Parham Sendi

Pathogenesis of implant-associated infection: the role of the host

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.

Invasive group B Streptococcal disease in non-pregnant adults : a review with emphasis on skin and soft-tissue infections.

Streptococcus agalactiae, commonly referred as group B Streptococcus (GBS), is a major cause of neonatal sepsis and infections in pregnant women. However, the number of invasive infections in non-pregnant adults is growing. Elderly patients and those with chronic underlying conditions, such as diabetes mellitus or compromised immune defence, are at increased risk of invasion. The spectrum of clinical manifestations is broad and includes necrotizing fasciitis and toxic shock syndrome. Although, primary bacteremia and skin and soft-tissue infections are the most frequently reported diagnosis. This article reviews the epidemiology, pathogenesis and treatment of invasive GBS disease in non-pregnant adults, with an emphasis on skin and soft-tissue infections.

Cathelicidin LL-37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans

ABSTRACT Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococci (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial loads in the tissue even late after the onset of infection. Antimicrobial peptides are important components of the innate host defense, and cathelicidins have been shown to protect against murine necrotic skin infections caused by GAS. However, it has been demonstrated that the streptococcal cysteine protease SpeB proteolytically inactivates the human cathelicidin LL-37 in vitro. Here we have investigated the expression of LL-37 and its interaction with GAS and SpeB during acute severe soft tissue infections by analyses of patient tissue biopsy specimens. The results showed large amounts of LL-37, both the proform (hCAP18) and the mature peptide, in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct colocalization between the bacteria and LL-37 could be noted, and bacterial loads showed positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with large amounts of SpeB. Confocal microscopy confirmed strong colocalization of GAS, SpeB, and LL-37 at the bacterial surface. Taken together, the findings of this study provide in vivo support of the hypothesis that SpeB-mediated inactivation of LL-37 at the streptococcal surface represents a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections.

Antimicrobial treatment concepts for orthopaedic device-related infection

Successful management of orthopaedic device-related infections requires combined surgical and antimicrobial therapy. Because of the heterogeneity of clinical situations, controlled trials are lacking. Although rational concepts for surgical treatment have been published, many aspects of antimicrobial therapy are still not well documented. In this review, some of these knowledge gaps are discussed, and rational arguments for initial parenteral treatment are presented. In addition, the interpretation of data regarding bone penetration is discussed. Whereas rifampin is now a standard combination partner in the treatment of staphylococcal infections, its role against other microorganisms is still unclear. Finally, in view of the increasing prevalence of methicillin-resistant staphylococci and their decreasing susceptibility to vancomycin, data are provided on linezolid and daptomycin, which can potentially be used in bone and joint infections.

