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Background: Historically, patients with human immunodeficiency virus (PWH) were at higher risk for pulmonary morbidities than patients without HIV. Lung transplantation in PWH has been limited by uncertain outcomes and a lack of guidelines for transplantation and immunosuppression. However, several case reports in the United States and Europe have demonstrated that lung transplantation in PWH is feasible. Although there remain concerns regarding these patients as higher-risk recipients, lung transplantation is feasible with careful modification of immunosuppression and close monitoring., Methods: We performed lung transplantation on three PWHs and analyzed their post-transplant outcomes to determine the feasibility of lung transplant in PWH., Results: We found that all three patients (mean age 59, SD 10.98) with HIV underwent lung transplantation. Two of the three patients experienced acute cellular rejection that resolved with intravenous corticosteroids. None had long-term complications including chronic rejection, antibody-mediated rejection, or infections. All three patients maintained baseline HIV therapy following transplantation with adequate HIV disease control., Conclusion: Although PWH has an increased risk of pulmonary comorbidities compared to the general population, lung transplantation appears to be a feasible treatment option supported by the growing body of literature and the three cases described here., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Deep-seated Candida spp. infections may necessitate extended durations of antifungal therapy. Increasing resistance to first-line antifungals threatens the most common options for long-term treatment. In this issue, Ponta et al. (Antimicrob Agents Chemother 68:e00750-24, 2024, https://doi.org/10.1128/aac.00750-24) present cases in which they used rezafungin, a novel long-acting echinocandin antifungal, for extended durations. While excellent clinical evidence supports the short-term safety of rezafungin, these cases demonstrate that rezafungin may additionally have a role in long-term suppressive therapy for antifungal-resistant Candida spp. infections., Competing Interests: The authors declare no conflict of interest.

