Mycoplasma hominis infections in solid organ transplant recipients: Clinical characteristics, treatment outcomes, and comparison of phenotypic and genotypic susceptibility profiles.

BACKGROUND: Mycoplasma hominis can cause significant infections after solid organ transplantation (SOT). Treatment should be guided by susceptibility testing, but conventional lab methods are laborious with prolonged turnaround time (TAT). This case series compares the phenotypic and genotypic susceptibility profiles of M. hominis isolates identified from SOT patients. METHODS: This is a single-center retrospective study evaluating SOT recipients with confirmed M. hominis infections. Patients' demographic, clinical, microbiological, and radiographic data were collected. Culture of M. hominis isolates was performed according to current Clinical and Laboratory Standards Institute guidelines. Phenotypic susceptibility testing was performed by University of Alabama Diagnostic Mycoplasma Laboratory. Whole genome sequencing (WGS) was performed followed by bioinformatic analysis of known genetic determinants of resistance. RESULTS: Seven SOT recipients with M. hominis infections were identified. Two out of seven (28.5%) patients had resistance detected by phenotypic susceptibility testing (Case 5 to levofloxacin and Case 7 to tetracycline). Genomic analyses confirmed the presence of mutations in the parC and parE topoisomerase genes at positions conferring to fluoroquinolone resistance in the isolate from Case 5, while the tetracycline-resistant isolate from Case 7 harbored the tetM gene. The median TAT from the date of specimen collection was 24 days for phenotypic susceptibility testing and 14 days for genotypic susceptibility testing. All seven patients received antimicrobials directed toward M. hominis and recovered with complete resolution of infection. CONCLUSIONS: WGS may offer a novel and more rapid methodology for M. hominis susceptibility testing to help optimize antimicrobial usage, but more data are needed.

Spectrum of Coronavirus Disease 2019 Outcomes in Kidney Transplant Recipients: A Single-Center Experience.

PURPOSE: We reviewed the clinical experience of kidney transplant recipients diagnosed with severe acute respiratory syndrome coronavirus 2 infection in order to understand the impact of the current coronavirus disease 2019 (COVID-19) pandemic infection on transplant recipients. Given that early reports from heavily affected areas demonstrated a very high mortality rate amongst kidney transplant recipients, ranging between 30% and 40%, we sought to evaluate outcomes at a center with a high burden of cases but not experiencing acute crisis due to COVID-19. PROCEDURES: In this single center retrospective observational study, medical records of all kidney transplant recipients at the UCLA Medical Center were reviewed for a diagnosis of COVID-19 by polymerase chain reaction, followed by chart review to determine kidney transplant characteristics and clinical course. MAIN FINDINGS: A total of 41 kidney transplant recipients were identified with COVID-19 positive polymerase chain reaction. Recipients had been transplanted for a median of 47 months before diagnosis. The large proportion of infected individuals were minorities (Hispanic 65.9%, black 14.6%), on prednisone, tacrolimus, and mycophenolate mofetil (95.1%, 87.8%, and 87.8%, respectively), and had excellent allograft function (median 1.25 mg/dL). The most common presenting symptoms were fever, dyspnea, or cough. Most patients were hospitalized (63.4%); mortality was 9.8% and occurred only in patients in the intensive care unit. The most common treatment was reduction or removal of antimetabolite (77.8%). Approximately 26.9% presented with AKI. CONCLUSIONS: COVID-19 infection in kidney transplant recipients results in a higher rate of hospitalization and mortality than in the general population. In an area with a high number of infections, the mortality rate was lower compared with earlier reports from areas experiencing early surge and strain on the medical system. Minorities were disproportionately affected. Future studies are needed to determine optimal approach to treatment and management of immunosuppression in kidney transplant recipients with COVID-19 infection.

Heart transplantation in the early phase of the COVID-19 pandemic: A single-center case series.

The infectious disease coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID-19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re-evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID-19 screening scrutiny and recipient waiting list management in anticipation of COVID-19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end-stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020.

Hepatitis E Virus-Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing.

Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.

Dental treatment in the cardiothoracic intensive care unit for patients with ventricular assist devices awaiting heart transplant: a case series.

