Seasonal variations and risk factors of Streptococcus pyogenes infection: a multicenter research network study.

Background: Streptococcus pyogenes, or Group A Streptococcus (GAS), causes acute pharyngitis and necrotizing fasciitis. Seasonal variations in GAS infections are not robustly characterized. We assessed seasonal variations and risk factors of GAS pharyngitis and ICD-10-diagnosed necrotizing fasciitis. Methods: From the period 2010-2019, we conducted a case-control study using laboratory-confirmed cases of GAS pharyngitis and a descriptive observational study of necrotizing fasciitis using ICD-10 codes. Data were collected from TriNetX, a federated research network. We extracted seasonal (quarterly) incidence rates. We used an autoregressive integrated moving average (ARIMA) model to assess seasonal variations. Demographic characteristics and 1-month outcomes were compared among adults with or without GAS pharyngitis. Results: We identified 224,471 adults with GAS pharyngitis (test-positive) and 546,142 adults without it (test-negative). GAS pharyngitis adults were younger (25.3 versus 30.2 years of age, p < 0.0001), more likely to be Hispanic individuals (10% versus 8%, p < 0.0001) and slightly more likely to be Black or African American individuals (14% versus 13%, p < 0.0001). Propensity score matching found that adults with test-positive cases of GAS pharyngitis had a higher risk of acute rheumatic fever while having no significant differences in risk of intensive care unit admission and mortality compared with test-negative cases. GAS pharyngitis average incidence peaked in the winter while dipping in the summer (0.32 versus 0.18 and 4.07 versus 1.78 per 1000 adults and pediatric patients, respectively). Necrotizing fasciitis diagnoses were highest during summer (0.032 per 1000 adults). There was a significant ARIMA seasonal variation in the time series analysis for adult and pediatric GAS pharyngitis (p < 0.0001 and p = 0.014, respectively). Necrotizing fasciitis diagnosis was not associated with seasonal variation (p = 0.861). Conclusion: Peaks in GAS pharyngitis occur in the winter months. ICD code-based necrotizing fasciitis did not show a quarterly seasonal variation.

Bartonella quintana Infection in People Experiencing Homelessness in the Denver Metropolitan Area.

BACKGROUND: Bartonella quintana is an important cause of infection amongst people experiencing homelessness that is underdiagnosed due to its nonspecific clinical manifestations. We reviewed cases identified in the Denver metropolitan area in 2016-2021. METHODS: The electronic medical records from 2 large academic medical centers in Colorado were reviewed for demographic, clinical, and laboratory features of patients with B. quintana infection confirmed by blood culture, serologies, and/or molecular testing from July 2016 to December 2021. RESULTS: Fourteen patients with B. quintana infection were identified. The mean age was 49.5 years (SD 12.7 years) and 92.9% of patients were male. Twelve patients had history of homelessness (85.7%) and 11 were experiencing homelessness at the time of diagnosis (78.6%). Most frequent comorbidities included substance use (78.6%), of which 42.9% had alcohol use disorder. The average time to blood culture positivity was 12.1 days (SD 6.2 days). Three patients with bacteremia had negative B. quintana IgG, and 6 of 14 (42.8%) patients had evidence of endocarditis on echocardiography. CONCLUSIONS: B. quintana is an underrecognized cause of serious infection in individuals experiencing homelessness. Serologic and microbiologic testing, including prolonged culture incubation, should be considered in at-risk patients due to ongoing transmission in homeless populations.

False-positive rapid diagnostic test for malaria in new world cutaneous leishmaniasis: a tale of two travelers.

We report two immigrants from Cuba seen in a US travel clinic with a confirmed diagnosis of cutaneous leishmaniasis in whom we also suspected malaria co-infection. Both individuals likely acquired leishmaniasis in the Darien Gap region of Panama during their migratory path to the United States. As part of their clinical workup to rule out malaria, a rapid malaria antigen testing for P. falciparum was obtained and reported positive in both patients, However, both a qualitative reverse transcription-polymerase chain reaction (RT-PCR) for Plasmodium falciparum in blood and repeated thick-and-thin smear direct microscopy were negative in both, deeming the rapid malaria test as a false-positive. Thus, confirmation of malaria in travelers requires thick-and-thin film microscopy. Clinicians should be aware of the growing recognition of the possibility of false-positive malaria rapid diagnostic tests in those with some forms of leishmaniasis.

Factors Associated with Retention and Adherence in a Comprehensive, Diverse HIV Pre-Exposure Prophylaxis Clinic.