Background: The COVID-19 pandemic has led to an increase in SARS-CoV-2-test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19-positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19-positive donors at a single center are presented here., Methods: A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19-positive (n = 29 total; 25 index, 4 redo) and COVID-19-negative (n = 472 total; 454 index, 18 redo) deceased donor liver grafts were compared., Results: COVID-19-positive donors were significantly younger ( P  = 0.04) and had lower kidney donor profile indices ( P  = 0.04) than COVID-19-negative donors. Recipients of COVID-19-positive donor grafts were older ( P  = 0.04) but otherwise similar to recipients of negative donors. Donor SARS-CoV-2 infection status was not associated with a overall survival of recipients (hazard ratio, 1.11; 95% confidence interval, 0.24-5.04; P  = 0.89). There were 3 deaths among recipients of liver grafts from COVID-19-positive donors. No death seemed virally mediated because there was no qualitative association with peri-LT antispike antibody titers, post-LT prophylaxis, or SARS-CoV-2 variants., Conclusions: The utilization of liver grafts from COVID-19-positive donors was not associated with a decreased overall survival of recipients. There was no suggestion of viral transmission from donor to recipient. The results from this large single-center study suggest that COVID-19-positive donors may be used safely to expand the deceased donor pool., Competing Interests: R.M.G. is a member of the advisory board for TransMedics and has received stock in the company., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Solid organ transplant (SOT) recipients are at risk of bloodstream infections (BSIs) with MDR organisms (MDROs)., Objectives: To describe the epidemiology of BSI in the year after several types of SOT, as well as the prevalence of MDRO infections in this population., Methods: We conducted a single-centre, retrospective study of kidney, liver, heart, and multi-organ transplantation patients. We examined BSIs ≤1 year from SOT and classified MDRO phenotypes for Staphylococcus aureus , enterococci, Enterobacterales, Pseudomonas aeruginosa and Candida spp. We compared BSI characteristics between SOT types and determined risk factors for 90 day mortality., Results: We included 2293 patients [1251 (54.6%) kidney, 663 (28.9%) liver, 219 (9.6%) heart and 160 (7.0%) multi-organ transplant]. Overall, 8.5% of patients developed a BSI. BSIs were most common after multi-organ (23.1%) and liver (11.3%) transplantation ( P  < 0.001). Among 196 patients with BSI, 323 unique isolates were recovered, 147 (45.5%) of which were MDROs. MDROs were most common after liver transplant (53.4%). The most frequent MDROs were VRE (69.8% of enterococci) and ESBL-producing and carbapenem-resistant Enterobacterales (29.2% and 27.2% of Enterobacterales, respectively). Mortality after BSI was 9.7%; VRE was independently associated with mortality (adjusted OR 6.0, 95% CI 1.7-21.3)., Conclusions: BSI incidence after SOT was 8.5%, with a high proportion of MDROs (45.5%), especially after liver transplantation. These data, in conjunction with local antimicrobial resistance patterns and prescribing practices, may help guide empirical antimicrobial selection and stewardship practices after SOT., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Competing Interests: Potential conflicts of interest . E. J. S. reports a grant or contract from the Agency for Healthcare Research and Quality and leadership or fiduciary roles with the Infectious Diseases Society of America Sepsis Task Force. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Objectives: To determine the association between time period of hospitalization and hospital mortality among critically ill adults with coronavirus disease 2019., Design: Observational cohort study from March 6, 2020, to January 31, 2021., Setting: ICUs at four hospitals within an academic health center network in Atlanta, GA., Patients: Adults greater than or equal to 18 years with coronavirus disease 2019 admitted to an ICU during the study period (i.e., Surge 1: March to April, Lull 1: May to June, Surge 2: July to August, Lull 2: September to November, Surge 3: December to January)., Measurements and Main Results: Among 1,686 patients with coronavirus disease 2019 admitted to an ICU during the study period, all-cause hospital mortality was 29.7%. Mortality differed significantly over time: 28.7% in Surge 1, 21.3% in Lull 1, 25.2% in Surge 2, 30.2% in Lull 2, 34.7% in Surge 3 (p = 0.007). Mortality was significantly associated with 1) preexisting risk factors (older age, race, ethnicity, lower body mass index, higher Elixhauser Comorbidity Index, admission from a nursing home); 2) clinical status at ICU admission (higher Sequential Organ Failure Assessment score, higher d-dimer, higher C-reactive protein); and 3) ICU interventions (receipt of mechanical ventilation, vasopressors, renal replacement therapy, inhaled vasodilators). After adjusting for baseline and clinical variables, there was a significantly increased risk of mortality associated with admission during Lull 2 (relative risk, 1.37 [95% CI = 1.03-1.81]) and Surge 3 (relative risk, 1.35 [95% CI = 1.04-1.77]) as compared to Surge 1., Conclusions: Despite increased experience and evidence-based treatments, the risk of death for patients admitted to the ICU with coronavirus disease 2019 was highest during the fall and winter of 2020. Reasons for this increased mortality are not clear., Competing Interests: Dr. Auld received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem "mono-resistant") represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown., Methods: We analyzed surveillance data from 9 CDC Emerging Infections Program (EIP) sites. A case was the first isolation of a carbapenem-resistant Enterobacter cloacae complex, Escherichia coli , Klebsiella aerogenes , K. oxytoca , K. pneumoniae, or K. variicola from a normally sterile site or urine in an EIP catchment area resident in 2016-2017. We compared risk factors, carbapenemase genes, antibiotic susceptibility, and mortality of ertapenem "mono-resistant" cases to "other" CRE cases (resistant to ≥1 carbapenem other than ertapenem) and analyzed risk factors for mortality., Results: Of 2009 cases, 1249 (62.2%) were ertapenem-mono-resistant and 760 (37.8%) were other CRE. Ertapenem-mono-resistant CRE cases were more frequently ≥80 years old (29.1% vs 19.5%; P  < .0001) and female (67.9% vs 59.0%; P  < .0001). Ertapenem-mono-resistant isolates were more likely to be Enterobacter cloacae complex (48.4% vs 15.4%; P  < .0001) but less likely to be isolated from a normally sterile site (7.1% vs 11.7%; P  < .01) or to have a carbapenemase gene (2.4% vs 47.4%; P  < .0001). Ertapenem-mono-resistance was not associated with 90-day mortality in logistic regression models. Carbapenemase-positive isolates were associated with mortality (odds ratio, 1.93; 95% CI, 1.30-2.86)., Conclusions: Ertapenem-mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics from other CRE. These findings may inform antibiotic choice and infection prevention practices, particularly when carbapenemase testing is not available., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Updated Clostridioides difficile infection (CDI) guidelines published in 2018 recommend vancomycin as first-line treatment. Of 833 community-onset CDI cases in metropolitan Atlanta, Georgia in 2018, over half did not receive first-line treatment, although guideline adherence increased over the year. Second-line treatment was more common in patients treated in ambulatory settings., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

