Carbapenem-resistant Enterobacteriaceae Research Articles

Use of Fourier-transform infrared spectroscopy for real-time outbreak investigation of OXA-48-producing Escherichia coli.

Efficient infection control during carbapenem-resistant Enterobacterales outbreaks demands rapid and simple techniques for outbreak investigations. WGS, the current gold standard for outbreak identification, is expensive, time-consuming and requires a high level of expertise. Fourier-transform infrared (FTIR) spectroscopy (IR Biotyper) is a rapid typing method based on infrared radiation applied to samples, which provides a highly specific absorption spectrum. To investigate an outbreak of OXA-48-producing Escherichia coli in real-time using FTIR and subsequently compare the results with WGS. Twenty-one isolates were collected during a nosocomial outbreak, and identification and antibiotic susceptibilities were confirmed by VITEK®2. FTIR was conducted for all isolates, and nine representative isolates were sequenced. FTIR was able to correctly determine the clonal relatedness of the isolates and to identify the outbreak cluster, as confirmed by WGS. By WGS, isolates in the main FTIR cluster belonged to the same MLST type and core-genome MLST type, and they harboured similar plasmids and resistance genes, whereas the singletons external to the FTIR cluster had different genetic content. FTIR can operate as a rapid, efficient and reliable first-line tool for outbreak investigations during a real-time ongoing E. coli outbreak, which can contribute to limiting the spread of pathogens.

The experience of an antimicrobial stewardship program and antibiotic consumption and resistance trends during the COVID-19 pandemic at a tertiary care center in Beirut

BackgroundAntimicrobial Resistance, a global concern, worsened with the COVID-19 pandemic that caused a surge of critically ill patients, increased antimicrobial consumption, and the spread of infections with multidrug-resistant organisms (MDROs). Antimicrobial Stewardship Programs (ASP) aim to optimize antimicrobial utilization to fight resistance. We aim to describe the ASP experience and to study antimicrobial consumption and MDRO rates among COVID-19 patients at a tertiary care center in Beirut. MethodsWe compiled the ASP interventions, defined as ASP team recommendations, from January 2019 until December 2021. Data on antimicrobial consumption, expressed as a defined daily dose (DDD) per 100 patient days, was collected per quarter for all antimicrobials and restricted antimicrobials per ASP guidance. Our primary objective was to report on the ASP experience, and the secondary objective was to reflect on the rates of MDROs among hospitalized COVID-19 patients with respiratory or bloodstream bacterial co-infections between March 2020 and September 2021. Results9922 ASP interventions were documented during this study period, with a noticeable correlation between COVID-19 surges in Lebanon and the number of ASP interventions. Acceptance rates for these recommendations improved over time, with a noticeable decrease in the proportion of interventions related to de-escalation and discontinuation of broad-spectrum antimicrobials. We noted an increase in all antimicrobial consumption after the onset of the pandemic, peaking in Q4 2020 (142.8 DDD of anti-infectives/100 patient days) and Q1 2021 (79.1 DDD of restricted anti-infectives/100 patient days). As expected, MDROs, particularly ESKAPE organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Carbapenem-resistant Enterobacteriaceae) accounted for 24% of isolates obtained from this cohort. ConclusionThis study highlights the experience of the ASP as we adapted to the COVID-19 pandemic. The ASP team maintained its operations and continued to monitor antibiotic consumption and provide recommendations to limit antibiotic misuse in an effort to mitigate the impact of the pandemic on antimicrobial resistance.

Role of Probiotics in Preventing Carbapenem-Resistant Enterobacteriaceae Colonization in the Intensive Care Unit: Risk Factors and Microbiome Analysis Study.

Older patients with multiple comorbidities often necessitate prolonged hospital stays and antibiotic treatment in the intensive care unit (ICU), leading to a rise in multidrug-resistant organisms like carbapenem-resistant Enterobacteriaceae (CRE). This study examined risk factors for carbapenem-resistant Enterobacteriaceae colonization in the ICU and assessed probiotics' preventive role. In this single-center, retrospective study, 9099 ICU patients were tested for stool CRE culture from March 2017 to April 2022. We excluded 136 patients with CRE colonization within one week post-admission and 26 who received probiotics before CRE colonization. Ultimately, 8937 CRE-negative patients were selected. Logistic analysis identified CRE colonization risk factors and evaluated probiotics' influence, including Saccharomyces boulardii or Lactobacillus rhamnosus, used by 474 patients (5.3%) in the ICU. Compared with data on initial admission, 157 patients (1.7%) had newly discovered CRE colonization before discharge. In a multivariate analysis, coronavirus disease 2019, the ICU, tube feeding, antibiotics such as aminoglycoside, extended-spectrum penicillin, stool vancomycin-resistance enterococci colonization, and chronic kidney disease were significantly associated with de novo CRE infection. However, probiotic use was negatively correlated with CRE infection. Managing risk factors and administering probiotics in the ICU may help prevent CRE colonization; large randomized prospective studies are needed.

