Carbapenem-resistant Pseudomonas Research Articles

Carbapenem Resistance in Animal-Environment-Food from Africa: A Systematic Review, Recommendations and Perspectives.

The World Health Organization (WHO) has classified carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa (P. aeruginosa), and Acinetobacter baumannii (A. baumannii) as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been reported to spread between humans, animals, and the environment. This study aimed to conduct a systematic review of carbapenem resistance in animals, foods, and the environment on the African continent and to provide recommendations and perspectives for better prevention and control of carbapenem resistance in Africa. A total of 137 research articles collected from 2009 to 2023 were selected for this review, including articles reporting carbapenem-resistant bacteria in animals (81/137; 59.1%), the environment (66/137; 48.2%), and foods (26/137; 19%). Carbapenem-resistant bacterial species belonged to 31 genera and 17 families, including mainly Escherichia spp. (68/127; 53.5%); Klebsiella spp. (45/127; 35.4%); Pseudomonas spp. (20/127; 15.7%), Enterobacter spp. (19/127; 15%) and Acinetobacter spp. (15/127; 11.8%). The prevalence of CRBs by country ranged from 1.1% to 48.5%, and the pooled prevalence of CRBs isolated from animal-environment-food in Africa was 19.1% (2804/14,684; Standard Deviation = 15). Twenty carbapenemase families belonging to A, B, C, and D Ambler classes were reported, including mainly carbapenemase genes from blaOXA (44/84; 52.4%), blaNDM (34/84; 40.5%), blaSHV (23/84; 27.4%), blaKPC (22/84; 26.2%), blaVIM (19/84; 22.6%), and blaIMP (12/84; 14.3%) families. The reported mobile genetic elements (MGE) carrying carbapenemase-encoding genes included plasmids (16/19; 84.2%), integrons (3/19; 15.8%), transposons (3/19; 15.8%), and insertion sequences (2/19; 10.5%). blaOXA-48 was often carried by (60kb-65kb) IncL/M-type pOXA-48 plasmids, while blaNDM-5 was often carried by (45-50kb) IncX-type plasmids. Moreover, 25 articles investigated and reported virulent and hypervirulent CRBs that carried multiple virulence factors. Animal-environment-food ecosystems would constitute reservoirs of CRBs involved in human infections. The One Health approach and constant collaboration between governments are necessary to drastically reduce the mortality rates linked to antimicrobial resistance.

Emergence of aztreonam/avibactam and tigecycline-resistant Pseudomonas putida group Co-producing blaIMP-1, blaAFM-4 and blaOXA-1041 with a novel sequence type ST268 in Southwestern China

ObjectivesThe emergence of carbapenem-resistant Pseudomonas putida (CRPP) has raised public awareness. This study investigated two strains from the Pseudomonas putida group that were resistant to carbapenem, tigecycline, and aztreonam-avibactam (ATM−AVI), with a focus on their microbial and genomic characteristics. MethodsWe assessed the antibiotic resistance profile using broth dilution, disk diffusion, and E-test methods. Efflux pump phenotype testing and real-time quantitative PCR were employed to evaluate efflux pump activity in tigecycline resistance, while polymerase chain reaction was utilized to detect common carbapenem genes. Additionally, whole-genome sequencing was performed to analyze genomic characteristics. The transferability of blaIMP-1 and blaAFM-4 was assessed through a conjugation experiment. Furthermore, growth kinetics and biofilm formation were examined using growth curves and crystal violet staining. ResultsBoth strains demonstrated resistance to carbapenem, tigecycline, and ATM-AVI. Notably, NMP can restore sensitivity to tigecycline. Subsequent analysis revealed that they co-produced blaIMP-1, blaAFM-4, tmexCD-toprJ, and blaOXA-1041, belonging to a novel sequence type ST268. Although they were closely related on the phylogenetic tree, they exhibited different levels of virulence. Genetic environment analysis indicated variations compared to prior studies, particularly regarding the blaIMP-1 and blaAFM-4 genes, which showed limited horizontal transferability. Moreover, it was observed that temperature exerted a specific influence on their biological factors. ConclusionWe initially identified two P. putida ST268 strains co-producing blaIMP-1, blaAFM-4, blaOXA-1041, and tmexCD-toprJ. The resistance to tigecycline and ATM-AVI can be attributed to the presence of multiple drug resistance determinants. These findings underscore the significance of P. putida as a reservoir for novel antibiotic resistance genes. Therefore, it is imperative to develop alternative antibiotic therapies and establish effective monitoring of bacterial resistance.

