Efficacy and safety of rifampin containing regimen for staphylococcal prosthetic joint infections treated with debridement and retention.

The aim of this study was to evaluate the efficacy and safety of rifampin for Staphylococcus aureus (SA) or coagulase negative staphylococci (CNS) prosthetic joint infection (PJI) treated with debridement and retention (D/R). We calculated the treatment failure cumulative incidence (TF) of a cohort of 101 patients with SA or CNS PJI treated with D/R and antimicrobial therapy. The effect of the use of a rifampin-based regimen was evaluated. Cox proportional hazards regression evaluated the association between treatment and time-to-TF controlling for the propensity to treat with rifampin and temporal confounders. Seven percent (1/14) of the prospective rifampin-treated patients, 32% (10/31) of the historical rifampin-treated patients and 38% (21/56) of the historical non-rifampin treated patients developed TF. After controlling for the propensity to treat with rifampin and American Society of Anesthesia scores, patients in the prospective cohort had a lower risk of TF compared to patients in the historical cohort not treated with rifampin (HR 0.11; 95%CI 0.01-0.84). None (0/14) of the patients in the prospective study developed hepatotoxicity. The outcome of staphylococcal PJI treated with D/R and rifampin-based regimens was better when compared with a historical cohort treated without rifampin.

Evaluation of antibiotic therapy following valve replacement for native valve endocarditis.

We retrospectively evaluated 105 patients at the Mayo Clinic between 1970 and 2006 with native valve endocarditis who underwent acute valve surgery. The objective was to determine if outcomes differed based on whether they had received an antibiotic regimen recommended for native valve endocarditis or one for prosthetic valve endocarditis. Fifty-two patients had streptococcal and 53 had staphylococcal infections. Patients with each type of infection were divided into two groups: the first received postoperative monotherapy (with a beta-lactam or vancomycin), and the second received combination therapy (with an aminoglycoside for streptococcal infection, and gentamicin and/or rifampin for staphylococcal infection). The duration and types of antibiotics given pre- and postoperatively, valve cultures results, antibiotic-related adverse events, relapses, and mortality rates within 6 months of surgery were analyzed. Cure rates were similar regardless of the regimen administered. With the small number of patients in each group, a multicenter study with a larger cohort of patients is needed to better define optimal postoperative treatment regimens in this population.

Follow-up MR imaging in patients with pyogenic spine infections: lack of correlation with clinical features.

BACKGROUND AND PURPOSE: Follow-up MR imaging examinations are increasingly used to monitor response to treatment in patients with spine infection. We aim to describe follow-up MR imaging examination findings 4-8 weeks after diagnosis and initiation of treatment of spine infections and to compare with clinical findings. MATERIALS AND METHODS: Thirty-three patients with spinal infection and available baseline and 4-8-week follow-up MRIs were included in this retrospective cohort study. Baseline and follow-up MR imaging were graded by 2 neuroradiologists blinded to clinical characteristics and outcome. Clinical findings and outcomes were independently obtained by retrospective review of the medical record. RESULTS: Compared with baseline MR imaging examinations, follow-up MR imaging more frequently demonstrated vertebral body loss of height (26/33 [79%] versus 14/33 [47%]; P < .001) and less frequently demonstrated epidural enhancement (19/32 [59%] versus 29/33 [88%]; P = .008), epidural canal abscess (3/32 [9%] versus 15/33 [45%]; P = .001), and epidural canal compromise (10/32 [31%] versus 19/33 [58%]; P = .008). Most follow-up MR imaging examinations demonstrated less paraspinal inflammation and less epidural enhancement compared with baseline. However, vertebral body enhancement, disk space enhancement, and bone marrow edema more often were equivocal or appeared worse compared with baseline. Twenty-one of 32 (66%) follow-up MR imaging examination overall grades were considered improved, 5 (16%) were equivocal, and 6 (19%) were worse. No single MR imaging finding was associated with clinical status. CONCLUSION: Soft tissue findings, not bony findings, should be the focus of clinicians interpreting follow-up MR imaging results. No single MR imaging parameter was associated with the patients' clinical status.

International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.

OBJECTIVE: The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. METHODS: Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. RESULTS: The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. CONCLUSION: Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics.

Outcome of prosthetic joint infections treated with debridement and retention of components.

