Carbapenem-resistant Organisms Research Articles

Rise of Carbapenem-Resistant Escherichia coli and the Concerning Existence of blaNDM-1 Gene in Gut Microbiota of Rural Populations

In rural communities, the blaNDM-1 gene in the gut microbiota may be contributing to the growing issue of antibiotic resistance. This gene enables bacteria to produce enzymes that break down antibiotics, making treatments less effective. The limited healthcare resources and frequent exposure to resistant bacteria in these areas could further amplify this problem, increasing the risk of difficult-to-treat infections among the population. The objective of this study was to evaluate the antimicrobial susceptibility of Escherichia coli [E. coli] strains isolated from healthy individuals and to assess the prevalence of blaNDM-1 gene carriage. The samples were cultured and identified as gut commensal by conventional method. Then antibiotic susceptibility test using the Kirby Bauer disc diffusion method were carried out. Carbapenem-resistant organisms were isolated, and the blaNDM-1 was identified by polymerase chain reaction. This study includes 187 Healthy participants faecal samples were obtained from people in and around the Chengalpattu area. Out of 187 samples, 110 showed E. coli growth, 63 showed Enterococci species growth, and 14 showed no growth. Among the 110 E. coli isolates, 24 (21.8%) were sensitive to all drug classes, and 86 (78.2%) were multidrug resistant. Only 8(7.27%) of the 110 E. coli tested positive for carbapenem resistance. Out of 110 E. coli isolates, only (2.7%) had the blaNDM-1 gene. This study discovered that rural communities that are unlikely to be subjected to obvious antibiotic pressure had a high incidence of MDR microorganism faecal carriage. Finding resistance genes in commensal bacteria is alarming. This has the ability to spread and emerge in the environment.

Clinical characteristics and prognosis of bloodstream infections with carbapenem-resistant Gram-negative organisms in patients with hematological malignancies: A multicenter case-control study in China

To investigate clinical characteristics of hematological malignancy (HM) patients with carbapenem-resistant gram-negative organism (CRO) bloodstream infections (BSI) in China, and to elucidate the prognostic risk factors of CRO BSI. We conducted a multicenter case-control study of 201 HM patients with CRO BSI between 2018-2020. Antimicrobial susceptibility testing and whole genome sequencing were performed for CRO isolates. Independent risk factors for 28-day crude mortality of were analyzed using Cox proportional hazards regression models. The subgroups of major species were also evaluated. The pathogens responsible for CRO BSI in HM patients dominated by ST11 CRKP, ST167 CREC and ST463 CRPA. Most isolates produced carbapenemases with KPC and NDM being the main. CRO isolates had resistance rates to conventional antimicrobials ranging from 55%-100% and poor susceptibility to novel antimicrobials related to carbapenemases and species. The 28-day crude mortality was 24.2%. Non-Hodgkin lymphoma, heart disease, blaKPC-2 positive, empirical antibiotic therapy with linezolid, Pitt bacteremia score >3.5 were risk factors for 28-day mortality and appropriate definitive antibiotic therapy, tigecycline-containing therapy and aminoglycoside-containing therapy were protective factors. blaKPC-2 positive in CRKP and ST463 in CRPA were associated with Pitt bacteremia score > 3.5. Solid tumor and other site infections before BSI were risk factors for ST463 CRPA BSI and Pulmonary infection before BSI was risk factor for KPC-KP BSI. The antimicrobial resistance of CRO isolates for BSI in HM patients is critical. HM patients with CRO BSI should be treated with appropriate definitive antibiotic therapy based on early clarification of pathology and their antimicrobial susceptibility.

Comparison of two commercial broth microdilution panels for multidrug-resistant Gram-negative bacteria: Thermo Scientific™ Sensititre DKMGN vs. Beckman Coulter MicroScan NMDRM1.