OBJECTIVE: This report aims to describe the dental protocol for treating in the intensive care unit patients with end-stage heart failure who have had ventricular assist devices (VADs) emergently implanted as a bridge to heart transplant. This protocol permitted the rendering of safe and effective dental care in this setting and did not result in near-term (1-30 days) excessive hemorrhage, local and systemic infection, or contamination of the VAD. STUDY DESIGN: This descriptive cross-sectional study by the University of California, Los Angeles, Hospital Dental Service examined the dental care of 9 patients (mean age, 50 ± 12.9 years) with class IV stage D heart failure. RESULTS: Nine patients, 22 days (mean) after VAD placement, received dental treatment after intravenous prophylactic antibiotics and maintenance of prior anticoagulation, antiplatelet, or antithrombin regimen. Eight patients had extractions (mean, 4; range, 1-12), and one of them also required scaling and root planing (SRP) of the remaining teeth. A ninth individual only required SRP of 4 quadrants. No adverse outcomes developed. CONCLUSIONS: Emergent removal of active dental disease in patients with VAD awaiting heart transplant can be safely accomplished using established protocols with extended vigilance.

Extended spectrum ß-lactamase-producing Enterobacteriaceae infection in heart and lung transplant recipients and in mechanical circulatory support recipients.

BACKGROUND: Extended spectrum ß-lactamase (ESBL)-producing gram-negative bacilli are increasingly reported in patients with a variety of risk factors including prior cephalosporin and antibiotic usage, prolonged hospitalizations, existence of comorbid conditions, and critical illness. METHODS: Retrospective review of infections caused by ESBL-producing Enterobacteriaceae was performed in heart transplant (HTx), lung transplant (LTx), and mechanical circulatory support (MCS) device recipients at a large transplant center. RESULTS: Among 1065 patients transplanted/implanted, the incidence of ESBL-related infections (bacteremia, urinary tract infections, pneumonia, central venous catheter-associated infection, and wound infections) in HTx, LTx, and MCS device recipients was reported at 2.2%, 5.5%, and 10.7%, respectively, caused by ESBL-producing Klebsiella pneumoniae, Escherichia coli, Klebsiella oxytoca, and Citrobacter freundii. CONCLUSIONS: Early detection and adequate duration of therapy for ESBL-producing Enterobacteriaceae in solid organ transplants and MCS device recipients are essential in successful patient outcomes including prevention of recurrent infection.

HIV stroke risk: evidence and implications.

An estimated 34 million men, women, and children are infected with human immunodeficiency virus type 1 (HIV-1), the virus that causes acquired immunodeficiency syndrome (AIDS). Current technology cannot eradicate HIV-1, and most patients with HIV-1-infection (HIV+) will require lifelong treatment with combined antiretroviral therapy (cART). Stroke was recognized as a complication of HIV-1 infection since the early days of the epidemic. Potential causes of stroke in HIV-1 include opportunistic infections, tumors, atherosclerosis, diabetes, hypertension, autoimmunity, coagulopathies, cardiovascular disease, and direct HIV-1 infection of the arterial wall. Ischemic stroke has emerged as a particularly significant neurological complication of HIV-1 and its treatment due to the aging of the HIV+ population, chronic HIV-1 infection, inflammation, and prolonged exposure to cART. New prevention and treatment strategies tailored to the needs of the HIV+ population are needed to address this issue.

Characteristics of untreated AIDS-related cytomegalovirus retinitis. II. Findings in the era of highly active antiretroviral therapy (1997 to 2000).

