Carbapenem-resistant Organisms Research Articles

Hospital water environment and antibiotic use: Key factors in a nosocomial outbreak of carbapenemase-producing Serratia marcescens

BackgroundThe healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). Here, we report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). MethodsThe outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case–control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analyzed. . ResultsThe outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics were associated with acquisition of KPC-SM (p < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. ConclusionOur study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant microorganisms, underscoring the necessity of enhancing infection control practices in these areas.

Tackling carbapenem resistance: ceftazidime - avibactam in contemporary clinical scenarios

Antimicrobial resistance poses a formidable challenge in treating severe infections, with the prevalence of extended-spectrum beta-lactamase (ESBL) - producing, Klebsiella pneumoniae carbapenemase (KPC) - producing, and multidrug-resistant (MDR) organisms on the rise. This necessitates careful consideration of various factors, including local resistance patterns, patient-specific characteristics, and drug properties, in treatment decisions for critically ill patients. Ceftazidime-Avibactam demonstrates efficacy against aerobic Gram-negative bacteria and offers a crucial advancement against carbapenem-resistant organisms (CRO) with its effectiveness against key pathogens, including ESBL, AmpC, KPC, and OXA-48-producing Enterobacteriaceae and drug-resistant P. aeruginosa. Ceftazidime-Avibactam emerges as a valuable option for critically ill patients with limited treatment choices. The drug's excellent safety profile demonstrated in clinical trials, further positions it as a crucial addition to antimicrobial treatment options. As the global threat of drug-resistant bacteria grows, Ceftazidime-Avibactam plays a pivotal role in addressing this challenge and offers a promising solution for critically ill patients facing infections caused by antimicrobial-resistant pathogens. The article delves into therapeutic efficacy and the prospective role of Ceftazidime-Avibactam in managing MDR Gram-negative organisms, underscoring the critical role of appropriate antibiotic administration in reducing mortality associated with Gram-negative infections.

Evaluation of Oral Amoxicillin/Clavulanate for Urinary Tract Infections Caused by Ceftriaxone Non-Susceptible Enterobacterales.

Urinary tract infections (UTIs) are one of the most common infections and are frequently caused by Gram-negative organisms. The rise of resistant isolates has prompted evaluation of alternative therapies, including amoxicillin-clavulanate which has potent activity against Ambler class A enzymes. This study sought to evaluate clinical outcomes of patients with ceftriaxone non-susceptible UTIs receiving amoxicillin-clavulanate or standard of care (SOC). This was a single-center, retrospective, cohort study of adult patients with urinary tract infections caused by a ceftriaxone non-susceptible pathogen who received amoxicillin-clavulanate or SOC. The primary outcome was clinical failure at 90 days. Secondary outcomes included time to failure, isolation of a resistant organism, and hospital length of stay. Fifty-nine patients met study inclusion: 26 received amoxicillin/clavulanate and 33 received SOC. Amoxicillin-clavulanate recipients did not have higher failure rates compared to SOC recipients. For patients requiring hospital admission, hospital length of stay was numerically shorter with amoxicillin-clavulanate. The frequency of amoxicillin-clavulanate and carbapenem-resistant organisms did not differ significantly between groups. Amoxicillin-clavulanate may be a useful alternative therapy for the treatment of ceftriaxone non-susceptible Enterobacterales UTIs.

Impact of Immunosuppressed Status on Prognosis of Carbapenem-Resistant Organisms Bloodstream Infections.

The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74-18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60-3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58-3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Study of Empiric Antibiotic Prescription Patterns and Microbiological Isolates in Hemodynamically Stable and Unstable ICU Patients With Community-Acquired Sepsis.

