Carbapenem-resistant Gram-negative Bacteria Research Articles

In vitro activity of cefiderocol and other newly approved antimicrobials against multi-drug resistant Gram-negative pathogens recovered in intensive care units in Spain and Portugal.

The antimicrobial resistance is a significant public health threat, particularly for healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens which are increasingly reported worldwide. The aim of this study was to provide data on the in vitro antimicrobial activity of cefiderocol and that of commercially available comparator antibiotics against a defined collection of recent clinical multi-drug resistant (MDR) microorganisms, including carbapenem resistant Gram-negative bacteria collected from different regions in Spain and Portugal. A total of 477 clinical isolates of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia were prospectively (n=265) and retrospectively (n=212) included (2016-2019). Susceptibility testing was performed using standard broad microdilution and results were interpreted using CLSI-2021 and EUCAST-2021 criteria. Overall, cefiderocol showed a good activity against Enterobacterales isolates, being 99.5% susceptible by CLSI and 94.5% by EUCAST criteria. It also demonstrated excellent activity against P. aeruginosa and S. maltophilia isolates, all being susceptible to this compound considering CLSI breakpoints. Regarding A. baumannii (n=64), only one isolate was resistant to cefiderocol. Our results are in agreement with other studies performed outside Spain and Portugal highlighting its excellent activity against MDR gram-negative bacteria. Cefiderocol is a therapeutic alternative to those available for the treatment of infections caused by these MDR bacteria.

Cefiderocol use for the treatment of infections by carbapenem-resistant Gram-negative bacteria: an Italian multicentre real-life experience.

Cefiderocol is a novel siderophore cephalosporin with promising activity against most carbapenem-resistant Gram-negative bacteria (CRGNB). However, extensive postmarketing experiences are lacking. This study aimed to analyse the early experience on cefiderocol postmarketing use at three tertiary care hospitals in Italy. We retrospectively included patients with infections caused by CRGNB treated with cefiderocol at three Italian tertiary care hospitals from 1 March 2021 to 30 June 2022. A multivariate Cox model was used to identify predictors of 30 day mortality. A propensity score (PS) analysis with inverse probability weighting (IPW) was also performed to compare the treatment effect of cefiderocol monotherapy (CM) versus combination regimens (CCRs). The cohort included 142 patients (72% male, median age 67 years, with 89 cases of Acinetobacter baumannii infection, 22 cases of Klebsiella pneumoniae, 27 cases of Pseudomonas aeruginosa and 4 of other pathogens). The 30 day all-cause mortality was 37% (52/142). We found no association between bacterial species and mortality. In multivariate analysis, a Charlson Comorbidity Index >3 was an independent predictor of mortality (HR 5.02, 95% CI 2.37-10.66, P < 0.001). In contrast, polymicrobial infection (HR 0.41, 95% CI 0.21-0.82, P < 0.05) was associated with lower mortality. There was no significant difference in mortality between patients receiving CM (n = 70) and those receiving a CCR (n = 72) (33% versus 40%, respectively), even when adjusted for IPW-PS (HR 1.11, 95% CI 0.63-1.96, P = 0.71). Real-life data confirm that cefiderocol is a promising option against carbapenem-resistant Gram-negative infections, even as monotherapy.

Analysis of Pathogenic Bacterial Spectrum, Drug Resistance and Risk Factors for Mortality of Bloodstream Infection in Patients with Hematologic Diseases

