Streptococcal infective endocarditis: clinical features and outcomes according to species.

PURPOSE: Infective endocarditis (IE) is frequently caused by streptococcal species, yet clinical features and mortality are poorly investigated. Our aim was to examine patients with streptococcal IE to describe clinical features and outcomes according to streptococcal species. METHODS: From 2002 to 2012, we investigated patients with IE admitted to two tertiary Danish heart centres. Adult patients with left-sided streptococcal IE were included. Adjusted multivariable logistic regression analyses were performed, to assess the association between streptococcal species and heart valve surgery or 1-year mortality. RESULTS: Among 915 patients with IE, 284 (31%) patients with streptococcal IE were included [mean age 63.5 years (SD 14.1), 69% men]. The most frequent species were S. mitis/oralis (21%) and S. gallolyticus (17%). Fever (86%) and heart murmur (81%) were common symptoms, while dyspnoea was observed in 46%. Further, 18% of all cases were complicated by a cardiac abscess/pseudoaneurysm and 25% by an embolic event. Heart valve surgery during admission was performed in 55% of all patients, and S. gallolyticus (OR 0.28 [95% CI 0.11-0.69]) was associated with less surgery compared with S. mitis/oralis. In-hospital mortality was 7% and 1-year mortality 15%, without any difference between species. CONCLUSION: S. mitis/oralis and S. gallolyticus were the most frequent streptococcal species causing IE. Further, S. gallolyticus IE was associated with less heart valve surgery during admission compared with S. mitis/oralis IE. Being aware of specific symptoms, clinical findings, and complications related to different streptococcal species, may help the clinicians in expecting different outcomes.

Shorter Total Length of Stay After Intraperitoneal Fosfomycin, Metronidazole, and Molgramostim for Complicated Appendicitis: A Pivotal Quasi-Randomized Controlled Trial.

Background: We aimed to investigate the difference in the total length of hospital stay (LOS) after intraperitoneal vs. intravenous antibiotic treatment in patients with complicated appendicitis. Methods: We conducted a quasi-randomized prospective clinical trial. The intervention group received 4 g fosfomycin, 1 g metronidazole, and 50 µg recombinant human granulocyte-macrophage colony-stimulating factor intraperitoneally, which was left in the abdominal cavity, immediately after laparoscopic appendectomy. Postoperatively, this group received antibiotics orally. The control group received intravenous antibiotics both during surgery and postoperatively. We primarily evaluated total LOS within 30 days. Furthermore, we evaluated harms and adverse events, Gastrointestinal Quality of Life Index, postoperative complications, and convalescence. Participants were followed for 30 days postoperatively. Results: A total of 12 participants concluded the trial. The total LOS was significantly shorter in the intervention group (six participants, median 13 h; range 2-21 h) than in the control group (six participants, median 84 h; range 67-169 h), p = 0.017. Comparable harms and Gastrointestinal Quality of Life Index scores were found in the two groups. The time to return to normal activities was median 6 and 10 days for the intervention and the control group, respectively. There were no serious adverse events related to the trial nor any complications in the intervention group. In the control group, two patients developed intraabdominal abscesses. Conclusions: The intervention group had a significantly shorter total LOS. The study was not powered to assess differences in complications, but the results indicate that the intervention seems to be a safe regimen, which can be investigated further to treat patients with complicated appendicitis. Identifiers: EudraCT no. 2017-004753-16. ClinicalTrials: https://clinicaltrials.gov/ct2/show/NCT03435900?term=NCT03435900&draw=2&rank=1">draw=2&rank=1.

Does an Antimicrobial Incision Drape Prevent Intraoperative Contamination? A Randomized Controlled Trial of 1187 Patients.

