High-Loading-Dose Colistin with Nebulized Administration for Carbapenem-Resistant Acinetobacter baumannii Pneumonia in Critically Ill Patients: A Retrospective Cohort Study.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections pose a serious threat, with high morbidity and mortality rates. This retrospective cohort study, conducted at Nakornping Hospital between January 2015 and October 2022, aimed to evaluate the efficacy and safety of a high loading dose (LD) of colistin combined with nebulized colistin in critically ill patients with CRAB pneumonia. Of the 261 patients included, 95 received LD colistin, and 166 received LD colistin with nebulized colistin. Multivariate Cox regression analysis, adjusted for baseline covariates using inverse probability weighting, showed no significant difference in 30-day survival between patients who received LD colistin and those who received LD colistin with nebulized colistin (adjusted hazard ratio [aHR]: 1.17, 95% confidence interval [CI]: 0.80-1.72, p = 0.418). Likewise, there were no significant differences in clinical response (aHR: 0.93, 95% CI: 0.66-1.31, p = 0.688), microbiological response (aHR: 1.21, 95% CI: 0.85-1.73, p = 0.279), or nephrotoxicity (aHR: 1.14, 95% CI: 0.79-1.64, p = 0.492) between the two treatment groups. No significant adverse events related to nebulized colistin were reported. These findings suggest that the addition of nebulized colistin may not offer additional benefits in terms of 30-day survival, clinical or microbiological response, or nephrotoxicity in these patients.

Comparative effectiveness and mortality of colistin monotherapy versus colistin-fosfomycin combination therapy for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections: A propensity score analysis.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infections pose a significant threat to global health due to limited treatment options and high mortality rates. Colistin-based regimens have emerged as a primary treatment approach, but the effectiveness and mortality outcomes of colistin monotherapy versus colistin-fosfomycin combination therapy remain uncertain. This study aims to compare the effectiveness and mortality of colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. Notably, our study is the first to undertake a comprehensive examination of the effectiveness and mortality outcomes between colistin monotherapy and colistin-fosfomycin combination therapy in the context of CRE infections. METHODS: A retrospective cohort study was conducted using data from patients diagnosed with carbapenem-resistant Enterobacteriaceae (CRE) infections at Nakornping Hospital during 2015 to 2022. Inverse probability weighting (IPW) was employed to create balanced cohorts of patients receiving either colistin monotherapy or colistin-fosfomycin combination therapy. The primary outcome measure was treatment effectiveness, assessed by 30-day mortality. Secondary outcome measures included clinical response, mortality at the end of treatment, and microbiologic response. Univariate and multivariate logistic regression analysis were employed after applying propensity score weighting using inverse probability of weighting (IPW). RESULTS: A total of 220 patients were included in the analysis, with 67 receiving colistin monotherapy and 153 receiving colistin-fosfomycin combination therapy. Propensity score weighting using IPW balanced the baseline characteristics between the two groups. The effectiveness of treatment, as measured by 30-day mortality, was not significantly different between the colistin monotherapy group and the colistin-fosfomycin combination therapy group (adjusted odds ratio [aOR] = 1.51, 95% confidence interval [CI]: 0.60-3.78, p = 0.383). Similarly, no significant difference was observed in the mortality at the end of treatment between the two groups (aOR = 1.26, 95% CI: 0.55-2.90, p = 0.576). The clinical response (aOR = 1.48, 95% CI: 0.61-3.59, p = 0.383) and microbiologic response (aOR = 0.66, 95% CI: 0.18-2.38, p = 0.527) were similar between the colistin monotherapy and colistin-fosfomycin combination therapy groups. CONCLUSION: The propensity score analysis among 220 matched patients showed comparable treatment effectiveness and mortality between colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. These results suggest that colistin monotherapy may be as effective as combination therapy. More prospective randomized controlled trials are needed to confirm these findings and establish optimal CRE treatment strategies.

Utilizing liposomal encapsulation approach to address nephrotoxic challenges of colistimethate sodium through a preclinical study.