To analyze the pathogenic bacterial spectrum, drug resistance, and risk factors associated with multidrug-resistant bacterial infection and mortality in patients with hematologic diseases complicated by bloodstream infections, so as to provide reference for rational drug use and improving prognosis. Positive blood culture specimens of patients with hematologic diseases in two Class A tertiary hospitals of Shanxi province from January 2019 to December 2021 were retrospectively analyzed. Pathogen distribution, drug resistance and outcomes of patients with bloodstream infection were investigated, then the multivariate logistic analysis was performed to analyze the risk factors of multidrug-resistant bacterial infection and factors affecting prognosis. 203 strains of pathogens were identified, mainly Gram-negative bacteria (GNB) (69.46%, 141/203), of which Escherichia coli (E.coli) had the highest incidence (41.13%, 58/141), followed by Klebsiella pneumoniae (20.57%, 29/141) and Pseudomonas aeruginosa (12.77%, 18/141). Extended-spectrum beta-lactamase (ESBL)-producing E.coli and Klebsiella pneumoniae were 46.55% (27/58) and 37.93% (11/29), respectively. Carbapenem-resistant Gram-negative bacteria accounted for 10.64% (15/141). And Gram-positive bacteria accounted for 27.59% (56/203), Staphylococcus epidermidis, Streptococcus pneumoniae, and Staphylococcus aureus were the most frequently isolated pathogen among Gram-positive bacteria (14.29%, 12.50% and 10.71%, respectively), of which methicillin-resistant Staphylococcus aureus accounted for 33.33% (2/6), coagulase-negative staphylococci accounted for 87.50% (7/8), without vancomycin- or linezolid-resistant strain. Additionally, fungi accounted for 2.95% (6/203), all of which were Candida. Multidrug-resistant Gram-negative bacteria (MDR-GNB) accounted for 53.90% (76/141). Duration of neutropenia >14 days was a risk factor for developing MDR-GNB infection. The 30-day all-cause mortality was 10.84%. Multivariate logistic regression analysis showed that the significant independent risk factors for mortality were age≥60 years (P <0.01, OR =5.85, 95% CI: 1.80-19.07) and use of vasopressor drugs (P <0.01, OR =5.89, 95% CI: 1.83-18.94). The pathogenic bacteria of bloodstream infection in patients with hematological diseases are widely distributed, and the detection rate of multidrug-resistant bacteria is high. The clinicians should choose suitable antibiotics according to the results of bacterial culture and antibiotic susceptibility test.

Kolistin direncinin moleküler tespitinde yanlış tanı: kolistine duyarlı Acinetobacter baumannii izolatlarında yanlış mcr-1-PCR pozitifliği

Purpose: The aim of this study was to investigate the presence of the mcr-1 gene, which is responsible for colistin resistance, in carbapenem-resistant Gram-negative bacteria that cause difficult-to-treat infections in a research hospital in Turkey. &#x0D; Materials and Methods: The mcr-1 gene was examined using PCR in 103 carbapenem-resistant isolates, including 75 Acinetobacter baumannii, 19 Pseudomonas aeruginosa, and 9 Klebsiella pneumoniae. DNA sequencing was performed to confirm the mcr-1 positivity. Other antimicrobial resistance genes were investigated in isolates that were found to be mcr-1-positive by PCR and colistin-resistant isolates. &#x0D; Results: Four (3.9% of the 103 carbapenem-resistant isolates and 5.3% of the 75 A. baumannii isolates) A. baumannii isolates, all susceptible to colistin, were found to be mcr-1-positive by PCR, whereas mcr-1 was not detected in four colistin-resistant isolates, one in A. baumannii and three in K. pneumoniae. DNA sequencing analysis determined that none of the amplification products was the targeted fragment, but they matched more than 70% with the chromosomal DNA fragments of A. baumannii strains. Therefore, these results were considered false-positive. Although these false-positive isolates were susceptible to colistin, they were extensively drug-resistant (XDR). Two of them were found to carry blaOXA23-like and blaTEM genes, another blaOXA23-like, blaTEM and blaOXA48-like genes, and the fourth one to have blaOXA23-like and blaCTXM genes. &#x0D; Conclusion: Although the specificity of the primers used to detect the mcr-1 gene by PCR was reported as 100% in most studies, we concluded that PCR tests are insufficient yet to use alone or with antibiotic susceptibility tests in rapid routine diagnosis. Confirming at least PCR-positive samples using DNA sequence analysis would be appropriate for a certain period.

Colistin Susceptibility Testing by Colistin Broth Disk Elution MIC Method among Carbapenem-resistant Gram-negative Blood Culture Clinical Isolates in a Tertiary Care Setting, East Delhi, India.

