Yi Hui Wu

Impact of toxigenic Clostridium difficile colonization and infection among hospitalized adults at a district hospital in southern Taiwan.

Background The impact of toxigenic Clostridium difficile colonization (tCDC) in hospitalized patients is not clear. Aim To study the significance of tCDC in hospitalized patients. Methods A prospective study in the medical wards of a regional hospital was performed from January to June 2011. Fecal samples collected from patients at the time of admission were tested for tcdB by real-time polymerase chain reaction (PCR) and cultured for C. difficile. The patients were followed up weekly or when they developed diarrhea during hospitalization. If C. difficile was isolated, tcdA and tcdB would be tested by multiplex PCR. The primary outcome was the development of C. difficile-associated diarrhea (CDAD). Findings Of 168 patients enrolled, females predominated (87, 51.8%), and the mean patient age was 75.4 years old. Approximately 70% of the patients were nursing home residents, and one third had a recent hospitalization within the prior three months. Twenty-eight (16.7%) patients had tCDC, including 16 (9.5%) patients with tCDC at the time of admission and 12 (7.2%) with tCDC during the follow-up period. With regard to the medications taken during hospitalization, the patients were more likely to have tCDC if they had received more than one class of antibiotics than if they had received monotherapy (odds ratio [OR] 6.67, 95% confidence interval [CI] 1.41–31.56, P = 0.01), particularly if they received a glycopeptide in combination with a cephalosporin or penicillin or a cephalosporin and a carbapenem. More patients with tCDC developed CDAD than those without tCDC (17.9%, 5/28 vs. 1.4%, 2/140, P = 0.002). Overall 7 (4.2%) of the 168 patients developed CDAD, and crude mortality rate of those with and without tCDC was similar (21.4%, 6/28 vs. 19.4%, 27/140, P = 0.79). Conclusion Recent use of glycopeptides and β-lactam antibiotics is associated with toxigenic C. difficile colonization, which is a risk factor for developing C. difficile-associated diarrhea.

Risk factors and clinical impact of levofloxacin or cefazolin nonsusceptibility or ESBL production among uropathogens in adults with community-onset urinary tract infections.

BACKGROUND Gram-negative bacilli causing community-onset urinary tract infections (CoUTIs) are getting increasingly resistant to antimicrobial agents. Clinical significance and risk factors of the acquisition of antimicrobial-nonsusceptible pathogens are still under investigation. METHODS A prospective study was performed in the medical wards of two hospitals in southern Taiwan between August 2009 and January 2012. Patients were enrolled if they were aged >18, admitted through the emergency department, and had CoUTI due to Enterobacteriaceae isolates. RESULTS Overall 136 adults with CoUTI were enrolled. Their mean age was 67 years and females were predominant (68.4%). Comorbidities, such as diabetes mellitus (30.1%) and hypertension (54.4%), were common. Escherichia coli (111, 81.6%) was the predominant species, followed by Klebsiella pneumoniae (11, 8.1%), and Proteus mirabilis (7, 5.1%). Nine (8.0%) of E. coli isolates and 5 (45%) of K. pneumoniae isolates had extended-spectrum β-lactamase (ESBL) production. Out of 122 non-ESBL producing isolates, 35 (28.7%) and 31 (25.4%) were nonsusceptible to levofloxacin and cefazolin, respectively. In the multivariate analysis, several clinical characters were found to be independently associated with CoUTIs due to levofloxacin-nonsusceptible (i.e. males, recent hospitalization, underlying old stroke, diabetes mellitus, and altered consciousness, or absence of chills, pyuria, or tachycardia), cefazolin-nonsusceptible (i.e. males, recent hospitalization, underlying old stroke, absence of fever or chills), or ESBL-producing isolates (i.e. recent hospitalization or antimicrobial therapy). All patients survived and discharged. However, the patients with CoUTIs due to levofloxacin-nonsusceptible (16.1 vs. 7.5 days, p < 0.01), cefazolin-nonsusceptible (15.4 vs. 8.4 days, p < 0.01) or ESBL-producing (16.7 vs. 9.6 days; p < 0.01) pathogens had a longer hospitalization stay than those due to their susceptible comparators. CONCLUSION Several host factors were recognized to be independently associated with the acquisition of UTIs due to levofloxacin- or cefazolin- nonsusceptible, or ESBL-producing Gram-negative bacilli. The clinical impact of UTIs due to nonsusceptible uropathogens is that they result in the prolongation of hospital stays.

