The American Association of Tissue Banks tissue donor screening for Mycobacterium tuberculosis-Recommended criteria and literature review.

After two multistate outbreaks of allograft tissue-transmitted tuberculosis (TB) due to viable bone, evidence-based donor screening criteria were developed to decrease the risk of transmission to recipients. Exclusionary criteria, commentary, and references supporting the criteria are provided, based on literature search and expert opinion. Both exposure and reactivation risk factors were considered, either for absolute exclusion or for exclusion in combination with multiple risk factors. A criteria subset was devised for tissues containing viable cells. Risk factors for consideration included exposure (e.g., geographic birth and residence, travel, homelessness, incarceration, healthcare, and workplace) and reactivation (e.g., kidney disease, liver disease, history of transplantation, immunosuppressive medications, and age). Additional donor considerations include the possibility of sepsis and chronic illness. Donor screening criteria represent minimal criteria for exclusion and do not completely exclude all possible donor TB risks. Additional measures to reduce transmission risk, such as donor and product testing, are discussed but not included in the recommendations. Careful donor evaluation is critical to tissue safety.

Dangerous Risk Group-4 (RG-4) emergent viruses.

World Health Organization (WHO) Risk Group-4 (RG-4) pathogens are among the most dangerous of the emergent and re-emergent viruses. International health agencies, working in concert, bridge the gaps in health care for populations at risk for RG-4 viral pathogen exposure. RG-4 virus research incorporates Biodefense Program and Biosafety Laboratory (BSL)-4 technologies. RG-4 viruses include Arena-viridae, Filo-viridae, Flavi-viridae, Herpes-viridae, Nairo-viridae, Paramyxo-viridae, and Pox-viridae.

The vanRCd Mutation 343A>G, Resulting in a Thr115Ala Substitution, Is Associated with an Elevated Minimum Inhibitory Concentration (MIC) of Vancomycin in Clostridioides difficile Clinical Isolates from Florida.

Clostridioides difficile, the primary cause of nosocomial antibiotic-associated diarrhea, has a complex relationship with antibiotics. While the use of broad-spectrum antibiotics disrupts the gut microbiota and increases the risk of C. difficile infection (CDI), antibiotics are also the primary treatment for CDI. However, only a few antibiotics, including vancomycin, fidaxomicin, and rifaximin, are effective against CDI, and resistance to these antibiotics has emerged recently. In this study, we report the identification of two RT027 C. difficile clinical isolates (TGH35 and TGH64) obtained from symptomatic CDI-diagnosed patients in Tampa, Florida in 2016. These two strains showed an elevated minimum inhibitory concentration (MIC) of vancomycin (MIC = 4 µg/mL, compared to the EUCAST breakpoint of 2 µg/mL) and contained a vanRCd 343A>G mutation resulting in a Thr115Ala substitution in the VanRCd response regulator. This mutation was absent in the vancomycin-sensitive control epidemic strain RT027/R20291. TGH64 was also resistant to rifaximin (MIC ≥ 128 µg/mL) and carried the previously reported Arg505Lys and Ile548Met mutations in RpoB. Furthermore, we report on the antimicrobial resistance (AMR) and genomic characterization of additional C. difficile isolates, including RT106/TGH120, RT017/TGH33, and RT017/TGH51, obtained from the same patient sample cohort representing the highly prevalent and regionally distributed C. difficile ribotypes worldwide. Considering that the VanRCd Thr115Ala mutation was also independently reported in seven C. difficile clinical isolates from Texas and Israel in 2019, we recommend epidemiological surveillance to better understand the impact of this mutation on vancomycin resistance. IMPORTANCE The perpetually evolving antimicrobial resistance (AMR) of C. difficile is an important contributor to its epidemiology and is a grave concern to global public health. This exacerbates the challenge of treating the infections caused by this multidrug-resistant causative organism of potentially life-threatening diarrhea. Further, the novel resistance-determining factors can be transferred between different strains and species of bacteria and cause the spread of AMR in clinical, environmental, and community settings. In this study, we have identified a mutation (vanRCd 343A>G) that causes a Thr115Ala substitution and is linked to an increased MIC of vancomycin in clinical isolates of C. difficile obtained from Florida in 2016. Understanding the mechanisms of AMR, especially those of newly evolving strains, is essential to effectively guide antibiotic stewardship policies to combat antibiotic resistance as well as to discover novel therapeutic targets.