Disease burden of bacteraemia with extended-spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales in Korea

Despite the significant impact of multi-drug-resistant bacteraemia, especially extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE), the burden of disease has not been investigated thoroughly. To evaluate the clinical outcomes and socio-economic burden of ESBL-E and CRE bacteraemia nationwide in the Republic of Korea. A search was undertaken for all cases of ESBL-E and CRE bacteraemia and matched controls in 10 hospitals in the Republic of Korea over 6 months. Patients with ESBL-E or CRE bacteraemia were classified as the R group, and matched controls with antibiotic-susceptible bacteraemia and without infection were classified as the S and N groups, respectively. Patients' clinical data were collected, and the economic burden was estimated based on medical expenses, loss of productivity and total costs. In total, 795 patients were identified, including 265 patients with ESBL-E or CRE bacteraemia and their matched controls. The mean total length of stay for patients with ESBL-E and CRE in the R group was 1.53 and 1.90 times that of patients in the S group, respectively. The 90-day mortality rates for ESBL-E in the R and S groups were 12.1% and 5.6%, respectively, and the corresponding figures for CRE were 28.6% and 12.0%. There were significant differences in the total costs between the R, S and N groups for both ESBL-E and CRE (ESBL-E: $11,151 vs $8712 vs $6063, P=0.004; CRE: $40,464 vs $8748 vs $7279, P=0.024). The clinical and economic burden imposed by ESBL-E or CRE bacteraemia was extremely high. These findings suggest that efforts to control resistant bacteraemia are necessary to reduce this burden.

Magnitude of extended-spectrum β-lactamase and carbapenemase producing Enterobacteriaceae among commonly vended street foods in Arba Minch town, southern Ethiopia

BackgroundThe rising prevalence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae (ESβL-PE) in street foods poses a significant risk to human health due to its epidemiological significance. Thus, the aim of this study was to determine the magnitude of foodborne Enterobacteriaceae that produce carbapenemase and ESβL, as well as their patterns of antibiotic resistance, in the studied area.MethodsA community-based cross-sectional study was carried out from January 1st, 2023, to February 30th, 2023. One hundred randomly chosen street-vended food items (one hundred grams of each food item) were aseptically collected, and aliquots of 0.1 ml from the homogenized (25 g of samples into 225 ml of buffered peptone water (BPW)) were inoculated on MacConkey agar and Xylose Lysine Deoxycholate Agar (XLD). Enterobacteriaceae isolates were identified using various biochemical tests. ESβL and carbapenemase were first screened by indicator cephalosporins and carbapenem antibiotics, respectively. ESβL and carbapenemase were confirmed by a double-disc synergy test and modified carbapenem inactivation methods, respectively. Kirby-Bauer disc diffusion method was used for the antimicrobial-resistant test.ResultsA total of 112 Enterobacteriaceae belonging to six different genera were isolated. E. coli was attributed 39 (34.8%), followed by Citrobacter spp. 22 (19.6%) and K. pneumoniae 18 (16.1%), with only 8 (7.1%) isolated Salmonella spp. About 15.2% (n = 17) and 8.9% (n = 10) of Enterobacteriaceae were phenotypically confirmed to be extended-spectrum beta-lactamase (ESβL) and carbapenemase producers, respectively. The highest percentage of ESβL-producing isolates was attributed to K. pneumoniae (n = 5), E. coli (n = 4), and Enterobacter spp. (n = 3). Proteus spp. and Salmonella spp. isolates were carbapenemase-negative. All carbapenemase-positive isolates were found to be ESβL-producers. 70.6% (12/17) of ESβL-producing Enterobacteriaceae were found to be multidrug-resistant (MDR).ConclusionA considerable number of multidrug-resistant ESβL and carbapenemase-producing Enterobacteriaceae were identified, suggesting that street foods may be a potential source of MDR foodborne infections. Consequently, it is important to conduct routine examinations of street food items and track trends in medication resistance.

Carbapenem resistant Enterobacterales in the United Arab Emirates: a retrospective analysis from 2010 to 2021.

