Enterobacter Cloacae Bacteremia Research Articles

Avatrombopag Safe and Effective in Treatment of Severe Refractory Thrombocytopenia in a Pediatric Patient with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation

Background: Persistent thrombocytopenia following allogeneic stem cell transplantation (alloHSCT) leads to an increase in morbidity and mortality. Causes of severe thrombocytopenia following HSCT include poor graft function, graft-versus-host disease (GVHD), infections, drug toxicities, underlying autoimmune diseases and relapse of underlying disease. Treatments can include thrombopoietin receptor agonists (TPO-RA), immunomodulators, and stem cell boost. Avatrombopag is a second generation TPO-RA approved for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients with poor response to standard treatments or in patients with chronic liver disease (CLD) associated thrombocytopenia requiring surgical interventions. Phase III clinical trials have shown greater platelet responses in chronic ITP and reduced transfusion needs in patients with CLD. Avatrombopag differs from other TPO-RA medications due to majority of elimination occurring in the gut, thus avoiding hepatic toxicity. Additionally, it does not require dietary restrictions. As there is limited literature in pediatric patients following alloHSCT, we describe the use of avatrombopag in a pediatric patient with chronic severe thrombocytopenia (<10 x10 3/uL) post HSCT. Objective: To describe the use of avatrombopag for severe refractory thrombocytopenia in a pediatric alloHSCT recipient. Case Presentation: We present a 14-year-old Hispanic male with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who received a maternal haploidentical HSCT with myeloablative conditioning and post-transplant cyclophosphamide. His post HSCT course was complicated by adenoviremia, hepatic variant GVHD, Enterobacter cloacae bacteremia and poor graft function. Seven months following HSCT, patient was found to be severely pancytopenic. Bone marrow morphology demonstrated 20-30% cellularity without evidence of leukemia relapse or GVHD. Lab evaluation was not consistent with transplant associated thrombotic microangiopathy. He received a stem cell boost for presumed poor graft function. Patient demonstrated partial response by resolution of neutropenia and anemia; however, severe thrombocytopenia persisted. Multiple bone marrow evaluations remained negative for disease with full donor chimerism and negative TCR clonality. CXCL9 was noted to be elevated at 4270 and Immature Platelet fraction was elevated at 8.8. Platelet antibodies remained negative and all findings consistent with persistent severe ITP. Multiple treatments including romiplostim; eltrombopag; high dose immune globulin (IVIG); rituximab; methylprednisolone; and decitabine were not successful in improving platelet count (Figure 1). Evaluation for severe thrombocytopenia remained negative. During the course of severe thrombocytopenia, patient required several hospitalizations for symptomatic thrombocytopenia, requiring multiple platelet transfusions. Due to the severity of disease, he was granted a compassionate use investigational new drug (IND 165837) for avatrombopag and began on day +332. Dosing was initiated at 20 mg daily with a dosage adjustment to achieve platelet recovery to >50 x10 3/uL free from transfusion. The dose was titrated per manufacturer to maximum dose of 40 mg daily with response to platelet count >100 x10 3/uL in approximately 6 weeks time. By three months of treatment, dose was titrated down 40 mg three times a week and 20 mg on alternating days. Patient continues to maintain platelets above 100 x10 3/uL with no medication toxicities or adverse events noted. Patient has been able to return to his pre-alloHSCT lifestyle including contact sports and re-immunizations.

Cefepime Dosing in a Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM).

We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an Enterobacter cloacae bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 mL/kg/hr; however, pharmacokinetic data on cefepime dosing in pediatric CRRT are scant. This case report describes the successful dosing strategy used for this patient while on various rates of continuous veno-venous hemodialysis with CARPEDIEM. Therapeutic drug monitoring of cefepime should be considered in critically ill pediatric patients on CARPEDIEM receiving CRRT.

Obstructive Jaundice Due to Duodenal Ulcer Induced by Lenvatinib Therapy for Hepatocellular Carcinoma

An 82-year-old man with hepatocellular carcinoma presented with upper abdominal pain, vomiting, and jaundice. He had been taking a standard lenvatinib dose for three months. Although acute cholangitis was suggested, imaging studies failed to detect the biliary obstruction site. An endoscopic examination following discontinuation of lenvatinib and aspirin revealed multiple duodenal ulcers, one of which was formed on the ampulla of Vater and causing cholestasis. Endoscopic biliary drainage and antibiotics improved concomitant Enterobacter cloacae bacteremia. Ulcer healing was confirmed after rabeprazole was replaced with vonoprazan and misoprostol. Our case shows that lenvatinib can induce duodenal ulcers resulting in obstructive jaundice.

Cluster Analysis and Genetic Characterization of Enterobacter cloacae Complex from Blood Cultures

Background: Enterobacter cloacae bacteremia is reported as an important cause of morbidity and mortality. The members of E. cloacae complex are clinically involved in nosocomial infections. Objectives: The purpose of this study was to investigate the prevalence of E. cloacae complex and its members in blood samples and conduct the hsp60 cluster analysis and genotyping of the isolates. Methods: Eight isolates of E. cloacae complex were collected from blood cultures of hospitalized patients during the study period (December 2012 to November 2013). The hsp60 sequencing was done for the genetic classification. Pulsed-field gel electrophoresis (PFGE) was used for genotyping of the isolates. Results: Fifty percent of the isolates belonged to two E. hormaechei subspecies. Three isolates (37.5%) clustered within genotype III while only one isolate fitted cluster XIII genotype (12.5%). Pulsed-field gel electrophoresis analysis revealed four different pulsotypes. Conclusions: Different E. cloacae complex species and subspecies unequally contribute to the pathogenesis of blood infections and the subspecies of E. hormaechei were found to be most prevalent. Moreover, the common E. cloacae pulsotypes were observed to essentially produce identical hsp60 sequence types, indicating the probable clonality of isolates with identical pulsotypes.

