Nosocomial carbapenem-drug resistant Acinetobacter baumannii, related factors and clinical outcomes in Northeast Iran.

BACKGROUND AND OBJECTIVES: Nosocomial infections, including drug-resistant Acinetobacter baumannii infections, continue to impact the health of hospitalized patients. This study sought to determine the prevalence of these infections and assess the associated risk factors and clinical outcomes in Gorgan, Iran. METHODS: A retrospective cross-sectional study was conducted on 143 infected patients with Acinetobacter baumannii in two educational hospitals in Gorgan city, Iran between 2016 and 2018. Patient information including age, gender, reason and duration of hospitalization, background of diseases, type of sample culture, symptoms, laboratory findings, prescribed antibiotics, and antibiogram were collected and analyzed. The Logistic regression and survival statistical methods were used by software of SPSS 26. RESULTS: A total of 37 patients (25.87%) died during hospitalization. The less than one year and 45-65 years age groups demonstrated more deaths (29.7%; p-value < 0.001). Being single (not being married) was found to be a risk factor in increasing the chance of death among patients (OR = 2.154, 95% CI: 1.02-4.53; p = 0.048). Hospitalization in intensive care units (ICUs) was a risk factor for the death of patients (OR = 4.655, 95% CI: 7.6-83.2). The resistance to carbapenems was reported to be an important risk factor for the death of patients. CONCLUSIONS: Acinetobacter baumannii infections, particularly those resistant to carbapenems, are a significant risk for patients in ICUs and can lead to higher mortality rates.

Mobile genetic elements contributing to horizontal gene transfer of blaNDM among Escherichia coli in the community setting.

OBJECTIVE: To investigate the distribution of carbapenem-resistant Enterobacterales (CRE) in the community and to describe the genomic characteristics. METHODS: CRE screened from fecal samples in healthy people at the health examination center of a tertiary hospital in China underwent Whole genome sequencing (WGS) to analyze genotypic characteristics of CRE. The flanking DNA sequence of blaNDM-5 and mcr1.1 genes were analyzed by Gcluster software. RESULTS: A total of 7187 fecal samples were screened, and CRE carriage was detected in 0.4 % of the sampled population. In total, 30 Escherichia coli, one Citrobacter freundii and one Klebsiella aerogene were screened. The 30 carbapenem-resistant Escherichia coli (CREC) isolates displayed slight resistance to amikacin (13.3 %) and aztreonam (20.0 %). All the CRE isolates contained blaNDM, and blaNDM-5 (84.4 %) was the most common one. B1 (n = 11) and A (n = 7) were predominant phylogroups. Furthermore, 34 distinct plasmid replicons, 67 different VFs, 22 distinct STs, 17 different FimH types, 26 O:H serotypes as well as 74 MGEs including 61 insertion sequences and 13 transposons were identified. The flanking DNA sequence analysis of blaNDM-5 and mcr1.1 genes indicates the key role of horizontal transfer of blaNDM-5 in the CRE development evidenced by diverse STs and phylogenetic tree. CONCLUSION: E. coli was the most predominant CRE isolates in community setting, and blaNDM (blaNDM-5) was the main CHßL encoding genes. The high prevalence of ARGs was associated with high resistance to commonly used antimicrobials. Besides, the genetic diversity of these isolates suggested the key role of blaNDM horizontal transfer in the CRE development. Thus, active screening of blaNDM in communities is particularly important for the prevention and control of CRE.

Evaluation of the CARBA PAcE test, a colorimetric imipenem hydrolysis test for rapid detection of carbapenemase activity.