BACKGROUND: The risk of periprosthetic joint infection (PJI), a serious complication after arthroplasty, has not changed for years. Interventions such as eradication of Staphylococcus aureus and antibiotic bone cement are used to diminish infection risk but despite these efforts, the percentage of infection in TKA remains constant. Antimicrobial drapes have a dual action, acting both as a physical and antimicrobial barrier to counter bacterial contamination of the surgical wound. To study the effect of antimicrobial drapes, we used intraoperative contamination as a proxy for infection in our investigation. QUESTIONS/PURPOSES: (1) Do antimicrobial surgical drapes reduce the risk of intraoperative microbial contamination in patients undergoing primary knee arthroplasty? (2) Are other factors such as sex, season, age, type of arthroplasty and duration of surgery associated with an increased risk of contamination in patients undergoing primary knee arthroplasty? (3) Does loosening of the antimicrobial drape increase contamination risk? METHODS: An investigator-initiated, two-arm, non-blinded, multicenter, randomized, controlled trial was performed at five different hospitals in the capital and central regions of Denmark. Twenty-four surgeons participated in the study. Participants were patients older than 18 years undergoing primary knee arthroplasty. We excluded patients with an iodine allergy, previous open knee surgery, previous septic arthritis, any antibiotics taken 4 weeks before surgery, and if they were unable to understand the implications of study participation. Patients were randomly assigned to operation with an antimicrobial drape (intervention group) or operation without (control group). We screened 1769 patients, of which 100 were ineligible and 10 declined to participate. In all, 94% (1659 of 1769) of patients consented and were randomized to the intervention group (51%, 838 of 1659) and control group (49%, 821 of 1659), respectively. In all, 36% (603 of 1659) of patients in the intervention group and 35% (584 of 1659) patients in the control group were available for final analysis. No crossover was performed, and analysis was done per-protocol. Patients were excluded due to logistic failures like lack of utensils, samples disappearing en route to the laboratory mainly caused by implementation of a new electronic patient chart (EPIC, Verona, WI, USA), and forgetful surgeons. Intraoperatively, we swabbed for bacteria at the surgical site and in a rinse from the surgeons' gloves. All samples were sent for cultivation, and colony forming units (CFUs) counts ≥ 1 were deemed contaminated. The primary outcome measure was the difference in the proportion of contaminated patients between the two randomized groups. Secondary outcome measures were the affiliation of sex, season, age, type of implant used, and duration of surgery on contamination risk. To investigate whether other factors were affiliated with contamination risk, we did a logistic regression to control for confounding variables, including sex, age, season, type of implant and duration of surgery. RESULTS: Use of iodinated drapes reduced contamination, with contamination detected in 10% (60 of 603) procedures where iodinated drapes were used compared with 15% (90 of 584) when they were not (odds ratio 0.61 [95% CI 0.43 to 0.87]; p = 0.005), with a relative risk reduction of 35% (95% CI 12.3 to 52.5) and a number needed to treat of 18 patients. After controlling for confounding variables such as sex, age, type of implant, and duration of surgery, we found that not using an antimicrobial drape increased contamination risk by a factor of 1.6 (95% CI 1.08 to 2.35; p = 0.02). Female sex and undergoing surgery in the central region were associated with lower odds of contamination (OR 0.55 [95% CI 0.39 to 0.8]; p = 0.002 and OR 0.45 [95% CI 0.25 to 0.8]; p = 0.006, respectively). Patients with more than a 10-mm separation of the drape from the skin had higher odds of contamination (OR 3.54 [95% CI 1.64 to 11.05]; p = 0.0013). CONCLUSIONS: The use of an antimicrobial drape resulted in lower contamination risk than operating without an antimicrobial drape. Our findings suggest that antimicrobial drapes are useful in infection prevention, but further studies are needed to investigate the effect of antimicrobial drapes on infection. LEVEL OF EVIDENCE: Level I, therapeutic study.

The plasma pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration in patients undergoing appendectomy for uncomplicated appendicitis.

