Robert M. Rakita

Mandatory Influenza Vaccination of Healthcare Workers: A 5-Year Study

BACKGROUND The rate of influenza vaccination among healthcare workers (HCWs) is low, despite a good rationale and strong recommendations for vaccination from many health organizations. OBJECTIVE To increase influenza vaccination rates by instituting the first mandatory influenza vaccination program for HCWs. DESIGN AND SETTING A 5-year study (from 2005 to 2010) at Virginia Mason Medical Center, a tertiary care, multispecialty medical center in Seattle, Washington, with approximately 5,000 employees. METHODS All HCWs of the medical center were required to receive influenza vaccination. HCWs who were granted an accommodation for medical or religious reasons were required to wear a mask at work during influenza season. The main outcome measure was rate of influenza vaccination among HCWs. RESULTS In the first year of the program, there were a total of 4,703 HCWs, of whom 4,588 (97.6%) were vaccinated, and influenza vaccination rates of more than 98% were sustained over the subsequent 4 years of our study. Less than 0.7% of HCWs were granted an accommodation for medical or religious reasons and were required to wear a mask at work during influenza season, and less than 0.2% of HCWs refused vaccination and left Virginia Mason Medical Center. CONCLUSION A mandatory influenza vaccination program for HCWs is feasible, results in extremely high vaccination rates, and can be sustained over the course of several years.

Clinical experience with linezolid for the treatment of Nocardia infection

Linezolid is an oxazolidinone that has activity against most gram-positive bacteria, including in vitro activity against all Nocardia species and strains. We describe 6 clinical cases of nocardiosis that were successfully treated with linezolid. Two patients had underlying X-linked chronic granulomatous disease, and 2 patients were receiving chronic corticosteroid therapy. Four of 6 patients had disseminated disease, and 2 of these 4 patients had multiple brain abscesses. Four patients primarily received monotherapy; for the fifth patient, linezolid was added to a failing multiple-drug regimen, and, for the sixth patient, it was used as part of combination therapy. All 6 patients were successfully treated, although 1 patient had a presumed relapse of central nervous system infection after premature discontinuation of the drug. Linezolid appears to be an effective alternative for the treatment of nocardiosis.

DAS181 treatment of severe parainfluenza type 3 pneumonia in a lung transplant recipient

Parainfluenza virus (PIV) may cause life‐threatening pneumonia in lung transplant patients and there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, to treat severe PIV type 3 pneumonia in a lung transplant patient. Treatment was well tolerated and associated with improvement in oxygenation and symptoms, along with rapid clearance of PIV. DAS181 should be systematically evaluated for treatment of PIV infection in transplant recipients.

Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa

A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 μg/mL.

Ventricular Assist Device Related Infections and Solid Organ Transplantation

A ventricular assist device (VAD) is a mechanical pump that augments the heart’s ability to provide appropriate blood flow. VAD therapy is well established for the management of patients with refractory heart failure. Compared to medical therapy alone it improves survival, functional status and quality of life (1–4). VADs may be used to support either the right ventricle (RVAD) or the left ventricle (LVAD), or both; the vast majority today is LVAD.

Risk factors for late-onset cytomegalovirus disease in donor seropositive/recipient seronegative kidney transplant recipients who receive antiviral prophylaxis.

A.A. Boudreault, H. Xie, R.M. Rakita, J.D. Scott, C.L. Davis, M. Boeckh, A.P. Limaye. Risk factors for late‐onset cytomegalovirus disease in donor seropositive/recipient seronegative kidney transplant recipients who receive antiviral prophylaxis.
Transpl Infect Dis 2011: 13: 244–249. All rights reserved

Short-course isoniazid plus rifapentine directly observed therapy for latent tuberculosis in solid-organ transplant candidates.

Background Short-course directly observed isoniazid plus rifapentine (INH/RPT) combination could have potential advantages over a standard 9-month INH regimen for the treatment of latent tuberculosis infection in solid-organ transplant (SOT) candidates. Methods We prospectively assessed the safety and tolerability of 12 weeks of INH/RPT given directly observed therapy in 17 consecutive SOT candidates with latent tuberculosis infection. Results The median age was 57 years and 82% were men. Of the 17 patients, 13 (76%) successfully completed therapy and 4 (24%) eventually underwent SOT. Treatment was prematurely discontinued in four patients. One of these patients underwent a kidney transplant. The overall dose compliance was 83% (169/204 scheduled doses), and 12 (71%) of 17 patients received 100% of scheduled doses. No patient developed transaminase elevations greater than twice baseline or greater than four times the upper limit of normal or clinical hepatotoxicity. No cases of TB developed during 20.4 months after transplant among INH/RPT–treated recipients. Conclusions For carefully selected SOT candidates, combination INH/RPT weekly given as directly observed therapy seems to be reasonably well tolerated and is associated with a relatively high completion rate. Future larger prospective studies to confirm the safety and high completion rates reported here and to identify the most appropriate SOT candidates for this regimen are warranted.

