Cloacae Infection Research Articles

Trends in infection incidence and antimicrobial resistance in the US Veterans Affairs Healthcare System: a nationwide retrospective cohort study (2007–22)

Antimicrobial resistance poses a major threat to public health. There are few comprehensive nationwide studies that quantify long-term trends in infection incidence and antimicrobial resistance for multiple pathogens. We aimed to analyse trends in inpatient infection incidence and antimicrobial resistance for nine pathogens over the past 15 years across the USA. In this US nationwide retrospective cohort study, we analysed clinical microbiology data from electronic health records from all patients admitted to all 138 Veterans Affairs (VA) Medical Centers with acute care wards across the USA from Feb 1, 2007, to March 31, 2022. We quantified inpatient antibiotic use as days of therapy (DOT) per 1000 patient-days and antimicrobial resistance by resistance proportion (proportion of incident isolates identified as resistant) and phenotypic incidence (incidence of infections per 1000 admissions classified as resistant, susceptible, or missing). To analyse trends before the COVID-19 pandemic and during the COVID-19 pandemic, we used generalised estimating equation models and reported average annual percentage changes (AAPC). We collected 991 527 30-day incident isolates from 507 760 patients in 138 VA Medical Centers and 50 states in the USA. Between Feb 1, 2007, and Dec 31, 2019, infection incidence and antimicrobial resistance declined for many pathogens and pathogen-drug combinations. The proportion of methicillin resistance in Staphylococcus aureus decreased from 57·7% (11 876 of 20 584 incident isolates) to 44·6% (5916 of 13 257) over these 13 years (AAPC -1·8%; 95% CI -2·4 to -1·2; p<0·0001), and vancomycin-resistant Enterococcus faecium infections decreased from 77·8% (2555 of 3285) to 65·1% (893 of 1371; AAPC -1·2%; 95% CI -2·5 to 0·0; p=0·052). Fluoroquinolone resistance declined in both proportion and incidence for most pathogens. These trends correlated with substantial reductions in fluoroquinolone use, from 125 DOT per 1000 patient-days to 20 DOT per 1000 patient-days. Third generation cephalosporin resistance increased steeply in Escherichia coli infections from 6·7% (942 of 14 042) in 2007 to 15·3% (2153 of 14 053) in 2019 (AAPC 8·5%; 95% CI 6·2 to 10·7; p<0·0001). Carbapenem resistance proportion increased in Enterobacter cloacae infections from 1·1% (30 of 2852) in 2007 to 7·3% (212 of 2919) in 2019 (AAPC 19·8%; 95% CI 13·7 to 26·2; p<0·0001), but remained low for Klebsiella pneumoniae and E coli. During the COVID-19 pandemic between Jan 1, 2020, and March 31, 2022, several pathogen-drug combinations increased in both incidence and resistance for hospital-associated infections. For some pathogen-drug combinations, trends in incidence of resistant and susceptible infections were divergent, whereas for other combinations, these trends were in the same direction. Significant reductions in methicillin resistance in S aureus, vancomycin-resistant E faecium, and fluoroquinolone resistance across multiple pathogens suggest that control efforts have had an effect on resistance. The rise in extended-spectrum β-lactamases-producing Enterobacterales and recent surge in hospital-associated infections emphasise the need for ongoing surveillance and interventions. Our study highlights how coupling the analysis of phenotypic incidence with resistance proportion can enhance interpretation of antimicrobial resistance data. US Centers for Disease Control and Prevention.

MiR-190 restores the innate immune homeostasis of Drosophila by directly inhibiting Tab2 in Imd pathway

The Drosophila Imd pathways are well-known mechanisms involved in innate immunity responsible for Gram-negative (G-) bacterial infection. The intensity and durability of immunity need to be finely regulated to keep sufficient immune activation meanwhile avoid excessive immune response. In this study, we firstly demonstrated that miR-190 can downregulate the expression levels of antimicrobial peptides (AMPs) in the Imd immune pathway after Escherichia coli infection using the miR-190 overexpression flies and the miR-190KO/+ flies. Secondly, miR-190 overexpression significantly reduces while miR-190 KO increases Drosophila survival rates upon lethal Enterobacter cloacae infection. Thirdly, we further demonstrated that miR-190 negatively regulates innate immune responses by directly targeting both RA/RB and RC isoforms of Tab2. In addition, the dynamic expression pattern of AMPs (Dpt, AttA, CecA1), miR-190 and Tab2 in the wild-type flies reveals that miR-190 play an important role in Drosophila immune homeostasis restoration at the late stage of E. coli infection. Collectively, our study reveals that miR-190 can downregulate the expression of AMPs by targeting Tab2 and promote immune homeostasis restoration in Drosophila Imd pathway. Our study provides new insights into the regulatory mechanism of animal innate immune homeostasis.

