Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes.

The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Febrile Infants Without Respiratory Distress.

We report 2 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time reverse-transcription polymerase chain reaction-based testing for SARS-CoV-2 for febrile infants in an outbreak setting.

Persistent hypogammaglobulinemia in pediatric solid organ transplant recipients.

INTRODUCTION: Hypogammaglobulinemia has not been well studied in pediatric solid organ transplant (SOT) recipients. We evaluated plasma immunoglobulin (Ig) and lymphocyte phenotypes among 31 pediatric heart and kidney recipients for two years post-transplant and from 10 non-transplanted children. METHODS: Plasma IgM, IgG, and IgA were quantified by immunoturbidimetric assays, IgG subclasses were quantified by bead-based multiplex immunoassay, and lymphocyte phenotypes were assessed by flow cytometry. RESULTS: Median age at transplant for SOT recipients was similar to that of the control cohort (15 vs. 12.5 years, respectively; P = .61). Mean plasma IgG and IgM levels for SOT recipients fell significantly below the control cohort means by 1 month post-transplant (P < .001 for both) and remained lower than control levels at 12-18 months post-transplant. Heart recipients had lower frequencies of a CD4+ naïve T lymphocytes relative to kidney recipients. CONCLUSIONS: Hypogammaglobulinemia was prevalent and persistent among pediatric SOT recipients and may be secondary to immunosuppressive medications, as well as loss of thymus tissue and CD45RA+   CD4+ T cells in heart recipients. Limitations of our study include but are not limited to small sample size from a single center, lack of samples for all participants at every time point, and lack of peripheral blood mononuclear cell samples for the non-transplanted cohort.

Neutrophilic panniculitis arising from hematogenous spread of methicillin-resistant Staphylococcus aureus.

Infectious panniculitis from hematogenous spread is uncommon and usually occurs in immunocompromised patients. Dissemination of gram-positive organisms to the subcutaneous tissue is rare with only several reports of disseminated panniculitis caused by Streptococcal species. We report a case of an immunocompetent 2-year-old boy presenting with diffuse neutrophilic panniculitis arising from methicillin-resistant Staphylococcus aureus septicemia. This case represents a highly atypical manifestation of severe MRSA infection and serves as a reminder to consider MRSA as a cause of disseminated neutrophilic panniculitis, particularly in high-risk populations.

Human herpesvirus 6, 7, and 8 in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HHV-6A, HHV-6B, HHV-7, and HHV-8 in the pre- and post-transplant period. The majority of HHV-6 (A and B) and HHV-7 infections in transplant recipients are asymptomatic; symptomatic disease is reported infrequently across organs. Routine screening for HHV-6 and 7 DNAemia is not recommended in asymptomatic patients, nor is prophylaxis or preemptive therapy. Detection of viral nucleic acid by quantitative PCR in blood or CSF is the preferred method for diagnosis of HHV-6 and HHV-7 infection. The possibility of chromosomally integrated HHV-6 DNA should be considered in individuals with persistently high viral loads. Antiviral therapy should be initiated for HHV-6 encephalitis and should be considered for other manifestations of disease. HHV-8 causes Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease and is also associated with hemophagocytic syndrome and bone marrow failure. HHV-8 screening and monitoring may be indicated to prevent disease. Treatment of HHV-8 related disease centers on reduction of immunosuppression and conversion to sirolimus, while chemotherapy may be needed for unresponsive disease. The role of antiviral therapy for HHV-8 infection has not yet been defined.

