Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 27, Number 6—June 2021
CME ACTIVITY - Research

HIV Infection as Risk Factor for Death among Hospitalized Persons with Candidemia, South Africa, 2012–2017

Nelesh P. GovenderComments to Author , Jim Todd, Jeremy Nel, Mervyn Mer, Alan Karstaedt, Cheryl Cohen, and for GERMS-SA1
Author affiliations: University of Cape Town, Cape Town, South Africa (N.P. Govender); University of the Witwatersrand, Johannesburg (N.P. Govender, J. Nel, M. Mer, A. Karstaedt, C. Cohen); National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Johannesburg, South Africa (N.P. Govender, C. Cohen); London School of Hygiene and Tropical Medicine, London, UK (J. Todd)

Main Article

Table 1

Comparison of baseline characteristics by HIV infection status among 1,040 persons with culture-confirmed candidemia at sentinel hospitals, South Africa, 2012–2017*

Variable No. patients† HIV-seronegative, n = 614 HIV-seropositive, n = 426 p value‡
Median age, y (IQR)
 1,037
 38.8 (16.1–57.6)
 36.4 (27.6–46.1)
 0.05§
Age group, y 1,037
<18 226 161 (71) 65 (29) <0.001
18–44 427 190 (45) 237 (55)
45–64 283 173 (61) 110 (39)
>65 101 88 (87) 13 (13)
Missing
 3
Sex 1,040
F 498 272 (55) 226 (45) 0.005
M
 542
 342 (63)
 200 (37)
Province 1,040
Other province 495 297 (60) 198 (40)
Gauteng
 545
 317 (58)
 228 (42)
 0.55
Year 1,040
2012 139 96 (69) 43 (31) <0.001
2013 185 117 (63) 68 (37)
2014 100 48 (48) 52 (52)
2015 91 45 (49) 46 (51)
2016 273 175 (64) 98 (36)
2017
 252
 133 (53)
 119 (47)
Community-onset infection, <72 h preadmission 1,035
No 747 454 (61) 293 (39) 0.05
Yes 288 156 (54) 132 (46)
Missing
 5
ICU admission 1,023
No 509 262 (51) 247 (49) <0.001
Yes 514 339 (66) 175 (34)
Missing
 17
CVC in situ 1,011
No 466 243 (52) 223 (48) <0.001
Yes 545 354 (65) 191 (35)
Missing
 29
Total parenteral nutrition 1,004
No 759 425 (56) 334 (44) <0.001
Yes 245 167 (68) 78 (32)
Missing
 36
Quick Pitt score >2¶ 652
No 503 278 (55) 225 (45) 0.27
Yes 149 90 (60) 59 (40)
Missing
 388
Candida species 946
C. albicans 425 221 (52) 204 (48) <0.001
Other Candida species# 521 336 (65) 185 (35)
Missing
 94
Mixed Candida species 1,040
No 1,007 590 (59) 417 (41) 0.11**
Yes
 33
 24 (73)
 9 (27)
Candida species resistant to fluconazole, voriconazole, or an echinocandin†† 764
No 610 345 (57) 265 (43) <0.001
Yes 154 114 (74) 40 (26)
Missing
 276
Receipt of systemic antifungal treatment 1,010
No 310 153 (49) 157 (51) <0.001
Yes 700 442 (63) 258 (37)
Missing
 30
Inappropriate antifungal treatment for candidemia‡‡ 419
No 381 247 (65) 134 (35) 0.21**
Yes 38 29 (76) 9 (24)
Missing
 621
Removal of CVC 488
No 127 75 (59) 52 (41) 0.08
Yes 361 244 (68) 117 (32)
Missing 552

*Values are no. (%) unless otherwise indicated. CVC, central venous catheter; ICU, intensive care unit.
†Total numbers for each category indicate number of patients for whom that information was available.
‡p values by Pearson’s χ2 test unless otherwise indicated. 
§By Wilcoxon rank-sum test. 
¶Quick Pitt score was calculated as the sum of individual scores for temperature <35oC (1), systolic blood pressure <90 mm Hg (1), cardiac arrest (1), mechanical ventilation (1), and altered mental status (1) at time of candidemia diagnosis. 
#Other Candida species in HIV-seronegative participants (Candida parapsilosis, n = 112; Candida glabrata, n = 84; Candida auris, n = 27; Candida tropicalis, n = 22; Candida krusei, n = 20; other species, n = 71) and HIV-seropositive participants (C. parapsilosis, n = 51; C. glabrata, n = 49; C. tropicalis, n = 20; C. auris, n = 8; C. krusei, n = 8; other species, n = 49). 
**By Fisher exact test. 
††Resistance was defined based on Clinical and Laboratory Standards Institute Candida species–specific breakpoints (18). 
‡‡Inappropriate treatment was defined as treatment with an antifungal agent to which the Candida species was resistant.

