Hans Jørn Kolmos

Development of cytomegalovirus (CMV) disease may be predicted in HIV-infected patients by CMV polymerase chain reaction and the antigenemia test

Objective:Cytomegalovirus (CMV) is a frequent opportunistic viral pathogen in patients with AIDS leading to retinitis and other serious manifestations. CMV disease may be successfully treated. Prophylactic antiviral therapy has been shown to reduce the risk of CMV disease if initiated early. We evaluated PCR and the antigenemia test as methods for early detection of CMV disease. Methods:Two-hundred HIV-seropositive subjects with CD4 T-cell counts below 100 × 106/l were monitored with CMV polymerase chain reaction (PCR), the antigenemia test, blood cultures and CMV immunoglobulin (Ig) G and IgM titres every second month for 1 year. Results:Thirty-eight patients (19%) developed CMV disease. The PCR test detected CMV DNA a median of 46 days before onset of disease. This was earlier than the median of 34 days for the antigenemia test and a median of 1 day for CMV blood cultures. Univariate analysis showed that the CMV PCR, the antigenemia test and blood cultures all had significant predictive values for subsequent development of CMV disease with odds ratios (OR) of 30, 22 and 20. CMV serology had no predictive value. Multivariate analysis showed that the PCR method was superior to the other tests; OR: CMV PCR 10.0, antigenemia test 4.4 and CMV cultures 4.3. No clinical parameters had any significant predictive value in the stepwise multivariate model. Conclusions:The CMV PCR and the CMV antigenemia tests are both sensitive methods that may predict development of CMV disease up to several months prior to clinical disease. These methods make it possible to select patients at high risk for CMV disease and suitable for prophylactic therapy against CMV.

High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease

AIMS Macrophages in atherosclerotic plaques secrete YKL-40. We tested the hypothesis if high serum YKL-40 concentration predicts coronary events and death of patients with stable coronary artery disease (CAD). METHODS AND RESULTS During the 2.6 years follow-up period (median 2.77 year, interquartile range 0.23 year), 270 patients among the 4298 patients with stable CAD in the CLARICOR trial suffered myocardial infarction (MI) and 377 died (187 classified as cardiovascular death). Serum YKL-40 transformed as Y=log[max(82, serum YKL-40/microg/L)] was significantly associated with cardiovascular death [hazard ratio (HR) = 1.88, 95% confidence interval (CI) = 1.54-2.31, P < 0.001], all-cause mortality (HR = 2.01, 95% CI = 1.75-2.31, P < 0.001), and MI (HR = 1.38, 95% CI = 1.13-1.68, P = 0.002). Following multivariable adjustment for cardiovascular risk factors (age, sex, previous MI, smoking status, hypertension, diabetes mellitus) and selected medical treatments Y contributed significantly to prediction of all-cause mortality (P < 0.001) and cardiovascular mortality (P = 0.001), but not MI (P = 0.25). CONCLUSION High serum YKL-40 is associated with MI, cardiovascular and all-cause mortality in patients with stable CAD.

Outbreak of infection in a burns unit due to Pseudomonas aeruginosa originating from contaminated tubing used for irrigation of patients

Five patients with extensive deep burns developed septicaemia due to Pseudomonas aeruginosa serogroup O-7.8 and phage type 21 or 21/188 shortly after they had been admitted to hospital. Four other burned patients became colonized with the same strain. The source of infection was contaminated tap water used for irrigation of the burns, as part of the first-aid treatment which the patients received when entering the hospital. Contamination was restricted to showers and tubing that were permanently connected to the taps, and the outbreak stopped after they had been disinfected. Tubing and showers used for irrigation of burns should be dismantled and heat-disinfected after each patient and not reconnected to the taps until immediately before the next treatment. Taps used for irrigation of burns should be monitored regularly for the presence of P. aeruginosa and other potentially pathogenic bacteria. Routine typing of P. aeruginosa isolates from burned patients is indicated in order to detect and eliminate hidden sources of infection.