Antimicrobial susceptibility testing (AST) using broth microdilution (BMD) is usually the reference method to obtain accurate minimum inhibitory concentrations and optimally manage infections with resistant organisms. Several commercial dry BMD are available for AST in clinical laboratories. Two commercial BMD panels for testing of multidrug-resistant Gram-negative bacteria were compared: the Thermo Scientific™ Sensititre DKMGN and the Beckman Coulter NMDRM1, for 17 antimicrobial agents. A total of 207 isolates were tested: three ATCC strains and one NCTC strain, six quality control strains from the Belgian National Antimicrobial Committee, and 197 clinical isolates, including carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 breakpoints version 13.1 were used to assign susceptibility categories. Overall, the categorical agreement (CA) and essential agreement (EA) were both above 90%, but several useful antibiotics for the treatment of multi-resistant organisms showed CA and EA under 90%, that is, meropenem, imipenem, and colistin for Enterobacterales and meropenem and colistin for P. aeruginosa. For Enterobacterales, the NMDRM1 panel showed a significantly higher resistance rate for meropenem, imipenem, amikacin, and colistin. For carbapenems, the minimal inhibitory concentrations (MICs) were underestimated by the DKMGN panel, as already pointed out by a warning on the EUCAST website. To better assess carbapenem susceptibility in carbapenem-resistant organisms, the DKMGN panel now requires the use of a higher inoculum in the insert kit. However, for a given isolate whose susceptibility to carbapenems is not known, there is a risk of underestimating the MIC values. Our results show that colistin testing remains a challenge, highlighting the urgent need for the development of more accurate commercial methods. The use of a single commercial method cannot guarantee good precision in the determination of the MIC value for colistin.

Environmental contamination with carbapenem resistant Acinetobacter baumannii in healthcare settings in Fiji: a potential source of infection.

There are multiple ongoing outbreaks of carbapenem resistant Acinetobacter baumannii (CRAb) infection in Fiji's hospitals. CRAb is able to colonize and persist on various hospital surfaces for extended periods. We conducted a study to understand the extent of hospital environmental contamination and phylogenetic links with clinical isolates. Swabs were collected from high-touch surfaces at Colonial War Memorial Hospital (CWMH) September 2021 and December 2022; Lautoka Hospital (LTKH) August 2022; and Labasa Hospital (LBSH) November 2022. All bacterial isolates were identified, and antimicrobial susceptibility testing (AST) performed; isolates resistant to carbapenems and producing a carbapenemase underwent whole genome sequencing. Comparison was made to clinical isolates obtained from CWMH in 2016-2017 and 2019-2021 and from LTKH and LBSH from 2020-2021. From the 180 environmental samples collected, ten (5.6%) CRAb were isolated; no other carbapenem-resistant gram-negative organisms were isolated. Seven (70%) of the CRAb were isolated from CWMH and three (30%) from LTKH; no CRAb were isolated from LBSH. Of the seven CWMH CRAb, two were sequence type 2 (ST2), three ST25, and two ST499. All LTKH isolates were ST499. The two environmental CRAb ST2 isolates were closely genetically linked to isolates obtained from patients in CWMH, LTKH, and LBSH 2020-2021. Similarly, the three environmental CRAb ST25 isolates were closely genetically linked to isolates obtained from patients admitted to CWMH in 2019-2021 and LBSH in 2020. The environmental CRAb ST499 isolates represented two distinct clones, with clone 1 comprising two genetically identical isolates from CWMH and clone 2 the three isolates from LTKH. Although no genetic linkages were observed when comparing environmental ST499 isolates to those from CWMH patients in 2020-2021, both clone 1 isolates were genetically identical to an isolate obtained from a patient admitted during the sampling period. Our study highlights the contamination of high-touch surfaces within Fiji hospitals with CRAb, suggesting that these may serve as important sources for CRAb. Phylogenetic linkages to CRAb isolated from patients since 2019 underscores the persistence of this resistant pathogen in hospital settings and the ongoing risk for hospital-acquired infections.

Experience oExperience of an antimicrobial stewardship programme in a tertiary care hospital in Sri Lankaf an Antimicrobial stewardship programme in a tertiary care hospital in Sri Lanka

