Guidance document for prevention of Clostridium difficile infection in acute healthcare settings.

SCOPE: Clostridium difficile infection (CDI) is the most important infective cause of healthcare-associated diarrhoea in high income countries and one of the most important healthcare-associated pathogens in both Europe and the United States. It is associated with high morbidity and mortality resulting in both societal and financial burden. A significant proportion of this burden is potentially preventable by a combination of targeted infection prevention and control measures and antimicrobial stewardship. The aim of this guidance document is to provide an update on recommendations for prevention of CDI in acute care settings to provide guidance to those responsible for institutional infection prevention and control programmes. METHODS: An expert group was set up by the European society of clinical microbiology and infectious diseases (ESCMID) Study Group for C. difficile (ESGCD), which performed a systematic review of the literature on prevention of CDI in adults hospitalized in acute care settings and derived respective recommendations according to the GRADE approach. Recommendations are stratified for both outbreak and endemic settings. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: This guidance document provides thirty-six statements on strategies to prevent CDI in acute care settings, including 18 strong recommendations. No recommendation was provided for three questions.

Clostridium difficile infections among adults and children in Mwanza/Tanzania: is it an underappreciated pathogen among immunocompromised patients in sub-Saharan Africa?

Little is known regarding the epidemiology Clostridium difficile in developing countries. Fresh stool samples from patients with diarrhoea were cultured anaerobically. C. difficile was detected in nine (6.4%) of 141 (95% confidence interval 4.2-13.1), of which seven (77.8%) were from children. HIV infection, prolonged hospitalization and antibiotic use were independent factors associated with the occurrence of C. difficile in the gastrointestinal tract. Two of the toxigenic isolates were typed as ribotype 045, and the other two had unknown ribotype. All C. difficile isolates were susceptible to metronidazole, moxifloxacin and clarithromycin, while three isolates were resistant to clarithromycin. C. difficile may be an important pathogen causing diarrhoea in sub-Saharan Africa among immunocompromised patients.

Combined stool-based multiplex PCR and microscopy for enhanced pathogen detection in patients with persistent diarrhoea and asymptomatic controls from Côte d'Ivoire.

Infectious diarrhoea ranks among the leading causes of morbidity worldwide. Although most acute diarrhoeal episodes are self-limiting, the diagnosis and treatment of persistent diarrhoea (≥2 weeks) are cumbersome and require laboratory identification of the causative pathogen. Stool-based PCR assays have greatly improved the previously disappointing pathogen detection rates in high-income countries, but there is a paucity of quality data from tropical settings. We performed a case-control study to elucidate the spectrum of intestinal pathogens in patients with persistent diarrhoea and asymptomatic controls in southern Côte d'Ivoire. Stool samples from 68 patients and 68 controls were obtained and subjected to molecular multiplex testing with the Luminex(®) Gastrointestinal Pathogen Panel (GPP), microscopy and rapid antigen detection tests for the diagnosis of diarrhoeagenic pathogens. Overall, 20 different bacteria, parasites and viruses were detected by the suite of diagnostic methods employed. At least one pathogen was observed in 84% of the participants, and co-infections were observed in >50% of the participants. Enterotoxigenic Escherichia coli (32%), Giardia intestinalis (29%) and Shigella species (20%) were the predominant pathogens, and Strongyloides stercoralis (10%) was the most prevalent helminth. Pathogen frequencies and numbers of co-infections were similar in patients and controls. Although the Luminex(®) GPP detects a broad range of pathogens, microscopy for helminths and intestinal protozoa remains necessary to cover the full aetiological spectrum in tropical settings. We conclude that highly sensitive multiplex PCR assays constitute a useful screening tool, but that positive results might need to be confirmed by independent methods to discriminate active infection from asymptomatic faecal shedding of nucleic acids.

Detection of nosocomial Clostridium difficile infections with toxigenic strains despite negative toxin A and B testing on stool samples.

A two-step diagnostic algorithm is recommended to detect Clostridium difficile infections; however, samples are regularly found that are glutamate dehydrogenase (GDH) positive but stool toxin negative. In the present single-centre prospective study we focused on these 'difficult-to-interpret' samples and characterized them by anaerobic culture, toxigenic culture, slpA sequence typing and multiplex PCR (GenoType CDiff). The majority of stool toxin A and B-negative samples have been caused by toxigenic strains including ribotype 027. The multiplex PCR was faster and more sensitive compared with culture and allowed preliminary identification of hypervirulent strains in stool samples on the same day.

[Current data and trends on the development of antibiotic resistance of Clostridium difficile]. / Aktuelle Daten und Trends zur Antibiotikaresistenzentwicklung von Clostridium difficile.

Clostridium difficile is the most common pathogen causing antibiotic-associated diarrhea. Antibiotic therapy also favors the development and the epidemic spreading of multiresistant strains. In this present retrospective study clinical isolates from the University of Saarland Medical Center and of other German isolate referring hospitals were characterized by genotyping and antibiotic resistance testing. The most prevalent strains were ribotypes 001 (18%), 014 (16%) and 027 (15%). Sensitivity to metronidazole and vancomycin was demonstrated for 99.7 % of the clinical isolates independent of the genotype. Of the isolates 96 % were rifampicin susceptible; however, significantly more cases of rifampicin resistance were found among 027 strains (12 %). Of the isolates 58% were clarithromycin sensitive and 57% moxifloxacin sensitive. In contrast to the various sporadic genotypes the majority of epidemic strains were macrolide or fluoroquinolone resistant (001, 027 and 078); however, discrimination between epidemic strains by antibiotic resistance profiles could not be discerned. A combination of consistent adherence to hygiene management guidelines and to a prudent and rational use of antimicrobials (antibiotic stewardship) may help to reduce the total number of C. difficile infections (CDI) and also the selection of multiresistant strains. On the other hand in the collection of isolates the sensitivity towards the standard oral antibiotic agents used for C. difficile treatment appears to be unimpaired by the global changes of C. difficile resistant profiles.

