Epidemiologic and Clinical Characteristics of Clostridioides difficile Infections in Hospitalized and Outpatient Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: The epidemiology and clinical course of Clostridioides difficile infection (CDI) in children, especially with cancer, are poorly defined. We aim to describe the epidemiology, clinical features and outcomes of CDI and to identify risk factors for recurrence in a pediatric oncology center. METHODS: This is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by positive C. difficile test in symptomatic patients. CDI episodes were classified as incident, duplicate or recurrent and community-onset, hospital-onset or community-onset healthcare facility-associated. Data about clinical course and outcomes were abstracted. Risk factors for CDI recurrence were assessed by logistic regression. RESULTS: One hundred seventy-eight patients 1 year of age and older developed 291 CDI episodes; 78% were incident and 22% recurrent. Underlying diagnoses were leukemia/lymphoma (57%) and solid/brain tumors (41%); 30% were HSCT recipients. Antibiotics, chemotherapy, antacids, steroids and laxatives were received by 96%, 82%, 70%, 47% and 15%, respectively. Half of the patients were neutropenic. Twenty-two percent of outpatients with CDI required hospitalization. Chemotherapy was delayed in 25%. There were no intensive care unit admissions nor deaths due to CDI. Exposure to H2-antagonists was identified as an independent risk factor for CDI recurrence. CONCLUSIONS: Although CDI in pediatric oncology and HSCT patients was associated with chemotherapy delay and hospitalization in approximately a quarter of patients, it was not associated with morbidity or mortality because patients had no attributable intensive care unit admission nor death. H2-antagonists are independent risk factors for CDI recurrence.

Prognostic role of perioperative acid-base disturbances on the risk of Clostridioides difficile infection in patients undergoing cardiac surgery.

BACKGROUND: It is unclear whether acid-base balance disturbances during the perioperative period may impact Clostridium difficile infection (CDI), which is the third most common major infection following cardiac surgery. We hypothesized that perioperative acid-base abnormalities including lactate disturbances may predict the probability of incidence of CDI in patients after cardiac procedures. METHODS: Of the 12,235 analyzed patients following cardiac surgery, 143 (1.2%) developed CDI. The control group included 200 consecutive patients without diarrhea, who underwent cardiac procedure within the same period of observation. Pre-, intra and post-operative levels of blood gases, as well as lactate and glucose concentrations were determined. Postoperatively, arterial blood was drawn four times: immediately after surgery and successively; 4, 8 and 12 h following the procedure. RESULTS: Baseline pH was lower and PaO2 was higher in CDI patients (p < 0.001 and p = 0.001, respectively). Additionally, these patients had greater base deficiency at each of the analyzed time points (p < 0.001, p = 0.004, p = 0.012, p = 0.001, p = 0.016 and p = 0.001, respectively). Severe hyperlactatemia was also more common in CDI patients; during the cardiac procedure, 4 h and 12 h after surgery (p = 0.027, p = 0.004 and p = 0.001, respectively). Multivariate logistic regression analysis revealed that independent risk factors for CDI following cardiac surgery were as follows: intraoperative severe hyperlactatemia (OR 2.387, 95% CI 1.155-4.933, p = 0.019), decreased lactate clearance between values immediately and 12 h after procedure (OR 0.996, 95% CI 0.994-0.999, p = 0.013), increased age (OR 1.045, 95% CI 1.020-1.070, p < 0.001), emergent surgery (OR 2.755, 95% CI 1.565-4.848, p < 0.001) and use of antibiotics other than periprocedural prophylaxis (OR 2.778, 95% CI 1.690-4.565, p < 0.001). CONCLUSION: This study is the first to show that perioperative hyperlactatemia and decreased lactate clearance may be predictors for occurrence of CDI after cardiac surgery.

Study on the interactive effect of deoxynivalenol and Clostridium perfringens on the jejunal health of broiler chickens.

