Publications by authors named "Luis Ostrosky-Zeichner"

137 Publications

Candidemia: An infection prevention issue?

Clin Infect Dis 2021 Feb 10. Epub 2021 Feb 10.

Division of Infectious Diseases, McGovern Medical School, Fannin, Houston, TX.

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http://dx.doi.org/10.1093/cid/ciab112DOI Listing
February 2021

Preface.

J Antimicrob Chemother 2021 Jan;76(Supplement_1):i1

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http://dx.doi.org/10.1093/jac/dkaa540DOI Listing
January 2021

Screening donors for COVID-19 convalescent plasma.

Transfusion 2021 04 1;61(4):1047-1052. Epub 2021 Feb 1.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.

Background: Convalescent plasma is used as a treatment for COVID-19. Only limited data describe the efforts to recruit COVID-19 convalescent plasma (CCP) donors. We describe our experience engaging persons recovered from COVID-19 to donate CCP.

Study Design And Methods: We performed a retrospective analysis of the CCP recruitment for an 11-hospital health system in Houston, Texas. We sought CCP donations from: a) "volunteers" responding to advertisements in social media, press releases, and websites and b) "referred" individuals directed to the program or identified from hospitalization records. We determined the proportions of donor candidates who passed initial telephone health screening, who qualified after diagnostic testing, who presented to the regional CCP donation center, and who completed CCP donation.

Results: There were 900 CCP donor candidates, including 363 volunteers and 537 referred donors. Of 360 contacted volunteers, 186 (5.7%) were excluded by interview; 133 were referred for additional diagnostic screening, 97 completed donor antibody and antigen testing, and 87 were qualified for CCP donation, resulting in 35 CCP donations (9.7% of initial telephone contacts). Among 533 referred donors, 448 (84.1%) were excluded by interview, 71 were referred for additional screening, 48 completed donor antibody and antigen testing, and 40 were qualified for CCP donation, resulting in one CCP donation (0.2% of initial telephone contacts).

Conclusion: In this community, screening of a high number of candidates yielded a limited number of CCP donations. These observations have important implications for CCP donor recruitment and community pandemic planning.
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http://dx.doi.org/10.1111/trf.16253DOI Listing
April 2021

Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance.

Lancet Infect Dis 2020 Dec 14. Epub 2020 Dec 14.

Faculty of Medicine, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany; Department I of Internal Medicine, European Excellence Center for Medical Mycology (ECMM), University Hospital Cologne, Cologne, Germany; Clinical Trials Centre Cologne, ZKS Köln, Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany. Electronic address:

Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
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http://dx.doi.org/10.1016/S1473-3099(20)30847-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833078PMC
December 2020

Isavuconazole: Mechanism of Action, Clinical Efficacy, and Resistance.

J Fungi (Basel) 2020 Nov 29;6(4). Epub 2020 Nov 29.

Division of Infectious Diseases, UT Health McGovern Medical School, Houston, TX 77030, USA.

Increasing incidence of invasive fungal infections combined with a growing population of immunocompromised hosts has created a rising need for antifungal agents. Isavuconazole, a second-generation broad-spectrum triazole with activity against yeasts, dimorphic fungi, and molds, has a favorable safety profile and predictable pharmacokinetics. Patients typically tolerate isavuconazole well with fewer drug-drug interactions. Clinical trials have found it to be noninferior to voriconazole for invasive aspergillosis, an alternative therapy for salvage treatment of mucormycosis, and suitable for stepdown therapy with invasive candidiasis. Cross-resistance with other triazoles is common. More studies are needed to determine the role of isavuconazole in anti-mold prophylaxis in high-risk patients.
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http://dx.doi.org/10.3390/jof6040324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712939PMC
November 2020

Povidone-iodine solution as SARS-CoV-2 prophylaxis for procedures of the upper aerodigestive tract a theoretical framework.

J Otolaryngol Head Neck Surg 2020 Oct 27;49(1):77. Epub 2020 Oct 27.

Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 5.036, Houston, TX, 77030, USA.

