The association between pre-operative sepsis and 30-day mortality in hip fracture patients-A cohort study.

BACKGROUND: Post-operative sepsis considerably increases mortality, but the extent of pre-operative sepsis in hip fracture patients and its consequences are sparsely elucidated. The aim of this study was to assess the association between pre-operative sepsis and 30-day mortality after hip fracture surgery. METHODS: We conducted a retrospective analysis of data collected among 1894 patients who underwent hip fracture surgery in the Capital Region of Denmark in 2014 (NCT03201679). Data on vital signs, cultures and laboratory data were obtained. Sepsis was defined as a positive culture of any kind and presence of systemic inflammatory response syndrome within 24 hours and was assessed within 72 hours before surgery and 30 days post-operatively. Primary outcome was 30-day mortality. Secondary outcomes included length of hospital stay and admission to intensive care unit. RESULTS: A total of 144 (7.6%) of the hip fracture patients met the criteria for pre-operative sepsis. The 30-day mortality was 13.9% in patients with pre-operative sepsis as compared to 9.0% in those without (OR 1.69, 95% CI [1.00; 2.85], P = .08). Patients with pre-operative sepsis had longer hospital stays (median 10 days vs 9 days, mean difference 2.1 [SD 9.4] days, P = .03), and higher frequency of ICU admission (11.1% vs 2.7%, OR 4.15, 95% CI [2.19; 7.87], P < .0001). CONCLUSION: Pre-operative sepsis in hip fracture patients was associated with an increased length of hospital stay and tended to increase mortality. Pre-operative sepsis in hip fracture patients merits more intensive surveillance and increased attention to timely treatment.

Evaluating antibiotic stewardship programs in patients with bacteremia using administrative data: a cohort study.

When introducing new antibiotic guidelines for empirical treatment of bacteremia, it is imperative to evaluate the performance of the new guideline. We examined the utility of administrative data to evaluate the effect of new antibiotic guidelines and the prognostic impact of appropriate empirical treatment. We categorized 2,008 adult patients diagnosed with bacteremia between 2010 and 2012 according to whether they received cephalosporins or fluoroquinolones (old regimen) or not (new regimen). We used administrative data to extract individual level data on mortality, readmission, and appropriateness of treatment, and computed adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 30-day mortality and post-discharge readmission by regimen and appropriateness of treatment. In total, 945 (47.1%) were treated by the old regimen and 1,063 (52.9%) by the new. The median length of stay (8 days) did not differ by regimen and neither did the proportion of those receiving appropriate empirical treatment (84.1% vs. 85.5%). However, fewer patients with the new regimen were admitted to the intensive care unit (ICU; 3.8% vs. 12.0%) and they had lower 30-day mortality (16.4% vs. 23.4%). The adjusted 30-day mortality HR for appropriate versus inappropriate treatment was 0.79 (95% CI 0.62-1.01) and 0.83 (95% CI 0.66-1.05) for the new versus the old regimen. The HR for 30-day readmission for appropriate versus inappropriate treatment was 0.91 (95% CI 0.73-1.13) and 1.05 (95% CI 0.87-1.25) for the new versus the old regimen. This study demonstrates that administrative data can be useful for evaluating the effect and quality of new bacteremia treatment guidelines.

Monitoring meticillin resistant Staphylococcus aureus and its spread in Copenhagen, Denmark, 2013, through routine whole genome sequencing.