With global warming and ban on antibiotics, it occurs occasionally that deoxynivalenol (DON) together with Clostridium perfringens impairs the gut health of broiler chickens. However, the interactive effect of DON and C. perfringens on intestinal health is still unknown. A total of 120 one-day-old Arbor Acres broilers were randomly distributed to 4 groups. Birds were gavaged with C. perfringens (8 × 108 CFU/d per bird) or sterile medium and fed a DON diet (0 or 5 mg of DON per kg diet) to investigate the interactive effects. The main effect analysis showed that DON diet significantly downregulated (P < 0.05) the mRNA expression of mucin-2, B-cell lymphoma-2-associated X, and cysteinyl aspartate-specific proteinase-3 of jejunal mucosa; decreased (P < 0.05) the indexes of ACE, Chao1, Shannon, and Simpson; and also decreased the relative abundance of the phylum Bacteroidete and the genera Lactococcus in jejunal contents of broilers chickens. Meanwhile, C. perfringens significantly increased (P < 0.05) crypt depth; decreased (P < 0.05) the ratio of villi height to crypt depth, the activity of jejunal diamine oxidase, and the relative abundance of Lactococcus; and upregulated (P < 0.05) the relative expression of B-cell lymphoma-2 and cysteinyl aspartate-specific proteinase-8. Furthermore, the interactions between DON and C. perfringens were most significant (P < 0.05) in the mRNA expression of lipopolysaccharide-induced TNF factor (LITAF) and TLR-4, the abundance of the genera Lactococcus in jejunal contents, and butyric acid concentrations in cecal contents of birds. Finally, Spearman correlation analysis suggested that the most negative correlations (P < 0.05) with the abundance of the genera except Lactobacillus were observed within the mRNA expression of LITAF. The abundance of Lactococcus had a positive correlation (P < 0.05) with the expression of Caspase-3. Most genera except Lactobacillus negatively correlated (P < 0.05) with acetic acid, butyric acid, and total short-chain fatty acids. In conclusion, dietary deoxynivalenol and C. perfringens challenge had a harmful effect on the jejunal health and should be carefully monitored in broiler production.

Differential expression of intestinal genes in necrotic enteritis challenged broiler chickens with 2 different Clostridium perfringens strains.

The primary cause of necrotic enteritis (NE) disease in chickens is the NetB-positive Clostridium perfringens bacterium. Many factors are known to affect the severity of NE in the challenge models of broiler chickens, and one of these factors is the virulence of C. perfringens strain. This study was conducted to evaluate the effect of 2 pathogenic C. perfringens strains in a NE challenge model on gut health and mRNA expression of genes encoding apoptosis, tight junction, immunity, and nutrient transporters in broilers. Day-old Ross-308 male broilers (n = 468) were allocated in a 2 × 3 factorial arrangement of treatments with in-feed antibiotics (no or yes) and challenge (Non, C. perfringens strain NE18, and C. perfringens strain NE36) as the factors. The birds in the challenged groups were inoculated with Eimeria species on day 9 and with a fresh suspension of C. perfringens NE18 or NE36 on day 14 and 15. Sample collection was performed on 2 birds of each pen on day 16. Necrotic enteritis challenge, impaired feed conversion ratio during day 0 to 16 compared with the control group where the effect of the NE36 challenge was more severe than that with NE18 (P < 0.001). The mRNA expression of mucin-2, immunoglobulin-G, occludin (P < 0.001), and tight junction protein-1 (P < 0.05) genes were downregulated in both challenged groups compared with the nonchallenged counterparts. Antibiotic supplementation, on the other hand, increased weight gain, and feed intake in all challenged birds (P < 0.01), but upregulated mucin-5ac and alanine, serine, cysteine, and threonine transporter-1 (P < 0.05) only in the NE18 challenged birds. The challenge with NE36 significantly upregulated caspase-8 and claudin-1 (P < 0.001), but downregulated glucose transporter-2 (P < 0.001) compared with the NE18 challenge. These results suggest that NE challenge is detrimental to the performance of broilers through compromised intestinal health, and different C. perfringens strains can affect the severity of the disease through modulating the expression of intestinal genes encoding proteins responsible for apoptosis, gut integrity, immunity, mucus production, and nutrient transporters.

Impact of Clostridioides difficile infection on the outcome of patients receiving a hematopoietic stem cell transplantation.