The use of Colistin, a last-resort antimicrobial drug, carries the risk of acute kidney injury. The objective of the study was to assess the effectiveness of colistin-encapsulated liposomes (CL) in reducing nephrotoxicity. Additionally, a liposomal preparation of colistimethate sodium was formulated using the reverse phase evaporation method with a 3:1 ratio of phospholipids to cholesterol. The liposomal properties were evaluated using scanning electron microscopy, photon correlation spectroscopy, and release kinetic assay. The killing kinetics of the formulations on embryonic kidney cells were assessed using in vitro MTT reduction assay. The nephrotoxicity of CL and colistimethate sodium solution (CS) was evaluated in vivo by administering a dose of 20 mg/kg to rats every 12 h for 3 days, with a negative control group receiving a 0.9% saline solution (NSS). The study results revealed that monodisperses of CL showed a smooth surface and distinct boundaries, with an average size of 151.50 ± 0.46 nm and a narrow size distribution of 0.25 ± 0.01. The liposomal particles showed high entrapment efficiency of 96.45% ± 0.41%, with a ζ-potential of -60.80 ± 1.01 mV and a release rate of 50% of colistimethate sodium within the first 480 min. The CL induced nephrocytotoxicity in a concentration- and time-dependent manner. However, CS had notably lower IC50 values compared to its liposome preparations at 48 and 72 h (p < 0.05). In vivo study results show that serum levels of symmetric dimethylarginine (SDMA) and total white blood cell count (WBC) were significantly lower in the CL group (SDMA = 8.33 ± 1.70 µg/dL; WBC = 7.29 ± 0.99 log10 cells/mL) compared to the CS group (SDMA = 15.00 ± 1.63 µg/dL; WBC = 9.73 ± 0.51 log10 cells/mL). Our study findings enhance the understanding of the safety profile of CL and its potential to improve patient outcomes through the use of liposomal colistin medication. Additional clinical studies are necessary to establish the optimal safety regiment in humans.

Comparative Safety and Effectiveness of Heterologous CoronaVac-ChAdOx1 versus Homologous CoronaVac Vaccination in a Real-World Setting: A Retrospective Cohort Study.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has outpaced vaccine availability and delivery from vaccine manufacturers, and thus, a scarcity of vaccines happened to many countries around the world. In Thailand, the mixing of different types of vaccines was approved and clinically implemented partially due to concerns about the availability and efficacy of one vaccine. Objective: This study aimed to investigate the effectiveness and safety of heterologous CoronaVac-ChAdOx1 nCoV-19 vaccines compared with the usual regimen of homologous CoronaVac-CoronaVac. A retrospective cohort study was conducted by dividing patients into the CoronaVac-CoronaVac group and the CoronaVac-ChAdOx1 group. Results: A total of 875 patients received vaccinations at Srisangwan Hospital between April to October 2021 and were included for analysis. The patients in both homologous and heterologous groups had low rates of COVID-19 infection. In addition, the hospitalization rates in the 40 days after the second vaccination were low in both regimens. Minimal adverse events (AE) were reported in both groups, including local AE (e.g., discomfort at the injection site, rash, soreness, swelling, and redness) and systemic AE (e.g., fever, headache, weariness, nausea, vomiting, diarrhoea, and myalgia). Moreover, several factors were associated with lower adverse events following immunization (AEFIs), including age ≥ 50 years, male, and body weight ≥ 50 kg. In contrast, thyroid disease, diabetes mellitus, allergic rhinitis, and psychiatric disorders were independent risk factors associated with an increase in AEFIs. Conclusions: The heterologous CoronaVac-ChAdOx1 and homologous CoronaVac-CoronaVac regimens were promising vaccination strategies for the prevention of SARS-CoV-2 infection. However, the heterologous CoronaVac-ChAdOx1 potentially caused fewer AEFIs compared with the homologous CoronaVac-CoronaVac regimen.

Short versus long course of colistin treatment for carbapenem-resistant A. baumannii in critically ill patients: A propensity score matching study.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most commonly found nosocomial infections in critically ill patients. However, the appropriate treatment period for a specific group of critically ill patients with CRAB infection is currently being debated. Therefore, our study aimed to evaluate the optimal courses of therapy for critically ill patients with CRAB infection by comparing the outcomes of colistin therapy of short duration (<14 days) versus long duration (≥ 14 days). METHODS: A retrospective cohort study was conducted at Nakornping Hospital on critically ill patients with CRAB infection who received either a short or long course of colistin treatment between 2015 and 2022. The primary outcome was the 30-day mortality rate while secondary outcomes were clinical response, microbiological response, and nephrotoxicity. Propensity score matching with a 1: 1 ratio was performed to reduce potential biases. Furthermore, a logistic regression model was used to estimate the odds ratio (OR). RESULTS: A total of 374 patients met the inclusion criteria. Two hundred and forty-eight patients were recruited after utilizing propensity scores to match patients at a 1: 1 ratio. The results from the propensity score matching analysis demonstrated that the long-course therapy group had a lower 30-day mortality rate compared to the short-course therapy group (adjusted OR (aOR) = 0.46, 95% CI: 0.26-0.83, p = 0.009). The clinical response and microbiological response rates were higher in patients who received the long course of colistin therapy compared to those receiving the short course (aOR = 3.24, 95% CI: 1.78-5.92, p = 0.001; aOR = 3.01, 95% CI: 1.63-5.57, p = 0.001). There was no significant different in the occurrence of nephrotoxicity (aOR = 1.28, 95% CI: 0.74-2.22, p = 0.368) between the two treatment groups. CONCLUSION: A long course of colistin therapy resulted in a lower 30-day mortality rate in critically ill patients, and better clinical and microbiological outcomes, but similar nephrotoxicity as compared to a short course of colistin therapy. Therefore, a specific subset of critically ill patients who had CRAB infection needed to be considered for a long course of therapy.