Carbapenem-resistant Enterobacterales (CRE) are spreading in the United Arab Emirates (UAE) where their dissemination is facilitated by international travel, trade, and tourism. The objective of this study is to describe the longitudinal changes of CRE as reported by the national AMR surveillance system of the UAE. In this study, we retrospectively describe CRE isolated from 317 surveillance sites, including 87 hospitals and 230 centers/clinics from 2010 to 2021. The associated clinical, demographic, and microbiological characteristics are presented by relying on the UAE national AMR surveillance program. Data was analyzed using WHONET microbiology laboratory database software (http://www.whonet.org). A total of 14,593 carbapenem resistant Enterobacterales were analyzed, of which 48.1% were carbapenem resistant Klebsiella pneumoniae (CRKp), 25.1% carbapenem resistant Escherichia coli (CREc), and 26.8% represented 72 other carbapenem resistant species. Carbapenem resistant strains were mostly associated with adults and isolated from urine samples (36.9% of CRKp and 66.6% of CREc) followed by respiratory samples (26.95% for CRKp) and soft tissue samples (19.5% for CRKp). Over the studied period carbapenem resistance rates remained high, especially in K. pneumoniae, and in 2021 were equivalent to 67.6% for imipenem, 76.2% for meropenem, and 91.6% for ertapenem. Nevertheless, there was a statistically significant decreasing trend for imipenem and meropenem resistance in Klebsiella species (p < 0.01) while the decrease in ertapenem resistance was non-significant. Concerning E. coli, there was a statistically significant decreasing trend for meropenem and imipenem resistance over the 12 years, while ertapenem resistance increased significantly with 83.8% of E. coli exhibiting ertapenem resistance in 2021. Resistance rates to ceftazidime and cefotaxime remained higher than 90% (in 2021) for CRKp and cefotaxime rates increased to 90.5% in 2021 for CREc. Starting 2014, resistance to colistin and tigecycline was observed in carbapenem resistant Enterobacterales. CRE were associated with a higher mortality (RR: 6.3), admission to ICU (RR 3.9), and increased length of stay (LOS; 10 excess inpatient days per CRE case). This study supports the need to monitor CRE in the UAE and draws attention to the significant increase of ertapenem resistance in E. coli. Future surveillance analysis should include a genetic description of carbapenem resistance to provide new strategies.

In Vitro Evaluation of Increasing Avibactam Concentrations on Ceftazidime Activity against Ceftazidime/Avibactam-Susceptible and Resistant KPC-Producing Klebsiella pneumoniae Clinical Isolates.

The novel β-lactam/β-lactamase inhibitor combinations (βL-βLICs) are one of the last-line resources available against multidrug-resistant (MDR) Gram-negative bacteria. Among βL-βLICs, ceftazidime/avibactam (CAZ-AVI) demonstrated strong activity against carbapenem-resistant Enterobacterales (CRE). Avibactam was proven to restore bactericidal activity of ceftazidime, inhibiting both KPC and OXA-48-like β-lactamases. Despite this, emergence of CAZ-AVI-resistant strains in Enterobacterales has been reported. Herein, we evaluated the in vitro ceftazidime activity in the presence of increasing concentrations of avibactam by the broth microdilution method against CAZ-AVI-susceptible and resistant genome-characterized KPC-producing K. pneumoniae (KPC-Kp) clinical isolates. Strains expressing KPC and co-expressing KPC/OXA-181 carbapenemase were selected on the basis of the different phenotypic traits for novel βL-βLICs and cefiderocol. Notably, avibactam at 8 mg/L maintained the MIC of ceftazidime above the clinical breakpoint in 14 out of 15 (93%) KPC-Kp resistant to CAZ-AVI. A high concentration of avibactam (i.e., 64 mg/L) is required to observe a bactericidal activity of ceftazidime against 9 out of 15 (60%) CAZ-AVI-resistant isolates. In vitro evaluation showed that with the increase in the concentration of avibactam, ceftazidime showed high activity against CAZ-AVI-susceptible strains. High concentrations of avibactam in vivo are required for ceftazidime to be active against CAZ-AVI-resistant KPC-Kp.

Investigation of carbapenem-resistant Enterobacterales isolates at a tertiary laboratory in Pretoria, South Africa.

