Steven K. Schmitt

Factors Influencing HLA Sensitization in Implantable LVAD Recipients

BACKGROUND Patients bridged to transplantation (TX) with the implantable left ventricular assist device (LVAD) may be at increased risk for the development of panel-reactive antibodies (PRA) during support. METHODS To investigate that, we evaluated 60 patients who received the HeartMate LVAD at our institution, of whom 53 had PRA results available for analysis. T lymphocyte PRA levels were examined before LVAD, at the peak PRA level during LVAD support (PEAK), and just before TX. A PRA level more than 10% was considered indicative of sensitization against HLA antigens. RESULTS The only factor that had a significant effect on PRA levels before LVAD was patients sex (1.3% for men versus 7.4% for women; p = 0.005). During LVAD support, peak PRA levels increased significantly and the sex-associated differences were no longer evident (33.3% men, 34.3% women; not significant). At the time of TX, PRAs decreased to 10.9% (men) and 7.0% (women) (not significant). We examined the influence of blood products received before TX on PRA levels. Patients who received less than the median number of total units (median). When examined by the type of blood product, only the number of platelet transfusions significantly increased the peak PRA (median: 46.9%; p = 0.03). Patients who received blood that was leukocyte-depleted tended to have lower TX PRA levels (2.9%) compared with those who did not (13.9%, p = 0.18). Forty-two patients were successfully bridged to TX, with three early and two late deaths after TX. Whereas 39 patients received transplants without intervention, 3 were treated by plasmapheresis with a 77% reduction in their HLA antibody levels at TX as measured by flow cytometry. CONCLUSIONS Patients with the implantable LVAD are at significant risk for the development of anti-HLA antibodies during support. Although this sensitization is often transient, intervention using plasmapheresis may be useful for some patients.

Cardiac implantable electronic device infections: Presentation, management, and patient outcomes

BACKGROUND Indications for cardiac implantable electronic devices (CIEDs) are increasing. Although CIED infections occur infrequently, the impact of this outcome is expected to be substantial. OBJECTIVE The purpose of this study was to the evaluate the outcome of patients undergoing removal of infected CIEDs. METHODS A retrospective study was conducted of all patients with proven or suspected infected CIEDs who were referred to the Cleveland Clinic for system removal from January 2002 through March 2007. RESULTS A total of 412 patients (age 68 +/- 15 years) were included in the study. The majority of patients (241 [59%]) presented with localized infection involving the device pocket. The remaining 171 patients (41%) presented with endovascular infection but no evidence of inflammation of the device pocket. Of the total 414 pathogens isolated, 366 (88%) were aerobic gram-positive organisms, of which 90% were Staphylococcus species, and almost half of these were methicillin resistant. In-hospital mortality was 4.6% (19 patients). Only 2 deaths were extraction related. One-year mortality was 17%. Among the total cohort, 8 (1.9%) patients had relapsing infection within the first year. Among patients who had device replacement during the same hospitalization, 6 (2.6%) had relapsing infections within 1 year of reimplantation; 5 of these patients had systemic symptoms and were bacteremic upon initial presentation. CONCLUSION CIED infections are most often caused by Staphylococcus species, half of which are methicillin resistant. Percutaneous lead and device removal along with antibiotic therapy are effective as primary interventions. The overall relapse rate is 1.9%, and the relapse rate among patients who had reimplantation during the same hospitalization is 2.6%.

Nosocomial bloodstream infections in patients with implantable left ventricular assist devices.

BACKGROUND Implantable left ventricular assist devices (LVAD) are used as a bridge to transplantation but are associated with a high risk of infection including nosocomial bloodstream infections (BSI). METHODS We retrospectively reviewed the medical records of all patients with implantable LVAD at the Cleveland Clinic with 72 hours or longer of LVAD support from January 1992 through June 2000, to determine the attack rate, incidence, and impact of nosocomial BSI in patients with LVAD. A nosocomial BSI was defined using Centers for Disease Control and Prevention definition. An LVAD-related BSI was defined as one where the same pathogen is cultured from the device and the blood with no other obvious source. Two hundred fourteen patients were included in the study (17,831 LVAD-days). RESULTS One hundred forty BSI were identified in 104 patients for an attack rate of 49% and incidence of 7.9 BSI per 1000 LVAD-days. Thirty-eight percent of the BSI were LVAD associated. The most common pathogens causing BSI were coagulase-negative staphylococci (n = 33), Staphylococcus aureus, and Candida spp. (19 each), and Pseudomonas aeruginosa (16 each). A Cox proportional hazard model found BSI in patients with LVAD to be significantly associated with death (hazard ratio = 4.02, p < 0.001). Fungemia had the highest hazard ratio (10.9), followed by gram-negative bacteremia (5.1), and gram-positive bacteremia (2.2). CONCLUSIONS Patients with implantable LVAD have a high incidence of BSI, which are associated with a significantly increased mortality. Strategies for prevention of infection in LVAD recipients should focus on the drive line exit site until technical advances can achieve a totally implantable device.

