Severity of Cytokine Release Syndrome and Its Association with Infections after T Cell-Replete Haploidentical Related Donor Transplantation.

An increased risk of infections has been described after T cell-replete haploidentical cell transplantation (haploHCT). Cytokine release syndrome (CRS) after haploHCT is a known phenomenon, but the impact of CRS severity on the risk of infections remains unexplored. We retrospectively evaluated 78 consecutive adult haploHCT recipients from 2012 to 2018 for the development of CRS (graded based on the criteria of Lee et al) and examined the incidence and mortality due to infections in correlation with CRS severity. In our study cohort, which was stratified into 3 groups by severity of CRS, 80% of the patients developed infections within 180 days of HCT. Significantly higher proportions of patients with CRS grade 2 (89%) and grade ≥3 (90%) than patients with CRS grade 0-1 (68%) had at least 1 infection in the first 100 days (P = .04). Bloodstream infections (BSIs) were seen more frequently in patients with CRS grade 2 and grade ≥3 in the first 6 months. Multivariable analysis for time to infection showed that CRS grade ≥3 was independently associated with an elevated risk of any infection compared with CRS grade 0-1 (hazard ratio [HR], 3.05; P = .007). CRS grade ≥3 was also associated with a higher hazard of viral (HR, 3.42; P = .04) and bacterial infections (HR, 2.83; P = .03) compared with CRS grade 0-1. After adjusting for time to neutrophil engraftment as a time-dependent covariate, CRS grade ≥3 still had a significant effect on viral infections (HR, 2.49; P = .03), but not on bacterial infections (HR, 1.32; P = .57). CRS grade was also a significant predictor for infection density (overall, bacterial, and viral). The incidence of infection-related mortality by day +100 was higher in patients with severe CRS. Severe CRS developing after post-transplantation cyclophosphamide-based haploHCT is independently associated with viral infections and an increased risk of bacterial infections, likely through delayed neutrophil engraftment.

A Novel Protocol Obviates Endoscope Sampling for Carbapenem-Resistant Enterobacteriaceae: Experience of a Center with a Prior Outbreak.

BACKGROUND: Numerous published outbreaks, including one from our institution, have described endoscope-associated transmission of multidrug-resistant organisms (MDROs). Individual centers have adopted their own protocols to address this issue, including endoscope culture and sequestration. Endoscope culturing has drawbacks and may allow residual bacteria, including MDROs, to go undetected after high-level disinfection. AIM: To report the outcome of our novel protocol, which does not utilize endoscope culturing, to address our outbreak. METHODS: All patients undergoing procedures with elevator-containing endoscopes were asked to permit performance of a rectal swab. All endoscopes underwent high-level disinfection according to updated manufacturer's guidance. Additionally, ethylene oxide (EtO) sterilization was done in the high-risk settings of (1) positive response to a pre-procedure risk stratification questionnaire, (2) positive or indeterminate CRE polymerase chain reaction (PCR) from rectal swab, (3) refusal to consent for PCR or questionnaire, (4) purulent cholangitis or infected pancreatic fluid collections. Two endoscopes per weekend were sterilized on a rotational basis. RESULTS: From September 1, 2015 to April 30, 2016, 556 endoscopy sessions were performed using elevator-containing endoscopes. Prompted EtO sterilization was done on 46 (8.3%) instances, 3 from positive/indeterminate PCR tests out of 530 samples (0.6%). No CRE transmission was observed during the study period. Damage or altered performance of endoscopes related to EtO was not observed. CONCLUSION: In this pilot study, prompted EtO sterilization in high-risk patients has thus far eliminated endoscope-associated MDRO transmission, although no CRE infections were noted throughout the institution during the study period. Further studies and a larger patient sample will be required to validate these findings.

Microbiology of explanted suture segments from infected and noninfected surgical patients.

