How useful is serum 1, 3-β-D-glucan in diagnosing Pneumocystis jiroveci pneumonia and invasive fungal disease?

Serum 1, 3-β-D-glucan (BG) is highly accurate for Pneumocystis jiroveci pneumonia (PJP), but only moderately accurate for diagnosing invasive fungal disease (IFD).

For PJP, a meta-analysis of studies looking at the performance of BG found a pooled sensitivity of 96%, specificity of 84% and area under receiver operating characteristic curve (AUC-ROC) of 0.96. 1 Thus, a negative BG essentially rules out PJP.

For IFD (primarily invasive candidiasis or aspergillosis), data based on 3 separate meta-analyses came to similar conclusions with a pooled sensitivity and specificity of ~80% and AUC-ROC of ~0.89 each.1-3 In some of the studies,2,3 the sensitivity of BG for IFD was between 50% to 60% which makes it difficult to exclude IFD when BG is normal.

Remember that BG may be false-positive in a variety of situations, including patients receiving immunological preparations (eg albumin or globulins), use of membranes and filters made from cellulose in hemodialysis, and use of cotton gauze swabs/packs/pads and sponges during surgery. 1 In addition, although BG is a component of the cell wall of most fungi, there are some exceptions including Zygomycetes and cryptococci.

Bonus pearl: Did you know that BG assay is based on Limulus amoebocyte lysate, extracted from amoebocytes of horseshoe crab species? 3

If you like this post, sign up under MENU and catch future pearls right in your inbox!

References

  1. Onishi A, Sugiyama D, Kogata Y, et al. Diagnostic accuracy of serum 1,3-β-D-glucan for Pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol 2012;50:7-15. https://www.ncbi.nlm.nih.gov/pubmed/22075593
  2. He S, Hang JP, Zhang L, et al. A systematic review and meta-analysis of diagnostic accuracy of serum 1,3–β-D-glucan for invasive fungal infection: focus on cutoff levels. J Microbiol Immunol Infect 2015;48:351-61. https://www.ncbi.nlm.nih.gov/pubmed/25081986
  3. Karageogopoulos DE, Vouloumanou EK, Ntziora F, et al. β-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis 2011;52:750-69. https://academic.oup.com/cid/article/52/6/750/361658/

 

How useful is serum 1, 3-β-D-glucan in diagnosing Pneumocystis jiroveci pneumonia and invasive fungal disease?

Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

Although there are many potential sources for Klebsiella sp. bacteremia, C. difficile infection (CDI) itself may be associated with GI translocation of enteric organisms.

A retrospective study of over 1300 patients found an incidence of 1.8% for CDI-associated bacteremia. E. coli, Klebsiella sp. , or Enterococcus sp. accounted for 72% of cases. History of malignancy, neutropenia (at the time of CDAD), and younger age (mean 59 y) were among the risk factors.1 Another study reported over 20 cases of bacteremia caused by C. difficile plus other bacteria often of enteric origin such the aforementioned organisms, Bacteroides sp, Candida sp, and Enterobacter sp.2

CDI is thought to predispose to bacterial translocation through the GI tract by alteration of mucosal indigenous microflora, overgrowth of certain pathogens, and presence of inflammation in the mucosa.3 Interestingly, C. difficile toxin A or B may play an active role in the bacterial adherence and penetration of the intestinal epithelial barrier.4  

Bonus pearl: Did you know that C. difficile may be found in the normal intestinal flora of 3% of healthy adults, 15-30% of hospitalized patients, and up to 50% of neonates? Why neonates seem immune to CDI is another fascinating story!

 

References

  1. Censullo A, Grein J, Madhusudhan M, et al. Bacteremia associated with Clostridium difficile colitis: incidence, risk factors, and outcomes. Open Forum Infectious Diseases, Volume 2, Issue suppl_1, 1 December 2015, 943, https://doi.org/10.1093/ofid/ofv133.659 https://academic.oup.com/ofid/article/2/suppl_1/943/2635179
  2. Kazanji N, Gjeorgjievski M, Yadav S, et al. Monomicrobial vs polymicrobial Clostridum difficile bacteremia: A case report and review of the literature. Am J Med 2015;128:e19-e26. https://www.amjmed.com/article/S0002-9343(15)00458-1/abstract
  3. Naaber P, Mikelsaar RH, Salminen S, et al. Bacterial translocation, intestinal microflora and morphological changes of intestinal mucosa in experimental models of Clostridium difficile infection. J Med Microbiol 1998; 47: 591-8. https://www.ncbi.nlm.nih.gov/pubmed/9839563 
  4. Clostridium difficile toxins may augment bacterial penetration of intestinal epithelium. Arch Surg 1999;134: 1235-1242. https://jamanetwork.com/journals/jamasurgery/fullarticle/390434
Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

Can oral candidiasis be symptomatic without actual pseudomembranes or “thrush”?

Yes!  Although we often associate oral candidiasis with thrush or pseudomembranous white plaques, another common form of oral candidiasis seen in hospitalized patients is “acute atrophic candidiasis” (AAC), also referred to as “antibiotic sore mouth” because of its association with use of broad spectrum antibiotics (1,2). 

Despite the absence of thrush, patients with AAC often have erythematous patches on the palate, buccal mucosa and dorsum of the tongue. Common symptoms include burning sensation in the mouth (especially with carbonated drinks in my experience), dry mouth and taste buds “being off” (2).  

Aside from antibiotics, other predisposing factors for AAC include corticosteroids, HIV disease, uncontrolled diabetes mellitus, iron deficiency anemia, and vitamin B12 deficiency.

So next time you see a hospitalized patient with new onset sore, burning mouth that wasn’t present on admission, think of antibiotic sore mouth!

Liked this post? Sign up under MENU and catch future pearls right into your inbox!

References

1. Stoopler ET, Sollecito TP. Oral mucosal diseases. Med Clin N Am 2014;98:1323-1352. https://www.ncbi.nlm.nih.gov/pubmed/25443679

2. Millsop JW, Fazel N. Oral candidiasis. Clin Derm 2016;34:487-94. https://www.ncbi.nlm.nih.gov/pubmed/27343964

Can oral candidiasis be symptomatic without actual pseudomembranes or “thrush”?