There is an urgent need for accurate and fast diagnostic tests to identify carbapenemase-producing bacteria. Here, we evaluated a colorimetric imipenem hydrolysis test, called the CARBA PAcE test, to detect carbapenemase-producing Gram-negative bacteria (GNB). We tested a collection of 270 GNB isolates with a characterized carbapenemase content. Our testing set included 205 carbapenemase-producing, carbapenemase-resistant Enterobacterales (CP CRE) with 40 Klebsiella pneumoniae carbapenemase (KPC), 49 New Delhi metallo beta lactamase (NDM), 49 OXA-48-like, 15 Verona integron-mediated metallo-ß-lactamase (VIM), three IMP, 43 IMI, six isolates producing more than one carbapenemase, and 65 non-carbapenemase-producing Enterobacterales (20 ESBL producers, 35 non-carbapenemase-producing, carbapenem-resistant [non-CP CRE], and 10 carbapenem-susceptible Enterobacterales [non-CP, non-CSE, third-generation cephalosporin and carbapenem susceptible]). We compared the performances of the CARBA PAcE test, the qualitative colorimetric ß-CARBA test, and the modified CarbaNP test to a gold standard of carbapenemase gene detection by PCR. Specificities of all tests were high: 95.4% (62/65) for CARBA PAcE test, 98.5% (64/65) for ß-CARBA test, and 100% (65/65) for the modified CarbaNP test. Sensitivity varied by carbapenemase: all three tests had a sensitivity of 100% for NDM, VIM, and IMP and 97.5% for KPC. Sensitivity to detect IMI was 0% for the CARBA PAcE and ß-CARBA tests and 11.6% for the modified CarbaNP test. Sensitivity to detect OXA-48-like was 89.7% for the CARBA PAcE test, 87.7% for the ß-CARBA test, and 14.2% for the modified CarbaNP test. Reading the results of the CARBA PAcE assay was difficult. The CARBA PAcE assay is highly sensitive for detecting NDM, VIM, IMP, and KPC, but slightly less sensitive for OXA-48-like. It does not detect IMI. It is highly specific, and its overall diagnostic accuracy is similar to that of ß-CARBA. Its operational advantages are rapid turnaround time, ease of use, and long shelf life, but reading of results is subjective.IMPORTANCEWe evaluated the ability of the CARBA PAcE test to detect carbapenemases in 274 Gram-negative isolates with a known carbapenemase content. Specificity was high for all carbapenemases tested (96.9%). Sensitivity was high for KPC, NDM, VIM, and IMP (97.5-100%); but lower for OXA-48-like (89.7%). Activity of IMI could not be detected. Taken together, our results indicate that CARBA PAcE is a useful alternative in regions where NDM and KPC are predominant. The limitations of the test are difficulty in reading results and incompatibility with mSuperCARBA.

Comparison of genotypic features between two groups of antibiotic resistant Klebsiella pneumoniae clinical isolates obtained before and after the COVID-19 pandemic from Egypt.

Klebsiella pneumoniae is a common pathogen capable of causing a wide range of infections. Antibiotic resistance complicates treatment of these infections significantly. We are comparing resistance levels and genotypes among two collections of K. pneumoniae clinical isolates from Alexandria Main University Hospital (AMUH). We used disc diffusion and Minimum Inhibitory Concentration (MIC) by microbroth dilution to assess resistance levels and performed whole genome sequencing (WGS) to describe multilocus sequence types (MLST) and resistance gene presence. Among a collection of 56 K. pneumoniae clinical isolates (19 from 2019 to 37 from 2021), multidrug resistance (MDR) was 33% and 10%, extended drug resistance (XDR) was 24% and 46% and pan-drug resistance (PDR) was 43% and 43%, respectively. We identified 15 MLST STs including two novel types (ST-6118 and ST-6119 ). ST-101 and ST-383 were common between the two collections; ST-101 was the most common genotype in 2019 (28.6%) and ST-147 was most common in 2021 (25%). Ampicillin/sulbactam, amikacin, cefepime, ceftriaxone and ertapenem MICs were significantly higher in 2021. Prevalence of aph(3') - Ia, aph(3')-VI, mphA was significantly higher in 2021. The increasing resistance levels and the persistence of some MDR/XDR genotypes is concerning. Understanding mechanisms of resistance will inform infection control and antimicrobial stewardship plans to prevent evolution and spread of XDR and PDR strains.

Insertion Sequences within Oxacillinases Genes as Molecular Determinants of Acinetobacter baumannii Resistance to Carbapenems-A Pilot Study.

Carbapenem-resistant Acinetobacter baumannii is one of the major problems among hospitalized patients. The presence of multiple virulence factors results in bacteria persistence in the hospital environment. It facilitates bacterial transmission between patients, causing various types of infections, mostly ventilator-associated pneumonia and wound and bloodstream infections. A. baumannii has a variable number of resistance mechanisms, but the most commonly produced are carbapenem-hydrolyzing class D ß-lactamases (CHDLs). In our study, the presence of blaOXA-23, blaOXA-40 and blaOXA-51 genes was investigated among 88 clinical isolates of A. baumannii, including 53 (60.2%) strains resistant to both carbapenems (meropenem and imipenem) and 35 (39.8%) strains susceptible to at least meropenem. Among these bacteria, all the isolates carried the blaOXA-51 gene. The blaOXA-23 and blaOXA-40 genes were detected in two (5.7%) and three (8.6%) strains, respectively. Among the OXA-23 carbapenemase-producing A. baumannii strains (n = 55), insertion sequences (ISAba1) were detected upstream of the blaOXA-23 gene in fifty-two (94.5%) carbapenem-resistant and two (3.6%) meropenem-susceptible isolates. A. baumannii clinical strains from Poland have a similar antimicrobial resistance profile as those worldwide, with the presence of ISAba1 among blaOXA-23-positive isolates also being quite common. Carbapenem resistance among A. baumannii strains is associated with the presence of CHDLs, especially when insertion sequences are present.