Clinical impact of Clostridium difficile colonization

Clostridium difficile can cause antibiotic-associated diarrhea in hospitalized patients. Asymptomatic colonization by C. difficile is common during the neonatal period and early infancy, ranging from 21% to 48%, and in childhood. The colonization rate of C. difficile in adult hospitalized patients shows geographic variation, ranging from 4.4% to 23.2%. Asymptomatic carriage in neonates caused no further disease in many studies, whereas adult patients colonized with toxigenic C. difficile were prone to the subsequent development of C. difficile-associated diarrhea (CDAD). However, the carriage of nontoxigenic C. difficile strains appears to prevent CDAD in hamsters and humans. Risk factors for C. difficile colonization include recent hospitalization, exposure to antimicrobial agents or gastric acid-suppressing drugs (such as proton-pump inhibitors and H2 blockers), a history of CDAD or cytomegalovirus infection, the presence of an underlying illness, receipt of immunosuppressants, the presence of antibodies against toxin B, and Toll-like receptor 4 polymorphisms. Asymptomatic C. difficile carriers are associated with significant skin and environmental contamination, similar to those with CDAD, and contact isolation and hand-washing practices should therefore be employed as infection control policies for the prevention of C. difficile spread. Treating patients with asymptomatic C. difficile colonization with metronidazole or vancomycin is not suggested by the currently available evidence. In conclusion, asymptomatic C. difficile colonization may lead to skin and environmental contamination by C. difficile, but more attention should be paid to the clinical impact of those with C. difficile colonization.

Risk factors for Clostridium difficile-associated diarrhea among hospitalized adults with fecal toxigenic C. difficile colonization.

BACKGROUND Patients with toxigenic Clostridium difficile colonization (tCDC) are at risk of developing C. difficile-associated diarrhea (CDAD). However, the risk factors of hospitalized patients with tCDC developing CDAD are not clear. METHODS We conducted an 18-month prospective study at a medical ward in a district hospital in southern Taiwan. Within 48 hours of admission, weekly stool samples from asymptomatic hospitalized patients were obtained to detect fecal CDC. A polymerase chain reaction for tcdB was performed to determine toxigenic isolates. CDAD was diagnosed if the patient had diarrhea and toxigenic C. difficile present in a stool sample. RESULTS A total 483 patients with stool samples were eligible for the study. Eighty-six (17.8%) patients had tCDC after screening, of whom 14 (16.3%) developed CDAD during follow-up. Among those with tCDC, patients with subsequent CDAD were more likely to have diabetes mellitus (p = 0.01) and to have received piperacillin-tazobactam (p = 0.04), or proton-pump inhibitors (PPIs; p = 0.04) than those without developing CDAD. The variables were statistically significant as determined by multivariate analysis. However, the 60-day crude mortality rates among tCDC patients with and without subsequent development of CDAD were similar. CONCLUSION Diabetes mellitus and recent receipt of piperacillin-tazobactam or PPIs are independent risk factors for the development of CDAD among hospitalized patients with tCDC.

Risk Factors of Fecal Toxigenic or Non-Toxigenic Clostridium difficile Colonization: Impact of Toll-Like Receptor Polymorphisms and Prior Antibiotic Exposure

Background This study is to investigate the significance and risk factors of fecal toxigenic (tCdC) or non-toxigenic Clostridium difficile colonization (ntCdC) among hospitalized patients. Methods Adults admitted to medical wards in a district hospital between January 2011 and June 2012 were enrolled, and those with a history of colectomy, C. difficile fecal colonization or infection or receipt of either metronidazole or oral vancomycin within 3 months, were excluded. Stools collected within 48 hours after admission and every week during hospitalization were cultured for C. difficile. Findings Among the 441 enrolled patients, 84 (20.0%) had CdC at initial screening, including 58 (13.2%) with tCdC and 26 (6.8%) with ntCdC. Among patients with initial negative fecal screening for CdC, it took an average of 70.6 days or 66.5 days to develop tCdC or ntCdC during the study period. Finally 78 (17.7%) had tCdC and 34 (7.7%) had ntCdC. During the follow-up period, the patients with tCdC had a higher risk of CDAD (11/79, 14.1%) than those without CdC (3/328, 0.9%) and those with ntCdC (0/34, 0%) (P<0.001). In multivariate analysis, the TLR4 rs1927914 polymorphism (GG genotype) (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.6–11.8, P = 0.003) and recent cefepime therapy (OR 5.3, 95% CI 2.1–13.2, P<0.001) were independently associated with tCdC, whereas recent cefuroxime (OR 11.7, 95% CI 2.3–60.2, P = 0.003) and glycopeptide therapy (OR 10.9, CI: 2.1–57.2, P = 0.005) associated with ntCdC. Conclusion The incidence of CDAD is highest in patients with tCdC and lowest in patients with ntCdC, and the TLR4 rs1927914 polymorphism GG genotype and recent cefepime therapy were independently associated with tCdC.

Cytomegalovirus disease in nonimmunocompromised, human immunodeficiency virus-negative adults with chronic kidney disease

BACKGROUND/PURPOSE(S) To identify the clinical characteristics of cytomegalovirus (CMV) disease in chronic kidney disease (CKD) patients. METHODS Patients from two sources were reviewed: (1) a retrospective study of hospitalized patients admitted between January 1990 and February 2009 was performed at a tertiary hospital in Taiwan; (2) the English literature from 1990 to 2009 was reviewed for additional cases, and adults with CKD and histopathologically documented cytomegalovirus disease were included. RESULTS Seven CKD patients from our hospital and seven from the literature were included. Nine (64.3%) patients were males, and the mean age was 66 years. Histopathologically proven CMV disease was present in the gastrointestinal (GI) tract of 13 (92.9%) and in the skin of one (7.1%) patient. GI symptoms included bleeding (78.6%), abdominal pain (35.7%), and diarrhea (28.6%).The most common comorbidities were diabetes mellitus (7, 50%) and hypertension (8, 57.1%). Thirteen patients had CMV GI disease. The endoscopic gross features of the GI tract lesions included single or multiple ulcers and a large polypoid or uneven surface mass. Of the seven cases with available data, a low body mass index (22.3 ± 1.3 kg/m(2)) and hypoalbuminemia (25 ± 7.0 g/L) were noted. Twelve patients had received ganciclovir or valganciclovir therapy. Five (35.7%) patients died, and the death of two patients was directly related to bowel perforation caused by CMV colitis. CONCLUSION CMV disease may occur in CKD patients without the presence of overt immunodeficiency. The gastrointestinal tract is the most common site of involvement. Clinicians should be aware of this possibility in CKD patients who have GI symptoms.

Long-term Characteristics of Healthcare-associated Infections in a Neonatal Intensive Care Unit

BACKGROUND/PURPOSE Healthcare-associated infections in neonatal intensive care units (NICUs) are associated with a significant risk of morbidity and mortality. Knowledge regarding pathogens, primary sources of infection and antibiotic resistance in the NICU is essential for developing management strategies. This study aimed to analyze the long-term characteristics of healthcare-associated infections in a tertiary referral center in southern Taiwan. METHODS Infants < 30 days old, with positive blood, cerebrospinal fluid, urine or tissue fluid cultures during hospitalization in the NICU of National Cheng Kung University Hospital from July 1989 to June 2008 were included in the study. RESULTS In total, 1,417 organisms and episodes were identified during the study period. Gram-positive organisms, Gram-negative organisms and fungi constituted 923 (65.1%), 358 (25.3%) and 136 (9.6%) of the pathogens, respectively. Of the Gram-positive organisms, coagulase-negative staphylococci (51.5%), Staphylococcus aureus (34.8%) and Enterococcus spp. (6.1%) were the major pathogens; and 27% of Staphylococcus aureus isolates were oxacillin-resistant. For the Gram-negative organisms, Klebsiella pneumoniae (22%), Pseudomonas aeruginosa (21.8%), Escherichia coli (16.7%) and Enterobacter cloacae (16.7%) were dominant. Also, Candida albicans accounted for 50% of fungal infections. The most common source of infection was bloodstream infection (59.0%), and 5.6% of these were catheter-related. Skin and soft tissue infections were also frequent (26.3%). CONCLUSION Bloodstream and skin/soft tissue infections caused by commensal species play an important role in healthcare-associated infections in the NICU. New measures should be developed in response to the changing patterns in the NICU.

