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.

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.

The association between the timing of valve surgery and 6-month mortality in left-sided infective endocarditis.

OBJECTIVE: The optimal timing of valve surgery in left-sided infective endocarditis (IE) is undefined. We aimed to examine the association between the timing of valve surgery after IE diagnosis and 6-month mortality among patients with left-sided IE. METHODS: We analysed data from a retrospective cohort of patients with left-sided IE who underwent valve surgery within 30 days of diagnosis at a tertiary centre. The association between time from IE diagnosis to surgery and all-cause 6-month mortality was assessed using Cox proportional hazards modelling after adjusting for the propensity score (to undergo surgery 0-11 days vs >11 days, median time, after IE diagnosis). RESULTS: Of 546 left-sided IE cases seen between 1980 and 1998, 129 (23.6%) underwent valve surgery within 30 days of diagnosis. The median time between IE diagnosis and surgery was 11 days (range 1-30). There were 35/129 (27.2%) deaths in the surgical group. Using Cox proportional hazards modelling, propensity score and longer time to surgery (in days) were associated with unadjusted HRs of (1.15, 95% CI 1.04 to 1.28, per 0.10 unit change, p = 0.009) and (0.93; 95% CI 0.88 to 0.99, per day, p = 0.03), respectively. In multivariate analysis, a longer time to surgery was associated with an adjusted HR (0.97; 95% CI 0.90 to 1.03). The propensity score and time from diagnosis to surgery had a correlation coefficient of r = -0.63, making multicollinearity an issue in the multivariable model. CONCLUSION: On univariate analysis, a longer time to surgery showed a significant protective effect for the outcome of mortality. After adjusting for the propensity to undergo surgery early versus late, a longer time to surgery was no longer significant but remained in the protective direction. Multicollinearity between the time to surgery and the propensity score may have hindered our ability to detect the independent effect of time to surgery.

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.

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.

Emergence of quinolone resistance among viridans group streptococci isolated from the oropharynx of neutropenic peripheral blood stem cell transplant patients receiving quinolone antimicrobial prophylaxis.

In neutropenic patients receiving quinolone prophylaxis, bacteremia with viridans group streptococci resistant to quinolones is a known complication. The frequency of occurrence of quinolone-resistant organisms colonizing the oropharynx during antibacterial prophylaxis with a quinolone is not well defined. In 48 patients undergoing hematopoietic stem cell transplantation, the prevalence of quinolone resistance in viridans group streptococci colonizing the oropharynx before and during antibacterial prophylaxis with gatifloxacin or moxifloxacin (most with concomitant penicillin) was determined. For quinolone-resistant isolates, mutations in the genes gyrA and parC, which confer resistance to quinolones, were analyzed. Seventy-four isolates before and 27 isolates during quinolone use were recovered from patients' oropharynxes. The numbers of susceptible isolates recovered before versus during quinolone use were as follows: 52 (70%) versus three (11%) for ciprofloxacin, 66 (89%) versus eight (30%) for levofloxacin, 66 (89%) versus ten (37%) for gatifloxacin, and 67 (91%) versus 11 (41%) for moxifloxacin (p<0.0001). Mutations in gyrA and/or parC were detected in quinolone-resistant isolates. Quinolone-resistant viridans group streptococci are frequently found in the oropharynx of neutropenic patients after a brief (median, 8 days) exposure to gatifloxacin or moxifloxacin.

Prosthetic joint infection diagnosed postoperatively by intraoperative culture.

The purpose of this study was to assess the outcome of prosthetic joint infection initially diagnosed by multiple positive intraoperative cultures after revision arthroplasty and treated by strategies that include less than 6 weeks of intravenous antimicrobial therapy. Between January 1995 and December 1999, 16 of 509 (3%) episodes of prosthetic joint infection in 16 patients initially were diagnosed by positive intraoperative cultures after revision arthroplasty. Patients were followed up for a median of 1057 days (range, 731-1969 days). The median age of the patients was 65 years, and 65% of patients had revision total hip arthroplasty. Coagulase-negative staphylococci and Propionibacterium spp were the main pathogens identified. Intravenous antimicrobial therapy was used in 81% of patients and chronic oral suppression was used in 56% of patients. Three patients received no antimicrobial therapy. The median duration of intravenous antimicrobial therapy was 28 days (range, 2-42 days). The 5-year survival free of treatment failure for the 16 episodes was 89%. These results suggest a favorable outcome of prosthetic joint infections because of low virulence pathogens initially diagnosed as positive intraoperative cultures after revision arthroplasty with a variety of medical treatment strategies, including strategies that contain less than 6 weeks intravenous antimicrobial therapy.

