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There are currently no guidelines for the management of infection and its prevention in mechanical circulatory support (MCS) device recipients. The International Society of Heart and Lung Transplantation (ISHLT) has initiated a multidisciplinary collaboration for the creation of a consensus document to guide clinicians in infection prevention and management in MCS patients. Most medical centers use local protocols that are based on expert opinion. MCS recipients are debilitated and have some immunological dysfunction. Over the years there have been technical advancements with smaller devices and drivelines with improved durability. The pulsatile devices have been replaced with newer-generation continuous-flow devices. Patient are living longer with MCSs for bridge to transplant (BTT) and destination therapy (DT). MCS centers have improved patient management by introducing standardized driveline protocols, leading to reduced infection rates among MCS recipients.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

Background Tenosynovitis is an uncommon manifestation of disseminated infection with Coccidioides fungal species. Most experts treat this infection with combined surgical debridement and antifungal medication. The aim of our study was to examine the outcomes of patients with coccidioidal tenosynovitis of the hand and wrist. Methods We retrospectively searched for the records of patients with coccidioidal tenosynovitis of the hand and wrist at our institution. between 1987 and 2013. We also conducted a review of the literature from 1950 to 2014 to identify additional cases. Results We identified 9 cases of coccidioidal tenosynovitis of the hand and wrist at our institution, along with 5 other cases found in a review of the literature. The relapse rate was high overall (50%) and was higher after discontinuation of antifungal therapy (71%) in both immunocompromised and immunocompetent patients. Results of serologic testing were not predictive of relapse. Conclusions A treatment strategy for coccidioidal tenosynovitis should focus on long-term administration of antifungal agents.

BackgroundThorn injuries are common in the desert Southwest; however, the frequency and microbiology of thorn-associated infections have not been systematically described. Most information comes from case reports describing infections from atypical or environmental microorganisms. Our aim was to summarize the spectrum of thorn-associated infections.MethodsWe conducted a retrospective review of electronic health records for patients presenting to our institution from January 1, 2005 to December 31, 2014 for treatment of thorn-associated injuries and then focused on the patients with cultures.ResultsOf 2758 records reviewed, 1327 patients had thorn-associated injuries; however, only 58 (4.4%) had cultures. Of these patients, 37 (64%) had positive findings; 5 had polymicrobial infection. The most commonly identified organisms were Staphylococcus aureus (n = 22, 59.0%) and coagulase-negative Staphylococcus species (n = 8, 21.6%). Other pathogens included Nocardia species (n = 3, 8.1%), Streptococcus species (n = 2, 5.4%), Gram-negative bacteria (n = 2, 5.4%), Aspergillus species (n = 2, 5.4%), Paecilomyces lilacinus (n = 1, 2.7%), and Candida species (n = 1, 2.7%). There were no infections caused by Pantoea agglomerans, Sporothrix schenckii, or Coccidioides spp.ConclusionsIn contrast to most published case reports, we found that typical cutaneous microorganisms, such as Staphylococcus species, caused the majority of culture-positive, thorn-related infections.

Background. Infection is a serious complication of left ventricular assist device (LVAD) therapy. Published data regarding LVAD-associated infections (LVADIs) are limited by single-center experiences and use of nonstandardized definitions. Methods. We retrospectively reviewed 247 patients who underwent continuous-flow LVAD implantation from January 2005 to December 2011 at Mayo Clinic campuses in Minnesota, Arizona, and Florida. LVADIs were defined using the International Society for Heart and Lung Transplantation criteria. Results. We identified 101 episodes of LVADI in 78 patients (32%) from this cohort. Mean age (± standard deviation [SD]) was 57±15 years. The majority (94%) underwent Heartmate II implantation, with 62% LVADs placed as destination therapy. The most common type of LVADIs were driveline infections (47%), followed by bloodstream infections (24% VAD related, and 22% non-VAD related). The most common causative pathogens included gram-positive cocci (45%), predominantly staphylococci, and nosocomial gram-negative bacilli (27%). Almost half (42%) of the patients were managed by chronic suppressive antimicrobial therapy. While 14% of the patients had intraoperative debridement, only 3 underwent complete LVAD removal. The average duration (±SD) of LVAD support was 1.5±1.0 years. At year 2 of follow-up, the cumulative incidence of all-cause mortality was estimated to be 43%. Conclusion. Clinical manifestations of LVADI vary on the basis of the type of infection and the causative pathogen. Mortality remained high despite combined medical and surgical intervention and chronic suppressive antimicrobial therapy. Based on clinical experiences, a management algorithm for LVADI is proposed to assist in the decision-making process.

