Risk and prognosis of infection and colonisation by carbapenemase-producing Citrobacter freundii in the North Denmark Region during 2012-2023: a matched case-control and cohort study.

New Delhi metallo-β-lactamase-1 -producing Klebsiella oxytoca sequence type 2 from toilets as the likely source of nosocomial transmission to patients – a root cause analysis

Selective ultrasound screening for developmental dysplasia of the hip (DDH) was implemented in the North Denmark Region, Denmark in 2010 but has yet to be evaluated. This study aimed to evaluate selective hip screening in the North Denmark Region from 2010 to 2021, focusing on referral rates, the incidence of DDH and referral causes. We retrospectively identified 3,812 infants (2,091 females) who were referred during a 12-year period for hip ultrasound at Aalborg University Hospital in Denmark. DDH was defined as an ultrasound classification of Graf type IIb or worse. Referral rates and the incidence of DDH and their development over the study period were examined. During the study period, there was a steadily increasing referral rate, with the annual referral rate doubling from 200 (3.3%) in 2010 to 402 (6.8%) in 2021, whereas the incidence rate increased only minimally from 0.15% to 0.22%. The most common referral causes were breech position (41.4%) and positive clinical exam (27.8%). During the study period, the annual referral rate nearly doubled without a corresponding increase in DDH incidence, suggesting that the screening programme has become less efficient over time. This might explain the relatively low incidence of DDH in the North Denmark Region compared with national and international studies. The authors received no financial support for the research, authorship and/or publication of this article. This study was registered in the North Denmark Regional internal Project Register as IDF2022-187.

