Extended systemic antibiotic prophylaxis in ventricular assist device recipients, an infectious disease perspective.

OBJECTIVES: To evaluate whether mediastinitis/deep sternal wound infection (Med/DSWI) is more common in ventricular assist device (VAD) with delayed sternal closure (DSC) compared to VAD with primary sternal closure (PSC). METHODS: A literature search was done over the last four decades for studies that addressed this comparison. RESULTS: Two studies met our inclusion criteria, and their results are contradictory. The first study compared 184 VAD recipients with PSC to 180 VAD recipients with DSC. There was no difference in VAD-related infections between DSC and PSC (15% vs. 16%, respectively; odds ratio = 0.965, 95% confidence interval [CI] = 0.525-1.635). The second study compared 464 VAD recipients with PSC to 94 VAD recipients with DSC. The rate of surgical site infection was higher in the DSC patients (12.5% vs. 1.4%, respectively; odds ratio = 10.1; 95% CI = 3.8-27.0). DSC was identified as an independent risk factor for postoperative mortality, but no detailed infection information was given. CONCLUSIONS: There is no clear evidence of the association between DSC, compared to PSC, and Med/DSWI. Therefore, DSC is not an absolute indication for extended systemic antibiotic prophylaxis. The decision to extend the duration of systemic antibiotic prophylaxis should be made on a case-by-case basis, in collaboration with an infectious disease specialist.

Tick-Borne Relapsing Fever in the White Mountains, Arizona, USA, 2013-2018.

Tick-borne relapsing fever (TBRF) is a bacterial infection transmitted by tick bites that occurs in several different parts of the world, including the western United States. We describe 6 cases of TBRF acquired in the White Mountains of Arizona, USA, and diagnosed during 2013-2018. All but 1 case-patient had recurrent fever, and some had marked laboratory abnormalities, including leukopenia, thrombocytopenia, hyperbilirubinemia, and elevated aminotransaminases. One patient had uveitis. Diagnosis was delayed in 5 of the cases; all case-patients responded to therapy with doxycycline. Two patients had Jarisch-Herxheimer reactions. The White Mountains of Arizona have not been previously considered a region of high incidence for TBRF. These 6 cases likely represent a larger number of cases that might have been undiagnosed. Clinicians should be aware of TBRF in patients who reside, recreate, or travel to this area and especially for those who sleep overnight in cabins there.

Post-transplant primary central nervous system lymphoma after Epstein-Barr virus cerebellitis.

Post-transplantation lymphoproliferative disorder (PTLD) is a complication of solid organ and hematopoietic stem cell transplantation. Cases with isolated central nervous system (CNS) disease are rare. Epstein-Barr virus (EBV) plays a causative role. We present a patient with EBV cerebellitis documented 5 months prior to development of primary CNS PTLD (PCNS-PTLD). This case report demonstrates progression from EBV CNS infection to lymphoproliferative disorder, highlighting the importance of serial clinical and imaging monitoring in transplant patients post-EBV CNS infection. PCNS-PTLD should always be considered in the differential diagnosis for transplant patients presenting with CNS symptoms, even in cases with no evidence of EBV viremia. Earlier diagnosis and appropriate treatment could result in improved outcomes.

Prevention and Infection Management in Mechanical Circulatory Support Device Recipients.

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.

Single-center experience of antifungal prophylaxis for coccidioidomycosis in heart transplant recipients within an endemic area.

In endemic regions, coccidioidomycosis causes substantial morbidity and mortality for patients receiving solid organ transplants. We aimed to demonstrate the effect of antifungal coccidioidal prophylaxis in heart transplant (HT) recipients. We retrospectively reviewed the electronic health records of all patients who received HTs between October 19, 2005, and December 13, 2014. We collected information regarding antifungal regimens and determined whether patients subsequently developed infections. Our 174-person cohort all received antifungal prophylaxis for at least 6 months (mean follow-up, 53.8 months). One proven and one probable coccidioidal infection (each, 0.6%) occurred during the study period. The incidence of coccidioidomycosis was 0.6% at 1 year and 2.3% at 5 years. No cases of proven coccidioidomycosis occurred within 2 years after transplantation. No patients developed disseminated disease, and no sentinel events were attributed to coccidioidomycosis. Both fluconazole and voriconazole were well tolerated. In the absence of intolerance or contraindication, we suggest continuing a universal antifungal prophylactic regimen with fluconazole for at least 6-12 months in HT recipients residing in a coccidioidomycosis-endemic area.