Retention in HIV pre-exposure prophylaxis (PrEP) care and adherence to PrEP have been suboptimal in some populations, despite evidence that high adherence dramatically enhances PrEP efficacy. A comprehensive PrEP Clinic with a retention specialist and clinical pharmacist could impact patient's retention and adherence in PrEP care. A retrospective electronic medical record review of patients attending an academic PrEP Clinic was conducted between June 2018 and June 2019 (at least one visit attended for PrEP was required). Retention was defined as a medical or laboratory visit every 3 months ±30 days, as recommended by CDC guidelines, but was analyzed using the number of visits and time between visits via multivariate regression analyses. PrEP adherence was calculated using a Medication-Possession Ratio (MPR) and compared between patient characteristics using Kruskal-Wallis tests. One hundred twenty-two patients were identified by chart review, 96 had sufficient data for follow-up and were included in at least one analysis. The population was primarily cisgender men who have sex with men and over half were African American or Hispanic. Overall, patient retention was 43%. The retention analysis demonstrated that individuals who self-identified as gay were more likely to be retained than those who identified as heterosexual (53% vs. 18%, hazard ratio = 1.75, 95% confidence interval = [1.01-3.03], p = .045). Although not statistically significant, African Americans and cisgender women were less likely to be retained in care. The adherence analysis identified higher median MPRs among patients not reporting previous incarceration (80% vs. 35%, p < .01). Although not statistically significant, there was lower adherence among youth 18-24 (11% vs. 54% MPR >80, p = .058). Despite comprehensive PrEP clinical care, heterosexual individuals were less likely to be retained in PrEP care than those who self-identified as gay and previously incarcerated individuals were less likely to be adherent to PrEP.

Facile accelerated specific therapeutic (FAST) platform develops antisense therapies to counter multidrug-resistant bacteria.

Multidrug-resistant (MDR) bacteria pose a grave concern to global health, which is perpetuated by a lack of new treatments and countermeasure platforms to combat outbreaks or antibiotic resistance. To address this, we have developed a Facile Accelerated Specific Therapeutic (FAST) platform that can develop effective peptide nucleic acid (PNA) therapies against MDR bacteria within a week. Our FAST platform uses a bioinformatics toolbox to design sequence-specific PNAs targeting non-traditional pathways/genes of bacteria, then performs in-situ synthesis, validation, and efficacy testing of selected PNAs. As a proof of concept, these PNAs were tested against five MDR clinical isolates: carbapenem-resistant Escherichia coli, extended-spectrum beta-lactamase Klebsiella pneumoniae, New Delhi Metallo-beta-lactamase-1 carrying Klebsiella pneumoniae, and MDR Salmonella enterica. PNAs showed significant growth inhibition for 82% of treatments, with nearly 18% of treatments leading to greater than 97% decrease. Further, these PNAs are capable of potentiating antibiotic activity in the clinical isolates despite presence of cognate resistance genes. Finally, the FAST platform offers a novel delivery approach to overcome limited transport of PNAs into mammalian cells by repurposing the bacterial Type III secretion system in conjunction with a kill switch that is effective at eliminating 99.6% of an intracellular Salmonella infection in human epithelial cells.

Cryptococcal pericarditis in a heart transplant recipient.

We present a case of Cryptococcus neoformans pericarditis in a cardiac transplant recipient. This article reviews the diagnosis, treatment, and complications of cryptococcosis specifically in transplant patients. While pericarditis is a rare manifestation of Cryptococcus infection, this case highlights that cryptococcosis should be considered in the differential diagnosis for solid organ transplant and immunocompromised patients presenting with pericardial effusions.

A Mixed Methods Evaluation of an Inclusive Sexual History Taking and HIV Prevention Curriculum for Trainees.

BACKGROUND: Health disparities exist in HIV risk in the USA among the lesbian-gay-bisexual-transgender-queer (LGBTQ) community. There is also scarce literature on curricula for HIV prevention and pre-exposure prophylaxis (PrEP) for trainees. AIM: To create a curriculum to train residents to perform inclusive sexual history taking and HIV prevention care. The curriculum covers sexual history, LGBTQ health, sexually transmitted infections, and HIV risk assessment and risk reduction counseling including use of PrEP. SETTING: A dedicated PrEP Clinic was created within an Academic Medical Center Outpatient HIV Clinic. Patients were primarily LGBTQ identified, but also included HIV sero-discordant couples, cisgender individuals, heterosexual invididuals, and those with experience of homelessness, sex work, and substance abuse. PARTICIPANTS: Thirty-four internal medicine residents completed the course between November 2017 and May 2018. PROGRAM DESCRIPTION: The curriculum was delivered as Just in Time Teaching (JiTT) via online virtual patient cases followed by directly observed clinical care at a large urban PrEP clinic. PROGRAM EVALUATION AND RESULTS: The effectiveness of the curriculum was assessed through paired pre/post-self-assessment surveys (n = 19), additional post-surveys on the online modules (n = 22), and interviews (n = 9). Many respondents reported no prior training or inadequate prior training in the course content. As a result of the course, participants reported statistically significant increased confidence and comfort in all seven HIV prevention topic areas, with the greatest gains in safe sex counseling for LGBTQ patients and in discussing PrEP (mean changes of 1.21, 1.58 on 5-point Likert scale, respectively, p < 0.0001). Six of nine interviewees post-course had applied what they learned to patient care; five indicated their learning would benefit patients. DISCUSSION: An HIV prevention curriculum focused on cultural humility in care can improve trainee's skills in HIV risk reduction counseling, including PrEP, among all patients including those identifying as LGBTQ.

Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation.

The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae. Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide-generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens.

Draft Genome Sequences of Clinical Isolates of Multidrug-Resistant Acinetobacter baumannii.

We report here the draft genome sequences of two clinically isolated Acinetobacter baumannii strains. These samples were obtained from patients at the University of Colorado Hospital in 2007 and 2013 and encode an estimated 20 and 13 resistance genes, respectively.

Draft Genome Sequence for a Clinical Isolate of Vancomycin-Resistant Enterococcus faecalis.

We report here the draft genome sequence of a multidrug-resistant Enterococcus faecalis strain, isolated from a patient at the University of Colorado Hospital. The genome assembly is 3,040,186 bp in length with 37.6% GC content. This isolate encodes eleven resistance genes, including those for glycopeptide, aminoglycoside, macrolide-lincosamide-streptogramin, and tetracycline resistance.

Photoexcited quantum dots for killing multidrug-resistant bacteria.

Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum ß-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.

Analysis of a panel of rapidly growing mycobacteria for resistance to aldehyde-based disinfectants.

After several accounts across the globe of mycobacteria outbreaks associated with medical procedures and aldehyde disinfectants resistance, we undertook an analysis of mycobacteria isolated from patients seen in a hospital in the United States between 1994 and 2008 to determine prevalence of resistance to aldehyde-based disinfectants. Out of the 117 clinical isolates screened, 6 isolates belonging to the emerging Mycobacterium abscessus group were found to display significant levels of resistance to glutaraldehyde and ortho-phthalaldehyde.

Azithromycin for prevention of exacerbations of COPD.

BACKGROUND: Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. METHODS: We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. RESULTS: A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). CONCLUSIONS: Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.).

Evaluation of vancomycin and daptomycin potency trends (MIC creep) against methicillin-resistant Staphylococcus aureus isolates collected in nine U.S. medical centers from 2002 to 2006.

Vancomycin MIC creep has been reported by some institutions but not confirmed in large surveillance studies. We evaluated the possible occurrence of MIC creep when testing vancomycin and daptomycin against methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA) by using precise incremental reference MIC methods. Nine hospitals (one in each U.S. census region) randomly selected bloodstream MRSA strains (target, 40/year) from 2002 to 2006. MICs were determined by the reference broth microdilution method using incremental dilutions (eight for each log(2) dilution step). Isolates for which vancomycin MICs were >1 microg/ml were typed by pulsed-field gel electrophoresis (PFGE). The vancomycin MIC mode was either 0.625 microg/ml (for eight hospitals) or 0.813 microg/ml (for one hospital), and vancomycin MIC results for 72.9% of strains were between 0.563 and 0.688 microg/ml. No yearly variation in the central tendency of vancomycin MICs for the wild-type population in any medical center was observed; however, when data were analyzed by the geometric mean statistic, vancomycin MIC increases (at three sites) and declines (at three sites) were observed. The daptomycin MIC mode varied from 0.156 microg/ml (2003 to 2005) to 0.219 microg/ml (2002 and 2006), and MIC results for 83.5% (80.3 to 89.2% in each of the centers) of isolates fell between these values. Among PFGE-typed strains, 43 of 55 (78%; from seven hospitals) showed a pattern consistent with that of the USA100 clone, which was represented by all strains from two hospitals and 64 to 88% of strains from five other medical centers; only one strain (2%) was USA300. In conclusion, the perception of MIC creep may vary according to the methods used to analyze the data. Geometric mean MIC data revealed a possible, very-low-level MIC creep at three of nine sites over the 5-year period, which was not evident using modal MICs or the data from all nine hospitals (+0.02 mug/ml). The occurrence of isolates for which the vancomycin MIC was >1 microg/ml was very unusual, with no increased trend, but these organisms were usually clonal (USA100).

Epidemiology of healthcare-associated bloodstream infection caused by USA300 strains of methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals.

