How might measuring viral load in respiratory specimens be helpful clinically in patients with Covid-19?

Although far from being perfect, there are emerging scientific data that suggest measuring viral load in respiratory specimens of patients with Covid-19 could be helpful in at least 2 ways: 1. Help determine who may be infectious (therefore isolated or undergo contact tracing); and 2. Identify patients at high risk for severe disease and death (1-4).

In a study involving 3,790 nasopharyngeal samples testing positive for SARS-CoV-2 by PCR, a significant correlation was found between isolation of the virus by culture—therefore potential contagiousness—and viral load determined by cycle threshold (CT) (ie, the number of cycles needed to detect the virus with higher numbers thought to be associated with lower risk of contagion) (2). Some have suggested that patients with CT above 33-34 are no longer contagious (3).

In another study involving 978 patients with Covid-19, high viral load in nasopharyngeal specimens was associated with higher risk of intubation (O.R. 2.7, 1.7-4.4), and mortality (6.1, 2.9-12.5) (4).

In addition, simultaneous presence of high viral loads in the respiratory specimens in the population suggests an expanding outbreak, while low viral loads may imply that the outbreak is waning (1).

Some have cautioned against over-reliance on viral loads in Covid-19 due to factors such as variation in the technique of obtaining specimens and testing instruments (5).

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References
1. Service RF. Covid-19. A call for diagnostic tests to report viral load. Science 2020, October 2;370:22. https://www.sciencemag.org/news/2020/09/one-number-could-help-reveal-how-infectious-covid-19-patient-should-test-results
2. Jaafar R, Aherfi S, Wurtz N, et al. Correlation between 3790 qPCR positives samples and positive cell cultures including 1941 SARS-CoV-2 isolates. Clin Infect Dis 2020, September. https://pubmed.ncbi.nlm.nih.gov/32986798/
3. La Scola B, Le Bideau M, Andreani J, et al. Viral RNA as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards. Eur J Clin Microbiol Infect Dis 2020;39:1059-1061. https://pubmed.ncbi.nlm.nih.gov/32342252/
4. Magleby R, Westblade LF, Trzebucki A, et al. Impact of severe acute respiratory syndrome coronavirus 2 viral load on risk of intubation and mortality among hospitalized patients with coronavirus disease 2019. Clin Infect Dis 2020. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa851/5865363
5. Rhoads D, Peaper DR, She RC, et al. College of American Pathologists (CAP) Microbiology Committee perspective: caution must be used in interpreting the cycle threshold (Ct) value. Clin Infect Dis 12 August, 2020. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1199/5891762

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How might measuring viral load in respiratory specimens be helpful clinically in patients with Covid-19?

Why would my patient with Covid-19 infection test negative by PCR?

There are several potential reasons why someone who is infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of Covid-19, may test negative by PCR. These including the threshold for detection of virus (which can vary among different manufacturers from as low as 100 viral copies/ml to >6,000 copies/ml),1 timing of the sample collection with respect to infection stage (lowest false-negative rate [~20%] on day 3 of symptoms or 8 days post-infection),specimen storage and transport and, particularly in the case of nasopharyngeal specimens, the adequacy of the sample obtained. 3

Suboptimal specimen collection from nasopharynx has long been suspected as an explanation for false-negative PCR tests in patients who subsequently have a positive test or are highly suspected of having Covid-19, but without any good support data. Until now…

A clever study looked at the presence of human DNA recovered from nasopharyngeal swabs as a marker for adequate specimen collection quality and found that human DNA levels were significantly lower in samples from patients with confirmed or suspected Covid-19 that yielded negative results compared to those of representative pool of samples submitted for Covid-19 testing.3

Interestingly, major commercial assays do not include any internal controls that ensure adequate sampling before testing for SARS-CoV2.

A typical microbiology lab can reject a sputum culture if gram-stain suggests poor quality specimen (eg, saliva only) but it looks like no similar rule exists for nasopharyngeal PCR tests for SARS-CoV-2 through commercial labs. Apparently, the US-CDC diagnostic panel does include a human RNAseP RNA-specific primer/probe set but the interpretation criteria for this control may also be too liberal.3

For these reasons, in patients highly suspected of having Covid-19 but with a negative initial PCR test, a repeat test on the same day or next 2 days is recommended.4

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References

  1. Prinzi A. False negatives and refinfections: the challenges of SARS-CoV-2 RT-PCR testing. Available at https://asm.org/Articles/2020/April/False-Negatives-and-Reinfections-the-Challenges-of     Accessed October 5, 2020.
  2. Kucirka LM, Lauer SA, Laeyendecker O, et al. Variation in false-negative rate of reverse transcriptase polymerase chain reaction-based SARS-CoV-2 tests by time since exposure. Ann Intern Med 2020 May 13:M20-1495. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240870/
  3. Kinloch NN, Ritchie G, Brumme CJ, et al. Suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results. J Infect Dis 2020;222:899-902. https://academic.oup.com/jid/article/222/6/899/5864227
  4. Green DA, Zucker J, Westbade LF, et al. Clinical performance of SARS-CoV-2 molecular testing. J Clin Microbiol 2020. DOI:10.1128/JCM.00995-20. https://jcm.asm.org/content/58/8/e00995-20

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Why would my patient with Covid-19 infection test negative by PCR?