Sutures under selective host/environmental factors can potentiate postoperative surgical site infection (SSI). The present investigation characterized microbial recovery and biofilm formation from explanted absorbable (AB) and nonabsorbable (NAB) sutures from infected and noninfected sites. AB and NAB sutures were harvested from noninfected (70.9%) and infected (29.1%) sites in 158 patients. At explantation, devices were sonicated and processed for qualitative/quantitative bacteriology; selective sutures were processed for scanning electron microscopy (SEM). Bacteria were recovered from 85 (53.8%) explanted sites; 39 sites were noninfected, and 46 were infected. Suture recovery ranged from 11.1 to 574.6 days postinsertion. A significant difference in mean microbial recovery between noninfected (1.2 isolates) and infected (2.7 isolates) devices (P < 0.05) was noted. Staphylococcus epidermidis, Staphylococcus aureus, coagulase-negative staphylococci (CNS), Peptostreptococcus spp., Bacteroides fragilis, Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa, and Serratia spp. were recovered from infected devices, while commensal skin flora was recovered from noninfected devices. No significant difference in quantitative microbial recovery between infected monofilament and multifilament sutures was noted. Biofilm was present in 100% and 66.6% of infected and noninfected devices, respectively (P < 0.042). We conclude that both monofilament and braided sutures provide a hospitable surface for microbial adherence: (i) a significant difference in microbial recovery from infected and noninfected sutures was noted, (ii) infected sutures harbored a mixed flora, including multidrug-resistant health care-associated pathogens, and (iii) a significant difference in the presence or absence of a biofilm in infected versus noninfected explanted devices was noted. Further studies to document the benefit of focused risk reduction strategies to minimize suture contamination and biofilm formation postimplantation are warranted.

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.

Background: Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown. Objectives: To assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how in COVID-19 populations Lp(a) and tPA change post infection. Methods: Endogenous tPA enzymatic activity, tPA or Lp(a) concentration were measured in plasma from hospitalized patients with and without COVID-19. The association between plasma tPA and adverse clinical outcomes was assessed. Results: In hospitalized patients with COVID-19, we found lower tPA enzymatic activity and higher plasma Lp(a) than that in non-COVID-19 controls. During hospitalization, Lp(a) increased and tPA activity decreased, which associates with mortality. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased during recovery. In patients with COVID-19, tPA activity is inversely correlated with tPA concentrations, thus, in another larger COVID-19 cohort, we utilized plasma tPA concentration as a surrogate to inversely reflect tPA activity. The tPA concentration was positively associated with death, disease severity, plasma inflammatory, and prothrombotic markers, and with length of hospitalization among those who were discharged. Conclusion: High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.

Cryptococcal infection with ruxolitinib in primary myelofibrosis: A case report and literature review.

Cryptococcus neoformans (CN) is an encapsulated yeast that is found worldwide. It causes self-limiting infections in immunocompetent hosts; however, infections due to CN could be disseminated and potentially life-threatening in immunocompromised hosts. Herein, we present a patient with primary myelofibrosis who received ruxolitinib and developed disseminated cryptococcosis due to CN. We further discuss immune compromising factors indigenous to myeloproliferative neoplasms, ruxolitinib, and immunological pathways associated with janus kinase inhibition. We further review other cases of cryptococcal infections in patients receiving ruxolitinib reported in the literature. The report underscores the importance of suspecting infections with intracellular pathogens early in the course of illness in patients with higher rates of cumulative immunosuppression. A high clinical suspicion should be maintained when caring for such immunosuppressed patients receiving immunomodulatory agents as severe, disseminated infections can present atypically and lead to worse outcomes.

Surveillance cultures following a regional outbreak of carbapenem-resistant Acinetobacter baumannii.

OBJECTIVES: The primary aim of this study was to assess the epidemiology of carbapenem-resistant Acinetobacter baumannii (CRAB) for 9 months following a regional outbreak with this organism. We also aimed to determine the differential positivity rate from different body sites and characterize the longitudinal changes of surveillance test results among CRAB patients. DESIGN: Observational study. SETTING: A 607-bed tertiary-care teaching hospital in Milwaukee, Wisconsin. PATIENTS: Any patient admitted from postacute care facilities and any patient housed in the same inpatient unit as a positive CRAB patient. METHODS: Participants underwent CRAB surveillance cultures from tracheostomy secretions, skin, and stool from December 5, 2018, to September 6, 2019. Cultures were performed using a validated, qualitative culture method, and final bacterial identification was performed using mass spectrometry. RESULTS: In total, 682 patients were tested for CRAB, of whom 16 (2.3%) were positive. Of the 16 CRAB-positive patients, 14 (87.5%) were residents from postacute care facilities and 11 (68.8%) were African American. Among positive patients, the positivity rates by body site were 38% (6 of 16) for tracheal aspirations, 56% (9 of 16) for skin, and 82% (13 of 16) for stool. CONCLUSIONS: Residents from postacute care facilities were more frequently colonized by CRAB than patients admitted from home. Stool had the highest yield for identification of CRAB.

Bronchoalveolar lavage-based COVID-19 testing in patients with cancer.

