Can my patient contract influenza more than once in a season?

It’s not common but reinfection with influenza can definitely occur, either due to the same viral strain, or due to a different one altogether.

One study reported influenza reinfection due to H1N1 in otherwise healthy patients within 12-20 days of the original infection after an apparent period of full recovery. 1 There was no evidence of resistance to oseltamivir among isolates and all patients recovered after the second infection.

Reinfection with the same viral strain within 2-3 weeks of the initial bout of influenza shouldn’t be too surprising since it takes 4-7 weeks for antibody response to the infection to peak. 2 Reexposure to the same circulating strain of influenza virus (the season can last 6 weeks or longer) can then result in reinfection when the body hasn’t had enough time to make significant amount of protective antibodies following the first infection.

Another explanation is that more than 1 strains of influenza virus often circulate during any given season.   This places patients at risk of infection due to strains of influenza virus that do not confer significant cross-immunity between each other,  resulting in getting “the flu twice in 1 season.” 3

References

  1. Perz CM, Ferres M, Labarca JA. Pandemic (H1N1) 2009 reinfection, Chile. Emerg Infect Dis 2010;16:156-57. https://wwwnc.cdc.gov/eid/article/16/1/pdfs/09-1420.pdf
  2. Treanor JJ. Influenza viruses, including avian influenza and swine influenza. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 7th ed. New York: Elsevier; 2010. p 2265-2293.
  3. Rettner R. Can you get the flu twice in 1 season? Scientific American, LiveScience, February 4, 2018. https://www.scientificamerican.com/article/can-you-get-the-flu-twice-in-1-season/ . Accessed February 5, 2018.

 

Can my patient contract influenza more than once in a season?

What does an “indeterminate” result in QuantiFERON Gold in-Tube test for latent tuberculosis really mean?

Anindeterminate” QuantiFeron Gold in-Tube (QFT-IT) simply means the result can’t be interpreted. It does NOT mean “intermediate” or “borderline positive”!

Although there are several reasons for an indeterminate QFT-IT, a common explanation is an immunocompromised state involving inadequate T-cell response (eg, corticosteroids, HIV, cancer). Improper storage of tubes and specimen handling, baseline elevated interferon (IFN)-ɣ due to heterophile antibodies, recovery phase of an infection or vaccination may also be associated with indeterminate QFT-IT results. 1,2 For these reasons, the test should be repeated for confirmation.

It all makes more sense if we understand the basis for the test. QFT-IT involves blood obtained in 3 separate test tubes:

  • Tube 1: Contains only the patient’s blood with nothing added (NIL) (“Negative control”)
  • Tube 2: Contains non-specific mitogens that stimulate patient’s T-cells (“Positive control”)
  • Tube 3: Contains specific TB antigens

Since QFT-IT is an IFN- ɣ release assay, IFN- ɣ is measured in each tube after 16-24 h incubation. A negative QFT-IT is when there is not much difference between IFN- ɣ levels in negative control and TB tubes (“TB-[minus]NIL”) AND the positive control works (“MITOGEN-[minus]NIL” is elevated).

You can now see why a negative result in the TB tube doesn’t mean much (ie, the result is “indeterminate”) when the T-cells don’t respond to non-specific antigens.  This situation is analogous to calling a PPD “negative” when a patient is anergic!

References

  1. Herrera V, Yeh E, Murphy K, et al. Immediate incubation reduces indeterminate results for QuantiFERON-TB Gold in-Tube assay. J Clin Microbiol 2010;48:2672-2676. http://jcm.asm.org/content/48/8/2672.full
  2. Bui DHP, Cruz AT, Graviss EA. Indeterminate QuantiFERON-TB Gold in-Tube assay results in children. Ped Infect Dis J 2014; 33: 220-22. https://www.ncbi.nlm.nih.gov/pubmed/24413410
What does an “indeterminate” result in QuantiFERON Gold in-Tube test for latent tuberculosis really mean?

Can I rely on the physical exam to rule out symptomatic urinary tract infection (UTI) in my hospitalized patient?

Suprapubic tenderness, costovertebral angle tenderness (CVAT) and fever seem to be more helpful in ruling in than ruling out infection. And, before you hang your hat on the available data, remember that most of the studies involve women with uncomplicated UTI in primary care or emergency department settings, not our older hospitalized patients at risk of complicated infections.  With these caveats in mind….

Suprapubic tenderness has been reported in only about 15-20% of women with acute cystitis. 1

CVAT has been associated with symptomatic UTI but with only a weakly positive LR (1.7, 1.1-2.5), and an insignificant negative LR. 2  In a single center study involving hospitalized patients (mean age 53 y), CVAT was either absent or “obscure” in about 10% of patients with acute pyelonephritis on CT.3

Fever was associated with a positive likelihood ratio (1.6, 1.0-2.6) by 1 systematic study 2 but not another, 4 with insignificant negative LR in both. Fever was also absent in about 10% of hospitalized patients with pyelonephritis in the single center study above.3

So, when evaluating a patient with possible symptomatic UTI (particularly cystitis), the presence of physical exam findings  may be more helpful than their absence.