Doxycycline and Tigecycline: Two Friendly Drugs with a Low Association with Clostridium Difficile Infection

Clostridium difficile infection (CDI) is known to be associated with prior exposure to many classes of antibiotics. Standard therapy for CDI (i.e., metronidazole and vancomycin) is associated with high recurrence rates. Although tetracycline derivatives such as tetracycline, doxycycline or tigecycline are not the standard therapeutic choices for CDI, they may serve as an alternative or a component of combination therapy. Previous tetracycline or doxycycline usage had been shown to have less association with CDI development. Tigecycline, a broad-spectrum glycylcycline with potency against many gram-positive or gram-negative pathogens, had been successfully used to treat severe or refractory CDI. The in vitro susceptibility of C. difficile clinical isolates to tigecycline in many studies showed low minimal inhibitory concentrations. Tigecycline can suppress in vitro toxin production in both historical and hypervirulent C. difficile strains and reduce spore production in a dose-dependent manner. Tetracycline compounds such as doxycycline, minocycline, and tigecycline possess anti-inflammatory properties that are independent of their antibiotic activity and may contribute to their therapeutic effect for CDI. Although clinical data are limited, doxycycline is less likely to induce CDI, and tigecycline can be considered one of the therapeutic choices for severe or refractory CDI.

The first case of severe Clostridium difficile ribotype 027 infection in Taiwan.

The authors are grateful to Dr. Evelina Menna and Dr. Fabio Soldani (Department of Pathology and Diagnostics, Section of Infectious Diseases, Verona) and to all the nurses working at the Section of Infectious Diseases of the “G.B. Rossi” Hospital of Verona for their invaluable help in carrying out this study. The authors also acknowledge Dr. Stanley Pang (Centre d’Immunologie et des Maladies Infectieuses, E13, Paris) for its contribution.

Effects of PPARγ and RBP4 Gene Variants on Metabolic Syndrome in HIV-Infected Patients with Anti-Retroviral Therapy

Background PPARγ and RBP4 are known to regulate lipid and glucose metabolism and insulin resistance. The influences of PPARγ (C1431T and Pro12Ala) and RBP4 (−803GA) polymorphisms on metabolic syndrome in HIV-infected patients receiving anti-retroviral therapy were examined in this study. Materials and Methods A cross-sectional study of HIV-1 infected adults with antiretroviral therapy for more than one year in the National Cheng Kung University Hospital was conducted. The gene polymorphisms were determined by quantitative PCR. Results Ninety-one patients were included in the study. Eighty-two (90.1%) patients were males with a mean age of 44.4 years. For the C1431T polymorphism in PPARγ, while patients with the T allele (48.4%) had trends toward lower rate of hypertriglyceridemia, the borderline significance together with insignificant power did not support the protective effect of the T allele against development of hypertriglyceridemia. For the Pro12Ala polymorphism in PPARγ, although patients with the Pro/Ala genotype (8.8%) had a higher level of serum LDL (138.0 vs. 111.5 mg/dl, P = 0.04) and trends toward higher rates of hypercholesterolemia and serum LDL>110 mg/dl, these variables were found to be independent of the Pro/Ala genotype in the multivariate analysis. For the −803GA polymorphism in RBP4, patients with the A allele (23.1%) more often had insulin resistance (HOMA>3.8; 33.3 vs. 8.7%, P = 0.01) and more often received anti-hypoglycemic drugs (14.3 vs. 1.4%, P = 0.04). The detrimental effect of the A allele in RBP4 −803GA polymorphism on development of insulin resistance was supported by the multivariate analysis adjusting for covariates. Conclusion The impacts of PPARγ C1431T and Pro12Ala polymorphisms on metabolism in HIV-infected patients are not significant. RBP4 −803GA polymorphism has increased risk of insulin resistance in HIV-infected patients with anti-retroviral therapy.