An Alternative to Cytology in Triaging Cisgender Men and Transgender Women With HIV for High-Resolution Anoscopy.

OBJECTIVES: To evaluate high-risk human papillomavirus testing (hrHPV) as an alternative for anal cytology in screening for high-grade anal neoplasia (AIN2-3) among males with HIV. To identify predictive risk factors for AIN2-3 and develop a clinical tool to triage males with HIV for high-resolution anoscopy (HRA) without cytology. DESIGN: Retrospective cohort study of 199 adult cisgender men and transgender women with HIV referred to an anal neoplasia clinic in the Southeastern United States between January 2018 and March 2021. METHODS: Each subject underwent cytology, hrHPV, and HRA. Clinical and sociodemographic risk factors were collected for each subject. Significant risk factors for AIN2-3 were identified using logistic regression, and a triage tool incorporating these factors was developed. Screening test characteristics were calculated for cytology with and without adjunct hrHPV, hrHPV alone, and the triage tool. RESULTS: In multivariate analysis, significant predictors of AIN2-3 were hrHPV positivity (odds ratio [OR] = 11.98, CI = 5.58-25.69) and low CD4 count (OR = 2.70, CI = 1.20-6.11). There was no significant difference in positive or negative predictive values among the tool, stand-alone hrHPV, and anal cytology with adjunct hrHPV. Sensitivity and specificity were not significantly different for stand-alone or adjunctive hrHPV testing. Compared with cytology, stand-alone hrHPV and the novel triage tool reduced unnecessary HRA referrals by 65% and 30%, respectively. CONCLUSIONS: Stand-alone hrHPV would have missed 11 of 74 AIN2-3 and generated 74 fewer unnecessary HRAs than current cytology-based screening patterns, which led to 115 unnecessary HRAs in our cohort. We propose triaging those with low CD4 count, hrHPV positivity, and/or smoking history for HRA.

Loss of Smell and Taste Among Healthcare Personnel Screened for Coronavirus 2019.

Among 283 symptomatic healthcare personnel (HCP) tested for SARS-CoV-2, 51 (18%) were positive. Among those 51 HCP, self reported loss of smell and taste were present in 51% and 52.9%, respectively, with either present in 60.8%. These symptoms had high specificity (93% each, 96% for either) for a positive SARS-CoV-2 test.

Effects of Patient Characteristics on Diagnostic Performance of Self-Collected Samples for SARS-CoV-2 Testing.

We evaluated the performance of self-collected anterior nasal swab (ANS) and saliva samples compared with healthcare worker-collected nasopharyngeal swab specimens used to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used the same PCR diagnostic panel to test all self-collected and healthcare worker-collected samples from participants at a public hospital in Atlanta, Georgia, USA. Among 1,076 participants, 51.9% were men, 57.1% were >50 years of age, 81.2% were Black (non-Hispanic), and 74.9% reported >1 chronic medical condition. In total, 8.0% tested positive for SARS-CoV-2. Compared with nasopharyngeal swab samples, ANS samples had a sensitivity of 59% and saliva samples a sensitivity of 68%. Among participants tested 3-7 days after symptom onset, ANS samples had a sensitivity of 80% and saliva samples a sensitivity of 85%. Sensitivity varied by specimen type and patient characteristics. These findings can help physicians interpret PCR results for SARS-CoV-2.

Functional-structural relationship in large-scale brain networks of patients with end stage renal disease after kidney transplantation: A longitudinal study.