BK virus (BKV) and John Cunningham virus (JCV) are nonenveloped icosahedral DNA viruses, members of the family Polyomaviridae. Studies have estimated that the adult population worldwide is approximately 80% seropositive for BKV and approximately 50%–70% seropositive for JCV, with JCV seropositivity increasing with age [1–3]. Primary infection normally occurs during childhood, with the viruses then establishing latency/persistence in different organs, including the kidney [4, 5]. BKV and JCV undergo periodic reactivation and replication, and may cause disease in immunosuppressed hosts [6–10]. It is not known exactly which factors control the balance between latency and reactivation of BKV and JCV, but available data suggest that the cellular immune response exerts important control over these viruses [6, 11–14]. BKV is known to cause diseases of the genitourinary tract, such as hemorrhagic cystitis in bone marrow and hematopoietic stem cell transplant recipients and ureteric stenosis in renal transplant patients. However, the virus is most frequently implicated with the development of polyomavirus-associated nephropathy (PVAN) in kidney transplant patients [6, 9, 15, 16]. Reduced host immunity seems to play an important role, as studies indicate that lowering of the level of immunosuppression is associated with a decrease in BKV viral load and reduction of allograft inflammation in kidney transplant patients [6, 8, 15, 16]. Progressive multifocal leukoencephalopathy is a disease of the central nervous system, characterized by multiple foci of demyelination caused by lytic JCV infection of oligodendrocytes [7, 10, 17, 18]. Progressive multifocal leukoencephalopathy has been reported among heart, kidney, and liver transplant recipients, but its true incidence in these patient groups is not known [6, 19–21]. In addition, JCV has also been associated with some cases of PVAN in kidney transplant recipients [22–24]. Data suggest that JCV-associated PVAN may be characterized by sparse cytopathic changes but significant inflammation and fibrosis in kidney transplant patients [24]. However, the relationship between JCV reactivation and renal dysfunction is not clear, as systematic monitoring of JCV infection is not performed in kidney and nonkidney transplant patients. A high incidence of renal dysfunction has been reported in nonrenal transplant recipients [25, 26]. This renal disease has been attributed to the cumulative toxicity of calcineurin inhibitors, but many of these patients are not monitored for polyomavirus reactivation, so it is possible that polyomaviruses are more commonly associated with this clinical syndrome than currently appreciated. There is a need, therefore, for prospective studies to examine the role of BKV and JCV in renal dysfunction among nonrenal organ transplant patients. In addition, some questions remain concerning the clinical management of BKV and JCV following organ transplantation, such as the dynamics of reactivation of individual viruses in different organ transplant groups and the advisability of viral monitoring. In this prospective study, we examined BKV and JCV urinary shedding and their relationship with creatinine clearance (CrCl) in outpatient liver and kidney transplant recipients to determine whether the patterns of viral reactivation were similar in the 2 patient groups and if viral shedding was associated with renal dysfunction in liver transplant recipients.

Background Coccidioidomycosis is a fungal infection of the desert southwestern United States. It may be self-limited or may require antifungal therapy. Currently used triazoles (eg, fluconazole and itraconazole) have largely supplanted amphotericin B, which is fraught with adverse effects. Limited case reports and small open-label trials show that voriconazole and posaconazole benefit patients with coccidioidomycosis refractory to first-line agents. Methods We conducted a retrospective review of patients prescribed voriconazole or posaconazole for coccidioidomycosis at our institution between 1 January 2006 and 1 August 2010. Outcomes were assessed with both a retrospectively applied Mycosis Study Group score (ie, a composite score for symptoms, serology, and radiographic findings) and the documented impressions of treating medical practitioners. Results Twenty-one patients who received voriconazole and 16 who received posaconazole met study criteria. After a median duration of 6 months of voriconazole treatment, 14 of 21 patients (67%) were improved in overall status, 5 were unchanged, and 2 were unresponsive to voriconazole. After a median of 17 months of posaconazole treatment, 12 of 16 patients (75%) showed improvement, 1 was unchanged, and 3 were unresponsive due to medication intolerance or relapsed infection. Conclusions Voriconazole and posaconazole are reasonable but not infallible options for salvage treatment of refractory coccidioidomycosis. Prospective comparative trials are required to provide further insights into their efficacy and utility.

BACKGROUND Clinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined. METHODS In a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days. RESULTS Renal failure (odds ratio [OR], 3.17; P = .010), diabetes mellitus (OR, 8.11; P < .001), and prior voriconazole and/or caspofungin use (OR, 4.41; P = .033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P = .002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P = .021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P < .001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P = .023) and disseminated disease (OR, 14.6; P = .027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P = .003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables. CONCLUSIONS The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis.