Background: The efficacy of combination empiric antibiotic therapy for all intensive care unit (ICU) patients with community-acquired sepsis is a subject of ongoing debate in the era of increasing antibiotic resistance. This study was conducted to evaluate the patterns of antibiotic usage and microbial resistance in sepsis patients admitted to the ICU with both hemodynamically stable (HS) and unstable states and to analyze their clinical outcomes. Methods: In this observational study, patients aged 18 years and above who received antibiotics upon admission and had a culture report were included. These patients were categorized into the following groups: HS and hemodynamically unstable (HU), single or combined antibiotics group (more than one antibiotic used empirically to cover one or more groups of organisms), culture-positive and culture-negative group. The microbiological isolates were grouped according to their identified resistance patterns. The outcome parameters involved assessing the differences in empiric antibiotics use upon admission and microbial resistance with hemodynamic stability and investigating any associations with ICU and hospital outcomes. Results: The study included a total of 2675 patients, of which 70.3% were in the HS group, and 29.7% in the HU group. The use of combination antibiotics was significantly higher (p < 0 .0001) across all groups. Carbapenems were used more frequently in the single antibiotic group (p < 0 .001). The culture was positive in 27.8% (n = 747) of patients. A significantly higher number of patients in the HU group (p < 0 .001) were found to have carbapenem-resistant and multidrug-resistant organisms. The ICU and hospital mortality rates were significantly higher in the HU group (p < 0 .001), the culture-positive group with resistance (p < 0 .001), and the HS patients who received combination antibiotics. Conclusion: The usage of combination antibiotics, coupled with the presence of resistant organisms, emerged as an important variable in predicting ICU and hospital mortality rates in cases of community-acquired sepsis.

Difference analysis and characteristics of incompatibility group plasmid replicons in gram-negative bacteria with different antimicrobial phenotypes in Henan, China

BackgroundMulti-drug-resistant organisms (MDROs) in gram-negative bacteria have caused a global epidemic, especially the bacterial resistance to carbapenem agents. Plasmid is the common vehicle for carrying antimicrobial resistance genes (ARGs), and the transmission of plasmids is also one of the important reasons for the emergence of MDROs. Different incompatibility group plasmid replicons are highly correlated with the acquisition, dissemination, and evolution of resistance genes. Based on this, the study aims to identify relevant characteristics of various plasmids and provide a theoretical foundation for clinical anti-infection treatment.Methods330 gram-negative strains with different antimicrobial phenotypes from a tertiary hospital in Henan Province were included in this study to clarify the difference in incompatibility group plasmid replicons. Additionally, we combined the information from the PLSDB database to elaborate on the potential association between different plasmid replicons and ARGs. The VITEK mass spectrometer was used for species identification, and the VITEK-compact 2 automatic microbial system was used for the antimicrobial susceptibility test (AST). PCR-based replicon typing (PBRT) detected the plasmid profiles, and thirty-three different plasmid replicons were determined. All the carbapenem-resistant organisms (CROs) were tested for the carbapenemase genes.Results21 plasmid replicon types were detected in this experiment, with the highest prevalence of IncFII, IncFIB, IncR, and IncFIA. Notably, the detection rate of IncX3 plasmids in CROs is higher, which is different in strains with other antimicrobial phenotypes. The number of plasmid replicons they carried increased with the strain resistance increase. Enterobacterales took a higher number of plasmid replicons than other gram-negative bacteria. The same strain tends to have more than one plasmid replicon type. IncF-type plasmids tend to be associated with MDROs. Combined with PLSDB database analysis, IncFII and IncX3 are critical platforms for taking blaKPC−2 and blaNDM.ConclusionsMDROs tend to carry more complex plasmid replicons compared with non-MDROs. The plasmid replicons that are predominantly prevalent and associated with ARGs differ in various species. The wide distribution of IncF-type plasmids and their close association with MDROs should deserve our attention. Further investigation into the critical role of plasmids in the carriage, evolution, and transmission of ARGs is needed.

Key microbial monitoring and clinical analysis of bloodstream infections and CRO colonization after hematopoietic stem cell transplantation in hematological patients

Objective: To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients. Methods: We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison. Results: The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM (P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM (P=0.035) . Conclusion: This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

Non-KPC Attributes of Newer β-lactamase/β-lactamase Inhibitors, Part 1: Enterobacterales and Pseudomonas aeruginosa.

Gram-negative antibiotic resistance continues to grow as a global problem due to the evolution and spread of β-lactamases. The early β-lactamase inhibitors (BLIs) are characterized by spectra limited to class A β-lactamases and ineffective against carbapenemases and most extended spectrum β-lactamases. In order to address this therapeutic need, newer BLIs were developed with the goal of treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically targeting the Klebsiella pneumoniae carbapenemase (KPC). These BL/BLI combination drugs, ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/relebactam, have proven to be indispensable tools in this effort. However, non-KPC mechanisms of resistance are rising in prevalence and increasingly challenging to treat. It is critical for clinicians to understand the unique spectra of these BL/BLIs with respect to non-KPC CRO. In Part 1of this two-part series, we describe the non-KPC attributes of the newer BL/BLIs with a focus on utility against Enterobacterales and Pseudomonas aeruginosa.