Typing of meticillin resistant Staphylococcus aureus (MRSA) by whole genome sequencing (WGS) is performed routinely in Copenhagen since January 2013. We describe the relatedness, based on WGS data and epidemiological data, of 341 MRSA isolates. These comprised all MRSA (n = 300) identified in Copenhagen in the first five months of 2013. Moreover, because MRSA of staphylococcal protein A (spa)-type 304 (t304), sequence type (ST) 6 had been associated with a continuous neonatal ward outbreak in Copenhagen starting in 2011, 41 t304 isolates collected in the city between 2010 and 2012 were also included. Isolates from 2013 found to be of t304, ST6 (n=14) were compared to the 41 earlier isolates. In the study, isolates of clonal complex (CC) 22 were examined in detail, as this CC has been shown to include the hospital-acquired epidemic MRSA (EMRSA-15) clone. Finally, all MRSA ST80 were also further analysed, as representatives of an important community-acquired MRSA in Europe. Overall the analysis identified 85 spa-types and 35 STs from 17 CCs. WGS confirmed the relatedness of epidemiologically linked t304 neonatal outbreak isolates. Several non-outbreak related patients had isolates closely related to the neonatal isolates suggesting unrecognised community chains of transmission and insufficient epidemiological data. Only four CC22 isolates were related to EMRSA-15. No community spread was observed among the 13 ST80 isolates. WGS successfully replaced conventional typing and added information to epidemiological surveillance. Creation of a MRSA database allows clustering of isolates based on single nucleotide polymorphism (SNP) calling and has improved our understanding of MRSA transmission.

Rhinopharynx irrigations and mouthwash with dissolved mupirocin in treatment of MRSA throat colonization - proof-of-concept study.

BACKGROUND: To prevent transmission of, and infection with, meticillin-resistant Staphylococcus aureus (MRSA), eradication treatment of colonized individuals is recommended. Throat colonization is a well-known risk factor for eradication failure. Staphylococcus aureus throat colonization is associated with colonization of the rhinopharynx, but in the currently recommended Danish MRSA eradication strategies, rhinopharynx colonization is not directly targeted. Rhinopharynx colonization could therefore be an important risk factor for prolonged MRSA throat carriage. AIM: To determine whether irrigation and wash of the rhinopharynx and mouth with dissolved mupirocin is a feasible and potentially efficacious supplementary strategy against treatment-resistant MRSA throat carriage. METHODS: The patient study was an open, non-blinded, trial including 20 treatment-resistant MRSA throat carriers. In the study, the patients received a supplementary treatment besides the standard treatment according to the Danish MRSA eradication strategy. The supplementary treatment consisted of rhinopharyngeal irrigation and mouth-gurgling twice a day for 14 days with a mupirocin ointment (22 g 2% ointment per litre of isotonic sterile saline solution) in a 37°C solution. FINDINGS: Eighteen patients (90%) complied with the treatment protocol and none ex-perienced any major adverse events. Out of the 18 patients who finished the study per protocol, 15 (83%) and seven (39%) patients had negative MRSA sampling results one and six months after end of treatment, respectively. CONCLUSION: This study demonstrates the feasibility and clinical potential of also targeting the rhinopharynx and oropharynx in non-systemic throat MRSA eradication strategies.

Staphylococcus aureus and hand eczema severity.

BACKGROUND: The role of bacterial infections in hand eczema (HE) remains to be assessed. OBJECTIVES: To determine the prevalence of Staphylococcus aureus in patients with HE compared with controls, and to relate presence of S. aureus, subtypes and toxin production to severity of HE. METHODS: Bacterial swabs were taken at three different visits from the hand and nose in 50 patients with HE and 50 controls. Staphylococcus aureus was subtyped by spa typing and assigned to clonal complexes (CCs), and isolates were tested for exotoxin-producing S. aureus strains. The Hand Eczema Severity Index was used for severity assessment. RESULTS: Staphylococcus aureus was found on the hands in 24 patients with HE and four controls (P < 0.001), and presence of S. aureus was found to be related to increased severity of the eczema (P < 0.001). Patients carried identical S. aureus types on the hands and in the nose in all cases, and between visits in 90% of cases. Ten different CC types were identified, no association with severity was found, and toxin-producing strains were not found more frequently in patients with HE than in controls. CONCLUSIONS: Staphylococcus aureus was present on hands in almost half of all patients with HE, and was significantly related to severity of the disease. This association indicates that S. aureus could be an important cofactor for persistence of HE.

Neonatal colonization with Staphylococcus aureus is not associated with development of atopic dermatitis.

