Guidelines for Antibacterial Treatment of Carbapenem-Resistant Enterobacterales Infections.

This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.

Epidemiological, Phylogenetic, and Resistance Heterogeneity Among Acinetobacter baumannii in a Large U.S. Deep South Healthcare system.

Background: Acinetobacter baumannii (Ab) disease in the United States is commonly attributed to outbreaks of 1 or 2 monophyletic carbapenem resistance (CR) Ab lineages that vary by region. However, there is limited knowledge regarding CRAb epidemiology and population structures in the U.S. Deep South, and few studies compare contemporary CR and carbapenem-susceptible (Cs) Ab, despite relative prevalence of the latter. Methods: We performed a multiyear analysis of 2462 Ab cases in a large healthcare system in Birmingham, AL, and 89 post-2021 Ab isolates were sequenced and phenotyped by antibiotic susceptibility tests. Results: Although the cumulative CR rate was 17.7% in our cohort, rates regularly increased in winter months as result of seasonal changes in case incidence of CsAb, specifically. Genotyped CRAb belonged to clonal group (CG) 1, CG2, CG108, CG250, or CG499, with local clones of CG108, CG250, and CG499 persisting over multiple months. There was no clonal expansion of any CsAb lineage. Among CRAb isolates, levels of ß-lactam antibiotic resistance and the repertoire of related genetic resistance determinants, which included the novel CR-conferring FtsI A515V polymorphism, differed according to CG. CG108 and CG499 isolates displayed specific heteroresistance to sulbactam and trimethoprim/sulfamethoxazole, respectively, which resulted in discrepant susceptibility results in microbroth versus agar-based antibiotic susceptibility tests modalities. Conclusions: We report an unusually high degree of CRAb phylogenetic diversity principally driven by emergent U.S. lineages harboring novel resistance elements that must be incorporated into diagnostic, surveillance, and preclinical research efforts.

KPC variants conferring resistance to ceftazidime-avibactam in Pseudomonas aeruginosa strains.

BACKGROUND: This study aimed to characterize three KPC variants (KPC-33, KPC-100, and KPC-201) obtained from a clinical isolate of Pseudomonas aeruginosa (#700), along with two induced strains C109 and C108. METHODS: Genomic DNAs of #700 (ST235), C109 (ST463), and C108 (ST1076) were sequenced using Illumina and Oxford Nanopore technologies. The transferability and stability of the plasmid was assessed through conjugation experiments and plasmid stability experiments, respectively. Minimum inhibitory concentrations of bacterial strains were determined using broth microdilution methods. In vitro induction was performed using ceftazidime-avibactam (CZA) at concentrations of 6/4 µg/ml. Linear genomic alignments were visualized using Easyfig, and protein structure modeling of the novel KPC variant (KPC-201) was conducted using PyMol. RESULTS: The plasmids carrying the KPC variants in the three CZA-resistant strains (C109, C108, and #700) had sizes of 39,251 bp (KPC-100), 394,978 bp (KPC-201), and 48,994 bp (KPC-33). All three plasmids belonged to the IncP-like incompatibility (Inc) groups, and the plasmid exhibited relatively high plasmid stability, KPC-33 and KPC-201-harboring plasmids were successfully transferred to the recipient strain P. aeruginosa PAO1rifR. The genetic environments of the three blaKPC genes differed from each other. The mobile elements of the three blaKPC genes were as follows, TnAS1-IS26-ΔISKpn27-blaKPC-33-ISKpn6-IS26, IS6-ΔISKpn27-blaKPC-100-ISKpn6-IS26-Tn3-IS26, and IS6100-ISKpn27-blaKPC-201-ISKpn6-TnAS1. Notably, the length of ΔISKpn27 upstream of the blaKPC-33 and blaKPC-100 genes were remarkably short, measuring 114 bp and 56 bp, respectively, deviating significantly from typical lengths associated with ISKpn27 elements. Moreover, the novel KPC variant, KPC-201, featured a deletion of amino acids LDR at positions 161-163 in KPC-3, resulting in a looser pocket structure contributing to its avibactam resistance. CONCLUSIONS: KPC-201, identified as a novel KPC variant, exhibits resistance to CZA. The presence of multiple mobile elements surrounding the blaKPC-variant genes on stable plasmids is concerning. Urgent preventive measures are crucial to curb its dissemination in clinical settings.

