J.T. van Dissel

European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI)

Clostridium difficile infection (CDI) is a potentially fatal illness with an increasing incidence worldwide. Despite extensive ongoing research into CDI treatment, management of CDI still poses important problems, such as a high propensity to relapse and refractoriness to treatment, especially when there is an ileus and oral drugs cannot be administered. This guideline evaluates the available literature, discusses criteria for disease severity and provides recommendations for CDI treatment, indicating level of evidence and strength of recommendation.

Clinical and microbiological characteristics of community-onset Clostridium difficile infection in The Netherlands.

To elucidate the prevalence, characteristics and risk factors of community-onset Clostridium difficile infection (CO-CDI), an uncontrolled prospective study was performed. For 3 months in 2007-2008, three laboratories in The Netherlands tested all unformed stool samples submitted by general practitioners (GPs) for C. difficile by enzyme immunoassay for toxins A and B, irrespective of whether GPs specifically requested this. Patients with positive results were asked to complete a questionnaire. Positive stool samples were cultured for C. difficile, and isolates were characterized. In all, 2443 stool samples from 2423 patients were tested, and 37 patients (1.5%) with positive toxin test results were identified. Mixed infections were not found. Age varied from 1 to 92 years, and 18% were under the age of 20 years. Diarrhoea was typically frequent and watery, sometimes with admixture of blood or fever. Eight of 28 patients (29%) suffered recurrences. Among 31 patients with toxin-positive stool samples for whom information was available, 20 (65%) had not been admitted to a healthcare institution in the year before, 13 (42%) had not used antibiotics during the 6 months before, and eight (26%) had neither risk factor. A separate analysis for patients whose samples were both toxin-positive and culture-positive produced similar results. Cultured C. difficile isolates belonged to 13 different PCR ribotypes, and 24% of the isolates were non-typeable (rare or new) PCR ribotypes. In conclusion, CO-CDI can affect all age groups, and many patients do not have known risk factors. Several PCR ribotypes not encountered in hospital-associated outbreaks were found, suggesting the absence of a direct link between outbreaks and community-onset cases.

PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever

Host genetic factors may contribute to susceptibility to and outcome in infectious diseases. Recently polymorphisms in PARK2/PACRG, a gene cluster linked to ubiquitination and proteasome‐mediated protein degradation, were found to be associated with manifest infection by M. leprae. Here, we address whether these polymorphisms are associated with susceptibility to infection with Salmonella typhi and S. paratyphi A, intracellular pathogens that upon infection of humans share with mycobacteria aspects of the hosts’ immune response. The polymorphisms of PARK_e01(−697), PARK2_e01(−2599), rs1333955 and rs1040079 were analysed by polymerase chain reaction and restriction fragment length polymorphism in a case‐control study of typhoid and paratyphoid fever patients in an endemic area in Jakarta, Indonesia. For this study, samples were obtained from patients with blood culture‐confirmed typhoid fever (n = 90), paratyphoid fever (n = 26) and fever controls (n = 337) in a passive, community‐based surveillance and compared to those of randomly selected community controls (n = 322) from the same city area. The PARK2_e01(−2599) allele T was significantly associated with typhoid and paratyphoid fever (OR: 1·51, 95%CI: 1·02–2·23) but the other polymorphisms, PARK2_e01(−697), rs1333955 and rs1040079, were not associated. Although within the PARK2/PACRG gene cluster the PARK2_e01(−2599) allele T was most strongly associated with leprosy (OR∼ 3–5), the association with typhoid is much less strong. Our findings suggest that this polymorphism in PARK2/PACRG plays a small but significant role in susceptibility to the intracellular pathogens S. typhi and S. paratyphi.

Beneficial effects of fumarate therapy in psoriasis vulgaris patients coincide with downregulation of type 1 cytokines

Background Fumarates have been shown to be effective in psoriasis vulgaris.

New perspectives on the kinetics of mononuclear phagocytes

During the last twenty years the origin and kinetics of macrophages and monocytes have been studied in great detail. This research can now be seen to have followed a certain line. First, studies with chimeras provided indications that macrophages originated in the bone marrow (1). Next, studies with labelled cells showed that the peritoneal macrophages involved in acute inflammatory response derived from circulating blood monocytes originating in the bone marrow (2–6). It was then found that in the normal steady state the peritoneal macrophages also arise from blood monocytes, and the kinetics of the blood monocytes and peritoneal macrophages were described (7). Later, the same was done for Kupffer cells (8), pulmonary macrophages (9, 10), and quite recently for spleen macrophages (11).

Evaluation of the antiviral response to zanamivir administered intravenously for treatment of critically ill patients with pandemic influenza A (H1N1) infection.