Does a positive routine PCR test for Covid-19 virus mean the person is infectious?

Not necessarily! Although a positive routine PCR test for Covid-19 indicates the presence of the virus in a clinical specimen, it does not mean that the virus is still viable or transmissible, particularly as the patient may be recovering from Covid-19. Viral cultures are often needed to help answer this question. 1-5

In a study of 9 hospitalized patients with Covid-19, no viable Covid-19 virus could be found by culture in any specimen beyond 8 days following onset of symptoms despite a positive routine PCR for up to 13 days. Successful growth of the virus was dependent in part on viral load, with samples containing <106 copies/mL never yielding any viable virus.1  

In the same study, none of stools that were positive for Covid-19 virus by PCR were positive by culture.  The authors concluded that there is “little residual risk of infectivity” beyond day 10 of symptoms when sputum contains less than 100,000 viral RNA copies /ml.  Of note, the patients in this study were young- to middle-aged without significant underlying disease and had milder disease, so the results may not necessarily be generalizable to other patients with Covid-19. 1

The discrepancy between a positive PCR and negative culture has been seen with other respiratory pathogens,  such as respiratory syncytial virus (RSV) and influenza. In a study involving experimentally infected subjects with RSV, the average duration of viral shedding was 9.2 days by PCR compared to 7.2 days by viral culture.2 In another study involving patients with symptomatic influenza, virus could be detected for up to 7 days with PCR compared to 1-2 days by viral culture.3

Factors that may explain this discrepancy include suboptimal sample transport, low viral titers,  and the presence of neutralizing antibody in the clinical specimen.2,3

So, despite our incomplete knowledge, don’t assume that PCR positivity means the presence of live virus capable of transmitting Covid-19!

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References

  1. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-19. Nature 2020; April 1. https://www.nature.com/articles/s41586-020-2196-x
  2. Falsey AR, Formica MA, Treanor JJ, et al. Comparison of quantitative reverse transcriptase-PCR to viral culture for assessment of respiratory syncytial virus shedding. J Clin Microbiol 2003;41:4160-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193781/pdf/0106.pdf
  3. Van Elden LJR, Nijhuis M, Schipper P, et al . Simultaneous detection of influenza viruses A and B using real-time quantitative PCR. J Clin Microbiol 2001;39:196-200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC87701/
  4. Cangelosi GA, Meschke JS. Dead or alive:molecular assessment of microbial viability. App Environ Microbiol 2014;80:5884-91.
  5. European Centre for Disease Prevention and Control. Novel coronavirus (SARS-CoV-2). https://www.ecdc.europa.eu/en/publications-data/novel-coronavirus-sars-cov-2-discharge-criteria-confirmed-covid-19-cases

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Does a positive routine PCR test for Covid-19 virus mean the person is infectious?

What’s the evidence that people without symptoms can transmit Covid-19 to those around them?

Rapid spread of Covid-19 virus has been attributed in large part to its ease of transmission from person to person even before symptoms develop, particularly since an estimated 18% to 75% of patients testing positive for Covid-19 have no symptoms. 1-4

Transmission before onset of symptoms (presymptomatic): Modeled estimates for the percentage of transmissions that occur from presymptomatic patients range from 37% to as high as 62% based on studies of patients in the cities of Tianjin and Guangzhou in China, as well as Singapore.5-7 Infectiousness appears to begin within 1-3 days prior to symptoms.8-10

Transmission when symptoms never develop (asymptomatic): Asymptomatic transmission was invoked in a familial cluster in Anyang, China where 5 patients developed Covid-19 after a 6th asymptomatic family member returned home from Wuhan, China. The asymptomatic patient never developed symptoms—such as fever or respiratory symptom— and had a normal chest CT, but briefly tested positive for Covid-19 by RT-PCR before testing negative later.11

It’s important to point out that up to ~75% of patients who are initially “asymptomatic” later develop symptoms. 12-14 So what we often call “asymptomatic” may actually be “presymptomatic.”

Transmission of Covid-19 before onset of symptoms is in distinct contrast to SARS, another coronavirus disease, which was transmitted only when a person was symptomatic and was easier to control. This unique property among coronaviruses may be explained by the high tropism of Covid-19 virus not only for the lungs (as in case of SARS virus) but also for the upper respiratory tract.15,16 As such, Covid-19 behaves more like influenza viruses whose upper respiratory tract binding is thought to promote their rapid transmission even before symptoms develop.17  No wonder, Covid-19 spread like wild fire!

