Search

Immune reconstitution inflammatory syndrome (IRIS) is a common complication following the initiation of antiretroviral therapy (ART). The most commonly associated pathogens include Mycobacterium tuberculosis and Cryptococcus spp.[1] IRIS following nontuberculosis mycobacteria (NTM) infection is uncommon, particularly, IRIS following NTM conjunctivitis.[2] Herein, we present a case of Mycobacterium scrofulaceum conjunctivitis with peripheral ulcerative keratitis and orbital cellulitis in a 45-year-old patient with AIDS who developed IRIS 1 month after starting ART therapy. A combination of both systemic and topical antibiotics together with corticosteroids were used and resulted in a satisfactory outcome with no early recurrence. This case demonstrated a rare ocular IRIS manifestation involving both the external eye and orbit and to the author's knowledge is the first case in the literature in which M. scrofulaceum has been found to be involved in the eye. [ABSTRACT FROM AUTHOR]

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

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: AUC0-24, 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, AUC0-24 400 - 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 AUC0-24 ≥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 AUC0-24 during early phase of administration for critically ill patients. [ABSTRACT FROM AUTHOR]

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

Objective: To study the minimum inhibitory concentration (MIC) of sulbactam against carbapenem-resistant Acinetobacter baumannii (CR-AB) and to determine the dosage regimens reaching target time of free drug concentration remaining above the MIC (fT >MIC). Methods: Clinical isolates of CR-AB from patients admitted to Phramongkutklao Hospital, Thailand from January 2014 to December 2015 were obtained. The MIC of sulbactam for each CR-AB isolate was determined using the agar dilution method. Each sulbactam regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) in critically ill patients. PTA was defined by how likely a specific drug dose was to reach 40%and 60% fT >MIC. The CFR was the probability of drug dose covering the MIC range of CR-AB. Dosing regimens reaching above 80%of PTA and CFR, were considered as the optimal dosage for documented and empirical therapy, respectively. Results: A total of 118 CR-AB isolates were included in the study. The percentile at the fiftieth and ninetieth MIC of sulbactam were 64 and 192 µg/mL, respectively. For a MIC of sulbactam of 4 µg/mL, all dosage regimens achieved PTA target. However, only a sulbactam dosage of 12 g intravenous daily using 2-4 h infusion or continuous infusion that covered for isolates with a sulbactam MIC of 96 µg/mL, met the PTA or CFR targets. Conclusions: The MIC of sulbactam against CR-AB is quite high. The sulbactam dose of 12 g/day using prolonged infusion was required to achieve the target fT >MIC for CR-AB treatment. [ABSTRACT FROM AUTHOR]

Background: Currently, third generation cephalosporin resistant Enterobacterales (3GCRE) are becoming more common in community-acquired infection, leading to increasing consumption of carbapenems. Because community-acquired 3GCRE infections are generally less severe and of lower pathogenicity, the impact of inappropriate empirical antibiotics among patients with community-acquired 3GCRE bacteremia remains unknown., Materials and Methods: This prospective cohort study included adult patients with 3GCRE bacteremia from April 2018 to December 2021. Participants were followed for 30 days to measure the primary outcome of mortality. Propensity score analysis was performed to adjust for treatment selection bias., Results: A total of 155 patients met the eligible criteria (42 participants in the appropriate antibiotics group, and 113 participants in the inappropriate antibiotics group). Eight participants in the inappropriate antibiotics group never received appropriate antibiotics, three of whom died before microbiological results were made available. The most common clinical syndromes were urinary tract infection (56.8%) and biliary tract infection (22.6%). The overall 30-day mortality rate was 12.9%, 14.3% in the appropriate empirical antibiotics group and 12.4% in the inappropriate empirical antibiotics group. After propensity score weighted adjustment, the 30-day mortality rate in the inappropriate group was non-inferior to the appropriate group (mean difference 1.9%; 95% confidence interval: -10.1 - 14.0). From the multivariate analysis, acute respiratory failure and primary bacteremia were associated with 30-day mortality., Conclusion: Among patients with community-acquired 3GCRE bacteremia, inappropriate empirical treatment given within 24 hours after the onset of bacteremia was non-inferior to appropriate antibiotics. In the setting of a high prevalence of 3GCRE carriage in community, adjustment to carbapenem might be tolerable among patients with community-acquired infections., Trial Registration: ClinicalTrials.gov Identifier: NCT03765749., Competing Interests: No conflict of interest., (Copyright © 2022 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

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.)

Purpose: HIV treatment involves antiretroviral therapy (ART) endeavoring to suppress viral load to an undetectable level. Virologic failure occurs when ART fails to suppress and sustain an individual's viral load to less than 200 copies/mL after 6 months of therapy. In Thailand, the data among first-line antiretroviral regimen failure and determinants remains limited, especially in urban HIV clinics. We aimed to demonstrate factors of first-line antiretroviral regimen failures in an urban HIV/AIDS clinic at Phramongkutklao Hospital., Patients and Methods: A nested case control 1:4 study was conducted. Data were collected from the electronic patient database among naïve people living with HIV/AIDS (PLWHA), aged ≥18 years and receiving ART continuously for at least 2 years at Phramongkutklao Hospital from 1 January 2000 to 31 December 2019. Multiple logistic regression was used to identify the determinants of virologic failure. Adjusted HRs (AHRs) with 95% CIs were used to declare statistical significance., Results: Of 200 PLWHA included in the study, 40 participants experienced HIV virologic failure. The median time after starting ART to virologic failure was 24 months (IQR 7-96.0). Univariate and multivariate analysis showed significant factors affecting first-line antiretroviral regimen failure included being female (37.5 vs 26.88%, adjusted odds ratio 5.08 [1.05-24.6, p-value 0.043], age ≤40 yr. (62.5 vs 49.6%, adjusted odds ratio 4.59 [1.47-14.37], p-value 0.009), CD4+count ≤200 cell/µL (77.5 vs 52.5%, adjusted odds ratio 4.83 [1.28-18.9], p value 0.02), tuberculosis (42.5 vs 7.5%, adjusted odds ratio 8.66 [2.37-31.56], p value <0.001) and initiation of ART at CD4+ count <350 cell/µL (72.5 vs 48.13%, adjusted odds ratio 31.36 [6.51-151.22], p value <0.001). Estimated prevalence of virologic failure in Phramongkutklao Hospital was 5.34%., Conclusion: Our study revealed factors favoring virologic failure included being female, younger age, CD4+ count <200 cells/µL, tuberculosis and initiation of ART at CD4+ count <350 cell/µL. Multidisciplinary HIV comprehensive care teams should encourage patient adherence and support patients along HIV continuum of care to prevent virologic failure and drug resistance, especially among patients initiating ART at low CD4+ count and tuberculosis co-infection., Competing Interests: The authors declare they have no existing or potential conflict of interest relevant to this work., (© 2021 Nasomsong et al.)