This study aimed to investigate phenotypic and genotypic characteristics of carbapenem-resistant Enterobacterales isolates (CRE) at a tertiary laboratory in South Africa. A total of 99 CRE isolates were collected between 2019 and 2021. Carbapenemase production was tested using modified carbapenem inhibitory method. Colistin susceptibility testing was performed using the ComASP™ Colistin broth microdilution method. Conventional PCR assays were conducted for detection of mcr-1 gene and common carbapenemase genes (blaVIM, blaNDM, blaIMP, blaKPC, blaOXA-23, blaOXA-51 and blaOXA-48). Rep-PCR assay was conducted to determine the genetic relatedness of the study isolates. Majority of the isolates were Klebsiella pneumoniae (83%). Carbapenem resistant K. pneumoniae cluster was observed from ICU and surgical ward samples. Colistin resistance was observed in 13% (12/93) of the isolates namely, in 11 K. pneumoniae and one Enterobacter cloacae. The blaOXA-48 (65%) was the most prevalent gene detected followed by blaNDM (25%) and blaVIM (22%). Several K. pneumoniae isolates concomitantly carried multiple carbapenemase genes with one isolate carry up to 5 five genes blaVIM, blaNDM, blaOXA-48, blaOXA-23 and blaOXA-51. The mcr-1 gene was not detected in the isolates. Rep-PCR assay showed that most isolates matched cluster A (50%). The high prevalence of blaOXA-48, blaNDM and emerging colistin resistant isolates is of concern for patient management at this institution and needs close monitoring. Rep-PCR is a valuable tool in establishing infection clusters in resource-limited settings.

Management of Carbapenem-Resistant Enterobacteriaceae Bloodstream Infections: An Experience from a Tertiary Care Centre in Oman

The emergence of Carbapenem-resistant Enterobacteriaceae (CRE)is a public health concern worldwide. It is associated with increased mortality due to limited antibiotics available to treat CRE infections. The aim of this study was to understand the epidemiology of CRE infections, associated mortality, and available treatment options. All patients with CRE isolated in blood culture were identified between December 2011 and October 2019. Risk factors and mortality associated with each risk factor at 14 and 30 days were determined.55 cases of CRE bloodstream infections were isolated, with a median age of 56 years. Eighty-four percent of patients received treatment in the ICU. All cases were caused by Klebsiella pneumonia. The rate of resistance to the tested antibiotics was as follows: meropenem 92% (50/54), imipenem 75% (40/53), etrapenam 95% (19/20), Amikacin 71% (37/52), cotrimoxazole 73% (40/53), Gentamicin 47% (25/53) and colistin 7% (3/41). Major risk factors associated were the presence of a urinary catheter (84%), central venous catheter (78%), mechanical ventilation (74%) and post-surgery (67%). Mortality at 14 days and 30 days was 41%, and 52%, respectively. Univariate analysis showed that 14 days mortality was higher in patients with central venous catheter (P=0.01). Charlson's comorbidity index was associated with an increased risk of death at 30 days (P=0.04). There was no statistically increased survival in those treated with combination therapy at 30 days (P=0.5). The mortality of CRE infections seems to be high and optimal therapy is not yet well defined. Combination therapy is not associated with increased survival in this cohort of patients.

An outbreak within an outbreak: The impact of Infection Prevention and Control strategies on hospital-acquired infections and the occurrence of multi-drug resistant organisms during the COVID-19 pandemic

Background. The coronavirus disease 2019 (COVID-19) pandemic placed an unprecedented strain on intensive care units (ICUs) in South Africa. Infection prevention and control (IPC) strategies were highlighted to minimise the risk to healthcare workers and for the protection of patients from contracting hospital-acquired infections (HAIs). During the third wave, our institution adopted a shift system to address severe burnout among ICU personnel. We noted an upstroke in the occurrence of HAIs, specifically carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant (MDR) Acinetobacter baumannii. Objectives. To report these outbreaks, compare the rate of CRE and A. baumannii infections with the first COVID-19 wave and to analyse its impact on patient outcomes. Method. We retrospectively analysed data from a prospectively collected registry involving all adult patients with severe COVID-19 admitted to the dedicated COVID-19 ICU from May 2021 to September 2021. Information from the admission database, including the patients’ demographics, comorbidities, laboratory results and length of ICU stay were extracted. Results. Ninety patients were admitted with severe COVID-19 during the third wave. There was an outbreak of both CRE (the majority Klebsiella pneumoniae) and A. baumannii. Furthermore, 18 patients cultured the same CRE organism, and 25 patients cultured the environmental organism A. baumannii. The HAI rate was significantly higher compared with the first wave published data: 59/90 (65.6%) v. 73/363 (20.1%, p&lt;0.01). Patients with any HAI had a longer mean stay in ICU (10.1 days v. 6.7 days (p&lt;0.01) and a higher mortality of 48/59 (81%) v. 19/31 (61%) (p=0.05). Conclusion. We observed a very significant rise in HAIs in the COVID-19 ICU during the third wave compared with the first, with almost three times as many patients developing HAIs. Unsurprisingly, it was associated with a longer mean stay in ICU and a higher mortality. The outbreak of both CRE and A. baumannii, and the fact that many patients cultured the same CRE organism and A. baumannii, strongly suggests that a critical breakdown in IPC measures had occurred.