Main Article

References
  1. van Schalkwyk  E, Mpembe  RS, Thomas  J, Shuping  L, Ismail  H, Lowman  W, et al.; GERMS-SA. GERMS-SA. Epidemiologic shift in candidemia driven by Candida auris, South Africa, 2016–2017. Emerg Infect Dis. 2019;25:1698–707. DOIPubMedGoogle Scholar
  2. Tsay  SV, Mu  Y, Williams  S, Epson  E, Nadle  J, Bamberg  WM, et al. Burden of Candidemia in the United States, 2017. Clin Infect Dis. 2020;71:e449–53. DOIPubMedGoogle Scholar
  3. Lee  RA, Zurko  JC, Camins  BC, Griffin  RL, Rodriguez  JM, McCarty  TP, et al. Impact of infectious disease consultation on clinical management and mortality in patients with candidemia. Clin Infect Dis. 2019;68:1585–7. DOIPubMedGoogle Scholar
  4. Kim  SH, Yoon  YK, Kim  MJ, Sohn  JW. Clinical impact of time to positivity for Candida species on mortality in patients with candidaemia. J Antimicrob Chemother. 2013;68:2890–7. DOIPubMedGoogle Scholar
  5. Keighley  C, Chen  SCA, Marriott  D, Pope  A, Chapman  B, Kennedy  K, et al. Candidaemia and a risk predictive model for overall mortality: a prospective multicentre study. BMC Infect Dis. 2019;19:445. DOIPubMedGoogle Scholar
  6. Tumbarello  M, Tacconelli  E, de Gaetano Donati  K, Morace  G, Fadda  G, Cauda  R. Candidemia in HIV-infected subjects. Eur J Clin Microbiol Infect Dis. 1999;18:478–83. DOIPubMedGoogle Scholar
  7. Bertagnolio  S, de Gaetano Donati  K, Tacconelli  E, Scoppettuolo  G, Posteraro  B, Fadda  G, et al. Hospital-acquired candidemia in HIV-infected patients. Incidence, risk factors and predictors of outcome. J Chemother. 2004;16:172–8. DOIPubMedGoogle Scholar
  8. Puig-Asensio  M, Padilla  B, Garnacho-Montero  J, Zaragoza  O, Aguado  JM, Zaragoza  R, et al.; CANDIPOP Project; GEIH-GEMICOMED (SEIMC); REIPI. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect. 2014;20:O245–54. DOIPubMedGoogle Scholar
  9. Grim  SA, Berger  K, Teng  C, Gupta  S, Layden  JE, Janda  WM, et al. Timing of susceptibility-based antifungal drug administration in patients with Candida bloodstream infection: correlation with outcomes. J Antimicrob Chemother. 2012;67:707–14. DOIPubMedGoogle Scholar
  10. Levine  AM, Karim  R, Mack  W, Gravink  DJ, Anastos  K, Young  M, et al. Neutropenia in human immunodeficiency virus infection: data from the women’s interagency HIV study. Arch Intern Med. 2006;166:405–10. DOIPubMedGoogle Scholar
  11. Kuritzkes  DR. Neutropenia, neutrophil dysfunction, and bacterial infection in patients with human immunodeficiency virus disease: the role of granulocyte colony-stimulating factor. Clin Infect Dis. 2000;30:256–60. DOIPubMedGoogle Scholar
  12. Ramos  A, Romero  Y, Sánchez-Romero  I, Fortún  J, Paño  JR, Pemán  J, et al. Risk factors, clinical presentation and prognosis of mixed candidaemia: a population-based surveillance in Spain. Mycoses. 2016;59:636–43. DOIPubMedGoogle Scholar
  13. Meintjes  G, Kerkhoff  AD, Burton  R, Schutz  C, Boulle  A, Van Wyk  G, et al. HIV-related medical admissions to a South African district hospital remain frequent despite effective antiretroviral therapy scale-up. Medicine (Baltimore). 2015;94:e2269. DOIPubMedGoogle Scholar
  14. Ntusi  N, Aubin  L, Oliver  S, Whitelaw  A, Mendelson  M. Guideline for the optimal use of blood cultures. S Afr Med J. 2010;100:839–43. DOIPubMedGoogle Scholar
  15. Vaquero-Herrero  MP, Ragozzino  S, Castaño-Romero  F, Siller-Ruiz  M, Sánchez González  R, García-Sánchez  JE, et al. The Pitt Bacteremia Score, Charlson Comorbidity Index and Chronic Disease Score are useful tools for the prediction of mortality in patients with Candida bloodstream infection. Mycoses. 2017;60:676–85. DOIPubMedGoogle Scholar
  16. Battle  SE, Augustine  MR, Watson  CM, Bookstaver  PB, Kohn  J, Owens  WB, et al. Derivation of a quick Pitt bacteremia score to predict mortality in patients with Gram-negative bloodstream infection. Infection. 2019;47:571–8. DOIPubMedGoogle Scholar