We aimed to investigate the pharmacokinetics of fosfomycin and metronidazole after intraperitoneal administration of the combination of fosfomycin and metronidazole in patients undergoing laparoscopic appendectomy for uncomplicated appendicitis. We included eight otherwise healthy men undergoing laparoscopic appendectomy. The trial treatment was administered at the end of the surgical procedure and left in the abdominal cavity. Trial drugs consisted of 4 g fosfomycin and 1 g metronidazole in a total volume of 500.2 mL. Blood samples were collected prior to and ½, 1, 2, 4, 8, 12 and 24 h after administration. High-performance liquid chromatography-mass spectrometry was used for the measurement of plasma concentrations, and pharmacokinetic calculations were undertaken. Antimicrobial susceptibility testing was undertaken on isolates from intraoperatively collected specimens. The median maximal concentration for fosfomycin in plasma was 104.4 mg/L, median time point for the maximal concentration was 1.5 h, median half-life 3.0 h, and median area under the curve 608 mg*h/L. The median maximal concentration for metronidazole in plasma was 13.6 mg/L, median time point for the maximal concentration was 2.0 h, median half-life 7.3 h, and median area under the curve was 164 mg*h/L. All aerobic bacteria were susceptible to fosfomycin, and all anaerobes were susceptible to metronidazole. Plasma concentrations of fosfomycin and metronidazole were in line with concentrations reported from pharmacokinetic studies after intravenous administration and were within therapeutic ranges.

Bacterial colonization of seromas after breast cancer surgery with and without local steroid prophylaxis.

BACKGROUND: Seroma formation is a frequent postoperative sequela after mastectomy for primary breast cancer. We investigated the role of bacterial colonization of seroma fluid with three different culture methods and the effect of intracavitary steroids. METHODS: The study group consisted of 212 patients scheduled for mastectomy from a previously performed double-blind randomized placebo-controlled intervention trial. The patients were allocated to a single dose of 80 mg of steroids (methylprednisolone) or saline, and the effect on seroma formation was investigated. From each aspiration, an equal volume of seroma fluid (10 mL) was distributed into one sterile transport tube (conventional method), one aerobic blood culture bottle and one anaerobic blood culture bottle. RESULTS: There was significant variation in the number of bacterial species detected in seroma samples among the three culture methods, ranging from 18 species with the conventional culture tubes to 40 species with aerobic blood culture bottles. Patients receiving prophylactic steroids had significantly more frequent colonization than those in the saline group. Nevertheless, the clinical surgical site infection rate of 7.0% was equal between the two groups. CONCLUSIONS: In general, data analysis of the entire set of case material did not succeed in demonstrating a relationship between a specific bacterial species or a combination of species and seroma formation. However, in the few patients with growth of a pathogenic species, both the duration of seroma formation and volume of seroma fluid were more pronounced. TRIAL REGISTRATION: Ethics Committee of Copenhagen (H-4-2009-137), (EudraCT number 2009-016650-40), the Danish Data Protection Agency (code J. no. F.750.75-2), and the Danish Health and Medicines Authority (sponsor protocol code number 23837). Start date November 2010.

Intraperitoneal administration of fosfomycin, metronidazole, and granulocyte-macrophage colony-stimulating factor in patients undergoing appendectomy is safe: a phase II clinical trial.

We aimed to investigate the safety of intraperitoneal administration of the combination of fosfomycin, metronidazole, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients undergoing appendectomy. We conducted a prospective phase II clinical trial in 14 otherwise healthy men suffering from uncomplicated appendicitis. After appendectomy, the trial treatment was administered intraperitoneally and left in the abdominal cavity. Trial treatment consisted of 4 g fosfomycin, 1 g metronidazole, and 50 µg rhGM-CSF in a total volume of 500 ml. Safety was evaluated through white blood cell count where a toxic effect was predefined. We evaluated harms and adverse events, repeated biochemical markers, vital signs, and length of stay. White blood cell count did not drop below the toxic range. The recorded harms were dizziness, discomfort when breathing deeply, no flatus, and bloating. Adverse events included three patients with diarrhoea after discharge and one patient with a hypotensive episode. No serious adverse events or infectious complications occurred. Intraperitoneal administration of fosfomycin, metronidazole, and rhGM-CSF was safe in otherwise healthy men undergoing laparoscopic appendectomy. There were some possible harms and adverse events but we were unable to assess if they were related to anaesthesia, surgery, or the trial treatment.

