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?

Why are antibiotics routinely administered in patients with cirrhosis and upper gastrointestinal (GI) bleed?

Antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleed (UGIB) reduce bacterial infections, all-cause mortality, bacterial infection, mortality, rebleeding events and hospitalization.1

A 2011 Cochrane meta-analysis involving 12 trials comparing antibiotic prophylaxis to no prophylaxis or placebo found reduction in bacterial infection (RR 0.35, 95% C.I., 0.26-0.47) and overall mortality (RR 0.79, 95% C.I. 0.63-0.98). It also found a significant reduction in rebleeding and days of hospitalization, based on more limited data. Trials in this meta-analysis involved a variety of antibiotics, including norfloxacin, ciprofloxacin, cefazolin, cefotaxime, ceftriaxone and ampicillin-sulbactam. 1

So why is ceftriaxone the often-favored bacterial prophylaxis in UGIB? First, infections in cirrhotic patients often originate from bacterial translocation through the GI tract with aerobic gram-negative GI flora expected to be susceptible to ceftriaxone.2 Second, the emerging quinolone resistance among aerobic Gram-negative bacteria 2 and frequent use of ciprofloxacin for prophylaxis against spontaneous bacterial peritonitis have made use of ceftriaxone in this setting more desirable than quinolones.

Of note, a 2006 study involving patients with advanced cirrhosis (Child Pugh B or C) and GI hemorrhage receiving either norfloxacin or ceftriaxone for 7 days found a significantly lower risk of suspected or proven infections (11% vs 33%) and bacteremia or spontaneous bacterial peritonitis (2% vs 12%) in the ceftriaxone group; there was no difference in hospital mortality. 3 Although the overall prevalence of quinolone-resistant gram-negatives was unknown, 6 of 7 gram-negative bacilli isolated in the norfloxacin group were quinolone resistant.

Bonus Pearl: Did you know that 30-40% of cirrhotic patients presenting with UGIB will develop a bacterial infection within a week of their admission? 1

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References

  1. Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila F, et al. Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding-an updated Cochrane review. Aliment Pharmacol Ther 2011;34:509-518. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2036.2011.04746.x
  2. Mallet M, Rudler M, Thabut D. Variceal bleeding in cirrhotic patients. Gastroenterology Reports 2017;5:185-192. https://academic.oup.com/gastro/article/5/3/185/4002779
  3. Fernandez J, del Arbo LR, Gomez C, et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology 2006;131:1049-1056. https://www.sciencedirect.com/science/article/abs/pii/S0016508506015356

 

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 are antibiotics routinely administered in patients with cirrhosis and upper gastrointestinal (GI) bleed?

Is cefepime an acceptable alternative to carbapenems in the treatment of cefepime susceptible extended spectrum beta-lactamase (ESBL) Gram-negatives?

Irrespective of in-vitro susceptibility results, cefepime should be avoided in the treatment of serious ESBL infections associated with bacteremia, pneumonia, intraabdominal infection, endocarditis, bone/joint infection or whenever a high bacterial inoculum is suspected. Cefepime should be considered only in non-severe infections (eg, uncomplicated urinary tract infection) when the minimum inhibitory concentration (MIC) is 2 mg/L or less (1).

 

To date, clinical studies comparing cefepime vs carbapenem have been small and/or retrospective, often with conflicting results (1). A 2016 propensity score-matched study of patients with ESBL bacteremia receiving cefepime therapy followed by carbapenem therapy vs carbapenem for the entire treatment duration found higher 14 day mortality in the cefepime group (41% vs 20% in the carbapenem group) (2).  Of note, 2 of the patients receiving cefepime who died were infected with an ESBL organism with MIC of 1 mcg/mL. 

 

Another study found cefepime to be inferior to carbapenem therapy in ESBL bacteremic patients with better outcome when cefepime MIC was 1 ug/m or less (3).

 

Two studies involving patients with ESBL UTIs found no significant difference between cefepime and carbapenem in clinical and microbiological response or in-hospital mortality, while another UTI study with a high rate of septic shock (33%) found that cefepime was inferior to carbapenem in clinical and microbiological response (2).

 

The diminished efficacy of cefepime for the treatment of ESBL infections may be related to its “inoculum effect” ie, marked increase in MIC with increased inoculum size compared to that used in standard laboratory susceptibility testing (1,4).   