Staphylococcus aureus carriage and infections among patients in four haemo- and peritoneal-dialysis centres in Denmark

A three-month prospective surveillance study was undertaken in four dialysis centres to establish the prevalence of Staphylococcus aureus carriage in a Danish population of patients on haemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD). General data such as sex, age, diagnosis, number of months in dialysis, hospital and ward were registered on a precoded form. Standardized nose and four skin swabs (axillae, groins, perineum) were performed on the first day of the survey. After one and two months, nose swabs were collected. Infections were registered and cultures were sent for phage-typing together with the S. aureus strains isolated from the swabs; 59.5% of HD patients and 51.2% of CAPD patients carried S. aureus. Permanent carriage was most frequent (P < 0.00009), primarily in the nose (44.0 and 34.9%, respectively in HD and CAPD). Skin carriage alone was rare (2.4 and 4.7%). Approximately one third (36.6 and 40.7%) of infections were caused by S. aureus. Although diabetics were not significantly more frequent carriers (60.5%) than non-diabetics (55.0%), the incidence of infection was much higher (26.3% vs. 10.3%, P = 0.004). In CAPD, peritonitis and tunnel/exit-site infections predominated (81.4%), often caused by S. aureus (34.8%). More than two thirds of the infections in HD patients were related to intravascular catheterization. The most serious infection was septicaemia, in all cases due to S. aureus. S aureus infections occurred significantly more frequently among carriers (P = 0.005), and more than half the patients were infected by the same or possibly the same strain as they carried in the nose or on skin. Different regimens for the elimination of S. aureus carriage in dialysis patients are discussed. A policy for risk assessment of patients should be developed, and the elimination of S. aureus carriage before dialysis should be encouraged. Controlled trials comparing the cost-effectiveness of recommended regimens to eliminate carriage in HD/CAPD patients are needed. Nose swabs are reliable indicators of carriage in dialysis patients.

Nosocomial epidemic of Serratia marcescens septicemia ascribed to contaminated blood transfusion bags.

Two cases of transfusion‐related Serratia marcescens bacteremia prompted extensive epidemiologic investigations in three independent hospitals. Test tubes and plasma from donors whose blood was drawn into bags from a single production batch were cultured. Analysis of the ribotype of S. marcescens isolates was performed. For comparison, a strain from the production plant and eight other, unrelated bacteremia isolates were examined. In addition, a retrospective national survey was carried out. S. marcescens was cultured from 11 (0.73%) of 1515 blood units, and an additional (third) bacteremic patient was identified. The clinical isolates from three patients, the three units of blood transfused, and the plant‐derived strain shared a unique ribotype. The incident is interpreted as a sporadic, bacterial contamination of blood bags with the S. marcescens epidemic strain, occurring during the manufacturing or packaging. A similar incident has not previously been reported. Attention is drawn to the possibility of significant contamination during the complex production of multiple‐bag blood collection systems. Guidelines for improved registration and handling of transfusion complications in wards are suggested. Manufacturers should be encouraged to provide blood packs with sterile exteriors, in appropriate, single, outer packages.

Clogging of Biliary Endoprostheses: A Morphologic and Bacteriologic Study

The main problem encountered with the use of biliary endoprostheses is their tendency to clog, which necessitates their exchange. We studied this problem by performing light and electron microscopy and bacterial cultures on both unused and clinically used endoprostheses. These examinations showed several basic defects in their manufacture, such as irregular inner surfaces and badly constructed side holes. The deposit that ultimately led to their occlusion was found mainly to be concentrated around the side holes. Minimizing the amount of material, bacteria, and plant fibres adhering to the endoprosthesis is the desired goal and may be achieved by improving their manufacture and design.

Detection and identification of Anaplasma phagocytophilum, Borrelia burgdorferi, and Rickettsia helvetica in Danish Ixodes ricinus ticks

