200 pearls and counting! Take the Pearls4Peers quiz #2!

Multiple choice (choose 1 answer)
1. Which of the following classes of antibiotics is associated with peripheral neuropathy?
a. Penicillins
b. Cephalosporins
c. Macrolides
d. Quinolones



2. The best time to test for inherited thrombophilia in a patient with acute deep venous thrombosis is…
a. At least 1 week after stopping anticoagulants and a minimum of 3 months of anticoagulation
b. Just before initiating anticoagulants
c. Once anticoagulation takes full effect
d. Any time, if suspected



3. All the following is true regarding brain MRI abnormalities following a seizure, except…
a. They are observed following status epilepticus only
b. They are often unilateral
c. They may occasionally be associated with leptomeningeal contrast enhancement
d. Abnormalities may persist for weeks or months



4. Which of the following is included in the quick SOFA criteria for sepsis?
a. Heart rate
b. Serum lactate
c. Temperature
d. Confusion



5. All of the following regarding iron replacement and infection is true, except…
a. Many common pathogens such as E.coli and Staphylococcus sp. depend on iron for their growth
b. Association of IV iron replacement and increased risk of infection has not been consistently demonstrated
c. A single randomized-controlled trial of IV iron in patients with active infection failed to show increased infectious complications or mortality with replacement
d. All of the above is true


True or false

1. Constipation may precede typical manifestations of Parkinson’s disease by 10 years or more
2. Urine Legionella antigen testing is >90% sensitive in legionnaire’s disease
3. Spontaneous coronary artery dissection should be particularly suspected in males over 50 years of age presenting with acute chest pain
4. Urine dipstick for detection of blood is >90% sensitive in identifying patients with rhabdomyolysis and CK >10,000 U/L
5. Diabetes is an independent risk factor for venous thrombophlebitis




Answer key
Multiple choice questions:1=d; 2=a;3=a;4=d;5=c
True or false questions:1=True; 2,3,4,5=False


200 pearls and counting! Take the Pearls4Peers quiz #2!

Should I use qSOFA to screen for severe infections in my non-ICU patient?

Sepsis-3 qSOFA criteria—systolic BP ≤100 mg Hg, altered mental state, and RR≥22, with ≥2 considered positive— should NOT be used as either a screening or diagnostic tool for sepsis until properly designed prospective studies validate its utility.1

An important issue with qSOFA is its poor sensitivity for identifying patients with sepsis and its complications.  In a retrospective study of over 30,000 hospitalized patients suspected of infection in the emergency department or hospital wards, qSOFA ≥2 had a sensitivity of only 54% and specificity of 67% for in-hospital mortality or ICU transfer vs a much higher sensitivity of 91% but lower specificity of 13% for SIRS ≥2. Interestingly, most patients in this study met qSOFA criteria only 5 h before the studied outcome vs 17 h for SIRS ≥2 criteria.2

In another retrospective study of over 15,000 patients presenting to the Emergency Department with suspected infection, qSOFA ≥2 had a sensitivity of  49% and a specificity of 79% for hospital mortality vs  84% and 35% for SIRS≥2, and 65% and 74% for “severe sepsis” (Sepsis-2), respectively.3

So, using qSOFA alone to decide who needs prompt management of their infection (eg, blood cultures, serum lactate, antibiotics, fluids) may delay timely intervention in a substantial proportion of patients with infection that may become complicated by ICU transfer or death.  As is usually the case in medicine, it pays to look at the entire picture!


  1. Machado FR, Nsutebu E, AbDulaziz S, et al. Sepsis 3 from the perspective of clinicians and quality improvement initiatives. J Crit Care 2017:40: 315-17. https://www.ncbi.nlm.nih.gov/pubmed/28478045
  2. Churpek MM, Synder A, Han X, et al. Quick sepsis-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores for detecting clinical deterioration n infected patients outside the intensive care unit. Am J Respir Crit Care Med 2017; 195: 906-11. https://www.ncbi.nlm.nih.gov/pubmed/27649072
  3. Lembke K, Parashar S, Simpson S. Sensitivity and specificity of SIRS, qSOFA, and severe sepsis for mortality of patients presenting to the emergency department with suspected infection. Chest Annual Meeting, Toronto, October 29, 2017. http://dx.doi.org/10.1016/j.chest.2017.08.427
Should I use qSOFA to screen for severe infections in my non-ICU patient?