[Meningoencephalitis and ventricular arrhythmia caused by yersiniosis]. / Meningoenzephalitis und ventrikuläre Rhythmusstörungen bei Yersiniose.

We report on a 19-year-old patient without any immunodeficiency and without a history of significant diseases in whom two seizure attacks as symptoms of meningoencephalitis occurred after he had suffered from abdominal symptoms for a week. Later, we could observe frequent polymorphic ventricular extrasystoles. A massive production of anti-Yersinia IgM, IgG and IgA as a sign of an acute infection could be found, although we were not able to detect the microbe itself with culturing methods. After targetted antibiotic treatment, the patient fully recovered within two weeks and could be discharged from hospital without clinical abnormalities and an almost normalised cell count in the cerebrospinal fluid. Possible ways of infection are mice which the patient kept as pets and his work in the sewer system. The present case reminds us to think of uncommon infectious agents even in young patients without a predisposition but unusual symptoms and/or potentially relevant anamnestic data.

[Multi-dose packaging of drugs as the causative vehicle for multidrug-resistant Enterobacter cloacae: new results from a case-control study]. / Mehrfach-Verpackungen oraler Medikamente als Ausbruchsvehikel multiresistenter Enterobacter cloacae: neue Erkenntnisse durch eine Fall-Kontroll-Studie.

Hospital hygiene faces cross-cutting and methodological challenges that are time consuming and require specialised knowledge. In outbreak situations German federal states can request assistance from infectious disease epidemiologists at the Robert Koch Institute (RKI). The presented study describes the successful collaboration of local hygienists, microbiologists, clinicians, health authorities and the epidemiologists of the RKI in the investigation of an outbreak of multidrug-resistant Enterobacter (E.) cloacae in 2009 in a children's hospital. The outbreak was discovered in July 2009 when E. cloacae was detected in 12 patients in the neonatal and paediatric intensive care unit (NICU). Hygiene measures were intensified for infection control, and the RKI was invited by the responsible regional health authorities in October 2009 to assist in the outbreak investigation. We conducted a retrospective matched case-control study to identify risk factors for E. cloacae colonisation and infection. We identified a case as any child in the NICU from 1st May to 5th October 2009 with laboratory confirmation of the outbreak clone. Controls were patients staying in the NICU (> 72 h before the case's diagnosis) and swab-negative for the outbreak clone. We used standardised questionnaires to collect demographic and medical information. Matched odds ratios (mOR) were calculated by bivariate and multivariable conditional logistic regression. Environmental investigations were conducted. We identified 28 colonised and 3 bacteraemic cases. 29 matched case-control pairs were included in the study. Multivariable analysis revealed an association between E. cloacae diagnosis and the receipt of oral drugs at the bed-side from multidose packaging (mOR=1.8/drug; p=0.006). No specific drug was identified; microbiological investigation of drugs was negative. This multiresistant E. cloacae outbreak was most likely distributed by oral application using contaminated multidose drug packaging extrinsically contaminated via hands of personnel. No further cases occurred for 6 weeks after protocols for handling oral drugs were changed (smaller packaging, patient-based storage, and limited circulation time). Special attention and thorough hygiene protocols are needed for the distribution of oral medication. In NICUs the use of multi-dose medications should be avoided. The cooperation between locally available expertise and infectious disease epidemiologists enabled the discovery of a previously unidentified risk factor.

Legionellosis must be kept in mind in case of pneumonia with lung abscesses in children receiving therapeutic steroids.

A 10-year-old boy, who had received recurrent short-course treatments with steroids to control severe autoimmune thrombocytopaenia, developed Legionnaires' disease as community-acquired pneumonia. Legionella pneumophila pneumonia was complicated by an extended abscess of the right inferior lobe, leading to residual lung cavities. Legionellosis must be kept in mind as the differential diagnosis in the case of severe pneumonia and with lung abscesses in children receiving therapeutic steroids. Legionella-specific diagnostic tests (polymerase chain reaction [PCR] in respiratory samples or urine antigen assay) and, also, specific empirical antibiotic combination therapy are required for the early detection and treatment of L. pneumophila pneumonia in childhood.

CMV monitoring using blood cells and plasma: a comparison of apples with oranges?

Quantitative cytomegalovirus (CMV) monitoring is still far from being standardized between transplant centers. In the present study, we compared assays for quantitative CMV monitoring using blood cells and plasma. Four hundred and thirty-five consecutive samples from 29 patients with active CMV infection after allogeneic T-cell-depleted hemopoietic stem cell transplantation were tested in parallel using pp65 antigenemia and quantitative CMV polymerase chain reaction (PCR) in blood cells and plasma (COBAS AMPLICOR CMV MONITOR). Although only 142 (53.1%) of 253 positive samples were concordantly identified by all three assays, the number of positive samples detected by each assay was not different and the quantitative values were correlated, provided that nucleic acid (NA) in plasma was isolated by COBAS AmpliPrep and not by the manual protocol. Six (18%) of 34 episodes with active CMV infection were not detected using CMV PCR in plasma; whereas in times of white blood cell aplasia or blast crisis of leukemia, samples with active CMV infection in plasma could not be detected using blood cells. We conclude that CMV monitoring in whole blood could be favorable compared with assays using plasma or blood cells alone. Automated NA isolation could become an attractive tool for a more sensitive and better standardized molecular diagnostics.