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ABSTRACT: Abstract Objective: To provide a comprehensive review of the literature relating to Clostridium difficile (C. difficile) infection (CDI) in the pediatric population. Methods: Two investigators conducted independent searches of PubMed, Web of Science, and Scopus until March 31st, 2013. All databases were searched using the terms Clostridium difficile, CDI, CDAD, antibiotic associated diarrhea, C. difficile in combination with Pediatric and Paediatric. Articles which discussed pediatric CDI were reviewed and relevant cross references also read and evaluated for inclusion. Selection bias could be a possible limitation of this approach. Findings: There is strong evidence for an increased incidence of pediatric CDI. Increasingly, the infection is being acquired from the community, often without a preceding history of antibiotic use. The severity of the disease has remained unchanged. Several medical conditions may be associated with the development of pediatric CDI. Infection prevention and control with antimicrobial stewardship are of paramount importance. It is important to consider the age of the child while testing for CDI. Traditional therapy with metronidazole or vancomycin remains the mainstay of treatment. Newer antibiotics such as fidaxomicin appear promising especially for the treatment of recurrent infection. Conservative surgical options may be a life-saving measure in severe or fulminant cases. Conclusions: Pediatric providers should be cognizant of the increased incidence of CDI in children. Early and judicious testing coupled with the timely institution of therapy will help to secure better outcomes for this disease.
Current Medical Research and Opinion 05/2013; · 2.38 Impact Factor
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ABSTRACT: OBJECTIVES: Antibiotic exposure is the most important risk factor for Clostridium difficile infection (CDI). Most evaluations of antimicrobial risk factors have been conducted in healthcare settings. The objective of this meta-analysis was to evaluate the association between antibiotic exposure and community-associated CDI (CA-CDI) (i.e. symptom onset in the community with no healthcare facility admission within 12 weeks) and to determine the classes of antibiotics posing the greatest risk. METHODS: We searched four electronic databases for subject headings and text words related to CA-CDI and antibiotics. Studies that investigated the risk of CA-CDI associated with antibiotic usage were considered eligible. Data from the identified studies were combined using a random-effects model and ORs were calculated. RESULTS: Of 910 citations identified, eight studies (n = 30 184 patients) met our inclusion criteria. Antibiotic exposure was associated with an increased risk of CA-CDI (OR 6.91, 95% CI 4.17-11.44, I(2) = 95%). The risk was greatest with clindamycin (OR 20.43, 95% CI 8.50-49.09) followed by fluoroquinolones (OR 5.65, 95% CI 4.38-7.28), cephalosporins (OR 4.47, 95% CI 1.60-12.50), penicillins (OR 3.25, 95% CI 1.89-5.57), macrolides (OR 2.55, 95% CI 1.91-3.39) and sulphonamides/trimethoprim (OR 1.84, 95% CI 1.48-2.29). Tetracyclines were not associated with an increased CDI risk (OR 0.91, 95% CI 0.57-1.45). CONCLUSIONS: Antibiotic exposure was an important risk factor for CA-CDI, but the risk was different amongst different antibiotic classes. The risk was greatest with clindamycin followed by fluoroquinolones and cephalosporins, whereas tetracyclines were not associated with an increased risk.
Journal of Antimicrobial Chemotherapy 04/2013; · 5.07 Impact Factor
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ABSTRACT: To determine whether the incidence of Clostridium difficile infection (CDI) continues to increase in hospitalized pediatric patients, we evaluated data from a United States national inpatient database. For the period of 2003 to 2009, we found an increasing trend in the incidence of CDI. These data suggest greater effort be given to prevent and treat this infection in children.