Antibiotic resistance is a growing concern for bloodstream infections (BSIs), especially with the emergence of multidrug-resistant (MDR) gram-negative bacteria. In this study, we aimed to assess the pattern of colistin susceptibility using the colistin broth disc elution (CBDE) method among carbapenem-resistant gram-negative clinical isolates from blood cultures in a high burden tertiary healthcare setting in East Delhi. A total of 106 carbapenem-resistant gram-negative clinical isolates were tested. The most common isolates were Klebsiella pneumoniae, Escherichia coli, Enterobacter species, and Klebsiella oxytoca by CBDE method. All the carbapenem resistant gram-negative bacterial blood culture isolates showed intermediate colistin susceptibility. This was statistically significant by chi-square test (p<0.5). This study highlights the need to monitor colistin resistance trends in the face of increasing antimicrobial resistance. Accurate surveillance of emerging colistin resistance is crucial for effective management of BSIs caused by carbapenem-resistant gram-negative bacteria.

Eugenol works synergistically with colistin against colistin-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae isolates by enhancing membrane permeability.

Colistin is a potent antibiotic for the treatment of carbapenem-resistant Gram-negative bacteria and is considered a last-resort drug. Unfortunately, the incidence of colistin-resistant bacteria isolated from patients is continuously growing due to clinical reuse of colistin. In this study, we found that the combination of colistin and eugenol has a significant synergistic antibacterial effect and reverses the sensitivity of colistin-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae against colistin, as confirmed by checkerboard and time-kill assays. Crystal violet staining and scanning electron microscopy revealed colistin and eugenol's synergistic antibiofilm action. Concerning the synergy mechanism, the results revealed that the combination of eugenol and colistin increases membrane permeability and causes considerable membrane damage, further inhibiting bacteria synergistically. Meanwhile, up to 500 µg/mL of eugenol is non-toxic to RAW 264.7 cells, and the colistin/eugenol combination is also efficacious in vivo, as demonstrated by the Galleria mellonella infection model. Our findings indicate that the colistin/eugenol combination is a viable treatment option for colistin-resistant P. aeruginosa and K. pneumoniae clinical infections. IMPORTANCE Colistin is used as a last resort for severe infections caused by multidrug-resistant Gram-negative bacteria, however, colistin resistance is increasing. As a result, we investigated the synergistic effect of eugenol/colistin combination, and the results revealed significant antibacterial and antibiofilm action. Eugenol may help clinical colistin-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae recover their susceptibility. These findings suggest that combining eugenol and colistin may be a viable treatment option for colistin-resistant pathogen clinical infections.

Clinical characteristics and prognosis of pneumonia-related bloodstream infections in the intensive care unit: a single-center retrospective study.

Bloodstream infections (BSI) are one of the most severe healthcare-associated infections in intensive care units (ICU). However, there are few studies on pneumonia-related BSI (PRBSI) in the ICU. This study aimed to investigate the clinical and prognostic characteristics of patients with PRBSI in the ICU and to provide a clinical basis for early clinical identification. We retrospectively collected data from patients with bacterial BSI in a single-center ICU between January 1, 2017, and August 31, 2020. Clinical diagnosis combined with whole-genome sequencing (WGS) was used to clarify the diagnosis of PRBSI, and patients with PRBSI and non-PRBSI were analyzed for clinical features, prognosis, imaging presentation, and distribution of pathogenic microorganisms. Of the 2,240 patients admitted to the MICU, 120 with bacterial BSI were included in this study. Thirty-two (26.7%) patients were identified as having PRBSI based on the clinical diagnosis combined with WGS. Compared to patients without PRBSI, those with PRBSI had higher 28-day mortality (81.3 vs.51.1%, p = 0.003), a higher total mortality rate (93.8 vs. 64.8%, p = 0.002), longer duration of invasive mechanical ventilation (median 16 vs. 6 days, p = 0.037), and prolonged duration of ICU stay (median 21 vs. 10 days, p = 0.004). There were no differences in other baseline data between the two groups, but patients with PRBSI had extensive consolidation on chest radiographs and significantly higher Radiographic Assessment of Lung Edema scores (mean 35 vs. 24, p < 0.001). The most common causative organisms isolated in the PRBSI group were gram-negative bacteria (n = 31, 96.9%), with carbapenem-resistant gram-negative bacteria accounting for 68.8% (n = 22) and multidrug-resistant bacteria accounting for 81.3% (n = 26). Pneumonia-related BSI is an important component of ICU-BSI and has a poor prognosis. Compared to non-PRBSI, patients with PRBSI do not have typical clinical features but have more severe lung consolidation lesions, and should be alerted to the possibility of their occurrence when combined with pulmonary gram-negative bacterial infections, especially carbapenem-resistant bacteria. Further multicenter, large-sample studies are needed to identify the risk factors for the development of PRBSI and prevention and treatment strategies.

