infection (adjusted OR, aOR 3.68; 95%CI 1.13-12.06) and the post-implementation period (aOR 0.21; 95%CI 0.06-0.83) were significant risk factors that were associated with unfavorable outcomes. Given the better clinical outcomes and the improved quality of septic patient care observed after implementation, pharmacist-led implementation should be adopted in healthcare settings.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a hospital-acquired pathogen with a high mortality rate and limited treatment options. We investigated the activity of ceftolozane/tazobactam (C/T) and its synergistic effects with amikacin to extend the range of optimal therapeutic choices with appropriate doses. The E-test method is used to determine in vitro activity. The optimal dosing regimens to achieve a probability of target attainment (PTA) and a cumulative fraction of response (CFR) of ≥90% were simulated using the Monte Carlo method. Of the 66 CRPA isolates, the rate of susceptibility to C/T was 86.36%, with an MIC50 and an MIC90 of 0.75 and 24 µg/mL, respectively. Synergistic and additive effects between C/T and amikacin were observed in 24 (40%) and 18 (30%) of 60 CRPA isolates, respectively. The extended infusion of C/T regimens achieved a ≥90% PTA of 75% and a 100% fT > MIC at C/T MICs of 4 and 2 µg/mL, respectively. Only the combination of either a short or prolonged C/T infusion with a loading dose of amikacin of 20−25 mg/kg, followed by 15−20 mg/kg/day amikacin dosage, achieved ≥90% CFR. The C/T infusion, combined with currently recommended amikacin dose regimens, should be considered to manage CRPA infections.

Given its safety and apparent low aqueous solubility, borneol may serve as a matrix forming component of anti-solvent based in situ forming matrixes (ISMs) for crevicular pocket targeting. Drug-free and vancomycin hydrochloride-loaded borneol ISMs were evaluated for pH, density, viscosity, contact angle, surface tension, matrix formation, drug release behavior, in vitro degradability and antimicrobial activities. Density and pH values of borneol-based ISMs decreased with increasing borneol concentration. Given their markedly low viscosity could facilitate better injectability. The contact angles of the drug-free and vancomycin HCl-loaded borneol ISMs increased after being in contact with the agarose gel or the bulge tissue of porcine due to phase inversion. A dense borneol crystal matrix formed after using the highly concentrated ISM corresponded to fast matrix formation. The borneol-based ISM exhibited a sustainable drug release longer than 14 days with a diffusion-controlled release mechanism. Moreover, the developed ISM exhibited strong antimicrobial activities against various microbes. Thus, the vancomycin HCl-loaded borneol-based ISM is a potentially effective local anti-solvent-based ISM for periodontitis treatment via crevicular pocket injection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The spread of carbapenem-resistant Enterobacterales (CRE) constitutes a global health burden. Antimicrobial susceptibility and types of carbapenemase differ by geographic region. This study aimed to (1) examine the minimum inhibitory concentrations (MICs) and antibiotic resistance genes and (2) investigate antibiotic dosing regimens against CRE using Monte Carlo simulation. Clinical carbapenem-resistant Klebsiella pneumoniae (CRKP), Escherichia coli (CREC), and Enterobacter cloacae (CREclo) isolates were collected from various hospitals in western Thailand. Broth microdilution was performed, and the types of carbapenemase and mcr-1 genes were detected using polymerase chain reaction (PCR). Monte Carlo simulation was used to establish optimal antimicrobial dosing regimens meeting the criterion of a cumulative fraction of response (CFR) >90%. A total of 150 CRE isolates from 12 hospitals were included. The proportion of CRKP (76%) was greater than that of CREC (22%) and CREclo (2%). Regional hospitals reported higher rates of resistance than general hospitals. Most isolates were resistant to aztreonam and ceftazidime/avibactam, whereas they were highly susceptible to aminoglycosides. Most carbapenemases were NDM (47.33%), OXA-48 (43.33%) and NDM plus OXA-48 (6.67%); five OXA-48 positive isolates carried mcr-1 genes. Currently, high-dose tigecycline is the only optimal regimen against CRE isolates. Further extensive research on antibiotic synergism or new antibiotics should be conducted.