There is increasing evidence for the importance of the gut microbiome in human health and disease. Traditional and modern technologies - from cell culture to next generation sequencing - have facilitated these advances in knowledge. Each of the tools employed in measuring the microbiome exhibits unique capabilities that may be leveraged for clinical diagnostics. However, much still needs to be done to standardize the language and metrics by which a microbiome is characterized. Here we review the capabilities of gut microbiome-based diagnostics, review selected examples, and discuss the outlook towards clinical application., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Mounting evidence demonstrates potential for fecal-oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration now requires SARS-CoV-2 testing of potential feces donors before the use of stool manufactured for fecal microbiota transplantation. We sought to develop and validate a high-sensitivity SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) procedure for testing stool specimens., Methods: A modified extraction method was used with an RT-PCR assay adapted from the Centers for Disease Control and Prevention PCR protocol for respiratory specimens. Contrived specimens were created using pre-COVID-19 banked stool specimens and spiking in known concentrations of SARS-CoV-2-specific nucleic acid. The highest transcript concentration at which 2/2 or 1/2 SARS-CoV-2 targets were detected in 9/10 replicates was defined as the dual-target limit and single-target limit of detection, respectively. The clinical performance of the assay was evaluated with stool samples collected from 17 nasopharyngeal swab RT-PCR-positive patients and 14 nasopharyngeal RT-PCR-negative patients., Results: The dual-target and single-target limit of detection were 56 copies/μL and 3 copies/μL, respectively. SARS-CoV-2 was detected at concentrations as low as 0.6 copies/μL. Clinical stool samples from known COVID-19-positive patients demonstrated the detection of SARS-CoV-2 in stool up to 29 days from symptom onset with a high agreement with nasopharyngeal swab tests (kappa statistic of 0.95, P value < 0.001)., Discussion: The described RT-PCR test is a sensitive and flexible approach for the detection of SARS-CoV-2 in stool specimens. We propose an integrated screening approach that incorporates this stool test to support continuation of fecal microbiota transplantation programs., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Purpose: To assess the prevalence of retinopathy and its association with systemic morbidity and laboratory indices of coagulation and inflammatory dysfunction in severe COVID-19., Design: Retrospective, observational cohort study., Methods: Adult patients hospitalized with severe COVID-19 who underwent ophthalmic examination from April to July 2020 were reviewed. Retinopathy was defined as one of the following: 1) Retinal hemorrhage; 2) Cotton wool spots; 3) Retinal vascular occlusion. We analyzed medical comorbidities, sequential organ failure assessment (SOFA) scores, clinical outcomes, and laboratory values for their association with retinopathy., Results: Thirty-seven patients with severe COVID-19 were reviewed, the majority of whom were female (n = 23, 62%), Black (n = 26, 69%), and admitted to the intensive care unit (n = 35, 95%). Fourteen patients had retinopathy (38%) with retinal hemorrhage in 7 (19%), cotton wool spots in 8 (22%), and a branch retinal artery occlusion in 1 (3%) patient. Patients with retinopathy had higher SOFA scores than those without retinopathy (8.0 vs. 5.3, p = .03), higher rates of respiratory failure requiring invasive mechanical ventilation and shock requiring vasopressors ( p < .01). Peak D-dimer levels were 28,971 ng/mL in patients with retinopathy compared to 12,575 ng/mL in those without retinopathy ( p = .03). Peak CRP was higher in patients with cotton wool spots versus those without cotton wool spots (354 mg/dL vs. 268 mg/dL, p = .03). Multivariate logistic regression modeling showed an increased risk of retinopathy with higher peak D-dimers (aOR 1.32, 95% CI 1.01-1.73, p = .04) and male sex (aOR 9.6, 95% CI 1.2-75.5, p = .04)., Conclusion: Retinopathy in severe COVID-19 was associated with greater systemic disease morbidity involving multiple organs. Given its association with coagulopathy and inflammation, retinopathy may offer insight into disease pathogenesis in patients with severe COVID-19.