Bloodstream infections and multidrug resistant bacteria acquisition among burns patients in Australia and New Zealand: A registry-based study

IntroductionThis study interrogates infection related data in the Burns Registry of Australia and New Zealand (BRANZ), to examine associations of multi-drug resistant organisms (MDROs) and blood stream infection (BSI). MethodsData between July 2016 and June 2021 were analysed to determine prevalence, risk factors and outcomes associated with BSIs and MDROs: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Pseudomonas spp. (CRP), and carbapenem-resistant Enterobacter (CRE). Data completeness and value for quality improvement activity were assessed. ResultsWe found a low incidence (3.4%) of the resistant organisms of interest, and no change over the study period. Fequency varied between services and increased with age and size of burn. MRSA was the commonest organism in all age groups. A positive BSI result occurred in 1.6% of patients (12.1% of cultures taken) at a median time of 10.2 days post injury. Free text identification of organisms was inconsistently documented. ConclusionsThe low rate and patterns of acquisition of MDROs of interest and BSIs is comparable with reports from countries with low incidence of massive burns. Wider adoption of a standardized laboratory reporting framework would help realise the potential of clinical quality registries to provide data which supports evidence based infection prevention initiatives.

Deciphering mechanisms affecting cefepime-taniborbactam in vitro activity in carbapenemase-producing Enterobacterales and carbapenem-resistant Pseudomonas spp. isolates recovered during a surveillance study in Spain.

To characterize the resistance mechanisms affecting the cefepime-taniborbactam combination in a collection of carbapenemase-producing Enterobacterales (CPE) and carbapenem-resistant Pseudomonas spp. (predominantly P. aeruginosa; CRPA) clinical isolates. CPE (n = 247) and CRPA (n = 170) isolates were prospectively collected from patients admitted to 8 Spanish hospitals. Susceptibility to cefepime-taniborbactam and comparators was determined by broth microdilution. Cefepime-taniborbactam was the most active agent, inhibiting 97.6% of CPE and 67.1% of CRPA (MICs ≤ 8/4 mg/L). All isolates with cefepime-taniborbactam MIC > 8/4 mg/L (5 CPE and 52 CRPA) and a subset with MIC ≤ 8/4 mg/L (23 CPE and 24 CRPA) were characterized by whole genome sequencing. A reduced cefepime-taniborbactam activity was found in two KPC-ST307-Klebsiella pneumoniae isolates with altered porins [KPC-62-K. pneumoniae (OmpA, OmpR/EnvZ), KPC-150-K. pneumoniae (OmpK35, OmpK36)] and one each ST133-VIM-1-Enterobacter hormaechei with altered OmpD, OmpR, and OmpC; IMP-8-ST24-Enterobacter asburiae; and NDM-5-Escherichia coli with an YRIN-inserted PBP3 and a mutated PBP2. Among the P. aeruginosa (68/76), elevated cefepime-taniborbactam MICs were mostly associated with GES-5-ST235, OXA-2+VIM-2-ST235, and OXA-2+VIM-20-ST175 isolates also carrying mutations in PBP3, efflux pump (mexR, mexZ) and AmpC (mpl) regulators, and non-carbapenemase-ST175 isolates with AmpD-T139M and PBP3-R504C mutations. Overall, accumulation of these mutations was frequently detected among non-carbapenemase producers. The reduced cefepime-taniborbactam activity among the minority of isolates with elevated cefepime-taniborbactam MICs is not only due to IMP carbapenemases but also to the accumulation of multiple resistance mechanisms, including PBP and porin mutations in CPE and chromosomal mutations leading to efflux pumps up-regulation, AmpC overexpression, and PBP modifications in P. aeruginosa.