Predicting the Area under the Plasma Concentration-Time Curve (AUC) for First Dose Vancomycin Using First-Order Pharmacokinetic Equations.

To treat critically ill patients, early achievement of the target area under the plasma concentration-time curve/minimum inhibitory concentration (AUC/MIC) in the first 24 h is recommended. However, accurately calculating the AUC before steady state is an obstacle to this goal. A first-order pharmacokinetic equation to calculate vancomycin AUC after a first dose of vancomycin has never been studied. We sought to estimate AUC using two first-order pharmacokinetic equations, with different paired concentration time points, and to compare these to the actual first dose vancomycin AUC calculated by the linear-log trapezoid rule as a reference. The equations were validated using two independent intensive first dose vancomycin concentration time data sets, one from 10 adults and another from 14 children with severe infection. The equation with compensation for the alpha distribution phase using a first vancomycin serum concentration from 60 to 90 min and the second concentration from 240 to 300 min after the completed infusion showed good agreement and low bias of calculated AUC, with mean differences <5% and Lin's correlation coefficient >0.96. Moreover, it gave an excellent correlation with Pearson's r > 0.96. Estimating the first dose vancomycin AUC calculated using this first-order pharmacokinetic equation is both reliable and reproducible in clinical practice settings.

Treatment costs for patients with Streptococcus suis infection in Northern Thailand: a hospital-based observational study of 14-year data.

BACKGROUND: Streptococcus suis (S.suis) is a neglected zoonotic disease that imposes a significant economic burden on healthcare and society. To our knowledge, studies estimating the cost of illness associated with S.suis treatment are limited, and no study focuses on treatment costs and potential key drivers in Thailand. This study aimed to estimate the direct medical costs associated with S.suis treatment in Thailand and identify key drivers affecting high treatment costs from the provider's perspective. METHODS: A retrospective analysis of the 14-year data from 2005-2018 of confirmed S.suis patients admitted at Chiang Mai University Hospital (CMUH) was conducted. Descriptive statistics were used to summarize the data of patients' characteristics, healthcare utilization and costs. The multiple imputation with predictive mean matching strategy was employed to deal with missing Glasgow Coma Scale (GCS) data. Generalized linear models (GLMs) were used to forecast costs model and identify determinants of costs associated with S.suis treatment. The modified Park test was adopted to determine the appropriate family. All costs were inflated applying the consumer price index for medical care and presented to the year 2019. RESULTS: Among 130 S.suis patients, the average total direct medical cost was 12,4675 Thai baht (THB) (US$ 4,016), of which the majority of expenses were from the "others" category (room charges, staff services and medical devices). Infective endocarditis (IE), GCS, length of stay, and bicarbonate level were significant predictors associated with high total treatment costs. Overall, marginal increases in IE and length of stay were significantly associated with increases in the total costs (standard error) by 132,443 THB (39,638 THB) and 5,490 THB (1,715 THB), respectively. In contrast, increases in GCS and bicarbonate levels were associated with decreases in the total costs (standard error) by 13,118 THB (5,026 THB) and 7,497 THB (3,430 THB), respectively. CONCLUSIONS: IE, GCS, length of stay, and bicarbonate level were significant cost drivers associated with direct medical costs. Patients' clinical status during admission significantly impacts the outcomes and total treatment costs. Early diagnosis and timely treatment were paramount to alleviate long-term complications and high healthcare expenditures.

Incidence of postpartum infections and outcomes associated with antibiotic prophylaxis after normal vaginal birth.