The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies. We compared antibody binding and live virus neutralization of sera from naturally infected and Moderna-vaccinated individuals against two SARS-CoV-2 variants: B.1 containing the spike mutation D614G and the emerging B.1.351 variant containing additional spike mutations and deletions. Sera from acutely infected and convalescent COVID-19 patients exhibited a 3-fold reduction in binding antibody titers to the B.1.351 variant receptor-binding domain of the spike protein and a 3.5-fold reduction in neutralizing antibody titers against SARS-CoV-2 B.1.351 variant compared to the B.1 variant. Similar results were seen with sera from Moderna-vaccinated individuals. Despite reduced antibody titers against the B.1.351 variant, sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351, suggesting that protective humoral immunity may be retained against this variant., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this patient-focused review, we present a 34-year-old previously healthy man admitted for fever and headache two weeks after a motor vehicle accident. On admission, his workup was concerning for meningoencephalitis based on elevated cerebrospinal fluid (CSF) white blood cell count and elevated CSF protein. He was admitted for management of meningoencephalitis. During his course, no causative infectious agent was identified despite an extensive workup. He additionally underwent an autoimmune and paraneoplastic workup that was negative. During his hospitalization, he developed acute transverse myelitis manifested by bilateral lower extremity paralysis. After four weeks marked by persistent clinical deterioration, brain biopsy was performed. Pathologic examination was consistent with neuromyelitis optica spectrum disorder (NMOSD). In this case report and literature review, we explore the presentations of NMOSD that mimic an infection. Clinicians should be aware of the possibility of NMOSD masquerading as infectious meningoencephalitis or acute transverse myelitis., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies to neutralize these variants. We compared antibody binding and live virus neutralization of sera from naturally infected and spike mRNA vaccinated individuals against a circulating SARS-CoV-2 B.1 variant and the emerging B.1.351 variant. In acutely-infected (5-19 days post-symptom onset), convalescent COVID-19 individuals (through 8 months post-symptom onset) and mRNA-1273 vaccinated individuals (day 14 post-second dose), we observed an average 4.3-fold reduction in antibody titers to the B.1.351-derived receptor binding domain of the spike protein and an average 3.5-fold reduction in neutralizing antibody titers to the SARS-CoV-2 B.1.351 variant as compared to the B.1 variant (spike D614G). However, most acute and convalescent sera from infected and all vaccinated individuals neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective immunity is retained against COVID-19.

Objectives: To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients., Data Sources: We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles., Study Selection: We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence., Data Extraction: We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review., Data Synthesis: C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk., Conclusions: Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery., Competing Interests: Dr. Woodworth’s institution received funding from National Institute of Allergy and Infectious Disease. Dr. Martin disclosed that he currently serves as president-elect for the Society of Critical Care Medicine. Dr. Kraft received funding from Rebiotix, and he is on the scientific advisory board of Rebiotix Inc. Dr. Shaffer disclosed that she does not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: Increasing time to mechanical ventilation and high-flow nasal cannula use may be associated with mortality in coronavirus disease 2019. We examined the impact of time to intubation and use of high-flow nasal cannula on clinical outcomes in patients with coronavirus disease 2019., Design: Retrospective cohort study., Setting: Six coronavirus disease 2019-specific ICUs across four university-affiliated hospitals in Atlanta, Georgia., Patients: Adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received high-flow nasal cannula or mechanical ventilation., Interventions: None., Measurements and Main Results: Among 231 patients admitted to the ICU, 109 (47.2%) were treated with high-flow nasal cannula and 97 (42.0%) were intubated without preceding high-flow nasal cannula use. Of those managed with high-flow nasal cannula, 78 (71.6%) ultimately received mechanical ventilation. In total, 175 patients received mechanical ventilation; 44.6% were female, 66.3% were Black, and the median age was 66 years (interquartile range, 56-75 yr). Seventy-six patients (43.4%) were intubated within 8 hours of ICU admission, 57 (32.6%) between 8 and 24 hours of admission, and 42 (24.0%) greater than or equal to 24 hours after admission. Patients intubated within 8 hours were more likely to have diabetes, chronic comorbidities, and higher admission Sequential Organ Failure Assessment scores. Mortality did not differ by time to intubation (≤ 8 hr: 38.2%; 8-24 hr: 31.6%; ≥ 24 hr: 38.1%; p = 0.7), and there was no association between time to intubation and mortality in adjusted analysis. Similarly, there was no difference in initial static compliance, duration of mechanical ventilation, or ICU length of stay by timing of intubation. High-flow nasal cannula use prior to intubation was not associated with mortality., Conclusions: In this cohort of critically ill patients with coronavirus disease 2019, neither time from ICU admission to intubation nor high-flow nasal cannula use were associated with increased mortality. This study provides evidence that coronavirus disease 2019 respiratory failure can be managed similarly to hypoxic respiratory failure of other etiologies.

