Ilker Uckay

Foreign body infections due to Staphylococcus epidermidis

Staphylococcal infections are one of the main causes of complications in patients with implanted foreign prosthetic material. Implants are associated with a significant reduction of the threshold at which contaminating Gram-positive bacteria, particularly Staphylococcus epidermidis, become infectious and develop a biofilm with phenotypic resistance to almost all antibiotics. A 1000-fold increase in minimal bactericidal levels against most antibiotics except rifampin has been repeatedly observed. Since only removal of the foreign material reverses these phenomena, the clinical challenge consists in finding approaches to cure the infection without removal of the implanted device. Rifampin combinations with other antibiotics, administration of exceedingly high antibiotic concentrations in situ, and early therapy before biofilm development are efficacious. Although these strategies have dramatically improved the outcome of foreign body infections, an improved understanding of biofilm-grown S. epidermidis is necessary to develop new antibacterial agents. Here, we review the pathogenesis, prevention, and treatment of implant infections due to S. epidermidis and highlight some new compounds with already promising in vitro results.

Preventing surgical site infections

The risk of surgical site infection (SSI) is approximately 1–3% for elective clean surgery. Apart from patient endogenous factors, the role of external risk factors in the pathogenesis of SSI is well recognized. However, among the many measures to prevent SSI, only some are based on strong evidence, for example, adequate perioperative administration of prophylactic antibiotics, and there is insufficient evidence to show whether one method is superior to any other. This highlights the need for a multimodal approach involving active post-discharge surveillance, as well as measures at every step of the care process, ranging from the operating theater to postoperative care. Multicenter or supranational intervention programs based on evidence-based guidelines, ‘bundles’ or safety checklists are likely to be beneficial on a global scale. Although theoretically reducible to zero, the maximal realistic extent by which SSI can be decreased remains unknown.

Staffing level: a determinant of late-onset ventilator-associated pneumonia

IntroductionThe clinical and economic burden of ventilator-associated pneumonia (VAP) is uncontested. We conducted the present study to determine whether low nurse-to-patient ratio increases the risk for VAP and whether this effect is similar for early-onset and late-onset VAP.MethodsThis prospective, observational, single-centre cohort study was conducted in the medical intensive care unit (ICU) of the University of Geneva Hospitals. All patients who were at risk for ICU-acquired infection admitted from January 1999 to December 2002 were followed from admission to discharge. Collected variables included patient characteristics, admission diagnosis, Acute Physiology and Chronic Health Evaluation II score, co-morbidities, exposure to invasive devices, daily number of patients and nurses on duty, nurse training level and all-site ICU-acquired infections. VAP was diagnosed using standard definitions.ResultsAmong 2,470 patients followed during their ICU stay, 262 VAP episodes were diagnosed in 209/936 patients (22.3%) who underwent mechanical ventilation. Median duration of mechanical ventilation was 3 days (interquartile range 2 to 6 days) among patients without VAP and 11 days (6 to 19 days) among patients with VAP. Late-onset VAP accounted for 61% of all episodes. The VAP rate was 37.6 episodes per 1,000 days at risk (95% confidence interval 33.2 to 42.4). The median daily nurse-to-patient ratio over the study period was 1.9 (interquartile range 1.8 to 2.2). By multivariate Cox regression analysis, we found that a high nurse-to-patient ratio was associated with a decreased risk for late-onset VAP (hazard ratio 0.42, 95% confidence interval 0.18 to 0.99), but there was no association with early-onset VAP.ConclusionLower nurse-to-patient ratio is associated with increased risk for late-onset VAP.

Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update

Prevention of surgical site infection in orthopaedic surgery and bone trauma has some hallmarks not shared with other surgical disciplines: low inoculum for implant infections; pathogenicity of coagulase-negative staphylococci and other skin commensals; possible haematogenous origin; and long post-discharge surveillance periods. Only some of the many measures to prevent orthopaedic surgical site infection are based on strong evidence and there is insufficient evidence to show which element is superior over any other. This highlights the need for multimodal approaches involving active post-discharge surveillance, as well as preventive measures at every step of the care process. These range from preoperative care to surgery and postoperative care at the individual patient level, including department-wide interventions targeting all healthcare-associated infections and improving antibiotic stewardship. Although theoretically reducible to zero, the maximum realistic extent to decrease surgical site infection in elective orthopaedic surgery remains unknown.

