JAC-Antimicrobial Resistance最新文献

Background: Bloodstream infections (BSIs) cause significant morbidity and mortality in solid organ transplant (SOT) recipients. There are few data regarding the contribution of MDR organisms (MDROs) to these infections. We evaluated the resistance percentage of MDRO BSIs in SOT recipients and the associated mortality.

Methods: A systematic review of MEDLINE and Embase databases up to January 2024, for studies of adult SOT recipients that quantified MDRO BSI resistance percentage and/or associated crude mortality. MDROs studied were carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA), third-generation cephalosporin-resistant Enterobacterales (3GCR-E), MRSA and VRE. Resistance percentage and mortality outcomes were reported as median (IQR) and crude mortality (%), respectively.

Results: Of 945 studies identified, 52 were included. Most were retrospective (41/52) and/or single centre (37/52), and liver transplantation was the most frequently studied SOT type (22/52). High resistance percentages of BSIs were noted, ranging from 13.6% CRE for Enterobacterales to 59.2% CRAB for A. baumannii. Resistance percentage trends decreased over time, but these changes were not statistically significant. Asia had the highest resistance percentages for MRSA [86.2% (IQR 77.3%-94.6%)], 3GCR-E [59.5% (IQR 40.5%-66.7%)] and CRE [35.7% (IQR 8.3%-63.1%)]. North America had the highest VRE resistance percentages [77.7% (IQR 54.6%-94.7%)]. Crude mortality was 15.4%-82.4% and was consistently higher than for non-MDRO BSIs.

Conclusions: MDRO BSI resistance percentages were high for all pathogens studied (IQR 24.6%-69.4%) but there was geographical and temporal heterogeneity. MDRO BSIs were associated with high mortality in SOT recipients. Microbiological and clinical data in this vulnerable population were incomplete, highlighting the need for robust international multicentre studies.

Background: Antimicrobial resistance is a global health threat resulting in significant morbidity and mortality worldwide. Until recently, in Ukraine, cumulative antibiograms (CuAbgms) have never been available.

Objectives: To describe the first CuAbgm developed in Ukraine.

Methods: We developed a CuAbgm for the Okhmatdyt National Specialized Children's Hospital using data from WHONET. Antimicrobial susceptibility testing was performed per EUCAST guidelines. The CuAbgm was developed using guidance from CLSI.

Results: For Escherichia coli, 66% and 69% of isolates were susceptible to ceftazidime and ceftriaxone, respectively, and 99% were susceptible to meropenem. For Klebsiella pneumoniae, 26% and 27% of isolates were susceptible to ceftazidime and ceftriaxone, respectively, and only 59% were susceptible to meropenem. Of the carbapenem-resistant K. pneumoniae isolates that underwent additional susceptibility testing, only 38% were susceptible to ceftazidime/avibactam. For Pseudomonas aeruginosa, only 53% were susceptible to meropenem. Of those that were resistant to meropenem and underwent additional susceptibility testing, only 12% were susceptible to ceftazidime/avibactam. Similarly, for Acinetobacter spp., only 37% of isolates were susceptible to meropenem. Susceptibility to ampicillin/sulbactam was also low at 45%. The oxacillin susceptibility rate for Staphylococcus aureus was 99%.

Conclusions: In this first-ever CuAbgm developed in Ukraine, high levels of resistance were demonstrated among Gram-negative bacteria. CuAbgms should be prioritized in laboratories in Ukraine to guide empirical antimicrobial therapy, infection control and antimicrobial stewardship policies. This is of heightened relevance during wartime, when there is a need for healthcare systems to treat complex and infected penetrating and blast-related injuries.

Objectives: The recent emergence of fusidic acid (FA)-resistant Staphylococcus aureus has underscored the importance of active surveillance in isolating these strains. The molecular basis of fusidic acid resistance and the carriage of virulence factors in four borderline oxacillin-resistant Staphylococcus aureus (BORSA) clinical strains was assessed through phenotypical and genotypical methods.

Methods: All S. aureus clinical strains were obtained from various hospital units in Sicily. In vitro antibiotic susceptibility testing was conducted. WGS was performed using the Illumina MiSeq Platform, and data analysis was carried out to determine ST, resistome and virulome profiles.

Results: Genotypic characterization revealed that the strains belong to four STs: ST630, ST8, ST15, and ST1. FA resistance was associated with mutations in the fusA gene or fusB and fusC genes. Additionally, one case exhibited resistance to mupirocin, related to the presence of the mupA gene. Borderline MIC values were observed for cefoxitin in three out of four cases, leading to their categorization as BORSA. Virulence gene content was complex and diversified, with one testing positive for the lukS/F genes, coding for PVL toxin.

Conclusions: Resistance to FA is multifactorial, involving point mutations in chromosomal genes or association with mobile genetic elements. Monitoring the resistance to these antibiotics might help to manage and eradicate mupirocin- and FA-resistant S. aureus strains, which are also known to be important carriers of virulence determinants.