Efficacy of Colistin with Carbapenems Combination by Checkerboard Assay against Carbapenem Resistant Non Lactose Fermenting Gram Negative Bacteria

Recent emergence of carbapenem resistant non-fermenting Gram negative bacteria (CRNFGNB) predominantly Pseudomonas and Acinetobacter species are responsible for significant proportion of nosocomial infections with increased mortality. Of the various mechanisms known, carbapenemases especially metallo beta lactamase (MBL) mediated resistance is the most concerning because of its easy transmissibility via mobile genetic elements and lack of MBL inhibitors for clinical use. In the present study we determined to estimate the prevalence of carbapenem resistant Pseudomonas and Acinetobacter species, their resistance mechanisms by phenotypic tests and synergistic studies with Colistin and carbapenems combination by checkerboard assay. Carbapenem resistance among these two bacteria is 53.2% being isolated predominantly from pus and endotracheal secretions and from patients within the age group of less than 9 years (44%) and more than 60 years (23%). The incidence of carbapenemase and MBL production in NFGNB is 89.8% and 87.9%, respectively. Only Colistin and Tigecycline show significant antibacterial activity while most of the tested antibiotics were found to be least effective against carbapenem resistant NFGNB. Colistin and Imipenem combination demonstrated synergistic activity in majority of the NFGNB species; however, translation of such in vitro efficacy models into highly variable in vivo conditions could be possible only with strong clinical support.

Bloodstream infections in neutropenic and non-neutropenic patients with haematological malignancies: epidemiological trends and clinical outcomes in Queensland, Australia over the last 20 years

Knowledge of the epidemiology of bloodstream infection (BSI) in haematology patients is essential to guide patient management. We investigated the epidemiology of BSI in patients with haematological malignancies in Queensland over the last 20 years (2000–2019), including all episodes diagnosed by the state-wide microbiology service. We identified 7749 BSI in 5159 patients, 58% associated with neutropenia. Gram-negatives were the main causative pathogens (58.3%), more frequent in neutropenic than non-neutropenic patients (3308/5309, 62.3% vs 1932/3678, 52.5%, p < 0.001). Amongst 8987 isolates the most common were E.coli (15.4%) and Pseudomonas spp. (14.2%). Pseudomonas spp. (16.6% vs 10.7%, p < 0.001), Klebsiella spp. (11.6% vs 6.8%, p < 0.001), viridans-group streptococci (4.4% vs 1.2%, p < 0.001) and E.faecium (2.4% vs 0.9%, p < 0.001) were more common in neutropenic than non-neutropenic patients, while S.aureus was less common (5.9% vs 15.6%, p < 0.001). Several antimicrobial resistance rates increased over time and had higher prevalence in neutropenic than non-neutropenic patients, including ciprofloxacin-resistant E.coli (94/758, 12.4% vs 42/506, 8.3%, p = 0.021), trimethoprim-sulfamethoxazole-resistant E.coli (366/764, 47.9% vs 191/517, 36.9%, p < 0.001), penicillin-resistant streptococci (51/236, 21.6% vs 28/260, 10.8%, p < 0.001) and vancomycin-resistant enterococci (46/250, 18.4% vs 9/144, 6.3%, p < 0.001). Carbapenem-resistant Pseudomonas spp. (OR 7.32, 95%CI 2.78–19.32) and fungi, including yeasts and moulds (OR 3.33, 95%CI 2.02–5.48) were associated to the highest odds of 30-day case-fatality at a multivariable logistic regression analysis. Neutropenia was associated with survival (OR 0.66, 95%CI 0.55–0.78). Differences were observed in the BSI epidemiology according to neutropenic status, with an overall increase of resistance over time associated to adverse outcome.

Functional Portrait and Genomic Feature of Carbapenem-Resistant Pseudomonas mendocina Harboring blaNDM-1 and blaIMP-1 in China.

The purpose of this research was to analyze the functional portraits and genomic features of carbapenem-resistant Pseudomonas mendocina carrying NDM-1 and IMP-1. The resistance mechanism of the strain was verified by in vivo experiments. Genomic data were aligned and analyzed in the NCBI database. Growth curve measurements were used to describe the growth characteristics of the bacteria. The virulence of P. mendocina strain was analyzed by serum killing assay and biofilm formation assay. Plasmid conjugation experiments were performed to verify the transferability of plasmids carrying drug-resistance genes. The P. mendocina strain was highly resistant to carbapenems. In addition, ST typing is unknown and has been submitted to Genebank. The strain carried two carbapenemase genes, including NDM-1 and IMP-1. Among them, blaNDM-1 was located on a 5.62832 Mb chromosome, and blaIMP-1 was located on a 172.851 Kb transferable plasmid, which was a very close relative of pIMP-NY7610 in China. The strain also had a variety of virulence genes, which were expressed in the siderophore, capsule, pilus, alginate, flagella, etc. The study suggests that the functional portrait and genomic features of carbapenem-resistant P. mendocina harboring blaNDM-1 and blaIMP-1 are unique to China. This outcome represents antibiotic resistance exhibited in the genus Pseudomonas by acquiring chromosomes and plasmid genes. The monitoring and supervision of antimicrobial usage must be strengthened since the multi-drug-resistant and moderately virulent P. mendocina will attract much attention in the near future.

