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7. Prospective multicenter international surveillance of Azole resistance in Aspergillus Fumigatus

Author

van der Linden, J.W.M., Arendrup, M.C., Warris, A., Lagrou, K., Pelloux, H., Hauser, P.M., Chryssanthou, E., Mellado, E., Kidd, S.E., Tortorano, A.M., Dannaoui, E., Gaustad, P., Baddley, J.W., Uekotter, A., Lass-Florl, C., Klimko, N., Moore, C.B., Denning, D.W., Pasqualotto, A.C., Kibbler, C., Arikan-Akdagli, S., Andes, D., Meletiadis, J., Naumiuk, L., Nucci, M., Melchers, W.J.G., and Verweij, P.E.

Subjects
Drug resistance in microorganisms -- Health aspects -- Research, Azoles (Class of compounds) -- Usage -- Health aspects, Aspergillosis -- Causes of -- Genetic aspects -- Drug therapy -- Research, Health
Abstract

Azole resistance is increasingly recognized as a problem in aspergillus diseases (1). Within the Aspergillus fumigatus species complex, new sibling species have been reported to cause invasive aspergillosis; these species [...]

Published
2015
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9. 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

Author

Donnelly, J.P., Chen, S.C., Kauffman, C.A., Steinbach, W.J., Baddley, J.W., Verweij, P.E., Clancy, C.J., Wingard, J.R., Lockhart, S.R., Groll, A.H., Sorrell, T.C., Bassetti, M., Akan, H., Alexander, B.D., Andes, D., Azoulay, E., Bialek, R., Bradsher, R.W., Bretagne, S., Calandra, T., Caliendo, A.M., Castagnola, E., Cruciani, M., Cuenca-Estrella, M., Decker, C.F., Desai, S.R., Fisher, B., Harrison, T., Heussel, C.P., Jensen, H.E., Kibbler, C.C., Kontoyiannis, D.P., Kullberg, B.J., Lagrou, K., Lamoth, F., Lehrnbecher, T., Loeffler, J., Lortholary, O., Maertens, J., Marchetti, O., Marr, K.A., Masur, H., Meis, J.F.G.M., Morrisey, C.O., Nucci, M., Ostrosky-Zeichner, L., Pagano, L., Patterson, T.F., Perfect, J.R., Racil, Z., Roilides, E., Ruhnke, M., Schaefer-Prokop, C.M., Shoham, S., Slavin, M.A., Stevens, David A., Thompson, G.R., Vazquez, J.A., Viscoli, C., Walsh, T.J., Warris, A., Wheat, L.J., White, P.L., Zaoutis, T.E., Pappas, P.G., Donnelly, J.P., Chen, S.C., Kauffman, C.A., Steinbach, W.J., Baddley, J.W., Verweij, P.E., Clancy, C.J., Wingard, J.R., Lockhart, S.R., Groll, A.H., Sorrell, T.C., Bassetti, M., Akan, H., Alexander, B.D., Andes, D., Azoulay, E., Bialek, R., Bradsher, R.W., Bretagne, S., Calandra, T., Caliendo, A.M., Castagnola, E., Cruciani, M., Cuenca-Estrella, M., Decker, C.F., Desai, S.R., Fisher, B., Harrison, T., Heussel, C.P., Jensen, H.E., Kibbler, C.C., Kontoyiannis, D.P., Kullberg, B.J., Lagrou, K., Lamoth, F., Lehrnbecher, T., Loeffler, J., Lortholary, O., Maertens, J., Marchetti, O., Marr, K.A., Masur, H., Meis, J.F.G.M., Morrisey, C.O., Nucci, M., Ostrosky-Zeichner, L., Pagano, L., Patterson, T.F., Perfect, J.R., Racil, Z., Roilides, E., Ruhnke, M., Schaefer-Prokop, C.M., Shoham, S., Slavin, M.A., Stevens, David A., Thompson, G.R., Vazquez, J.A., Viscoli, C., Walsh, T.J., Warris, A., Wheat, L.J., White, P.L., Zaoutis, T.E., and Pappas, P.G.

Abstract

Contains fulltext : 225781.pdf (Publisher’s version ) (Open Access), 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.

