Clinical Significance of Low Serum Cryptococcal Antigen Titers by Lateral Flow Assay in Immunocompromised Patients: a Retrospective Case-Control Study.

Cryptococcus species are associated with invasive fungal infections in immunosuppressed individuals. The clinical significance of low-titer cryptococcal antigen (CrAg) by lateral flow assay is frequently uncertain. We investigated the correlation of low CrAg titers with disease in an immunocompromised patient population. Patients with first-time positive CrAg results with low serum titers (≤1:10) at two medical centers (Los Angeles, CA) from April 2014 to July 2018 were included. Age-matched controls with high (≥1:20) and negative titers were selected. We extracted medical records for pertinent clinical, radiologic, and laboratory data for cryptococcal disease. From 2,196 serum samples submitted for CrAg testing, 96 cases were included (32 each in low-titer, high-titer, and negative-titer groups). One or more immunocompromising condition was identified in 95% of patients, including HIV infection (45%), solid organ transplant (26%), and cirrhosis (22%). Pulmonary cryptococcosis was diagnosed in 9 (28%) low-titer and 8 (25%) high-titer patients (P = 1.00). Disseminated cryptococcosis occurred in 7 (22%) low-titer and 15 (47%) high-titers cases (P = 0.064). Titers ≤1:10 more frequently represented isolated antigenemia in HIV-positive than non-HIV, immunocompromised patients (P < 0.001). Follow-up testing in patients with ≤1:5 titers (n = 21) showed persistently low titers in 6 of 12 instances and increased titers in 2 cases. Twenty-seven patients with low CrAg titers were treated with antifungal therapy and 22 (81%) responded well clinically. Low-serum CrAg titers (≤1:10) correlated with cryptococcal disease in a substantial proportion of non-HIV immunocompromised patients and should prompt careful clinical workup for cryptococcal infection.

Bacteriostatic Effect of Multidose Preservative-free Buffered Saline Used in Scleral Lens Wear.

SIGNIFICANCE: Scleral lenses have become an increasingly common treatment for ocular surface disease and irregular corneas. Multidose, preservative-free saline solutions are frequently used off-label to fill scleral lenses. Because the fluid resides over the ocular surface during lens wear, contaminated solutions may increase the risk of infectious complications. PURPOSE: We sought to assess the viability of skin microorganisms and pathogens associated with keratitis once introduced into a multidose preservative-free saline (MDPFS) solution containing the bacteriostatic agent boric acid (PuriLens Plus; The Lifestyle Co., Inc., Freehold, NJ). METHODS: Eleven bacterial and one yeast isolate were each inoculated to three lots of MDPFS as well as to sterile normal saline for comparison. Microorganism concentrations were enumerated at baseline and days 1, 3, 7, 14, 21, and 28. Persistence of microorganism viability was compared between MDPFS lots and between MDPFS and normal saline for each organism. RESULTS: Duration of microorganism viability was ≥24 hours in MDPFS with no significant difference in the distribution of survival duration of microorganisms in MDPFS versus normal saline (P = .15). Candida albicans concentrations declined 14 days earlier in MDPFS, whereas concentrations of viable organisms in MDPFS remained within 1 log of baseline for the longest durations for Pseudomonas aeruginosa (7 days), Escherichia coli (14 days), and Achromobacter xylosoxidans (≥28 days). Gram-positive organism concentrations remained within 1 log of baseline for no more than 3 days. Mild lot-to-lot variation in organism concentrations was noted near the end points of viability. Bacteriostasis was demonstrated in that concentrations of all organisms remained at or below baseline levels throughout the 28-day period. CONCLUSIONS: After microbial contamination, persistence of organism viability was similar in PuriLens and normal saline. Environmental gram-negative organisms, many of which can contribute to infectious keratitis, can persist for weeks once introduced into saline solutions.

In Vitro Activity of Rifabutin and Rifampin against Antibiotic-Resistant Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae.