2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

Infectious Diseases Specialty Intervention is Associated with Decreased Mortality and Lower Healthcare Costs

BACKGROUND Previous studies, largely based on chart reviews with small sample sizes, have demonstrated that infectious diseases (ID) specialists positively impact patient outcomes. We investigated how ID specialists impact mortality, utilization, and costs using a large claims dataset. METHODS We used administrative fee-for-service Medicare claims to identify beneficiaries hospitalized from 2008 to 2009 with at least 1 of 11 infections. There were 101 991 stays with and 170 336 stays without ID interventions. Cohorts were propensity score matched for patient demographics, comorbidities, and hospital characteristics. Regression models compared ID versus non-ID intervention and early versus late ID intervention. Risk-adjusted outcomes included hospital and intensive care unit (ICU) length of stay (LOS), mortality, readmissions, hospital charges, and Medicare payments. RESULTS The ID intervention cohort demonstrated significantly lower mortality (odds ratio [OR], 0.87; 95% confidence interval [CI], .83 to .91) and readmissions (OR, 0.96; 95% CI, .93 to .99) than the non-ID intervention cohort. Medicare charges and payments were not significantly different; the ID intervention cohort ICU LOS was 3.7% shorter (95% CI, -5.5% to -1.9%). Patients receiving ID intervention within 2 days of admission had significantly lower 30-day mortality and readmission, hospital and ICU length of stay, and Medicare charges and payments compared with patients receiving later ID interventions. CONCLUSIONS ID interventions are associated with improved patient outcomes. Early ID interventions are also associated with reduced costs for Medicare beneficiaries with select infections.

Outbreak of methicillin-resistant Staphylococcus aureus colonization and infection in a neonatal intensive care unit epidemiologically linked to a healthcare worker with chronic otitis.

OBJECTIVE To describe the investigation and interventions necessary to contain an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in a neonatal intensive care unit (NICU). DESIGN Retrospective case finding that involved prospective performance of surveillance cultures for detection of MRSA and molecular typing of MRSA by repetitive-sequence polymerase chain reaction (rep-PCR). SETTING Level III NICU in a tertiary care center. PARTICIPANTS Three neonates in a NICU were identified with MRSA bloodstream infection on April 16, 2004. A point prevalence survey identified 6 additional colonized neonates (attack rate, 75% [9 of 12 neonates]). The outbreak strain was phenotypically unusual. INTERVENTIONS Cohorting and mupirocin therapy were initiated for neonates who had acquired MRSA during the outbreak. Contact precautions were introduced in the NICU, and healthcare workers (HCWs) were retrained in cleaning and disinfection procedures and hand hygiene. Noncolonized neonates and newly admitted patients had surveillance cultures performed 3 times per week. RESULTS Two new colonized neonates were identified 1 month later. HCW X, who had worked in the NICU since June 2003, was identified as having chronic otitis. MRSA was isolated from cultures of swab specimens from HCW Xs ear canal and nares. HCW X was epidemiologically linked to the outbreak. Molecular typing (by rep-PCR) confirmed that the isolates from HCW X and from the neonates were more than 90% similar. Retrospective review of NICU isolates revealed that the outbreak strain was initially cultured from a neonate 2 months after HCW X began working on the unit. The epidemic strain was eradicated after removing HCW X from patient care in the NICU. CONCLUSION An outbreak of MRSA colonization and infection in a NICU was epidemiologically linked to a HCW with chronic otitis externa and nasal colonization with MRSA. Eradication was not achieved until removal of HCW X from the NICU. Routine surveillance for MRSA may have allowed earlier recognition of the outbreak and is now standard practice in our NICU.

Clinical characteristics of 13 solid organ transplant recipients with ganciclovir‐resistant cytomegalovirus infection

Abstract: Background. Ganciclovir‐resistant (GCV‐R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients. Objective. To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV‐R CMV seen between 1990 and 2000 at a single center. Methods. Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV‐R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data. Results. Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R–), and 11/13 (85%) had tissue‐invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV‐based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3×/week) IV ganciclovir for prophylaxis. Conclusions. GCV‐R CMV is associated with CMV D+/R– status, tissue‐invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV‐R CMV.