Introduction: Hospital-based antibiotic stewardship programmes are helpful to optimise the treatment of infectious diseases and to prevent the development of antibiotic resistance. The rise in multi-drug resistance in Sri Lankan hospitals including carbapenem-resistant organisms emphasises the need for implementation of effective AMS programmes and planned in national strategic plan to combat antimicrobial resistance. A sustainable approach towards an effective AMS pro-gramme is continuously needed. The data on experience in implementing AMS programmes in Sri Lanka is scares.Objective: To share the experiences and challenges faced while implementing an AMS programme in a hospital,.d. Guidelines on empirical and prophylactic use of anti-microbials and common infections were distributed to each unit. A list of antimicrobials prepared according to WHO AwaRe classification and drug chart designed for documentation of optimal prescribing.Results: There was a 27.3% reduction in mean carba-penem consumption after initial implementation and the consumption is gradually rising. 36% decrease in carbapenem resistance rate in Acinetobacter species, 33% reduction in carbapenem-resistant Pseudomonas species was observed. The point prevalence of anti-microbial use was found to be 45.5% and 49% in 2023 and 2024 respectively. The commonest indication for antimicrobial use in prescriptions was community-acquired infections. There was a reduction in continuing antibiotics for surgical prophylaxis after implementation of AMS programme.Conclusion: For successful implementation of an AMS programme in community acquired drug resistance also should be addressed. In hospital setting continuation of surgical prophylaxis is an area which can be improved easily. Adequate staff and time allocated for AMS activities will be beneficial for sustainable programmes.

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

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

Prevalence of Antimicrobial Resistance in Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli Isolates among Stillbirths and Deceased Under-Five Children in Sierra Leone: Data from the Child Health and Mortality Prevention Surveillance Sites from 2019 to 2022.

Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae are associated with most nosocomial infections worldwide. Although gaps remain in the knowledge of their susceptibility patterns, these are in antimicrobial stewardship. This study aimed to describe antimicrobial susceptibility profiles of the above organisms isolated from postmortem blood from stillbirths and under-five children enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) program in Sierra Leone. This was a surveillance study of bacteria isolates from postmortem blood cultures taken within 24 h of death from stillbirths and children aged 0-59 months between March 2019 and February 2022. This was followed by identification and antibiotic sensitivity testing using Becton Dickinson Phoenix M50 (USA). Descriptive analysis was used to characterize the isolates and their antimicrobial susceptibility patterns. Of 367 isolates, K. pneumoniae was the most frequently isolated organism (n = 152; 41.4%), followed by E. coli (n = 40; 10.9%) and E. cloacae (n = 35; 9.5%). Using BACTEC™ FX 40 (Franklin Lakes, NJ, USA), 367 isolates were identified from blood using bacteriological methods. Extended spectrum beta-lactamase (ESBL) was observed in 143 (94.1%) of K. pneumoniae isolates and 27 (65.5%) of E. coli isolates. Carbapenem-resistant organisms (CRO) were seen in 31 (20.4%) of K. pneumoniae and 5 (12.5%) of E. coli isolates. A multidrug resistance (MDR) pattern was most prevalent in E.cloacae (33/35; 94.3%), followed by K. pneumoniae (138/152; 90.8%). Our study showed a high prevalence of multidrug resistance among bacterial isolates in the catchment areas under surveillance by the CHAMPS sites in Sierra Leone.

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

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

High Burden of Carbapenem-Resistant Organisms Screened by Xpert Carba-R Assay Versus Culture from Intensive Care Patients in Indonesia

The World Health Organization (WHO) considers carbapenem-resistant organisms (CROs) to be critical-level pathogens. Regular screening for high-risk CRO colonization is essential, especially in the ICU. Direct detection of carbapenem-resistant genes is possible using the FDA-approved Xpert Carba-R assay. This study evaluated its reliability compared with the culture technique at a tertiary hospital in Indonesia. A high number of CRO colonization was found using the culture technique and the Xpert Carba-R assay with about 31 and 26 positive results out of 100 total samples, respectively. Both methods detected blaNDM in 11 samples, and the Xpert Carba-R assay detected one sample co-presenting with blaVIM that was not detected by PCR. The Xpert Carba-R assay did not detect the gene in 73 samples following negative results with the culture technique. Fifteen samples were detected gene by the Xpert Carba-R assay though there was no gene by the culture method, showing that the Xpert Carba-R assay demonstrated a high degree of sensitivity in identifying carbapenem-resistance genes. Carbapenem-resistance genes common in Indonesia other than those examined by Xpert Carba-R assay in this study (i.e., blaOXA-23 and blaOXA-24) or non-enzymatic mechanisms may also produce resistance in many colonies without the examined genes. Finally, the Xpert Carba-R assay produced faster findings than the culture technique.

