Coronary Plaque in People With HIV vs Non-HIV Asymptomatic Community and Symptomatic Higher-Risk Populations.

Background: People with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification. Objectives: The purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH. Methods: Nonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence. Results: Compared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 vs 57.3 ± 4.3 and 60.0 ± 8.0 years; P < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P < 0.001). Conclusions: Asymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque.

Retrospective cohort study comparing two versus three blood culture sets in people who inject drugs.

BACKGROUND: The current standard of drawing two vs three blood culture sets lacks adequate guidance. Because people who inject drugs are at higher risk for bacteraemia and life-threatening infection, consideration of a third blood culture becomes more important. AIM: To investigate the risks and benefits of obtaining two versus three blood culture sets. METHODS: Retrospective cohort study of adults who inject drugs at a multicentre catch-net hospital system from 2017-2022. FINDINGS: 998 people who inject drugs and 2278 blood culture sets were analysed. There were 1618 episodes with two blood culture sets and 660 episodes with three. A potential benefit of adding a third blood culture was seen in 30 (4.5%) episodes. However, only 13 (2.0%) episodes showed pathogen-identifying benefit, as 17 (2.6%) involved known inadequately treated infections or the same pathogen in another culture. The number of blood culture sets needed to achieve diagnostic benefit was 51. There were more contaminants for three blood culture sets (65, 9.8%) than for two (114, 7.0%) (p < 0.00001). By adding a third blood culture, the risk of a contaminant increased by 39.7%; the number of blood culture sets needed to find a contaminant was 36. Of 122 episodes with only contaminants and available for analysis, 111 (91.0%) experienced at least one complication. 33 (27.0%) patients experienced either prolonged admission, readmission, or unnecessary antibiotic administration. CONCLUSIONS: The benefits of possibly isolating a pathogen from a third blood culture set do not universally outweigh the risks for contaminant growth for people who inject drugs. A third blood culture should be considered in specific clinical scenarios (i.e. inadequately treated endocarditis and osteomyelitis).

Advancing Health Equity: The Role of a Community-Academic-Public Health-Practice (CAPP) Partnership in Addressing COVID-19 Disparities in Louisiana.

We assessed the impact of an innovative Louisiana community-academic-public health-practice (CAPP) partnership in addressing COVID-19-associated Black-White vaccination disparities over 19 months. Initially (April 2021), the cumulative vaccinations for Black versus White Louisianans were 54 542 per 100 000 versus 62 435 per 100 000, respectively. By October 2022, cumulative vaccinations for Black versus White Louisianans were 142 437 per 100 000 versus 132 488 per 100 000, respectively. The vaccination equity score increased from 908 out of 1000 in April 2021 to 942 out of 1000 in October 2022. CAPP partnership efforts contributed to addressing initial Black-White COVID-19 vaccination disparities. (Am J Public Health. 2024;114(S1):S55-S58. https://doi.org/10.2105/AJPH.2023.307509).

Let's Join the Lane: The Role of Infectious Diseases Physicians in Preventing Gun Violence.

On November 7, 2018, the National Rifle Association (NRA) issued a tweet advising "self-important anti-gun doctors to stay in their lane." The tweet has galvanized physicians to share their experiences with gun violence through the grassroots #ThisISOurLane campaign. Infectious diseases physicians are regularly called upon to manage complications such as infected wounds and osteomyelitis in gunshot victims. Yet, Infectious Diseases as a specialty has been poorly represented in the national dialogue on gun violence. Over 80 medical societies have endorsed statements on gun violence, including the American College of Physicians (ACP) and the American College of Cardiology; the Infectious Diseases Society of America has not. We argue that gun violence does affect the Infectious Diseases community and issue a call to action to engage in the conversation, advocate for our patients, and join with other medical societies in affirming a commitment to gun violence prevention.

Risk Factors for Low CD4+ Count Recovery Despite Viral Suppression Among Participants Initiating Antiretroviral Treatment With CD4+ Counts > 500 Cells/mm3: Findings From the Strategic Timing of AntiRetroviral Therapy (START) Trial.