To the Editor: New Delhi metallo-β-lactamase (NDM) is an example of a successful antimicrobial drug resistance determinant and has become one of the most clinically significant carbapenemases. The gene blaNDM was first described in India in 2009. Its dispersion is epidemiologically linked to the Indian subcontinent, from which increased international transmission has been detected in nosocomial, community, and environmental isolates (1). Currently, the main acquired carbapenemases around the world are Klebsiella pneumoniae carbapenemase (KPC), oxacillinase-48 (OXA-48), and NDM. KPC is broadly detected and endemic to some areas; OXA-48 has been widely disseminated throughout European countries and has been reported in other regions. NDM is reported almost worldwide but did not successfully spread in most countries of Europe except the United Kingdom and recently, France, as has been found in Enterobacteriaceae (2) and in nonfermenting gram-negative bacilli, with progression toward rapid global prevalence. NDM producers were detected most recently in South America (3). However, an increase in cases of NDM-producing bacteria has been noted. Carvalho-Assef et al. (4) described characterization of NDM in Brazil, in Providencia rettgeri isolated from a tissue sample excised from a patient in a hospital in Rio Grande do Sul state in southern Brazil, in 2013. Reports by Carvalho-Assef et al. (5) and Rozales et al. (6) have highlighted that P. rettgeri and isolates from the Enterobacter cloacae complex, clonally and nonclonally related, have been increasingly detected in the southern region of Brazil. In addition, retrospective studies have shown that NDM-1–producing Enterobacter have been present in Brazil since 2012 and have also been detected in Rio Grande do Sul (5). NDM-1–producing Morganella morganii (6), Escherichia coli, Klebsiella pneumoniae (7), Acinetobacter baumannii (8), and Citrobacter freundii (J. Campos, et al., https://www.escmid.org/escmid_library/online_lecture_library/?search=1&current_page=1&search_term=Citrobacter+freundii+NDM) have also been reported. Initial reports from Brazil also indicate that NDM producers have displayed characteristics such as co-resistance (5,9,10) and heteroresistance (11), but to date, occurrence in the community has not been reported. NDM producers were originally detected in the southern and southeastern regions of Brazil and have since moved into the northern states. Brazil is a country of extremes that has industrialized and nonindustrialized regions, and this situation converges with social, economic, and infrastructure problems (e.g., sanitation and health care public services). This scenario is similar to the initial conditions that contributed to worldwide dissemination of NDM from the Indian subcontinent. Successful and widespread international high-risk clones and epidemic plasmids have been detected in Brazil and could have a critical role in rapid national expansion of NDM-encoding genes and NDM producers. Brazil is under imminent threat of national spread and prevalence of NDM. Lessons learned from management of KPC-production bacteria will help infection prevention and control teams, clinicians, and microbiology laboratories in Brazil more effectively manage patients with infections caused by NDM producers. Moreover, because of knowledge gained associated with global KPC dissemination, including in Brazil, this country is better prepared to face the other β-lactamases emerging worldwide. Initiatives of regional agencies and the Brazilian Health Surveillance Agency include dissemination of risk alerts to health professionals and guidelines for technical standardization and management of multidrug-resistant bacterial infection. These alerts focus on NDM producers and specific prevention and control measures; therapeutic orientation; and interpretive criteria for the assessment of bacterial antimicrobial drug susceptibility. These efforts are aimed at rapid microbiology detection and clinical and epidemiologic measures to control infections caused by NDM producers and blaNDM dissemination (e.g., using simple tests to detect carbapenemases, searching for colonized patients, and evaluating/monitoring hospital discharge of patients after NDM infection). Another type of mobilization was promoted during the 27th Brazilian Congress of Microbiology, 29 September–3 October, 2013 in Natal, Brazil, in which a special symposium was dedicated to discussing and improving NDM counterattacks ( http://www.sigeventos.com.br/sbmicrobiologia/admin/pro_lista_programa.asp?eveId=5&tipId=22 [in Portugese]). This symposium gathered a team of experts, including government representatives, to try to minimize the spread and effect of the entry of NDM into Brazil, as well as the future complications and consequences of national dissemination These efforts are crucial and have strategic significance that affect major events in Brazil, such as the 2014 FIFA World Cup, which brought people from all around the world to all regions of Brazil, and the upcoming Games of the XXXI Olympiad, which will occur in Rio de Janeiro in August 2016. Also of importance to this issue are the geopolitical and economic characteristics of Brazil. Because of Brazil’s global influence related to national and international movement of people and products, broad prevalence of NDM producers in Brazil could contribute to acceleration of the global spread of blaNDM. Microbiologists, clinicians, and their respective organizations, as well as the government of Brazil, through its health and disease control agencies, should continue to strive to contain NDM dispersion and limit the possible global impact of the spread and prevalence of NDM producers in Brazil.

IntroductionThe human gut microbiota is associated with gestational diabetes mellitus (GDM), which imposes a risk of developing long-term health problems for mother and child. Most studies on GDM and microbiota...

Bacteria producing New Delhi metallo-beta-lactamase-1 (NDM-1) exhibit high level resistance to beta-lactams including carbapenems. This broad-spectrum resistance limits treatment options for infections caused by NDM-1 producers. NDM-1 was first isolated from an Indian patient in Sweden; since then, NDM-1 producing isolates have been identified in many countries including Turkey. In this study, we investigated the presence of NDM-1 by PCR method in various gram-negative isolates recovered from clinical specimens in tertiary care hospitals in Samsun, Turkey. A total of 210 carbapenem-resistant gram-negative isolates (132 Acinetobacter baumannii, 54 Pseudomonas aeruginosa, 5 Pseudomonas putida, 8 Enterobacter cloacae, 3 Enterobacter aerogenes, 3 Klebsiella pneumoniae, 2 Providencia rettgeri, 2 Escherichia coli and 1 Citrobacter freundii) were included in the study. Identification and antibiotic susceptibility testing of the isolates were performed by using Vitek-2 Compact (bioMerieux, France) and BD Phoenix (BD Diagnostic Systems, MD) automated systems. The results of antibiotic susceptibility testing were interpreted according to the CLSI recommendations. In our study, NDM-1 gene was not detected in any of the clinical isolates by PCR. There was only one case study that reported the presence of NDM-1 in clinical isolates from Turkey [Poirel L et al. Antimicrob Agents Chemother 2012;56:2784]. Our data, together with the others, indicated that the existence of NDM-1 in clinical isolates is not common in Turkey. However, since NDM-1 is a plasmid-encoded enzyme, there is always a risk of spread of this resistance through the bacterial strains in our country. Therefore, continuous surveillance and investigation of carbapenem-resistant isolates with resistance patterns suggestive of NDM-1 may enable to identify NDM-1 producing isolates. Meanwhile special care should be given on rational antibiotic use and establishment of appropriate infection control policies to prevent the spread of NDM-1 producers and other potential resistant strains.