Phytochemical examination of Clausena lenis Drake (Rutaceae), collected in Thailand, led to the isolation of seven coumarins, four furoquinolines, two amides, and one flavonoid glycoside. Four of these compounds, one coumarine derivative named as gravelliferone A ( 3 ), two furoquinoline derivatives (kokusagenin A ( 8 ) and B ( 9 )) and one amide, clausenalansamide H ( 13 ), are reported for the first time. Compound 3 was isolated from the root bark, compound 8 from the stem bark and compounds 9 and 13 from the leaves. The molecular structures of all isolated compounds were established by means of NMR experiments combined with mass spectrometry. Preliminary tests of the lipophilic stem bark extract against various human pathogenic bacteria strains revealed promising effects against Staphylococcus aureus ATCC 43300.

Background: Linezolid, an oxazolidinone antibiotic, is recommended for vancomycin-resistant enterococci (VRE). However, 100% free-drug concentration above the minimum inhibitory concentration ( f T>MIC) and an area under the curve of free drug to MIC ratio ( f AUC24/MIC) >100 were associated with favorable clinical outcome with less emerging resistance. A plasma trough concentration (C trough ) 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 ( f AUIC 24 ) was used to calculate the f AUC24/MIC 80 - 100 and f T/MIC >85 - 100% of the interval time of administration for clinical response and microbiological eradication as well as the C trough ≥9 μg/mL for the probability of hematologic toxicity., Results: For linezolid MIC determination, the MIC median (MIC 50 ), MIC for 90% growth (MIC 90 ), 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 f AUC24/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 f T>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 f AUC24/MIC and a f T>MIC and the target CFR, but those regimens gave C trough ≥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., Competing Interests: No conflicts of interest., (Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Carbapenem-resistant Enterobacteriaceae (CRE), especially carbapenem-resistant Klebsiella pneumoniae (CRKP), are among the largest pathogenic threats to humans. The available antibiotic treatment options for combating CRKP are limited. Colistin-resistant Enterobacteriaceae (CoRE) have also been reported worldwide, including in Thailand. Therefore, this study aimed (1) to determine minimum inhibitory concentrations (MICs) and synergistic activities of antibiotics of CRKP, and (2) to determine the probability target of attainment (PTA) and cumulative fraction of response (CFR) using pharmacokinetic/pharmacodynamic (PK/PD) data. Clinical CRKP isolates were obtained from Phramongkutklao Hospital (June to November 2020). Broth microdilution and checkerboard techniques were used to determine the mono- and synergistic activities of antibiotics. Carbapenemase and mcr-1 genes were also identified by polymerase chain reaction (PCR). The optimal antibiotic regimens were evaluated using Monte Carlo simulations. Forty-nine CRKP isolates were collected, 40 of which were CoRKP strains. The MIC50 and MIC90 of tigecycline, amikacin, and gentamicin were 1 and 2 µg/mL, 4 and 16 µg/mL, and 0.25 and 4 µg/mL, respectively. None of any isolates expressed the mcr-1 gene, whereas bla OXA-48 (53.1%) and bla OXA-48 plus bla NDM (42.9%) were detected. Synergistic activity was observed in 8.2% of isolates for tigecycline combined with amikacin or gentamicin. Additive activity was observed in 75.5% of isolates for tigecycline-amikacin and 69.4% for tigecycline-gentamicin, and no antagonism was observed. High-dose antibiotic regimens achieved the PTA target. The general recommended dose of combination regimens began with 200 mg tigecycline and 25 mg/kg amikacin, or 7 mg/kg gentamicin, followed by 100 mg tigecycline every 12 h and 15 mg/kg amikacin or 5 mg/kg gentamicin every 24 h. In conclusion, tigecycline plus aminoglycosides might be a potential regimen against CRKP and CoRKP. The appropriate combination regimen based on MIC-based dose adjustment can improve optimal antibiotic dosing. Further research via clinical studies will be necessary to confirm these results.