Published
2020

11. Risk of Hospitalized Bacterial Infections Associated with Biologic Treatment Among U.S. Veterans with Rheumatoid Arthritis

Author

Curtis, J.R., Yang, S., Patkar, N. M., Chen, L., Singh, J. A., Cannon, G. W., Mikuls, T.R., Delzell, E., Saag, K.G., Safford, M.M., DuVall, S., Alexander, K., Napalkov, P., Winthrop, Kevin L, Burton, M.J., Kamauu, A., and Baddley, J.W.

Subjects
Male, Immunoconjugates, Tumor Necrosis Factor-alpha, Incidence, Bacterial Infections, Comorbidity, Middle Aged, Risk Assessment, Article, United States, Abatacept, Arthritis, Rheumatoid, Hospitalization, Antibodies, Monoclonal, Murine-Derived, Antirheumatic Agents, Humans, Female, Rituximab, Glucocorticoids, Aged, Retrospective Studies, Veterans
Abstract

The comparative risk of infection associated with non-anti-tumor necrosis factor (anti-TNF) biologic agents is not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non-anti-TNF biologic agents in US veterans with rheumatoid arthritis (RA).Using 1998-2011 data from the US Veterans Health Administration, we studied RA patients initiating rituximab, abatacept, or anti-TNF therapy. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions). Treatment episodes were defined as new biologic agent use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hospitalization for a bacterial infection were estimated from Cox proportional hazards models, adjusting for potential confounders.Among 3,152 unique RA patients contributing 4,158 biologic treatment episodes to rituximab (n = 596), abatacept (n = 451), and anti-TNF agents (n = 3,111), the patient mean age was 60 years and 87% were male. The most common infections were pneumonia (37%), skin/soft tissue (22%), urinary tract (9%), and bacteremia/sepsis (7%). Hospitalized infection rates per 100 person-years were 4.4 (95% CI 3.1-6.4) for rituximab, 2.8 (95% CI 1.7-4.7) for abatacept, and 3.0 (95% CI 2.5-3.5) for anti-TNF. Compared to etanercept, the adjusted rate of hospitalized infection was not different for adalimumab (HR 1.4, 95% CI 0.9-2.2), abatacept (HR 1.1, 95% CI 0.6-2.1), or rituximab (HR 1.4, 0.8-2.6), although it was increased for infliximab (HR 2.3, 95% CI 1.3-4.0). Infection risk was greater for those taking prednisone7.5 mg/day (HR 1.8, 95% CI 1.3-2.7) and in the highest quartile of C-reactive protein (HR 2.3, 95% CI 1.4-3.8) and erythrocyte sedimentation rate (HR 4.1, 95% CI 2.3-7.2) compared to the lowest quartile.In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.

Published
2014

13. Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

Author

Linden, J.W.M. van der, Arendrup, M.C., Warris, A., Lagrou, K., Pelloux, H., Hauser, P.M., Chryssanthou, E., Mellado, E., Kidd, S.E., Tortorano, A.M., Dannaoui, E., Gaustad, P., Baddley, J.W., Uekötter, A., Lass-Flörl, C., Klimko, N., Moore, C.B., Denning, D., Pasqualotto, A., Kibbler, C., Arikan-Akdagli, S., Andes, D., Meletiadis, J., Naumiuk, L., Nucci, M., Melchers, W.J.G., Verweij, P.E., Linden, J.W.M. van der, Arendrup, M.C., Warris, A., Lagrou, K., Pelloux, H., Hauser, P.M., Chryssanthou, E., Mellado, E., Kidd, S.E., Tortorano, A.M., Dannaoui, E., Gaustad, P., Baddley, J.W., Uekötter, A., Lass-Flörl, C., Klimko, N., Moore, C.B., Denning, D., Pasqualotto, A., Kibbler, C., Arikan-Akdagli, S., Andes, D., Meletiadis, J., Naumiuk, L., Nucci, M., Melchers, W.J.G., and Verweij, P.E.

