Clostridium difficile infection in patients with unexplained leukocytosis

PURPOSE: To determine whether unrecognized Clostridium difficile infection is responsible for a substantial proportion of cases of unexplained leukocytosis in a tertiary care hospital setting. METHODS: We prospectively identified 60 patients who had unexplained leukocytosis (white blood cell count > or =15,000/mm3). Fecal specimens were tested for C. difficile toxin using an enzyme immunosorbent assay. We compared the clinical features of patients who had positive or negative assay results, as well as of 26 hospitalized control patients who did not have unexplained leukocytosis. RESULTS: Thirty-five (58%) of the patients with unexplained leukocytosis had C. difficile toxin in at least one fecal specimen as compared with 3 (12%) of the controls (P <0.001). Symptoms of colitis were often mild or absent at the time the white blood cell count was first elevated or, if present, had not been recognized by the attending physicians. Leukocytosis resolved promptly in most patients who were treated with metronidazole. In the 25 patients (42%) who had a negative test for C. difficile toxin, leukocytosis also tended to resolve during empiric therapy with metronidazole; some of these patients may have had C. difficile infection. CONCLUSION: The majority of patients in our hospital who had unexplained leukocytosis had C. difficile infection. Unexplained leukocytosis in hospitalized patients should prompt a search for symptoms and signs consistent with C. difficile infection and a study to detect C. difficile. Empiric therapy with metronidazole may be effective in the appropriate epidemiologic setting.     

Prediction of Clostridium difficile infection based on gut microbial traits in patients with Clostridium difficile colonization

正To the Editor : Cirrhotic patients usually require multiple hospitalizations due to upper gastrointestinal hemorrhage, abdominal infection, and hepatic encephalopathy. These patients need long-term hospital stay, and long-term application of proton pump inhibitors and antibiotics, which may result in Clostridium difficile infection(CDI) [1]. To our best knowledge, Clostridium difficile colonization(CDC) is the major risk factor for the pathogenesis of CDI.     

Clostridium difficile infection

Summary Considering the current wide use of antimicrobial agents, the general internist is commonly faced with the patient at risk for diarrhea due toC. difficile. The diagnosis should be considered for any patient with diarrhea who has received any type of antibiotic therapy in the preceding 4–6 weeks. Symptoms may range from a minor bout of diarrhea to fulminant and fatal colitis. Diagnosis usually requires demonstration of the toxin in stool; culture of the organism and fiberoptic endoscopy may play an adjunctive role in selected clinical settings. The ultimate goal in the treatment forC. difficile infection is to repopulate the normal colonic flora in the most efficacious manner. Minimally symptomatic patients may respond to discontinuing the offending antimicrobial agent or using nonspecific binding agents. Oral vancomycin continues to be the “gold standard” for specific treatment, while metronidazole therapy is considered the first-line agent for individuals with milder infection. Oral bacitracin shows promise, though large studies are lacking. Patients with multiple relapses ofC. difficile diarrhea can be treated with prolonged courses of vancomycin or a combination of vancomycin and rifampin. Intensive care unit patients who are NPO have few therapeutic options besides intravenous administration of metronidazole and oral administration of vancomycin via clamped nasogastric tube. Preventive efforts are directed at cautious use of antibiotics and the use of vinyl gloves when caring for patients with known infection.     

Clostridium difficile infection

Clostridium difficile infection is the leading cause of antibiotic- and healthcare-associated diarrhea, and its containment and treatment imposes a significant financial burden, estimated to be over $3 billion in the USA alone. Since the year 2000, CDI epidemics/outbreaks have occurred in North America, Europe and Asia. These outbreaks have been variously associated with, or attributed to, the emergence of Clostridium difficile strains with increased virulence, an increase in resistance to commonly used antimicrobials such as the fluoroquinolones, or host susceptibilities, including the use of gastric acid suppressants, to name a few. Efforts to elucidate C. difficile pathogenic mechanisms have been hampered by a lack of molecular tools, manipulatable animal models, and genetic intractability of clinical C. difficile isolates. However, in the past 5 y, painstaking efforts have resulted in the unraveling of multiple C. difficile virulence-associated pathways and mechanisms. We have recently reviewed the disease, its associated risk factors, transmission and interventions (Viswanathan, Gut Microbes 2010). This article summarizes genetics, non-toxin virulence factors, and host-cell biology associated with C. difficile pathogenesis as of 2011, and highlights those findings/factors that may be of interest as future intervention targets.     