Background: Cannabinoids; tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN), might show antibacterial activity. Trema orientalis is a species in the Cannabaceae that is closely related to Cannabis through plastome phylogenetic evidence. This species is widely distributed throughout tropical Asia and is used as traditional medicine, particularly for the treatment of infectious diseases. However, no studies on the antibacterial activity of cannabinoid-containing inflorescences extracts are available. Thus, the aim of this study was to determine cannabinoid content and antibacterial activity of inflorescences fractions from T. orientalis native to Thailand., Methods: We hypothesized that inflorescences from T. orientalis might display cannabinoids similar to Cannabis because of their close taxonomic relationship. We extracted the mature inflorescences and infructescence of T. orientalis in three disparate populations from different Thailand floristic regions. Extractions were subsequently partitioned into hydrophilic and lipophilic fractions using distilled water and chloroform. The lipophilic extracts were further fractionated by the column chromatography with gradient elution and analyzed by gas chromatography-mass spectrometry (GC-MS). Characterized cannabinoids were used in bioassays with multidrug-resistance bacteria., Results: Lipophilic extracts and fractions of inflorescences from all Thailand floristic regions consistently displayed cannabinoids (THC, CBD and CBN) in various quantities. These extracts exhibited inhibitory activity for Staphylococcus aureus , Pseudomonas aeruginosa , and Acinetobacter baumannii strains with minimum inhibitory concentration values varying from 31.25 to 125 µg/mL., Conclusion: Our study is the first to report cannabinoid detection in extracts from inflorescences of T. orientalis, a species in the Cannabaceae. These extracts and their fractions containing cannabinoids showed pronounced antibacterial activity. The use of analytic methods also demonstrated reproducible cannabinoid extraction., Competing Interests: The authors declare there are no competing interests., (©2021 Napiroon et al.)

Methicillin-resistant Staphylococcus aureus (MRSA) is mostly found in Thailand in the hospital as a nosocomial pathogen. This study aimed to report the genetic characterization of a clinical community-acquired MRSA (CA-MRSA) isolate collected from hospitalized patients in Thailand. Among 26 MRSA isolates, S. aureus no. S17 preliminarily displayed the presence of a staphylococcal cassette chromosome mec (SCC mec ) type IV pattern. The bacterial genomic DNA was subjected to whole-genome sequencing. Panton-Valentine leukocidin (PVL) production, virulence toxins, and antibiotic resistance genes were identified, and multi-locus sequence typing (MLST) and spa typing were performed. The strain was matched by sequence to MLST type 2885 and spa type t13880. This strain carried type IV SCC mec with no PVL production. Five acquired antimicrobial resistance genes, namely blaZ , mecA , Inu(A) , tet(K) , and dfrG conferring resistance to β-lactams, lincosamides, tetracycline, and trimethoprim, were identified. The detected toxins were exfoliative toxin A, gamma-hemolysin, leukocidin D, and leukocidin E. Moreover, there were differences in seven regions in CR-MRSA no. S17 compared to CA-MRSA type 300. In summary, we have reported the ST2885-SCC mec IV CA-MRSA clinical strain in Thailand for the first time, highlighting the problem of methicillin resistance in community settings and the consideration in choosing appropriate antibiotic therapy.