Subarachnoid haemorrhage associated with infectious endocarditis: case report and literature review.

Cases of subarachnoid haemorrhage (SAH) as a presenting feature or soon after initiation of antibiotics in infectious endocarditis (IE) have been reported. However, most had documented mycotic aneurysms as the source of haemorrhage. Reports of IE associated with SAH of unclear source are rare. A case of SAH associated with IE is reported. We also reviewed our data set on neurological complications of IE at Mayo Clinic Rochester from 1980 to 1996 for additional cases. In addition to the index case, we identified seven cases of SAH amongst 489 patients (1%) with IE for a total of eight cases. In six patients, initial cerebral angiography, magnetic resonance angiography or autopsy did not show aneurysm or other aetiology for the SAH. A mycotic aneurysm was noted in one case and the other patient had an unruptured mycotic aneurysm of the tip of basilar artery. SAH was located in the basal cistern in two patients, sylvian fissure in three, and hemispheric sulci in three. SAH is an uncommon complication of IE, and in the setting of IE a specific cause, such as mycotic aneurysm, may not be identified.

Linezolid therapy of vancomycin-resistant Enterococcus faecium experimental endocarditis.

We compared the activities of linezolid (25 mg/kg of body weight, administered intraperitoneally every 8 h) and of vancomycin (25 mg/kg of body weight, administered intraperitoneally every 8 h) in a rat model of vanA vancomycin-resistant Enterococcus faecium experimental endocarditis. Results were expressed as median log(10) CFU per gram of vegetation after 3 days of treatment. The median log(10) CFU per gram of vegetation was 10.1 among 7 untreated control animals, 10.2 among 9 vancomycin-treated animals, and 7.9 among 10 linezolid-treated animals. Linezolid treatment was more active (P < 0.05) than vancomycin treatment or no treatment.

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.

Frequency of isolation of Staphylococcus lugdunensis among staphylococcal isolates causing endocarditis: a 20-year experience.

Eighty-nine staphylococcal isolates recovered from patients with bacterial endocarditis at the Mayo Clinic from 1980 to 1999 were studied to determine the prevalence of Staphylococcus lugdunensis among clinical isolates of staphylococci causing endocarditis. Four isolates, all from patients with native mitral valve endocarditis, were identified as S. lugdunensis.

Linezolid therapy of Staphylococcus aureus experimental osteomyelitis.

The in vivo activity of linezolid or cefazolin against a clinical isolate of methicillin-susceptible Staphylococcus aureus (linezolid MIC, 2 microg/ml) was studied in a rat model of experimental osteomyelitis. Sixty rats with experimental S. aureus osteomyelitis were treated for 21 days with no antimicrobial, with 25 microg of linezolid per kg of body weight administered intraperitoneally twice or three times a day, or with 50 microg of cefazolin per kg administered intramuscularly three times a day. After treatment, the animals were sacrificed and the infected tibiae were processed for quantitative bacterial cultures. The results of treatment were expressed as log(10) CFU/gram of bone and analyzed by rank sum analysis. The results of linezolid treatment were not significantly different from those of untreated controls, while cefazolin treatment was significantly more active than no treatment or linezolid treatment.

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.

Trovafloxacin treatment of viridans group Streptococcus experimental endocarditis.