[Diagnosis of vaginal discharge].

Changes in vaginal discharge are often caused by imbalance in the vaginal microflora, and laboratory testing is usually of little use, as most microbes detected are commensals. In-office diagnosis in general practice using wet mount microscopy and Amsel criteria is helpful and often sufficient to ensure correct diagnosis and treatment. Laboratory testing of vaginal discharge should only be performed, if sexually transmitted disease is suspected, if there is treatment failure or inconclusive wet mount prior to gynaecological surgery, and in pregnant women with recurrent miscarriage or preterm birth.

The Combination of Fosfomycin, Metronidazole, and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor is Stable in vitro and Has Maintained Antibacterial Activity.

BACKGROUND: Treatment of secondary peritonitis includes surgery and antimicrobial agents. Antimicrobial agents are often administered intravenously, however, the alternative route intraperitoneal administration could be considered. Investigations must be conducted prior to clinical application. Therefore, we aimed to investigate the combination of fosfomycin, metronidazole, and recombinant human granulocyte-macrophage colony-stimulating factor with regard to its chemical properties and the solution's stability. In addition, the antibacterial effect of the mixed drug solution was compared with the effect of the individual antibacterial agents. METHODS: The drugs were mixed to an aqueous solution. Basic chemical investigations of pH, precipitation, and calculated osmolarity of the drug combination were conducted. Fosfomycin and metronidazole's chemical stability was investigated using High Pressure Liquid Chromatography-Mass Spectrometry. Microbiological investigations using the agar cup method were carried out to measure the antibacterial effect of fosfomycin and metronidazole. RESULTS: The aqueous solution of the combination of the three drugs had a pH of 7.46-7.62, which was stable during 24 h, was without precipitation, and had a calculated osmolarity of 293 mOsm/l. High Pressure Liquid Chromatography-Mass Spectrometry found stable concentrations of fosfomycin and metronidazole both alone and in combination during 24 h. The antibacterial effect of the drug combination solution was similar to the antibacterial effects of fosfomycin and metronidazole alone. CONCLUSION: The drug combination had neutral and stable pH, was iso-osmotic, and had stable concentrations during 24 h of storage. The antibacterial effect of fosfomycin and metronidazole were not altered when the drugs were mixed.

Characterisation and Safety of Intraperitoneal Perioperative Administration of Antibacterial Agents: A Systematic Review.

Background Intraperitoneal drug administration applies treatment at the site of diseases with gynaecological, urological, or gastrointestinal origin. The objective of this systematic review was to investigate perioperative intraperitoneal administration of antibacterial agents to characterise the drugs used and their safety profile. Methods A protocol was registered at PROSPERO (CRD42016038956). A systematic review was conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A search was performed in PubMed and EMBASE on the 22nd of April 2016. The inclusion criteria were original articles involving at least 5 patients where antibacterial agents were administered intraperitoneally during or after abdominal surgery as prophylaxis or treatment of infection. Languages were limited to English, German, Danish, Norwegian, or Swedish articles. Results 79 studies were included which used a total of 12 different antibacterial classes. Aminoglycosides, 1st and 2nd generation cephalosporins, tetracyclines, and penicillins were most commonly administered intraperitoneally during or after surgery. The antibacterial agent was usually administered intraperitoneally as monotherapy. However, some studies administered combination regimens with heparin or with another antibacterial agent. The most frequent combination was aminoglycosides and lincosamides. In total, 43% of studies lacked information regarding adverse events. The most frequently reported adverse event was discomfort or pain during administration, especially with use of oxytetracycline. Conclusion At least 12 different classes of antibacterial agents have been administered intraperitoneally during or after surgery as prophylaxis or treatment of intraabdominal infections. Intraperitoneal administration seems safe although use of oxytetracycline may cause discomfort or pain.