Clinical Efficacy and Safety of Colistin Sulfate in the Treatment of Carbapenem-Resistant Organism Infections in Patients with Hematological Diseases.

Carbapenem-resistant organisms (CRO) have emerged as a significant worldwide issue. However, the availability of efficacious antibiotics for treating CRO infections remains limited. Polymyxins, including colistin sulfate, represent the last-line therapeutic option against CRO infections. This study aims to retrospectively evaluate the clinical effectiveness and safety of colistin sulfate in managing CRO infections among patients with hematological diseases. Between April 2022 and January 2023, a total of 118 hematological patients diagnosed with CRO infection were treated with colistin sulfate at Suzhou Hongci Hospital of Hematology. The assessment encompassed the clinical efficacy, bacterial clearance rate, adverse reactions, and 30-day all-cause mortality. The study found that the total effective rate of colistin sulfate in the treatment of CRO infection was 74.6%, with a bacterial clearance rate of 72.6%. Throughout the treatment, nephrotoxicity occurred in 7.6% of cases, neurotoxicity in 2.5% of cases, and the 30-day all-cause mortality rate was 22.9%. Multivariate logistic analysis revealed that the treatment course and combination medication with other antimicrobials were independent factors affecting the clinical efficacy of colistin sulfate. Our study demonstrates that the treatment of colistin sulfate can achieve high clinical efficacy and microbial responses, with a low risk of nephrotoxicity. This study provides evidence of the positive clinical efficacy and safety of colistin sulfate treatment in these patients. High-quality randomized controlled trials are still needed to further confirm the beneficial role of colistin sulfate.

A preliminary exploration on the mechanism of the carbapenem-resistance transformation of Serratia marcescens in vivo

BackgroundThe infection of carbapenem-resistant organisms was a huge threat to human health due to their global spread. Dealing with a carbapenem-resistant Serratia marcescens (CRSM) infection poses a significant challenge in clinical settings. This study aims to provide insights into strategies for controlling CRSM infection by exploring the transformation mechanism of carbapenem-resistance.MethodsWe used whole genome sequencing (WGS) to investigate the mechanism of carbapenem resistance in 14 S. marcescens isolates in vivo. The expression level of related genes and the minimum inhibitory concentration of meropenem (MICMEM) were also evaluated to confirm the mechanism of carbapenem resistance.ResultsSeven groups of S. marcescens, each consisting of two strains, were collected from a hospital and displayed a shift in MICMEM from low to high levels. Homology analysis revealed that the isolates in five groups were significantly different from the remaining two. WGS and experimental evidence indicated that four groups of strains developed carbapenem resistance by acquiring the blaKPC (obtaining group), while two groups (persisting group) increased the expression level of the blaKPC. In contrast, isolates in the last group (missing group) did not carry the blaKPC. All strains possessed multiple β-lactamase genes, including blaCTX−M−14, blaSRT−1, and blaSRT−2. However, only in the missing group, the carbapenem-resistant strain lost an outer membrane protein-encoding gene, leading to increased blaCTX−M−14 expression compared to the carbapenem-susceptible strain.ConclusionThe study findings suggest that S. marcescens strains developed diverse carbapenem resistance in vivo through the evolution of drug resistance, rather than through clone replacement. We hypothesize that carbapenem resistance in S. marcescens was due to certain clonal types with a distinct mechanism.

Epidemiology of carbapenem-resistant organisms in Alameda County, California, 2019-2021.

Carbapenem-resistant organisms (CROs) are an urgent health threat. Since 2017, Alameda County Health Public Health Department (ACPHD) mandates reporting of carbapenem-resistant Enterobacterales (CRE) and encourages voluntary reporting of non-CRE CROs including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Surveillance data from ACPHD were analyzed to describe the epidemiology of CROs and target public health interventions. Healthcare facilities in Alameda County reported CRO cases and submitted isolates to ACPHD to characterize carbapenemase genes; deaths were identified via the California Electronic Death Registration System. CRO cases with isolates resistant to one or more carbapenems were analyzed from surveillance data from July 2019 to June 2021. Four hundred and forty-two cases of CROs were reported to Alameda County from 408 patients. The county case rate for CROs was 29 cases per 100,000 population, and cases significantly increased over the 2-year period. CRPA was most commonly reported (157 cases, 36%), and cases of CRAB increased 1.83-fold. One-hundred eighty-six (42%) cases were identified among residents of long-term care facilities; 152 (37%) patients had died by January 2022. One hundred and seven (24%) cases produced carbapenemases. The high burden of CROs in Alameda County highlights the need for continued partnership on reporting, testing, and infection prevention to limit the spread of resistant organisms. A large proportion of cases were identified in vulnerable long-term care residents, and CRAB was an emerging CRO among this population. Screening for CROs and surveillance at the local level are important to understand epidemiology and implement public health interventions.