Objectives: To determine mortality rates among adults with critical illness from coronavirus disease 2019., Design: Observational cohort study of patients admitted from March 6, 2020, to April 17, 2020., Setting: Six coronavirus disease 2019 designated ICUs at three hospitals within an academic health center network in Atlanta, Georgia, United States., Patients: Adults greater than or equal to 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease who were admitted to an ICU during the study period., Interventions: None., Measurements and Main Results: Among 217 critically ill patients, mortality for those who required mechanical ventilation was 35.7% (59/165), with 4.8% of patients (8/165) still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 30.9% (67/217) and 60.4% (131/217) patients have survived to hospital discharge. Mortality was significantly associated with older age, lower body mass index, chronic renal disease, higher Sequential Organ Failure Assessment score, lower PaO2/FIO2 ratio, higher D-dimer, higher C-reactive protein, and receipt of mechanical ventilation, vasopressors, renal replacement therapy, or vasodilator therapy., Conclusions: Despite multiple reports of mortality rates exceeding 50% among critically ill adults with coronavirus disease 2019, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness.

The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.

We report preliminary data from a cohort of adults admitted to COVID-designated intensive care units from March 6 through April 17, 2020 across an academic healthcare system. Among 217 critically ill patients, mortality for those who required mechanical ventilation was 29.7% (49/165), with 8.5% (14/165) of patients still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 25.8% (56/217), and 40.1% (87/217) patients have survived to hospital discharge. Despite multiple reports of mortality rates exceeding 50% among critically ill adults with COVID-19, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness., Competing Interests: Conflict of interest disclosures: None reported.

Background: The World Health Organization (WHO) recommends active tuberculosis (TB) case finding and a rapid molecular diagnostic test (Xpert MTB/RIF) to detect TB among people living with HIV (PLHIV) in high-burden settings. Information on the cost-effectiveness of these recommended strategies is crucial for their implementation., Methods: We conducted a model-based cost-effectiveness analysis comparing 2 algorithms for TB screening and diagnosis at Ethiopian HIV clinics: (1) WHO-recommended symptom screen combined with Xpert for PLHIV with a positive symptom screen and (2) current recommended practice algorithm (CRPA; based on symptom screening, smear microscopy, and clinical TB diagnosis). Our primary outcome was US$ per disability-adjusted life-year (DALY) averted. Secondary outcomes were additional true-positive diagnoses, and false-negative and false-positive diagnoses averted., Results: Compared with CRPA, combining a WHO-recommended symptom screen with Xpert was highly cost-effective (incremental cost of $5 per DALY averted). Among a cohort of 15 000 PLHIV with a TB prevalence of 6% (900 TB cases), this algorithm detected 8 more true-positive cases than CRPA, and averted 2045 false-positive and 8 false-negative diagnoses compared with CRPA. The WHO-recommended algorithm was marginally costlier ($240 000) than CRPA ($239 000). In sensitivity analysis, the symptom screen/Xpert algorithm was dominated at low Xpert sensitivity (66%)., Conclusions: In this model-based analysis, combining a WHO-recommended symptom screen with Xpert for TB diagnosis among PLHIV was highly cost-effective ($5 per DALY averted) and more sensitive than CRPA in a high-burden, resource-limited setting.

We present the case of a 28-year-old woman with Salmonella serovar Schwarzengrund gastroenteritis acquired during foreign travel. Her case was complicated by superinfection of a pre-existing ovarian endometrioma with a quinolone-resistant organism; the resultant ovarian abscess ultimately required surgical removal for resolution. We review the key features of this case and the previous literature on Salmonella ovarian abscess. This report highlights (1) the potential for metastatic spread of Salmonella to the ovary in women with pre-existing cysts or endometriomas and (2) the increasing worldwide burden of quinolone-resistant Salmonella .