Background: Septic shock is a serious condition leading to increased mortality. Despite previous report of no benefit, thiamine has emerged as potential therapy to reduce mortality in septic shock patients. This study aimed to investigate the effect of thiamine in mortality rate in patients with septic shock., Methods: Eight databases, including MEDLINE, EMBASE, Science Direct, Scopus, Cochrane, CINAHL, Open Grey, and Dart-Europe, were systematically searched from the inception of the database up to August 21, 2020. Studies evaluating the effectiveness of thiamine on mortality rate in septic shock patients compared between thiamine and placebo were included. We used random-effects model to analyze the mortality with risk ratio (RR) and 95% confidence interval (95% CI). The subgroup and sensitivity analysis were performed to examine the influence of variables. Publication bias was considered using funnel plot, Begg's test, and Egger's test., Results: A total of 3,658 studies were retrieved and reviewed. Five studies were included for meta-analysis. In random-effects meta-analysis of the randomized controlled trials, although not statistically significant, there was a trend which suggested that thiamine may reduce mortality rate in septic shock patients (RR, 0.96; 95% CI: 0.72-1.28, P = 0.774). The result of sensitivity and subgroup analyses also supported the suggestion that thiamine may decrease mortality in septic shock patients. The Begg's test ( P = 0.624) and Egger's test ( P = 0.777) revealed no publication bias., Conclusions: Although not statistically significant, thiamine may reduce mortality rate in septic shock patients. Further prospective studies with larger sample size are warranted., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 International Journal of Critical Illness and Injury Science.)

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 MIC 50 and MIC 90 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 ( f AUC24)/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., Competing Interests: No conflicts of interest., (Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

The prevalence of enterococcal infection, especially E. faecium, is increasing, and the issue of the impact of vancomycin resistance on clinical outcomes is controversial. This study aimed to investigate the clinical outcomes of infection caused by E. faecium and determine the risk factors associated with mortality. This retrospective study was performed at the Phramongkutklao Hospital during the period from 2014 to 2018. One hundred and forty-five patients with E. faecium infections were enrolled. The 30-day and 90-day mortality rates of patients infected with vancomycin resistant (VR)- E. faecium vs. vancomycin susceptible (VS)- E. faecium were 57.7% vs. 38.7% and 69.2% vs. 47.1%, respectively. The median length of hospitalization was significantly longer in patients with VR- E. faecium infection. In logistic regression analysis, VR- E. faecium , Sequential Organ Failure Assessment (SOFA) scores, and bone and joint infections were significant risk factors associated with both 30-day and 90-day mortality. Moreover, Cox proportional hazards model showed that VR- E. faecium infection (HR 1.91; 95%CI 1.09-3.37) , SOFA scores of 6-9 points (HR 2.69; 95%CI 1.15-6.29), SOFA scores ≥ 10 points (HR 3.71; 95%CI 1.70-8.13), and bone and joint infections (HR 0.08; 95%CI 0.01-0.62) were significant risk factors for mortality. In conclusion, the present study confirmed the impact of VR- E. faecium infection on mortality and hospitalization duration. Thus, the appropriate antibiotic regimen for VR- E. faecium infection, especially for severely ill patients, is an effective strategy for improving treatment outcomes.