A retrospective nationwide study on the use of intravenous (IV) zanamivir in patients receiving intensive care who were pretreated with oseltamivir in the Netherlands was performed. In 6 of 13 patients with a sustained reduction of the viral load, the median time to start IV zanamivir was 9 days (range, 4–11 days) compared with 14 days (range, 6–21 days) in 7 patients without viral load reduction (P = .052). Viral load response did not influence mortality. We conclude that IV zanamivir as late add-on therapy has limited effectiveness. The effect of an immediate start with IV zanamivir monotherapy or in combination with other drugs need to be evaluated.

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.

M.G.J. de Boer, F.P. Kroon, S. le Cessie, J.W. de Fijter, J.T. van Dissel. Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.
Transpl Infect Dis 2011: 13: 559–569. All rights reserved

Cavitating pneumonia after treatment with infliximab and prednisone.

Tumor necrosis factor (TNF)-α antagonists constitute a novel class of immunomodulating drugs that are used for the treatment of an increasing number of inflammatory disorders. These agents are associated with an increased risk of tuberculosis, but the risk of other infections is less clear. Reported here is the case of a patient who developed cavitary pneumonia after treatment with infliximab (monoclonal TNF-α antibodies) and corticosteroids for rheumatoid arthritis. Cryptococcus neoformans was the only pathogen isolated from bronchoalveolar lavage fluid. The patient responded well to fluconazole. The risk of infection after treatment with TNF-α antagonists and the possible causative microorganisms are discussed.

The contribution of the peripheral chemoreceptors to the ventilatory response to CO2 in anaesthetized cats during hyperoxia

Abstract Experiments were performed on nine adult cats anaesthetized with chloralose and urethane. The ventilatory response to CO2 during hyperoxia (FlO2) was determined before and after denervation of the peripheral chemoreceptors. We observed flattening of the upper part of the CO2 response curve occurring at lower levels of V e after vagotomy. The part of the V e vs. PaCO2 curve could be described by a linear relation with slope S and intercept B at zero ventilation. In four cats both the slope and B value remained essentially the same after vagotomy. After subsequent sinus neurotomy a reduction in S in the range of 32–46% (mean 41%) was observed with no systematic change in B. In five cats the sequence of the denervation procedures was reversed. After carotid chemodenervation the slope decreased in the range of 23–54% (mean 41%) with no systematic change in B. When subsequent vagotomy was performed the changes in slope were negligible, except for one experiment where a further reduction in slope of 15% was observed. The arterial blood pressure and the stability of the respiratory variables tended to be more affected when both vagotomy and sinus neurotomy were performed. It is concluded from the slope reductions that in the presence of hyperoxia the contribution of the carotid chemoreceptors to the respiratory response to CO2 amounts to about 40%, and that the relative contribution of the aortic bodies to the ventilation is negligible.

Prospective cohort study of acute pyelonephritis in adults: safety of triage towards home based oral antimicrobial treatment.

OBJECTIVE Home-based treatment of acute pyelonephritis (AP) is generally reserved for young non-pregnant women who lack co-morbidity. This study, focusing on the elderly and patients with co-morbidity, evaluates the Dutch primary care guideline that recommends referral to hospital only in case of suspected deterioration to severe sepsis or failure of antibiotic treatment, irrespective of patients age, sex or co-morbidity. METHODS A prospective observational cohort study including consecutive non-pregnant adults with AP. Clinical and microbiological outcome measures of non-referred patients from 35 primary health care centres (PHC) were compared to patients referred to two affiliating emergency departments (EDs). RESULTS Of 395 evaluable patients, 153 were treated by PHCs and 242 referred to EDs. The median age was 63years [IQR 43-77], 34% were male, 58% had co-morbidity; all comparable between the PHC and ED group. Referred ED patients were more likely to have signs of sepsis and to have been pre-treated with antibiotics. Bacteraemia was present in 10% of patients in the PHC group and 27% in the ED group (RR 2.83; 95% CI: 1.64-4.86, p<0.001). Eight (5%) PHC patients were admitted during outpatient treatment but otherwise no major complications occurred. Clinical failure rates at 30days were similar between PHC patients and ED patients; 9% and 10% respectively. Mortality rates of PHC patients versus ED patients were 1% versus 5% at 30days (p=0.058) and 1% versus 7% at 90days (p=0.007). Complicated outcome occurred in 6% of the PHC patients versus 12% in the patients referred to ED (p=0.067). CONCLUSION In a health care system with a well-organized primary care system and clear guideline, the outcome of adults with acute pyelonephritis, including men, the elderly and patients with co-morbidity, selected for oral antibiotic treatment at home did not lead to major complications.