Citations

Abstract Background Mycobacterium septicum is a rapidly growing non-tuberculous mycobacterium. It is a ubiquitous organism capable of causing infections in both healthy and immunocompromised individuals. Only a few cases have been reported to date, and standard therapeutic regimens, and optimal treatment duration have not been defined. Methods We conducted a retrospective chart review of all patients seen at Mayo Clinic in Rochester, MN from July 2014 to March 2020 from whom Mycobacterium septicum was isolated in culture by our clinical microbiology laboratory. Results There were 12 patients identified with M. septicum infection – 7 males and 5 females. The average age was 67 years, with an age range of 48 to 80 years. Seven of 12 isolates obtained were from sputum samples. Only one patient was on immunosuppressive medication. Three cases were considered clinically significant infections for which directed anti-mycobacterial therapy was instituted. In two of these three cases, co-infection with Mycobacterium avium complex (MAC) was seen. Underlying structural lung disease was present in the two cases of pulmonary infections. Peritoneal dialysis catheter-related peritonitis was seen in the third case. All the isolates were susceptible to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX). The isolates were resistant to clarithromycin and doxycycline. Patient Characteristics, Associated M. septicum Illness, and Therapy Provided Antimicrobial Susceptibility Profiles of the Mycobacterium septicum Isolates, MIC (mcg/mL) and Interpretation Patient Demographics and Specimen Source of Mycobacerium septicum Isolates Conclusion M. septicum is an unusual cause of non-tuberculous mycobacterial infection. The presence of a foreign body may increase the risk of infection. Individuals with underlying structural lung disease are also likely to be at increased risk of developing pulmonary infection. Generalized treatment recommendations are limited by the lack of prospective controlled trials; hence, optimal antibiotic regimen and treatment duration have not been firmly established. Susceptibility testing should be performed to guide treatment selection, but the use of combination therapy with potentially empiric agents like amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and TMP-SMX as demonstrated in this small study, can be considered. A high rate of macrolide resistance was noted in our study. Disclosures All Authors: No reported disclosures

The American Board of Neurological Surgery (ABNS) was incorporated in 1940 in recognition of the need for detailed training in and special qualifications for the practice of neurological surgery and for self-regulation of quality and safety in the field. The ABNS believes it is the duty of neurosurgeons to place a patient’s welfare and rights above all other considerations and to provide care with compassion, respect for human dignity, honesty, and integrity. At its inception, the ABNS was the 13th member board of the American Board of Medical Specialties (ABMS), which itself was founded in 1933. Today, the ABNS is one of the 24 member boards of the ABMS. To better serve public health and safety in a rapidly changing healthcare environment, the ABNS continues to evolve in order to elevate standards for the practice of neurological surgery. In connection with its activities, including initial certification, recognition of focused practice, and continuous certification, the ABNS actively seeks and incorporates input from the public and the physicians it serves. The ABNS board certification processes are designed to evaluate both real-life subspecialty neurosurgical practice and overall neurosurgical knowledge, since most neurosurgeons provide call coverage for hospitals and thus must be competent to care for the full spectrum of neurosurgery. The purpose of this report is to describe the history, current state, and anticipated future direction of ABNS certification in the US.

Mycobacterium septicum is a rarely identified nontuberculous mycobacterium capable of causing infections in both healthy and immunocompromised individuals. Only a few cases of M. septicum infections have been reported, which makes recognizing corresponding clinical disease more challenging for clinicians. Antimicrobial susceptibility profiles for this organism are not well described, and corresponding optimal therapeutic regimens have not been established. We report a tertiary care center’s experience with M. septicum from 2014 to 2020.

