Respiratory infections

Are GI symptoms such as nausea, vomiting, and diarrhea common in patients with influenza?

FA Manian MD, MPH, , , , , , , Leave a comment

Typically, GI symptoms are more prominent in children with influenza than adults but during the H1N1 epidemic in 2009 (which has subsequently become endemic), up to 26% of hospitalized adults with H1N1 infection had abdominal pain or vomiting and up to 25% had diarrhea (1). 

In fact, H1N1 virus has been isolated from stool of adult hospitalized patients (2,3) and receptors of influenza virus have been identified in human GI epithelial cells, the correlation between GI symptoms and isolation of virus from stool is poorly defined (4).

Interestingly, the mechanism involved in influenza-mediated intestinal injury may have less to do with direct invasion of the intestinal mucosa by the virus and more to do with immune mediated changes  related to alterations in the intestinal microbiota induced by influenza virus infection itself (4,5)! 

Aside from direct or indirect effects of influenza virus on the GI tract, oseltamivir and non-steroidal anti-inflammatory use may also contribute to GI symptoms (4).

 

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References

  1. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 influenza. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 2010;362:1708-19. https://www.ncbi.nlm.nih.gov/pubmed/20445182
  2. Yoo SJ, Moon SJ, Kuak E-Y, et al. Frequent detection of pandemic (H1N1) 2009 virus in stools of hospitalized patients. J Clin Microbiol 2010; 48:2314-2315. https://www.ncbi.nlm.nih.gov/pubmed/20375236
  3. Minodier L, Charrel RN, Ceccaldi PE, et al. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know? Virol J 2015;12:215. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676820/
  4. Shu Y, Li CK, Gao R, et al. Avian influenza A(H5N1) viruses can directly infect and replicate in human gut tissues. J Infect Dis 2010;201:1173-7. https://www.ncbi.nlm.nih.gov/pubmed/20210629
  5. Wang J, Li F, Wei H, et al. Respiratory influenza virus infection induces intestinal immune injury via microbiota mediated Th17 cell-dependent inflammation. J Exp Med 2014;211:2397-2410. http://europepmc.org/article/PMC/4235643
Are GI symptoms such as nausea, vomiting, and diarrhea common in patients with influenza?

Should corticosteroids (CS) be routinely considered in the treatment of hospitalized patients with community-acquired pneumonia (CAP)?

FA Manian MD, MPH, , Leave a comment

A recent systematic review on the subject concluded that for hospitalized adults with CAP, systemic CS may reduce mortality by about ~3% (primarily in severe CAP), mechanical ventilation need by ~5%, and hospital stay by ~1 day (1). But determining who might benefit the most and at what CS dosage regimen without undue risk of side effects (e.g. hyperglycemia) may be tricky.  

A randomized control trial of patients with CAP on prednisone 50 mg daily x 7d (vs placebo) showed a significant shorter time to clinical stability (3 vs 4.4 d) and higher in-hospital hyperglycemia in the CS group (2).; this study was not powered to detect significant difference in mortality, however.  Less treatment failure with adjunctive CS but without impact on mortality was recently reported in a small study involving patients with serum CRP >150 mg/L (i.e. high inflammatory state) (3).

Fortunately, a multicenter trial (ESCAPe, Extended Steroid in CAP) is currently underway. In the meantime, before considering CS, we need to be confident of the diagnosis and severity of CAP, its potential adverse effects in individual patients, and the appropriateness of the antibiotic (s) on board.

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References

1. Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med 2015;165:519-528. https://www.ncbi.nlm.nih.gov/pubmed/26258555

2. Blum CA, Nigro N, Briel M. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multi-centre, double-blind randomized, placebo-controlled trial. Lancet 2015;385:1511-1518. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62447-8/abstract

3. Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA 2015;313:677-86. https://www.ncbi.nlm.nih.gov/pubmed/25688779

 

Should corticosteroids (CS) be routinely considered in the treatment of hospitalized patients with community-acquired pneumonia (CAP)?

What new treatment options are available for my patient with cystic fibrosis (CF) who has had recurrent pulmonary exacerbations requiring frequent hospitalizations?