Identification of TMexCD-TOprJ-producing carbapenem-resistant Gram-negative bacteria from hospital sewage.

Carbapenems and tigecycline are crucial antimicrobials for the treatment of gram-negative bacteria infections. Recently, a novel resistance-nodulation-division (RND) efflux pump gene cluster, tmexCD-toprJ, which confers resistance to tigecycline, has been discovered in animals and clinical isolates. It was reported that hospital sewage could act as a reservoir for gram-negative bacteria with high antimicrobial resistance genes. In this study, we analyzed 84 isolates of carbapenem-resistant gram-negative bacteria (CR-GNB) from hospital sewage, and identified five isolates of TMexCD-ToprJ-producing CR-GNB, including one Raoultella ornithinolytica isolate and four Pseudomonas spp. isolates. All these five isolates carried at least one carbapenem resistance gene and were resistant to multiple antibiotics. Multiple tmexCD-toprJ clusters were detected, including tmexC2D2-toprJ2, tmexC3D3-toprJ3, tmexC3.2D3.3-toprJ1b and tmexC3.2D3-toprJ1b. Among these clusters, the genetic construct of tmexC3.2D3-toprJ1b showed 2-fold higher minimum inhibitory concentration (MIC) of tigecycline than other three variants. In addition, it was found that the tmexCD-toprJ gene cluster was originated from Pseudomonas spp. and mainly located on Tn6855 variants inserted in the same umuC-like genes on chromosomes and plasmids. This unit co-localized with blaIMP or blaVIM on IncHI5-, IncpJBCL41- and IncpSTY-type plasmids in the five isolates of TMCR-GNB. The IncHI5- and IncpSTY-type plasmids had the ability to conjugal transfer to E. coli J53 and P. aeruginosa PAO1, highlighting the potential risk of transfer of tmexCD-toprJ from Pseudomonas spp. to Enterobacterales. Importantly, genomic analysis showed that similar tmexCD-toprJ-harboring IncHI5 plasmids were also detected in human samples, suggesting transmission between environmental and human sectors. The emergence of TMCR-GNB from hospital sewage underscores the need for ongoing surveillance of antimicrobial resistance genes, particularly the novel resistance genes such as the tmexCD-toprJ gene clusters in the wastewater environment.

Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Gram-Negative Bacteria in a Pediatric Intensive Care Unit

AbstractWe aimed to analyze risk factors of ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR), pan-drug-resistant (PDR), and extensively drug-resistant (XDR) gram-negative bacteria (GNB) in a pediatric intensive care unit (PICU). This retrospective study evaluated pediatric patients diagnosed with VAP at a tertiary referral hospital. Of the 46 children in the present study, 40 (86.9%) had VAP caused by MDR-, XDR-, and PDR-GNB. Most patients (60.9%) had spent &gt;28 days in the PICU at the time of diagnosis. Respiratory failure necessitating PICU admission was associated with XDR infection-induced VAP (p = 0.034). High rates of prior broad-spectrum antibiotic use were observed in patients with XDR GNB-induced VAP. VAP induced by MDR-, XDR-, and PDR-GNB occurred more frequently than that caused by drug-susceptible GNB in PICU patients. Long stays for more than 28 days in the PICU and past use of broad-spectrum antibiotics can lead to the development of XDR-GNB-induced VAP. The high antibiotic resistance rates detected in our study highlight the importance of strict infection control measures and antimicrobial stewardship programs in PICUs.

Comparison of the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of ventilator-associated pneumonia caused by carbapenem-resistant gram-negative bacteria: a retrospective cohort study.