BackgroundCarbapenemase-producing Enterobacteriaceae infections are associated with high mortality. We aimed to compare the clinical outcomes of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and those with New-Delhi-Metallo-beta-lactamase-1 (NDM-1)-producing Enterobacteriaceae.MethodsWe performed a retrospective cohort study of all adult patients (> 16 years old) with KPC or NDM-1-producing Enterobacteriaceae isolates in a 2,700-bed tertiary referral hospital in Seoul, South Korea between 2010 and 2019. Primary outcomes were infection within 30 days and 30-day mortality after the first isolation of KPC or NDM-1-producing Enterobacteriaceae.ResultsA total of 859 patients were identified during the study period. Of them, 475 (55%) were KPC group and 384 (45%) were NDM-1 group. KPC group tended to develop infection within 30 days after first isolation more frequently than NDM-1 group (31% vs. 26%; P = 0.07). Thirty-day mortality was significantly higher in KPC group compared to NDM-1 group (KPC, 17% (81/475) versus NDM-1, 9% (33/384), P < 0.001). Multivariate analysis revealed that APACHE II score (adjusted odds ratio [aOR], 1.12; P < 0.001), solid cancer (aOR, 2.56; P < 0.001), previous carbapenem therapy (aOR, 1.93; P = 0.004), development of infection of KPC or NDM-1-producing Enterobacteriaceae within 30 days (aOR, 2.63; P < 0.001), and KPC-producing Enterobacteriaceae (aOR, 1.62; P = 0.045) were independent risk factors for 30-day mortality.Table 1. Results of analyses of risk factors for 30-day mortality from initial positive culture date in patients with KPC or NDM-1- producing EnterobacteriaceaeFigure 1. Kaplan–Meier survival estimates of patients with KPC or NDM-1-producing Enterobacteriaceae for 30-day mortality after first isolation: KPC (continuous line) versus NDM (dotted line). (log-rank test).ConclusionOur study suggests that KPC-producing Enterobacteriaceae is associated with poorer outcome compared to NDM-1-producing Enterobacteriaceae. Therefore, patients with KPC-producing Enterobacteriaceae colonization should be monitored carefully for development of infection, and appropriate antibiotics should be initiated as soon as possible.DisclosuresAll Authors: No reported disclosures

Comparison of clinical outcomes of patients infected with KPC- and NDM-producing Enterobacterales: a retrospective cohort study

Reconstructing patient treatment trajectories is important to generate real-world evidence for epidemiological studies. The Danish National Patient Registry (DNPR) contains information about drug prescriptions and could therefore be used to reconstruct treatment trajectories. We aimed to evaluate and enhance two existing methods to reconstruct systemic anticancer treatment trajectories. This study was based on data from 8738 consecutive patients with solid tumors treated in the North Denmark Region between 2009 and 2019. Two approaches found in the literature as well as two new approaches were applied to the DNPR data. All methods relied on time intervals between two consecutive drug administrations to determine if they belonged to the same treatment line. MedOnc, a local dataset from the Department of Oncology, Aalborg University Hospital was used as a reference. To evaluate the performance of each method, F1-scores were calculated after matching the lines identified in both datasets. We used three different matching strategies: stringent matching, loose matching, and matching based on line numbers, controlling for overfitting. Overall, the two new approaches outperformed the simpler and best performing of the two existing methods, with F1-scores of 0.47 and 0.45 vs 0.44 for stringent matching and 0.84 and 0.83 vs 0.82 for loose matching. Nevertheless, only one of the new methods outperformed the existing simpler method when matching on the number of lines (0.73 vs 0.72). Large differences were seen by cancer site, especially for the stringent and line number matchings. Performances were relatively stable by calendar year. The high F1-scores for the new methods confirm that they should be generally preferred to reconstruct systemic anticancer treatment trajectories using the DNPR.

