From Epidemiology of Community-Onset Bloodstream Infections to the Development of Empirical Antimicrobial Treatment-Decision Algorithm in a Region with High Burden of Antimicrobial Resistance.

Antimicrobial-resistant (AMR) infections have increased in community settings. Our objectives were to study the epidemiology of community-onset bloodstream infections (BSIs), identify risk factors for AMR-BSI and mortality-related factors, and develop the empirical antimicrobial treatment-decision algorithm. All adult, positive blood cultures at the emergency room and outpatient clinics were evaluated from 08/2021 to 04/2022. AMR was defined as the resistance of organisms to an antimicrobial to which they were previously sensitive. A total of 1151 positive blood cultures were identified. There were 450 initial episodes of bacterial BSI, and 114 BSIs (25%) were AMR-BSI. Non-susceptibility to ceftriaxone was detected in 40.9% of 195 E. coli isolates and 16.4% among 67 K. pneumoniae isolates. A treatment-decision algorithm was developed using the independent risk factors for AMR-BSI: presence of multidrug-resistant organisms (MDROs) within 90 days (aOR 3.63), prior antimicrobial exposure within 90 days (aOR 1.94), and urinary source (aOR 1.79). The positive and negative predictive values were 53.3% and 83.2%, respectively. The C-statistic was 0.73. Factors significantly associated with 30-day all-cause mortality were Pitt bacteremia score (aHR 1.39), solid malignancy (aHR 2.61), and urinary source (aHR 0.30). In conclusion, one-fourth of community-onset BSI were antimicrobial-resistant, and one-third of Enterobacteriaceae were non-susceptible to ceftriaxone. Treatment-decision algorithms may reduce overly broad antimicrobial treatment.

In Vitro Activity of Cefiderocol, Cefepime-Zidebactam, and ß-Lactam Combinations Versus Other Antibiotic Classes Against Various Sequence Types of Clinically Isolated Carbapenemase-Producing Klebsiella pneumoniae.

Aim: This study aimed to establish the in vitro efficacy and susceptibility profiles of new ß-lactam antibiotics against clinically isolated carbapenemase-producing Klebsiella pneumoniae (CPKP) strains. Materials and Methods: A total of 117 nonduplicated CPKP isolates were tested against cefiderocol, cefepime-zidebactam, ceftazidime-avibactam, tigecycline, and other 20 antibiotics by broth microdilution. The carbapenemase genes were identified using PCR and sequencing, while multilocus sequence typing established the bacterial strains. Results: Three significant sequence types (STs), including ST147, ST16, and ST11, were shown to be the dominant STs, which occupied ∼90% of the tested population. Three carbapenemase genes, blaNDM-1, blaOXA-181, and blaOXA-232, were detected. The blaNDM-1 was found in ST147 and ST16 but not in ST11, while the blaOXA-232 was not detected in ST147. The majority of ST16 isolates contained both blaNDM-1 and blaOXA-232, which was not seen in other strains. Cefiderocol, cefepime-zidebactam, and tigecycline were the most active agents against CPKP. Both MIC50 and MIC90 of these three antibiotics remained within the susceptible categories, while nearly all other antibiotics were in the resistant levels. However, in ST11, which carried only blaOXA genes without blaNDM-1, ceftazidime-avibactam was effective with the MIC90 at 2 µg/mL. In addition, amikacin was shown to have good activity in ST11. In contrast, gentamicin was active in only ST16 and ST147. Conclusions: This study is the first report that demonstrates the prevalence of CPKP, distribution of strains, resistant genes, and antimicrobial susceptibility profiles in northern Thailand. These data would contribute to appropriate individual treatment and the selection of infection control strategies.

Rapid screening and early precautions for carbapenem-resistant Acinetobacter baumannii carriers decreased nosocomial transmission in hospital settings: a quasi-experimental study.

Background: Active surveillance has the potential to prevent nosocomial transmission of carbapenem-resistant Acinetobacter baumannii (CRAB). We assessed whether rapid diagnosis using clinical specimen-direct loop-mediated isothermal amplification (LAMP), a rapid molecular diagnostic assay, and subsequent intervention, could reduce CRAB nosocomial transmission in intensive care units (ICUs). Methods: A before and after (quasi-experimental) study was conducted in two ICUs at the Mahidol University Faculty of Medicine Ramathibodi Hospital with 3 months of observational period followed by 9 months of interventional period. All patients were screened for CRAB using both the culture and LAMP method from rectal swab and/or bronchial aspirates (intubated patients only) upon admission, weekly thereafter, and upon discharge. During the pre-intervention period, we performed contact precautions based on culture results. In contrast, during the intervention period, we initiated contact precautions within a few hours after sample collection on the basis of LAMP results. Results: A total of 1335 patients were admitted to the ICUs, of which 866 patients (pre-intervention period: 187; intervention period: 679) were eligible for this study. Incidence rate of CRAB infection decreased to 20.9 per 1000 patient-days in the intervention period from 35.2 in the pre-intervention period (P < 0.02). The calculated hazard ratio of CRAB transmission was 0.65 (95% confidence interval [CI], 0.44-0.97). Risk factors for CRAB acquisition included exposure to carbapenem (hazard ratio, 2.54 [95% CI: 1.61-5.57]). Conclusions: LAMP screening for CRAB upon ICU admission proved feasible for routine clinical practice. Rapid screening using LAMP followed by early intervention may reduce CRAB transmission rates in ICUs when compared to conventional intervention.