Detection of Curli Biogenesis Genes Among Enterobacter cloacae Isolated From Blood Cultures

Background: Enterobacter cloacae bacteremia infection is an significant cause of morbidity and mortality in both developing and developed countries. Curli fibrils are considered the most important virulence factor in these bacteria. Objectives: The purpose of this research was to detect curli biogenesis genes among Enterobacter cloacae isolated from blood cultures. Materials and Methods: Nine E. cloacae isolates were collected from blood cultures of inpatients admitted to three hospitals in the Tehran, Iran during December 2012 to November 2013. Confirmation of identity of the infecting organism as E. cloacae was performed by API20E system and the presence of a csgA and csgD genes by PCR using csgA and csgD specific primers. Results: All of E. cloacae bloodstream strains (100%) harbored csgD gene (curli biogenesis activator) and seven (77.75%) carried csgA gene (curli major subunit) which is indicative of wide distribution of this virulence factor among our isolates. Conclusions: Extensive presence of curli biogenesis genes (csgD and csgA) among E.cloacae strains and probably expression of those crucial role of this virulence factor in E. cloacae pathogenesis and invasiveness.

Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates

A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 μg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.

717Clinical characteristics and outcome of metallo-β-lactamase-producing Enterobacter cloacae bacteremia at a tertiary care cancer center in Japan

717Clinical characteristics and outcome of metallo-β-lactamase-producing Enterobacter cloacae bacteremia at a tertiary care cancer center in Japan

A Study of 5 Cases of Enterobacter cloacae Bacteremia Caused by Nosocomial Infection

A Study of 5 Cases of Enterobacter cloacae Bacteremia Caused by Nosocomial Infection

Comparison of the clinical and microbiologic characteristics of patients with Enterobacter cloacae and Enterobacter aerogenes bacteremia: a prospective observation study

We compared the characteristics and outcomes of 172 Enterobacter cloacae bacteremia and 67 Enterobacter aerogenes bacteremia (EAB) cases. Antimicrobial resistance rates to E. cloacae were higher than those to E. aerogenes. However, EAB more frequently presented as septic shock and was associated with poorer outcomes.

Retrospective analysis of bacteremia because of Enterobacter cloacae compared with Escherichia coli bacteremia

A total of 52 patients of Enterobacter cloacae bacteremia from a University hospital during the period from January 2000 to June 2005 were analysed and compared with a reference group comprising 52 patients of Escherichia coli bacteremia. Overall, E. cloacae ranked the tenth in all pathogens of bacteremia accounting for 2.8% of the total patients. Although the incidence of E. cloacae bacteremia was low, the attributable mortality rate till achieved 13.5%. Most patients (86.5%) with E. cloacae bacteremia were hospital-acquired. The overwhelming majority of patients (92.3%) were men, while almost half of the patients (48.1%) were from the Department of Urological Surgery with underlying diseases such as urinal obstruction, kidney transplantation and kidney tumours. Possible risks factors associated with E. cloacae bacteremia included immunocompromised status, long-term hospitalisation and invasive procedures or surgeries. E. cloacae bacteremia significantly differed from E. coli bacteremia in a number of clinical aspects, including underlying diseases, portal of entry, infection type, risks factors, laboratory findings and appropriateness of empirical antibiotic therapy. Besides the high prevalence of resistance to cephalosporins, most E. cloacae blood isolates were also resistant to ciprofloxacin (resistance rate, 67.3%), gentamicin (73.1%) and tobramycin (73.1%). Based on the findings of the present study, E. cloacae is probably an important pathogen of bacteremia occurring in male patients with underlying urinal system illnesses.

Mechanism of cross-contamination of blood culture bottles in a pseudoepidemic of Enterobacter cloacae bacteremia.

Mechanism of cross-contamination of blood culture bottles in a pseudoepidemic of Enterobacter cloacae bacteremia.

Enterobacter Cloacae Bacteremia in Children: A Review of 30 Cases in 12 Years

A review was performed of the 30 cases of pediatric Enterobacter cloacae (EBC) bacteremia which occurred at our institution during a 12-year period. These 30 cases represented 88% of all cases in which EBC was isolated by blood culture (four other instances were considered contaminants); the rate of isolation of this organism relative to all positive blood cultures was 0.6%. There were 14 patients less than 12 months of age, with 10 less than 2 months of age. Infection was nosocomially-acquired in 17 cases. At the time the positive blood culture was obtained, 5 patients were afebrile, and 8 patients (five immunocompromised) had been receiving parenteral antibiotic therapy to which the organism exhibited in-vitro sensitivity for at least 24 hours. EBC was a constituent of polymicrobial bacteremia in 6 cases; in 5 instances the associated organisms were also gram-negative bacteria. There were a total of 33 underlying medical conditions or foci of infection associated with EBC bacteremia identified in 27 patients, the most common of which were immune-deficiency state (17) and gastrointestinal tract lesions (6). There were 3 patients who died. EBC bacteremia is a relatively rare pediatric infection. It is commonly nosocomially-acquired, and afflicts children who are younger-aged or compromised by underlying medical problems.

Postoperative endocarditis due to Enterobacter cloacae. Report of a case cured by antibiotic therapy.

A girl with congenital aortic stenosis underwent open commissurotomy. Postoperatively, she developed Enterobacter cloacae bacteremia followed by endocarditis. The combination of carbenicillin disodium and kanamycin sulfate was shown by in vitro tests to have a synergistic, bactericidal effect against this organism. The administration of these antibiotics resulted in cure of the endocarditis. Carbenicillin may be useful in the treatment of endocarditis due to gram-negative bacteria.