PurposeRoutinely collected clinical data are a valuable resource for epidemiological research in infectious diseases. We examined the validity of the ICD-10 diagnosis code K75.0 for pyogenic liver abscess (PLA) from hospital discharge registries.Patients and MethodsThis validation study was conducted in the North Denmark Region, using data from Aalborg University Hospital and the North Denmark Regional Hospital, along with their smaller regional satellite hospitals. The study period extended from January 1, 2010, to June 30, 2022, covering a catchment population of approximately 590,000 inhabitants. We identified patients with a first diagnosis (primary or secondary) of PLA (ICD-10 code K75.0) recorded in the Danish National Patient Registry and estimated the positive predictive value (PPV) of the PLA diagnosis using medical records as the reference standard. Subanalyses of PPV were conducted based on the department setting (emergency, medical, or surgical).ResultsA total of 297 patients received an ICD-10 diagnosis code of K75.0 during the study period. Five (2.0%) patients were excluded due to initial hospitalization outside the North Denmark Region, and 67 (23%) were misclassified. The overall PPV for the K75.0 diagnosis code during the study period was 77% (95% CI: 72–82%). The highest PPV, 88% (95% CI: 81–93%), was observed in patients diagnosed in medical departments, while the lowest PPV, 56% (95% CI: 30–80%), was observed in patients diagnosed in emergency wards. The PPV for surgical departments was 69% (95% CI: 61–77%).ConclusionThe overall PPV of the ICD-10 diagnosis code K75.0 for PLA was 77%. Variability in PPVs across departments suggested differences in diagnostic accuracy, with medical departments demonstrating the highest PPV.

The use of microbiological services in general practice has raised concerns about overtesting and its impact on patient care. This study aimed to describe the patterns and variety of microbiological test requisitions from general practitioner (GP) clinics in the North Denmark Region. A descriptive analysis was performed using data from the microbiology laboratory information system at Aalborg University Hospital from 2019 to 2023. GP clinics that were active for at least three consecutive years were included. Test requisitions were grouped into nine categories and standardised per 1,000 individuals. Practices exceeding the upper threshold (Q3 + 1.5 × IQR) were identified as outliers. A total of 690,559 tests from 153 GP clinics were analysed. Urine cultures were the most frequently requested tests (median: 89 per 1,000 individuals annually), whereas respiratory and parasitological specimens were the least common tests (median: 1-2 per 1,000 individuals annually). A total of 54 GP clinics (35.3%) were identified as outliers. Notably, outliers were predominantly associated with less common test categories as follows: respiratory (n = 17), parasitological (n = 13), PCR (n = 12), STD/gynaecological (n = 12) and serology tests (n = 11). Variability in microbiological test use was substantial, with one-third of GP clinics being identified as outliers. A few GP clinics accounted for most requisitions for less common tests. These findings highlight the need for strengthened diagnostic stewardship in general practice. None. Not relevant.