Insights into the Rising Threat of Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa Epidemic Infections in Eastern Europe: A Systematic Literature Review.

BACKGROUND: Antimicrobial resistance is a major global public health challenge, particularly with the rise of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA). This study aimed to describe the characteristics of CRE and CRPA infections in Eastern Europe, focusing on Bulgaria, Croatia, Czechia, Greece, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia. METHODS: Following MOOSE and PRISMA guidelines, a systematic literature review of articles published between 1 November 2017 and 1 November 2023 was conducted using the MEDLINE, Embase, Web of Science, CDSR, DARE, and CENTRAL databases. The search strategy used a combination of free text and subject headings to gather pertinent literature regarding the incidence and treatment patterns of CRE and CRPA infections. A total of 104 studies focusing on infections in both children and adults were included in this review. RESULTS: This review revealed a significant prevalence of carbapenem-resistant Gram-negative isolates and underscored the effectiveness of imipenem/relebactam and ceftazidime/avibactam (CAZ/AVI) against Klebsiella pneumoniae carbapenemase-producing Enterobacterales and of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against non-metallo-ß-lactamase-producing CRPA strains. CONCLUSIONS: This study highlights the urgent need for comprehensive measures to combat the escalating threat of CRE and CRPA infections in Eastern European countries. At the same time, it shows the activity of the standard of care and new antimicrobials against carbapenem-resistant Gram-negative pathogens in Eastern Europe. Clinical real-world data on the treatment of carbapenem-resistant infections in Eastern Europe are needed.

The Synergy of Machine Learning and Epidemiology in Addressing Carbapenem Resistance: A Comprehensive Review.

BACKGROUND/OBJECTIVES: Carbapenem resistance poses a significant threat to public health by undermining the efficacy of one of the last lines of antibiotic defense. Addressing this challenge requires innovative approaches that can enhance our understanding and ability to combat resistant pathogens. This review aims to explore the integration of machine learning (ML) and epidemiological approaches to understand, predict, and combat carbapenem-resistant pathogens. It examines how leveraging large datasets and advanced computational techniques can identify patterns, predict outbreaks, and inform targeted intervention strategies. METHODS: The review synthesizes current knowledge on the mechanisms of carbapenem resistance, highlights the strengths and limitations of traditional epidemiological methods, and evaluates the transformative potential of ML. Real-world applications and case studies are used to demonstrate the practical benefits of combining ML and epidemiology. Technical and ethical challenges, such as data quality, model interpretability, and biases, are also addressed, with recommendations provided for overcoming these obstacles. RESULTS: By integrating ML with epidemiological analysis, significant improvements can be made in predictive accuracy, identifying novel patterns in disease transmission, and designing effective public health interventions. Case studies illustrate the benefits of interdisciplinary collaboration in tackling carbapenem resistance, though challenges such as model interpretability and data biases must be managed. CONCLUSIONS: The combination of ML and epidemiology holds great promise for enhancing our capacity to predict and prevent carbapenem-resistant infections. Future research should focus on overcoming technical and ethical challenges to fully realize the potential of these approaches. Interdisciplinary collaboration is key to developing sustainable strategies to combat antimicrobial resistance (AMR), ultimately improving patient outcomes and safeguarding public health.

Characterization of four novel bacteriophages targeting multi-drug resistant Klebsiella pneumoniae strains of sequence type 147 and 307.

The global dissemination of multi-drug resistant (MDR) pathogenic bacteria requires the rapid research and development of alternative therapies that can support or replace conventional antibiotics. Among MDR pathogens, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are of particular concern due to their extensive resistance profiles, global dissemination in hospital environments, and their major role in some life-threatening infections. Phages, or some of their components, are recognized as one of the potential alternatives that might be helpful to treat bacterial infections. In this study, we have isolated and characterized four lytic bacteriophages targeting K. pneumoniae strains of Sequence Type (ST) 307 or ST147, two predominant high-risk clones of CR-Kp. Phages, designated vB_KpS_GP-1, vB_KpP_GP-2, vB_KpP_GP-4, and vB_KpP_GP-5, were isolated from sewage wastewater samples. The vB_KpS_GP-1 phage was a siphovirus unable to establish lysogeny with its host, while the other three were podoviruses. While 85.7% of K. pneumoniae strains of ST307 were selectively lysed by the phages vB_KpS_GP-1 or vB_KpP_GP-5, the other two phages were able to lyse all the tested strains of ST147 (n = 12). Phages were stable over a broad pH and temperature range and were characterized by burst sizes of 10-100 plaque forming units and latency periods of 10-50 minutes. Genome sequencing confirmed the absence of antibiotic resistance genes, virulence factors or toxins and revealed that two phages were likely members of new genera. Given their strictly lytic nature and high selectivity towards two of the major high-risk clones of K. pneumoniae, cocktails of these phages could represent promising candidates for further evaluation in in vivo experimental models of K. pneumoniae infection.