Prevalence and susceptibility profile of carbapenem-resistant pseudomonas aeruginosa (CRPA) at Dr. Soetomo Public Hospital, Surabaya, from January to December 2021

Introduction: Pseudomonas aeruginosa is a pathogen that frequently causes healthcare-associated infections (HAI), which has also been associated with high mortality and morbidity rates. Carbapenems have been widely utilized as empiric therapy for P. aeruginosa infections since these organisms have intrinsic resistance to various antibiotics. Therefore, the high rate of CRPA infection became the reason for conducting this study to determine the prevalence and susceptibility pattern of CRPA in Dr. Soetomo Public Hospital, Surabaya, from January to December 2021. Method: The researcher employed descriptive observational study from secondary data with the first isolate sample of P. aeruginosa per specimen per patient that has been identified by the BD Phoenix™ automated identification and susceptibility testing system from specimens of urine, blood, sterile fluid, pus, tissue, and sputum that are phenotypically resistant to meropenem or imipenem antibiotics, examined at the Clinical Microbiology Unit of Dr. Soetomo Public Hospital, Surabaya, from January to December 2021. Result: Of the total P. aeruginosa isolates, 149 CRPA isolates were obtained. The researcher conveyed that the majority of the samples were male (59.1%); the most comorbid cases were diabetes mellitus with complications (22.4%) found in the intensive care unit (40.3%); the majority of specimens were from the respiratory tract (43%); the highest antibiotic susceptibility was amikacin (62.4%); the prevalence of CRPA in Dr. Soetomo Public Hospital, Surabaya, from January to December 2021 reached 21.25%. Conclusion: In this study, CRPA isolates showed the highest sensitivity to amikacin, and the highest distribution of CRPA events was found in the intensive care unit.

Evaluation of and risk factors for the metallo-beta-lactamase enzyme with respect to production of carbapenem-resistant Pseudomonas and Acinetobacter species

Purpose: To investigate the frequency of MBLs in Pseudomonas and Acinetobacter species with E-test, to determine the risk factors and to evaluate the demographic and clinical features of infected patients. Materials and methods: Imipenem or meropenem resistance of Pseudomonas and Acinetobacter isolated from several clinical samples with conventional methods were evaluated with imipenem EDTA E-test and the presence of Metallo-β-lactameses MBL was examined. Several isolates were screened for VIM-1, VIM-2, IMP-1, and IMP-2 with a PCR test. Results: Of 46 carbapenem resistant Acinetobacter isolates, 41 (89%), as well as of 19 carbapenem resistant Pseudomonas isolates, 5 (26%) had MBL positivity with imipenem-EDTA E-test. A history of Intensive Care Unit stay, mechanical ventilation and cephalosporin use were found to be significant risk factors with respect to MBL production. Conclusion: Detection of MBL production in Acinetobacter and Pseudomonas species especially in ICU patients is of prime importance to control infection rapidly and effectively, which contribute to prevention of outbreaks.

1223. The Impact of the COVID-19 Pandemic on the Prevalence of Multidrug-resistant Organisms in Veterans Affairs Nursing Homes