BACKGROUND: Debridement and retention of the prosthesis represents an attractive surgical modality for treatment of prosthetic joint infection, but risk factors for treatment failure require clarification. METHODS: We conducted a retrospective cohort analysis of all patients with a prosthetic joint infection who were treated with debridement and retention of the prosthesis at the Mayo Clinic (Rochester, Minnesota) between 1995 and 1999. RESULTS: Debridement and retention of the prosthesis was the initial treatment modality for 99 episodes of prosthetic joint infection that occurred in 91 patients who presented to the Mayo Clinic during 1995-1999. A total of 32% and 23% of all episodes were due to Staphylococcus aureus and coagulase-negative staphylococci, respectively. The median duration of intravenous antimicrobial therapy was 28 days (range, 1-90 days). Oral antimicrobial suppression was used in 89% of the episodes, for a median duration of 541 days (range, 5-2673 days). Treatment failure occurred in 53 episodes during a median follow-up period of 700 days (range, 1-2779 days). The 2-year survival rate free of treatment failure was 60% (95% confidence interval [CI], 50%-71%). Variables associated with an increased risk of treatment failure in multivariable analysis included the presence of a sinus tract (hazard ratio, 2.84; 95% CI, 1.48-5.44; P = .002) and a duration of symptoms prior to debridement of > or = 8 days (hazard ratio, 1.77; 95% CI, 1.02-3.07; P = .04). CONCLUSIONS: Debridement and retention of the prosthesis is a common surgical modality at our institution to treat prosthetic joint infection. Risk factors independently associated with treatment failure include the presence of a sinus tract and duration of symptoms prior to debridement of > or = 8 days.

Influence of referral bias on the apparent clinical spectrum of infective endocarditis.

PURPOSE: To assess the effect of referral bias on the clinical spectrum of infective endocarditis. PATIENTS AND METHODS: We performed a retrospective study comparing a population-based cohort of incidence cases from Olmsted County, Minnesota, with a cohort of referred cases from the practice of the Mayo Clinic during the period from 1970 to 1987. RESULTS: In the community cohort, age was an important risk factor for acquiring endocarditis (incidence rate ratio 8.8:1 for age 65 years or older versus age less than 65 years), but episodes in elderly patients were underrepresented in the referral practice. The proportion of cases due to Staphylococcus aureus was greater in the community than in the referral practice (p less than 0.02), while a trend toward overrepresentation of enterococcal endocarditis was seen in the referral population (p = 0.057). Symptom duration prior to diagnosis was significantly shorter in the community. Overall, measures of in-hospital morbidity and mortality were similar in the two populations, but advanced age was associated with adverse outcome in the community cohort. CONCLUSION: The clinical spectrum of infective endocarditis may be distorted by referral. The increased risk of endocarditis in the elderly underscores the importance of adherence to recommendations for prophylaxis in this patient population.

Serologic testing for human immunodeficiency virus antibodies.

Familiarity with available serologic tests for antibodies to human immunodeficiency virus (HIV) has become increasingly important in a wide variety of clinical settings. Enzyme-linked immunosorbent assay (ELISA) commercial kits are most often used as Enzyme-linked immunosorbent assay (ELISA) commercial kits are most often used as screening tests, and Western blot techniques are used for confirmation of positive results. ELISA specificity and sensitivity exceed 98%; the predictive value of a positive test varies from 2% for a weakly positive test in a low-prevalence population to 99% for a strongly positive test in a high-risk group. Confirmatory Western blot testing identifies antibodies with affinity for specific HIV antigens. Indeterminate Western blot antibody patterns necessitate subsequent testing or alternative methods for interpretation. A "window" period of up to 3 or more months follows acute HIV infection before seropositivity occurs.

Cephalosporin antimicrobial agents and related compounds.

Cephalosporins are broad-spectrum antimicrobial agents that are often used empirically to treat suspected bacterial infections and also to treat culture-proven infections due to selected gram-positive and gram-negative microorganisms. Cephalosporins differ widely in their spectrum of activity, susceptibility to beta-lactamases, serum half-life, and penetration of the central nervous system. In general, the first-generation and second-generation agents are most active against staphylococci and streptococci, and the third-generation agents are most active against the Enterobacteriaceae and Pseudomonas. As a group, cephalosporins have a favorable profile of toxicity in comparison with other antimicrobial agents. The development of bacterial resistance has affected all steps of the cephalosporin mechanism of action, including production of beta-lactamases, alterations in penicillin-binding proteins, and modification of the cell wall. New cephalosporins are among the most expensive pharmaceutical agents in use today. Maintaining expertise in the choice and use of these agents will remain a challenge to physicians as additional investigational cephalosporins continue to be developed and introduced into clinical practice.