Design, synthesis, and bioactivity investigation of novel cyclic lipopeptide antibiotics targeting top-priority multidrug-resistant gram-negative bacteria.

OBJECTIVES: Polymyxins are the last-line therapy for top-priority multidrug-resistant (MDR) gram-negative bacteria. However, polymyxin nephrotoxicity impedes its clinical application. This study aimed to design, synthesize, and identify a novel and promising polymyxin derivative with high efficacy and low toxicity. METHODS: To design polymyxin derivatives, we reduced the hydrophobicity of the two hydrophobic domains (fatty acyl chain and D-Phe6-L-Leu7) and modified the positive charged L-2,4-diaminobutyric acid (Dab) residues. Twenty-five derivatives were synthesized, and their antibacterial activities in vitro and renal cytotoxicities were determined. The nephrotoxicity and pharmacokinetic parameters of compound 12 were examined in rats. Antibacterial efficacy in vivo was evaluated using a mouse systemic infection model. Surface plasmon resonance analysis, compound 12-rifampicin combination therapy, and scanning electron microscopy were used to study the mechanism of action of compound 12. RESULTS: This research found a new compound, identified as compound 12, which showed similar or increased antibacterial activity against all tested sensitive and carbapenem-resistant gram-negative bacteria. It exhibited reduced renal cytotoxicity and nephrotoxicity, a favorable pharmacokinetic profile, and maintained or improved antibacterial efficacy in vivo. Importantly, its anti-Pseudomonas aeruginosa activity significantly improved. Compound 12, when combined with rifampicin, enhanced the activity of rifampin against gram-negative bacteria. Compound 12 also showed a high affinity for lipopolysaccharide and disrupted cell membrane integrity. CONCLUSION: Reducing the hydrophobicity of the two domains reduced renal cytotoxicity and nephrotoxicity. Shortening the side chain of Dab3 by one carbon maintained or increased its antibacterial activity both in vitro and in vivo. Furthermore, only the length of the side chain of Dab9 could be shortened by one carbon among the Dab1,5 and Dab8,9 residues. The bactericidal effects of compound 12 were related to the disruption of cell membrane integrity. Compound 12 may be a promising candidate for combating sensitive and carbapenem-resistant gram-negative bacterial infections, especially Pseudomonas aeruginosa.

Molecular Detection of Carbapenemases in Acinetobacter baumannii Strains of Portugal and Association With Sequence Types, Capsular Types, and Virulence.

PURPOSE: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important nosocomial pathogen. The capsular type (K-type) is considered a major virulence factor, contributing to the evasion of host defenses. The global spread and dissemination dynamics between K-types, sequence types (ST), antibiotic resistance genes, and virulence factors remain largely unknown in Portugal. METHODS: A collection of 96 CRAB clinical samples collected between 2005 and 2019 in the northern region of Portugal were tested for antimicrobial susceptibility profile and screened by polymerase chain reaction for resistance genetic determinants. A subset of 26 representative isolates was subjected to whole-genome sequencing to assess K types, ST types, and genomic relatedness. The pathogenicity of distinct K-types was also tested using Galleria mellonella model. FINDINGS: For the 96 CRAB isolates analyzed, high antimicrobial resistance (>90%) was observed to the carbapenems, fluoroquinolones, and miscellaneous agents. Greater antimicrobial susceptibility (∼30%-57%) was observed for aminoglycosides, particularly tobramycin, and amikacin. Genotypically, 75 strains (78.5%) carried blaOXA-23-like, 18 strains (18.8%) carried blaIMP-like, and 11 strains (14.9%) carried blaOXA-40-like carbapenem resistance genes, respectively. Associations between OXA and ST/capsular locus (KL) types were observed over the years (eg, OXA-40-like/ST46Past/KL120 and OXA-23-like/ST2Past/KL2). ST2Past of clonal complex II was present in most strains, a dominant drug-resistant lineage in the United States and Europe. KL7 was also the most prevalent KL-type (38.5%), followed by KL2 (34.6%), KL120 (23.1%), and KL9 (3.8%). Virulence assessment for different K-types in a Galleria mellonella model revealed a significantly increased virulence for KL120 when compared with KL7, KL9, and KL2. IMPLICATIONS: There are specific CRAB serotypes circulating in Portugal, accounting by the low diversity of acquired carbapenemase genes (OXA-23-like and OXA-40-like), ST types (ST2 and ST46) and KL types (KL2, KL7, KL9, and KL120) identified. The high prevalent of ST2, especially when associated with KL2 and blaOXA-23-like, suggest that antibiotic resistance has been driven by clonal expansion of clonal complex II. Such findings provide useful information on the diversity of multidrug-resistant bacterium that might be relevant for antibacterial interventions.