PURPOSE: To describe host characteristics (use of highly active antiretroviral therapy [HAART]; CD4+ T-lymphocyte count; HIV ribonucleic acid [RNA] blood level) of people who were diagnosed with AIDS-related cytomegalovirus (CMV) retinitis after HAART became available and to investigate effects of HAART on ophthalmic findings. DESIGN: Retrospective, observational case series. METHODS: We collected demographic, medical, laboratory, and ophthalmic data for all patients with AIDS and newly diagnosed, untreated CMV retinitis from January 1997 through December 2000 at 10 sites in Los Angeles and Orange Counties, California. RESULTS: The proportions of Hispanic and African-American patients were equivalent to or greater than their prevalences in the AIDS and general populations of Los Angeles County. Most patients (n = 80; 63.5%) were known to be receiving HAART at the time of CMV retinitis diagnosis; only 22 patients (17.5%) were HAART-naïve. Median CD4+ T-lymphocyte count was 15 cells/microl and median HIV RNA blood level was 103,000 copies/ml for all patients, but in 10 patients, CMV retinitis developed despite good immunologic and virologic responses to HAART. When compared with HAART-naïve patients, HAART-failure patients with CMV retinitis had more asymptomatic disease (P = .073), better visual acuity in the better eye (P = .003), more bilateral disease (P = .007), less zone 1 involvement (P = .042), and lower lesion border opacity scores (P = .054). CONCLUSIONS: Most patients with AIDS and newly diagnosed CMV retinitis in an urban setting are HAART-experienced. HAART may influence characteristics of new CMV retinitis lesions at presentation, despite laboratory evidence of treatment failure, possibly because of residual CMV-specific immunity.

Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial.

CONTEXT: Three-drug antiretroviral regimens are standard of care for initial treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen. OBJECTIVE: To compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection. DESIGN: The AIDS Clinical Trials Group (ACTG) A5095 study, a randomized, double-blind, placebo-controlled study with enrollment and follow-up conducted from March 22, 2001, to March 1, 2005, and enrolling treatment-naive, HIV-1-infected patients with HIV-1 RNA levels of 400 copies/mL or greater from US clinical trials units of the ACTG. INTERVENTIONS: Zidovudine/lamivudine plus efavirenz (3-drug regimen) vs zidovudine/lamivudine/abacavir plus efavirenz (4-drug regimen). MAIN OUTCOME MEASURES: Time to virologic failure (defined as time to first of 2 successive HIV-1 RNA levels > or =200 copies/mL at or after week 16), CD4 cell count changes, and grade 3 or 4 adverse events. HIV-1 RNA data were intent-to-treat, regardless of treatment changes. RESULTS: Seven hundred sixty-five patients with a baseline mean HIV-1 RNA level of 4.86 log10 (72,444) copies/mL and CD4 cell count of 240 cells/mm3 were randomized. After a median 3-year follow-up, 99 (26%) of 382 and 94 (25%) of 383 patients receiving the 3-drug and 4-drug regimens, respectively, reached protocol-defined virologic failure; time to virologic failure was not significantly different (hazard ratio, 0.95; 97.5% confidence interval, 0.69-1.33; P = .73). In planned subgroup analyses, increased risk for virologic failure was seen in non-Hispanic black patients (adjusted hazard ratio, 1.66; 95% confidence interval, 1.18-2.34; P = .003). At 3 years, the HIV-1 RNA level was less than 200 copies/mL in 152 (90%) of 169 and 143 (92%) of 156 patients receiving the 3-drug and 4-drug regimens, respectively (P = .59), and less than 50 copies/mL in 144 (85%) of 169 and 137 (88%) of 156 patients (P = .39). CD4 cell count increases and grade 3 or 4 adverse events were not significantly different. CONCLUSIONS: In treatment-naive patients, there were no significant differences between the 3-drug and 4-drug antiretroviral regimens; overall, at least approximately 80% of patients had HIV-1 RNA levels less than 50 copies/mL through 3 years. These results support current guidelines recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection; adding abacavir as a fourth drug provided no additional benefit. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov Identifier: NCT00013520.

A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in non-nucleoside reverse transcriptase inhibitor-naive HIV-infected adults.