 

Coauthor, Bruce Tiu, Harvard Medical Student, Boston, MA

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References

 

  1. Mizumoto K, Kagaya K, Zarebski A, et al. Estimating the asymptomatic proportion of coronavirus diseae 2019 (COID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill.2020;25(10):pii=2000180 https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.10.2000180?ftag=MSF0951a18
  2. Kimaball, A, Hatfield KM, Arons M, et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility—King County, Washington, March 2020. MMWR 2020;69:377-381. https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm
  3. Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci 2020 Mar 4. https://www.ncbi.nlm.nih.gov/pubmed/32146694
  4. Day M. Covid-19: identifying and isolating asymptomatic people helped eliminate virus in Italian village. BMJ 2020;368 https://www.bmj.com/content/368/bmj.m1165
  5. He X, Lau E, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. medRxiv. https://www.medrxiv.org/content/10.1101/2020.03.15.20036707v2
  6. Ferretti L, Wymant C, Kendall M, et al. Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing [published online ahead of print, 2020 Mar 31]. Science. 2020; eabb6936. https://science.sciencemag.org/content/early/2020/03/30/science.abb6936
  7. Ganyani T, Kremer C, Chen D, et al. Estimating the generation interval for COVID-19 based on symptom onset data. medRxiv. https://www.medrxiv.org/content/10.1101/2020.03.05.20031815v1
  8. Wei WE, Li ZB, Chiew CJ, et al. Presymptomatic transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020. MMWR Morb Mortal Wkly Rep. ePub: 1 April 2020. https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e1.htm
  9. He X, Lau E, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. medRxiv. https://www.medrxiv.org/content/10.1101/2020.03.15.20036707v2
  10. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020;382(10):970–971. https://www.nejm.org/doi/full/10.1056/NEJMc2001468
  11. Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19 [published online ahead of print, 2020 Feb 21]. JAMA. 2020;e202565. https://jamanetwork.com/journals/jama/fullarticle/2762028
  12. Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility — King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020;69:377–381 https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm
  13. Chen, C. “What We Need to Understand About Asymptomatic Carriers if We’re Going to Beat Coronavirus”. ProPublica. 2020. https://www.propublica.org/article/what-we-need-to-understand-about-asymptomatic-carriers-if-were-going-to-beat-coronavirus
  14. WHO. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). 2020. https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf
  15. Woelfel R, Corman VM, Guggemos W, et al. Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster. medRxiv. https://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1
  16. Peiris JS, Chu CM, Cheng VC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767–1772. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)13412-5/fulltext
  17. van Riel D, den Bakker MA, Leijten LM, et al. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses. Am J Pathol. 2010;176(4):1614–1618. https://wwwnc.cdc.gov/eid/article/26/6/20-0357_article

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s the evidence that people without symptoms can transmit Covid-19 to those around them?

How “sensitive” is the PCR in diagnosing coronavirus/Covid-19?

A definite diagnosis of Covid-19 requires viral testing, usually through PCR performed on upper (nasopharyngeal or oropharyngeal) or lower respiratory samples (sputum, bronchoalveolar lavage [BAL] fluid). Rates of positive PCR may be affected by stage of the disease and/or its severity.
Nasopharyngeal sample: This seems to be the most practical and readily available means of confirming Covid-19 diagnosis, with positive rates of ~75% during the first 2 weeks of illness in patients considered to have severe disease. For patients with mild Covid-19, a positive PCR rate of 72% has been reported during the 1st week, dropping to 54% during the 2nd week (1).
Oropharyngeal sample: Lower positive PCR rates have been observed with throat swabs, as low as ~30% in mild Covid-19 during the 2nd week of the illness and ~60% in severe disease during the first week of illness (2).
Sputum: Sputum may have the highest positive rates ranging from ~75% in mild disease during the second week of illness to ~90% during the 1st week of severe disease. The problem with sputum sampling is that less than one-third of patients with Covid-19 can provide a sample given the usually dry nature of their cough (1,4).
BAL fluid: In a limited number of patients with severe disease who had bronchoalveolar lavage sampling during the 2nd week of illness, 3 (25%) of 12 patients with positive PCR on BAL had negative upper respiratory samples (1). So in severe disease, the virus definitely prefers to replicate in the lower respiratory tract.
Potential explanations for a negative PCR include low viral titers and specimen handling. So, in patients suspected of having Covid-19 based on clinical/laboratory/radiograph grounds, a negative upper respiratory sample, particularly oropharyngeal source, should not rule out this disease.