Effectiveness and Safety of Cefiderocol in Clinical Practice for Treatment of Patients with Gram-Negative Bacterial Infections: US Interim Results of the PROVE Study.

Purpose: The international PROVE retrospective chart-review study aims to assess the real-world effectiveness and safety of cefiderocol for treatment of patients with carbapenem-resistant Gram-negative infections. Patients and Methods: US centers selected hospitalized patients receiving their first cefiderocol treatment for ≥72 hours for a Gram-negative bacterial infection (November 2020-March 2023). Patient demographics, clinical characteristics, hospitalization, course of infection, antibiotic use, clinical cure (excluding patients with a relapse/reinfection), clinical response at the end of treatment, microbiology, in-hospital all-cause mortality (IH-ACM) at Day 30, and safety were analyzed using descriptive statistics. Results: This interim analysis included 244 patients. The most frequent infection sites were respiratory tract (55.7%), skin and skin structure (16.8%), and blood (9.8%). The median duration of cefiderocol use was 12 days (interquartile range 8-18.5). Clinical cure was reported for 64.8% (158/244) of patients, clinical response for 74.2% (181/244), and 9.4% (23/244) had relapse/reinfection; 30-day IH-ACM was 18.4% (45/244). Of 82 patients with monomicrobial Pseudomonas aeruginosa infections, 64.6% (n = 53) and 74.4% (n = 61) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 25.6%. Among 43 patients with monomicrobial Acinetobacter baumannii infections, 60.5% (n = 26) and 74.4% (n = 32) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 18.6%. Five patients experienced six adverse drug reactions (one serious event: interstitial nephritis/acute kidney injury), and cefiderocol was discontinued in two cases. Conclusion: Cefiderocol had similar clinical cure and response rates to previous retrospective studies and lower mortality. Cefiderocol was well tolerated in real-world settings in critically ill US patients with problematic Gram-negative pathogens.

The draft genome sequence of a carbapenem-resistant Klebsiella pneumoniae strain belonging to sequence type 11 and capsular type 62.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) of sequence type 11 (ST11) and capsular type KL47 or KL64 are dominant in China. We report the draft genome sequence of an ST11 blaKPC-2-carrying CRKP strain belonging to uncommon capsular type KL62. This strain carries virulence factors encoding multiple iron acquisition systems and mucoid regulators.

High frequency of acquired virulence factors in carbapenemase-producing Klebsiella pneumoniae isolates from a large German university hospital, 2013-2021.

Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) isolates are a public health concern as they can cause severe hospital-acquired infections that are difficult to treat. It has recently been shown that CP-Kp can take up virulence factors from hypervirulent K. pneumoniae lineages. In this study, 109 clinical CP-Kp isolates from the University Hospital Cologne were examined for the presence of acquired virulence factors using whole-genome sequencing and phenotypic tests, and results were linked to clinical data. The virulence factor iuc was present in 18/109 of the CP-Kp isolates. Other acquired virulence factors, such as ybt, cbt, iro, rmpA/rmpA2, peg-344, and hypervirulence-associated capsule types were detected in various combinations among these isolates. The iuc-positive isolates produced OXA-232 (n = 7), OXA-48 (n = 6), OXA-48+NDM (n = 3), NDM, and KPC (each n = 1), and 7/18 isolates were resistant to ceftazidime-avibactam, colistin, and/or cefiderocol. Four isolates carried hybrid plasmids that harbored acquired virulence factors alongside the carbapenemase genes blaNDM-1/5 or blaOXA-48. In 15/18 patients, iuc-positive CP-Kp were isolated from a clinically manifest infection site. Among these, four patients had osteomyelitis, and four patients died from pneumonia with OXA-232-producing ST231 isolates, three of them as part of an outbreak. In conclusion, acquired virulence factors are frequently detected in various combinations in carbapenemase-producing K. pneumoniae isolates in Germany, warranting continuous monitoring of infections caused by these strains.

