Steckelberg, James M.

Abstract Background. The objectives of this study were to estimate the incidence and evaluate risk factors for development of minocycline-induced cutaneous hyperpigmentation in patients with orthopedic infections. Methods. Patients with orthopedic infections evaluated at Mayo Clinic (Rochester, MN) and treated with minocycline from 1 January 2002 to 31 December 2011 were retrospectively identified. Long-term minocycline suppression was defined as daily minocycline use for at least 3 months. A proportional hazards model was used to evaluate potential risk factors. Results. Of 291 patients receiving long-term minocycline suppression, 54% (156 of 291) developed hyperpigmentation after a mean follow-up of 4.8 years (range, 0.3–13.2 years); 88% involved blue-gray pigmentation of normal skin that appeared most commonly in the lower (75%) and upper extremities (44%). The mean duration of minocycline therapy before hyperpigmentation was 1.5 years (range, 0.1–9 years) with a mean cumulative dosage of 107.3 g (range, 8.6–657 g). Notable risk factors include a history of vitamin D deficiency (relative risk [RR], 6.29; 95% confidence interval [CI], 1.91–15.27; P = .0052), presence of a shoulder prosthesis (RR, 3.2; 95% CI, 1.23–6.56; P = .0062), noncirrhotic liver pathology (RR, 3.63; 95% CI, 1.11–8.75; P = .0359), and use of a concurrent medication also known to cause hyperpigmentation (RR, 4.75; 95% CI, 1.83–10.1; P = .0029). Conclusions. Hyperpigmentation associated with the use of long-term minocycline suppression in patients with orthopedic infections is common.

ABSTRACT We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome.

Abstract Background. The purpose of this study was to determine the risk of prosthetic joint infection (PJI) as a complication of routine genitourinary (GU) procedures in patients with total hip arthroplasty (THA) or total knee arthroplasty (TKA) and to study the impact of antibiotic prophylaxis administered prior to these procedures. Methods. We conducted a prospective, single-center, case-control study between December 1, 2001 and May 31, 2006. Case patients were hospitalized with total hip or knee PJI. Control subjects underwent a THA or TKA and were hospitalized during the same period on the same orthopedic floor without a PJI. Data regarding demographic features and potential risk factors were collected. The outcome measure was the odds ratio (OR) of PJI after GU procedures performed within 2 years of admission. Results. A total of 339 case patients and 339 control subjects were enrolled in the study. Of these, 52 cases (15%) and 55 controls (16%) had undergone a GU procedure in the preceding 2 years. There was no increased risk of PJI for patients undergoing a GU procedure with or without antibiotic prophylaxis (adjusted OR [aOR] = 1.0, 95% confidence interval [CI] = 0.2–4.5, P = .95 and aOR = 1.0, 95% CI = 0.6–1.7, P = .99, respectively). Results were similar in a subset of patients with a joint age less than 6 months, less than 1 year, or greater than 1 year. Conclusions. Genitourinary procedures were not risk factors for subsequent PJI. The use of antibiotic prophylaxis before GU procedures did not decrease the risk of subsequent PJI in our study.

Background— Prompt recognition of underlying cardiovascular implantable electronic device (CIED) infection in patients presenting with Staphylococcus aureus bacteremia (SAB) is critical for optimal management of these cases. The goal of this study was to identify clinical predictors of CIED infection in patients presenting with SAB and no signs of pocket infection. Methods and Results— All cases of SAB in CIED recipients at Mayo Clinic from 2001 to 2011 were retrospectively reviewed. We identified 131 patients with CIED who presented with SAB and had no clinical signs of device pocket infection. Forty-five (34%) of these patients had underlying CIED infection based on clinical or echocardiographic criteria. The presence of a permanent pacemaker rather than an implantable cardioverter-defibrillator (odds ratio, 3.90; 95% confidence interval, 1.65–9.23; P =0.002), >1 device-related procedure (odds ratio, 3.30; 95% confidence interval, 1.23–8.86; P =0.018), and duration of SAB ≥4 days (odds ratio, 5.54; 95% confidence interval, 3.32–13.23; P <0.001) were independently associated with an increased risk of CIED infection in a multivariable model. The area under the receiver operating characteristics curve for the multivariable model was 0.79, indicating a good discriminatory capacity to distinguish SAB patients with and without CIED infection. Conclusions— Among patients presenting with SAB and no signs of pocket infection, the risk of underlying CIED infection can be calculated based on the type of device, number of device-related procedures, and duration of SAB. We propose that patients without any of these high-risk features have a low risk of underlying CIED infection and may be monitored closely without immediate device extraction. Prospective studies are needed to validate this risk prediction model.

AbstractBackground. The long-term outcome of patients with pyogenic vertebral osteomyelitis (PVO) has not been fully assessed.Methods. We conducted a retrospective cohort study to describe the long-term outcome of PVO and to assess risk factors for treatment failure in patients evaluated at our institution between 1994 and 2002. Patients were observed until July 1, 2013.Results. Two hundred sixty patients with PVO were included in this study. Twenty-seven percent (70) of patients developed their infection after an invasive spinal procedure. Staphylococcus aureus accounted for 40% (103) of infections. Forty-nine percent (128) of patients underwent spinal surgery as part of their initial therapy. The median duration of parenteral antimicrobial therapy was 42 days (interquartile range, 38–53). The estimated 2-, 5-, and 10-year cumulative probability of treatment failure-free survival was 72%, 69%, and 69%, respectively. Seventy-five percent of patients who developed treatment failure did so within 4.7 months of diagnosis. Residual neurological defects and persistent back pain were seen in 16% and 32% of patients, respectively. In a multivariate analysis, longer duration of symptoms before diagnosis and having an infection with S. aureus were associated with increased risk of treatment failure.Conclusions. Increasing duration of symptoms and infection with S. aureus were associated with treatment failure in patients with PVO. Most treatment failures occurred early after initiation of treatment. Pyogenic vertebral osteomyelitis is associated with a high 2-year failure rate. Persistent neurological deficits and back pain are common after therapy.

A technique for the prevention of staphylococcal adhesion by electrical current exposure was investigated. Teflon coupons were exposed to a continuous flow of 10 3 cfu/ml Staphylococcus epidermidis with or without 2000 microA DC electrical current delivered by electrodes on opposite sides of a coupon, touching neither each other nor the coupon. A mean 3.46 (SD, 0.20) and 5.70 (SD, 1.03) log 10 cfu/cm 2 were adhered to the non-electrical current exposed coupons after 4 h and 24 h, respectively. A mean 2.46 (SD, 0.31) and 1.47 (SD, 0.73) log 10 cfu/cm 2 were adhered after 4 h and 24 h with exposure to 2000 microA electrical current delivered by graphite electrodes. A mean 2.21 (SD, 0.14) and 0.55 (SD, 0.00) log 10 cfu/cm 2 were adhered after 4 h and 24 h with exposure to 2000 microA electrical current delivered by stainless steel electrodes. Electrical current may be useful in the prevention of staphylococcal adhesion to biomaterials.

ABSTRACT We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee ( n = 272) or hip ( n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture ( P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure.