High Prevalence of Panton-Valentine Leukocidin Among Staphylococcus aureus Causing Acute Hematogenous Bone and Joint Infections From a Tertiary Children's Hospital in Vietnam.

BACKGROUND: We aimed to investigate the clinical features, antimicrobial susceptibility and pvl gene expression in Staphylococcus aureus causing acute hematogenous bone and joint infections (BJIs) in children in Vietnam. METHODS: In this prospective study, the demographics, microbiology and clinical outcomes of pediatric patients with acute hematogenous BJIs were collected from September 2022 to September 2023. Antimicrobial susceptibility profiles were determined using VITEK2 Compact system. The pvl gene encoding the Panton-Valentine leukocidin (PVL) toxin was detected by using polymerase chain reaction. Mann-Whitney, χ2 and Fisher test were used for statistical analysis. RESULTS: In total, 78 patients (46 boys) with S. aureus acute hematogenous BJIs were recruited at the National Children's Hospital, Hanoi, Vietnam. Of all S. aureus isolates, 84.6% were methicillin-resistant S. aureus. All S. aureus isolates were susceptible to vancomycin, ciprofloxacin and levofloxacin; 97% of methicillin-resistant S. aureus isolates was resistant to clindamycin (minimum inhibitory concentration ≥8 µg/mL). The pvl gene was detected in 83.3% of isolates, including 57 methicillin-resistant S. aureus isolates. Patients in the pvl-positive group had significantly higher C-reactive protein levels than those in the pvl-negative group (P = 0.04). In addition, all 8 children with septic shock were infected with pvl-positive S. aureus. CONCLUSIONS: PVL is a prevalent virulence factor of S. aureus in Vietnam. Furthermore, high inflammatory parameters (C-reactive protein) may be present at the time of diagnosis in PVL positivity-related acute hematogenous BJIs. Further research is necessary to enhance our understanding of the varying correlations between virulence factors and outcomes of S. aureus BJIs.

Antibiotic Resistance, Biofilm Formation, and Persistent Phenotype of Klebsiella pneumoniae in a Vietnamese Tertiary Hospital: A Focus on Amikacin.

Klebsiella pneumoniae stands out as a major opportunistic pathogen responsible for both hospital- and community-acquired bacterial infections. This study comprehensively assesses the antibiotic resistance, amikacin persistent patterns, and biofilm-forming ability of 247 isolates of K. pneumoniae obtained from an intensive care unit of a tertiary hospital in Vietnam. Microdilution assays, conducted on a 96-well plate, determined the minimum inhibitory concentrations (MICs) of amikacin. Susceptibility data for other antibiotics were gathered from the antibiogram profile. Stationary-phase bacteria were exposed to 50 × MIC, and viable bacteria counts were measured to determine amikacin persistence. Biofilm forming capacity on 96-well polystyrene surfaces was assessed by biomass and viable bacteria. The prevalence of resistance was notably high across most antibiotics, with 64.8% classified as carbapenem-resistant K. pneumoniae and 81.4% as multidrug resistant. Amikacin, however, exhibited a relatively low rate of resistance. Of the isolates, 58.2% demonstrated a moderate to strong biofilm formation capacity, and these were found to be poorly responsive to amikacin. K. pneumoniae reveals a significant inclination for amikacin persistence, with ∼45% of isolates displaying an antibiotic antibiotic-survival ratio exceeding 10%. The study sheds light on challenges in treating of K. pneumoniae infection in Vietnam, encompassing a high prevalence of antibiotic resistance, a substantial ability to form biofilm, and a notable rate of antibiotic persistence.

Optimizing Meropenem in Highly Resistant Klebsiella pneumoniae Environments: Population Pharmacokinetics and Dosing Simulations in Critically Ill Patients.

Critically ill patients are characterized by substantial pathophysiological changes that alter the pharmacokinetics (PK) of hydrophilic antibiotics, including carbapenems. Meropenem is a key antibiotic for multidrug-resistant Gram-negative bacilli, and such pathophysiological alterations can worsen treatment outcomes. This study aimed to determine the population PK of meropenem and to propose optimized dosing regimens for the treatment of multidrug-resistant Klebsiella pneumoniae in critically ill patients. Two plasma samples were collected from eligible patients over a dosing interval. Nonparametric population PK modeling was performed using Pmetrics. Monte Carlo simulations were applied to different dosing regimens to determine the probability of target attainment and the cumulative fraction of response, taking into account the local MIC distribution for K. pneumoniae. The targets of 40% and 100% for the fraction of time that free drug concentrations remained above the MIC (ƒT>MIC) were tested, as suggested for critically ill patients. A one-compartment PK model using data from 27 patients showed high interindividual variability. Significant PK covariates were the 8-h creatinine clearance for meropenem and the presence of an indwelling catheter for pleural, abdominal, or cerebrospinal fluid drainage for the meropenem volume of distribution. The target 100% ƒT>MIC for K. pneumoniae, with a MIC of ≤2 mg/liter, could be attained by the use of a continuous infusion of 2.0 g/day. Meropenem therapy in critically ill patients could be optimized for K. pneumoniae isolates with an MIC of ≤2 mg/liter by using a continuous infusion in settings with more than 50% isolates have a MIC of ≥32mg/L.