BACKGROUND: Staphylococcus aureus in atopic skin has been associated with exacerbation of eczema. Objectives To investigate a possible association between neonatal colonization with S. aureus and the risk of atopic dermatitis (AD) during the first 3 years of life. MATERIALS AND METHODS: The study participants were 356 children born of mothers with asthma from the Copenhagen Prospective Study on Asthma in Childhood. Swabs from the vestibulum nasi and the perineum were cultured at 1 month and 1 year, from acute eczema, and from parents (vestibulum nasi and pharynx). AD development and severity were monitored prospectively. RESULTS: Of the neonates, 5.3% had positive swabs for S. aureus cultured from the vestibulum nasi (51.3%) and/or the perineum (11.3%). Forty-two per cent developed AD, but without association between colonization with S. aureus at 1 month of age and risk of developing AD at 3 years of age. There was a 70% concordance for S. aureus carriage between neonates and parents. At 1 year of age 11.3% children had swabs positive for S. aureus. Fourteen per cent of children tested at the 1-year visit developed AD after the visit but before 3 years of age, but again, there was no association between colonization with S. aureus and the risk of AD. In children seen at acute visits the severity of AD measured by scoring of atopic dermatitis (SCORAD) was significantly higher in children with a positive culture for S. aureus in lesions. CONCLUSIONS: Colonization with S. aureus at 1 month of age is not associated with an increased risk of developing AD during the first 3 years of life.

Screening for vancomycin-resistant enterococci with Xpert® vanA/vanB: diagnostic accuracy and impact on infection control decision making.

Vancomycin-resistant enterococci (VRE) are increasingly important nosocomial pathogens and screening for colonization status is a mainstay in infection control. We implemented PCR-based screening during vanA-positive Enterococcus faecium outbreaks in four university hospitals in Copenhagen, Denmark. Xpert®vanA/vanB was performed directly on rectal swabs and the vanA PCR result was used to guide infection control measures. Concurrently, all samples were selectively cultured including an overnight enrichment step. Diagnostic accuracy was calculated as well as turnaround time and the impact of the earlier available PCR results on infection control decision making. In all, 1110 samples were analysed. The vanA PCR positivity rate was 13.8% and culture positivity rate was 15.2%. The diagnostic accuracy of the vanA part of the assay was high with a sensitivity of 87.1%, a specificity of 99.7%, and positive and negative predictive values of 98.0% and 97.7%, respectively. The vanB PCR had a considerably lower specificity of 77.6% and a positive predictive value of 0.4%. In 1067 (96.1%) samples, PCR results were reported within 1 day, whereas median culture turnaround time was 3 days. The saving of time to available results corresponded to 141 saved isolation days and 292 saved transmission risk days. False-negative or false-positive PCR results led to six additional transmission risk days and 13 additional isolation days, respectively. The vanA PCR had high diagnostic accuracy and the prompt availability of results gave a considerable benefit for infection control decision making.

Coagulase-negative staphylococci in a major Danish university hospital: diversity in antibiotic susceptibility between wards.

Over a one-year period, all coagulase-negative staphylococci (CoNS) from blood cultures, cerebrospinal fluids and peritoneal effluents from patients in a major Danish university hospital were investigated for susceptibility to penicillin G; methicillin; gentamicin; netilmicin; amikacin; erythromycin; clindamycin; fusidic acid; rifampicin; tetracycline; chloramphenicol; ciprofloxacin; teicoplanin; and vancomycin. Among the CoNS-isolates, 56% were resistant to methicillin, 51% to gentamicin, 28% to ciprofloxacin, and 5% to teicoplanin. Blood culture CoNS-isolates from patients with a central venous catheter (CVC) were more often resistant to various antibiotics compared to CoNS-isolates from patients without a CVC, e.g. methicillin (72% vs 21%), gentamicin (65% vs 22%) (p<0.00000001). Great diversity in antibiotic resistance between the wards was found; methicillin resistance (in most cases multiple antibiotic resistance) was in particular associated with consumption of broad-spectrum beta-lactams, quinolones, and total antibiotic consumption in a ward. Thus, the antibiotic policy of a ward is an important factor for antibiotic resistance among CoNS.