Isolation of antibiotic-resistant gram-negative organisms from donor respiratory culture does not impact non-lung solid organ recipient management.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) gram-negative bacteria may be transmitted from organ donors to solid organ transplant recipients and are associated with poor outcomes post-transplant. METHODS: We reported the prevalence of MDR/XDR gram-negative respiratory colonization among 702 deceased organ donors in the New York City area from 2011 to 2014 and performed chart reviews for a subset of recipients to determine whether donor respiratory culture results were predictive of subsequent recipient infection or used to guide post-transplant antimicrobial therapy. RESULTS: Fifty donors (7% of the cohort) had MDR or XDR gram-negative bacteria isolated from endotracheal aspirate or bronchoalveolar lavage culture. Organs from these 50 donors were transplanted into 120 recipients; chart review was performed for 89 of these recipients (38 kidney, 32 liver, 11 heart, 6 kidney/pancreas, 1 liver/kidney, 1 lung). None of the 89 recipients of organs from donors with MDR/XDR gram-negative respiratory colonization were reported to have a donor-derived infection post-transplant, and chart review for the 88 non-lung recipients indicated that peri-transplant antibiotics were not adjusted specifically for donor respiratory culture results. CONCLUSION: These results suggest that donor respiratory culture results are not predictive of post-transplant infection in non-lung recipients and are unlikely to impact post-transplant management.

Pediatric transplantation case conference: Update on cytomegalovirus.

The prevention and management of cytomegalovirus (CMV) remain challenging in children who have undergone solid organ transplantation, despite the availability of effective antiviral medications and sensitive diagnostic assays. The primary objective of this invited commentary is to provide an updated and multidisciplinary approach to persistently challenging CMV cases that commonly occur in pediatric transplantation candidates and recipients, including cases for which published data are frequently lacking.

Poor Uptake of MMR Vaccine 1-year Post-Measles Outbreak: New York City and Israel.

BACKGROUND: In 2018-2019, large outbreaks of measles occurred in Israel and in New York City, driven in part by travel of unimmunized children between the 2 communities. METHODS: A retrospective chart review was conducted for children tested for measles (March 2018-September 2019) at NYU Langone Health in New York, NY, and in Ramla subdistrict, Israel. Vaccination records were reviewed to determine vaccination status for measles, mumps, and rubella (MMR) at the time of measles testing and 1-year post-testing. RESULTS: A total of 264 children were tested for measles, and 102 (38.6%) had confirmed measles. Only 20 (19.6%) of measles-positive cases received a full 2-dose course of vitamin A. 82.4% of children with measles were ≥1 year at the time of diagnosis and fully eligible for MMR vaccine. Of the 100 measles-positive cases with available vaccine records, 63 were unvaccinated at testing, and 27 remained unimmunized against MMR 1 year later. At testing, measles-negative children were significantly more likely to have received MMR than measles-positive children (65.4% vs 37%, P < .01). One year later, 70.4% of measles-negative cases and only 57.1% of measles-positive cases had received MMR vaccine (P = .18). CONCLUSIONS: The majority of measles cases occurred in unimmunized children eligible for vaccination, and >25% of children in both measles-positive and -negative groups remained unimmunized for MMR 1-year post-outbreak. Our results suggest the need for novel, longitudinal vaccination strategies and increased awareness of the role of vitamin A.

Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women.

INTRODUCTION: Innate activity against Escherichia coli in female genital secretions may represent contributions from vaginal bacteria and host soluble immune mediators. We analyzed the relationship between E. coli inhibitory activity, soluble immune mediators, and vaginal bacteria in participants in MTN-004, a placebo-controlled trial of VivaGel(®) , a candidate product for topical HIV pre-exposure prophylaxis. METHODS: Escherichia coli inhibitory activity was quantified by colony reduction assay. Endocervical concentrations of interleukin (IL)-1ß, IL-6, IL-12p40, macrophage inflammatory protein (MIP)-1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), lactoferrin, and secretory leukocyte protease inhibitor (SLPI) were quantified to generate a cumulative mediator score. Vaginal bacteria were characterized by quantitative cultures. RESULTS: In the two placebo arms, higher soluble immune mediator score was associated with greater E. coli inhibitory activity (ß = 17.49, 95% CI [12.77, 22.21] and ß = 13.28, 95% CI [4.76, 21.80]). However, in the VivaGel arm, higher concentrations of E. coli (ß = -3.80, 95% CI [-6.36, -1.25]) and group B Streptococcus (ß = -3.91, 95% CI [-6.21, -1.60]) were associated with reduced E. coli inhibitory activity. CONCLUSIONS: Both host mediators and vaginal bacteria impact E. coli inhibition in genital secretions. The relative contributions of host mediators and bacteria varied between women who used VivaGel vs placebos.

Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition.

Greater inhibitory activity against Escherichia coli and levels of human ß defensin (HBD)-2 in genital tract secretions predicted HIV acquisition in women in the HPTN 035 trial. We investigated whether higher levels of E. coli inhibitory activity and antimicrobial peptides in cervicovaginal lavage (CVL) samples predicted HIV acquisition in women in the CAPRISA 002 Acute Infection Study. E. coli inhibitory activity and antimicrobial peptides were quantified in CVL from a subset of CAPRISA 002 participants who did not seroconvert (n=39) and from seroconverting women prior to infection (n=17) and during acute infection (n=11). Women who acquired HIV had significantly greater preinfection CVL E. coli inhibitory activity (p=0.01) and HBD-1 levels (p=0.02) compared to women who remained uninfected. Preinfection E. coli inhibitory activity remained significantly associated with seroconversion following adjustment for the presence of bacterial vaginosis (OR 1.45; 95% CI 1.07, 1.97). Partial least squares discriminant analysis confirmed that preinfection CVL E. coli inhibitory activity, together with higher CVL concentrations of HBD-1 and secretory leukocyte protease inhibitor, distinguished seroconverters from nonseroconverters with 67% calibration accuracy. CVL concentrations of human neutrophil peptides (HNP) 1-3 increased significantly with acute infection (p=0.001) and correlated with plasma viral set point (r=0.66, p=0.03). E. coli inhibitory activity in genital tract secretions could provide a biomarker of HIV risk. The correlation between HNP 1-3 and viral set point merits further investigation of the relationship between mucosal inflammation during early HIV infection and disease progression.

Microbiological and Genetic Characterization of Carbapenem-Resistant Klebsiella pneumoniae Isolated From Pediatric Patients.

This manuscript reports the clinical, microbiological, and genetic characteristics of carbapenem-resistant K. pnuemoniae isolates from pediatric patients at a tertiary-care children's hospital. Although there is an extensive body of literature describing carbapenem-resistant Klebsiella infections in adults, pediatric data are comparatively limited.

A pilot program to evaluate deceased donor disease transmission risk: the New York Organ Donor Network Infectious Disease Working Group.

BACKGROUND: Recent cases of donor-derived infections raise the question of how best to screen donors without excessive restriction of the donor pool. METHODS: The New York Organ Donor Network (NYODN) established an Infectious Diseases Working Group (IDWG) in 2008, which established an on-call schedule of voluntary transplant infectious disease physicians to provide remote evaluations for donors at increased risk for disease transmission. RESULTS: Data were reviewed from 40 available IDWG evaluations from 2008 to 2011. Eighteen cases (45%) were considered to be at unacceptable risk for infection transmission. Sixteen of these cases were excluded from donation secondary to IDWG recommendation; there was limited recipient center interest in the remaining two cases. Approximately 22 (55%) cases were categorized by the IDWG as acceptable, with 14 proceeding to recovery of 49 organs. IDWG physician recommendations were conveyed to recipient centers, and screening guidelines for donors were revised based on the IDWG experiences. CONCLUSION: Establishment of a donation service area disease transmission evaluation service is a valuable program for donor screening and may promote dissemination of more detailed donor information to recipient centers.

HIV, sexual violence and special populations: adolescence and pregnancy.

The risk of male to female transmission of HIV is impacted by baseline inflammation in the female genital tract, semen viral load and seminal plasma's ability to induce specific patterns of cervical cytokine signalling and influx of immune cell populations. Disruption of the epithelial barrier during non-consensual intercourse may trigger further inflammation and initiation of cell-signalling pathways, thus facilitating transmission of HIV and expansion of local infection. Adolescent and pregnant women are at high risk for sexual violence and may exhibit alterations of genital mucosal immunity that promote immune activation, making them uniquely vulnerable to HIV acquisition.