IntroductionEnterococcus species are associated with an increased morbidity in intraabdominal infections (IAI). However, their impact on mortality remains uncertain. Moreover, the influence on outcome of the appropriate or inappropriate status of initial antimicrobial therapy (IAT) is subjected to debate, except in septic shock. The aim of our study was to evaluate whether an IAT that did not cover Enterococcus spp. was associated with 30-day mortality in ICU patients presenting with IAI growing with Enterococcus spp.Material and methodsRetrospective analysis of French database OutcomeRea from 1997 to 2016. We included all patients with IAI with a peritoneal sample growing with Enterococcus. Primary endpoint was 30-day mortality.ResultsOf the 1017 patients with IAI, 76 (8%) patients were included. Thirty-day mortality in patients with inadequate IAT against Enterococcus was higher (7/18 (39%) vs 10/58 (17%), p = 0.05); however, the incidence of postoperative complications was similar. Presence of Enterococcus spp. other than E. faecalis alone was associated with a significantly higher mortality, even greater when IAT was inadequate. Main risk factors for having an Enterococcus other than E. faecalis alone were as follows: SAPS score on day 0, ICU-acquired IAI, and antimicrobial therapy within 3 months prior to IAI especially with third-generation cephalosporins. Univariate analysis found a higher hazard ratio of death with an Enterococcus other than E. faecalis alone that had an inadequate IAT (HR = 4.4 [1.3–15.3], p = 0.019) versus an adequate IAT (HR = 3.1 [1.0–10.0], p = 0.053). However, after adjusting for confounders (i.e., SAPS II and septic shock at IAI diagnosis, ICU-acquired peritonitis, and adequacy of IAT for other germs), the impact of the adequacy of IAT was no longer significant in multivariate analysis. Septic shock at diagnosis and ICU-acquired IAI were prognostic factors.ConclusionAn IAT which does not cover Enterococcus is associated with an increased 30-day mortality in ICU patients presenting with an IAI growing with Enterococcus, especially when it is not an E. faecalis alone. It seems reasonable to use an IAT active against Enterococcus in severe postoperative ICU-acquired IAI, especially when a third-generation cephalosporin has been used within 3 months.

Invited commentary

AimsRisk factors for systemic anticancer therapies (SACTs) administered close to death derived from existing quality indicators are not directly applicable in the clinic, because they condition on future events, which leads to selection bias. This study aimed to adapt a previously suggested indicator for its use in a clinical context and to evaluate it in a real-world, population-based cohort of cancer patients. Materials and methodsAn improved version of the ‘30-day mortality after SACT’ indicator suggested by Wallington et al. (Lancet Oncol 2016; 17:1203–16) was defined. All SACTs (n = 16 622) for all patients (n = 10 213) treated for common malignancies between 2009 and 2019 in the North Denmark Region were included. The results for the improved and Wallington's indicators were calculated and compared. ResultsOverall, the association between clinical variables and 30-day mortality following SACT was similar for both indicators, except for the 75+ years age group. However, Wallington's indicator showed varying absolute risk when comparing values for quarterly and yearly observation intervals. The improved and Wallington's indicators showed large differences between curative (1.0% and 1.1%, respectively) and palliative SACTs (9.1% and 11.7%, respectively). For palliative SACTs, different types of malignancy presented with large variations for the improved indicator, ranging from above 10% for gastroesophageal, pancreatic and lung cancers to below 4% for prostate cancers. The value of the improved indicator was significantly lower in the last years of the study period compared with the 2009–2011 period. The type of malignancy was also associated with significant differences. ConclusionsWe defined an indicator adapted to the clinical context evaluating 30-day mortality following SACT. This indicator can be used to identify risk factors to help with clinical decision-making. A significant downward trend was observed in the 30-day mortality following palliative SACT over an 11-year period.