Executive Summary: 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis.

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.

2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis.

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.

Coccidioidomycosis in Patients with Selected Solid Organ Cancers: A Case Series and Review of Medical Literature.

Coccidioidomycosis is a common infection in the desert southwestern USA; approximately 3 % of healthy persons in Arizona alone become infected annually. Coccidioidomycosis may be severe in immunocompromised persons, but experience among patients with solid organ cancer has not been fully described. Therefore, we aimed to describe the clinical courses of patients whose cancers were complicated by coccidioidomycosis at our institution, which is located in an area with endemic Coccidioides. To do so, we conducted a retrospective review from January 1, 2000, through December 31, 2014, of all patients with breast, colorectal, or ovarian cancer whose cancer courses were complicated by coccidioidomycosis. We identified 17,576 cancer patients; 14 (0.08 %) of these patients met criteria for proven or probable coccidioidomycosis diagnosed within the first 2 years after the cancer diagnosis. All of these patients had primary pulmonary coccidioidomycosis, none had relapsed prior infection, and 1 had possible extrapulmonary dissemination. Five had active coccidioidal infection during chemotherapy, 1 of whom was hospitalized for coccidioidal pneumonia. All were treated with fluconazole, and all improved clinically. Eleven did not require prolonged courses of fluconazole. There were no clearly demonstrated episodes of relapsed infection. In conclusion, coccidioidomycosis was not a common complication of breast, colorectal, or ovarian cancers in patients treated at our institution, and it was not commonly complicated by severe or disseminated infection.

Coccidioidal Tenosynovitis of the Hand and Wrist: Report of 9 Cases and Review of the Literature.

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.

Characteristics of patients with mild to moderate primary pulmonary coccidioidomycosis.

In Arizona, USA, primary pulmonary coccidioidomycosis accounts for 15%-29% of community-acquired pneumonia. To determine the evolution of symptoms and changes in laboratory values for patients with mild to moderate coccidioidomycosis during 2010-2012, we conducted a prospective 24-week study of patients with primary pulmonary coccidioidomycosis. Of the 36 patients, 16 (44%) were men and 33 (92%) were White. Median age was 53 years, and 20 (56%) had received antifungal treatment at baseline. Symptom scores were higher for patients who received treatment than for those who did not. Median times from symptom onset to 50% reduction and to complete resolution for patients in treatment and nontreatment groups were 9.9 and 9.1 weeks, and 18.7 and 17.8 weeks, respectively. Median times to full return to work were 8.4 and 5.7 weeks, respectively. One patient who received treatment experienced disseminated infection. For otherwise healthy adults with acute coccidioidomycosis, convalescence was prolonged, regardless of whether they received antifungal treatment.

Stability in the cumulative incidence, severity and mortality of 101 cases of invasive mucormycosis in high-risk patients from 1995 to 2011: a comparison of eras immediately before and after the availability of voriconazole and echinocandin-amphotericin combination therapies.

As invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti-fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk-groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995-2003) and E2, (2004-2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while 'other' dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin-echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90-day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti-fungal therapy has not improved survival.

Clinical manifestations and management of left ventricular assist device-associated 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.

Polyomavirus JC urinary shedding in kidney and liver transplant recipients associated with reduced creatinine clearance.