PCR-Dipstick-Oriented Surveillance and Characterization of mcr-1- and Carbapenemase-Carrying Enterobacteriaceae in a Thai Hospital.

Colistin is used as an alternative therapeutic for carbapenemase-producing Enterobacteriaceae (CPE) infections which are spreading at a very high rate due to the transfer of carbapenemase genes through mobile genetic elements. Due to the emergence of mcr-1, the plasmid-mediated colistin resistance gene, mcr-1-positive Enterobacteriaceae (MCRPEn) pose a high risk for the transfer of mcr-1-carrying plasmid to CPE, leading to a situation with no treatment alternatives for infections caused by Enterobacteriaceae possessing both mcr-1 and carbapenemase genes. Here, we report the application of PCR-dipstick-oriented surveillance strategy to control MCRPEn and CPE by conducting the PCR-dipstick technique for the detection of MCRPEn and CPE in a tertiary care hospital in Thailand and comparing its efficacy with conventional surveillance method. Our surveillance results showed a high MCRPEn (5.9%) and CPE (8.7%) carriage rate among the 219 rectal swab specimens examined. Three different CPE clones were determined by pulsed-field gel electrophoresis (PFGE) whereas only two MCRPEn isolates were found to be closely related as shown by single nucleotide polymorphism-based phylogenetic analysis. Whole genome sequencing (WGS) and plasmid analysis showed that MCRPEn carried mcr-1 in two plasmids types-IncX4 and IncI2 with ~99% identity to the previously reported mcr-1-carrying plasmids. The identification of both MCRPEn and CPE in the same specimen indicates the plausibility of plasmid-mediated transfer of mcr-1 genes leading to the emergence of colistin- and carbapenem-resistant Enterobacteriaceae. The rapidity (<2 h) and robust sensitivity (100%)/specificity (~99%) of PCR-dipstick show that this specimen-direct screening method could aid in implementing infection control measures at the earliest to control the dissemination of MCRPEn and CPE.

PCR-Dipstick Chromatography for Differential Detection of Carbapenemase Genes Directly in Stool Specimens.

A PCR-dipstick chromatography technique was designed and evaluated for differential identification of blaNDM, blaKPC, blaIMP, and blaOXA-48 carbapenemase genes directly in stool specimens within 2 h. It is a DNA-DNA hybridization-based detection system where PCR products can be easily interpreted by visual observation without electrophoresis. The PCR-dipstick showed high sensitivity (93.3%) and specificity (99.1%) in directly detecting carbapenemase genes in stool specimens compared with multiplex PCR for genomic DNA of the isolates from those stool specimens.

EPIDEMIOLOGY AND CONTROL OF THE FIRST REPORTED VANCOMYCIN-RESISTANT ENTEROCOCCUS OUTBREAK AT A TERTIARY-CARE HOSPITAL IN BANGKOK, THAILAND.

This retrospective study described the first reported vancomycin-resistant enterococci (VRE) outbreak from June 2013 through January 2014 at a tertiary-care hospital in Bangkok, Thailand. After the index case was detected in an 18-bed medical intermediate care unit, a number of interventions was implemented, including targeted active surveillance for VRE, strict contact precautions, enhanced standard precautions, dedicated units for VRE cases, extensive cleaning of the environment and the restricted use of antibiotics. VRE isolates were evaluated by polymerase chain reaction and random amplified polymorphic DNA (RAPD) testing. A prevalence case-control study was conducted. Among 3,699 culture samples from 2,671 patients screened, 74 patients (2.8%) had VRE. The positivity rate declined from 15.1% during week 1 to 8.2% during week 2 and then 1.4% during week 3. By weeks 4-9, the prevalences were 0-2.7%. However, the prevalence rose to 9.4% during week 10 and then subsequently declined. All VRE isolates were Enterococcus faecium and had the vanA gene. RAPD analysis revealed a single predominant clone. Multivariate analysis showed mechanical ventilation for ≥ 7 days was a predictive factor for VRE colonization [odds ratio (OR) 11.47; 95% confidence interval (CI): 1.75-75.35; p = 0.011]. This experience demonstrates VRE can easily spread and result in an outbreak in multiple-bed units. Active surveillance, early infection control interventions and rapid patient cohorting were important tools for control of this outbreak. Patients requiring mechanical ventilator for ≥ 7 days were at higher risk for VRE acquisition.