Trends in Incidence of Carbapenem-Resistant Enterobacterales in 7 US Sites, 2016─2020.

We described changes in 2016─2020 carbapenem-resistant Enterobacterales (CRE) incidence rates in 7 US sites that conduct population-based CRE surveillance. An incident CRE case was defined as the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to ≥1 carbapenem from a sterile site or urine in a surveillance area resident in a 30-day period. We reviewed medical records and classified cases as hospital-onset (HO), healthcare-associated community-onset (HACO), or community-associated (CA) CRE based on healthcare exposures and location of disease onset. We calculated incidence rates using census data. We used Poisson mixed effects regression models to perform 2016─2020 trend analyses, adjusting for sex, race/ethnicity, and age. We compared adjusted incidence rates between 2016 and subsequent years using incidence rate ratios (RRs) and 95% confidence intervals (CIs). Of 4996 CRE cases, 62% were HACO, 21% CA, and 14% HO. The crude CRE incidence rate per 100 000 was 7.51 in 2016 and 6.08 in 2020 and was highest for HACO, followed by CA and HO. From 2016 to 2020, the adjusted overall CRE incidence rate decreased by 24% (RR, 0.76 [95% CI, .70-.83]). Significant decreases in incidence rates in 2020 were seen for HACO (RR, 0.75 [95% CI, .67-.84]) and CA (0.75 [.61-.92]) but not for HO CRE. Adjusted CRE incidence rates declined from 2016 to 2020, but changes over time varied by epidemiologic class. Continued surveillance and effective control strategies are needed to prevent CRE in all settings.

An insight into genes responsible for fosfomycin resistance among uropathogens of asymptomatic bacteriuria during pregnancy: A North Indian study.

Asymptomatic bacteriuria (ASB) is a common finding during pregnancy. Effective antibiotic treatment could reduce its adverse effects on both mother and fetus. However, emerging antimicrobial resistance limits the treatment options. Fosfomycin might be a promising drug in this regard, as its resistance is still low. The aim of the study was to determine the antimicrobial susceptibility pattern of fosfomycin in isolates causing ASB by disc diffusion and agar dilution (in selected isolates), determine minimum inhibitory contribution (MIC) by agar dilution in isolates resistant by disc diffusion and detect the genes responsible for fosfomycin resistance. This was a 2-year study carried in the Department of Microbiology, Jawaharlal Nehru Medical College and Hospital (JNMCH), Aligarh Muslim University (AMU), Aligarh. A total of 10 252 urine samples from asymptomatic pregnant females (18-45 years) attending the antenatal care (ANC) outpatient department (OPD) were submitted. Identification of pathogen and antimicrobial susceptibility testing (AST) was carried out as per standard methods of CLSI. There was phenotypic detection of methicillin-resistant Staphylococcus aureus (MRSA) and other Staphylococcus species (MRSS), high-level aminoglycoside resistance (HLAR), vancomycin resistant Enterococci (VRE) and S. aureus (VRSA), extended spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacterales (CRE). All the fosfomycin-resistant isolates (by disk diffusion) were tested by agar dilution. Conventional PCR was performed for murA, fosA, uhpT and glpT genes on all resistant isolates. In this study, the prevalence of ASB among pregnant females was 1173(11.4 %), in which Escherichia coli 495(42 %) was the predominant organism. The overall sensitivity of fosfomycin among Gram-positive cocci (GPC) and Gram-negative bacilli (GNB) was 99 % and 97.6 %, respectively. MRSA and MRSS accounted for 50 (66.6 %) and 71 (76 %), respectively. The highest rates of MIC >2048 µg ml-1 were shown by most isolates (mainly E. coli ) on agar dilution. PCR studies revealed four E. coli strains possessed both murA (also present in one K. pneumoniae strain) and glpT genes. While only one isolate ( E. faecalis ) was positive for fosA gene. But none of the strain possessed the uhpT gene. According to this study, murA and glpT genes were more frequent than fosA. We cannot comment on the prevalence and regional distribution of fosfomycin-resistant genes based on this preliminary study. Therefore, more Indian studies should be carried out to create awareness about the presence of genes in a particular area.