e20057 Background: T-cell lymphomas (TCL) are a heterogeneous group of rare, but aggressive non-Hodgkin lymphomas. CD4+ and CD8+ T-cell function plays a vital role in the immunologic response to P.jirovecii infection. Our study aims to define the prevalence of Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected TCL patients. Methods: All patients at Mayo Clinic, Rochester MN diagnosed with TCL and a positive Pneumocystis PCR assay from either bronchoalveolar lavage (BAL) fluid or other respiratory specimens were identified from March 2005 until November 2019. Patients with TCL and a diagnosis of PJP made outside of our medical center were identified through Advanced Cohort Explorer, a query building tool. Results: A total of 922 patients with TCL were identified, and only 14 cases (1.5%) had confirmed PJP. In confirmed PJP cases, the median age of TCL diagnosis was 62 years (IQR 51-70 years), 79% were male, and the median number of chemotherapy lines was 1.5 (IQR of 1-3). Half of the cases (6/12) received CHOP as first-line of therapy, followed by CHOEP (25%, 3/12). The median time to PJP diagnosis relative to chemotherapy was 18 days (IQR 14-27 days). Peripheral TCL, not otherwise specified was the most common TCL, followed by angioimmunoblastic TCL, and CD30+ T-cell lymphoproliferative disorders (64%, 29% and 7%, respectively). The primary specimen type sampled for PJP diagnosis was BAL fluid (n = 9, 64%), followed by sputum (n = 3, 22%), induced sputum (n = 1, 7%), and transbronchial lung biopsy (n = 1, 7%). Three patients had a prior autologous stem cell transplant (ASCT), and all three cases had relapsed TCL one year after ASCT. 77% of cases received oral prednisone equivalents (median dose of 25 mg, IQR 20-40 mg) 30 days prior to PJP diagnosis. Two patients developed PJP despite anti- Pneumocystis prophylaxis with aerosolized pentamidine. At the time of PJP diagnosis, most patients had lymphopenia (88%, 8/9), and CD4+ T-cells measurement was obtained only in one patient (CD4+ of 100 cells/mL). 71% of the cases were treated with trimethoprim/sulfamethoxazole (TMP/SMX). After the initial PJP episode, 36% of the cases were transitioned to TMP/SMX for secondary prophylaxis. All cause 30-day and 90-day mortality was 7% and 29%, respectively. Mortality attributed to PJP was 7% (n = 1). Conclusions: In our TCL cohort, the occurrence of PJP was low. Primary prophylaxis should be individualized in this population.

BACKGROUND: To examine the utilization of the Tuberculosis (TB) Centers of Excellence (COE) medical consultation service and evaluate how these services were being employed for patients in relation to multidrug-resistant TB (MDR-TB).METHODS: Medical consults are documented in a secure database. The database was queried for MDR-TB consultations over the period 1 January 2013–31 December 2017. All were analyzed to assess provider type, center, setting, year of call, and type of patient (pediatric vs. adult). A subgroup was randomly selected for thematic analysis.RESULTS: The centers received 1560 MDR-TB consultation requests over this period. Providers requesting consults were primarily physicians (55%). The majority of requests were from public health departments (64%) and for adult patients (80%). Four major topic areas emerged: 1) initial management of MDR-TB, 2) MDR-TB longitudinal treatment and complications, 3) management of persons exposed to MDR-TB, and 4) MDR-TB treatment completion.CONCLUSIONS: Analysis of these consultations provides insight into the type of expert advice about MDR-TB that was provided. These findings highlight topics where increased medical training and education may help to improve MDR-TB-related practices.

ABSTRACT Evaluation of drug resistance by human immunodeficiency virus (HIV) genotyping has proven to be useful for the selection of drug combinations with maximum antiretroviral activity. We compared three genotyping methods for identification of mutations known to confer drug resistance in the reverse transcriptase (RT) and protease genes of HIV type 1 (HIV-1). The HIV-GenotypR method (GenotypR; Specialty Laboratories, Inc., Santa Monica, Calif.) with the ABI 377 DNA sequencer (Applied Biosystems Inc.), the HIV PRT GeneChip assay (GeneChip; Affymetrix, Santa Clara, Calif.), and the HIV-1 RT Line Probe Assay (LiPA; Innogenetics, Alpharetta, Ga.) were used to genotype plasma samples from HIV-infected patients attending the University of Wisconsin Hospitals and Clinics and the Mayo Clinic. At the time of analysis, patients were failing combination therapy ( n = 18) or were treatment naive ( n = 6). Forty codons of the RT and protease genes were analyzed by GenotypR and GeneChip for resistance-associated mutations. LiPA analyzed seven RT codons for mutations. Each sample was genotyped by all three assays, and each assay was subjected to pairwise comparisons. At least 92% of the codons tested (by the three assays) in paired comparisons were concordant. GenotypR and GeneChip demonstrated 96.6% concordance over the 40 codons tested. GenotypR identified slightly more mutations than GeneChip and LiPA; GeneChip identified all primary mutations that corresponded to failing treatment regimens. Each assay identified at least 84% of the mutations identified by the other assays. Mutations that were discordant between the assays mainly comprised secondary mutations and natural polymorphisms. The assays had better concordance for mutations that corresponded to current failing regimens, present in the more predominant viral quasispecies. In the treatment-naive patients, GenotypR, GeneChip, and LiPA mainly identified wild-type virus. Only the LiPA identified K70R, a possible transmitted zidovudine resistance mutation, in the RT gene of a treatment-naive patient. We conclude that although discrepancies in results exist between assays, each assay showed a similar capacity to identify potentially clinically relevant mutations related to patient treatment regimens.

Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2‐fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.