Clinical outcome assessment of colistin sulphate in children with carbapenem-resistant organism infections: First data from China

ObjectivesColistin sulphate for injection (CSI) became clinically available in China in July 2019. To date, there is no published data regarding its usage in children. Our research group has been following data on the efficacy and safety of CSI in Chinese paediatric patients with carbapenem-resistant organism infections. The purpose of this short communication is to provide a brief overview of the findings to date. MethodsWe reviewed the electronic medical records of paediatric patients (aged 9–17 y) who were administered CSI during their hospital stay at Tongji Hospital in Wuhan, China, between June 2021 and November 2023. Drug efficacy was evaluated based on clinical and microbiological outcomes, while drug safety was assessed using surveillance markers that reflect adverse reactions. ResultsA total of 20 patients met the inclusion criteria. The predominant pathogens were Klebsiella pneumoniae (8 strains), followed by Acinetobacter baumannii (5 strains) and Pseudomonas aeruginosa (2 strains). The clinical response rate of CSI was 85%, with a bacterial clearance rate of 79%. None of the patients experienced colistin-related nephrotoxicity or neurotoxicity during the treatment. ConclusionsIn this real-world setting, CSI demonstrated a high level of clinical response and was well tolerated for the treatment of carbapenem-resistant organism infections in Chinese children.

Double blaKPC-2 copies quadrupled minimum inhibitory concentration of ceftazidime-avibactam in hospital-derived Klebsiella pneumoniae.

To illustrate the genomic and drug resistance traits of the Klebsiella pneumoniae Kpn_XM9, which harbors a transposon (Tn) As1 and was barely susceptible to ceftazidime-avibactam (CZA). Whole-genome sequencing, gene deletion, antimicrobial susceptibility, and conjugation tests were carried out to illustrate the traits of Kpn_XM9. As confirmed by whole-genome sequencing, the Kpn_XM9 harbored a 5,523,536 bp chromosome and five plasmids with lengths being 128,129, 196,512, 84,812, 43,695, and 5,596 bp, respectively. Plasmid p1_Kpn_XM9 (128,219 bp) contained four resistance genes, blaCTX-M-65, blaTEM-1B, rmtB, and two copies of blaKPC-2. Genes blaKPC-2 were bracketed by ISKpn17 and ISKpn16 within a new composite Tn3-like TnAs1. The two tandem repeats, positioned opposite each other, were spaced 93,447 bp apart in p1_Kpn_XM9. Kpn_XM9 belonged to K64 and sequence type (ST) 11. The Kpn_XM9 was resistant to amikacin, aztreonam, ticarcillin/clavulanic acid, piperacillin/tazobactam, ceftazidime, cefepime, imipenem, meropenem, tobramycin, ciprofloxacin, levofloxacin, doxycycline, minocycline, tigecycline, colistin, and trimethoprim/sulfamethoxazole; it was barely susceptible to CZA with a minimum inhibitory concentration of 8/4 µg/mL, which declined to 2/4 µg/mL after a 18,555 bp nucleotide was knocked out and one copy of blaKPC-2 was sustained on p1_Kpn_XM9. Kpn_XM9 had virulence genes encoding Types 1 and 3 fimbriae, four siderophores, and capsular polysaccharide anchoring protein but no genes upregulating capsular polysaccharide synthesis. The Kpn_XM9 presented a classical phenotype with extreme drug resistance. The emergence of double copies of blaKPC-2 in a single plasmid from the predominant ST11 K. pneumoniae represents a new therapeutic challenge.IMPORTANCEWith the wide use of ceftazidime-avibactam against carbapenem-resistant organisms, its resistance is increasingly documented; among the corresponding resistance mechanisms, mutations of blaKPC-2 or blaKPC-3 into other subtypes are dominant to date. However, more copies of blaKPC-2 may also greatly increase the minimum inhibitory concentration of ceftazidime-avibactam, which could be conferred by transposon As1 and insertion sequence 26 and should be of concern.

Assessment of in vitro antimicrobial activity of ceftazidime-avibactam and phenotypic synergy testing with aztreonam against carbapenem resistant Gram-negative bacilli in a tertiary care hospital

Objectives: Ceftazidime avibactam (CZA) is a drug used against carbapenemase producing Gram-negative bacterial infections. Avibactam (AVI) is a non-beta-lactam-beta-lactamase inhibitor which has no action against metallo-β-lactamase (MBL) enzymes. This inadequacy is counteracted by combining CZA with aztreonam (ATM). The present study aims to denote the in vitro susceptibility pattern of the CZA and CZA-ATM combination in our area. Materials and Methods: In this study conducted prospectively from January to June 2023, the samples growing Enterobacterales and Pseudomonas aeruginosa were proceeded for carbapenemase detection by phenotypic testing for EDTA carbapenem inactivation method and modified carbapenem inactivation method. The minimum inhibitory concentration MIC of CZA was determined by E-strip and interpreted as per clinical and laboratory standard institute (CLSI) guidelines, while synergy testing of CZA and ATM was performed using ATM discs. Statistical Analysis: All data were entered in Microsoft Excel and analyzed for basic statistics. Results: The study included 150 carbapenem resistant organisms (131 Enterobactarales and 19 P. aeruginosa). Among these Enterobacterale strains, 72 (54.9%) were MBL producers. CZA resistance was detected in 69.3% of Klebsiella spp., 61.53% of Escherichia coli, and 50% of Serratia spp. Among Klebsiella spp. and E. coli, 88.9% and 65.2% of MBL isolates showed in vitro synergy to CZA-ATM. Conclusions: The study highlights a good in vitro sensitivity pattern of the CZA and ATM combination. However, we also highlight a growing percentage of non-synergistic interactions that need further genetic evaluation.

Community-associated Carbapenem-Resistant Organism Case Investigations in New York City, December 2020-May 2023

Epidemiology of carbapenem-resistant organisms (CRO) has focused on transmission in acute care hospital or long-term care facility (LTCF) settings. Few investigations have examined community-associated (CA)-CRO, with no consensus about common exposures. To explore possible exposures, the New York City (NYC) Department of Health and Mental Hygiene investigated suspected CA-CRO cases through routine surveillance among NYC residents with specimens collected during December 2020-May 2023. CA-CRO cases were defined as urine or skin specimens with bacterial cultures exhibiting carbapenem resistance, among individuals aged ≤70 years with no international travel, hospitalization, or LTCF stays within 12 months before specimen collection. Inclusion was determined by reviewing data from health information exchanges, when available electronic medical records, and telephone screening for those not excluded through record review. We identified 426 suspected cases for review, those not meeting the case definition were excluded; 44 individuals were not reached for screening. A preliminary questionnaire was fielded with 12 individuals and then refined to capture additional potential exposures. Analyses were completed with 23 individuals interviewed with the refined questionnaire. Of the 23, 70% were female; 39% were Hispanic, 17% Black, and 17% White; their median age was 60 years (range: 26-70 years). Further, 83% reported an outpatient appointment, 48% reported an outpatient procedure/surgery, and 9% reported having a hospitalized household member, all within 12 months before specimen collection; 26% had a urinary catheter or indwelling device within 2 days of specimen collection. Additionally, 30% reported taking antibiotics within 3 months of specimen collection, 52% denied taking antibiotics, 9% were unsure about antibiotic use, and 9% did not answer the question. Whole genome sequencing (WGS) was performed on 14 available isolates from CA-CRO cases by the NYC Public Health Laboratory or Wadsworth Center (WC), of which only 7 could be compared with isolates previously sequenced at WC (2017-2023). Six isolates were separated by &gt;50 mutation events, suggesting no close genomic relationship. One isolate from 2021 was 11 mutation events from a 2018 isolate from the same individual, consistent with the expected evolutionary rate. While infrequent, CA-CRO cases occur in NYC. Outpatient healthcare, antibiotic use, and urinary catheters or indwelling devices were common self-reported exposures. Analyses were limited by screening non-response. Increased specimen availability for WGS could enhance investigation of CA-CRO exposure patterns. Health information exchange data were often incomplete and future surveillance could benefit from healthcare and public health partnerships and better documentation for more complete electronic medical histories.