In my patient with sepsis, is administration of proper antibiotics within an hour compared to 1-3 hours associated with better outcome?

The weight of the evidence based on observational studies suggests that the earlier the antibiotics are administered even within the first 3 hrs of the diagnosis of sepsis,  the better the patient outcome.

A 2017 study analyzing data from 37 studies (primarily observational) involving ~20,000 patients with severe sepsis and/or shock found a 10% increase in hospital mortality for every 1 hr delay in initiation of antibiotic therapy1. Two multicenter studies (1 in Pennsylvania2 and another in California3) and a New York State data base study involving patients with severe sepsis or septic shock4 similarly reported decreased survival with each 1- hr delay in antibiotic therapy. Another study of patients with severe sepsis found that each hour delay in first antibiotic dose administration was associated with an 8% increased risk of progression to shock5.

Despite the emphasis on the timing of the first dose of antibiotics, let’s not forget that the second dose of antibiotics should also be given on time in sepsis; a >25% delay is associated with increased mortality, length of stay and requirement for mechanical ventilation6.

So, yes, antibiotics should be given within 3 hours of diagnosis of sepsis, but within an hour followed by a timely second dose is even better!

Final Pearl: Did you know that sepsis is the 3rd leading cause of death in the US and contributes to 1 in every 2 to 3 hospital deaths7?



  1. Kalil AC, Johnson DW, Lisco SJ, et al. Early goal-directed therapy for sepsis: a novel solution for discordant survival outcomes in clinical trials. Crit Care Med 2017;45:607-14. https://www.ncbi.nlm.nih.gov/pubmed/28067711
  2. Seymour CW, Kahn JM, Martin-Gill, et al. Delays from first medical contact to antibiotic administration for sepsis. Crit Care Med 2017;45:759-65. https://insights.ovid.com/pubmed?pmid=28234754
  3. Liu VX, Fielding-Singh V, Greene JD, et al. Th timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit care Med 2017; 196;858-63. https://www.ncbi.nlm.nih.gov/pubmed/28345952
  4. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017;376:2235-44. http://www.nejm.org/doi/full/10.1056/NEJMoa1703058
  5. Whiles BB, Deis AS, Simpson SQ. Increased time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients. Crit Care Med 2017; 45:623-29. https://www.ncbi.nlm.nih.gov/pubmed/28169944
  6. Leisman D, Huang V, Zhou Q, et al. Delayed second dose antibiotics for patients admitted from the emergency department with sepsis: prevalence, risk factors, and outcomes. Crit Care Med 2017;45:956-65. https://www.ncbi.nlm.nih.gov/pubmed/28328652
  7. https://www.ecri.org/components/HRC/Documents/Sepsis%20at%20a%20Glance.pdf


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In my patient with sepsis, is administration of proper antibiotics within an hour compared to 1-3 hours associated with better outcome?

Are two sets of blood cultures adequate for evaluation of bacteremia in my febrile patient?

For great majority of patients, more than 2 sets of blood cultures is not likely to significantly improve the yield of detecting bacteremia. 

Although a 2004 report suggested that 2 sets of blood cultures over 24 h period had a sensitivity of only 80% for bacteremia, several other studies have found much higher sensitivities, ranging from ~90%- 99% 2-3. When broken down by organism, sensitivity of 2 sets of blood cultures may be highest for Staphylococcus aureus (97%), followed by E. coli (91%), and Klebsiella pneumoniae (90%) 2.  The Clinical and Laboratory Standards Institute guidelines recommend paired blood culture sets (each set with 2 bottles, 10 ml of blood in each) to detect about 90-95% of patients with documented bacteremia, and 3 sets for 95-99% detection rate 4.

It seems prudent to strike a balance between drawing more than 2 sets of blood cultures—with its attendant risk of picking up contaminants— and what may be a definite but small incremental increase in the rate of detection of true bacteremia.

Whatever you do,  please don’t order only 1 set of blood cultures! Aside from its generally low yield, when positive it may be difficult to distinguish contaminants from true invaders.