Infective endocarditis in patients receiving long-term hemodialysis.

OBJECTIVE: To ascertain the predominant characteristics of patients receiving long-term dialysis who develop infective endocarditis (IE). PATIENTS AND METHODS: We reviewed the records of all chronic hemodialysis patients who had IE at Mayo Clinic, Rochester, Minn, between 1983 and 1997. RESULTS: Twenty episodes of IE occurred in 17 patients. One patient had 3 episodes of IE, and 1 patient had 2 episodes of IE; each episode was caused by a different organism. The mean +/- SD age of our patients was 63 +/- 11 years; there were 13 males; 6 patients had diabetes mellitus; and the mean +/- SD duration of hemodialysis prior to IE was 24.2 +/- 20.5 months. This analysis included 10 episodes of IE (occurring in 9 patients) within the Mayo Clinic Dialysis System during which time 223,358 hemodialysis treatments were delivered, giving a rate of 10 IE episode per 223,336 hemodialysis treatments. Among all 20 IE episodes, there were 14 synthetic arteriovenous grafts, 4 permanent venous dialysis catheters, 2 temporary venous dialysis catheters, and 2 native arteriovenous fistulas (2 accesses in 2 patients), and access had been in place for a mean +/- SD of 15.9 +/- 18.6 months. The portal of infection was the hemodialysis access in 13 episodes of IE. The causative organisms for IE were Staphylococcus aureus in 8 cases, Enterococcus sp in 4 cases, viridans streptococcus in 3 cases, Staphylococcus epidermidis in 2 cases, and 1 case each of Streptococcus bovis, group G beta-hemolytic streptococcus, and Aspergillus sp. The mitral valve was involved in 9 cases, the aortic valve was involved in 5 cases, and the tricuspid and pulmonic valves were involved in 1 case each. Patient survival (after the first episode of IE) was 71% at 30 days; 53% at 60 days; and 35% at 1 year. Echocardiography was performed in 19 episodes of IE. The transthoracic echocardiogram was 62.5% sensitive and 40% specific for the presence of definite or probable vegetations. Univariate analysis for factors affecting 60-day survival show that presence of right-sided IE, vegetation size greater than 2.0 cm3, diagnosis of diabetes mellitus, and initial leukocyte count greater than 12.5 x 10(9)/L were poor prognostic factors. Aortic valve involvement carried a better prognosis. CONCLUSIONS: Infective endocarditis in hemodialysis patients is relatively infrequent but has a high mortality. Patients with synthetic intravascular dialysis angioaccess (synthetic grafts and venous catheters) are more likely to develop IE than patients with native arteriovenous fistulas. Transesophageal echocardiography is a preferred echocardiographic study for suspected cases of IE. Prolonged antibiotic therapy is needed for all patients, and close monitoring is needed for patients with right-sided IE, large vegetations, diabetes mellitus, and an elevated leukocyte count.

Clinical aspects of antimicrobial resistance.

Soon after penicillin was introduced into clinical use, an enzyme (penicillinase) that inactivated it was discovered. Since then, the variety of antimicrobial agents has increased substantially, along with a parallel increase in resistant pathogenic microorganisms. Resistance is now recognized against all available antimicrobial agents. Factors influencing the emergence of resistance include indiscriminate use of antibiotics, prolonged hospitalizations, increasing numbers of immunocompromised patients, and medical progress resulting in increased use of invasive procedures and devices. This article provides an update on clinical aspects of a few commonly found resistant microorganisms relevant to day-to-day clinical practice. A discussion of all resistant organisms is beyond the scope of this report. Both viral and mycobacterial resistance have been addressed in previous articles in this symposium.

Infective endocarditis due to unusual or fastidious microorganisms.

Infective endocarditis due to fastidious microorganisms is commonly encountered in clinical practice. Some organisms such as fungi account for up to 15% of cases of prosthetic valve infective endocarditis, whereas organisms of the HACEK group (Haemophilus parainfluenzae, H. aphrophilus, and H. paraphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) cause 3% of community-acquired cases of infective endocarditis. Special techniques are necessary to identify these microorganisms. A history of contact with mammals or birds may suggest infection caused by Coxiella burnetii (Q fever), Brucella species, or Chlamydia psittaci. A nosocomial cluster of postsurgical infective endocarditis may be caused by Legionella species or Mycobacterium species. If risk factors that are commonly associated with fungal infections (cardiac surgical treatment, prolonged hospitalization, indwelling central venous catheters, and long-term antibiotic use) are present, fungal endocarditis is possible. Patients with endocarditis and a history of periodontal disease or dental work in whom routine blood cultures are negative might have infection due to nutritionally variant streptococci or bacteria of the HACEK group. Communication between the microbiologist and the clinician is of crucial importance for identification of these microorganisms early during the course of the infection before complications such as embolization or valvular failure occur. In this article, we review the microbiologic and clinical features of these organisms and provide recommendations for diagnosis and treatment.