Ceftazidime/avibactam alone or in combination with an aminoglycoside for treatment of carbapenem-resistant Enterobacterales infections: a retrospective cohort study.

BACKGROUND: Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear. OBJECTIVES: To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam. METHODS: This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed. RESULTS: A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013-1.093), presence in the ICU (aOR 2.704, 95% CI 1.071-6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797-11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n=77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089-1.155). CONCLUSIONS: In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill.

Clinical Effectiveness and Safety of Colistin Sulphate in Treating Infections Caused by Carbapenem-Resistant Organisms and Analysis of Influencing Factors.

Objective: To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness. Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors. Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels >34 g/L, APACHE II scores <13, and treatment duration >10 days correlated with better clinical efficacy. Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application.

The effect of combinations of a glyphosate-based herbicide with various clinically used antibiotics on phenotypic traits of Gram-negative species from the ESKAPEE group.

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-ß-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity.

Biological studies of the activity of Manuka honey against Carbapenem-resistant Enterobacterales (CRE) bacteria.

OBJECTIVES: To evaluate the potency of Manuka honey UMF +15 against Carbapenem-resistant Enterobacterales (CRE). Bacterial resistance is a worldwide problem that is increasing year by year, especially Carbapenem resistance. Alternatives to antibiotics are needed to both reduce costs, and to reduce the spread of antibiotic resistance, with the ultimate goal of saving lives. METHODS: The efficacy of Manuka honey UMF +15 was tested by 2 methods; Well diffusion assay and minimum bactericidal concentration (MBC) against twenty Carbapenem-resistant isolates which collected from Makkah city hospitals during three months of study from 1st of September 2023 up to 1st of December 2023. RESULTS: The growth of all isolates of Carbapenem-resistant Enterobacterales (CRE) was severely inhibited by low concentrations of Manuka honey, affecting 25% of isolates at 15% and 75% of isolates at 18% of Manuka honey. In addition, using the honey at different concentrations in a well diffusion assay resulted, as expected, in a variable zone diameter, ranging from large zones(14mm) to small zones (2 mm) according to the concentration of the honey. CONCLUSION: This study shows the remarkable antibacterial activity of Manuka honey and suggests that this natural remedy might be used in the future as an alternative treatment option against Carbapenem-resistant Enterobacterales (CRE); however, further clinical trials should be performed to corroborate our initial findings.

Clinical outcomes and safety of polymyxin B versus tigecycline combination therapy for pneumonia of carbapenem-resistant Klebsiella pneumoniae: a retrospective cohort study.

PURPOSE: Infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) has high mortality. There is no clear optimal therapeutic choice for pneumonia caused by CRKP. The aim of this study was to compare the clinical outcomes and safety of the standard doses of polymyxin B-based regimens vs tigecycline-based regimens and to identify risk factors for mortality. METHODS: This retrospective cohort study included patients with pneumonia caused by CRKP between January 1, 2020 and December 31, 2022. The primary outcomes were 7-day bacterial eradication rate and 14- and 28-day all-cause mortality. The secondary outcome was incidence of acute kidney injury. RESULTS: Seventy-three patients were included in this study, 29 in the polymyxin B-based combination therapy group and 44 in tigecycline-based combination therapy group. There were no significant differences between the two groups in terms of the 7-day bacterial eradication rate (31.03% vs 20.45%, p = 0.409), the 14-day all-cause mortality (37.93% vs 22.73%, p = 0.160), and the incidence of acute kidney injury (14.29% vs 6.82%, p = 0.526). The 28-day all-cause mortality in the polymyxin B-based therapy group was higher than in the tigecycline-based group (75.86% vs 45.45%, p = 0.010). Binary logistic regression analysis revealed that male and previous use of carbapenems were independent factors associated with 28-day all-cause mortality for patients treated with polymyxin B (p < 0.05). CONCLUSIONS: Polymyxin B-based combination therapy at the standard dose should be used with caution for patients with CRKP-induced pneumonia, especially for men who used carbapenems prior to CRKP detection.