Abstract Background Multidrug-resistant organisms (MDRO) in long-term care facilities are prevalent and pose a major health concern for their residents. During the COVID-19 pandemic, infection control measures were justifiably heightened in every aspect of health care, including nursing homes. There are reports depicting decreasing prevalence of MDRO in hospital settings during the pandemic. We compared the prevalence of MDRO in our facility’s nursing homes in the two-year period before vs. the two years of the pandemic. Methods Northport Veterans Affairs Medical Center provides long-term nursing home care structured as community living centers including mental health and hospice care; a 139 total bed capacity. A retrospective review of culture data collected by infection control preventionists comparing the prevalence of MDROs between 1 March 2018 to 28 February 2022 was performed. Data included: Nasopharyngeal MRSA swabs, urine, wound, blood, sputum cultures, C. difficile toxin and PCR assays. MDRO included ESBL E. coli, K. pneumoniae, P. mirabilis, MDR Pseudomonas spp (resistance to 2/3 antibiotics: cefepime/piperacillin-tazobactam/ciprofloxacin), carbapenem-resistant Pseudomonas spp, and vancomycin-resistant Enterococcus spp. Results There were 75209 bed days of care from 1 March 2018 to 28 February 2020 vs. 77531 from 1 March 2020 to 28 February 2022. The MRSA rate per 1000 patient days decreased from 4.98 pre-COVID to 2.70 during-COVID, P &amp;lt; 0.001. Similarly, there was a decrease in C. difficile 0.69 vs. 0.13, P&amp;lt; 0.001, ESBL E. coli 0.53 vs. 0.51, P&amp;lt; 0.001 and S. maltophilia (no cases during COVID). There was an increase in ESBL K. pneumoniae 0.51 vs. 0.63, P&amp;lt; 0.001, MDR Pseudomonas 0.05 vs. 0.49, P&amp;lt; 0.001, carbapenem-resistant Pseudomonas 0.026 vs. 0.077, P&amp;lt; 0.001 and VRE 0.22 vs. 0.31, P&amp;lt; 0.001. There were no Candida auris or Acinetobacter spp detected in the study period. MDRO occurrences before and during COVID-19 pandemic Conclusion While increased awareness and implementation of infection control measures during the years of the COVID-19 pandemic led to decrease in certain infections in our nursing homes, like C. difficile, a surprising uptick in ESBL K. pneumoniae and MDR Pseudomonas was noted. This is a concerning trend that merits further study to identify molecular factors and increase stewardship efforts in diligent use of carbapenems. Disclosures All Authors: No reported disclosures.

Effect of restricting piperacillin/tazobactam prescription on rates of antimicrobial resistance in gram-negative bacteria and antibiotic consumption.

The increasing resistance of gram-negative bacteria is a serious global public health concern. One way to prevent increasing antibiotic resistance is by implementing the antibiotic stewardship program. This study aimed to assess the changes in the consumption of antimicrobials and antimicrobial resistance rates after implementing piperacillin/tazobactam restriction. This study was conducted at Kandong Sacred Heart Hospital. We retrospectively collected and analysed data between October 2018 and May 2021 to evaluate antibiotic consumption and resistance patterns after restricting piperacillin/tazobactam. This study included two periods, a 16-month pre-restriction period and a 16-month post-restriction period. During the study period, there was a significant decrease in the consumption of piperacillin/tazobactam after implementing the restriction policy (127.82 ± 9.39 to 104.82 ± 15.66 defined daily doses/1000 patient days, p < 0.001). A significant decrease in the resistance rate of Acinetobacter spp. was observed for cefepime (p = 0.001), ceftazidime (p = 0.004), levofloxacin (p = 0.021), meropenem (p = 0.002) and piperacillin (p = 0.028). The introduction of piperacillin/tazobactam restriction reduced their use and positively impacted the resistance rates of Acinetobacter spp., carbapenem-resistant Pseudomonas spp. and carbapenem-resistant Enterobacteriaceae which are major threats to nosocomial infections.

DETECTION OF METALLO-BETA-LACTAMASE PRODUCING PSEUDOMONAS AND ACINETOBACTER SPECIES FROM DIFFERENT CLINICAL SPECIMENS IN A TERTIARY CARE HOSPITAL AT PUDUCHERRY.

Introduction Pseudomonas and Acinetobacter species are frequently isolated non-fermenting gram negative bacteria in a variety of hospital acquired infections. Metallo-beta-lactamases have become a serious threat in treating infections because of their multiple drug resistance including carbapenems. To determine Objectives the prevalence of MBL production among Pseudomonas and Acinetobacter species and to evaluate the different phenotypic MBL detection methods. A total of 104 isolates of carbapenem resistant Pseudomonas (78) and Materials and methods Acinetobacter (26) from different clinical specimens were tested for MBL production by Modied Hodge Test, Combined Disk Test and Double Disk Synergy Test. Antibiotic susceptibility was performed by Kirby- Bauer Disk Diffusion method. Results Pseudomonas aeruginosa (11.29%) Acinetobacterbaumanii (11.53%) were the predominant MBL producers. MBL production was detected 61.53%, 84.61% and 38.46 % by DDST( Doule disc synergy test), CDT (Combined disc test), and MHT (Modied Hodge test) respectively. Colistin and Polymyxin B are the only option available for treating such infections. MBL Conclusion production among Pseudomonas and Acinetobacter species are increasing due to the continuous use of carbapenems and selective antibiotic pressure. Strict antibiotic policy and infection control practices help prevent the further spread.