BackgroundEmergency departments handle a large proportion of acute patients. In 2007, it was recommended centralizing the Danish healthcare system and establishing emergency departments as the main common entrance for emergency patients. Since this reorganization, few studies describing the emergency patient population in this new setting have been carried out and none describing diagnoses and mortality. Hence, we aimed to investigate diagnoses and 1- and 30-day mortality of patients in the emergency departments in the North Denmark Region during 2014–2016.MethodsPopulation-based historic cohort study in the North Denmark Region (580,000 inhabitants) of patients with contact to emergency departments during 2014–2016. The study included patients who were referred by general practitioners (daytime and out-of-hours), by emergency medical services or who were self-referred.Primary diagnoses (ICD-10) were retrieved from the regional Patient Administrative System. For non-specific diagnoses (ICD-10 chapter ‘Symptoms and signs’ and ‘Other factors’), we searched the same hospital stay for a specific diagnosis and used this, if one was given. We performed descriptive analysis reporting distribution and frequency of diagnoses. Moreover, 1- and 30-day mortality rate estimates were performed using the Kaplan-Meier estimator.ResultsWe included 290,590 patient contacts corresponding to 166 ED visits per 1000 inhabitants per year. The three most frequent ICD-10 chapters used were ‘Injuries and poisoning’ (38.3% n = 111,274), ‘Symptoms and signs’ (16.1% n = 46,852) and ‘Other factors’ (14.52% n = 42,195). Mortality at day 30 (95% confidence intervals) for these chapters were 0.86% (0.81–0.92), 3.95% (3.78–4.13) and 2.84% (2.69–3.00), respectively.The highest 30-day mortality were within chapters ‘Neoplasms’ (14.22% (12.07–16.72)), ‘Endocrine diseases’ (8.95% (8.21–9.75)) and ‘Respiratory diseases’ (8.44% (8.02–8.88)).ConclusionsPatients in contact with the emergency department receive a wide range of diagnoses within all chapters of ICD-10, and one third of the diagnoses given are non-specific. Within the non-specific chapters, we found a 30-day mortality, surpassing several of the more organ specific ICD-10 chapters.Trial registrationObservational study - no trial registration was performed.

Background: New Delhi Metallo-β-lactamase (NDM)–producing Escherichia coli are highly resistant organisms that spread quickly. In the United States, organisms with blaNDM are rare and mostly associated with healthcare settings. However, in other countries, blaNDM can be relatively common and are found in community settings. State veterinary and public health partners detected NDM E. coli in a dog from Iran living at a Wisconsin animal rescue facility (ARF), where 40% of dogs had international origins. We investigated to determine spread among dog and human contacts and prevent further transmission. Methods: We screened dogs and humans at the ARF, a local veterinary clinic (clinic A), and ARF staff homes (homes A and B) for colonization with blaNDM. We reviewed veterinary records and conducted a case–control analysis to identify risk factors for blaNDM acquisition among dogs. We evaluated ARF infection control practices. Screening specimens that were positive for blaNDM were cultured. We conducted an analysis of short- and long-read whole-genome sequencing data to evaluate isolate relatedness. We compared NDM E. coli sequences from dogs to all NDM E. coli sequences from humans collected in Wisconsin and nearby states. Results: Screening identified blaNDM colonization in 27 (37%) of 73 ARF dogs and 4 (56%) of 7 dogs in home A, but not in ARF or staff in clinic A. Among ARF dogs with blaNDM, 20 (74%) 27 had international origins and 22 (81%) had ≥1 medical condition. Dogs sharing the same space (OR, 5.1; 95% CI, 1.8–14.7) were associated with blaNDM acquisition. We observed high animal density, soiled environments, and insufficient hand hygiene. ARF staff wore workwear and work shoes off site, including to home A. Sequencing identified 3 multilocus sequence types (STs) using the Achtman scheme among 27 isolates with blaNDM-5. Most isolates were ST361 (20 of 27, 74%) followed by ST167 (6 of 27, 22%) and ST1163 (1 of 27, 4%). Within-MLST cluster variability was &lt;1–3 high-quality single-nucleotide variant differences, each harboring a ST-specific plasmid with blaNDM-5. No NDM-E. coli sequences from humans appeared related. Conclusions: Investigation of a single isolate led to identification of widespread NDM-E. coli transmission among dogs at an ARF. There were multiple NDM E. coli introductions to the ARF, likely by dogs of international origin. Poor hygiene contributed to transmission among ARF dogs and to dogs outside the ARF. Transmission of blaNDM-5 at the ARF and offsite spread to home A demonstrate the potential for unrecognized community sources to disseminate NDM E. coli in community settings. Strategies and lessons learned from interventions to prevent antibiotic resistance in human healthcare settings may inform and support prevention in animal care.Disclosures: None