Factors influencing mortality in intracranial infections caused by carbapenem-resistant Klebsiella Pneumoniae.

It remains that intracranial infection has an alarming mortality and morbidity. Klebsiella pneumoniae (KP) have increasingly been isolated in ventriculitis and meningitis episodes. Intracranial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) account for high mortality. To understand its clinical impact and related risk factors accurately are crucial in the management of bacterial intracranial infection. The retrospective study aimed to delineate the clinical risk of death from intracranial infection and analyze the risk factors. A total of 176 Klebsiella pneumoniae intracranial infectious patients were available to divide into CRKP group and carbapenem-susceptive Klebsiella Pneumoniae (CSKP) group. We performed survival analysis and estimate the time-varying effects of CRKP and CSKP infection on 30-day mortality. Infectious patients caused by CSKP was associated with lower mortality than CRKP group. The risk factors associated with death from intracranial infection caused by Klebsiella pneumoniae included SOFA scores, ventilator therapy, CRKP, and heart failure. Longer hospital stays are independently associated with lower mortality rates. Intracranial infection caused by CRKP was associated with excess mortality. Complex comorbidities mean higher mortality. Active supportive treatment is required for complicated patients with intracranial infections caused by carbapenem-resistant Klebsiella pneumoniae.

In Vitro Synergistic Effect of Colistin with Fosfomycin Against Carbapenem-Resistant Klebsiella pneumoniae.

BACKGROUND: The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. Klebsiella pneumoniae, a gram-negative encapsulated member of the Enterobacteriaceae family, is one such pathogenic bacteria. Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method. METHODS: A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. Klebsiella pneumoniae isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method. RESULTS: Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001). CONCLUSION: This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit.

Molecular epidemiology, microbiological features and infection control strategies for carbapenem-resistant Acinetobacter baumannii in a German burn and plastic surgery center (2020-2022).

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) frequently causes both healthcare-associated infections and nosocomial outbreaks in burn medicine/plastic surgery and beyond. Owing to the high antibiotic resistance, infections are difficult to treat, and patient outcomes are often compromised. The environmental persistence capability of CRAB favors its transmission in hospitals. A comprehensive analysis and understanding of CRAB epidemiology and microbiology are essential for guiding management. METHODS: A three-year retrospective cohort study (2020-2022) was conducted in a German tertiary burn and plastic surgery center. In addition to epidemiological analyses, microbiological and molecular techniques, including whole-genome sequencing, were applied for the comprehensive examination of isolates from CRAB-positive patients. RESULTS: During the study period, eight CRAB cases were found, corresponding to an overall incidence of 0.2 CRAB cases per 100 cases and an incidence density of 0.35 CRAB cases per 1000 patient-days. Six cases (75%) were treated in the burn intensive care unit, and four cases (50%) acquired CRAB in the hospital. Molecular analyses comprising 74 isolates supported the epidemiologic assumption that hospital acquisitions occurred within two separate clusters. In one of these clusters, environmental CRAB contamination of anesthesia equipment may have enabled transmission. Furthermore, molecular diversity of CRAB isolates within patients was observed. CONCLUSIONS: CRAB can pose a challenge in terms of infection prevention and control, especially if cases are clustered in time and space on a ward. Our study demonstrates that high-resolution phylogenetic analysis of several bacterial isolates from single patients can greatly aid in understanding transmission chains and helps to take precision control measures.

Epidemiology of subsequent Carbapenem-Resistant Enterobacterales (CRE) infection among rectal carriers: a meta-analysis of incidence, risk factors and their association with geographic region and age.