Background: Infections by Carbapenem-Resistant Enterobacteriaceae (CRE) remain a leading cause of death in critically ill patients. Fosfomycin has been regarded as an alternative therapy for treatment of infections caused by CRE organisms. The purpose of this study is to evaluate clinical outcomes amongst patients with CRE infection who are receiving a fosfomycin dosing regimen using a Monte Carlo simulation and fosfomycin minimum inhibitory concentration (MIC)., Materials and Methods: Fosfomycin MIC was defined by the E-test method. We used Fosfomycin pharmacokinetic parameters from a previously published study. The percent of the time period in which the drug concentration exceeded the MIC, or %T>MIC, used in this study were determined to be 70% of T>MIC and 100% of T>MIC, respectively. All dosing regimens were estimated for the probability of target attainment using a Monte Carlo simulation., Results: In this study, we found the MIC's of fosfomycin against CRE isolates ranged from 8 mg/L to 96 mg/L. The total daily dose of fosfomycin ranged from 16 - 24 g and was administered utilizing various fosfomycin dosing regimens to achieve the pharmacokinetic/pharmacodynamic (PK/PD) target in pathogens with a MIC of 32 mg/L for 70%T>MIC and a MIC of 12 mg/L for 100%T>MIC, respectively. For the twelve patients who received the recommended fosfomycin dosing regimen, eleven achieved bacterial eradication for a microbiological cure rate of 91%; and of those patients achieving eradication, two died despite having negative cultures for CRE; the one remaining patient had bacterial persistence. The most commonly observed adverse drug reactions were hypernatremia (3 cases) and hypokalemia (3 cases) and acute kidney injury (3 cases)., Conclusion: Our findings suggest fosfomycin has tended to good efficacy when using dosing regimens that achieve the PK/PD target. Nonetheless, further validation of these regimens in larger populations is needed., Competing Interests: No conflicts of interest., (Copyright © 2020 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: Currently, the achievement of the target area under the curve (AUC)/minimum inhibitory concentration ratio during the first 24 - 48 h of treatment is associated with reduced 30-day mortality and greater microbiological eradication in patients with methicillin-resistant Staphylococcus aureus bacteremia. This study aimed to determine the AUC and pharmacokinetic parameters on the first day of vancomycin administration based on the Bayesian theorem to optimize the dosing regimen in critically ill patients., Materials and Methods: This retrospective study included participants meeting the following criteria: 1) ≥18 years old; 2) receipt of at least one dose of vancomycin; 3) measurement of 2 vancomycin serum concentrations during the first 24 h of treatment; and 4) an intensive care unit admission, mechanical ventilator use, or an Acute Physiology and Chronic Health Evaluation II score >15 points. The AUC on day 1 of treatment and the estimated vancomycin pharmacokinetic parameters were measured using PrecisePK software based on the Bayesian theorem., Results: We obtained 132 vancomycin concentrations from 66 patients. The vancomycin pharmacokinetic parameters were as follows: AUC 0-24 , 571.09 (± standard deviation [SD] 188.62) mg/L·h; clearance (CL), 2.97 (± SD 1.81) L/h; volume of distribution (Vd), 50.60 (± SD 13.91) L; elimination rate constant, 0.062 (± SD 0.039) h -1 ; and half-life, 18.19 (± SD 15.96) h. Focusing on the vancomycin loading dose, AUC 0-24 400 - 600 was achieved in 41.7, 46.1, 44.4, and 26.3% of patients with loading doses of <20, 20 - 24.9, 25 - 30, and >30 mg/kg, respectively. Whereas AUC 0-24 ≥521 was achieved in 50, 50, 77.8, and 84.2% of patients with loading doses of <20, 20 - 24.9, 25 - 30, and >30 mg/kg, respectively. The CL of vancomycin was correlated with creatinine CL, whereas the Vd of vancomycin was significantly correlated with age and body weight., Conclusion: This study revealed that the higher Vd and CL values on the first day of vancomycin therapy were found in critically ill patients. Additionally, a higher vancomycin loading dose (25 - 30 mg/kg) might be required to achieve target of AUC 0-24 during early phase of administration for critically ill patients., Competing Interests: No conflicts of interest., (Copyright © 2020 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Optimal early vancomycin target exposure remains controversial. To clarify the therapeutic exposure range, we investigated the association between vancomycin exposure and treatment outcomes or nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. This retrospective study reviewed clinical data obtained from 131 patients with MRSA infections between January 2017 and September 2019. Clinical outcomes included treatment failure, 30-day mortality, microbiological failure, and acute kidney injury. We measured serum vancomycin levels after the first dose to 48 h and estimated vancomycin exposure using the Bayesian theorem. The minimum inhibitory concentration (MIC) of antimicrobial agents was determined using the broth microdilution method. Classification and Regression Tree analyses identified day 1 and 2 exposure thresholds associated with an increased risk of failure and nephrotoxicity. Treatment failure (27.9% vs. 33.3%) and 30-day mortality (26.6% vs. 31.74%) were numerically but not significantly reduced in patients with the area under the curve (AUC) 24-48h /MIC BMD ≥ 698. Patients with AUC ss /MIC BMD ≥ 679 exhibited a significantly increased risk of acute kidney injury (27.9% vs. 10.9%, p = 0.041). These findings indicate that AUC ss /MIC BMD ratios > 600 may cause nephrotoxicity. AUC/MIC BMD at days 1 and 2 do not appear to be significantly associated with particular clinical outcomes, but further studies are needed.