Risk Factors for Multi-Drug Resistant Gram-negative Infections across a Pediatric Hospital System

Background: Infections due to antibiotic resistant bacteria are increasing worldwide and while, the epidemiology of these pathogens is well described in adults, pediatric specific data are lacking. We sought to gain an understanding of the risk factors for multi-drug resistant Gram-negative (MDRGN) infections in our pediatric population. Methods: We performed a retrospective review of pediatric patients seen at a pediatric hospital system in 2022 who had a culture-positive MDRGN, which was defined as a gram-negative bacteria resistant or intermediate to at least 1 antibiotic in ≥ 3 antibiotic groups. Repeat positive cultures for the same MDRGN were considered a single infection episode if occurring within a 14-day period. Demographic, clinical, and microbiologic data was obtained from the electronic medical record. Fisher’s exact was used for analysis. Results: One hundred and seventy-nine children had 237 infection episodes during the study period. Eighty-one patients (45%) were male and the median age was 5.3 years. The most prevalent MDRGNs included: Escherichia coli (154, 65%), Klebsiella spp (52, 22%), and Enterobacter spp (16, 7%). Escherichia coli was significantly more likely than other pathogens to be isolated from the urine (P = 0.008). Compared to multi-drug resistant E. coli, patients with a non-E. coli MDRGN were significantly more likely to have an underlying medical condition, recent hospitalization and antibiotic use (P≤0.001 for each, Table 1). A carbapenem was administered in 32% (75/237) of infection episodes. There were only 6 carbapenem resistant organisms. Conclusions: In our study, E. coli was the most frequent MDRGN. Most patients with a non-E. coli MDRGN infection episode had an underlying medical condition, recent hospitalization and antibiotic use. Carbapenem resistance was infrequent, though surveillance studies are needed to identify changing antibiotic resistance patterns and to direct prevention measures.

Evaluation of Vulnerabilities for the Spread of Carbapenem Resistant Organisms at Five Hospitals in India

Background: The 2022 WHO global survey on infection prevention and control (IPC) exposes significant gaps in IPC in the WHO Southeast Asia region. A better understanding of IPC vulnerabilities will inform improvement initiatives. We describe an evaluation of IPC practices known to prevent and contain carbapenem-resistant organisms (CROs) at hospitals participating in the United States Centers for Disease Control Global Action in Healthcare Network –Antimicrobial Resistance in India. Prior hospital evaluations suggest resistance to carbapenems among gram-negative isolates is up to 45%. Methods: We conducted a mixed methods evaluation including cross-sectional surveys, semi-structured interviews, and site observations at five hospitals (one government, two private tertiary care, and two private teaching) located in three cities. The number of hospital beds ranged from 362 to 2,011. Hospital and IPC program characteristics, and CRO prevention and containment activities were examined virtually. Site observations focused on hand hygiene, environmental cleaning, personal protective equipment (PPE), CRO containment practices and use of water for patient care. Results: All sites had IPC programs with established policies and qualified IPC staff. The IPC nurse-to-bed ratio ranged from 1:73 to 1:432 (mean, 1:209). Due to the integral role of microbiology staff in IPC at these hospitals, the two departments had strong communication channels associated with CRO identification. Screening for CRO colonization, if done, targeted patients from outside hospitals. Three of the five hospitals routinely implemented contact precautions for patients with identified CROs, displayed isolation signage at the bedside, and provided adequate PPE at point-of-use; however, all sites reported barriers to effective isolation and/or cohorting patients with CROs. Timely communication of CROs to clinical staff varied and no sites effectively relayed CRO status upon patient discharge to another facility. IPC teams identified gaps in environmental cleaning procedures and practices related to medical devices and equipment. All sites used alternatives to tap water for clinical care and sink etiquette was evident. Each IPC team performed audits of patient isolation and hand hygiene practices. Despite the considerable proportion of IPC resources dedicated to daily education and feedback in clinical areas, the IPC teams reported that improvement was often difficult to achieve. Conclusion: Given the high burden of CROs and limited IPC resources, detailed knowledge of IPC opportunities for improvement will help hospitals target novel interventions for CRO prevention and containment. Further investigation of colonization rates and effective performance improvement methods in these settings is needed.Disclosure: Patricia Simner: Research Contracts: BD Diagnostics, OpGen Inc., Qiagen Sciences Inc, T2 Diagnostics, Accelerate Diagnostics; Research Collaborators:Ares Genetics, CosmosID, IDbyDNA, Illumina; Consulting: OpGen Inc., BD Diagnostics, Shionogi Inc., GeneCapture, Qiagen Sciences Inc, Entasis, Day Zero Diagnostics, Next Gen Diagnostics

Evolving resistance landscape in gram-negative pathogens: An update on β-lactam and β-lactam-inhibitor treatment combinations for carbapenem-resistant organisms.

Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β-lactamases diminishing the activity of classic β-lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β-lactamase inhibitors (BLIs) with activity against extended-spectrum β-lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo-β-lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem-resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β-lactamases including MBL and OXA-enzymes.

Clinical Utility of Follow-Up Blood Cultures Among Adult Cancer Patients with Gram-Negative Bacilli Bacteremia

Background: Gram-negative bacilli (GNB) bacteremia is a common and potentially fatal infection with mortality rates estimated to be 14-34%, despite effective antimicrobial treatments. Follow-up blood cultures (FUBCs) are blood cultures that are repeated after an initial positive culture and are indicated in certain clinical scenarios, such as in candidemia or Staphylococcus aureus bacteremia to ensure clearance of the bloodstream infection. FUBCs are used in bacteremia to assess the appropriateness and duration of antimicrobial therapy. Currently, there are no guidelines in place regarding the use of FUBC for GNB bacteremia. Furthermore, the utility of FUBCs is not well-studied in adults living with cancer. The purpose of this study is to identify risk factors associated with persistent GNB bacteremia in adult patients with cancer. Methods: We conducted a single-center, retrospective study in patients aged ≥18 years, hospitalized during calendar year 2022, living with cancer, and with laboratory confirmed GNB bloodstream infection. FUBC was defined as a blood culture performed within 7 days of the initial positive blood culture. Patients were grouped as having the same organism on FUBC (+/same), FUBC with no growth (NG) (+/NG), and different organism on FUBC (+/Different). Patients with a different organism on FUBC were excluded from analysis. We gathered demographic information, suspected source of bacteremia, type of malignancy, identified organisms, presence of antimicrobial resistance, and comorbidities (eg. presence of central venous catheters, urinary catheters, end-stage renal disease). Categorical variables were compared using Chi-square or Fisher’s exact test. Continuous variables were compared using Wilcoxon rank sum tests. Logistic regression analysis was used to identify the independent predictors of persistent GNB bacteremia. Results: 356 unique patients with FUBC were identified after inclusion/exclusion criteria. 93/356 (26%) of patients had persistent GNB bacteremia (+/same). Multivariate analysis identified history of bacteremia within the preceding year (OR 2.95, 95% CI [1.6-5.6]) and Achromobacter spp. bacteremia (OR 10.03, 95% CI [1.59-63.23] as independent risk factors for persistence. Organisms with multidrug resistance such as extended-spectrum beta-lactamase (OR 2.47, 95% CI [1.21-5.07]) and carbapenem-resistant organisms (OR 3.35, 95% CI [1.04-10.81]) were also associated with persistent GNB bacteremia. Conclusions: This is the first study to specifically identify risk factors for persistent GNB bacteremia in patients living with cancer. FUBC may be useful in GNB bacteremia with less common organisms and/or if they exhibit multidrug resistance on susceptibility testing. The utility of FUBC should be further explored in patients with cancer with certain risk factors.

