James M. Steckelberg

Outcome of Prosthetic Joint Infections Treated with Debridement and Retention of Components

BACKGROUNDnDebridement and retention of the prosthesis represents an attractive surgical modality for treatment of prosthetic joint infection, but risk factors for treatment failure require clarification.nnnMETHODSnWe 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.nnnRESULTSnDebridement 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).nnnCONCLUSIONSnDebridement 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.

Risk Factor Analysis of Permanent Pacemaker Infection

Background. Several host- and procedure-related factors have been reported to increase the risk of permanent pacemaker (PPM) infection on the basis of descriptive analyses of case series. The purpose of this study is to assess the risk factors for PPM infection using case-control study methods.Methods. All patients who had a PPM implanted at our institution from January 1991 to December 2003 were retrospectively reviewed. Each patient who experienced a PPM infection was matched with 2 control subjects by age, sex, year of implantation, and duration of follow-up. Univariate and multivariable analyses were performed to identify significant risk factors for PPM infection.Results. Twenty-nine case patients and 58 control subjects met inclusion criteria. The majority (83%) of case patients presented with a pocket infection; a minority (10%) had PPM-related endocarditis. Staphylococcus species (69%) were the most common pathogens. On univariate analysis, previous PPM infection, malignancy, long-term corticosteroid use, multiple device revisions, a permanent central venous catheter, the presence of >2 pacing leads, and a lack of antibiotic prophylaxis at the time of PPM placement were associated with an increased risk of PPM infection. A multivariable logistic regression model identified long-term corticosteroid use (odds ratio [OR], 13.90; 95% confidence interval [CI], 1.27-151.7; P=.03) and the presence of >2 pacing leads versus 2 leads (OR, 5.41; 95% CI, 1.44-20.29; P=.01) as independent risk factors for PPM infection. In contrast, use of antibiotic prophylaxis prior to PPM implantation had a protective effect (OR, 0.087; 95% CI, 0.016-0.48; P=.005).Conclusions. These findings should assist clinicians in identifying patients who are at increased risk of PPM infection, as well as in developing strategies to minimize the modifiable risks.

Frequency of Permanent Pacemaker or Implantable Cardioverter-Defibrillator Infection in Patients with Gram-Negative Bacteremia

BACKGROUNDnDespite the frequent occurrence of bacteremia due to gram-negative organisms in patients with underlying permanent pacemakers (PPMs) or implantable cardioverter defibrillators (ICDs), the outcome and treatment of these patients has received scant attention. In patients with PPMs or ICDs who have Staphylococcus aureus bacteremia, 45% have PPM/ICD infection.nnnMETHODSnWe conducted a retrospective cohort study over a 7-year period to assess the clinical features and frequency of PPM/ICD infection in patients with gram-negative bacteremia, as well as the incidence of relapse in patients for whom the device was not removed.nnnRESULTSnForty-nine patients were included in the study; 3 (6%) had either definite (2 patients) or possible (1 patient) PPM/ICD infection. Both patients with definite PPM/ICD infection had clear infection of the generator pocket. None of the other patients with alternate sources of bacteremia developed PPM/ICD infection. Thirty-four patients with retained PPM/ICD were observed for >12 weeks (median time, 759 days), and 2 (6%) developed relapsing bacteremia, although they each had alternative sources of relapse.nnnCONCLUSIONSnIn sharp contrast to S. aureus infection, PPM/ICD infection in patients with gram-negative bacteremia was rare, and no patients appeared to have secondary PPM/ICD infection due to hematogenous seeding of the system. Despite infrequent system removal in these patients, relapsing bacteremia among patients who survived initial bacteremia was rarely seen. If secondary PPM/ICD infection occurs in patients with gram-negative bacteremia, it is either uncommon or it is cured with antimicrobial therapy despite device retention.

The Management and Outcome of Spinal Implant Infections: Contemporary Retrospective Cohort Study

BACKGROUNDnSpinal implant infections provide unique diagnostic and therapeutic challenges.nnnMETHODSnWe conducted a retrospective cohort study to evaluate risk factors for treatment failure in patients with early- and late-onset spinal implant infections at the Mayo Clinic (Rochester, MN) during 1994-2002.nnnRESULTSnWe identified 30 patients with early-onset spinal implant infection and 51 patients with late-onset spinal implant infection. Twenty-eight of 30 patients with early-onset infection were treated with debridement, implant retention, and antimicrobial therapy. The estimated 2-year cumulative probability of survival free of treatment failure for patients with early-onset infection was 71% (95% confidence interval [CI], 51%-85%). Thirty-two of 51 patients with late-onset infection were treated with implant removal. Their estimated 2-year cumulative probability of survival free of treatment failure was 84% (95% CI, 66%-93%). For patients with early-onset infections, receiving oral antimicrobial suppression therapy was associated with increased cumulative probability of survival (hazard ratio, 0.2; 95% CI, 0.1-0.7). For patients with late-onset infections, implant removal was associated with increased cumulative probability of survival (hazard ratio, 0.3; 95% CI, 0.1-0.7).nnnCONCLUSIONSnEarly-onset spinal implant infections are successfully treated with debridement, implant retention, and parenteral followed by oral suppressive antimicrobial therapy. Implant removal is associated with successful outcomes in late-onset infections.