Background: The COVID-19 pandemic has raised concerns of inadvertent SARS-CoV-2 transmission to healthcare workers during routine procedures of the aerodigestive tract in asymptomatic COVID-19 patients. Current efforts to mitigate this risk focus on Personal Protective Equipment, including high-efficiency filtration as well as other measures. Because the reservoir for SARS-CoV-2 shedding is in the nasopharynx and nasal and oral cavities, the application of viricidal agents to these surfaces may reduce virus burden. Numerous studies have confirmed that povidone-iodine inactivates many common respiratory viruses, including SARS-CoV-1. Povidone-iodine also has good profile for mucosal tolerance. Thus, we propose a prophylactic treatment protocol for the application of topical povidone-iodine to the upper aerodigestive tract.

Conclusion: Such an approach represents a low-cost, low-morbidity measure that may reduce the risks associated with aerosol-generating procedures performed commonly in otorhinolaryngology operating rooms.
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http://dx.doi.org/10.1186/s40463-020-00474-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590913PMC
October 2020

Reprocessing N95s with hydrogen peroxide vaporization: A robust system from collection to dispensing.

Am J Infect Control 2021 04 20;49(4):508-511. Epub 2020 Oct 20.

Memorial Hermann Texas Medical Center, Houston, TX; Division Pediatric Infectious Disease, UT Health Medical School Houston, Houston, TX.

The SARS-CoV2 pandemic has created extreme shortages of N95 mask necessitating the need for rapid development of reuse and reprocessing plans. Our aim was to create a process to recapture, reprocess, and redistribute N95 masks using hydrogen peroxide vapor as a real time disinfection method within a large hospital system. We were able to recapture and reprocess 29, 706 N95 masks using hydrogen peroxide vapor with approximately 25% loss due to damage.
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http://dx.doi.org/10.1016/j.ajic.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572504PMC
April 2021

A sentinel COVID-19 case in Houston, Texas: Informing frontline emergency department screening and preparedness.

J Am Coll Emerg Physicians Open 2020 Apr 19;1(2):92-94. Epub 2020 Apr 19.

McGovern Medical School at University of Texas Health Science Center at Houston (UTHealth) Memorial Hermann Health System Houston Texas USA.

In December 2019, a cluster of severe pneumonia cases of unknown cause was reported in Wuhan, Hubei province, China. A novel strain of coronavirus belonging to the same family of viruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) was identified. In February 2020, cases began being identified in the United States. We describe a sentinel COVID-19 patient in Houston, Texas, who first presented on March 1, 2020. The patient did not meet criteria for a Person Under Investigation (PUI) as recommended by the Centers for Disease Control and Prevention (CDC) at the time. This case has broad implications for emergency department screening and preparedness for COVID-19 and other future infectious diseases.
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http://dx.doi.org/10.1002/emp2.12068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493469PMC
April 2020

Rezafungin versus Caspofungin in a Phase 2, Randomized, Double-Blind Study for the Treatment of Candidemia and Invasive Candidiasis- The STRIVE Trial.

Clin Infect Dis 2020 Sep 21. Epub 2020 Sep 21.

Dept of Internal Medicine Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Background: Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC).

Methods: Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤ 4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up.

Results: Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS.

Conclusions: RZF was safe and efficacious in the treatment of candidemia and/or IC.
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http://dx.doi.org/10.1093/cid/ciaa1380DOI Listing
September 2020

Integration of aeromedicine in the response to the COVID-19 pandemic.

J Am Coll Emerg Physicians Open 2020 Jun 4. Epub 2020 Jun 4.

Department of Internal Medicine University of Texas Health Science Center's McGovern Medical School Houston Texas USA.

There is limited guidance on the use of helicopter medical personnel to facilitate care of critically ill COVID-19 patients. This manuscript describes the emergence of this novel virus, its mode of transmission, and the potential impacts on patient care in the unique environment of rotor wing aircraft. It details the development of clinical and operational guidelines for flight crew members. This allows other out-of-hospital clinicians to utilize our framework to augment or supplement their own for the current response effort to COVID-19. It further serves as a road map for future response to the care of high consequence infectious disease patients.
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http://dx.doi.org/10.1002/emp2.12117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283804PMC
June 2020

Successful implementation of the CDC recommendations during the care of 2 patients with Candida auris in in-patient rehabilitation and intensive care settings.

Am J Infect Control 2021 04 20;49(4):525-527. Epub 2020 Aug 20.

Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center, McGovern School of Medicine, Houston, TX.