ENTEROBACTER CLOACAE CARDIAC IMPLANTABLE ELECTRONIC DEVICE INFECTION.

Enterobacter cloacae cardiac implantable electronic device infections are rare but can be associated with significant morbidity and mortality. We report an 11-year-old female with Enterobacter cloacae infection of a dual-chamber transvenous pacemaker pocket. The report is supplemented by a comprehensive review of the literature on Enterobacter cloacae cardiac implantable electronic device infections.

Molecular epidemiology of multidrug-resistant Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli outbreak among neonates in Tembisa hospital, South Africa.

An outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. Bacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. The outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemase-positive, but four bla OXA-48 isolates were susceptible to carbapenems. Bla NDM-1 (n = 13) and bla OXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. The outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally.

Therapeutic Potential of a Novel Lytic Phage, vB_EclM_ECLFM1, against Carbapenem-Resistant Enterobacter cloacae.

The global rise of multidrug-resistant Enterobacter cloacae strains, especially those that are resistant to carbapenems and produce metallo-β-lactamases, poses a critical challenge in clinical settings owing to limited treatment options. While bacteriophages show promise in treating these infections, their use is hindered by scarce resources and insufficient genomic data. In this study, we isolated ECLFM1, a novel E. cloacae phage, from sewage water using a carbapenem-resistant clinical strain as the host. ECLFM1 exhibited rapid adsorption and a 15-min latent period, with a burst size of approximately 75 PFU/infected cell. Its genome, spanning 172,036 bp, was characterized and identified as a member of Karamvirus. In therapeutic applications, owing to a high multiplicity of infection, ECLFM1 showed increased survival in zebrafish infected with E. cloacae. This study highlights ECLFM1's potential as a candidate for controlling clinical E. cloacae infections, which would help address challenges in treating multidrug-resistant strains and contribute to the development of alternative treatments.

Diversity of MrTolls and their regulation of antimicrobial peptides expression during Enterobacter cloacae infection in Macrobrachium rosenbergii

Toll/Toll-like receptor (TLR) is an important pattern recognition receptor that plays an important role in the immunity of animals. Six Toll genes were identified in Macrobrachium rosenbergii, namely, MrToll, MrToll1, MrToll2, MrToll3, MrToll4, and MrToll5. SMART analysis showed that all six Tolls have a transmembrane domain, a TIR domain, and different number of LRR domains. The phylogenetic tree showed that six Tolls were located in six different branches. Among these six Tolls, only MrToll4 contains the QHR motif, which is similar to insect Toll9. MrToll4 belongs to V-type/scc Toll with only one LRRCT domain. MrToll1 and MrToll5 are classical P-type/mcc Toll with two LRRCT domains and an LRRNT. MrTolls were distributed in the hemocytes, heart, hepatopancreas, gills, stomach, and intestine. During the infection of Enterobacter cloacae, the expression level of MrToll and MrToll1-4 was upregulated in the intestine of M. rosenbergii. RNA interference experiments showed that the expression of most antimicrobial peptide (AMP) genes was negatively regulated by MrTolls during E. cloacae infection. On the contrary, crustin (Cru) 3 and Cru4 were inhibited after the knockdown of MrToll, and Cru1 and Cru4 were significantly downregulated with the knockdown of MrToll4 during E. cloacae challenge. These results suggest that MrTolls may be involved in the regulation of AMP expression in the intestine during E. cloacae infection.