  17. Patterson  L, McMullan  R, Harrison  DA. Individual risk factors and critical care unit effects on Invasive Candida Infection occurring in critical care units in the UK: A multilevel model. Mycoses. 2019;62:790–5. DOIPubMedGoogle Scholar
  18. Clinical and Laboratory Standards Institute. Performance standards for antifungal susceptibility testing of yeasts (M60). Wayne (PA): The Institute; 2017.
  19. Toda  M, Williams  SR, Berkow  EL, Farley  MM, Harrison  LH, Bonner  L, et al. Population-based active surveillance for culture-confirmed candidemia—four sites, United States, 2012–2016. MMWR Surveill Summ. 2019;68:1–15. DOIPubMedGoogle Scholar
  20. World Health Organization. Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy [cited 2021 Jan 14]. https://www.who.int/hiv/pub/guidelines/advanced-HIV-disease/en
  21. Carmona  S, Bor  J, Nattey  C, Maughan-Brown  B, Maskew  M, Fox  MP, et al. Persistent high burden of advanced HIV disease among patients seeking care in South Africa’s national HIV program: data from a nationwide laboratory cohort. Clin Infect Dis. 2018;66(suppl_2):S111–7. DOIPubMedGoogle Scholar
  22. Olsen  MF, Abdissa  A, Kæstel  P, Tesfaye  M, Yilma  D, Girma  T, et al. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia. BMJ. 2014;348:g3187. DOIPubMedGoogle Scholar
  23. Luzzati  R, Merelli  M, Ansaldi  F, Rosin  C, Azzini  A, Cavinato  S, et al. Nosocomial candidemia in patients admitted to medicine wards compared to other wards: a multicentre study. Infection. 2016;44:747–55. DOIPubMedGoogle Scholar
  24. Scudeller  L, Bassetti  M, Concia  E, Corrao  S, Cristini  F, De Rosa  FG, et al.; MEDICAL group; Società Italiana di Terapia Antinfettiva (SITA); Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI). MEDical wards Invasive Candidiasis ALgorithms (MEDICAL):Consensus proposal for management. Eur J Intern Med. 2016;34:45–53. DOIPubMedGoogle Scholar
  25. Sbrana  F, Sozio  E, Bassetti  M, Ripoli  A, Pieralli  F, Azzini  AM, et al. Independent risk factors for mortality in critically ill patients with candidemia on Italian Internal Medicine Wards. Intern Emerg Med. 2018;13:199–204. DOIPubMedGoogle Scholar
  26. Naidoo  K, Singh  JA, Lalloo  UG. Survey of ethical dilemmas facing intensivists in South Africa in the admission of patients with HIV infection requiring intensive care. South Afr J Crit Care. 2013;29:1–10. DOIGoogle Scholar
  27. Mkoko  P, Raine  RI. HIV-positive patients in the intensive care unit: A retrospective audit. S Afr Med J. 2017;107:877–81. DOIPubMedGoogle Scholar
  28. Garnacho-Montero  J, Díaz-Martín  A, García-Cabrera  E, Ruiz Pérez de Pipaón  M, Hernández-Caballero  C, Lepe-Jiménez  JA. Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections. J Antimicrob Chemother. 2013;68:206–13. DOIPubMedGoogle Scholar
  29. Lockhart  SR, Etienne  KA, Vallabhaneni  S, Farooqi  J, Chowdhary  A, Govender  NP, et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017;64:134–40. DOIPubMedGoogle Scholar
  30. Govender  NP, Magobo  RE, Mpembe  R, Mhlanga  M, Matlapeng  P, Corcoran  C, et al. Candida auris in South Africa, 2012-2016. Emerg Infect Dis. 2018;24:2036–40. DOIPubMedGoogle Scholar
  31. Govender  NP, Patel  J, Magobo  RE, Naicker  S, Wadula  J, Whitelaw  A, et al.; TRAC-South Africa group. Emergence of azole-resistant Candida parapsilosis causing bloodstream infection: results from laboratory-based sentinel surveillance in South Africa. J Antimicrob Chemother. 2016;71:1994–2004. DOIPubMedGoogle Scholar

Main Article

1Members of GERMS-SA are listed at the end of this article.

Page created: April 13, 2021
Page updated: May 19, 2021
Page reviewed: May 19, 2021
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external