The Pediatric Infectious Disease Journal 03/2013; · 3.58 Impact Factor
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ABSTRACT: BACKGROUND:: Children with inflammatory bowel disease (IBD), similar to adults, are at increased risk of acquiring a Clostridium difficile infection (CDI). Our objective was to characterize the health care burden associated with CDI in hospitalized pediatric patients with IBD. METHODS:: We extracted and analyzed cases with a discharge diagnosis of IBD or CDI from the U.S. Healthcare Cost and Utilization Project Kids' Inpatient Database. RESULTS:: In our primary analysis, we evaluated pediatric cases with a principal diagnosis of IBD or CDI. For the year 2009, we identified 12,610 weighted cases with IBD of which 3.5% had CDI. In children with IBD, CDI was independently associated with lengthier hospital stays (8.0 versus 6.0 days; adjusted regression coefficient, 2.1 days; 95% confidence interval [CI], 1.4-2.8), higher charges ($45,126 versus $34,703; adjusted regression coefficient, $11,506; 95% CI, 6192-16,820), and greater need for parenteral nutrition (15.9% versus 12.1%; adjusted odds ratio, 1.5; 95% CI, 1.1-2.0) and blood transfusion (17.7% versus 9.8%; adjusted odds ratio, 1.8; 95% CI, 1.4-2.4). There were no deaths. We made similar observations in a subanalysis of cases with principal or secondary diagnoses of IBD or CDI. The incidence of CDI in patients with IBD increased between 2000 and 2009 from 21.7 to 28.0 cases per 1000 IBD cases per year (P < 0.001). There was a significant increase in CDI complicating ulcerative colitis (28.1 versus 42.2, P < 0.001) but not for Crohn's disease (18.3 versus 20.3). CONCLUSIONS:: CDI represents a significant health care burden in hospitalized children with IBD.
Inflammatory Bowel Diseases 03/2013; · 4.86 Impact Factor
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ABSTRACT: BACKGROUND AND AIM: Proton pump inhibitors (PPI) and H(2) -receptor antagonists (H(2) RA) are frequently prescribed in hospitalized patients with cirrhosis. There are conflicting reports regarding the role of acid suppressive therapy in predisposing hospitalized patients with cirrhosis to spontaneous bacterial peritonitis (SBP).The aim of this meta-analysis was to evaluate the association between acid-suppressive therapy and the risk of SBP in hospitalized patients with cirrhosis. METHODS: We searched MEDLINE and 4 other databases for subject headings and text words related to SBP and acid-suppressive therapy. All observational studies that investigated the risk of SBP associated with PPI/H2RA therapy and utilized SBP as an endpoint were considered eligible. Data from the identified studies were combined by means of a random-effects model and odds ratios (ORs) were calculated. RESULTS: Eight studies (n=3,815 patients) met inclusion criteria. The risk of hospitalized cirrhotic patients developing SBP increased when using acid-suppressive therapy. The risk was greater with PPI therapy (n= 3,815; OR 3.15, 95% CI 2.09-4.74) as compared to those on H2RA therapy (n=562; OR 1.71, 95% CI 0.97- 3.01). CONCLUSIONS: Pharmacologic acid-suppression was associated with a greater risk of SBP in hospitalized patients with cirrhosis. Cirrhotic patients receiving a PPI have approximately 3 times the risk of developing SBP compared to those not receiving this medication. Prospective studies may help clarify this relationship and shed light on the mechanism(s) by which acid-suppressive therapy increases the risk of SBP in hospitalized patients with cirrhosis.
Journal of Gastroenterology and Hepatology 11/2012; · 2.87 Impact Factor
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ABSTRACT: Dear Editor: We recognize the concerns raised by Drs Mahady and
Webster in their letter to the editor. We agree that quality
appraisal of individual studies is indeed important for any
meta-analysis, and that the validity of the summary estimates
depends on the quality of the included studies. We have now
used the Newcastle–Ottawa scale1 to evaluate the 30 studies
included in our original meta-analysis. When only high quality
studies (score �7, n � 25) were analyzed separately, proton
pump inhibitor (PPI) therapy continued to be associated with a
2-fold increase in risk for Clostridium difficile infection (odds
ratio (OR), 2.24; 95% confidence interval [CI], 1.87–2.69), and
high heterogeneity persisted.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2012; 10(9):1057-1058. · 5.64 Impact Factor
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Abhishek Deshpande,
Vinay Pasupuleti,
Preethi Patel, Chaitanya Pant,
Mangesh Pagadala,
Geraldine Hall,
Bo Hu,
Anil Jain,
David D K Rolston,
Thomas J Sferra,
Ashish Atreja
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ABSTRACT: Abstract Background: The incidence and severity of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is increasing. CDI is diagnosed by toxin enzyme immunoassay (EIA) or real-time polymerase chain reaction (PCR) performed on stool samples. An earlier study evaluating EIA in IBD patients with CDI suggested that more than one stool sample be tested to increase diagnostic yield. We investigated whether repeat stool testing improves diagnostic accuracy for CDI in hospitalized IBD patients compared to hospitalized patients with CDI and no IBD. Methods: We performed retrospective data analysis from January 2005-May 2011 on 63,086 hospitalized patients who were tested for CDI using EIA or PCR. Of these, 2579 patients had IBD. Transition probabilities were calculated based on results from repeated tests. Results: Inclusive of all inpatients tested for CDI, 56,583 were tested using toxin EIA and 6503 were tested using PCR. In patients with no IBD, the first stool sample tested was positive in 90% and 94% with EIA and PCR respectively. In IBD patients tested using EIA, 101 were diagnosed with CDI. The first stool sample tested was positive in 81% of patients. Successive second and third stool samples yielded additional 14% and 5% CDI positive IBD patients. Conclusions: Approximately one in five IBD patients with CDI required repeat testing to yield a positive result with EIA. There are minimal diagnostic gains of repeat testing by EIA or PCR in patients without IBD. We recommend repeat stool testing for CDI when using EIA to increase diagnostic yield in IBD patients.