Relish-facilitated lncRNA-CR11538 suppresses Drosophila Imd immune response and maintains immune homeostasis via decoying Relish away from antimicrobial peptide promoters

Innate immunity plays a crucial role in host defense against pathogen invasion and its strength and duration requires precise control. Long non-coding RNAs (lncRNAs) have become important regulators of innate immunity, yet their roles in Drosophila immune responses remain largely unknown. In this study, we identified that the overexpression of lncRNA-CR11538 inhibits the expression of antimicrobial peptides (AMPs) Dpt and AttA in Drosophila upon Escherichia coli (E. coli) infection, and influences the survival rate of flies after E. cloacae infection. Mechanically, lncRNA-CR11538 decoys Relish away from AMPs promoter region. We further revealed that Relish can promote the transcription of lncRNA-CR11538. After analyzing the dynamic expression profile of lncRNA-CR11538 during Imd immune response, we put forward a hypothesis that in the late stage of Imd immune response, lncRNA-CR11538 can be activated by Relish and further decoy Relish away from the AMPs promoter to suppress excessive immune signal and maintain immune homeostasis. This mechanism we proposed provides insights into the complex regulatory networks controlling immune responses in Drosophila and suggests potential targets for therapeutic intervention in diseases involving dysregulated immune responses.

Enterobacter cloacae infection characteristics and outcomes in battlefield trauma patients.

Enterobacter cloacae is a Gram-negative rod with multidrug-resistant potential due to chromosomally-induced AmpC β-lactamase. We evaluated characteristics, antibiotic utilization, and outcomes associated with battlefield-related E. cloacae infections (2009-2014). Single initial and serial E. cloacae isolates (≥24 hours from initial isolate from any site) associated with a clinical infection were examined. Susceptibility profiles of initial isolates in the serial isolation group were contrasted against last isolate recovered. Characteristics of 112 patients with E. cloacae infections (63 [56%] with single initial isolation; 49 [44%] with serial isolation) were compared to 509 patients with bacterial infections not attributed to E. cloacae. E. cloacae patients sustained more blast trauma (78%) compared to non-E. cloacae infections patients (75%; p<0.001); however, injury severity scores were comparable (median of 34.5 and 33, respectively; p = 0.334). Patients with E. cloacae infections had greater shock indices (median 1.07 vs 0.92; p = 0.005) and required more initial blood products (15 vs. 14 units; p = 0.032) compared to patients with non-E. cloacae infections. Although E. cloacae patients had less intensive care unit admissions (80% vs. 90% with non-E. cloacae infection patients; p = 0.007), they did have more operating room visits (5 vs. 4; p = 0.001), longer duration of antibiotic therapy (43.5 vs. 34 days; p<0.001), and lengthier hospitalizations (57 vs. 44 days; p<0.001). Patients with serial E. cloacae had isolation of infecting isolates sooner than patients with single initial E. cloacae (median of 5 vs. 8 days post-injury; p = 0.046); however, outcomes were not significantly different between the groups. Statistically significant resistance to individual antibiotics did not develop between initial and last isolates in the serial isolation group. Despite current combat care and surgical prophylaxis guidelines recommending upfront provision of AmpC-inducing antibiotics, clinical outcomes did not differ nor did significant antibiotic resistance develop in patients who experienced serial isolation of E. cloacae versus single initial isolation.

Transcriptomic profiling and characterization of microRNAs in Macrobrachium rosenbergii potentially involved in immune response to Enterobacter cloacae infection

Enterobacter cloacae is a member of the Enterobacter family, which could prevent Macrobrachium rosenbergii from growing and cause mass mortality. However, no research has focused on microRNA immunity in M. rosenbergii infected with E. cloacae. To clarify the immune response mechanisms, transcriptomic analysis was performed on the miRNAs of M. rosenbergii infected with E. cloacae YZ3 strain. Following quality screening, 10,616,712 clean reads were obtained from the control group and 12,726,421 from the infected group. Among 899 known miRNAs, 446 differentially expressed miRNAs (DEMs) were identified. Meanwhile, 59 novel miRNAs were predicted, along with 39 DEMs. Target genes of DEMs have been predicted in order to gain a deeper understanding of the immune-related functions. GO and KEGG pathway analysis revealed the biological functions and signaling pathways of target genes. The results indicated that E. cloacae significantly affected the NOD-like receptor, RIG-I-like receptor and Toll-like receptor pathways. Ten DEMs were randomly selected, and their expression level was verified by Quantitative Real-time PCR technology. Overall, this study highlights the influential role of miRNAs in the innate immune system of M. rosenbergii, which has important implications for developing new strategies to prevent and treat related diseases in the future.