 

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References

  1. Karaiskos I, Giamarellou H. Carbapenem-sparing strategies for ESBL producers: when and how. Antibiotics 2020;9,61. https://pubmed.ncbi.nlm.nih.gov/32033322/
  2. Wang R, Cosgrove S, Tschudin-Sutter S, et al. Cefepime therapy for cefepime-susceptible extended-spectrum beta-lactamase-producing Enerobacteriaceae bacteremia. Open Forum Infect Dis 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942761/
  3. Lee NY, Lee CC, Huang WH, et al. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. Clin Infect Dis 203;56:488-95. https://academic.oup.com/cid/article/56/4/488/351224
  4. Smith KP, Kirby JE. The inoculum effect in the era of multidrug resistance:minor differences in inoculum have dramatic effect on MIC determination. Antimicrob Agents Chemother 2018;62:e00433-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105823/

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!

Is cefepime an acceptable alternative to carbapenems in the treatment of cefepime susceptible extended spectrum beta-lactamase (ESBL) Gram-negatives?

What is the utility of nasal screen for methicillin-resistant Staphylococcus aureus (MRSA) in patients with skin and soft tissue infections?

In patients at high risk of MRSA infection (eg, prior history of MRSA colonization or infection, recent hospitalization/antibiotics, intravenous drug use, traumatic injury),1 particularly in the presence of an open wound or purulent drainage, a negative MRSA nasal screen does not rule out MRSA skin and soft tissue infection (SSTI), nor does a positive MRSA nasal screen reliably predict MRSA SSTI. In contrast, in low risk patients without severe disease, a negative MRSA nasal screen may be helpful in deescalating empiric anti-MRSA coverage.

The sensitivity of MRSA nasal screen by culture or PCR for SSTIs may be as low as 40%, higher among those with an ulcer (70%), with negative predictive values of 80% to 98% depending on the prevalence of MRSA in the population; its specificity is better (72% to 96%) with positive predictive values of 7% to 76%. 2

In a retrospective study involving 57 diabetic patients hospitalized with foot wound infection, the sensitivity of MRSA nasal screen was only ~40% with a negative predictive value of 80%. 3 Another study found a negative predictive value of ~90% for MRSA nasal screen among patients with a diabetic foot infection when MRSA isolation from wounds was uncommon (7.5%).4

Several reasons explain why patients with a negative MRSA nasal screen could still have MRSA SSTI, including colonization in other body sites known to harbor MRSA (eg, rectum, axilla, groin, oropharynx) 6-9 or direct wound contamination with MRSA in the absence of carriage, particularly in healthcare facilities.10

Bonus Pearl: Did you know that dogs, particularly those owned by healthcare workers, may also carry MRSA in their nostrils?.11,12

 

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References

  1. Stevens DL, Bisno AL, Chambers H, et al. Practice guidelines for the diagnosis and treatment of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014; 59:e10-52. https://www.idsociety.org/practice-guideline/skin-and-soft-tissue-infections/
  2. Carr AL, Daley MJ, Merkel KG, et al. Clinical utility of methicillin-resistant Staphylococcus aureus nasal screening for antimicrobial stewardship: A review of current literature. Pharmacotherapy 2018;38:1216-1228. https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/phar.2188
  3. Lavery LA, La Fonatine J, Bhavan K, et al. Risk factors for methicillin-resistant Staphylococcus aureus in diabetic foot infections. Diabet Foot Ankle 2014;5:10.3402/dfa.v5.23575. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984406/
  4. Mergenhagen KA, Croix M, Starr KE, et al. Utility of methicillin-resistant Staphylococcus aureus nares screening for patients with a diabetic foot infection. Antimicrob Agents Chemother 2020;64:e02213-19. https://pubmed.ncbi.nlm.nih.gov/31988097/  
  5. Currie A, Davis L, Odrobina E, et al. Sensitivities of nasal and rectal swabs for detection of methicillin-resistant Staphylococcus aureus colonization in an active surveillance program. J Clin Microbiol 2008;46:3101-3103. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2546770/
  6. Mermel LA, Cartony JM, Covington P, et al. Methicillin-resistant Staphylococcus aureus colonization at different body sites: a prospective, quantitative analysis. J Clin Microbiol 2011;49:1119-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067701/#B4
  7. Baker SE, Brecher SM, Robillar E, et al. Extranasal methicillin-resistant Staphylococcus aureus colonization at admission to an acute care Veterans Affairs Hospital. Infect Control Hosp Epidemiol 2010;31:42-6. https://pubmed.ncbi.nlm.nih.gov/19954335/
  8. Manian FA, Senkel D, Zack J et al. Routine screening for methicillin-resistant Staphylococcus aureus among patients newly admitted to an acute rehabilitation unit. Infect Control Hosp Epidemiol 2002;23:516-9. https://pubmed.ncbi.nlm.nih.gov/12269449/
  9. Lautenbach E, Nachamkin I, Hu B, et al. Surveillance culture for detection of methicillin-resistant Staphylococcus aureus: diagnostic yield of anatomic sites and comparison of provider- and patient-collected samples. Infect Control Hosp Epidemiol 2009;30:380-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665909/
  10. Boyce JM, Bynoe-Potter G, Chenevert C, et al. Environmental contamination due to methicillin-resistant Staphylococcus aureus: possible infection control implications 1997;18:622-7. https://pubmed.ncbi.nlm.nih.gov/9309433/  
  11. Boost MV, O’donaghue MM, James A. Prevalence of Staphylococcus aureus among dogs and their owners. Epidemiol Infect 2008;136:953-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870875/#ref017
  12. Manian FA. Asymptomatic carriage of mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA) in a pet dog associated with MRSA infection in household contacts. Clin Infect Dis 2003;36;e26-28. https://academic.oup.com/cid/article/36/2/e26/317343