Rectal culture could predict carbapenem-resistant organism bloodstream infection and reduce the mortality in haematological patients: A retrospective cohort study

The objective is to explore the correlation between rectal swab culture and the overall 30-d survival of hematologic patients diagnosed with carbapenem-resistant organism (CRO) bloodstream infection. A total of 434 haematological patients who were complicated with Gram-negative bacilli (GNB) bloodstream infections (BSIs) caused by Gram-negative bacteria between January 2020 and December 2021 were included in our retrospective study. Based on their drug susceptibility results, we classified patients into CRO BSIs and non-CRO BSIs cases. Through group comparison, to uncover the correlation between the positive screening of rectal swabs and reducing the mortality of CRO BSI in patients with haematological diseases. Among the 434 cases of Gram-negative bacteria bloodstream infection, 96 were identified as carbapenem-resistant bloodstream infection, which consisted of 57 cases of carbapenem-resistant Klebsiella pneumoniae (CR-KP), 19 cases of carbapenem-resistant Pseudomonas aeruginosa (CR-PA), 11 cases of carbapenem-resistant Escherichia coli (CR-CO), 5 cases of carbapenem-resistant Acinetobacter baumannii (CR-AB), and 4 cases of other Enterobacteriaceae. Before the onset of CRO bloodstream infection, rectal swab cultures were conducted on 36 patients, and the positive result rate was 75.0% (27/36), with 20 cases of CR-KP, 6 cases of CR-CO, and one case of carbapenem-resistant Enterobacter cloacae. It was observed that the rectal and blood cultures had matching outcomes in 75.0% of cases. The mortality rate within 30 d for CRO BSIs was 53.1% (51/96), while for carbapenem-resistant Enterobacteriaceae (CRE) BSIs it was 62.5% (45/72). Univariate analysis showed that 30-d mortality was significantly reduced when there were positive rectal culture results preceding bloodstream infection (P < 0.001), as well as preemptive anti-infection treatment (P < 0.001). Multivariate analysis demonstrated that preemptive adjustment to an effective antibiotic regimen, guided by positive rectal culture results, had a significant effect on decreasing 30-d mortality following CRO BSIs (P= 0.002). Furthermore, for the management of CRE BSIs, antibiotic treatments utilising ceftazidime/avibactam (CAV/AVI) may be more beneficial compared to those that use tigecycline (TGC) or polymyxin (PMB). CRO BSI, especially CRE BSI, can be life-threatening for those with haematological diseases. Utilising rectal culture can effectively identify CRO strains with high sensitivity and specificity. Adjusting antibiotic treatment based on the preemptive positive rectal culture results may significantly decrease 30-d mortality rates for haematological patients with CRO BSIs.

Molecular Patterns of Resistance in Carbapenem Resistant Organisms Detected in Stool Surveillance Cultures in Patients Undergoing Hematopoietic Cell Transplant