Identification of coagulase-negative staphylococci and typing of Staphylococcus epidermidis by a 4 h micromethod.

A new 4 h micromethod (Minibact-S) for identification of coagulase-negative staphylococci (CNS) important in human medicine, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus and Staphylococcus saprophyticus, has been investigated. The reproducibility for species identification was 100% and the reproducibility for the single reactions was 95%. When compared to a modified Kloos & Schleifer conventional identification method, discrepant identification was obtained with the Minibact-S in only 8 of 382 clinical and reference strains. The system has been used for typing and biotyping of 201 S. epidermidis strains, and gave a subdivision in 69 different types; 4 related types accounted for 91 (45%) of the isolates, whereas 44 types were represented by only 1 isolate. The discriminatory index was 0.82. In a comparison with other typing methods performed on 81 isolates from 15 patients Minibact-S gave about the same number of types as antibiograms, but in 20% of the patients extra types were obtained with Minibact-S alone compared to antibiogram alone and vice versa. The Minibact-S is of some value in the routine clinical microbiology laboratory as a first screening method for identification of coagulase-negative staphylococci and typing of S. epidermidis in combination with the antibiogram.

Coagulase-negative staphylococci in a newborn with a cardiac vascular prosthesis. Case report.

A case of septicemia with coagulase-negative staphylococci in a newborn with a vascular graft is discussed. Nineteen different isolates of coagulase-negative staphylococci were isolated from four different blood cultures. Eleven of the isolates belonged to one strain, which showed slight variation; the remaining seven isolates belonged to six different strains. The patient was treated for a prolonged period with antibiotics and seemed to respond. The diagnosis and proper treatment are discussed.

Evaluation of staphylococci isolated from a blood culture system (Colorbact).

During a one-year period, all blood cultures positive for staphylococci from two of the smaller Danish counties with non-university hospitals only were evaluated. The isolates were speciated and coagulase-negative staphylococci (CoNS) were biotyped. Furthermore, antibiogram, phage typing and lectin typing were performed for all isolates. Clinical information was obtained by telephone, and before any bacteriological identification was performed, a preliminary judgment was made as to whether the positive blood culture was of clinical significance. A total of 3,500 blood cultures were evaluated and 426 (12.2%) were positive. One hundred and sixty blood cultures from 137 patients contained staphylococci; 36 of these patients had a pure culture of Staphylococcus aureus. One hundred and twenty-four CoNS were found and identified as S. epidermidis (81), S. hominis (19), S. haemolyticus (8), S. simulans (1), and Micrococcus species (3), and another 12 staphylococcal isolates which could not be identified to species level. A total of 35 patients had mixed cultures, including 6 with S. aureus as one of the isolates and 15 with mixed CoNS. Clinical relevance was estimated in 90% of cases where the later bacterial identification showed S. aureus, whereas clinical relevance was absent in the majority of cases including CoNS. Methicillin and gentamicin resistance was absent among S. aureus, but frequent among CoNS, especially S. epidermidis, where 40% were resistant to methicillin and 30% to gentamicin.

Lectin typing of methicillin-resistant Staphylococcus aureus from Singapore, England and Wales, and Denmark.

Methicillin-resistant Staphylococcus aureus (MRSA) isolates from a possible outbreak in Singapore (84) were examined together with all MRSA isolated in Denmark in 1986-1990 (58) and 14 distinct epidemic and 10 distinct single hospital strains from England and Wales. All 84 Singapore isolates were phage typed routinely and 52 isolates were further analysed together with the Danish isolates with an additional set of experimental phages and by lectin typing. The British strains, previously phage typed in the same way, were lectin typed. The following lectins were used: wheat-term agglutinin, soy-bean agglutinin, tomato lectin and Concanavalin-A. Routine phage typing of the Danish isolates showed that 41 isolates belonged to 19 different types; 17 isolates were non-typable (NT). Addition of experimental phage typing and lectin typing enhanced discrimination to 47 types. The 24 British strains could be divided into eight [corrected] "lectin types". Sixty-one of the isolates from Singapore were non-typable by phage typing; the remaining 23 strains belonged to five types. Further examination of 52 isolates with the experimental set of phages and by lectin typing gave 14 closely related types; 48% of these isolates belonged to only two types.