High prevalence of diarrhea but infrequency of documented Clostridium difficile in autologous peripheral blood progenitor cell transplant recipients

Autologous peripheral blood progenitor cell (PBPC) transplant recipients frequently receive multiple antibiotics for neutropenic fever in addition to high-dose chemotherapy. Although there are many possible causes for diarrhea in this population, empiric therapy for possible C. difficile colitis is common in some centers. This study sought to define the frequency of diarrhea and of a positive C. difficile toxin assay in PBPC transplant recipients. Data were collected on 80 patients enrolled in a randomized trial of two different antibiotic regimens during PBPC transplant. Data included the presence or absence of diarrhea, all microbiologic studies performed during the transplant admission, and all antimicrobials administered during the transplant admission. Of 80 patients enrolled, 61 (76.3%) developed diarrhea. Only 3/61 (4.9%) had a positive C. difficile toxin assay. A total of 122 C. difficile toxin assays were performed; for each positive C. difficile assay, 41 stool samples were analyzed. Twenty courses of oral metronidazole (18/20 empiric) and 10 courses of oral vancomycin (8/10 empiric) were given. A total of 25 of 61 patients with diarrhea (41%) received therapy for possible C. difficile. Diarrhea is common during autologous PBPC transplant but a positive C. difficile assay is uncommon. The practice of empiric therapy for C. difficile in this population in a non-outbreak setting should be re-evaluated. Bone Marrow Transplantation (2000) 25, 67–69.

Secular Trends in Nosocomial Bloodstream Infections in a 55-Bed Cardiothoracic Intensive Care Unit

BACKGROUND Although bloodstream infections (BSIs) occur more frequently in intensive care unit patients than in ward patients, most studies of nosocomial BSIs in critically ill patients have not distinguished between intensive care unit populations beyond surgical, medical, and pediatric patients. METHODS The primary objective of this study was to characterize the secular trends in rates of nosocomial BSIs for all pathogens among patients admitted to a busy cardiothoracic intensive care unit in a single tertiary care institution between January 1986 and December 1995. Patients with nosocomial BSIs were identified through continual prospective surveillance. RESULTS A total of 40,207 patients were admitted to the cardiothoracic intensive care unit during the 10-year study period, and 804 episodes of nosocomial BSIs among 681 patients were identified. The mean crude BSI infection rate was 6.0 per 1,000 patient-care days and increased linearly during the study period (range, 4.4 to 8.1 per 1000 patient-care days), and approached statistical significance (p value = 0.07). The most common organisms causing BSIs were Staphylococcus aureus (12%), coagulase-negative staphylococci (11%), Candida albicans (11%), Pseudomonas aeruginosa (10%), and Enterococci (9%). The leading sources of nosocomial BSIs were primary BSIs (33%), intravascular devices (27%), lower respiratory tract infections (17%), and surgical wound infections (12%). The etiologic fraction or the proportion of deaths in cardiothoracic intensive care unit patients with BSIs was 15-fold higher than those patients without BSIs (37% versus 2.5%, p < 0.001). CONCLUSIONS Rates of nosocomial BSIs among patients in our cardiothoracic intensive care unit have increased linearly during the past decade and patients with nosocomial BSIs have an increased risk of in hospital mortality.

Chronic Suppression of Periprosthetic Joint Infections with Oral Antibiotics Increases Infection-Free Survivorship.

BACKGROUND The clinical benefit of chronic suppression with oral antibiotics as a salvage treatment for periprosthetic joint infection is unclear. The purpose of this study was to compare infection-free prosthetic survival rates between patients who received chronic oral antibiotics and those who did not following irrigation and debridement with polyethylene exchange or two-stage revision for periprosthetic joint infection. METHODS We reviewed the records on all irrigation and debridement procedures with polyethylene exchange and two-stage revisions performed at our institution from 1996 to 2010 for hip or knee periprosthetic joint infection. Of 625 patients treated with a total of 655 eligible revisions, ninety-two received chronic oral antibiotics for a minimum of six months and were eligible for inclusion in our study. These patients were compared with a matched cohort (ratio of 1:3) who did not receive chronic oral antibiotics. RESULTS The five-year infection-free prosthetic survival rate was 68.5% (95% confidence interval [CI] = 59.2% to 79.3%) for the antibiotic-suppression group and 41.1% (95% CI = 34.9% to 48.5%) for the non-suppression group (hazard ratio [HR] = 0.63, p = 0.008). Stratification by the type of surgery and the infecting organism showed a higher five-year survival rate for the patients in the suppression group who underwent irrigation and debridement with polyethylene exchange (64.7%) compared with those in the non-suppression group who underwent irrigation and debridement with polyethylene exchange (30.4%, p < 0.0001) and a higher five-year survival rate for the patients in the suppression group who had a Staphylococcus aureus infection (57.4%) compared with those in the non-suppression group who had a Staphylococcus aureus infection (40.1%, p = 0.047). CONCLUSIONS Chronic suppression with oral antibiotics increased the infection-free prosthetic survival rate following surgical treatment for periprosthetic joint infection. Patients who underwent irrigation and debridement with polyethylene exchange and those who had a Staphylococcus aureus infection had the greatest benefit.