Antibiotic consumption accounted for approximately 15-20% of total drug costs in Thailand. From 2017 to 2018, 24.86% of Thai women who experienced vaginal delivery during normal term labour received antibiotics for postpartum infection. The Thai national practice guidelines set the target use of antibiotic prophylaxis in women following vaginal delivery of normal term labour to be no more than 10%. This study aimed to determine the incidence of postpartum infections and the outcomes and factors associated with antibiotic prophylaxis in women following vaginal delivery. The prospective cohort study was collected from 909 eligible patients who delivered infants in 7 secondary hospitals in Chiang Mai from July 2020 to February 2021. Antibiotic prescribing data and infections in women experiencing vaginal delivery during normal term labour were collected. The incidence of postpartum infections was calculated at 2 periods, 48 h and 6 weeks, after labour. Factors associated with the prescription of antibiotic prophylaxis in vaginal delivery were analysed using multivariate logistic regression. The results showed that the prevalence of antibiotic prescribing was 12.87% in a cohort of 117 patients. Postpartum infection was reported in 3 of 117 patients with antibiotics prophylaxis and 11 of 792 without antibiotics, with no statistically significant difference (RR: 1.04, 95% CI: 0.26-4.14; p = 0.956). Postpartum hygiene self-care practices were collected in the 6th week. The results found that there were no statistical differences in mean scores for all questions on postpartum hygiene self-care practices between the infected and non-infected groups (p-value > 0.05). One of the factors associated with antibiotic prophylaxis was third to fourth degree of tear and episiotomy (OR: 7.72, 95% CI: 1.13-52.75; p = 0.037 and OR: 2.41, 95% CI: 1.24-4.70; p = 0.010, respectively). There was no significance difference in postpartum infection among patients receiving antibiotic and those who did not receive antibiotics. Third to fourth degree of tear and episiotomy were significantly factors related to antibiotic prophylaxis in women with vaginal delivery after labour. This study supports practice guidelines and helps healthcare team to be assured on the use of antibiotics in no more than 10% of women experiencing normal vaginal delivery.

Effectiveness and Nephrotoxicity of Loading Dose Colistin-Meropenem versus Loading Dose Colistin-Imipenem in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Infection.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is becoming more widely recognized as a serious cause of nosocomial infections, and colistin has been reintroduced in recent years for the treatment of CRAB infection. Combinations of colistin and meropenem or imipenem have been found to be effective against CRAB isolates, whereas clinical investigations have not definitively demonstrated the theoretical benefits of colistin combined therapy in patients with CRAB infections. The objective of this study was to compare the primary outcome (30-day survival rate) and secondary outcomes (clinical response, microbiological response and nephrotoxicity) between patients who received loading dose (LD) colistin−meropenem and LD colistin−imipenem for the treatment of CRAB infection. A retrospective cohort analysis was performed at Chiang Mai University Hospital in patients with CRAB infection who received LD colistin−meropenem or LD colistin−imipenem between 2011 and 2017, and 379 patients fulfilled the requirements for the inclusion criteria. The results of this study showed that patients who received LD colistin−imipenem had a lower 30-day survival rate (adjusted HR = 0.57, 95% CI: 0.37−0.90; p = 0.015) and a lower clinical response (aHR = 0.56, 95% CI: 0.35−0.90; p = 0.017) compared with those who received LD colistin−meropenem. The microbiological response in patients with LD colistin−imipenem was 0.52 times (aHR) lower than that in those who received colistin−meropenem (95% CI: 0.34−0.81; p = 0.004); however, there was no significant difference in nephrotoxicity (aHR = 1.03, 95% CI: 0.67−1.57; p = 0.897) between the two combination regimens. In conclusion, when comparing the combination of LD colistin with imipenem or meropenem, the combination of LD colistin and meropenem provides a better survival rate for treating CRAB. Thus, we suggest that combinations of LD colistin and meropenem should be considered when treating CRAB infections.

Factors Predicting Practices in Prevention of COVID-19 and Impacts among Population in Chiang Mai, Thailand.

Background and objectives: The pandemic of COVID-19 is a global concern requiring urgent and effective action. However, the data on prevention practices and the impact of COVID-19 among the Thai population have not been clearly described. This study aimed to examine the knowledge, attitudes, perception, practices, and factors predicting practices in the prevention of COVID-19 and to study the impact of COVID-19 on people's livelihoods. Materials and Methods: A cross-sectional study was performed between April and November 2020. A questionnaire eliciting demographic data and information on knowledge, attitudes, perception, prevention practices, and impact of COVID-19 was given to 500 people who lived in Chiang Mai, and 480 usable questionnaires were returned, for a response rate of 96.0%. Data were analyzed using descriptive statistics and multivariate linear regression. Results: Less than half of the participants had a high level of knowledge (45.4%) about COVID-19. Most of them had a high level of attitudes (95.6%), perception (72.1%), and prevention practices (90.4%). Female (ß = 0.11, p = 0.006), patient status (ß = 0.17, p < 0.001), knowledge (ß = −0.10, p = 0.020), attitudes (ß = 0.37, p < 0.001), and perception (ß = 0.21, p < 0.001) about COVID-19 prevention were the predicting factors for overall prevention practices (R2 = 0.288). Most participants perceived the overall impact of COVID-19 at moderate and high levels (47.1 and 37.8%, respectively). The highest impact was an economic burden, followed by psychological, social, and physical impacts. Conclusions: Policymakers should enhance attitudes and perception about COVID-19 prevention to improve the COVID-19 prevention practices. This may help to reduce the new cases of COVID-19 and may result in reducing the impact of COVID-19 on people's livelihoods.