References

  1. Kurowski K. The woman with dysuria. Am Fam Physician 1998, 57:2155-2164. https://www.aafp.org/afp/1998/0501/p2155.html
  2. Bent S, Nallamothu BK, Simel DL, et al. Does this woman have an acute uncomplicated urinary tract infection? JAMA 2002;287:2701-2710. https://www.ncbi.nlm.nih.gov/pubmed/12020306
  3. Lee Y-J, Cho S, Kim SR. Unilateral and bilateral acute pyelonephritis: differences in clinical presentation, progress and outcome. Postgrad Med 2014;90:80-85. https://www.ncbi.nlm.nih.gov/pubmed/24255118
  4. Median-Bombardo D, Jover-Palmer A. Does clinical examination aid in the diagnosis of urinary tract infections in women? A systematic review and meta-analysis. BMC Family Practice 2011;12:111. https://bmcfampract.biomedcentral.com/articles/10.1186/1471-2296-12-111
Can I rely on the physical exam to rule out symptomatic urinary tract infection (UTI) in my hospitalized patient?

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!

My previously healthy 55 year old patient is admitted with a respiratory tract infection and a respiratory rate of 22 breaths/min. Should I be concerned?

Any respiratory rate (RR) greater than 20/min in an adult patient may be cause for concern, particularly in the setting of potentially serious disease and absence of an obvious cause such as pain or fever.

Our patient’s RR is outside the commonly cited normal range of 12-20/min. It indicates increased alveolar ventilation which may in turn be caused by hypoxia, hypercapnea, and metabolic acidosis, all portending possibly poor outcome, if left untreated.1It’s no surprise that an abnormal RR is often the first sign of clinical deterioration.2 RR is also the least likely of the vital signs to be affected by polypharmacy (eg, NSAIDs affecting temperature, beta-blockers affecting heart rate and blood pressure). 

Another reason for not dismissing an RR of 22 in our patient is the common practice of guessing rather than measuring the RR by healthcare providers in part likely due to the  more “labor-intensive” nature of measuring RRs compared to other vital signs and lack of appreciation for its importance in assessing severity of disease. 1 Of note, in an experimental study of doctors viewing videos of mock patients, over 50% failed to detect abnormal RR when using the “spot” technique of estimating without a timer.3 Even when presented with a RR of 30/min, over 20% of doctors reported it as normal (12-20/min)!

Final tidbit: Do you want to know what a RR of 20/min really feels like? Take a breath every 3 seconds.  If you are like most, it doesn’t feel “normal”!

References
1. Cretikos MA, Bellomo R, Hillman K. Respiratory rate: the neglected vital sign. MJA 2008;188:657-59. https://www.ncbi.nlm.nih.gov/pubmed/18513176
2. Flenady T, Dwer T, Applegarth J. Accurate respiratory rates count: So should you! Australas Emerg Nurs J 2017; 20:45-47. https://www.ncbi.nlm.nih.gov/pubmed/28073649
3. Philip KEJ, Pack E, Cambiano V et al. The accuracy of respiratory rate assessment by doctors in a London teaching hospital: a cross-sectional study. J Clin Monit Comput2015;29:455-60. https://www.ncbi.nlm.nih.gov/pubmed/25273624

My previously healthy 55 year old patient is admitted with a respiratory tract infection and a respiratory rate of 22 breaths/min. Should I be concerned?

My diabetic patient complains of new onset tingling, burning, and numbness in her feet and ankles while taking levofloxacin for sinusitis. Could it be the antibiotic?

Although there are numerous culprits in peripheral neuropathy (PN), fluoroquinolones (FQs) are increasing reported as a potential cause, affecting about 1% of patients. 1

Besides many case reports, couple of large epidemiologic studies support the association between PN and FQs. A case-control pharmacoepidemiologic study of a cohort of men aged 45-80 years without diabetes found that current users of FQs were nearly twice as likely to develop PN (RR 1.83, 95% C.I. 1.49-2.27), with the highest risk found among current new users of FQ.2 The risk appeared similar among the 3 most commonly used FQs (levofloxacin, ciprofloxacin, moxifloxacin).

Another epidemiologic study with “pharmacovigilance analysis” based on the FDA Adverse Event Reporting System found significant disproportionality of PN for FQs compared to many other antibiotics. 3 The median onset of PN after exposure to FQ was 4 days (range 0-91). Contrary to initial reports of the mild and reversible course of FQ-associated PN, 1 study reported that 58% of patients had symptoms lasting greater than 1 year.4`

These findings prompted the FDA to update its boxed warnings for FQs in 2016 to stress the potential rapidity of onset and permanence of FQ-associated PN while strongly discouraging their use in conditions for which alternative therapy exists, such as in acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated UTI.5

So while our patient may have other causes for her neurologic complaints, FQ exposure should also be in the differential!