Objective: To investigate the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of VAP caused by CR-GNB. Additionally, among patients treated with nebulized polymyxin monotherapy, we compared the clinical efficacy and toxicity of polymyxin B and polymyxin E. Methods: This study was a single-center, retrospective study. Included patients received aerosolized polymyxin for at least 72h with or without intravenous polymyxin for the management of CR-GNB VAP. The primary endpoint was clinical cure at the end of polymyxin therapy. Secondary endpoints included AKI incidence, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU, and all-cause ICU mortality. Results: 39 patients treated with nebulized polymyxin monotherapy were assigned to the NL-polymyxin group. 39 patients treated with nebulized polymyxin combined with intravenous use of polymyxin were assigned to the IV-NL-polymyxin group. Among the NL-polymyxin group, 19 patients were treated with polymyxin B and 20 with polymyxin E. The clinical baseline characteristics before admission to the ICU and before nebulization of polymyxin were similar between the two groups. No differences were found between the two study groups in terms of microorganism distribution, VAP cure rate, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU and all-cause ICU mortality. Similarly, survival analysis did not differ between the two groups (χ2 = 3.539, p = 0.06). AKI incidence was higher in the IV-NL-polymyxin group. When comparing the clinical efficacy and toxicity to polymyxin B and polymyxin E, there was no difference between the two groups in terms of VAP cure rate, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU, SOFA score, CPIS, AKI incidence and all-cause ICU mortality. Conclusion: Our study found that nebulized polymyxin monotherapy was non-inferior to combination therapy with intravenous polymyxin in treating CR-GNB-VAP. Furthermore, we observed no differences in clinical efficacy or related toxic side effects between polymyxin B and polymyxin E during nebulized polymyxin therapy as monotherapy. However, future prospective studies with larger sample sizes are required to confirm these findings.

Evaluation of the liquid colony for identification and antimicrobial susceptibility testing directly from positive blood cultures

BackgroundSepsis represents a time-sensitive disease requiring early therapeutical intervention to avoid adverse patient outcomes. Rapid microbiological diagnosis is essential to investigate sepsis aetiological agents. The FAST™ system (Qvella, ON, Canada) provides a concentrated microbial suspension, known as a Liquid Colony™ (LC), directly from positive blood samples (PBCs) in 30–40 min to perform rapid identification (ID) and antimicrobial susceptibility testing (AST).MethodsQvella’s FAST™ System and FAST PBC Prep cartridges were tested on PBCs from the Policlinico Hospital of Catania during a six-month study. Two millilitres of PBC were converted into an LC for rapid ID and AST using Bruker Biotyper Sirius MALDI and BD Phoenix systems. Standard of care (SOC) methods were used as a reference, requiring 48–72 h. Agreement between the innovative technology and the standard method was calculated.ResultsFAST System processing was performed on 100 monomicrobial PBCs. Median turnaround times from blood cultures flagging positive to ID and AST completion were 2 and 26 h respectively. Therefore, the LC procedure was 24 h faster than the median turnaround times for SOC methods. 100% ID identification concordance was observed across 48 Gram-negative bacteria, 42 Gram-positive bacteria and 11 yeast for the genus level. 78% of Gram-negative and 95% of Gram-positive bacteria were resistant to ≥ 2 antimicrobial agents, including 45% (15/33) carbapenem-resistant enteric Gram-negative bacteria and 90% (28/31) oxacillin-resistant staphylococci. An AST essential agreement of 100% was observed due to the absence of MIC discrepancies > 1-fold dilution. Categorical errors were not observed due to the absence of MIC categorization discordances. Yeast AST was not performed.ConclusionsThe Qvella FAST System produces an LC that reliably reflects the MALDI spectra and phenotypic antimicrobial susceptibility profile of microbial cells growing in the blood culture. Timely processing of PBCs with the Qvella FAST System enables sepsis diagnostic confirmation 1 day sooner than the standard methods. In line with these results, it is vital now to focus attention on establishing best practices for incorporating this strategic tool into the clinical microbiology laboratory workflow.