Prevalence of and risk factors for intestinal colonisation by multidrug-resistant Gram-negative bacteria in patients with haematological malignancies: A systematic review and meta-analysis

BackgroundPatients with haematological malignancies (HM patients) are at high risk of infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). MDR-GNB intestinal colonisation is associated with MDR-GNB infections. The aim of this systematic review and meta-analysis on HM patients was to pool the prevalence of and risk factors for intestinal colonisation by MDR-GNB, including carbapenem-resistant Enterobacterales (CRE) and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, reported in previous studies. MethodsThis study was conducted according to the protocol registered in PROSPERO (CRD42022374425). PubMed, Embase, Web of Science, Ovid MEDLINE(R) ALL and Cochrane Library were searched from inception to 25 October 2022. Observational studies reporting CRE and/or ESBL intestinal colonisation in HM patients were included. Subgroup analyses were conducted by study region. ResultsA total of 21 402 HM patients from 32 studies were analysed. The pooled CRE and ESBL colonisation rates were 21.7% [95% confidence interval (95%CI) 18.7–24.8] and 19.2% (95%CI 13.9–24.5), respectively. Prior exposure to tigecycline [odds ratio (OR) 3.99, 95%CI 2.08–7.68], carbapenem (OR 1.84, 95%CI 1.13-2.97) or penicillin (OR 1.72, 95%CI 1.05–2.83), as well as chemotherapy (OR 2.45, 95%CI 1.05–5.73), neutropenia (OR 1.88, 95%CI 1.08–3.26) and acute myeloid leukaemia (AML; OR 1.86, 95%CI 1.33–2.61), were risk factors for CRE colonisation in HM patients. Prior antibiotic exposure was a risk factor for ESBL colonisation in HM patients (OR 4.90, 95%CI 2.76–8.70). ConclusionsThis study shows the high prevalence of MDR-GNB (CRE and ESBL) colonisation in HM patients and explains associated factors for the colonisation. The results provide evidence for MDR-GNB infection control in HM management.

Detection of Carbapenem Resistance among Enterobacteriaceae Pathogens Isolated from Clinical Samples in Shendi locality

Introduction: The majority of antimicrobial agents are ineffective against carbapenem-resistant Enterobacteriaceae (CRE) infections, leading to unfavorable clinical consequences. This fact is associated with higher mortality and morbidity rates, prolonged hospital stays, and increased treatment-related costs. Carbapenems are the last line for the treatment of infection caused by bacteria resistance to a broad spectrum of antibiotics. Objective: This study aimed to detect the Distribution of Carbepanems Resistance in Enterobacteriaceae Pathogens Isolated from Clinical Samples in the Shendi locality. Methods: A cross-sectional study and a laboratory-based study were carried out on 63 isolates from different specimens, 63 types of pathogenic bacteria were isolated and identified using Gram stain, biochemical reactions, and testing for their susceptibility to Carbapenems antibiotics was performed for all Enterobacteriaceae isolates. Result: The isolated Enterobacteriaceae comprising of 19.0(30.2%) E.coli, 17 (27.0%) K. pneumoniae, 13(20.6%) P. vulgaris, 5(7.9%) P. mirabilis, 1(1.6%) Enterobacter species, 3(4.8%) C. freundii and 5(7.9%) M. morganii. Carbapenem (Imipenem and meropenem) susceptibility testing showed that 36.0% of Enterobacteriaceae isolates were Carbapenem-resistant. Conclusions: The study revealed the low resistance pattern of Enterobacteriaceae to Carbapenems. Despite that E.coli (19.0, 30.0%) was the most isolated organism, and K. pneumonia (7.0, 11.0%) was the most resistant isolate to Carbapenems. The urine sample had the highest degree of resistance. There was a correlation between patients with chronic diseases such as cancer and the resistance level to Carbapenems, while there was no statistical significance between the period of antibiotics usage and the degree of resistance.

Clinical Features and Outcomes of Infections Caused by Metallo-β-Lactamase-Producing Enterobacterales: A 3-Year Prospective Study From an Endemic Area.

Metallo-β-lactamase (MBL)-producing Enterobacterales are increasing worldwide. Our aim was to describe clinical features, treatments, and outcomes of infections by MBL-Enterobacterales. A prospective observational study conducted in the Pisa University Hospital (January 2019 to October 2022) included patients with MBL-producing Enterobacterales infections. The primary outcome measure was the 30-day mortality rate. Multivariable Cox regression analysis was performed to identify factors associated with that mortality rate, and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated. The study's 343 patients included 15 with Verona integron-encoded MBL (VIM)- and 328 with New Delhi MBL (NDM)-producing Enterobacterales infections; there were 199 patients (58%) with bloodstream infections, 60 (17.5%) with hospital-acquired or ventilator-associated pneumonia, 60 (17.5%) with complicated urinary tract infections, 13 (3.8%) with intra-abdominal infections, and 11 (3.2%) with skin and soft-tissue infections. The 30-day mortality rate was 29.7%. Of 343 patients, 32 did not receive in vitro active antibiotic therapy, 215 (62.7%) received ceftazidime-avibactam plus aztreonam, 33 (9.6%) received cefiderocol-containing regimens, 26 (7.6%) received colistin-containing regimens, and 37 (10.8%) received other active antibiotics. On multivariable analysis, septic shock (aHR, 3.57 [95% CI, 2.05-6.23]; P < .001) and age (1.05 [1.03-1.08]; P < .001) were independently associated with the 30-day mortality rate, while in vitro active antibiotic therapy within 48 hours after infection (0.48 [.26-.8]; P = .007) and source control (0.43 [.26-.72]; P = .001) were protective factors. Sensitivity analysis showed that ceftazidime-avibactam plus aztreonam, compared with colistin, was independently associated with a reduced 30-day mortality rate (aHR, 0.39 [95% CI, .18-.86]; P = .02). Propensity score analyses confirmed these findings. MBL-producing carbapenem-resistant Enterobacterales infections are associated with high 30-day mortality rates. Patients with MBL-producing Enterobacterales infections should receive early active antibiotic therapy.