It is unclear how the brain network changed after kidney transplantation (KT). We explored the patterns of large-scale complex network after KT in end-stage renal disease (ESRD) patients with resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Twenty-one ESRD patients (14 men; mean age, 31.5 ± 9.9 years) scheduled for KT and 17 age- and gender-matched healthy controls (HC) (8 men; mean age, 28.9 ± 7.2 years) were enrolled in this study. Each participant underwent rs-fMRI and DTI scans in three time points (pre-KT, 1 and 6 months after KT [for ESRD]). Graph theory analysis was used to characterize the topological properties by using functional and structural network connectivities intergroup correlation analysis was performed between functional/structural MR indexes and clinical markers. Compared with HC, pre-KT ESRD patients showed an altered topological organization in both functional and structural networks. Compared with pre-KT, increased node degree and node efficiency were observed for both functional and structural networks at 1 month after KT (all p < .05), which were further increased at 6 months after KT (p < .05). Both functional and structural networks did not recover completely at 6 months after KT (all p < .05). The patients showed an increased functional-structural connectivity coupling at 1 month after KT compared with HC (p = .041). A trend of progressive recovery of functional and structural connectivity networks was observed in ERSD patients after KT, which did not recover to the normal levels even in 6 months after KT. The study results underlie cognitive function recovery in ESRD patients following KT in the neuropathophysiological perspective.

Routine HIV Test Results in 6 US Clinical Laboratories Using the Recommended Laboratory HIV Testing Algorithm With Geenius HIV 1/2 Supplemental Assay.

BACKGROUND: Geenius HIV 1/2 Supplemental Assay (Geenius; Bio-Rad Laboratories) is the only Food and Drug Administration-approved HIV-1/HIV-2 antibody differentiation test for the second step in the HIV laboratory testing algorithm. We characterized the occurrence of true HIV-1 and HIV-2 infections as well as false results in 6 US clinical laboratories using Geenius. METHODS: We examined routine HIV testing outcome data from the time the laboratories began using the algorithm with Geenius until September 30, 2017. We calculated the positive predictive value for Geenius HIV-1 and HIV-2 reactivity separately. RESULTS: Of 5,046,684 specimens tested, 41,791 had reactive antigen/antibody test results. Most specimens with reactive antigen/antibody results were HIV-1 antibody-positive established infections (n = 32,421), 1,865 of which also had indeterminate HIV-2 bands present. Ninety-three specimens were HIV-2 antibody positive or untypable for HIV-1/HIV-2 antibody. Acute HIV-1 infections were found in 528 specimens; 881 specimens lacked the nucleic acid test to determine the possibility of acute HIV-1 infection. False-positive antigen/antibody test results were present in 7505 specimens. Few specimens (n = 363) had false-positive antigen/antibody results with indeterminate Geenius and negative HIV-1 nucleic acid test results. The positive predictive values of Geenius reactivity were 99.4% for HIV-1 and 4.3% for HIV-2. CONCLUSIONS: Routine testing using the laboratory testing algorithm with Geenius resulted in most specimens resolving as HIV negative or HIV-1 positive. The occurrence of indeterminate HIV-2 bands with a Geenius final assay interpretation of HIV-1 positive was more common than true HIV-2 infections. Reporting indeterminate HIV-2 results in this situation may cause confusion with interpreting HIV infection status.

Incidence of invasive Haemophilus influenzae infections in children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for invasive infection with encapsulated bacteria. Antibiotic prophylaxis and immunizations against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) have decreased the overall incidence of invasive infections and have shifted distribution of serotypes causing disease toward those not covered by immunizations. We sought to determine the current incidence of invasive H. influenzae infections in children with SCD and to describe the clinical features and management of these infections. METHODS: Microbiology reports of a large pediatric tertiary care center were reviewed to identify all isolates of H. influenzae detected in sterile body fluid cultures from January 1, 2010 to December 31, 2017. Results were compared with the center's comprehensive clinical database of all children with SCD to identify all cases of children ages 0 to18 years with SCD with invasive H. influenzae disease for the same time period. RESULTS: We captured 2444 patients with SCD, with 14,336 person-years. There were eight episodes of H. influenzae bacteremia in seven children with SCD (five type f, two non-typable, one type a). Most episodes (7 of 8) were in children < 5 years. The incidence rate of invasive H. influenzae in SCD was 0.58/1000 person-years for ages 0 to 18 years and 1.60/1000 person-years for children age < 5 years. There were no deaths from H. influenzae infection. CONCLUSIONS: In the era of universal antibiotic prophylaxis and immunization against Hib, invasive H. influenzae disease due to nonvaccine serotypes remains a risk for children with SCD, particularly those under five years of age.

