Werner Zimmerli

Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the Infectious Diseases Society of America

These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based recommendations for the diagnosis and management of patients with PJI treated with debridement and retention of the prosthesis, resection arthroplasty with or without subsequent staged reimplantation, 1-stage reimplantation, and amputation.

Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial

CONTEXT In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs). OBJECTIVE To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes. DESIGN, SETTING, AND PATIENTS A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008. INTERVENTION Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based. MAIN OUTCOME MEASURES Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics. RESULTS The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%). CONCLUSION In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN95122877.

Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation.

Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.

Management of infection associated with prosthetic joints.

Abstract.In orthopedic implant surgery, infection is rare, but difficult to eradicate. Neither diagnosis nor treatment of such infections is standardized. A MEDLINE search with the keywords “orthopedic implant-related infection” and “joint replacement and infection” identified studies published from 1982–2002. One single randomized controlled trial could be found. In addition, larger retrospective case series and observational studies with clear definition of the observed intervention were also selected for inclusion. A rational algorithm based on clinical experience in orthopedic implant-related infections, observational studies and the controlled trial is presented. The conditions for the different therapeutic options (debridement with retention, one-stage exchange, two-stage exchange, removal without reimplantation or suppressive antibiotic treatment) are presented. The proposed algorithm is based on the interval after implantation (early, delayed, late), the type of infection (exogenous vs hematogenous), the condition of the implant and the soft tissue, as well as comorbidity of the patient. Considering both surgical and antimicrobial therapy, our algorithm facilitates either retrospective evaluation of case series or the planning of well-defined prospective studies.

Executive Summary: Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the Infectious Diseases Society of America

These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based recommendations for the diagnosis and management of patients with PJI treated with debridement and retention of the prosthesis, resection arthroplasty with or without subsequent staged reimplantation, 1-stage reimplantation, and amputation.

Clinical practice. Vertebral osteomyelitis.

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Management of infection associated with total hip arthroplasty according to a treatment algorithm.

Abstract.Background:An algorithm for the management of hip arthroplasty-associated infections was validated in a cohort study.Patients:60 patients with 63 episodes of total hip arthroplasty-associated infections observed from 1985 to 2001 were included. The treatment algorithm was based on the time of manifestation, pathogenesis, and condition of implant and soft tissue. Three treatment options were proposed, namely debridement with retention, one-stage and two-stage replacement.Results:The median patients’ age was 72 years, the median follow-up 28 months; 29% were early, 41% delayed, and 30% late infections, 57% of the infections were exogenously and 43% hematogenously acquired. The overall success rate for the first treatment attempt was 83% (52/63). Patients treated according to the algorithm had a better outcome than the others (44/50 = 88% vs 8/13 = 62%, Relative risk (RR) 0.31, 95% confidence interval (CI): 0.11–0.86, p < 0.03); those treated with adequate antimicrobial therapy had a better success rate (87% vs. 50%, p < 0.01).Conclusion:The proposed algorithm defines a rational surgical/antibiotic treatment strategy.

Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia : a prospective cohort trial

BACKGROUND Guidelines recommend blood culture sampling from hospitalized patients with suspected community-acquired pneumonia (CAP). However, the yield of true-positive results is low. We investigated the benefit of procalcitonin (PCT) on hospital admission to predict blood culture positivity in CAP. METHODS This was a prospective cohort study with a derivation and validation set including 925 patients with CAP who underwent blood culture sampling on hospital admission. RESULTS A total of 73 (7.9%) patients had true bacteremia (43 of 463 in the derivation cohort, 30 of 462 in the validation cohort). The area under the receiver operating characteristics curve of PCT in the derivation and validation cohorts was similar (derivation cohort, 0.83; 95% CI, 0.78-0.89; validation cohort, 0.79; 95% CI, 0.72-0.88). Overall, PCT was a significantly better predictor for blood culture positivity than WBC count, C-reactive protein, and other clinical parameters. In multivariate regression analysis, only antibiotic pretreatment (adjusted odds ratio, 0.25; P < .05) and PCT serum levels (adjusted odds ratio, 3.72; P < .001) were independent predictors. Overall, a PCT cutoff of 0.1 microg/L would enable reduction of the total number of blood cultures by 12.6% and still identify 99% of the positive blood cultures. Similarly, 0.25 microg/L and 0.5 microg/L cutoffs would enable reduction of blood cultures by 37% and 52%, respectively, and still identify 96% and 88%, respectively, of positive blood cultures. CONCLUSIONS Initial PCT level accurately predicted blood culture positivity in patients with CAP. PCT measurement has the potential to reduce the number of drawn blood cultures in the emergency department and to implement a more targeted allocation of limited health-care resources.

Antimicrobial agents in orthopaedic surgery: Prophylaxis and treatment.

The pathogenesis of implant-associated infection involves interaction between the microorganisms (biofilm formation), the implant and the host. Despite improvement of perioperative prophylaxis, orthopaedic implants still remain highly susceptible to bacterial or fungal contamination, generally resulting in persistent implant-associated infection. Therefore, perioperative and life-long prevention of infection is important. For perioperative prophylaxis, a first- or second-generation cephalosporin is recommended, which should be administered between 60 and 30 minutes before incision. The duration of prophylaxis should not exceed 1 day. In centres with a low incidence of infection, a single dose is sufficient. Treatment of infections associated with orthopaedic devices usually requires appropriate surgical intervention combined with prolonged antimicrobial therapy. The choice of the antimicrobial regimen depends on the duration and pathogenesis of infection, stability of the implant, antimicrobial susceptibility of the pathogen and condition of the surrounding soft tissue. The role of rifampicin (rifampin), which has excellent activity on adherent staphylococci, in combination with β-lactams, glycopeptides, fluoroquinolones, minocycline, cotrimoxazole or fusidic acid, in the treatment of staphylococcal infections is outlined. Increasing antimicrobial resistance requires the use of alternative agents, such as quinupristin/dalfopristin, linezolid and daptomycin, but results of clinical trials with these agents are limited. Also reviewed are potential new antimicrobial agents currently undergoing investigation, such as the novel oxazolidinone RWJ-416457, the new glycopeptide dalbavancin, the glycylcycline compound tigecycline, the new carbacephem BP-102 and novel rifamycin derivatives. Vaccination against Staphylococcus aureus with StaphVAX® induced specific antibodies potentially preventing bacteraemia; however, there are no studies on efficacy in the prophylaxis of device-associated infections with this vaccine.

CD14, new aspects of ligand and signal diversity.

The glycosyl-phosphatidylinositol-linked glycoprotein CD14 is expressed in myeloid cells and serum. It binds Gram-negative and -positive bacterial cell wall components and endogenous phospholipids. Toll-like receptors, NF-kappaB and MAP kinases participate in CD14 signaling of inflammation. Alterations of CD14 in inflammatory diseases support a pathogenic role for this microbial receptor.