OBJECTIVES: Clostridioides difficile infections (CDI) are common in autologous (auto-HSCT) or allogenic hematopoietic stem cell transplant (allo-HSCT) recipients. However, the impact of CDI on patient outcomes is controversial. We conducted this study to examine the impact of CDI on patient outcomes. METHODS: We performed a retrospective single-center study, including 191 lymphoma patients receiving an auto-HSCT and 276 acute myeloid leukemia (AML) patients receiving an allo-HSCT. The primary endpoint was overall survival (OS). Secondary endpoints were causes of death and, for the allo-HSCT cohort, GvHD- and relapse-free survival (GRFS). RESULTS: The prevalence of CDI was 17.6% in the AML allo-HSCT and 7.3% in the lymphoma auto-HSCT cohort. A higher prevalence of bloodstream infections, but no differences concerning OS or cause of death were found for patients with CDI in the auto-HSCT cohort. [AU] In the allo-HSCT cohort, OS and GRFS were similar between CDI and non-CDI patients. However, the leading cause of death was relapse among non-CDI patients, but it was infectious diseases in the CDI group with fewer deaths due to relapse. CONCLUSIONS: CDI was not associated with worse survival in patients receiving a hematopoietic stem cell transplantation, and there were even fewer relapse-related deaths in the AML allo-HSCT cohort.

Necrotizing Soft Tissue Infections: A Focused Review of Pathophysiology, Diagnosis, Operative Management, Antimicrobial Therapy, and Pediatrics.

Background: Necrotizing fasciitis is a major health problem throughout the world. The purpose of this review is to assist providers with the care of these patients through a better understanding of the pathophysiology and management options. Methods: This is a collaborative review of the literature between members of the Surgical Infection Society of North America and World Society of Emergency Surgery. Results: Necrotizing fasciitis continues to be difficult to manage with the mainstay being early diagnosis and surgical intervention. Recognition of at-risk populations assists with the initiation of treatment, thereby impacting outcomes. Conclusions: Although there are some additional treatment strategies available, surgical debridement and antimicrobial therapy are central to the successful eradication of the disease process.

A new role for heat shock factor 27 in the pathophysiology of Clostridium difficile toxin B.

Clostridiumdifficile (CD) is a common pathogen that causes severe gastrointestinal inflammatory diarrhea in patients undergoing antibiotic therapy. Its virulence derives from two toxins, toxin CD, A and B (TcdA and TcdB) (Borriello et al. Rev Infect Dis 12, Suppl 2: S185-191, 1990). Among the prime candidates for CD colonization are patients with cystic fibrosis (CF), who are routinely treated with antibiotics and frequently hospitalized. Indeed, ~50% of patients with CF are colonized with virulent forms of CD but do not exhibit diarrhea (Bauer et al. Clin Microbiol Infect 20: O446-O449, 2014; Binkovitz et al. Am J Roentgenol 172: 517-521, 199; Zemljic et al. Anaerobe 16: 527-532, 2010). We found that TcdB has global effects on colonic cells, including reducing the steady-state levels of sodium-proton exchange regulatory factors, reducing the levels of heat shock protein (Hsp) 27, and increasing the fraction of total Hsp27 bound to the cystic fibrosis transmembrane conductance regulator (CFTR). Also, since some mutations in CFTR seem to be protective, we asked whether CFTR is a target of TcdB. We show here that TcdB increases the maturation of CFTR and transiently increases its function. These combined effects promote increased surface expression of CFTR, resulting in a transient increase in Cl- secretion. This increase is followed by a precipitous decline in both CFTR-dependent Cl- secretion and transepithelial resistance (TER), suggesting a breakdown in the epithelial cells' tight junctions. We also found that overexpressing Hsp27 reverses some of the deleterious effects of TcdB, in particular preserving TER and therefore likely the maintenance of barrier function. Thus, our data suggest that Hsp27 plays a role in the diarrhea generated by CD infection and is a potential therapeutic target for treating this diarrhea.NEW & NOTEWORTHYClostridium difficile (CD) is a common pathogen that causes severe gastrointestinal inflammatory diarrhea in patients undergoing antibiotic therapy. We provide new evidence that heat shock protein (Hsp) 27 is one of the key players in CD pathology and that increasing Hsp27 can prevent the decrease in transepithelial resistance induced by toxin CD B, pointing the way for pharmacologic therapies for patients with chronic CD infection that can increase Hsp27 as a means to mitigate the effects of CD on gastrointestinal pathology.