Predicting mortality in intensive care unit patients infected with Klebsiella pneumoniae: A retrospective cohort study.

INTRODUCTION: Although several models to predict intensive care unit (ICU) mortality are available, their performance decreases in certain subpopulations because specific factors are not included. Moreover, these models often involve complex techniques and are not applicable in low-resource settings. We developed a prediction model and simplified risk score to predict 14-day mortality in ICU patients infected with Klebsiella pneumoniae. METHODOLOGY: A retrospective cohort study was conducted using data of ICU patients infected with Klebsiella pneumoniae at the largest tertiary hospital in Northern Vietnam during 2016-2018. Logistic regression was used to develop our prediction model. Model performance was assessed by calibration (area under the receiver operating characteristic curve-AUC) and discrimination (Hosmer-Lemeshow goodness-of-fit test). A simplified risk score was also constructed. RESULTS: Two hundred forty-nine patients were included, with an overall 14-day mortality of 28.9%. The final prediction model comprised six predictors: age, referral route, SOFA score, central venous catheter, intracerebral haemorrhage surgery and absence of adjunctive therapy. The model showed high predictive accuracy (AUC = 0.83; p-value Hosmer-Lemeshow test = 0.92). The risk score has a range of 0-12 corresponding to mortality risk 0-100%, which produced similar predictive performance as the original model. CONCLUSIONS: The developed prediction model and risk score provide an objective quantitative estimation of individual 14-day mortality in ICU patients infected with Klebsiella pneumoniae. The tool is highly applicable in practice to help facilitate patient stratification and management, evaluation of further interventions and allocation of resources and care, especially in low-resource settings where electronic systems to support complex models are missing.

Whole exome sequencing revealed a pathogenic variant in a gene related to malignant hyperthermia in a Vietnamese cardiac surgical patient: A case report.

INTRODUCTION: Malignant hyperthermia (MH) is a rare autosomal dominant pharmacogenetic disorder which known associated with some genes such as CACNA1S and RYR1. Using whole exome analysis, we aimed to find out the genetic variant data in a malignant hyperthermia patient undergoing cardiac surgery. PRESENTATION OF CASE: Patient was 59 years old male with dull left chest pain, mild breathing difficulty, thrombosis in the left atrium, mitral valve stenosis that needed a surgery to remove the thrombus and replace the mitral valve. After 5-h operation of left mitral heart valve replacement using both intravenous and inhaled anaesthetics, the patient showed suddenly hyperthermia (39.5 °C), low blood pressure (90/50 mmHg), heavy sweating, 1 mm dilated pupils on both sides, positive light reflection. Whole exome analysis showed 96,286 of SNPs including 11,705 of synonymous variants, 11,388 of missense variants, 106 of stop gained, and 39 of stop lost. One variant of RYR1 gene was found as mutation point at c.7048G > A (p.Ala2350Thr) known related to MH. DISCUSSION: This was a rare case of MH during cardiac surgery reported in Vietnam that might related to mutation point at c.7048G > A (p.Ala2350Thr) of RYR1 gene. CONCLUSION: Patient carried a mutant of RYR1 gene could possibly lead to MH development post anaesthesia of cardiac surgery.

Phylogeny and species identification of the family Enterobacteriaceae based on dnaJ sequences.

Phylogenetic relations within the family Enterobacteriaceae were analyzed using partial dnaJ sequences of 165 strains belonging to 93 species from 27 enterobacterial genera. The dnaJ phylogeny was in relative agreement with that constructed by 16S rDNA sequences, but more monophyletic groups were obtained from the dnaJ tree than from the 16S rDNA tree. The degree of divergence of the dnaJ gene was approximately 6 times greater than that of 16S rDNA. Also, the dnaJ gene showed the most discriminatory power in comparison with tuf and atpD genes, facilitating clear differentiation of any 2 enterobacterial species by dnaJ sequence analysis. The application of dnaJ sequences to the identification was confirmed by assigning 72 clinical isolates to the correct enterobacterial species. Our data indicate that analysis of the dnaJ gene sequences can be used as a powerful marker for phylogenetic study and identification at the species level of the family Enterobacteriaceae.