Enfuvirtide is a novel antiretroviral that blocks HIV-1 cell fusion and viral entry. This Phase II, controlled, open-label, randomized, multicentre dose-ranging trial explored the safety, antiviral activity and pharmacokinetics of enfuvirtide, administered by subcutaneous (s.c.) injection, in 71 HIV-1-infected, protease inhibitor-experienced, non-nucleoside reverse transcriptase inhibitor (NNRTI)-naive adults for 48 weeks. Study participants were randomized to receive enfuvirtide at a deliverable dose of 45, 67.5 or 90 mg twice daily; the 45 mg twice daily dose required 2 injections/day, while the higher doses required 4 injections/day. A background oral antiretroviral (ARV) regimen of abacavir (300 mg twice daily), amprenavir (1200 mg twice daily), ritonavir (200 mg twice daily) and efavirenz (600 mg once daily) was provided with enfuvirtide. A control group received the background ARV regimen alone. All potential participants underwent an HIV genotype at screen to ensure a homogenous population and to exclude patients with evidence of genotypic resistance to NNRTIs. Overall, the tolerability of the combination of abacavir, amprenavir, ritonavir, efavirenz and enfuvirtide was generally comparable to control through 48 weeks. No enfuvirtide dose-dependent adverse events (AEs) were observed across treatment groups. Injection site reactions (ISRs) occurred at least once in 68.5% of the enfuvirtide-treated population, and most ISRs were mild to moderate in severity, with no apparent dose relationship. Excluding ISRs, the most common treatment-emergent AEs were nausea, diarrhoea, dizziness and fatigue; with no clinically significant differences in the incidence of AEs observed between the control and enfuvirtide groups. Each treatment group benefited from ARV therapy, with a trend of increasing antiviral and immunological activity associated with increasing enfuvirtide dose. At 48 weeks, the median HIV-1 RNA change from baseline for the ITT population was -2.24 log10 copies/ml for the combined enfuvirtide groups compared with -1.87 log10 copies/ml for the control group. In addition, 54.9% of patients in the enfuvirtide group achieved HIV-1 RNA < or = 400 copies/ml versus 36.8% of patients in the control group. These results indicate that enfuvirtide has a favourable safety profile and is a promising new antiviral agent for HIV-infected patients who have been on previously failing ARV regimens.

A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy.

OBJECTIVES: The primary objective was to determine the long-term safety of the subcutaneous self-administration of enfuvirtide. Secondary objectives included the determination of enfuvirtide pharmacokinetics and antiviral activity and the immunological response to the enfuvirtide-containing regimen. METHODS: A multicenter 48-week uncontrolled open-label rollover study was conducted on 71 HIV-infected adults recruited from previous enfuvirtide clinical trials. Patients with extensive previous use of protease and reverse transcriptase inhibitors received a twice-daily dose of 50 mg enfuvirtide subcutaneously (45 mg deliverable) combined with two or more antiretroviral drugs selected for each individual, guided by resistance testing and previous treatment history. RESULTS: The mean baseline plasma HIV-RNA level was 4.81 log(10) copies/ml and the mean CD4 cell count was 134.8 cells/microl. The majority (86.9%) of treatment-emergent adverse events were grade 2 or less in severity. Injection site reactions were common, but no patients discontinued treatment. A mean HIV-RNA change of -1.33 log(10) was achieved within 14 days of treatment initiation. At week 48, approximately one-third of all patients in the intent-to-treat population maintained significant suppression of plasma HIV RNA, with either less than 400 copies/ml or more than a 1.0 log(10) decline from baseline. The mean gain in absolute CD4 cell counts at 48 weeks was 84.9 cells/microl. Trough plasma concentrations of enfuvirtide were consistently higher than target concentrations. CONCLUSION: Self-administration of enfuvirtide is not associated with unexpected toxicities for up to one year, and combined with oral antiretroviral drugs was associated with a significant decrease in HIV RNA and an increase in CD4 cell counts.

The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults.

Enfuvirtide (T-20) is a novel antiretroviral agent that blocks HIV-1 cell fusion. A 28-day randomized dose-comparison study was conducted to determine the safety, pharmacokinetics, and antiviral activity of enfuvirtide in 78 HIV-infected adults, most with extensive treatment experience. Patients received enfuvirtide, added to a failing regimen, either by continuous subcutaneous infusion (CSI: 12.5, 25, 50 or 100 mg/day) or by subcutaneous (SC) injection (50 or 100 mg twice daily). Dose-related decreases in viral load were observed, with a maximum mean reduction from baseline of 1.6 log(10) copies/ml (p< 0.001) seen in the 100 mg bid SC group. Most responses diminished by 28 days. Plasma pharmacokinetics and antiviral responses were more consistent for SC injection than for CSI because of technical difficulties experienced with CSI. Injection site reactions were common but generally mild. These results indicate that enfuvirtide is a promising new therapeutic agent for HIV-infected patients, including those with prior antiretroviral treatment.