Outcome of orthopedic implant infections due to different staphylococci

BACKGROUND Comparisons of different staphylococci in orthopedic implant infections have rarely been reported. In this study we assessed total joint arthroplasty infections and other orthopedic implant infections due to methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and coagulase-negative staphylococci (CoNS). METHODS This was a retrospective study performed at the Geneva University Hospitals for the period January 1996 to June 2008. RESULTS There were 44 infections due to MRSA, 58 due to MSSA, and 61 due to CoNS. Overall cure was achieved in 57% (25/44) of MRSA infections, 72% (42/58) of MSSA infections, and 82% (50/61) of CoNS infections, after a minimum follow-up of 1 year. In the subgroup of arthroplasty infections only, cure was achieved in 39% (7/18) of MRSA, 60% (15/25) of MSSA, and 77% (30/39) of CoNS episodes. In multivariate analysis, arthroplasty (odds ratio (OR) 0.2, 95% confidence interval (95% CI) 0.1-0.6) and MRSA infections (OR 0.3, 95% CI 0.1-0.9) were inversely associated with overall cure for all implants. CoNS infection (OR 3.0, 95% CI 1.2-8.0) and the insertion of a new implant (OR 4.5, 95% CI 1.6-13.1) were associated with higher cure results. Methicillin resistance, immunosuppression, sex, age, duration of antibiotic therapy, one-stage revision, rifampin use, and total number of surgical interventions did not influence cure. MRSA-infected patients had more post-infection sequelae than patients with MSSA or CoNS (Chi-square test 13/44 vs. 93/119, OR 3.4, 95% CI 1.3-8.9, p=0.004). CONCLUSIONS In orthopedic implant infections, S. aureus is more virulent than CoNS. MRSA has the worst outcome and CoNS the best.

Secular trends of nocardia infection over 15 years in a tertiary care hospital

Aims: To assess the incidence of nocardia infection over 15 years in a tertiary care hospital. Methods: Over a 15 year period, Nocardia spp were isolated from 20 patients hospitalised at the Geneva University Hospitals, Switzerland. Results: Sixteen patients had one or more underlying conditions. The median time between symptom onset and diagnosis was 30 days. The most common initial unconfirmed diagnosis was pulmonary tuberculosis (four). The lung was involved in 16 cases, followed by the central nervous system (two) and skin (two); one patient had disseminated infection. The most common species identified was N asteroides. In vitro susceptibility testing was performed on 14 of 20 strains. All strains were susceptible to imipenem and amikacin. Initial treatment with trimethoprim/sulfamethoxazole (TMP/SMX) was started in 14 patients, although five patients had to be switched to another treatment because of side effects or lack of efficacy. A cure was observed in 15 patients, death in three, and relapse or complications in two. Conclusions: Nocardiosis can become a severe infection and mainly affects profoundly immunocompromised patients. Differential diagnosis often delays the time to diagnosis, which worsens the outcome. New diagnostic tools, such as the polymerase chain reaction, could provide more rapid and reliable results. TMT/SMX was the most commonly prescribed treatment, but needed to be changed for another treatment because of side effects or lack of efficacy in a considerable proportion of patients. Imipenem should be used as an alternative treatment for severely ill patients, and the sulfa combination for less severe infections.

Six weeks of antibiotic treatment is sufficient following surgery for septic arthroplasty

OBJECTIVES In the treatment of prosthetic joint infections (PJI), the benefit of antibiotic therapy for more than 6 weeks after surgery is uncertain. We compared PJI cure rates according to the duration of antibiotics, 6 versus 12 weeks. METHODS A prospective observational non-randomized study in Geneva University Hospitals 1996-2007. RESULTS A total of 144 PJI (62 hip arthroplasties, 62 knee arthroplasties, and 20 hip hemiarthroplasties) were included with a prolonged follow-up ranging from 26 to 65 months. Surgical treatment included 60 débridements with implant retention, 10 one-stage exchanges of the prosthesis, 57 two-stage exchanges, and 17 Girdlestone procedures or knee arthrodeses. Seventy episodes (49%) received 6 weeks antibiotic therapy and 74 episodes, 12 weeks. Cure was achieved in 115 episodes (80%). Cure rate did not change according to the duration of intravenous antibiotics (>8 days, 8-21 days, >21 days) (Kruskal-Wallis-test; p = 0.37). In multivariate analysis, none of the following parameters was statistically significantly associated with cure: two-stage exchange (odds ratio 1.1,95%CI 0.2-4.8); number of débridements (0.9, 0.4-1.9); six weeks antibiotherapy (2.7, 0.96-8.3); duration of intravenous course (1.0, 0.96-1.03); sinus tract (0.6, 0.2-1.7); or MRSA infection (0.5, 0.2-1.5), although implant retention showed a tendency for less cure (0.3, 0.1-1.1). CONCLUSIONS Following surgery for treatment of PJI, antibiotic therapy appears able to be limited to a 6-week course, with one week of intravenous administration. This approach needs confirmation in randomized trials.