Are Clostridium difficile toxins nephrotoxic?

Clostridium difficile-associated disease (CDAD) occurs along a spectrum from simple uncomplicated enteritis to a multi-system disease which may include nephropathy. Pathology is attributed to bacterial toxins, but it is unclear if the latter are directly nephrotoxic. Anecdotes of renal disease from human biopsy findings suggest a variation of histopathologies, but data are relatively limited. Acute renal failure does occur in patients with advanced morbidity. CDAD can complicate chronic renal failure. Kidney tissue culture cytotoxicity has long been known. Kidney function alterations among animal models or diseased humans are relatively uncommon in mild to moderate enteritis. Rare findings of toxinemia are reported. Some have proposed that renal dysfunction arises more from pre-renal compromises. Direct toxin studies on whole kidney are sparse. The role of direct toxin-associated renal disease is worthy of further investigation given the current impetus towards the development of protective and therapeutic passive and active immunity. Hypotheses of toxin-direct or pre-renal toxin compromise of renal function prevail.

Clostridium sordelli causing malignant edema in a trauma patient: a case report and review of literature.

Clostridium sordelli infection is a rare but potentially lethal infection associated with abortions, injury, contaminated wounds, and illicit drug use. It causes a recognizable syndrome with marked leukocytosis. Rapid diagnosis and aggressive sepsis management is required for optimal outcome. We report a case in a trauma patient with delayed presentation after sustaining facial trauma with soil contamination. The critical care management is summarized and a review of the literature.

Clostridium difficile infection in oncology patients: epidemiology, pathophysiology, risk factors, diagnosis, and treatment.

Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the United States. Its incidence has been increasing in the recent years despite preventative measures. CDI increases annual expenses by 1.5 billion dollars. Cancer patients are at higher risk to acquire CDI, as explained by their frequent exposure to risk factors. CDI in cancer patients is associated with higher mortality rates and prolonged hospitalization. Furthermore, CDI affects the course of the disease by delaying treatments such as chemotherapy. Chemotherapeutics drugs are considered independent risk factors for CDI. This review discusses Clostridium difficile infection in cancer patients, including those who are receiving chemotherapy. Herein, we summarize recent data regarding the epidemiology, risk factors, including chemotherapy regimens, pathogenesis, diagnostic techniques and treatment options, including newer agents. Method: A literature search was performed using the PubMed and Google Scholar databases. The MeSH terms utilized in different combinations were 'clostridium difficile', 'neoplasia/cancer/oncology', 'chemotherapy', 'diagnosis', and 'treatment', in addition to looking up each treatment option individually to generate a comprehensive search. The articles were initially screened by title alone, followed by screening through abstracts. Full texts of pertinent articles (including letters to editors, case reports, case series, cohort studies, and clinical trials) were included in this review.

Sarcina ventriculi : Review of the Literature.

Sarcina ventriculi is an increasingly common gram-positive coccus, recognized in gastric biopsies, particularly of patients with delayed gastric emptying. It occurs most commonly in adult women and can be identified easily by its characteristic morphologic features, such as basophilic staining, cuboid shape, tetrad arrangement, red blood cell-sized packets, flattened cell walls, and refractile nature on light microscopy. Although the pathogenesis of the organism is debated, it has been implicated in cases of gastric perforation, emphysematous gastritis, and peritonitis as well as occurring in the background of gastric adenocarcinomas. This review of the literature discusses the clinical features, endoscopy findings, histopathology, ancillary studies, microbiology, pathogenesis, differential diagnosis, treatment, and prognosis of this bacterium based on 19 published cases.