Objectives: EUCAST has established clinical breakpoints and epidemiological cutoff values (ECOFFs) for Candida spp. However, limited data are available for 5-flucytosine (5-FC). We assessed the in vitro susceptibility of 5-FC against a large collection of clinical Candida species using EUCAST methodology and determined the associated ECOFFs.

Methods: A total of 5622 Candida isolates were collected from patients across the Netherlands between 2008 and 2024. 5-FC MICs were determined using the EUCAST microbroth dilution reference method. Furthermore, MICs were extracted from the EUCAST website. The MICs from this study and those extracted were used to determine ECOFFs and local ECOFFs (L-ECOFFs).

Results: 5-FC exhibited potent in vitro activity against C. albicans, N. glabratus and C. parapsilosis, while decreased susceptibility was observed for C. tropicalis, Pichia species, K. marxianus, Y. lipolytica, and C. auris. The ECOFFs (mg/L) and the percentages of WT isolates for 5-FC were: C. albicans: 0.5 (97.2%), N. glabratus: 0.5 (96.6%), C. parapsilosis: 0.5 (99.5%) and P. kudriavzevii: 8 (99.4%). The L-ECOFF (mg/L) and the percentages of WT isolates for 5-FC were: C. dubliniensis: 0.25 (96.8%), C. tropicalis: 0.25 (67.2%), K. marxianus: 0.25 (48.0%), C. lusitaniae: 0.25 (86.5%), M. guillermondii: 0.125 (95.9%) and P. norvegiensis: 8 (94.2%).

Conclusions: 5-FC remains a valuable drug to manage difficult-to-treat invasive Candida infections. In vitro susceptibility cannot be predicted based on species identification for most Candida species, but requires MIC-testing. ECOFFs will help to interpret the MICs to support treatment decisions.

Life-saving immunosuppressive treatments including intensive chemotherapy and bone marrow transplantation expose patients to a considerable risk of death from infection globally. With evolving AMR and transmission, this could spell disaster for patients across the world and society at large. Antimicrobial stewardship (AMS) and prompt appropriate management of potentially fatal, emergent infections are essential. It is now apparent that antibacterial prophylaxis in patients with haematological cancer may not provide survival benefit while simultaneously increasing risks for AMR carriage. With evolving AMR and increasing immunosuppressed populations across the world, we must institute robust AMS practices. Significant resources are used to combat the impact of AMR on immunosuppressed patients. For lower-middle income countries (LMICs) these resources may not be available and as such the impact caused by AMR is greater. By considering the patient journey holistically we consider risk of infection presented to patients temporally and geographically. A short-term and easy to implement approach of multi-disciplinary team (MDT)-style advance care planning for infection is advocated. Antimicrobials, when used appropriately, enable healthcare procedures to occur and exist. Indeed, the very future of clinical medicine will rely on this yet to be realized value of enablement. Proactive effort and change must occur across all sectors with holism; hence our impetus for convening a joint industry and clinical working group. With at-risk immunosuppressed groups being a sentinel for change, awareness and implementation of patient-centric actions for infection are essential and our recommendations serve as an urgent call to action.

Background: Antimicrobial resistance (AMR) of pathogens such as Pseudomonas aeruginosa is among the top 10 threats to global health. However, clinical and molecular data are scarce in Zambia. We, therefore, evaluated the AMR profiles of P. aeruginosa nosocomial infections (NIs).

Methods: A year-long hospital-based cross-sectional study was conducted at two large tertiary-level hospitals in Zambia. Patients with current or previous hospital contact were screened for NIs. The current study focused on patients diagnosed with P. aeruginosa NIs. Clinical specimens were collected for bacteriological culture, and PCR amplification of 16S rRNA gene fragments was performed on pure isolates. Hospital or NIs were defined as infections that arise during hospitalization, occurring at least 48 h after admission. The Kirby-Bauer's disk diffusion method was used to evaluate antibiotic resistance patterns. The association between AMR and risk factors was analysed using the χ² test.

Results: Eight hundred and forty-one patients were screened, and clinical specimens were collected and analysed. Of them, 116 (13.7%) were diagnosed with P. aeruginosa NIs. The participants' ages ranged from 15 to 98 years, with a mean of 51 (SD ± 18). Catheter-associated urinary tract infections (57%) were the most common, followed by pressure sores (38.7%). P. aeruginosa isolates were primarily susceptible to amikacin, which had the highest resistance to FEP. We observed a high prevalence of multidrug resistance (73.6%). The AMR was associated with carbapenem-hydrolysing β-lactamase gene blaOXA-51 and surgical care.

Conclusions: This study has demonstrated that multidrug-resistant P. aeruginosa is prevalent in hospitals in Zambia's Lusaka and Ndola districts and possibly countrywide.

Background: Cefiderocol exhibits potent in vitro activity against carbapenem-resistant Acinetobacter baumannii (CRAb), but this activity has not consistently translated to improved outcomes among patients. Cefiderocol heteroresistance, or the presence of a resistant subpopulation, has been proposed as one possible explanation. The objective of this study was to explore associations between heteroresistance and outcomes of patients with CRAb infections.

