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

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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?

How accurate are peripheral thermometers for estimating body temperature in my patient with chills?

Though convenient, oral, tympanic membrane, axillary, and temporal artery thermometers (AKA “peripheral thermometers”) may not be highly accurate in measuring body temperature.

A 2015 systematic review and meta-analysis of the performance of peripheral thermometers involving 75 studies (mostly in adults) found that compared to central thermometers (eg, pulmonary artery, urinary bladder, rectal), peripheral thermometers had a low sensitivity (64%, 95% CI 55%-72%), but much better specificity (96%, 95% CI 93%-97%) for fever (most commonly defined as 37.8° C [100° F] or greater).1

In the same study, for oral electronic thermometers, sensitivity was 74% with a specificity of 86%. For temporal artery thermometers, sensitivities ranged from 26% to 91%, while specificities ranged from 67% to 100%. For tympanic membrane thermometers, sensitivities ranged from 23% to 87%, with a specificity of 57% to 99%.

A 2016 study involving adult emergency department patients reported the sensitivity of peripheral thermometers (vs rectal temperature 38 C [100.4] or higher) as follows: oral (37%), tympanic membrane (68%), and temporal artery (71%). Specificity for fever was >90% for all peripheral thermometers. 2

So, it looks like while we may be pretty comfortable with a diagnosis of “fever” when our patient with chills has a high temperature recorded by a peripheral thermometer, lack of fever alone by these devices should not veer us away from the possibility of systemic infection. When in doubt and if possible, check a rectal temperature.

References

  1. Niven DJ, Gaudet JE, Laupland KB. Accuracy of peripheral thermometers for estimating temperature: A systematic and meta-analysis. Ann Intern Med 2015;163:768-777. https://www.ncbi.nlm.nih.gov/pubmed/26571241
  2. Bijur PE, Shah PD, Esses D. Temperature measurement in the adult emergency department: oral tympanic membrane and temporal artery temperatures versus rectal temperature. Emerg Med J 2016;33:843-7. https://www.ncbi.nlm.nih.gov/pubmed/27334759

 

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How accurate are peripheral thermometers for estimating body temperature in my patient with chills?

What is the sensitivity of nose swabs in detecting methicillin-resistant Staphylococcus aureus (MRSA) pneumonia?

In MRSA pneumonia, the sensitivity of nasal swab PCR may vary from as low as 24.2% to 88% (1-3). A 2018 meta-analysis found an overall sensitivity of 70.9% (community-acquired pneumonia/healthcare-associated pneumonia [HCAP] 85%, ventilator-associated pneumonia 40%) with overall negative predictive value of 96.5% (based on an overall MRSA pneumonia prevalence of 10%) (4). 

A single center  study involving  patients with possible HCAP and a low clinical pulmonary infection score (CPIS) — for whom antibiotics may not be necessary anyway (5)—suggested that discontinuation of empiric vancomycin in patients without an adequate respiratory culture and a negative nose and throat culture may be reasonable (6).

However, a prospective study of ICU patients concluded that “clinicians cannot reliably use the results of initial negative MRSA nasal swab results to withhold empirical MRSA coverage from patients who otherwise are at risk for MRSA infection” (3).

The previously cited 2018 meta-analysis study (4) cautions against use of MRSA screening in patients with structural lung disease (eg, cystic fibrosis or bronchiectasis) because colonization may be more frequent in the lower respiratory tract in these patients and screening tests may therefore be discordant (4).

Collectively, the available data suggest that it is reasonable to use a negative MRSA screen to help exclude pneumonia due to this pathogen in patients in whom MRSA infection is not highly suspected or those who are not severely ill.

 

References

  1. Rimawi RH, Ramsey KM, Shah KB, et al. Correlation between methicillin-resistant Staphylococcus aureus nasal sampling, and S. aureus pneumonia in the medical intensive care unit. Infect Control Hosp Epidemiol 2014;35:590-92. https://www.ncbi.nlm.nih.gov/pubmed/24709733
  2. Dangerfield B, Chung A, Webb B, et al. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother 2014;58:859-64. https://www.ncbi.nlm.nih.gov/pubmed/24277023
  3. Sarikonda KV, Micek ST, Doherty JA, et al. Methicillin-resistant Staphylococcus aureus nasal colonization is a poor predictor of intensive care unit-acquired methicillin-resistant Staphylococcus aureus infections requiring antibiotic treatment. Crit Care Med 2010;38:1991-1995. https://www.ncbi.nlm.nih.gov/pubmed/20683260
  4. Parente DM Cunha CB Mylonakis E et al. The clinical utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA pneumonia: A diagnostic meta-analysis with antimicrobial stewardship implications. Clin Infect Dis 208;67:1-7.
  5. Napolitano LM. Use of severity scoring and stratification factors in clinical trials of hospital-acquired and ventilator-associated pneumonia. Clin Infect Dis 2010;51:S67-S80. https://www.ncbi.nlm.nih.gov/pubmed/20597675
  6. Boyce JM, Pop O-F, Abreu-Lanfranco O, et al. A trial of discontinuation of empiric vancomycin therapy in patients with suspected methicillin-resistant Staphylococcus aureus health care-associated pneumonia. Antimicrob Agents Chemother 2013;57:1163-1168. http://aac.asm.org/content/57/3/1163.full.pdf
What is the sensitivity of nose swabs in detecting methicillin-resistant Staphylococcus aureus (MRSA) pneumonia?