The context of blaOXA-23 gene in Iraqi carbapenem-resistant Acinetobacter baumannii isolates belonging to global clone 1 and global clone 2.

BACKGROUND AND OBJECTIVES: Of the genes conferring resistance to carbapenems in Acinetobacter baumannii, the blaOXA-23 gene is the most widely found across the world. The gene carrying blaOXA-23 transposons in A. baumannii isolates of global clones GC1 and GC2 is found worldwide. Here, we examined whether transposons play a role in the dissemination of the blaOXA-23 in globally distributed clones, GC1 and GC2 A. baumannii isolates from Iraq. MATERIALS AND METHODS: The 119 non-repetitive A. baumannii isolates including 94 recovered from clinical specimens and 25 isolates from hospital environment between September 2021 and April 2022 from different medical centers located at various regions in Baghdad, Iraq. The global clones (GC) and the genes encoding carbapenem resistance, including blaOXA-23, blaOXA-24, and blaOXA-58 were identified using multiplex PCR assays. Antibiotic susceptibility testing was performed by the Kirby-Bauer disk diffusion susceptibility method. The transposons carrying blaOXA-23 were examined using PCR mapping. In cases when carbapenem susceptible A. baumannii isolates were found, they were subjected to E test, full length sequencing of blaOXA-Ab (blaOXA-51-like) and Institut Pasteur multi-locus sequence typing scheme. RESULTS: All but two isolates (92 clinical and 25 environmental) were identified carbapenem-resistant A. baumannii (CRAB). Of 117 CRAB isolates, 20 belong to GC1, 19 contained blaOXA-23; of them, 17 isolates harbored the blaOXA-23 located on Tn2006. Among the 46 CRAB belonging to GC2, 39 contained blaOXA-23; of them, 34 carried the blaOXA-23 located on Tn2006. The remaining GC1 and GC2 isolates, one GC1 as well as one GC2 isolate, were susceptible to imipenem, doripenem, and meropenem and considered carbapenem-susceptible A. baumannii (CSAB). Full-length sequencing of the blaOXA-Ab and MLST for the two CSAB isolates belonging to GC1 and GC2 confirmed that the GC1 isolate belongs to ST 623 and contained an allele that encodes an blaOXA-69 variant of the blaOXA-Ab while the GC2 belong to ST2 and carried an blaOXA-66 variant. CONCLUSION: This study provides evidence for the dissemination of blaOXA-23 on the Tn2006 in CRAB isolates in Baghdad, Iraq. It appears that this transposon is widespread in GC1 and 2 isolates as in the other parts of the world. Interestingly, one GC1 and one GC2 isolate from Iraq were found to be susceptible to carbapenem while the isolates belonging to GC1 and GC2 have so far rarely been found to be susceptible to carbapenem globally.

Emergence of drug-resistant Elizabethkingia anophelis clinical isolates in Myanmar.

Seven drug-resistant Elizabethkingia anophelis isolates were obtained from inpatients in three medical settings in Myanmar between February 2017 and January 2021. All isolates were resistant to ß-lactams and colistin. Among these, four isolates were resistant to amikacin with minimum inhibitory concentration (MIC) of ≥64 µg ml-1. Six of the seven isolates harboured genes encoding intrinsic ß-lactamases, including bla B, bla CME and bla GOB, whereas one isolate harboured bla B, bla CME and an incomplete bla GOB gene. Phylogenetic analysis based on whole-genome sequences revealed that several E. anophelis isolates in Myanmar formed their own clusters, whereas others were similar to isolates found in the USA. This is the first report of the emergence of Elizabethkingia species in Myanmar.

The prevalence of carbapenem-resistant Enterobacterales and the emergence of novel ST11-KL30 carbapenem-resistant Klebsiella pneumoniae in Xinjiang, China.