 

 

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 is the utility of nasal screen for methicillin-resistant Staphylococcus aureus (MRSA) in patients with skin and soft tissue infections?

How does iron overload increase the risk of infection?

Iron overload, either primary (eg, hereditary hemochromatosis) or secondary (eg, hemolysis/frequent transfusion states), may increase the risk of infections through at least 2 mechanisms: 1. Enhancement of the virulence of the pathogen; and 2. Interference with the body’s normal defense system.1-7

Excess iron has been reported to enhance the growth of numerous organisms, ranging from bacteria (eg, Yersinia, Shigella, Vibrio, Listeria, Legionella, Ehrlichia, many other Gram-negative bacteria, staphylococci, streptococci), mycobacteria, fungi (eg, Aspergillus, Rhizopus/Mucor, Cryptococcus, Pneumocystis), protozoa (eg, Entamaeba, Plasmodium, Toxoplasma) and viruses (HIV, hepatitis B/C, cytomegalovirus, parvovirus). 1-7

In addition to enhancing the growth of many pathogens, excess iron may also inhibit macrophage and lymphocyte function and neutrophil chemotaxis .1,2 Iron loading of macrophages results in the inhibition of interferon-gamma mediated pathways and loss of their ability to kill intracellular pathogens such as Legionella, Listeria and Ehrlichia. 2

Not surprisingly, there are numerous reports in the literature of infections in hemochromatosis, including Listeria monocytogenes meningitis, E. Coli septic shock, Yersinia enterocolitica sepsis/liver abscess, Vibrio vulnificus shock (attributed to ingestion of raw oysters) and mucormycosis causing periorbital cellulitis. 2

Bonus pearl: Did you know that the ascitic fluid of patients with cirrhosis has low transferrin levels compared to those with malignancy, potentially enhancing bacterial growth and increasing their susceptibility to spontaneous bacterial peritonitis? 8

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 References

  1. Weinberg ED, Weinberg GA. The role of iron in infection. Curr Opin Infect Dis 1995;8:164-69. https://journals.lww.com/co-infectiousdiseases/abstract/1995/06000/the_role_of_iron_in_infection.4.aspx
  2. Khan FA, Fisher MA, Khakoo RA. Association of hemochromatosis with infectious diseases: expanding spectrum. Intern J Infect Dis 2007;11:482-87. https://www.sciencedirect.com/science/article/pii/S1201971207000811
  3. Thwaites PA, Woods ML. Sepsis and siderosis, Yersinia enterocolitica and hereditary haemochromatosis. BMJ Case Rep 2017. Doi:10.11336/bvr-206-218185. https://casereports.bmj.com/content/2017/bcr-2016-218185
  4. Weinberg ED. Iron loading and disease surveillance. Emerg Infect Dis 1999;5:346-52. https://wwwnc.cdc.gov/eid/article/5/3/99-0305-t3
  5. Matthaiou EI, Sass G, Stevens DA, et al. Iron: an essential nutrient for Aspergillus fumigatus and a fulcrum for pathogenesis. Curr Opin Infect Dis 2018;31:506-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579532/
  6. Alexander J, Limaye AP, Ko CW, et al. Association of hepatic iron overload with invasive fungal infection in liver transplant recipients. Liver Transpl 12:1799-1804. https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/lt.20827
  7. Schmidt SM. The role of iron in viral infections. Front Biosci (Landmark Ed) 2020;25:893-911. https://pubmed.ncbi.nlm.nih.gov/31585922/
  8. Romero A, Perez-Aurellao JL, Gonzalez-Villaron L et al. Effect of transferrin concentration on bacterial growth in human ascetic fluid from cirrhotic and neoplastic patients. J Clin Invest 1993;23:699-705. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2362.1993.tb01289.x

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 does iron overload increase the risk of infection?