Emergence of High-Level Daptomycin Resistance in Corynebacterium striatum in Two Patients with Left Ventricular Assist Device Infections

INTRODUCTION We describe the clinical and microbiologic courses of two patients with ventricular assist device infections secondary to Corynebacterium striatum treated with daptomycin. In both cases, the pathogen was initially susceptible to daptomycin (minimum inhibitory concentration [MIC] <0.125 mg/L) but became resistant (MIC >256 mg/L) during therapy. METHODS The clonal nature of the isolates was determined by pulse-field gel electrophoresis (PFGE). Daptomycin binding was assessed by fluorescence microscopy using daptomycin-boron-dipyrromethene (bodipy). Induction and stability of daptomycin resistance were assessed by culturing strains in the presence of low concentrations of daptomycin or passage of resistant strains on daptomycin-free medium and repeat MIC testing, respectively. RESULTS PFGE revealed that resistant clinical isolates were genetically indistinguishable from their parent strains, but the two pairs were unrelated to each other. The resistant strains had 7.5-15 times lower binding of daptomycin-bodipy compared to the related susceptible strains (p ≤ 0.0002). High-level daptomycin resistance (MIC >256 mg/L) was generated in vitro for both susceptible parent strains after overnight culture in the presence of daptomycin. One of the resistant strains maintained a high-level resistance phenotype up to 5 days of passage on daptomycin-free medium, whereas the other strain reverted back to a susceptible phenotype (MIC = 0.38 mg/L) after one passage on daptomycin-free medium, with a concomitant increase in daptomycin binding. CONCLUSIONS High-level daptomycin resistance in C. striatum was readily generated in vitro and during the course of therapy in these patients. This resistance appears to be mediated by reduced daptomycin binding. Providers should be cautious about using long-term daptomycin monotherapy for C. striatum infections.

Risk Factors and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infection in Solid Organ Transplant Recipients

Background Ganciclovir-resistant (ganR) cytomegalovirus (CMV) is an emerging and important problem in solid organ transplant (SOT) recipients. Only through direct comparison of ganR- and ganciclovir-sensitive (ganS) CMV infection can risk factors and outcomes attributable specifically to ganciclovir resistance appropriately be determined. Methods We performed a retrospective, case-control (1:3) study of SOT recipients with genotypically confirmed ganR-CMV (n = 37) and ganS-CMV infection (n = 109), matched by donor/recipient CMV serostatus, year and organ transplanted, and clinical manifestation. We used χ2 (categorical) and Mann-Whitney (continuous) tests to determine predisposing factors and morbidity attributable to resistance, and Kaplan-Meier plots to analyze survival differences. Results The rate of ganR-CMV was 1% (37/3467) overall and 4.1% (32/777) among CMV donor-positive, recipient-negative patients, and was stable over the study period. GanR-CMV was associated with increased prior exposure to ganciclovir (median, 153 vs 91 days, P < .001). Eighteen percent (3/17) of lung transplant recipients with ganR-CMV had received <6 weeks of prior ganciclovir (current guideline-recommended resistance testing threshold), and all non-lung recipients had received ≥90 days (median, 160 [range, 90-284 days]) prior to diagnosis of ganR-CMV. GanR-CMV was associated with higher mortality (11% vs 1%, P = .004), fewer days alive and nonhospitalized (73 vs 81, P = .039), and decreased renal function (42% vs 19%, P = .008) by 3 months after diagnosis. Conclusions GanR-CMV is associated with longer prior antiviral duration and higher attributable morbidity and mortality than ganS-CMV. Upcoming revised CMV guidelines should incorporate organ transplant-specific thresholds of prior drug exposure to guide rational ganR-CMV testing in SOT recipients. Improved strategies for prevention and treatment of ganR-CMV are warranted.

Multidrug-Resistant Corynebacterium striatum Associated with Increased Use of Parenteral Antimicrobial Drugs

Device-related infections with this pathogen frequently require prolonged parenteral therapy.