Introduction Patients undergoing hematopoietic stem cell transplant (HSCT) are at high risk of life-threatening bacterial infections. Although the prevalence and pattern of resistance varies amongst centres and countries, there is a growing global problem of resistance to antibiotics. The increased use of broad-spectrum antibiotics and injudicious antibiotic policies have contributed to the selection of multidrug resistant(MDR) pathogens. Translocation of organisms which normally colonize the gut into the bloodstream during the febrile neutropenia has long been postulated as a pathogenic factor for life-threatening gram-negative infections. We routinely do stool surveillance culture of all patients admitted for autologous and allogenic stem cell transplant to guide us on empirical antibiotic usage. This analysis was conducted to evaluate the incidence of carbapenem resistant organisms (CROs) and their molecular pattern of resistance in stool surveillance cultures. Methods This is a single centre retrospective analysis of patients who underwent autologous and allogenic stem cell transplant for haematological malignancies from December 2021 to January 2023. In all patients stool surveillance cultures were sent at baseline during admission and then weekly thereafter till discharge . A blood Biofire syndromic multiplex PCR was performed in a fraction of stool isolates to identify the gene responsible for carbapenem resistance. Biofire syndromic multiplex PCR was performed only once for one patient on the first stool culture that grew a CRO. Biofire is a multiplex PCR that identifies Gram negative organisms including Acinetobacter Baumanni, Bacteroides Fragilis, Enterobacter cloacae, E. coli, Klebsiella, Proteus, Salmonella, Serratia, H. influenza, Neisseria meningitides, Pseudomonas aeruginosa, Stenotrophomonas maltophilia; it also identifies the gene responsible for resistance. The Carbapenem resistant genes included in the Biofire syndromic multiplex PCR were IMP Carbapenemase, KPC Carbapenamase, OXA-48, NDM, VIM, CTXM. Results Seventy-one patients underwent HSCT from December 2021 to January 2023. These included 39 allogenic and 32 autologous stem cell transplants. The median age of the cohort was 33 years (range 3-63 years) with 48 males and 23 females. The diagnoses were AML(n=8), ALL(n=14), CML(n=14), HL(n=10), Multiple Myeloma(n=19), Myelofibrosis(n=1), Non-Hodgkin Lymphoma (n=5). A total of 430 stool surveillance cultures from 71 patients were analysed. Of 430, 90 (20.9%) stool samples in 30 (42%) patients grew carbapenem resistant organism. Of these 90 CROs, twenty-three stool culture isolates belonging to 23 different patients were analysed for genotypic resistance. These 23 CROs included Escherichia coli 12 (52%) and Klebsiella pneumonia 11 (48%). On phenotypic sensitivity testing, the CROs were sensitive to Ceftriaxone-Sulbactam-EDTA (23/23, 100%), Ceftazidime-Avibactam (2/15, 13%), Colistin (23/23, 100%), Aztreonam (3/23, 13%), Tigecycline (17/23, 74%), Minocycline (9/23, 39%) and Aminoglycosides (11/23, 48%) shown in Figure 1a Resistance gene panel in these 23 stool isolates revealed NDM alone in 7 (31%), CTX-M along with NDM in 9 (39%), CTX-M along with OXA 48 like in 2(9%), CTX-M, OXA 48 along with NDM in 4 (17%) and NDM with OXA 48 in 1 (4%) (Figure 1b). Of the remaining 67 stools in which Biofire was not performed, Escherichia coli grew in 31 (46%) and Klebsiella pneumonia grew in 35 (52%) and Pseudomonas Aeruginosa in 1 (2%). On drug sensitivity testing, these CROs were sensitive to Ceftriaxone-Sulbactam-EDTA (65/67, 97%), Ceftazidime-Avibactam (4/15, 26%), Colistin (65/67, 97%), Aztreonam (7/65, 11%), Tigecycline (39/57, 68%), Minocycline (24 /62, 39%) and Aminoglycosides (33/67, 49%). Conclusion: About 40% of our patients were colonized with CROs at some point during their transplant. Molecular patterns identified NDM alone or in combination with other resistance genes in more than 90% of stools where molecular testing was performed. The antibiotics to which these MDR organisms were most susceptible included Ceftriaxone-sulbactam-EDTA, Colistin and tigecycline. Our study suggests that NDM is the most common resistance gene responsible for carbapenem resistance in our patients. Thus, antibiotics or antibiotic combinations that target NDM should be considered early in patients with MDR sepsis.