Impact of Prior Antiplatelet Therapy on Risk of Embolism in Infective Endocarditis

BACKGROUNDnEmbolism is a dreaded complication of infective endocarditis (IE). Currently, antimicrobial therapy is the only medical intervention proven to decrease the risk of embolism associated with IE. We hypothesized that, because platelet aggregation is operative in the pathogenesis of vegetation formation, embolism associated with IE should occur less frequently among patients who have received prior, continuous daily antiplatelet therapy for noninfectious reasons.nnnMETHODSnWe studied a retrospective cohort of adult patients with a diagnosis of IE who presented to the Mayo Clinic (Rochester, MN) during 1980-1998. The cohort was divided into 2 groups on the basis of whether they had received continuous daily antiplatelet therapy for at least 6 months prior to the time of hospitalization for IE. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine, or any of combination of these agents. The primary end point was a symptomatic embolic event that occurred prior to or during hospitalization. Multivariable logistic regression was used to assess the impact of continuous daily antiplatelet therapy on risk of symptomatic emboli associated with IE.nnnRESULTSnOne hundred forty-seven (24.5%) of 600 patients experienced a symptomatic embolic event; the most common embolic manifestation was stroke (in 48.2% of patients). Embolic events occurred significantly less often among those who had received prior, continuous daily antiplatelet therapy (12.0% of patients who had received therapy vs. 27.8% patients who had not receive therapy; P<.001). After adjustment for several covariates known to influence both risk of embolism and propensity for antiplatelet use, the adjusted odds ratio for a symptomatic embolic event was 0.36 (95% confidence interval, 0.19-0.68; P=.002) for patients receiving continuous daily antiplatelet therapy.nnnCONCLUSIONSnThe risk of symptomatic emboli associated with IE was reduced in patients who received continuous daily antiplatelet therapy before onset of IE.

Do Follow-Up Imaging Examinations Provide Useful Prognostic Information in Patients with Spine Infection?

BACKGROUNDnThe ability of follow-up imaging examinations to predict treatment failure in patients with spine infections has not been well studied.nnnMETHODSnWe conducted a retrospective cohort analysis of patients with spine infection who had both baseline and 4-8-week follow-up imaging results available at the Mayo Clinic (Rochester, MN) during the period of 1994-2002. Follow-up imaging findings were categorized as improved, equivocal, or worse, compared with the baseline findings, on the basis of a simple grading system that focused on associated soft-tissue findings.nnnRESULTSnBaseline and 4-8-week follow-up imaging findings were available for 79 patients with spine infection who presented to the Mayo Clinic during 1994-2002. Thirty-five infections (44%) were due to Staphylococcus aureus, 9 (11%) were due to coagulase-negative staphylococci, and 16 (20%) were culture negative. Twenty-seven (34%), 38 (48%), and 14 (18%) follow-up images were graded improved, equivocal, or worse, respectively. The cumulative rates of 1-year survival free of microbiologically confirmed treatment failure were 100%, 89% (95% CI, 74%-96%), and 56% (95% CI, 24%-83%) for patients with improved, equivocal, and worse follow-up imaging findings, respectively (P=.004). Only 3 (6%) of 52 patients deemed to have had clinical improvement at the time of the follow-up imaging study experienced treatment failure. Elevated levels of inflammatory biomarkers identified 2 of these patients as high risk for treatment failure, and the levels were not performed for the third patient.nnnCONCLUSIONSnApplying a simple grading scale to assess follow-up imaging examinations for patients with spinal infection stratifies their risk of treatment failure. Patients clinical statuses and inflammatory biomarker responses may be helpful for selecting patients at high risk for treatment failure who should undergo follow-up magnetic resonance imaging.