Bacteriological profile of paediatric skin and soft tissue infections and their antibiogram at a tertiary care teaching hospital in north India.

The increasing complexity of wound care in pediatric patients along with delay in the initiation of treatment predisposes these patients to many complications such as pressure ulcers, non-healing surgical wounds and skin damage. A retrospective study was conducted over a period of five years to gain insight into the etiology of pediatric wound infection. A total of 2819 wound culture positive cases were included. Most samples were from the burn ward (30.15%) followed by the general surgery ward (20.46%). Overall, the most common isolate was Staphylococcus aureus (39.73%) followed by Pseudomonas spp (19.12%). The prevalence of MRSA (Methicillin resistant S. aureus), CRE (Carbapenem-resistant Enterobacteriaceae), CRP (Carbapenem resistant Pseudomonas), CRAB (Carbapenem resistant Acinetobacter baumannii) was 47.3%, 62.5%, 70.5%, 96.4%, respectively. The high degree of resistance in children highlights the importance of regular surveillance for identification of common pathogens and optimization of antimicrobial treatment for multidrug resistant organisms.

A clinical Pseudomonas juntendi strain with bla IMP-1 carried by an integrative and conjugative element in China.

ObjectiveTo precisely determine the species of a carbapenem-resistant Pseudomonas strain 1809276 isolated from the urine of a Chinese patient and analyze its integrative and conjugative element (ICE) 1276 formation mechanism.MethodsSingle-molecule real-time (SMRT) sequencing was carried out on strain 18091276 to obtain the complete chromosome and plasmid (pCN1276) sequences, and average nucleotide identity (ANI) was used for precise species identification. The ICEs in GenBank with the same integrase structure as ICE 1276 were aligned. At the same time, the transfer ability of blaIMP−1 and the antibiotic sensitivity of Pseudomonas juntendi 18091276 were tested.ResultsThis bacterium was P. juntendi, and its drug resistance mechanism is the capture of the accA4' gene cassette by the Tn402-like type 1 integron (IntI1-blaIMP−1) to form In1886 before its capture by the ΔTn4662a-carrying ICE 1276. The acquisition of blaIMP−1 confers carbapenem resistance to P. juntendi 18091276.ConclusionThe formation of blaIMP−1-carrying ICE 1276, its further integration into the chromosomes, and transposition and recombination of other elements promote bacterial gene accumulation and transmission.

Co-production of Classes A and B Carbapenemases BKC-1 and VIM-2 in a Clinical Pseudomonas Putida Group Isolate from Brazil.

Emergence of resistance to classical antimicrobial agents is a public health issue, especially in countries with high antimicrobial consumption rates. Carbapenems have been employed as first-choice option for empirical treatment complicated infections. However, in the last decades, frequency of carbapenemase-producing Gram-negative bacteria has rising, demanding the use of alternative antimicrobial agents. By sequencing the entire genomes with short and long reads technologies, we report the isolation and genomic characterization of a carbapenem-resistant Pseudomonas clinical isolate. The identification based on average nucleotide identity indicates a putative new species into the Pseudomonas putida Group, which carries both the blaBKC-1 and blaVIM-2 carbapenemase genes. The blaBKC-1 was found to be on a transferable IncQ plasmid backbone, whereas blaVIM-2 was found in a new integron, In2126 (intl1∆-blaVIM-2-aacA7-blaVIM-2∆-aacA27-3'CS), described in this study. Our findings indicate that co-occurrence of classes A and B carbapenemase enzymes underscores the evolving emergence of more complex antimicrobial resistance in opportunistic pathogens.