Current Medical Research and Opinion 08/2012; 28(9):1553-60. · 2.38 Impact Factor
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ABSTRACT: In the past decade, there has been a growing epidemic of Clostridium difficile infection (CDI). During this time, use of proton pump inhibitors (PPIs) has increased exponentially. We evaluated the association between PPI therapy and the risk of CDI by performing a meta-analysis.
We searched MEDLINE and 4 other databases for subject headings and text words related to CDI and PPI in articles published from 1990 to 2010. All observational studies that investigated the risk of CDI associated with PPI therapy and used CDI as an end point were considered eligible. Two investigators screened articles independently for inclusion criteria, data extraction, and quality assessment; disagreements were resolved based on consensus with a third investigator. Data were combined by means of a random-effects model and odds ratios were calculated. Subgroup and sensitivity analyses were performed based on study design and antibiotic use.
Thirty studies (25 case-control and 5 cohort) reported in 29 articles met the inclusion criteria (n = 202,965). PPI therapy increased the risk for CDI (odds ratio, 2.15, 95% confidence interval, 1.81-2.55), but there was significant heterogeneity in results among studies (P < .00001). This association remained after subgroup and sensitivity analyses, although significant heterogeneity persisted among studies.
PPI therapy is associated with a 2-fold increase in risk for CDI. Because of the observational nature of the analyzed studies, we were not able to study the causes of this association. Further studies are needed to determine the mechanisms by which PPI therapy might increase risk for CDI.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2012; 10(3):225-33. · 5.64 Impact Factor
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Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 02/2012; · 5.64 Impact Factor
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ABSTRACT: To investigate the association of Clostridium difficile infection (CDI) with the outcomes of hospitalized patients with end-stage renal disease (ESRD).
We extracted all adult cases with a discharge diagnosis of ESRD or CDI from the United States Nationwide Inpatient Sample 2009 database. Outcome variables (mortality, length of hospital stay [LOS], and hospitalization charges), demographic information, and comorbidity data were collected. Data were evaluated by univariate and multiple regression analyses.
We identified 184,139 cases with ESRD of which 2.8% had CDI. Comparison of patients with ESRD + CDI to those with only ESRD revealed in-hospital mortality (13.2% vs 5.3%; P < 0.001), LOS (17.3 vs 7.1 days; P < 0.001), and charges ($124,846 vs $56,663; P < 0.001) to be more than 2-fold greater. In the ESRD cohort (ESRD only and ESRD + CDI), CDI was independently associated with greater mortality (adjusted odds ratio, 2.15; 95% CI, 2.07-2.24; P < 0.001), longer LOS (mean difference, 9.4 days; 95% CI, 9.2-9.5; P < 0.001), and higher charges (mean difference, $62,824; 95% CI, 61,615-64,033; P < 0.001).
Clostridium difficile infection is associated with significantly worse outcomes in hospitalized patients with ESRD.
Journal of Investigative Medicine 02/2012; 60(2):529-32. · 1.96 Impact Factor
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ABSTRACT: The rising incidence of Clostridium difficile (C. difficile) infection or CDI is now a problem of pandemic proportions. The NAP1 hypervirulent strain of C. difficile is responsible for a majority of recent epidemics and the widespread use of fluoroquinolone antibiotics may have facilitated the selective proliferation of this strain. The NAP1 strain also is more likely to cause severe and fulminant colitis characterized by marked leukocytosis, renal failure, hemodynamic instability, and toxic megacolon. No single test suffices to diagnose severe CDI, instead; the clinician must rely on a combination of clinical acumen, laboratory testing, and radiologic and endoscopic modalities. Although oral vancomycin and metronidazole are considered standard therapies in the medical management of CDI, recently it has been demonstrated that vancomycin is the more effective antibiotic in cases of severe disease. Moreover, early surgical consultation is necessary in patients who do not respond to medical therapy or who demonstrate rising white blood cell counts or hemodynamic instability indicative of fulminant colitis. Subtotal colectomy with end ileostomy is the procedure of choice for fulminant colitis. When applied to select patients in a judicious and timely fashion, surgery can be a life-saving intervention. In addition to these therapeutic approaches, several investigational treatments including novel antibiotics, fecal bacteriotherapy and immunotherapy have shown promise in the care of patients with severe CDI.