Characteristics of trauma patients with multidrug-resistant bacteria from an epidemiological, clinical, and microbiological perspective

Trauma, healthcare-associated infections, and antimicrobial resistance are three major public health issues worldwide due to the high probability of patient morbidity and, ultimately, a tragic outcome. In the current study included all patients admitted to The NRI Medical College Hospital, (Mangalagiri, Andhra Pradesh, India) intensive care units between May 1, 2021 and August 31, 2022. Patients with first bacteremia were found to have MRSA, VRE, and carbapenem-resistant Gram-negative bacteria. We included 1528 patients, 302 of whom had trauma and 66 (4.3%) of whom had MR-agent-induced bacteremia. Mechanical ventilation, renal replacement therapy, and surgery were all independent risk factors for MR agent bacteremia. In the trauma cohort, haemodialysis alone was associated with an increased risk of MR agent bacteremia. S. aureus, MRSA (n=27), and K. pneumoniae (n=26) were the two most common isolating agents. The blaKPC gene was found in 83% of the K. pneumoniae strains (while the NDM gene was found in only one). Injuries have no effect on the development of bacteremia caused by MR agents. Certain risk factors appear to be associated with the severity of MR bacteremia cases. &#x0D;

Research of antibiotics resistance of gram-negative bacteria strains causing urinary tract infections isolatedat Nghe An Friendship General Hospital

Urinary tract infection is one of the common infections, which can recur many times if not diagnosed early and treated effectively. Gram-negative bacteria are the most common pathogens. In this study, the author determined the pathogenic gram-negative bacteria and their level of antibiotic resistance with the aim of making the treatment effective, reducing the cost of treatment, and limiting the proliferation of antibiotic-resistant bacteria. A descriptive cross-sectional study on 400 strains of gram-negative bacteria showed that the most common bacteria were Escherichia coli 38.48%, Pseudomonas aeruginosa 14.15%, Klebsiella pneumoniae 13.32%. E. coli is resistant to Cephalosporine, Quinolone antibiotics from 65.0-74.8%, Carbapenem 6.8-8.6%, producing extended-spectrum beta-lactamase (ESBL) 58.4%. K. pneumoniae is resistant to Cephalosporine, Quinolone 66.7-76.9%, Carbapenem 29.7-35.9%. P. aeruginosa was resistant to the tested antibiotics from 58.7 to 77.5%. The study results showed that the isolated bacteria were resistant to many commonly used antibiotics to varying degrees. Carbapenem-resistant gram-negative bacteria appeared at a high rate.

Propranolol restores susceptibility of XDR Gram-negative pathogens to meropenem and Meropenem combination has been evaluated with either tigecycline or amikacin

BackgroundInfection with extensive-drug-resistant (XDR) carbapenem-resistant (CR) Gram-negative bacteria (GNB) are viewed as a serious threat to human health because of the limited therapeutic options. This imposes the urgent need to find agents that could be used as adjuvants or combined with carbapenems to enhance or restore the susceptibility of XDR CR- GNB. Therefore, this study aimed to examine the effect of propranolol (PR) in combination with Meropenem (MEM) on the susceptibility profile of XDR CR-GNB recovered from severely infected patients as well as to evaluate combining MEM with either tigecycline (TGC) or amikacin (AK).MethodsA total of 59 non-duplicate CR- GNB were investigated for carbapenemase production by the major phenotypic methods. Molecular identification of five major carbapenemase-coding genes was carried out using polymerase chain reactions (PCR). Antimicrobial susceptibility tests were carried out using standard methods. Phenotypic and genotypic relatedness was carried out using the heatmap and ERIC PCR analysis. PR, 0.5 -1 mg/mL against the resulting non-clonal XDR CR-GNB pathogens were evaluated by calculating the MIC decrease factor (MDF). A combination of MEM with either AK or TGC was performed using the checkerboard assay.ResultsA total of 21 (35.6%) and 38 (64.4%) CR-GNB isolates were identified as enterobacterial isolates (including 16 (27.1%) Klebsiella Pneumoniae and 5 (8.5%) Escherichia coli) and non-fermentative bacilli (including, 23 (39%), Acinetobacter baumannii, and 15 (25.4%) Pseudomonas aeruginosa). The heatmap and ERIC PCR analysis resulted in non-clonal 28 XDR CR isolates. PR, at a concentration of 0.5 mg /ml, decreased MICs values of the tested XDR CR isolates (28; 100%) and restored susceptibility of only 4 (14.3%) isolates. However, PR (1 mg/mL) when combined with MEM has completely (28; 100%) restored the susceptibility of the tested XDR CR- GNB to MEM. The MEM + AK and MEM + TGC combination showed mostly additive effects (92.8% and 71.4%, respectively).ConclusionPR at a concentration of 1 mg/mL restored the susceptibility of XDR CR- GNB to MEM which is considered a promising result that should be clinically investigated to reveal its suitability for clinical use in patients suffering from these life-threatening pathogens.