Draft Genome Sequences and Genome Characterization of Three Toxigenic and Two Nontoxigenic Clostridioides difficile Clinical Isolates from Florida, USA.

Draft genome sequences of five Clostridioides difficile clinical isolates were obtained in Florida, USA. Three isolates, designated TGH29 (sequence type 1 [ST1]/clade 2), TGH79 (ST11/clade 5), and TGH91 (ST35/clade 1), contained toxin-encoding genes. The two nontoxigenic strains were classified as TGH114 (ST109/clade 4) and TGH132 (ST15/clade 1). Antimicrobial resistance determinants and plasmids were detected and putative prophages predicted in some isolates.

Disseminated blastomycosis in a patient with polycythemia vera on ruxolitinib.

Ruxolitinib (RUX) is a kinase inhibitor used in the treatment of various medical conditions and its mechanism of action involves suppression of the immune system. While beneficial in treatment of polycythemia vera, myelofibrosis and other indications, it can also increase a patient's susceptibility to various infections, including bacterial, viral and fungal. We present a case of a patient being treated with RUX who presented with a disseminated fungal infection. This case emphasises the need for vigilance of endemic fungal infections in individuals who are on RUX therapy.

Safety, Resistance, and Efficacy Results from a Phase IIIb Study of Conventional- and Double-Dose Oseltamivir Regimens for Treatment of Influenza in Immunocompromised Patients.

INTRODUCTION: Immunocompromised patients infected with influenza exhibit prolonged viral shedding and higher risk of resistance. Optimized treatment strategies are needed to reduce the risk of antiviral resistance. This phase IIIb, randomized, double-blind study (NCT00545532) evaluated conventional-dose or double-dose oseltamivir for the treatment of influenza in immunocompromised patients. METHODS: Patients with primary or secondary immunodeficiency and influenza infection were randomized 1:1 to receive conventional-dose oseltamivir (75 mg adolescents/adults [≥ 13 years]; 30-75 mg by body weight in children [1-12 years]) or double-dose oseltamivir (150 or 60-150 mg, respectively), twice daily for an extended period of 10 days. Nasal/throat swabs were taken for virology assessments at all study visits. Co-primary endpoints were safety/tolerability and viral resistance. Secondary endpoints included time to symptom alleviation (TTSA) and time to cessation of viral shedding (TTCVS). RESULTS: Of 228 patients enrolled between February 2008 and May 2017, 215 (199 adults) were evaluable for safety, 167 (151 adults) for efficacy, and 152 (138 adults) for resistance. Fewer patients experienced an adverse event (AE) in the conventional-dose group (50.5%) versus the double-dose group (59.1%). The most frequently reported AEs were nausea, diarrhea, vomiting, and headache. Fifteen patients had post-baseline resistance, more commonly in the conventional-dose group (n = 12) than in the double-dose group (n = 3). In adults, median TTSA was similar between arms, while median TTCVS was longer with conventional dosing. CONCLUSIONS: Oseltamivir was well tolerated, with a trend toward better safety/tolerability for conventional dosing versus double dosing. Resistance rates were higher with conventional dosing in this immunocompromised patient population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00545532. FUNDING: F. Hoffmann-La Roche Ltd.

Successful use of subcutaneous ivermectin for the treatment of Strongyloides stercoralis hyperinfection in the setting of small bowel obstruction and paralytic ileus in the immunocompromised population.

Severe Strongyloides stercoralis, such as hyperinfection syndrome, carries a high mortality risk. Even with appropriate treatment, patients may experience infectious complications and failure of therapy. Currently, there are no Food and Drug Administration-approved parenteral therapies available for treatment in patients who develop gastrointestinal complications from hyperinfection, including small bowel obstruction. A veterinary form of ivermectin is available as a subcutaneous injection, although current literature in humans is limited. We report on the successful treatment of two surviving immunocompromised patients with S. stercoralis hyperinfection syndrome after prompt recognition and initiation of veterinary subcutaneous ivermectin therapy.