  1. Cockerill FR, Reed GS, Hughes JG, et al. Clinical comparison of BACTEC 9240 Plus Aerobic/F resin bottles and the Isolator aerobic cultures. Clin Infect Dis 2004;38:1724-30. https://www.ncbi.nlm.nih.gov/pubmed/9163464
  2. Lee A, Mirrett S, Reller LB, et al. Detection of bloodstream infections in adults: how many cultures are needed? J Clin Microbiol 2007; 45:3546-48. http://jcm.asm.org/content/45/11/3546
  3. Towns ML, Jarvis WR, Hsueh PR. Guidelines on blood cultures. J Microbiol Immunol Infect 2010;43:347-49. https://www.ncbi.nlm.nih.gov/pubmed/20688297
  4. Weinstein MP, Reller LB, Murphy JR, et al. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and eipidemiologic observations. Rev Infect Dis 1982;5:35-53. https://www.ncbi.nlm.nih.gov/pubmed/6828811
Are two sets of blood cultures adequate for evaluation of bacteremia in my febrile patient?

In my critically ill patient with infection, is capillary refill time greater than 2 seconds indicative of septic shock?

The data on the performance of capillary refill time (CRT) in adults is quite limited and what’s available does not suggest that the commonly cited 2 seconds cutoff is useful in assessing peripheral perfusion in critically ill adults1,2.

For example, a large study involving 1000 healthy adults reported that 45% of participants had a CRT > 2 seconds3.  Age also affects CRT with its 95 percentile upper limits reaching 4.5 seconds among healthy adults >60 y old3

Among patients with septic shock, a baseline median CRT of 5 seconds has been reported.  Values <5.0 seconds within 6 hours of treatment of septic shock has also been highly associated with successful resuscitation even before normalization of lactate levels4.

For these reasons, if CRT is used as a measure of peripheral perfusion in critically ill adults, a cut off of 5 seconds, not 2 seconds, may be more appropriate. But just like many other diagnostic tests, CRT should never be interpreted in isolation from other clinical parameters. 


  1. Lima A, Bakker J. Clinical Assessment of peripheral circulation. Critical Care 2015:21: 226-31. https://www.ncbi.nlm.nih.gov/pubmed/25827585  
  2. Lewin J, Maconochie I. Capillary refill time in adults. Emerg Med J 2008;25:325-6. https://www.ncbi.nlm.nih.gov/pubmed/18499809
  3. Anderson B, Kelly AM, Kerr D, et al. Impact of patient and environmental factors on capillary refill time in adults. Am J Emerg Med 2008;26:62-65. https://www.ncbi.nlm.nih.gov/pubmed/18082783
  4. Hernandez G, Pedreros C, Veas E, et al. Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study. J Crit Care 2012;27:283-288.  https://www.ncbi.nlm.nih.gov/pubmed/21798706
In my critically ill patient with infection, is capillary refill time greater than 2 seconds indicative of septic shock?

Should male patients with suspected urinary tract infection routinely undergo a prostate exam?

Yes! That’s because any urinary tract infection (UTI) in men has the potential for prostatic involvement1 —-as high as 83% by one report2.  

To make the matters more confusing, patients with acute bacterial prostatitis (ABP) often present with symptoms just like those of UTI such as urinary frequency, dysuria, malaise, fever, and myalgias3.  In the elderly, atypical presentation is not uncommon (eg, confusion, incontinence, fall)4.  Under these circumstances, bacteriuria and pyuria may also be related to ABP and the prostate exam should be an important part of your evaluation.

Although the sensitivity of prostate tenderness on digital rectal exam varies widely for ABP (9%-100%), a painful exam should raise suspicion for ABP, and by itself may be an independent predictor for clinical and bacteriologic failure of therapy1. Along with tenderness, fluctuance of prostate, particularly in the setting of voiding difficulties and longer duration of symptoms, may also suggest the presence of prostatic abscess5,6

But be gentle when performing a prostate exam and don’t massage it because you could potentially cause bacteremia and worsening of sepsis!1,7