Xanthomonas maltophilia: an emerging nosocomial pathogen.

Xanthomonas maltophilia is a potentially pathogenic organism with a broad clinical spectrum. Nosocomial colonization and infection are the most common manifestations. The incidence of clinical isolation of X. maltophilia is on the rise, possibly in part because of the selective pressure from the new antimicrobial agents to which it is resistant. The organism is usually resistant to commonly used antimicrobial agents, including most cephalosporins, aztreonam, antipseudomonal penicillins, imipenem, and the quinolones.

Quantitative blood cultures in candidemia.

The relationship between quantitative data on peripheral blood cultures and source of infection was studied in 172 episodes of candidemia that occurred in 169 patients. Clinically, the source of candidemia was an intravascular device in 67 episodes, an extravascular source in 73 episodes, and endocarditis in 2 patients; no source was identified for the other 30 episodes. Colony counts were determined in peripheral blood specimens on the first day of candidemia by the lysis-centrifugation system. High-grade and low-grade candidemia were defined as 25 colony-forming units or more per 10 ml and 10 colony-forming units or fewer per 10 ml of blood, respectively. Of 48 episodes of high-grade candidemia, 43 (90%) were associated with an infected intravascular device; therefore, the presence of high-grade candidemia should prompt the removal of intravascular devices. In contrast, 92 of the 112 episodes of low-grade candidemia (82%) had an extravascular or an unidentified source of candidemia. In patients with infections associated with an intravascular device, colony counts declined significantly within 72 hours after removal of the device in the absence of antifungal therapy; failure to decline suggests an alternative source of persistent infection. Quantitative data from peripheral blood cultures may help distinguish intravascular from extravascular sources of candidemia and aid in assessing the response to the removal of infected intravascular devices.

Infectious rates of central venous pressure catheters: comparison between newly placed catheters and those that have been changed.

OBJECTIVE: To analyze the rate of infection of de novo, guidewire exchanged, and new site replacement catheters in a cohort of patients in whom catheters were changed on the basis of the clinical discretion of the attending physicians. DESIGN: We conducted an observational cohort study in catheterized patients in the intensive-care unit (ICU). MATERIAL AND METHODS: ICU patients admitted between Jan. 1, 1991, and Dec.31, 1992, were eligible for enrollment in the study. Catheter care, replacement, and duration were prospectively documented. Catheter-related infection was prospectively evaluated. Rates of catheter-related infection were determined for de novo, guidewire exchanged, and new site replacement catheters and analyzed relative to the duration of placement of individual catheters and the total duration of central venous catheterization for a specific patient. RESULTS: Fifty catheter-related infections developed in 2,470 patients. When the rate of catheter-associated infection was determined for each type of catheterization, de novo catheters had a lower observed rate of infection than either replacement type (P < or = 0.0001). After controlling for the effect of time, we found that the rate of catheter-related infections associated with a de novo catheter was less than the rate in guidewire exchanged catheters (P = 0.035). Rates of infection were similar between guidewire exchanged catheters and catheters replaced to a new site. CONCLUSION: In a population of ICU patients in whom catheter change was governed by clinical judgement, no differences were noted between the observed rates of infection of new site replacement catheters and guidewire exchange catheters.

Staphylococcus lugdunensis endocarditis: a complication of vasectomy?

Three cases of Staphylococcus lugdunensis endocarditis have been reported in patients with a history of vasectomy preceding the development of endocarditis. We describe a new case of a 39-year-old man who developed infective endocarditis due to S. lugdunensis after vasectomy. He was successfully treated with a 7-week course of intravenous antibiotics and subsequently underwent mitral valve reconstruction for severe mitral regurgitation. The present case further supports an association between vasectomy and S. lugdunensis endocarditis.

Early and late survival after surgical treatment of culture-positive active endocarditis.