The activity of trovafloxacin was compared with those of vancomycin and penicillin in a model of Streptococcus sanguis species group (trovafloxacin MIC, 0.125 microg/ml) and Streptococcus mitis species group (trovafloxacin MIC, 0.125 microg/ml) experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no treatment, trovafloxacin at 15 mg/kg of body weight three times a day (t.i.d.), vancomycin at 15 mg/kg twice a day, or penicillin at 1. 2 x 10(6) IU t.i.d. After 3 days of treatment, the animals were sacrificed; cardiac valve vegetations were aseptically removed and cultured quantitatively. Penicillin was as active as vancomycin as measured by in vivo clearance of bacteria. Trovafloxacin was less active (P < 0.05) than vancomycin or penicillin against S. sanguis species group infection but had similar efficacy against S. mitis species group infection. Quinolones, despite MICs in the susceptible range, may not be active for serious infections caused by some viridans group streptococci.

Ciprofloxacin inhibition of experimental fracture healing.

BACKGROUND: Fluoroquinolones, such as ciprofloxacin, have an adverse effect on growing cartilage and endochondral ossification in children. This study was carried out to determine whether ciprofloxacin also has an adverse effect on the healing of experimental fractures. METHODS: Sixty male 300-gram Wistar rats were divided equally into three groups, which received ciprofloxacin, cefazolin, or no treatment for three weeks, beginning seven days after production of a closed, nondisplaced, bilateral femoral fracture. The serum concentrations of the ciprofloxacin and the cefazolin were 2.4 and 146 micrograms per milliliter, respectively. Radiographic, histological, and biomechanical studies were used to evaluate fracture-healing. RESULTS: Radiographs revealed significantly more advanced healing of the control fractures compared with the fractures in the ciprofloxacin-treated group (average stage, 2.1 compared with 1.5, p = 0.01). The cefazolin-treated group was not different from the controls with respect to radiographic healing (average stage, 1.8 compared with 2.1, p = 0.18). Torsional strength-testing of fracture callus exposed to ciprofloxacin revealed a 16 percent decrease in strength compared with the controls (284 compared with 338 newton-millimeters, p = 0.04) and a 49 percent decrease in stiffness (twenty compared with thirty-nine newton-millimeters per degree, p = 0.001). The biomechanical strength in the cefazolin-treated group was not different from that of the controls. Fracture calluses in the animals treated with ciprofloxacin showed abnormalities in cartilage morphology and endochondral bone formation and a significant decrease in the number of chondrocytes compared with the controls (0.77 x 10(4) compared with 1.3 x 10(4) cells per square millimeter, p = 0.004). CONCLUSIONS: These data suggest that experimental fractures exposed to therapeutic concentrations of ciprofloxacin in serum demonstrate diminished healing during the early stages of fracture repair. The administration of ciprofloxacin during early fracture repair may compromise the clinical course of fracture-healing.

The biopesticide Paenibacillus popilliae has a vancomycin resistance gene cluster homologous to the enterococcal VanA vancomycin resistance gene cluster.

We have previously identified, in Paenibacillus popilliae, a 708-bp sequence which has homology to the sequence of the enterococcal vanA gene. We have performed further studies revealing five genes encoding homologues of VanY, VanZ, VanH, VanA, and VanX in P. popilliae. The predicted amino acid sequences are similar to those in VanA vancomycin-resistant enterococci: 61% identity for VanY, 21% for VanZ, 74% for VanH, 77% for VanA, and 79% for VanX. The genes in P. popilliae may have been a precursor to or have had ancestral genes in common with vancomycin resistance genes in enterococci. The use of P. popilliae biopesticidal preparations in agricultural practice may have an impact on bacterial resistance in human pathogens.

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.

Lack of benefit of intravenous immune globulin in a murine model of group A streptococcal necrotizing fasciitis.

Penicillin, clindamycin, and intravenous immune globulin (Venoglobulin-S; IVIG) alone and in combination were studied in a murine model of group A streptococcal necrotizing fasciitis. As assessed by bacterial clearance, treatment with IVIG was not significantly different from no treatment. All treatment regimens that contained penicillin or clindamycin were more effective (P<.05) than no treatment or treatment with IVIG alone. No significant differences were detected among results of treatment with penicillin, penicillin/clindamycin, penicillin/IVIG, clindamycin/IVIG, or all agents combined. Clindamycin alone was less effective than penicillin/IVIG (P=.02), penicillin/clindamycin (P=.009), clindamycin/IVIG (P=.04), or all agents combined (P=.02). No antagonism was observed with the addition of clindamycin or IVIG to penicillin.