Time to Sputum Culture Conversion and Treatment Outcomes Among Patients with Isoniazid-Resistant Tuberculosis in Atlanta, Georgia.

BACKGROUND: Although isoniazid-resistant tuberculosis is more common than multidrug-resistant tuberculosis, it has been much less studied. We examined the impact of isoniazid resistance and treatment regimen, including use of a fluoroquinolone, on clinical outcomes. METHODS: A retrospective cohort study among patients with sputum culture-positive tuberculosis was performed. Early fluoroquinolone (FQ) use was defined as receiving ≥5 doses during the first month of treatment. The primary outcome was time to sputum culture conversion (tSCC). A multivariate proportional hazards model was used to determine the association of isoniazid resistance with tSCC. RESULTS: Among 236 patients with pulmonary tuberculosis, 59 (25%) had isoniazid resistance. The median tSCC was similar for isoniazid-resistant and -susceptible cases (35 vs 29 days; P = .39), and isoniazid resistance was not associated with tSCC in multivariate analysis (adjusted hazard ratio = 0.83; 95% confidence interval [CI], .59-1.17). Early FQ use was higher in isoniazid-resistant than -susceptible cases (20% vs 10%; P = .05); however, it was not significantly associated with tSCC in univariate analysis (hazard ratio = 1.48; 95% CI, .95-2.28). Patients with isoniazid-resistant tuberculosis were treated with regimens containing rifampin, pyrazinamide, and ethambutol +/- a FQ for a median of 9.7 months. Overall, 191 (83%) patients were cured. There was no difference in initial treatment outcomes; however, all cases of acquired-drug resistance (n = 1) and recurrence (n = 3) occurred among patients with isoniazid-resistant tuberculosis. CONCLUSIONS: There was no significant association with isoniazid resistance and tSCC or initial treatment outcomes. Although patients with isoniazid-resistant tuberculosis had a high cure rate, the cases of recurrence and acquired drug resistance are concerning and highlight the need for longer-term follow-up studies.

Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings.

BACKGROUND: The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. METHODS: Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. RESULTS: Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. CONCLUSIONS: In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.

Induction of human plasmablasts during infection with antibiotic-resistant nosocomial bacteria.

OBJECTIVES: Nosocomial pathogens such as Acinetobacter baumannii are a growing public health threat, due in part to their increasing resistance to antibiotics. Since some strains are resistant to all available antibiotics, novel therapies are urgently needed. Plasmablasts are short-lived B cells found in the blood that can be collected and harnessed to produce therapeutic antibodies. We set out to determine whether plasmablasts are induced during infection with A. baumannii and other nosocomial pathogens. METHODS: We obtained blood samples from patients infected with antibiotic-resistant nosocomial pathogens, and analysed their plasmablast response by flow cytometry. RESULTS: We observed a strong induction of plasmablasts in patients with antibiotic-resistant A. baumannii infection. Furthermore, plasmablasts were also induced in response to other drug-resistant nosocomial pathogens. CONCLUSIONS: These data suggest that plasmablasts may be broadly harnessed to develop therapeutic antibodies to combat otherwise untreatable antibiotic-resistant infections.

The impact of implementation of rapid blood culture identification panels on antimicrobial optimization: a retrospective cohort study.

Objective: Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel. Design: Retrospective cohort study. Methods: From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques. The primary outcomes assessed were time to optimal therapy, time to de-escalation of anti-MRSA (methicillin-resistant Staphylococcus aureus) agents, and time to de-escalation of anti-pseudomonal agents. Additional analysis investigated the impact of the availability of antimicrobial stewardship program support. This study was conducted at Grady Health System, a large metropolitan safety-net hospital in the southeastern United States. Results: A total of 253 blood cultures were included in this study (153 BCID and 100 standard). Blood culture identification use was associated with a reduction in median time to optimal antimicrobial therapy (43.4 vs 72.1 h, P < .001) and median time to de-escalation of anti-MRSA agents (27.7 vs 46.7 h, P = .006), and a trend towards reduction of median time to de-escalation of anti-pseudomonal agents (38.8 vs 54.8 h, P = .07). These reductions persisted when controlling for patient age, sex, intensive care unit status, Charlson Comorbidity Index, and antimicrobial stewardship program availability. Conclusions: Despite restricted use and lack of 24/7 antimicrobial stewardship program availability, BCID panel utilization was associated with earlier initiation of optimal therapy and pathogen identification with subsequent de-escalation of broad-spectrum antimicrobials, as compared to standard antimicrobial techniques. This suggests the potential for benefit from adopting novel diagnostic technologies outside of idealized fully-resourced settings.