European Journal of Internal Medicine 12/2011; 22(6):561-8. · 2.00 Impact Factor
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ABSTRACT: Current detection methods for Clostridium difficile infection (CDI) can be time-consuming and have variable sensitivities. Real-time polymerase chain reaction (PCR) may allow earlier and more accurate diagnosis of CDI than other currently available diagnostic tests. A meta-analysis was performed to determine the diagnostic accuracy of real-time PCR.
We searched MEDLINE (Pubmed/Ovid) and 4 other online electronic databases (1995-2010) to identify diagnostic accuracy studies that compared PCR with cell culture cytotoxicity neutralization assay (CCCNA) or anaerobic toxigenic culture (TC) of C. difficile. Screening for inclusion, data extraction, and quality assessment were carried out independently by 2 investigators and disagreements resolved. Data were combined by means of a random-effects model, and summary receiver operating characteristic curves and diagnostic odds ratios were calculated.
Nineteen studies (7392 samples) met our inclusion criteria. The overall mean sensitivity of PCR was 90% (95% confidence interval [CI]: 88%-91%), specificity 96% (CI: 96%-97%), positive likelihood ratio 26.89 (CI: 20.81-34.74), negative likelihood ratio 0.11 (CI: .08-.15), diagnostic odds ratio 278.23 (CI: 213.56-362.50), and area under the curve 0.98 (CI: .98-.99). Test accuracy depended on the prevalence of C. difficile but not on the reference test used. At C. difficile prevalence of <10%, 10%-20% and >20% the positive predictive value and the negative predictive value were 71%, 79%, 93% and 99%, 98% and 96%, respectively.
Real-time PCR has a high sensitivity and specificity to confirm CDI. Overall diagnostic accuracy is variable and depends on CDI prevalence.
Clinical Infectious Diseases 10/2011; 53(7):e81-90. · 9.15 Impact Factor
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ABSTRACT: The aim of this brief review is to summarize the literature as it relates to the potential value of repeat stool testing for Clostridium difficile (C. difficile) toxin using an enzyme immunoassay (EIA) for toxin A&B and also propose a potential newer algorithm for diagnosing C. difficile.
Two investigators conducted independent literature searches using PubMed, Web of Science, and Scopus until May 1st, 2010. All databases were searched using the terms Clostridium difficile, CDAD, antibiotic associated diarrhea, C. difficile in combination with enzyme immunoassay, enzyme linked immunosorbent assay, Clostridium difficile toxin A, Clostridium difficile toxin B, Clostridium difficile toxin and repeat stool testing. Articles which discussed EIA in C. difficile infection (CDI) patients were reviewed and relevant cross references also read and evaluated for inclusion. Selection bias could be a possible limitation of the approach used in selecting or finding articles for this article.
The evidence for repeat stool testing for C. difficile toxin detection using toxin EIA is becoming weaker. Most recent published practice guidelines recommend a two- or three-step testing algorithm for the detection of C. difficile.
EIA for C. difficile stool toxin has a limited sensitivity, but, it does not warrant repeat stool testing. The data for this are suggestive but not conclusive. More studies and better tests are needed to have clear guidelines which can specify the number of tests needed in a diagnostic workup of suspected C. difficile infection. A two-step or three-step method in the diagnosis of C. difficile-associated diarrhea offered a marked increase in sensitivity compared to that of toxin A&B EIA alone.
Current Medical Research and Opinion 10/2010; 26(11):2635-41. · 2.38 Impact Factor
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Clinical Pediatrics 09/2010; 49(9):907; author reply 908. · 1.15 Impact Factor
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Journal of Investigative Medicine 08/2010; 58(6):807. · 1.96 Impact Factor
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ABSTRACT: We report a patient with carcinomatous meningitis secondary to known transitional cell carcinoma of the bladder. The patient presented with multiple focal neurological signs and symptoms. Diagnosis was suggested by magnetic resonance imaging and confirmed by analysis of the cerebrospinal fluid. He received whole brain radiotherapy despite a poor prognosis. To our knowledge, this is only the fifth reported case of neoplastic meningitis due to bladder cancer with confirmatory imaging and cytology and only the fourth reported case that presented with cranial nerve involvement.