OBJECTIVES: To address the lack of research on the prevalence of carbapenem-resistant Enterobacterales (CREs) in Xinjiang, China, and elucidate the genomic characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) ST11-KL30. METHODS: CREs were collected in Xinjiang from 2021 to 2023. The antimicrobial susceptibility testing of carbapenems was performed via agar dilution method. Whole-genome sequencing was completed on the Illumina platform, and subsequent genomic analyses of CRKP, such as sequencing typing, K-locus and O-locus identification, virulence score assessment, and phylogenetic analysis, were performed. The virulence of CRKP isolates was determined in vitro and in vivo, and biofilm formation was assessed by crystal violet staining. Additionally, the virulence plasmid was reconstructed, and the formation of CRKP ST11-KL30 was revealed based on genome data from public database. RESULTS: Eighty-five CRE isolates were collected, among which CRKP was most prevalent (68/85). KPC was the most dominant carbapenemase (60/68) in CRKP, while NDM-type carbapenemase was more prevalent in other species. ST11 was the dominant CRKP clone, and was phylogenetically divided into three clusters: ST11-KL64, ST11-KL47, and ST11-KL30. CRKP ST11-KL30 is a novel recombinant clone that harbours a pK2044-like virulence plasmid and can be derived from ST11-KL64 by obtaining an ∼57 kb region from ST29-KL30. Compared to ST11-KL47 and ST11-KL64, ST11-KL30 had lower virulence, but had enhanced biofilm formation. CONCLUSIONS: We describe the prevalence of CRE prevalence southern Xinjiang and report the emergence of a region-specific clone. Our findings underscore the potential dissemination of ST11-KL30, which warrants increased monitoring in the future.

Association between inappropriate empirical antimicrobial therapy and mortality in gram-negative bloodstream infections in patients with febrile neutropenia and hematological malignancy.

BACKGROUND AND OBJECTIVE: Inappropriate initial antimicrobial therapy has been associated with high mortality in patients with gram-negative bacilli bloodstream infections during febrile neutropenia following chemotherapy for hematological malignancies. The aim of this study is to determine this association in our hospital. METHODS: A single center, retrospective, cohort study of bloodstream infection due to gram-negative bacilli and febrile neutropenia was conducted. Clinical characteristics, microbiological etiology, antimicrobial resistance profile, empirical and targeted antibiotic therapy, intensive care unit admission, persistent bacteremia and mortality were analyzed. RESULTS: Of the 171 episodes of bloodstream infection due to gram-negative bacilli, empirical antimicrobial therapy was inappropriate in 43 episodes (25.1 %). There was a significant difference in mortality at 7 and 30 days between patients who received appropriate versus inappropriate empirical treatment (4.6 % versus 13.9 %, p = 0.04; 15.6 % versus 32.5 %, p = 0.016). Inappropriate empirical treatment (RR, 2.97 [95 % CI, 1.01-8.74]), shock at the time of febrile neutropenia diagnosis (RR, 6.5 [95 % CI, 1.83-23.05]) carbapenem-resistant microorganism (RR, 3.73 [95 % CI, 1.14-12.24]) and persistent bacteremia (RR, 84.6 [95 % CI, 11.3-629.4]) were associated with an increased mortality at 7 and 30 days. In the multivariate analysis, shock (RR, 4.85 [95 % CI, 2.10-11.65]) and persistent bacteremia was independently associated with increased 30-day mortality, but inappropriate empirical antimicrobial therapy was not an independent prognostic determinant (RR, 1.66 [0.53-4.82]). CONCLUSION: Shock at the time of febrile neutropenia diagnosis contributes to mortality in patients with gram-negative bacilli bloodstream infection, in this scenario, appropriate empirical antimicrobial therapy should be encouraged.

Bacterial Epidemiology and Antimicrobial Resistance Profiles of Bloodstream Infections Caused by Negative Bacteria in Children's: A Multicenter Study in China (2016-2022).

Objective: Aim to investigate the pathogens distribution and drug resistance of gram-negative bacteria causing bloodstream infection (BSIs) in Infectious Disease Surveillance of Pediatric from 2016 to 2022. The prevalence of four important drug resistance phenotypes was studied: difficult-to-treat resistance, fluoroquinolone resistance, carbapenem resistance, and extended-spectrum cephalosporin resistance, and to provide reference basis for preventing and treating BSIs diseases in children. Methods: Strain identification and antimicrobial susceptibility tests were independently performed at each hospital. Data were analyzed using Whonet 5.6 and GraphPad Prism 8 software. The Mann-Whitney U-test was used to examine and compare temporal changes. Results: A total of 39977 BSIs strains were isolated, with 27.1% of the negative bacteria causing BSIs (10824 strains). The highest bacteria detected were E. coli and S. maltophilia in the neonatal and pediatric groups. The detection rate of carbapenem-resistant-K. pneumoniae (CRKPN) in neonate group was 31.4%, significantly increased compared with pediatric group, whose detection rate was 24.7%. The rates of resistance to levofloxacin and trimethoprim/sulfamethoxazole were significantly lower in neonatal groups than pediatric groups in BSIs caused by K. pneumoniae. To imipenem and meropenem were 3.6% and 3.9% among neonatal isolates, which was lower than 4.7% and 5.8 among pediatric BSIs caused by E. coli. Isolated from neonatal BSIs caused by A. baumannii showed lower resistance ratios to all the agents tested than those from pediatric. However, only the prevalence of piperacillin/tazobactam resistance was statistically lower than that in pediatric BSIs caused by P. aeruginosa. The average detection rates of carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance for K. pneumoniae and E. coli were 28.1%,41.4%,11.6% and 4.0%,24.3%,31.1%, respectively. Conclusion: The detection rate of gram-negative pathogens showed an increasing trend among the bloodstream infection. The detection rate of CRKPN assumed a downward trend in 2018. There are differences types of pathogens between the neonatal group and the pediatric group, The detection rate of CRKPN in the neonate group was significantly higher than pediatric group. The first average detection rates for carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance were obtained for A. baumannii, K. pneumoniae, and Escherichia coli, respectively. Those data showed a high level of antimicrobial resistance, which has posed an urgent threat to Children's health, suggested that effective monitoring of antimicrobial resistance and antimicrobial stewardship among children in China are required.