Knee joint infection following total knee arthroplasty (TKA) is a serious condition and the treatments are complicated. The intra-articular solvent exchange-induced in situ forming matrix is of interest for modulating the release of antibiotics with a high drug concentration and a long period of exposed time at the target site. Stearic acid (S) and lauric acid (L) at various ratios were used as matrix formers by dissolving them in biocompatible solvents such as N-methyl pyrrolidone (NMP) and dimethyl sulfoxide (DMSO). Their matrix formation behaviors in phosphate buffer (pH7.4) and hyaluronic acid (HA) solution were evaluated. Also, the density, viscosity, injectability, solvent diffusion, in vitro degradability and drug release using the dialysis tube method were investigated. The L:S ratio of 1:1 in DMSO exhibited rapid matrix formation and a remarkably low viscosity (7.67±0.03 cp) with acceptable injectability (0.608±0.027N and 0.867±0.010N through 18-G and 27-G, respectively). Vancomycin HCl (V)-loaded L/S in situ forming matrix still provided ease of injection (1.079±0.215N and 1.230±0.145N through 18-G and 27-G needle, respectively) with fatty acid matrix formation after solvent exchange within 1min, whilst V sustainably released over 6days. It also presented effective antimicrobial activities against standard Staphylococcus aureus and methicillin-resistant Staphylococcus aureus strains. Therefore, V-loaded solvent exchange-induced in situ forming matrix using L and S as the matrix formers may be a potential local delivery system for treating knee joint infections occurring after TKA in the future., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest with this investigation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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) ( f AUIC 24 ), 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 f AUIC 24 >17.9, and PTA exceeded 90% for MIC ≤0.38 μg/mL. Meanwhile, this dose gave the target attainment of f AUIC 24 >6.9, and PTA exceeded 90% for MIC ≤1 μg/mL. All simulated tigecycline dosing regimens met the f AUIC 24 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., Competing Interests: No conflicts of interest., (Copyright © 2020 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

In recent years, the world has faced the issue of antibiotic resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is a significant problem in various treatments and control of infections. Biocompatible materials with saturated fatty acids of different chain lengths (C 8 -C 18 ) were studied as matrix formers of localized injectable vancomycin HCl (VCM)-loaded antisolvent-induced in situ forming matrices. The series of fatty acid-based in situ forming matrices showed a low viscosity (5.47-13.97 cPs) and pH value in the range of 5.16-6.78, with high injectability through a 27-G needle (1.55-3.12 N). The preparations exhibited low tolerance to high concentrations of KH 2 PO 4 solution (1.88-5.42% v/v ) and depicted an electrical potential change during phase transformation. Their phase transition and matrix formation at the microscopic and macroscopic levels depended on the chain length of fatty acids and solvent characteristics. The VCM release pattern depended on the nucleation/crystallization and solvent exchange behaviors of the delivery system. The 35% w/v of C 12 -C 16 fatty acid-based in situ forming matrix prolonged the VCM release over seven days in which C 12 , C 14 , C 16 -based formulation reached 56, 84, and 85% cumulative drug release at 7 th day. The release data fitted well with Higuchi's model. The developed formulations presented efficient antimicrobial activities against standard S. aureus , MRSA, Escherichia coli , and Candida albicans . Hence, VCM-loaded antisolvent-induced fatty acid-based in situ forming matrix is a potential local delivery system for the treatment of local Gram-positive infection sites, such as joints, eyes, dermis of surgery sites, etc., in the future.