OBJECTIVE/BACKGROUND: A few case reports in the setting of coronavirus disease 2019 (COVID-19) and multiplex polymerase chain reaction (PCR)-based assays for common respiratory pathogens have shown a higher yield of bronchoalveolar lavage (BAL) samples than upper airway specimens in immunocompromised patients. METHODS: A retrospective study was conducted reviewing patients diagnosed with COVID-19 at the Medical College of Wisconsin (Milwaukee, WI, USA) between March 13, 2020 and June 11, 2020. All patients tested positive for SARS-CoV-2 via real-time reverse transcriptase PCR (RT-PCR), through a nasopharyngeal or a bronchoscopy specimen. RESULTS: During the study period, 53 bronchoscopy procedures were performed at the institution, of which five patients tested positive for COVID-19. Of the five patients, three underwent BAL testing based on high clinical suspicion for COVID-19 after the nasopharyngeal (NP) swab(s) was negative. All three patients had underlying cancers and had lymphopenia for a considerable duration prior to being diagnosed with COVID-19. Two patients had better outcomes that could be attributed to earlier BAL specimen testing resulting in timely medical intervention. CONCLUSION: This study underscores the need for early lower respiratory tract sampling, whenever possible, in patients with cancer and prolonged lymphopenia. High clinical suspicion ought to supersede false-negative NP reverse transcriptase-PCR as early bronchoscopic evaluation in cancer patients, who are either receiving active treatment or are immunosuppressed, can allow timely institution of efficacious treatment, enrollment into clinical trials, as well as effective infection control. In the apt clinical setting in patients with cancer, presumptive treatment may also be considered to minimize exposure to healthcare providers and proceduralists.

Toxigenic Clostridioides difficile colonization as a risk factor for development of C. difficile infection in solid-organ transplant patients.

BACKGROUND: The association between Clostridioides difficile colonization and C. difficile infection (CDI) is unknown in solid-organ transplant (SOT) patients. We examined C. difficile colonization and healthcare-associated exposures as risk factors for development of CDI in SOT patients. METHODS: The retrospective study cohort included all consecutive SOT patients with at least 1 screening test between May 2017 and April 2018. CDI was defined as the presence of diarrhea (without laxatives), a positive C. difficile clinical test, and the use of C. difficile-directed antimicrobial therapy as ordered by managing clinicians. In addition to demographic variables, exposures to antimicrobials, immunosuppressants, and gastric acid suppressants were evaluated from the time of first screening test to the time of CDI, death, or final discharge. RESULTS: Of the 348 SOT patients included in our study, 33 (9.5%) were colonized with toxigenic C. difficile. In total, 11 patients (3.2%) developed CDI. Only C. difficile colonization (odds ratio [OR], 13.52; 95% CI, 3.46-52.83; P = .0002), age (OR, 1.09; CI, 1.02-1.17; P = .0135), and hospital days (OR, 1.05; 95% CI, 1.02-1.08; P = .0017) were independently associated with CDI. CONCLUSIONS: Although CDI was more frequent in C. difficile colonized SOT patients, the overall incidence of CDI was low in this cohort.

SARS-CoV-2 receptor binding domain-specific antibodies activate platelets with features resembling the pathogenic antibodies in heparin-induced thrombocytopenia.

Severe COVID-19 is associated with unprecedented thromboembolic complications. We found that hospitalized COVID-19 patients develop immunoglobulin Gs (IgGs) that recognize a complex consisting of platelet factor 4 and heparin similar to those developed in heparin-induced thrombocytopenia and thrombosis (HIT), however, independent of heparin exposure. These antibodies activate platelets in the presence of TLR9 stimuli, stimuli that are prominent in COVID-19. Strikingly, 4 out of 42 antibodies cloned from IgG1+ RBD-binding B cells could activate platelets. These antibodies possessed, in the heavy-chain complementarity-determining region 3, an RKH or Y5 motif that we recently described among platelet-activating antibodies cloned from HIT patients. RKH and Y5 motifs were prevalent among published RBD-specific antibodies, and 3 out of 6 such antibodies tested could activate platelets. Features of platelet activation by these antibodies resemble those by pathogenic HIT antibodies. B cells with an RKH or Y5 motif were robustly expanded in COVID-19 patients. Our study demonstrates that SARS-CoV-2 infection drives the development of a subset of RBD-specific antibodies that can activate platelets and have activation properties and structural features similar to those of the pathogenic HIT antibodies.

How frequently should sink drains be disinfected?

Previously, we showed that disinfection of sink drains is effective at decreasing bacterial loads. Here, we report our evaluation of the ideal frequency of sink-drain disinfection and our comparison of 2 different hydrogen peroxide disinfectants.

