Faculty Bibliography

We represent a group of investigators funded by the National Institutes of Health (R01AI120938, U01AI134591, U01AI138897) to conduct a prospective multicenter study of the landscape of HIV-infected (HIV+) donors and two prospective multicenter trials comparing outcomes between HIV+ recipients of HIV+ and non-HIV+ donor kidneys and livers. These clinical trials are ongoing (NCT02602262, NCT03500315, NCT03734393).

Background. Strongyloidiasis can lead to hyperinfection and dissemination afer transplantation with signifcant morbidity and mortality. Treatment for Strongyloidiasis prior to transplantation can reduce the risk of disseminated infection. Targeted screening based on travel history and country of origin incompletely identifes at-risk patients. Data on universal screening prior to solid-organ (SOT) or hematopoietic stem cell transplantation (HSCT) are limited. We implemented universal serology-based screening for strongyloides at our transplant center, located in a metropolitan non-ndemic area. Methods. We identifed patients screened with serum Strongyloides IgG by ELISA during pre-transplant evaluation for SOT or HSCT from August 1, 2017 to April 25, 2018. We reviewed adherence to the screening recommendation by program type and the medical record of seropositive patients for country of origin, history of eosinophilia (>500 cell/muL), Gram-negative bacteremia, ova and parasite (O&P) examination and treatment. Results. A total of 812 patients were evaluated for transplant during the study period: 484 for kidney, 152 for liver, 12 for liver/kidney transplant, 40 for heart, 24 for lung, and 100 for HSCT. 201 (24.7%) of the 812 patients were screened for Strongyloides; 107 (17%) evaluated for abdominal transplant, 32 (50%) for thoracic transplant, and 62 (60%) for HSCT. Seventeen (8.4%) of 201 patients screened tested positive: nine evaluated for kidney transplant, four for heart, one for liver, and three for HSCT. Nine of 17 patients (53%) were treated with Ivermectin or referred to Infectious Diseases clinic prior to our review. Ten (59%) seropositive patients were from the United States and 70% had no documented travel to endemic areas; six patients were from countries other than the United States; and one from Puerto Rico. Two patients with Strongyloidiasis had eosinophilia, one had history of Klebsiella pneumoniae bac-teremia and one had stool O&P examination. Screening was higher when using an electronic order set (57% vs. 17%). Conclusion. Universal screening for Strongyloidiasis identifed individuals with latent infection who did not have epidemiological or clinical fndings suggestive of Strongyloidiasis. Screening for Strongyloidiasis was higher in transplant programs that incorporated the recommendation into an electronic order set

Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10 versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P = 0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.

Data that can be used to guide perioperative antibiotic prophylaxis in our era of emerging antibiotic resistance are limited. We reviewed orthopedic surgeries complicated by surgical site infections (SSIs). Eighty percent of 69 arthroplasty and 80 spine fusion SSIs were infected with Gram-positive bacteria; most were staphylococcal species; and more than 25% of Staphylococcus aureus and more than 65% of coagulase-negative staphylococci were methicillin-resistant. Gram-negative bacteria were isolated from 30% of arthroplasty SSIs and 25% of spine fusion SSIs. Resistance to cefazolin was higher than 40%. A significant proportion of SSIs were caused by resistant organisms, and antibiotic guidelines were altered to provide more adequate surgical prophylaxis.

Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.

BACKGROUND: Hospital-acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a source of morbidity and mortality. S. aureus is the most common pathogen in prosthetic joint infections and the incidence of MRSA is increasing. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine the MRSA prevalence density rate at a specialty orthopaedic hospital before and after implementation of a screening and decolonization protocol, (2) to compare our prevalence density with that of an affiliated university hospital to control for changes in MRSA prevalence density that might have been independent of the decolonization protocol, and (3) to measure the admission prevalence density rate of MRSA in an elective orthopaedic surgery population and the compliance rate of 26 patients with the protocol. METHODS: In October 2008, we implemented a MRSA screening and decolonization protocol for patients undergoing elective orthopaedic surgery. Nasal swabs were used for screening and mupirocin nasal ointment and chlorhexidine skin antisepsis where prescribed for decolonization to all patients. At the surgical visit, compliance was measured and the patients who were MRSA positive received vancomycin for antibiotic prophylaxis. Institution wide surveillance for multidrug-resistant organisms, including MRSA provided a comparison of the change in MRSA burden at the orthopaedic hospital versus the university hospital. RESULTS: Before implementation of the preoperative staphylococcal decolonization protocol there were 79 MRSA-positive cultures in 64,327 patient-days for a prevalence density rate of 1.23 per 1000 patient-days. After protocol implementation, 53 MRSA-positive cultures were identified in 63,860 patient-days for a rate of 0.83 per 1000 patient-days. Before the protocol, the MRSA prevalence density at the specialty hospital was similar to that of the university hospital; after implementation of the protocol, the prevalence density at the specialty hospital was 33% lower than that of the university hospital. The MRSA admission prevalence was 3.02%. The compliance rate was greater than 95%. CONCLUSIONS: Implementation of a staphylococcal decolonization protocol at a single specialty orthopaedic hospital decreased the prevalence density of MRSA.