Frequency, Bacteriological Profile, and Outcome of Neonatal Sepsis with Carbapenem-Resistant Gram-Negative Bacteria at the Tertiary Neonatal Intensive Care Unit, Ahvaz, Iran

Background: One of the leading causes of neonatal mortality in low- and middle-income countries (LMICs) is neonatal sepsis caused by carbapenem-resistant gram-negative bacteria. Objectives: This study aimed to determine the frequency, bacterial profile, and outcome of carbapenem-resistant Gram-negative neonatal sepsis in southwest Iran. Methods: This 15-month retrospective cross-sectional descriptive study was conducted at a level 3 referral training hospital. The study included all neonates hospitalized from birth who had positive blood cultures for Gram-negative bacteria. Patients were divided into carbapenem-resistant and carbapenem-sensitive groups. Results: During the study, Gram-negative bacteria were isolated from the blood cultures of 113 neonates. Positive Gram-negative bacteria blood cultures and carbapenem-resistant cases were 2.38% and 1.52%, respectively. In these cases, 66 (58.4%) of the infants were males, 100 (88.4%) were preterm, and 74 (65.4%) required mechanical ventilation within the first three days of life. The study found 45 (39.8%) infants with early-onset sepsis. Acinetobacter was the most common isolated organism, while Enterobacter had the lowest isolation rate. Carbapenem resistance was discovered in 72 (63.7%) positive blood cultures. Acinetobacter had the highest prevalence of carbapenem resistance, while Pseudomonas had the lowest. Mortality rates in infants infected with carbapenem resistance bacteria (CRB) were 89.3% compared to 10.7% in those infected with carbapenem-sensitive bacteria (CSB). Conclusions: The frequency of carbapenem-resistant Gram-negative sepsis in our ward was 1.52 percent of all admissions, and Acinetobacter bacteria was the most common cause of this type of neonatal sepsis. Infants infected with CRB had a higher mortality rate than those infected with CSB, 89.3% versus 10.7%.

Crude Mortality Associated With the Empirical Use of Polymyxins in Septic Patients in a Setting of High Prevalence of Carbapenem-Resistant Gram-negative Bacteria: Retrospective Analysis of a Cohort.

Our aim in this retrospective cohort study was to assess the impact on mortality of the empirical use of polymyxin as therapy for carbapenem-resistant gram-negative bacteria (CR-GNB) in septic patients. The study was performed at a tertiary academic hospital in Brazil, from January 2018 to January 2020, the pre-coronavirus disease 2019 period. We included 203 patients with suspected sepsis. The first doses of antibiotics were prescribed from a "sepsis antibiotic kit", which contained a selection of drugs, including polymyxin, with no preapproval policy. We developed a logistic regression model to assess risk factors associated with 14-day crude mortality. Propensity score for polymyxin was used to control biases. Seventy (34%) of 203 patients had infections with at least 1 multidrug-resistant organism isolated from any clinical culture. Polymyxins in monotherapy or in combination therapy were prescribed to 140 of the 203 (69%) patients. The overall 14-day mortality rate was 30%. The 14-day crude mortality was associated with age (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .01), SOFA (sepsis-related organ failure assessment) score value (aOR, 1.2; 95% CI, 1.09-1.32; P < .001), CR-GNB infection (aOR, 3.94; 95% CI, 1.53-10.14; P = .005), and time between suspected sepsis and antibiotic administration (aOR, 0.73; 95% CI, .65-.83; P < .001). The empirical use of polymyxins was not associated with decreased crude mortality (aOR, 0.71; 95% CI, .29-1.71; P = .44). Empirical use of polymyxin for septic patients in a setting with high CR-GNB prevalence was not associated with decreased crude mortality.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

Characteristics, Outcomes, and Clinical Indicators of Bloodstream Infections in Neutropenic Patients with Hematological Malignancies: A 7-Year Retrospective Study.