Global infections with colistin-resistant Pseudomonas aeruginosa (CoR-PA) are increasing; there are currently very few studies focused on the antimicrobial susceptibility of CoR-PA isolates, and none from Thailand. Here, we investigated the impact of various antimicrobials, alone and in combination, via the in vitro testing of CoR-PA clinical isolates. Eighteen CoR-PA isolates were obtained from patients treated at Phramongkutklao Hospital from January 2010 through June 2019; these were classified into six different clonal types by using the enterobacterial repetitive intergenic consensus (ERIC)-PCR method, with a high prevalence of Group A (27.8%). The antimicrobial susceptibility was determined as the minimal inhibitory concentrations (MICs) using the epsilometer-test (E-test) method. The synergistic activities of six antimicrobial combinations were reported via the fractional-inhibitory-concentration index. All CoR-PA isolates were susceptible to amikacin, meropenem, and ceftolozane/tazobactam, but only 5.56% were susceptible to imipenem. In vitro synergistic activities were detected for amikacin with aztreonam, piperacillin/tazobactam, meropenem, and ceftazidime for 16.67%, 11.11%, 11.11%, and 5.55%, respectively. One CoR-PA isolate carried the bla VIM metallo-β-lactamase gene; none carried mcr-1 genes or detected plasmid-mediated AmpC β-lactamase or an overproduction of chromosomal AmpC β-lactamase. Seven CoR-PA isolates (38.89%) were capable of biofilm formation. In conclusion, CoR-PA isolates are highly susceptible to antimicrobials; the synergy observed in response to the various agents should be examined in a clinical setting.

Daptomycin, a lipopeptide antibiotic, is one of the therapeutic options used for the treatment of vancomycin-resistant enterococci (VRE). Recently, the Clinical and Laboratory Standards Institute (CLSI) M100 30th edition has removed the susceptibility (S) breakpoint for E nterococcus faecium and replaced it with a susceptible dose-dependent (SDD) breakpoint of ≤4 μg/mL, with a suggested dosage of 8-12 mg/kg/day. Herein, we aimed to determine the minimum inhibitory concentration (MIC) values of daptomycin against clinical VRE isolates and to study the appropriate daptomycin dosing regimens among critically ill patients based on the new susceptibility CLSI breakpoint. The MIC determination of daptomycin was performed using E-test strips among clinical VRE strains isolated from patients at the Phramongkutklao Hospital. We used Monte Carlo simulation to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the ratio of the free area under the curve to MIC ( f AUC 0 - 24 /MIC) > 27.4 and f AUC 0-24 /MIC > 20 for survival and microbiological response, respectively, at the first day and steady state. Further, we determined that the simulated daptomycin dosing regimen met the minimum concentration (Cmin) requirements for safety of being below 24.3 mg/L. All of the 48 VRE isolates were E . faecium strains, and the percentiles at the 50th and 90th MIC of daptomycin were 1 and 1.5 μg/mL, respectively. At MIC ≤ 2 μg/mL, a daptomycin dosage of 12 mg/kg/day achieved the PTA target of survival and microbiological response at the first 24 h time point and steady state. For a MIC of 4 μg/mL, none of the dosage regimens achieved the PTA target. For CFR, a dosage of 8-12 mg/kg/day could achieve the 90% CFR target at the first day and steady state. All dosing regimens had a low probability of Cmin being greater than 24.3 mg/L. In conclusion, the MIC of VRE against daptomycin is quite low, and loading and maintenance doses with 8 mg/kg/day were determined to be optimal and safe., Competing Interests: The authors report no conflicts of interest.