Correlation between in vitro cytotoxicity and in vivo lethal activity in mice of epsilon toxin mutants from Clostridium perfringens.

Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein with a lethal effect on livestock, producing severe enterotoxemia characterized by general edema and neurological alterations. Site-specific mutations of the toxin are valuable tools to study the cellular and molecular mechanism of the toxin activity. In particular, mutants with paired cysteine substitutions that affect the membrane insertion domain behaved as dominant-negative inhibitors of toxin activity in MDCK cells. We produced similar mutants, together with a well-known non-toxic mutant (Etx-H106P), as green fluorescent protein (GFP) fusion proteins to perform in vivo studies in an acutely intoxicated mouse model. The mutant (GFP-Etx-I51C/A114C) had a lethal effect with generalized edema, and accumulated in the brain parenchyma due to its ability to cross the blood-brain barrier (BBB). In the renal system, this mutant had a cytotoxic effect on distal tubule epithelial cells. The other mutants studied (GFP-Etx-V56C/F118C and GFP-Etx-H106P) did not have a lethal effect or cross the BBB, and failed to induce a cytotoxic effect on renal epithelial cells. These data suggest a direct correlation between the lethal effect of the toxin, with its cytotoxic effect on the kidney distal tubule cells, and the ability to cross the BBB.

Recent changes in Clostridium difficile infection / Recentes mudanças da infecção por Clostridium difficile

Clostridium difficile is the main cause of nosocomial diarrhea. Diarrhea associated with C. difficile has increased incidence, morbidity, and mortality in the last few years. The major related risk factors include use of antibiotics, elderly patients and prolonged hospital stay. Many patients receive combinations of antibiotics or multiple antibiotics, which represents the main risk to develop diarrhea associated to C. difficile or its recurrence. Therefore, interventions to improve antibiotic prescribing, as well as compliance with infection control measures can reduce hospital-acquired C. difficile infections. This review addresses the epidemiological changes in C. difficile disease and its treatment.

Clostridium difficile é a principal causa de diarreia hospitalar. A diarreia por C. difficile aumentou sua incidência e sua morbiletalidade nos últimos anos. Os principais fatores de risco relacionados são uso de antibióticos, idosos e permanência hospitalar prolongada. Muitos pacientes recebem combinação de antibióticos ou múltiplos antibióticos, constituindo-se, assim, o principal fator de risco para o desenvolvimento de infecção ou de recorrência de diarreia associada ao C. difficile. Por isso, intervenções que otimizem a prescrição de antibióticos associado à aderência de medidas de controle de infecção podem reduzir aquisição dessa infecção. Assim, esta revisão aborda a mudança da epidemiologia da infecção por C. difficile e seu tratamento.

Clostridium difficile infection: clinical spectrum and approach to management.

Clostridium difficile is recognized globally as an important enteric pathogen associated with considerable morbidity and mortality due to the widespread use of antibiotics. The overall incidence of C. difficile-associated diarrhea (CDAD) is increasing due to the emergence of a hypervirulent strain known as NAP1/BI/027. C. difficile acquisition by a host can result in a varied spectrum of clinical conditions inclusive of both colonic and extracolonic manifestations. Repeated occurrence of CDAD, manifested by the sudden re-appearance of diarrhea and other symptoms usually within a week of stopping treatment, makes it a difficult clinical problem. C. difficile infection has also been reported to be involved in exacerbation of inflammatory bowel diseases. The first step in the management of a suspected CDAD case is the withdrawal of the offending agent and changing the antibiotic regimens. Antimicrobial therapy directed against C. difficile viz. metronidazole for mild cases and vancomycin for severe cases is needed. For patients with ileus, oral vancomycin with simultaneous intravenous (IV) metronidazole and intracolonic vancomycin may be given. Depending on the severity of disease, the further line of management may include surgery, IV immunoglobulin treatment or high dose of vancomycin. Adjunctive measures used for CDAD are probiotics and prebiotics, fecotherapy, adsorbents and immunoglobulin therapy. Among the new therapies fidaxomicin has recently been approved by the American Food and Drugs Administration for treatment of CDAD.