Comparison of heat inactivation and cell disruption protocols for identification of mycobacteria from solid culture media by use of vitek matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Two novel protocols for inactivation and extraction were developed and used to identify 107 Mycobacterium clinical isolates, including Mycobacterium tuberculosis complex, from solid cultures using Vitek matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The protocol using heat inactivation with sonication and cell disruption with glass beads resulted in 82.2% and 88.8% species and genus level identifications, respectively.

Rapid identification of bacteria and yeasts from positive-blood-culture bottles by using a lysis-filtration method and matrix-assisted laser desorption ionization-time of flight mass spectrum analysis with the SARAMIS database.

Rapid identification of microorganisms causing bloodstream infections directly from a positive blood culture would decrease the time to directed antimicrobial therapy and greatly improve patient care. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) is a fast and reliable method for identifying microorganisms from positive culture. This study evaluates the performance of a novel filtration-based method for processing positive-blood-culture broth for immediate identification of microorganisms by MALDI-TOF with a Vitek MS research-use-only system (VMS). BacT/Alert non-charcoal-based blood culture bottles that were flagged positive by the BacT/Alert 3D system were included. An aliquot of positive-blood-culture broth was incubated with lysis buffer for 2 to 4 min at room temperature, the resulting lysate was filtered through a membrane, and harvested microorganisms were identified by VMS. Of the 259 bottles included in the study, VMS identified the organisms in 189 (73%) cultures to the species level and 51 (19.7%) gave no identification (ID), while 6 (2.3%) gave identifications that were considered incorrect. Among 131 monomicrobic isolates from positive-blood-culture bottles with one spot having a score of 99.9%, the IDs for 131 (100%) were correct to the species level. In 202 bottles where VMS was able to generate an ID, the IDs for 189 (93.6%) were correct to the species level, whereas the IDs provided for 7 isolates (3.5%) were incorrect. In conclusion, this method does not require centrifugation and produces a clean spectrum for VMS analysis in less than 15 min. This study demonstrates the effectiveness of the new lysis-filtration method for identifying microorganisms directly from positive-blood-culture bottles in a clinical setting.

Pichia anomala (Candida pelliculosa) fungemia in a patient with sickle cell disease.

This case report discusses a patient with sickle cell disease who presented with fungemia from Pichia anomala (teleomorph: Candida pelliculosa). The organism was identified as P. anomala by MALDI-TOF VITEK mass spectrometry and VITEK 2 yeast identification card. Pichia anomala should be considered in sickle cell patients with recurrent fungemia.

Diagnostic stewardship for human immunodeficiency virus (HIV) testing using computerized physician order entry.

Altering the appearance of a computerized physician order entry (CPOE) interface reduces misuse of an HIV diagnostic test by 87%, demonstrating that CPOE design is a key component of diagnostic stewardship. Collaboration between infectious disease providers, clinical laboratorians, and information technology (IT) professionals can result in improved quality and decreased costs.

Outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in hospitalized hemodialysis patients: An epidemiologic and genomic investigation.

We performed an epidemiological investigation and genome sequencing of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to define the source and scope of an outbreak in a cluster of hospitalized patients. Lack of appropriate respiratory hygiene led to SARS-CoV-2 transmission to patients and healthcare workers during a single hemodialysis session, highlighting the importance of infection prevention precautions.

Utility of a Viral Vesicular Panel Multiplex Polymerase Chain Reaction Assay for the Diagnosis of Monkeypox, Herpes Simplex, and Varicella Zoster Viruses.