Methods: Baseline CRAb isolates were collected from 27 consecutive patients in the USA and Italy. Cefiderocol susceptibility was tested by broth microdilutions in triplicate. Heteroresistance was defined by population analysis profiling in duplicate. Resistance mechanisms and strain relatedness were evaluated through comparative genomic analysis.

Results: Overall, 59% of infecting CRAb isolates were identified as cefiderocol-heteroresistant; rates were higher among isolates from Italy (79%) than the USA (38%). The median Charlson Comorbidity and SOFA scores were 4 and 5, respectively; 44% of patients had pneumonia, which was the most common infection type. Rates of 28-day clinical success and survival were 30% and 73%, respectively. By broth microdilution, cefiderocol MICs ≥1 mg/L were associated with higher failure rates than MICs ≤0.5 mg/L (81% versus 55%). Rates of clinical failure were numerically higher among patients infected by cefiderocol-heteroresistant compared with susceptible CRAb (81% versus 55%). Whole-genome sequencing identified a premature stop codon in the TonB-dependent receptor gene piuA in six isolates, all of which were heteroresistant.

Conclusions: This pilot study supports the hypothesis that cefiderocol treatment failure may be associated with higher MICs and/or the presence of heteroresistance. Further studies are needed to confirm these findings.

Background: Cefiderocol (FDC) or ceftazidime-avibactam with aztreonam (CZA-ATM) are frontline agents for New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales; however, clinical data are scarce, and mechanisms of treatment-emergent resistance are ill-defined. Our objectives were to characterize serial isolates and stool microbiota from a liver transplant recipient with NDM-producing Escherichia coli bacteraemia.

Methods: Isolates collected pre- and post-CZA-ATM treatment underwent broth microdilution susceptibility testing and whole-genome sequencing. Longitudinal stool collected during CZA-ATM therapy underwent metagenomic sequencing (Nanopore MinION).

Results: The baseline isolate exhibited elevated MICs for ATM-AVI (16/4 µg/mL) and FDC (8 µg/mL). Posttreatment, a rectal surveillance isolate exhibited high-level resistance to ATM-AVI (> 128/4 µg/mL) and FDC (32 µg/mL). Both isolates belonged to ST361 and harboured WT bla _NDM-5. The baseline isolate contained wild type (WT) bla _CMY-145 and mutations in ftsI (which encodes PBP3), including a YRIN insertion at residue 338 and the non-synonymous substitutions Q227H, E353K and I536L. The posttreatment isolate harboured new mutations in ftsI (A417 V) and bla _CMY-145 (L139R and N366Y). Analysis of four stool samples collected during CZA-ATM treatment revealed high E. coli abundance. E. coli relative abundance increased from 34.5% (first sample) to 61.9% (last sample).

Conclusions: Baseline mutations in ftsI were associated with reduced susceptibility to ATM-AVI and FDC in an ST361 NDM-5-producing E. coli bloodstream isolate. High-level resistance was selected after CZA-ATM treatment, resulting in new ftsl and bla _CMY-145 mutations. These findings underscore the need for ATM-AVI susceptibility testing for NDM producers, and the potential for PBP3 mutations to confer cross-resistance to ATM-AVI and FDC, which can emerge after CZA-ATM treatment.

Background: Healthcare-associated wastewater and asymptomatic patient reservoirs colonized by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination, but the characteristics and dynamics of this remain unclear.

Methods: We systematically sampled wastewater sites (n = 4488 samples; 349 sites) and patients (n = 1247) across six wards over 6-12 months to understand bla_KPC-associated CPE (KPC-E) diversity within these reservoirs and transmission in a healthcare setting. Up to five KPC-E-positive isolates per sample were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based approaches were used to characterize antimicrobial resistance genes, insertion sequences (ISs) and Tn4401 types/target site sequences. The accessory genome was evaluated in some of the largest clusters, and those crossing reservoirs.

Results: Wastewater site KPC-E-positivity was substantial [101/349 sites (28.9%); 228/5601 (4.1%) patients cultured]. Thirteen KPC-E species and 109 strains were identified using genomics, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured one or more strains. Most diversity was explained by the individual niche, suggesting localized factors are important in selection and spread. Tn4401 + flanking target site sequence diversity was greater in wastewater sites (P < 0.001), which might favour Tn4401-associated transposition/evolution. Shower/bath- and sluice/mop-associated sites were more likely to be KPC-E-positive (adjusted OR = 2.69; 95% CI: 1.44-5.01; P = 0.0019; and adjusted OR = 2.60; 95% CI: 1.04-6.52; P = 0.0410, respectively). Different strains had different bla_KPC dissemination dynamics.

Conclusions: We identified substantial and diverse KPC-E colonization of wastewater sites and patients in this hospital setting. Reservoir and niche-specific factors (e.g. microbial interactions, selection pressures), and different strains and mobile genetic elements likely affect transmission dynamics. This should be considered in surveillance and control strategies.