Identification and characterisation of carbapenem-resistant Streptococcus nidrosiense sp. nov. isolated from blood culture.

Background: This study aimed to investigate a highly resistant strain of Streptococcus sp. isolated from a patient with bloodstream infection and determine its taxonomic classification. Methods: The strain was isolated from blood culture from a 65-year-old male patient admitted to St. Olavs University hospital, Trondheim, Norway, in 2023. Antimicrobial susceptibility testing as well as phenotypic and biochemical characterization were performed. Whole genome sequencing was conducted and genomic comparison to Streptococcus type strains was carried out. Results: The strain was initially identified as Streptococcus mitis/oralis but showed significant genetic differences, suggesting that it belonged to an undescribed species within the Streptococcus genus. Phenotypic and biochemical characterization identified the strain as a non-motile, facultative anaerobic bacterium with α-hemolysis. Antimicrobial susceptibility testing showed resistance to all beta-lactams tested. Genomic analyses confirmed the classification of the strain as a novel species, which was designated Streptococcus nidrosiense. Conclusion: This study combines conventional phenotypic tests with whole genome sequencing for accurate taxonomic classification of a bacterial strain isolated from blood culture. The identification of a novel species within the Streptococcus genus contributes to the understanding of microbial diversity and antibiotic resistance of the Streptococcus genus in clinical settings.

Molecular genotyping reveals multiple carbapenemase genes and unique blaOXA-51-like (oxaAb) alleles among clinically isolated Acinetobacter baumannii from a Philippine tertiary hospital.

BACKGROUND: Acinetobacter baumannii continued to be an important Gram-negative pathogen of concern in the clinical context. The resistance of this pathogen to carbapenems due to the production of carbapenemases is considered a global threat. Despite the efforts to track carbapenemase synthesis among A. baumannii in the Philippines, local data on its molecular features are very scarce. This study aims to characterize A. baumannii clinical isolates from a Philippine tertiary hospital through genotyping of the pathogen's carbapenemase genes. METHODS: Antibiotic susceptibility profiling, phenotypic testing of carbapenemase production, and polymerase chain reaction assays to detect the different classes of carbapenemase genes (class A blaKPC, class B blaNDM, blaIMP, blaVIM, and class D blaOXA-23-like, blaOXA-24/40-like, blaOXA-48-like, blaOXA-51-like, ISAba1-blaOXA-51-like, blaOXA-58-like) were performed in all collected A. baumannii, both carbapenem resistant and susceptible (n = 52). RESULTS: Results showed that the majority of the carbapenem-resistant strains phenotypically produced carbapenemases (up to 84% in carbapenem inactivation methods) and possessed the ISAba1-blaOXA-51-like gene complex (80%). Meanwhile, both carbapenem-resistant and carbapenem-susceptible isolates possessed multi-class carbapenemase genes including blaNDM (1.9%), blaVIM (3.9%), blaOXA-24/40-like (5.8%), blaOXA-58-like (5.8%), blaKPC (11.5%), and blaOXA-23-like (94.2%), which coexist with each other in some strains (17.3%). In terms of the intrinsic blaOXA-51-like (oxaAb) genes, 23 unique alleles were reported (blaOXA-1058 to blaOXA-1080), the majority of which are closely related to blaOXA-66. Isolates possessing these alleles showed varying carbapenem resistance profiles. CONCLUSIONS: In summary, this study highlighted the importance of molecular genotyping in the characterization of A. baumannii by revealing the carbapenemase profiles of the pathogen (which may not be captured accurately in phenotypic tests), in identifying potent carriers of transferrable carbapenemase genes (which may not be expressed straightforwardly in antimicrobial susceptibility testing), and in monitoring unique pathogen epidemiology in the local clinical setting.