Transmission of lymphocytic choriomeningitis virus by organ transplantation.

BACKGROUND: In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized. METHODS: We examined clinical specimens from the two donors and eight recipients, using viral culture, electron microscopy, serologic testing, molecular analysis, and histopathological examination with immunohistochemical staining to identify a cause. Epidemiologic investigations, including interviews, environmental assessments, and medical-record reviews, were performed to characterize clinical courses and to determine the cause of the illnesses. RESULTS: Laboratory testing revealed lymphocytic choriomeningitis virus (LCMV) in all the recipients, with a single, unique strain of LCMV identified in each cluster. In both investigations, LCMV could not be detected in the organ donor. In the 2005 cluster, the donor had had contact in her home with a pet hamster infected with an LCMV strain identical to that detected in the organ recipients; no source of LCMV infection was found in the 2003 cluster. The transplant recipients had abdominal pain, altered mental status, thrombocytopenia, elevated aminotransferase levels, coagulopathy, graft dysfunction, and either fever or leukocytosis within three weeks after transplantation. Diarrhea, peri-incisional rash, renal failure, and seizures were variably present. Seven of the eight recipients died, 9 to 76 days after transplantation. One recipient, who received ribavirin and reduced levels of immunosuppressive therapy, survived. CONCLUSIONS: We document two clusters of LCMV infection transmitted through organ transplantation.

The relevance of sink proximity to toilets on the detection of Klebsiella pneumoniae carbapenemase inside sink drains.

We report a higher prevalence of blaKPC in patient room sink drains located next to toilets (87.0%) when compared with sink drains located farther away from toilets (21.7%) using direct polymerase chain reaction assay. However, culture methods were only able to recover blaKPC-positive isolates from 16% of polymerase chain reaction-positive drains.

Use of a cohorting-unit and systematic surveillance cultures to control a Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae outbreak.

OBJECTIVE: Describe the epidemiological and molecular characteristics of an outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and the novel use of a cohorting unit for its control. DESIGN: Observational study. SETTING: A 566-room academic teaching facility in Milwaukee, Wisconsin. PATIENTS: Solid-organ transplant recipients. METHODS: Infection control bundles were used throughout the time of observation. All KPC cases were intermittently housed in a cohorting unit with dedicated nurses and nursing aids. The rooms used in the cohorting unit had anterooms where clean supplies and linens were placed. Spread of KPC-producing organisms was determined using rectal surveillance cultures on admission and weekly thereafter among all consecutive patients admitted to the involved units. KPC-positive strains underwent pulsed-field gel electrophoresis and whole-genome sequencing. RESULTS: A total of 8 KPC cases (5 identified by surveillance) were identified from April 2016 to April 2017. After the index patient, 3 patients acquired KPC-producing organisms despite implementation of an infection control bundle. This prompted the use of a cohorting unit, which immediately halted transmission, and the single remaining KPC case was transferred out of the cohorting unit. However, additional KPC cases were identified within 2 months. Once the cohorting unit was reopened, no additional KPC cases occurred. The KPC-positive species identified during this outbreak included Klebsiella pneumoniae, Enterobacter cloacae complex, and Escherichia coli. blaKPC was identified on at least 2 plasmid backbones. CONCLUSIONS: A complex KPC outbreak involving both clonal and plasmid-mediated dissemination was controlled using weekly surveillances and a cohorting unit.

Immediate impact of healthcare-facility-onset Clostridium difficile laboratory-identified events reporting methodology change on standardized infection ratios.

In 2018, the Clostridium difficile LabID event methodology changed so that hospitals doing 2-step tests, nucleic acid amplification test (NAAT) plus enzyme immunofluorescence assay (EIA), had their adjustment modified to EIA-based tests, and only positive final tests (eg, EIA) were counted in the numerator. We report the immediate impact of this methodological change at 3 Milwaukee hospitals.

The detection of monkeypox in humans in the Western Hemisphere.