A Monocentric Retrospective Study of AUC/MIC Ratio of Vancomycin Associated with Clinical Outcomes and Nephrotoxicity in Patients with Enterococcal Infections.

Vancomycin is an antibiotic commonly used for the treatment of enterococcal infections. However, there is no clear correlation regarding of vancomycin area under the curve/minimum inhibitory concentration (AUC/MIC) ratio and clinical outcomes for the treatment of enterococcal infections. The aims of this study were to evaluate the relationship of vancomycin AUC/MIC ratio in patients with clinical outcomes and nephrotoxicity for patients with documented enterococcal infections. A Bayesian technique was used to calculate the average vancomycin AUC0-24. The MIC was determined using the VITEK 2 automated microbiology system, and the average AUC0-24/MIC value was calculated for the first 72 h of therapy. All medical records of patients prescribed vancomycin with therapeutic drug monitoring were collected during January 2010-October 2020 at Chiang Mai University Hospital (CMUH). A retrospective single-center cohort of 312 participants were met the inclusion criteria. The results of this study showed that, a vancomycin AUC/MIC of ≥400 mg·h/L was associated with significant differences in clinical response compared to a vancomycin AUC/MIC of <400 mg·h/L (aHR: 0.50, 95% CI: 0.26-0.97; p = 0.042). Likewise, a vancomycin AUC/MIC of ≥400 mg·h/L was associated with significant differences in the microbiological response (aHR: 0.37, 95% CI: 0.14-0.94; p = 0.036), compared to a vancomycin AUC/MIC of <400 mg·h/L. However, nephrotoxicity in patients with a vancomycin AUC/MIC of ≥400 mg·h/L was higher than those with a vancomycin AUC/MIC of <400 mg·h/L (aHR: 3.96, 95% CI: 1.09-14.47; p = 0.037). Declining renal function may be a result of high vancomycin concentrations. In addition, declining renal function (e.g., failure to resolve the focus of infection, co-administration of other antibiotics) might result in higher AUC/MIC. We found a target vancomycin AUC/MIC of ≥400 mg·h/L and this AUC/MIC target value could be optimal for the use for monitoring treatment of enterococcal infections. Thus, vancomycin dosage must be adjusted to achieve the AUC/MIC target and closely monitored for renal function. These findings are not transferable to critically ill patients.

Preclinical Evaluations of Modified Rice Hydrogel for Topical Ophthalmic Drug Delivery of Praziquantel on Avian Philophalmiasis.

The present study aims to evaluate the efficacy of a novel drug delivery system of the modified rice hydrogel containing praziquantel (PZQ) against Philophthalmus gralli isolated from ostrich eyes and determine the toxicity of the preparation on chicken eye model. The parasiticidal activity of PZQ (0, 1, 10, and 100 µg/mL) was tested on P. gralli. The ophthalmic antiparasitic hydrogel was formulated with appropriate amount of PZQ and chemically modified rice gel. The parasitic morphology after exposure with the preparation was examined under scanning electron microscope (SEM). The anthelminthic efficacy of the preparation on motility and mortality of parasites was performed by visual inspection and vital dye staining. The ocular irritation of the preparation was evaluated for 21 days using standard avian model followed by OECD 405. The results demonstrated that the parasiticidal activity of PZQ against P. gralli appears to be in a concentration- and time-dependent manner. In addition, the concentration of PZQ 10 µg/mL (Chi squared test, p = 0.003) and exposure time for 24 h (log-rank test, p = 0.0004) is sufficient to kill parasites, when statistically compared to negative control group. Rice hydrogel containing a lethal concentration of 10 µg/mL PZQ was successfully prepared. The preparation illustrated good parasitic killing and motile inhibiting effect on P. gralli compared with PZQ 10 µg/mL and its control (p < 0.05). An appearance under SEM of non-viable parasite after being incubated with the preparation, showing parasitic deformity, was observed comparing with the viable parasite in 0.9% normal saline solution (NSS). Moreover, no irritation of chicken eyes was also observed. Our results contribute to understanding the efficacy and the safety of the rice hydrogel of PZQ which have a predictive value for controlling P. gralli on the animal eyes. However, the pharmacological application needs to be further investigated for the best possible therapeutic approach.

