Biofilms cause chronic infections in tissues or by developing on the surfaces of medical devices. Biofilm infections persist despite both antibiotic therapy and the innate and adaptive defence ...mechanisms of the patient. Biofilm infections are characterized by persisting and progressive pathology due primarily to the inflammatory response surrounding the biofilm. For this reason, many biofilm infections may be difficult to diagnose and treat efficiently. It is the purpose of the guideline to bring the current knowledge of biofilm diagnosis and therapy to the attention of clinical microbiologists and infectious disease specialists. Selected hallmark biofilm infections in tissues (e.g. cystic fibrosis with chronic lung infection, patients with chronic wound infections) or associated with devices (e.g. orthopaedic alloplastic devices, endotracheal tubes, intravenous catheters, indwelling urinary catheters, tissue fillers) are the main focus of the guideline, but experience gained from the biofilm infections included in the guideline may inspire similar work in other biofilm infections. The clinical and laboratory parameters for diagnosing biofilm infections are outlined based on the patient’s history, signs and symptoms, microscopic findings, culture-based or culture-independent diagnostic techniques and specific immune responses to identify microorganisms known to cause biofilm infections. First, recommendations are given for the collection of appropriate clinical samples, for reliable methods to specifically detect biofilms, for the evaluation of antibody responses to biofilms, for antibiotic susceptibility testing and for improvement of laboratory reports of biofilm findings in the clinical microbiology laboratory. Second, recommendations are given for the prevention and treatment of biofilm infections and for monitoring treatment effectiveness. Finally, suggestions for future research are given to improve diagnosis and treatment of biofilm infections.
Implanted devices are mainly used to improve impaired function or to replace missing anatomic structures. They are made of synthetic material or devitalized biological structures. In contrast to ...vital transplants, they are not rejected by the body. However, the host reacts against these foreign bodies, a process which can be designated as biocompatibility. The interaction of the device with adjacent granulocytes and complement not only induces various degrees of inflammation but also impairs local microbial clearance. Foreign surfaces are a preferred target for bacterial adherence. While adhering bacteria are highly resistant to the bactericidal activity of phagocytes, they are also resistant to most antimicrobial agents. Certain bacteria may reside within host cells, and hence, evade host defense mechanisms by persisting intracellularly around implants. Nanotechnology minimizes clotting activation and bacterial adhesion by intravascular devices. Furthermore, surface coating with appropriate substances favorably influences biocompatibility as well as susceptibility to infection. In the future, “Microsystems Technology” deployed as intelligent device may decrease the risk of implant failure due to infection.
The added value of biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC), as adjuncts to clinical risk scores for predicting the outcome of patients with ...community-acquired pneumonia (CAP) is in question. We investigated the prognostic accuracy of initial and follow-up levels of inflammatory biomarkers in predicting death and adverse clinical outcomes in a large and well-defined cohort of CAP patients.
We measured PCT, CRP and WBC on days 1, 3, 5, and 7 and followed the patients over 30 days. We applied multivariate regression models and area under the curve (AUC) to investigate associations between these biomarkers, the clinical risk score CURB-65, and clinical outcomes i.e., death and intensive care unit (ICU) admission.
Of 925 patients with CAP, 50 patients died and 118 patients had an adverse clinical outcome. None of the initial biomarker levels significantly improved the CURB-65 score for mortality prediction. Follow-up biomarker levels showed significant independent association with mortality at days 3, 5, and 7 and with improvements in AUC. Initial PCT and CRP levels were independent prognostic predictors of adverse clinical outcome, and levels of all biomarkers during the course of disease provided additional prognostic information.
This study provides robust insights into the added prognostic value of inflammatory markers in CAP. Procalcitonin, CRP, and to a lesser degree WBC provided some prognostic information on CAP outcomes, particularly when considering their kinetics at days 5 and 7 and when looking at adverse clinical outcomes instead of mortality alone.
Propionibacterium acnes is an important cause of orthopedic-implant-associated infections, for which the optimal treatment has not yet been determined. We investigated the activity of rifampin, alone ...and in combination, against planktonic and biofilm P. acnes in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration (MBC) were 0.007 and 4 μg/ml for rifampin, 1 and 4 μg/ml for daptomycin, 1 and 8 μg/ml for vancomycin, 1 and 2 μg/ml for levofloxacin, 0.03 and 16 μg/ml for penicillin G, 0.125 and 512 μg/ml for clindamycin, and 0.25 and 32 μg/ml for ceftriaxone. The P. acnes minimal biofilm eradication concentration (MBEC) was 16 μg/ml for rifampin; 32 μg/ml for penicillin G; 64 μg/ml for daptomycin and ceftriaxone; and ≥128 μg/ml for levofloxacin, vancomycin, and clindamycin. In the animal model, implants were infected by injection of 109 CFU P. acnes in cages. Antimicrobial activity on P. acnes was investigated in the cage fluid (planktonic form) and on explanted cages (biofilm form). The cure rates were 4% for daptomycin, 17% for vancomycin, 0% for levofloxacin, and 36% for rifampin. Rifampin cured 63% of the infected cages in combination with daptomycin, 46% with vancomycin, and 25% with levofloxacin. While all tested antimicrobials showed good activity against planktonic P. acnes, for eradication of biofilms, rifampin was needed. In combination with rifampin, daptomycin showed higher cure rates than with vancomycin in this foreign-body infection model.