Low Completeness of Bacteraemia Registration in the Danish National Patient Registry.

Bacteraemia is associated with significant morbidity and mortality and timely access to relia-ble information is essential for health care administrators. Therefore, we investigated the complete-ness of bacteraemia registration in the Danish National Patient Registry (DNPR) containing hospital discharge diagnoses and surgical procedures for all non-psychiatric patients. As gold standard we identified bacteraemia patients in three defined areas of Denmark (~2.3 million inhabitants) from 2000 through 2011 by use of blood culture data retrieved from electronic microbiology databases. Diagnoses coded according to the International Classification of Diseases, version 10, and surgical procedure codes were retrieved from the DNPR. The codes were categorized into seven groups, ranked a priori according to the likelihood of bacteraemia. Completeness was analysed by contin-gency tables, for all patients and subgroups. We identified 58,139 bacteraemic episodes in 48,450 patients; 37,740 episodes (64.9%) were covered by one or more discharge diagnoses within the sev-en diagnosis/surgery groups and 18,786 episodes (32.3%) had a code within the highest priority group. Completeness varied substantially according to speciality (from 17.9% for surgical to 36.4% for medical), place of acquisition (from 26.0% for nosocomial to 36.2% for community), and mi-croorganism (from 19.5% for anaerobic Gram-negative bacteria to 36.8% for haemolytic strepto-cocci). The completeness increased from 25.1% in 2000 to 35.1% in 2011. In conclusion, one third of the bacteraemic episodes did not have a relevant diagnosis in the Danish administrative registry recording all non-psychiatric contacts. This source of information should be used cautiously to iden-tify patients with bacteraemia.

Antibiotic prophylaxis for transrectal prostate biopsy-a new strategy.

BACKGROUND: Fluoroquinolones are extensively used as prophylaxis for transrectal ultrasound-guided biopsy of the prostate (TRUBP). Emerging fluoroquinolone resistance and selection of multiresistant organisms warrant new prophylactic strategies. Pivmecillinam and amoxicillin/clavulanic acid have mutual synergistic activity and the combination of these agents has a broad coverage of the majority of microorganisms causing infectious complications after TRUBP and may be a valuable future prophylactic regimen. PATIENTS AND METHODS: This was a retrospective cohort study of 2624 men that underwent TRUBP at a Danish university hospital. The patients were divided into three groups. Group 1 (n = 1220) received ciprofloxacin before TRUBP, Group 2 (n = 240) received a combination of pivmecillinam and amoxicillin/clavulanic acid before TRUBP and Group 3 (n = 1161) received an extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid before and for 2 days after TRUBP. RESULTS: One hundred and ten out of 148 (74.3%) post-TRUBP infections were caused by Escherichia coli, Klebsiella pneumoniae or Enterococcus faecalis. Group 3 with the extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid had a significantly lower rate of bacteraemia (0.9%) as compared with Group 1 (1.8%) and Group 2 (3.7%). A significant fall in the proportion of ESBL-producing Enterobacteriaceae was observed from the period when ciprofloxacin was used as prophylaxis (8.1%) compared with the subsequent period when pivmecillinam and amoxicillin/clavulanic acid was used (5.9%). CONCLUSIONS: The combination of pivmecillinam and amoxicillin/clavulanic acid is an attractive prophylaxis for TRUBP from a clinical, bacteriological and ecological point of view as compared with ciprofloxacin.

Characterization of carbapenem nonsusceptible Pseudomonas aeruginosa in Denmark: a nationwide, prospective study.

