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.

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.

Safety and Tolerability of V114 Pneumococcal Vaccine in Infants: A Phase 3 Study.

BACKGROUND AND OBJECTIVES: Disease caused by Streptococcus pneumoniae is associated with considerable morbidity and mortality in children. Pneumococcal conjugate vaccines (PCVs) are well tolerated and effective at reducing pneumococcal disease caused by vaccine serotypes. VAXNEUVANCE (V114) is a 15-valent PCV containing 13 serotypes in Prevnar 13 (PCV13), plus serotypes 22F and 33F. This large phase 3 study evaluated safety and tolerability of V114 in infants. METHODS: In total, 2409 infants were randomized to receive V114 or PCV13 at 2, 4, 6, and 12 to 15 months of age. Safety was evaluated as the proportion of participants with adverse events (AEs). Solicited and unsolicited injection-site and systemic AEs were collected for 14 days after each study vaccination, and serious AEs up to 6 months after the last PCV dose. RESULTS: The proportions of participants with injection-site, systemic, vaccine-related, and serious AEs were generally comparable between recipients of V114 and PCV13. The most frequently reported AEs were solicited, with irritability and somnolence being the most frequent in both groups. Although the incidence of some AEs was higher in the V114 group, the between-group differences were small. The majority of experienced AEs were of mild-to-moderate intensity and lasted ≤3 days. There were 2 vaccine-related serious AEs of pyrexia in the V114 group, and 2 nonvaccine-related deaths, 1 in each group. No participant discontinued study vaccine because of AEs. CONCLUSIONS: V114 is well tolerated and has a generally comparable safety profile to that of PCV13. These study results support routine use of V114 in infants.

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.

A phase 3, multicenter, randomized, double-blind study to evaluate the interchangeability of V114, a 15-valent pneumococcal conjugate vaccine, and PCV13 with respect to safety, tolerability, and immunogenicity in healthy infants (PNEU-DIRECTION).

BACKGROUND: Pneumococcal disease (PD) remains a major health concern globally. In children, pneumococcal conjugate vaccines (PCVs) provide protection against PD from most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and public health important serotypes 22F and 33F. This phase 3 study evaluated safety and immunogenicity of mixed PCV13/V114 regimens using a 3 + 1 dosing schedule when changing from PCV13 to V114 at doses 2, 3, or 4. METHODS: 900 healthy infants were randomized equally to 5 intervention groups. PCVs were administered in a 3-dose infant series at 2, 4, and 6 months of age followed by a toddler dose at 12-15 months along with concomitant routine vaccines. Safety was evaluated as the proportion of participants with adverse events (AEs). Immunoglobulin G (IgG) responses to the 15 serotypes in V114 were measured at 30 days post-dose 3 and 30 days post-dose 4 (PD4). RESULTS: Frequencies of injection-site and systemic AEs were generally comparable across all intervention groups. At 30 days PD4 (primary endpoint), IgG geometric mean concentrations (GMCs) for the 13 shared serotypes were generally comparable between mixed V114/PCV13 and 4-dose regimens of PCV13 or V114. In mixed regimens at 30 days PD4, a toddler dose of V114 was sufficient to achieve IgG GMCs comparable to a 4-dose regimen of V114 for serotype 22F, while at least one infant dose was needed in addition to the toddler dose to achieve IgG GMCs comparable to a 4-dose regimen of V114 for serotype 33F. CONCLUSIONS: V114 was well tolerated with a generally comparable safety profile to PCV13. For 13 shared serotypes, both mixed regimens and the V114 4-dose regimen induced generally comparable antibody responses to 4-dose regimen with PCV13. Study results support interchangeability of V114 with PCV13 in infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03620162; EudraCT: 2018-001151-12.

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.

Clinical and economic outcomes attributable to carbapenem-resistant Enterobacterales and delayed appropriate antibiotic therapy in hospitalized patients.

OBJECTIVE: To assess the impact of carbapenem resistance and delayed appropriate antibiotic therapy (DAAT) on clinical and economic outcomes among patients with Enterobacterales infection. METHODS: This retrospective cohort study was conducted in a tertiary-care medical center in Thailand. Hospitalized patients with Enterobacterales infection were included. Infections were classified as carbapenem-resistant Enterobacterales (CRE) or carbapenem-susceptible Enterobacterales (CSE). Multivariate Cox proportional hazard modeling was used to examine the association between CRE with DAAT and 30-day mortality. Generalized linear models were used to examine length of stay (LOS) and in-hospital costs. RESULTS: In total, 4,509 patients with Enterobacterales infection (age, mean 65.2 ±18.7 years; 43.3% male) were included; 627 patients (13.9%) had CRE infection. Among these CRE patients, 88.2% received DAAT. CRE was associated with additional medication costs of $177 (95% confidence interval [CI], 114­239; P < .001) and additional in-hospital costs of $725 (95% CI, 448­1,002; P < .001). Patients with CRE infections had significantly longer LOS and higher mortality rates than patients with CSE infections: attributable LOS, 7.3 days (95% CI, 5.4­9.1; P < .001) and adjusted hazard ratios (aHR), 1.55 (95% CI, 1.26­1.89; P < .001). CRE with DAAT were associated with significantly longer LOS, higher mortality rates, and in-hospital costs. CONCLUSION: CRE and DAAT are associated with worse clinical outcomes and higher in-hospital costs among hospitalized patients in a tertiary-care hospital in Thailand.

Safety and Immunogenicity of a New Inactivated Polio Vaccine Made From Sabin Strains: A Randomized, Double-Blind, Active-Controlled, Phase 2/3 Seamless Study.