Serious infection due to strains of Pseudomonas aeruginosa that exhibit resistance to all common antipseudomonal antimicrobials increasingly is a serious problem. Colistin was used as salvage therapy for 23 critically ill patients with multidrug-resistant P. aeruginosa infection. Twenty-two patients who had septic shock (n=14) and/or renal failure (n=21) received mechanical ventilatory support at baseline. The most common types of infection were pneumonia (n=18) and intra-abdominal infection (n=5). Colistin was administered for a median of 17 days (range, 7-36 days). Seven patients died during therapy, at a median of 17 days (range, 4-26 days) after initiation of treatment. A favorable clinical response was observed in 14 patients (61%); only 3 patients experienced relapse. Bacteremia was the only significant factor associated with treatment failure (P=.02). One patient manifested diffuse weakness that resolved after temporary cessation of colistin therapy. Colistin provides an important salvage therapeutic option for patients with otherwise untreatable serious P. aeruginosa infection.

Invasive aspergillosis (IA) in liver transplant recipients is associated with poor response rates and a very high mortality rate, despite administration of therapy with conventional amphotericin B. We conducted a single-center, retrospective study to compare the outcome of liver transplant recipients with IA who received amphotericin B lipid complex (ABLC) or conventional amphotericin B. IA was present in 12 ABLC-treated patients (definite, 4; probable, 8) and 29 amphotericin B recipients (definite, 11; probable, 18) in the historical cohort. The 60-day mortality rate was lower in the ABLC cohort: 4 (33%) of 12 patients versus 24 (83%) of 29 patients (P=.006). Only 1 of 4 ABLC recipients with definite IA died, compared with all 11 in the amphotericin B group. Sixty-day survival probability curves was significantly lower in the amphotericin B cohort (P=.008). ABLC therapy was the only independent mortality-protective variable (odds ratio, 0.31; 95% confidence interval, 0.07-0.44; P=.02). First-line or early salvage therapy for IA with ABLC was associated with significantly improved survival relative to a comparable historical group treated with amphotericin B.

To discern whether the characteristics and outcome of invasive aspergillosis in liver transplant recipients have evolved during the past decade, 26 patients who underwent transplantation during 1990-1995 (known as "the earlier cohort") were compared with 20 patients who underwent transplantation during 1998-2001 (known as "the later cohort"). Twenty-three percent of the Aspergillus infections in the earlier cohort occurredor =90 days after transplantation, compared with 55% of such infections in the later cohort (P=.026). The earlier cohort was significantly more likely to have disseminated infection (P=.034) and central nervous system (CNS) involvement (P=.0004) than was the later cohort. The mortality rate was significantly higher for the earlier cohort (92%) than for the later cohort (60%; P=.012). Only disseminated infection (not the year of transplantation) approached statistical significance as an independent predictor of outcome. In the current era, invasive aspergillosis occurs later in the posttransplantation period, is less likely to be associated with CNS infection, and is associated with a lower mortality rate, compared with invasive aspergillosis in the early 1990s.

Human parainfluenza virus (HPIV) is a common cause of seasonal respiratory tract infections. However, little is known about the clinical presentation and impact of HPIV infections in lung transplant recipients. We reviewed HPIV infections at the University of Pittsburgh Medical Center. From January 1990 through May 2000, 32 cases of HPIV infection were identified. HPIV infection was found in 24 lung transplant recipients (75%), all of whom were included in the study group. Diagnosis was established at a median of 2.1 years after transplantation (range, 0.6-5 years). Presenting symptoms included cough (17 patients), shortness of breath (16), and temperature elevation (4). Respiratory failure occurred in 5 patients (21%). The HPIV serotypes were HPIV-1 (7 patients), HPIV-2 (2), and HPIV-3 (15 [63%]). Twenty-two patients underwent transbronchial biopsy, and 18 (82%) showed signs of acute allograft rejection. Seven patients (32%) subsequently were found to have bronchiolitis obliterans.

Legionella pneumophila is an important pathogen that may cause nosocomial and community-acquired pneumonia in patients with normal or altered immunity. The epidemiology of 40 cases of legionella pneumonia in patients hospitalized between 1986 and 1994 was studied. Fourteen patients (35%) were solid organ transplant recipients. The calculated annual incidence of L. pneumophila infection was highest among lung transplant recipients (2.07 cases per 1,000 transplant-years). There was a trend toward reduced mortality rates and less severe disease among transplant patients vs. nontransplant patients: mortality rate, 36% vs. 54%; incidence of intubation, 50% vs. 69%; rate of concurrent infections, 29% vs. 38%; and overall rate of complications, 86% vs. 96%; respectively. In a multivariate analysis, factors independently associated with an increased mortality rate were nosocomial acquisition, need for intubation, formation of lung abscess or cavitation, and presence of pleural effusion. Thus, despite differing host immune responses, the most important prognostic factors affecting the outcome of legionellosis are nosocomial acquisition and the development of pulmonary complications.