The NF-κB/Relish Activates miR-308 to Negatively Regulate Imd Pathway Immune Signaling in Drosophila.

The strength and duration of the NF-κB signaling response must be tightly modulated to avoid an inadequate or excessive immune response. Relish, a core NF-κB transcription factor of the Drosophila Imd pathway, can control the expression of antimicrobial peptides, including Dpt and AttA, to defend against Gram-negative bacterial infections, but whether Relish may regulate miRNA expression to participate in the immune response remains unclear. In this study, taking advantage of Drosophila S2 cells and different overexpression/knockout/knockdown flies, we first found that Relish could directly activate the expression of miR-308 to negatively regulate the immune response and promote the survival of Drosophila during Enterobacter cloacae infection. Second, our results demonstrated that Relish-mediated expression of miR-308 could suppress target gene Tab2 to attenuate the Drosophila Imd pathway signal during the middle and late stages of the immune response. Third, we detected the dynamic expression patterns of Dpt, AttA, Relish, miR-308, and Tab2 in wild-type flies after E. coli infection, which further revealed that the feedback regulatory loop of Relish-miR-308-Tab2 plays a crucial role in the immune response and homeostasis maintenance of the Drosophila Imd pathway. Overall, our present study not only illustrates an important mechanism by which this Relish-miR-308-Tab2 regulatory axis can negatively control the Drosophila immune response and participate in homeostasis maintenance but also provides new insights into the dynamic regulation of the NF-κB/miRNA expression network of animal innate immunity.

Vertebral Osteomyelitis in a Black Spiny-Tailed Iguana (Ctenosaura similis) and a Red Tegu (Salvator rufescens)

The present report describes the clinical, gross pathologic and radiologic features of vertebral osteomyelitis in a black spiny-tailed iguana (Ctenosaura similis) and a red tegu (Salvator refuscens). Both lizards were presented with hind limb ataxia and proprioception deficits and based on radiographic and computed tomographic imaging, a presumptive diagnosis of vertebral osteomyelitis was made. Microbiological examination of vertebral body biopsies revealed Morganella morganii and Enterococcus faecalis infection in the iguana and Enterobacter cloacae infection in the tegu. Failure of antimicrobial treatment in both lizards was considered to be at least partly attributable to the tardy onset of clinical signs resulting in a late diagnosis and pronounced chronicity of the vertebral lesions. While vertebral osteomyelitis has been repeatedly reported in snakes, reports in saurian species are scarce and rather anecdotal. Based on the findings in these cases, however, vertebral osteomyelitis should be considered as an important differential diagnosis for hind limb ataxia in lizards.

The Epidemiological Pattern, Resistance Characteristics and Clinical Outcome of Enterobacter cloacae: Recent Updates and Impact of COVID-19 Pandemic.

E. cloacae is an opportunistic organism that causes serious infections, particularly in immuno-compromised and hospitalized patients, along with the emergence of resistance traits. The COVID-19 pandemic has impacted the epidemiological pattern and resistance traits of E. cloacae infections as well as those of other bacteria. The study aims to assess the epidemiological patterns, resistance characteristics and clinical outcomes of E. cloacae in Saudi Arabia and the impact of the COVID-19 pandemic. King Fahad Medical City in Riyadh provided the data between January 2019 and December 2021 for the retrospective study of 638 isolates of E. cloacae. The clinical outcome of an E. cloacae infection was also determined by collecting and statistically analyzing the clinical records of 153 ICU patients. The total percentage of resistant E. cloacae isolates decreased from 48.36% in 2019 to 38% in 2020 and 37.6% in 2021. The overall mortality rate among ICU patients was 40.5%, with an adult age group having a substantial relative risk value of 1.37. E. cloacae is a prevalent nosocomial infection in which adult age is a significant risk factor for mortality. Moreover, this study emphasizes the importance of comparing E. cloacae resistance trends before and throughout the pandemic period in order to better understand the bacteria's behaviour.