Treatment of Clostridium difficile infection in pediatric patients

Clostridium difficile causes infections that can either remain asymptomatic or manifest as clinical disease. In this report, problems, possible solutions, and future perspectives on the treatment of C. difficile infections (CDIs) in pediatric patients are discussed. CDI, despite increasing as a consequence of the overuse and misuse of antibiotics, remains relatively uncommon in pediatrics mainly because younger children are poorly susceptible to the action of C. difficile toxins. In most such cases, C. difficile disease is mild to moderate and discontinuation of the administered antibiotics in patients receiving these drugs when CDI develops, or administration of metronidazole, is sufficient to solve this problem. In severe or frequently relapsing cases, vancomycin is the drug of choice. Probiotics do not seem to add significant advantages. Other treatment options must be reserved for severe cases and be considered as a salvage treatment, although potential advantages in pediatric patients remain unclear.     

Systemic absorption of oral vancomycin in patients with Clostridium difficile infection

Oral vancomycin is utilized in the treatment of severe Clostridium difficile infection (CDI). We prospectively measured serum vancomycin concentrations (SVC) in patients treated with oral vancomycin. The SVC was measured by immunoassay prior to, and at least 3 days after, the administration of oral vancomycin 125 mg every 6 h. Patients treated with intravenous vancomycin were excluded. Fifty-seven patients with a mean age of 74 y (± 18) were enrolled. There was no detectable SVC in 56 patients (98%); 1 patient had a transient SVC of 6.7 μg/ml that was not detectable on subsequent testing. The severity of the CDI and/or renal failure did not have an effect on SVC. Orally administered vancomycin at 125 mg 4 times daily was not absorbed from the gastrointestinal tract.     

Risk factors for Clostridium difficile infection in cirrhotic patients

BackgroundCirrhotic patients are susceptible to Clostridium difficile infection (CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI.MethodsA total of 526 cirrhotic patients admitted to our hospital between May 2015 and October 2015 were included in this study. Stool samples were collected upon admission for the detection of CDI and toxin. CDI was monitored during the hospital stay. In total, 34 cases showed CDI. Then we analyzed the effects of age, sex, C. difficile colonization (CDC), multiple hospitalization, extended hospital stay, elevation of total bilirubin (TBIL), creatinine (Cr), Child-Pugh grade C, hepatic encephalopathy, hepatorenal syndrome, upper gastrointestinal hemorrhage, and exposure of antibiotics and proton pump inhibitor (PPI) on the CDI in cirrhotic patients.ResultsPatients in the CDI group had more frequent CDC, multiple hospitalization, and extended hospital stay compared to those in the non-C. difficile infection (NCDI) group. Patients in the CDI group had higher TBIL and Cr, and higher frequency of Child-Pugh grade C, hepatic encephalopathy, upper gastrointestinal hemorrhage compared with those in the NCDI group. Multiple logistic regression analysis indicated that age >60 years (OR=1.689; 95% CI: 1.135–3.128), multiple hospitalization (OR=3.346; 95% CI: 1.392–8.043), length of hospital stay >20 days (OR=1.564; 95% CI: 1.113–2.563), hypoproteinemia (OR=4.962; 95% CI: 2.053–11.996), CDC (OR=18.410; 95% CI: 6.898–49.136), hepatic encephalopathy (OR=1.357; 95% CI: 1.154–2.368), and exposure of antibiotics (OR=1.865; 95% CI: 1.213–2.863) and PPI (OR=3.125; 95% CI: 1.818–7.548) were risk factors of CDI.ConclusionsAge >60 years, multiple hospitalization, length of hospital stay >20 days, hypoproteinemia, CDC, hepatic encephalopathy, and exposure of antibiotics and PPI were risk factors for CDI in cirrhotic patients. These may contribute to the early diagnosis and monitoring of CDI in clinical practice.     

Clostridium tertium septicemia in patients with neutropenia

Eighteen adult patients with hematologic malignancy developed bacteremia due to Clostridium tertium while neutropenic. Fifteen had accompanying abdominal pain, colonic bleeding, or diarrhea, and three had perianal cellulitis. Fourteen recovered with antibiotic therapy alone; no patient was treated by surgery. C. tertium is an unusual Clostridium because it is resistant to many beta-lactam antibiotics and to metronidazole but is susceptible to vancomycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. It is possible that use of third-generation cephalosporins (cefotaxime, ceftizoxime, ceftazidime) for treating febrile episodes in the absence of any selective intestinal decontamination with trimethoprim-sulfamethoxazole or ciprofloxacin may have resulted in selection for C. tertium in our patients.     