BACKGROUND: During May and June 2003, an outbreak of febrile illness with vesiculopustular eruptions occurred among persons in the midwestern United States who had had contact with ill pet prairie dogs obtained through a common distributor. Zoonotic transmission of a bacterial or viral pathogen was suspected. METHODS: We reviewed medical records, conducted interviews and examinations, and collected blood and tissue samples for analysis from 11 patients and one prairie dog. Histopathological and electron-microscopical examinations, microbiologic cultures, and molecular assays were performed to identify the etiologic agent. RESULTS: The initial Wisconsin cases evaluated in this outbreak occurred in five males and six females ranging in age from 3 to 43 years. All patients reported having direct contact with ill prairie dogs before experiencing a febrile illness with skin eruptions. We found immunohistochemical or ultrastructural evidence of poxvirus infection in skin-lesion tissue from four patients. Monkeypox virus was recovered in cell cultures of seven samples from patients and from the prairie dog. The virus was identified by detection of monkeypox-specific DNA sequences in tissues or isolates from six patients and the prairie dog. Epidemiologic investigation suggested that the prairie dogs had been exposed to at least one species of rodent recently imported into the United States from West Africa. CONCLUSIONS: Our investigation documents the isolation and identification of monkeypox virus from humans in the Western Hemisphere. Infection of humans was associated with direct contact with ill prairie dogs that were being kept or sold as pets.

Impact of Clostridium difficile on inflammatory bowel disease.

BACKGROUND & AIMS: Clostridium difficile-associated disease has increased significantly in North American medical centers. The impact of C difficile on patients with IBD (Crohn's disease, ulcerative colitis) at the present time is unknown. METHODS: A retrospective, observational study evaluating IBD patients followed in a referral center to evaluate the impact of C difficile was performed. Diagnosis was confirmed with stool toxin analysis. Demographic information, diagnosis, anatomic location, IBD therapy, antibiotic exposure, hospitalizations, and surgeries were recorded. Available endoscopic and histologic data were evaluated. RESULTS: Rate of C difficile infection increased from 1.8% of IBD patients in 2004 to 4.6% in 2005 (P < .01). Proportion of IBD patients within the total number of C difficile infections at our institution increased from 7% in 2004 to 16% in 2005 (P < .01). IBD colonic involvement was found in the majority of C difficile-infected patients in 2005 (91%), and the majority contracted infection as an outpatient (76%). Antibiotic exposure was identified in 61% of IBD patients with C difficile infection in 2005. Pseudomembranes and fibrinopurulent eruptions were not seen endoscopically or histologically. During 2004-2005 more than half of the infected IBD patients required hospitalization, and 20% required colectomy. Univariate and multivariate analysis identified maintenance immunomodulator use and colonic involvement as independent risk factors for C difficile infection in IBD. CONCLUSIONS: C difficile infection has increased significantly in IBD patients and negatively impacts clinical outcome. Increased vigilance regarding this infection in IBD patients with colitis activity is warranted.

Elizabethkingia anophelis: Clinical Experience of an Academic Health System in Southeastern Wisconsin.

In late 2015 and early 2016, 11 patients were identified with cultures positive for Elizabethkingia anophelis in our health system. All patients had positive blood cultures upon admission. Chart review showed that all had major comorbidities and recent health care exposure. The attributable mortality rate was 18.2%.

Clinical characteristics of human monkeypox, and risk factors for severe disease.

BACKGROUND: Human monkeypox is an emerging smallpox-like illness that was identified for the first time in the United States during an outbreak in 2003. Knowledge of the clinical manifestations of monkeypox in adults is limited, and clinical laboratory findings have been unknown. METHODS: Demographic information; medical history; smallpox vaccination status; signs, symptoms, and duration of illness, and laboratory results (hematologic and serum chemistry findings) were extracted from medical records of patients with a confirmed case of monkeypox in the United States. Two-way comparisons were conducted between pediatric and adult patients and between patients with and patients without previous smallpox vaccination. Bivariate and multivariate analyses of risk factors for severe disease (fever [temperature, > or =38.3 degrees C] and the presence of rash [> or =100 lesions]), activity and duration of hospitalization, and abnormal clinical laboratory findings were performed. RESULTS: Of 34 patients with a confirmed case of monkeypox, 5 (15%) were defined as severely ill, and 9 (26%) were hospitalized for >48 h; no patients died. Previous smallpox vaccination was not associated with disease severity or hospitalization. Pediatric patients (age, < or =18 years) were more likely to be hospitalized in an intensive care unit. Nausea and/or vomiting and mouth sores were independently associated with a hospitalization duration of >48 h and with having > or =3 laboratory tests with abnormal results. CONCLUSION: Monkeypox can cause a severe clinical illness, with systemic signs and symptoms and abnormal clinical laboratory findings. In the appropriate epidemiologic context, monkeypox should be included in the differential diagnosis for patients with unusual vesiculopustular exanthems, mucosal lesions, gastrointestinal symptoms, and abnormal hematologic or hepatic laboratory findings. Clinicians evaluating a rash illness consistent with possible orthopoxvirus infection should alert public health officials and consider further evaluation.