Southern medical journal 08/2010; 103(8):809-12. · 0.92 Impact Factor
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ABSTRACT: Clostridium difficile infection (CDI) has emerged as a problem of epidemic proportions. Previous exposure to broad-spectrum antibiotics remains the most important predisposing factor for the disease. However, PPIs are increasingly being overprescribed and recent research has, therefore, focused on the association between PPI therapy and CDI. While the data remain observational, increasing evidence exists for at least a modest association between PPI use and CDI.
Nature Reviews Gastroenterology & Hepatology 10/2009; 6(9):555-7. · 8.10 Impact Factor
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ABSTRACT: Previous studies have identified laboratory markers for severe Clostridium difficile infection (CDI). The most consistent of these markers is the presence of marked leukocytosis. We examined the validity of these markers as predictors of mortality in patients with CDI. We excluded patients with preexisting hematologic conditions that would be expected to impair their ability to demonstrate leukocytosis. On univariate analysis, marked leukocytosis (P = 0.02), thrombocytopenia (P = 0.008), and increased blood urea nitrogen (P < 0.001) and creatinine (P = 0.001) levels were found to be significantly associated with mortality in patients with CDI. However, on logistic regression analysis, only renal impairment was found to be an independent predictor (odds ratio, 5.07). Importantly, in our study, leukocytosis was not an independent predictor after adjustment for other variables, which may be due to our selection criteria when adjusting for confounding variables. We are therefore of the opinion that in immunocompromised hosts who are leukopenic at the time of CDI diagnosis, other laboratory markers should be identified to serve as indicators for severe disease.
Journal of Investigative Medicine 09/2009; 58(1):43-5. · 1.96 Impact Factor
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ABSTRACT: : Recent research has recognized surrogate markers for Clostridium difficile-associated diarrhea (CDAD). Among the most consistently identified markers are the leukocyte count, platelet count, and albumin level. Previous investigators failed to exclude patients with hematologic disorders that may have confounded their results. Therefore, the exclusion of this subset from our study lends it a unique perspective.
: We undertook a retrospective review of inpatients at our institution that were diagnosed with nosocomial diarrhea and subsequently had a stool sample sent for C. difficile toxins A and B. Patients with major hematologic disorders were excluded.
: A total of 77 C. difficile-positive patients and 91 C. difficile-negative patients were studied. Patients with CDAD had a significantly higher leukocyte and platelet count but a lower albumin level compared with patients without CDAD.
: Our results support the conclusion of preceding studies that leukocytosis, thrombocytosis, and hypoalbuminemia are reliable clinical predictors for CDAD even after careful exclusion of confounding factors.
Journal of Investigative Medicine 01/2009; 57(1):40-2. · 1.96 Impact Factor
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ABSTRACT: Clostridium difficile associated diarrhea (CDAD) is an important cause of hospital-acquired diarrhea, and increasingly of community-acquired diarrhea. The occurrence of CDAD in the hospitalized patient is associated with increased length of stay, morbidity, mortality, and healthcare costs. Exposure to antimicrobials is the single most important predisposing factor for acquiring CDAD. The data suggesting that fluoroquinolones are an important risk factor for CDAD is becoming stronger. Also, different fluoroquinolones may pose different risks for CDAD development.
The aim of this commentary is to summarize the literature as it relates to the role that fluoroquinolones may have in CDAD.
PubMed and Ovid MEDLINE were searched using the terms fluoroquinolones, ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin in combination with C. difficile, CDAD, pseudomembranous colitis and antibiotic associated diarrhea.
The evidence for an association between fluoroquinolone use and CDAD, especially CDAD due to the hypervirulent NAP1 strain or the polymerase chain reaction ribotype 027, is becoming stronger.
Fluoroquinolones appear to predispose patients to CDAD. The data are suggestive but not conclusive. More studies are needed to define the role that fluoroquinolones play in the development of CDAD. Meticulous and enhanced infection control practices at all times and the judicious use of antimicrobials will help contain the epidemic of CDAD.
Current Medical Research and Opinion 03/2008; 24(2):329-33. · 2.38 Impact Factor