BACKGROUND: Low CD4 recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4 counts of >500 cells/mm. SETTING: United States, Africa, Asia, Europe and Israel, Australia, Latin America. METHODS: Among participants randomized to immediate antiretroviral therapy (ART) in the Strategic Timing of AntiRetroviral Therapy trial, low CD4 recovery was defined as a CD4 increase of <50 cells/mm from baseline after 8 months despite viral load of ≤200 copies/mL. Risk factors for low recovery were investigated with logistic regression. RESULTS: Low CD4 recovery was observed in 39.7% of participants. Male sex [odds ratio (OR), 1.53; P = 0.007], lower screening CD4 cell counts (OR, 1.09 per 100 fewer cells/mm; P = 0.004), higher baseline CD8 cell counts (OR, 1.05 per 100 more cells/mm; P < 0.001), and lower HIV RNA levels (OR, 1.93 per log10 decrease; P < 0.001) were associated with low CD4 recovery. D-dimer had a quadratic association with low CD4 recovery, with lowest odds occurring at 0.32 µg/mL. At lower HIV RNA levels, the odds of low CD4 recovery were elevated across the levels of screening CD4 count; but at higher HIV RNA levels, the odds of low CD4 recovery were higher among those with lower vs. higher screening CD4. CONCLUSIONS: Low CD4 recovery is frequent among participants starting ART at high CD4 counts. Risk factors include male sex, lower screening CD4 cell counts, higher CD8 cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4 recovery on clinical outcomes.

IKBKG (NEMO) 5' Untranslated Splice Mutations Lead to Severe, Chronic Disseminated Mycobacterial Infections.

Four patients with adult-onset, disseminated mycobacterial infection had 5' UTR mutations in IKBKG without clear physical stigmata of NEMO deficiency. These mutations caused decreased levels of NEMO protein and Toll-like receptor driven cytokine production. Three patients died from disseminated disease. These mutations may be missed by whole exome sequencing.

AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial.

BACKGROUND: Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS: We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per µL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 µL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964. FINDINGS: Between Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2-4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference -6·1%, 95% CI -14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI -5·6 to 23·8). INTERPRETATION: The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended. FUNDING: US Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO.

Nocardia exalbida blebitis: a case report.

PURPOSE: To report the first documented case of Nocardia exalbida blebitis. METHODS: A 57-year-old immunocompetent African American man with a long-standing history of open-angle glaucoma in both eyes treated with trabeculectomy presented with a diffusely hyperemic, thin, cystic, leaky bleb with no discharge in his left eye. The patient underwent bleb revision using an amniotic membrane patch graft followed by 1 month of antibiotics. He presented second time with an inflamed eye and brisk leakage and underwent a second bleb revision. His cultures remained negative. Two months after this second surgery, an anterior staphyloma had formed within the bleb area, and visible leakage of purulent material and a dense hypopyon was noted. Gram stain of the material showed rare long-branching rods. The material was sent to an outside laboratory for culture and identification. RESULTS: All 6 cultures were positive for N. abscessus complex and N. exalbida. The patient underwent 6 months of Bactrim therapy with topical sulfonamide and amikacin, leading to the disappearance of the hypopyon and an inflammation-free eye. CONCLUSIONS: N. exalbida is a newly identified Nocardia species that must be considered as a possible infectious agent in immunocompetent patients with blebitis refractive to initial topical antibiotic therapy. Delay in diagnosis and initiation of appropriate antibiotic regimen can result in an aggressive inflammatory process and vision loss.

MSG-01: A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting.

BACKGROUND: Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-ß-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline. RESULTS: The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P = .14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P = .04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences. CONCLUSIONS: Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study. CLINICAL TRIALS REGISTRATION: NCT00520234.

Successful transplantation of HIV patients: the Louisiana experience.

Human immunodeficiency virus (HIV) seropositivity has historically been an absolute contraindication for solid organ transplantation. However, the successful application of HAART (highly active anti-retroviral therapy) drug regimens has greatly prolonged the life expectancy of HIV-positive patients. Therefore, it has become appropriate to consider this patient population for transplantation. HIV positive transplants are being performed around the country in controlled settings, usually as part of a research protocol. The aim of our study is to describe the Louisiana experience with organ transplantation into HIV-positive patients. We identified seven HIV-positive patients who underwent kidney or kidney/pancreas transplantation at our center between 2007 and 2010. We performed a retrospective chart review to ascertain graft function, as well as virologic and immunologic status post-transplant. Renal function (glomerular filtration rate and serum creatinine concentrations) improved in all subjects post-transplant, and six of seven (85.8%) subjects remained virologically suppressed with no progression to Acquired Immunodeficiency Syndrome (AIDS). Overall, two-year graft and patient survival rates were 85.5%. HIV seropositive End Stage Renal Disease (ESRD) patients represent a new population of patients that can be successfully transplanted. This offers a new dimension in care for successful HAART therapy to prolong the life of HIV-infected patients.