The typing of Staphylococcus epidermidis by a lectin-binding assay.

A new typing method for Staphylococcus epidermidis was developed. Four biotinylated lectins--wheat germ agglutinin (WGA), soy bean agglutinin (SBA), lentil agglutinin (LCA) and Concanavalin A (ConA)--were added to immobilised whole cells of coagulase-negative staphylococci (CNS) in microtitration plates. The amount of bound lectin was measured by peroxidase-conjugated avidin followed by a peroxidase reaction. The method was compared to antibiotic-resistance analysis, phage typing, plasmid DNA profiles and slime production. A total of 113 isolates of CNS from 21 patients was investigated and 71 strains of CNS, including 64 strains of S. epidermidis, were detected if all typing methods were taken into consideration. If only one typing method was used the highest discriminatory power among the S. epidermidis isolates was obtained with the lectin-binding assay which allowed 49 different strains to be detected. If the lectin-binding assay was combined with plasmid-profile analysis, all 64 different strains could be identified. The typability of lectin-binding assay was 96.9% among the S. epidermidis isolates and 25 different lectin-binding patterns were established among the 64 strains. The highest number of strains belonging to one lectin-binding pattern was 13 (20.3%). The assay was reproducible, easy to perform, relatively inexpensive and therefore applicable to large scale typing of S. epidermidis.

Autologous transfusion of shed mediastinal blood after coronary artery bypass grafting and bacterial contamination.

BACKGROUND: Autologous transfusion of shed mediastinal blood is often used after coronary artery bypass grafting (CABG). Shed blood has in a few studies been cultured during the first postoperative hours. However, autologous transfusion might in some cases be continued for several hours and no study has yet examined the bacterial contamination of shed blood later than 6 hours postoperatively. METHODS: Seventy-five patients undergoing electively performed CABG were included. Cultures of shed blood were taken at initiation of the autologous transfusion and the following morning. Infection variables were measured preoperatively and postoperatively. Infectious complications during the first postoperative week were registered. RESULTS: The frequency of patients with bacterial growth in the first culture was 0.22 (95% confidence interval: 0.12 to 0.31) compared with 0.04 (95% confidence interval: -0.044 to 0.087) in the second culture (p < 0.002). We found no significant difference in infection variables between patients with or without bacterial growth in the cultures. No patients suffered from early postoperative infectious complications. CONCLUSIONS: There is no further contamination of the shed blood during the period between initiating the autologous transfusion and the following morning.

Coagulase-negative Staphylococci in Danish blood cultures: species distribution and antibiotic susceptibility.

The distribution and antibiotic susceptibility of coagulase-negative staphylococci (CoNS) isolated from blood cultures was examined in samples from hospitals covering most of Denmark. A total of 499 CoNS isolates were detected in 477 blood cultures from 340 patients and speciated as Staphylococcus epidermidis, 285; Staphylococcus hominis, 61; Staphylococcus haemolyticus, 43; Staphylococcus warneri, 12; Staphylococcus cohnii, 7; Staphylococcus saprophyticus, 4; Staphylococcus capitis, 2 and Staphylococcus lugdunensis, 1. Seventy-eight isolates could not be identified to species level and six were Micrococcus spp. In 108 (22.6%) blood culture sets, more than one CoNS strain were found, as detected by species identification, antibiogram and biotyping. Significantly more blood cultures from patients in university hospitals were drawn from central venous catheters. Comparing university and non-university hospitals, the overall antibiotic susceptibility among CoNS was only slightly different, except for methicillin and amikacin. The prevalence of methicillin-resistant strains was 35.1% in the university hospital strains vs. 25.3% in the non-university hospital strains. The overall prevalence of methicillin resistance was 32%. Great geographic variation in both species distribution and antibiotic resistance was observed. The high prevalence of S. epidermidis makes subtyping of this species important.