Fecal microbiota transplantation outcomes in immunocompetent and immunocompromised patients: A single-center experience.

BACKGROUND: Clostridium difficile infection (CDI) is a major infectious disease focus for which fecal microbiota transplantation (FMT) has been used with success in various patient populations. METHODS: We conducted a retrospective study of FMT in immunocompetent and immunocompromised patients to review outcomes at our center, with a focus on identifying risk factors for FMT failure in solid organ transplant (SOT) patients. FMT was conducted using universal banked frozen stool via naso-duodenal tube in patients with recurrent CDI of 3 or more episodes per our institutional protocol. RESULTS: Thirteen patients were included in the analysis, 6 who were immunocompetent and 7 who were immunocompromised. Of these, 6 patients had a history of SOT and were primarily abdominal organ recipients. All immunocompetent patients experienced success with FMT, while 3 immunocompromised SOT patients experienced failure. Two patients who failed FMT had a second FMT, which was successful in one patient and failed in the second patient. No adverse events were noted with FMT administration. A predictor of FMT failure was antimicrobial exposure pre-FMT. CONCLUSIONS: This study highlights the safe use of FMT for recurrent CDI with variable efficacy in immunocompromised patients. Antimicrobial exposure prior to FMT was an identified risk factor for FMT failure. The use of sequential FMT in SOT patients may be considered but ultimately requires further investigation.

Antibiotic Resistance and Toxin Production of Clostridium difficile Isolates from the Hospitalized Patients in a Large Hospital in Florida.

Clostridium difficile is an important cause of nosocomial acquired antibiotic-associated diarrhea causing an estimated 453,000 cases with 29,000 deaths yearly in the U.S. Both antibiotic resistance and toxin expression of C. difficile correlate with the severity of C. difficile infection (CDI). In this report, a total of 139 C. difficile isolates from patients diagnosed with CDI in Tampa General Hospital (Florida) in 2016 were studied for antibiotic resistance profiles of 12 types of antibiotics and toxin production. Antibiotic resistance determined by broth microdilution method showed that strains resistant to multi-antibiotics are common. Six strains (4.32%) showed resistance to six types of antibiotics. Twenty strains (14.39%) showed resistance to five types of antibiotics. Seventeen strains (12.24%) showed resistance to four types of antibiotics. Thirty-nine strains (28.06%) showed resistance to three types of antibiotic. Thirty-four strains (24.46%) showed resistance to two types of antibiotics. While, all isolates were susceptible to metronidazole, and rifaximin, we found that one isolate (0.72%) displayed resistance to vancomycin (MIC ≥ 8 µg/ml), and another one was resistant to fidaxomicin (MIC >1 µg/ml). The percentage of isolates resistant to cefoxitin, ceftriaxone, chloramphenicol, ampicillin, clindamycin, erythromycin, gatifloxacin, and moxifloxacin was 75.54, 10.79, 5.76, 67.63, 82.70, 45.32, 28.06, and 28.78%, respectively. Toxin profiling by PCR showed the isolates include 101 (72.66%) A+B+CDT-strains, 23 (16.55%) A+B+CDT+ strains, 3 (2.16%) A-B+CDT+ strains, 1 (0.72%) A-B+CDT-strains, and 11 (7.91%) A-B-CDT-strains. Toxin production determined by ELISA using supernatants of bacterial culture harvested at 12, 24, 48, and 72 h of post inoculation (hpi) showed that the toxins were mainly produced between 48 and 72 hpi, and toxin B (TcdB) was produced faster than toxin A (TcdA) during the experimental time (72 hpi). In addition, the binary-positive strains were likely to yield more toxins compared to the binary-negative strains. This work contributes to the current understanding of the antibiotic resistance and virulence of C. difficile clinical strains.

Mycobacterium abscessus ventriculoperitoneal shunt infection and review of the literature.