Complications infectieuses liées à l’utilisation du propofol : une nouvelle série de cas et revue de la littérature

Propofol is the most commonly used hypnotic agent for the induction and maintenance of general anesthesia. Due to its lipid-based composition, propofol requires a strict handling protocol to avoid an increased risk of extrinsic contamination. On September 09, 2021, 05patients with post-anaesthetic Enterobacter cloacae infections were identified in the pediatric exploration department of the Hassan II University Hospital of Fez in Morocco. We describe the investigation into this outbreak. All patient medical records were reviewed to determine patient characteristics and potential risk factors. For the literature review, we identified relevant articles by searching PubMed, Medline, Embase and Science Direct. Our study included five patients, 80% were boys. The average age was 4.6years (1-7years), with no medical history. All five patients underwent exploratory procedures. Immediately after the procedures, all 5patients presented with chills, tachycardia and fever in the same order of admission. They were all admitted to hospital and blood samples were taken. Blood cultures were positive for E.cloacae. All patients had elevated levels of C-reactive protein (CRP) and an elevated white blood cell count. Bacteriological investigation revealed that the infection was caused by extrinsic contamination of the intravenous anesthetic propofol by E.cloacae. Fatal infections due to contaminated drugs, including propofol, have been reported worldwide. Propofol is a potential source of infections due to its lipophilic nature which promotes microbial growth. This probably remains an underestimated problem that deserves awareness for early recognition.

Regulation of Host Immune Response against Enterobacter cloacae Proteins via Computational mRNA Vaccine Design through Transcriptional Modification.

Enterobacter cloacae is mainly responsible for sepsis, urethritis, and respiratory tract infections. These bacteria may affect the transcription of the host and particularly their immune system by producing changes in their epigenetics. In the present study, four proteins of Enterobacter cloacae were used to predict the epitopes for the construction of an mRNA vaccine against Enterobacter cloacae infections. In order to generate cellular and humoral responses, various immunoinformatic-based approaches were used for developing the vaccine. The molecular docking analysis was performed for predicting the interaction among the chosen epitopes and corresponding MHC alleles. The vaccine was developed by combining epitopes (thirty-three total), which include the adjuvant Toll-like receptor-4 (TLR4). The constructed vaccine was analyzed and predicted to cover 99.2% of the global population. Additionally, in silico immunological modeling of the vaccination was also carried out. When it enters the cytoplasm of the human (host), the codon is optimized to generate the translated mRNA efficiently. Moreover, the peptide structures were analyzed and docked with TLR-3 and TLR-4. A dynamic simulation predicted the stability of the binding complex. The assumed construct was considered to be a potential candidate for a vaccine against Enterobacter cloacae infections. Hence, the proposed construct is suitable for in vitro analyses to validate its effectiveness.

Case Study of a 70-Year-Old Man Admitted to ICU during the First Wave of the COVID-19 Pandemic

Abstract A patient with coronavirus disease 2019 (COVID-19) was admitted to the intensive care unit (ICU) because of decrease in oxygen saturation in connection with COVID-19 pneumonia. An intensivist and a general practitioner (GP)-homeopath worked together on the patient with the approval of his three children. His consent was not possible because he was in a coma. When additional homeopathic treatment started, the patient had a 10% chance of survival. No direct contact with the patient was possible. The GP could only treat remotely and only received second-hand information. The patient achieved complete recovery without long COVID-19 symptoms. Before admission to the ICU, I thought Kalium sulphuricum was his constitutional medicine. But this remedy did not prevent admission. Various homeopathic medicines are prescribed each time based on the patient's unique symptoms. During the ICU admission, the patient contracted an Enterobacter cloacae infection, developed renal failure, myocardial infarction and finally a haemorrhage in the right hemisphere of the brain, resulting in paralysis in the left side of the body. Due to his behaviour towards the end of his stay at the hospital, I found his constitutional remedy, which was Veratrum album. Each time, only a single dose of the homeopathic medicine was administered.

Characterization of a novel, biofilm dispersing, lytic bacteriophage against drug-resistant Enterobacter cloacae.