Candida auris presents a unique challenge to practitioners and infection control teams worldwide because of its virulence, alarming resistance profile, environmental fitness, and risk of nosocomial transmission. We describe 2 cases of Candida auris infection managed with the CDC recommendations with no evidence of in-hospital transmission.
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http://dx.doi.org/10.1016/j.ajic.2020.08.027DOI Listing
April 2021

Measles or Not Measles? That Is the Question!

Open Forum Infect Dis 2020 Aug 22;7(8):ofaa311. Epub 2020 Jul 22.

Department of Internal Medicine, Division of Infectious Diseases, The University of Texas Health Science Center, McGovern Medical School, Houston, Texas, USA.

We present a diagnostically challenging case of a patient who presented with fever and rash during a measles outbreak. The diagnosis was complicated by the interpretation of the results of serological tests, which resulted in implementation of major preventive measures in the hospital. The patient was later confirmed to have murine typhus.
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http://dx.doi.org/10.1093/ofid/ofaa311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423290PMC
August 2020

Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity.

JCI Insight 2020 09 17;5(18). Epub 2020 Sep 17.

Metastasis Research Center, Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR-confirmed, SARS-CoV-2-hospitalized patients, as well as 464 healthy and non-COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD-binding antibodies exhibited neutralizing capacity, but only 74% of N-protein-positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein-binding antibodies does not always correlate with presence of S-RBD-neutralizing antibodies and caution against the extensive use of N-protein-based serology testing for determination of potential COVID-19 immunity.
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http://dx.doi.org/10.1172/jci.insight.142386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526535PMC
September 2020

Core Recommendations for Antifungal Stewardship: A Statement of the Mycoses Study Group Education and Research Consortium.

J Infect Dis 2020 08;222(Suppl 3):S175-S198

Department of Infectious Diseases, Infection Control and Employee Health, MD Anderson Cancer Center, Houston, Texas, USA.

In recent years, the global public health community has increasingly recognized the importance of antimicrobial stewardship (AMS) in the fight to improve outcomes, decrease costs, and curb increases in antimicrobial resistance around the world. However, the subject of antifungal stewardship (AFS) has received less attention. While the principles of AMS guidelines likely apply to stewarding of antifungal agents, there are additional considerations unique to AFS and the complex field of fungal infections that require specific recommendations. In this article, we review the literature on AMS best practices and discuss AFS through the lens of the global core elements of AMS. We offer recommendations for best practices in AFS based on a synthesis of this evidence by an interdisciplinary expert panel of members of the Mycoses Study Group Education and Research Consortium. We also discuss research directions in this rapidly evolving field. AFS is an emerging and important component of AMS, yet requires special considerations in certain areas such as expertise, education, interventions to optimize utilization, therapeutic drug monitoring, and data analysis and reporting.
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http://dx.doi.org/10.1093/infdis/jiaa394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403757PMC
August 2020

Mind the gap: The hospital breakroom.

Am J Infect Control 2020 10 17;48(10):1285. Epub 2020 Jun 17.

Division of Infectious Diseases, UT Health Medical School at Houston, Houston, TX.

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http://dx.doi.org/10.1016/j.ajic.2020.06.179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832819PMC
October 2020

Antifungal Susceptibility Testing: Current Approaches.

Clin Microbiol Rev 2020 06 29;33(3). Epub 2020 Apr 29.

Division of Infectious Diseases, University of Texas Health Science Center, Houston, Texas, USA.

Although not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations: broth dilution, disk diffusion, and azole agar screening for Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of data.
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http://dx.doi.org/10.1128/CMR.00069-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194854PMC
June 2020

Invasive Candidiasis.

Semin Respir Crit Care Med 2020 02 30;41(1):3-12. Epub 2020 Jan 30.

Division of Infectious Diseases, University of Texas Health Medical School, Houston, Texas.