Epstein-Barr virus (EBV) plays a major role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD). Patients who undergo primary EBV infection after transplantation are at greater risk of developing PTLD. In this retrospective study, the incidence of EBV infection and associated PTLD in 40 consecutive adult recipients who were seronegative for EBV at the time of liver transplantation were investigated, and risk factors for PTLD were analyzed. Of 37 patients with available timely posttransplant serum samples, 35 (95%) developed primary EBV infection. Of the 40 patients, 13 (33%) developed PTLD a median of 126 days (range, 48-776) after liver transplantation. The factor significantly associated with the development of PTLD was cytomegalovirus disease (relative risk, 7.3; 95% confidence interval, 2.36-22.6; P = .0006). Cytomegalovirus disease is a predictor for the development of PTLD in primary EBV infection after liver transplantation, and it may be a target for prophylactic intervention.

In 35 cytomegalovirus (CMV)-seronegative recipients of livers from CMV-seropositive donors, 32 (91%) developed CMV infection and 24 of them (75%) experienced disease. Polymerase chain reaction for CMV DNA in leukocytes had the best positive and negative predictive values for the development of disease within 2 months from transplantation, and shell-vial or tube culture viremia was the best predictor thereafter. In patients who developed CMV disease, CMV DNA was first detected at 46 days (median; range, 13-128) after transplantation, significantly earlier than the 77 days (range, 46-174) for those who did not develop CMV disease (P = .02). By a semiquantitative method, the CMV DNA level in the first positive sample did not predict disease development. However, the maximum CMV DNA level during infection was significantly higher in patients who developed CMV disease. In CMV-seronegative recipients of livers from CMV-seropositive donors, the time to DNA positivity following transplantation may predict disease progression and be useful as a guide for the initiation of preemptive therapy.

Amphotericin B colloidal dispersion (ABCD), a novel formulation of amphotericin B and cholesteryl sulfate in a 1 :1 ratio, was developed to reduce the toxicity of amphotericin B yet retain its antifungal efficacy. In an open-label trial, ABCD at dosages as high as 6 mg/(kg.d) was administered to 168 patients with documented or presumed systemic mycoses. All patients had responded incompletely to at least 7 days' treatment with conventional amphotericin B (CAB), had experienced CAB-induced nephrotoxic effects, had preexisting renal impairment, or had experienced other CAB-related, treatment-limiting toxic effects. The clinical response to ABCD could be evaluated in 97 patients. Complete clinical response or improvement was noted in 48 (49%) of them after a mean treatment duration of 18.5 days. All 168 enrolled patients were evaluated with regard to safety of the treatment. Even at daily doses as high as 6 mg/kg, and mean and median cumulative doses of 4.0 g and 2.4 g, respectively, ABCD had little renal toxicity : the mean change in serum level of creatinine from baseline to final value was -0.02 mg/dL. Hypokalemia developed in eight patients (5%). This study provides preliminary evidence that ABCD is effective in treating invasive mycoses and lacks the dose-limiting nephrotoxicity of CAB.

A 68-year-old liver transplant recipient who was being treated with FK 506 and immunosuppressive steroid therapy was admitted to our medical center because of a tonic-clonic seizure. Computed tomography of the head revealed multiple discrete cerebral abscesses, and culture of fluid drained intraoperatively yielded a dematiaceous fungus. The isolate was susceptible to amphotericin B and itraconazole but was resistant to flucytosine and fluconazole. The patient was successfully treated with a prolonged course of amphotericin B colloidal dispersion and itraconazole, as evidenced by both clinical and radiographic resolution of disease over a 2-year follow-up.

From January 1981 to December 1990, 2180 patients underwent orthotopic liver transplantation at the University of Pittsburgh. Thirty-two patients (1.5%) were identified with invasive aspergillosis (29 lung, 2 intraabdominal, 1 meningitis). Of 29 patients with invasive lung disease, only 23 (79%) had positive culture (Aspergillus fumigatus, 20; Aspergillus flavus, 3). Forty-eight variables were analyzed and compared in 23 patients with invasive disease with positive cultures and 9 patients with colonization only. The variables associated with pulmonary invasive disease, by univariate analysis, were surgical time (P = .03), presence of laparotomies (P = .02), higher creatinine level at time of Aspergillus isolation (P = .01), and use of OKT3 (P = .02). However, in a multivariate analysis, only the last two (creatinine, OKT3) were associated with invasive lung aspergillosis. Of 4 patients with positive abdominal wound culture, 2 had local invasive aspergillosis. Therefore, positive cultures of Aspergillus organisms from respiratory secretions and wound drainage may represent invasive disease and should not be ignored.