Borreliosis is an endemic infection in Denmark. Recent serosurveys have indicated that human anaplasmosis may be equally common. The aim of this study was to look for Anaplasma phagocytophilum and related pathogens in Ixodes ricinus ticks and estimate their prevalence, compared to Borrelia, using PCR. Ticks were collected from three locations in Denmark: Jutland, Funen, and Bornholm. Ticks from Jutland and Funen were analysed individually, ticks from Bornholm were analysed in pools of 20. A. phagocytophilum was found in ticks from all areas. A. phagocytophilum was found in 23.6% of ticks from Jutland and Funen, while 11% were positive for Borrelia burgdorferi. The Borrelia genotype B. afzelii was most prevalent, followed by B. valaisiana, B. burgdorferi s.s. and B. garinii.A. phagocytophilum was found in 14.5% of nymphs and 40.5% of adult ticks, while Borrelia was found in 13% of nymphs and 8% of adult ticks. The difference in prevalence between Anaplasma and Borrelia in adult ticks supports the idea that their maintenance cycles in nature may be different. Ticks were also infected with Rickettsia helvetica. Our study indicates that A. phagocytophilum prevalence in ticks in Denmark is as high as Borrelia prevalence and that human anaplasmosis may be unrecognized.

The surgical team as a source of postoperative wound infections caused by Streptococcus pyogenes

Postoperative wound infection, caused by Streptococcus pyogenes transmitted during the operation from members of the surgical team, is a rare but serious complication of surgery. This study describes three cases, which could be traced to an orthopaedic surgeon, who carried the epidemic strain in this throat. Epidemiological characteristics of 14 other outbreaks, published in the English-language literature, are summarized. In total, these 15 outbreaks involved 136 patients. The overall case fatality rate was 12%. Anaesthesiologists and other assisting staff members were involved more often than surgeons and obstetricians. In outbreaks where an attack rate could be calculated, it was at least 7%. T-28 was the most commonly involved T-type, accounting for seven outbreaks. The anus and vagina were the most common carrier sites in staff members. A combination of penicillin and oral vancomycin seemed to be the most efficient treatment for anal and vaginal carriage. Relapse of carriage could occur several months after apparent eradication, and was often associated with a carrier in the family household.

Reversal of methicillin resistance in Staphylococcus aureus by thioridazine

OBJECTIVES Thioridazine has been shown to reverse oxacillin resistance in methicillin-resistant Staphylococcus aureus (MRSA) in vitro. The aim of this study was to investigate whether thioridazine alone or in combination with oxacillin affects the transcription of the methicillin resistance gene mecA and the protein level of the encoded protein PBP2a. METHODS Viability of MRSA was determined in liquid media in the presence of oxacillin or thioridazine alone or in combination. Transcription of mecA was analysed by primer extension, and the protein level of PBP2a was analysed by western blotting in the presence of thioridazine and oxacillin. RESULTS We observed an increased susceptibility of MRSA towards oxacillin in the presence of thioridazine compared with bacteria grown with oxacillin or thioridazine alone. Transcription of mecA was reduced with increasing concentrations of thioridazine in the presence of a fixed amount of oxacillin. Furthermore, the protein level of PBP2a was reduced when bacteria were treated with the combination of oxacillin and thioridazine. The two drugs also affected the mRNA level of the beta-lactamase gene, blaZ. CONCLUSIONS The present study indicates that reversal of methicillin resistance by thioridazine in MRSA may be explained by a reduced transcription of mecA and blaZ, resulting in a reduced protein level of PBP2a.

Experimental Clogging of Biliary Endoprostheses. Role of Bacteria, Endoprosthesis Material, and Design

The major problem facing patients treated with biliary endoprostheses is their frequent clogging, necessitating their exchange. Clogged endoprostheses contain mainly bacteria embedded in an amorphous proteinaceous material with the occasional presence of food fibres. We studied this problem in an in vitro model, evaluating the role of bacteria, endoprosthesis design, and material in sludge formation. We found endoprostheses perfused with artificially contaminated bile to contain significantly more sludge than those perfused with sterile bile (p less than 0.05). The amount of sludge varied with the bacterial species used. Endoprostheses perfused with bacteria producing beta-glucuronidase were not associated with a particularly large amount of sludge. Endoprostheses with side holes contained significantly more sludge than those without (p less than 0.05). Furthermore, endoprostheses made of material with a low friction coefficient, such as Teflon, contained significantly less sludge than endoprostheses made of materials with a higher friction coefficient, such as polyethylene and polyurethane (p less than 0.05). These results emphasize the role of bacteria in endoprostheses clogging and clearly demonstrate the harmful effect that side holes have on endoprosthesis function.