Short-Course Versus Long-Course Colistin for Treatment of Carbapenem-Resistant A.baumannii in Cancer Patient.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most commonly reported nosocomial infections in cancer patients and could be fatal because of suboptimal immune defenses in these patients. We aimed to compare clinical response, microbiological response, nephrotoxicity, and 30-day mortality between cancer patients who received short (<14 days) and long (≥14 days) courses of colistin for treatment of CRAB infection. A retrospective cohort study was conducted in cancer patients with CRAB infection who received short or long courses of colistin between 2015 to 2017 at Chiang Mai University Hospital (CMUH). A total of 128 patients met the inclusion criteria. The results of this study show that patients who received long course of colistin therapy had a higher rate of clinical response; adjusted odds ratio (OR) was 3.16 times in patients receiving long-course colistin therapy (95%CI, 1.37-7.28; p value = 0.007). Microbiological response in patients with long course was 4.65 times (adjusted OR) higher than short course therapy (95%CI, 1.72-12.54; p value = 0.002). Moreover, there was no significant difference in nephrotoxicity (adjusted OR, 0.91, 95%CI, 0.39-2.11; p value = 0.826) between the two durations of therapy. Thirty-day mortality in the long-course therapy group was 0.11 times (adjusted OR) compared to the short-course therapy group (95%CI, 0.03-0.38; p value = 0.001). Propensity score analyses also demonstrated similar results. In conclusion, cancer patients who received a long course of colistin therapy presented greater clinical and microbiological responses and lower 30-day mortality but similar nephrotoxicity as compared with those who a received short course. Therefore, a long course of colistin therapy should be considered for management of CRAB infection in cancer patients.

Clinical Efficacy and Nephrotoxicity of Colistin Alone versus Colistin Plus Vancomycin in Critically Ill Patients Infected with Carbapenem-Resistant Acinetobacter baumannii: A Propensity Score-Matched Analysis.

Acinetobacter baumannii has emerged as a significant concern worldwide. The mortality rate of carbapenem-resistant A. baumannii (CRAB) is increasing, especially in the intensive care unit (ICU). Thus, the objective of this study is to compare the efficacy and safety of colistin plus vancomycin for the treatment of critically ill patients with CRAB in Chiang Mai University Hospital. We conducted a retrospective cohort study of critically ill patients in the ICU with CRAB infection who received colistin alone or colistin-vancomycin combination therapy at Chiang Mai University Hospital. A total of 365 critically ill patients met the inclusion criteria. The results in this study showed that after propensity score matching, colistin plus vancomycin showed no significant differences in the 30-day mortality compared to colistin alone. Likewise, for colistin plus vancomycin, compared with colistin therapy alone, there were no significant differences in the clinical response, microbiological response and nephrotoxicity. In conclusion, colistin plus vancomycin was no significant differences in 30-day mortality, clinical response, microbiological response compared to colistin alone for infections due to CRAB. The nephrotoxicity rates were similar for both groups, so colistin combination with vancomycin was not necessary for the management of infection caused by CRAB.

Efficacy of loading dose colistin versus carbapenems for treatment of extended spectrum beta lactamase producing Enterobacteriaceae.

Colistin provides in vitro activity against numerous ESBL-producing and carbapenem-resistant bacteria. However, clinical information with respect to its utilization in infection caused by ESBL producers is limited. The aim of this study was a comparison of mortality rates of loading dose (LD) colistin and carbapenems as definitive therapies in a cohort of patients with infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae. A retrospective cohort study in 396 patients with ESBL-producing E.coli and K.pneumoniae infection at a university-affiliated hospital was conducted between 1 January 2005 and 30 June 2015 to compare outcomes of infected patients who received LD colistin (95 patients) with carbapenems (301 patients). The three primary outcomes were 30-day mortality, clinical response and microbiological response. The most common infection types were urinary tract infection (49.49%), followed by pneumonia (40.66%), bacteremia (13.64%), skin and soft tissue infections (4.80%) and intra-abdominal infection (3.03%). LD colistin group provided higher 30-day mortality when compared with carbapenems group (HR 7.97; 95% CI 3.68 to 17.25; P = 0.001). LD colistin was also independently associated with clinical failure (HR 4.30; 95% CI 1.93 to 9.57; P = 0.001) and bacteriological failure (HR 9.49; 95% CI 3.76 to 23.96; P = 0.001) when compared with those who received carbapenems. LD colistin treatment was associated with poorer outcomes, i.e. mortality rate, clinical response and microbiological response. Moreover, when adjusted confounding factors, LD colistin was still less effective than carbapenems. It should be noted that, however, the use of Vitek-2 to assess colistin susceptibility could provide inaccurate results. Also, the difference in baseline characteristics could still remain in retrospective study although compensation by hazard ratio adjustment was performed. Therefore, clinical utilization of LD colistin should be recommended as an alternative for treatment ESBL-producing Enterobacteriaceae only in the circumstances where carbapenems cannot be utilized, but this recommendation must be considered carefully.