OBJECTIVES: This study aimed to assess the incidence and risk factors of subsequent CRE infection among rectal carriers, and their association with geographic region and age. METHODS: A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to January 31st, 2024). This study is registered with PROSPERO, CRD42023444420. RESULTS: Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9-25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2-34.5), followed by Europe (20.9%, 95% CI 12.5-30.8) and Asia (19.8%, 95% CI 12.7-27.9). Children had a greater incidence (26.7%, 95% CI 21.3-32.3) than adults (19.8%, 95% CI 14.9-25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (OR 4.95 95% CI 1.87-13.11). In Europe, admission to ICU was prominent (OR 2.76 95% CI 1.14-6.65). In America, use of a urinary foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to ICU was most notable in adult (OR 3.01 95% CI 1.80-5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39-55.47). CONCLUSIONS: Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help developing more potent prevention and control measures to reduce CRE infection.

Characterization of the Chromosomally Located Metallo-ß-Lactamase Genes blaIMP-45 and blaVIM-2 in a Carbapenem-Resistant Pseudomonas aeruginosa Clinical Isolate.

Objective: Characterization of the multidrug resistance (MDR) region in P. aeruginosa strain PA59 revealed the presence of antibiotic resistance genes, including blaIMP-45 and blaVIM-2, within a complex genetic landscape of mobile genetic elements. Methods: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains were isolated from Shanghai Changhai Hospital. Polymerase chain reaction (PCR) was used to detect the ß-lactamase genes in the isolated strains. Strains carrying two or more genes were subjected to whole-genome sequencing (WGS) and in-depth bioinformatics analysis. Results: A total of 94 CRPA strains were isolated, among which PA59 was determined to carry blaIMP-45 and blaVIM-2 genes. Compared with single-gene positive or other blaIMP and blaVIM dual-gene positive strains reported, PA59 exhibited a broader range of drug resistance. We discovered a multidrug resistant (MDR)-related region composed of various mobile elements in the PA59 chromosome. This region carried many resistance genes, including the target genes blaIMP-45 and blaVIM-2. By further comparing the mobile elements GI13 and Ph08, we speculated that this integron structure carrying blaIMP-45 and blaVIM-2 was initially integrated into the genomic island or prophage, forming a more complex genetic structure, and then further integrated into the PA59 chromosome through plasmids. Phylogenetic tree analysis showed limited sequence similarity between PA59 and other CRPA strains. Conclusions: This study identified PA59 as the first reported P. aeruginosa strain carrying both blaIMP-45 and blaVIM-2 on the chromosome. The assembly and annotation of the PA59 genome provide valuable insights into the genomic diversity and gene content of this clinically important pathogen, aiding the development of effective strategies against antibiotic resistance.

Comparative Evaluation of Colistin-Susceptibility Testing in Carbapenem-Resistant Klebsiella pneumoniae Using VITEK, Colistin Broth Disc Elution, and Colistin Broth Microdilution.

PURPOSE: The study aimed to compare the results of colistin-susceptibility testing performed using the automated VITEK system, colistin broth microdilution (BMD), and colistin broth disk elution (CBDE) methods. MATERIALS AND METHODS: This exploratory study was conducted in a tertiary care center in South India. Carbapenem-resistant Klebsiella pneumoniae (n = 49) isolates collected from a clinical microbiology laboratory over six months (March-September 2023) were used for the study. RESULTS: Among the 49 carbapenem-resistant Klebsiella pneumoniae isolates, 42 were found to be susceptible to carbapenem by all three methods. Seven isolates were found to be resistant to colistin using BMD and CBDE methods. Two isolates were incorrectly detected as colistin-susceptible, and one isolate was wrongly categorized as colistin-resistant using the automated VITEK system. CONCLUSION:  CBDE is a reliable and cost-effective method that can be adopted in the routine microbiology laboratory for colistin-susceptibility testing, as it does not require any specialized equipment or techniques and is 100% consistent with the gold standard BMD method. Although the automated VITEK system is used in most routine microbiological laboratories for antibiotic-susceptibility testing, it cannot be reliably used for colistin-susceptibility testing due to its high error rates (very major error rate of 28.5%; major error rate of 2.4%).

High drug-pathogen mismatch in the management of invasive carbapenem-resistant Enterobacteriaceae infections at a tertiary hospital in Nigeria.