Patterns of multidrug resistant organism acquisition in an adult specialist burns service: a retrospective review

BackgroundMultidrug resistant organisms (MDROs) occur more commonly in burns patients than in other hospital patients and are an increasingly frequent cause of burn-related mortality. We examined the incidence, trends and risk factors for MDRO acquisition in a specialist burns service housed in an open general surgical ward, and general intensive care unit.MethodsWe performed a retrospective study of adult patients admitted with an acute burn injury to our specialist statewide tertiary burns service between July 2014 and October 2020. We linked patient demographics, injury, treatment, and outcome details from our prospective burns service registry to microbiology and antimicrobial prescribing data. The outcome of interest was first MDRO detection, stratified into the following groups of interest: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), two groups of Pseudomonas (carbapenem resistant, and piperacillin-tazobactam or cefepime resistant), carbapenem-resistant Acinetobacter species, Stenotrophomonas maltophilia, carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE). We used a Cox proportional hazards model to evaluate the association between antibiotic exposure and MDRO acquisition.ResultsThere were 2,036 acute admissions, of which 230 (11.3%) had at least one MDRO isolated from clinical specimens, most frequently wound swabs. While acquisition rates of individual MDRO groups varied over the study period, acquisition rate of any MDRO was reasonably stable over time. Carbapenem-resistant Pseudomonas was acquired at the highest rate over the study period (3.5/1000 patient days). The 12.8% (29/226) of MDROs isolated within 48 h were predominantly MRSA and Stenotrophomonas. Median (IQR) time from admission to MDRO detection was 10.9 (5.6–20.5) days, ranging from 9.8 (2.7–24.2) for MRSA to 23.6 (15.7–36.0) for carbapenem-resistant P. aeruginosa. Patients with MDROs were older, had more extensive burns, longer length of stay, and were more likely to have operative burn management. We were unable to detect a relationship between antibiotic exposure and emergence of MDROs.ConclusionsMDROs are a common and consistent presence in our burns unit. The pattern of acquisition suggests various causes, including introduction from the community and nosocomial spread. More regular surveillance of incidence and targeted interventions may decrease their prevalence, and limit the development of invasive infection.

Susceptibility results discrepancy analysis between NHSN Antibiotic Resistance (AR) Option and laboratory instrument data

Background: The NHSN Antibiotic Resistance (AR) Option can serve as a useful tool for tracking antibiotic-resistant infections and can aid in the development of inpatient antibiograms. We recently described the frequency of antibiotic suppression in NHSN AR Option data. In this analysis, we describe the effects of suppression on practical uses of the NHSN AR Option, specifically selected agent antibiogram development, and detection of reportable conditions. Methods: Antibiotic susceptibility data were collected from the NHSN AR Option and commercial automated antimicrobial susceptibility testing instruments (cASTI) from 3 hospital networks. Data were obtained from January 1, 2017, to December 31, 2018. The clinical susceptibility data for third-generation cephalosporins and carbapenems against carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii were included. Susceptibility results were defined as suppressed when susceptibility results were observed from the laboratory instrument but not from NHSN data. For the overall percentage susceptibility estimation, isolates with &lt;30 susceptibility results were excluded. Percentage susceptibility of NHSN results were compared to their counterparts from cASTI. Results: Of the 852 matched isolates in the primary analysis, 804 had at least 1 suppressed result. Of the 804 isolates, 16.9% were P. aeruginosa, 67.3% by E. coli, and 11.1% by Klebsiella spp. The following pathogen–drug combinations had no difference observed in the percentage susceptible between the 2 systems: ceftazidime tested against P. aeruginosa, ceftriaxone tested against Klebsiella spp, ertapenem tested against Klebsiella spp, imipenem tested against E. coli and P. aeruginosa, and meropenem tested against P. aeruginosa. Significant differences were observed for the following drugs tested against E. coli: ceftazidime (11.1%), cefotaxime (8.6%), and ceftriaxone (8.3%). In the NHSN AR Option, the following isolates showed suppressed results related to their phenotypic case definition: 17 (3%) CRE isolates, 7 (28%) carbapenem-resistant Acinetobacter baumannii (CRAB) isolates, 511 (93.2%) extended spectrum β-lactamase (ESBL) isolates, and 94 (66.7%) carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates. Conclusions: For select isolates, notably E. coli, we observed a large difference in the percentage of susceptible isolates reported into the NHSN AR Option compared to the cASTI data. This difference significantly limits the ability of the AR Option to create valid antibiograms for select pathogen–drug combinations. Moreover, significant numbers of CRAB, ESBL, and CRPA isolates would not be identified from NHSN AR Option because of suppression. This finding warrants the need for antimicrobial stewardship teams to regularly assess the impact of selective reporting in identifying pathogens of public health importance.Funding: NoneDisclosures: None