Abstract

Contains fulltext : 153751.pdf (publisher's version ) (Open Access)

Published
2015

15. Prospective Multicenter International Surveillance of Azole Resistance inAspergillus fumigatus

Author

van der Linden, J.W.M., primary, Arendrup, M.C., additional, Warris, A., additional, Lagrou, K., additional, Pelloux, H., additional, Hauser, P.M., additional, Chryssanthou, E., additional, Mellado, E., additional, Kidd, S.E., additional, Tortorano, A.M., additional, Dannaoui, E., additional, Gaustad, P., additional, Baddley, J.W., additional, Uekötter, A., additional, Lass-Flörl, C., additional, Klimko, N., additional, Moore, C.B., additional, Denning, D.W., additional, Pasqualotto, A.C., additional, Kibbler, C., additional, Arikan-Akdagli, S., additional, Andes, D., additional, Meletiadis, J., additional, Naumiuk, L., additional, Nucci, M., additional, Melchers, W.J.G., additional, and Verweij, P.E., additional

Published
2015
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16. Molecular Identification of Aspergillus Species Collected for the Transplant-Associated Infection Surveillance Network

Author

Balajee S.A., Kano R., Baddley J.W., Moser S.A., Marr K.A., Alexander B.D., Andes D., Kontoyiannis D.P., Perrone G., Peterson S., Brandt M.E., Pappas P.G., and Chiller T.

Abstract

A large aggregate collection of clinical isolates of aspergilli (n=218) from transplant patients with proven or probable invasive aspergillosis was available from the Transplant-Associated Infection Surveillance Network, a 6-year prospective surveillance study. To determine the Aspergillus species distribution in this collection, isolates were subjected to comparative sequence analyses by use of the internal transcribed spacer and beta-tubulin regions. Aspergillus fumigatus was the predominant species recovered, followed by A. flavus and A. niger. Several newly described species were identified, including A. lentulus and A. calidoustus; both species had high in vitro MICs to multiple antifungal drugs. Aspergillus tubingensis, a member of the A. niger species complex, is described from clinical specimens; all A. tubingensis isolates had low in vitro MICs to antifungal drugs.

Published
2009

17. Clinical Research In The Lay Press: Irresponsible Journalism Raises A Huge Dose Of Doubt

Author

Anaissie, E.J, Segal, B.H, Graybill, J.R, Arndt, C, Perfect, J.R, Kleinberg, M, Pappas, P, Benjamin, D, Rubin, R, Aberg, J.A, Adderson, E.E, Adler-Shohet, F.C, Akan, H, Akova, M, Almyroudis, N.G, Alexander, B.D, Andes, D, Arrieta, A, Baddley, J.W, Barron, M.A, Belzberg, H, Boucher, H.W, Boyce, T.G, Casadevall, A, Chandrasekar, P.H, Cleary, J.D, Cordonnier, C, Cornely, O.A, Cuenca-Estrella, M, Daly, J.S, Daoura, N, Denning, D.W, DePauw, B, De Repentigny, L, Dignani, M.C, Dismukes, W.E, Donnelly, J.P, Donowitz, G.R, Dupont, B, Drusano, G, Ellis, M, Espinel-Ingroff, A, Fishman, J.A, Fleming, R, Forrest, G, Ghannoum, M, Goldman, M, Grazziutti, M, Greene, J.H, Greenberg, R.N, Gubbins, P.O, Hadley, S, Herbrecht, R, Hiemenz, J.W, Hope, W, Hospenthal, D.R, Husain, S, Ito, J.I, Jacobson, R.M, Johnson, M, Keating, M.R, Kett, D.H, Knapp, K, Kontoyiannis, D.P, Krcmery, V.C, Larsen, R, Laverdiere, M, Ljungman, P, Lortholary, O, Maertens, J, Marriott, D, Mattiuzzi, G, McGinnis, M.R, Morris, M, Nucci, M, Odds, F.C, Pankey, G.A, Patterson, T, Pfaller, M, Razonable, R.R, Reboli, A.C, Rinaldi, M.G, Roberts, G.D, Rodriguez Tudela, J.L, Rotstein, C, Ruhnke, M, Schuster, M, Shoham, S, Sia, I.G, Siebel, N, Silviera, F, Singh, N, Sobel, J, Solomkin, J.S, Sorrell, T.C, Steinbach, W.J, Temesgen, Z, Tortorano, A, Vartivarian, S, Verweij, P, Viscoli, C, Viviani, M.A, Walker, R.C, Wheat, J.L, Wiley, J, Williamson, P, Wingard, J.R, Yu, V.L, Zaoutis, T., and İç Hastalıkları

Published
2006

20. Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant‐Associated Infection Surveillance Network (TRANSNET)

Author

Kauffman, C.A., primary, Freifeld, A.G., additional, Andes, D.R., additional, Baddley, J.W., additional, Herwaldt, L., additional, Walker, R.C., additional, Alexander, B.D., additional, Anaissie, E.J., additional, Benedict, K., additional, Ito, J.I., additional, Knapp, K.M., additional, Lyon, G.M., additional, Marr, K.A., additional, Morrison, V.A., additional, Park, B.J., additional, Patterson, T.F., additional, Schuster, M.G., additional, Chiller, T.M., additional, and Pappas, P.G., additional

Published
2014
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21. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials.