Objectives: This study aims to provide lacking data on antibiotics and treatment strategies used in the management of carbapenem-resistant Enterobacteriaceae (CRE) infections in Nigeria. Methods: A cross-sectional study was carried out at the University College Hospital in Ibadan. CRE isolated from routine culture of specimens from hospitalized patients from December 2021 to September 2022 was identified. Treatment information and other data were collected from the patients' medical records. Results: The hospital laboratory isolated CRE from 55 patients during the study period and 27 (49.1%) of them had data available for the study. The most frequently isolated CRE was Klebsiella spp. (13 of 27, 48.1%). Of the 24 patients who received empiric antibiotics, only two (8.3%) of their CRE isolates were susceptible. After receiving culture results, 18 (66.7%) patients were treated with at least one antibiotic, to which resistance was documented. Only three (11.1%) patients overall commenced or remained on an antibiotic, to which their CRE isolate was susceptible. Conclusions: Despite culture data, we found a high prevalence of drug-pathogen mismatch in CRE treatment, including new or persistent use of antibiotics, to which resistance was documented. Antimicrobial stewardship efforts need to be strengthened to specifically address CRE treatment and effective antibiotics need to be made accessible.

Genome-wide sRNA and mRNA transcriptomic profiling insights into carbapenem-resistant Acinetobacter baumannii.

Introduction: Acinetobacter baumannii (AB) is rising as a human pathogen of critical priority worldwide as it is the leading cause of opportunistic infections in healthcare settings and carbapenem-resistant AB is listed as a "super bacterium" or "priority pathogen for drug resistance" by the World Health Organization. Methods: Clinical isolates of A. baumannii were collected and tested for antimicrobial susceptibility. Among them, carbapenem-resistant and carbapenem-sensitive A. baumannii were subjected to prokaryotic transcriptome sequencing. The change of sRNA and mRNA expression was analyzed by bioinformatics and validated by quantitative reverse transcription-PCR. Results: A total of 687 clinical isolates were collected, of which 336 strains of A. baumannii were resistant to carbapenem. Five hundred and six differentially expressed genes and nineteen differentially expressed sRNA candidates were discovered through transcriptomic profile analysis between carbapenem-resistant isolates and carbapenem-sensitive isolates. Possible binding sites were predicted through software for sRNA21 and adeK, sRNA27 and pgaC, sRNA29 and adeB, sRNA36 and katG, indicating a possible targeting relationship. A negative correlation was shown between sRNA21 and adeK (r = -0.581, P = 0.007), sRNA27 and pgaC (r = -0.612, P = 0.004), sRNA29 and adeB (r = -0.516, P = 0.020). Discussion: This study preliminarily screened differentially expressed mRNA and sRNA in carbapenem-resistant A. baumannii, and explored possible targeting relationships, which will help further reveal the resistance mechanism and provide a theoretical basis for the development of drugs targeting sRNA for the prevention and treatment of carbapenem-resistant A. baumannii infection.

Ceftazidime-avibactam: Combination therapy versus monotherapy in the challenge of pneumonia caused by carbapenem-resistant Klebsiella pneumoniae.

This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits.

Characterization of a novel phage against multidrug-resistant Klebsiella pneumoniae.

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant challenge in global healthcare, underscoring the urgency for innovative therapeutic approaches. Phage therapy emerges as a promising strategy amidst rising antibiotic resistance, emphasizing the crucial need to identify and characterize effective phage resources for clinical use. In this study, we introduce a novel lytic phage, RCIP0100, distinguished by its classification into the Chaoyangvirus genus and Fjlabviridae family based on International Committee on Taxonomy of Viruses (ICTV) criteria due to low genetic similarity to known phage families. Our findings demonstrate that RCIP0100 exhibits broad lytic activity against 15 out of 27 tested MDR-KP strains, including diverse profiles such as carbapenem-resistant K. pneumoniae (CR-KP). This positions phage RCIP0100 as a promising candidate for phage therapy. Strains resistant to RCIP0100 also showed increased susceptibility to various antibiotics, implying the potential for synergistic use of RCIP0100 and antibiotics as a strategic countermeasure against MDR-KP.