Clinical Efficacy and Nephrotoxicity of the Loading Dose Colistin for the Treatment of Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most common causes of nosocomial infections in critically ill patients. Colistin methanesulfonate (CMS), an inactive prodrug, has been considered as a last-resort treatment for CRAB infection in critically ill patients. The objective of this study was to assess 30-day survival and nephrotoxicity in critically ill patients who received non-loading dose (LD) versus LD of CMS for CRAB infection treatment. Between 2012 and 2017, this retrospective cohort analysis was performed at Chiang Mai University Hospital (CMUH), focusing on critically ill patients with CRAB infection who received either non-LD or LD of CMS. A total of 383 patients met the criteria for inclusion. At the 30th day of treatment, the survival rate of patients in the LD CMS group was 1.70 times (adjusted HR) of those in the non-LD group (95% CI = 1.17-2.50, p = 0.006). Clinical response was significantly higher in the LD CMS group than non-LD CMS group (aHR, 1.35, 95% CI, 1.01-1.82, p = 0.046). In addition, a microbiological response-eradication of pre-treatment isolated pathogens in post-treatment cultures-in patients with LD CMS was 1.57 times that of patients with non-LD CMS (95% CI, 1.15-2.15, p = 0.004). Additionally, there was a significant difference in nephrotoxicity between LD CMS and non-LD CMS (aHR, 1.57, 95% CI, 1.14-2.17, p = 0.006). Based on these results, LD CMS should be used to increase the opportunity of patients to achieve favourable outcomes. However, LD CMS was found associated with an increase in nephrotoxicity, so renal function should be closely monitored when LD colistin was administered.

Influence of Concentration and Temperature on Stability of Imipenem Focused on Solutions for Extended Infusion.

BACKGROUND: Imipenem remains active against most Gram-positive and Gram-negative organisms. This study aimed to evaluate chemical stability of imipenem in 2 commonly used concentrations when stored in 3 various temperatures. METHODS: Imipenem injection powder was used to prepare 5 mL and 10 mg/mL of imipenem in .9% sodium chloride solution. Prepared solutions in PVC bags were stored at 25°C, 30°C, and 40°C. The solutions were investigated over 0, 1, 2, 3, 4, and 6 hours using HPLC analysis. The association between drug stability, temperature, and concentration was determined. RESULTS: The 5 mg/mL solutions of brand A and B imipenem mL were stable for 6 hours at 25°C, 30°C, and 40°C, respectively. For 10 mg/mL, the solution of brand A was stable for 3 hours and brand B was stable for 6 hours at 25°C. Also, brand A and B imipenem solutions at the concentration of 10 mg/mL were stable for less than 1 hour at 30°C and 40°C. CONCLUSION: The stability of imipenem injection solution was affected by temperature and concentration. Increasing in temperature and drug concentration resulted in decreased stability of imipenem. Suitable temperature and drug concentration should be concerned when this drug is given by extended infusion.

The Thirty-Day Mortality Rate and Nephrotoxicity Associated With Trough Serum Vancomycin Concentrations During Treatment of Enterococcal Infections: A Propensity Score Matching Analysis.