Author

Andes, D.R., Safdar, N., Baddley, J.W., Playford, G., Reboli, A.C., Rex, J.H., Sobel, J.D., Pappas, P.G., Kullberg, B.J., Andes, D.R., Safdar, N., Baddley, J.W., Playford, G., Reboli, A.C., Rex, J.H., Sobel, J.D., Pappas, P.G., and Kullberg, B.J.

Abstract

1 april 2012, Item does not contain fulltext, BACKGROUND: Invasive candidiasis (IC) is an important healthcare-related infection, with increasing incidence and a crude mortality exceeding 50%. Numerous treatment options are available yet comparative studies have not identified optimal therapy. METHODS: We conducted an individual patient-level quantitative review of randomized trials for treatment of IC and to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Studies were identified by searching computerized databases and queries of experts in the field for randomized trials comparing the effect of >/=2 antifungals for treatment of IC. Univariate and multivariable analyses were performed to determine factors associated with patient outcomes. RESULTS: Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, and the rate of treatment success was 67.4%. Logistic regression analysis for the aggregate data set identified increasing age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P = .02), the Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08-1.14; P = .0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18-2.44; P = .001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P = .01) as predictors of mortality. Conversely, removal of a central venous catheter (CVC) (OR, 0.50; 95% CI, .35-.72; P = .0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P = .02) were associated with decreased mortality. Similar findings were observed for the clinical success end point. CONCLUSIONS: Two treatment-related factors were associated with improved survival and greater clinical success: use of an echinocandin and removal of the CVC.

Published
2012

22. Reply to Anaissie and Nucci and to Cisneros et al.

Author

Andes, D., Safdar, N., Baddley, J.W., Kullberg, B.J., Pappas, P.G., Andes, D., Safdar, N., Baddley, J.W., Kullberg, B.J., and Pappas, P.G.

Abstract

Item does not contain fulltext

Published
2012

23. Aspergillus alabamensis, a new clinically relevant species in the section Terrei

Author

Balajee, S., Baddley, J.W., Peterson, S.W., Nickle, D., Varga, J., Boey, A., Lass-Florl, C., Frisvad, J.C., Samson, R.A., Balajee, S., Baddley, J.W., Peterson, S.W., Nickle, D., Varga, J., Boey, A., Lass-Florl, C., Frisvad, J.C., and Samson, R.A.

Abstract

Phylogenetic analyses of sequences generated from portions of three genes coding for the proteins enolase (enoA), beta-tubulin (benA), and calmodulin (calM) of a large number of isolates within the section Terrei, genus Aspergillus, revealed the presence of a new cryptic species within this section, Aspergillus alabamensis. Most members of this new cryptic species were recovered as colonizing isolates from immunocompetent patient populations, had decreased in vitro susceptibilities to the antifungal drug amphotericin B, and were morphologically similar to but genetically distinct from Aspergillus terreus isolates., Phylogenetic analyses of sequences generated from portions of three genes coding for the proteins enolase (enoA), beta-tubulin (benA), and calmodulin (calM) of a large number of isolates within the section Terrei, genus Aspergillus, revealed the presence of a new cryptic species within this section, Aspergillus alabamensis. Most members of this new cryptic species were recovered as colonizing isolates from immunocompetent patient populations, had decreased in vitro susceptibilities to the antifungal drug amphotericin B, and were morphologically similar to but genetically distinct from Aspergillus terreus isolates.