  1. Etienne M, Chavanet P, Sibert L, et al. Acute bacterial prostatitis: heterogeneity in diagnostic criteria and management. Retrospective multicentric analysis of 371 patients diagnosed with acute prostatitis. BMC Infectious Diseases 2008;8:12. https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/1471-2334-8-12?site=bmcinfectdis.biomedcentral.com
  2. Ulleryd P, Zackrisson B, Aus G, et al. Prostatic involvement in men with febrile urinary tract infection as measured by serum prostate-specific antigen and transrectal ultrasonography. BJU Int 1999;84:470-4. http://onlinelibrary.wiley.com/doi/10.1046/j.1464-410x.1999.00164.x/pdf
  3. Krieger JN, Nyberg L, Nickel JC. NIH consensus definition and classification. JAMA 1999;282:236-37. http://jamanetwork.com/journals/jama/article-abstract/1030245
  4. Harper M, Fowlis. Management of urinary tract infections in men. Trends in Urology Gynaecology & Sexual Health. January/February 2007. http://onlinelibrary.wiley.com/doi/10.1002/tre.8/pdf
  5. Lee DS, Choe HS, Kim HY, et al. Acute bacterial prostatitis and abscess formation. BMC Urology 2016;16:38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936164/
  6. Oliveira P, Andrade JA, Porto HC, et al. Diagnosis and treatment of prostatic abscess. International Braz J Urol 2003;29: 30-34. http://www.scielo.br/pdf/ibju/v29n1/v29n1a06.pdf
  7. Lipsky BA, Byren I, Hoey CT. Treatment of bacterial prostatitis. Clin Infect Dis 2010; 50:1641-52. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/50/12/10.1086/652861/2/50-12-1641.pdf?Expires=1501276981&Signature=X5SLG2Pq5IpbsjDigES70~Nk6g5onrPwhrFClIAFIvdFiEyCsc1~2aWN9LpR~56DlGqxjmZuIX33JtOn-tURGG0puEwnulZDEDXFjFt6fXucSgtKMDOmGXSKoMvgtPZe86nduJMNDuaifEZXITpDXjSLXAJXVamJ-bbSUMEqSysnCCMxZx~5MaAb6WEikqG5Vi~Xnp58fXABG7BJS~ZFRn2~BTlVEEvmIIDDaY5cJjgUcN7SNOhs0rOS71WzlNtlXSqnXffZEdFSJ~iDcbyRL-wh-9OZqZ2fwojdk8Be89DsKJg8rIh8dlLc5O7v92yL~cZ6iieiP8xTGOU-21tVeA__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q
Should male patients with suspected urinary tract infection routinely undergo a prostate exam?

What is the mechanism of anemia of chronic disease in my patient with rheumatoid arthritis?

Anemia of chronic disease (ACD)—or more aptly “anemia of inflammation”— is the second most common cause of anemia after iron deficiency and is associated with numerous acute or chronic conditions (eg, infection, cancer, autoimmune diseases, chronic organ rejection, and chronic kidney disease)1.

The hallmark of ACD is disturbances in iron homeostasis which result in increased uptake and retention of iron within cells of the reticuloendothelial system, with its attendant diversion of iron from the circulation and reduced availability for erythropoiesis1. More specifically, pathogens, cancer cells, or even the body’s own immune system stimulate CD3+ T cells and macrophages to produce a variety of cytokines, (eg, interferon-ɤ, TNF-α, IL-1, IL-6, and IL-10) which in turn increase iron storage within macrophages through induction of expression of ferritin, transferrin and divalent metal transporter 1.

In addition to increased macrophage storage of iron, ACD is also associated with IL-6-induced synthesis of hepcidin, a peptide secreted by the liver that decreases iron absorption from the duodenum and its release from macrophages2. TNF-α and interferon-ɤ also contribute to ACD by inhibiting the production of erythropoietin by the kidney.  Finally, the life span of RBCs is adversely impacted in AKD due to their reduced deformability and increased adherence to the endothelium in inflammatory states3.

Of interest, it is often postulated that by limiting access to iron through inflammation, the body hinders the growth of pathogens by depriving them of this important mineral2.



  1. Weiss, G and Goodnough, L. Anemia of chronic disease. N Engl J Med 2005; 352; 1011-23. http://www.med.unc.edu/medclerk/medselect/files/anemia2.pdf
  2. D’Angelo, G. Role of hepcidin in the pathophysiology and diagnosis of anemia. Blood Res 2013; 48(1): 10-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624997/pdf/br-48-10.pdf                                                                                                                                  
  3. Straat M, van Bruggen R, de Korte D, et al. Red blood cell clearance in inflammation. Transfus Med Hemother 2012;39:353-60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678279/pdf/tmh-0039-0353.pdf


Contributed by Amir Hossein Ameri, Medical Student, Harvard Medical School


What is the mechanism of anemia of chronic disease in my patient with rheumatoid arthritis?