2795. Cefepime Versus Meropenem for Infections Due to HECCcK-YeS-MAm Organisms with Cefepime MICs of 4-8 mCg/mL (S-DD)

Abstract Background Recent guidance from IDSA recommends meropenem for treatment of organisms at moderate-high risk for inducible chromosomal AmpC β-lactamase hyperproduction (AmpC organisms) with a cefepime minimum inhibitory concentration (MIC) of 4-8 mCg/mL (susceptible dose-dependent or S-DD).1 This runs contrary to pharmacokinetic/pharmacodynamic data and Clinical and Laboratory Standards Institute (CLSI) M100 guidance, which considers organisms ≥ 16 mCg/mL resistant.2 The purpose of this study is to evaluate the clinical efficacy of cefepime versus meropenem for the treatment of infections caused by AmpC organisms with a S-DD cefepime MIC. Methods This was a retrospective study evaluating patients treated within Indiana University Health from 2015-2022. All cefepime S-DD AmpC isolates were included. Exclusion criteria were &amp;lt; 48 hours of treatment, multiple days of therapy with another active agent, inadequate dosing, extended spectrum β-lactamase (ESBL) co-production, and carbapenem resistance. The primary endpoint of this study was a composite of in-hospital all-cause mortality and antibiotic escalation due to clinical worsening. Secondary endpoints include positive repeat blood cultures within 7 days of treatment initiation, and ESBL or carbapenem resistant organism isolation during or following treatment. Results 355 isolates were screened. 71 patients were included in the final analysis, 43 in the cefepime group and 28 in the meropenem group. Baseline characteristics were not significantly different. Enterobacter cloacae made up 79% of cases. The primary endpoint occurred in 13/43 (30%) of patients on cefepime and 7/28 (25%) of patients on meropenem (P=0.63). Treatment escalation and escalation due to clinical worsening was higher in the cefepime group with 7 (16%) and 6 (14%) incidents respectively compared to none in the meropenem group (P=0.03; P=0.04). No other endpoints, including all-cause mortality, were significantly different between groups. Conclusion Cefepime remains a viable treatment option for ESBL-negative, AmpC organisms with MICs in the S-DD range. Disclosures All Authors: No reported disclosures

Dissecting bloodstream infections in febrile neutropenic patients with hematological malignancies, a decade-long single center retrospective observational study (2009–2019)

BackgroundThe use of ill-suited antibiotics is a significant risk factor behind the increase in the mortality, morbidity, and economic burden for patients who are under treatment for hematological malignancy (HM) and bloodstream infections (BSI). Such unfitting treatment choices intensify the evolution of resistant variants which is a public health concern due to possible healthcare-associated infection spread to the general population. Hence, this study aims to evaluate antibiograms of patients with BSI and risk factors associated with septicemia. MethodsA total of 1166 febrile neutropenia episodes (FNE) among 513 patients with HM from the National Center for Cancer Care and Research (NCCCR), Qatar, during 2009–2019 were used for this study. The socio-demographic, clinical, microbial, and anti-microbial data retrieved from the patient’s health records were used. ResultsWe analyzed the sensitivity of gram-negative and gram-positive bacilli reported in HM-FN-BSI patients. Out of the total 512 microorganisms isolated, 416 (81%) were gram-negative bacteria (GNB), 76 (15%) were gram-positive bacteria (GPB) and 20 (4%) were fungi. Furthermore, in 416 GNB, 298 (71.6%) were Enterobacteriaceae sp. among which 121 (41%) were ESBL (Extended Spectrum Beta-Lactamase) resistant to Cephalosporine third generation and Piperacillin-Tazobactam, 54 (18%) were Carbapenem-resistant or multidrug-resistant organism (MDRO). It's noteworthy that the predominant infectious agents in our hospital include E. coli, Klebsiella species, and P. aeruginosa. Throughout the study period, the mortality rate due to BSI was 23%. Risk factors that show a significant correlation with death are age, disease status, mono or polymicrobial BSI and septic shock. ConclusionDecision pertaining to the usage of antimicrobials for HM-FN-BSI patients is a critical task that relies on the latest pattern of prevalence, treatment resistance, and clinical outcomes. Analysis of the antibiogram of HM-FN-BSI patients in Qatar calls for a reconsideration of currently followed empirical antibiotic therapy towards better infection control and antimicrobial stewardship.

Efficacy and nephrotoxicity of polymyxin B in elderly patients with carbapenem resistant bacterial infection

BackgroundTo study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection.MethodsThe clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared.ResultsThe effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2–37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931.ConclusionsRational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI.

Acetylcysteine increases sensitivity of ceftazidime-avibactam–resistant enterobacterales with different enzymatic resistance to ceftazidime-avibactam in vitro and in vivo

BackgroundCeftazidime-avibactam (CZA) improves treatment outcomes for infections caused by carbapenem-resistant organisms, but has led to serious bacterial resistance. Acetylcysteine (NAC) is an approved medication that protects the respiratory tract through antioxidant and anti-inflammatory effects.ResultsThis study found that NAC combined with CZA effectively inhibits the growth of CZA-resistant clinical Enterobacterales strains. The CZA/NAC combination inhibits biofilm formation in vitro and decreases bacterial burden in a mouse thigh infection model. The combination is biocompatible and primarily increases cell membrane permeability to cause bacterial death.ConclusionsThese findings prove that the CZA/NAC combination has potential as a treatment for CZA-resistant Enterobacterales infections.