[The risk of ornithosis among the staff of Copenhagen Zoo]. / Ornitoserisiko hos ansatte i Københavns Zoologiske Have.

Because a keeper in Copenhagen ZOO had developed ornithosis, clinical and serological examination of the staff of the ZOO was instituted. The object was to demonstrate any possible threatening epidemic and also to demonstrate if the staff of the ZOO were particularly exposed to the risk of ornithosis. Neither of these could be confirmed.

[Typhoid and paratyphoid fever in Denmark 1986-1990. Epidemiologic aspects and the extent of bacteriological follow-up of patients]. / Tyfus og paratyfus i Danmark 1986-1990. Epidemiologiske aspekter samt omfang af bakteriologisk opfølgning af patienter.

A retrospective survey of all notified cases of typhoid and paratyphoid fever in Denmark 1986-1990 was carried out by extracting epidemiological data from the mandatory notification forms; laboratory results of diagnostic and follow-up bacteriological investigations of the patients were also obtained. A total of 161 patients were identified, corresponding to a mean incidence of 0.6 per 100,000 inhabitants per year. Salmonella typhi was isolated in 107 cases and S. paratyphi A and S. paratyphi B in 27 cases each. Median age was 21 years, range 2 months to 74 years. All but six patients probably contracted the infection abroad, most often in Pakistan or other Asian countries. Of six cases with no travel history, two were laboratory associated and two had had relevant foreign contacts. Forty percent of the patients were immigrants now resident in Denmark but infected while visiting their home countries. Only one third of the patients strictly fulfilled the recommendations for follow-up laboratory screenings. It is concluded that the incidence of typhoid and paratyphoid fever is low in Denmark and that nearly all cases are imported; secondary cases are uncommon. There is a need for simplification and modernization of the present recommendations for follow-up laboratory screenings, which date from 1943.

Detection of candidaemia in patients with and without underlying haematological disease.

Diagnosing candidaemia remains difficult despite the development of new diagnostics. We report a direct comparison of three different blood-culture systems and four indirect tests. One hundred and fourteen episodes either with haematological disease and fever despite antibacterials, or with documented invasive candidiasis, were enrolled prospectively. Clinical, para-clinical information and surveillance cultures were obtained. Blood culture was performed using conventional blood-culture bottles, mycosis bottles, and the Isolator 10 lysis centrifugation system. Serum D-arabinitol/L-arabinitol (DA/LA) ratios were determined by gas chromatography mass spectrometry. Antigen, mannan-antigen (Ag) and anti-mannan antibody (Ab) were detected by CandTec, Platelia Candida Ag ELISA and Candida AB/AC/AK kits, respectively. Episodes were classified as proven (n = 24), probable (n = 14), possible (n = 52) or unlikely (n = 24) invasive candidiasis. Candidaemia involved C. albicans (17), C. albicans + C. glabrata (3), C. tropicalis (1) and yeast (1). Mycosis bottles yielded two additional positives and the conventional blood culture yielded one positive not identified by other blood-culture methods. Considering proven and unlikely episodes, respectively, sensitivity and specificity were as follows: mannan-Ag and/or anti-mannan Ab: 83.3%, 78.3%; DA/LA ratio: 41.7%, 86.4%; and CandTec Candida Ag: 66.6%, 70.8%. Lowering the cut-off values to mannan-Ag 0.10 ng/mL and anti-mannan Ab 4 AU/mL, the values were: 100%, 73.9%. Applying the DA/LA ratio to only patients with haematological neutropenia the values were: 75%, 90.5%. Fungal blood culture allowed slightly improved detection of candidaemia. The best indirect test performance was obtained from combined mannan-Ag and anti-mannan Ab detection, especially with lower cut-offs. DA/LA ratio appears to be useful in the context of haematological neutropenia.