Pure white cell aplasia (PWCA) is a rare hematologic disorder characterized by the absence of neutrophil lineages in the bone marrow with intact megakaryopoiesis and erythropoiesis. PWCA has been associated with autoimmune, drug-induced, and viral exposures. Here, we report a case of a 74-year-old female who presented with severe proximal weakness without pain and was found to have PWCA with nonspecific inflammatory necrotizing myositis and acute liver injury on biopsies. These findings were associated with a recent course of azithromycin and her daily use of a statin. Myositis improved on prednisone but PWCA persisted. With intravenous immunoglobulin and granulocyte-colony stimulating factor therapies, her symptoms and neutrophil counts improved and were sustained for months.

Setting: Human immunodeficiency virus (HIV) clinic in Addis Ababa, Ethiopia. The World Health Organization (WHO) recommends active tuberculosis (TB) case-finding among people living with HIV (PLHIV) in high-burden settings., Objective: To evaluate the effectiveness of combining a WHO-recommended symptom screen and the Xpert(®) MTB/RIF test to enhance TB case finding., Design: In this cross-sectional study, PLHIV were screened for TB using a WHO-recommended symptom-based algorithm (cough, fever, night sweats, weight loss). Those with a positive symptom screen (⩾1 symptom) underwent diagnostic testing with smear microscopy, culture, and Xpert., Results: Of 828 PLHIV (89% on antiretroviral therapy), 321 (39%) had a positive symptom screen. In multivariate analysis, an unscheduled clinic visit (aOR 3.78, 95%CI 2.69-5.32), CD4 count <100 cells/μl (aOR 2.62, 95%CI 1.23-5.59) and previous history of TB (aOR 1.62, 95%CI 1.12-2.31) were predictors of a positive symptom screen. Among those with a positive symptom screen, 6% had active pulmonary TB. Smear microscopy sensitivity for TB was poor (30%) compared to culture and Xpert., Conclusions: A positive symptom screen was common among PLHIV, creating a substantial laboratory burden. Smear microscopy had poor sensitivity for active TB disease. Given the high rate of positive symptom screen, substantial additional resources are needed to implement intensified TB case finding among PLHIV in high-burden areas.

Introduction: The Centers for Disease Control and Prevention has recommended using a nucleic acid amplification test (NAAT) for diagnosing pulmonary tuberculosis (TB) but there is a lack of data on NAAT cost-effectiveness., Methods: We conducted a prospective cohort study that included all patients with an AFB smear-positive respiratory specimen at Grady Memorial Hospital in Atlanta, GA, USA between January 2002 and June 2008. We determined the sensitivity, specificity, and positive and negative predictive value of a commercially available and FDA-approved NAAT (amplified MTD, Gen-Probe) compared to the gold standard of culture. A cost analysis was performed and included costs related to laboratory tests, hospital charges, anti-TB medications, and contact investigations. Average cost per patient was calculated under two conditions: (1) using a NAAT on all AFB smear-postive respiratory specimens and (2) not using a NAAT. One-way sensitivity analyses were conducted to determine sensitivity of cost difference to reasonable ranges of model inputs., Results: During a 6 1/2 year study period, there were 1,009 patients with an AFB smear-positive respiratory specimen at our public urban hospital. We found the NAAT to be highly sensitive (99.6%) and specific (99.1%) on AFB smear-positive specimens compared to culture. Overall, the positive predictive value (PPV) of an AFB smear-positive respiratory specimen for culture-confirmed TB was 27%. The PPV of an AFB smear-positive respiratory specimen for culture-confirmed TB was significantly higher for HIV-uninfected persons compared to those who were HIV-seropositive (152/271 [56%] vs. 85/445 [19%]; RR = 2.94, 95% CI 2.36-3.65, p<0.001). The cost savings of using the NAAT was $2,003 per AFB smear-positive case., Conclusions: Routine use of the NAAT on AFB smear-positive respiratory specimens was highly cost-saving in our setting at a U.S. urban public hospital with a high prevalence of TB and HIV because of the low PPV of an AFB smear for culture-confirmed TB.