Hoonmo L. Koo

Noroviruses: The Most Common Pediatric Viral Enteric Pathogen at a Large University Hospital After Introduction of Rotavirus Vaccination

We conducted an 8.5-year study examining enteric viruses at Texas Childrens Hospital (TCH) before and after rotavirus vaccine introduction. Norovirus prevalence was 10.9%. Rotavirus prevalence decreased 64% after vaccine licensure. Noroviruses are the most common TCH enteropathogen and will likely eclipse rotaviruses as the most important US pediatric gastroenteritis pathogen.

Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance

Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospitalized patients. The incidence and severity of CDIs are increasing. The increased incidence and severity of the disease has sparked interest in the optimal treatment of CDI as well as the use of new therapies and drug discovery. Current treatment strategies are inadequate with decreased response rates to metronidazole, and high recurrence rates with the use of metronidazole and oral vancomycin. Although incidence rates continue to be low, in vitro resistance to antibiotics used for the treatment of CDI has been noted. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new antibiotic treatment options for CDI. This review will focus primarily on scientific studies published in the last 36 months in order to provide an up-to-date review on the topic.

Real-Time Polymerase Chain Reaction Detection of Asymptomatic Clostridium difficile Colonization and Rising C. difficile –Associated Disease Rates

OBJECTIVE To evaluate the accuracy of real-time polymerase chain reaction (PCR) for Clostridium difficile-associated disease (CDAD) detection, after hospital CDAD rates significantly increased following real-time PCR initiation for CDAD diagnosis. DESIGN Hospital-wide surveillance study following examination of CDAD incidence density rates by interrupted time series design. SETTING Large university-based hospital. PARTICIPANTS Hospitalized adult patients. METHODS CDAD rates were compared before and after real-time PCR implementation in a university hospital and in the absence of physician and infection control practice changes. After real-time PCR introduction, all hospitalized adult patients were screened for C. difficile by testing a fecal specimen by real-time PCR, toxin enzyme-linked immunosorbent assay, and toxigenic culture. RESULTS CDAD hospital rates significantly increased after changing from cell culture cytotoxicity assay to a real-time PCR assay. One hundred ninety-nine hospitalized subjects were enrolled, and 101 fecal specimens were collected. C. difficile was detected in 18 subjects (18%), including 5 subjects (28%) with either definite or probable CDAD and 13 patients (72%) with asymptomatic C. difficile colonization. CONCLUSIONS The majority of healthcare-associated diarrhea is not attributable to CDAD, and the prevalence of asymptomatic C. difficile colonization exceeds CDAD rates in healthcare facilities. PCR detection of asymptomatic C. difficile colonization among patients with non-CDAD diarrhea may be contributing to rising CDAD rates and a significant number of CDAD false positives. PCR may be useful for CDAD screening, but further study is needed to guide interpretation of PCR detection of C. difficile and the value of confirmatory tests. A gold standard CDAD diagnostic assay is needed.

Norovirus gastroenteritis successfully treated with nitazoxanide.

Infectious diarrhea is a common occurrence in the immunosuppressed population. We present a 43-year-old individual with large-volume stool output Norovirus acute gastroenteritis in the setting of relapsed refractory acute myelogenous leukemia, hematopoietic stem cell transplantation, and biopsy-proven cutaneous and pulmonary graft-versus-host disease. Therapeutic options such as intravenous immunoglobulin or reduction of immunosuppressants were not a feasible choice. A prompt clinical cure was achieved with nitazoxanide, a broad-spectrum antimicrobial agent. Nitazoxanide may be a safe therapeutic alternative, in which a reduction in immunosuppression may not be a viable option.

Antimotility Agents for the Treatment of Clostridium difficile Diarrhea and Colitis

Antimotility agent use for the treatment of Clostridium difficile infection (CDI) is discouraged. We reviewed the literature and unpublished postmarketing surveillance reports regarding antimotility treatment of CDI. Twenty reports met inclusion criteria, describing 55 patients with CDI who were exposed to antimotility agents. All studies were case reports or series, with the exception of 1 retrospective review. Nineteen patients (35%) improved, with clinical resolution. Nine patients (16%) died, and 27 patients (49%) had unknown outcomes. Seventeen patients (31%) with CDI developed colonic dilation; 5 of these patients with severe CDI died. However, all patients who experienced complications or died were given antimotility agents alone initially, without an appropriate antibiotic. Twenty-three patients who received metronidazole or vancomycin coadministered with the antimotility agent experienced no complications. Evidence supporting the hypothesis that worsened outcomes are associated with antimotility therapy of CDI is lacking. Further study of the role of antimotility agents in providing symptomatic relief and reducing environmental contamination with infectious stool may be warranted.

Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients.

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Childrens Hospital and submitted stool for enteric testing. Noroviruses were detected by real‐time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non‐norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1–324 days); 29% developed diarrhea recurrence. Fifty‐five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non‐norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.