FA Manian MD, MPH, , Leave a comment

CF is caused by gene mutations that result in deficient or dysfunctional transmembrane conductance regulator (CFTR) protein, an anion channel that is normally present in the epithelial membrane. Two FDA- approved drugs may provide new options for at least some CF patients. Ivacaftor (Kalydeco) is a CFTR protein potentiator that increases the probability that the CFTR channels are open in vitro and improves clinical outcomes in patients ≥12 years of age with at least one copy of G551D mutation, present in ~5% of CF patients (1). 

Orkambi is a combination of ivacaftor and lumacaftor – a drug that prevents intracellular destruction of CFTR –for patients with the Phe508del CFTR mutation, present in ~50% of CF patients.   Its use has been associated with fewer pulmonary exacerbations and hospitalization in patients (≥ 6 years of age) homozygous for this gene (2). Ivacaftor and Orkambi are priced at over $300,000/year and $295,000/year, respectively (http://www.nytimes.com/2015/07/03/business/orkambi-a-new-cystic-fibrosis-drug-wins-fda-approval.html?_r=0).

1. Ramsey BW, Davies J, McElvaney NG, et al. A CFTR Potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365:1663-1672.

2. Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med 2015;373:220-231.

Contributed by Cynthia M. Cooper, MD, Boston, MA

What new treatment options are available for my patient with cystic fibrosis (CF) who has had recurrent pulmonary exacerbations requiring frequent hospitalizations?

In hospitalized patients with community-acquired pneumonia (CAP), has empiric treatment with beta-lactam plus macrolide or a quinolone been shown to be superior to beta-lactam monotherapy ?

FA Manian MD, MPH, , , , , , , Leave a comment

Actually no!

In fact, a 2015 study of CAP from Netherlands, published in New England Journal of Medicine, demonstrated that empiric treatment with beta-lactam monotherapy was not inferior to strategies using a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality, or length of hospital stay (1). To help exclude Legionella pneumonia (often accounting for <5% of CAP[2]), urine Legionella antigen was routinely performed in this study.

So once Legionella has been reasonably excluded, unless suspicion for other atypical causes of CAP (i.e. Mycoplasma pneumoniae or Chlamydophila pneumoniae) remains high, empiric monotherapy with a beta-lactam (e.g. ceftriaxone) may be just as effective in many cases of CAP.

References

1. Postma DF1, van Werkhoven CH, van Elden LJ, et al. CAP-START Study Group Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015;372:1312-23.  https://www.ncbi.nlm.nih.gov/pubmed/25830421  

2. von Baum H, Ewig S, Marre R, et al. Competence Network for Community Acquired Pneumonia Study Group. Community-acquired Legionella pneumonia: new insights from the German competence network for community acquired pneumonia. Clin Infect Dis 2008;46:1356. https://www.ncbi.nlm.nih.gov/pubmed/18419436

Contributed by Jessica A. Hennessey, MD, PhD, Mass General Hospital, Boston, MA

In hospitalized patients with community-acquired pneumonia (CAP), has empiric treatment with beta-lactam plus macrolide or a quinolone been shown to be superior to beta-lactam monotherapy ?

My 65 year old patient has had several bouts of bacterial pneumonia in the past 2 years. Her total serum immunoglobulins are within normal range. Could she still be immunodeficient?

FA Manian MD, MPH, , , , , , , Leave a comment

Absolutely! Besides HIV infection which should be excluded in all patients with recurrent bouts of bacterial pneumonia irrespective of age, “selective polysaccharide antibody deficiency”, also known as “specific antibody deficiency” or SAD, should also be excluded (1-3). SAD in adults with recurrent pneumonia is not rare, having been reported in about ~8% of such patients (4).  

Think of SAD when your adult patient presents with recurrent bouts of bacterial pneumonia  despite having normal serum total immunoglobulin (IgG, IgA, and IgM) levels and IgG subtypes (1-3).  These patients have a normal response to tetanus toxoid (a protein) but cannot mount adequate antibody response against polysaccharide antigens of pathogens such as pneumococcus.  