Are there Patients with Peritonitis Who Require Empiric Therapy for Enterococcus

Enterococci are an increasingly important cause of nosocomial infections. While the clinical impact of enterococci in cases of bacteremia and super-infections in selected patient populations has been well-established, their role as primary pathogens in polymicrobial intra-abdominal infections remains controversial. While it has been suggested that the presence of enterococci increases the rate of infectious post-operative complication, it has also been demonstrated that polymicrobial intra-abdominal infections involving enterococci can be treated successfully with appropriate surgical drainage and antibiotics, such as cephalosporins, that are not active against enterococci. Therefore, the question arises of whether or not antibiotic coverage against enterococci should be included in the empirical treatment of peritonitis in certain high-risk patient populations. An extensive literature review revealed some evidence arguing in favour of using empirical therapy with enterococcal coverage for intra-abdominal infections in the following cases: (i) immunocompromised patients with nosocomial, post-operative peritonitis; (ii) patients with severe sepsis of abdominal origin who have previously received cephalosporins and other broad-spectrum antibiotics selecting for Enterococcus spp.; (iii) patients with peritonitis and valvular heart disease or prosthetic intravascular material, which place them at high risk of endocarditis. The ideal therapeutic regimen for these high-risk patients remains to be determined, but empirical therapy directed against enterococci should be considered.

Spondylodiscitis due to Propionibacterium acnes: report of twenty-nine cases and a review of the literature

Propionibacterium acnes is the most frequent anaerobic pathogen found in spondylodiscitis. A documented case required microbiological proof of P. acnes with clinical and radiological confirmation of inflammation in a localized region of the spine. Microbiological samplings were obtained by surgery or aspiration under radiological control. Twelve males and 17 females (median age, 42 years) with spondylodiscitis due to P. acnes were diagnosed within the last 15 years. Three patients were immunosuppressed. All patients reported back pain as the main symptom, and most were afebrile. Three patients had a peripheral neurological deficit, one a motor deficit, and two a sensory deficit attributable to the infection; and six patients had an epidural abscess. The most frequent risk factor was surgery, which was present in the history 28 of 29 (97%) patients. The mean delay between spinal surgery and onset of disease was 34 months, with a wide range of 0-156 months. Osteosynthesis material was present in twenty-two cases (76%). In 24 (83%) patients, additional surgery, such as débridement or spondylodesis, was performed. Previous osteosynthesis material was removed in 17 of the 22 (77%) patients where it was present. Total cure was reported in all patients, except one, after a mean duration of antibiotic therapy of 10.5 weeks (range, 2-28 weeks). In conclusion, spondylodiscitis due to P. acnes is an acute infection closely related to previous surgery. The most prominent clinical feature is pain, whereas fever is rare, and the prognosis is very good.

Cost‐effectiveness of universal MRSA screening on admission to surgery

Policy-makers have recommended universal screening to reduce nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection. Risk profiling of MRSA carriers and rapid PCR tests are now available, yet cost-effectiveness data are limited. The present study assessed the cost-effectiveness of universal PCR screening on admission to surgery. A decision analysis model from the hospital perspective compared costs and the probability of any MRSA infection across three strategies: (i) PCR screening; (ii) screening for risk factors (prior hospitalization or antibiotic use) combined with pre-emptive isolation and contact precautions pending chromogenic agar results; and (iii) no screening. Clinical data were taken from studies at a Swiss teaching hospital as well as from published literature. Costs were derived from hospital accounting systems. Compared to no screening, the PCR strategy resulted in higher costs (CHF 10503 vs. 10358) but a lower infection probability (0.0041 vs. 0.0088), producing a base-case incremental cost-effectiveness ratio of CHF 30784 per MRSA infection avoided. The risk factor strategy was more costly yet less effective than PCR, although, after varying epidemiologic inputs, the costs and effects of both screening strategies were similar. Sensitivity analyses suggested that on-admission prevalence of MRSA carriage predicts cost-effectiveness, alongside the probability of cross-transmission, and the costs of MRSA infection, screening and contact precautions. Although reducing the risk of MRSA infection, universal PCR screening is not strongly cost-effective at our centre. However, local epidemiology plays a critical role. Settings with a higher prevalence of MRSA colonization may find universal screening cost-effective and, in some cases, cost-saving.