 

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References

1. Yang Y, Yang M, Shen C, et al. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. MedRxiv. 2020. DOI: http://doi.org/10.1101/2020.02.11.20021493
2. Ai T, Yang Z, Hou H, et al. Correlation of chest CT and RT-PCR testing in Coronavirus disease 2019 (COVID-19) in China: A report of 1014 cases. Radiology 2020. https://pubs.rsna.org/doi/10.1148/radiol.2020200642
3. Bai HX, Hsieh B, Xiong Z, et al. Performance of radiologists in differentiaging COVID-19 from viral pneumonia on chest CT. Radiology 2020. https://pubs.rsna.org/doi/10.1148/radiol.2020200823 
4. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext
Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How “sensitive” is the PCR in diagnosing coronavirus/Covid-19?

What changes should I consider in my treatment of hospitalized patients with community-acquired pneumonia (CAP) in light of the 2019 guidelines of the American Thoracic society (ATS) and Infectious Diseases Society of America (IDSA)?

Compared to 2007,1 the 2019 ATS/IDSA guidelines2 propose changes in at least 4 major areas of CAP treatment in inpatients, with 2 “Do’s” and 2 “Dont’s”:

  • Do select empiric antibiotics based on severity of CAP and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (see related pearl on P4P)
  • Do routinely treat CAP patients who test positive for influenza with standard CAP antibiotics
  • Don’t routinely provide anaerobic coverage in aspiration pneumonia (limit it to empyema and lung abscess) (see related pearl on P4P)
  • Don’t routinely treat CAP with adjunctive corticosteroids in the absence of refractory shock

β-lactam plus macrolide is recommended for both non-severe and severe CAP.  β-lactam plus respiratory fluoroquinolone is an alternative regime in severe CAP, though not endorsed as strongly as β-lactam plus macrolide therapy (low quality of evidence).  Management per CAP severity summarized below:

  • Non-severe CAP
    • β-lactam (eg, ceftriaxone, cefotaxime, ampicillin-sulbactam and newly-added ceftaroline) plus macrolide (eg, azithromycin, clarithromycin) OR respiratory fluoroquinolone (eg, levofloxacin, moxifloxacin)
    • In patients at risk of MRSA or P. aeruginosa infection (eg, prior isolation of respective pathogens, hospitalization and parenteral antibiotics in the last 90 days or locally validated risk factors—HCAP has been retired), obtain cultures/PCR
    • Hold off on MRSA or P. aeruginosa coverage unless culture/PCR results return positive.
  • Severe CAP
    • β-lactam plus macrolide OR β-lactam plus respiratory fluoroquinolone (see above)
    • In patients at risk of MRSA or P. aeruginosa infection (see above), obtain cultures/PCR
    • Add MRSA coverage (eg, vancomycin or linezolid) and/or P. aeruginosa coverage (eg, cefepime, ceftazidime, piperacillin-tazobactam, meropenem, imipenem) if deemed at risk (see above) while waiting for culture/PCR results

Duration of antibiotics is for a minimum of 5 days for commonly-targeted pathogens and a minimum of 7 days for MRSA or P. aeruginosa infections, irrespective of severity or rapidity in achieving clinical stability.

For patients who test positive for influenza and have CAP, standard antibacterial regimen should be routinely added to antiinfluenza treatment.

For patients suspected of aspiration pneumonia, anaerobic coverage (eg, clindamycin, ampicillin-sulbactam, piperacillin-tazobactam) is NOT routinely recommended in the absence of lung abscess or empyema.

Corticosteroids are NOT routinely recommended for non-severe (high quality of evidence) or severe (moderate quality of evidence) CAP in the absence of refractory septic shock.

Related pearls on P4P:

2019 CAP guidelines on diagnostics:                                        https://pearls4peers.com/2020/02/14/what-changes-should-i-consider-in-my-diagnostic-approach-to-hospitalized-patients-with-community-acquired-pneumonia-cap-in-light-of-the-2019-guidelines-of-the-american-thoracic-society-ats-and-inf/ 

Anerobic coverage of aspiration pneumonia: https://pearls4peers.com/2019/07/31/should-i-routinely-select-antibiotics-with-activity-against-anaerobes-in-my-patients-with-presumed-aspiration-pneumonia/

References

  1. Mandell LA, Wunderink RG, Anzueto A. Infectious Disease Society of America/American Thoracic Society Consensus Guidelines on the Management guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27-72. https://www.ncbi.nlm.nih.gov/pubmed/17278083
  2. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. Am J Respir Crit Care Med 2019;200:e45-e67. https://www.ncbi.nlm.nih.gov/pubmed/31573350

 

What changes should I consider in my treatment of hospitalized patients with community-acquired pneumonia (CAP) in light of the 2019 guidelines of the American Thoracic society (ATS) and Infectious Diseases Society of America (IDSA)?

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?