Published
2009

25. Clinical research in the lay press: irresponsible journalism raises a huge dose of doubt.

Author

Anaissie, E., Segal, B.H., Graybill, J.R., Arndt, C., Perfect, J.R., Kleinberg, M., Pappas, P.G., Benjamin, D., Rubin, R., Aberg, J.A., Adderson, E.E., Adler-Shohet, F.C., Akan, H., Akova, M., Almyroudis, N.G., Alexander, B.D., Andes, D., Arrieta, A., Baddley, J.W., Barron, M.A., Belzberg, H., Boucher, H.W., Boyce, T.G., Casadevall, A., Chandrasekar, P.H., Cleary, J.D., Cordonnier, C., Cornely, O.A., Cuenca-Estrella, M., Daly, J.S., Daoura, N., Denning, D.W., Pauw, B.E. de, Repentigny, L. de, Dignani, M.C., Dismukes, W.E., Donnelly, J.P., Donowitz, G., Dupont, B., Drusano, G., Ellis, M., Espinel-Ingroff, A., Fishman, J.A., Fleming, R., Forrest, G., Ghannoum, M.A., Goldman, M, Grazziutti, M., Greene, J.N., Greenberg, R.N., Gubbins, P.O., Hadley, S., Herbrecht, R., Hiemenz, J.W., Hope, W., Hospenthal, D.R., Husain, S., Ito, J.I., Jacobson, R.M., Johnson, M., Keating, M.R., Kett, D.H., Knapp, K., Kontoyiannis, D.P., Krcmery, V., Larsen, R., Laverdiere, M., Ljungman, P., Lortholary, O., Maertens, J., Marriott, D., Mattiuzzi, G., McGinnis, M.R., Morris, M., Nucci, M., Odds, F.C., Pankey, G.A., Patterson, T., Pfaller, M., Razonable, R.R., Reboli, A.C., Rinaldi, M.G., Roberts, G.D., Rodriguez-Tudela, J.L., Rotstein, C., Ruhnke, M., Schuster, M., Shoham, S., Sia, I.G., Siebel, N., Silviera, F, Singh, N., Sobel, J., Solomkin, J.S., Sorrell, T.C., Steinbach, W.J., Temesgen, Z., Tortorano, A., Vartivarian, S., Anaissie, E., Segal, B.H., Graybill, J.R., Arndt, C., Perfect, J.R., Kleinberg, M., Pappas, P.G., Benjamin, D., Rubin, R., Aberg, J.A., Adderson, E.E., Adler-Shohet, F.C., Akan, H., Akova, M., Almyroudis, N.G., Alexander, B.D., Andes, D., Arrieta, A., Baddley, J.W., Barron, M.A., Belzberg, H., Boucher, H.W., Boyce, T.G., Casadevall, A., Chandrasekar, P.H., Cleary, J.D., Cordonnier, C., Cornely, O.A., Cuenca-Estrella, M., Daly, J.S., Daoura, N., Denning, D.W., Pauw, B.E. de, Repentigny, L. de, Dignani, M.C., Dismukes, W.E., Donnelly, J.P., Donowitz, G., Dupont, B., Drusano, G., Ellis, M., Espinel-Ingroff, A., Fishman, J.A., Fleming, R., Forrest, G., Ghannoum, M.A., Goldman, M, Grazziutti, M., Greene, J.N., Greenberg, R.N., Gubbins, P.O., Hadley, S., Herbrecht, R., Hiemenz, J.W., Hope, W., Hospenthal, D.R., Husain, S., Ito, J.I., Jacobson, R.M., Johnson, M., Keating, M.R., Kett, D.H., Knapp, K., Kontoyiannis, D.P., Krcmery, V., Larsen, R., Laverdiere, M., Ljungman, P., Lortholary, O., Maertens, J., Marriott, D., Mattiuzzi, G., McGinnis, M.R., Morris, M., Nucci, M., Odds, F.C., Pankey, G.A., Patterson, T., Pfaller, M., Razonable, R.R., Reboli, A.C., Rinaldi, M.G., Roberts, G.D., Rodriguez-Tudela, J.L., Rotstein, C., Ruhnke, M., Schuster, M., Shoham, S., Sia, I.G., Siebel, N., Silviera, F, Singh, N., Sobel, J., Solomkin, J.S., Sorrell, T.C., Steinbach, W.J., Temesgen, Z., Tortorano, A., and Vartivarian, S.

Abstract

Contains fulltext : 50792.pdf (publisher's version ) (Open Access)

Published
2006

31. Hospital-Onset Clostridium difficileInfection Among Solid Organ Transplant Recipients

Author

Donnelly, J.P., Wang, H.E., Locke, J.E., Mannon, R.B., Safford, M.M., and Baddley, J.W.