Broad-range PCR in selected episodes of prosthetic joint infection

The use of eubacterial PCR of the 16S rRNA (PCR) for diagnosing prosthetic-joint-associated infections (PJIs) is still a matter of debate. Several drawbacks need to be considered when using this technique, including the lack of susceptibility results (except for methicillin-resistant Staphylococcus aureus) and problems in identifying a mixture of bacterial species in a single specimen [1]. A number of studies have indicated that the routine use of PCR in PJIs does not offer a diagnostic advantage over bacterial culture [2–4]. However, this molecular method can detect bacterial DNA in samples when conventional cultures are negative due to previous antimicrobial exposure or unfavorable growth conditions. Taking these considerations into account, we use PCR only if the chance of bacterial growth is low because of previous surgical and antimicrobial treatment or previous negative culture results. In order to (re)assess the diagnostic value of PCR in those selected episodes of suspected PJI in which this method had been applied, we performed a retrospective study to define patient characteristics and to estimate the specificity and sensitivity of PCR versus bacterial culture. Our orthopedic surgery clinic is a 48-bed unit that acts as a primary care center for all types of orthopedic surgery of the extremities and as a tertiary care center for patients needing revision arthroplasty. The study population consisted of patients with a joint prosthesis who were seen at our clinic from 2001 through 2005, and from whom specimens for bacterial culture and PCR were obtained because of possible PJI. The suspicion of PJI was based on clinical signs such as joint pain, effusion, erythema and warmth at the implant site, and/or implant loosening. Patient history prior to the diagnostic intervention was assessed for (1) antimicrobial treatment, (2) number of revisions performed on the affected joint, (3) confirmed and treated infection involving the affected joint within the last 24 months, and (4) implant loosening £ 12 months after implantation without other clinical signs of infection. Specimens (synovial fluid and/or biopsies from periprosthetic tissue) were obtained either during aspiration prior to surgery or during arthroscopy or open surgery. Bacterial culture and histopathologic diagnostics were performed as described previously [5]. The decision whether or not to use PCR was made by the physicians in charge following a review of the patient’s history and prior to the intervention. However, the physicians were not involved in either analyzing or interpreting the data. Specimens were sent to a reference laboratory for analysis [6]. The technique is based on the amplification of bacterial 16S ribosomal DNA [6]. Criteria for definite PJI included the presence of a sinus tract communicating with the prosthesis or purulence surrounding the prosthesis at the time of surgery or acute or chronic inflammation consistent with infection on histopathologic examination [1, 7]. Infection was excluded when the above-mentioned criteria were not fulfilled, no antimicrobial treatment was administered after the episode, and no relapse occurred for at least 1 year. Specimens for both PCR and bacterial culture were obtained in 29 episodes of possible PJI among 26 patients. This number accounted for 7.6% (23 episodes) of all revision arthroplasties (n = 301) and 6.8% (6 episodes) of all joint punctures (n = 88) during the study period. Patient characteristics are presented in table 1. Most episodes (48%) included a history of three or more surgical interventions (median 4, IQR 3–5) on the affected joint within a median time of 3.25 years (IQR 0.9–10.5) prior to the diagnostic intervention. The median number of obtained specimens per patient for bacterial culture was five (IQR 3–7) and for PCR, one (IQR 1–2). No infection was present in 17 (59%) of the 29 episodes, although the duration of follow-up was £ 12 months in

Periprosthetic joint infection following Staphylococcus aureus bacteremia

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.

Non-phenotypic tests to detect and characterize antibiotic resistance mechanisms in Enterobacteriaceae

In the past 2 decades, we have observed a rapid increase of infections due to multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes encoding for extended-spectrum β-lactamases (e.g., blaCTX-M, blaTEM, blaSHV) or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last-generation cephalosporins. Furthermore, other resistance traits against quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also frequently co-associated. Even more concerning is the rapid increase of Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g., blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our antibiotic options. Unfortunately, standard microbiological procedures require several days to isolate the responsible pathogen and to provide correct antimicrobial susceptibility test results. This delay impacts the rapid implementation of adequate antimicrobial treatment and infection control countermeasures. Thus, there is emerging interest in the early and more sensitive detection of resistance mechanisms. Modern non-phenotypic tests are promising in this respect, and hence, can influence both clinical outcome and healthcare costs. In this review, we present a summary of the most advanced methods (e.g., next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays, MALDI-TOF MS, and PCR/ESI MS) presently available for the rapid detection of antibiotic resistance genes in Enterobacteriaceae. Taking into account speed, manageability, accuracy, versatility, and costs, the possible settings of application (research, clinic, and epidemiology) of these methods and their superiority against standard phenotypic methods are discussed.

Clinical comparison between exogenous and haematogenous periprosthetic joint infections caused by Staphylococcus aureus

Patient-related risk factors for invasive Staphylococcus aureus infection overlap with those for periprosthetic joint infections (PJIs). We compared these factors and clinical characteristics between 17 exogenous and 40 haematogenous PJIs caused by S. aureus. Exogenous cases presented significantly more often with damaged periprosthetic soft tissue, whereas haematogenous cases more often had systemic signs of infection, such as fever, chills, and sepsis syndrome. However, comorbid conditions associated with S. aureus infection and/or PJIs did not differ between the two groups. These findings imply that patient-related risk factors for S. aureus infection do not help to predict the mode of infection acquisition in prosthetic joints.