A 30-year-old man with history of neonatal hydrocephalus requiring ventriculoperitoneal shunt placement presented with Mycobacterium abscessus shunt infection despite no shunt manipulation over 10 years prior to presentation. Cure was not achieved until complete removal of all CNS shunt foreign body was performed despite initial adequate antimicrobial therapy.

Survey of physicians' perspectives and knowledge about diagnostic tests for bloodstream infections.

BACKGROUND: Physicians rely on blood culture to diagnose bloodstream infections (BSI) despite its limitations. As new technologies emerge for rapid BSI diagnosis, optimization of their application to patient care requires an understanding of clinicians' perspectives on BSI diagnosis and how a rapid test would influence medical decisions. METHODS: We administered a 26-question survey to practitioners in infectious diseases/microbiology, critical care, internal medicine, and hematology/oncology services in USA and Germany about current standards in diagnosing and treating BSI and a hypothetical rapid BSI test. RESULTS: Responses from 242 providers had roughly equal representation across specialties. For suspected BSI patients, 78% of practitioners would administer empiric broad spectrum antibiotics although they estimated, on average, that 31% of patients received incorrect antibiotics while awaiting blood culture results. The ability of blood culture to rule in or rule out infection was very/extremely acceptable in 67% and 36%, respectively. Given rapid test results, 60-87% of practitioners would narrow the spectrum of antimicrobial therapy depending on the microorganism detected, with significantly higher percentages when resistance determinants were also tested. Over half of respondents felt a rapid test would be very/extremely influential on clinical practice. CONCLUSIONS: Limitations of blood culture were perceived as a barrier to patient care. A rapid test to diagnose BSI would impact clinical practice, but the extent of impact may be limited by prevailing attitudes and practices. Opportunities exist for interventions to influence practitioners' behaviors in BSI management particularly with emergence of newer diagnostic tests.

The Role of Corticosteroids in Adult Respiratory Distress Syndrome caused by Viridans Group Streptococci Bacteremia in Neutropenic Patients.

In the past decades, viridans group Streptococci (VGS) have emerged as an important cause of bacteremia in neutropenic patients with cancer. The clinical course of VGS bacteremia can be devastating including septic shock and adult respiratory distress syndrome (ARDS). It has been suggested that septicemia with VGS triggers the development of noncardiogenic pulmonary edema in patients with pre-existing damage of the lungs due to aggressive cytotoxic treatment. Thus, the preemptive administration of corticosteroid to patients diagnosed with VGS bacteremia with early onset of respiratory failure has been employed to prevent ARDS. While this management strategy has been suggested in the literature, little published data are available to validate this practice. In this study, we sought to review the benefit of early administration of corticosteroid to patients who developed symptom or early signs of respiratory failure while being neutropenic with VGS bacteremia.

Early identification and control of carbapenemase-producing Klebsiella pneumoniae, originating from contaminated endoscopic equipment.

Klebsiella producing carbapenemase is an emerging pathogen. We report transmission of this organism by contaminated endoscopic instruments. Quick identification of source, staff education, contact precautions, and emphasis on hand and environmental hygiene led to case control and prevention of outbreak.

The HIV Virologic Outcomes of Different Interventions Among Treatment-Experienced Patients With 2 Consecutive Detectable Low-Level Viremia.

BACKGROUND: Approaches to treatment-experienced HIV-infected patients with persistent low-level viremia are limited by current commercial resistance genotyping assays when the viral load (VL) is <500 copies/mL. The best intervention to achieve virologic suppression in this population is unclear. METHODS: This is a case control retrospective chart review study of 149 HIV-infected patients with a VL of 50 to 1000 copies/mL. Patients were in either regimen unchanged group or intervention group (intensification of regimen or switch without guidance from resistance testing). End point was VL < 100 copies/mL. RESULTS: At 6 months post change, 30.8% of patients with intervention versus 36.6% with no intervention achieved a complete virologic suppression. There were no statistically significant differences between these 2 groups (P = .254). The majority of patients without regimen change eventually progressed to complete virologic failure. CONCLUSION: Patients with persistent low levels of viremia are likely to progress to have virologic failure. This supports the adoption of a more proactive approach to treatment and more sensitive technique to identify drug resistance.