Invasive candidiasis (IC) is the most frequent health care associated invasive fungal infection. It is also associated with high morbidity, mortality, and cost. The most frequent etiologic agent is , but non-albicans species are increasing and associated with reduced antifungal susceptibility and outbreaks. is an emerging multidrug-resistant species recently described. IC presents as a spectrum of disease, going from fungemia to deep-seated candidiasis, and to septic shock with multiorgan failure. Diagnosis of IC is challenging. Several biomarkers and molecular methods are available for improving diagnosis. Early initial treatment with echinocandins is the treatment of choice. Step-down therapy when antifungal susceptibility is available is possible. Several new antifungal agents for the treatment of IC are in clinical development.
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http://dx.doi.org/10.1055/s-0040-1701215DOI Listing
February 2020

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

Clin Infect Dis 2020 Sep;71(6):1367-1376

Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Background: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.

Methods: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.

Results: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.

Conclusions: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.
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http://dx.doi.org/10.1093/cid/ciz1008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486838PMC
September 2020

Drunk Without Drinking: A Case of Auto-Brewery Syndrome.

ACG Case Rep J 2019 Sep 9;6(9):e00208. Epub 2019 Sep 9.

Division of General Internal Medicine, Department of Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX.

Information on auto-brewery syndrome is limited in the medical literature. This rare syndrome occurs when yeast overgrowth leads to ethanol fermentation in the gut. We present a patient presenting with symptoms of alcohol intoxication with objective laboratory data of elevated blood ethanol levels without a history of alcohol consumption. We reviewed the literature and have discussed the current diagnostic and therapeutic options.
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http://dx.doi.org/10.14309/crj.0000000000000208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831150PMC
September 2019

Simultaneous Infection with and Pseudomonas aeruginosa Harboring Multiple Carbapenemases in a Returning Traveler Colonized with Candida auris.

Antimicrob Agents Chemother 2020 01 27;64(2). Epub 2020 Jan 27.

Center for Antimicrobial Resistance and Microbial Genomics, University of Texas Health Science Center, McGovern School of Medicine, Houston, Texas, USA

We report our clinical experience treating a critically ill patient with polymicrobial infections due to multidrug-resistant , , and in a 56-year-old woman who received health care in India and was also colonized by A precision medicine approach using whole-genome sequencing revealed a multiplicity of mobile elements associated with NDM-1, NDM-5, and OXA-181 and, supplemented with susceptibility testing, guided the selection of rational antimicrobial therapy.
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http://dx.doi.org/10.1128/AAC.01466-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985746PMC
January 2020

Candida auris: what have we learned so far?

Curr Opin Infect Dis 2019 12;32(6):559-564

Division of Infectious Diseases, University of Texas McGovern Medical School, Houston, Texas, USA.

Purpose Of Review: The increasing prevalence of fungal infections due to Candida species has been well described in critically ill patient populations, but in recent years a new species, Candida auris has received attention from the medical community worldwide. We aim to summarize the current knowledge related to C. auris, as new identification techniques, novel antifungal agents and more experience with outbreak management have been published in the past few years.

Recent Findings: C. auris has been described in several countries, arising independently in separate clades. Its resistance to multiple antifungals and persistent colonization of patients and medical surfaces have become a therapeutic and infection control challenge. Recent elucidation of some of the molecular mechanisms related to pathogenicity and studies of in-vitro efficacy of novel antifungal agents can better guide therapy.

Summary: As C. auris continues to cause outbreaks worldwide, newer, and more efficient identification techniques, novel antifungals, and more knowledge in effective infection control techniques will allow better clinical outcomes in the management and control of invasive fungal disease.
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http://dx.doi.org/10.1097/QCO.0000000000000603DOI Listing
December 2019

Point-Counterpoint: Should Serum β-d-Glucan Testing Be Used for the Diagnosis of Pneumocystis jirovecii Pneumonia?

J Clin Microbiol 2019 12 23;58(1). Epub 2019 Dec 23.

Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA

INTRODUCTIONDespite the widespread use of prophylactic antibiotics in high-risk individuals, remains an important cause of pneumonia in immunocompromised patients. During the peak of the AIDS epidemic, many hospitals and outpatient clinics were very proficient at collecting induced sputum specimens for the diagnosis of pneumonia (PJP). With the dramatic reduction in the occurrence PJP in the current era of highly effective antiretroviral therapy, many centers no longer collect induced sputum samples. Thus, the diagnosis of PJP requires bronchoalveolar lavage (BAL) specimens or a decision to treat the patient empirically without a definitive diagnosis. Sputum or BAL specimens are tested for using special stains or molecular assays, which require highly trained staff that may not be available with a rapid turnaround time. Given the invasive nature of collecting BAL specimens and the expertise needed for interpreting PJP test results, there is interest in using serum 1,3-β-d-glucan (BDG) testing for the diagnosis of PJP. In this point-counterpoint, Luis Ostrosky-Zeichner and Gabriela Corsi-Vasquez discuss the pro view of using BDG testing for the diagnosis of PJP, while Paul E. Sax and Edward F. Pilkington III present the con view of using BDG testing for the diagnosis of PJP.
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http://dx.doi.org/10.1128/JCM.01340-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935916PMC
December 2019