One way to diagnose SAD in a suspected patient is through vaccination with 23-valent pneumococcal polysaccharide vaccine (PPSV23).  In patients with low baseline antibody titers to many of the capsular types of pneumococcus included in the PPSV23,  a suboptimal response (defined by the lab) 4 weeks after vaccination with PPSV23 is suggestive of SAD. Remember that if your patient has already been vaccinated with the 13 valent pneumococcal conjugate vaccine (PCV13), you can only evaluate for the response to serotypes included in the  PPSV23 only.

Although there are no randomized-controlled studies and treatment should be individualized, immunoglobulin replacement may reduce the risk of future bouts of pneumonia in SAD (2-3). 

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References

1. Cohn JA, Skorpinski E, Cohn JR. Prevention of pneumococcal infection in a patient with normal immunoglobulin levels but impaired polysaccharide antibody production. Ann Allergy Asthma Immunol 2006;97:603-5. https://www.ncbi.nlm.nih.gov/pubmed/17165266

2. Cheng YK, Kecker PA, O’Byrne MM, Weiler CR. Clinical and laboratory characteristics of 75 patients with specific polysaccharide antibody deficiency syndrome. Ann Alergy Asthma Immunol 2006;97:306-311. https://www.ncbi.nlm.nih.gov/pubmed/17042135

3. Perez E, Bonilla FA, Orange JS, et al. Specific antibody deficiency: controversies in diagnosis and management. Front Immunol 207;8:586. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439175/pdf/fimmu-08-00586.pdf

4. Ekdahl K, Braconier JH, Svanborg C. Immunoglobulin deficiencies and impaired immune response to polysaccharide antigens in adult patients with recurrent community acquired pneumonia. Scand J Infect Dis 1997;29:401-7. https://www.ncbi.nlm.nih.gov/pubmed/9360257

 

My 65 year old patient has had several bouts of bacterial pneumonia in the past 2 years. Her total serum immunoglobulins are within normal range. Could she still be immunodeficient?

Is the “8 day rule” for treatment of healthcare-associated pneumonia (HAP) appropriate irrespective of etiologic agent?

FA Manian MD, MPH, , Leave a comment

Not necessarily.  In fact, an often-quoted study showed more relapses among patients with Pseudomonas aeruginosa nosocomial pneumonia treated for 8 days compared to 15 days, and concluded that the results did not apply to “non-fermenting gram negative bacilli” (1).

For methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, the data on the effectiveness of the shorter course therapy is also quite limited (1,2) .  So for patients with pneumonia due to organisms such as P. aeruginosa or MRSA I decide on the duration of therapy on case-by-case basis depending on the overall stability of the patient and their progress in recovery.

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References

1. Chastre J, Wolff M, Fagon JY. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003;290:2588-98. 

2. Rubinstein E, Kollef MH, Nathwani D. Pneumonia caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008;46 (Suppl5):S378-385.

Is the “8 day rule” for treatment of healthcare-associated pneumonia (HAP) appropriate irrespective of etiologic agent?

How should follow-up serum C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) be interpreted?

FA Manian MD, MPH, , , Leave a comment
CRP level should drop to less than one-half of its value on admission after a couple of days of antibiotic therapy, since CRP half-life is less than a day following zero order elimination kinetics. 

 

Of interest, in a study of serial CRP in severe CAP (1), a CRP ratio >0.5 by day 3 was associated with non-resolving pneumonia ( sensitivity 91%, specificity 55%)   performing significantly better than body temperature or WBC count.  

 

So if there is any doubt about how a patient is doing clinically, a repeat CRP looking for a drop of greater than on-half after 3-4 days of therapy may be helpful.

 

Bonus Pearl: Did you know that the half-life of CRP is 19 h?

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Reference

1. Coelho L, Povoa P, Almenda E, et al. Usefulness of C-reactive protein in monitoring the severe community-acquired pneumonia clinical course.  Critical Care 2007;11:R92 https://ccforum.biomedcentral.com/articles/10.1186/cc6105

 

 

How should follow-up serum C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) be interpreted?