BACKGROUND: A new inactivated polio vaccine made from Sabin strains (sIPV) was developed as part of the global polio eradication initiative. METHODS: This randomized, double-blind, active-controlled, phase 2/3 seamless study was conducted in 2 stages. Healthy infants aged 6 weeks were randomly assigned to receive 3 doses of 1 of 4 study vaccines at 6, 10, and 14 weeks of age (336 received low-, middle-, or high-dose sIPV, or conventional IPV [cIPV] in stage I, and 1086 received lot A, B, or C of the selected sIPV dose, or cIPV in stage II). The primary outcome was the seroconversion rate 4 weeks after the third vaccination. RESULTS: In stage I, low-dose sIPV was selected as the optimal dose. In stage II, consistency among the 3 manufacturing lots of sIPV was demonstrated. The seroconversion rates for Sabin and wild strains of the 3 serotypes after the 3-dose primary series were 95.8% to 99.2% in the lot-combined sIPV group and 94.8% to 100% in the cIPV group, proving the noninferiority of sIPV compared to cIPV. No notable safety risks associated with sIPV were observed. CONCLUSIONS: Low-dose sIPV administered as a 3-dose vaccination was safe and immunogenic compared to cIPV. CLINICAL TRIALS REGISTRATION: NCT03169725.

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.

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.

Immunogenicity and safety profiles of a new MAV/06 strain varicella vaccine in healthy children: A multinational, multicenter, randomized, double-blinded, active-controlled phase III study.

Immunization is the most effective preventive strategy against varicella. While the Oka strain is commonly used for varicella vaccination worldwide, Korea widely uses the MAV/06 strain. A new live attenuated MAV/06 strain varicella vaccine (MG1111), which uses the new cell line Medical Research Council-5 for better viral propagation, was developed. MG1111 was approved by Korean health authorities. Here, we report the results of phase III, randomized, double-blind, multicenter study conducted in Korea and Thailand, which compared the immunogenicity and safety profiles of MG1111 versus the control vaccine, VarivaxTM. In total, 515 healthy children (12 month-12 years) were randomized 1:1 to receive either the MG1111 or control vaccine (MG1111: 258, Control: 257). The seroconversion rate (SCR) and geometric mean titer (GMT) were measured using the fluorescent antibody to membrane antigen (FAMA) test. The MG1111 group achieved a SCR of 97.9% (95% CI: 95.2-99.3) after vaccination. The lower limit of 95% CI for SCR difference (MG1111-VarivaxTM) was -4.0%, which was higher than the specified non-inferiority margin of -10%. Further, the GMT of the MG1111 increased from 2.0 to 74.2 (95% CI: 65.0-84.8) and the lower limits of the 95% CI for post-vaccination GMT ratios (MG1111/VarivaxTM) were 0.55 higher than the specified parameter of 0.5. Therefore, the MG1111 group was not statistically inferior to the control vaccine group in terms of SCR and GMT. Furthermore, the MG1111 and control vaccine groups were not significantly different in the percentage of participants showing adverse events-solicited, local, or systemic during 43-day period of observation and serious adverse events during 6 month of observation. The present results indicate that MG1111was not immunologically inferior to VarivaxTM, and safety profiles of MG1111 are similar to those of VarivaxTM.

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.

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.

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.

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.

The effectiveness and nephrotoxicity of loading dose colistin combined with or without meropenem for the treatment of carbapenem-resistant A. baumannii.

INTRODUCTION: Acinetobacter baumannii has emerged as an important nosocomial pathogen worldwide. In Thailand, the incidence and mortality rate of carbapenem-resistant A. baumannii (CRAB) is continuously increasing. This organism is a common pathogen that can cause HAP and VAP. CRAB tends to be susceptible to only colistin, so colistin would be the last line of treatment for CRAB. The recent data from in-vitro studies found that colistin and meropenem combination therapy could exert synergistic effects. However, some in-vivo studies have shown no significant difference in antibacterial effect between colistin monotherapy and colistin plus meropenem. Moreover, the clinical data are recently limited and not clear. Thus, the objective of this study was to compare clinical outcome, microbiological response, mortality rate and nephrotoxicity between loading dose (LD) colistin monotherapy and LD colistin-meropenem for treatment of infection caused by CRAB in Maharaj Nakorn Chiang Mai Hospital. MATERIALS AND METHODS: This study is a retrospective analytical study. The data were collected from patients who received LD colistin monotherapy or LD colistin plus meropenem combination therapy for treatment of CRAB from 1 January 2013 to 31 August 2017 at Maharaj Nakorn Chiang Mai Hospital. A total of 324 patients met the inclusion criteria. The data were analyzed by descriptive statistics and inferential statistics, and were adjusted for confounding factors by logistic regression analysis. RESULTS: The adjusted OR of good clinical outcome of patients who received LD colistin plus meropenem was 1.05 times that of patients who received loading dose colistin monotherapy (95%CI 0.62-1.74, p=0.860). Patients who received LD colistin plus meropenem had 0.93 times (adjusted OR) mortality rate at the end of treatment compared to patients who received LD colistin monotherapy (95%CI=0.51-1.71, p=0.935). In addition, microbiological response was defined as eradication of pre-treatment isolated pathogens in post-treatment cultures. Patients who received LD colistin plus meropenem could eradicate pathogens 1.28 times more than LD colistin monotherapy (95% CI=0.74-2.20, p=0.371). Also there was no significant difference in nephrotoxicity (adjusted OR=0.84, 95% CI 0.52-1.36, p=0.492) between LD colistin monotherapy and LD colistin plus meropenem. CONCLUSION: There were no significant differences in effectiveness and nephrotoxicity of LD colistin monotherapy versus LD colistin plus meropenem for treatment of CRAB infection, so colistin combination therapy was not necessary for the management of infection caused by CRAB.