Abstract

Clostridium difficileinfection (CDI) is a considerable health issue in the United States and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can affect both graft and patient survival. However, little is known about the impact of CDI on health services utilization posttransplantation. We examined hospital-onset CDI from 2012 to 2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center–affiliated hospitals in the United States. Infection was five times more common among transplant recipients than among general medicine inpatients (209 vs 40 per 10 000 discharges), and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional risk-standardized CDI varied more than 3-fold across high-volume hospitals (infection ratio 0.54–1.82, median 1.04, interquartile range 0.78–1.28). CDI was associated with increased 30-day readmission, transplant organ complications, cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were substantially higher than risk-standardized expected values (40 094 vs 22 843 days, costs $198 728 368 vs $154 020 528). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted.

Published
2015
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32. Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus ( HIV)-infected and HIV-uninfected persons.

Author

McKinnell, J.A., Cannella, A.P., Kunz, D.F., Hook 3rd, E.W., Moser, S.A., Miller, L.G., Baddley, J.W., and Pappas, P.G.

Subjects
PNEUMOCYSTIS pneumonia, HOSPITAL patients, HIV-positive persons, HEALTH outcome assessment, THERAPEUTICS, HIV infections, MEDICAL centers
Abstract

Background Pneumocystis jirovecii pneumonia ( PCP) is a life-threatening infection for immunocompromised individuals. Robust data and clear guidelines are available for prophylaxis and treatment of human immunodeficiency virus ( HIV)-related PCP ( HIV- PCP), yet few data and no guidelines are available for non- HIV-related PCP ( NH- PCP). We postulated that prevention and inpatient management of HIV- PCP differed from NH- PCP. Methods We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV- PCP and NH- PCP. Results Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non- HIV cases. Non- HIV cases rarely received primary prophylaxis (4% vs. 38%, P = 0.01) and received appropriate antibiotics later in the course of hospitalization (5.2 days vs. 1.1 days, P < 0.005). Among transplant patients, NH- PCP was diagnosed a mean of 1066 days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, P = 0.39) and 90-day mortality (41% vs. 28%, P = 0.20) were detected. Conclusions Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH- PCP were rarely given prophylaxis, and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV- PCP. Medical providers should be aware of the ongoing risk for NH- PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empirical therapy for PCP. [ABSTRACT FROM AUTHOR]

Published
2012
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33. Transmission of Balamuthia mandrillarisThrough Solid Organ Transplantation: Utility of Organ Recipient Serology to Guide Clinical Management

Author

Gupte, A.A., Hocevar, S.N., Lea, A.S., Kulkarni, R.D., Schain, D.C., Casey, M.J., Zendejas-Ruiz, I.R., Chung, W.K., Mbaeyi, C., Roy, S.L., Visvesvara, G.S., da Silva, A.J., Tallaj, J., Eckhoff, D., and Baddley, J.W.

Abstract

A liver, heart, iliac vessel and two kidneys were recovered from a 39-year-old man who died of traumatic head injury and were transplanted into five recipients. The liver recipient 18 days posttransplantation presented with headache, ataxia and fever, followed by rapid neurologic decline and death. Diagnosis of granulomatous amebic encephalitis was made on autopsy. Balamuthia mandrillarisinfection was confirmed with immunohistochemical and polymerase chain reaction (PCR) assays. Donor and recipients’ sera were tested for B. mandrillarisantibodies. Donor brain was negative for Balamuthiaby immunohistochemistry and PCR; donor serum Balamuthiaantibody titer was positive (1:64). Antibody titers in all recipients were positive (range, 1:64–1:512). Recipients received a four- to five-drug combination of miltefosine or pentamidine, azithromycin, albendazole, sulfadiazine and fluconazole. Nausea, vomiting, elevated liver transaminases and renal insufficiency were common. All other recipients survived and have remained asymptomatic 24 months posttransplant. This is the third donor-derived Balamuthiainfection cluster described in solid organ transplant recipients in the United States. As Balamuthiaserologic testing is only available through a national reference laboratory, it is not feasible for donor screening, but may be useful to determine exposure status in recipients and to help guide chemotherapy.

Published
2014
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