To characterize a novel bacteriophage, En5822, isolated from the environment against Enterobacter cloacae and exploring its application as an alternate antimicrobial. Bacteriophage was isolated from sewage sample by membrane-filtration immobilization technique. It was purified and studied for its various physical properties like microscopic structure, thermal and pH stability, latent period and burst time, antimicrobial and anti-biofilm activity as well as molecular aspects by genome sequencing and analysis. En5822 is a myovirus with relative pH and thermal stability. En5822 shows a notable reduction of host bacterial biofilm as well as planktonic cultures. Whole genome sequence analysis revealed that the En5822 genome does not contain undesirable temperate lifestyle genes, antibiotic resistance genes and toxin-encoding genes. En5822 displays high lytic activity, specificity and biofilm reduction capability. It has a short latent period and high burst size that aid faster activity. Its genomic and physical attributes offer possibilities for its as an alternative antimicrobial for the treatment of drug-resistant E. cloacae infections. The study describes a novel, naturally virulent bacteriophage from environment capable of lysing multi-drug resistant E. cloacae effectively. The phage could potentially serve as an alternative strategy for treating antibiotic-resistant infections.

788. Enterobacter cloacae Infection Characteristics and Outcomes in Military Personnel who Sustained Trauma in Iraq and Afghanistan

Background Enterobacter cloacae is a Gram-negative rod with chromosomally-induced Amp-C β-lactamase with multidrug-resistant potential. Joint Trauma System guidelines for treating combat wounds include prophylaxis with cefazolin and ertapenem, potent inducers of Amp-C. We evaluated clinical characteristics, antibiotic utilization, and outcomes associated with battlefield-related E. cloacae infections. MethodsAll initial solitary (those with single isolates) and serial E. cloacae isolates (≥24 hours from initial isolate from any site) were collected from the Trauma Infectious Disease Outcomes Study (6/2009-12/2014). Inclusion required E. cloacae isolation from a clinical infection. Amp-C-inducing β-lactams were classified based on induction potential and lability to the Amp-C β-lactamase as Amp-C induction levels. ResultsOf 653 E. cloacae isolates, 253 met inclusion criteria – 64 patients had only initial isolates, 54 patients had serial isolates. Patients were largely male (99%), median age 23 years (IQR 21-27), with injury severity score of 34 (IQR 24-45). Initial isolates were wound (70%), respiratory (22%), blood (7%), urine (1%), and other (1%). Patients commonly had blast injuries (89%), required ICU admission (95%), and had a median hospital stay of 57 days (IQR 39-82). Patients with serial isolates showed a trend towards earlier clinical infection (5 vs 8 days, P = 0.07). They were also less likely to receive carbapenems prior to E. cloacae isolation compared to those with only initial isolates (4% vs 38%) and more likely to receive 1st generation cephalosporins (79% vs 58%, P = 0.01). The serial isolate group received more days of 1st generation cephalosporins (median 6 days vs 2.5 days, P = 0.01). Cumulative antimicrobial therapy trended towards significance and was greater with the serial isolates (median 100 days vs 74 days, P = 0.08). There was no difference in number of surgical interventions between those with and without serial isolates (P = 0.54). Overall, 6 patients died. Conclusion E. cloacae infections after battlefield trauma were frequently encountered and associated with exposure to 1st generation cephalosporins. Serial infections did not correlate to worse patient outcomes but displayed a trend towards an overall greater duration of antibiotic use.Disclosures William N. Bennett, V, MD, Abbvie (Shareholder)Amgen (Shareholder)Nabriva (Shareholder)

Enterobacter cloacae infection of the shoulder in a 52-year-old woman without apparent predisposing risk factor: a case report and literature review

BackgroundEnterobacter cloacae (E. cloacae) is one of the commensal flora in the human intestinal tract and a prevalent nosocomial pathogen, which rarely causes infectious osteoarthritis in immunocompetent patients without recent trauma or surgery. Here, we report the first case of septic monoarthritis of the shoulder caused by E. cloacae in an immunocompetent patient.Case presentationA 52-year-old female with a 6-year history of right shoulder pain was referred to our emergency department due to fever, acute severe shoulder pain, and swelling. Blood test showed elevated inflammatory markers. The patient denied any recent invasive surgical procedure and trauma. She was misdiagnosed with a frozen shoulder, and the anti-inflammatory painkiller celecoxib for symptomatic treatment was ineffective. Magnetic resonance imaging (MRI) showed a shoulder joint abscess and supraspinatus tendon tear. The joint aspirate culture showed E. cloacae. After late diagnosis, she was treated with levofloxacin and underwent surgical debridement and irrigation. Her follow-up data revealed that she did not suffer from shoulder swelling and severe pain.ConclusionThis is a rare case of E. cloacae infected arthritis of the shoulder in an immunocompetent patient with a rotator cuff tear, indicating that even if the symptoms and age of the patients match the characteristics of frozen shoulder, the possibility of septic arthritis should be considered in the presence of fever and increasing inflammatory markers. The cases of our literature review suggest that the patients subjected to invasive procedure may develop a subsequent E. cloacae osteoarticular infection, regardless of being asymptomatic after the procedure.