The Comparative Efficacy of Ceftazidime–Avibactam with or without Aztreonam vs Polymyxins for Carbapenem-resistant Enterobacteriaceae Infections: A Prospective Observational Cohort Study

The Comparative Efficacy of Ceftazidime–Avibactam with or without Aztreonam vs Polymyxins for Carbapenem-resistant Enterobacteriaceae Infections: A Prospective Observational Cohort Study

Mortality Risk and the Clinical Outcome of Carbapenem-Resistant Enterobacteriaceae Carriers with Neutropenia: A Matched Case-Control Study

Patients with hematologic diseases are often accompanied by immunodeficiency, treatments as well as the disease itself can lead to granulocyte deficiency. Patients with granulocyte deficiency are under the high risk of infection. In recent years, the rate of Carbapenem-resistant Enterobacteriaceae (CRE) infection has gradually increased. Treatment options of CRE infection is limited, and effective anti-infection treatment is usually delayed, leading to the death of patients due to infection. CRE screening can provide clinical evidence for early detection of CRE by clinicians, thereby formulating antimicrobial treatment strategies. However, whether the initial empirical treatment covering CRE can improve the adverse outcomes of patients still lacks a definitive conclusion. We collected clinical data on patients with neutropenia who also undergoing CRE screening between January 2017 and December 2022. To further analyze the impact of CRE positivity on patient mortality risk and the clinical effectiveness of initial empirical treatment for CRE, we conducted two case-cohort studies with clinical baseline data matching. In total, we performed 3529 fecal CRE screenings from 664 patients. Out of these, 345 screenings from 135 patients tested positive for CRE. We identified 16 different strains, with the most common being Klebsiella pneumoniae (184/345), followed by Escherichia coli (76/345). To determine the influence of CRE positivity on patient mortality rates, we conducted a 1:2 case matching based on age, gender, diagnosis, and medical history of CRE-positive patients (Table 1). The results showed that in the overall analysis, CRE positivity, age over 60, and male gender were adverse factors influencing mortality. However, in the subgroup analysis of CRE-positive patients, no adverse factors affecting mortality were observed. To further assess the impact of CRE positivity on patient infection outcomes, we defined the initial antibiotic treatment strategies for a total of 4,872 infection events in screened patients. We divided them into the following groups: the empirical treatment group without CRE results (n=3,954), the empirical treatment group not covering CRE (n=122), and the CRE based empirical treatment group (n=796). The CRE based empirical treatment group had a higher success rate in initial empirical treatment compared to the group without covering CRE (65.5% vs. 59.0%). To further investigate the differences in initial empirical treatment success rates and 30-day mortality rates between patients in the CRE-based empirical treatment group and empirical treatment group without CRE covering, we performed 1:2 case matching for clinical baseline data on age, sex, diagnosis, past history, and disease status at infection according to the clinical characteristics of the CRE-based anti-infection treatment group. The results indicated that there were no significant differences in initial empirical treatment success rate and 30-day mortality rate between the CRE-based empirical treatment group and case-matched controls. In conclusion, diagnosing and treating patients with CRE infection presents significant challenges. Early screening for CRE and empirical treatment targeting CRE can increase the success rate of initial empirical treatment in CRE-positive patients.