References

  1. Dudewich M, Danesh A, Onyima C, et al. Intractable acute pain related to fluoroquinolone-induced peripheral neuropathy. J Pain Pall Care Pharmacotherapy 2017;31:144-7. https://www.ncbi.nlm.nih.gov/pubmed/28358229
  2. Etminan M, Brophy JM, Samii A. Oral fluoroquinolone use and risk of peripheral neuropathy: A pharmacoepidemiologic study.Neurology 2014;83:1261-63. https://www.ncbi.nlm.nih.gov/pubmed/25150290
  3. Ali AK. Peripheral neuropathy and Guillain-Barre syndrome risks associated with exposure to systemic fluorquinolones: a pharmacovigilance analysis. Ann Epidemiol 2014; 24:279-85. https://www.ncbi.nlm.nih.gov/pubmed/24472364
  4. Francis JK, Higgins E. Permanent peripheral neuropathy: A case report on a rare but serious debilitating side-effect of fluroquinolone administration. Journal Investigative Medicine High Impact Case Reports 2014; 1-4. DOI:10.1177/2324709614545225. https://www.ncbi.nlm.nih.gov/pubmed/26425618
  5. FDA.https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm.  Accessed December 8, 2017.
My diabetic patient complains of new onset tingling, burning, and numbness in her feet and ankles while taking levofloxacin for sinusitis. Could it be the antibiotic?

My elderly patient on chronic warfarin with recent hospitalization for soft tissue infection is now readmitted with gastrointestinal bleed and a newly-discovered supra-therapeutic INR? Why did her INR jump?

Assuming no recent changes in the dose of warfarin, one potential culprit may be her recent antibiotic exposure. Of the long list of antibiotics associated with elevated INR, quinolones (e.g. ciprofloxacin, levofloxacin), trimethoprim-sulfamethoxazole, macrolides (e.g. azithromycin), and azole antifungals (e.g. fluconazole) are generally thought to carry the highest risk of warfarin toxicity, while amoxacillin and cephalexin may be associated with a more modest risk. 1-3

Other drugs such as amiodarone (Did she have atrial fibrillation during her recent hospitalization?), acetaminophen (Has she been receiving at least 2 g/day for several consecutive days?), and increasing dose of levothyroxine (Was she thought to be hypothyroid recently?) should also be considered.3,4

Also remember to ask about herbal supplements (eg, boldo-fenugreek, dong quai, danshen) that may potentiate the effect of warfarin. 3 Of course, poor nutrition in the setting of recent illness might have also played a role.5

As far as the mechanisms for drug interaction with warfarin, some drugs act as cytochrome p450 inhibitors (thus reducing the metabolism of warfarin), while others influence the pharmacodynamics of warfarin by inhibiting the synthesis or increasing the clearance of vitamin K-2 dependent coagulation factors.3

Antibiotics may increase the risk of major bleeding through disruption of intestinal flora that synthesize vitamin K-2 with or without interference with the metabolism of warfarin through cytochrome p450 isozymes inhibition.

Check out a related pearl on P4P: https://pearls4peers.com/2015/06/25/is-there-anyway-to-predict-a-significant-rise-in-inr-from-antibiotic-use-in-patients-who-are-also-on-warfarin  

 

References

  1. Baillargeon J, Holmes HM, Lin Y, et al. Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med. 2012 February ; 125(2): 183–189. https://www.ncbi.nlm.nih.gov/pubmed/22269622
  2. Juurlink DN. Drug interactions with warfarin: what every physician should know. CMAJ, 2007;177: 369-371. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1942100/pdf/20070814s00018p369.pdf
  3. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. doi:10.1378/chest.11-2292.  https://www.ncbi.nlm.nih.gov/pubmed/22315269
  4. Hughes GJ, Patel PN, Saxena N. Effect of acetaminophen on international normalized ratio in patients receiving warfarin therapy. Pharmacotherapy 2011;31:591-7. https://www.ncbi.nlm.nih.gov/pubmed/21923443
  5. Kumar S, Gupta D, Rau SS. Supratherapeutic international normalized ratio: an indicator of chronic malnutrition due to severely debilitating gastrointestinal disease. Clin Pract. 2011;1:e21. doi:10.4081/cp.2011.e21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981245

 

Contributed by Rachel Weitzman, Medical Student, Harvard Medical School, Boston, MA.

My elderly patient on chronic warfarin with recent hospitalization for soft tissue infection is now readmitted with gastrointestinal bleed and a newly-discovered supra-therapeutic INR? Why did her INR jump?