Can I use fist bump when I greet my patients or coworkers in the hospital?

Fist bump may be a safer practice than handshake with respect to transfer of potential pathogens but should not be considered a “safe”’ alternative. Studies to date have demonstrated transfer of bacteria even with fist bump, albeit often at lower counts. 1-3

In an experimental study involving healthcare workers in a hospital,1 fist bump was still associated with bacterial colonization, albeit at levels 4 times less than that of palmar surfaces following handshakes. Smaller contact surface area and reduced total contact time were thought to contribute to lower risk of bacterial transfer via fist bump.

In another experiment involving E. coli, fist bump was associated with ~75% less transfer of bacteria relative to “moderate handshake”.2

Interestingly, in a 2020 study of 50 methicillin-resistant Staphylococcus aureus (MRSA)-colonized patients,3 the rate of MRSA isolated from the fist after a fist bump was not significantly lower than that of the dorsal surface of the hand after a handshake (16% vs 22%, P=0.6).  

In contrast, “cruise tap”, defined as contact between 2 knuckles alone, may be safer than fist bump. In the MRSA study above, cruise tap was associated with significantly lower rate of bacterial transfer compared to handshakes (8% vs 22%, P=0.02).3

Even a safer alternative is to avoid skin-to-skin contact altogether by using elbow bump, or no “bump” at all, particularly in the Covid-19 era!

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References

  1. Ghareeb PA, Bourlai T, Dutton W, et al. Reducing pathogen transmission in a hospital setting. Handshake verses fist bump: a pilot study. https://pubmed.ncbi.nlm.nih.gov/24144553/
  2. Mela S, Withworth DE. The fist bump: A more hygienic alternative to the handshake. Am J Infect Control 2014;42:916-7. http://www.apic.org/Resource_/TinyMceFileManager/Fist_bump_article_AJIC_August_2014.pdf
  3. Pinto-Herrera NC, Jones LD, Ha W, et al. Transfer of methicillin-resistant Staphylococcus aureus by first bump versus handshake. Infect Control Hospital Epidemiology 2020;41:962-64. https://pubmed.ncbi.nlm.nih.gov/32456719/

 

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!

Can I use fist bump when I greet my patients or coworkers in the hospital?

How often is Covid-19 in hospitalized patients complicated by bacterial infection?

Despite frequent use of empiric antibiotics in hospitalized patients with Covid-19,current data suggests a low rate of documented bacterial co-infection (BCI) in such patients. In fact, the overall reported rate of BCI in hospitalized patients with Covid-19 is generally no greater than 10%.1-3   It’s quite likely that most patients with Covid-19 and chest radiograph changes solely have a coronavirus (SARS-CoV-2) lung infection,4 particularly early in the course of the disease.  

A meta-analysis involving 30 studies (primarily retrospective) found that overall 7% of hospitalized Covid-19 patients had a laboratory-confirmed BCI with higher proportion among ICU patients (14%).Mycoplasma pneumoniae was the most common (42% of BCIs), followed by Pseudomonas aeruginosa and H. influenzae.  Notably, diagnosis of M. pneumoniae infection was based on antibody testing for IgM, which has been associated with false-positive results. Other caveats include lack of a uniform definition of respiratory tract infection among studies and potential impact of concurrent or prior antibiotic therapy on the yield of bacteriologic cultures. 5,6

A low prevalence of BCI was also found in a UK study involving 836 hospitalized Covid-19 patients: 3.2% for early BCI (0-5 days after admission) and 6.1% throughout hospitalization, including hospital-acquired infections.Staphylococcus aureus was the most common respiratory isolate among community-acquired cases, while Pseudomonas spp. was the predominant healthcare associated respiratory isolate.  Similarly, S. aureus. and Streptococcus pneumoniae were the most commonly isolated organisms from blind bronchoalveolar lavage of critically ill patients with Covid-19 during their first 5 days of admission, while gram-negative bacilli became dominant later during the hospitalization.8

The discordance between high rates of antibiotic treatment and confirmed bacterial co-infection in Covid-19 patients is likely a reflection of the difficulty in distinguishing Covid-19 pneumonia from bacterial pneumonia based on clinical or radiographic findings alone.