Treatment with Linezolid or Vancomycin in Combination with Rifampin Is Effective in an Animal Model of Methicillin-Resistant Staphylococcus aureus Foreign Body Osteomyelitis

ABSTRACT Rifampin monotherapy was compared to the combination of linezolid or vancomycin with rifampin in an experimental rat model of methicillin-resistant Staphylococcus aureus (MRSA) chronic foreign body osteomyelitis. MRSA was inoculated into the proximal tibia, and a titanium wire was implanted. Four weeks after infection, rats were treated intraperitoneally for 21 days with rifampin alone (n = 16), linezolid plus rifampin (n = 14), or vancomycin plus rifampin (n = 13). Thirteen animals received no treatment. At completion of treatment, qualitative cultures of the wire and quantitative cultures of the bone (reported as median values) were performed. Quantitative cultures from the control, rifampin monotherapy, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups revealed 4.54, 0.71, 0.10, and 0.50 log10 CFU/gram of bone, respectively. The bacterial load was significantly reduced in all treatment groups compared to that in the control group. Rifampin resistance was detected in isolates from 10, 2, and 1 animal in the rifampin, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups, respectively. Cultures of the removed wire revealed bacterial growth in 1 and 2 animals in the rifampin and linezolid-plus-rifampin groups, respectively, with no growth in the vancomycin-plus-rifampin group and growth from all wires in the untreated group. In conclusion, we demonstrated that combination treatment with linezolid plus rifampin or vancomycin plus rifampin is effective in an animal model of MRSA foreign body osteomyelitis in the context of retention of the infected foreign body.

Implant sonication for the diagnosis of prosthetic elbow infection

BACKGROUNDnPeriprosthetic infection is a potentially devastating complication of elbow arthroplasty, associated with formation of microbial biofilm on the implant surface. The definitive microbiologic diagnosis of periprosthetic infection after elbow arthroplasty may be difficult to establish. Our study aim was to compare the diagnostic accuracy of conventional periprosthetic tissue culture and culture of fluid derived from vortexing and bath sonication of the explanted hardware (a biofilm-sampling strategy).nnnMATERIALS AND METHODSnPatients undergoing revision elbow arthroplasty at our institution between July 2007 and July 2010, from each of whom 2 or more periprosthetic tissue cultures and 1 implant sonicate culture were obtained, were studied. A standardized definition of orthopedic implant-associated infection was applied.nnnRESULTSnWe identified 27 subjects with aseptic failure and 9 with prosthetic elbow infection. Rheumatoid arthritis was the most common underlying disorder. The Coonrad-Morrey prosthesis was the most common type of implant used. The sensitivities of implant sonicate and periprosthetic tissue culture were 89% and 55%, respectively (P = .18), and the specificities were 100% and 93%, respectively (P = .16). Coagulase-negative staphylococci (n = 7) and Staphylococcus aureus (n = 2) were isolated in cases of infection.nnnCONCLUSIONnCulture of the implant by sonication is at least as sensitive as periprosthetic tissue culture to detect prosthetic elbow infection.

Ciprofloxacin therapy of experimental endocarditis caused by methicillin-resistant Staphylococcus epidermidis.

Ciprofloxacin or rifampin was significantly (P less than 0.05) more effective than vancomycin or the combination of vancomycin plus gentamicin for the treatment of Staphylococcus epidermidis experimental endocarditis. There were no significant differences in efficacy among any of the combinations of antimicrobial agents that included ciprofloxacin or rifampin. One animal treated with rifampin alone and one treated with the combination of vancomycin, rifampin, and gentamicin were found to be infected with rifampin-resistant strains of S. epidermidis during therapy. Resistant subpopulations of S. epidermidis were not detected during therapy with any other antimicrobial agent used alone or in combination. Ciprofloxacin alone or in combination with rifampin was effective therapy against S. epidermidis experimental endocarditis.

Relative efficacies of broad-spectrum cephalosporins for treatment of methicillin-susceptible Staphylococcus aureus experimental infective endocarditis.

The effects of treatment with broad-spectrum parenterally administered cephalosporins and cefuroxime, cefazolin, or nafcillin were compared in an experimental model of Staphylococcus aureus infective endocarditis, and the results in vivo were compared with the activities of the study drugs in vitro. After 3 days of treatment, all antimicrobial agents tested were more effective than no treatment in reducing the number of surviving bacteria in cardiac valve vegetations. Nafcillin was the most effective agent studied and was significantly more active than was ceftizoxime, ceftriaxone, cefotaxime, cefoperazone, cefuroxime, or cefazolin (P < or = 0.05). Cefpirome and ceftazidime were the most effective broad-spectrum cephalosporins. The outcome of treatment with cefpirome or ceftazidime was similar to that of treatment with nafcillin and significantly better than that of treatment with ceftizoxime or cefotaxime (P < or = 0.05). Treatment outcome correlated closely with the MICs of the antimicrobial agents for the study strain with the exception of ceftazidime, which was significantly more active in vivo in comparison with other agents than predicted by its MIC (P < or = 0.0003). When ceftazidime was excluded as an outlier, treatment outcome correlated with the MICs of the remaining study drugs (Spearmans correlation coefficient, 0.95; P < or = 0.0004), as well as with the estimated percentage of time during which the concentration of total drug (correlation coefficient, -0.85; P < or = 0.007) or free drug (correlation coefficient, -0.90; P < or = 0.003) exceeded the MIC. A consideration of total or free drug concentrations in relation to MICs did not significantly improve the correlation with outcome observed with the MICs alone.