Cefiderocol: a novel siderophore cephalosporin against multi-drug resistant Gram-negative bacilli infections

Antimicrobial resistance is one of the critical public health issues in the world. There is an urgent need to develop effective broad-spectrum antibiotics to treat the infection of multi-drug resistant Gram-negative bacilli. Cefiderocol, developed by the Shionogi Inc. in Japan, is a new type of iron carrier cephalosporin antibiotics, which overcomes the drug resistance of Gram-negative bacilli due to the down-regulation of outer membrane pore protein and the up-regulation of efflux pump, and has good stability to serine- and metallo-carbapenemases. This drug has a broad spectrum and strong antibacterial activity against carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Cefiderocol can be used to treat complex urinary tract infections (including pyelonephritis), hospital-acquired pneumonia, and ventilator-associated pneumonia. By summarizing the chemical structure, antibacterial mechanism, in vitro antibacterial activity, pharmacokinetics, pharmacodynamics, and clinical treatment of cefiderocol, this review shows the application potential of cefiderocol as a new iron carrier cephalosporin in the treatment of multi-drug resistant Gram-negative bacilli infections.

Ceftolozane/tazobactam for difficult-to-treat Gram-negative infections: A real-world tertiary hospital experience.

To evaluate the real-world clinical efficacy of ceftolozane/tazobactam (C/T) in difficult-to-treat infections caused by multi-drug resistant Gram-negative microorganisms, including carbapenem-resistant Pseudomonas aeruginosa. Retrospective cohort study of adult patients treated with C/T for at least 48 hours for infections caused by multi-drug resistant Gram-negative bacteria in a tertiary hospital from May 2016 until August 2019. The primary outcome analysed was clinical failure, defined as a composite of symptomatology persistence after 7 days of C/T treatment, infection recurrence, and/or all-cause mortality within 30 days of follow-up. 96 episodes of C/T treatment were included, mostly consisting of targeted treatments (83.9%) for the following sources of infection: intra-abdominal (22.6%), urinary tract (25.8%), skin and soft tissue (19.4%), hospital-acquired pneumonia (14%), and other (6.4%). The most frequently isolated bacteria were carbapenem-resistant (88, 94.6%). Clinical failure rate was 30.1%, due to persistent infection at day 7 (4.3%), recurrence of the initial infection (16.1%), or 30-day all-cause mortality (8.6%). Adverse events most frequently reported were Clostridium difficile infection (9%) and cholestasis (8%). C/T showed a favourable clinical profile for difficult-to-treat multidrug-resistant and carbapenem-resistant Gram-negative infections, regardless of the source of infection.

The role of Gram-negative bacteria in skin and soft tissue infections.

Skin and soft tissue infections (SSTIs) are a leading cause of morbidity, emergency department visits and hospitalization. In recent years, the spread of carbapenem-resistant gram-negative bacteria (GNB) is also increasing in SSTIs. However, the armamentarium of available drugs is recently expanding as well. In this review, we reported the most recent data and about management and treatment of SSTIs caused by GNB, mainly for the treatment of carbapenem-resistant Enterobacterales (CRE), Pseudomonas spp and Acinetobacter spp. The increasing incidence of carbapenem-resistant GNB is challenging for management and treatment, considering the high rate of inappropriate empiric and targeted antimicrobial treatments. The role of new antibiotics, mainly licensed for the treatment of other infections, is an object of continuous debate. As a matter of fact, no specific clinical trials on SSTIs have been performed for new drugs; however, recent data about the use in real life of new compounds in clinical practice are available. Some recently approved drugs are actually considered the backbone of targeted therapy in patients with severe infections caused by susceptible carbapenem-resistant GNB strains. Prompt diagnosis of cSSTIs is crucial and, when necessary, surgical debridement for source control of infection is the milestone of the treatment. The physicians should be confident to identify patients at high risk for multidrug-resistant pathogens to minimize inappropriate empiric therapy.