We need better tests to help distinguish bacterial vs Covid-19 pneumonia. Some have suggested using a low serum procalcitonin to help guide the withholding of or early discontinuation of antibiotics, especially in less severe Covid-19 cases. Formal studies of the accuracy of procalcitonin in Covid-19 are needed to test this hypothesis, given its suboptimal sensitivity in bacterial community-acquired pneumonia. 

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Reference

  1. Stevens RW, Jensen K, O’Horo JC, et al. Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care. Infect Control Hosp Epidemiology 2020. https://reference.medscape.com/medline/abstract/32703323
  2. Lansbury L, Lim B, Baskaran V, et al. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect 2020;81:266-75. https://pubmed.ncbi.nlm.nih.gov/32473235/
  3. Rawson TM, Moore LSP, Zhu N. Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis 2020 (Manuscrpit published online ahead of print 2 June ). Doi:10.1093/cid/ciaa530.https://pubmed.ncbi.nlm.nih.gov/32358954/
  4. Metlay JP, Waterer GW. Treatment of community-acquired pneumonia during the coronavirus 2019 (COVID-19) pandemic. Ann Intern Med 2020; 173:304-305. https://pubmed.ncbi.nlm.nih.gov/32379883/
  5. Chang CY, Chan KG. Underestimation of co-infections in COVID-19 due to non-discriminatory use of antibiotics. J Infect 2020;81:e29-30. https://pubmed.ncbi.nlm.nih.gov/32628960/
  6. Rawson TM, Moore LSP, Zhu N, et al. Bacterial pneumonia in COVID-19 critically ill patients: A case series. Reply letter. Clin Infect Dis 2020. https://academic.oup.com/cid/advance-
  7. Hughes S, Troise O, Donaldson H, et al. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting. Clin Microbiol Infect 2020. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30369-4/fulltext
  8. Dudoignon E, Camelena F, Deniau B, et al. Bacterial pneumonia in COVID-19 critically ill patients: A case series. Clin Infect Dis 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337703/

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 often is Covid-19 in hospitalized patients complicated by bacterial infection?

How might categorizing severity of illness help in the management of my patient with Covid-19?

Although the criteria for Covid-19 severity of illness categories may overlap at times or vary across guidelines and clinical trials, I have found those published in the National Institute of Health (USA) Covid-19 Treatment Guidelines most useful and uptodate.1  Keep in mind that the primary basis for severity categories in Covid-19 is the degree by which it alters pulmonary anatomy and physiology and respiratory function (see my table below).

The first question to ask when dealing with Covid-19 patients is whether they have any signs or symptoms that can be attributed to the disease (eg, fever, cough, sore throat, malaise, headache, muscle pain, lack of sense of smell). In the absence of any attributable symptoms, your patient falls into “Asymptomatic” or “Presymptomatic” category.  These patients should be monitored for any new signs or symptoms of Covid-19 and should not require additional laboratory testing or treatment.

If symptoms of Covid-19 are present (see above), the next question to ask is whether the patient has any shortness of breath or abnormal chest imaging. If neither is present, the illness can be classified as “Mild” with no specific laboratory tests or treatment indicated in otherwise healthy patients. These patients may be safely managed in ambulatory settings or at home through telemedicine or remote visits. Those with risk factors for severe disease (eg, older age, obesity, cancer, immunocompromised state), 2 however, should be closely monitored as rapid clinical deterioration may occur.

Once lower respiratory tract disease based on clinical assessment or imaging develops, the illness is no longer considered mild. This is a good time to check a spot 02 on room air and if it’s 94% or greater at sea level, the illness qualifies for “Moderate” severity. In addition to close monitoring for signs of progression, treatment for possible bacterial pneumonia or sepsis should be considered when suspected. Corticosteroids are not recommended here and there are insufficient data to recommend either for or against the use of remdesivir in patients with mild/moderate Covid-19.