Background: A large number of secondary metabolites can be obtained from plants used for traditional medicine in two related genera ( Ixora and Greenea ) in the subfamily Ixoroideae (Rubiaceae), but there are only a few detailed studies on their bioactivities. Therefore, the main goals of this study were to determine the antibacterial activities of lipophilic extracts from plants of some Ixora and Greenea species native to Thailand, and to isolate some pure compounds from those extracts. Moreover, we compared the occurrence of compounds in different plant parts of samples from different habitats to better understand their variation., Methods: A total of 56 lipophilic extracts were obtained from the leaves, stem bark, and root bark of eight Ixora and two Greenea species collected at various locations in Thailand. Isolated compounds were identified using nuclear magnetic resonance. Antimicrobial activities were evaluated against four Gram-positive and nine Gram-negative human pathogenic bacterial strains., Results: Extracts from I. javanica, I. nigricans, I. brunonis, and G. montana , along with isolated scopoletin, exhibited antibacterial activities against Gram-positive methicillin-resistant Staphylococcus aureus ATCC 43300, with minimum inhibitory concentration values ranging from 64 to 256 µg/mL. The occurrence of scopoletin, isofraxidin, and geniposidic acid in lipophilic extracts showed some variation among different plant parts and species., Conclusions: Lipophilic extracts of Ixora and Greenea species have the potential to be developed as anti-Gram-positive agents, in particular to counter infections of methicillin-resistant S. aureus strains. The chemical profiles showed differences between floristic regions but similarity within the same plant parts., Competing Interests: The authors declare that they have no competing interests.

The efficacy and safety of intrathecal (ITH) or intraventricular (IVT) colistin in addition to intravenous (IV) colistin for meningitis and ventriculitis due to carbapenem-resistant Acinetobacter baumannii (CRAB) is unclear. In this retrospective observational study of 40 patients with post-neurosurgical meningitis and ventriculitis due to CRAB, 33 patients without concomitant infection received appropriate dosage regimens of IV colistin. Of the 33 patients, 17 received additional ITH/IVT colistin and 16 received only IV colistin. The 14-day, 30-day and in-hospital mortality rates were nominally lower for patients who received ITH/IVT colistin adjunctive therapy versus patients who received only IV colistin (24% vs. 38%, 29% vs. 56% and 29% vs. 56%, respectively). The costs of treatment were significantly lower, the lengths of hospital and intensive care unit (ICU) stay were significantly shorter, and the number of ventilator days was significantly less among patients who received ITH/IVT colistin compared with patients who did not receive ITH/IVT colistin. The initial Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale (GCS) scores were associated with 30-day mortality with odds ratios (95% confidence intervals) of 1.21 (1.08-1.46) and 0.77 (0.44-0.85), respectively. Chemical meningitis from ITH/IVT colistin was mild and resolved spontaneously. Treatment of post-neurosurgical CRAB meningitis and ventriculitis with ITH/IVT colistin as an adjunct to IV colistin was associated with shorter lengths of hospital and ICU stay and a trend to lower mortality, especially among severely ill patients., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

This in vitro study aimed to determine the activity of colistin plus sulbactam and colistin plus fosfomycin against carbapenem-resistant A. baumannii (CRAB). Fifteen clinical isolates were obtained from patients admitted to Phyathai II International Hospital, Bangkok, Thailand, from August 2014 to April 2015. The antimicrobial susceptibilities of colistin, sulbactam, and fosfomycin were evaluated using the E-test or broth microdilution and the synergistic activity of the antibacterial combinations (colistin plus sulbactam or fosfomycin) was determined using the chequerboard method. Clonal relationships were explored using repetitive element palindromic- (REP-) PCR. The CRAB isolates were categorized by REP-PCR in 8 groups [A-H]. All CRAB isolates were universally susceptible to colistin but only 20.0% were susceptible to sulbactam. The MIC ranges for colistin, sulbactam, and fosfomycin were 0.75-2 mg/L, 2-96 mg/L, and 64-256 mg/L, respectively. A chequerboard assay revealed that the rates of synergistic and additive effect rates of colistin plus sulbactam and colistin plus fosfomycin were 53.3% and 73.3% of isolates, respectively. No antagonistic effect in any colistin-based combination was observed. However, almost CRAB strains in clone A showed the synergy or additive effects of colistin-sulbactam combination, whereas the other clone (B-H) mostly showed indifferent effects. In conclusion, colistin plus sulbactam and colistin plus fosfomycin against CRAB seem to be interesting option but the efficacy in clinical use has to be evaluated.