We recently reported that the antimicrobial activity of rifabutin against Acinetobacter baumannii is best modeled by the use of RPMI for in vitro susceptibility testing. Here, we define the effects of medium on the susceptibility and frequency of resistance emergence in a panel of A. baumannii, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa clinical isolates. Only A. baumannii was hypersusceptible to rifabutin in vitro and in vivo using a Galleria mellonella infection model. In vitro, the frequency of resistance emergence was greater when the bacteria were selected on RPMI versus tryptic soy agar (TSA) or Mueller-Hinton II (MHII) agar plates. However, the frequency of resistance emergence was lower in vivo than in the RPMI in vitro condition. IMPORTANCE Rifabutin has been recently described as a potential adjunctive therapy for antibiotic-resistant A. baumannii infections due to hypersensitivity in iron-depleted media, which may more closely mimic an in vivo environment. Here, we report that this hyperactivity is specific for A. baumannii, rather than being a general effect for other pathogens.

Predictors of SARS-CoV-2 Infection in Youth at a Large, Urban Healthcare Center in California, March-September 2020.

Objective: To understand which social, epidemiologic, and clinical risk factors are associated with SARS-CoV-2 infection in youth accessing care in a large, urban academic institution. Methods: We conducted a prospective cohort study with case-control analyses in youth who received testing for SARS-CoV-2 at our academic institution in Los Angeles during the first wave of the COVID-19 pandemic (March-September 2020). Results: A total of 27,976 SARS-CoV-2 assays among 11,922 youth aged 0-24 years were performed, including 475 youth with positive SARS-CoV-2 results. Positivity rate was higher among older, African American, and Hispanic/Latinx youth. Cases were more likely to be from non-English-speaking households and have safety-net insurance. Zip codes with higher proportion of Hispanic/Latinx and residents living under the poverty line were associated with increased SARS-CoV-2 cases. Youth were more likely to have positive results if tested for exposure (OR 21.5, 95% CI 14.6-32.1) or recent travel (OR 1.5, 95% CI 1.0-2.3). Students were less likely to have positive results than essential worker youth (OR 0.5, 95% CI 0.3-0.8). Patterns of symptom presentation varied significantly by age group; number of symptoms correlated significantly with age in SARS-CoV-2 cases (r = 0.030, p < 0.001). SARS-CoV-2 viral load did not vary by symptom severity, but asymptomatic youth had lower median viral load than those with symptoms (21.5 vs. 26.7, p = 0.009). Conclusions: Socioeconomic factors are important drivers of SARS-CoV-2 infection in youth. Presence of symptoms, exposure, and travel can be used to drive testing in older youth. Policies for school reopening and infection prevention should be tailored differently for elementary schools and universities.

Antibacterial activity of varying UMF-graded Manuka honeys.

Honey has been used as a traditional remedy for skin and soft tissue infections due to its ability to promote wound healing. Manuka honey is recognized for its unusually abundant content of the antibacterial compound, methylglyoxal (MGO). The Unique Manuka Factor (UMF) grading system reflects the MGO concentration in Manuka honey sold commercially. Our objective was to observe if UMF values correlated with the antibacterial activity of Manuka honey against a variety of pathogens purchased over the counter. The antibacterial effect of Manuka honey with UMF values of 5+, 10+, and 15+ from the same manufacturer was assessed by the broth microdilution method. Minimum inhibitory concentration (MIC) values were determined against 128 isolates from wound cultures representing gram-positive, gram-negative, drug-susceptible, and multi-drug resistant (MDR) organisms. Lower MICs were observed with UMF 5+ honey for staphylococci (n = 73, including 25 methicillin-resistant S. aureus) and Pseudomonas aeruginosa (n = 22, including 10 MDR) compared to UMF 10+ honey (p<0.05) and with UMF 10+ compared to UMF 15+ (p = 0.01). For Enterobacteriaceae (n = 33, including 14 MDR), MIC values were significantly lower for UMF 5+ or UMF 10+ compared to UMF 15+ honey (p<0.01). MIC50 for UMF 5+, UMF 10+, and UMF 15+ honey against staphylococci was 6%, 7%, and 15%, and for Enterobacteriaceae was 21%, 21%, and 27%, respectively. For Pseudomonas aeruginosa MIC50 was 21% and MIC90 was 21-27% for all UMFs. Manuka honey exhibited antimicrobial activity against a spectrum of organisms including those with multi-drug resistance, with more potent activity overall against gram-positive than gram-negative bacteria. Manuka honey with lower UMF values, in our limited sampling, paradoxically demonstrated increased antimicrobial activity among the limited samples tested, presumably due to changes in MGO content of honey over time. The UMF value by itself may not be a reliable indicator of antibacterial effect.