Seroprevalence of Strongyloides stercoralis and Evaluation of Universal Screening in Kidney Transplant Candidates: A Single-Center Experience in Houston (2012-2017).

Open Forum Infect Dis 2019 Jul;6(7)

Division of Infectious Diseases, McGovern Medical School, University of Texas Health Science Center at Houston.

Background: Disseminated strongyloidiasis in solid organ transplant recipients is a rare but devastating infection. In our center, we implemented a universal screening of all candidates for kidney transplantation. We assessed the seroprevalence and utility of universal screening for strongyloidiasis in our center.

Methods: Patients were identified from our transplant referral list (from July 2012 to June 2017). Demographics, pretransplant laboratory, and serological screenings were retrospectively collected. For Strongyloides-seropositive (SSp) patients, data on travel history, symptoms, treatment, and stool ova and parasite examinations were extracted. Logistic regression and multiple imputation for missing data were performed.

Results: A total of 1689 patients underwent serological screening, of whom 168 (9.9%) were SSp. Univariate analysis revealed that SSp patients had higher rates of eosinophilia, diabetes mellitus, latent tuberculosis and were likely to be either Hispanic or Asian (P < .05). In multivariate analysis, eosinophilia (P = .01), diabetes mellitus (P = .02), and Asian race (P = .03) were associated with being SSp, but 45 (27%) of the SSp patients did not have any of these 3 factors, and 18 SSp patients (11%) had no epidemiological risk factors. All patients received ivermectin, and none developed disseminated strongyloidiasis. Of patients who underwent serological screening on multiple occasions, 6.8% seroconverted while waiting for kidney transplantation.

Conclusions: We found a high rate of Strongyloides seropositivity among our kidney transplantation candidates. No epidemiological risk factors effectively predicted SSp status in our population, and universal screening identified a large number of patients without such factors. Serial screening should be considered when a long wait time is expected before transplantation.
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http://dx.doi.org/10.1093/ofid/ofz172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656655PMC
July 2019

Extensively Drug-Resistant ST309 Harboring Tandem Guiana Extended Spectrum β-Lactamase Enzymes: A Newly Emerging Threat in the United States.

Open Forum Infect Dis 2019 Jul 6;6(7):ofz273. Epub 2019 Jun 6.

Center for Antimicrobial Resistance and Microbial Genomics, McGovern School of Medicine, Houston.

Background: Treatment of serious infections due to multidrug-resistant (MDR) remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 resistant to all β-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam.

Methods: Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with PAO1), and reconstruct a phylogenetic tree. A pair of β-lactamases, Guiana extended spectrum β-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of to examine their relative impact on resistance. Using cell lysates from expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime.

Results: Two ST309 clinical isolates were found to harbor the extended spectrum β-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 are closely related to MDR strains from Mexico also carrying tandem GES.

Conclusions: The presence of tandem GES-19 and GES-26 is associated with resistance to all β-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 may be an emerging threat in the United States.
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http://dx.doi.org/10.1093/ofid/ofz273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602888PMC
July 2019

Azole resistance and cyp51A mutation screening in Aspergillus fumigatus in Mexico.

J Antimicrob Chemother 2019 07;74(7):2047-2050

Clinical Microbiology Laboratory, Instituto Nacional de Ciencias Médicasy Nutrición Salvador Zubirán, 15 Vasco de Quiroga Ave, Belisario Domínguez Sección XVI, Tlalpan, México City, México.

Background: Fungicide exposure in the environment has driven the emergence of azole-resistant Aspergillus fumigatus worldwide. A screening test allows identification of resistant isolates.