Development and validation of a prognostic nomogram to predict 30-day all-cause mortality in patients with CRO infection treated with colistin sulfate.

Background: Carbapenem-resistant Gram-negative organism (CRO) infection is a critical clinical disease with high mortality rates. The 30-day mortality rate following antibiotic treatment serves as a benchmark for assessing the quality of care. Colistin sulfate is currently considered the last resort therapy against infections caused by CRO. Nevertheless, there is a scarcity of reliable tools for personalized prognosis of CRO infections. This study aimed to develop and validate a nomogram to predict the 30-day all-cause mortality in patients with CRO infection who underwent colistin sulfate treatment. Methods: A prediction model was developed and preliminarily validated using CRO-infected patients treated with colistin sulfate at Tongji Hospital in Wuhan, China, who were hospitalized between May 2018 and May 2023, forming the study cohort. Patients admitted to Xianning Central Hospital in Xianning, China, between May 2018 and May 2023 were considered for external validation. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of 30-day all-cause mortality. The receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and the calibration curve were used to evaluate model performance. The decision curve analysis (DCA) was used to assess the model clinical utility. Results: A total of 170 patients in the study cohort and 65 patients in the external validation cohort were included. Factors such as age, duration of combination therapy, nasogastric tube placement, history of previous surgery, presence of polymicrobial infections, and occurrence of septic shock were independently associated with 30-day all-cause mortality and were used to construct the nomogram. The AUC of the nomogram constructed from the above six factors was 0.888 in the training set. The Hosmer-Lemeshow test showed that the model was a good fit (p = 0.944). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the reliability of the prediction nomogram. Conclusion: A nomogram was developed and validated to predict the occurrence of 30-day all-cause mortality in patients with CRO infection treated with colistin sulfate. This nomogram offers healthcare providers a precise and efficient means for early prediction, treatment management, and patient notification in cases of CRO infection treated with colistin sulfate.

Carbapenem-resistant Enterobacterales sepsis following endoscopic retrograde cholangiopancreatography: risk factors for 30-day all-cause mortality and the development of a nomogram based on a retrospective cohort.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has become a routine endoscopic procedure that is essential for diagnosing and managing various conditions, including gallstone extraction and the treatment of bile duct and pancreatic tumors. Despite its efficacy, post-ERCP infections - particularly those caused by carbapenem-resistant Enterobacterales (CRE) - present significant risks. These risks highlight the need for accurate predictive models to enhance postprocedural care, reduce the mortality risk associated with post-ERCP CRE sepsis, and improve patient outcomes in the context of increasing antibiotic resistance. OBJECTIVE: This study aimed to examine the risk factors for 30-day mortality in patients with CRE sepsis following ERCP and to develop a nomogram for accurately predicting 30-day mortality risk. METHODS: Data from 195 patients who experienced post-ERCP CRE sepsis between January 2010 and December 2022 were analyzed. Variable selection was optimized via the least absolute shrinkage and selection operator (LASSO) regression model. Multivariate logistic regression analysis was then employed to develop a predictive model, which was evaluated in terms of discrimination, calibration, and clinical utility. Internal validation was achieved through bootstrapping. RESULTS: The nomogram included the following predictors: age > 80 years (hazard ratio [HR] 2.61), intensive care unit (ICU) admission within 90 days prior to ERCP (HR 2.64), hypoproteinemia (HR 4.55), quick Pitt bacteremia score ≥ 2 (HR 2.61), post-ERCP pancreatitis (HR 2.52), inappropriate empirical therapy (HR 3.48), delayed definitive therapy (HR 2.64), and short treatment duration (< 10 days) (HR 5.03). The model demonstrated strong discrimination and calibration. CONCLUSIONS: This study identified significant risk factors associated with 30-day mortality in patients with post-ERCP CRE sepsis and developed a nomogram to accurately predict this risk. This tool enables healthcare practitioners to provide personalized risk assessments and promptly administer appropriate therapies against CRE, thereby reducing mortality rates.