OBJECTIVE: To describe a 30-year experience with surgically treated culture-positive active endocarditis. DESIGN: We retrospectively reviewed the microbiologic, clinical, and operative findings and the survival data in 151 patients with culture-positive active endocarditis encountered between 1961 and 1991. RESULTS: The mean age of the 110 male and 41 female patients was 49.8 years. Native valve endocarditis was present in 86 patients, and prosthetic valve endocarditis (PVE) was diagnosed in 65. The aortic valve was involved in 62% of patients, the mitral valve in 25%, and both valves in 10%. The operative mortality was 26%. The most important univariate determinants of mortality were an abscess at operation (P = 0.01) and renal failure (P = 0.03). A trend toward a higher mortality with PVE and staphylococcal infection was noted. For hospital survivors, the 5- and 10-year survival was 71% and 60%, respectively. Univariate determinants of an adverse long-term survival were annular abscess (P = 0.01), renal impairment (P = 0.01), heart failure (P = 0.02), and aortic valve involvement (P = 0.05). On multivariate analysis, the most important adverse determinants of long-term survival were heart failure (P = 0.02), renal impairment (P = 0.02), and PVE (P = 0.03). Thirty patients required a subsequent reoperation; of these, seven required a second and two a third operation. The most common reason for reoperation was periprosthetic regurgitation without infection (N = 19). Four operations were performed for recurrent endocarditis. At 5 and 10 years, the risk of reoperation was 23% and 36%, respectively. CONCLUSION: Although surgical treatment of culture-positive active endocarditis is still associated with substantial mortality, the long-term outcome of hospital survivors is excellent. Subsequent reoperations for periprosthetic leak are common, but recurrent infection is uncommon.

Mitral stenosis associated with valvular tophi.

Chronic tophaceous gout has become less common since the introduction of allopurinol and probenecid. Cardiac tophi have rarely been reported. In this article, we report a case of severe mitral stenosis in which valvular tophi played a major role in the pathogenesis. The case was well substantiated by echocardiography, surgical pathology, and chemical analysis.

Staphylococcus aureus prosthetic joint infection treated with prosthesis removal and delayed reimplantation arthroplasty.

OBJECTIVE: To estimate in patients with Staphylococcus aureus prosthetic joint infection after total hip arthroplasty (THA) or total knee arthroplasty (TKA) the microorganism-specific cumulative probability of treatment failure after prosthesis removal and delayed reimplantation arthroplasty. PATIENTS AND METHODS: All patients with S aureus THA or TKA infection, according to a strict case definition, who were treated with prosthesis removal and delayed reimplantation arthroplasty at Mayo Clinic Rochester between 1980 and 1991 were identified. The study group comprised patients who were free of infection at the time of reimplantation arthroplasty. This cohort was followed up until treatment failure, infection with another organism, prosthesis removal, death, or loss to follow-up occurred. The Kaplan-Meier survival method was used to estimate the cumulative probability of treatment failure. RESULTS: Among 120 S aureus prosthetic joint infections treated with prosthesis removal during the study period, 38 episodes (22 THA, 16 TKA) in 36 patients met the study inclusion criteria. After a median of 7.4 years (range, 0.9 year-16.4 years) of follow-up, treatment failure occurred in 1 (2.6%) of 38 episodes 1.4 years after reimplantation arthroplasty. The 5-year cumulative probability of treatment failure was 2.8% (95% confidence interval, 0%-8.2%). CONCLUSIONS: These data suggest that prosthesis removal and delayed reimplantation arthroplasty is an effective treatment to limit the recurrence of S aureus prosthetic joint infection, provided there is no evidence of infection at the time of reimplantation arthroplasty.

Risk factors for infective endocarditis.

The incidence of endocarditis is increased in patients with cardiac lesions causing turbulent flow. A 400-fold increase is observed in patients with prosthetic valves and a prior history of endocarditis. Other high risk lesions include rheumatic valvular disease, cyanotic congenital heart disease, and degenerative valve lesions. The smaller increased incidence in patients with mitral valve prolapse is important because of the high prevalence of mitral valve prolapse in the population. In addition, intravenous drug use and nosocomial bacteremia have emerged as important factors among patients with endocarditis.

In vitro activity of GAR-936 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.

We report the activity of the new glycylcycline antimicrobial agent GAR-936 against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 30 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant S. pneumoniae were inhibited by < or = 1, < or = 2, or < or = 0.25 microg/ml of GAR-936, respectively. Time kill experiments using vancomycin-resistant enterococci did not demonstrate synergy or antagonism between 2 microg/ml of GAR-936 and 0.25 microg/ml of quinupristin/dalfopristin.