Esquer Garrigos, Zerelda

Abstract Based on expert consensus, the American Society of Transplantation recommends 7–14 days of preventive antibiotic therapy for solid organ transplant recipients from donors with positive blood cultures. We evaluated management and outcomes of kidney transplant recipients from these donors.

Summary We describe a case of culture-negative infective endocarditis due to Neisseria gonorrhoeae, where the application of metagenomics shotgun sequencing in blood played a pivotal role in elucidating the underlying aetiology, guiding targeted therapy and ultimately resulting in the patient’s complete recovery. Beyond its immediate clinical impact, prompt treatment bears significant implications for public health. The utilisation of molecular testing emerges as a valuable strategy to enhance diagnostic accuracy, particularly in cases involving fastidious organisms that are infrequently associated with infective endocarditis.

Abstract Background Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum may cause post-transplant infections in lung transplant recipients. We evaluated routine pretransplant screening for these Mollicutes. Methods We retrospectively reviewed records of lung transplant recipients at our tri-site institution from 01/01/2015 to 11/15/2019. M. hominis and/or Ureaplasma polymerase chain reaction (PCR) was performed on pretransplant recipient urine specimens and donor bronchial swabs at the time of transplantation. Development of Mollicute infection and hyperammonemia syndrome (HS) was recorded. Results A total of 268 patients underwent lung transplantation during the study period, of whom 105 were screened with at least 1 Mollicute PCR. Twelve (11%) screened positive; 10 donors, 1 recipient, and 1 both. Among positive donors, 3 were positive for M. hominis, 5 for U. urealyticum, and 4 for U. parvum. Preemptive therapy included doxycycline, levofloxacin, and/or azithromycin administered for 1–12 weeks. Despite therapy, 1 case of M. hominis mediastinitis and 1 case of HS associated with Ureaplasma infection occurred, both donor-derived. Of those screened before transplant, cases with positive screening were more likely (P < 0.05) to develop Mollicute infection despite treatment (2/12, 17%) than those who screened negative (1/93, 1%). Conclusions Pretransplant recipient urine screening had a low yield and was not correlated with post-transplant Mollicute infection, likely because most M. hominis and U. parvum/urealyticum infections in lung transplant recipients are donor-derived. Routine donor bronchus swab PCR for M. hominis, U. urealyticum, and U. parvum followed by preemptive therapy did not obviously impact the overall incidence of Mollicute infection or HS in this cohort.

Abstract Background Conventional blood cultures were compared to plasma cell-free DNA–based 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR)/next-generation sequencing (NGS) for detection and identification of potential pathogens in patients with sepsis. Methods Plasma was prospectively collected from 60 adult patients with sepsis presenting to the Mayo Clinic (Minnesota) Emergency Department from March through August 2019. Results of routine clinical blood cultures were compared to those of 16S rRNA gene NGS. Results Nineteen (32%) subjects had positive blood cultures, of which 13 yielded gram-negative bacilli, 5 gram-positive cocci, and 1 both gram-negative bacilli and gram-positive cocci. 16S rRNA gene NGS findings were concordant in 11. For the remaining 8, 16S rRNA gene NGS results yielded discordant detections (n = 5) or were negative (n = 3). Interestingly, Clostridium species were additionally detected by 16S rRNA gene NGS in 3 of the 6 subjects with gastrointestinal sources of gram-negative bacteremia and none of the 3 subjects with urinary sources of gram-negative bacteremia. In the 41 remaining subjects, 16S rRNA gene NGS detected at least 1 potentially pathogenic organism in 17. In 15, the detected microorganism clinically correlated with the patient’s syndrome. In 17 subjects with a clinically defined infectious syndrome, neither test was positive; in the remaining 7 subjects, a noninfectious cause of clinical presentation was identified. Conclusions 16S rRNA gene NGS may be useful for detecting bacteria in plasma of septic patients. In some cases of gram-negative sepsis, it may be possible to pinpoint a gastrointestinal or urinary source of sepsis based on the profile of bacteria detected in plasma.

Lawsonella clevelandensis, an emerging pathogen, was first described in 2016, and has been implicated in abdominal, breast and spinal abscesses in a limited number of cases. Being a fastidious organism, it is primarily identified with molecular methods. With the incorporation of broad-range PCR testing in clinical diagnostics, L. clevelandensis has been increasingly reported in the literature. We describe a case of a 65-year-old man who presented with bilateral psoas abscesses secondary to aorto-bi-iliac vascular graft infection with L. clevelandensis identified using 16S rRNA/PCR sequencing. The patient underwent surgical resection and replacement of infected graft, followed by 6 weeks of intravenous antibiotic therapy and then chronic suppression with doxycycline and cefadroxil. He was infection-free at last follow-up.