From January 1st 2011 through June 30th 2011, 116 nonreplicate, noncystic fibrosis-related Pseudomonas aeruginosa isolates with reduced carbapenem susceptibility were collected from 12 out of 13 Danish departments of clinical microbiology. The presence of acquired ß-lactamases was assessed with combination tablet-diffusion methodology and polymerase chain reaction. In addition, antimicrobial susceptibility testing, an efflux pump inhibitor assay, and pulsed-field gel electrophoresis (PFGE) were performed. Isolates producing acquired ß-lactamases were further investigated by serotyping and multi locus sequence typing. Eight isolates produced the metallo-ß-lactamase (MBL) VIM-2, and one isolate produced OXA-10 and VEB-1-like extended-spectrum beta-lactamase (ESBL). Phenotypic indications of derepressed AmpC and efflux pump were seen in 56 and 43 isolates, respectively. Overall, the results indicate that mutational factors related to permeability--often combined with derepressed, chromosomal AmpC--is the main factor behind carbapenem nonsusceptibility in Danish P. aeruginosa isolates. The ESBL producer and all the VIM producers belonged to international clones. PFGE revealed that most of the isolates were unrelated, but clonal spread was seen; the 116 isolates distributed in 97 PFGE types, with the largest cluster consisting of 4 isolates (including three isolates from the same hospital with 100% similarity). Thirty-two isolates were pair-wise related, while the remaining isolates were clonally unrelated, as were all nine ESBL/MBL producers.

Rising incidence of Enterococcus species in microbiological specimens from orthopedic patients correlates to increased use of cefuroxime: a study concentrating on tissue samples.

BACKGROUND AND PURPOSE: Enterococci are emerging causes of severe infections, including wound and bone infections in orthopedic patients. The main purpose of this study was to determine whether there was a correlation between the incidence of enterococci in tissue samples (biopsies) from orthopedic patients and consumption of cefuroxime in the orthopedic department. METHODS AND RESULTS: Data were obtained from the department of clinical microbiology and the hospital pharmacy. The consumption of cefuroxime successively increased from 40 defined daily doses (DDD)/10(3) bed days in 2002 to 212 DDD/10(3) bed days in 2009. The incidence of patients with enterococci in tissue samples increased steadily from 1.03/10(3) bed days in 2002 to 5.90/10(3) bed days in 2009. Regression analysis revealed a significant correlation between the consumption of cefuroxime and the incidence of enterococci. INTERPRETATION: Continuous surveillance of species distribution, resistance rates, and antibiotic consumption is of utmost importance for optimal antibiotic strategy in orthopedic patients.

Oral chlorhexidine and microbial contamination during endoscopy: possible implications for transgastric surgery. A randomized, clinical trial.

BACKGROUND: One of the biggest concerns associated with transgastric surgery is contamination and risk of intra-abdominal infection with microbes introduced from the access route. The purpose of this study was to evaluate the effect of oral decontamination with chlorhexidine on microbial contamination of the endoscope. METHODS: In a prospective, randomized, single-blinded, clinical trial the effect of chlorhexidine mouth rinse was evaluated. As a surrogate for the risk of intra-abdominal contamination during transgastric surgery, microbial contamination of the endoscope during upper endoscopy was examined. Patients referred to upper endoscopy were assessed for eligibility and randomized to either chlorhexidine or no mouth rinse. Culture samples were collected from gastric aspirates and endoscopes. The primary outcome measure was colony forming units (CFU) in the endoscope samples. Secondary outcome measures were species specific effect of chlorhexidine on micro-organisms with abscess forming capabilities and the effect of proton pump inhibitor (PPI) treatment on CFU. RESULTS: Chlorhexidine mouth rinse resulted in a significant reduction of CFU in the endoscope samples (p = 0.001). There was no species specific effect and micro-organisms with abscess forming capabilities were equally present. PPI treatment was associated with significantly higher CFU counts in both the gastric (p = 0.004) and endoscope samples (p = 0.049). CONCLUSIONS: Chlorhexidine mouth rinse was effective in reducing microbial contamination of the endoscope, but micro-organisms with abscess forming capabilities were still present. PPI treatment significantly increased CFU and should be discontinued before transgastric surgery.