The modern day masquerader: a rare case of acute HIV infection with neurologic complications and a review of the literature.

Our case demonstrates a rare presentation of acute HIV infection (AHI) with myoclonus, rhabdomyolysis, and aseptic meningitis. It is imperative for primary care physicians to consider AHI. In this patient, laboratory findings demonstrated infection three to four months before presentation. The diagnosis of AHI is critical for early intervention and for decreasing transmission. We review the CNS manifestations of AHI, the laboratory stages of AHI, and discuss treatment options.

Tetanus: a review.

Tetanus is a preventable illness occurring worldwide with a high mortality, mostly affecting neonates in developing countries. Effects are toxin mediated and the diagnosis is clinical. Antibiotics, antitoxin, immunoglobulin and wound care are the mainstays of management.

Gender differences in HIV drug resistance mutations and virological outcome.

BACKGROUND: Previous studies have shown that female gender has higher odds of developing HIV drug resistance mutations. We aimed to evaluate the gender differences in HIV drug resistance mutation patterns and outcomes in a cohort of an HIV-infected population who underwent genotype resistance testing (GRT). METHODS: We conducted a retrospective study from January 2004 to April 2007 of patients >12 years of age who underwent GRT in the HIV Outpatient Program Clinic (HOP) at the Medical Center of Louisiana at New Orleans. RESULTS: Among 391 patients included in the analysis, 130 were females and 261 were males. There were no major statistically significant differences in the baseline demographic, clinical, or genotypic characteristics between males and females before GRT except for race, presence of coexisting hepatitis B and C infection, prior diagnosis of tuberculosis, presence of thymidine analogue mutations (TAMs), and protease inhibitor (PI) mutations L90M and I84V (p < 0.05). Females showed a 1.6 fold probability of carrying nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.02-2.6), whereas males showed a 2-fold probability of carrying PI mutations (OR 2, 95% CI 1.12-3.8). Sixty-seven percent of males achieved virological suppression compared with 57% of females at 1 year (±6 months). Independent of history of optimal treatment and race, females showed 2-fold odds of having virological failure compared with males at 1 year (±6 months) after GRT (OR 2.0, 95% CI 1.04-3.8). CONCLUSIONS: Females did worse than males in regard to viral load suppression at the end of 1 year if they had documented HIV drug resistance at baseline. Further longitudinal studies are needed to confirm our findings.

Final report of the Lyme disease review panel of the Infectious Diseases Society of America.

In April 2008, the Infectious Diseases Society of America (IDSA) entered into an agreement with Connecticut Attorney General Richard Blumenthal to voluntarily undertake a special review of its 2006 Lyme disease guidelines. This agreement ended the Attorney General's investigation into the process by which the guidelines were developed. The IDSA agreed to convene an independent panel to conduct a one-time review of the guidelines. The Review Panel members, vetted by an ombudsman for potential conflicts of interest, reviewed the entirety of the 2006 guidelines, with particular attention to the recommendations devoted to post-Lyme disease syndromes. After multiple meetings, a public hearing, and extensive review of research and other information, the Review Panel concluded that the recommendations contained in the 2006 guidelines were medically and scientifically justified on the basis of all of the available evidence and that no changes to the guidelines were necessary.

Klebsiella pneumoniae endophthalmitis secondary to liver abscess presenting as acute iridocyclitis.

A 51-year-old man presented with acute iridocyclitis with no evidence of vitritis on B-scan that progressed to endogenous endophthalmitis. Systemic work-up revealed a large liver abscess. Urine, blood, liver abscess, and vitreous aspirate cultures all grew Klebsiella pneumoniae. The eye was enucleated secondary to severe pain from neovascular glaucoma and loss of vision.

Antibiotic dosing in slow extended daily dialysis.

Slow extended daily dialysis (SLEDD) is the newest form of dialysis that is being used increasingly to replace continuous venovenous hemodialysis (CVVHD) for critically ill patients; it is less expensive to administer and has similar safety for patients who are prone to hemodynamic instability. Unfortunately, there are limited data regarding the appropriate dosing of antimicrobial agents for patients undergoing SLEDD. Furthermore, many nonnephrologists are not familiar with the differences between SLEDD, other continuous renal replacement therapies--for example, CVVHD--and routine hemodialysis. Thus, there is potential for inaccurate and, at worst, inadequate dosing of critical antimicrobial agents for this patient population. We review the available pharmacokinetic data on SLEDD and give preliminary recommendations for how to approach dosing in this situation.