Abstract Background: Neutropenia is the most common predisposing factor that increases the susceptibility of cancer patients (pts) to infection. The use of fluoroquinolones (FQs) as prophylaxis during chemotherapy-induced neutropenia has been shown to decrease the frequency of gram-negative (GN) infections (Cullen et al. NEJM 2005) with the benefit of reduced infection-related mortality in neutropenic pts with cancer (Bucaneve et al. NEJM 2005) and was instituted as part of our institution-wide standard clinical practice in January 2006. The widespread use of FQs for prophylaxis of pts with neutropenia and hematologic malignancies raises concerns about the evolving resistance of organisms. Methods: This retrospective observational study compared acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) pts, ages 18 and older who were admitted to the hematology service and received levofloxacin prophylaxis (LEVP) within 60 days of admission with those who were admitted but did not receive LEVP during the period of chemotherapy-induced neutropenia. Pts had to have a positive sterile site culture up to 96 hours prior to admission excluding Staphylococcus coagulase negative, Propionibacterium, Corynebacterium, and other common colonizing organisms. Analysis also compared the rates of Methicillin-resistant Staphylococcus aureus (MRSA) infections, positive Vancomycin-resistant Enterococci (VRE) swabs, and positive Clostridium difficile cultures and evaluated them for a correlation LEVP. Results: A total of 213 pts were evaluated between September 2004 and May 2007. Ninety-four pts received LEVP and 119 did not. Patient characteristics were similar between groups. There was a shift from almost equal incidence of gram-positive (GP) and GN cultures in the group without prophylaxis (51% vs 49%, respectively) to a predominance of GP cultures with LEVP (68% vs 32%, respectively). There was a significant decrease in the number of sterile site cultures of GN organisms (n = 94 vs 37, respectively), while cultures of GP organisms remained similar (n = 98 vs. 77, respectively). GN organisms in sterile site cultures occurred less often in the LEVP group, however; the incidence of resistance to levofloxacin in GN was higher (32% vs 15%), particularly the susceptibility profiles of Pseudomonas sp., Escherichia coli, and Stenotrophomonas maltophilia. Both groups had equal cultures of Staphylococcus aureus, but the group receiving LEVP had a greater incidence of MRSA (55% vs 30%). Rates of positive VRE swabs declined and had no apparent correlation with the use of levofloxacin as prophylaxis. There were more documented positive Clostridium difficile cultures in the pts receiving LEVP (29% vs 22%, respectively), but rates of Clostridium difficile have shown a constant increase throughout the institution; therefore, LEVP should not be considered the sole contributing factor to an increased rate of positive cultures. Conclusions: The epidemiology and microbial susceptibility profile of positive sterile site cultures of acute leukemia pts receiving LEVP during chemotherapy-induced neutropenia differed from those that did not. The LEVP group had a decrease in the absolute number of sterile site cultures, number and percent of GN sterile site cultures. There was an increase in GN organism resistance to levofloxacin and the incidence of several GP organisms increased with the number of GP organisms remaining constant.

Abstract Background Voriconazole is a common antifungal medication used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. In solid organ transplantation, multiple studies have associated the use of voriconazole with the development of squamous cell carcinoma (SCC) post-transplant, but its association with SCC in allo-HSCT patients is unknown. We sought to determine this association. Methods After IRB approval, Mayo Clinic’s transplant database (2007-2012) was accessed and electronic charts of allo-HSCT patients were retrospectively reviewed. Voriconazole exposure was defined as exposure to voriconazole at any time during treatment of primary disease, prior to or following HSCT. Cumulative voriconazole exposure was defined as total days of voriconazole use following HSCT; days were not required to be consecutive. Two time-dependent voriconazole exposure variables were defined: (1) history of voriconazole exposure (yes/no) over time, and (2) cumulative days on voriconazole over time. Results 404 patients underwent allo-HSCT during this timeframe, and 381 patients (table 1) were included in the final analysis. 23 patients were excluded (8 patients received multiple transplants, 9 patients were treated under pediatric protocols, 6 patients lacked research consent). 312/381 received voriconazole; other antifungal therapy included fluconazole (n=40), posaconazole (n=23), anidulafungin (n=1), and caspofungin (n=5). Median duration of cumulative days of voriconazole was 214 (range 2 -1553). SCC developed in 26/312 exposed to voriconazole and in 1/69 who received alternative antifungals. Cumulative incidence of SCC at 1 year was 3%, 2 years was 8%, 3 years was 13%, 4 years was 14%, and at 5 years was 19% (figure 1). Cumulative days of voriconazole use was found to be a risk factor for the development of SCC, and this relationship persisted in a multivariate model using previously identified risk factors (gender, age at transplant, TBI conditioning regimen, skin cancer pre-HSCT, chronic GVHD) as covariates (HR 1.859 for each 180 days of use, p<0.001). History of prior voriconazole exposure was not associated with an increased risk of SCC after covariate adjustment (HR 2.436, p=0.2369). Conclusion This is the first study to establish cumulative days of voriconazole use as a risk factor for SCC development following allo-HSCT, and may help guide appropriate antifungal prophylaxis in this patient population which is already at an increased risk of developing skin cancers. Disclosures: No relevant conflicts of interest to declare.