Risk Factors and Outcomes of Candida auris in Southeast Michigan

Background: Candida auris is an emerging multidrug resistant fungus that presents a serious global health threat and causes severe infections with a high mortality rate in hospitalized patients with significant underlying comorbidities. We describe the risk factors and clinical outcomes associated with C. auris in Southeast Michigan. Methods: This is a retrospective case series of culture-positive C. auris patients who had contact with our healthcare facility in Detroit from 2021 to 2023. We evaluated demographics, comorbidities, risk factors, and outcomes. A comparative analysis of colonized and infected patients was performed. Results: Forty-eight (81%) colonized and 11 (19%) infected patients were included (Table); 70% were male with median age of 66 years. All variables were comparable between the two groups except chronic kidney disease, which was significantly more prevalent among colonized patients (40% vs 0, p=0.011). All patients had prior exposure to acute care hospital (ACH), 37% to long-term acute care hospital, and 42% to skilled nursing facility within 1 year of diagnosis. Chronic wounds, prior broad-spectrum antibiotic use, and indwelling devices were prevalent in both groups; more than half required mechanical ventilation in the last month, and one third had tracheostomy at the time of C. auris detection. Almost 60% had a prior history of drug-resistant organisms, including multi-drug resistant gram negative (37%) and carbapenem-resistant (20%) organisms. Blood (82%) and wound (18%) were sources of invasive candidiasis. More than half (61%) of the testing was performed at ACH. Nine patients (82%) with invasive disease were treated with echinocandins (88%); among the colonized, two (4%) were treated with echinocandins but had persistent colonization. Thirty-day mortality was not significantly different among the two groups and was nearly 20%. Conclusions: In this large cohort study, a history of healthcare exposure, drug-resistant organisms, use of broad-spectrum antibiotics, indwelling devices, and chronic wounds were common risk factors among C. auris patients. Limiting the use of broad-spectrum antimicrobials and invasive devices, adherence to infection prevention and control practices, and interfacility transfer communication are important mitigating strategies to reduce the incidence and spread of C. auris.

Impact of Discontinuing Contact Precautions for Multidrug-resistant Gram-negative Enterobacteriaceae in a Large Health System

Background: Contact precautions (CP) to prevent transmission of multidrug-resistant gram-negative (MDRGN) Enterobacteriaceae are recommended, although studies of discontinuation of CP (DcCP) have found no change in healthcare associated infections (HAI) due to extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. Limited data exists on DcCP for MDRGN in a large health system. Methods: We performed a retrospective observational study analyzing the relationship between use of CP and HAI due to two definitions of MDRGN Enterobacteriaceae: ESBL, and non-susceptibility to ≥3 drug classes (3DC-GNR), with carbapenem resistant Enterobacteriaceae (CRE) serving as control. The study included all inpatient admissions from 2/2017 through 9/2022 at 21 acute care hospitals. Hospitals had latitude to determine CP practices based on local risk assessment, but in 2/2018, system-wide transmission-based precautions guidance was updated to recommend DcCP for MDRGN Enterobacteriaceae and in 12/2019 was updated to clarify DcCP specifically for ESBL and 3DC-GNR while continuing CP for carbapenem-resistant organism carriage. We interviewed infection preventionists to define when CP were used for CRE, ESBL, and 3DC-GNR Enterobacteriaceae. HAI were defined using National Healthcare Safety Network criteria including all HAI categories. We compared the incidence rate of HAI attributable to the two MDRGN types in hospital months with and without use of CP, with HAI due to CRE as a comparison group since all hospitals used CP for CRE throughout the study period. Results: The periods of CP use, by hospital, are shown in Figure 1. Throughout the study period, there were 987 HAI attributed to ESBL Enterobacteriaceae, 579 due to 3DC-GNR Enterobacteriaceae, and 329 due to CRE. Figure 2 shows the unadjusted aggregate rate of HAI for each of the three MRGN types, including among hospitals with and without CP in each month, for ESBL and 3DC-GNR. In months with and without CP, the rate of HAI was 1.482/10,000 and 1.093/10,000 patient days (incidence rate ratio [IRR], 1.356 [95% confidence interval, 1.195-1.540]) for ESBL Enterobacteriaceae. In months with and without CP, the rate of HAI was 1.071/10,000 and 0.493/10,000 patient days (IRR,2.173[95% confidence interval, 1.838-2.569]) for 3DC-GNR Enterobacteriaceae. Conclusion: DcCP was not associated with an increase in HAI due to ESBL and 3DC-GNR Enterobacteriaceae in aggregated facilities that self-selected for DcCP. Facilities that used CP were associated with significantly higher rates of ESBL and 3DC-GNR Enterobacteriaceae, a relationship that did not change as hospitals DcCP for these MDRGN. Further analyses are necessary to assess for a causal relationship.

Occurrence of carbapenem-resistant organisms among pet animals suffering from respiratory illness: a possible public health risk

Occurrence of carbapenem-resistant organisms among pet animals suffering from respiratory illness: a possible public health risk