老年住院患者艰难梭菌感染的危险因素分析

目的 分析老年住院患者艰难梭菌感染(CDI)的影响因素。方法 回顾性分析2013年11月至2021年9月于空军军医大学西京医院老年病科收治的具有腹痛、腹胀及腹泻等症状114例患者的临床资料。采用多重聚合酶链式反应方法对艰难梭菌毒素进行检测,根据检测结果将患者分为毒素阴性组(47例)及毒素阳性组(67例),比较2组患者的一般资料及实验室化验指标。采用SPSS 25.0软件进行数据分析。根据数据类型,分别采用独立样本t检验、秩和检验和χ²检验进行组间比较;采用多因素二元logistic回归分析CDI的影响因素。结果 与阳性组相比,阴性组的谷草转氨酶[29.0(22.0,49.0)和20.0(15.0,34.0)U/L]、谷丙转氨酶[21.0(14.0,41.0)和16.0(8.0,20.0)U/L]、白蛋白[(33.22±4.94)和(31.53±3.49) g/L]、碱性磷酸酶[113.0(69.0,163.0)和74.0(56.0,101.0)U/L]、γ-谷氨酰转肽酶[64.0(23.0,157.0)和35.0(22.0,76.0)U/L]和凝血酶时间[18.6(17.6,20.4)和17.8(16.7,18.9)s]显著升高,差异均有统计学意义(均P＜0.05);与阳性组相比,阴性组冠心病发病率[8(17.0%)和32(47.8%)]、质子泵抑制剂[16(34.0%)和42(62.7%)]及抗生素[9(19.1%)和39(58.2%)]的使用率降低,差异均有统计学意义(均P＜0.05)。多因素二元logistic回归分析显示:白蛋白水平是CDI的保护性因素(OR=0.894,95%CI 0.802~0.996;P=0.041);抗生素使用率是CDI的独立危险因素(OR=18.398,95%CI 1.225～276.346;P=0.035)。结论 CDI的发生率与白蛋白水平呈负相关,与抗生素使用率呈正相关;抗生素的使用会升高CDI发生率,在老年住院患者中需动态监测并及时干预。     

Update on Clostridium difficile infection

Clostridium difficile is a major cause of antibiotic-associated diarrhea in hospital and community settings, spreading endemic and epidemic disease in developed and developing areas throughout the world. Its toxins A and B cause epithelial disruption, inflammation, and secretion. Diagnosis of infection with C. difficile is based on appropriate clinical presentation and demonstration of the presence of either toxin A or B, or both. Established treatment is still predominantly metronidazole and vancomycin. The association of antibiotic therapy with recurrent disease and antimicrobial resistance, especially vancomycin-resistant enterococci, highlights the need for new approaches to managing C. difficile infection.     

Use of probiotics in prevention and treatment of patients with Clostridium difficile infection

Clostridium difficile is an anaerobic, gram positive, sporulating, toxin-producing bacillus which causes a spectrum of clinical disease ranging from an asymptomatic carrier state to toxic megacolon and fulminant disease. Infection with C. difficile is an expensive and pervasive health care burden. The current theory regarding the development of C. difficile infection (CDI) suggests that disruption of the structure and/or function of an individual's normal intestinal microbiota enables colonization by C. difficile, and in the absence of an effective immune response, the bacteria causes illness. In this article we discuss the role of the colonic microbiota in the development of CDI and the potential role of probiotics in preventing and treating CDI. We review the evidence from in vitro laboratory and pre-clinical studies, as well as evidence from clinical studies and discuss the current recommendations for the use of probiotics for CDI in clinical practice.     

Reducing the risk of severe complications among patients with Clostridium difficile infection

BACKGROUND:

The incidence and severity of Clostridium difficile infections are increasing, and there is a need to optimize the prevention of complicated disease.

OBJECTIVE:

To identify modifiable processes of care associated with an altered risk of C difficile complications.

METHODS:

A retrospective cohort study (with prospective case ascertainment) of all C difficile infections during 2007/2008 at a tertiary care hospital was conducted.

RESULTS:

Severe complications were frequent (occurring in 97 of 365 [27%] C difficile episodes), with rapid onset (median three days postdiagnosis). On multivariable analysis, nonmodifiable predictors of complications included repeat infection (OR 2.67), confusion (OR 2.01), hypotension (OR 0.97 per increased mmHg) and elevated white blood cell count (OR 1.04 per 10⁹ cells/L). Protection from complications was associated with initial use of vancomycin (OR 0.24); harm was associated with ongoing use of exacerbating antibiotics (OR 3.02).

CONCLUSION:

C difficile infections often occur early in the disease course and are associated with high complication rates. Clinical factors that predicted a higher risk of complications included confusion, hypotension and leukocytosis. The most effective ways to improve outcomes for patients with C difficile colitis are consideration of vancomycin as first-line treatment for moderate to severe cases, and the avoidance of unnecessary antibiotics.