Objectives: We screened clinical samples for azole-resistant Aspergillus through azole-containing agar plates and identified mutations in the cyp51A gene of A. fumigatus.

Methods: Aspergillus isolates from clinical samples collected in a tertiary care centre from 2014 to 2017 were screened for azole resistance. Samples were subcultured in azole-containing agar plates. Isolates with a positive screening test were subject to DNA extraction, DNA amplification and sequencing of the cyp51A gene (coding and promoter regions). Clinical data were obtained from medical records.

Results: We screened 43 Aspergillus isolates from 39 patients for azole resistance. Three isolates from three patients grew on azole-containing agar plates: two A. fumigatus and one Aspergillus flavus. PCR analysis and cyp51A sequencing identified the TR34/L98H mutation in both A. fumigatus isolates. The prevalence of cyp51A mutations among A. fumigatus was 8.3% (2/24). Both patients with TR34/L98H mutants were azole naive and presented with invasive aspergillosis; one had multiple myeloma and the other was a liver retransplant recipient. They suffered progressive disease and failed voriconazole therapy.

Conclusions: To the best of our knowledge, this is the first report of azole-resistant A. fumigatus with the TR34/L98H mutation in two azole-naive patients with refractory invasive aspergillosis in Mexico.
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http://dx.doi.org/10.1093/jac/dkz121DOI Listing
July 2019

Hurricane-Associated Mold Exposures Among Patients at Risk for Invasive Mold Infections After Hurricane Harvey - Houston, Texas, 2017.

MMWR Morb Mortal Wkly Rep 2019 May 31;68(21):469-473. Epub 2019 May 31.

In August 2017, Hurricane Harvey caused unprecedented flooding and devastation to the Houston metropolitan area (1). Mold exposure was a serious concern because investigations after Hurricanes Katrina and Rita (2005) had documented extensive mold growth in flood-damaged homes (2,3). Because mold exposure can cause serious illnesses known as invasive mold infections (4,5), and immunosuppressed persons are at high risk for these infections (6,7), several federal agencies recommend that immunosuppressed persons avoid mold-contaminated sites (8,9). To assess the extent of exposure to mold and flood-damaged areas among persons at high risk for invasive mold infections after Hurricane Harvey, CDC and Texas health officials conducted a survey among 103 immunosuppressed residents in Houston. Approximately half of the participants (50) engaged in cleanup of mold and water-damaged areas; these activities included heavy cleanup (23), such as removing furniture or removing drywall, or light cleanup (27), such as wiping down walls or retrieving personal items. Among immunosuppressed persons who performed heavy cleanup, 43% reported wearing a respirator, as did 8% who performed light cleanup. One participant reported wearing all personal protective equipment (PPE) recommended for otherwise healthy persons (i.e., respirator, boots, goggles, and gloves). Immunosuppressed residents who are at high risk for invasive mold infections were exposed to mold and flood-damaged areas after Hurricane Harvey; recommendations from health care providers to avoid exposure to mold and flood-damaged areas could mitigate the risk to immunosuppressed persons.
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http://dx.doi.org/10.15585/mmwr.mm6821a1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542480PMC
May 2019

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia.

Vaccine 2019 05 6;37(25):3352-3361. Epub 2019 May 6.

Pfizer, Inc. Collegeville, PA, USA.

Background: Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults.

Methods: This observational, prospective surveillance study recruited hospitalized adults aged ≥18 years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30 days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13.

Results: Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged ≥65 years. Among patients aged 18-64 years PCV13 serotypes were detected in 3.8-5.3% of patients depending on their risk status.

Conclusions: After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population.
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http://dx.doi.org/10.1016/j.vaccine.2019.04.087DOI Listing
May 2019

Changes in Prevalence of Health Care-Associated Infections.

N Engl J Med 2019 03;380(11):1085

McGovern Medical School, Houston, TX.

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http://dx.doi.org/10.1056/NEJMc1817140DOI Listing
March 2019

Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial.

Clin Infect Dis 2019 05;68(12):1981-1989

Department of Medicine, University of California Davis.

Background: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis.

Methods: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety.

Results: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9--1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups.

Conclusions: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups.

Clinical Trials Registration: NCT00413218.
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http://dx.doi.org/10.1093/cid/ciy827DOI Listing
May 2019