BACKGROUND: Polyomavirus reactivation can cause significant morbidity in solid organ transplant recipients, particularly BK virus (BKV) in kidney transplant patients. Less is known about dynamics of John Cunningham virus (JCV) in nonkidney organ transplant patients. METHODS: We examined the frequency of urinary shedding of polyomaviruses BKV and JCV and their relationship to creatinine clearance (CrCl) in a longitudinal study of 41 kidney and 33 liver transplant recipients. RESULTS: Any polyomavirus urinary shedding was more frequent in liver than kidney recipients (64% vs 39%; P= .03). JCV was excreted more frequently by liver than kidney recipients (71% vs 38%), whereas BKV was shed more often by kidney than liver patients (69% vs 52%). Mean JCV loads were significantly higher than those of BKV in both patient groups (P< .0001). Lower mean CrCl values were significantly associated with JCV shedding in both kidney and liver recipients (P< .001). CONCLUSIONS: These findings suggest that BKV and JCV display different patterns of reactivation and shedding in kidney and liver transplant patients and that JCV may have a role in renal dysfunction in some solid organ transplant recipients.

Thymidine auxotrophic Staphylococcus aureus small-colony variant endocarditis and left ventricular assist device infection.

We describe a thymidine-dependent small-colony variant of Staphylococcus aureus associated with left ventricular assist device infection and prosthetic valve and pacemaker endocarditis.

Treatment of refractory coccidioidomycosis with voriconazole or posaconazole.

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.

The utility of Coccidioides polymerase chain reaction testing in the clinical setting.

Coccidioidomycosis, the fungal infection caused by dimorphic Coccidioides sp., is typically diagnosed by histopathologic identification of spherules in affected secretions and tissues or by culture. These tests are reliable but time-intensive, delaying diagnosis and treatment. To evaluate a polymerase chain reaction (PCR) test developed to detect Coccidioides sp. in clinical specimens, we conducted a retrospective chart review of all patients (N = 145) who underwent Coccidioides PCR at our institution between April 27, 2007, and May 6, 2008, abstracting clinical, microbiologic, serologic, radiographic, treatment, and follow-up data. One hundred fifty-eight PCR tests (153 respiratory; 5 cerebrospinal fluid) produced 5 positive and 153 negative findings. Five of nine patients (56%) with confirmed or highly probable pulmonary coccidioidomycosis had a positive PCR on respiratory specimens, and four of nine (44%) had a positive culture. Among two patients with coccidioidal meningitis, none had a positive PCR, whereas Coccidioides sp. in fungal culture grew for one of two. Among six asymptomatic patients with probable coccidioidomycosis, none had a positive culture or PCR. Compared with culture of respiratory specimens, PCR demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 75, 99, 60, and 99%, respectively. Coccidioides PCR appears accurate in identifying negative results, and its sensitivity is similar to that of fungal culture.

The prevention of recrudescent coccidioidomycosis after solid organ transplantation.

BACKGROUND: Coccidioidomycosis is an endemic fungal infection of the southwestern United States that causes considerable morbidity and mortality in transplant recipients, often as the result of reactivated infection. METHODS: A retrospective review of the medical records of 47 patients with prior coccidioidomycosis who underwent solid organ transplantation (18 liver, 24 kidney, 3 pancreas, and 2 combined organ) at our tertiary care academic medical center. RESULTS: Of 47 transplant recipients with a history of coccidioidomycosis, 44 had quiescent infection at transplantation. Of the three with active coccidioidomycosis at transplantation, two were taking azole prophylaxis and had no further coccidioidal infection after transplantation. One of the three had positive serologic findings identified only on the day of transplantation, and prophylaxis was initiated a few hours after surgery along with immunosuppression; nevertheless, the treatment course was complicated by disseminated coccidioidomycosis. Seven patients did not initiate or self-discontinued prophylaxis; one patient who discontinued prophylaxis experienced recurrent pulmonary infection. CONCLUSIONS: For patients undergoing transplantation in an area endemic for coccidioidomycosis, we recommend routine evaluation for evidence of prior infection and initiation of azole prophylaxis. For our patients with quiescent infection, azoles suppressed any recrudescent coccidioidomycosis after transplantation. The selection of patients who would benefit from prophylaxis and the optimal dose and duration of such prophylaxis should be studied further.

Culture-Proven Thorn-Associated Infections in Arizona: 10-Year Experience at Mayo Clinic.

BACKGROUND: Thorn 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. METHODS: We 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. RESULTS: Of 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. CONCLUSIONS: In 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.

Invasive aspergillosis in liver transplant recipients: outcome comparison of therapy with amphotericin B lipid complex and a historical cohort treated with conventional amphotericin B.

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.