Characterization of an New Delhi-Metallo-1-Producing Enterobacter cloacae ST418 Strain from a Patient in Guangzhou, China.

New Delhi-Metallo-1-producing (NDM-1-producing) Enterobacter cloacae is one of the highly resistant pathogens affecting the intensive care unit. A previous study reported that ST418 was the main epidemic type of NDM-1-producing E. cloacae in Shenzhen, China. However, few NDM-1-producing carbapenem-resistant Enterobacter cloacae ST418 strains have been described. In this study, we collected and characterized an NDM-1-producing carbapenem-resistant E. cloacae strain, E70, from a patient in Guangzhou. E70 was resistant to multiple antibiotics, including imipenem and meropenem. S1-Pulsed field gel electrophoresis and southern blotting showed that E70 harbored four plasmids and that the blaNDM-1 gene was located on an ∼50 kb plasmid. Conjugation experiments revealed that the two smaller plasmids were transferable and that transconjugants obtaining one or both plasmids acquired different antimicrobial resistances. Whole-genome sequencing and analysis revealed that E70 belonged to ST418. The blaNDM-1 and blaSHV-12 genes coexisted on the 53.7 kb IncX3 plasmid pE70-NDM1, whereas the blaCTX-M-3 and blaTEM-1 genes were located on another untyped 26.0 kb plasmid, pE70-TEM1. The blaNDM-1 plasmids in Enterobacter cloacae ST418 may serve as an important vehicle in the dissemination of NDM, and the coexistence of transferable plasmids increases the possibility of rapid horizontal spread of multidrug resistance genes. Long-term monitoring and detailed study are necessary for the prevention of blaNDM-1-carrying E. cloacae infection.

Cluster of Infections Associated With Contaminated Stem-Cell Products

Background: The unapproved and unregulated use of umbilical stem-cell products has been identified as a possible source of adverse events and infection. In 2018, a national outbreak of multiple bacterial infections was associated with use of umbilical stem cells products. From December 2018 through March 2019, the Los Angeles County Department of Public Health (LACDPH) identified 4 cases of bacterial infection in patients that had received therapies using umbilical stem-cell products. Although 2 cases were associated with the national outbreak of a single company’s product, 2 additional cases of Enterobacter cloacae were instead associated with a second stem-cell distributer. Methods: In December 2018, LACDPH staff received notification from a hospital infectious disease physician of 2 cases of E. cloacae infection in patients of a freestanding ambulatory surgery center following allogenic umbilical cord stem-cell injections on the same day in August 2018. LACDPH reviewed the medical records of these patients and conducted an on-site visit to the ambulatory surgery center, which included observation of infection prevention practices, interview of staff, and review of logs. The 2 isolates from each patient were sent to the CDC laboratory for relatedness testing. Results: The 2 case patients received products via intra-articular injection from different lot and donor numbers for lumbar spine pain. In addition to the stem-cell product, both patients also received antibiotics and pain medications during their procedures, though from different vials. Both patients were seen by the same surgeon, anesthesiologist, and nurse during their procedures. No additional cases occurred. The case patients were hospitalized for 12 and 27 days, respectively. Whole-genome sequencing indicated that the isolates from the 2 patients were related. No major gaps in infection prevention practices were identified at the surgery center. Conclusion: This report describes a cluster of 2 E. cloacae infections in patients who had received unapproved-use stem-cell products via spinal injection. Given molecular laboratory results and infection prevention observations, we hypothesize that the stem-cell products used on these 2 cases were likely contaminated before distribution. This cluster demonstrates that contamination of stem-cell products extends beyond the single outbreak previously described and points to the systematic inability to ensure the safety of unapproved use of umbilical stem- cell products.Funding: NoneDisclosures: None