Antimicrobial susceptibility and clinical characteristics of multidrug-resistantpolymicrobial infections in Pakistan, aretrospective study2019-2021.

Background: We determined the prevalence of antimicrobial resistance (AMR) in polymicrobial pathogens in Pakistan. Methods: A total of70,518 clinical samples were collected aseptically and confirmation of isolates andantibiogram wereperformed by the VITEK 2 system. Results: Of 70,518 samples, 441 (0.62%) were polymicrobial samples, with 882 (1.2%) polymicrobial pathogens with689 (78.1%) Gram-negative rods (GNRs), 166 (18.8%)Gram-positive cocciand 27 (3.1%) Candida albicans. Among GNRs, 28.8% were Escherichia coli and 25.9%were Klebsiella pneumoniae. Majority, 15.1% of Pseudomonas aeruginosa and K. pneumoniae were found in combination. 30.1% of isolates were ESBL producers, 9.7% carbapenem-resistant organisms, 35.5% MRSA and 6.0% VRE. 100% of E. coli were resistant to ampicillin and 98% of K. pneumoniae were resistant to piperacillin. Conclusion: A high prevalence of AMR in polymicrobial pathogens was observed.

CLINICAL CHARACTERISTICS AND OUTCOME OF VENTILATOR ASSOCIATED PNEUMONIA IN PATIENTS WITH RENAL FAILURE

Background: Ventilator associated pneumonia (VAP) causes significant morbidity and mortality. Data from patients with preexisting renal failure is limited. Our aim was to evaluate the clinical characteristics and outcome of VAP in patients with renal failure and/or on maintenance hemodialysis. Material and Methods: A prospective observational study was conducted from February 2022 to February 2023. Patients &gt;18 years, on mechanical ventilation (MV) for &gt;48 hours, having underlying deranged renal function and who developed VAP were included. Demographics, cause of intubation, day of onset of VAP, clinical features, laboratory parameters and tracheal cultures were noted. Patients were followed till day 14 of VAP for mortality. Results: Out of 165 MV patients, 67 (40.60%) developed VAP, 33 (49.25%) in ≤ 4 days. The cause of intubation was respiratory distress in 58(86.8%) patients. In 61(91%) patients tracheal cultures were positive with Acinetobacter species (64%) as the most common organism and 93% of which were carbapenem resistant. Carbapenem resistant organisms were more frequently in case of late onset VAP (91.2% versus 72.7% p=0.049). A total of 42 patients (62%) died, 76 % within 7 days of VAP and 13 patients (19.40%) recovered with successful extubation. There was no significant difference in 14 days mortality between early or late VAP. Conclusion: VAP rates in patients with preexisting renal failure were 40%. Half of them developed in &lt;4 days. Acinetobacter spp. was the predominant causative agent. Attributed mortality was high at 63% where two thirds of patients died within 14 days. Keywords: Outcome, Renal failure, Ventilator associated pneumonia, Mechanical ventilator

Prevalence and Impact on Mortality of Colonization and Super-Infection by Carbapenem-Resistant Gram-Negative Organisms in COVID-19 Hospitalized Patients.

The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients. Herein, a retrospective study was carried out using data from adult patients hospitalized for COVID-19. The interaction between in-hospital mortality and rectal carriage and superinfection by carbapenemase-producing Enterobacterales and/or carbapenem-resistant Acinetobacter baumannii was assessed. The incidence of KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage was 30%. Bloodstream infection and/or pneumonia due to KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii occurred in 20% of patients. A higher Charlson comorbidity index (OR 1.41, 95% CI 1.24-1.59), being submitted to invasive mechanical ventilation/ECMO ≥ 96 h (OR 6.34, 95% CI 3.18-12.62), being treated with systemic corticosteroids (OR 4.67, 95% CI 2.43-9.05) and having lymphopenia at the time of admission (OR 0.54, 95% CI 0.40-0.72) were the features most strongly associated with in-hospital mortality. Although KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage, and/or bloodstream infection/pneumonia were diagnosed in a remarkable percentage of COVID-19 patients, their impact on in-hospital mortality was not significant. Further studies are needed to assess the burden of antimicrobial resistance as a legacy of COVID-19 in order to identify future prevention opportunities.