The aim of this study was to investigate the current epidemiology, its changes during the study years, and inflammatory biomarkers of bacterial bloodstream infections (BSIs) in neutropenic patients with hematological malignancies. We assessed mortality risk factors and multidrug-resistant (MDR) gram-negative BSI predictors. We conducted a retrospective study from January 2015 to December 2021, which included adult neutropenic oncohematological patients with confirmed BSIs. We used univariable and multivariable analyses to analyze the risk factors. Each index's reliability for bacterial BSI diagnosis was assessed using the receiver-operating characteristic curve and area under the curve. A total of 514 isolates were obtained from the 452 patients. The average mortality was 17.71%. Gram-negative organisms were the predominant causes of BSI. Escherichia coli was the most common microorganism (49.90%). The overall variation trend of the isolation rate of MDR and carbapenem-resistant gram-negative bacteria increased. Multivariate analysis indicated that: 1) neutropenia that lasted for more than 7 days, patients ≥ 60 years of age, septic shock, hospitalization for >20 days, BSI with a carbapenem-resistant strain, and treatment with linezolid or vancomycin in infections lasting less than 30 days were independent mortality risk factors; 2) severe neutropenia exceeding 7 days, unreasonable empirical therapy, and receipt of aminoglycosides or 3rd or 4th generation cephalosporins in infections lasting less than 30 days were independent risk factors of MDR gram-negative bacteria. Procalcitonin, absolute neutrophil count, and white blood cell indicate higher diagnostic accuracy for BSIs. Moreover, bacteria time to detection was better at differentiating Gram-negative and Gram-positive bacterial infections. We analyzed the risk factors for BSI neutropenic patients with hematological malignancies, the distribution of bacteria, antibiotic resistance, and the changes in clinical parameters. This single-center retrospective study may provide clinicians with novel insights into the diagnosis and treatment of BSI to improve future clinical outcomes.

Predictors of Mortality in Patients with Infections Due to Carbapenem-Resistant Gram-Negative Bacteria.

Infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day all-cause mortality in patients with CR-GNB infections. We conducted a cohort study from 1 January 2019 to 30 April 2022. The primary outcome was death from any cause during the first 90 days after the date of the first CR-GNB-positive culture. Secondary outcomes included infection relapse, invasive mechanical ventilation during follow-up, need for additional source control, acute kidney injury, Clostridioides difficile infection, and all-cause hospital admission after initial discharge. Bivariate and multivariate Cox-proportional hazards models were constructed to identify the factors independently associated with 90-day all-cause mortality. A total of 225 patients with CR-GNB infections were included. Death occurred in 76 (34%) cases. The most-reported comorbidities were immunosuppression (43%), arterial hypertension (35%), and COVID-19 (25%). The median length of stay in survivors was 18 days (IQR 10-34). Mechanical ventilation and ICU admission after diagnosis occurred in 8% and 11% of cases, respectively. Both infection relapse and rehospitalisation occurred in 18% of cases. C. difficile infection was diagnosed in 4% of cases. Acute kidney injury was documented in 22% of patients. Mechanical ventilation after diagnosis, ICU admission after diagnosis, and acute kidney injury in the first ten days of appropriate treatment were more frequently reported among non-survivors. In the multivariate analysis, age (HR 1.19 (95%CI 1.00-1.83)), immunosuppression (HR 1.84 (95%CI 1.06-3.18)), and septic shock at diagnosis (HR 2.40 (95% 1.41-4.08)) had an independent association with death during the first 90 days after the CR-GNB infection diagnosis. Receiving antibiogram-guided appropriate treatment was independently associated with a lower risk of death (HR 0.25 (95%CI 0.14-0.46)). The presence of advanced age, immunosuppression, septic shock at diagnosis, and inappropriate treatment are associated with higher 90-day all-cause mortality in hospitalised patients with infections due to CR-GNB. Recognition of the risk factors for adverse outcomes could further assist in patient care and the design of interventional studies that address the severe and widespread problem that is carbapenem resistance.

Polymyxin B therapy based on therapeutic drug monitoring in carbapenem-resistant organisms sepsis: the PMB-CROS randomized clinical trial

BackgroundThe appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance.MethodsIn China’s Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration–time curve across 24 h at a steady state (ssAUC0–24) of 50–100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality.ResultsThis trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan–Meier’s 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0–24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups.ConclusionA fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results were valued to prevent AKI.Trial registration Trial registration ClinicalTrials.gov: ChiCTR2100043208, Registration date: January 26, 2021.