Clostridium difficile infection in cancer patients and hematopoietic stem cell transplant recipients.

Clostridium difficile has become the most common bacterial cause of nosocomial diarrhea. High rates of C. difficile infection (CDI) coupled with increasing morbidity and mortality attributed to CDI have sparked a renewed interest in this disease. Emergence of hypervirulent strains, rising rates of severe and recurrent infection and associated infection control challenges, and diagnostic and therapeutic dilemmas are major issues in the non-oncology population. Scant data on CDI exist in the cancer/transplant population. The purpose of this article is to describe the epidemiology, pathogenesis and management of CDI in patients receiving cancer chemotherapeutic agents, and in hematopoietic stem cell transplant recipients.

Clostridium difficile associated infection, diarrhea and colitis.

A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods: pulsed-field gel electrophoresis (NAP1), restriction endonuclease analysis (BI) and polymerase chain reaction (027). In 2004 and 2005, the US Centers for Disease Control and Prevention (CDC) emphasized that the risk of C. difficile-associated diarrhea (CDAD) is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors (PPIs) have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. difficile-associated colitis (CDAC), was rare, but its incidence has increased dramatically. Up to two-thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease (IBD). C. difficile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficile-associated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate specific therapy and implement effective control measures. A comprehensive C. difficile infection control management rapid response team (RRT) is recommended for each health care facility. A communication network between RRTs is recommended, in coordination with each country's department of health. Our aim is to convey a comprehensive source of information and to guide healthcare professionals in the difficult decisions that they face when caring for these oftentimes very ill patients.

Neuromuscular and central nervous system manifestations of Clostridium perfringens infections.

Infections with Clostridium perfringens usually manifest locally or spread to sepsis with multiorgan involvement, hemolysis or septic shock. Central nervous system (CNS) manifestations are rare and most frequently comprise meningitis with or without pneumencephalon, encephalitis, plexitis, cerebral abscess, or subdural empyema. The course of CNS affections is usually foudroyant and the outcome fatal. Neuromuscular manifestations of C. perfringens infections are much more frequent than CNS manifestations and comprise myonecrosis (gas gangrene), rhabdomyolysis, myositis, fasciitis, affection of the neuromuscular transmission, or affection of the peripheral nerves. C. perfringens infections usually start from the site of a recent surgical wound or trauma, a gastrointestinal or urogenital problem, or occur in association with malignancy. In quite a number of cases the source of origin remains speculative. Treatment of choice is surgical debridement of the infectious focus with radical removal of all necrotic tissue, resection of the corresponding lymphatics in addition to antibiotic therapy with penicillin G, aminoglycosides, or clindamycin or hyperbaric oxygenation. Despite these therapeutic options, the prognosis of CNS and neuromuscular involvement in an infection with C. perfringens is still poor. Only focal infections or clostridial brain abscesses may eventually have a more favorable outcome, if surgery and antibiotics are instantly provided. Generally, early recognition of the infectious agent is of paramount importance to prevent from spreading and the development of severe hemolysis, septic shock, or death.

The leukemoid reaction in Clostridium sordellii infection: neuraminidase induction of promyelocytic cell proliferation.

Life-threatening Clostridium sordellii infections have recently been reported in women undergoing therapeutic abortion, during natural childbirth, and in injection drug users. Shock, diffuse capillary leak, and a leukemoid reaction (LR) are cardinal features of these infections. The magnitude of the LR is highly correlated with mortality. We have isolated a 42-kDa extractable protein from C. sordellii culture supernatant that stimulates proliferation of promyelocytic HL-60 cells in vitro. Using mass spectrometry, we have identified this protein as the C. sordellii neuraminidase, NanS. Recombinant NanS (rNanS) dose dependently stimulated HL-60 cell proliferation. Increased proliferation was observed when HL-60 cells were cocultured with both rNanS and granulocyte-macrophage colony stimulating factor. In addition, NanS also modified vascular cell adhesion molecule 1, which orchestrates the release of mature and immature granulocytes from bone marrow stromal cells. Thus, neuraminidase likely plays an important role in the characteristic LR in C. sordellii infection.