Local injection of methylprednisolonacetat to prevent seroma formation after mastectomy.

INTRODUCTION: This study served the following three purposes: To evaluate the prophylactic effect against seroma of a single dose of steroid in the mastectomy cavity, to evaluate the thesis that there is a connection between subclinical bacterial colonization and seroma formation and to evaluate if a simple urine stix test can detect postmastectomy infection. MATERIAL AND METHODS: This was a double-blinded and randomized study of injection of methylprednisolonacetate versus saline in the mastectomy cavity at the time of drain removal. A total of 160 females were enrolled after mastectomy. The study parameters were as follows: seroma volume, number of seroma punctures, frequency of clinical infections, degree and type of subclinical colonization, complications and evaluation of the microbiological results of the stix test with automatically read glucose, ketones, blood, pH, protein, nitrite and leucocytes. The degree of inflammation was monitored by measurement of 15 cytokines in each sample of seroma fluid. The study was initiated in August 2010 and is expected to run for three years. DISCUSSION: Some reports have concluded that seroma formation forms part of postsurgical inflammation. Steroids are effective against inflammation and accumulation of fluid at the surgical site after several types of surgery and have also proved valuable in the treatment of seroma formation. In the present study, the prophylactic effect of steroids on seroma formation is investigated. CONCLUSION: As the incidence of postmastectomy seroma formation is 80%, there is a need for improvement in the prophylaxis and treatment of this condition. FUNDING: not relevant. TRIAL REGISTRATION: Medicines Agency The EudraCT number 2009-016650-40 has been issued for your Sponsor's Protocol Code Number 23837. Data protection agency J.no. F.750.75-2. The study is perfomed in collaboration with the GCP Unit, capital Region, Bispebjerg Hospital under the EudraCT number: 2009-016650-40.

Comparison of heart valve culture between two Danish endocarditis centres.

BACKGROUND: The degree to which the results of valve culture depend on different laboratory procedures as well as other factors is unknown. The aim of this study was to compare the results of heart valve culture at 2 different endocarditis centres in order to clarify this. METHODS: The study included 223 patients with definitive endocarditis undergoing heart valve surgery at 2 Danish endocarditis centres (96 at the East centre and 127 at the West centre). The following data related to the samples were registered: transportation, time to inoculation, culture media used and duration of incubation, species distribution, and preoperative duration of appropriate antimicrobial treatment (DAAT). 16S polymerase chain reaction (PCR) of valve tissue was used to estimate the frequency of non-cultivable bacteria. RESULTS: Valve culture was positive in 12.5% of cases at the East centre and 36.2% at the West centre (p < 0.001). Valve cultures were positive in 10%, 45%, and 58% of cases of streptococcal, staphylococcal, and enterococcal infections, respectively. The median DAAT was 3 days for valve culture-positive cases and 11 days for valve culture-negative cases (p < 0.001). By logistic regression analysis, DAAT, species distribution, and laboratory protocol were identified as independent risk determinants for positive valve culture. The adjusted odds ratio for positive culture by the West centre protocol was 3.0 (confidence interval 1.3-6.9; East = 1, p < 0.01). The valve culture contamination rate was 4% at the East centre and 31% at the West centre (p < 0.01). CONCLUSIONS: Our study showed that the duration of preoperative antibiotic treatment and species distribution must be taken into account when comparing valve culture results. Differences in laboratory protocol explained the 3-fold higher sensitivity of heart valve culture observed in the West centre compared to the East centre.

Bilateral polymicrobial osteomyelitis with Candida tropicalis and Candida krusei: a case report and an updated literature review.