AbstractBackgroundNeutropenia is a risk factor for development of infections; however, the direct effect of neutropenia on development of bloodstream infection (BSI) is not known. D‐index, which is area between the neutrophil time curve and a neutrophil count of 0.5 × 109/L, incorporates the combined effect of severity and duration of neutropenia. We aimed to evaluate whether D‐index can be used as a marker for BSI in patients with allogeneic stem cell transplantation.MethodWe conducted a retrospective cohort study of patients undergoing allogeneic stem cell transplantation between January 1, 2005, and September 30, 2015. The primary outcome measure was the development of BSI within 30 days of transplantation.ResultsA total of 714 patients were included in the study of whom 101 developed BSI. Patients with BSI had a significantly higher median D‐index value compared with patients who did not have BSI (4990 vs. 3570, P < .001). As a marker, the performance of the D‐index was similar to that of the duration of profound neutropenia (P = .18) and significantly better than the total duration of neutropenia (P = .001).ConclusionThe D‐index performed better than the total duration of neutropenia as a marker for BSI in patients with allogeneic stem cell transplantation. There was no difference between D‐index and, a more easily calculable indicator, duration of profound neutropenia.

AbstractBackgroundAscertaining involvement of left ventricular assist device (LVAD) in a patient presenting with bloodstream infection (BSI) can be challenging, frequently leading to use of chronic antimicrobial suppressive (CAS) therapy. We aimed to assess the efficacy of CAS therapy to prevent relapse of BSI from LVAD and non-LVAD sources.MethodsWe retrospectively screened adults receiving LVAD support from 2010 through 2018, to identify cases of BSI. Bloodstream infection events were classified into LVAD-related, LVAD-associated, and non-LVAD BSIs.ResultsA total of 121 episodes of BSI were identified in 80 patients. Of these, 35 cases in the LVAD-related, 14 in the LVAD-associated, and 46 in the non-LVAD BSI groups completed the recommended initial course of therapy and were evaluated for CAS therapy. Chronic antimicrobial suppressive therapy was prescribed in most of the LVAD-related BSI cases (32 of 35, 91.4%) and 12 (37.5%) experienced relapse. Chronic antimicrobial suppressive therapy was not prescribed in a majority of non-LVAD BSI cases (33, 58.9%), and most (31, 93.9%) did not experience relapse. Chronic antimicrobial suppressive therapy was prescribed in 9 of 14 (64.2%) cases of LVAD-associated BSI and none experienced relapse. Of the 5 cases in this group that were managed without CAS, 2 had relapse.ConclusionsPatients presenting with LVAD-related BSI are at high risk of relapse. Consequently, CAS therapy may be a reasonable approach in the management of these cases. In contrast, routine use of CAS therapy may be unnecessary for non-LVAD BSIs.

In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between <5% to >30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed.

Abstract Background Post-operative management of patients undergoing cardiac transplantation with an infected left ventricular assist device (LVAD) is unclear. Methods We retrospectively screened all adults with an LVAD who underwent cardiac transplantation at our institution from 2010 through 2018. We selected all cases of LVAD-specific and LVAD-related infections who were receiving antimicrobial therapy as initial treatment course or chronic suppression at the time of cardiac transplantation. Non-LVAD infections, superficial driveline-infection, or concurrent use of right ventricular assist device or extracorporeal membrane oxygenation device were excluded. Results A total of 54 cases met study criteria with 18/54 (33.6%) classified as LVAD- specific or related infections and 36/54 (66.6%) as non-infected. Cases of LVAD-infection had a higher median Charlson Comorbidity Index score at the time of transplantation compared to non-infected cases (P=.005). Of the 18 cases of infection, 13/18 (72.2%) were classified as LVAD-specific and 5/18 (27.8%) as LVAD-related. A total of 9/13 (69.2%) cases had proven LVAD-specific infections. Antimicrobial therapy was extended post-transplant to treat preceding LVAD-specific infection in all nine cases (9/13, 69.2%) with a median duration of 14 days (IQR 14-28). Following LVAD removal, antimicrobial treatment was not continued for preceding LVAD-related infections. Conclusions Patients with an LVAD-specific infection were treated with two weeks of pathogen-directed therapy post heart transplant without any relapses. For those without LVAD-specific infection or uncomplicated LVAD-related bacteremia who had completed antimicrobial therapy pre-transplant, antibiotics were discontinued after standard peri-operative prophylaxis and no relapses were observed.