Once spot 02 on room air drops below 94%, Covid-19 illness is considered “Severe”; other parameters include respiratory rate >30, Pa02/Fi02 < 300 mmHg or lung infiltrates >50%. Here, patients require further evaluation, including pulmonary imaging, ECG, CBC with differential and a metabolic profile, including liver and renal function tests. C-reactive protein (CRP), D-dimer and ferritin are also often obtained for their prognostic value. These patients need close monitoring, preferably in a facility with airborne infection isolation rooms.  In addition to treatment of bacterial pneumonia or sepsis when suspected, consideration should also be given to treatment with corticosteroids. Remdesivir is recommended for patients who require supplemental oxygen but whether it’s effective in those with more severe hypoxemia (eg, those who require oxygen through a high-flow device, noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation-ECMO) is unclear. Prone ventilation may be helpful here in patients with refractory hypoxemia as long as it is not used to avoid intubation in those who otherwise require mechanical ventilation.

“Critical” illness category is the severest forms of Covid-19 and includes acute respiratory distress syndrome (ARDS), septic shock, cardiac dysfunction and cytokine storm. In addition to treatment for possible bacterial pneumonia or sepsis when suspected, corticosteroids and supportive treatment for hemodynamic instability and ARDS, including prone ventilation, are often required. The effectiveness of remdesivir in patients with severe hypoxemia (see above) is unclear at this time.

 

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 References

  1. NIH COVID-19 Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov/. Accessed Aug 27, 2020.
  2. CDC. Covid-19.  https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html/. Accessed Aug 27, 2020.  

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 categorizing severity of illness help in the management of my patient with Covid-19?

Does tuberculosis (TB) increase the risk of cancer?

Ample reports in the literature suggest that TB is associated with the development of certain cancers, including lung cancer, lymphoma and urothelial cancers of the genitourinary tract. 1-5

A 2010 literature review including 9 retrospective studies found that several (not all) studies reported a significant association between prior history of TB and lung cancer, with odds ratios as high as 20.5 ( C.I. 8.1-51.8) at 1-5 years following TB.1 One study involving non-smoking women found a lung cancer (mostly adenocarcinoma) prevalence of 18% among those with prior history of TB (O.R. 5.9, CI 1.3-25.9).5 Cases of “pyothorax-associated lymphoma” of the pleural cavity have also been attributed to TB diagnosed as remote as 40 years or greater before the diagnosis of cancer.1

Urinary tuberculosis was associated with the development of urothelial carcinoma (including bladder, ureteral, renal pelvic transitional cell carcinoma) but not renal cell carcinoma in a nationwide cohort study from Taiwan (hazard ratio 3.4, C.I. 2.0-5.7). 2 The mean interval between the index date of TB and the diagnosis of urinary tract cancer was about 5 years in this study.

Several potential mechanisms for TB predisposing to malignancy have been proposed.1,6 Chronic inflammation associated with higher rate of cell turnover may increase the risk of genetic mutation and subsequent malignancy, as observed in other conditions such as gastroesophageal reflux disease and esophageal cancer and inflammatory bowel disease and colon cancer. The ability of Mycobacterium tuberculosis to induce DNA damage, inhibit apoptosis and augment concentrations of leukotrienes, prostaglandins and vascular endothelial growth factors have also been implicated.

And don’t forget that active TB may not only coexist with but may also mimic malignancy (see related pearl on P4P).

 

Bonus Pearl: Did you know that the association of TB with cancer was first described in 1810 by Gaspard Laurent Bayle, a French physician who considered “cavitation cancereuse” as a distinct TB category? 1

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 References

  1. Falagas ME, Kouranos VD, Athanassa Z, et al. Tuberculosis and malignancy. Q J Med 2010;103: 461-87. Doi:10.1093/qjmed/hcq068 https://pubmed.ncbi.nlm.nih.gov/20504861/
  2. Lien YC, Wang JY, Lee MC, et al. Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan. B J Cancer 2013;109:2933-2940. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844900/
  3. Chin SN, Foster T, Char G, et al. Concomitant urothelial cancer and renal tuberculosis. Case Reports in Urology. Volume 2014, Aricle ID 625153. https://www.hindawi.com/journals/criu/2014/625153/
  4. Dobler CC, Cheung K, Nguyen J, et al. Risk of tuberculosis in patients with solid cancers and haematological malignancies: a systematic review and meta-analysis. Eur Respir J 2017;50:1700157. https://doi.org/10.1183/13993003.00157-2017.
  5. Ko YC, Lee CH, Chen MJ, et al. Risk factors for primary lung cancer amng non-smoking women in Taiwan. Int J Epidemiol 1997;26:24-31. https://pubmed.ncbi.nlm.nih.gov/9126500/
  6. Ling S, Chang X, Schultz L, et al. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. Cancer Res 2011;71:3812-21. https://pubmed.ncbi.nlm.nih.gov/21512138/ 

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 tuberculosis (TB) increase the risk of cancer?