OBJECTIVES: We present a case of bilateral polymicrobial osteomyelitis with Candida tropicalis and Candida krusei, and review the literature on Candida osteomyelitis. METHODS: PubMed was searched for cases of Candida osteomyelitis published in the English-language literature between 1970 and 2010. CASE: A 60-year-old previously healthy man was hospitalized with gallstone pancreatitis. Between 3 weeks and 6 months after hospitalization, he developed bilateral osteomyelitis of the feet with C. tropicalis and C. krusei. The patient was treated with surgery, fluconazole, and a liposomal formulation of amphotericin B. The left lower limb was amputated, and at a 2-year follow-up, the patient had almost no pain in his right foot. LITERATURE REVIEW: We identified 40 new cases in the literature since the latest review in 2004. Most cases of Candida osteomyelitis are caused by Candida albicans, but an increasing number are caused by non-albicans species. The prognosis is favorable, with full recovery in the majority of cases. CONCLUSIONS: Candida osteomyelitis should be considered when a patient presents with risk factors and pain without previous trauma, because Candida, despite being part of the normal flora, is the fourth leading cause of hematogenous nosocomial infections. The recommended treatment is surgery and fluconazole as monotherapy or initially combined with a fungicidal agent, either a different amphotericin B formulation or an echinocandin.

Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography.

AIMS: Staphylococcus aureus infective endocarditis (IE) is a critical medical condition associated with a high morbidity and mortality. In the present study, we prospectively evaluated the importance of screening with echocardiography in an unselected S. aureus bacteraemia (SAB) population. METHODS AND RESULTS: From 1 January 2009 to 31 August 2010, a total of 244 patients with SAB at six Danish hospitals underwent screening echocardiography. The inclusion rate was 73% of all eligible patients (n= 336), and 53 of the 244 included patients (22%; 95% CI: 17-27%) were diagnosed with definite IE. In patients with native heart valves the prevalence was 19% (95% CI: 14-25%) compared with 38% (95% CI: 20-55%) in patients with prosthetic heart valves and/or cardiac rhythm management devices (P= 0.02). No difference was found between Main Regional Hospitals and Tertiary Cardiac Hospitals, 20 vs. 23%, respectively (NS). The prevalence of IE in high-risk patients with one or more predisposing condition or clinical evidence of IE were significantly higher compared with low-risk patients with no additional risk factors (38 vs. 5%; P < 0.001). IE was associated with a higher 6 months mortality, 14(26%) vs. 28(15%) in SAB patients without IE, respectively (P < 0.05). CONCLUSION: SAB patients carry a high risk for development of IE, which is associated with a worse prognosis compared with uncomplicated SAB. The presenting symptoms and clinical findings associated with IE are often non-specific and echocardiography should always be considered as part of the initial evaluation of SAB patients.

Broad-range PCR as a supplement to culture for detection of bacterial pathogens in patients with a clinically diagnosed spinal infection.

We aimed to evaluate broad-range PCR and subsequent sequencing compared to conventional culture in the diagnosis of spinal infection. The method was a prospective study of all patients admitted to Aarhus University Hospital for surgery during a 12-months period with a clinically diagnosed infection of the spine. Samples from patients undergoing surgery for non-infectious causes (malignancy etc.) were included as control group. Specimens were submitted to conventional culture and molecular investigation with 16S rRNA gene amplification and sequence analysis. 38 patients were included in the study (clinically diagnosed spinal infections=18; non-infectious diseases=20). The specificity was excellent for both culture and PCR (95% and 100%, respectively). A true culture positive result was obtained in 50% of patients (9/18) and 61% was positive (11/18) by broad-range PCR. When combined, culture and PCR allowed for a microbiological diagnosis in 72% of patients (13/18). A positive culture was found only in patients treated < or =7 d compared to < or =16 d for PCR. However, PCR and culture result were equally negatively affected by duration of treatment. The combination of culture and broad-range PCR substantially adds to the number of microbiological diagnoses obtained, and improves the clinician's opportunity to tailor therapy to individual patients.