Escherichia coli Variants in Periprosthetic Joint Infection: Diagnostic Challenges with Sessile Bacteria and Sonication

ABSTRACT The diagnostic yield of prosthetic joint-associated infection is hampered by the phenotypic change of bacteria into a sessile and resistant form, also called biofilm. With sonication, adherent bacteria can be dislodged from the prosthesis. Species identification may be difficult because of their variations in phenotypic appearance and biochemical reaction. We have studied the phenotypic, genotypic, and biochemical properties of Escherichia coli variants isolated from a periprosthetic joint infection. The strains were collected from synovial fluid, periprosthetic tissue, and fluid from the explanted and sonicated prosthesis. Isolates from synovial fluid revealed a normal phenotype, whereas a few variants from periprosthetic tissue and all isolates from sonication fluid showed different morphological features (including small-colony variants). All isolates from sonication fluid were beta-galactosidase negative and nonmotile; most were indole negative. Because of further variations in biochemical properties, species identification was false or not possible in 50% of the isolates included in this study. In contrast to normal phenotypes, variants were resistant to aminoglycosides. Typing of the isolates using pulsed-field gel electrophoresis yielded nonidentical banding patterns, but all strains were assigned to the same clonal origin when compared with 207 unrelated E. coli isolates. The bacteria were repeatedly passaged on culture media and reanalyzed. Thereafter, most variants reverted to normal phenotype and regained their motility and certain biochemical properties. In addition, some variants displayed aminoglycoside susceptibility after reversion. Sonication of an explanted prosthesis allows insight into the lifestyle of bacteria in biofilms. Since sonication fluid also reveals dislodged sessile forms, species identification of such variants may be misleading.

Risk Factors for Periprosthetic Ankle Joint Infection: A Case-Control Study

BACKGROUND Periprosthetic ankle joint infection is a feared complication of total ankle arthroplasty because the implant fails in the majority of cases. However, risk factors for developing these infections are unknown. METHODS We aimed to determine risk factors for infection in a matched case-control study that included twenty-six patients with periprosthetic ankle joint infection and two control groups, each consisting of fifty-two patients. RESULTS The prevalence of periprosthetic ankle joint infection within our cohort was 4.7%. Four infections (15%) had a hematogenous origin and twenty-two (85%), an exogenous origin. Staphylococcus aureus was the most common pathogen, followed by coagulase-negative staphylococci. Preoperative predisposing factors associated with infection included prior surgery at the site of infection (odds ratio [OR] = 4.56, 95% confidence interval [CI] = 0.98 to 21.35, and OR = 4.78, 95% CI = 1.53 to 14.91, in comparison with the two control groups) and a low American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score (35.8 versus 49.8 and 47.6 in the two control groups, p ≤ 0.02). The mean duration of the index surgery was significantly longer in the case group than in both control groups (119 versus eighty-four and ninety-three minutes, p ≤ 0.02). After surgery, persistent wound dehiscence (OR = 15.38, 95% CI = 2.91 to 81.34, p = 0.01, in comparison with both control groups) and secondary wound drainage (OR = 7.00, 95% CI = 1.45 to 33.70, and OR = 5.31, 95% CI = 1.01 to 26.78, in comparison with the two control groups, p ≤ 0.04) were associated with the development of a periprosthetic ankle joint infection. CONCLUSIONS Patients at risk for periprosthetic ankle joint infection following total ankle arthroplasty include those with a history of surgery on the ankle, a low preoperative AOFAS hindfoot score, and a long operative time. Postoperatively, patients with a prolonged wound dehiscence or a secondary wound-healing problem are also at risk for infection.