OBJECTIVE: To describe the epidemiology of bloodstream infection caused by USA300 strains of methicillin-resistant Staphylococcus aureus (MRSA), which are traditionally associated with cases of community-acquired infection, in the healthcare setting. DESIGN: Retrospective cohort study. SETTING: Three academically affiliated hospitals in Denver, Colorado. METHODS: Review of cases of S. aureus bloodstream infection during the period from 2003 through 2007. Polymerase chain reaction was used to identify MRSA USA300 isolates. RESULTS: A total of 330 cases of MRSA bloodstream infection occurred during the study period, of which 286 (87%) were healthcare-associated. The rates of methicillin resistance among the S. aureus isolates recovered did not vary during the study period and were similar among the 3 hospitals. However, the percentages of cases of healthcare-associated MRSA bloodstream infection due to USA300 strains varied substantially among the 3 hospitals: 62%, 19%, and 36% (P<.001) for community-onset cases and 33%, 3%, and 33% (P=.005) for hospital-onset cases, in hospitals A, B, and C, respectively. In addition, the number of cases of healthcare-associated MRSA bloodstream infection caused by USA300 strains increased during the study period at 2 of the 3 hospitals. At each hospital, USA300 strains were most common among cases of community-associated infection and were least common among cases of hospital-onset infection. Admission to hospital A (a safety-net hospital), injection drug use, and human immunodeficiency virus infection were independent risk factors for healthcare-associated MRSA bloodstream infection due to USA300 strains. CONCLUSIONS: The prevalence of USA300 strains among cases of healthcare-associated MRSA bloodstream infection varied dramatically among geographically clustered hospitals. USA300 strains are replacing traditional healthcare-related strains of MRSA in some healthcare settings. Our data suggest that the prevalence of USA300 strains in the community is the dominant factor affecting the prevalence of this strain type in the healthcare setting.

Evidence for dendritic cell-dependent CD4(+) T helper-1 type responses to commensal bacteria in normal human intestinal lamina propria.

Reactivity of lamina propria (LP) T cells to commensal bacteria has been demonstrated in animal models of inflammatory bowel disease (IBD) and in humans with IBD, but few studies have evaluated the function of such cells in normal individuals. LP mononuclear cells (LPMC) were disaggregated from healthy human intestinal tissue and cultured with heat-killed commensal and pathogenic bacteria. CD3(+)CD4(+) IFN-gamma-producing (Th1) cells reactive to commensal bacteria were demonstrated at frequencies ranging from 0.05 to 2.28% in LPMC. Bacteria-specific Th1 responses were inhibited by anti-HLA-DR antibodies and chloroquine exposure, were enriched in LP relative to peripheral blood, and expressed effector memory cell markers. Bacteria-specific CD4(+) T cell proliferation in vitro was dependent on the presence of LP dendritic cells (DCs), which produced pro-inflammatory cytokines upon bacterial exposure. These results suggest that bacteria-reactive DCs and CD4(+) T cells in normal LP have substantial pro-inflammatory potential that is revealed upon disaggregation in vitro.

Development of herpes simplex virus disease in patients who are receiving cidofovir.

BACKGROUND: Cidofovir is a nucleotide analogue with antiviral activity against a wide range of DNA viruses, including herpes simplex virus (HSV). In vitro resistance to cidofovir has been reported with use of laboratory HSV strains; clinical failure of cidofovir therapy for HSV disease has also been reported with an isolate that was susceptible by in vitro testing. PATIENTS AND METHODS: Three patients with HSV disease that was unresponsive to cidofovir therapy had viral isolates obtained and stored; the isolates were analyzed for antiviral susceptibility by an antigen reduction assay (ARA). PCR cloning and automated sequencing were performed for isolates that displayed in vitro resistance. Mutations were identified by comparison with the appropriate HSV consensus sequence. RESULTS: An HSV type 2 (HSV-2) isolate recovered from patient 2 displayed in vitro cidofovir resistance with an inhibitory concentration of 50% (IC50) of 13.06 microg/mL. HSV type 1 isolates recovered from patients 1 and 3 had elevated IC50s to cidofovir (7.32 and 8.23 microg/mL, respectively); however, these isolates did not meet the cutoff point for resistance according to the ARA. Sequencing of a cidofovir-resistant HSV-2 isolate revealed several DNA polymerase mutations that had not been previously described during in vitro resistance selection. CONCLUSIONS: To our knowledge, this is the first report of cidofovir resistance in HSV developing in vivo. The 3 sequenced clones all contained mutations truncating the pol C' end, suggesting that this region may be critical for cidofovir antiviral activity. In addition, the presence of multiple mutations suggests that the altered DNA polymerase of cidofovir-resistant virus may have introduced additional mutations into the viral genome. Introduction of the mutations identified in wild-type HSV strains is needed before the resistance phenotype can be definitively associated with any of the mutations found. Additional studies are needed to delineate the mechanisms of cidofovir resistance in HSV.