Mpox (monkeypox) represents a diagnostic challenge due to varied clinical presentations and multiple mimics. A commercially available multiplex polymerase chain reaction panel accurately detects mpox virus as well as common mimics (herpes simplex virus, varicella zoster virus) in clinical specimens and could be used in routine clinical, surveillance, and outbreak settings.

Severe Acute Respiratory Syndrome Coronavirus 2 Evolution and Escape From Combination Monoclonal Antibody Treatment in a Person With HIV.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from combination monoclonal antibody treatment is rarely reported. We describe an immunocompromised individual with human immunodeficiency virus and persistent SARS-CoV-2 infection in whom substantial SARS-CoV-2 evolution occurred, including the emergence of 2 mutations associated with escape from the monoclonal antibody cocktail received.

Probability of negative mycobacterium tuberculosis complex cultures based on time to detection of positive cultures: a multicenter evaluation of commercial-broth-based culture systems.

We conducted a multicenter study to determine whether Mycobacterium tuberculosis complex (MTBC) cultures in automated broth-based systems could reliably be considered negative sooner than 6 weeks. Laboratory sites used Bactec MGIT or BacT/Alert and tracked results of time to detection of all mycobacteria (TTD-all, n = 1547) and of MTBC (TTD-MTBC, n = 466) over 6-month periods from primarily (93%) respiratory specimens. Cumulative percentages by day detected and median TTD of initial and follow-up specimens were analyzed. The median TTD-MTBC for MGIT (n = 6 sites) was 14 days. For laboratories using standard processing procedures, 100% of MTBC were detected from initial and follow-up specimens in 28 and 35 days, respectively, and no yield of MTBC on solid or MGIT liquid media was observed after 5 weeks. The median TTD-MTBC for BacT/Alert (n = 3 sites) was 18 days, with 95% and 100% detected within 37 and 42 days, respectively. Analysis of TTD of positive MTBC cultures in broth can predict the probability of culture negativity at defined time points. Receipt of interim negative reports earlier than 6 weeks could assist clinicians in considering alternative diagnoses and could alter the timing and prioritization of public health interventions. Laboratories should analyze their own TTD data to inform protocol decisions. Laboratories using MGIT could issue reports of no growth of MTBC on initial specimens as early as 4 weeks and for patients undergoing treatment as early as 5 weeks postinoculation.

In vitro synergistic antifungal activities of caspofungin in combination with fluconazole or voriconazole against Candida species determined by the Etest method.

OBJECTIVES: Increased resistance of Candida species, especially Candida. glabrata is problematic. Combination antifungal therapies were studied to solve the problem. METHODS: In this study, combinations of caspofungin with fluconazole and voriconazole were evaluated in 28 Candida species (including 15 C. glabrata and 12 with FKS mutation) at 24 and 48 hours using two Etest methods (direct cover method and MIC/MIC method). RESULTS: For Candida isolates, direct cover method showed synergy of caspofungin-fluconazole and caspofungin-voriconazole against 12/28 (43%) isolates at 24 hours, and against 16/28 (57%) isolates at 48 hours. The MIC/MIC method showed synergy of caspofungin-fluconazole and caspofungin-voriconazole against 11/28 (39%) and 12/28 (43%) isolates at 24 hours, and against 16/28 (57%) and 17/28 (61%) isolates at 48 hours, respectively. For C. glabrata, direct cover method showed synergy of caspofungin-fluconazole and caspofungin-voriconazole against 11/15 (73%) and 10/15 (67%) isolates at 24 hours, and 11/15 (73%) and 13/15 (87%) isolates at 48 hours, respectively. The MIC/MIC method showed synergy of caspofungin-fluconazole and caspofungin-voriconazole against both 11/15 (73%) isolates at 24 hours, and 10/15 (67%) and 14/15 (93%) isolates at 48 hours, respectively. CONCLUSION: A combination of caspofungin and fluconazole or voriconazole might be effective against infections caused by Candida species, especially C. glabrata with FKS mutation.