The objective of this study was to evaluate the relationship between vancomycin trough levels in patients with documented enterococcal infections and mortality, clinical outcomes, microbiological outcomes, and nephrotoxicity. We conducted a retrospective cohort study of patients with enterococcus infections who were prescribed vancomycin with therapeutic drug monitoring during January 2010 and December 2019 at Chiang Mai University Hospital (CMUH). The study enrolled 300 participants who met the inclusion criteria and were prescribed vancomycin with therapeutic drug monitoring. The results of this study showed that, after propensity score matching, a vancomycin trough of ≥15 mg/L was associated with significant differences in 30-days mortality compared to a vancomycin trough of <15 mg/L (aHR: 0.41, 95% CI: 0.21-0.82; p = 0.011). Likewise, a vancomycin trough of ≥15 mg/L was associated with significant differences in the clinical response (aHR: 0.49, 95% CI: 0.26-0.94; p = 0.032), microbiological response (aHR: 0.32, 95% CI: 0.12-0.87; p = 0.025) and nephrotoxicity (aHR: 3.17, 95% CI: 1.39-7.23; p = 0.006), compared with a vancomycin trough of <15 mg/L. However, sub-group analysis found that very high trough levels (>20 mg/L) were also associated with a high rate of nephrotoxicity (aHR: 3.55, 95% CI 1.57-8.07, p = 0.002), when compared with a vancomycin trough of <15 mg/L. The target vancomycin trough concentration was ≥15 mg/L and this target can be an optimal alternative to the use of area under the curve (AUC) values for monitoring the treatment of enterococcal infection.

Serotypes and Vaccine Coverage of Streptococcus Pneumoniae Colonization in the Nasopharynx of Thai Children in Congested Areas in Chiang Mai.

Streptococcus pneumoniae causes around 10% of all deaths in children younger than five years of age. This study aimed to examine the serogroups/serotypes of S. pneumoniae colonization and vaccine serotype coverage of this organism among Thai children. Nasopharyngeal swabs of children less than or equal to 15 years of age were obtained in congested areas in Chiang Mai from 1 February 2013 to 1 August 2013. The serotyping of S. pneumoniae isolates was performed using the ImmuLex™ kit and the vaccine serotype coverage for this organism was evaluated. A total of 292 children were enrolled. One hundred and thirty children (44.5%) had nasopharyngeal colonization with Streptococcus pneumoniae. Eighty-seven (66.9%) isolates were from children younger than five years of age, seventeen (13.1%) were from children aged 6-10 years, and twenty-six (20%) were from children aged 11-15 years. The five most common serogroups/serotypes isolated were 6 (6A, 6B, 6C) (46.1%), 23 (23F, 23A, 23B) (14.6%), 19 (19F, 19A, 19B, 19C) (8.5%), 15 (15F, 15A, 15B, 15C) (6.9%), and 14 (6.1%). Vaccine serotype coverages in pneumococcal conjugate vaccines (PCV):PCV7, PCV10, and PCV13 were 79.1%, 83.6%, and 85.9%, respectively. There were significant increases in coverage between PCV7 and PCV10 (from 79.1% to 83.6%, p < 0.001), PCV7 and PCV13 (from 79.1% to 85.9%, p < 0.001), and PCV10 and PCV13 (from 83.6% to 85.9%, p < 0.001). The majority of pneumococcal serogroup/serotype colonization in the nasopharynx of Thai children in the studied areas was included in the current licensed pneumococcal conjugated vaccines (PCVs). PCV vaccination should be considered for high-risk children to reduce the incidence of invasive pneumococcal disease among Thai children.

A Comparison of Colistin versus Colistin Plus Meropenem for the Treatment of Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients: A Propensity Score-Matched Analysis.

Carbapenem-resistant Acinetobacter baumannii (CRAB), an important nosocomial pathogen, occurs particularly in the intensive care unit (ICU). Thus, the aim of this study was to compare the efficacy and safety of documented treatment with colistin monotherapy versus colistin plus meropenem in critically ill patients with CRAB infections at Chiang Mai University Hospital (CMUH). We conducted a retrospective cohort study of critically ill patients with CRAB infections in an ICU from 2015 to 2017, who received colistin monotherapy versus colistin plus meropenem. After propensity score matching, an adjusted odds ratio (aOR) of a 30-day mortality rate in patients who received colistin plus meropenem was 0.43 compared to those who received colistin monotherapy (95% CI, 0.23-0.82, p = 0.01). aORs of clinical response and microbiological response were also higher in patients who received colistin plus meropenem (1.81, 95% CI 1.01-3.26, p = 0.048 and 2.08, 95% CI 1.11-3.91, p = 0.023, respectively). There was no significant difference in nephrotoxicity (aOR, 0.76, 95% CI, 0.43-1.36, p = 0.363) between colistin monotherapy and colistin plus meropenem. In conclusion, the addition of meropenem to colistin caused a reduction in 30-day mortality, higher clinical and microbiological responses, and did not increase nephrotoxicity compared to colistin monotherapy. Furthermore, 30-day mortality was significantly related with age, receiving vasopressor, having malignancy, and the APACHE II score.