Ceftazidime-Avibactam in the Treatment of Bacteremia Due to Carbapenem-Resistant Gram-Negative Bacteria in Hematological Patients: Experience in a Single Center

Background: Experience with ceftazidime-avibactam (CAZ-AVI) for bacteremia caused by carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) in hematological patients is limited. Methods: We performed a single-center, retrospective, observational study including patients receiving CAZ-AVI for bacteremia due to CRE or CRPA between 2018 and 2022. The primary outcome was 30-day survival. To identify predictors of survival, multivariable analysis was performed. Results: 56 patients were included and 57 (41 CRE and 16 CRPA) strains were isolated. 35 strains produced carbapenemase (25 MBL, 10 serine-beta-lactamase). 48 (85.7%) patients received combination therapy. All patients with MBL-CRE bacteremia (n=24) received combination therapy with aztreonam. The susceptibility rates to CAZ-AVI were only 25.0% (10/40) in CRE and 80.0% (8/10) in CRPA. The 30-day survival rates were 85.0% (34/40) and 81.3% (13/16) in CRE and CRPA group, respectively. In patients with MBL-CRE bacteremia, 30-day survival was high to 91.7% (22/24) due to combination with aztreonam. Ceftazidime did not influence the activity of aztreonam-avibactam against MBL-CRE in-vitro. Multivariable cox analysis revealed neutropenia &amp;gt; 14 days (P=0.002, HR: 0.029, 95%CI: 0.003~0.260) and higher Pitt bacteremia score (P=0.005, HR: 0.482, 95%CI: 0.291~0.798) were risk factors of 30-day survival. Conclusions: CAZ-AVI is highly effective for bacteremia due to CRPA and serine-beta-lactamase CRE. Avibactam in combination with aztreonam is highly active for bacteremia due to aztreonam-resistant MBL producers.

Effectiveness of tailored screening for multidrug-resistant organisms upon admission to an intensive care unit in the United Arab Emirates.

Multidrug-resistant organism (MDRO) screening may identify high-risk patients for MDRO infection and curb the spread of these resistant pathogens. However, the heterogeneous practices in MDRO screening and the diversity of MDRO risk factors necessitate a tailored approach for successful implementation. This study aimed to evaluate the performance of tailored MDRO screening in predicting MDRO carriage compared to universal screening. Critically ill patients who underwent MDRO screening tests upon intensive care unit admission between September 2015 and December 2019 were included in the study. A risk-predicting model was developed using risk factors identified through multivariable logistic regression analysis. If an individual had one or more identified risk factors, the individual was deemed to be at risk of MDRO carriage and undergo tailored screening. The sensitivity of tailored screening was compared with universal screening for methicillin-resistant Staphylococcus aureus (MRSA)and multidrug-resistant Gram-negative bacilli (carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Enterobacterales). The use of tracheostomy or endotracheal tubes, previous antibiotic exposure, previous multidrug-resistant Gram-negative bacilli carriage history, admission to the medical department, peripheral vascular disease, and liver disease were associated with positive screening for multidrug-resistant Gram-negative bacilli. These six risk factors accounted for all positive screening for multidrug-resistant Gram-negative bacilli, requiring 38.6% of all tests. Notably, MRSA had different risk factor profiles, and the risk factor-based screening approach detected only 43.1% (31 out of 72) of MRSA-positive cases. Tailored screening based on identified risk factors showed variable sensitivities to individual MDROs compared to universal screening. A tailored screening approach for individual MDROs may enhance the overall effectiveness of MDRO screening programs.

Colonization with extended spectrum beta-lactamase and carbapenemases producing Enterobacteriaceae among hospitalized patients at the global level: A systematic review and meta-analysis.

Gut commensal bacteria can mediate resistance against pathogenic bacteria. However, exposure to antibiotics and hospitalization may facilitate the emergence of multidrug resistant bacteria. We aimed to conduct a systematic review and meta-analysis to provide comprehensive evidence about colonization rate of extended spectrum beta-lactamase and carbapenemases producing Enterobacteriaceae. We used PubMed, Google Scholar and Web of Science data bases to search studies from January 1, 2016 to August10, 2022 about colonization rate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae. Data were extracted from eligible studies and analyzed using Stata version 16 software. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools, and publication bias was assessed using funnel plot and eggers test. We identified 342 studies from the comprehensive data search and data were extracted from 20 studies. The pooled estimate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae were 45.6%(95%CI: 34.11-57-10) and 16.19% (95% CI: 5.46-26.91) respectively. The predominant extended spectrum beta-lactamase producers were E. coli,32.99% (95% CI: 23.28-42.69) and K. pneumoniae, 11.43% (95% CI:7.98-14.89). Prolonged hospitalization was linked to carbapenemase producing Enterobacteriaceae colonization with the odds of 14.77 (95% CI: -1.35-30.90) at admission and 45.63 (95% CI: 0.86-92.12) after ≥7 days of admission. The pooled estimate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae were high. This indicates the need for strong mitigation strategies to minimize the spread of multidrug-resistant bacteria at the healthcare facilities.