Future novel therapeutic agents for Clostridium difficile infection.

Importance of the field: Clostridium difficile is the most important definable cause of healthcare acquired diarrhea. The increasing incidence and mortality associated with this enteric pathogen and the significant rate of treatment failures and recurrences with current antibiotics emphasize the need for the discovery of new and improved therapeutic and preventative agents. What the reader will gain: We review upcoming novel therapeutic agents and the clinical evidence to support their efficacy in treating C. difficile infection. We also provide an extensive comparison of antimicrobial susceptibilities of C. difficile based on in vitro susceptibilities published in the literature. Areas covered in this review: This review was conducted by a thorough examination of the public sources, including journals and scientific meeting abstracts, up to February 2009. Take home message: A number of new therapeutic agents are in development and being tested in clinical trials. However, high costs and concerns for resistance may limit the use of these antimicrobials for the treatment of C. difficile infection. Passive and active immunotherapy may have important future roles as therapeutic and preventative strategies for C. difficile infection.

Drug-Drug Interaction between Itraconazole and Efavirenz in a Patient with AIDS and Disseminated Histoplasmosis

Although there is a presumed drug-drug interaction between itraconazole and nonnucleoside reverse-transcriptase inhibitors, the medical literature lacks such documentation. We describe a drug-drug interaction between itraconazole and efavirenz in a patient with disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS). The drug combination resulted in persistently elevated urinary Histoplasma antigen levels and subtherapeutic plasma itraconazole concentrations. Changing treatment from efavirenz to a protease inhibitor was accompanied by improvements in the desired urinary Histoplasma antigen level and plasma itraconazole concentration.

Clinical Practice Patterns in Hospitalized Patients at Risk for Invasive Candidiasis Role of Antifungal Stewardship Programs in an Era of Rapid Diagnostics

Background: Rapid diagnostic tests for Candida are becoming available that may supplement traditional microbiological identification. Objective: Assess clinical practice patterns in patients with or at risk of candidiasis who may benefit from the use of rapid diagnostic tests. Methods: This was a prospective cohort study of patients with candidemia or receiving systemic antifungals conducted at a university-affiliated tertiary care hospital. Time to initiation of therapy, Candida species, time to identification, and indications for antifungal use were assessed. Results: A total of 162 patients with candidemia aged 58 ± 17 years were identified. Average time to yeast identification yeast was 2.2 ± 1.3 days and varied by Candida species (range = 0.6-7.9 days). Average time for patient to start antifungal therapy was 3.5 ± 2.1 days. In Monte Carlo simulations, average time to initiation of antifungal therapy was 0.6 ± 0.2 days for T2Candida, 2.6 ± 1.3 days for PNA-FISH (fluorescence in situ hybridization using peptide nucleic acid probes), and 2.5 ± 1.4 days for MALDI-TOF (matrix-assisted laser desorption/ionization time of flight). Use of T2Candida on the day of the blood culture collection resulted in 3136 to 6078 fewer doses of echinocandins annually per 5000 patients. Conclusion: Many interventions are possible for antifungal stewardship programs to improve care of patients at risk for systemic candidiasis, including rapid identification of yeast species and limiting unnecessary antifungal agents. Technology enabling rapid diagnosis of Candida will be paramount to appropriate, cost-effective treatment of patients with or at risk for candidiasis.

Characterization of Norovirus-Associated Traveler's Diarrhea

BACKGROUND Travelers diarrhea is the most common medical complaint of international visitors to developing regions. Previous findings suggested that noroviruses (NoVs) are an underappreciated cause of travelers diarrhea. METHODS. In the present study, we sought to define the presence of NoVs in 320 acute diarrheic stool samples collected from 299 US students who traveled to Guadalajara, Cuernavaca, or Puerto Vallarta, Mexico, during the period from 2007 through 2008. Conventional and quantitative real-time polymerase chain reaction assays were used to detect and determine NoV loads in stool samples. NoV strains were characterized by purification of viral RNA followed by sequencing of the viral capsid protein 1 gene. Sequences were compared using multiple sequence alignment, and phylogenetic trees were generated to evaluate the evolutionary relatedness of the viral strains associated with cases of travelers diarrhea. RESULTS NoV RNA was detected in 30 (9.4%) of 320 samples. Twelve strains belonged to genogroup I, and 18 strains belonged to genogroup II. NoV prevalence was higher in the winter season than in the summer season (23% vs 7%, respectively; P = .001). The cDNA viral loads of genogroup I viruses were found to be 500-fold higher than those of genogroup II strains. Phylogenetic analysis revealed a diverse population of NoV strains over different locations and years. CONCLUSIONS NoV strains are important causes of travelers diarrhea in Mexico, especially during the wintertime, and US students in Mexico may represent a suitable group for future NoV vaccine efficacy trials.