Summary Background Clinical trials yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of community-acquired pneumonia. We assessed whether short-term ...corticosteroid treatment reduces time to clinical stability in patients admitted to hospital for community-acquired pneumonia. Methods In this double-blind, multicentre, randomised, placebo-controlled trial, we recruited patients aged 18 years or older with community-acquired pneumonia from seven tertiary care hospitals in Switzerland within 24 h of presentation. Patients were randomly assigned (1:1 ratio) to receive either prednisone 50 mg daily for 7 days or placebo. The computer-generated randomisation was done with variable block sizes of four to six and stratified by study centre. The primary endpoint was time to clinical stability defined as time (days) until stable vital signs for at least 24 h, and analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00973154. Findings From Dec 1, 2009, to May 21, 2014, of 2911 patients assessed for eligibility, 785 patients were randomly assigned to either the prednisone group (n=392) or the placebo group (n=393). Median time to clinical stability was shorter in the prednisone group (3·0 days, IQR 2·5–3·4) than in the placebo group (4·4 days, 4·0–5·0; hazard ratio HR 1·33, 95% CI 1·15–1·50, p<0·0001). Pneumonia-associated complications until day 30 did not differ between groups (11 3% in the prednisone group and 22 6% in the placebo group; odds ratio OR 0·49 95% CI 0·23–1·02; p=0·056). The prednisone group had a higher incidence of in-hospital hyperglycaemia needing insulin treatment (76 19% vs 43 11%; OR 1·96, 95% CI 1·31–2·93, p=0·0010). Other adverse events compatible with corticosteroid use were rare and similar in both groups. Interpretation Prednisone treatment for 7 days in patients with community-acquired pneumonia admitted to hospital shortens time to clinical stability without an increase in complications. This finding is relevant from a patient perspective and an important determinant of hospital costs and efficiency. Funding Swiss National Science Foundation, Viollier AG, Nora van Meeuwen Haefliger Stiftung, Julia und Gottfried Bangerter-Rhyner Stiftung.
Rifampin has been used as an agent in combination therapy in orthopedic device-related infections (ODRI) for almost three decades. The aim of this review is to provide data regarding the role of ...rifampin against biofilm infection
, in animal models, and in clinical ODRI. Available data are gathered in order to present the rational use of rifampin combinations in patients with periprosthetic joint infection (PJI). The role of rifampin is well defined in patients with PJI and is indicated in those who fulfill the Infectious Diseases Society of America criteria for debridement and implant retention or one-stage exchange. It should be used with care because of the danger of rapid emergence of resistance. Potential drug interactions should be considered.
Summary Objectives The incidence of haematogenous periprosthetic joint infections (PJI) among patients with remote infections has been reported to be less than 1%. This incidence may be much higher ...in cases after documented Staphylococcus aureus bacteremia (SAB). We evaluated the incidence of haematogenous PJI following SAB in patients with previously uninfected arthroplasties. Methods A retrospective analysis of our cohort including patients with SAB and prosthetic joints at the Basel University Medical Clinic Liestal from 1998 to 2008. Results We identified 31 patients with 45 uninfected prosthetic joints in situ at the time of SAB. In 12 patients (39%) and 13 arthroplasties (29%), SAB caused PJI. In comparison to nosocomial SAB, infections occurred only in cases with community-acquired SAB ( p = 0.002). PJI was diagnosed within a median time of 2.5 days (IQR 1–3.5) after admission. The comparison between patients with and without PJI revealed no significant difference in gender, age, comorbidities and number of prostheses per patient and age of the prosthesis. Conclusions The rate of PJI after SAB is high, ranging from 30% to 40%, and clearly higher than rates reported for bacteremia with other pathogens. PJIs were observed in community-onset bacteremia, in which there is a typically delay from symptoms to antimicrobial treatment.
Implant-associated infections are caused by microorganisms growing in biofilms, rendering these infections difficult to diagnose and to eradicate. Delayed-onset low-grade infection is difficult to ...distinguish from aseptic failure, often presenting without signs of infection, but only with early loosening and persisting pain. A combination of criteria is needed for an accurate diagnosis: clinical signs and symptoms, laboratory signs of infection, microbiology, histology, and imaging. The treatment goals in prosthetic joint-associated infection are eradication of infection and an optimal functional result. The goal in internal fixation device-associated infection is consolidation of the fracture and avoidance of chronic osteomyelitis. Successful treatment requires an adequate surgical procedure combined with long-term antimicrobial therapy, ideally with an agent acting on adhering biofilm microorganisms. This article reviews the epidemiology, pathogenesis, diagnosis, and management of implant-associated infections, and presents pathogenesis and risk of hematogenous infection.
Many infections of the musculoskeletal system are biofilm infections that develop on non‐living surfaces. Microorganisms adhere either on dead bone (sequesters) or implants. As a rule for a curative ...concept, chronic osteomyelitis or implant‐associated bone infection must be treated with a combination of surgery and antimicrobial therapy. If an implant is kept in place, or a new device is implanted before complete healing of infection, a biofilm‐active antibiotic should be used. Rifamycins are active against biofilms of staphylococci, and fluoroquinolones against those of Gram‐negative bacilli. In this review, the management of chronic osteomyelitis, periprosthetic joint infection and implant‐associated osteomyelitis of long bones is presented.
Rifampin is a potent antibiotic against staphylococcal implant-associated infections. In the absence of implants, current data suggest against the use of rifampin combinations. In the past decades, ...abundant preclinical and clinical evidence has accumulated supporting its role in biofilm-related infections.In the present article, experimental data from animal models of foreign-body infections and clinical trials are reviewed. The risk for emergence of rifampin resistance and multiple drug interactions are emphasized. A recent randomized controlled trial (RCT) showing no beneficial effect of rifampin in patients with acute staphylococcal periprosthetic joint infection treated with prosthesis retention is critically reviewed and data interpreted. Given the existing strong evidence demonstrating the benefit of rifampin, the conduction of an adequately powered RCT with appropriate definitions and interventions would probably not comply with ethical standards.
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